Fall 2011 - Institute of Medical Science - University of Toronto

IMSMAGAZINE 

FALL 

THINK, LEARN, DISCOVER. 2011 

CANCER DONATIONS 

Find out where your money goes 

BIAS IN RANDOMIZED 

CLINICAL TRIALS 

Learn about evaluating bias in 

RCTs from this year’s SURP 

Writing Competition winner 

PROSTATE 

CANCER 

IN A NUTSHELL 

Screening protocols, preventative 

measures, and therapies related to 

the most common cancer in men

IN THIS 

ISSUE... 

TABLE OF CONTENTS 

Philosophy of Science painting: The School of Athens (1510-1511) by Raphael, IMS SURP Highlight photo courtesy of the IMS Office 

Commentary ...................................03 

Letter from the Editor .....................04 

News at a Glance ...........................05 

Director’s Message ........................08 

IMS SURP Highlight ........................09 

Feature ...........................................13 

Spotlight .........................................25 

Close Up .........................................27 

SURP Research Focus ....................29 

Philosophy of Science ....................31 

Behind the Scenes .........................35 

Future Directions .............................37 

Funding ...........................................39 

Ask the Experts ..............................40 

Past Events .....................................41 

Diversions .......................................42 

MAGAZINE STAFF 

Editor-in-Chief 

Managing Editor 

Assistant Managing Editors 

Departmental Advisor 

Content Committee 

Design Editors 

Photography 

Acknowledgements 

Natalie Venier 

Nina Bahl 

Allison Rosen 

Meghna Rajaprakash 

Adam Santoro 

Kamila Lear 

S. Amanda Ali 

Tetyana Pekar 

Aaron Kucyi 

Rickvinder Besla 

Wenjun Xu 

Zeynep Yilmaz 

Tobi Lam 

Andreea Margineanu 

Merry Wang 

Minyan Wang 

Paulina Rzeczkowska 

Connie Sun 

Mohammed Sabri 

Yekta Dowlati 

Diego Accorsi, Joyce Hui, 

Beatrice Lau, Julie Man, 

Avi Vandersluis, Atiqa Malik 

Copyright © 2011 by Institute of Medical Science, University of Toronto. All 

rights reserved. Reproduction without permission is prohibited. 

13 

FEATURE 

Prostate Cancer 

Learn the ins and outs of prostate cancer from our 

very own experts in the field. 

09 

IMS SURP Highlight 

Check out the highlights from this year’s Summer 

Undergraduate Research Program (SURP) 

and Summer Student Research Day. 

31 

Philosophy of Science 

Read about how a lack of philosophical 

knowledge of the scientific method may affect 

our research. 

Cover Art 

By Minyan Wang 

The cover features two of prostate cancer’s 

most recognizable symbols: the walnut 

and blue ribbon. The prostate is classically 

described as a walnut-shaped organ, while 

the blue ribbon stands as a symbol of prostate 

cancer support. We include both to encourage 

awareness of the most common cancer in men. 

IMS MAGAZINE FALL 2011 PROSTATE CANCER | 02

COMMENTARY 

Tell us what you think 

“Just a quick email to congratulate [your 

team] on the IMS Magazine. Very interesting 

content and nice to get a flavour of 

what else is happening at IMS.” 

– Colin McCartney, Associate IMS Member 

“Congratulations! The magazine looks brilliant.” 

– Santhosh, IMS student 

“[The magazine] looks great and the content 

is interesting and well put together… 

Looking forward to future issues.” 

– Wilfred Ip, IMS student 

“The magazine looks fantastic and reads 

extremely well with an excellent balance of 

interesting articles about students, faculty, 

staff and the life as an IMS student. ” 

– Dr. Karen Davis, IMS Associate Director 

What to look for next issue: 

The Surgical Management of Obesity by 

Dr. Teodor Grantcharov 

Commentary 

Dear Editor: 

I read the most recent (Summer 2011) edition 

of the IMS Magazine with great interest 

and enjoyed its focus on obesity/BMI. The 

magazine only briefly mentioned that BMI 

varies across ethnic groups. I would like to 

elaborate more on these ethnic variations using 

empirical evidence from my IMS PhD 

thesis findings. 

Many agree that the definition of obesity 

(BMI≥30) is inappropriate in non-white 

populations and that lower cutoff values are 

required for Asian populations, however no 

previous study has been able to pinpoint exactly 

what the BMI cutoff values should be 

for specific Asian ethnic groups. I therefore 

conducted a multiethnic cohort study of approximately 

60,000 non-diabetic adults aged 

30 years or over living in Ontario. Subjects 

were identified from Statistics Canada’s population 

health surveys and were followed for 

up to 12.8 years for diabetes incidence using 

record linkages to multiple health administrative 

databases. 

The study found that for the equivalent incidence 

rate of diabetes at BMI 30 in the 

White group, the BMI cutoff value was 24 

in the South Asian group, 25 in the Chinese 

group, and 26 in the Black group. Moreover, 

the risk of diabetes was significantly higher 

among the South Asian (hazard ratio (HR): 

3.40, p

LETTER FROM THE EDITOR 

Letter from 

the Editor 

I 

am always fascinated to learn about new scientific research. Having the privilege to study at 

the IMS has undoubtedly shown me the many ways in which science can be used to improve 

patient care - one of my own inspirations for starting the IMS Magazine. In the past three 

issues, we have explored a variety of research areas, from the genetics of childhood aggression, 

to multiple sclerosis and binge eating disorders. I have found them all very intriguing topics and 

rewarding to learn about. 

In this issue of the IMS Magazine, I would like to turn your attention to the topic of my area 

of research, prostate cancer. With the help of our very own world-class experts, Dr. Laurence 

Klotz, Dr. Neil Fleshner, Dr. Masoom Haider, and Dr. Vasundara Venkateswaran, we hope to 

provide you with a better understanding of prostate cancer prevention measures, management 

options, and future research strategies. Further, we give you a look into the Active Surveillance 

program, a management strategy initiated at Sunnybrook Hospital by Dr. Laurence Klotz, which 

is increasingly used worldwide for low-risk prostate cancer patients. 

In light of November, prostate cancer awareness month, I hope that this issue of the IMS Magazine 

will not only enhance your understanding of the disease, but also emphasize the importance of 

early detection. I encourage all those participating in the moustache-growing Movember charity 

event to submit your photos to the IMS Magazine Movember Contest (see page 43 for more 

information). 


Editor-In-Chief 

Natalie Venier is a third year PhD Candidate 

at the Institute of Medical Science. 

She is currently studying prostate cancer 

chemoprevention at Sunnybrook Health 

Sciences Centre. 

I am also proud to announce the success of the Summer Student Writing Competition, which 

was met with great enthusiasm by this year’s SURP students. We received a number of excellent 

submissions, including one by Roman Shapiro, the winner of the competition. I encourage you 

to read through his interesting article on biases in Randomized Controlled Trials. We hope to 

continue to publish some of the other excellent submissions in future issues of the IMS Magazine. 

I would also like to take this opportunity to thank the IMS Community for their insightful 

feedback in response to the last issue, which I encourage you to read about in our new 

Commentary section. 

In closing, I would like to thank Dr. Allan Kaplan and the IMS department for their on-going 

support with the IMS Magazine. Additionally, I must acknowledge the phenomenal IMS 

Magazine Team, whose contributions are invaluable to its production. I’m looking forward to 

your feedback. 

Enjoy! 

Photo by Paulina Rzeczkowska 


Editor-In-Chief, IMS Magazine 


NEWS AT A GLANCE 

NEWS&VIEWS 

OCTOBER 

19 

28 

TBA 

OGS scholarship 

applications due to IMS 

office; OGS application 

goes offline 

Banting PDF University 

Support Letter ready for 

applicants 

Interdepartmental 

Halloween party 

NOVEMBER 

7 

CIHR 

7 

Frederick 

IMS STAFF ANNOUNCEMENTS 

CGSM, SSHRC CGSM 

& SSHRC Doctoral/CGSD 

scholarship applications due 

to IMS Office 

Banting and Charles 

Best Canada Graduate 

Scholarships (Masters Award) 

due at IMS Office. 

We are delighted to announce that Professor Brenda Toner has been was appointed as the 

new Graduate Coordinator at the Institute of Medical Science. 

Dr. Brenda Toner is the Co-Head for the Social Equity & Health Research unit in the Social, 

Prevention and Health Policy Research department. Dr. Toner is also a Professor and 

Head of the Women’s Mental Health Program, and Director of Fellowship Program in the 

Department of Psychiatry at the University of Toronto. Congratulations to Professor Toner 

on her new appointment! 

at a glance... 

DECEMBER 

1 

Deadline 

5 

Delta 

TBA 

for John C. 

Polanyi Prize nominations 

to IMS Office 

Kappa Gamma 

World Fellowship Award 

applications due at SGS 

IMSSA Holiday party 

We extend our sincere thanks and gratitude to Dr. Mary Seeman for all her guidance and 

contributions as Graduate Coordinator of the IMS. 

We regret to inform you that Dianne Fukunaga is leaving the Institute of Medical Science 

 

last day with the IMS was on Friday, September 30th. 

 

up the ranks to assume the role of Student and Faculty Affairs Coordinator, where she 

provided exemplary service and demonstrated excellence and commitment to her work. 

Dianne has become an indispensable colleague and she will be greatly missed by everyone 

in the Department. We extend our best wishes to Dianne in her future endeavors. 

We will be posting a recruitment notice to hire a replacement. In the interim, Kaki Narh 

Blackwood has kindly offered to step into the position to cover some of the responsibilities. 

Please contact sf.medscience@utoronto.ca or call 416-946-7143 for student and faculty 

related inquiries. We will be monitoring both email and voice mail message systems. 

Dr. Brenda Toner 

IMS Graduate Coordinator 

For more information on 

IMSSA/IMSSA-related events, please visit: 

http://imssa.sa.utoronto.ca 

For information on IMS news and events, please see: 

http://www.ims.utoronto.ca 

Please send your comments and suggestions to: 

theimsmagazine@gmail.com 

Photo courtesy of IMS Office 

05 | IMS MAGAZINE FALL 2011 PROSTATE CANCER

NEWS AT A GLANCE 

IMSSA ANNOUNCEMENTS 

IMSSA Executive Council 2011-2012 

 

students who submitted nominations and participated so eagerly in this year’s election. 

 

The elections for the 2011-2012 IMSSA Executive 

Council took place on October 3, 2011. IMSSA is proud 

to announce the names of the newly elected council 

members. 

President: 

Ilyse Darwish 

AWARDS & SCHOLARSHIPS 

CIHR Research Awards 

Master’s Award: Frederick Banting and Charles Best Canada Graduate 

Scholarships 

The Canada Graduate Scholarships Master’s Awards administered by CIHR are intended 

to provide special recognition and support to students who are pursuing a Master’s 

 

exceptionally high potential for future research achievement and productivity. 

 

Students may only apply to one council (CIHR, NSERC or SSHRC) in a given year. 

CIHR Doctoral Research Award 

Doctoral Research Awards are intended to provide special recognition and support to 

 

These candidates are expected to have an exceptionally high potential for future 

research achievement and productivity. 

Applications for the CIHR Doctoral Research Award are submitted directly to CIHR. 

The full program description, application form and instructions are now available on 

the CIHR website. 

Ontario Graduate Scholarships (OGS) 

The Ontario Graduate Scholarship program is designed to encourage excellence in 

graduate studies at the master and doctoral levels. An OGS is awarded for one academic 

year, which may consist of two or three consecutive terms. The current value of OGS is 

$5,000 per term. Students may receive a total of $10,000 for two consecutive terms or a 

total of $15,000, for three consecutive terms. 

 

SSHRC Doctoral Fellowships 

Through its Doctoral Awards funding opportunity, SSHRC offers two types of funding 

for doctoral students, which applicants apply for by completing one application form: 

1. SSHRC Doctoral Fellowships;; and 

ships. 

The SSHRC Doctoral Fellowships and Joseph-Armand Bombardier CGS Doctoral 

Scholarships aim to develop research skills and assist in the training of highly 

arly 

achievement in undergraduate and graduate studies in the social sciences and humanities. 

- 

 

 

the number of months of full-time study (or equivalent) the applicant will have completed 

at the proposed start date of the award. 

The full program description, application form and instructions are now available on 

the SSHRC website and in SSHRC’s new Resource Centre. 

Vice-Presidents: 

Melanie Guenette 

Vanessa Zannella 

Treasurer: 

Nicholas Howell 

Secretary: 

Laura Park 

Director of Academic Affairs: 

Leanne De Souza 

Director of Social Affairs: 

Ilya Mukovozov 

Director of Sporting Events: 

Yi-an Chen 

Director of Communications: 

 

GSU Representative: 

Laura Finkelberg 

Arash Ghashghai 

Katarina Lakovic 

CIP Representative: 

George Ibrahim 

IMS Magazine Representative: 

Amanda Ali 

Toronto General Hospital Site Director: 

Priyanka Patel 

MSB/CCBR/Tanz Site Directors: 

Amy Oh 

Mount Sinai Hospital Site Director: 

Tetyana Pekar 

MaRS Site Directors: Wilfred Ip 

Anna Podnos 

Toronto Western Hospital Site Directors: 

Eric Monsalves 

Allison Rosen 

Centre for Addiction and Mental Health 

Site Directors: Yekta Dowlati 

 

Hospital for Sick Children Site Directors: 

Anathavalli Kumarappah 

Vivian Szeto 

Princess Margaret Hospital Site Director: 

Ryan Rumantir 

Sunnybrook Health Sciences Centre 

Site Directors: Otilia Cristina Nasui 


St. Michael’s Hospital Site Directors: 

 

Tony Lin 

You can stay up to date on IMSSA events and 

workshops by checking out the IMSSA 

website at http://imssa.sa.utoronto.ca, or 

 

group at Institute of Medical Science (U of T). 


DIRECTOR’S MESSAGE 

Director’s 

Message 

The IMS Magazine has been a tremendous success and is just one of the many wonderful studentinitiated 

projects that make the IMS such a very special institute. I fully support the ongoing 

publication of the IMS Magazine and look forward to the many opportunities the magazine can 

afford us for recruitment and for publicizing the outstanding research that is being conducted by 

our faculty and our trainees. 

