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IMRT vs. 3D Conformal Neoadjuvant Chemoradiation for Resectable and Borderline Resectable Pancreatic Cancer
I. J. Radiation Oncology d Biology d Physics
S320
Volume 78, Number 3, Supplement, 2010
Results: Twenty-nine patients with ASCC who underwent C-IMRT were identified. The median age was 48 years (range: 3278) and 16 (55%) were male. Eleven patients (38%) were HIV positive. Stage breakdown is as follows: stage I, 31%; stage II, 14%; stage III, 48%; and stage IV, 7%. All patients received concurrent chemotherapy; 19 patients (66%) received mitomycin-c based chemotherapy, 8 patients (28%) received cisplatin based chemotherapy, and 2 patients (7%) received 5-fluorouracil alone. The median RT dose was 5400 cGy in 30 fractions (range: 432-6120 cGy; 2-34 fractions). The maximum lower GI, skin, and hematologic toxicity scores during C-IMRT were a median of 2, 2, and 3, respectively. Grade 4 skin toxicity was observed in one patient and grade 4 hematologic toxicity was observed in two patients. One grade 5 hematologic toxicity occurred following two fractions of mitomycin-c based C-IMRT. When compared to simultaneously integrated boost, use of sequential boost IMRT was significantly associated with higher grade skin toxicity (p = 0.04). HIV positive status was significantly associated with higher hematologic toxicity (p = 0.01). Other factors examined, including BMI, radiation dose, type of chemotherapy, weight loss during treatment, and presence of previous tumor-directed therapy did not correlate with observed toxicities. At median follow-up of 17 months, 2-year LC, CFS, and OS rates for patients treated with curative intent were 90%, 96%, and 80%, respectively. Conclusions: C-IMRT yields acceptable toxicity rates for treatment of ASCC. Use of sequential boost IMRT was associated with higher grade skin toxicity compared to integrated boost IMRT. HIV positive patients have worse hematologic toxicity but equivalent skin and lower GI toxicity. LC, CFS, and OS compare favorably to conventional treatment but further follow-up is needed. Author Disclosure: B.M. Prendergast, None; M.C. Dobelbower, None; S.A. Spencer, None; J.J. Caudell, None; K.S. Keene, None; T. Wood, None; J. Posey, None; R. Jacob, None.
2261
IMRT vs. 3D Conformal Neoadjuvant Chemoradiation for Resectable and Borderline Resectable Pancreatic Cancer
C. Wood, T. Kelly, D. Prah, P. Ritch, D. Evans, B. Erickson Medical College of Wisconsin, Milwaukee, WI Purpose/Objective(s): Neoadjuvant chemoradiation (N-CRT) for pancreatic cancer (PC) has emerged as a new strategy to downstage nodal disease, enable margin-negative resections, and increase the number of patients who receive trimodality therapy. Criticisms of this approach include fear of toxicity preventing definitive surgery and increased surgical complications. Efforts to minimize toxicity in the setting of potent radiation sensitizing drugs have included smaller, 3D conformal radiation fields (3D) and use of intensity modulated radiation therapy (IMRT) to further spare abdominal organs. Criticisms of IMRT include irradiation of large volumes of the upper abdomen to low doses (V5-V15) and small volumes to higher maximum doses. Materials/Methods: From March 2009 through December 2009, 20 patients with resectable/borderline resectable PC received N-CRT as part of their treatment course. IMRT plans were generated for treatment for all patients and 3D-conformal plans were generated retrospectively for dosimetric comparison. The PTV included the pancreatic head/body and any enlarged lymph nodes with a 1-2 cm margin. The PTV was treated to 5040 cGy using daily IGRT with concurrent weekly gemcitabine. The following were compared for IMRT vs. 3D: V5-V15 for small bowel; V15 and V20 for kidneys; V30 and mean dose for liver, and maximum doses in the stomach and duodenum. Acute toxicity (CTC v 2.0) during N-CRT, surgical feasibility, timing, and outcomes were assessed. Results: N-CRT was well tolerated. All patients received a median of 5040 cGy. Mean weight loss was 3 lbs. Three patients required a treatment break and 5 patients were hospitalized. Complications included 4 grade 3 GI (3 dehydration, 1 duodenitis), 3 grade 3 hematologic (requiring transfusions), 1 grade 4 hematologic (febrile neutropenia), and 1 grade 4 GI (anorexia) complication. No patient had diarrhea. V5, V10, V15 for small bowel were 78%, 62%, 46% for IMRT vs. 73%, 66%, and 61% for 3D. V15 and V20 for the right kidney were 16% and 8% for IMRT vs. 43% and 37% for 3D. V15 and V20 for the left kidney were 8% and 2% for IMRT vs. 12% and 8% for 3D. Mean dose and V30 for liver were 1005 cGy and 5.6% for IMRT vs. 1020 cGy and 8% for 3D. Average max dose to the duodenum and stomach was 5270 cGy and 4508 cGy for IMRT vs. 5240 cGy and 4704 cGy for 3D respectively. Nineteen patients had surgery within a mean of 43 days, of which 16 patients had resection, and 3 had metastases. All 16 had negative surgical margins. The mean hospital stay was 10 days. One perioperative death occurred. Conclusions: IMRT-based N-CRT is both feasible and efficacious with the majority of patients able to go on to definitive surgical resection with negative margins. Minimization of normal organ irradiation can be achieved with IMRT and contributes to the successful delivery of preoperative therapy. Author Disclosure: C. Wood, None; T. Kelly, None; D. Prah, None; P. Ritch, None; D. Evans, None; B. Erickson, None.
