Brachytherapy Should Not be Omitted When Treating Locally Advanced Neuroendocrine Cervical Cancer with Definitive Chemoradiation Therapy

International Journal of Radiation Oncology  Biology  Physics

E290

2710

Abstract 2708; Table 1. Cox Regression Analysis (MVA): Overall Survival 95% Confidence Interval

Variable

Reference Group

Hazard Ratio

Upfront Chemotherapy Positive margins African-American race Increasing Grade Stage III Higher Charlson Score Older Age

Upfront Radiotherapy

0.85

0.75-0.97

Negative margins Non-African American/Others Grade 1 Stage II Continuous Variable

1.9 1.7

1.6-2.2 1.4-2.1

<0.001 <0.001

1.6 1.3 1.2

1.5-1.8 1.1-1.7 1.1-1.3

<0.001 0.013 0.004

Continuous variable

1.04

1.03-1.04

<0.001

P Value 0.014

Measurements (ICRU). D. Scartoni: None. I. Giacomelli: None. G. Rao: None. D.M. Roque: None. N. Hanna: None. E.M. Nichols: None.

2709 Access to Health Care and Disparities in Cervical Cancer Diagnosis, Treatment, and Survival S. Acharya1 and P.W. Grigsby2; 1Washington University in St. Louis Department of Radiation Oncology, Saint Louis, MO, St. Louis, MO, 2 Washington University School of Medicine, St. Louis, MO Purpose/Objective(s): To determine the association of health care access, as measured by insurance status, with cervical cancer stage at diagnosis, treatment and survival in non-elderly patients in the United States. Materials/Methods: Patients with cervical cancer <65 years of age were identified from the National Cancer Data Base (NCDB; 2004 e 2013) and from the Surveillance, Epidemiology and End Results (SEER; 2007 e 2011) database. Multivariate logistic regression was used to identify predictors of early stage (FIGO stage I) vs. advanced stage (FIGO stage II-IV) disease at diagnosis and to identify factors influencing receipt of standard treatment, adjusting for age, histology, race/ethnicity, income, education, insurance, facility volume, distance to treatment facility, tumor size and FIGO stage. Prognostic factors affecting overall survival (OS) were evaluated using Kaplan Meier product-limit method and Cox proportional hazards. Results: A total of 54,151 women from NCDB (60.5% with private insurance, 27.2% with Medicaid, 12.3% without insurance) were identified. The adjusted odds of presenting with advanced stage disease approximately doubled for uninsured patients (Odds ratio [OR]: 2.02, 95% Confidence Interval [CI]: 1.91 e 2.14, P<0.001) and Medicaid patients (OR: 1.86, 95% CI: 1.78 e 1.94, P<0.001) compared to privately insured patients. For women with FIGO stage I disease, the adjusted odds of undergoing surgery approximately halved for uninsured (OR: 0.50, 95% CI: 0.46 e 0.55, P<0.001) and Medicaid patients (OR: 0.60, 95% CI: 0.56 e 0.64, P<0.001) compared to privately insured patients. For women with locally advanced disease, the adjusted odds of undergoing chemoradiation, including brachytherapy, also decreased for both uninsured (OR: 0.85, 95% CI: 0.73 e 0.96, P Z 0.012) and Medicaid patients (OR: 0.81, 95% CI: 0.73 e 0.90, P<0.001) compared to privately insured patients. With regard to survival, on multivariate analysis, non-privately insured patients experienced a higher risk of mortality compared to privately insured patients (Hazard Ratio [HR]: 1.30, 95% CI: 1.23 e 1.37, P<0.001). These findings were externally validated in a cohort of 29,595 women from the SEER database. Conclusion: Compared to privately insured patients, uninsured and Medicaid patients are more likely to present with advanced stage disease, less likely to undergo surgery for early stage disease or chemoradiation for locally advanced disease, and less likely to survive. Identifying and reducing barriers to health care delivery in this patient population is essential to ameliorating disparities in cancer care and survival. Author Disclosure: S. Acharya: None. P.W. Grigsby: None.

