The Role of Axillary Lymph Node Dissection versus Sentinel Lymph Node Dissection in Breast Cancer Patients with Clinical N2b-N3c Disease Who Receive Adjuvant Radiotherapy.

BACKGROUND: For breast cancer with advanced regional lymph node involvement, axillary lymph node dissection (ALND) remains the standard of care for staging and treating the axilla despite the presence of undissected lymph nodes. The benefit of ALND in this setting is unknown. OBJECTIVES: We sought to describe national patterns of care of axillary surgery and its association with overall survival (OS) among women with cN2b-N3c breast cancer who receive adjuvant radiotherapy. PATIENTS AND METHODS: We identified female patients with cN2b-N3c breast cancer from 2012 to 2017 from the National Cancer Database. Clinical and demographic information were analyzed using Wilcoxon rank sum and χ2 tests. Predictors of receipt of ALND and predictors of death were identified with multivariable logistic regression modeling. Inverse probability of treatment weighting was implemented to adjust for differences in treatment cohorts. The Kaplan-Meier method was used to evaluate OS. RESULTS: We identified 7167 patients. Of these, 922 (13%) received SLNB and 6254 (87%) received ALND; 7% were cN2b, 19% cN3a, 24% cN3b, 19% cN3c, and 31% cN3, not otherwise specified. Predictors of receipt of ALND were age 50-69 years [odds ratio (OR) 1.3, p < 0.01], cN3a (OR 7.6, p < 0.01), cN3b (OR 2.8, p < 0.01), and cN3c (OR 4.2, p < 0.01). Predictors of death included cN3c (OR 1.9, p < 0.01), age 70-90 years (OR 1.5, p = 0.01), and positive surgical margins (OR 1.5, p < 0.01). After cohort balancing, ALND was not associated with improved OS when compared with SLNB (HR 0.99, p = 0.91). CONCLUSIONS: ALND in patients with advanced nodal disease was not associated with improved survival compared with SLNB for women who receive adjuvant radiotherapy.

Multiagent induction chemotherapy followed by chemoradiation is associated with improved survival in locally advanced pancreatic cancer.

BACKGROUND: The role of chemoradiotherapy (CRT) in locally advanced pancreatic cancer (LAPC) is uncertain after multiple randomized clinical trials have yielded mixed results. The authors used the National Cancer Data Base (NCDB) to determine whether CRT yields a survival benefit compared with chemotherapy alone (CT). METHODS: Patients with nonmetastatic LAPC diagnosed during 2004 through 2014 were identified in the NCDB. Patients who received CT were compared with those who received CRT using chi-square analysis. Univariate and multivariate Cox regression analyses were used to compare demographic, clinical, and treatment characteristics that were predictive of survival. Propensity score matching and shared frailty analysis were done. Subgroup analyses were undertaken to examine patients who underwent pancreatectomy and cohorts of patients who received different CT or CRT regimens. RESULTS: In total, 8689 patients with LAPC were identified. CRT was associated with improved survival (median survival [MS], 13.5 months) compared with CT (MS, 10.6 months) on multivariate analysis (hazard ratio [HR], 0.80; P < .001). Induction chemotherapy before CRT (HR, 0.67; P < .001) and multiagent chemotherapy (HR, 0.72; P < .001) were also identified as independent predictors of survival compared with concurrent CRT and single-agent CT, respectively. Patients in the CRT group who received multiagent induction chemotherapy had superior MS and pancreatectomy rates (MS, 17.5 months; HR, 0.70; P < .001; pancreatectomy rate, 10%) compared with those who received multiagent CT alone (MS, 12.4 months; pancreatectomy rate, 3.3%). Patients who underwent pancreatectomy experienced improved survival (MS, 22 vs 10.6 months; HR, 0.39; P < .001). CONCLUSIONS: In this NCDB analysis, maximizing systemic chemotherapy before CRT improved survival compared with CT alone in patients with LAPC. Continued analysis of CRT in properly selected patients after maximized systemic therapy is needed. Cancer 2017;123:3816-24. © 2017 American Cancer Society.

