Factors Predictive of Receiving Adjuvant Radiotherapy in High-Intermediate-Risk Stage I Endometrial Cancer.

OBJECTIVES: Randomized trials have shown a local control benefit with adjuvant radiotherapy (RT) in high-intermediate-risk endometrial cancer patients, although not all such patients receive RT. We reviewed the National Cancer Data Base to investigate which patient/tumor-related factors are associated with delivery of adjuvant RT. METHODS: The National Cancer Data Base was queried for patients diagnosed with International Federation of Gynecology and Obstetrics 2009 stage I endometrioid adenocarcinoma from 1998 to 2012 who underwent surgery +/- adjuvant RT. Exclusion criteria were unknown stage/grade, nonsurgical primary therapy, less than 30 days' follow-up, RT of more than 6 months after surgery, or palliative treatment. High-intermediate risk was defined based on Post Operative Radiation Therapy in Endometrial Carcinoma 2 criteria: older than 60 years with stage IA grade 3 or stage IB grade 1-2. RESULTS: Seventeen thousand five hundred twenty-four met inclusion criteria, and the 13,651 patients with complete data were subjected to a multiple logistic regression analysis; 7814 (57.2%) received surgery alone, and 5837 (42.8%) received surgery + RT. Receipt of adjuvant RT was more likely among black women and women with higher income, Northeastern residence, diagnosis after 2010, greater than 50% myometrial invasion, and receipt of adjuvant chemotherapy (P < 0.05). Patients older than 80 years or those undergoing lymph node dissection were less likely to receive adjuvant RT (P < 0.05). Of those treated with RT, 44.0% received external beam therapy, 54.8% received vaginal cuff brachytherapy, and 0.6% received both. Among irradiated women, patients older than 80 years and those with Northeastern residence, treatment at academic facilities, diagnosis after 2004, and lymph node dissection were more likely to undergo brachytherapy over external beam radiation therapy (P < 0.05). Overall use of adjuvant RT was 28.8% between 1998 and 2004, 42.0% between 2005 and 2010, and 43.4% between 2011 and 2012; the difference between 1998-2004 and 2005-2010 was not statistically significant. CONCLUSIONS: Fewer than half of patients with high-intermediate-risk endometrial cancer by Post Operative Radiation Therapy in Endometrial Carcinoma 2 criteria received adjuvant RT despite evidence demonstrating improved local control. Both patient- and tumor-related factors are associated with delivery of adjuvant RT and the modality selected.

Adjuvant radiation therapy is associated with improved overall survival in high-intermediate risk stage I endometrial cancer: A national cancer data base analysis.

PURPOSE: Adjuvant radiation therapy (RT) was shown to improve local control in patients with high-intermediate risk (HIR) stage I endometrial cancer (EC) in randomized trials. Overall survival (OS) was not significantly different with adjuvant RT in these trials or subsequent meta-analyses; however, they were underpowered to assess OS. We used the National Cancer Data Base (NCDB) to examine the impact of adjuvant RT on OS in HIR EC patients. METHODS: The NCDB was queried for patients diagnosed with FIGO (2009) Stage I endometrioid adenocarcinoma from 1998 to 2012 who underwent surgery±adjuvant RT. Per ASTRO guidelines, HIR risk was defined as stage IB and/or grade 3. Patients were excluded if: non-surgical primary therapy, RT>180days after surgery, unknown stage/grade/RT status, or RT to targets outside pelvis/vagina. Kaplan-Meier plots and Cox proportional hazards regression were used. RESULTS: 33,600 patients met criteria. 18,070 patients (53.8%) received surgery alone, 15,530 patients (46.2%) received surgery+adjuvant RT. Of patients who received adjuvant RT, 42.2% received external beam RT, 44.7% brachytherapy, and 13.1% received both. 5-year OS was 79.2% for the surgery alone group and 83.3% for the surgery+adjuvant RT (p<0.0001). On multivariate analysis, adjuvant RT was independently associated with improved OS vs. surgery alone (HR 0.7; 95% CI 0.8-0.9, p<0.0001). CONCLUSIONS: Our results show that surgery+adjuvant RT was associated with a statistically significant 4.1% improvement in 5-year OS vs. surgery alone in stage I HIR EC. This data along suggests that the improvement in local control with adjuvant RT leads to improved OS.

Survival Differences Among Uterine Papillary Serous, Clear Cell and Grade 3 Endometrioid Adenocarcinoma Endometrial Cancers: A National Cancer Database Analysis.

