Objective: To evaluate whether hypofractionated radiotherapy (HF-RT) in node-negative intact breast cancer significantly increased after guideline updates, trial publications, and COVID-19. Methods: Patients with node-negative breast cancer undergoing lumpectomy and adjuvant RT were identified in the National Cancer Database. Receiving ≥25 and <50 Gy in 5-20 fractions defined HF-RT. Receiving 50 to 66 Gy in >20 fractions defined conventional RT (CF-RT). Patient characteristics were compared with X 2 testing. Joinpoint analysis identified when fractionation significantly changed. Variables associated with HF-RT were identified by univariate and multivariate (MVA) logistic regression. Two-sided P -value <0.05 was significant. Results: Patients meeting criteria totaled 236,336; 54.8% received CF-RT and 45.2% HF-RT. HF-RT and 5-fraction RT significantly increased after 2015 and 2019, respectively ( P <0.05). On MVA, HF-RT was positively associated with: age older than or equal to 65 years (OR 2.14, P <0.001); private insurance (OR 1.27, P =0.03); treatment in Midwest (OR 1.66, P <0.001) or Western United States (US) (OR 3.77, P <0.001); distance ≥50 miles (OR 1.16, P =0.001); later year of diagnosis (OR 1.44, P <0.001); and partial breast irradiation (OR 2.08, P <0.001). HF-RT was negatively associated with: community (OR 0.49, P <0.001) or integrated network (0.55, P <0.001) centers; grade 2 (OR 0.83, P <0.001) or 3 (OR 0.49, P <0.001), hormone receptor negative (OR 0.66, P <0.001), and HER2+ (OR 0.74, P <0.001) disease; positive surgical margins (OR 0.61, P <0.001); and presence of lympho-vascular invasion (OR 0.86, P <0.001). Conclusions: HF-RT in node-negative intact breast cancer increased after 2015, coinciding with US and European guideline updates. Five-fraction RT increased after 2019, coinciding with COVID-19 and FAST-Forward trial results.

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. 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. 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. We identified 7167 patients. Of these, 922 (13

A tumor bed boost is commonly implemented in HER2-positive breast cancer patients undergoing breast-conserving surgery and adjuvant radiation. This data supports previous retrospective and post-hoc trial analyses in omitting the tumor bed boost and treating patients who will receive adjuvant systemic therapy with whole breast radiation alone, provided that the patient receives HER2-directed therapy.

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.

Therapeutic applications for radiation therapy followed quickly from the discovery of X-rays by Roentgen in 1895. The first radiation treatment is credited to Grubbe, who reported the external beam treatment of breast cancer in 1896. Application to gynaecological cancers was almost immediate. However, the limited penetrating ability of the low-energy radiation of early X-ray tubes and isotopes was a major limitation. Consequently, brachytherapy and near-contact external beam therapy were preferred for gynaecological cancer until the advent of cobalt-60—the first source of a penetrating beam of megavoltage photons with a high dose rate, long half-life, and reasonable cost. This led to cobalt-60 machines becoming the most widely utilized treatment machine from the 1950s to 1970s. Radar research during World War II dramatically improved microwave technology. Linear accelerator-based machines (linacs) applied these advances to use microwaves to accelerate electrons onto a tungsten target and emit a fraction of their kinetic energy as mega-electron volt energy X-rays. The emitted X-rays are collimated into a beam and directed towards the patient. Advantages of linacs over cobalt-60 include higher dose rates, sharper beam edges, higher energies, and simplified radiation protection. This chapter describes the basic principles of radiotherapy and the role of radiotherapy in the management of gynaecological cancers, including cervix cancer, uterine cancer, and rarer tumours such as those arising from vaginal, vulvar, and ovarian cancers.

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.

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.

