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Comparison of Overall Survival for Esophageal Cancer Patients Treated With Neoadjuvant Proton or Photon Chemoradiation: A Multi-institutional Analysis
Volume 93 Number 3S Supplement 2015 We conducted a prospective phase 1/2 clinical trial to explore the safety and feasibility of using a simultaneous integrated boost (SIB) of 63 Gy to the GTV, while keeping the dose to the planning target volume (PTV) at 50.4 Gy. Secondary outcomes included overall survival (OS) and failure patterns. Materials/Methods: From June 2010 through July 2014, 44 patients with esophageal cancer at high-risk for surgical complications were prospectively treated with definitive chemoradiation using a SIB to deliver 63 Gy to the GTV, while the PTV was tread to 50.4 Gy, all in 28 fractions. The boost length was limited to 10 cm. Toxicity was classified with the Common Terminology Criteria for Adverse Events v4.0. Overall survival was calculated from the start of treatment until death or last follow-up. All patients were evaluated for recurrence with imaging. Recurrences were categorized in relation to the planned radiation fields. Results: At the time of this analysis, 38 patients were evaluable (median age, 65 y); most (71%) were male and presented with T3 (84%), N1 (34%) or N2 (24%), M1 (13%) disease and moderately differentiated tumors (42%); half (50%) were adenocarcinomas. At a median followup time of 16.8 months, grade 3 GI adverse events were esophagitis (8%), dysphagia (24%), nausea (5%), and anorexia (8%). No grade 4 or 5 toxicities were present. Fifteen patients (40%) developed strictures and four (11%) required stents. Median OS time was 30.8 months, and 23 patients were alive at the time of analysis. Fifteen patients (39%) had no evidence of failure. Twenty-three patients (61%) experienced failures, most of which were distant. Of 14 (37%) patients with locoregional failure, eleven (28%) and three (8%) had failures inside and outside of the treatment field. Of patients with infield failures, five (13%) were in the GTV only, five (13%) in both GTV and distant, two (5%) in both GTV and clinical target volume (CTV), and one (3%) in the GTV and PTV. Patients with T2 disease (11%) have not experienced recurrence. Nine patients received salvage surgery, but only five had residual disease. Conclusion: This is the first prospective data investigating SIB doseescalation for patients with advanced esophageal cancer who are high-risk surgical candidates. There appears to be a slight increase in acute toxicity and may be a higher rate of stricture. SIB dose escalation to gross primary disease may improve local control, but longer follow-up is needed to assess the long term morbidity. Prospective randomized trials comparing Simultaneous integrated boost dose-escalation to standard dose radiation are needed for patients who cannot tolerate trimodality therapy. Author Disclosure: J.W. Welsh: None. S.N. Seyedin: None. W.L. Hofstetter: None. J.A. Ajani: None. J.Y. Chang: None. D.R. Gomez: None. S.G. Swisher: None. M.A. Blum: None. Q. Nguyen: None. B.D. Minsky: None. J. Erasmus: None. J.H. Lee: None. M.S. Bhutani: None. R.U. Komaki: None.
