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A Comparison of 3 Treatment Strategies for Locally Advanced and Borderline Resectable Pancreatic Cancer
Volume 84 Number 3S Supplement 2012
Oral Scientific Sessions
4% for 5-FU/RT (p Z 0.02). Patients treated with GEM + BEV had both higher OS and DMFR at 1 and 2 years compared to GEM alone or with tarceva (p Z 0.0007 and p Z 0.0002, respectively). Furthermore, patients given maintenance GEM after GEM/RT CRT had an OS rate at 1 and 2 years of 64% and 20% compared to 50% and 10% for maintenance GEM after 5-FU/RT (p Z 0.07). Additionally, progression free survival at 1 and 2 years for maintenance GEM after GEM/RT was 51% and 14% versus 25% and 5% for maintenance GEM after 5-FU/RT (p Z 0.04). Conclusions: Full dose GEM with concurrent 36 Gy radiation therapy had lower rates of acute and late grade 3 GI toxicity, higher DMFR rates, and an improved OS. Author Disclosure: S. Rakhra: None. J. Robertson: None. C.J. McGinn: None. A. Chung: None. J. Huang: None. A. Blake: None. I. Helenowski: None. J. Hayes: None. M. Mulcahy: None. W. Small: None.
recurrences. Local failures occurred in 50% (3/6) of patients with a margin 1 mm compared to 3% (1/35) with a margin >1 mm (p Z 0.007). In resected patients, the median survival is not met with median follow-up of 18 months. The 2 year overall survival is 57%. Conclusions: Neoadjuvant chemoXRT can facilitate margin negative resection and histologic response in regional lymph nodes in patients with localized PCa. Margin distance may be an important variable predictive of local recurrence. IMRT in the preoperative setting allows for customized coverage of high-risk volumes and decreased dose to organs at risk without compromise in local control. Author Disclosure: J.R. Kharofa: None. T. Kelly: None. C. Wood: None. B. George: None. S. Tsai: None. P. Ritch: None. L. Wiebe: None. K. Christians: None. D. Evans: None. B. Erickson: None.
220
219 Neoadjuvant Chemoradiation With Intensity Modulated Radiation Therapy in Resectable and Borderline Resectable Pancreatic Cancer (PCa) J.R. Kharofa,1 T. Kelly,1 C. Wood,2 B. George,1 S. Tsai,1 P. Ritch,1 L. Wiebe,1 K. Christians,1 D. Evans,1 and B. Erickson1; 1Medical College of Wisconsin, Milwaukee, WI, 2Advanced Radiation Oncology, Greenwood, SC Purpose/Objective(s): To report the clinical outcomes and failure patterns in patients with resectable and borderline resectable PCa treated with neoadjuvant chemoradiation (chemoXRT) using IMRT. Materials/Methods: All patients with resectable and borderline resectable PCa treated between January 2009 and November 2011 were reviewed. Borderline resectable was defined as SMA abutment 180 degrees, SMV occlusion, or findings suspicious but not diagnostic for metastatic disease. The CTV included the primary mass, the SMA origin, the SMA and SMV vessels adjacent to the pancreatic head, enlarged lymph nodes, +/- the celiac axis with a 1 cm expansion to PTV. Patients were treated with image guidance, respiratory gating if motion was >1.0 cm, and an ITV if motion was <1.0 cm. Survival outcomes were assessed using Kaplan Meier analysis. Cumulative incidence of local failures was assessed with the competing the risk of death. Treatment plans were reviewed in patients with local regional failures to analyze the PTV relationship. Results: Seventy-one patients (43 borderline resectable and 28 resectable) were treated with neoadjuvant therapy for PCa. Induction chemotherapy was used in 72% of patients with borderline resectable disease prior to chemoXRT (FOLFIRINOX Z 12, gemcitabine based Z 19). Resectable patients were treated with chemoXRT alone. 