Purpose Radiation therapy (RT) may work synergistically with cancer immunotherapies but clinical trial data is needed to validate this paradigm. We isolated the portfolio of trials that investigate the primary immunomodulatory properties of RT and examined recent trends in clinical trials that combine immunotherapy and RT (ITRT). MethodsWe queried clinicaltrials.gov for trials initiated since 2002 using both radiation and immunotherapy as mandated interventions. We designated the trials that examine the specific aspects of RT or its abscopal properties as "Primary RT Immunomodulation" trials. Chi-squared analysis determined differences between primary RT immunomodulation trials and those that incorporate RT as a secondary intervention. Joinpoint regression modeling determined the rate of change of the introduction of new trials over time. ResultsOne hundred and ninety trials met inclusion criteria. Targeted immunostimulatory agents, including checkpoint inhibitors, were the most common immunotherapy (n = 79 [41.6%]). Sixty-six (34.7%) trials included RT as the primary intervention, with 50 (75.6%) of these utilizing stereotactic body radiation (SBRT). All ITRT trials increased at a rate of 14.8% per year. Primary RT immunomodulation trials increased at a rate of 26.8% per year. Primary RT immunomodulation trials were more likely to utilize targeted immunostimulatory agents (p < 0.01), and SBRT (p < 0.01), and more likely to involve metastatic sites (p < 0.01). The number of ITRT studies increased drastically in the latest two years of the study. ConclusionThe number of new ITRT clinical trials is increasing rapidly. This increase in quantity may improve the clinical application of the immunomodulatory properties of RT.

We aimed to investigate the patterns of care and overall survival (OS) for metastatic rectal cancer patients treated with chemotherapy, radiation therapy (RT), or with a multimodality approach, utilizing a large national registry of patients.

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.

Objectives We investigated the effect of neoadjuvant versus adjuvant chemoradiotherapy on overall survival as well as the impact of demographic and clinical factors for the selection of each approach utilizing the National Cancer Data Base. Methods Adult patients with stage II and stage III adenocarcinoma of the rectum diagnosed from 2004 to 2013 were included. Chi-square analysis was used to compare demographic variables and clinical stage between the patients receiving neoadjuvant and adjuvant chemoradiotherapy. Univariate and multivariate logistic regression modeling was used to identify factors predictive of each treatment strategy. Kaplan-Meier and log-rank analysis and Cox proportional hazard modeling along with propensity score matching using variables known at the time of treatment sequence decision was performed to determine the effect on survival. A separate survival analysis was conducted including margin status to illustrate its effect on survival relative to adjuvant or neoadjuvant chemoradiation therapy. Results A total of 20,114 patients were identified: 17,612 (87.6%) received neoadjuvant chemoradiotherapy. Factors associated with receipt of neoadjuvant chemoradiotherapy on multivariate analysis include the following: income greater than $46,000 ( p < 0.01), treatment at an academic institution ( p < 0.01), living greater than 50 miles from the treatment facility ( p < 0.01), and year of diagnosis ( p < 0.01). Compared to adjuvant chemoradiotherapy, neoadjuvant chemoradiotherapy was associated with a decreased risk of death on multivariate analysis ( p = 0.05). When taking margin status into account, margin positivity in neoadjuvant chemoradiotherapy (NCRT) patients was shown to be a poor prognostic factor. Margin-negative NCRT patients had improved survival compared to margin negative adjuvant chemoradiotherapy (ACRT) patients. Conclusions The use of neoadjuvant chemoradiotherapy for locally advanced rectal cancer is possibly associated with an overall survival benefit compared to ACRT subject to the limitations of this analysis. Margin status affects survival greatly.

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.

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.

BACKGROUNDThe 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).METHODSPatients 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.RESULTSIn 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).CONCLUSIONSIn 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.