29 Phase 2 Study of Simultaneous Modulated Accelerated Radiation Therapy Combined With Chemotherapy for Esophageal Squamous Cell Carcinoma: Early Outcomes J. Chen,1 D. Li,1 T. Zhai,1 D.T. Chang,2 H. Guo,1 W. Zhang,1 L. Guo,1 M. Zhou,1 D. Li,1 and C. Chen1; 1Cancer Hospital of Shantou University Medical College, Shantou, China, 2Stanford University, Stanford, CA Purpose/Objective(s): The outcomes for patients with esophageal cancer who underwent standard-dose radiation therapy are still disappointing. Rapid advances of radiation therapy techniques have provided potentials for radiation dose-escalation while maintaining sparing of critical structures. This phase 2 study aimed to determine the safety, feasibility and efficacy of simultaneous modulated accelerated radiation therapy (SMART) combined with chemotherapy for patients with esophageal squamous cell carcinoma (SCC). Materials/Methods: Patients with primary esophageal SCC, ECOG PS 0 w 2 without distant metastasis (except supraclavicular lymph node)
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were enrolled to receive definitive chemoradiation therapy using SMART. Radiation therapy consisted of 66 Gy at 2.2 Gy/fraction to gross tumor, and 54 Gy at 1.8 Gy/fraction to subclinical disease simultaneously in 30 fractions. Four cycles of chemotherapy including cisplatin (75 mg/m2, day 1) and 5fluorouracil 0.5/m2 (day 1 to 4) were administered to all patients during and after radiation therapy. The primary endpoints were Grade 3 acute and late toxicities, which were assessed using Common Terminology Criteria for Adverse Events Version 4.0. The secondary endpoints included local control and overall survival rates. Results: From August 2012 to April 2014, a total of 60 patients were accrued and one patient (1.7%) dropped out of the study. Among the 59 patients, there were 49 males and 10 females with a median age of 62 (range, 45e73 years). Tumors were stage II (n Z 22), stage III (n Z 26) and stage IV (n Z 11), according to AJCC 6th staging system. Only 1 patient (1.7%) did not complete the whole course of radiation therapy due to thrombocytopenia. Fifty-eight patients (98.3%) finished at least 2 cycles of concurrent chemotherapy. The median follow-up time was 19 months (range, 5e30 months) for all patients and 22 months (range, 10e30 months) for those still alive. The most common grade 3 acute toxicities were neutropenia (17%), followed by esophagitis (8.5%) and thrombopenia (5.1%). Ten patients (16.9%) developed Grade 3 late toxicities of esophagus (esophageal ulceration and fistula) and 2 of them (3.4%) died subsequently. Two patients (3.4%) had Grade 3 radiation pneumonitis. The 1 and 2-year local control, regional control, distant metastasis-free survival, disease progression-free survival, and overall survival rates were 94.3% and 90.4%, 90.7% and 88.3%, 83.8% and 78.8%, 74.7% and 62.4%, and 88.0% and 70.5%, respectively. Conclusion: Simultaneous modulated accelerated radiation therapy, combined with chemotherapy, showed a trend of significant improvements in local control and overall survival rates in patients with esophageal SCC. Further randomized trials are warranted; however, additional strategies should be performed to reduce the substantially increased treatmentrelated modality due to late toxicities of esophagus. Author Disclosure: J. Chen: None. D. Li: None. T. Zhai: None. D.T. Chang: None. H. Guo: None. W. Zhang: None. L. Guo: None. M. Zhou: None. D. Li: None. C. Chen: None.
30 Comparison of Overall Survival for Esophageal Cancer Patients Treated With Neoadjuvant Proton or Photon Chemoradiation: A Multi-institutional Analysis K.W. Merrell,1 C.L. Hallemeier,1 S.E. James,1 N. Bhooshan,2 L. Wang,3 A.M. Correa,4 Z. Liao,4 P.F. Thall,4 R.U. Komaki,4 M. Suntharalingam,2 M.P. Mehta,2 R.J. Mehran,4 M.G. Haddock,1 M.D. Chuong,2 and S.H. Lin4; 1Mayo Clinic, Rochester, MN, 2University of Maryland School of Medicine, Baltimore, MD, 3University of Michigan, Ann Arbor, MI, 4MD Anderson Cancer Center, Houston, TX Purpose/Objective(s): Trimodality therapy with neoadjuvant chemoradiation and surgery is the treatment of choice for non-metastatic esophagus cancer. We evaluated the rates of survival and prognostic factors for patients receiving 3D-conformal radiation therapy (3D), intensity modulated RT (IMRT), and proton beam therapy (PBT) in a large, multiinstitutional pooled analysis. Materials/Methods: From January 2007 to July 2013, 582 patients with non-metastatic esophagus cancer underwent definitive treatment with chemoradiation and surgery at 3 major academic institutions. A total of 215 patients (37%) received 3D, 256 (44%) received IMRT, and 111 (19%) received PBT. The median RT dose was 50.4 Gy (range, 27e63) in 28 fractions (range, 15e30). The most frequent concurrent chemotherapy was oxaliplatin and 5-flourouracil (5FU) (25.7%, n Z 150) and cisplatin and 5FU (24%, n Z 141). Overall survival (OS) was estimated using the Kaplan-Meier method. Univariate (UVA) and multivariate analyses (MVA)
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were performed using step-wise Cox proportional hazards regression models. Results: The median patient age was 61 years (range, 21e88 years). Median follow up was 2.5 years (range, 0.2e7.6 years). Most patients were male (n Z 496, 85%). Tumor grade was 1 (1.6%), 2 (33.3%), or 3 (63.1%). Clinical T stage was T1 (1%), T2 (15%), T3 (83%), or T4 (1%). Most tumors were adenocarcinoma (n Z 537, 92%) and located in the distal esophagus (n Z 541, 93%). Clinically node-positive disease was observed in 379 (69%) patients. Median OS was 4.4 years for all patients and 3.3 years, 5.3 years, and not yet reached for 3D, IMRT and PBT, respectively. Patients treated with PBT had superior OS compared to 3D (P Z .003; HR [95% CI], 0.6 [0.4e0.8]) and IMRT (P Z .1; HR [95% CI], 0.7 [0.5e1.1]). Proton beam therapy was associated with superior OS compared to photon RT (P Z .03; HR [95% CI], 0.7 [0.5e0.96]). On MVA, significant predictors of OS included age (P Z .01) pathologic complete response (pCR) (P Z .001), tumor grade (P < .001) and clinical stage (P Z .04). Propensity score-matched analysis confirmed RT modality was not significantly associated with OS. Conclusion: Neoadjuvant PBT for esophagus cancer is associated with numerically and clinically relevant improvement in OS, an effect that loses statistical significance on MVA. The strongest predictors of OS were pCR and tumor grade. A prospective, randomized trial is warranted to compare neoadjuvant treatment with PBT and photon RT, with appropriate power to determine whether a statistically meaningful improvement in OS can be achieved. Author Disclosure: K.W. Merrell: None. C.L. Hallemeier: None. S.E. James: None. N. Bhooshan: None. L. Wang: None. A.M. Correa: None. Z. Liao: None. P.F. Thall: None. R.U. Komaki: None. M. Suntharalingam: None. M.P. Mehta: None. R.J. Mehran: None. M.G. Haddock: Speaker; Imedex medical education. Board member; ISIORT. M.D. Chuong: None. S.H. Lin: None.
(P < .001). A clinical nomogram containing the seven factors for the prediction of 5-year overall survival was created (c-index 0.66). The calibration curves showed well agreement between nomogram prediction and actual observation. Conclusion: A risk-adapted treatment approach can be applied for thoracic esophageal carcinoma after radical surgery using RPA categories and/or nomogram-based risk estimates. Postoperative irradiation could improve survival for high-risk patients. Prospective clinical trials of postoperative radiation are warranted for selective patients. Author Disclosure: S. Yu: None. Author Disclosure: Z. Xiao: None. W. Zhang: None.
31 A Clinical Nomogram and Recursive Partitioning Analysis to Determine Five-Year Survival in Patients With Thoracic Esophageal Carcinoma After Radical Surgery S. Yu,1 Z. Xiao,2 and W. Zhang3; 1Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China, 2Cancer Hospital, Chinese Academy of Medical Science, Peking Union Medical College, Beijing, China, 3Tianjin Cancer Hospital, Tianjin, China Purpose/Objective(s): This investigation defined patient populations at high, intermediate, and low-risk of death with thoracic esophageal carcinoma after radical surgery using clinical nomograms and recursive partitioning analysis (RPA). Materials/Methods: A retrospective review of 3,480 patients diagnosed with esophageal carcinoma in Chinese Academy of Medical Science Cancer Hospital from January 2004 to May 2009 was performed. A database compiling 1,119 patents with thoracic esophageal carcinoma after surgery, with or without postoperative radiation, was