This fourth issue of the magazine focuses on the important area of prostate cancer and highlights 

some of the important research that IMS faculty is conducting. Congratulations to Natalie Venier 

and her team for their continued hard work and collective creative energies in producing this 

wonderful publication. Thanks as well to Kamila Lear for her ongoing assistance in this project. 

This summer, the IMS moved into its new space on the main floor of MSB, room 2374. Please 

come and visit us as soon you can. We also welcomed two new administrative assistants to our 

administrative team: Kaki Narh Blackwood, whose portfolio includes coordinating student defense 

examinations and monitoring program progress and completion; and Marika Galadza, whose 

portfolio includes general inquiries, room bookings, and the summer undergraduate program. I 

look forward to working with Kaki and Marika, as well as with Kamila Lear, our program and 

business officer, Hazel Pollard, who is responsible for admissions and enrollment issues, and Dianne 

Fukunaga, who deals with awards, faculty appointments, and courses. 

I am also pleased to announce the appointment of Professor Brenda Toner as our new Graduate 

Coordinator. Professor Toner is currently a Senior Scientist in Social and Epidemiologic Research at 

the Center for Addiction and Mental Health, Director of the Fellowship Program and Acting Head 

of the Women’s Mental Health Program in the Department of Psychiatry. She brings a wealth of 

experience in mentoring students from many disciplines. Dr. Toner will be replacing Professor Mary 

Seeman, who will be retiring after almost a decade of involvement as an IMS Graduate Coordinator. 

We thank Professor Seeman for her enormous and invaluable contribution to IMS. She has been a 

mentor for us all, especially to our students. 

Allan S Kaplan, MSc, MD, 

FRCP(C) 

Director, IMS 

Dr. Allan Kaplan became the IMS 

Director in July 2011. He is the 

Chief of Clinical Research and 

Director of Research Training at the 

Centre for Addiction and Mental 

Health (CAMH), and a Senior 

Clinician-Scientist in CAMH’s Mood 

and Anxiety Program. He is also 

the Vice Chair of Research, Director 

of the Clinician Scientist Program 

and Professor of Psychiatry at the 

University of Toronto. 

As I mentioned in my previous Director’s Message, for the first time, the IMS is about to embark 

on an extensive strategic planning initiative. Towards that end, we have engaged the assistance of 

the Potential Group to help lead us through this process. Over the next six months, the Strategic 

Planning Committee will be seeking your input in helping to create a vision for the IMS for the next 

5 years. Please participate in this important process; it is a unique opportunity for you to help shape 

an inspirational future for the IMS. I look forward to working with all of you as we embark on this 

journey together. 

Sincerely, 

Photo by Mohammed Sabri 

Allan S Kaplan MD FRCP(C) 

Director, Institute of Medical Science 


IMS SURP HIGHLIGHT 

SUMMER UNDERGRADUATE 

RESEARCH PROGRAM 

Special thanks to all who participated 

in this year’s lecture series: 

Dr. Moloo Badru 

Director, Animal Resources Centre, University 

Health Network 

Dr. Jay Keystone 

Professor of Medicine, Tropical Disease 

Unit, Toronto General Hospital 

Prof. Nick Woolridge 

Professor and Director, Biomedical Communications, 

University of Toronto 

Dr. Bharati Bapat 

Staff Scientist, Mount Sinai Hospital 

Mr. Neil Winegarden 

Head of Operations, Microarray Centre, 

University Health Network 

Dr. Lucy Osborne 

Affiliate Scientist, Division of Genomic 

Medicine, Toronto General Research Institute, 


Dr. Karen Davis 

Professor of Surgery, Associate Director, 

Institute of Medical Science, Canada 

Research Chair in Brain and Behaviour, 


Dr. Linda Sugar 

Professor, Laboratory Medicine and Pathology, 

University of Toronto and Staff 

Pathologist, Sunnybrook Health Sciences 

Centre 

The Institute of Medical Science Summer 

Student Program provides an 

opportunity for undergraduate BSc. 

and medical students to become involved 

in projects in biomedical research ranging 

across a broad spectrum of areas, from 

molecular biology and cognitive science to 

clinical investigation and bioethics. 

Participants spend the summer in a laboratory, 

working on a research project in biomedi- 

cal research. These students are encouraged 

to participate in individual laboratory meetings, 

data analysis sessions, journal clubs, 

and appropriate clinical research rounds 

at the affiliated teaching hospitals. In addition, 

the IMS offers a weekly lecture series 

to complement the students’ research. The 

lecture series includes research presentations 

by IMS faculty, graduate studies information 

sessions, and practical skills workshops. 

Dr. Ori Rotstein 

Surgeon-in-Chief, St. Michael’s Hospital 

IMSSA: Student Presentations 

Dr. Michael Szego 

Fellow of the Joint Centre for Bioethics 

Dr. Vasundara Venkateswaran 

SURP Director 

Photos courtesy of the IMS Office 



IMS SUMMER INTERNATIONAL PROGRAM 

Canadian Students 

York University (2) 

University of Ottawa (2) 

Guelph University (2) 

University of Western Ontario (17) 

University of Toronto (47) 

Queen’s University (10) 

McMaster University (11) 

Concordia University (1) 

McGill University (3) 

University of Manitoba (1) 

St. Francis Xavier University (2) 

Dalhousie University (1) 

University of Oshawa Institute of Technology (1) 

International Students 

The National University of Ireland, Ireland (1) 

University of Edinburgh, UK (1) 

City University, UK (1) 

Shandong University, China (7) 

Shantou University, China (4) 

King Saud, Saudi Arabia (8) 

Hacettepe University, Turkey (2) 

George Washington University, USA (1) 

Wayne State University, USA (1) 

Yeshiva University, USA (1) 

Hillsdale College, USA (1) 

National Chiao Tung University, Japan (6) 

The IMS SURP program offers a special opportunity 

to host international undergraduate 

students. Students work on one regular 

research project in a laboratory, and participate 

with domestic students in their weekly 

seminars, and IMS Summer Research Day 

presentations. This year a large number of 

students participated in the SURP program 

from various international universities. 

Photos courtesy of the IMS Office; SURP photo courtesy of Mohammed Sabri 

IMS MAGAZINE FALL 2011 PROSTATE CANCER | 

10

IMS SURP HIGHLIGH T 

IMS SUMMER STUDENT RESEARCH DAY 

In early August, summer students participate 

in the annual IMS Summer Student Research 

Day, which includes a keynote speaker, oral 

and poster presentations of their research. 

Supervisors, along with other IMS faculty, 

serve as judges for the summer student presentations. 

As Professor Ori Rotstein’s term as IMS Director 

ended this past July, IMS faculty, staff 

and alumni established an annual lectureship 

series in his honour. The Ori Rotstein 

Lecture in Translational Research provides a 

wonderful opportunity to recognize Professor 

Rotstein’s commitment to the ongoing 

development of the Institute, by bringing 

together faculty and students for annual scientific 

exchanges. 

Dr. Lyle Palmer, Executive Scientific Director, 

Ontario Health Study gave the inaugural 

Ori Rotstein Lecture in Translational Research 

at the annual SURP Research Day. Dr. 

Palmer’s presentation was titled, “The Ontario 

Health Study: Creating Platforms for 

revolutionary science and transformational 

biology.” 




SURP Day Winners 

Justin Wang (Oral Presentation) 

Laureen Hachem (Poster Presentation) 

Olesya Solomonova (Poster Presentation) 

Judy Qjang (Poster Presentation) 

Joshua Rosenblat (Poster Presentation) 

Alannah Smrke (Poster Presentation) 

Anna Artymowicz (Poster Presentation) 

Vanja Cabric (Poster Presentation) 

Melanie Kalbfleisch (Poster Presentation) 

Paymon Azizi (Poster Presentation) 

Cynthia Chan (Poster Presentation) 

Julie Anh Dung Van (Poster Presentation) 

Zhe Liang (Poster Presentation) 

Michael Catapano (Poster Presentation) 

Dylan Kain (Poster Presentation) 

Runner Up Winners 

Bradley Kaplansky (Oral Presentation) 

Katrine De Asis (Poster Presentation) 

Amy Lu (Poster Presentation) 

Grace Phillips (Poster Presentation) 

Brian Vadasz (Poster Presentation) 

Annabelle Ong (Poster Presentation) 

Adrian Budhram (Poster Presentation) 

Jean Michelle Legasto (Poster Presentation) 

Miyuki Kumagai (Poster Presentation) 

Jai Prashanth Jayakar (Poster Presentation) 

Santina Lee (Poster Presentation) 

Sonam Maghera (Poster Presentation) 

Taylor Kain (Poster Presentation) 

Vivian Szeto (Poster Presentation) 



Illustrations by Andreea Margineanu 


FEATURE 

 

The prostate is a walnut-shaped exocrine 

gland located between the bladder and the 

rectum. It has three main functions: production 

of fluid for semen, production of 

prostate specific antigen (PSA), and control 

of urine flow. 

 

 

 

 

 

 

 

 

Like most malignancies, prostate cancer 

develops when cells within the prostate grow 

uncontrollably. This irrepressible growth 

causes the development of small tumours. In 

most cases, these prostate tumours grow 

relatively slowly. It usually takes years for 

tumours to become large enough to be 

detectable and it takes even longer for them 

to spread out of the prostate. Unfortunately, a 

small number of men have aggressive 

prostate cancers that grow and spread 

quickly. 

 

Prostate cancer is typically classified into different stages based on whether it is confined to the prostate or has spread to other parts 

of the body. The staging of prostate cancer is important for selecting various management and treatment strategies. 

 

In stage I disease, the cancer is confined to the 

prostate only. It usually is very minimal, and 

requires multiple types of testing modalities to be 

detected (i.e. PSA testing and biopsy). 

 

 

In stage II disease, the cancer is a more advanced than stage I, although it has not spread beyond 

the prostate. It can be classified as stage IIA or stage IIB. In Stage IIA, the cancer is localized to 

one lobe of the prostate. In Stage IIB, the cancer is present in both lobes of the prostate. 

Illustrations by Oilvia Shim and Andreea Margineanu 

 

In stage III disease, the cancer has spread beyond 

the outer layer of the prostate on one or both sides 

and may have spread to the seminal vesicles. 

 

In stage IV disease, the cancer has spread beyond 

the seminal vesicles to nearby tissue or organs, such 

as the rectum, bladder, or pelvic wall; may include 

lymph nodes or bones. 

 

For more detailed information 

on prostate cancer and the 

specific staging classifications, 

visit: 

www.cancer.gov 

or 

www.prostatecancer.ca 


FEATURE 

Prostate Cancer Prevention 

An Overview 

Prostate cancer is the commonest non-cutaneous human malignancy and second most 

frequent cause of cancer death in males. Recent published data has established that 

prostate cancer is preventable. Substantial pre-clinical and epidemiologic studies 

have identified antioxidants and other micronutrients as promising agents for prostate 

cancer prevention. Key agents currently include vitamin D, lycopene, capsaicin, soy 

products, 5ARIs (alpha reductase inhibitors), and dietary and weight modification. 

Dr. Laurence Klotz 

MD, FACS, FRCSC 

Professor of Surgery, 


T 

here is increasing evidence 

that the evironment plays an important 

role in the progression of 

prostate cancer. There is a one hundred fold 

variation in age-adjusted mortality rates 

from prostate cancer between high and low 

risk geographic and racial groups. In marked 

contrast to this large global variation, autopsy 

studies confirm that micro foci of prostate 

cancer exist ubiquitously in 42-80% of males 

over 50 years. In nations with a high incidence 

of prostate cancer deaths, these foci 

appear to be characterized by higher volume, 

grade and multifocality compared to patients 

from nations with low rates of the disease. 

Studies of migrating populations reveal that 

men from countries with a low incidence 

of prostate cancer (i.e. Japan) acquire an increased 

incidence rate within 20 years upon 

emigration to the West, approaching that of 

the host country. A detailed autopsy study in 

American trauma victims found that 30% of 

men between 30 and 39 had microfocal prostate 

cancer 1 leading to the hypothesis that 

environmental influences stimulate latent 

prostate cancer to progress to biologically 

significant disease. 

Despite the evidence that substances can help 

prevent or slow prostate cancer progression, 

not all results have been positive. Vitamin E 

and selenium, both of which appeared very 

promising in epidemiologic, pre-clinical, 

and clinical studies, were evaluated in a huge 

prospective randomized trial with prostate 

cancer incidence as the primary endpoint. 

The SELECT trial randomized 31,000 men 

between groups given placebo, vitamin E, 

selenomethionine, and the combination. 

The study was stopped early after a futility 

analysis showed absolutely no difference in 

prostate cancer incidence (or, indeed, in any 

other cancer rate). Further, there was a modest 

but statistically significant increase in diabetes 

in the selenium arm. Thus, the current 

recommendation is that patients not take 

these 2 agents for prostate cancer prevention. 

The Prostate Cancer Prevention Trial (PCPT) 

and REDUCE trial addressed the role of 5 

alpha reductase inhibitors in prostate cancer 

prevention. The PCPT trial randomized 

18,000 healthy men between finasteride 

(5ARI) and placebo. Following 7 years of 

treatment, the incidence of prostate cancer 

on biopsy was decreased by 24.8% in the 

finasteride arm. Importantly, the incidence 

of high-grade prostate cancers in the finasteride-treated 

patients was increased. The 

REDUCE trial tested the preventive value 

of dutasteride in 8231 men with an elevated 

PSA (an indicator of possible prostate cancer) 

and a negative prior biopsy. The results were 

similar; a 23% reduction in the risk of prostate 

cancer being diagnosed on biopsy after 4 

years on the drug compared to placebo. The 

initial analysis did not show a significant difference 

in high-grade cancer; a subsequent 

Photo by Connie Sun 


FEATURE 

analysis suggested a small increase in highgrade 

cancer in the dutasteride arm. One patient 

(0.04%) was found to have Gleason 8-10 

cancer in the placebo arm compared to 12 

patients (0.5%) in the dutasteride arm. While 

there is evidence that this increase in grade 

was an artifact, it has led to concern about 

the widespread implementation of 5ARIs for 

prevention in healthy men. These patients 

also more commonly experienced sexual side 

effects. These studies provide further impetus 

for developing safe preventive agents that 

have more acceptable side-effect profiles and 

avoid the increased grade phenomenon. 

