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.

Impact of hematologic toxicities during concurrent chemoradiation for cervical cancer.

OBJECTIVE: To evaluate the prognostic significance of hematological toxicities during cervical cancer treatment. METHODS: Patients treated for cervical carcinoma with definitive chemoradiation were identified. Toxicities were assessed during weeks 1 to 6 of concurrent external beam radiation and chemotherapy. Outcomes were analyzed using Cox regression analysis. RESULTS: One hundred twenty-one patients with Federation of Gynecology and Obstetrics stage I-III disease were eligible for analysis. Median age at diagnosis was 45 years (interquartile range, 40-52) with median follow-up time of 34 months (95% confidence interval, 30.8-37.2). All patients experienced some grade of hematologic toxicity. The most common grade 3+ toxicities were low absolute lymphocyte count (n=115, 95%), low white blood cell count (n=21, 17%), and anemia (n=11, 9%). The most common grade 4 toxicity was lymphopenia, experienced by 36% of patients (n=44). Grade 4 lymphopenia was associated with reduced overall survival (hazard ratio [HR], 4.5; P=0.005), progression-free survival (HR, 3.4; P=0.001), and local control (HR, 4.1; P=0.047). Anemia grade 3, 4 was also associated with reduced overall survival (HR, 4.1; P=0.014). After controlling for disease and treatment variables, grade 4 lymphopenia remained significantly associated with reduced overall survival (HR, 9.85; P=0.007). The association with grade 4 lymphopenia only remained significant in women of Hispanic ethnicity. CONCLUSION: Severe lymphopenia was associated with reduced overall survival and progression-free survival in Hispanic women undergoing definitive chemoradiation for cervical cancer, but not associated with outcomes in non-Hispanic women.

Radiation therapy in primary mediastinal large B-cell lymphoma treated with DA-R-EPOCH.

DA-R-EPOCH is used in PMBCL due to its good outcomes without radiation. We present three cases that required consolidation with radiation despite using this regimen. More studies are needed before considering DA-R-EPOCH standard of care.

Non-invasive stereotactic ablative boost in patients with locally advanced cervical cancer.

INTRODUCTION: The current literature is insufficient to guide care for patients with cervical cancer ineligible for brachytherapy. Stereotactic ablative radiotherapy boost is a clinical necessity for these patients, but highly debated among radiation oncologists. OBJECTIVE: To report toxicity and survival outcomes in a large cohort of patients with locally advanced cervical cancer treated with a non-invasive stereotactic ablative radiotherapy boost instead of brachytherapy METHODS: Patients with locally advanced cervical cancer were entered, between January 2008 and December 2018, who were recommended definitive intent external boost after pelvic radiotherapy to 45-50.4 Gy concurrent with weekly cisplatin and simultaneous/sequential nodal boost up to 55-66 Gy. Simulation CT was facilitated using radio-opaque fiducials, empty rectum, dedicated bladder filling, and whole body vaculoplastic immobilization. Kaplan-Meier survival estimates were used to report local/regional recurrences, distant metastases, cancer-specific survival, and overall survival. RESULTS: A total of 25 patients were analyzed. Median follow-up was 25 months (range 6-54). Patients received stereotactic ablative radiotherapy due to refusal of brachytherapy (9/25, 36%), medical co-morbidities limiting implantation (9/25, 36%), or technical infeasibility (7/25, 28%). Typical fractionation was 24-30 Gy in 4-5 fractions (24/25, 96%). The most common long-term toxicity was grade 1-2 vaginal dryness, discomfort, stenosis, and/or dyspareunia (4/25, 16%). One patient had new post-treatment grade 4 fistula in an area of previous tumor erosion (1/25, 4%). Overall survival, cancer specific survival, loco-regional control, and distant control were 95.5%, 100%, 95.5%, and 89.1%, respectively, at 2 years. CONCLUSION: Further study of stereotactic ablative radiotherapy boost for cervical cancer is needed; a brachytherapy-similar approach portends clinical success with 95.5% overall survival and loco-regional control at 2 years.

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.

Novel Radiotherapy Technologies in the Treatment of Gastrointestinal Malignancies.

Over the past 2 decades, major technical advances in radiation therapy planning and delivery have made it possible to deliver higher doses to select high-risk volumes. This has helped to expand the role of radiation therapy in the treatment of gastrointestinal malignancies. Whereas dose escalation was previously limited by the radiosensitivity of normal tissues within and adjacent to the gastrointestinal tract, advances in target delineation, patient immobilization, treatment planning, and image-guided treatment delivery have greatly improved the therapeutic ratio. More conformal radiation modalities can offer further dose optimization to target volumes while sparing normal tissue from toxicity.

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.

Laparoscopic Allograft Spacer Placement to Minimize Bowel Dose During Re-irradiation with Interstitial Brachytherapy.

In primary or re-irradiation of gynecologic malignancies, achieving optimal dosimetry with adjacent normal tissue becomes challenging. Surgical spacers are tissue-equivalent materials placed within the patient to protect organs at risk from long-term radiation effects and are commonly used in prostate cancer. We report the use of an allograft mesh to protect adhesed bowel from high-dose radiation for definitive treatment of recurrent endometrial cancer. An 88-year-old female was diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage II endometrial cancer after she developed urinary frequency, hesitancy, and hematuria. She underwent neoadjuvant chemoradiation, followed by laparoscopic hysterectomy with bilateral salpingo-oophorectomy and adjuvant vaginal cuff brachytherapy. She developed 1.8 cm bilateral vaginal cuff recurrence and was dispositioned for interstitial brachytherapy. An allograft mesh spacer was placed laparoscopically before repeat, high dose rate brachytherapy to protect nearby structures. Dose-escalation was achieved without compromising normal tissue constraints. The patient tolerated the procedure without evidence of long-term toxicity at one year. Multidisciplinary discussion may help identify patients who would benefit from spacer placement before select dose-escalated radiation therapy. Laparoscopic allograft mesh is one of many types of surgical spacers available for such patients.

Community-based Disparities in the Treatment and Outcomes of Early-stage Non-small-cell Carcinoma.

Introduction Lung cancer is the most common malignancy in men and women combined. It is also the leading cause of cancer-related deaths in the US. The objective of this study is to report the treatment and survival outcomes for early-stage non-small-cell lung carcinoma (NSCLC) when stratified by urban versus rural geography. Methods A dataset of 62,213 patients, all aged 60 years or above, with stage-1 NSCLC, who underwent treatment from 2004 to 2012 was retrieved from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute (NCI). Patients were divided into metropolitan, urban, or rural (in descending order of population density) based on their location of cancer treatment using the US Rural-Urban Continuum Code Definitions for 2003. Patient characteristics were compared using the chi-square test, and survival statistics were calculated using the Kaplan-Meier estimator. Results Rural or urban stage-1 NSCLC patients are more likely to be white, young, male, poor, and uninsured or Medicaid-dependent. They generally have squamous histology and receive radiation therapy when compared to metropolitan counterparts [probability value (p): <0.0001]. Median overall survival was shorter for rural and urban patients than metropolitan patients (41, 41, and 52 months respectively; p: <0.0001). Conclusion Tertiary care centers in metropolitan areas continue to demonstrate superior outcomes in the treatment of stage-1 NSCLC. This is presumably due to the existing disparities in patient access to care. Rural and urban stage-1 NSCLC patients (who tend to be younger, poorer, and more likely to be treated with radiation than surgery) are likely to be disproportionately impacted by changes in health policy.

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.