How Important Is Chemotherapy Timing and Treatment Duration in the Adjuvant Management of Cervical Cancer? O.M.E.E. Mahmoud,1 M. Gabel,2 S. Jhawar,3 D. Gibbon,4 B. Cracchiolo,5 A. Leiser,4 S. Isani,4 A.J. Khan,1 and M.A. Elshaikh6; 1Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 2CINJ/RWJ, Trenton, NJ, 3 Rutgers-Robert Wood Johnson Medical School/Cancer Institute of New Jersey, New Brunswick, NJ, 4CINJ, New Brunswick, NJ, 5NJMS, Newark, NJ, 6Henry Ford Health System, Detroit, MI Purpose/Objective(s): Several studies illustrated inferior disease-free and overall survival (OS) precipitated by overall treatment time (OTT) prolongation during definitive chemoradiation therapy (CRT) of Cervical cancer (CC) a disease characterized by rapid cellular proliferation rate. In the adjuvant setting, data on the relative importance of treatment duration and/or CRT timing are scarce. Using the National Cancer Data Base (NCDB), we aim to evaluate the impact of these treatment variables on OS outcomes in the postoperative CRT setting. Materials/Methods: The analysis included non-metastatic CC patients who underwent hysterectomy followed by adjuvant CRT from 2004 to 2013. Time variables such as surgery to CRT start interval, OTT (from CRT start to end dates) and package time (from diagnosis date to CRT end date) were divided each into two groups using 6, 7 weeks and 12 weeks cut points, respectively. CRT timing variable was defined as optimum (same start date), 1 week, or more than 1 week if CT and RT start dates coincided, separated by 1 week or more than one week apart, respectively. KaplanMeier method estimated OS. Proportional hazards model estimated OS hazard ratios for other prognostic factors including age, comorbidity, race, stage, tumor size, grade and histology, lymph node status. Results: The analysis comprised 8226 patients with age at diagnosis ranging from 18 to 90 years (median 46 years). High-Grade, squamous histology and tumor 4 cm or larger formed 53%, 69% and 35% of the cohort, while 26% and 36% had positive surgical margins and lymph nodes, respectively. At median follow up period of 46 months, the 5-year OS was 75% (95% confidence interval (CI): 74.2%-76.5%). On Univariate analysis (UVA), OTT (hazards ratio (HR): 1.36; P<0.001) and package time (HR: 1.23; P<0.001) respectively exceeding 7 and 12 weeks and/or radiation therapy (RT) and chemotherapy (CT) start dates more than 1 week apart (HR: 1.39; P<0.001) were associated with inferior survival HR. Interval from surgery to CRT was not significant on UVA. On multivariate analysis, high comorbidity score, large tumor, high grade, OTT more than 7 weeks, treatment package time exceeding 12 weeks and CT/RT start more than one week apart were significant predictor of inferior survival. Conclusion: Our analysis suggests that prolongation of the treatment time beyond 7 weeks is detrimental even in the adjuvant setting. Concurrent administration of CT and RT is essential for maximum radiosensitization that translates in better treatment outcomes. Author Disclosure: O.M. Mahmoud: None. M. Gabel: None. S. Jhawar: None. D. Gibbon: None. B. Cracchiolo: None. A. Leiser: None. S. Isani: None. A.J. Khan: None. M.A. Elshaikh: None.

2711 Brachytherapy Should Not be Omitted When Treating Locally Advanced Neuroendocrine Cervical Cancer with Definitive Chemoradiation Therapy T.P. Robin,1 A. Amini,2 K. Behbakht,3 and C.M. Fisher1; 1Department of Radiation Oncology, University of Colorado Cancer Center, Aurora, CO, 2 Department of Radiation Oncology, University of Colorado Denver, Aurora, CO, 3Department of Gynecologic Oncology, University of Colorado Cancer Center, Aurora, CO Purpose/Objective(s): Neuroendocrine cervical cancer is a rare malignancy with a poor prognosis, yet there is a paucity of data to guide treatment decisions when managing patients with this disease. Specifically, there is little data to aid practitioners in deciding if there is added value to