68 patients proceeded to chemoXRT (50.4 Gy [1.8 Gy/fx] with concurrent gemcitabine [n Z 59] or capecitabine [n Z 7]). Patients did not undergo resection due to metastases (n Z 17), tumor anatomy (n Z 3), comorbidities (n Z 3), or patient preference (n Z 1). Following neoadjuvant treatment, 48 (62%) of patients were resected with 47 (98%) RO resections. In 31 patients with SMA abutment or SMV occlusion, 61% were surgically resected and all had RO resections. 29% of patients had pathologic lymph node metastases. The disease free survival at 1 year with and without lymph node metastases was 45% and 80% respectively (p Z 0.008). The first site of failure in resected patients was distant (52%), liver (33%), distant and local (14%), local only (0%). Cumulative incidence of local failure at 1 and 2 years from surgery was 8% and 15%. All local failures occurred within the PTV with no marginal
Oral Scientific Abstract 220; Table
CRT CCRT C
S89
A Comparison of 3 Treatment Strategies for Locally Advanced and Borderline Resectable Pancreatic Cancer S. Lloyd and B.W. Chang; Yale School of Medicine, New Haven, CT Purpose/Objective(s): The optimal treatment strategy for locally advanced and borderline resectable pancreatic cancer is not known. We sought to compare overall survival (OS), local control (LC), metastasis free survival (MFS), and percent of patients who were able to undergo successful surgical resection for three treatment strategies. Materials/Methods: We retrospectively reviewed 114 sequentially treated cases of locally advanced (T4) or borderline resectable (T3 but unresectable) pancreatic cancer. All patients were examined by a surgeon and felt to be unresectable at the time of diagnosis. Patients were treated with either chemotherapy alone (C), up-front chemoradiation therapy (CRT), or chemotherapy followed by chemoradiation therapy (CCRT). We calculated survival using Kaplan-Meier analysis and used log-rank analysis to compare survival between groups. A multivariate survival analysis was performed using a Cox-proportional hazards model. Results: Median follow-up was 17.4 months. The mean age was 64.3 years. Fifty-six (49.1%) patients had locally advanced disease. Of the patients who received chemotherapy up-front, 89% received gemcitabinebased chemotherapy. During concurrent radiation therapy, patients received either 5-FU (21%), Capecitabine (72%), or Gemcitabine (7%). See the table below for a summary of the outcomes. Patients treated with CCRT experienced statistically significant improved OS and MFS compared to C alone (p Z 0.019 and p Z 0.041 respectively). Of the patients receiving C alone, 5/64 (7.8%) were diagnosed with distant metastases before 3 months. There was no statistically significant difference in OS or MFS between C and CRT or between CRT and CCRT. There was no statistically significant difference in LC between any of the treatment groups. There was a trend towards improved OS in patients with borderline resectable disease (p Z 0.064). On multivariate analysis only younger age (p Z 0.025) was associated with improved OS. There was a trend toward improved OS in patients who achieved successful surgical resection (p Z 0.084). Treatment type, T stage, and N stage were not statistically significant. Conclusions: Treatment with CCRT is associated with improved median OS and MFS compared to C alone. This strategy may select for patients who are less likely to develop early metastases and therefore have a worse prognosis. The rate of successful surgical resection was greater than 20% in patients treated with CCRT. Author Disclosure: S. Lloyd: None. B.W. Chang: None.
