Annual Meeting Proceedings Part 1 - American Society of Clinical ...

648s Sarcoma
10072 General Poster Session (Board #51A), Sun, 8:00 AM-12:00 PM
Effect of anti-�1 integrin antibody on lung seeding of osteosarcoma cells in
live mice visualized by single-cell in vivo imaging. Presenting Author:
Hiroaki Kimura, Department of Orthopaedic Surgery, Graduate School of
Medical Science, Kanazawa University, Kanazawa, Japan
Background: Integrins play a role in tumor growth and metastasis (Int. J.
Cancer 129, 2905-2915, 2011). However, the effect of integrin inhibition
has not been visualized on single cancer cells in vivo. In this study, we used
a powerful subcellular in vivo imaging model to demonstrate how an
anti-integrin antibody affects seeding and growth of osteosarcoma cells on
the lung. Methods: The 143B human osteosarcoma cell line expressing red
fluorescent protein (RFP) in the cytoplasm and green fluorescent protein
(GFP) in the nucleus was established. Using the double-labeled osteosarcoma
cells, single cancer-cell seeding in the lung after i.v. injection of
osteosarcoma cells was imaged in live mice. Results: The anti-b1 integrin
monoclonal antibody, AIIB2, greatly inhibited the seeding of cancer cells
on the lung while a control antibody had no effect. To image the efficacy of
the anti-integrin antibody on spontaneous metastasis, mice with orthotopically-growing
143B-RFP cells in the tibia were also treated with AIIB2 or
control anti-rat IgG1 antibody. After 3 weeks treatment, mice were
sacrificed and primary tumors and lung metastases were evaluated with
fluorescence imaging. AIIB2 significantly inhibited spontaneous lung
metastasis but not primary tumor growth. In a separate experiment, the
anti-�1 integrin antibody increased survival in the orthothopic osteosarcoma
model. Conclusions: The efficacy of the anti-�1 integrin antibody
against metastasis may be due to inhibition of lung seeding of the cancer
cells. The increased survival of mice with orthotopically-growing 143B-RFP
treated with AIIB2 may be due to inhibition of metastasis, which in turn
may be inhibited by effect of the anti-�1 integrin on cancer-cell seeding in
the lung.
10074 General Poster Session (Board #51C), Sun, 8:00 AM-12:00 PM
Age as a prognostic factor in osteosarcoma: Survival analysis. Presenting
Author: Maria Pallotta Guadalupe, Hospital Italiano de Buenos Aires,
Ciudad Autonoma de Buenos Aires, Argentina
Background: Studies comparing survival between adult and paediatric
population with osteosarcoma are scarce and contradictory. Generally
adults were excluded from analysis in historical series. End Point: evaluate
age as prognostic factor in ostosarcomas IIb treated exclusively by a
multidisciplinary group in a single institution. Methods: 132/278 patients
with histological diagnosis of osteosarcoma IIb were selected. All were
treated exclusively in our hospital from July 1988 until December 2010.
Patients 17 years old or younger were considered paediatric. They all
received presurgical chemotherapy with the same scheme: ifosfamide �
doxorrubicin � high dose methotrexate. Univariate analysis was made
(Fischer exact test). Survival was calculated wih Kaplan-Meier actuarial
method. Curves were compared with log rank test. Multivariate Cox analysis
was made. Results: Median age was 19.6 years (std: 9,1; range 5-58).
Adults: 77, children: 55. No differences were detected between the two
age groups regarding: elevated alkaline phosphatase, kind of surgery
(amputation vs. limb sparing), relapse site (lung, local, other), necrosis
greater than 90% or number of lung resections. There was a tendency
towards axial localization in adults (p�0.05). No paediatric patient had
inadequate medical intervention, but it was present in 14.3% of adults
(p�0.002). 5 year Overall survival (5y OS) in children was 85,2%
compared with 61,8% in adults (p�0.005); Disease free survival (DFS)
had a non significant tendency to be better in children (69.6% vs. 51,3%).
Variables associated with worse OS were: axial location (p�0.01), elevated
alkaline phosphatase (0.003), amputation (p�0.008), local relapse or
systemic non-lung metastasis (p� 0.001), necrosis less than 90% (0.001).
Multivariate Cox analysis showed association between OS and paediatric
population (p�0.01) and necrosis greater than 90% (p�0.001), while
DFS was associated with necrosis greater than 90% (p�0.01) and elevated
alkaline phosphatase (p�0.05). Conclusions: Paediatric population presents
better survival compared to adults in our institution. Differences in
tumour biology and in the mode of presentation related to age may be the
explanation.