The mechanism by which high-fat diets contribute 

to cancer progression is thought likely 

to be related to increased insulin and/or related 

growth factor levels. Low-carbohydrate 

diets are based on maintaining low insulin 

levels. Our hypothesis is that a low-insulinemic 

diet, by virtue of reducing circulating 

insulin and IGF levels, may protect against 

the carcinogenic effect associated with highfat 

intake. 

In our laboratory, we have studied the influence 

of vitamin E, selenium, lycopene, flavonoids, 

and dietary intervention with a low 

carbohydrate diet on the growth, progression, 

and gene expression of a transgenic prostate 

cancer model (Lady TRAMP). This work was 

carried out by Dr. Vasu Venkateswaran and 

a number of fellows and graduate students. 

Our results are summarized as follows 5-11 : 

Experimental Results 

We have also evaluated the relationship between 

diet, exercise, and prostate cancer 

progression in a xenograft model. This study, 

carried out by our IMS graduate students, 

compared cancer progression in mice exercised 

on a treadmill for several hours per 

day, maintained on either a standard, or high 

fat-high carbohydrate diet. This study found, 

perhaps not surprisingly, that regular exercise 

in conjunction with a normal diet inhibited 

cancer growth. However, the group with 

the most rapid cancer progression was the 

exercising mice on a high fat-high carbohydrate 

diet. These animals had a higher energy 

intake than the non-exercising animals. Our 

hypothesis is that the exercise stimulated an 

increase in dietary intake of a ‘bad’ diet, resulting 

in increased cancer cell proliferation. 

We believe this process is mediated through 

the insulin-IGF1 axis as well as other pathways. 

This is something to consider the next 

time you eat a Big Mac after a workout! 

The relationship between dietary intake 

and prostate cancer incidence and mortality 

is complex. Extensive epidemiologic data 

points to a strong positive relationship between 

fat intake and prostate cancer progression; 

while a diet rich in fruits and vegetables 

(particularly lycopene containing plants like 

tomatoes) as well as soy products are suggested 

to have protective effects. The Japanese 

have shifted to a more Western diet over the 

last 20 years, and this has been accompanied 

by a rapid increase in prostate cancer incidence 

and mortality, which is now approaching 

North American rates. Specifically, with 

approximately one half the population of the 

US, the number of cases has increased over 

the last 20 years from 10% to 65% of the US 

incidence. Of course, separating the impact 

Vitamin E, selenium, and lycopene dramatically inhibit the development of prostate cancer in this model. 

Lycopene is a necessary component of this effect. 

Several flavonoids dramatically inhibit the growth of prostate cancer in a xenograft model. This is mediated 

through a number of cell cycle specific genes and pathways. 

A low carbohydrate diet reduces the growth rate of prostate cancer xenografts in mice on a high-fat diet 

compared to an isocaloric high-carbohydrate diet. This is mediated through the IGF family of mitogens. 

of increased case detection by PSA screening 

on these figures is challenging. Nonetheless, 

the overwhelming weight of evidence suggests 

that a diet more oriented towards plants 

and away from animal fat is prostate healthy. 

This dietary shift also results in lower cholesterol 

and triglycerides, leading to improved 

cardiovascular health, which shows that a 

prostate-healthy diet is really a diet healthy 

for the whole body. 

References 

1. Sakr WA, Grignon DJ, Crissman JD, Heilbrun LK, 

Cassin BJ, Pontes JJ, Haas GP. High grade prostatic intraepithelial 

neoplasia (HGPIN) and prostatic adenocarcinoma 

between the ages of 20-69: an autopsy study of 

249 cases. In Vivo. 1994 May-Jun;8(3):439-43. 

2. Lippman SM, Klein EA, Goodman PJ, Lucia MS, 

Thompson IM, Ford LG, Parnes HL, Minasian LM, et 

al. Effect of selenium and vitamin E on risk of prostate 

cancer and other cancers: the Selenium and Vitamin E 

Cancer Prevention Trial (SELECT). JAMA. 2009 Jan 

7;301(1):39-51. 

3. Thompson IM, Goodman PJ, Tangen CM, Lucia MS, 

Miller GJ, Ford LG, Lieber MM, Cespedes RD, Atkins 

JN, Lippman SM, Carlin SM, Ryan A, Szczepanek CM, 

Crowley JJ, Coltman CA Jr. The influence of finasteride 

on the development of prostate cancer. N Engl J Med. 

2003 Jul 17;349(3):215-24. 

4. Andriole GL, Bostwick DG, Brawley OW, Gomella 

LG, Marberger M, Montorsi F, Pettaway CA, Tammela 

TL, Teloken C, Tindall DJ, Somerville MC, Wilson TH, 

Fowler IL, Rittmaster RS; REDUCE Study Group. Effect 

of dutasteride on the risk of prostate cancer. Engl J Med. 

2010 Apr 1;362(13):1192-202. 

5. Haddad AQ, Venkateswaran V, Viswanathan L, Teahan 

SJ, Fleshner NE, Klotz LH. Novel antiproliferative flavonoids 

induce cell cycle arrest in human prostate cancer 

cell lines. Prostate Cancer Prostatic Dis. 2006;9(1):68-76. 

6. Venkateswaran V, Fleshner NE, Sugar LM, Klotz LH. 

Antioxidants block prostate cancer in lady transgenic 

mice. Cancer Res. 2004 Aug 15;64(16):5891-6. 

7. Venkateswaran V, Klotz LH. Diet and prostate cancer: 

mechanisms of action and implications for chemoprevention. 

Nat Rev Urol. 2010 Aug;7(8):442-53. Epub 2010 

Jul 20. Review. 

8. Haddad AQ, Fleshner N, Nelson C, Saour B, Musquera 

M, Venkateswaran V, Klotz L. Antiproliferative 

mechanisms of the flavonoids 2,2’-dihydroxychalcone 

and fisetin in human prostate cancer cells. Nutr Cancer. 

2010;62(5):668-81. 

9. Hou M, Venier N, Sugar L, Musquera M, Pollak M, 

Kiss A, Fleshner N, Klotz L, Venkateswaran V. Protective 

effect of metformin in CD1 mice placed on a high 

carbohydrate-high fat diet. Biochem Biophys Res Commun. 

2010 Jul 2;397(3):537-42. Epub 2010 Jun 2. 

10. Cervi D, Pak B, Venier NA, Sugar LM, Nam RK, 

Fleshner NE, Klotz LH, Venkateswaran V. Micronutrients 

attenuate progression of prostate cancer by elevating 

the endogenous inhibitor of angiogenesis, platelet 

factor-4..BMC Cancer. 2010 Jun 4;10:258. 

11. Venkateswaran V, Klotz LH, Ramani M, Sugar 

LM, Jacob LE, Nam RK, Fleshner NE. A combination 

of micronutrients is beneficial in reducing the incidence 

of prostate cancer and increasing survival in the 

Lady transgenic model. Cancer Prev Res (Phila). 2009 

May;2(5):473-83. 


FEATURE 

The Role of Diet and Exercise 

in Prostate Cancer 

Dr. Vasundara Venkateswaran 

PhD 

Associate Professor of Surgery, 


The fact that prostate cancer 

is one of the most prevalent cancers 

has enormous public health significance. 

With nearly 25,000 new cases each 

year, prostate cancer is a growing problem. 

Hence, strategies for prevention of this disease 

would attenuate its economic, emotional, 

physical and social impact. Both the substantial 

variation in the incidence of prostate 

cancer worldwide and the increased risk in 

the migrant population (moving from lowrisk 

to high-risk countries) provide strong 

support for modifiable environmental factors 

– particularly diet – in prostate cancer 

etiology. Over the years, dietary agents have 

gained considerable attention as chemopreventive 

agents against prostate cancer. Studies 

suggest that men can reduce their risk of 

prostate cancer by making sure they maintain 

a healthy diet. Dietary factors are one of 

the major elements accounting for the international 

and inter-ethnic differences in the 

rate of prostate cancer 1 . Many agents have 

been evaluated for their primary and secondary 

chemopreventive capacities, including 

soy proteins, tomatoes and lycopene, vitamin 

E, selenium, fish and marine fats, ω-3 fatty 

acids, cholesterol, polyphenols, isoflavones, 

red meat, pomegranate, cruciforms and 

green tea 2-7 . There are numerous review articles 

that discuss mechanisms of action and 

implications of dietary agents for chemoprevention 

of prostate cancer 8 . These compounds 

potentially interact with a range of 

carcinogenic pathways, including androgen 

metabolism, cell cycle processes and apoptosis, 

maintenance of mitochondrial membrane 

potentials, insulin-like growth factor 

(IGF)-Akt signaling and response to oxidative 

stress. It is interesting to note that nutrient 

intake can modify genetic susceptibility 

to diseases such as cancer 9 . This information 

is helpful in providing a scientific basis for 

cancer prevention via dietary modification. 

It is essential to appreciate that diet provides 

multiple micronutrients and macronutrients 

packaged in their most effective form, since 

diet is an important aspect of health that an 

individual can control. Currently, the strongest 

association between diet and prostate 

cancer appears to be obesity. Prior research 

conducted in our laboratory has suggested 

that energy balance and fat intake influence 

prostate cancer progression. However, the influence 

of dietary carbohydrates on prostate 

cancer progression has not been well characterized. 

Hence, we tested if hyperinsulinemia 

resulting from high intake of refined carbohydrates 

would lead to more rapid growth 

of tumors in the xenograft mouse model of 

prostate cancer. Interestingly, this diet was 

associated with increased tumor growth, 

with activation of signaling pathways distal 

to the insulin receptor 10 . Our research lends 

support to the concept that diets associated 

with a reduction in insulin levels may have 

benefits for prostate cancer patients, particularly 

for a hyperinsulinemic subset of the 

population. Furthermore, it also provides the 

rationale for clinical research attempting to 

determine if lower prostate cancer risk and/ 

or improved prostate cancer prognosis can 

be obtained through minimization of insulin 

levels and optimization of macronutrient 

intake to meet, but not exceed, nutritional 

requirements. Ongoing investigations of 

pharmacologic agents such as metformin (a 

compound that reduces hyperinsulinemia 

and associated metabolic abnormalities) examine 

if such compounds may also have a 

role to play in the treatment of metabolicallydefined 

subsets of prostate cancer patients. 

Besides identification of molecular targets, 

other methods of prevention would have to 

be incorporated into a prostate cancer prevention 

strategy. These include personalized 

risk assessment and discovery of biomarkers, 



FEATURE 

Photo courtesy of http://www.sxc.hu/photo/816375 

sensitivity to preventive agents, and surrogate 

molecular markers serving as intermediate 

end points. Despite all this, one has to 

recognize that the intrinsic heterogeneity of 

any given study population makes nutritional 

studies difficult to perform. This is due to 

several factors including variations in individual 

lifestyles, complexity in food and food 

products, as well as the levels of consumption 

of such foods. Laboratory studies in 

preclinical animal models provide important 

guidelines in designing, conducting, and interpreting 

large studies in humans; however, 

complications and errors arise while translating 

data from animal studies to the clinical 

setting. This demonstrates the complexity 

in interpreting many of the contradictory 

reports that can confuse researchers, physicians 

and the public alike. 

Recent evidence highlights not only the role 

of dietary factors but also the inclusion of 

physical activity as a key component in the 

development and progression of prostate 

cancer. Epidemiological and laboratory investigations 

indicate a negative relationship 

between regular exercise and the risk of certain 

malignancies, including prostate cancer. 

A recent review 11 has discussed the influence 

of physical activity on the carcinogenic 

process, where physical activity is dependent 

on energy contribution and the duration of 

exercise. There are several probable biological 

mechanisms projected to explain the cancer-preventive 

effects of exercise, including 

changes in endogenous metabolic or sex hormone 

levels and growth factors, decreased 

obesity and central adiposity, alterations in 

immune functions, and alternations in reactive 

oxygen species (ROS). Interestingly, 

different levels of exercise may influence the 

ROS generation in different ways. In fact, it 

has been suggested that moderate levels of 

exercise may have protective effects while too 

much exercise can be harmful. Thus, the determination 

of the optimal load of physical 

activity that can elicit cancer-preventive effects 

warrants further investigation. 

It is imperative to determine the best approach 

to keep prostate cancer at bay. Although 

much research still needs to be 

accomplished regarding the effect of micronutrients 

and macronutrients in prostate 

cancer progression, it is suggested that one 

can maintain overall good health by eating a 

well-balanced diet that is low in fat and carbohydrates, 

but rich in fruits and vegetables, 

and accompanied by moderate exercise. 

References 

1. Chan, J. M., et.al. Role of diet in prostate cancer development 

and progression. J. Clin. Oncol. 23: pp 8152– 

8160, 2005. 

2. Fleshner, NE., et al. Dietary Fat and Prostate Cancer. 

The Journal of Urology.171 (2): pp S19-S24, 2004. 

3. Venkateswaran, V., et al. Antioxidants block prostate 

cancer in Lady transgenic mice. Cancer Research. 64: pp 

5891-5896, 2004. 

4. Haddad, A., et al. Novel antiproliferative flavonoids 

induce cell cycle arrest in prostate cancer cell lines. Prostate 

Cancer Prostatic Diseases. 9 (1): pp 68-76, 2005. 

5. Venkateswaran, V. Selenium and Prostate Cancer: 

Biological Pathways and Biochemical Nuances. Cancer 

Therapy. 4: pp 73-80, 2006. 

6. Venkateswaran, V., et al. Early commencement of 

micronutrients is beneficial in reducing the incidence 

of prostate cancer and increasing survival in the Lady 

transgenic model. Cancer Prevention Research. 2 (5): pp 

473-483, 2009. 

7. Venier N., et al. Chemopreventative Strategies in 

Prostate Cancer: Role of Dietary Agents. Invited Review. 

Current Cancer Therapy Reviews. 6: pp 308-316, 2010. 

8. Venkateswaran, V., et al. Diet and prostate cancer: 

mechanisms of action and implications for chemoprevention. 

Nature Reviews Urology. 7: pp 442-453, 2010. 

9. Huang, H.Y., et al. Customized diets for cancer prevention 

according to genetic polymorphisms: are we 

ready yet? Journal of the National Cancer Institute. 

98(22): 1590-1, 2006. 

10. Venkateswaran, V., et al. Association of diet induced 

hyperinsulinemia with accelerated growth of prostate 

cancer (LNCaP) xenografts. Journal of the National 

Cancer Institute. 99: pp 1793-800, 2007. 