2262
Radiation Dose $54 Gy is Associated with Improved Survival for Unresectable Pancreatic Cancer
D. W. Golden1, C. J. Novak2, B. Minsky1, S. L. Liauw1 1
University of Chicago Medical Center, Chicago, IL, 2University of Illinois at Chicago College of Medicine, Chicago, IL
Purpose/Objective(s): To investigate a single institution experience using chemoradiation (CRT) as definitive treatment for unresectable pancreatic adenocarcinoma (UPA) and to analyze patient and treatment related factors in relation to overall survival (OS), local failure (LF), and distant failure (DF). Materials/Methods: From 1997-2009 46 patients were treated with CRT for nonmetastatic UPA. Median prescribed RT dose was 54 Gy (range, 50.4-59.4). RT volumes encompassed the pancreatic bed plus draining lymphatics. 30/46 (65%) were treated with IMRT. Two patients received neoadjuvant chemotherapy, all patients received concurrent chemotherapy (41 5FU, 5 other), and 24 patients received adjuvant chemotherapy (20 gemcitabine, 4 other). Kaplan-Meier, log-rank, and Cox proportional hazards models were used to analyze the data. Results: At analysis 37/46 patients were deceased and 9 patients were alive or lost to follow-up (median follow-up 5.9 months, range, 0.9-81.2 months). Median age was 61.1 years (range, 40.9-85.5) with 27 females and 19 males. 38 patients were inoperable due to T4 disease and 8 patients were medically inoperable with T3 disease. Five patients did not complete CRT due to progressive
S320
Volume 78, Number 3, Supplement, 2010
Results: Twenty-nine patients with ASCC who underwent C-IMRT were identified. The median age was 48 years (range: 3278) and 16 (55%) were male. Eleven patients (38%) were HIV positive. Stage breakdown is as follows: stage I, 31%; stage II, 14%; stage III, 48%; and stage IV, 7%. All patients received concurrent chemotherapy; 19 patients (66%) received mitomycin-c based chemotherapy, 8 patients (28%) received cisplatin based chemotherapy, and 2 patients (7%) received 5-fluorouracil alone. The median RT dose was 5400 cGy in 30 fractions (range: 432-6120 cGy; 2-34 fractions). The maximum lower GI, skin, and hematologic toxicity scores during C-IMRT were a median of 2, 2, and 3, respectively. Grade 4 skin toxicity was observed in one patient and grade 4 hematologic toxicity was observed in two patients. One grade 5 hematologic toxicity occurred following two fractions of mitomycin-c based C-IMRT. When compared to simultaneously integrated boost, use of sequential boost IMRT was significantly associated with higher grade skin toxicity (p = 0.04). HIV positive status was significantly associated with higher hematologic toxicity (p = 0.01). Other factors examined, including BMI, radiation dose, type of chemotherapy, weight loss during treatment, and presence of previous tumor-directed therapy did not correlate with observed toxicities. At median follow-up of 17 months, 2-year LC, CFS, and OS rates for patients treated with curative intent were 90%, 96%, and 80%, respectively. Conclusions: C-IMRT yields acceptable toxicity rates for treatment of ASCC. Use of sequential boost IMRT was associated with higher grade skin toxicity compared to integrated boost IMRT. HIV positive patients have worse hematologic toxicity but equivalent skin and lower GI toxicity. LC, CFS, and OS compare favorably to conventional treatment but further follow-up is needed. Author Disclosure: B.M. Prendergast, None; M.C. Dobelbower, None; S.A. Spencer, None; J.J. Caudell, None; K.S. Keene, None; T. Wood, None; J. Posey, None; R. Jacob, None.