The appropriate sequence of chemotherapy and radiation is unknown. We aimed to evaluate the impact of chemotherapy and radiation sequence on overall survival (OS). Endometrial cancer patients that received adjuvant chemotherapy and radiation were selected from the SEER-Medicare database. Early chemotherapy was defined as receiving chemotherapy before or concurrent with radiotherapy. All other patients received a full course of radiation prior to chemotherapy. Univariate and multivariate cox proportional hazards regression was utilized to assess the impact of clinical and demographic factors on OS. Propensity score matching was performed to address selection bias and potential confounding variables. Eight hundred and ninety-six patients were selected for analysis. Median age was 71 years. The cohort included FIGO stage IB (33%), II (11%), and III (56%) patients. Adenocarcinoma (72%), papillary serous (23%), and clear cell (4%) histology were represented. Seventy-three percent (n=654) received early chemotherapy: 14% (n=94) concurrent radiation and chemotherapy with or without additional chemotherapy (CRT), 13% (n=86) chemotherapy followed by radiation and then additional chemotherapy (CRC), and 72% (n=474) chemotherapy followed by radiation (CR). Five year OS was improved among those receiving early chemotherapy (46.8% vs 62.3%, p<0.01). In addition, early chemotherapy improved OS on univariate (HR 0.61; 95% confidence interval [CI] 0.49-0.78, p<0.01), and multivariate analysis (HR 0.65; 95% CI 0.50-0.83, p<0.01). Additional clinical factors predictive of OS included FIGO stage III (HR 1.44, 95% CI 1.10-1.88, p=0.01) and age older than 75 years (HR 2.39, 95% CI 1.15-4.97, p=.02). The benefit of early chemotherapy persisted a shared frailty univariate cox proportional hazards analysis following propensity score-matching (HR 0.56; 95% CI 0.41-0.77, p<0.01). No differences in OS were present between CRT, CRC, and CR (p=0.29). Among elderly patients receiving adjuvant chemotherapy and radiation, those receiving early chemotherapy were associated with prolonged OS.

Parotid tumors are rare, and no clinical trial data exists to guide postoperative radiation therapy (PORT) usage. We sought to determine the impact of PORT on the overall survival (OS) of patients with parotid malignancies.

Esthesioneuroblastoma (ENB) is a rare neuroendocrine malignancy of cranial nerve I that is typically staged using a system first proposed by Kadish et al. and later modified by Morita et al. We sought to determine if this system provides good survival discrimination, and propose a revision to the system. The National Cancer Data Base was used to identify 1,124 adults with ENB. Patients were assigned a stage according the Kadish system, as well as an alternative stage where nasal cavity-limited disease is combined with paranasal extension, and those with distant metastases are separated from those with regional lymph node involvement (r-Kadish). Survival discrimination was compared between the two systems using Cox, log-rank and Kaplan-Meyer methodologies as well as Harrell's C and Somers' D statistics of concordance. Over the median follow-up period of 46 months, 264 patients (23.6%) died. Kadish stage A and B patients did not differ in their survival (log-rank p= 0.26). Within Kadish stage D, patients with lymph node only disease and those with distant metastatic disease demonstrated significantly different survival (log-rank p< 0.01). Log-likelihood scores for the Kadish staging system and the proposed r-Kadish system were -1710 vs. -1698, respectively (less negative values indicate superior survival discrimination between stages). Both Harrell's C (0.659 vs. 0.674 p=0.02) and Somers' D (0.330 vs. 0.347, p= 0.02) statistics of concordance were superior for the revised staging system (larger values indicate superior concordance between stage and observed survival). Patients with Kadish stage A and B disease demonstrated similar survival. Patients grouped as kadish stage D experienced dissimilar survival if their disease was metastatic versus limited to lymph nodes. A revision to the system is proposed that improves survival discrimination based on anatomic extension.

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.

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.

We assessed the role of radiotherapy in nodular lymphocytic Hodgkin lymphoma, particularly among patients with advanced stage disease, and B symptoms. We found that among patients with nodular lymphocytic Hodgkin lymphoma, radiotherapy had a potential role in advanced-stage disease and those with B symptoms, suggesting further exploratory studies. 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.