11. Na, HK., et al. Effects of physical activity on cancer 

prevention. Ann. N.Y. Acad. Sci. Issue: Nutrition and 

Physical Activity in Aging, Obesity, and Cancer. 1229: 

176–183, 2011. 


FEATURE 

Imaging and Prostate Cancer 

Applications of MRI 

Dr. Masoom Haider 

MD, FRCPC 

Clinician Scientist, Ontario Institute for 

Cancer Research 

Associate Member, Institute of Medical 

Science 

Associate Professor of Radiology, University 

of Toronto, Faculty of Medicine, Department 

of Medical Imaging 

One of the primary goals of current 

cancer research is to develop 

patient-specific personalized therapeutic 

approaches that maximize treatment 

efficacy while minimizing morbidity. In the 

current era of serum prostate specific antigen 

(PSA) screening for prostate cancer, detection 

is occurring at an earlier stage; however, 

prostate cancer has a highly variable natural 

history and in many cases the cancer will remain 

indolent throughout the patient’s lifetime. 

There is a consensus that in the PSA 

screening era prostate cancer is being overtreated 

1 . 

There is a wide array of options for therapy 

including active surveillance (see page 21), 

prostatectomy (laproscopic, robotic, retropubic), 

hormonal therapy, and radiation 

therapy (external beam, intensity modulated 

radiation therapy, brachytherapy). Selection 

of the appropriate treatment is based on risk 

stratification. The primary method for risk 

stratification hinges on obtaining tissue using 

a random prostate biopsy of the gland 

guided by transrectal ultrasound (TRUS) 

consisting of at least 8 needle cores. Using the 

histologic Gleason grade of the tissue sample, 

the PSA, and the result of digital rectal exam, 

the patient is placed in a risk category and 

this helps guide management choices. This 

approach suffers from two shortcomings. 

The first is the sampling problem. TRUS biopsy 

even with 10 cores is not representative 

of the tumor grade at prostatectomy in about 

30% of cases and thus the patient’s risk category 

can be misclassified 2 . Secondly, the risk 

stratification currently used is predictive but 

when applied on a patient-by-patient basis 

does not always reliably predict an individual 

patient’s long-term outcome. Furthermore, 

prostate biopsy is painful and caries a small 

but significant risk of urosepsis 3 , while whole 

gland therapies carry the risk of sexual dysfunction 

and urinary continence problems 4 . 

Thus, finding a non-invasive biomarker of 

outcome in prostate cancer is one of the principal 

aims of current research. 

In recent years, of all imaging methods available 

for clinical use, MRI has shown the 

greatest promise of addressing these issues in 

the short term. In particular the use of multiparametric 

MRI, which combines two or 

more MRI acquisitions such as T2 weighted 

imaging, diffusion weighted imaging, dynamic 

contrast enhanced imaging or proton 

spectroscopy, has been successful in localizing 

prostate cancer for directed biopsy 5-8 and 

shown promise in predicting Gleason grade 

without the need for biopsy 9, 10 . There remain 

shortcomings. Much of the data supporting 

the MRI approach comes from single center 

trials, and there are too few prospective trials 

showing improved survival. Training of radiologists 

is lacking and MRI availability is limited, 

although this is expected to change as 

standards develop and evidence of improvements 

in patient outcome is published over 

the next few years. A prospective multicenter 

trial is underway in select centers – including 

our group, funded by the Ontario Institute 

of Cancer Research – to evaluate MRI use 

with specific treatments such as active surveillance 

to see if patients can be better se- 



FEATURE 

T ADC DCE MRI - K ep 

map 

Fig 1 Multi-parametric MRI of Patient on Active Surveillance 

The T2 weighted image shows a vague area of lenticular shaped altered texture in the anterior prostate. A corresponding and more obvious region of relative low diffusion is seen 

on the apparent diffusion coefficient map generated from a diffusion-weighted image (b-value 600s/mm2). A corresponding area of relatively elevated reflux constant (k ep 

), generated 

from a Toft’s model applied to dynamic contrast enhanced MRI [DCE MRI] is also seen. The combination of altered texture on the T2 weighted images, corresponding low ADC and 

elevated k ep 

is typical of cancer. Targeted biopsy showed performed 24 days later showed a Gleason 7 (3+4) in both directed cores occupying 40 and 70% of the core length. 

Figure reference: Orit Raz, et al. MRI for men undergoing active surveillance or with rising PSA and negative biopsies. Nature Reviews Urology 2010: 7, 543-551 

lected for treatment or have their treatment 

deferred through better surveillance using 

imaging and directed biopsy. Research is also 

underway to develop computer-aided diagnostic 

algorithms to reduce interobserver 

variability and improve diagnostic performance 

of radiologists 11, 12 . 

The ability to localize prostate cancer using 

MRI has applications other than improved 

sampling and Gleason grade prediction. 

Studies are underway to further personalize 

medicine by applying “dose painting”, a 

technique where higher radiation doses are 

delivered to prostate regions where highergrade 

tumors are suspected based on MRI, 

thus improving therapeutic ratios. Urologists 

are studying approaches such as MRI-guided 

laser thermal therapy 13 and high intensity focused 

ultrasound 14 to guide delivery of focal 

therapy. MRI has the advantage of not only 

being able to localize the cancer but also 

monitor tissue temperature changes, thus allowing 

for maximal delivery of thermal doses 

while sparing critical structures such as the 

rectum and neurovascular bundles, reducing 

complications related to continence and 

sexual potency. 

If multiparametric MRI proves successful, 

then one can picture a near future where a 

patient only undergoes a prostate biopsy 

when necessary and then has access to highly 

effective low morbidity image guided therapies. 

References 

1. Schroder FH, Hugosson J, Roobol MJ, et al. Screening 

and prostate-cancer mortality in a randomized 

European study. N Engl J Med. 2009;360(13):1320-8. 

2. San Francisco IF, DeWolf WC, Rosen S, Upton M, 

Olumi AF. Extended prostate needle biopsy improves 

concordance of Gleason grading between prostate 

needle biopsy and radical prostatectomy. J Urol. 

2003;169(1):136-40. 

3. Mosharafa AA, Torky MH, El Said WM, Meshref A. 

Rising incidence of acute prostatitis following prostate 

biopsy: fluoroquinolone resistance and exposure is a 

significant risk factor. Urology. 2011;78(3):511-4. 

4. Potosky AL, Legler J, Albertsen PC, et al. Health outcomes 

after prostatectomy or radiotherapy for prostate 

cancer: results from the Prostate Cancer Outcomes 

Study. J Natl Cancer Inst. 2000;92(19):1582-92. 

5. Haider MA, van der Kwast TH, Tanguay J, et al. 

Combined T2-weighted and diffusion-weighted MRI 

for localization of prostate cancer. AJR Am J Roentgenol. 

2007;189(2):323-8. 

6. Futterer JJ, Heijmink SW, Scheenen TW, et al. 

Prostate cancer localization with dynamic contrastenhanced 

MR imaging and proton MR spectroscopic 

imaging. Radiology. 2006;241(2):449-58. 

7. Mazaheri Y, Shukla-Dave A, Hricak H, et al. Prostate 

cancer: identification with combined diffusionweighted 

MR imaging and 3D 1H MR spectroscopic 

imaging--correlation with pathologic findings. Radiology. 

2008;246(2):480-8. 

8. Hambrock T, Somford DM, Hoeks C, et al. Magnetic 

resonance imaging guided prostate biopsy in men with 

repeat negative biopsies and increased prostate specific 

antigen. J Urol. 2010;183(2):520-7. 

9. Zakian KL, Sircar K, Hricak H, et al. Correlation of 

proton MR spectroscopic imaging with gleason score 

based on step-section pathologic analysis after radical 

prostatectomy. Radiology. 2005;234(3):804-14. 

10. Hambrock T, Somford DM, Huisman HJ, et al. 

Relationship between apparent diffusion coefficients 

at 3.0-T MR imaging and Gleason grade in peripheral 

zone prostate cancer. Radiology. 2011;259(2):453-61. 

11. Artan Y, Haider MA, Langer DL, et al. Prostate cancer 

localization with multispectral MRI using cost-sensitive 

support vector machines and conditional random 

fields. IEEE Trans Image Process. 2010;19(9):2444-55. 

12. Langer DL, van der Kwast TH, Evans AJ, Trachtenberg 

J, Wilson BC, Haider MA. Prostate cancer detection 

with multi-parametric MRI: logistic regression 

analysis of quantitative T2, diffusion-weighted imaging, 

and dynamic contrast-enhanced MRI. J Magn Reson 

Imaging. 2009;30(2):327-34. 

13. Raz O, Haider MA, Davidson SR, et al. Real-Time 

Magnetic Resonance Imaging-Guided Focal Laser 

Therapy in Patients with Low-Risk Prostate Cancer. Eur 

Urol. 2010. 

14. Siddiqui K, Chopra R, Vedula S, et al. MRI-guided 

transurethral ultrasound therapy of the prostate gland 

using real-time thermal mapping: initial studies. Urology. 

2010;76(6):1506-11. 


FEATURE 

Active Surveillance 

Why an increasing number of prostate 

cancer patients are opting to wait and see 

rather than obtain treatment 

Philip A. Alves, HBSc 

Summer Student 

IMS Summer Research Program 

Supervisor: Dr. Laurence Klotz 

MD Candidate 

Schulich School of Medicine & Dentistry 

The University of Western Ontario 

Prostate cancer is the most prevalent 

non-skin cancer diagnosed in 

men. It is the second most common 

cause of cancer death in men. However, a diagnosis 

of prostate cancer is not necessarily a 

death sentence. Men diagnosed with prostate 

cancer currently have a 97% cancer-specific 

survival rate after 5 years 1 . This impressive 

survival statistic is due in part to adoption of 

the prostate specific antigen (PSA) blood test 

in the mid 1990s and its widespread use as a 

screening tool 2 . This results in a significant 

lead time in diagnosis. As a large proportion 

of prostate cancers are very slow growing and 

never metastasize, the ubiquity of PSA testing 

is also responsible for the current overdiagnosis 

and over-treatment of prostate 

cancer. Radical treatments, such as radiation 

therapy and surgery, may result in urinary 

incontinence and impotence - considerable 

consequences for quality of life. 

Active surveillance is a conservative management 

option that closely follows men with 

low-risk prostate cancer with regularity to 

ensure that aggressive cancers are detected 

and amenable to cure, yet avoids overtreating 

men with insignificant disease. 

Prostate cancer is classified as low-risk based 

on the tumour grade on biopsy, stage of progression, 

and PSA value. Patients with lowrisk 

prostate cancer may opt to defer treatment 

in lieu of active surveillance. This will 

Photo by Connie Sun; Ribbon photo courtesy of www.istockphoto.com; ID # 12562292 


FEATURE 

Pick Your Brain... 

A column by Aaron Kucyi 

Chronic prostatitis is a disorder that occurs in 

5-10% of men and is associated with pain of the 

prostate and surrounding areas. Also known as 

chronic pelvic pain syndrome (CPPS), the disorder 

is unrelated to prostate cancer, and its cause is 

uncertain. Most research on CPPS has focused 

on factors such as inflammation, endocrine involvement, 

and pelvic floor muscle abnormalities. 

However, spontaneous pain perception in 

CPPS is ultimately a result of brain activity – an 

underexplored phenomenon that was recently 

investigated for the first time by researchers at 

Northwestern University. 

In an MRI study of a group of 19 male CPPS patients, 

activity in the right anterior insula (a painrelated 

brain region) was associated with fluctuations 

in the intensity of spontaneous pain over 

time. In terms of brain structure, there were no differences 

in total volume or volume of pain-related 

regions between patients and healthy controls. 

However, higher gray matter density in the right 

anterior insula was associated with higher overall 

pain experienced by a patient. Also, the relationship 

between brain gray matter (neuronal cell 

bodies) and white matter (axonal tracts) was disrupted 

in patients relative to controls. The neural 

changes in CPPS are both similar and unique from 

other chronic pain disorders. As CPPS is poorly understood 

and difficult to treat, this work provides 

important insights that can open up new directions 

for research on the mechanisms underlying the 

disorder, and potentially pain management. 

Reference: 

Farmer MA, Chanda ML, Parks EL, Baliki MN, Apkarian AV, 

Schaeffer AJ (2011) Brain functional and anatomical changes 

in chronic prostatitis/chronic pelvic pain syndrome. J Urol 

186:117-124. 

allow them an opportunity to monitor the 

disease through regular follow up appointments. 

Curative therapies are recommended 

if the preceding criteria advance to indicate 

grade progression or volume progression. 

Follow up is important. At enrolment, men 

have their PSA measured and undergo a digital 

rectal exam (DRE). PSA values are drawn 

and DREs undertaken every 3 and 6 months, 

respectively, for the first two years. A confirmatory 

biopsy will also be scheduled within 

the first year after diagnosis to ensure that a 

more high-risk tumour was not missed. After 

the first two years, individuals undergo 

PSA measurements every six months and 

DREs annually, as well as re-biopsy every two 

to three years. Patients will remain on this 

schedule of care indefinitely unless there is 

tumour grade progression. At this point, radiation 

therapy or surgical excision with curative 

intent will be scheduled, although this 

is necessary only for a minority of patients. 

A rapid rise in PSA, particularly a PSA doubling 

time faster than 3 years, should necessitate 

a repeat biopsy or multiparametric MR 

imaging. Importantly, patients that progress 

to high-risk disease appear no more likely to 

die than patients who were treated radically 

at the outset of their diagnosis 2 . Why should 

a prostate cancer patient with low-risk disease 

opt for active surveillance over radical 

treatment? Firstly, prostate cancer is very 

common: Roughly 1 in 7 men will be diagnosed 

with prostate cancer during their life 1 , 

although many of these men harbour clinically 

insignificant disease. Perhaps more surprising 

is that upwards of 1 in 2 men will have 

previously undetected tumours at death 3 . 

Furthermore, prostate cancer is slow growing: 

Tumours often grow over the course of 

several decades – many do not transform 

into aggressive cancers, therefore offering 

a long timeframe for surveillance 4 . Finally, 

men with localized prostate cancer are more 

likely to die of other causes than prostate cancer. 

Patients diagnosed with microfocal low 

grade cancer based on an elevated PSA managed 

with active surveillance are 19 times 

more likely to die of other causes than die of 

the disease 2 . These facts support the notion 

that radical treatment is often unnecessary, 

and many with the disease are well suited for 

close monitoring of disease progress. 

