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A Comparison of Chemotherapy Regimens in the Treatment of Esophageal Cancer With Chemoradiation Therapy With or Without Surgery
E146
International Journal of Radiation Oncology Biology Physics
2351
high-grade toxicities is associated with inferior disease specific outcomes. RTOG 0529 demonstrated decreased high-grade toxicity and less treatment breaks using IMRT compared to RTOG 9811 historical controls. This is unlikely to be assessed in a randomized trial. We evaluated the impact of IMRT on treatment time and survival in SCC of the anal canal using population-based data from the NCDB. Materials/Methods: The NCDB was used to identify patients with anal cancer from 2004-2013. Inclusion criteria were: age 18; SCC; Stage IIII; no surgery; had radiation (RT) and chemotherapy; no palliation; all RT performed at same institution; total RT dose 36-59.4 Gy; RT to pelvis, nodes, and soft tissue only; RT fractions 25-40; RT time from 25-180 days; and IMRT or 3D only. RT total dose included target volume plus any boost. Long treatment time was defined as greater than the upper quartile (54 days). A high volume facility was defined as greater than the upper quartile for the frequency of anal cancer cases per reporting facility (18 cases). Statistical analyses were performed using logistic regression, KaplanMeier, and Cox proportional hazards. Results: There were a total of 6814 patients that met the inclusion criteria. The average length of RT for all patients was 48.9 days (range: 25-176) with a median total RT dose of 54 Gy (range: 36-59.4 Gy). 57.4% of patients were treated with 3D while 42.6% were treated with IMRT. 17.0% of patients treated with 3D had a long treatment time versus 8.6% treated with IMRT (p<0.0001). Those treated with IMRT had a significantly reduced risk of having a long treatment (OR Z 0.60; 95% CI Z 0.54-0.67; p < 0.001). After controlling for sex, race, comorbidity score, stage, income, and volume of center, IMRT still had a significantly reduced risk of having a long treatment time in multiple logistic regression analysis (OR Z 0.62; 95% CI Z 0.55-0.69; p<0.001). The unadjusted KaplanMeier plot demonstrated improved OS for IMRT vs 3D (p Z 0.0036). This method also demonstrated improved OS for females (p<0.0001), upper income earners (p<0.0001), and high volume facilities (p Z 0.0011). Using a multivariate Cox proportional hazards analysis, IMRT demonstrated a 15% decrease in hazard of death as compared to 3D after controlling for age, sex, comorbidity score, treatment time, race, income, stage, and volume of center (HR Z 0.85; 95% CI Z 0.76-0.95; p Z 0.0049). Conclusion: This population-based analysis suggests fewer prolonged treatment delays and improved overall survival with IMRT compared to conventional radiation therapy when treating SCCA. This is potentially explained by a decrease in high grade toxicity. Despite the limitations of the NCDB, these results reaffirm the rationale for conformal radiation modalities in the treatment of SCCA. Author Disclosure: J.K. Elson: None. J.R. Kharofa: None.
A Comparison of Chemotherapy Regimens in the Treatment of Esophageal Cancer With Chemoradiation Therapy With or Without Surgery M. Edmunds IV,1 E. McTyre,2 M. Soike,2 D.N. Ayala-Peacock,1,3 R.T. Hughes,2 Y. Zhou,1 R.F. Munden,1 R. Desnoyers,1 E. Levine,1 and A.W. Blackstock1; 1Wake Forest University Medical Center, WinstonSalem, NC, 2Wake Forest Baptist Medical Center, Winston-Salem, NC, 3 Vanderbilt University Medical Center, Nashville, TN Purpose/Objective(s): In this study we compare the efficacy and toxicity of chemotherapy regimens commonly used in the treatment of esophageal cancer with chemoradiotherapy (CRT) with or without esophagectomy. Materials/Methods: We reviewed records of 290 patients with histologically confirmed stage I to IVA esophageal cancer receiving CRT with or without resection with curative intent. For stratified comparisons of baseline and treatment variables by chemotherapy, chi-squared tests were performed for categorical variables, t-tests were performed for normally-distributed continuous variables, and Mann-Whitney U tests were performed for non-normal continuous and ordinal