created. Logistic analysis was performed to identify factors to be included in a RPA to predict for 5-year survival. A 5-year survival clinical nomogram was conducted. The predictive accuracy was measured by concordance index (c-index). Results: Median follow-up time was 48.1 months for all the patients. Length of tumor, treatment modality, upper margin, T stage, lymph node metastatic ratio, differentiation, vascular carcinomatous thrombus were found to be statistically significant predictors of the 5-year overall survival. Recursive partitioning analysis classifications were defined as follows: low-risk (5-year survival: >50%): negative lymph node AND high/ intermediate differentiation; intermediate-risk (5-year survival 30e50%): negative lymph node and poor differentiation OR with positive lymph nodes but lymph node metastatic ratio (LNMR) 0.15 OR LNMR >0.15 and received postoperative irradiation; high-risk (5-year survival <30%): LMNR >0.15 and without postoperative irradiation. These classifications were highly statistically significant for overall survival
31.5 Neoadjuvant IMRT with Chemotherapy for Esophageal Cancer Allows Cardiac Sparing Without Increasing Postoperative Pulmonary Complications V.L. Patel,1 T. Millington,1 G.C. Sharp,1 A. Niemierko,1 T.I. Yock,1 N.C. Choi,1 T.S. Hong,2 D.J. Mathisen,1 H. Willers,1 and H.A. Gaissert1; 1 Massachusetts General Hospital, Boston, MA, 2Massachusetts General Hospital, Harvard Medical School, Boston, MA Purpose/Objective(s): The therapeutic ratio of intensity modulated radiation therapy (IMRT) in trimodality therapy for esophageal cancer is poorly defined. The purpose of this retrospective analysis was to analyze the association of IMRT parameters with postoperative pulmonary complications in a tertiary center of surgical excellence. Materials/Methods: We retrospectively reviewed our institutional surgical database to identify patients with distal and mid esophageal cancer treated 2001e2011. Patients were treated neoadjuvantly with conventional 2D, 3D conformal radiation therapy (3DCRT) or IMRT with concurrent chemotherapy at our institution and outside institutions. Intensity modulated radiation therapy was chosen to improve cardiac sparing. Radiation plans at our institution were reviewed to extract doses and normal tissue parameters. Resection was by Ivor Lewis, thoracoabdominal, or minimally invasive technique. Postoperative complications, including pulmonary complications (pneumonia, ARDS, reintubation), were recorded for 30 days. Fisher exact test, logistic regression, and multivariate analysis using stepwise backward-selection estimation, were used to determine associations between patient and treatment characteristics and pulmonary complications. The Mann-Whitney test was used to compare dosimetric indices between radiation modalities. Results: A total of 229 consecutive patients underwent trimodality therapy; thirty-day mortality was 1.3%, and the incidence of postoperative pulmonary complications was 15.3%. A subset of 63 patients received IMRT at our institution, and in 8 patients IMRT was combined with 3DCRT. Median radiation dose was 50.4 Gy (range, 45.0e51.8 Gy). Normal organ dosimetrics were: heart max dose Z 56.7 Gy, median V40 Z 9% (range, 0e84%); combined lungs mean dose Z 11 Gy, median V5 Z 59% (range, 26e98%) and V20 Z 20% (range, 0e45%). The incidence of postoperative pulmonary complications in our institutional cohort was 17.5% (P Z .5, compared to all other patients). No patient experienced radiation pneumonitis. The only treatment-associated predictor of pulmonary complications was use of combined 3DCRT/IMRT (5/8 complications) compared to IMRT only (6/55) in both univariate and multivariate analysis (P < .01). The incidence of pulmonary complications in patients with the highest quartile of lung V5 was 18.8% (V5 Z 75e98%) compared to 17.0% in all other patients (P Z 1.0). Conclusion: Intensity modulated radiation therapy for esophageal cancer achieved a median heart V40 that was several-fold lower than typically seen with 3DCRT. The low dose bath associated with IMRT, even with a lung V5 >75%, did not result in increased pulmonary complications in expert surgical hands. Our data support the use of IMRT, but without the addition of 3DCRT, in trimodality therapy of esophageal cancer.
