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Replicating Landoni’s Study in the Era of Chemotherapy: Postoperative or Radical Concurrent Chemoradiation Therapy in Early-Stage Cervical Cancer?
E300
International Journal of Radiation Oncology Biology Physics
2733
radiation dose of 45 Gy or 50 Gy or 50.4 Gy with no missing survival and boost radiation data. Median age at diagnosis was 63 years representing stage I (44%), II (21%) and III (35%) groups. Grade distribution was well differentiated (24%), moderately differentiated (41%), poorly differentiated (27%), undifferentiated (2%) or not available (6%). Race distribution was 88% White, 7% African-American (AA) and 5% others. The primary endpoint was overall survival (OS). Chi-square test for categorical variables and Kaplan-Meier survival analysis was performed with log-rank test for univariate and Cox regression for multivariate analyses (MVA). Results: Regional radiation dose was 45 Gy (N Z 10,237; 73%) and 50/ 50.4 Gy (N Z 3,762; 27%). Boost use was none (43%), beam radiation (14%) and brachytherapy (43%). Chemotherapy was used in 26% patients. Lower regional dose (45 Gy) was more likely to be used in patients receiving a boost (P < 0.001), African-Americans (P Z 0.033), recent years of diagnosis analyzed as quartiles of years (P<0.001) and in stage I vs stage III disease (P < 0.001). With a median follow up of 49 m (Range 0-119 m), the 5-year OS was better with use of 50/50.4 Gy when no boost was given (78.9% vs 75.6%, P < 0.001). In patients receiving a boost, there was a trend towards inferior OS with a higher regional dose (73.6% vs 76.6%, P Z 0.067). Results of MVA are shown in the table with retained statistical significance of WPRT dose in patients with no boost. Conclusion: With the limitations of analysis in a large national database, we observed a 3.3% benefit (95% CI: 0.7-5.1%) in 5-year OS for patients receiving WPRT to 50/50.4 Gy alone with no boost. In absence of randomized data, the choice of WPRT dose should be guided by clinical factors.
Replicating Landoni’s Study in the Era of Chemotherapy: Postoperative or Radical Concurrent Chemoradiation Therapy in Early-Stage Cervical Cancer? O.M.E.E. Mahmoud,1 W.R. Green,2 M. Gabel,3 D. Gibbon,4 A. Leiser,4 S. Isani,4 B. Cracchiolo,5 A.J. Khan,1 and M.A. Elshaikh6; 1Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 2Rutgers - Cancer Institute of New Jersey, New Brunswick, NJ, 3CINJ/RWJ, Trenton, NJ, 4 CINJ, New Brunswick, NJ, 5NJMS, Newark, NJ, 6Henry Ford Health System, Detroit, MI Purpose/Objective(s): Current guidelines recommend Surgery (S) and/or radiation therapy (RT) for early stage (IB-IIA) cervical carcinoma (CC) based on the pivotal Landoni et al randomized study published twenty years ago. Currently, combined Chemotherapy (CT) and RT (RT) in the postoperative (PO) or the definitive (DEF) setting is considered standard of care in high-risk features tumors. Using the National Cancer Data Base (NCDB), our study aims to compare the outcomes of PO_CRT versus DEF_CRT in the CT era. Materials/Methods: Between 2004 and 2013, 13338 CC patients were diagnosed with early stage (IB-IIA) node negative disease. CRT formed 80% of 3839 patients receiving DEF RT while PORT and PO_CRT were respectively delivered in 10% and 23% of 4083 patients undergoing radical hysterectomy. Chi-square test assessed the distribution of demographic, tumor and treatment variables in PO_CRT (1063) versus DEF_CRT (3075) groups. Kaplan-Meier method estimated overall survival (OS) Proportional hazards model estimated OS hazard ratios for prognostic factors including age, comorbidity, race, tumor size, grade, lymph node status, and histology. Results: With a median follow up period of 34 months, the cohort included 4138 patients with age at diagnosis ranging from 19 to 90 years (median 48 years). Larger tumor size, advanced age, higher grade and squamous histology were significantly more frequent in the DEF_CRT group. The 5-year OS was 80% vs. 68% (P<0.0001) favoring PO_CRT, which reduced mortality hazards ratio (HR) to 0.56 (95% confidence intervals (CI) 0.46-0.67) vs. DEF_CRT. On multivariate analysis, age older than 65 years (HR: 1.36; P Z 0.03), high Charlson comorbidity score (HR: 1.32; P Z 0.01) and high-grade (HR: 1.8; P Z 0.01), were significant predictors of poor outcome. PO_CRT (HR: 0. 59; P Z 0.005), and negative lymph nodes (HR: 0. 54; P Z 0.003), significantly predicted better survival. Adjusted HR using propensity score matching did not alter the results. Conclusion: In spite of the retrospective nature of the study and the covariates’ imbalance, our analysis hints that adjuvant chemoradiation therapy leads to better survival in early stage cervical carcinoma compared to definitive chemoradiation therapy. Further studies are warranted to establish this paradigm in the chemotherapy era. Author Disclosure: O.M. Mahmoud: None. W.R. Green: None. M. Gabel: None. D. Gibbon: None. A. Leiser: None. S. Isani: None. B. Cracchiolo: None. A.J. Khan: None. M.A. Elshaikh: None.
