Quality Assurance for Stereotactic Body Radiation Therapy for Gynecologic Malignancies.

The use of stereotactic body radiation therapy (SBRT) is not well studied or reported in the treatment of gynecologic malignancies, despite its success in the definitive management of other cancer sites. This report describes a rigorous quality assurance process for patients to undergo dose escalation to the pelvis via stereotactic photon beam irradiation. Patients who receive SBRT must be ineligible for conventional brachytherapy boost and undergo comprehensive informed consent. Fiducial placement, bowel prep, Foley catheter placement with standardized bladder filling, computerized tomography (CT) simulation with whole-body immobilization, magnetic resonance imaging (MRI)-assisted target delineation, planning aims based on the established brachytherapy literature, and physics consultation for SBRT plan optimization are necessary. Prior to each fraction, the simulation position is reproduced and verified with on-table cone beam CT, and the position is maintained with whole-body immobilization. Following treatment, the treating physician is active in survivorship and toxicity management. Gynecologic SBRT is an ongoing area of study, and preliminary successes in delivering high-quality stereotactic dose escalation suggest prospective investigation is warranted. By adhering to strict quality control measures and following a pre-defined best standard of practice, patients with gynecologic malignancies who are ineligible for traditional brachytherapy procedures can be safely treated with SBRT.

Computational approaches for drug repurposing in oncology: untapped opportunity for high value innovation.

Historically, the effort by academia and industry to develop new chemical entities into lifesaving drugs has limited success in meeting the demands of today's healthcare. Repurposing drugs that are originally approved by the United States Food and Drug Administration or by regulatory authorities around the globe is an attractive strategy to rapidly develop much-needed therapeutics for oncologic indications that extend from treating cancer to managing treatment-related complications. This review discusses computational approaches to harness existing drugs for new therapeutic use in oncology.

Family Planning, Fertility, and Career Decisions Among Female Oncologists.

Importance: Female oncologists often spend their childbearing years in training and establishing careers, with many later experiencing fertility issues when starting a family. Physician fertility and family planning are rarely discussed during training. Attitudes among female oncologists regarding family planning are unknown. Objectives: To understand barriers to family planning as well as the association of fertility treatment with career decisions and to assess experiences of pregnancy-based discrimination among female oncologists. Design, Setting, and Participants: In this survey study, a novel 39-item questionnaire was distributed to US female oncologists from May 7 to June 30, 2020, via email and social media channels. Questions regarding factors associated with family planning, maternity leave, and discrimination were included. Main Outcomes and Measures: The distribution of survey responses was compared by oncology subspecialty. Multivariable logistic regression was performed to determine independent variables for discrimination experienced during maternity leave. Results: Responses were collected from 1004 female oncologists. Most respondents (847 [84.4%]) were married, and 713 (71.0%) were currently working full-time. A total of 351 oncologists (35.0%) worked in radiation oncology, 344 (34.3%) in medical oncology, 186 (18.4%) in surgical oncology, and 91 (9.1%) in pediatric oncology. A total of 768 respondents (76.5%) had children, and of these, 415 (41.3%) first gave birth during postgraduate training, and 275 (27.4%) gave birth in years 1 to 5 as an attending physician. Almost all respondents (951 [94.7%]) stated that their career plans were at least somewhat associated with the timing of when to start a family. Having a supportive partner was the most commonly cited positive association with family planning (802 [79.9%]), while long work hours and heavy workload (669 [66.6%]) were the most common negative factors. One-third (318 [31.7%]) had miscarried, and 315 (31.4%) reported difficulty with infertility that required fertility counseling and/or treatment; 660 (65.7%) thought fertility preservation should be discussed with women during medical school and/or residency. One-third (312 [31.1%]) reported experiencing discrimination during pregnancy, and 332 (33.1%) stated they experienced discrimination for taking maternity leave. On multivariable logistic regression, having more than 1 child was associated with increased likelihood of experiencing discrimination during maternity leave (2 children: odds ratio, 1.62 [95% CI, 1.10-2.39]; P = .02; ≥3 children: odds ratio, 1.84 [95% CI, 1.14-2.95; P = .01). Conclusions and Relevance: In this survey study of female oncologists, 1 in 3 reported experiencing infertility and 1 in 3 stated they experienced discrimination during pregnancy and/or for taking maternity leave. Systemic changes are necessary to ensure women are supported and able to advance equitably in the field.

Analyzing factors associated with clinical trial publication in radiation oncology.