29 Phase 2 Study of Simultaneous Modulated Accelerated Radiation Therapy Combined With Chemotherapy for Esophageal Squamous Cell Carcinoma: Early Outcomes J. Chen,1 D. Li,1 T. Zhai,1 D.T. Chang,2 H. Guo,1 W. Zhang,1 L. Guo,1 M. Zhou,1 D. Li,1 and C. Chen1; 1Cancer Hospital of Shantou University Medical College, Shantou, China, 2Stanford University, Stanford, CA Purpose/Objective(s): The outcomes for patients with esophageal cancer who underwent standard-dose radiation therapy are still disappointing. Rapid advances of radiation therapy techniques have provided potentials for radiation dose-escalation while maintaining sparing of critical structures. This phase 2 study aimed to determine the safety, feasibility and efficacy of simultaneous modulated accelerated radiation therapy (SMART) combined with chemotherapy for patients with esophageal squamous cell carcinoma (SCC). Materials/Methods: Patients with primary esophageal SCC, ECOG PS 0 w 2 without distant metastasis (except supraclavicular lymph node)
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were enrolled to receive definitive chemoradiation therapy using SMART. Radiation therapy consisted of 66 Gy at 2.2 Gy/fraction to gross tumor, and 54 Gy at 1.8 Gy/fraction to subclinical disease simultaneously in 30 fractions. Four cycles of chemotherapy including cisplatin (75 mg/m2, day 1) and 5fluorouracil 0.5/m2 (day 1 to 4) were administered to all patients during and after radiation therapy. The primary endpoints were Grade 3 acute and late toxicities, which were assessed using Common Terminology Criteria for Adverse Events Version 4.0. The secondary endpoints included local control and overall survival rates. Results: From August 2012 to April 2014, a total of 60 patients were accrued and one patient (1.7%) dropped out of the study. Among the 59 patients, there were 49 males and 10 females with a median age of 62 (range, 45e73 years). Tumors were stage II (n Z 22), stage III (n Z 26) and stage IV (n Z 11), according to AJCC 6th staging system. Only 1 patient (1.7%) did not complete the whole course of radiation therapy due to thrombocytopenia. Fifty-eight patients (98.3%) finished at least 2 cycles of concurrent chemotherapy. The median follow-up time was 19 months (range, 5e30 months) for all patients and 22 months (range, 10e30 months) for those still alive. The most common grade 3 acute toxicities were neutropenia (17%), followed by esophagitis (8.5%) and thrombopenia (5.1%). Ten patients (16.9%) developed Grade 3 late toxicities of esophagus (esophageal ulceration and fistula) and 2 of them (3.4%) died subsequently. Two patients (3.4%) had Grade 3 radiation pneumonitis. The 1 and 2-year local control, regional control, distant metastasis-free survival, disease progression-free survival, and overall survival rates were 94.3% and 90.4%, 90.7% and 88.3%, 83.8% and 78.8%, 74.7% and 62.4%, and 88.0% and 70.5%, respectively. Conclusion: Simultaneous modulated accelerated radiation therapy, combined with chemotherapy, showed a trend of significant improvements in local control and overall survival rates in patients with esophageal SCC. Further randomized trials are warranted; however, additional strategies should be performed to reduce the substantially increased treatmentrelated modality due to late toxicities of esophagus. Author Disclosure: J. Chen: None. D. Li: None. T. Zhai: None. D.T. Chang: None. H. Guo: None. W. Zhang: None. L. Guo: None. M. Zhou: None. D. Li: None. C. Chen: None.
