- Email: [email protected]
Chemoradiation Therapy Versus Chemotherapy for Unresectable Pancreatic Cancer: A Systematic Review and Meta-analysis
E174
International Journal of Radiation Oncology Biology Physics
those tumors invading the duodenum due to the potential for increased GI mucosal complications. We analyzed our non-trial patients to determine the impact of SBRT in the setting of known duodenal invasion. Materials/Methods: An IRB-approved institutional database was queried to identify all 220 localized borderline resectable or locally advanced pancreatic cancer patients treated with SBRT from 2009 to 2015. Eligibility included patients with head tumors, a minimum of 6 months of follow up, and duodenal invasion assessed by pretreatment endoscopic ultrasound (EUS). Dose painted SBRT delivered 25-30 Gy to the tumor abutting the duodenum and up to 50 Gy to the focal tumor/vessel abutment. Analysis evaluated whether patients with duodenal invasion had an increased incidence of grade 3 (G3+) toxicity, GI ulceration or bleeding, or worsened overall survival (OS). Fisher’s Exact Test (2-tailed) compared patient characteristics and binary outcomes. Survival was estimated by Kaplan-Meier method and compared by log-rank test. Results: The study population included 126 patients with a minimum of 6 months follow up (median F/U 14.1 months). Of 23 patients with duodenal invasion, 14 (61%) underwent resection, 3 (13%) developed radiationrelated G3+ toxicity and 1 (4%) had acute pre-op G3 GI bleeding that was controlled endoscopically prior to Whipple procedure. Of 103 without duodenal invasion, 48 (47%) underwent resection, 9 (9%) suffered G3+ toxicity and 7 (7%) had any GI bleed or ulceration. None of the 7 patients with GI bleeding or ulceration underwent pancreatectomy, and 3 had bleeding due to duodenal tumor progression. No association was observed between duodenal invasion and the incidence of G3+ toxicity (pZ0.76) or GI ulceration/bleeding (pZ1.0). There was no worsened OS (pZ0.17) or G3+ toxicity (pZ0.22) for patients with EUS documented duodenal invasion. Patients with a GI bleeding or ulceration event had decreased OS (pZ.014). Conclusion: Duodenal invasion noted on EUS prior to SBRT did not worsen GI bleeding risk or survival. Our data suggests that it is unnecessary to exclude pancreatic adenocarcinoma patients with duodenal invasion from SBRT when using a dose-painted approach. Author Disclosure: G.Z. Murimwa: None. E.A. Mellon: None. J.M. Frakes: None. W. Jin: None. P. Hodul: None. J. Pimiento: None. R. Kim: None. H. Soares: None. M. Malafa: None. S.E. Hoffe: None.
0.60, P < 0.0001, I2 Z 6%), which was likely due to a result of imbalance in tumour characteristics between the two groups. Conclusion: As most of the published studies have methodological limitations, there is no clear evidence of an effect on progression free and overall survival for adding RT to chemotherapy for patients with unresectable pancreatic cancer. Future research with high quality randomized trials is warranted to determine the role of RT for this group of patients. Author Disclosure: I.W. Ng: None. Y. Soon: None. D. Chen: None. J. Tey: None.