Abstract 2734; Table 1. Cox Regression Analysis (MVA) in patients with WPRT alone: Overall Survival
Variable
Reference Group
WPRT dose 50/50.4 Gy 45 Gy African-American race Non-African American/Others Increasing Stage Stage I Higher Charlson Score Continuous Variable Increasing Grade Grade not available Older Age Continuous variable Recent years of Quartiles of Diagnosis years (1998-2012)
95% Hazard Confidence Ratio Interval P Value 0.88 1.6
0.78-0.98 1.3-1.9
0.024 <0.001
1.4 1.3 1.09 1.055 0.94
1.3-1.5 1.2-1.5 1.06-1.1 1.05-1.06 0.89-0.99
<0.001 <0.001 <0.001 <0.001 0.047
Author Disclosure: P. Mohindra: Research Grant; Department of Radiation Oncology, University of Maryland School of Medicine. S.M. Bentzen: Leadership position; International Commission on Radiation Units and Measurements (ICRU). I. Giacomelli: None. D. Scartoni: None. D.M. Roque: None. G. Rao: None. N. Hanna: None. E.M. Nichols: None.
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Adjuvant Whole-Pelvic Radiation Therapy (WPRT) for Endometrioid Adenocarcinoma (EA): 45 Gy or 50/50.4 Gy? P. Mohindra,1 S.M. Bentzen,2 I. Giacomelli,2 D. Scartoni,2 D.M. Roque,2 G. Rao,2 N. Hanna,2 and E.M. Nichols2; 1University of Maryland Medical Center, Baltimore, MD, 2University of Maryland School of Medicine, Baltimore, MD
Rectal Balloon Use in Intensity Modulated Radiation Therapy Planning for Posthysterectomy Gynecological Malignancies Can Limit Rectal Dose and Toxicity as Well as Limit Vaginal Displacement C.C. Wu, T. Yanagihara, Y.R. Wuu, A. Jani, E.P. Xanthopoulos, A. Tiwari, and I. Deutsch; Department of Radiation Oncology, Columbia University Medical Center, New York, NY
Purpose/Objective(s): The recommended WPRT dose for adjuvant therapy of EA is 45-50.4 Gy. In absence of randomized data, decision regarding the choice of dose between 45 Gy vs 50/50.4 Gy is primarily guided by institutional practices. We seek to test the hypothesis that a doseresponse effect exists for adjuvant WPRT in EA. Materials/Methods: The National Cancer Database (NCDB) was queried to identify all women with EA, NOS histology. From a total of 273,841 cases diagnosed between the years 1998-2012, we identified 13,999 patients with NCDB analytic stage group I-III, who were treated to a regional
Purpose/Objective(s): Pelvic radiation therapy for gynecologic malignancies status post hysterectomy has traditionally been administered with a four field box technique. Multiple trials have shown the feasibility of using intensity modulated radiation therapy (IMRT) to minimize dose to normal tissue. While the use of rectal balloon (RB) has been investigated in the setting of IMRT for prostate cancer, little is known regarding its role in treating patients with gynecologic malignancies and IMRT in the posthysterectomy setting. We hypothesize that the use of a RB during
International Journal of Radiation Oncology Biology Physics
2733
radiation dose of 45 Gy or 50 Gy or 50.4 Gy with no missing survival and boost radiation data. Median age at diagnosis was 63 years representing stage I (44%), II (21%) and III (35%) groups. Grade distribution was well differentiated (24%), moderately differentiated (41%), poorly differentiated (27%), undifferentiated (2%) or not available (6%). Race distribution was 88% White, 7% African-American (AA) and 5% others. The primary endpoint was overall survival (OS). Chi-square test for categorical variables and Kaplan-Meier survival analysis was performed with log-rank test for univariate and Cox regression for multivariate analyses (MVA). Results: Regional radiation dose was 45 Gy (N Z 10,237; 73%) and 50/ 50.4 Gy (N Z 3,762; 27%). Boost use was none (43%), beam radiation (14%) and brachytherapy (43%). Chemotherapy was used in 26% patients. Lower regional dose (45 Gy) was more likely to be used in patients receiving a boost (P < 