Clinical trials are considered the gold standard of clinical research and are sought in the medical literature for the goal of providing quality care. To identify factors associated with successful or unsuccessful publication of clinical trials in radiation oncology, data on trial characteristics were collected from the National Institutes of Health database on clinicaltrials.gov. To assess studies that had adequate time to accrue, trials between 2000 and 2005 were extracted by filtering for "radiation oncology". Studies were excluded if they were incomplete, observational, Phase 4, or lacked sufficient method descriptions. Included studies underwent independent samples t-tests and Pearson Chi-Square bivariate analyses. 538 studies were candidates for analysis of clinical trial characteristics. United States (US) origin, multi-center sites, government funding, Phase III status, and randomized allocation were factors associated with increased publication rate. The number of study arms, study length, and number of participants were significantly greater in published trials. The review's results demonstrate potential barriers or facilitators to publication, and they suggest that publication status may be influenced by geographic, financial, and temporal characteristics of clinical trials. Understanding trial background factors that may impact publication improve data visibility and clinical advancements for all.

Association Between Metabolic Syndrome and Endometrial Cancer Survival in a SEER-Medicare Linked Database.

BACKGROUND: Metabolic syndrome has previously been linked to increased risk of endometrial cancer. This study examines the association between metabolic syndrome and cancer-specific survival (CSS) in early stage and locoregionally advanced endometrial cancer. METHODS: The SEER-Medicare linked database was used to identify a cohort of patients with endometrial cancer between 1992 and 2011 who underwent hysterectomy. Patients with incomplete stage or grade information were excluded. Patients were stratified into early stage (stage I to II) or locoregionally advanced (stage III to IVa) disease. Metabolic syndrome status was determined through Medicare claims 1 year before diagnosis. The relationship between metabolic syndrome and CSS was evaluated using univariable and multivariable Cox proportional hazards regression analyses. RESULTS: A total of 10,090 patients with endometrial cancer were identified. The mean age was 75 and the majority (91.5%) were white. At diagnosis, 86.6% of patients were early stage and 13.4% were locoregionally advanced. Sixteen percent of patients had metabolic syndrome. On stage stratified multivariable analysis, race, income quartile, year of diagnosis, histopathology, and adjuvant treatment were associated with CSS in early stage disease. Presence of metabolic syndrome was associated with worse CSS in early stage disease (hazard ratio=1.28, 95% confidence interval: 1.09-1.53); this difference did not exist for locoregionally advanced disease (hazard ratio=1.18, 95% confidence interval: 0.93-1.49). CONCLUSIONS: In elderly early stage endometrial cancer patients, metabolic syndrome is associated with worse CSS. Control of metabolic syndrome through lifestyle and pharmacologic therapies may improve cancer prognosis in this population.

Risk of thyroid cancer after therapeutic irradiation in adult patients: An Age-Based surveillance, epidemiology, and end results analysis.

OBJECTIVES/HYPOTHESIS: One risk of radiation therapy exposure (XRTe) is second primary thyroid cancer (SPTC). Previous reports examined this in children, but no population-based studies have explored XRTe and SPTC across all ages or stratified by histological subtypes. STUDY DESIGN: Database study. METHODS: We report patient characteristics of a Surveillance, Epidemiology, and End Results (SEER) dataset of SPTC (n = 4,669) using χ2 and t tests. Odds ratio (OR) for SPTC was determined based on age, histology, and XRTe compared to expected values in the SEER database. Kaplan-Meier survival and Cox proportional hazard ratios were reported to determine factors influencing latent survival (LS; time from initial diagnosis to SPTC) and overall survival in univariate and multivariate models. RESULTS: Extrathyroid extension and node status based on XRTe were similar (P = .684 and P = .776, respectively). XRTe patients were more likely to have smaller tumors (17.6 vs. 19.3 mm, P = .007). XRTe patients were diagnosed with SPTC at younger ages (59.8 vs. 62.7 years, P < .001) without a difference in LS (7.45 vs. 7.50 years, P = .426). Patients aged 1 to 14 years and 15 to 29 years at diagnosis of first cancer are at higher risk of SPTC after XRTe (OR = 1.89, P = .005 and OR = 2.35, P = .001, respectively), unlike patients age 30 to 44 years and 45+ years (OR = 1.03, P = .823 and OR = 0.97, P = .624, respectively). This difference is not present for follicular and medullary SPTC. CONCLUSIONS: Patients aged 30+ years receiving radiation therapy (XRT) do not have an increased risk of SPTC. Deliberation is necessary in recommending, planning, and delivering XRT to minimize risk of subsequent malignancy in younger patients. LEVEL OF EVIDENCE: NA Laryngoscope, 130: 2081-2086, 2020.

A Matter of Comprehensive Informed Consent: Short-Term Mortality Rates With Definitive Treatment Options in Elderly Stage I NSCLC.