2419 Chemoradiation Therapy Versus Chemotherapy for Unresectable Pancreatic Cancer: A Systematic Review and Meta-analysis I.W. Ng,1 Y.Y. Soon,2 D. Chen,3 and J. Tey3; 1National University Cancer Institute Singapore, Singapore 119228, Singapore, 2National University Cancer Institute (Singapore), Singapore, Singapore, 3National University Cancer Institute, Singapore, Singapore, Singapore Purpose/Objective(s): To determine the benefit of adding radiotherapy (RT) to chemotherapy for patients with unresectable pancreatic cancer. Materials/Methods: We searched MEDLINE for comparative studies comparing chemoradiotherapy with chemotherapy for patients with unresectable pancreatic cancer. We assessed the methodological quality of the included studies using the MERGE criteria. We performed the metaanalysis with random effects model using Revman 5.3 to estimate the pooled hazard ratios (HR), confidence intervals (CI), P values (P) and I squared statistic (I2). The primary outcome was overall survival (OS); secondary outcomes include progression-free survival (PFS) and adverse events (AE). We used the GRADE approach to appraise the quality of evidence from randomized trials. Results: We found five randomised and three retrospective comparative studies including 830 patients. Only two randomized trials were judged to have low to moderate risk of bias while the other included studies had moderate to high risk of bias in their methodology. For the randomised trials, the addition of radiotherapy did not improve PFS (HR 0.90, 95% CI 0.74 to 1.10, P Z 0.30, I2 Z 11%, moderate quality evidence) or OS (HR 0.87, 95% CI 0.63 to 1.21, P Z 0.41, I2 Z 67%, very low quality evidence) and was associated with more frequent grade 3 or 4 gastrointestinal AE. Retrospective studies showed an improvement in PFS (HR 0.58, 95% CI 0.37 to 0.92, P Z 0.02, I2 Z 32%) and OS (HR 0.48, 95% CI 0.35 to
2420 Induction Chemotherapy Reduces PatientReported Toxicities During Neoadjuvant Chemoradiation with Intensity Modulated Radiation Therapy for Rectal Cancer S.Y. Ng,1 K. Colborn,2 L. Cambridge,1 A. Cercek,3 D. Reidy,3 N. Segal,3 Z. Stadler,3 L. Saltz,3 J. Garcia-Aguilar,4 and K.A. Goodman5; 1 Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 22Division of Health Care Policy and Research, Adult and Child Consortium for Health Outcomes Research and Delivery Science, University of Colorado Denver School of Medicine, Denver, CA, 3 Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 4Memorial Sloan Kettering Cancer Center, New York, NY, 5 Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO Purpose/Objective(s): Initial treatment with either neoadjuvant chemoradiation (CRT) or induction FOLFOX chemotherapy followed by CRT is considered standard treatment for locally advanced rectal cancer. We describe patient-reported outcomes (PROs) during CRT and compared patient-reported outcomes (PROs) during CRT in patients who had received induction chemotherapy versus those who did not. We also evaluated potential predictive factors associated with worse PROs during chemoradiation. Materials/Methods: We retrospectively reviewed records of patients with locally advanced primary rectal cancer who were treated with CRT between September 2009 and October 2014. Weekly PROs using a 7 or 14item questionnaire based on the NCI PRO-CTCAE and Bowel Problems Scale were collected for each patient during treatment. Symptom frequency, severity and interference with daily activities were measured 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. Those who had completed 4 PRO assessments during treatment were included for analysis. We fit binomial generalized linear mixed models to repeated measurements of toxicity across all patients. Results: Of 123 patients, 66 (53.7%) were male, the majority had clinical T3 node-positive disease, and 84 patients (68.3%) had undergone induction chemotherapy prior to chemoradiation. Majority of patients (95%) received FOLFOX, three received capecitabine and oxaliplatin (CAPOX) and one received 5FU, irinotecan and leucovorin (FOLFIRI). During CRT, all patients received concurrent 5-FU or capecitabine. Eighty-seven patients (71%) reported a clinically meaningful PRO score of 3 or higher for diarrhea during one or more weeks of treatment, corresponding to ‘very frequent’ or worse and 91 patients (74%) reported the same score for urgency. About half of the patients complained of very frequent rectal pain, tenesmus and mucus from the rectum (57%, 52% and 48% respectively). Fewer experienced rectal bleeding and abdominal cramping (36% and 43% respectively). Patients who had undergone induction chemotherapy had 68% lower odds of experiencing significant urgency (OR 0.32, 95%CI 0.11-0.95, p<0.04), 76% lower odds of bleeding (OR 0.24, 95%CI 0.10.62, p<0.01) and 75% lower odds of tenesmus (OR 0.25, 95%CI 0.11-0.6, p<0.01) versus those treated with upfront CRT. Another factor associated with PROs during CRT was older age, where patients 55 and older had 70% lower odds of bleeding (OR 0.30, 95%CI 0.12-0.74, pZ0.01). Our analysis also suggests that as BMI increases from 20 to 30, the probability of pain goes up about 30%. Conclusion: Our PRO analysis demonstrated that the delivery of induction chemotherapy followed by CRT was associated with lower odds of
International Journal of Radiation Oncology Biology Physics
those tumors invading the duodenum due to the potential for increased GI mucosal complications. We analyzed our non-trial patients to determine the impact of SBRT in the setting of known duodenal invasion. Materials/Methods: An IRB-approved institutional database was queried to identify all 220 localized borderline resectable or locally advanced pancreatic cancer patients treated with SBRT from 2009 to 2015. Eligibility included patients with head tumors, a minimum of 6 months of follow up, and duodenal invasion assessed by pretreatment endoscopic ultrasound (EUS). Dose painted SBRT delivered 25-30 Gy to the tumor abutting the duodenum and up to 50 Gy to the focal tumor/vessel abutment. Analysis evaluated whether patients with duodenal invasion had an increased incidence of grade 3 (G3+) toxicity, GI ulceration or bleeding, or worsened overall survival (OS). Fisher’s Exact Test (2-tailed) compared patient characteristics and binary outcomes. Survival was estimated by Kaplan-Meier method and compared by log-rank test. Results: The study population included 126 patients with a minimum of 6 months follow up (median F/U 14.1 months). Of 23 patients with duodenal invasion, 14 (61%) underwent resection, 3 (13%) developed radiationrelated G3+ toxicity and 1 (4%) had acute pre-op G3 GI bleeding that was controlled endoscopically prior to Whipple procedure. Of 103 without duodenal invasion, 48 (47%) underwent resection, 9 (9%) suffered G3+ toxicity and 7 (7%) had any GI bleed or ulceration. None of the 7 patients with GI bleeding or ulceration underwent pancreatectomy, and 3 had bleeding due to duodenal tumor progression. No association was observed between duodenal invasion and the incidence of G3+ toxicity (pZ0.76) or GI ulceration/bleeding (pZ1.0). There was no worsened OS (pZ0.17) or G3+ toxicity (pZ0.22) for patients with EUS documented duodenal invasion. Patients with a GI bleeding or ulceration event had decreased OS (pZ.014). Conclusion: Duodenal invasion noted on EUS prior to SBRT did not worsen GI bleeding risk or survival. Our data suggests that it is unnecessary to exclude pancreatic adenocarcinoma patients with duodenal invasion from SBRT when using a dose-painted approach. Author Disclosure: G.Z. Murimwa: None. E.A. Mellon: None. J.M. Frakes: None. W. Jin: None. P. Hodul: None. J. Pimiento: None. R. Kim: None. H. Soares: None. M. Malafa: None. S.E. Hoffe: None.
0.60, P < 0.0001, I2 Z 6%), which was likely due to a result of imbalance in tumour characteristics between the two groups. Conclusion: As most of the published studies have methodological limitations, there is no clear evidence of an effect on progression free and overall survival for adding RT to chemotherapy for patients with unresectable pancreatic cancer. Future research with high quality randomized trials is warranted to determine the role of RT for this group of patients. Author Disclosure: I.W. Ng: None. Y. Soon: None. D. Chen: None. J. Tey: None.