In summary, active surveillance is a prostate 

cancer management strategy that allows for 

patients with low-risk disease to avoid the 

consequences of overtreatment yet feel confident 

that they will benefit from curative 

treatment if necessary. Active surveillance 

serves as a prudent model for individualized, 

patient-centred cancer care. 

References 

1. Klotz L, Zhang L, Lam A, Nam R, Mamedov A, 

Loblaw A. Clinical results of long-term follow-up of a 

large, active surveillance cohort with localized prostate 

cancer. J Clin Oncol 2010;28:126–31 

2. Croswell JM, Kramer BS, Crawford ED. Screening 

for prostate cancer with PSA testing: current status 

and future directions. Oncology (Williston Park). 2011 

May;25(6):452-60, 463. 

3. Sakr WA, Haas GP, Cassin BF, Pontes JE, Crissman 

JD. The frequency of carcinoma and intraepithelial 

neoplasia of the prostate in young male patients. J Urol 

1993;150:379–85. 

4. Soloway, M. S. et al. Careful selection and close 

monitoring of low-risk prostate cancer patients on active 

surveillance minimizes the need for treatment. Eur. 

Urol. 58, 831–835 (2010). 


FEATURE 

The Future of 

Prostate Cancer Research 

Dr. Neil Fleshner 

MD, FRCSC, MPH 

Head of Urology, 


Professor of Surgery, 


Prostate cancer is the most commonly diagnosed cancer 

among men and the second most common cause of cancer 

related deaths. This cancer is generally underfunded 

relative to its prevalence and mortality rate when compared 

to the amount of money that has been devoted towards 

breast cancer research. It is hoped that this gap 

will shrink over the coming years. 

Photo courtesy of www.istockphoto.com; ID # 7627557 


FEATURE 

I 

n line with this hope, it seems that research into prostate 

cancer will flourish over the coming years. With the advent 

of novel genetic and molecular tools, new target discovery for 

prostate cancer drugs seems likely, and will only continue to improve 

in tandem with technological advances. 

In this article, the future of prostate cancer research will be discussed 

within the context of three sub-topics. 

Prevention 

The trend of novel studies hints that prevention research will continue 

to grow from an epidemiologic point of view. We will continue 

to learn more about the causes of prostate cancer, particularly the 

impact of the environment on this disease. We will also learn more 

about genetic risks of this disease; the development of a prostate risk 

chip that will better personalize prostate cancer risk for men is likely 

in the coming decades. Some of these risk-assessment techniques are 

now on the market, and as additional risk SNPs (single nucleotide 

polymorphisms in one’s DNA that indicate a higher risk of developing 

a certain disease) are found, this progress towards individualized 

prevention strategies and treatment planning will continue. 

Knowledge of the fundamental biology of advanced prostate cancer 

will continue to grow as new discoveries are made. The International 

Gene Consortium is planning to sequence a number of prostate tumours, 

which will improve our understanding of the genetic changes 

seen in this disease. Continued exploitation of the androgen receptor, 

a target for therapy, can therefore become more selective and efficacious. 

Genetic studies have already resulted in the development of 

new compounds such as Abiraterone and MDV3100. Targeting other 

novel pathways, such as the phospho-AKT and PTEN pathways, may 

give rise to novel agents with the ability to improve overall survival 

and quality of life among patients with advanced prostate cancer. 

In summary, the future for prostate cancer research looks bright. One 

of the main challenges facing us is the translation of fundamental 

discoveries into targetable agents. If this can be accomplished, there 

is hope that these discoveries can help to improve the quality of life 

for patients with prostate cancer. 

Early Detection 

We will continue to incorporate modern imaging into the early 

detection of prostate cancer. At this point, men at risk are simply 

offered an ultrasound guided prostate biopsy. There is increased 

concern about the safety of these biopsies with the increased rise 

of ciprofloxacin-resistant E. Coli infections. As a result of this risk, 

clinicians are becoming increasingly pressed to utilize less invasive 

magnetic resonance imaging (MRI) techniques in the detection of 

prostate cancer. Despite the advantages of an MRI-based diagnostic 

technique, research is still needed to better develop the imaging protocols 

to improve this technology. 


Treatment 

With respect to early stage prostate cancer, there is an increasing 

realization that our current therapies, while effective, can have 

a significant impact on quality of life, particularly for urinary and 

sexual functions. Thus there will likely be increased research over 

the next decade on the topic of focal therapy. This technique aims 

to identify the areas of the prostate where there is disease and to use 

energy technologies such as heat or freezing to ablate these areas. 

This technique is essentially akin to the lumpectomy technique used 

to remove breast cancer tumours. Some trials of focal therapy are 

now underway, and even more research will be done as technology 

improves. 


SPOTLIGHT 

Transcranial magnetic stimulation 

An investigational tool and potential therapeutic option in movement disorders 

By Nina Bahl 

Arguably the most important 

organ in the body, the brain is also 

the least understood; comprised of 

a staggering one hundred billion neurons, 

the complexity of the connectivity between 

these cells seems nearly incomprehensible. 

Accordingly, our understanding of human 

neurophysiology has benefited tremendously 

from the advent of sophisticated investigational 

tools, including transcranial magnetic 

stimulation (TMS) – a non-invasive method 

of stimulating the brain. For Dr. Robert 

Chen, a senior scientist and movement disorders 

specialist at Toronto Western Hospital, 

the utility of TMS has proven invaluable 

to his investigations of motor cortex functionality 

and of the pathophysiology and associated 

treatments of movement disorders. 

Stimulation is produced by generating a 

brief, high-current pulse in a magnetic coil 

that is placed on the scalp of the subject. This 

transient current induces a large and changing 

magnetic field, which subsequently produces 

an electric current in the underlying 

brain 1,2 . 

For studies involving the motor cortex, as in 

Chen’s lab, TMS pulses are typically administered 

to the region of the brain that controls 

a specific hand muscle. Here, stimulation 

produces a focal twitch in the target muscle, 

which is measured with surface electrodes 

placed on the hand, and visualized on an 

electromyogram. This muscle response to 

TMS is termed the motor-evoked potential, 

the amplitude of which is thought to reflect 

motor cortex excitability 2,3 . Thus, human 

cortical excitability can be assessed using a 

number of specific TMS measures that are 

based on this fundamental principle. 

While using TMS techniques during a research 

fellowship at the National Institutes of 

Health, Chen quickly appreciated the versatility 

and uniqueness of TMS as a neurophysiological 

probe. “It really is a fascinating way 

to study the brain,” he affirms. “By stimulating 

neural regions without any sort of invasive 

method, you can measure a subject’s re- 

sponse in a number of ways and reveal fairly 

specific information about their [cortical] 

physiology. There aren’t many other methods 

that can offer such a direct investigation in 

humans, so [TMS] is a very powerful tool.” 

Upon establishing his laboratory at the Toronto 

Western Research Institute in 1998, 

Chen predominantly adopted TMS techniques 

for use in his lab, which currently 

focuses its studies on patient populations to 

elucidate pathological mechanisms in a number 

of movement disorders. One of the most 

commonly studied pathologies in the lab is 

Parkinson’s disease (PD), a neurodegenerative 

disorder that causes a variety of debilitating 

motor symptoms, including bradykinesia, 

rigidity, and tremor. “Our [studies] 

have revealed several cortical changes in PD 

patients – as one example, we see a reduction 

in one form of motor cortical inhibition,” he 

notes. By understanding details such as these, 

the hope is to be able to piece together how 

neuronal degeneration in a disorder like PD 

translates into its overt symptoms, which is 

currently not well understood. 

Chen’s team has also used TMS techniques 

to explore deep-brain stimulation (DBS), 

which is one of the most remarkable neurosurgical 

advances for PD and a handful 

of other movement disorders. “When DBS 

emerged as a new treatment around 2000, 

our lab began investigating it soon after. One 

of the challenges is that we still don’t know 

how it works.” Chen aims to reveal potential 

mechanisms of action of DBS, and specifically, 

explore how deep-brain nuclei (where 

DBS implants are located) may be modulating 

the motor cortex to produce clinical improvements 

in patients with disordered motor 

control. 

Other major TMS investigations in his lab include 

studies of normal human motor physiology, 

including the examination of how 

different neuronal circuits interact with one 

another in the motor cortex. As well, his lab 

uses genetic techniques as an adjunct to examine 

the effects of selected single nucleotide 

polymorphisms on brain functionality and 

its ability to undergo plasticity and learning. 

Undeniably, for Dr. Chen, TMS has proven 



SPOTLIGHT 

itself as a versatile and invaluable research 

tool. 

Magnetic Stimulation for the Treatment 

of Motor and Mood Symptoms 

of Parkinson’s disease (MASTER-PD): 

A multicentre clinical trial 

Beyond its use as a neural probe, TMS has 

also been studied for its therapeutic potential. 

A recent meta-analysis by Chen’s team 

involving small pilot trials has revealed a reduction 

of motor symptoms in Parkinson’s 

disease patients following high-frequency 

repetitive TMS (rTMS) to the motor cortex. 

High-frequency rTMS is known to induce 

long-lasting, enhanced excitation in 

the brain. Thus, the clinical benefit seen in 

PD supports the hypothesis that rTMS may 

modulate underactive brain regions to improve 

symptoms of the disease 4 . 

Larger clinical trials have shown high-frequency 

rTMS to also be effective in reducing 

symptoms of depression when administered 

regularly to the left dorsolateral prefrontal 

cortex (DLPFC), a region of hypometabolism 

in depressed patients 2,3 . With depression as 

one of the most common and incapacitating 

non-motor symptoms in PD, these results are 

also critical for the PD patient population. 

“There have been a number of studies proving 

rTMS efficacy in treating depression, 

including a large randomized controlled 

clinical trial,” notes Chen. “It is an approved 

treatment for depression in Canada, and 

more recently, in the US as well.” Despite 

the promising rTMS results in PD, however, 

Chen realizes that its effectiveness is not yet 

as conclusive and explains its lack of approval 

as a treatment option. “The problem [with regards 

to PD] is that there has not yet been any 

large-scale clinical trial. The sample sizes so 

far have been small – typically only 10 to 20 

patients per study,” he explains. “Our metaanalysis 

tells us there are encouraging results, 

but we need to build on that.” 

and the Cleveland Clinic – Chen is leading 

the sole Canadian site at the University of 

Toronto. 

MASTER-PD’s researchers hope to recruit 

160 PD patients experiencing depressive 

symptoms to participate in a randomized, 

double-blinded, placebo-controlled study. 

Participants will be randomly assigned to 

receive either real or sham (placebo) rTMS 

via four possible treatment combinations: 

1) rTMS to bilateral motor cortex + sham 

rTMS to the left DLPFC, 2) rTMS to left 

DLPFC + sham rTMS to bilateral motor cortex, 

3) rTMS to both bilateral motor cortex 

and left DLPFC, or 4) sham rTMS to both 

bilateral motor cortex and left DLPFC. The 

rTMS interventions will be administered 

over the course of two weeks, and all subjects 

will undergo a comprehensive assessment of 

motor, mood, cognition and quality of life at 

different intervals for up to 6 months posttreatment. 

“Certainly, this will be the largest study of 

rTMS in PD. Hopefully it will be able to 

address whether rTMS can be used for the 

treatment of motor and mood symptoms in 

this patient population.” 

And with that, we are reminded of the ultimate 

goals of Chen’s TMS investigations: to 

disentangle the complexities of the brain, and 

more pointedly, to use this knowledge to better 

serve those who suffer from neurological 

disease. 

*The MASTER-PD trial is supported by the Michael J Fox Foundation. 

References 

1. Hallett M. (2000). Transcranial magnetic stimulation and the 

human brain. Nature, 406(6792): 147-150. 

2. Chen R. (2000). Studies of human motor physiology with 

transcranial magnetic stimulation. Muscle& Nerve, S9: S26-S32. 

3. Hallett M. (2007). Transcranial magnetic stimulation: a 

primer. Neuron, 55(2): 187-189. 

4. Elahi B, Elahi B, Chen R. (2009). Effect of transcranial magnetic 

stimulation on Parkinson motor function – systematic 

review of controlled clinical trials. Movement Disorders, 24(3): 

357-363. 


To that end, Chen is currently involved in a 

North American multicentre clinical trial, 

termed MASTER-PD, that aims to determine 

the efficacy of rTMS in modulating brain activity 

to treat both motor and mood symptoms 

in PD. Of the five centres participating 

– including Harvard, the University of Florida, 

the University of California Los Angeles, 

The versatility of TMS has allowed Dr. Robert Chen to examine human motor cortex physiology, the pathological 

disruptions that can lead to movement disorders, and potential therapeutic options. 


CLOSE UP 

Interdisciplinary Collaboration in 

Critical Care 

The holistic approach is greater than the sum of the scientist and the clinician 

By S. Amanda Ali 

Interdisciplinary collaborations between 

science and medicine are growing 

in recognition, for justified reasons. The 

comprehensive and holistic approach offered 

by a team of experts is more successful than 

the sum of each individual effort when striving 

to cure disease, improve patient care, and 

reduce health care expenditure. Encouraging 

a collaborative atmosphere among professionals 

discourages the competitive environments 

that are so frequently encountered in 

research and medicine, and augments scientific 

discovery and quality of patient care. An 

exceptional group of women investigating 

the long-term sequelae after critical illness 

offer an example of interdisciplinary collaboration 

within the University of Toronto. This 

group works on the RECOVER Program of 

Research, and is lead by Dr. Jane Batt, Dr. 

Claudia dos Santos, Dr. Jill Cameron, and Dr. 

Margaret Herridge. Their overarching aims 

are to identify the molecular mechanisms 

underlying neuromuscular disability, to determine 

disruption of quality of life, and to 

assess the economic burden placed on families 

and society at large. 

The various educational backgrounds of the 

collaborators give them each a unique perspective 

on how to achieve the aims of the 

RECOVER Program. Batt and dos Santos 

are both Assistant Professors of Medicine 

at the University of Toronto, and Clinician- 

Scientists at St. Michael’s Hospital, specializing 

in internal medicine and respirology, and 

critical care medicine, respectively. Cameron 

completed her graduate training in the IMS 

and is now a tenure stream faculty member 

in the Department of Occupational Science 

and Occupational Therapy in the Faculty of 

Medicine at the University of Toronto. Herridge 

is an Associate Professor of Medicine 

and Clinician-Scientist at University Health 

Network, focusing in critical care medicine. 

