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Patient and Clinician Reported Acute Toxicity During Preoperative Chemoradiation for Locally Advanced Rectal Cancer
S126
International Journal of Radiation Oncology Biology Physics
287
toxicity graded according to the CTCAE v3.0, was collected. Weekly PROs using a 7 or 14-item questionnaire based on the Bowel Problems Scale, and NCI PRO-CTCAE were also collected for 150 patients treated with IMRT from 2009e2014. Symptom frequency, severity and interference with daily activities were reported on a 5-point Likert-type scale between 1-“not at all” and 5-“very frequently” A clinically meaningful PRO score was defined as 3. Fisher exact test was used to test for statistical differences. Results: The median age was 56 years (range, 22e93) and 202 (60%) patients were male. The majority of patients had clinical stage T3 (79%) and N+ (79%) disease. Of the 335 patients, 229 (68%) were treated with IMRT and 106 (32%) with 3DCRT. All patients received concurrent 5-FUbased chemotherapy with no significant difference in the median RT dose between the two cohorts. Significantly fewer patients experienced grade 2 diarrhea in the IMRT group compared to the 3DCRT group (11% vs 22%, P Z .02). While no grade 3 cystitis or proctitis occurred in either groups, fewer patients experienced grade 2 cystitis in the IMRT group (5% vs 12% 3DCRT, P Z .02), and there was a trend towards decreased grade 2 proctitis in the IMRT group (19% vs 28% 3DCRT, P Z .06). Of the 150 IMRT patients who completed PROs, a high proportion reported PRO scores 3 for diarrhea (65%) and urgency (73%). About half of the patients experienced rectal pain (53%) and tenesmus (49%), with fewer complaining of abdominal cramping (42%), rectal bleeding (34%) and loss of bowel control (30%). Conclusion: In this large cohort of patients undergoing preoperative chemoradiation for locally advanced rectal cancer, compared to the use of 3DCRT, the use of IMRT significantly reduced lower gastrointestinal and genitourinary toxicity during treatment as measured by clinicians. Patient reported outcomes show that lower gastrointestinal toxicity is experienced frequently amongst patients treated with IMRT. Further studies are needed to determine the best method to assess the impact of IMRT on treatment related toxicities. Author Disclosure: S.Y. Ng: None. L. Cambridge: None. C. Hajj: None. T. Yang: None. A.J. Wu: None. K.A. Goodman: None.
Pathological Response Is a Marker But Not a Cause of Good Prognosis in Rectal Cancer: 15-year Follow-up of the Lyon R90-01 Randomized Trial J.P. Gerard,1 E. Cotte,2 E. Decullier,3 J. Doyen,1 J.M. Hannoun-Levi,4 and O. Chapet5; 1Centre Antoine Lacassagne, Nice, France, 2CHU Lyon Sud, Lyon, France, 3Hospice Civil de Lyon e POLE IMER, Lyon, France, 4 Antoine Lacassagne Cancer Center, Nice, France, 5Centre Hospitalier Lyon Sud, Lyon, France Purpose/Objective(s): In the 1990s, this Lyon trial investigated the influence of interval between preoperative radiation therapy (RT) and surgery. The main endpoint was sphincter-saving surgery. We reported the results after 15 years of follow-up. Materials/Methods: From 1991e1995, 210 patients (median age: 65 y) were randomly assigned to preoperative RT (39 Gy/13 fr./17 days) with short (SI) (2 weeks) or long interval (LI)(7 weeks) before surgery. No chemotherapy was given (either concomitant or adjuvant). Out of 176 pts staged with endorectal ultrasound T2: 48 and T3e4: 124. Results: The two groups were comparable at baseline (1). There was no significant difference in sphincter-saving surgery because the rate of cCR was low: 4% (no significant difference between both groups). Main results at 15-year median follow-up are shown in table. Most local recurrences occurred before 5 years (12%). The overall survival and local recurrence rate was identical in both groups. At 15 years, the rate of second new cancer was 9.4% with no difference between both groups. Conclusion: Despite increased pathological response with longer interval even at 15-year follow-up there is no impact of LI on local recurrence or overall survival. ypCR is a marker of good prognosis but not the cause of it, and long interval is only migrating stages as in the Will Rogers phenomenon (2). Secondary malignancies induced by radiation therapy are not counterbalancing its benefit. The main benefit of long interval when using neoadjuvant chemoradiation therapy is to increase cCR (3) in order to increase either sphincter saving surgery or organ preservation. Oral Scientific Abstracts 287; Table 1 ypCR + few N cCR ypCR residual cells Sph. saving Loc Rec 15y OS 15y Short Int 99 2 Long Int 102 6 P NS
7 14 0.16
10 26 0.005
68% 75% NS
12% 14% NS
40% 42% NS
Author Disclosure: J. Gerard: None. E. Cotte: None. E. Decullier: None. J. Doyen: None. J. Hannoun-Levi: None. O. Chapet: None.
