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Preoperative hyperfractionated chemoradiation of locally recurrent rectal cancer in patients previously irradiated on the pelvis: a multicentric phase I-II study
Proceedings of the 45th Annual ASTRO Meeting
2071
Preoperative Hyperfractionated Chemoradiation of Locally Recurrent Rectal Cancer in Patients Previously Irradiated on the Pelvis: A Multicentric Phase I-II Study
M. Gambacorta,1 V. Valentini,1 M. Mohiuddin,5 A. Morganti,1 G. Doglietto,1 C. Coco,1 A. De Paoli,2 C. Rossi,2 A. Di Russo,3 F. Valvo,3 G. Bolzicco,4 M. Della Palma4 1 Radiotherapy, Universita’ Cattolica del Sacro Cuore, Rome, Italy, 2Radiotherapy, Centro di Riferimento Oncologico, Aviano Italy, 3Radiotherapy, Istituto Nazionale Tumori, Milano, Italy, 4Radiotherapy, Azienda Ospedaliera ULSS6, Vicenza, Italy, 5Radiotherapy, University of Kentucky Medical Center, Lexington, KY Purpose/Objective: Aim of this multicentric phase I-II Italian study is to evaluate the response rate, resectability and treatment-related toxicity of a treatment protocol based on preoperative hyperfractionated chemoradiation, in patients with local recurrent rectal carcinoma previously irradiated on the pelvis. Materials/Methods: Eligibility criteria included: histologically proven LR of rectal carcinoma, no extrapelvic disease, no bony involvement, previous pelvic irradiation; age ⬎18 years; PS ⬎60; written informed consent. Radiotherapy was delivered to the GTV plus a 4 cm margin (PTV2), with a dose of 30 Gy (1.2 Gy bid). A boost of 10.8 Gy was delivered to the GTV plus a 2-cm margin (PTV1). Concurrent c.i. of 5FU (225 mg/sm/day) was delivered during radiation. 4-6 weeks after the end of chemoradiation, patients were re-evaluated for tumor resectability, and, when feasible, surgical resection of recurrence was performed 6-8 weeks from the end of chemoradiation. Adjuvant chemotherapy was prescribed to all patients, using raltitrexed, 3 mg/sm, for a total of 5 cycles. Pts were staged using the F-classification F0: anastomotic relapse; F1, F2 and F3: 1, 2 and more than 2 side walls involved, respectively. Toxicity was evaluated based on the RTOG criteria. Results: 57 pts (M/F: 36/21; median age: 61 yrs) where enrolled in the study, by 12 different italian radiotherapy departments. Previous radiotherapy dosage ranged between 30 and 55 Gy (median: 50.4 Gy); 42 pts (73.7%) had previously received some form of chemotherapy. 49 pts (86.0%) completed chemoradiation without interruptions. Due to toxicity or patients’ compliance, 6 pts (10.5%) had temporary treatment interruption and 2 patients (3.5%) had definitive interruption. Grade 3 acutetoxicity was intestinal (5.3%). After chemoradiation, 2 pts (3.5%) showed PD, 30 pts (52.6%) had NC, 20 pts (35.1%) had PR and 5 pts (8.8%) had CR. Overall, the response rate (PR⫹CR) was 43.9% (CI: 28.6%-59.0%). 18 out of 22 pts (81.8%) with pelvic pain at diagnosis had symptomatic response. Tumor resection was performed in 36/57 pts (63.2%). Surgical resection resulted as R0, R1 and R2 in 21 pts (58.4%), 3 pts (8.3%) and 12 pts (33.3%), respectively. Twenty-two pts where excluded from adjuvant chemotherapy, due to intercurrent disease, disease progression, patient refusal or prolonged delay due to surgical complications. Thirty-five patients received adjuvant chemotherapy that was completed in 30 (52.6%). During the follow-up (median: 34 months, range: 6-66) 26 pts (45.6%) developed LR or tumor progression, 10 pts (17.5%) developed distant metastasis and 16 pts (28.1%) showed pelvic pain. Seven pts showed late toxicity: 2 skin fibrosis, 2 impotence, 2 urinary complications requiring nephrostomy, and 1 small bowel fistula requiring surgical diversion. Median actuarial OS and DFS were 23 months and 17 months, respectively. 3 year overall survival was 40.3%. Median OS in patients with radical resection was not reached and in patients without radical resection was 18 months (p⫽0.017). Median DFS in patients with radical resection was 27 months and in patients without radical resection was 12 months (p⫽0.005). Conclusions: Use of hyperfractionated chemoradiation was associated with a low rate of acute toxicity and an acceptable incidence of late complications (5.3%). Pain control was excellent (81.8%). An interesting response rate (43.9%) and downstaging rate (37.8%) were observed. However, due to the significant correlation between radical tumor resection and to the relatively high local failure rate (45.6%) further studies are necessary to improve the local tumor response and control.
