1. Patterns of Care in Medical Oncology Neoadjuvant and Adjuvant Treatment of Rectal Cancer

2. To approximately how many patients with rectal cancer have you administered neoadjuvant chemoradiation therapy in the past year? Median168 In approximately what percent of these patients was an endorectal ultrasound performed? Average percent89%64% Clinical investigators Practicing oncologists

3. 5-FU + radiation therapy Source: NSABP-R-04 Protocol, November 24, 2008. Same as arm 1, with oxaliplatin 50 mg/m 2 weekly x 5 during RT* R Preoperative radiation therapy combined with capecitabine and oxaliplatin versus radiation therapy combined with 5-FU and oxaliplatin for patients with resectable rectal cancer Continuous infusion 5-FU 225 mg/m 2 per day for 5 days per week on days of planned radiation therapy (RT*) 5-FU + radiation therapy + oxaliplatin Protocol ID: NSABP-R-04, Target Accrual: 1,606 (Open) * 4,500 cGy in 25 fractions over five weeks with a 540-cGy boost in three fractions for nonfixed tumors or a 1,080-cGy boost in six fractions for fixed tumors

4. Capecitabine + radiation therapy Source: NSABP-R-04 Protocol, November 24, 2008. Same as arm 3, with oxaliplatin 50 mg/m 2 weekly x 5 during RT* R Preoperative radiation therapy combined with capecitabine and oxaliplatin versus radiation therapy combined with 5-FU and oxaliplatin for patients with resectable rectal cancer Capecitabine 825 mg/m 2 BID 5 days per week on days of planned RT* Capecitabine + radiation therapy + oxaliplatin Protocol ID: NSABP-R-04, Target Accrual: 1,606 (Open) * 4,500 cGy in 25 fractions over five weeks with a 540-cGy boost in three fractions for nonfixed tumors or a 1,080-cGy boost in six fractions for fixed tumors

5. When administering a fluoropyrimidine during radiation therapy, which regimen do you generally recommend? Continuous infusion 5-FU/LV 68%67% Capecitabine32%31% Bolus 5-FU/LV0%2% Clinical investigators Practicing oncologists

6. Patients who receive 5-FU/LV with radiation therapy for neoadjuvant treatment of rectal cancer and have positive nodes in the resection specimen postoperatively should generally receive which of the following regimens? FOLFOX 100%73% FOLFOX + biologic (bev or cetuximab) 0%13% 5-FU/LV 0%8% Capecitabine 0%5% FOLFIRI 0%1% Clinical investigators Practicing oncologists

7. Have you used oxaliplatin off protocol as part of neoadjuvant chemoradiation therapy for rectal cancer? % answering yes 48%22% For approximately how many patients have you used oxaliplatin off protocol as part of neoadjuvant chemoradiation therapy for rectal cancer? Median 133 Clinical investigators Practicing oncologists CI n = 12; PO n = 22

8. Have you used bevacizumab off protocol as part of neoadjuvant chemoradiation therapy for rectal cancer? % answering yes 0%7% For approximately how many patients have you used bevacizumab off protocol as part of neoadjuvant chemoradiation therapy for rectal cancer? Median 05 Clinical investigators Practicing oncologists CI n = 0; PO n = 7

9. For the patient with rectal cancer at the anal verge who achieves a clinical complete response with a negative biopsy of the primary site after neoadjuvant chemoradiation therapy, surveillance with delayed resection at recurrence is acceptable. Agree 4%29% In between 8%22% Disagree 88%29% I don’t know 0%20% Clinical investigators Practicing oncologists

10. Case 6: Rectal Cancer Clinical investigators Practicing oncologists Which of the following treatment strategies are you most likely to recommend for this patient? Chemoradiation therapy followed by resection + chemotherapy 76%58% Chemoradiation therapy followed by resection alone 8%14% Resection followed by adjuvant chemotherapy 8%2% Neoadj radiation therapy followed by resection and chemotherapy 4%10% Immediate resection 4%2% Resection followed by adjuvant chemoradiation therapy 0%8% Other 0%6% A 65-year-old man in average health T3N0 rectal cancer by endoscopic ultrasound Lesion is 8 centimeters from the anal verge

11. Case 7: Rectal Cancer Clinical investigators Practicing oncologists Which of the following treatment strategies are you most likely to recommend for this patient? Chemoradiation therapy followed by resection + chemotherapy 88%68% Radiation therapy followed by resection + chemotherapy 12%11% Resection followed by adjuvant chemoradiation therapy 0%5% Chemoradiation therapy followed by resection alone 0%5% Chemotherapy followed by resection + chemoradiation therapy 0%5% Other 0%6% A 65-year-old man in average health T3N1 rectal cancer (2 enlarged lymph nodes on endoscopic ultrasound) Lesion is 8 centimeters from the anal verge

12. Case 8: Rectal Cancer After Neoadjuvant Treatment and with Complete Pathologic Response Evident on Resection, Including Absence of Residual Nodal Disease Clinical investigators Practicing oncologists Which postoperative therapy are you most likely to recommend for this patient? FOLFOX 64%49% XELOX/CAPOX 24%19% 5-FU/LV (infusion or bolus) ± biologic 8%7% FOLFOX + bevacizumab 0%6% FLOX 0%6% Other systemic therapy 4%6% Observation / I would not recommend systemic therapy 0%7% Man in average health T3N1 rectal cancer (2 enlarged lymph nodes on endoscopic ultrasound) Lesion is 8 centimeters from the anal verge Undergoes neoadjuvant chemoradiation therapy with XELOX/CAPOX Complete pathologic response evident on resection