288 Patient and Clinician Reported Acute Toxicity During Preoperative Chemoradiation for Locally Advanced Rectal Cancer S.Y. Ng, L. Cambridge, C. Hajj, T.J. Yang, A.J. Wu, and K.A. Goodman; Memorial Sloan Kettering Cancer Center, New York, NY Purpose/Objective(s): Preoperative pelvic radiation therapy (RT) with concurrent 5-Fluorouracil (FU)-based chemotherapy is the standard of care for patients with locally advanced rectal cancer. Pelvic RT is associated with significant acute toxicities that can adversely impact a patient’s quality of life. As opposed to 3D conformal RT (3DCRT), intensity modulated RT (IMRT) allows for more focal dose delivery, thus sparing normal tissues. We compared clinician reported acute toxicity profiles between patients treated with IMRT and 3DCRT and described patient reported outcomes (PROs) for IMRT patients. Materials/Methods: We retrospectively reviewed records of 335 consecutive rectal cancer patients treated with preoperative pelvic RT at our institution from 2007e2014. Clinical information, including weekly acute
289 Phase 2 Trial of Preoperative Radiation With Concurrent Capecitabine, Oxaliplatin, and Bevacizumab Followed by Surgery and Postoperative 5-FU, Leucovorin, Oxaliplatin (FOLFOX), and Bevacizumab in Patients With Locally Advanced Rectal Cancer: ECOG 3204 R.S. Prabhu,1 Y. Feng,2 J.C. Landry,3 S.J. Cohen,4 C.A. Staley,5 R. Whittington,6 E.R. Sigurdson,4 H. Nimeiri,7 U. Verma,8 and A.B. Benson7; 1Southeast Radiation Oncology Group, Levine Cancer Institute, Charlotte, NC, 2Dana-Farber Cancer Institute, Boston, MA, 3 Emory University, Winship Cancer Institute, Atlanta, GA, 4Fox Chase Cancer Center, Philadelphia, PA, 5Winship Cancer Institute, Atlanta, GA, 6 VA New Jersey Health Care System, East Orange, NJ, 7Northwestern University, Chicago, IL, 8University of Texas Southwestern Medical Center, Dallas, TX Purpose/Objective(s): As previously reported, the neoadjuvant regimen of capecitabine, oxaliplatin, and bevacizumab with radiation therapy (RT) for locally advanced rectal cancer resulted in a pathologic complete response (path CR) rate of 17%, which did not meet prespecified criteria of significant improvement; however, the effect of the intensified adjuvant regimen of 5-FU, leucovorin, oxaliplatin (FOLFOX) and bevacizumab is not reflected in path CR rate. The purpose of this report was to describe the 5-year oncologic outcomes of this regimen. Materials/Methods: Fifty-seven patients (pts) with resectable T3/T4 rectal adenocarcinoma were enrolled onto ECOG trial E3204 from 2006 to 2010. Preoperative treatment: capecitabine (825 mg/m2 BID M-F), oxaliplatin (50 mg/m2 weekly), bevacizumab (5 mg/kg D1, 15, 29), and RT (50.4 Gy). Surgery was performed by 8 weeks after RT. Beginning 8 e 12 weeks after surgery, patients received FOLFOX plus bevacizumab (5 mg/kg) Q2 weeks for 12 cycles (oxaliplatin stopped after 9 cycles). Recurrence-free survival
International Journal of Radiation Oncology Biology Physics
287
toxicity graded according to the CTCAE v3.0, was collected. Weekly PROs using a 7 or 14-item questionnaire based on the Bowel Problems Scale, and NCI PRO-CTCAE were also collected for 150 patients treated with IMRT from 2009e2014. Symptom frequency, severity and interference with daily activities were reported on a 5-point Likert-type scale between 1-“not at all” and 5-“very frequently” A clinically meaningful PRO score was defined as 3. Fisher exact test was used to test for statistical differences. Results: The median age was 56 years (range, 22e93) and 202 (60%) patients were male. The majority of patients had clinical stage T3 (79%) and N+ (79%) disease. Of the 335 patients, 229 (68%) were treated with IMRT and 106 (32%) with 3DCRT. All patients received concurrent 5-FUbased chemotherapy with no significant