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GASTROINTESTINAL (COLORECTAL) CANCER Locally Advanced Rectal Cancer: Time for Change? CHAIR Martin R. Weiser, MD Memorial Sloan Kettering Cancer Center New York, NY SPEAKERS Zhen Zhang, MD, PhD Fudan University, Shanghai Cancer Center Shanghai, China Deborah Schrag, MD, MPH Dana-Farber Cancer Institute Boston, MA
WEISER, ZHANG, AND SCHRAG Locally Advanced Rectal Cancer: Time for Precision Therapeutics Martin R. Weiser, MD, Zhen Zhang, MD, PhD, and Deborah Schrag, MD, MPH OVERVIEW The year 2015 marks the 30th anniversary of the publication of NSABP-R01, a landmark trial demonstrating the benefit of adding pelvic radiation to the treatment regimen for locally advanced rectal cancer with a resultant decrease in local recurrence from 25% to 16%. These results ushered in the era of multimodal therapy for rectal cancer, heralding modern treatment and changing the standard of care in the United States. We have seen many advances over the past 3 decades, including optimization of the administration and timing of radiation, widespread adoption of total mesorectal excision (TME), and the implementation of more effective systemic chemotherapy. The current standard is neoadjuvant chemoradiation with 5-fluorouracil (5-FU) and a radiosensitizer, TME, and adjuvant chemotherapy including 5-FU and oxaliplatin. The results of this regimen have been impressive, with a reported local recurrence rate of less than 10%. However, the rates of distant relapse remain 30% to 40%, indicating room for improvement. In addition, trimodality therapy is arduous and many patients are unable to complete the full course of treatment. In this article we discuss the current standard of care and alternative strategies that have evolved in an attempt to individualize therapy according to risk of recurrence. The current standard of care for patients with stage II (T3/ T4N0) and stage III rectal cancer (TanyN1/N2) is trimodality therapy including chemotherapy, radiation, and surgery with complete TME. 1 The primary rationale for systemic chemotherapy is to reduce the risk of distant recurrence, whereas the rationale for pelvic radiation is to prevent local recurrence and, in some cases, convert a patient from requiring abdominoperineal resection—which requires a permanent ostomy—to a sphincter-sparing low anterior resection. The trimodality approach has gained widespread acceptance, with numerous publications reporting a substantial reduction in local recurrence rates and prolongation of disease-free survival. 2-6 Since its inception, progress within each of the three therapeutic modalities has continued. The decision to use short-course radiotherapy (25 Gy in 5 fractions) versus long-course therapy (50.4 Gy delivered in 28 fractions with concurrent fluoropyrimidine) has largely depended on geography. Short-course regimens are generally favored in Northern Europe and Scandinavia, whereas long-course chemoradiation is advocated in North America and Central Europe. A Polish randomized trial compared long-course and short-course radiochemotherapy in patients with T3/4 mid- to low-lying rectal tumors, investigating the effıcacy of each regimen. Higher rates of complete pathologic response were observed in patients treated with long-course chemoradiotherapy (16% vs. 1%). Although the rate of positive circumferential resection margin (CRM) was signifıcantly higher in patients receiving short-course therapy (13% vs. 4%; p 0.017), no differences in local recurrence, diseasefree survival, or overall survival were observed. The German CAO/ARO/AIO 94 trial, published 11 years ago, compared preoperative and postoperative long-course chemoradiotherapy for stage II and III rectal cancer. 7 The preoperative treatment group demonstrated a signifıcant (p 0.006) decrease in local recurrence rate after 5 years, without a difference in rates of distant metastasis or overall survival. Additional benefıts of preoperative versus postoperative chemoradiation included a signifıcant decrease in short-term and long-term toxicity; for example, the incidence of grade 3 or higher toxicity was reduced from 40% in the postoperative group to 27% in the preoperative group (p 0.001). Over the past decade, preoperative chemoradiation has become the standard of care in the United States. Although this shift has certainly reduced treatment toxicity for many patients, many clinicians have questioned whether it has also resulted in excessive radiation exposure for individuals with easily resectable tumors (e.g., T3N0) who might not have required any pelvic radiation at all had they fırst undergone surgery. TME involves removal of the rectum together with its cylindrical mesentery and associated nodal tissue. The development and dissemination of this technique represented an incremental advance in oncologic surgery. TME involves sharp dissection between the visceral and parietal layers of From the Memorial Sloan Kettering Cancer Center, New York, NY; Shanghai Cancer Center, Fudan University, Shanghai, China; Dana-Farber Cancer Institute, Boston, MA. Disclosures of potential conflicts of interest are found at the end of this article. Corresponding author: Martin R. Weiser, MD, Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065; email: weiser1@mskcc.org. © 2015 by American Society of Clinical Oncology. e192 2015 ASCO EDUCATIONAL BOOK | asco.org/edbook