variables (including extent of pathologic response). Overall survival was estimated using the Kaplan-Meier method, with the logrank test performed for stratified outcomes. Incidence was estimated for local and distant failure, with Gray’s test performed for stratified outcomes. Results: Of 290 patients, 161 patients (55.5%) received CRT and 129 patients (44.5%) received trimodality therapy. Histology was adenocarcinoma in 214 patients (74.8%) and squamous cell carcinoma in 72 patients (25.2%). The majority of tumors were in the lower thoracic (121, 41.7%) and gastroesophageal junction (106, 36.6%) regions. One-hundred and twenty-five patients (46.1%) received cisplatin/5-FU, 66 patients (24.4%) received carboplatin/ paclitaxel, 31 patients (11.4%) received carboplatin/5-FU, 14 patients (5.2%) received xeloda, and 35 patients (12.9%) received other chemotherapy. Median radiotherapy dose was 50.4 Gy (IQR: 50.4-50.4 Gy). Weight loss during CRT was lower in patients receiving carboplatin/paclitaxel (median: 6.0 lb; 4.1% body weight) v cisplatin/5-FU (median: 11.0 lb; 6.6% body weight) (p Z 0.006). In trimodality patients, surgical complications occurred in 4.0% (1/25) of patients receiving carboplatin/paclitaxel v 21.1% (12/57) of patients receiving cisplatin/5-FU (p Z 0.11). Pathologic complete response with carboplatin/paclitaxel v cisplatin/5-FU was 36.4% (8/22) v 22.2% (12/54), partial response was 54.5% (12/22) v 46.3% (25/54), and stable/progressive disease was 9.1% (2/22) v 31.5% (17/54), p Z 0.03. Median overall survival for trimodality patients was 27.2 mo. (95% CI: 13.5-NA mo.) with carboplatin/ paclitaxel v 21.2 mo. (95% CI: 15.9-35.8 mo.) with cisplatin/5-FU (log-rank pvalue Z 0.91). Incidence of local failure in trimodality patients at two years was 4.8% with carboplatin/paclitaxel v 16.4% with cisplatin/5-FU (p Z 0.24). Incidence of distant failure in trimodality patients at two years was 59.6% with carboplatin/paclitaxel v 46.3% with cisplatin/5-FU (p Z 0.15). Conclusion: Carboplatin/paclitaxel chemotherapy was associated with improved pathologic response in trimodality patients and decreased weight loss in all patients, as compared to cisplatin/5-FU chemotherapy. There were no differences in overall survival, local failure, or distant failure by chemotherapy regimen. Author Disclosure: M. Edmunds: None. E. McTyre: None. M. Soike: None. D.N. Ayala-Peacock: Employee; Anesthesia Medical Group. ; NRG. R.T. Hughes: None. Y. Zhou: None. R.F. Munden: None. R. Desnoyers: None. E. Levine: ; Comprehensive Cancer Center. A. Blackstock: ; Wake Forest University Radiation Oncology, Comprehensive Cancer Center.
2352 IMRT Improves Survival and Reduces Treatment Time in Squamous Cell Carcinoma of the Anal Canal: A National Cancer Database Study J.K. Elson and J.R. Kharofa, Jr; University of Cincinnati, Cincinnati, OH Purpose/Objective(s): Chemoradiation with 5-FU and Mitomycin remains the standard of care in SCCA. Prolonged treatment time due to
2353 Is Higher Dose Radiation Beneficial As Part of a Neoadjuvant Chemoradiation Therapy Protocol for Resectable Esophageal Cancer? A Meta-analysis A.W. Awerbuch,1 S. Engel,1 O. Picado,2 D. Yakoub,2 and R. Yechieli3; 1 Department of Radiation Oncology, University of Miami Miller School of Medicine/Sylvester Comprehensive Cancer Center, Miami, FL, 2Division of Surgical Oncology at the Department of Surgery, University of Miami Miller School of Medicine/Sylvester Comprehensive Cancer Center, Miami, FL, 3Department of Radiation Oncology, University of Miami / Sylvester Comprehensive Cancer Center, Miami, FL Purpose/Objective(s): Neoadjuvant chemoradiation therapy (NCRT) for resectable esophageal carcinoma has improved survival rates in patients with locally advanced disease. However, the appropriate neo-adjuvant radiation dose is debated. This meta-analysis aims to evaluate if as part of a NCRT protocol, radiation dose affects survival in patients with locally advanced esophageal cancer. Materials/Methods: A comprehensive search of MEDLINE, EMBASE, PubMed, SCOPUS and the Cochrane database was conducted (1996-present). All randomized control trials of patients with esophageal carcinoma undergoing NCRT compared to surgery alone were included; study quality was assessed using CONSORT checklist. Pooled risk ratio along with the