difference in the median RT dose between the two cohorts. Significantly fewer patients experienced grade 2 diarrhea in the IMRT group compared to the 3DCRT group (11% vs 22%, P Z .02). While no grade 3 cystitis or proctitis occurred in either groups, fewer patients experienced grade 2 cystitis in the IMRT group (5% vs 12% 3DCRT, P Z .02), and there was a trend towards decreased grade 2 proctitis in the IMRT group (19% vs 28% 3DCRT, P Z .06). Of the 150 IMRT patients who completed PROs, a high proportion reported PRO scores 3 for diarrhea (65%) and urgency (73%). About half of the patients experienced rectal pain (53%) and tenesmus (49%), with fewer complaining of abdominal cramping (42%), rectal bleeding (34%) and loss of bowel control (30%). Conclusion: In this large cohort of patients undergoing preoperative chemoradiation for locally advanced rectal cancer, compared to the use of 3DCRT, the use of IMRT significantly reduced lower gastrointestinal and genitourinary toxicity during treatment as measured by clinicians. Patient reported outcomes show that lower gastrointestinal toxicity is experienced frequently amongst patients treated with IMRT. Further studies are needed to determine the best method to assess the impact of IMRT on treatment related toxicities. Author Disclosure: S.Y. Ng: None. L. Cambridge: None. C. Hajj: None. T. Yang: None. A.J. Wu: None. K.A. Goodman: None.
Pathological Response Is a Marker But Not a Cause of Good Prognosis in Rectal Cancer: 15-year Follow-up of the Lyon R90-01 Randomized Trial J.P. Gerard,1 E. Cotte,2 E. Decullier,3 J. Doyen,1 J.M. Hannoun-Levi,4 and O. Chapet5; 1Centre Antoine Lacassagne, Nice, France, 2CHU Lyon Sud, Lyon, France, 3Hospice Civil de Lyon e POLE IMER, Lyon, France, 4 Antoine Lacassagne Cancer Center, Nice, France, 5Centre Hospitalier Lyon Sud, Lyon, France Purpose/Objective(s): In the 1990s, this Lyon trial investigated the influence of interval between preoperative radiation therapy (RT) and surgery. The main endpoint was sphincter-saving surgery. We reported the results after 15 years of follow-up. Materials/Methods: From 1991e1995, 210 patients (median age: 65 y) were randomly assigned to preoperative RT (39 Gy/13 fr./17 days) with short (SI) (2 weeks) or long interval (LI)(7 weeks) before surgery. No chemotherapy was given (either concomitant or adjuvant). Out of 176 pts staged with endorectal ultrasound T2: 48 and T3e4: 124. Results: The two groups were comparable at baseline (1). There was no significant difference in sphincter-saving surgery because the rate of cCR was low: 4% (no significant difference between both groups). Main results at 15-year median follow-up are shown in table. Most local recurrences occurred before 5 years (12%). The overall survival and local recurrence rate was identical in both groups. At 15 years, the rate of second new cancer was 9.4% with no difference between both groups. Conclusion: Despite increased pathological response with longer interval even at 15-year follow-up there is no impact of LI on local recurrence or overall survival. ypCR is a marker of good prognosis but not the cause of it, and long interval is only migrating stages as in the Will Rogers phenomenon (2). Secondary malignancies induced by radiation therapy are not counterbalancing its benefit. The main benefit of long interval when using neoadjuvant chemoradiation therapy is to increase cCR (3) in order to increase either sphincter saving surgery or organ preservation. Oral Scientific Abstracts 287; Table 1 ypCR + few N cCR ypCR residual cells Sph. saving Loc Rec 15y OS 15y Short Int 99 2 Long Int 102 6 P NS
7 14 0.16
10 26 0.005
68% 75% NS
12% 14% NS
40% 42% NS
Author Disclosure: J. Gerard: None. E. Cotte: None. E. Decullier: None. J. Doyen: None. J. Hannoun-Levi: None. O. Chapet: None.