2419 Chemoradiation Therapy Versus Chemotherapy for Unresectable Pancreatic Cancer: A Systematic Review and Meta-analysis I.W. Ng,1 Y.Y. Soon,2 D. Chen,3 and J. Tey3; 1National University Cancer Institute Singapore, Singapore 119228, Singapore, 2National University Cancer Institute (Singapore), Singapore, Singapore, 3National University Cancer Institute, Singapore, Singapore, Singapore Purpose/Objective(s): To determine the benefit of adding radiotherapy (RT) to chemotherapy for patients with unresectable pancreatic cancer. Materials/Methods: We searched MEDLINE for comparative studies comparing chemoradiotherapy with chemotherapy for patients with unresectable pancreatic cancer. We assessed the methodological quality of the included studies using the MERGE criteria. We performed the metaanalysis with random effects model using Revman 5.3 to estimate the pooled hazard ratios (HR), confidence intervals (CI), P values (P) and I squared statistic (I2). The primary outcome was overall survival (OS); secondary outcomes include progression-free survival (PFS) and adverse events (AE). We used the GRADE approach to appraise the quality of evidence from randomized trials. Results: We found five randomised and three retrospective comparative studies including 830 patients. Only two randomized trials were judged to have low to moderate risk of bias while the other included studies had moderate to high risk of bias in their methodology. For the randomised trials, the addition of radiotherapy did not improve PFS (HR 0.90, 95% CI 0.74 to 1.10, P Z 0.30, I2 Z 11%, moderate quality evidence) or OS (HR 0.87, 95% CI 0.63 to 1.21, P Z 0.41, I2 Z 67%, very low quality evidence) and was associated with more frequent grade 3 or 4 gastrointestinal AE. Retrospective studies showed an improvement in PFS (HR 0.58, 95% CI 0.37 to 0.92, P Z 0.02, I2 Z 32%) and OS (HR 0.48, 95% CI 0.35 to
2420 Induction Chemotherapy Reduces PatientReported Toxicities During Neoadjuvant Chemoradiation with Intensity Modulated Radiation Therapy for Rectal Cancer S.Y. Ng,1 K. Colborn,2 L. Cambridge,1 A. Cercek,3 D. Reidy,3 N. Segal,3 Z. Stadler,3 L. Saltz,3 J. Garcia-Aguilar,4 and K.A. Goodman5; 1 Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 22Division of Health Care Policy and Research, Adult and Child Consortium for Health Outcomes Research and Delivery Science, University of Colorado Denver School of Medicine, Denver, CA, 3 Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 4Memorial Sloan Kettering Cancer Center, New York, NY, 5 Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO Purpose/Objective(s): Initial treatment with either neoadjuvant chemoradiation (CRT) or induction FOLFOX chemotherapy followed by CRT is considered standard treatment for locally advanced rectal cancer. We describe patient-reported outcomes (PROs) during CRT and compared patient-reported outcomes (PROs) during CRT in patients who had received induction chemotherapy versus those who did not. We also evaluated potential predictive factors associated with worse PROs during chemoradiation. Materials/Methods: We retrospectively reviewed records of patients with locally advanced primary rectal cancer who were treated with CRT between September 2009 and October 2014. Weekly PROs using a 7 or 14item questionnaire based on the NCI PRO-CTCAE and Bowel Problems Scale were collected for each patient during treatment. Symptom frequency, severity and interference with daily activities were measured 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. Those who had completed 4 PRO assessments during treatment were included for analysis. We fit binomial generalized linear mixed models to repeated measurements of toxicity across all patients. Results: Of 123 patients, 66 (53.7%) were male, the majority had clinical T3 node-positive disease, and 84 patients (68.3%) had undergone induction chemotherapy prior to chemoradiation. Majority of patients (95%) received FOLFOX, three received capecitabine and oxaliplatin (CAPOX) and one received 5FU, irinotecan and leucovorin (FOLFIRI). During CRT, all patients received concurrent 5-FU or capecitabine. Eighty-seven patients (71%) reported a clinically meaningful PRO score of 3 or higher for diarrhea during one or more weeks of treatment, corresponding to ‘very frequent’ or worse and 91 patients (74%) reported the same score for urgency. About half of the patients complained of very frequent rectal pain, tenesmus and mucus from the rectum (57%, 52% and 48% respectively). Fewer experienced rectal bleeding and abdominal cramping (36% and 43% respectively). Patients who had undergone induction chemotherapy had 68% lower odds of experiencing significant urgency (OR 0.32, 95%CI 0.11-0.95, p<0.04), 76% lower odds of bleeding (OR 0.24, 95%CI 0.10.62, p<0.01) and 75% lower odds of tenesmus (OR 0.25, 95%CI 0.11-0.6, p<0.01) versus those treated with upfront CRT. Another factor associated with PROs during CRT was older age, where patients 55 and older had 70% lower odds of bleeding (OR 0.30, 95%CI 0.12-0.74, pZ0.01). Our analysis also suggests that as BMI increases from 20 to 30, the probability of pain goes up about 30%. Conclusion: Our PRO analysis demonstrated that the delivery of induction chemotherapy followed by CRT was associated with lower odds of