Chemoradiation Therapy for Unresected Extrahepatic Cholangiocarcinoma: A Propensity Score-Matched Analysis.

BACKGROUND: Unresected extrahepatic cholangiocarcinoma (uEHCC) remains a deadly disease. Guidelines for uEHCC recommend either chemotherapy alone (CT) or chemoradiotherapy (CRT). This study used the National Cancer Database (NCDB) to compare outcomes for patients treated with CT and those who underwent CRT. METHODS: Patients with initially diagnosed non-metastatic uEHCC from 2004 to 2014 were identified. Using Chi square analysis, patients who underwent CT were compared with those who received CRT. Uni- and multivariate Cox regression analyses were used to compare characteristics related to survival. Propensity score matching and shared frailty analysis were undertaken to correct for baseline differences between the two groups. Additional analyses were performed to compare survival for the minority of patients who underwent surgery and advanced-stage patients. RESULTS: The study identified 2996 patients with uEHCC. Chemoradiation was associated with better survival (median survival [MS], 14.5 months; hazard ratio [HR] 0.84; p < 0.001) than CT alone (MS, 12.6 months). Induction of CT before CRT was associated with a trend toward decreased risk of death compared with concurrent CRT (HR 0.81; p = 0.051). For the patients able to undergo surgery after initial treatment, MS was 24.5 months (HR 0.38; p < 0.001) versus 12.2 months for those who had no surgery. For these patients, CRT also was associated with better survival (MS, 31.2 months; HR 0.66; p = 0.001) than CT (MS, 22.1 months). Positive margins at surgery yielded survival equivalent to that with no surgery. CONCLUSION: Although CRT may be associated with slightly better survival in uEHCC than CT alone, the majority of the benefit was observed for patients able to undergo eventual surgery.

Disparities in care for elderly women with endometrial cancer adversely effects survival.

PURPOSE: Elderly women with endometrial cancer are at increased risk of local recurrence and cancer-specific death compared to younger women. We sought to investigate adjuvant radiotherapy (RT) practice patterns and effects on survival in elderly women with endometrial cancer. METHODS: Women from the National Cancer Data Base (NCDB) with FIGO IA grade 3 to FIGO IVA endometrial cancer diagnosed from 2004-2013 were included. Chi square analysis was used to compare the elderly (80+) and non-elderly women (18-79) and women who received RT and those that did not. Univariate and multivariate logistic regression were used to determine predictors of receipt of oncologic surgery and adjuvant RT. Univariate and multivariate Cox survival analyses were performed to examine the effect of radiotherapy on survival. Propensity score matching and shared frailty analysis were done in the elderly cohort. RESULTS: We identified 48,871 women for analysis. Rates of oncologic surgery were higher in the women 80+ compared with rates of adjuvant RT (95% versus 34%). Rates of RT receipt were higher in non-elderly women (48% versus 34%, p<0.001). Age over 80 was a negative predictive factor (OR 0.62, p<0.001) for receipt of adjuvant RT and oncologic surgery (OR 0.81, p=0.03). Adjuvant RT was associated with a decreased risk of death in elderly (HR 0.79, p<0.001) and non-elderly women (HR 0.77, p<0.001). CONCLUSION: Endometrial cancer patients over age 80 have similar rates of oncologic surgery as younger women but are significantly less likely to receive adjuvant RT, and this negatively impacts their survival.

The Addition of Adjuvant Chemotherapy to Radiation in Early-Stage High-Risk Endometrial Cancer: Survival Outcomes and Patterns of Care.