BACKGROUND: Although lobectomy is the standard of care in stage I non-small cell lung cancer (NSCLC), medical comorbidities increase surgical risk in elderly patients. No population-based studies compare short-term mortality (STM) for surgery (STM-S), radiation (STM-R), and observation (STM-O) in elderly patients with stage I NSCLC. METHODS: A total of 60,466 biopsy-proven stage I NSCLC cases diagnosed between 2004 and 2012 were retrieved from the Surveillance, Epidemiology, and End Results Program. Patient characteristics were compared using χ test. Age was divided into 5-year subsets (60 to 64 to 90+ y) for analysis. Similar to other series, STM was defined as death within 2 months of diagnosis. Univariate and multivariate analysis for STM was performed using odds ratio, Kaplan-Meier actuarial method, and Cox proportional hazard ratio. RESULTS: In younger patients, STM-S rates are lower compared with STM-R (1.6% vs. 3.4% in patients 60 to 64 y, P<0.001). However, STM-S rates surpass STM-R with increasing age (up to 8.1% vs. 2.3% in patients 90+ y, P<0.001) becoming significant in the 75- to 79-year age group (4.7% vs. 2.2%, P<0.001). There is an inflection point in the 65- to 69-year age group where STM-S and STM-R rates are similar (2.6% vs. 3.0%, P=0.090). STM for observation reflected the poor health of this cohort with high STM rates in all age groups (19.5% for age 60 to 64 y to 25.3% for age 90+ y, P=0.005). Sex, race, Hispanic ethnicity, age group, and treatment were associated with higher STM on the multivariable analysis (all P<0.001). CONCLUSION: STM in elderly stage I NSCLC patients treated with surgery increases with advancing age but remains stable for patients receiving radiation. Given the success of stereotactic body radiation therapy, radiation should be considered for patients with high STM risk associated with surgery.

Socioeconomic Factors Associated with Lack of Treatment in Early Stage Non-Small Cell Lung Cancer.

With modern radiotherapy, stage I non-small cell lung cancer (S1NSCLC) cure is extended to nonsurgical candidates. Despite this, some S1NSCLC remains untreated. We aim to identify factors associated with no treatment. 62,213 S1NSCLC cases were identified (SEER: 2004-2012). Demographics were compared using Chi-squared. Multivariate analysis was performed using COX proportional HR. 11.9% of the 7373 patients lacked treatment. No insurance, Medicaid-dependence, unmarried status, advancing age, lower income, African American and Asian/Pacific Islander race, and male sex are associated with no treatment (p < .0001). No treatment portends a worse cancer-specific survival (21% vs 66% at 5Y, p < .0001) and OS (10% vs 50% at 5Y, p < .0001).

The Role of Adjuvant Radiotherapy in the Treatment of Pleural Mesothelioma.

BACKGROUND: Pleural mesothelioma is a rare but aggressive form of cancer. Local recurrence represents the majority of treatment failures and overall survival (OS) outcomes remain dismal. Adding locoregional treatment with radiotherapy after surgical resection has been considered but its role remains uncertain. OBJECTIVE: The purpose of this study was to evaluate the outcomes of adjuvant radiation therapy (RT) for patients with malignant pleural mesothelioma. METHODS: The National Cancer Data Base (NCDB) was queried (2004-2013) for patients with malignant mesothelioma. Patients were divided into three groups: observation, surgery alone, and surgery followed by adjuvant RT. Statistics included Fisher's exact or Chi square tests to analyze categorical proportions between groups, Kaplan-Meier analysis to evaluate OS, and Cox proportional hazards modeling to determine variables associated with OS. Propensity matching was performed to make comparisons between homogenous groups. RESULTS: Overall, the surgery plus radiotherapy group had a higher median survival (21.4 months) compared with surgery alone (16.59 months) [p < 0.001]. RT was more likely to be delivered after extrapleural pneumonectomy than with lung-sparing surgical approaches. On multivariable analysis, receipt of surgery plus radiotherapy, chemotherapy administration, and higher socioeconomic status were associated with improved OS (p < 0.0001). After propensity matching, receipt of surgery plus radiotherapy and chemotherapy administration were still associated with improved OS (p < 0.05). CONCLUSIONS: In the treatment of malignant pleural mesothelioma, adjuvant radiotherapy after surgical intervention was associated with improved OS. This study is the largest study of adjuvant radiotherapy to date, and our findings highlight the need for additional prospective data.

Disparities in the Treatment and Outcome of Stage I Non-Small-Cell Lung Cancer in the 21st Century.