Volume 96  Number 2S  Supplement 2016 brachytherapy given the additional time, cost, discomfort, and toxicity to patients. Materials/Methods: We utilized the National Cancer Database (NCDB) to identify women with locally advanced neuroendocrine cervical cancer treated with definitive chemoradiation therapy to determine if the addition of brachytherapy improves outcomes in this disease. We also assessed outcomes based on chemotherapy timing in this cohort. Results: We identified 109 patients with locally advanced neuroendocrine cervical cancer that were treated with definitive chemoradiation therapy between 2004 and 2012 and had complete datasets necessary for analysis. There was a substantial improvement in overall survival when brachytherapy was administered in addition to external beam radiation therapy in this population. The addition of brachytherapy compared with external beam radiation therapy alone was associated with a greater than doubling of the median survival of 48.6 versus 20.0 months, respectively. The substantial overall survival benefit associated with brachytherapy versus external beam radiation therapy alone was also observed in multivariate analysis accounting for additional relevant variables including age, race, comorbidity score, year of diagnosis, and stage (HR Z 0.403, 95% CI 0.223-0.730, P Z 0.003). Thirty-five percent of patients received neoadjuvant chemotherapy and 65% of patients received chemotherapy started concurrently with radiation. We observed no difference in overall survival for patients treated with neoadjuvant chemotherapy compared with the group that received chemotherapy started concurrently with radiation (HR 0.888, P Z 0.665). Conclusion: Brachytherapy should be considered an essential component of definitive chemoradiation therapy for the treatment of neuroendocrine cervical cancer. Chemotherapy timing, whether neoadjuvant or concurrent regimens, did not supplant the overall survival benefit of brachytherapy in this patient cohort derived from the NCDB. Author Disclosure: T.P. Robin: None. A. Amini: None. K. Behbakht: None. C.M. Fisher: None.

2712 Utilization of Adjuvant Chemotherapy, Radiation Therapy, or Combined Modality Therapy and the Impact on Survival for Uterine Carcinosarcoma A.T. Wong,1,2 D. Schwartz,1,2 A. Lee,1,2 M. Shao,1,2 P.Y. Han,2 and D. Schreiber1,2; 1Veterans Affairs NY Harbor Healthcare System, Brooklyn, NY, 2SUNY Downstate Medical Center, Brooklyn, NY Purpose/Objective(s): Clinical outcomes for patients with uterine carcinosarcoma are poor following surgical management alone. Adjuvant therapies including chemotherapy (CT) and/or radiation therapy (RT) have been previously investigated, but the optimal management of this disease remains controversial. The purpose of this study was to analyze the patterns of utilization of adjuvant CT and RT and to assess the impact on survival of each of these treatment regimens using the National Cancer Data Base (NCDB). Materials/Methods: We identified patients in the NCDB diagnosed with non-metastatic uterine carcinosarcoma who had undergone total abdominal hysterectomy/bilateral salpingo-oophorectomy between 2004 and 2011. We excluded patients if they survived <4 months after diagnosis. Data regarding CT and RT utilization were collected. Kaplan-Meier analysis was performed to compare overall survival (OS). We compared OS between patients receiving RT and those not receiving RT as well as OS between patients receiving CT and those not receiving CT. We further compared OS between patients that received no additional therapy, RT alone, CT alone, and both CT and RT. Multivariable analysis (MVA) was performed using Cox proportional hazards modeling to evaluate the effect of covariates on OS. Results: A total of 5,006 patients were included, of whom 2,199 patients (43.9%) received RT and 2,146 (42.9%) received CT. Of those receiving CT, 1,010 (47%) also received RT. Median age was 67 years (IQR 60-70 years). Median follow-up was 28.4 months (IQR 15.2-52.1 months). Adjuvant RT was associated with significantly improved OS (5-year OS 54.3% with RT vs. 45.2% without RT, P<0.001) and adjuvant CT was also

