1. Addition of Chemotherapy to Preoperative Radiotherapy Improves Outcomes in Rectal Cancer Slideset on: Bosset JF, Calais G, Mineur L, et al. Enhanced tumorocidal effect of chemotherapy with preoperative radiotherapy for rectal cancer: preliminary results--EORTC 22921. J Clin Oncol. 2005;23:5620-5627.

2. clinicaloptions.com/onco Oncology Journal Options Bosset JF, et al. J Clin Oncol. 2005;23:5620-5627. Background and Rationale  Chemotherapy (CT) and radiotherapy (RT) both beneficial for patients with rectal cancer –In the United States, postoperative chemoradiotherapy (RT-CT) accepted as standard treatment of stage II and III disease –European studies show benefit with preoperative RT alone  Current report examines effect of RT on tumor pathology at surgery both with and without addition of preoperative fluorouracil/leucovorin (FU/LV)

3. clinicaloptions.com/onco Oncology Journal Options Bosset JF, et al. J Clin Oncol. 2005;23:5620-5627. Baseline Characteristics CharacteristicRT Group (n = 505)RT-CT Group (n = 506) Male, n (%)368 (72.9)371 (73.3) Median age, yrs (range)63.3 (23.3-79.4)62.9 (22.0-79.6) Tumor distance from anal margin, n (%)  0-5 cm  6-10 cm  > 10 cm 246 (48.7) 215 (42.6) 41 (8.1) 250 (49.4) 227 (44.9) 26 (5.1) Tumor stage, n (%)  T3  T4 452 (89.5) 51 (10.1) 453 (89.5) 50 (9.9) Histologic type, n (%)  Adenocarcinoma  Mucinous 499 (98.8) 3 (0.6) 496 (98.0) 6 (1.2) Differentiation, n (%)  Well differentiated  Moderately differentiated 186 (36.8) 185 (36.6) 188 (37.2) 201 (39.7)

4. clinicaloptions.com/onco Oncology Journal Options Bosset JF, et al. J Clin Oncol. 2005;23:5620-5627. Summary of Study Design Patients with T3 or resectable T4 M0 rectal cancer (N = 1011) Preoperative RT-CT 45 Gy total with Leucovorin (20 mg/m 2 /day) plus Fluorouracil (350 mg/m 2 /day) in 5-day courses on Weeks 1, 5 (n = 506) Preoperative RT 45 Gy total (n = 505) Surgery* 3-10 wks after preoperative treatments Week 5 *Anterior resection or abdominoperineal resection. Week 1

5. clinicaloptions.com/onco Oncology Journal Options Bosset JF, et al. J Clin Oncol. 2005;23:5620-5627. Main Findings ParameterRT Group (n = 476)RT-CT Group (n = 473)P Value Median tumor size, mm (range) 30.0 (10.0-70.0)25.0 (8.0-110.0)<.0001 Tumor stage, n (%)  T0  T1  T2  T3  T4 25 (5.3) 36 (7.6) 141 (29.6) 233 (48.9) 25 (5.3) 65 (13.7) 49 (10.4) 156 (33.0) 175 (37.0) 18 (3.8) <.001 Lymph nodes examined, mean n (range)9 (0.0-45.0)7 (0.0-39.0).046 Lymph node involvement, n (%)  N0  N1  N2 288 (60.5) 108 (22.7) 57 (12.0) 340 (71.9) 84 (17.8) 34 (7.2) <.001 Tumor type, n (%)  Adenocarcinoma  Mucinous  Other (including signet ring type) 415 (87.2) 18 (3.8) 27 (5.7) 372 (78.6) 36 (7.6) 57 (12.1) <.001 Microinvasion, n (%)  Lymphatic  Venous  Perineural 83 (17.4) 66 (13.9) 68 (14.3) 54 (11.4) 43 (9.1) 36 (7.6).008.001

6. clinicaloptions.com/onco Oncology Journal Options Bosset JF, et al. J Clin Oncol. 2005;23:5620-5627. Key Conclusions  Preoperative RT-CT associated with more favorable pathologic staging and tumor differentiation at time of surgery compared with RT alone –Smaller, more mucinous tumors –Less advanced tumor (pT) and nodal (pN) substaging –Fewer recoverable lymph nodes –Decreased perineural, venous, and lymphatic invasion  Further clinicopathologic correlation required