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AMERICAN SOCIETY OF CLINICAL ONCOLO
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American Society of Clinical Oncolo
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Controversies in Neoadjuvant Therap
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Clinical Trials of Precision Medici
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Managing Ovarian Cancer in the Olde
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Updates in the Multimodality Manage
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PEDIATRIC ONCOLOGY Real-Time Molecu
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2015 ASCO Annual Meeting Disclosure
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2015 Educational Book Expert Panel
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James Marshall, PhD Roswell Park Ca
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2015 Annual Meeting Supporters* MIS
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David Yurman Corporate Allies Conqu
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GYNECOLOGIC CANCER Cervical Cancer
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GYNECOLOGIC CANCER Managing Ovarian
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GYNECOLOGIC CANCER Treatment of the
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HEALTH SERVICES RESEARCH AND QUALIT
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INDUSTRY AND ONCOLOGY KEY POINTS F
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INDUSTRY AND ONCOLOGY by (covered)
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CANCER CARE QUALITY: CURRENT STATE
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TREATMENT OF PHILADELPHIA CHROMOSOM
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CD19 CAR THERAPY FOR ALL FIGURE 1.
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CD19 CAR THERAPY FOR ALL 5. Zhou G,
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NEW TARGETED THERAPIES FOR iNHL New
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NEW TARGETED THERAPIES FOR iNHL TAB
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GERBER, PAIK, AND DOWLATI gression
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BERNARDO H.L. GOULART lung-cancer/l
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LUNG CANCER Updates in the Multimod
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WOODARD AND JABLONS section, becaus
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NASSER HANNA culty of this task. Va
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LYMPHOMA AND PLASMA CELL DISORDERS
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NOWAKOWSKI AND CZUCZMAN sociated wi
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LYMPHOMA AND PLASMA CELL DISORDERS
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MANAGEMENT OF CLL Up-Front Manageme
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MANAGEMENT OF CLL than 17p-/TP53mut
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MANAGEMENT OF CLL could be associat
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MANAGEMENT OF CLL tion by nonmalign
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MANAGEMENT OF CLL lymphocytic leuke
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PROGNOSTIC FACTORS AND ADJUVANT RAD
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MERKEL CELL CARCINOMA Merkel Cell C
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MERKEL CELL CARCINOMA 32. Leonard J
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PERFUSION AND INFUSION IN THE ERA O
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NEOADJUVANT THERAPY OF MELANOMA Neo
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SULLIVAN ET AL FIGURE 1. Relevant S
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SULLIVAN ET AL Resistance to BRAF i
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SULLIVAN ET AL 17. Halait H, Demart
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SULLIVAN ET AL NRAS-mutant melanoma
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KLEPIN, RODIN, AND HURRIA Treating
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KLEPIN, RODIN, AND HURRIA plication
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KLEPIN, RODIN, AND HURRIA plan was
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KLEPIN, RODIN, AND HURRIA patient-s
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KLEPIN, RODIN, AND HURRIA 62. Blanc
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PERIPHERAL NEUROTOXICITY IN CANCER