10073 General Poster Session (Board #51B), Sun, 8:00 AM-12:00 PM
Navigation-assisted surgery for bone and soft tissue tumors with bony
extension. Presenting Author: Makoto Ieguchi, Department of Orthopedic
Surgery, Yodogawa Christian Hospital, Osaka, Japan
Background: In recent times,minimally invasive surgery, such as endoscopic
surgery, has gained a lot of popularity.The navigation system was
introduced to orthopedic surgery in the 1990s. These days, computed
tomography (CT)-based navigation systems are commonly used in spine
and joint replacement surgery because of their precision. The aim of our
study was to evaluate the accuracy and efficacy of navigation-assisted
excision of bone and soft tissue tumors. Methods: From January 2006 to
December 2009, we performed navigation-assisted surgery in 16 patients
(11 men and 5 women; mean age, 39 years; range, 13-70 years). We
diagnosed 9 benign bone tumors and 7 malignant bone and soft tissue
tumors. In 2 patients, the malignant soft tissue tumors infiltrated the
adjacent bones. We performed excisional biopsies for the benign tumors
and en bloc excisions for the malignant tumors. In all the cases, the point
registration method was used with 10 skin markers that were placed around
the tumor. Each excisional difference between the preoperative and
postoperative plans was evaluated histologically or by postoperative CT.
Results: The mean preoperative registration matching time was 12.8 min
(range, 8-25 min). The total mean preparation time was 24 min (range,
16-35 min). The mean accuracy of this system, which was determined
using the skin markers, was 0.93 mm (range, 0.6-1.5 mm). All biopsied
and excised specimens were evaluated by pathologic examination and
postoperative CT imaging. The mean difference between the planned
margin and postoperative CT or the excised histological specimen was 0 to
4 mm. The mean follow-up period was 53.2 months (range, 10-70
months). There were no local recurrences, except for a case of chordoma
that required excision of skip metastases and a case of extraskeletal
osteosarcoma, in which the patient died from the disease. Conclusions: We
report our experience with navigation-assisted surgery for bone and soft
tissue tumors performed using skin markers. Navigation-assisted surgery
was indicated in the case of sufficiently reliable, accurate, and minimally
invasive resections.
10075 General Poster Session (Board #51D), Sun, 8:00 AM-12:00 PM
Efficacy of newly developed platinum complexes against osteosarcoma,
bone-targeting platinum, and proteasome inhibitory platinum. Presenting
Author: Kentaro Igarashi, Department of Orthopaedic Surgery, Kanazawa
University, Kanazawa, Japan
Background: Cisplatin is one of the most effective anti-cancer drugs
available for the treatment of human solid tumors including osteosarcoma.
As we had already reported, we have utilized caffeine in our chemotherapy
protocol. And we achieved excellent clinical results. But effectiveness of
cisplatin has been limited by side effects, and resistance. Here we
developed two novel platinum compounds. 3Pt is trinuclear platinum
complex bearing geminal bisphosphonate moieties, 1Pt is mononuclear
platinum complex which has proteasome inhibitory activity. We performed
comparative studies of our novel platinum compounds with osteosarcoma.
Methods: Two novel platinum complexes were synthesized by Prof. Odani at
school of pharmaceutical sciences of our university and cisplatin and
caffeine were obtained from constructor. Three cell lines (MG63, 143B,
and LM8) were used. Cell survival after a 72 hrs exposure to these
compounds was assessed by WST-8 assay, and IC50 value was calculated
for each compound. Apoptosis was assessed by DNA fragmentation and
Annexin V-FITC/propidium iodine assay. Results: Each compound strongly
caused concentration-dependent cytocidal effect. IC50 value of trinuclear
compound is superior to cisplatin, and both complexes showed caffeine
potentiation. Apoptosis induction and acetylation of histon H2AX were
observed. In vivo, 1Pt showed almost same, 3Pt showed strong antitumor
effect compared to cisplatin. Conclusions: Two novel platinum compounds
that we developed showed strong ant-tumor effect in osteosarcoma in vitro
and in vivo. As bisphosphonate has high affinity to calcium ions, 3Pt targets
bone tissue and expected to reduce side effects at extraskeletal sites and to
overcome the drug resistance. Proteasome inhibitory platinum compound
has never been reported before, we will investigate its anti-tumor mechanism
precisely.
Visit abstract.asco.org and search by abstract for the full list of abstract authors and their disclosure information.