0.001), African-Americans (P Z 0.033), recent years of diagnosis analyzed as quartiles of years (P<0.001) and in stage I vs stage III disease (P < 0.001). With a median follow up of 49 m (Range 0-119 m), the 5-year OS was better with use of 50/50.4 Gy when no boost was given (78.9% vs 75.6%, P < 0.001). In patients receiving a boost, there was a trend towards inferior OS with a higher regional dose (73.6% vs 76.6%, P Z 0.067). Results of MVA are shown in the table with retained statistical significance of WPRT dose in patients with no boost. Conclusion: With the limitations of analysis in a large national database, we observed a 3.3% benefit (95% CI: 0.7-5.1%) in 5-year OS for patients receiving WPRT to 50/50.4 Gy alone with no boost. In absence of randomized data, the choice of WPRT dose should be guided by clinical factors.
Replicating Landoni’s Study in the Era of Chemotherapy: Postoperative or Radical Concurrent Chemoradiation Therapy in Early-Stage Cervical Cancer? O.M.E.E. Mahmoud,1 W.R. Green,2 M. Gabel,3 D. Gibbon,4 A. Leiser,4 S. Isani,4 B. Cracchiolo,5 A.J. Khan,1 and M.A. Elshaikh6; 1Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 2Rutgers - Cancer Institute of New Jersey, New Brunswick, NJ, 3CINJ/RWJ, Trenton, NJ, 4 CINJ, New Brunswick, NJ, 5NJMS, Newark, NJ, 6Henry Ford Health System, Detroit, MI Purpose/Objective(s): Current guidelines recommend Surgery (S) and/or radiation therapy (RT) for early stage (IB-IIA) cervical carcinoma (CC) based on the pivotal Landoni et al randomized study published twenty years ago. Currently, combined Chemotherapy (CT) and RT (RT) in the postoperative (PO) or the definitive (DEF) setting is considered standard of care in high-risk features tumors. Using the National Cancer Data Base (NCDB), our study aims to compare the outcomes of PO_CRT versus DEF_CRT in the CT era. Materials/Methods: Between 2004 and 2013, 13338 CC patients were diagnosed with early stage (IB-IIA) node negative disease. CRT formed 80% of 3839 patients receiving DEF RT while PORT and PO_CRT were respectively delivered in 10% and 23% of 4083 patients undergoing radical hysterectomy. Chi-square test assessed the distribution of demographic, tumor and treatment variables in PO_CRT (1063) versus DEF_CRT (3075) groups. Kaplan-Meier method estimated overall survival (OS) Proportional hazards model estimated OS hazard ratios for prognostic factors including age, comorbidity, race, tumor size, grade, lymph node status, and histology. Results: With a median follow up period of 34 months, the cohort included 4138 patients with age at diagnosis ranging from 19 to 90 years (median 48 years). Larger tumor size, advanced age, higher grade and squamous histology were significantly more frequent in the DEF_CRT group. The 5-year OS was 80% vs. 68% (P<0.0001) favoring PO_CRT, which reduced mortality hazards ratio (HR) to 0.56 (95% confidence intervals (CI) 0.46-0.67) vs. DEF_CRT. On multivariate analysis, age older than 65 years (HR: 1.36; P Z 0.03), high Charlson comorbidity score (HR: 1.32; P Z 0.01) and high-grade (HR: 1.8; P Z 0.01), were significant predictors of poor outcome. PO_CRT (HR: 0. 59; P Z 0.005), and negative lymph nodes (HR: 0. 54; P Z 0.003), significantly predicted better survival. Adjusted HR using propensity score matching did not alter the results. Conclusion: In spite of the retrospective nature of the study and the covariates’ imbalance, our analysis hints that adjuvant chemoradiation therapy leads to better survival in early stage cervical carcinoma compared to definitive chemoradiation therapy. Further studies are warranted to establish this paradigm in the chemotherapy era. Author Disclosure: O.M. Mahmoud: None. W.R. Green: None. M. Gabel: None. D. Gibbon: None. A. Leiser: None. S. Isani: None. B. Cracchiolo: None. A.J. Khan: None. M.A. Elshaikh: None.