OBJECTIVE: Early-stage high-risk endometrial cancer (HREC) treated with adjuvant radiotherapy (aRT) alone has been associated with an increased risk of distant relapse. The addition of chemotherapy to radiotherapy (aCRT) may benefit overall survival (OS). We investigated the patterns-of-care and OS benefit of aCRT in HREC by analyzing a large national registry. METHODS: Our query was limited to patients with the International Federation of Gynecology and Obstetrics stage IB and II HREC with either papillary serous, clear cell, or grade 3 adenocarcinoma, diagnosed between 2004 and 2012. Logistic and Cox regression analyses were utilized to identify predictors of aCRT use and OS, respectively. Survival analysis was performed with Kaplan Meier and log-rank methods. Propensity score matching was employed to decrease the potential influence of selection bias. RESULTS: A total of 11,746 patients were identified for analysis with 8206 (69.9%) receiving aCRT, and 3540 (30.1%) received aRT. Predictors of aCRT included International Federation of Gynecology and Obstetrics stage II (odds ratio [OR], 1.39; 95% confidence interval [CI], 1.22-1.57), papillary serous (OR, 9.44; 95% CI, 8.22-10.85) or clear cell (OR, 3.21; 95% CI, 2.59-3.97) histology, lymph nodes removed (OR, 1.48; 95% CI, 1.31-1.69), and receipt of brachytherapy alone (OR, 1.55; 95% CI, 1.36-1.78). Estimated 5-year OS was 75.2% for patients receiving aRT only and 79.2% for those receiving aCRT (P < 0.001). When compared with aRT, aCRT was associated with improved OS on multivariate (hazard ratio, 0.78; 95% CI, 0.61-0.99) analysis. A univariate shared-frailty Cox regression after propensity score matching revealed persistence of the OS benefit with aCRT (hazard ratio, 0.74; 95% CI, 0.65-0.84). CONCLUSIONS: The addition of adjuvant chemotherapy to radiation in HREC is associated with improved OS. Multiple demographic and clinical factors significantly influence the choice of adjuvant therapy in this setting.

Chemoradiation versus chemotherapy or radiation alone in stage III endometrial cancer: Patterns of care and impact on overall survival.

PURPOSE: We aimed to investigate the patterns-of-care and overall survival (OS) benefit of aCRT versus adjuvant monotherapy (aMT), defined as either chemotherapy or radiation alone, utilizing a large national registry of patients. PATIENTS AND METHODS: Adult patients with stage III endometrial adenocarcinoma diagnosed from 2004 to 2013 were included. Logistic and Cox regression modeling was used to identify factors predictive of receipt of aCRT and OS, respectively. Survival analysis was performed with Kaplan Meier and log-rank analysis. Propensity score matching and sensitivity analysis was performed to address selection bias and presence of potential confounding variables. RESULTS: A total of 21,027 patients were identified: 11,435 (54.4%) patients received aMT, while 9592 (45.6%) received aCRT. Utilization of aCRT increased over the study period (p<0.01). Factors predictive of receiving aCRT include private insurance (OR: 1.67, 95% CI: 1.30-2.14), Medicare (OR: 1.33, 95% CI: 1.01-1.75), FIGO stage IIIC disease (OR: 1.36, 95% CI: 1.19-1.54), lymphovascular space invasion (OR: 1.14, 95% CI: 1.03-1.27), and lymph node surgery performed (OR: 1.42, 95% CI: 1.15-1.74). Median survival in years for aCRT, RT, and CT was 10.3, 7.1, and 5.6, respectively (p<0.001). Compared to aMT, aCRT was associated with a decrease risk of death on multivariate analysis (HR: 0.62, 95% CI: 0.56-0.70). The benefit of aCRT over aMT persisted after propensity score matching. CONCLUSION: The use of aCRT for stage III endometrial cancer is increasing. Multiple clinical and demographic factors were predictive of aCRT use. When compared to chemotherapy or radiation alone, aCRT is associated with an OS benefit.

Brachytherapy improves survival in primary vaginal cancer.