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Page 768 and 769:
Page 770 and 771:
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PARTRIDGE, JACOBSEN, AND ANDERSEN C
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PARTRIDGE, JACOBSEN, AND ANDERSEN c
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PARTRIDGE, JACOBSEN, AND ANDERSEN w
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PARTRIDGE, JACOBSEN, AND ANDERSEN v
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LESLIE R. SCHOVER Sexual Healing in
Page 782 and 783:
LESLIE R. SCHOVER tinuous ADT in pr
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LESLIE R. SCHOVER 12. Potosky AL, H
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CATHERINE H. VAN POZNAK TABLE 1. Wo
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CATHERINE H. VAN POZNAK (tamoxifen,
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CATHERINE H. VAN POZNAK TABLE 3. FD
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CATHERINE H. VAN POZNAK premenopaus
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SHARI GOLDFARB KEY POINTS Brea
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SHARI GOLDFARB and friction with va
Page 798 and 799:
SHARI GOLDFARB importance both duri
Page 800 and 801:
PATIENT AND SURVIVOR CARE Moving Su
Page 802 and 803:
MAYER ET AL TABLE 1. Quality Metric
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MAYER ET AL to enhance the quality
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MAYER ET AL FIGURE 2. (A) Infertili
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MAYER ET AL efıcial suggests that
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PATIENT AND SURVIVOR CARE The Chall
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BRUERA AND PAICE Choice of Opioid a
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BRUERA AND PAICE toxicity and proce
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BRUERA AND PAICE effective. Basic s
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PEDIATRIC ONCOLOGY Real-Time Molecu
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CARROLL, RAETZ, AND MEYER KEY POINT
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CARROLL, RAETZ, AND MEYER most are
Page 824 and 825:
CARROLL, RAETZ, AND MEYER markers a
Page 826 and 827:
PEDIATRIC ONCOLOGY Translating Surv
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REDUCING THE BURDEN OF LATE EFFECTS
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Page 832 and 833:
Page 834 and 835:
Page 836 and 837:
PROFESSIONAL DEVELOPMENT The Challe
Page 838 and 839:
ADVANCES IN WEBSITE INFORMATION RES
Page 840 and 841:
Page 842 and 843:
Page 844 and 845:
Page 846 and 847:
COMMUNICATION AND TECHNOLOGY: IT’
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Page 850 and 851:
Page 852 and 853:
PATIENT-REPORTED OUTCOMES IN ONCOLO
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PATIENT-REPORTED OUTCOMES IN ONCOLO
Page 856 and 857:
PROFESSIONAL DEVELOPMENT Trends, An
Page 858 and 859:
CLINICAL ONCOLOGY PRACTICE 2015 FIG
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CLINICAL ONCOLOGY PRACTICE 2015 (6.
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CLINICAL ONCOLOGY PRACTICE 2015 Pro
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ADJUVANT/NEOADJUVANT MEDICAL THERAP
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Page 868 and 869:
Page 870 and 871:
INDICATIONS FOR ADJUVANT RADIATION
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Page 874 and 875:
Page 876 and 877:
Page 878 and 879:
SARCOMA Latest Advances in Systemic
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SYSTEMIC THERAPY FOR OSTEOSARCOMA A
Page 882 and 883:
SYSTEMIC THERAPY FOR OSTEOSARCOMA A
Page 884 and 885:
RETHINKING TREATMENT FOR CHONDROSAR
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Page 888 and 889:
Page 890 and 891:
Page 892 and 893:
BONE SARCOMAS IN ADULTS local disea
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BONE SARCOMAS IN ADULTS structure a
Page 896 and 897:
SARCOMA Well-Differentiated and Ded
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ABBAS MANJI ET AL ticular region. 7
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ABBAS MANJI ET AL MYXOID (ROUND CEL
Page 902 and 903:
ABBAS MANJI ET AL versus doxorubici
Page 904 and 905:
SHLUSH AND HERSHKOVITZ Clonal Evolu
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SHLUSH AND HERSHKOVITZ FIGURE 1. Ti
Page 908 and 909:
TUMOR BIOLOGY New Strategies to Und
Page 910 and 911:
KNAPP, DHAWAN, AND OSTRANDER in dog
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KNAPP, DHAWAN, AND OSTRANDER TABLE
Page 914 and 915:
KNAPP, DHAWAN, AND OSTRANDER 14. Fe
Page 916 and 917:
SOURBIER, SRINIVASAN, AND LINEHAN M
Page 918 and 919:
SOURBIER, SRINIVASAN, AND LINEHAN F
Page 920 and 921:
SOURBIER, SRINIVASAN, AND LINEHAN T
Page 922:
Author Index Abbas Manji, Gulam ...
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