Despite their diverse career paths, their common 

interest in understanding the molecular 

mediation and social implications of skeletal 

muscle atrophy has united this group into an 

interdisciplinary collaborative team. 

Dr. Jane Batt 

Critical illness and prolonged life support is 

associated with the development of severe 

muscle weakness. This association is known 

as intensive care unit (ICU) acquired muscle 

dysfunction. Dos Santos works to understand 

the molecular mechanism behind mechanical 

ventilation-induced lung injury and 

multi-organ failure, including failure of the 

musculoskeletalsystem. This is largely attributable 

to loss of muscle tissue, or polymyopathy, 

but can also be due to nerve damage, or 

polyneuropathy. Batt is interested in the molecular 

regulation of muscle atrophy in acute 

illness and end-stage respiratory diseases. 

Among other techniques, microarray analysis 

is used to identify differentially expressed 

genes and signalling networks in healthy versus 

diseased muscle biopsies from a single 

patient. According to Batt, “It now seems 

Dr. Claudia dos Santos 

Photos by Yekta Dowlati 


CLOSE UP 

Dr. Jill Cameron 

many of the cellular signalling mechanisms 

that induce muscle atrophy across a myriad 

of disease processes are the same. Working 

to understand this process for the purpose of 

introducing interventions to combat muscle 

atrophy and loss of independence will be applicable 

across many disease states. Muscle 

weakness and dysfunction in respiratory 

disease are key causes of poor quality of life, 

which massively increase health resource utilization 

and rob people of independence.” 

critical illness. Herridge’s collaborative efforts 

include other intensivists across the 

University of Toronto, province, and country, 

as well as other professional team members, 

such as physiotherapists and physiatrists at 

Toronto Rehabilitation Institute. 

Working together on the RECOVER Program 

of Research, this team studies the neuromuscular 

disability incurred by long term 

ventilation in the ICU and its impact on the 

individual and the family. Their achievements 

have been recognized by the prestigious Canadian 

Institutes of Health Research (CIHR). 

The current RECOVER Program was initiated 

in 2008 with funding from CIHR, and 

Batt, dos Santos, and Cameron each hold a 

CIHR Career Scientist award. Conducted 

with the Canadian Critical Care Trials Group, 

the RECOVER Program involves 11 centres 

across Canada, and exemplifies a successful 

model of collaborative, translational, and interdisciplinary 

research. Inter-professional 

leadership of core projects is encouraged, for 

example, one sub-study that examines early 

mobility and electrical muscle stimulation 

is lead by physiotherapists. The objective of 

the RECOVER Program is to serve as a national 

and international model of effectively 

integrated professionals working to enhance 

rehabilitation for patients and families following 

critical illness. 

When asked about the factors that are necessary 

to facilitate collaborative projects across 

disciplines and medical specialties, dos Santos 

replied, “Although as critical care intensivists 

we train as subspecialists – we treat 

patients as a whole, we take care of all the 

organs. Consequently, we have a tradition of 

multidisciplinary medicine that is engrained 

in the fabric of our practice. Our daily patient 

assessment rounds are multidisciplinary: 

doctors, nurses, pharmacists, physiotherapists, 

social workers, dieticians, respiratory 

therapists, chaplains, as well as others. This 

strong collaborative and entrepreneurial 

spirit, combined with our clear sense of purpose 

(excellence in patient care) and respect 

for the work and contribution of each member 

of the team provides the foundation for 

all the work we do: patient care, research, and 

teaching.” 

As clinicians and scientists specializing in 

biomedical and socioeconomic aspects of 

ICU acquired muscle dysfunction, the collaborative 

effort of this team is stronger than 

any one of the individual projects. Because 

their multidisciplinary training facilitates 

understanding from the bench to bedside 

and beyond, they are able to synergistically 

focus their efforts on maximizing recovery 

and rehabilitation for patients and their 

families. 

Dr. Margaret Herridge 

Photos by Yekta Dowlati 

Having a family member in critical care can 

be devastating to relatives, as it can trigger 

shock, anxiety, depression, and stress - all 

of which can have detrimental health effects 

over time. Cameron’s primary research interest 

is to examine the experiences of family 

members who assume the role of caregiver 

for individuals with disability, with the goal 

of improving the health outcomes of the 

care-giving population. She aims to understand 

caregivers’ needs, and develop timely 

and relevant programs to assist them as they 

provide support to patients undergoing longterm 

recovery and rehabilitation. Herridge’s 

interest stems from earlier work done by her 

group on long-term outcomes in survivors 

of severe lung injury. Along with Cameron, 

the goal is to build a rehabilitation and educational 

strategy for ICU patients, one which 

effectively meets the needs of a family after 


SURP RESEARCH FOCUS 

Bias in the 

Reporting of 

Randomized 

Clinical Trials 

Roman Shapiro 

Summer Student Writing Competition 

winner 

SUPERVISOR: Drs. Francisco Vera-Badillo and 

Ian F. Tannock 

Randomized clinical trials 

(RCTs) yield the highest grade of 

evidence of the efficacy and safety 

of cancer treatment 1 . Most new therapies, 

be they drug, radiation, surgery, or some 

combination thereof, are evaluated in RCTs 

before being approved for routine use in patients 

2 . What makes RCTs useful is the rigour 

of their design - they employ randomization 

when assigning treatment 3 , they rely on a 

treatment allocation concealment method 

to ensure that the randomization scheme 

is properly implemented 4 , and ideally they 

blind patients and researchers to treatment 

allocation 5 . With a representative patient 

sample, RCTs are expected to approximate 

the benefits and harms of a treatment within 

the general population. The amount of literature 

generated from the results of RCTs is a 

testament to their importance in therapeutic 

decision-making. 

Flask photo courtesy of http://www.sxc.hu/photo/1266835; Author photo by Paulina Rzeczkowska 


SURP RESEARCH FOCUS 

Given the rigour of their design, are the results 

of RCTs fool-proof? There are several 

examples where the results of such trials did 

not seem to agree with clinical reality. Rofecoxib 

is a cyclooxygenase-2 inhibitor whose 

use for the treatment of arthritis became 

widespread after favourable results from 

RCTs, only to be taken off the market a few 

years later when it was found to increase the 

risk of cardiovascular complications 6 . Reboxetine 

was touted as an effective anti-depressant 

until it was discovered that publication 

of data had been highly selective – once the 

complete body of data concerning drug efficacy 

and safety were evaluated, it was found 

that the drug was not only ineffective in the 

treatment of depression, but harmful 7 . 

In the above examples, the reported results 

of RCTs did not correspond with reality because 

of bias in trial conduct, analysis, or 

publication 6,8 . Unfortunately, the degree to 

which this sort of bias affects the published 

results of any RCT is unknown. 

Methods to evaluate bias in RCTs are important 

for physicians who use results of RCTs 

to guide treatment decisions. There is no 

objective gold standard to evaluate bias because 

it is difficult to measure and can only 

be estimated 9 . An optimal assessment of bias 

requires unrestricted access to both the procedures 

used by the trial researchers and the 

complete raw data, but such access is very 

difficult to attain 10 . Nevertheless, there are 

Adverse 

Event 

Not in results 

table (NOT R) 

In results table 

(R) 

Not in abstract 

(NOT A) 

In Abstract (A) 

Not in discussion 

(NOT D) 

In discussion 

(D) 

Not in concluding 

statement 

(NOT C) 

In concluding 

statement (C) 

certain criteria that can be used to estimate 

the degree of bias in RCTs. 

One criterion used to assess bias is the systematic 

evaluation of the reporting of trial 

endpoints. Endpoints are outcomes being 

measured by the trial, which may include 

overall survival, disease-free survival, quality 

of life and response rate, among others. RCTs 

are designed to recruit a predefined number 

of people, and to determine if a statistically 

significant difference in primary endpoints 

exists 9 . This does not mean that significant 

differences in other endpoints are not important, 

but statistical tests applied to them are 

subject to misinterpretation 8 . The evaluation 

of secondary endpoints should therefore be 

regarded as exploratory. If a publication does 

not clearly indicate the results relating to the 

primary endpoint of the trial and does not 

describe the results of secondary endpoints 

in its concluding statements, it is biased 8 . 

Another possible criterion for the systematic 

evaluation of bias is the reporting of adverse 

events (AEs) associated with the experimental 

treatment. We developed a method to 

evaluate this bias, which employed a hierarchy 

of AE reporting based on the sections of 

a publication where AEs are most likely to be 

read (Figure 1). 

In each of 168 publications of RCTs evaluating 

breast cancer treatment, every reported 

moderate to severe AE that was statistically 

Not in 

discussion 

(NOT D) 

In discussion 

(D) 

Not in 

discussion 

(NOT D) 

In discussion 

(D) 

NOT R 

R + (NOT A) + 

(NOT D) 

R + (NOT A) + D 

R + A + (NOT C) + 

(NOT D) 

R + A + (NOT C) + 

D 

R + A + C + 

(NOT D) 

R + A + C + D 

Inadequate 

reporting of 

adverse events 

Less adequate 



Adequate 



Figure 1. Hierarchy of adverse events (AE) reporting. One possible hierarchy scheme is shown, where 

the top represents the least adequate reporting of a moderate to severe AE. 

different between the experimental and control 

arms received a score based on its position 

in the hierarchy. This score was used to 

cluster publications that had a similar reporting 

of AEs. With a large enough sample of 

publications, individual clusters could be defined 

where each represents a certain degree 

of bias. A survey querying oncologists about 

where they most commonly see the reporting 

of AEs in publications of RCTs has been designed 

to test the validation of the hierarchy 

in Figure 1. The results are pending. 

There is substantial evidence that bias exists 

in the conduct, analysis, and reporting 

of RCTs 8-10 . A measure of the degree of this 

bias would be of great help to those who must 

decide how much to trust the results of these 

RCTs, especially when deciding whether 

to apply the results to patients. Although 

no gold standard exists that can be used to 

evaluate the degree of bias in a publication, 

methods are being developed for the purpose 

of estimating this bias with the hope of minimizing 

its effect on clinical decision-making. 

References 

1. Concato J, Shah N, Horwitz RI. Randomized controlled 

trials, observational studies, and the hierarchy of 

research designs. NEJM 2000; 342(25): 1887-92. 

2. FDA approval of new cancer treatment uses for marketed 

drug and biological products. Food and Drug 

Administration; c1998. Available from: http://www.fda. 

gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm071657.pdf 

(accessed 

August 2011) 

3. Altman DG, Bland JM. How to randomize. BMJ 1999; 

319: 703-4. 

4. Schulz KF, Grimes DA. Allocation concealment in 

randomised trials: defending against deciphering. Lancet 

2002; 359: 614-8. 

5. Schulz KF, Grimes DA. Blinding in randomised trials: 

hiding who got what. Lancet 2002; 359: 696-700. 

6. Roth-Cline MD. Clinical trials in the wake of Vioxx. 

Circulation 2006; 113: 2253-59. 

7. Eyding D, Lelgemann M, Grouven U, Harter M, 

Kromp M, Kaiser T, Kerekes MF, Gerken M, Wieseler 

B. Reboxetine for acute treatment of major depression: 

systematic review and meta-analysis of published 

and unpublished placebo and selective serotonin reuptake 

inhibitor controlled trials. BMJ 2010; 341: c4737 

doi:10.1136/bmj.c4737 

8. Boutron I, Dutton S, Ravaud P, Altman DG. Reporting 

and interpretation of randomized controlled trials 

with statistically nonsignificant results for primary outcomes. 

JAMA 2010; 303(20): 2058-64. 

9. Chan AW, Hrobjartsson A, Haahr MT, Gotzsche PC, 

Altman DG. Empirical evidence for selective reporting 

of outcomes in randomized trials. JAMA 2004; 291(20): 

2457-65. 

10. Chan AW. Bias, spin, and misreporting: time for 

full access to trial protocols and results. PLoS Medicine 

2008; 5(11): 1533-35. 


VIEWPOINT 

Darwin. Newton. Einstein. Popper? 

By Adam Santoro 

Should science students be formally educated in the philosophy of science? 

Empirical science is characterized 

by its ability to construct universal 

statements, or ‘theories,’ from singular 

observations 1 . The formulation of a theory 

from singular observations requires inductive 

logic; for example, with enough observed 

instances of objects falling to the ground 

when dropped, one inductively infers that all 

objects fall to the ground when dropped. Yet 

the philosophical justification for the use of 

inductive logic in science is not entirely obvious. 

Consider the following: if an observer 

views 10 000 swans and notes that each swan 

is white, is he justified in concluding that all 

swans are white? Why or why not? The lack 

of justification for the use of inductive logic 

is aptly named the ‘problem of induction.’ 

There is no universally-accepted solution to 

this problem, despite the efforts of some of 

the greatest thinkers to have lived. 

Karl Popper proposed that science should not 

be defined by its use of inductive methods to 

construct theories, since in his view there is 

no such thing as confirmation by evidence 1 . 

To Popper, the solution to the problem of 

induction was simple: no justification exists 

for the use of inductive logic to formulate 

universal statements. Instead, empirical science 

is demarcated from pseudo-science by a 

principle of ‘falsifiability.’ Theories are never 

confirmed or made more probable. Rather, 

Popper’s principle proposes that scientists 

should try to falsify theories, and those 

theories that best withstand falsification are 

‘corroborated.’ Popper’s idea is ingenious, as 

it shifts the focus away from inductive logic 

and onto deductive logic. If a theory does not 

withstand such a test, then it is inarguably 

deduced that it is false. Nonetheless, Popper’s 

philosophy is not without its faults. Hypothetico-deductivists 

contend that – Wait a 

moment. Hypothetico-deductivist? Popper? 

Isn’t he the guy on the popcorn box? 

Science education at numerous ‘top’ universities 

does not include requisite training 

in the philosophical issues underpinning 

scientific practice. When does evidence sufficiently 

justify a theory? How do we know 

when inductive inference provides us with 

true knowledge? Students must partake in 

self-study to answer these questions – if they 

are inquisitive. But are science students failing 

to benefit from a formal education in the 

philosophy of science? 

A general understanding of the philosophy 

of science is clearly advantageous for science 

students. A philosophical foundation can allow 

students to tackle numerous contentious 

issues – such as the interpretation of negative 

results. Above all, it can teach students to 

think; it can teach them to consider science 

from a broader perspective, and to eliminate 

inherent biases in their thought processes. 