PURPOSE: Prospective, randomized data does not exist to guide treatment in primary vaginal cancer (PVC). We evaluated the impact of brachytherapy on survival in women with PVC. METHODS AND MATERIALS: Women who received radiotherapy for PVC were identified using the Surveillance, Epidemiology, and End Result database. Two retrospective cohorts were created; women who received external beam radiotherapy (EBRT) alone and those who received brachytherapy (alone or in combination of EBRT). Nearest-neighbor propensity score matching was used to balance the groups according to measured covariates. Cox proportional hazard regression modeling was used to estimate the effect of receipt of brachytherapy on survival. RESULTS: Two thousand five hundred seventeen vaginal cancer patients were identified. Squamous cell carcinoma made up 75% of tumors. Median overall survival (OS) for patients receiving EBRT alone was 3.6years (95% CI, 3.0-4.2years) versus 6.1years (95% CI 5.2-7.2years) for patients receiving brachytherapy (p=<0.001). Cox proportional hazard model revealed decrease risk of death among patients that received brachytherapy in the matched cohort (HR 0.77; 95% CI 0.68-0.86). Brachytherapy reduced risk of death among patients in all stage groups. No patient demographic or tumor variables favored the use of EBRT alone. Brachytherapy was associated with a decreased risk of death for all FIGO stages. Brachytherapy benefited patients with squamous cell carcinoma (HR 0.80; 95% CI 0.70-0.92) and adenocarcinoma (HR 0.69; 95% CI 0.49-0.95). Tumors larger than 5cm had the greatest benefit from brachytherapy (HR 0.68; 95% CI 0.50-0.91). CONCLUSIONS: Brachytherapy should be encouraged for all suitable patients with PVC.

Analysis of Nonsurgical Treatment Options for Metastatic Rectal Cancer.

INTRODUCTION: Using a large national registry, we investigated patterns of care and overall survival (OS) for metastatic rectal cancer patients treated with chemotherapy or radiotherapy (RT), or with a multimodal approach. PATIENTS AND METHODS: Adult patients with metastatic rectal cancer who did not undergo resection diagnosed from 2004 to 2014 were included. Kaplan-Meier, log-rank, and Cox regression analyses were performed. RESULTS: We identified 2385 patients. Of these, 1020 patients (43%) received chemotherapy alone, 228 (10%) received RT alone, 850 (36%) received chemotherapy and RT, and 287 (12%) received no treatment. Receipt of chemotherapy alone increased over the study period, and receipt of chemoradiotherapy decreased (P < .01). The only factor predictive of receiving any RT on multivariate analysis was clinical stage T3 disease. Factors predictive of OS on multivariate analysis included receipt of chemotherapy, Hispanic race, income greater than $46,000, and presence of lung metastasis. The OS for patients treated with chemotherapy and RT was not significantly different than chemotherapy alone. Five-year OS with chemotherapy alone, RT alone, chemoradiotherapy, and no treatment were, respectively, 84%, 56%, 79%, and 46%. CONCLUSION: Metastatic rectal cancer patients with T3 tumors were more likely to receive RT. Local RT does not improve survival for patients with metastatic rectal cancer who do not also undergo surgery. The use of chemotherapy alone for metastatic rectal cancer is increasing, and chemotherapy is associated with higher OS compared to no treatment and RT alone. This remained true even in patients older than 80 years.

A zyxin head-tail interaction regulates zyxin-VASP complex formation.

Zyxin is an adhesion protein that regulates actin assembly by binding to VASP family members through N-terminal proline-rich motifs. Evidence suggests that zyxin's C-terminal LIM domains function as a negative regulator of zyxin-VASP complexes. Zyxin LIM domains access to binding partners is negatively regulated by an unknown mechanism. One possibility is that zyxin LIM domains mediate a head-tail interaction, blocking interactions with other proteins. Such a mechanism might prevent both zyxin-VASP complexes activity and LIM domain access. In this report, the effect of LIM domains on zyxin-VASP complex assembly is defined. We find that zyxin LIM domains associate with zyxin's VASP binding sites, preventing zyxin from binding to PKA-phosphorylated VASP. Unphosphorylated VASP overcomes the head-tail interaction, a result of a direct interaction with the LIM domain region. Zyxin, like a growing number of actin regulators, is controlled by intramolecular interactions.