BACKGROUND: African American (AA) individuals are less likely to receive treatment and more likely to die from cancer compared with Caucasian (C) individuals. Recent advancements in surgery and radiation have improved outcomes in early stage non-small-cell lung cancer (ESNSCLC). We studied racial disparities in ESNSCLC in the past decade. PATIENTS AND METHODS: The Surveillance, Epidemiology, and End Results database was used to retrieve data of 62,312 ESNSCLC patients age 60 years and older diagnosed between 2004 and 2012. Patients were divided into racial cohorts: C, AA, American Indian (AI), Asian/Pacific Islander (API), or unknown. Demographics characteristics, therapy, and survival were compared using χ2 test, Kaplan-Meier method, and Cox multivariate analysis. RESULTS: AA and AI individuals were less likely to receive surgery than typical ESNSCLC patients (55.9% and 57.6% vs. 66.7%; P < .0001). Two-year overall survival (OS) for C individuals was 70%, for AA 65%, AI 60%, and API 76% (P < .0001). Two-year cancer-specific survival (CSS) for C individuals was 79%, AA 76%, AI 73%, and API 84% (P < .0001). Median CSS for AI and AA individuals was less than that of typical ESNSCLC patients (49 and 80 months vs. 107 months; P < .0001). This difference disappeared in multivariate analysis, accounted by sex, age, treatment, histology, and T stage (all P < .0001). CONCLUSION: Despite treatment advancements in the past decade, AA and AI individuals continue to have worse OS and CSS from ESNSCLC. This might be because of the association with more adverse risk factors, including older age, squamous histology, male sex, T2 stage, and tendency to forgo treatment.

R0 resection and reconstruction for a large, rapidly progressive chest wall sarcoma.

BACKGROUND: Chest wall sarcomas are a rare group of soft tissue malignancies with variable presentations. Here we describe the definitive management of a large, rapidly progressing chest wall sarcoma arising from the pectoralis major muscle. CASE REPORT: An obese 42-year-old African American male with multiple medical comorbidities presented with new onset right-sided chest pain and a palpable right chest mass. Initial CT chest demonstrated a 9x9x9cm necrotic mass arising from the pectoralis major. CT-guided core biopsy was positive for high-grade spindle cell neoplasm (positive for smooth muscle actin, desmin, S100, and CD31; negative for CD34, PAX8, and beta-catenin). Staging imaging 2 months later demonstrated growth of the mass to 21.4 × 17.8 × 13.7 cm. The patient underwent neoadjuvant chemoradiation with surveillance CT imaging demonstrating a stable tumor. Then he underwent wide local excision of the mass followed by delayed local myocutaneous flap reconstruction and skin grafting. Final pathology was R0 resection, 38x20x18 cm tumor with 70% gross necrosis. Microscopic examination confirmed high-grade sarcoma with smooth muscle differentiation. Final pathologic staging was Stage III G3 pT2bNxMx. CONCLUSIONS: This patient presented with a rare, rapidly enlarging high-grade leiomyosarcoma of the chest wall without metastases or violation of the thorax. We describe the definitive management including a multidisciplinary team to manage a complex and rapidly progressive sarcoma of the chest wall.

Practice Patterns and Outcomes in Elderly Stage I Non-Small-cell Lung Cancer: A 2004 to 2012 SEER Analysis.

BACKGROUND: We reviewed the population-based treatment patterns and outcomes for elderly patients with stage I non-small-cell lung cancer (NSCLC) treated from 2004 to 2012. PATIENTS AND METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified biopsy-proven stage I NSCLC cases diagnosed from 2004 to 2012. The patients were divided into 5-year age subsets (60-64, 65-69, 70-74, 75-79, 80-84, 85-89, and ≥ 90 years). The demographic data, therapy, and survival were compared by year. Trends in overall survival (OS), cancer-specific survival (CSS), and practice patterns were analyzed. RESULTS: A total of 62,213 cases were identified. The use of surgery declined sharply with age. Patients aged 60 to 64 years had a surgical rate of 81% compared with 21% for those aged ≥ 90 years (P < .0001). Radiation use increased (from 11% to 39%; P < .0001), as did the receipt of neither surgery nor radiation (from 7% to 40%; P < .0001). When analyzing the annual trends, radiation use increased, with fewer patients forgoing treatment from 2004 to 2012 (P < .0001). From 2004 to 2011, CSS at 2 years improved significantly for patients treated with radiation alone (from 48% to 72%; P < .0001) and more subtly for those receiving surgery alone (from 87% to 91%; P < .0001). The outcomes were stable for those receiving neither surgery nor radiation (38% to 45%; P = NS). Surgical outcomes declined with advancing age (P < .0001); however, the radiation outcomes did not (P = NS). CONCLUSION: With advancing age, radiation replaces surgery as the most used treatment for early-stage NSCLC. OS and CSS have improved significantly for elderly stage I NSCLC patients treated with radiation alone during a timeline concurrent with the widespread adoption of stereotactic body radiation therapy. Dedicated prospective studies are indicated, because these findings are limited by the inherent biases of using the SEER database alone.