Students will no doubt formulate their own 

opinions on important philosophical issues; 

they may, like Hempel 1 , argue that diversity, 

variety, and precision of evidence are of upmost 

importance, or they may be predictionists 

and assert that scientific truth can only be 

validated by the confirmation of novel predictions. 

However, if these opinions do not 

arise via consideration from formal education, 

then they inevitably develop from personal 

contemplation, subconscious (or even 

conscious) bias from the literature, and opinions 

of their supervisor and colleagues. Thus, 

students may not be fully equipped with the 

knowledge and perspective necessary for insightful 

deliberation. 

Albert Einstein wrote to a colleague 2 : “When 

Image: The School of Athens, (1510-1511), Raphael. 


VIEWPOINT 

I think about the ablest students whom I 

have encountered in my teaching, that is, 

those who distinguish themselves by their 

independence of judgment and not merely 

their quick-wittedness, I can affirm that they 

had a vigorous interest in epistemology. They 

happily began discussions about the goals 

and methods of science, and they showed 

unequivocally, through their tenacity in defending 

their views, that the subject seemed 

important to them.” If it is a philosophical 

drive that distinguishes the ‘ablest students,’ 

then this drive should be encouraged, lest 

the future of science be plagued by a glut of 

monotonous, formulaic, non-truth seeking 

endeavours. 

I had the opportunity to take an excellent 

graduate class this year. In the class, each student 

argued in favour of a prominent scientific 

theory from the literature. Unknowingly 

at the time, the class provided me with great 

insight into the thought processes students 

had about serious philosophical issues. For 

example, it was a common theme for a presenter 

to argue in favour of a theory because 

much more evidence was available. However, 

it was never stressed as to why an abundance 

of evidence should offer indubitable support 

for a theory (see: problem of induction). Do 

inductive conclusions have more credence if 

they are supported by a greater variety of evidence? 

What about theories that have withstood 

falsification? Do scientists even try to 

directly falsify their own theories? 

I met with the course coordinator, Dr. Jennifer 

Ryan, to discuss the course and her 

opinions on graduate education. Dr. Ryan 

echoed many of my beliefs; she felt that it is 

extremely important for students to be formally 

introduced to reasoning and problem 

solving. Her course was initially structured 

to have students present various theories 

in the literature (rather than have a debate 

about them). “When I first taught the course, 

I found that students had a very difficult time 

writing their own thoughts. [After restructuring 

the course], the students were forced 

to come down on one side of an issue. I think 

that when students feel that it is OK to question 

the status quo, it becomes amazing. They 

question the evidence and the methods. They 

need to be pushed to think outside the box.” 

However, she also stated that the issue is complex; 

there is also an onus on the supervisor 

to encourage outside-the-box thinking. The 

effects of education in the classroom would 

be limited if there is pressure from above. 

Popper’s influence might be relatively unknown 

among science students, but Albert 

Einstein’s is not. In a letter, he states 3 : “I fully 

agree with you about the significance and 

educational value of methodology as well as 

history and philosophy of science. So many 

people today – and even professional scientists 

– seem to me like somebody who has 

seen thousands of trees but has never seen 

a forest. A knowledge of the historic and 

philosophical background gives that kind of 

independence from prejudices of his generation 

from which most scientists are suffering. 

This independence created by philosophical 

insight is – in my opinion – the mark of distinction 

between a mere artisan or specialist 

and a real seeker after truth.” 

Perhaps it is time for students to be trained 

as real seekers of scientific truth rather than 

highly advanced ‘doers’ of science. A good 

start towards this goal would be to introduce 

requisite training in the philosophy of science. 

Disclaimer: The opinions expressed by the author 

are in no way affiliated with the Institute of Medical 

Science or the University of Toronto. Comments 

are welcome at theimsmagazine@gmail. 

com. 

References 

1. Curd, Martin, and J. A. Cover. Philosophy of Science: 

The Central Issues. New York: W.W. Norton &, 1998. 

Print. 

2. Einstein, Albert. “Ernst Mach.” Physikalische 

Zeitschrift 17: 101–104. 

3. Einstein to Thornton, 7 December 1944, EA 61-574. 


VIEWPOINT 

POSITIVE PRESSURE 

The research bias towards positive results 

Science involves the discovery of new results, both positive and negative. Negative results can be just 

as important as positive results, as the dissemination of negative results can prevent other scientists 

from needlessly repeating the same experiment, therefore saving time and resources. However, negative 

results are often taboo in individual labs and in peer-reviewed publications in major journals. Why 

does this bias exist, and what can be done about it? 

By Allison Rosen 

The scientific process involves 

studying the world through observation 

and experimentation in order 

to attain knowledge (the word science 

comes from the Latin word scientia, meaning 

knowledge). Hypotheses are formed and 

experiments are conducted to assess the validity 

of these hypotheses. This is a self-correcting 

cycle and it is designed to hone in on 

increasingly precise and accurate theories. 

At the onset of a study, a hypothesis is created, 

and a corresponding null hypothesis 

is also formed. While a hypothesis asserts a 

relationship between two variables, the null 

hypothesis is a default position; for example, 

the null hypothesis states that there is no relationship 

between the two variables under 

study. A key concept in science is that experimental 

results are interpreted relative to the 

null hypothesis. At their most basic, positive 

results reject the null hypothesis, while negative 

results fail to reject it. It is important to 

note that rejecting the null hypothesis means 

that there is a high degree of probability it is 

incorrect and that the alternative hypothesis 

may be true – this is never absolute. Thus, 

a hypothesis can never be fully proven; evidence 

either supports or falsifies it. 

Despite the lucid nature of the scientific 

method, the idea of science as a pure practice 

striving towards truth is flawed. There 

are a number of scientific biases, despite 

many countermeasures put in place to combat 

them. Scientists at every level encounter 

a multitude of problems – for example, funding 

issues, equipment problems, and pressures 

– that often occlude their ability to treat 

all results as equally important. In particular, 

publication bias is the tendency to publish 

positive results more than negative results. 

Since this leads to an overrepresentation of 

positive data, it can also lead to an overall bias 

in published literature; therefore, addressing 



VIEWPOINT 

this bias should be of high importance to the 

scientific community. 

Negative results from lab to 

publication 

In medical research, discovering that a drug 

is efficacious, for example, or that a lifestyle 

factor influences health, is clearly important. 

But is it any less important to discover that a 

drug does not work, or that a lifestyle factor 

has no effect on a health outcome? Much of 

academia is focused on the ethos of “publish 

or perish,” yet the world of publishing is built 

around positive, rather than negative, results. 

A recent correspondence in Nature further 

expounds the issue by illustrating how repressing 

negative results can skew the literature. 

National Institutes of Health researcher 

Nitin Gupta (2011) writes that it is important 

to publish negative results because, when 

combined with significant results from other 

studies in meta-analyses or reviews, less robust 

results may be discovered. Inclusion of 

negative results in these compilations can aid 

in more accurate comparisons and corrections 

across studies. 

Gupta explains his opinions using a hypothetical 

experiment that failed to reach the 

P

BEHIND THE SCENES 

Spotlight on 

Kamila Lear 

An inspiring balancing act 

By Meghna Rajaprakash 


BEHIND THE SCENES 

Most students know Kamila 

Lear as the friendly Program and 

Business Officer of the Institute 

of Medical Science. But little do they realize 

that in addition to playing a critical role at the 

IMS, Lear is a part-time Sociology student at 

U of T, a mother of two, a fitness enthusiast, 

and an avid cook. Lear has a remarkable ability 

to juggle numerous responsibilities and 

adapt quickly to dynamic situations, qualities 

that likely stem from her interesting past. 

Lear was born in England, but her parents 

immigrated to Canada when she was very 

young. She was raised in Pointe-Claire, a municipality 

located on the West Island of Montreal. 

Although most of the residents in her 

town were English-speaking, Lear’s parents 

insisted that she learn French – a skill that 

she began to appreciate more as she matured. 

“I strongly believe that being raised as a bilingual 

child provided me with a significant 

advantage when it came to education, employment, 

and social situations,” Lear attests. 

Lear nurtured her interest in French language 

and culture by enrolling at a French private 

school called College Saint-Anne de Lachine. 

She continued her education in French as she 

pursued post-secondary training in Business 

Administration. Alongside her studies, she 

also took interest in learning culinary arts, 

sign language, life drawing, art history and 

needlepoint design. Lear’s early talent for 

balancing many interests and activities was 

the foundation to her later successful career. 

Despite her love for Montreal, Lear settled 

down in Toronto, where she has lived for 

the past 25 years with her husband and two 

sons. She began working at the University of 

Toronto as the Student Liaison Officer and 

Graduate Administrator in the Department 

of Occupational Science and Occupational 

Therapy. During this period, she was granted 

an Excellence in Service award for her commitment 

to student services. 

recruitment, student services, and business 

administration,” she says. 

Currently, Lear is involved in many key aspects 

of the IMS department, including strategic 

planning, preparing complex statistical 

reports and reviews, advising and implementing 

departmental policy, assisting in the 

development of new courses and programs, 

and managing budgets and student issues. 

Although she carries a heavy workload, Lear 

enjoys her multifaceted job, particularly because 

she has an opportunity to work with 

students. 

“There are a number of things I enjoy about 

my job. But, first and foremost would be 

my interaction with IMS students. The IMS 

seems to attract the best and the brightest 

students. I believe that building stronger connections 

with IMS students will help us understand 

where we need to focus our efforts 

to improve their graduate experience.” 

Lear envisions a bright future for the IMS as 

the department launches new initiatives. She 

is especially excited about bringing about 

positive change for students through a new 

strategic planning process in the upcoming 

year. 

“There have been a lot of changes at the IMS 

recently, which makes for an exciting time. 

We moved to our newly renovated location 

Insiders Information 

Favourite food: Seafood pasta 

Favourite sports team: The Habs, naturellement! 

Favourite quote: “Education is the most powerful 

weapon which you can use to change the world.” - 

Nelson Mandela 

Favourite subject in school: Literature 

on the second floor. It is also a pleasure to 

have our recently appointed IMS Director, 

Dr. Allan Kaplan, join our IMS team. Under 

Dr. Kaplan’s directorship, we will be launching 

a new and important strategic plan that 

will give the IMS the integrity to make informed 

decisions as we move forward.” 

Besides her work responsibilities, Lear serves 

in many support roles for students. She is the 

Departmental Advisor for the IMS Magazine 

and played a critical role in the initiation and 

development of the magazine. She also prepares 

content for publication in the “News & 

Views at a glance” and “Ask the Experts” sections 

of the magazine. Lear is very happy to 

work with Natalie Venier and the IMS Magazine 

team towards what she describes as “one 

of the best publications around campus.” 

Through her dedication to students, her ability 

to multitask, and her inspiring vision for 

the future of the IMS, Lear truly distinguishes 

herself as a very valuable member of the 

IMS team. Her passion for the IMS resonates 

in her advice to students: 

“Take advantage of this wonderful time in 

your student-life by getting involved in extra-curricular 

activities through the IMS and 

IMSSA. These opportunities will allow you 

to develop important life skills and network 

with students and faculty.” 

Most interesting life experience: Climbing the Sydney 

Harbour Bridge, in Sydney, Australia. At the top of the 

bridge is the most breathtaking view of Sydney Harbour 

and the Opera House. 

Pet Peeve: Pessimism 

Who inspires you? My family – they are the reason I 

strive to do my best in everything I take on in my life. 

Photos courtesy of Kamila Lear 

Shortly thereafter, Lear took on the role of 

IMS Program and Business Officer, a position 

that enabled her to capitalize on her 

skills sets and interests. 

“I was attracted to the position because it 

gave me the opportunity to draw on my previous 

experience in admissions and awards, 


FUTURE DIRECTIONS 

Dr. Aristotle Voineskos By Zeynep Yilmaz 

Combining Genetics and Neuroimaging to Understand the Etiology of Psychiatric Disorders 

How many graduates do you 

know who have earned their 

academic appointment only six 

months after completing their PhD? In a day 

and age where academic jobs are sparse and 

highly competitive, most of us may think of 

such an accomplishment as unlikely and farfetched. 

But then again, Dr. Aristotle Voineskos 

is not your average young researcher. 

Having graduated from the IMS with a PhD 

in September 2010, he has become an Assistant 

Professor in the Department of Psychiatry 

at the University of Toronto in March 

2011 and an Associate Member at the IMS in 

July 2011. The fact that he has received funding 

from some of the most prestigious and 

competitive funding agencies such as the Canadian 

Institutes of Health Research (CIHR) 

and National Alliance for Research on 

Schizophrenia and Depression (NARSAD) 

further shows that Dr. Voineskos has proven 

himself to be a role model to which many 

young medical and research trainees aspire. 

Born and raised in Toronto, Dr. Voineskos attended 

the University of Western Ontario for 

his undergraduate studies and was accepted 

to the University of Toronto Medical School 

after his third year at UWO. It was during 

this time that he started developing an in- 



FUTURE DIRECTIONS 

terest in genetics and the brain. Following 

completion of his medical degree, his combined 

clinical and research interests led to 

a residency choice in psychiatry at the University 

of Toronto. He recalls his rotation at 

the First Episode Schizophrenia Program at 

the Centre for Addiction and Mental Health 

(CAMH) as a third-year resident, and how 

this experience shaped his future research 

interest in schizophrenia as a brain disorder. 

During the fourth year of his residency training, 

he started his PhD with the IMS under 

the primary supervision of Dr. James Kennedy. 

A year later, he had the serendipitous opportunity 

to spend six months at the Harvard 

Medical School to learn about brain imaging 

techniques. This opportunity opened doors 

for fruitful collaborations as well as new ways 

to think about neuropsychiatry, leading Dr. 

Voineskos to go back to Boston later on during 

his PhD studies to continue learning 

about these cutting-edge techniques. 

Having started his graduate training in Dr. 

Kennedy’s neurogenetics laboratory, Dr. 

Voineskos has also done some work in PET 

imaging in the earlier days of his training. 

Under the mentorship of Dr. Martha Shenton 

at the Brigham and Women’s College at the 

Harvard Medical School, he gained vast experience 

working with diffusor tensor imaging 

(DTI), a more advanced MRI technique. 