Lymphovascular Invasion in Endometrial Cancer: Prognostic Value and Implications on Adjuvant Radiation Therapy Use.

OBJECTIVES: Lymphovascular space invasion (LVSI) is a known prognostic factor for endometrial carcinomas. However, LVSI as a determinant of treatment benefit has not been fully elucidated. METHODS AND MATERIALS: Data from the National Cancer Database for endometrial cancer from 2004 to 2012 was obtained. Univariate and multivariate analysis was performed to assess the impact of LVSI on overall survival (OS). Survival analysis was performed utilizing log-rank and Kaplan-Meier analyses. The difference in OS between external beam radiation therapy (EBRT) and vaginal brachytherapy (VBT) in LVSI-positive patients was analyzed with propensity score matching. RESULTS: A total of 32,150 patients with surgical stage I to III endometrial carcinomas were available for analysis with a median follow-up of 30 months. Twenty-nine percent were LVSI positive and received adjuvant radiotherapy (aRT) more often than if LVSI negative (57% vs. 37%). On multivariate analysis, LVSI (hazard ratio, 1.94; P<0.01) was associated with an increased risk of death. aRT improved OS for LVSI-negative patients (87% without aRT, 90% with aRT; P=0.006). aRT was particularly effective in LVSI-positive patients: all stages of LVSI-positive patients were associated with an OS benefit (P<0.01), whereas among LVSI-negative patients, only stage III benefited from aRT (P<0.01). After propensity score match, there was no OS difference between EBRT and VBT among LVSI-positive patients (hazard ratio, 1.15; P=0.44). CONCLUSIONS: LVSI is an independent prognostic factor in locoregional endometrial carcinomas. aRT benefited all stages of LVSI-positive patients, but only stage III of LVSI-negative patients. Among LVSI-positive patients, we did not find an OS difference between adjuvant EBRT versus VBT.

Does Early Chemotherapy Improve Survival in Advanced Endometrial Cancer?

OBJECTIVES: In endometrial cancer, the appropriate sequence of adjuvant chemotherapy (aCT) and adjuvant radiation therapy (aRT) is unclear. We aim evaluated whether early chemotherapy is associated with improved overall survival (OS) and cancer-specific survival (CSS). METHODS: Endometrial cancer patients that received aCT and aRT were selected from the SEER-Medicare database. Early chemotherapy was defined as receiving aCT before aRT, with or without additional aCT ("sandwich" regimens). All other patients received a full course of aRT before chemotherapy with or without concurrent chemotherapy. Univariate and multivariate Cox proportional hazards regression was utilized to assess the impact of clinical and demographic factors on OS. RESULTS: We selected 597 patients for analysis. Median age and was 72 years; 85% of patients were white. Overall, 68% of women had FIGO (International Federation of Gynecology and Obstetrics) stage III disease and 77% received 4 to 6 cycles of chemotherapy. Five-year OS (66.6% vs. 62.4%, P=0.46) and 5-year CSS (71.1% vs. 71.2%, P=0.88) was not significantly improved among those receiving early chemotherapy. In addition, early chemotherapy did not improve OS (hazard ratio [HR]=0.87; 95% confidence interval [CI]: 0.56-1.34, P=0.53) or CSS (HR=1.21; 95% CI: 0.82-1.79, P=0.34) on multivariate analysis. Compared with 1 to 3 cycles, receiving 4 to 6 (HR=0.48, 95% CI: 0.26-0.87, P=0.02), and ≥7 cycles (HR=0.42, 95% CI: 0.20-0.89, P=0.02) of chemotherapy was associated with improved OS. CONCLUSION: No differences in OS or CSS were noted among endometrial patients receiving early chemotherapy. However, the number of chemotherapy cycles was associated with prolonged survival.