2072
Adjuvant External Beam Radiotherapy with Concurrent Chemotherapy Following Resection of Primary Gallbladder Carcinoma: A 23-Year Experience
B. Czito,1 R. Clough,1 D. Tyler,3 H. Hurwitz,2 C. Lee,1 B. Clary,3 M. Morse,2 J. Blobe,2 T. Pappas3 Radiation Oncology, Duke University, Durham, NC, 2Medical Oncology, Duke University, Durham, NC, 3Surgery, Duke University, Durham, NC 1
Purpose/Objective: Carcinoma of the gallbladder is a relatively uncommon malignancy that has been reported to have a poor prognosis. Most pts present with advanced disease. In the minority who are resectable, there is a high incidence of local-regional
S385
2071
Preoperative Hyperfractionated Chemoradiation of Locally Recurrent Rectal Cancer in Patients Previously Irradiated on the Pelvis: A Multicentric Phase I-II Study
M. Gambacorta,1 V. Valentini,1 M. Mohiuddin,5 A. Morganti,1 G. Doglietto,1 C. Coco,1 A. De Paoli,2 C. Rossi,2 A. Di Russo,3 F. Valvo,3 G. Bolzicco,4 M. Della Palma4 1 Radiotherapy, Universita’ Cattolica del Sacro Cuore, Rome, Italy, 2Radiotherapy, Centro di Riferimento Oncologico, Aviano Italy, 3Radiotherapy, Istituto Nazionale Tumori, Milano, Italy, 4Radiotherapy, Azienda Ospedaliera ULSS6, Vicenza, Italy, 5Radiotherapy, University of Kentucky Medical Center, Lexington, KY Purpose/Objective: Aim of this multicentric phase I-II Italian study is to evaluate the response rate, resectability and treatment-related toxicity of a treatment protocol based on preoperative hyperfractionated chemoradiation, in patients with local recurrent rectal carcinoma previously irradiated on the pelvis. Materials/Methods: Eligibility criteria included: histologically proven LR of rectal carcinoma, no extrapelvic disease, no bony involvement, previous pelvic irradiation; age ⬎18 years; PS ⬎60; written informed consent. Radiotherapy was delivered to the GTV plus a 4 cm margin (PTV2), with a dose of 30 Gy (1.2 Gy bid). A boost of 10.8 Gy was delivered to the GTV plus a 2-cm margin (PTV1). Concurrent c.i. of 5FU (225 mg/sm/day) was delivered during radiation. 4-6 weeks after the end of chemoradiation, patients were re-evaluated for tumor resectability, and, when feasible, surgical resection of recurrence was performed 6-8 weeks from the end of chemoradiation. Adjuvant chemotherapy was prescribed to all patients, using raltitrexed, 3 mg/sm, for a total of 5 cycles. Pts were staged using the F-classification F0: anastomotic relapse; F1, F2 and F3: 1, 2 and more than 2 side walls involved, respectively. Toxicity was evaluated based on the RTOG criteria. Results: 57 pts (M/F: 36/21; median age: 61 yrs) where enrolled in the study, by 12 different italian radiotherapy departments. Previous radiotherapy dosage ranged between 30 and 55 Gy (median: 50.4 Gy); 42 pts (73.7%) had previously received some form of chemotherapy. 49 pts (86.0%) completed chemoradiation without interruptions. Due to toxicity or patients’ compliance, 6 pts (10.5%) had temporary treatment interruption and 2 patients (3.5%) had definitive interruption. Grade 3 acutetoxicity was intestinal (5.3%). After chemoradiation, 2 pts (3.5%) showed PD, 30 pts (52.6%) had NC, 20 pts (35.1%) had PR and 5 pts (8.8%) had CR. Overall, the response rate (PR⫹CR) was 43.9% (CI: 28.6%-59.0%). 18 out of 22 pts (81.8%) with pelvic pain at diagnosis had symptomatic response. Tumor resection was performed in 36/57 pts (63.2%). Surgical resection resulted as R0, R1 and R2 in 21 pts (58.4%), 3 pts (8.3%) and 12 pts (33.3%), respectively. Twenty-two pts where excluded from adjuvant chemotherapy, due to intercurrent disease, disease progression, patient refusal or prolonged delay due to surgical complications. Thirty-five patients received adjuvant chemotherapy that was completed in 30 (52.6%). During the follow-up (median: 34 months, range: 6-66) 26 pts (45.6%) developed LR or tumor progression, 10 pts (17.5%) developed distant metastasis and 16 pts (28.1%) showed pelvic pain. Seven pts showed late toxicity: 2 skin fibrosis, 2 impotence, 2 urinary complications requiring nephrostomy, and 1 small bowel fistula requiring surgical diversion. Median actuarial OS and DFS were 23 months and 17 months, respectively. 3 year overall survival was 40.3%. Median OS in patients with radical resection was not reached and in patients without radical resection was 18 months (p⫽0.017). Median DFS in patients with radical resection was 27 months and in patients without radical resection was 12 months (p⫽0.005). Conclusions: Use of hyperfractionated chemoradiation was associated with a low rate of acute toxicity and an acceptable incidence of late complications (5.3%). Pain control was excellent (81.8%). An interesting response rate (43.9%) and downstaging rate (37.8%) were observed. However, due to the significant correlation between radical tumor resection and to the relatively high local failure rate (45.6%) further studies are necessary to improve the local tumor response and control.
2072
Adjuvant External Beam Radiotherapy with Concurrent Chemotherapy Following Resection of Primary Gallbladder Carcinoma: A 23-Year Experience
B. Czito,1 R. Clough,1 D. Tyler,3 H. Hurwitz,2 C. Lee,1 B. Clary,3 M. Morse,2 J. Blobe,2 T. Pappas3 Radiation Oncology, Duke University, Durham, NC, 2Medical Oncology, Duke University, Durham, NC, 3Surgery, Duke University, Durham, NC 1
Purpose/Objective: Carcinoma of the gallbladder is a relatively uncommon malignancy that has been reported to have a poor prognosis. Most pts present with advanced disease. In the minority who are resectable, there is a high incidence of local-regional
S385