2261
IMRT vs. 3D Conformal Neoadjuvant Chemoradiation for Resectable and Borderline Resectable Pancreatic Cancer
C. Wood, T. Kelly, D. Prah, P. Ritch, D. Evans, B. Erickson Medical College of Wisconsin, Milwaukee, WI Purpose/Objective(s): Neoadjuvant chemoradiation (N-CRT) for pancreatic cancer (PC) has emerged as a new strategy to downstage nodal disease, enable margin-negative resections, and increase the number of patients who receive trimodality therapy. Criticisms of this approach include fear of toxicity preventing definitive surgery and increased surgical complications. Efforts to minimize toxicity in the setting of potent radiation sensitizing drugs have included smaller, 3D conformal radiation fields (3D) and use of intensity modulated radiation therapy (IMRT) to further spare abdominal organs. Criticisms of IMRT include irradiation of large volumes of the upper abdomen to low doses (V5-V15) and small volumes to higher maximum doses. Materials/Methods: From March 2009 through December 2009, 20 patients with resectable/borderline resectable PC received N-CRT as part of their treatment course. IMRT plans were generated for treatment for all patients and 3D-conformal plans were generated retrospectively for dosimetric comparison. The PTV included the pancreatic head/body and any enlarged lymph nodes with a 1-2 cm margin. The PTV was treated to 5040 cGy using daily IGRT with concurrent weekly gemcitabine. The following were compared for IMRT vs. 3D: V5-V15 for small bowel; V15 and V20 for kidneys; V30 and mean dose for liver, and maximum doses in the stomach and duodenum. Acute toxicity (CTC v 2.0) during N-CRT, surgical feasibility, timing, and outcomes were assessed. Results: N-CRT was well tolerated. All patients received a median of 5040 cGy. Mean weight loss was 3 lbs. Three patients required a treatment break and 5 patients were hospitalized. Complications included 4 grade 3 GI (3 dehydration, 1 duodenitis), 3 grade 3 hematologic (requiring transfusions), 1 grade 4 hematologic (febrile neutropenia), and 1 grade 4 GI (anorexia) complication. No patient had diarrhea. V5, V10, V15 for small bowel were 78%, 62%, 46% for IMRT vs. 73%, 66%, and 61% for 3D. V15 and V20 for the right kidney were 16% and 8% for IMRT vs. 43% and 37% for 3D. V15 and V20 for the left kidney were 8% and 2% for IMRT vs. 12% and 8% for 3D. Mean dose and V30 for liver were 1005 cGy and 5.6% for IMRT vs. 1020 cGy and 8% for 3D. Average max dose to the duodenum and stomach was 5270 cGy and 4508 cGy for IMRT vs. 5240 cGy and 4704 cGy for 3D respectively. Nineteen patients had surgery within a mean of 43 days, of which 16 patients had resection, and 3 had metastases. All 16 had negative surgical margins. The mean hospital stay was 10 days. One perioperative death occurred. Conclusions: IMRT-based N-CRT is both feasible and efficacious with the majority of patients able to go on to definitive surgical resection with negative margins. Minimization of normal organ irradiation can be achieved with IMRT and contributes to the successful delivery of preoperative therapy. Author Disclosure: C. Wood, None; T. Kelly, None; D. Prah, None; P. Ritch, None; D. Evans, None; B. Erickson, None.
2262
Radiation Dose $54 Gy is Associated with Improved Survival for Unresectable Pancreatic Cancer
D. W. Golden1, C. J. Novak2, B. Minsky1, S. L. Liauw1 1
University of Chicago Medical Center, Chicago, IL, 2University of Illinois at Chicago College of Medicine, Chicago, IL
Purpose/Objective(s): To investigate a single institution experience using chemoradiation (CRT) as definitive treatment for unresectable pancreatic adenocarcinoma (UPA) and to analyze patient and treatment related factors in relation to overall survival (OS), local failure (LF), and distant failure (DF). Materials/Methods: From 1997-2009 46 patients were treated with CRT for nonmetastatic UPA. Median prescribed RT dose was 54 Gy (range, 50.4-59.4). RT volumes encompassed the pancreatic bed plus draining lymphatics. 30/46 (65%) were treated with IMRT. Two patients received neoadjuvant chemotherapy, all patients received concurrent chemotherapy (41 5FU, 5 other), and 24 patients received adjuvant chemotherapy (20 gemcitabine, 4 other). Kaplan-Meier, log-rank, and Cox proportional hazards models were used to analyze the data. Results: At analysis 37/46 patients were deceased and 9 patients were alive or lost to follow-up (median follow-up 5.9 months, range, 0.9-81.2 months). Median age was 61.1 years (range, 40.9-85.5) with 27 females and 19 males. 38 patients were inoperable due to T4 disease and 8 patients were medically inoperable with T3 disease. Five patients did not complete CRT due to progressive