Chemoradiation Versus Chemotherapy in Uterine Carcinosarcoma: Patterns of Care and Impact on Overall Survival.

OBJECTIVES: Uterine carcinosarcoma (UCS) is a rare and aggressive cancer with poor survival. Our purpose was to evaluate the patterns-of-care and overall survival (OS) benefit of adjuvant chemoradiation (aCRT) compared with adjuvant chemotherapy (aCT) among UCS patients. METHODS: A query was made in the National Cancer Database to identify patients with UCS diagnosed between 2004 and 2012. Factors predictive of OS were determined using univariate and multivariate Cox regression analysis, as well as Kaplan-Meier and log-rank analysis. Propensity-score matching was employed to decrease the potential influence of selection bias. RESULTS: A total of 3538 patients were identified for analysis, consisting of 1787 patients (50.5%) receiving aCT and 1751 (49.5%) receiving aCRT. The median age of patients was 65 years. The majority of patients in our cohort were white (68.6%), on Medicare insurance (47.9%), with >5 cm tumor size (59.9%), and received a lymph node surgery (87.9%). The following factors were predictive of aCRT use: undergoing lymph node surgery (odds ratio, 1.59, P=0.01), and FIGO stage II (odds ratio, 1.71, P=0.01). Median survival for the aCT and aCRT groups was 24 months and 31.3 months, respectively. When compared with aCT alone, aCRT was associated with a benefit in OS on multivariate analysis (hazard ratio, 0.65, P<0.01). CONCLUSIONS: When compared with aCT alone, the use of aCRT in UCS patients was associated with a significant OS benefit. Multiple demographic and clinical factors significantly influence the choice of adjuvant therapy in this setting.

Esthesioneuroblastoma: A Patterns-of-Care and Outcomes Analysis of the National Cancer Database.

BACKGROUND: The available literature to guide treatment decision making in esthesioneuroblastoma (ENB) is limited. OBJECTIVE: To define treatment patterns and outcomes in ENB according to treatment modality using a large national cancer registry. METHODS: This study is a retrospective cohort analysis of 931 patients with a diagnosis of ENB who were treated with surgery, radiation therapy, and/or chemotherapy in the United States between the years of 2004 and 2012. Log-rank statistics were used to compare overall survival by primary treatment modality. Logistic regression modeling was used to identify predictors of receipt of postoperative radiotherapy (PORT). Cox proportional hazards modeling was used to determine the survival benefit of PORT. Subgroup analyses identified subgroups that derived the greatest benefit of PORT. RESULTS: Primary surgery was the most common treatment modality (90%) and resulted in superior survival compared to radiation (P < .01) or chemotherapy (P < .01). On multivariate analysis, PORT was associated with decreased risk of death (hazard ratio [HR] 0.53, P < .01). PORT showed a survival benefit in Kadish stage C (HR 0.42, P < .01) and D (HR 0.09, P = .01), but not Kadish A (HR 1.17, P = .74) and B (HR 1.37, P = .80). Patients who received chemotherapy derived greater benefit from PORT (HR 0.22, P < .01) compared with those who did not (HR 0.68, P = .13). Predictors of PORT included stage, grade, extent of resection, and chemotherapy use. CONCLUSION: Best outcomes were obtained in patients undergoing primary surgery. The benefit of PORT was driven by patients with stages C and D disease, and by those also receiving chemotherapy.

Academic Facility Utilization and Survival Outcomes in Adult Head and Neck Sarcomas: An NCDB Analysis.