OBJECTIVES: High-risk histology including UPSC, CC, and high-grade (G3) endometrioid adenocarcinoma (EAC) have a worse prognosis compared to G1-2 EAC. It is unknown whether G3EAC outcomes are more similar to UPSC/CC or to G1-2 EAC. The purpose of this study was to compare overall survival (OS) among UPSC, CC, and G1-3 EAC, for International Federation of Gynecology and Obstetrics stages I to III. METHODS: The National Cancer Data Base was queried for patients diagnosed with International Federation of Gynecology and Obstetrics (1988 classification) Stage I-III UPSC, CC, and EAC from 1998 to 2012 who underwent surgery as definitive treatment. Patients with unknown grade/stage, nonsurgical primary therapy, other histologies, and less than 30-day follow-up were excluded. Overall survival was calculated using the Kaplan-Meier product-limit method and compared using log-rank tests. RESULTS: 219,934 patients met our inclusion criteria. For patients with stage I disease (n = 174,361), 5-year OS was for 92.4% for G1EAC, 87.8% for G2EAC, 77.5% for G3EAC, 74.9% for CC, and 74.6% for UPSC. For stage II patients (n = 17,361), 5-year OS was 86.7% for G1EAC, 80.2% for G2EAC, 62.7% for G3EAC, 64.3% for CC, and 56.7% for UPSC. For stage III patients (n = 28,212), 5-year OS was 79.7% for G1EAC, 68.9% for G2EAC, 49.6% for G3EAC, 40.2% for CC, and 35.7% for UPSC (P <0.0001). On multivariate analysis, black race, age 60 years and older, higher stage, higher grade, high-risk histologies, receiving chemotherapy, and higher comorbidity scores were all significantly (P < 0.0001) predictive of death while receiving radiation therapy was protective (hazards ratio, 0.7; 95% confidence interval, 2.6-2.9). CONCLUSIONS: The results suggest that G3 EAC has a slightly more favorable survival than UPSC and CC but predictably does poorer than G1-2 EAC. Further research is warranted to determine if G3 EAC should be reclassified as a type II cancer.

Characterization of cerebral radiation necrosis following the treatment of sinonasal malignancies.

Objectives: Our study aims to determine the incidence and potential risk factors for cerebral radiation necrosis (CRN) following treatment of sinonasal malignancies. Methods: One hundred thirty-two patients diagnosed with sinonasal malignancies over an 18-year period were identified at two institutions. Forty-six patients meeting inclusion criteria and treated with radiation therapy were included for analysis. Demographic and clinical-pathologic characteristics were collected and reviewed. Post-treatment magnetic resonance imaging (MRI) at least 1 year following treatment was reviewed to determine presence or absence of CRN. Results: CRN was identified on MRI in 8 of 46 patients (17.4%) following radiation treatment. Patients with a history of reirradiation were more likely to develop CRN (50% vs. 10.5%, p < .05). The BEDs of radiation were also higher in CRN patients compared to non-CRN patients, but this difference was not significant (p > .05). CRN patients had a higher proportion of tumors with skull base involvement than non-CRN patients (100% vs. 57.9%, p = .037). Demographics, comorbidities, pathology, primary tumor subsite, chemotherapy use, and stage of disease demonstrated no significant increase in risk of CRN. Conclusions: Reirradiation and tumor skull base involvement were significant risk factors associated with CRN. Higher average total prescribed and BEDs of radiation were seen in the CRN groups, but these differences were not statistically significant. Gender, comorbidities, tumor subsite, tumor location, and treatment type were not significantly different between groups. Level of evidence: Level 3.

Radiation Modalities Used in Lung Cancer: An Overview for Thoracic Surgeons.

Radiation is a constantly evolving technology which plays a role in the management of lung cancer in a variety of settings: as an adjunct to surgery, definitively, and palliatively. Key aspects of radiation oncology-including acute and chronic toxicities of thoracic radiation and rationale for choosing one modality of radiation over another-may be obscure to those outside the field. We aim to provide a useful overview relevant for the thoracic surgeon of radiation technology and delivery. A review was performed of salient articles identifying radiation technologies used in lung cancer which were summarized and expounded upon with focus on integrating their history, evolution, and landmark trials establishing basis of their use. This article reviews the four fundamental means of external beam radiation employed in managing lung cancer and provides visual examples of comparison plans. We also touch on potential practice-changing developments in regards to proton therapy and radiation in the era of immunotherapy. Radiation oncology has evolved considerably over time to become a critical part of lung cancer management, particularly in early-stage inoperable disease and locally advanced disease. Maximizing tumor control while minimizing toxicity drives treatment strategies. Knowledge of these fundamentals will help the thoracic surgeon answer many questions patients pose regarding radiation.

Stereotactic Body Radiation Therapy: A Versatile, Well-Tolerated, and Effective Treatment Option for Extracranial Metastases From Primary Ovarian and Uterine Cancer.