Abstract 2734; Table 1. Cox Regression Analysis (MVA) in patients with WPRT alone: Overall Survival
Variable
Reference Group
WPRT dose 50/50.4 Gy 45 Gy African-American race Non-African American/Others Increasing Stage Stage I Higher Charlson Score Continuous Variable Increasing Grade Grade not available Older Age Continuous variable Recent years of Quartiles of Diagnosis years (1998-2012)
95% Hazard Confidence Ratio Interval P Value 0.88 1.6
0.78-0.98 1.3-1.9
0.024 <0.001
1.4 1.3 1.09 1.055 0.94
1.3-1.5 1.2-1.5 1.06-1.1 1.05-1.06 0.89-0.99
<0.001 <0.001 <0.001 <0.001 0.047
Author Disclosure: P. Mohindra: Research Grant; Department of Radiation Oncology, University of Maryland School of Medicine. S.M. Bentzen: Leadership position; International Commission on Radiation Units and Measurements (ICRU). I. Giacomelli: None. D. Scartoni: None. D.M. Roque: None. G. Rao: None. N. Hanna: None. E.M. Nichols: None.
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Adjuvant Whole-Pelvic Radiation Therapy (WPRT) for Endometrioid Adenocarcinoma (EA): 45 Gy or 50/50.4 Gy? P. Mohindra,1 S.M. Bentzen,2 I. Giacomelli,2 D. Scartoni,2 D.M. Roque,2 G. Rao,2 N. Hanna,2 and E.M. Nichols2; 1University of Maryland Medical Center, Baltimore, MD, 2University of Maryland School of Medicine, Baltimore, MD
Rectal Balloon Use in Intensity Modulated Radiation Therapy Planning for Posthysterectomy Gynecological Malignancies Can Limit Rectal Dose and Toxicity as Well as Limit Vaginal Displacement C.C. Wu, T. Yanagihara, Y.R. Wuu, A. Jani, E.P. Xanthopoulos, A. Tiwari, and I. Deutsch; Department of Radiation Oncology, Columbia University Medical Center, New York, NY
Purpose/Objective(s): The recommended WPRT dose for adjuvant therapy of EA is 45-50.4 Gy. In absence of randomized data, decision regarding the choice of dose between 45 Gy vs 50/50.4 Gy is primarily guided by institutional practices. We seek to test the hypothesis that a doseresponse effect exists for adjuvant WPRT in EA. Materials/Methods: The National Cancer Database (NCDB) was queried to identify all women with EA, NOS histology. From a total of 273,841 cases diagnosed between the years 1998-2012, we identified 13,999 patients with NCDB analytic stage group I-III, who were treated to a regional
Purpose/Objective(s): Pelvic radiation therapy for gynecologic malignancies status post hysterectomy has traditionally been administered with a four field box technique. Multiple trials have shown the feasibility of using intensity modulated radiation therapy (IMRT) to minimize dose to normal tissue. While the use of rectal balloon (RB) has been investigated in the setting of IMRT for prostate cancer, little is known regarding its role in treating patients with gynecologic malignancies and IMRT in the posthysterectomy setting. We hypothesize that the use of a RB during