Objectives To investigate clinicopathologic and treatment factors associated with survival in adult head and neck sarcomas in the National Cancer Database (NCDB). To analyze whether treatment settings and therapies received influence survival outcomes and to compare trends in utilization via an aggregated national data set. Study Design Prospectively gathered data. Setting NCDB. Subjects and Methods The study comprised a total of 6944 adult patients treated for a head and neck sarcoma from January 2004 to December 2013. Overall survival (OS) was the primary outcome. Results Increased age and tumor size, nodal involvement, and poorly differentiated histology had significantly reduced OS ( P < .001). Angiosarcoma, malignant nerve sheath tumor, malignant fibrous histiocytoma, osteosarcoma, and rhabdomyosarcoma histologic subtypes had significantly reduced OS, while liposarcoma, chondrosarcoma, and chordoma had improved OS ( P < .001). Utilization of surgical therapy was associated with improved OS, while positive surgical margins were associated with treatment at a community-based cancer program and had reduced OS ( P < .001). On multivariate analysis, treatment with radiation and/or chemotherapy was not significantly associated with OS; however, primary treatment with definitive chemoradiotherapy had significantly reduced OS. Patients treated at academic/research cancer programs (n = 3874) had significantly improved 5- and 10-year OS (65% and 54%, respectively) when compared with patients treated at community-based cancer programs (n = 3027; 49% and 29%; P < .001). The percentage utilization of these programs (56% vs 44%) did not change over the study period. Conclusion For adult head and neck sarcomas, treatment at an academic/research cancer program was associated with improved survival; however, despite increasing medical specialization, the percentage utilization of these programs for this rare tumor remains constant.

The Role of Radiation in All Stages of Nodular Lymphocytic Predominant Hodgkin Lymphoma.

BACKGROUND: The goal of this study was to assess the survival differences seen in early-stage and advanced-stage nodular lymphocytic predominant Hodgkin lymphoma (NLPHL) based on treatment modality. PATIENTS AND METHODS: The National Cancer Database was queried to identify patients diagnosed with NLPHL between 2004 and 2012. Overall survival (OS) was determined using univariate and multivariate Cox regression analysis. Kaplan-Meier and log-rank analysis were used to estimate differences in OS between treatment groups. RESULTS: A total of 1968 patients were identified for analysis, consisting of stage I (40.4%), stage II (29.3%), stage III (22.3%), and stage IV (8.0%) disease. The median age of patients was 46 years. The following factors were predictive of radiotherapy (RT) omission in treatment: increasing age, black race, Medicare insurance, chemotherapy use, stage II to IV disease, and the presence of B-symptoms. On survival analysis, RT was associated with prolonged OS in all stages of NLPHL (50.1 vs. 42.4 months; P < .01). The OS benefit of RT persisted on multivariate analysis (hazard ratio, 0.37; P < .01). On subset analysis, RT was associated with prolonged OS in early disease (49.8 vs. 45.5 months; P < .01), whereas a trend towards an OS benefit was observed in advanced-stage (54.1 vs. 39.6 months; P = .06) NLPHL. Radiotherapy was also associated with prolonged OS among patients with B-symptoms (49.0 vs. 42.6 months; P < .01). CONCLUSION: The use of RT in NLPHL is less likely among those with advanced-stage disease and B-symptoms. However, we found RT to be associated with prolonged OS in all stages of NLPHL, including those with B-symptoms.

Brachytherapy Improves Survival in Stage III Endometrial Cancer With Cervical Involvement.