30 Comparison of Overall Survival for Esophageal Cancer Patients Treated With Neoadjuvant Proton or Photon Chemoradiation: A Multi-institutional Analysis K.W. Merrell,1 C.L. Hallemeier,1 S.E. James,1 N. Bhooshan,2 L. Wang,3 A.M. Correa,4 Z. Liao,4 P.F. Thall,4 R.U. Komaki,4 M. Suntharalingam,2 M.P. Mehta,2 R.J. Mehran,4 M.G. Haddock,1 M.D. Chuong,2 and S.H. Lin4; 1Mayo Clinic, Rochester, MN, 2University of Maryland School of Medicine, Baltimore, MD, 3University of Michigan, Ann Arbor, MI, 4MD Anderson Cancer Center, Houston, TX Purpose/Objective(s): Trimodality therapy with neoadjuvant chemoradiation and surgery is the treatment of choice for non-metastatic esophagus cancer. We evaluated the rates of survival and prognostic factors for patients receiving 3D-conformal radiation therapy (3D), intensity modulated RT (IMRT), and proton beam therapy (PBT) in a large, multiinstitutional pooled analysis. Materials/Methods: From January 2007 to July 2013, 582 patients with non-metastatic esophagus cancer underwent definitive treatment with chemoradiation and surgery at 3 major academic institutions. A total of 215 patients (37%) received 3D, 256 (44%) received IMRT, and 111 (19%) received PBT. The median RT dose was 50.4 Gy (range, 27e63) in 28 fractions (range, 15e30). The most frequent concurrent chemotherapy was oxaliplatin and 5-flourouracil (5FU) (25.7%, n Z 150) and cisplatin and 5FU (24%, n Z 141). Overall survival (OS) was estimated using the Kaplan-Meier method. Univariate (UVA) and multivariate analyses (MVA)
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were performed using step-wise Cox proportional hazards regression models. Results: The median patient age was 61 years (range, 21e88 years). Median follow up was 2.5 years (range, 0.2e7.6 years). Most patients were male (n Z 496, 85%). Tumor grade was 1 (1.6%), 2 (33.3%), or 3 (63.1%). Clinical T stage was T1 (1%), T2 (15%), T3 (83%), or T4 (1%). Most tumors were adenocarcinoma (n Z 537, 92%) and located in the distal esophagus (n Z 541, 93%). Clinically node-positive disease was observed in 379 (69%) patients. Median OS was 4.4 years for all patients and 3.3 years, 5.3 years, and not yet reached for 3D, IMRT and PBT, respectively. Patients treated with PBT had superior OS compared to 3D (P Z .003; HR [95% CI], 0.6 [0.4e0.8]) and IMRT (P Z .1; HR [95% CI], 0.7 [0.5e1.1]). Proton beam therapy was associated with superior OS compared to photon RT (P Z .03; HR [95% CI], 0.7 [0.5e0.96]). On MVA, significant predictors of OS included age (P Z .01) pathologic complete response (pCR) (P Z .001), tumor grade (P < .001) and clinical stage (P Z .04). Propensity score-matched analysis confirmed RT modality was not significantly associated with OS. Conclusion: Neoadjuvant PBT for esophagus cancer is associated with numerically and clinically relevant improvement in OS, an effect that loses statistical significance on MVA. The strongest predictors of OS were pCR and tumor grade. A prospective, randomized trial is warranted to compare neoadjuvant treatment with PBT and photon RT, with appropriate power to determine whether a statistically meaningful improvement in OS can be achieved. Author Disclosure: K.W. Merrell: None. C.L. Hallemeier: None. S.E. James: None. N. Bhooshan: None. L. Wang: None. A.M. Correa: None. Z. Liao: None. P.F. Thall: None. R.U. Komaki: None. M. Suntharalingam: None. M.P. Mehta: None. R.J. Mehran: None. M.G. Haddock: Speaker; Imedex medical education. Board member; ISIORT. M.D. Chuong: None. S.H. Lin: None.
(P < .001). A clinical nomogram containing the seven factors for the prediction of 5-year overall survival was created (c-index 0.66). The calibration curves showed well agreement between nomogram prediction and actual observation. Conclusion: A risk-adapted treatment approach can be applied for thoracic esophageal carcinoma after radical surgery using RPA categories and/or nomogram-based risk estimates. Postoperative irradiation could improve survival for high-risk patients. Prospective clinical trials of postoperative radiation are warranted for selective patients. Author Disclosure: S. Yu: None. Author Disclosure: Z. Xiao: None. W. Zhang: None.