Poster Viewing E291 associated with improved OS (5-year OS 55.0% with CT vs. 45.6% without CT, P<0.001). Five-year OS was highest among patients receiving both CT and RT (62.1%) compared to 44.7%, 47.1%, and 46.5% for patients receiving no additional therapy, RT alone, and CT alone, respectively. Combined modality CT and RT was associated with improved survival compared to all other subgroups (P<0.001) on pairwise comparison. On MVA, combination CT and RT (HR for death 0.50, 95% CI 0.44-0.57, P<0.001) and CT alone (HR 0.77, 95% CI 0.69-0.87, P<0.001) were significantly associated with improved OS whereas RT alone was not (HR 0.91, 95% CI 0.81-1.01, P Z 0.08). Conclusion: Combination therapy with CT and RT was associated with the highest survival rate. However, survival remains relatively poor despite combined modality therapy and more efficacious therapies are needed for the management this aggressive disease. Author Disclosure: A.T. Wong: None. D. Schwartz: None. A. Lee: None. M. Shao: None. P.Y. Han: None. D. Schreiber: None.

2713 Long-Term Outcomes of Carbon Ion Radiation Therapy for Locally Advanced Squamous Cell Carcinoma of the Uterine Cervix N. Okonogi,1 M. Wakatsuki,1 S. Kato,2 S. Shiba,1,3 H. Kiyohara,3 K. Karasawa,4 T. Ohno,5 T. Nakano,5 T. Kamada,6 and M. Shozu7; 1 National Institute of Radiological Sciences, Chiba, Japan, 2Saitama Medical University International Medical Center, Saitama, Japan, 3 Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Japan, 4Department of Radiation Oncology, Tokyo Women’s Medical University, Tokyo, Japan, 5Gunma University Heavy Ion Medical Center, Maebashi, Japan, 6Research Center Hospital for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan, 7Department of Reproductive Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan Purpose/Objective(s): To evaluate the long-term outcomes of carbon-ion radiation therapy (C-ion RT) for patients with locally advanced cervical squamous cell carcinoma (SqCC) in two prospective phase I/II studies. Materials/Methods: The eligibility criteria of the clinical trials were; (i) previously untreated histologically proven SqCC, (ii) tumor size >4 cm, and (iii) FIGO stage IIB, III, or IVA disease. Patients were excluded if they had severe pelvic infection, metastatic lesion or active double cancer. Thirty-six patients with locally advanced cervical SqCC were treated with C-ion RT in two dose escalation studies. Between December 1997 and January 2000, 14 patients were treated with a total dose of 68.8 or 72.8 Gy (RBE)/24 fractions (fr.); 44.8 Gy (RBE)/16 fr. to the whole pelvis and an additional 24.0 or 28.0 Gy (RBE)/8 fr. to the cervical tumor in the first study. Then, between April 2000 and January 2006, 22 patients were treated with a total dose of 64.0 to 72.0 Gy (RBE)/20fr.; 39 Gy (RBE)/13 fr. to whole pelvis, 15 Gy (RBE)/5 fr. to whole uterus and parametrium, and 10-18 Gy (RBE)/2 fr. to the cervical tumor, while the dose to all gastro-intestinal (GI) tracts was strictly limited to <60 Gy (RBE) in the second study. Local control (LC), disease free survival (DFS), and overall survival (OS) rates were calculated by the Kaplan-Meier method. Late toxicity was graded according to the RTOG/EORTC late radiation morbidity scoring scheme. Results: The median follow-up period was 103 months for surviving patients, 199 months in maximal length. Median age at the diagnosis was 57 years olds (range; 31-80). One patient had Stage II, 28 had Stage IIIB, and 8 had Stage IVA disease. Eighteen out of the 36 patients had pelvic lymph node metastases. Median tumor size was 6.5 cm (range, 4.2-12.0 cm). All patients completed the treatment schedule, 10 patients developed local recurrences within 2 years after the treatment and 23 patients were dead at the most recent follow-up; 18 patients died from cervical cancer, 2 died from other malignancies, the rest 3 died from non-malignant diseases. The 10-years LC, DFS, and OS rate was 72%, 49%, and 52%, respectively. The 10-year LC rates were 92% and 61% for the patients delivered a total dose of 72.0-72.8 Gy (RBE) and 64.0-68.8 Gy (RBE) to cervical tumor. Grade 2 late complication was found in 9 patients (25%); 3 with rectum, 5 with bladder, 1 with small intestine, and 1 with bone (1 patient showed both