International Journal of Radiation Oncology Biology Physics
2351
high-grade toxicities is associated with inferior disease specific outcomes. RTOG 0529 demonstrated decreased high-grade toxicity and less treatment breaks using IMRT compared to RTOG 9811 historical controls. This is unlikely to be assessed in a randomized trial. We evaluated the impact of IMRT on treatment time and survival in SCC of the anal canal using population-based data from the NCDB. Materials/Methods: The NCDB was used to identify patients with anal cancer from 2004-2013. Inclusion criteria were: age 18; SCC; Stage IIII; no surgery; had radiation (RT) and chemotherapy; no palliation; all RT performed at same institution; total RT dose 36-59.4 Gy; RT to pelvis, nodes, and soft tissue only; RT fractions 25-40; RT time from 25-180 days; and IMRT or 3D only. RT total dose included target volume plus any boost. Long treatment time was defined as greater than the upper quartile (54 days). A high volume facility was defined as greater than the upper quartile for the frequency of anal cancer cases per reporting facility (18 cases). Statistical analyses were performed using logistic regression, KaplanMeier, and Cox proportional hazards. Results: There were a total of 6814 patients that met the inclusion criteria. The average length of RT for all patients was 48.9 days (range: 25-176) with a median total RT dose of 54 Gy (range: 36-59.4 Gy). 57.4% of patients were treated with 3D while 42.6% were treated with IMRT. 17.0% of patients treated with 3D had a long treatment time versus 8.6% treated with IMRT (p<0.0001). Those treated with IMRT had a significantly reduced risk of having a long treatment (OR Z 0.60; 95% CI Z 0.54-0.67; p < 0.001). After controlling for sex, race, comorbidity score, stage, income, and volume of center, IMRT still had a significantly reduced risk of having a long treatment time in multiple logistic regression analysis (OR Z 0.62; 95% CI Z 0.55-0.69; p<0.001). The unadjusted KaplanMeier plot demonstrated improved OS for IMRT vs 3D (p Z 0.0036). This method also demonstrated improved OS for females (p<0.0001), upper income earners (p<0.0001), and high volume facilities (p Z 0.0011). Using a multivariate Cox proportional hazards analysis, IMRT demonstrated a 15% decrease in hazard of death as compared to 3D after controlling for age, sex, comorbidity score, treatment time, race, income, stage, and volume of center (HR Z 0.85; 95% CI Z 0.76-0.95; p Z 0.0049). Conclusion: This population-based analysis suggests fewer prolonged treatment delays and improved overall survival with IMRT compared to conventional radiation therapy when treating SCCA. This is potentially explained by a decrease in high grade toxicity. Despite the limitations of the NCDB, these results reaffirm the rationale for conformal radiation modalities in the treatment of SCCA. Author Disclosure: J.K. Elson: None. J.R. Kharofa: None.
A Comparison of Chemotherapy Regimens in the Treatment of Esophageal Cancer With Chemoradiation Therapy With or Without Surgery M. Edmunds IV,1 E. McTyre,2 M. Soike,2 D.N. Ayala-Peacock,1,3 R.T. Hughes,2 Y. Zhou,1 R.F. Munden,1 R. Desnoyers,1 E. Levine,1 and A.W. Blackstock1; 1Wake Forest University Medical Center, WinstonSalem, NC, 2Wake Forest Baptist Medical Center, Winston-Salem, NC, 3 Vanderbilt University Medical Center, Nashville, TN Purpose/Objective(s): In this study we compare the efficacy and toxicity of chemotherapy regimens commonly used in the treatment of esophageal cancer with chemoradiotherapy (CRT) with or without esophagectomy. Materials/Methods: We reviewed records of 290 patients with histologically confirmed stage I to IVA esophageal cancer receiving CRT with or without resection with curative intent. For stratified comparisons of baseline and treatment variables by chemotherapy, chi-squared tests were performed for categorical variables, t-tests were performed for normally-distributed continuous variables, and Mann-Whitney U tests were performed for non-normal continuous and ordinal variables (including extent of pathologic response). Overall survival was estimated using the