31 A Clinical Nomogram and Recursive Partitioning Analysis to Determine Five-Year Survival in Patients With Thoracic Esophageal Carcinoma After Radical Surgery S. Yu,1 Z. Xiao,2 and W. Zhang3; 1Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China, 2Cancer Hospital, Chinese Academy of Medical Science, Peking Union Medical College, Beijing, China, 3Tianjin Cancer Hospital, Tianjin, China Purpose/Objective(s): This investigation defined patient populations at high, intermediate, and low-risk of death with thoracic esophageal carcinoma after radical surgery using clinical nomograms and recursive partitioning analysis (RPA). Materials/Methods: A retrospective review of 3,480 patients diagnosed with esophageal carcinoma in Chinese Academy of Medical Science Cancer Hospital from January 2004 to May 2009 was performed. A database compiling 1,119 patents with thoracic esophageal carcinoma after surgery, with or without postoperative radiation, was created. Logistic analysis was performed to identify factors to be included in a RPA to predict for 5-year survival. A 5-year survival clinical nomogram was conducted. The predictive accuracy was measured by concordance index (c-index). Results: Median follow-up time was 48.1 months for all the patients. Length of tumor, treatment modality, upper margin, T stage, lymph node metastatic ratio, differentiation, vascular carcinomatous thrombus were found to be statistically significant predictors of the 5-year overall survival. Recursive partitioning analysis classifications were defined as follows: low-risk (5-year survival: >50%): negative lymph node AND high/ intermediate differentiation; intermediate-risk (5-year survival 30e50%): negative lymph node and poor differentiation OR with positive lymph nodes but lymph node metastatic ratio (LNMR) 0.15 OR LNMR >0.15 and received postoperative irradiation; high-risk (5-year survival <30%): LMNR >0.15 and without postoperative irradiation. These classifications were highly statistically significant for overall survival
31.5 Neoadjuvant IMRT with Chemotherapy for Esophageal Cancer Allows Cardiac Sparing Without Increasing Postoperative Pulmonary Complications V.L. Patel,1 T. Millington,1 G.C. Sharp,1 A. Niemierko,1 T.I. Yock,1 N.C. Choi,1 T.S. Hong,2 D.J. Mathisen,1 H. Willers,1 and H.A. Gaissert1; 1 Massachusetts General Hospital, Boston, MA, 2Massachusetts General Hospital, Harvard Medical School, Boston, MA Purpose/Objective(s): The therapeutic ratio of intensity modulated radiation therapy (IMRT) in trimodality therapy for esophageal cancer is poorly defined. The purpose of this retrospective analysis was to analyze the association of IMRT parameters with postoperative pulmonary complications in a tertiary center of surgical excellence. Materials/Methods: We retrospectively reviewed our institutional surgical database to identify patients with distal and mid esophageal cancer treated 2001e2011. Patients were treated neoadjuvantly with conventional 2D, 3D conformal radiation therapy (3DCRT) or IMRT with concurrent chemotherapy at our institution and outside institutions. Intensity modulated radiation therapy was chosen to improve cardiac sparing. Radiation plans at our institution were reviewed to extract doses and normal tissue parameters. Resection was by Ivor Lewis, thoracoabdominal, or minimally invasive technique. Postoperative complications, including pulmonary complications (pneumonia, ARDS, reintubation), were recorded for 30 days. Fisher exact test, logistic regression, and multivariate analysis using stepwise backward-selection estimation, were used to determine associations between patient and treatment characteristics and pulmonary complications. The Mann-Whitney test was used to compare dosimetric indices between radiation modalities. Results: A total of 229 consecutive patients underwent trimodality therapy; thirty-day mortality was 1.3%, and the incidence of postoperative pulmonary complications was 15.3%. A subset of 63 patients received IMRT at our institution, and in 8 patients IMRT was combined with 3DCRT. Median radiation dose was 50.4 Gy (range, 45.0e51.8 Gy). Normal organ dosimetrics were: heart max dose Z 56.7 Gy, median V40 Z 9% (range, 0e84%); combined lungs mean dose Z 11 Gy, median V5 Z 59% (range, 26e98%) and V20 Z 20% (range, 0e45%). The incidence of postoperative pulmonary complications in our institutional cohort was 17.5% (P Z .5, compared to all other patients). No patient experienced radiation pneumonitis. The only treatment-associated predictor of pulmonary complications was use of combined 3DCRT/IMRT (5/8 complications) compared to IMRT only (6/55) in both univariate and multivariate analysis (P < .01). The incidence of pulmonary complications in patients with the highest quartile of lung V5 was 18.8% (V5 Z 75e98%) compared to 17.0% in all other patients (P Z 1.0). Conclusion: Intensity modulated radiation therapy for esophageal cancer achieved a median heart V40 that was several-fold lower than typically seen with 3DCRT. The low dose bath associated with IMRT, even with a lung V5 >75%, did not result in increased pulmonary complications in expert surgical hands. Our data support the use of IMRT, but without the addition of 3DCRT, in trimodality therapy of esophageal cancer.