Outcomes by Treatment Strategy
N
Locally Advanced
Successful Surgical Resection, Borderline Resectable
Successful Surgical Resection, Locally Advanced
Median Survival in Months (95% CI)
1-year LC (95% CI)
2-year LC (95% CI)
1-year MFS (95% CI)
2-year MFS (95% CI)
22 28 64
13 (59%) 12 (43%) 31 (48%)
1/9 (11%) 3/16 (19%) 6/33 (18%)
1/13 (8%) 3/12 (25%) 0/31 (0%)
13.8 (10.8 to 30.5) 24.2 (20.1 to 46.8) 16.2 (14.1 to 19.0)
61% (43 to 87) 85% (72 to 99) 79% (69 to 91)
30% (14 to 63) 65% (48 to 89) 40% (27 to 59)
59% (41 to 84) 82% (69 to 98) 68% (58 to 81)
28% (14 to 57) 55% (39 to 78) 24% (15 to 38)
Oral Scientific Sessions
4% for 5-FU/RT (p Z 0.02). Patients treated with GEM + BEV had both higher OS and DMFR at 1 and 2 years compared to GEM alone or with tarceva (p Z 0.0007 and p Z 0.0002, respectively). Furthermore, patients given maintenance GEM after GEM/RT CRT had an OS rate at 1 and 2 years of 64% and 20% compared to 50% and 10% for maintenance GEM after 5-FU/RT (p Z 0.07). Additionally, progression free survival at 1 and 2 years for maintenance GEM after GEM/RT was 51% and 14% versus 25% and 5% for maintenance GEM after 5-FU/RT (p Z 0.04). Conclusions: Full dose GEM with concurrent 36 Gy radiation therapy had lower rates of acute and late grade 3 GI toxicity, higher DMFR rates, and an improved OS. Author Disclosure: S. Rakhra: None. J. Robertson: None. C.J. McGinn: None. A. Chung: None. J. Huang: None. A. Blake: None. I. Helenowski: None. J. Hayes: None. M. Mulcahy: None. W. Small: None.
recurrences. Local failures occurred in 50% (3/6) of patients with a margin 1 mm compared to 3% (1/35) with a margin >1 mm (p Z 0.007). In resected patients, the median survival is not met with median follow-up of 18 months. The 2 year overall survival is 57%. Conclusions: Neoadjuvant chemoXRT can facilitate margin negative resection and histologic response in regional lymph nodes in patients with localized PCa. Margin distance may be an important variable predictive of local recurrence. IMRT in the preoperative setting allows for customized coverage of high-risk volumes and decreased dose to organs at risk without compromise in local control. Author Disclosure: J.R. Kharofa: None. T. Kelly: None. C. Wood: None. B. George: None. S. Tsai: None. P. Ritch: None. L. Wiebe: None. K. Christians: None. D. Evans: None. B. Erickson: None.
220
219 Neoadjuvant Chemoradiation With Intensity Modulated Radiation Therapy in Resectable and Borderline Resectable Pancreatic Cancer (PCa) J.R. Kharofa,1 T. Kelly,1 C. Wood,2 B. George,1 S. Tsai,1 P. Ritch,1 L. Wiebe,1 K. Christians,1 D. Evans,1 and B. Erickson1; 1Medical College of Wisconsin, Milwaukee, WI, 2Advanced Radiation Oncology, Greenwood, SC Purpose/Objective(s): To report the clinical outcomes and failure patterns in patients with resectable and borderline resectable PCa treated with neoadjuvant chemoradiation (chemoXRT) using IMRT. Materials/Methods: All patients with resectable and borderline resectable PCa treated between January 2009 and November 2011 were reviewed. Borderline resectable was defined as SMA abutment 180 degrees, SMV occlusion, or findings suspicious but not diagnostic for metastatic disease. The CTV included the primary mass, the SMA origin, the SMA and SMV vessels adjacent to the pancreatic head, enlarged lymph nodes, +/- the celiac axis with a 1 cm expansion to PTV. Patients were treated with image guidance, respiratory gating if motion was >1.0 cm, and an ITV if motion was <1.0 cm. Survival outcomes were assessed using Kaplan Meier analysis. Cumulative incidence of local failures was assessed with the competing the risk of death. Treatment plans were reviewed in patients with local regional failures to analyze the PTV relationship. Results: Seventy-one patients (43 borderline resectable and 28 resectable) were treated with neoadjuvant therapy for PCa. Induction chemotherapy was used in 72% of patients with borderline resectable disease prior to chemoXRT (FOLFIRINOX Z 12, gemcitabine based Z 19). Resectable patients were treated with chemoXRT alone. 