Kaplan-Meier method, with the logrank test performed for stratified outcomes. Incidence was estimated for local and distant failure, with Gray’s test performed for stratified outcomes. Results: Of 290 patients, 161 patients (55.5%) received CRT and 129 patients (44.5%) received trimodality therapy. Histology was adenocarcinoma in 214 patients (74.8%) and squamous cell carcinoma in 72 patients (25.2%). The majority of tumors were in the lower thoracic (121, 41.7%) and gastroesophageal junction (106, 36.6%) regions. One-hundred and twenty-five patients (46.1%) received cisplatin/5-FU, 66 patients (24.4%) received carboplatin/ paclitaxel, 31 patients (11.4%) received carboplatin/5-FU, 14 patients (5.2%) received xeloda, and 35 patients (12.9%) received other chemotherapy. Median radiotherapy dose was 50.4 Gy (IQR: 50.4-50.4 Gy). Weight loss during CRT was lower in patients receiving carboplatin/paclitaxel (median: 6.0 lb; 4.1% body weight) v cisplatin/5-FU (median: 11.0 lb; 6.6% body weight) (p Z 0.006). In trimodality patients, surgical complications occurred in 4.0% (1/25) of patients receiving carboplatin/paclitaxel v 21.1% (12/57) of patients receiving cisplatin/5-FU (p Z 0.11). Pathologic complete response with carboplatin/paclitaxel v cisplatin/5-FU was 36.4% (8/22) v 22.2% (12/54), partial response was 54.5% (12/22) v 46.3% (25/54), and stable/progressive disease was 9.1% (2/22) v 31.5% (17/54), p Z 0.03. Median overall survival for trimodality patients was 27.2 mo. (95% CI: 13.5-NA mo.) with carboplatin/ paclitaxel v 21.2 mo. (95% CI: 15.9-35.8 mo.) with cisplatin/5-FU (log-rank pvalue Z 0.91). Incidence of local failure in trimodality patients at two years was 4.8% with carboplatin/paclitaxel v 16.4% with cisplatin/5-FU (p Z 0.24). Incidence of distant failure in trimodality patients at two years was 59.6% with carboplatin/paclitaxel v 46.3% with cisplatin/5-FU (p Z 0.15). Conclusion: Carboplatin/paclitaxel chemotherapy was associated with improved pathologic response in trimodality patients and decreased weight loss in all patients, as compared to cisplatin/5-FU chemotherapy. There were no differences in overall survival, local failure, or distant failure by chemotherapy regimen. Author Disclosure: M. Edmunds: None. E. McTyre: None. M. Soike: None. D.N. Ayala-Peacock: Employee; Anesthesia Medical Group. ; NRG. R.T. Hughes: None. Y. Zhou: None. R.F. Munden: None. R. Desnoyers: None. E. Levine: ; Comprehensive Cancer Center. A. Blackstock: ; Wake Forest University Radiation Oncology, Comprehensive Cancer Center.
2352 IMRT Improves Survival and Reduces Treatment Time in Squamous Cell Carcinoma of the Anal Canal: A National Cancer Database Study J.K. Elson and J.R. Kharofa, Jr; University of Cincinnati, Cincinnati, OH Purpose/Objective(s): Chemoradiation with 5-FU and Mitomycin remains the standard of care in SCCA. Prolonged treatment time due to
2353 Is Higher Dose Radiation Beneficial As Part of a Neoadjuvant Chemoradiation Therapy Protocol for Resectable Esophageal Cancer? A Meta-analysis A.W. Awerbuch,1 S. Engel,1 O. Picado,2 D. Yakoub,2 and R. Yechieli3; 1 Department of Radiation Oncology, University of Miami Miller School of Medicine/Sylvester Comprehensive Cancer Center, Miami, FL, 2Division of Surgical Oncology at the Department of Surgery, University of Miami Miller School of Medicine/Sylvester Comprehensive Cancer Center, Miami, FL, 3Department of Radiation Oncology, University of Miami / Sylvester Comprehensive Cancer Center, Miami, FL Purpose/Objective(s): Neoadjuvant chemoradiation therapy (NCRT) for resectable esophageal carcinoma has improved survival rates in patients with locally advanced disease. However, the appropriate neo-adjuvant radiation dose is debated. This meta-analysis aims to evaluate if as part of a NCRT protocol, radiation dose affects survival in patients with locally advanced esophageal cancer. Materials/Methods: A comprehensive search of MEDLINE, EMBASE, PubMed, SCOPUS and the Cochrane database was conducted (1996-present). All randomized control trials of patients with esophageal carcinoma undergoing NCRT compared to surgery alone were included; study quality was assessed using CONSORT checklist. Pooled risk ratio along with the