288 Patient and Clinician Reported Acute Toxicity During Preoperative Chemoradiation for Locally Advanced Rectal Cancer S.Y. Ng, L. Cambridge, C. Hajj, T.J. Yang, A.J. Wu, and K.A. Goodman; Memorial Sloan Kettering Cancer Center, New York, NY Purpose/Objective(s): Preoperative pelvic radiation therapy (RT) with concurrent 5-Fluorouracil (FU)-based chemotherapy is the standard of care for patients with locally advanced rectal cancer. Pelvic RT is associated with significant acute toxicities that can adversely impact a patient’s quality of life. As opposed to 3D conformal RT (3DCRT), intensity modulated RT (IMRT) allows for more focal dose delivery, thus sparing normal tissues. We compared clinician reported acute toxicity profiles between patients treated with IMRT and 3DCRT and described patient reported outcomes (PROs) for IMRT patients. Materials/Methods: We retrospectively reviewed records of 335 consecutive rectal cancer patients treated with preoperative pelvic RT at our institution from 2007e2014. Clinical information, including weekly acute
289 Phase 2 Trial of Preoperative Radiation With Concurrent Capecitabine, Oxaliplatin, and Bevacizumab Followed by Surgery and Postoperative 5-FU, Leucovorin, Oxaliplatin (FOLFOX), and Bevacizumab in Patients With Locally Advanced Rectal Cancer: ECOG 3204 R.S. Prabhu,1 Y. Feng,2 J.C. Landry,3 S.J. Cohen,4 C.A. Staley,5 R. Whittington,6 E.R. Sigurdson,4 H. Nimeiri,7 U. Verma,8 and A.B. Benson7; 1Southeast Radiation Oncology Group, Levine Cancer Institute, Charlotte, NC, 2Dana-Farber Cancer Institute, Boston, MA, 3 Emory University, Winship Cancer Institute, Atlanta, GA, 4Fox Chase Cancer Center, Philadelphia, PA, 5Winship Cancer Institute, Atlanta, GA, 6 VA New Jersey Health Care System, East Orange, NJ, 7Northwestern University, Chicago, IL, 8University of Texas Southwestern Medical Center, Dallas, TX Purpose/Objective(s): As previously reported, the neoadjuvant regimen of capecitabine, oxaliplatin, and bevacizumab with radiation therapy (RT) for locally advanced rectal cancer resulted in a pathologic complete response (path CR) rate of 17%, which did not meet prespecified criteria of significant improvement; however, the effect of the intensified adjuvant regimen of 5-FU, leucovorin, oxaliplatin (FOLFOX) and bevacizumab is not reflected in path CR rate. The purpose of this report was to describe the 5-year oncologic outcomes of this regimen. Materials/Methods: Fifty-seven patients (pts) with resectable T3/T4 rectal adenocarcinoma were enrolled onto ECOG trial E3204 from 2006 to 2010. Preoperative treatment: capecitabine (825 mg/m2 BID M-F), oxaliplatin (50 mg/m2 weekly), bevacizumab (5 mg/kg D1, 15, 29), and RT (50.4 Gy). Surgery was performed by 8 weeks after RT. Beginning 8 e 12 weeks after surgery, patients received FOLFOX plus bevacizumab (5 mg/kg) Q2 weeks for 12 cycles (oxaliplatin stopped after 9 cycles). Recurrence-free survival