68 patients proceeded to chemoXRT (50.4 Gy [1.8 Gy/fx] with concurrent gemcitabine [n Z 59] or capecitabine [n Z 7]). Patients did not undergo resection due to metastases (n Z 17), tumor anatomy (n Z 3), comorbidities (n Z 3), or patient preference (n Z 1). Following neoadjuvant treatment, 48 (62%) of patients were resected with 47 (98%) RO resections. In 31 patients with SMA abutment or SMV occlusion, 61% were surgically resected and all had RO resections. 29% of patients had pathologic lymph node metastases. The disease free survival at 1 year with and without lymph node metastases was 45% and 80% respectively (p Z 0.008). The first site of failure in resected patients was distant (52%), liver (33%), distant and local (14%), local only (0%). Cumulative incidence of local failure at 1 and 2 years from surgery was 8% and 15%. All local failures occurred within the PTV with no marginal
Oral Scientific Abstract 220; Table
CRT CCRT C
S89
A Comparison of 3 Treatment Strategies for Locally Advanced and Borderline Resectable Pancreatic Cancer S. Lloyd and B.W. Chang; Yale School of Medicine, New Haven, CT Purpose/Objective(s): The optimal treatment strategy for locally advanced and borderline resectable pancreatic cancer is not known. We sought to compare overall survival (OS), local control (LC), metastasis free survival (MFS), and percent of patients who were able to undergo successful surgical resection for three treatment strategies. Materials/Methods: We retrospectively reviewed 114 sequentially treated cases of locally advanced (T4) or borderline resectable (T3 but unresectable) pancreatic cancer. All patients were examined by a surgeon and felt to be unresectable at the time of diagnosis. Patients were treated with either chemotherapy alone (C), up-front chemoradiation therapy (CRT), or chemotherapy followed by chemoradiation therapy (CCRT). We calculated survival using Kaplan-Meier analysis and used log-rank analysis to compare survival between groups. A multivariate survival analysis was performed using a Cox-proportional hazards model. Results: Median follow-up was 17.4 months. The mean age was 64.3 years. Fifty-six (49.1%) patients had locally advanced disease. Of the patients who received chemotherapy up-front, 89% received gemcitabinebased chemotherapy. During concurrent radiation therapy, patients received either 5-FU (21%), Capecitabine (72%), or Gemcitabine (7%). See the table below for a summary of the outcomes. Patients treated with CCRT experienced statistically significant improved OS and MFS compared to C alone (p Z 0.019 and p Z 0.041 respectively). Of the patients receiving C alone, 5/64 (7.8%) were diagnosed with distant metastases before 3 months. There was no statistically significant difference in OS or MFS between C and CRT or between CRT and CCRT. There was no statistically significant difference in LC between any of the treatment groups. There was a trend towards improved OS in patients with borderline resectable disease (p Z 0.064). On multivariate analysis only younger age (p Z 0.025) was associated with improved OS. There was a trend toward improved OS in patients who achieved successful surgical resection (p Z 0.084). Treatment type, T stage, and N stage were not statistically significant. Conclusions: Treatment with CCRT is associated with improved median OS and MFS compared to C alone. This strategy may select for patients who are less likely to develop early metastases and therefore have a worse prognosis. The rate of successful surgical resection was greater than 20% in patients treated with CCRT. Author Disclosure: S. Lloyd: None. B.W. Chang: None.
Outcomes by Treatment Strategy
N
Locally Advanced
Successful Surgical Resection, Borderline Resectable
Successful Surgical Resection, Locally Advanced
Median Survival in Months (95% CI)
1-year LC (95% CI)
2-year LC (95% CI)
1-year MFS (95% CI)
2-year MFS (95% CI)
22 28 64
13 (59%) 12 (43%) 31 (48%)
1/9 (11%) 3/16 (19%) 6/33 (18%)
1/13 (8%) 3/12 (25%) 0/31 (0%)
13.8 (10.8 to 30.5) 24.2 (20.1 to 46.8) 16.2 (14.1 to 19.0)
61% (43 to 87) 85% (72 to 99) 79% (69 to 91)
30% (14 to 63) 65% (48 to 89) 40% (27 to 59)
59% (41 to 84) 82% (69 to 98) 68% (58 to 81)
28% (14 to 57) 55% (39 to 78) 24% (15 to 38)