DTI allows for the measurement of structural 

properties in different brain regions, which 

fits well with Dr. Voineskos’s passion for understanding 

how risk genes influence brain 

structures in patients with severe psychiatric 

disorders, particularly schizophrenia. He 

also credits the opportunities he had in the 

Geriatrics Program at CAMH for shaping 

his research scope. Being given a chance to 

work as a part of the team and be involved in 

data collection and scans led him to a whole 

different area of collaboration and research 

opportunities: recruitment of a healthy aging 

control cohort, as well as studying healthy 

aging and Alzheimer’s disease. His current 

research combines multi-modal neuroimaging 

and genetics approaches to map gene effects 

in the brain with the aim of discovering 

vulnerability pathways for severe mental illness. 

His research findings on the role of the 

BDNF gene in Alzheimer’s disease have been 

featured widely in the news media earlier this 

year. 

Dr. Voineskos recognizes the influence of 

many mentors on this work and credits them 

greatly with where he is now as a scientist. 

He emphasizes the importance of the mentorship 

of Dr. Shenton at Harvard and Dr. 

Kennedy as his supervisors, and states that 

apart from research training, he has learned 

so much from them about how to get funding, 

grant writing, and the importance of networking. 

He also thanks Dr. Nancy Lobaugh, 

his clinical mentors Drs. Gary Remington 

and Jeff Daskalakis in the Schizophrenia Program 

at CAMH, as well as Drs. Bruce Pollock 

and Benoit Mulsant in the Geriatrics 

Program for their mentorship and support. 

Last but not least, he acknowledges the role 

IMS has played in his training and career. 

“I’d like to thank Dr. Mary Seeman for being 

flexible and allowing me to be away for my 

imaging training,” he says and continues, “the 

door was always open at the IMS, and the 

staff has been wonderful and very helpful in 

answering my questions on procedures and 

timeline.” Having delivered the very prestigious 

Salter-Siminovich lecture in the 2011 

IMS Scientific Day this May, Dr. Voineskos 

has always seen the Scientific Day as a great 

opportunity to exchange ideas and learning 

more about the research of his peers. He also 

recalls having enjoyed taking IMS courses, 

which gave him the chance to meet faculty, 

explore areas relevant to his research in an 

in-depth fashion, as well as publish highcaliber 

scientific papers resulting form his 

course work. As the Director of the Kimel 

Family Translational Imaging-Genetics Research 

Laboratory at CAMH, Dr. Voineskos 

is eager to pass his research experience to 

a new generation of research trainees: he is 

currently supervising two Master’s level IMS 

students and is looking forward to expanding 

his laboratory. 

One piece of advice Dr. Voineskos has for 

IMS students has undoubtedly shaped his 

young but stellar career, “having a great set of 

mentors is at least as important as your specific 

research focus; keeping an open mind 

may open many doors for you in an unexpected 

fashion.” He highlights the benefits 

of learning as much as possible from each 

mentor and taking their best qualities to better 

yourself and your research skills. He also 

reminds the students the importance of hard 

work and staying motivated to succeed. Having 

been an avid participant in sports from 

a young age, he also emphasizes the importance 

of work-life balance. 

Indeed, this is not the typical career of a 

recent PhD graduate. At the age of 33, Dr. 

Voineskos has achieved success that many 

senior researchers have not had in their long 

careers. His stellar accomplishments surely 

are inspirational to graduate students interested 

in research as well as aspiring medical 

trainees and residents. Most importantly, the 

achievements of Dr. Voineskos serve as a testament 

to the importance of a solid research 

training, dedication, devotion, flexibility and 

eagerness to learn from others as the hallmarks 

of success and a fruitful research career. 


FUNDING 

Cancer Donations 

Making Your Dollar Count 

By Tetyana Pekar 

The canadian cancer society (ccs) 

came under scrutiny in early July 

when a CBC News story revealed that 

the organization spends proportionally more 

money on fundraising and administrative 

costs than on research. According to CBC’s 

Marketplace analysis, research spending decreased 

from 40.3% of the total expenditures 

in 2000 to 22% in 2011, while fundraising 

increased from 26% to 42.7% during that 

time 1 . Researchers quoted in the article and 

commentators on the webpage were angry 

at the “inefficient” and “wasteful” spending. 

Although many believe that the CBC story 

is misleading, it highlights the importance 

of identifying charities whose mandate and 

spending align with donor’s priorities. 

What should individuals look for in a 

charity and where would donations make 

the most impact? 

Firstly, it is important to examine the charity’s 

mandate, which should be readily available 

on its website. The CCS, for example, in 

addition to funding cancer research, seeks to 

decrease cancer incidence rates and improve 

the quality of life for those living with cancer. 

It accomplishes this goal through health promotion 

and public policy changes and by developing 

and funding programs for patients 

and caregivers 2 . Therefore, it is not surprising 

that the CCS has made a decision to spend 

less money, proportionally, on research, in 

order to focus on these areas of their strategic 

plan. As such, when the priority is to contribute 

solely to research, individuals should 

donate directly to research institutions. 

It is also advisable to evaluate how the charity 

allocates their donations and revenue, and 

the transparency of this information on the 

organization’s website. For the CCS, this information 

is readily available on their website 

and a quick look reveals that some of the 

information in the CBC report is misleading. 

In particular, administration costs amount 

to just 4% of the CCS’s total revenue 4 . Low 

overhead costs may not necessarily be a good 

thing from a business standpoint, as employees 

need adequate salaries and equipment to 

be proficient at their jobs. The CBC Marketplace 

analysis also includes the money spent 

on marketing and prizes of lotteries under 

fundraising costs, artificially manipulating 

the relative percent spent on fundraising. In 

actuality, while the CCS spent $22,988 million 

on marketing and prizes, they made only 

$23,869 million in revenue, which results in a 

net gain of a modest $881 million 3, 4 . 

Finally, it is of benefit to consider the effectiveness 

of the programs that have been 

funded, supported or initiated by the charity. 

Without evidence of results, money spent on 

cancer education and promotion is not justified. 

Charities should have a method for evaluating 

the success of their programs. Monitoring, 

evaluating and openly disclosing the 

effectiveness of the organization’s programs 

are critical attributes of outstanding charities. 

In addition to the above considerations, it is 

important to identify a cause where donations 

make the most impact. Charity Intelligence 

Canada (CIC) facilitates this process 

by pinpointing the most effective and efficient 

charities, as well as underfunded causes. 

A recent CIC report focusing on cancer suggests 

donating to some of the least funded 

cancers in Canada: pancreatic, stomach, 

lung and colorectal. According to CIC, these 

cancers together represent 46% of potential 

years of life lost (an estimate of the average 

years of life an individual would have lived if 

they had not died prematurely) and have the 

lowest 5-year survival rates; yet, they receive 

only 15% of cancer-specific research funding 

and only 1.6% from cancer-specific charities 

5 . Unsurprisingly, the CIC report states 

that when evaluating the donations based 

on potentials years of life lost, Canadians donate 

151 times more to breast cancer-specific 

charities than to the four most lethal cancers 

combined 5 . 

Given these considerations, donors should 

be careful when considering potential charities 

and causes. A more detailed examination 

enables donors to make the most impact with 

their money by contributing to effective and 

underfunded charities. 

References 

1. http://www.cbc.ca/news/canada/story/2011/07/04/ 

cancer-society-funding.html 

2. http://www.cancer.ca/Canada-wide/About%20us. 

aspx?sc_lang=en 

3. http://www.globalphilanthropy.ca/index.php/blog/ 

comments/cbc_report_on_canadian_cancer_society_- 

thoughts_on_transparency_media_cover/ 

4. http://www.cancer.ca/Canada-wide/About%20us/ 

CW-Financial%20statements.aspx?sc_lang=en 

5. Charity Intelligence Canada - Cancer Report: Framing 

the Crisis and Previewing the Opportunity for 

Donors. Greg Thomson and Karen Greve Young April 

2011 



Ask 

Experts 

the 

Dear Experts, 

Last year I applied for several external Master’s 

student awards. Unfortunately, I did not 

receive any. I am planning to transfer to a 

PhD program next year; I haven’t had any 

publications since then. Should I apply for 

an external award again this year? Are there 

specific requirements about the number of 

publications a Master’s student or a PhD student 

must have in order to defend? 

- Award Woes 

Dear A.W., 

Both publications and awards are great to 

have on one’s CV. The more publications, the 

greater the likelihood of getting awards, and 

the more awards, the greater the likelihood 

of obtaining further awards. That being said, 

neither publications nor awards are prerequisites 

to either transfer or defend. 

Dear Experts, 

I am set to have my PAC meeting in a few 

weeks. I tend to get very nervous at my PAC 

meetings and often blank out on simple 

questions. Do you have any advice? 

- Presentation Jitters 

Dear P.J., 

It is a good idea to let your committee know 

in advance that you tend to become nervous 

during exam-like situations. Also let them 

know that you have studied hard and that 

when you blank out it is not because you 

don’t know the answer. It is also a good idea 

to consult with student services about programs 

that will help you with nervousness. 

The problem is a common one and lots of 

help is available. The graduate coordinators 

may be able to suggest specific avenues of 

help as well. 

Dear Experts, 

I’m hoping to start a Master’s program next 

year. What are some key qualities I should 

look for in a supervisor? 

- Searching for Supervisors 

Dear S.S., 

You will want a supervisor who is doing the 

kind of work you are interested in and who 

is doing it well (e.g. publishing, receiving external 

grants, enjoying the respect of peers). 

Visiting the laboratory and talking to present 

and past students will give you an idea 

of the supervisor’s accessibility, mentoring 

style, and general “likeability” – all important 

qualities. 

Dear Experts, 

Recently a graduate student, who is registered 

with the IMS, joined my lab. I have a 

cross-appointment with another graduate 

department which has very strict criteria for 

Program Advisory Committee (PAC) meetings 

(i.e. progress reports, time restrictions 

on presentations, etc.). Can I advise my IMS 

student to follow the same criteria for their 

PAC meetings? 

- PAC Concerns 

Dear P.C., 

It is up to the supervisor (in consultation 

with the student and the PAC members) 

to decide how the PAC meetings should be 

structured. The more formal, the better prepared 

the student will be to face exams. The 

students are advised to prepare an outline of 

their presentation beforehand and distribute 

it to the committee. They are also advised to 

take minutes during the meeting, write them 

up, and distribute them to the committee afterwards. 

Dear Experts, 

I recently was invited for an admissions 

interview from my graduate program. 

What kinds of questions can I expect? 

How can I prepare? 

- Imminent Interview 

Dear I.I., 

The interviewer will want to know what 

you are interested in doing during graduate 

school and why. Interest, understanding, 

curiosity and enthusiasm are usually 

what they look for. There won’t be any 

“trick” questions. They will want to know 

what motivates you and why you are applying. 

EXPERT TIP 

Grant writing is a skill that can only 

be perfected with practice. 

Do you have a question for the experts? 

Please send it to theimsmagazine@gmail. 

com (ATTN: Experts) 


PAST EVENTS 

IMS students reveal their hidden 

talents at IMSSA’s Annual 

Talent Show. This event 

raised $1100 for the construction 

of a hospital ward 

in Jinja, Uganda. (Sponsors: 

Steamwhistle and Pizza 

Nova.) 

Talent Show photos courtesy of IMSSA 

Summer student photo courtesy of Ryosuke Ikeda 

PAST 

EVENTS 

Summer Student photo by Mohammed Sabri 

Summer Research Day photos courtesy of IMSSA 

Left: Philip Alves, Ryosuke 

Ikeda and Fatma 

Aksoy enjoy their summer 

student experience 

at Sunnybrook Hospital. 

Right: Zeynep Yilmaz and 

Atiqa Malik volunteer 

their time to assist summer 

students at the IMS’ 

Summer Research Day. 

Left: Dr. Lyle Palmer gives 

the inaugural Ori Rotstein 

Lecture at this year’s 

Summer Research Day. 

Right: Later he assists in 

judging student presentations. 

(right) 


DIVERSIONS 

SUDOKU 

2 7 

1 

5 

8 

4 

9 

6 

2 

6 

9 

9 

1 

3 

1 

4 

WHAT’S UP, TORONTO? 

YOUR EVENTS GUIDE FOR THE SEASON 

For the Halloween buff 

6th Annual Toronto After Dark Film Festival – October 20-27, Toronto Underground Cinema 

(http://torontoafterdark.com/2011) 

Halloween Howl - October 22 & 29, Toronto Zoo 

(http://www.torontozoo.com/events/?pg=HalloweenHowl) 

For the budding philanthropist 

Ontario Lung Association – The Amazing Pace – October 29 – starting location Yonge/Dundas 

Square (http://www.theamazingpace.ca) 

3 

4 

6 

6 

1 

2 

1 

5 

5 

4 

3 

7 

3 

1 

8 

2 

Movember 

For the arts lover 

The Rendezvous with Madness Film Festival – November 4-12, multiple venues 

(http://www.rendezvouswithmadness.com) 

Maya: Secrets of their Ancient World - Opens November 19, Royal Ontario Museum 

(http://www.rom.on.ca/exhibitions) 

For the Holiday spirit enthusiast 

Cavalcade of Lights – November 26, Nathan Phillips Square (http://www.toronto.ca/special_events/cavalcade_lights) 

Skating at the Harbourfront Centre – starting November 

(http://www.harbourfr ontcentre.com/skating) 

Christmas by Lamplight (“Step into a Dickens Christmas”) - December 10, 17 & 18, Black 

Creek Pioneer Village (http://christmasbylamplight.ca) 

competition 

Movember (the month formerly known as November) is a moustache-growing charity event held 

during November of each year to raise funds and awareness for men’s health. If you plan on growing 

a moustache worthy of publication, please send your photo to theimsmagazine@gmail.com (ATTN: 

Movember Competition) by December 1, 2011. If you are voted to have the best ‘stash, we will 

publish a photo of you and your moustache in the next issue of the IMS Magazine! 

Solution to Sudoku from Summer 2011 issue of 

the IMS Magazine 

Answer: This is a magnified photo of… 

(1) A neural stem cell 

“Piled Higher and Deeper” by Jorge Cham http://www.phdcomics.com 


READ IT ONLINE 

IMSMAGAZINE 

http://issuu.com/imsmagazine 

www.facebook.com/groups/imsmagazine/ 

@IMSMagazine

Fall 2011 - Institute of Medical Science - University of Toronto

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