PURPOSE: Single extracranial metastases from ovarian and uterine malignancies have historically been treated with surgery or conventional radiation. We report mature local control (LC), overall survival (OS), progression free survival (PFS), and toxicity for patients who completed 5-fraction stereotactic body radiation therapy (SBRT). METHODS: Patients with biopsy-proven, single extracranial metastases from primary ovarian and uterine malignancies treated with 5-fraction SBRT were included. Patients were stratified based on tumor volume (small < 50 cc or large ≥ 50 cc) and dose (low dose < 35 Gy or high ≥ 35 Gy). Kaplan-Meier method was used to estimate LC, OS, and PFS. RESULTS: Between July 2007 and July 2012, 20 patients underwent SBRT to a single extracranial metastasis. Primary site was divided evenly between ovarian and uterine (n = 10 each). Metastases involved the liver (30%), abdominal lymph nodes (25%), lung (20%), pelvic lymph nodes (10%), spine (10%), and extremity (5%). The median gross tumor volume (GTV) was 42.5 cc (range, 5-273 cc) and the median dose to the GTV was 35 Gy (range, 30-50 Gy). At a median follow-up of 56 months, the 5-year LC and OS estimates were 73 and 46%. When stratified by tumor volume, the 5-year LC and OS for small tumors were significantly better at 100% (p < 0.01) and 65% (p < 0.02). When stratified by dose, the 5-year LC was 87.5% with high dose and 53.6% with low dose (p = 0.035). The 5-year PFS for the entire cohort was 20%. Four patients with small metastases who had complete response remained disease free at study completion and were considered cured (median PFS > 10 years). Treatment was generally well tolerated, and only one patient experienced a late grade III musculoskeletal SBRT related toxicity. CONCLUSIONS: SBRT is a versatile, well-tolerated, and effective treatment option for single extracranial metastases from ovarian and uterine primary tumors. 35 Gy in five fractions appears to be a practical minimum effective dose. Four patients with small metastases were disease free at the study completion and considered cured. However, patients with larger metastases (≥50 cc) may require higher SBRT dosing or alternative treatments.

Ethnicity and insurance status predict metastatic disease presentation in prostate, breast, and non-small cell lung cancer.

BACKGROUND: Ethnicity and insurance status have been shown to impact odds of presenting with metastatic cancer, however, the interaction of these two predictors is not well understood. We evaluate the difference in odds of presenting with metastatic disease in minorities compared to white patients despite access to the same insurance across three common cancer types. METHODS: Using the National Cancer Database, a multilevel logistic regression model that estimated the odds of metastatic disease was fit, adjusting for covariates including year of diagnosis, ethnicity, insurance, income, and region. We included adults diagnosed with metastatic prostate, non-small cell lung cancer (NSCLC), and breast cancer from 2004 to 2015. RESULTS: The study cohort consisted of 1 191 241 prostate cancer (PCa), 1 310 986 breast cancer (BCa), and 1 183 029 NSCLC patients. Private insurance was the most protective factor against metastatic presentation. Odds of presenting with metastatic disease were 0.190 [95% CI, 0.182-0.198], 0.616 [95% CI, 0.602-0.630], and 0.270 [95% CI, 0.260-0.279] for PCa, NSCLC, and BCa compared to uninsured patients, respectively. Private insurance provided the most significant benefit to non-Hispanic White PCa patients with 81% reduction in odds of metastatic presentation and conferred the least benefit to African-American NSCLC patients at 30.4% reduction in odds of metastatic presentation. CONCLUSIONS: Insurance status provided the single most protective effect against metastatic presentation. This benefit varied for minorities despite similar insurance. Reducing metastatic disease presentation rates requires addressing social barriers to care independent of insurance.

Rationale for Involved Field Stereotactic Body Radiation Therapy-Enhanced Intermittent Androgen Deprivation Therapy in Hormone-Sensitive Nodal Oligo-Recurrent Prostate Cancer Following Prostate Stereotactic Body Radiation Therapy.

Lymph node recurrent prostate cancer is a common clinical scenario that is likely to increase significantly with the widespread adoption of novel positron emission tomography (PET) agents. Despite increasing evidence that localized therapy is disease modifying, most men with lymph node recurrent prostate cancer receive only systemic therapy with androgen deprivation therapy (ADT). For men who receive localized therapy the intent is often to delay receipt of systemic therapy. Little evidence exists on the optimal combination of local and systemic therapy in this patient population. In this hypothesis generating review, we will outline the rationale and propose a framework for combining involved field SBRT with risk adapted intermittent ADT for hormone sensitive nodal recurrent prostate cancer. In patients with a limited number of nodal metastases, involved field stereotactic body radiation therapy (SBRT) may have a role in eliminating castrate-resistant clones and possibly prolonging the response to intermittent ADT. We hypothesize that in a small percentage of patients, such a treatment approach may lead to long term remission or cure.

Thinking That I Had Cancer Made Me a Better Oncologist.

This essay describes the author's experience with a cancer scare and the increased empathy and experience gained.