PURPOSE: To evaluate the survival benefit of adding vaginal brachytherapy (BT) to pelvic external beam radiation therapy (EBRT) in women with stage III endometrial cancer. METHODS AND MATERIALS: The National Cancer Data Base was used to identify patients with stage III endometrial cancer from 2004 to 2013. Only women who received adjuvant EBRT were analyzed. Women were grouped according to receipt of BT. Logistic regression modeling was used to identify predictors of receiving BT. Log-rank statistics were used to compare survival outcomes. Cox proportional hazards modeling was used to evaluate the effect of BT on survival. A propensity score-matched analysis was also conducted among women with cervical involvement. RESULTS: We evaluated 12,988 patients with stage III endometrial carcinoma, 39% of whom received EBRT plus BT. Women who received BT were more likely to have endocervical or cervical stromal involvement (odds ratios 2.03 and 1.77; P<.01, respectively). For patients receiving EBRT alone, the 5-year survival was 66% versus 69% with the addition of BT at 5 years (P<.01). Brachytherapy remained significantly predictive of decreased risk of death (hazard ratio 0.86; P<.01) on multivariate Cox regression. The addition of BT to EBRT did not affect survival among women without cervical involvement (P=.84). For women with endocervical or cervical stromal invasion, the addition of BT significantly improved survival (log-rank P<.01). Receipt of EBRT plus BT was associated with improved survival in women with positive and negative surgical margins, and receiving chemotherapy did not alter the benefit of BT. Propensity score-matched analysis results confirmed the benefit of BT among women with cervical involvement (hazard ratio 0.80; P=.01). CONCLUSIONS: In this population of women with stage III endometrial cancer the addition of BT to EBRT was associated with an improvement in survival for women with endocervical or cervical stromal invasion.

Outcomes and complications of radiation therapy in patients with familial adenomatous polyposis.

BACKGROUND: The outcomes, complications, and rates of secondary malignancies from radiation therapy (RT) are not known for patients with familial adenomatous polyposis (FAP). METHODS: We queried the Hereditary Gastrointestinal Cancer Registry (HGCR) for patients with FAP who received RT. Outcomes assessed included acute and late treatment toxicity and secondary malignancies. RESULTS: We identified 15 patients undergoing 18 treatment courses. Median follow-up was 3.1 years after RT. Treated sites included rectal cancer, desmoid, prostate cancer, breast cancer, melanoma, medulloblastoma, gastric cancer, and glioma. Secondary tumors occurred in two patients: a medulloblastoma was diagnosed in a patient treated for glioma, and a desmoid tumor was diagnosed in a patient treated for rectal cancer. All nine patients treated with intra-abdominal or pelvic RT had prior prophylactic proctocolectomies, yet only one patient experienced grade 3 gastrointestinal toxicity. Common Terminology Criteria for Adverse Events version 4 (CTCAE v4) toxicities were grade 1 in seven treatment courses (39%), grade 2 in five courses (28%), and grade 3 in two courses (11%). CONCLUSIONS: In this cohort, RT was well tolerated with adverse effects comparable with non-FAP patients. Secondary in-field tumors occurred in 2 of 15 patients and their increased risk in this cohort was likely due to prior predilection from FAP itself, although an increased role of RT cannot be ruled out.

Patterns of Care in Proton Radiation Therapy for Pediatric Central Nervous System Malignancies.

PURPOSE: Proton beam therapy (PBT) potentially allows for improved sparing of normal tissues, hopefully leading to decreased late side effects in children. Using a national registry, we sought to perform a patterns-of-care analysis for children receiving PBT for primary malignancies of the central nervous system (CNS). METHODS AND MATERIALS: Using the National Cancer Data Base, we identified pediatric patients with primary CNS malignancies that were diagnosed between 2004 and 2012. We used a standard t test for comparison of means and χ2 testing to identify differences in demographic and clinical characteristics. Univariate and multivariate logistical regression was applied to identify predictors of PBT use. RESULTS: We identified 4637 pediatric patients receiving radiation therapy from 2004 to 2012, including a subset of 267 patients treated with PBT. We found that PBT use increased with time from <1% in 2004 to 15% in 2012. In multivariate logistical regression, we found the following to be predictors of receipt of PBT: private insurance, the highest income bracket, younger age, living in a metropolitan area, and residing >200 miles from a radiation treatment facility (P<.05). CONCLUSIONS: We noted the proportion of children receiving PBT to be significantly increasing over time from <1% to 15% from 2004 to 2012. We also observed important disparities in receipt of PBT based on socioeconomic status. Children from higher-income households and with private insurance were more likely to use this expensive technology. As we continue to demonstrate the potential benefits of PBT in children, efforts are needed to expand the accessibility of PBT for children of all socioeconomic backgrounds and regions of the country.