Safety and Efficacy of Stereotactic Body Radiation Therapy for Ultra-central Thoracic Tumors: A Single Center Retrospective Review.

PURPOSE: We sought to evaluate the toxicity and efficacy of stereotactic body radiation therapy (SBRT) for ultracentral thoracic tumors at our institution. METHODS AND MATERIALS: Patients with ultracentral lung tumors or nodes, defined as having the planning target volume (PTV) overlapping or abutting the central bronchial tree and/or esophagus, treated at our institution with SBRT between 2009 and 2019 were retrospectively reviewed. All SBRT plans were generated with the goal of creating homogenous dose distributions. The primary endpoint was incidence of SBRT-related grade ≥3 toxicity, defined using the Common Terminology Criteria for Adverse Events (V5.0). Secondary endpoints included local failure (LF), progression-free survival (PFS), and overall survival. Competing risk analysis was used to estimate incidence and identify predictors of severe toxicity and LF, while the Kaplan-Meier method was used to estimate PFS and OS. RESULTS: A total of 154 patients receiving 162 ultracentral courses of SBRT were included. The most common prescription was 50 Gy in 5 fractions (42%), with doses ranging from 30 to 55 Gy in 5 fractions (BED10 range, 48-115 Gy). The incidence of severe toxicity was 9.4% at 3 years. The most common severe toxicity was pneumonitis (n = 4). There was 1 possible treatment-related death from pneumonitis/pneumonia. Predictors of severe toxicity included increased PTV size, decreased PTV V95%, lung V5 Gy, and lung V20 Gy. The incidence of LF was 14% at 3 years. Predictors of LF included younger age and greater volume of overlap between the PTV and esophagus. The median PFS was 8.8 months, while the median overall survival was 44.0 months. CONCLUSIONS: In the largest case series of ultracentral thoracic SBRT to date, homogenously prescribed SBRT was associated with relatively low rates of severe toxicity and LF. Predictors of toxicity should be interpreted in the context of the heterogeneity in toxicities observed.

Mapping the Current State of Canadian Medical School Oncology Interest Groups.

Cancer is the leading cause of mortality in Canada. Undergraduate medical education therefore must ensure adequate oncology education for all physicians and inspire some to make oncology their career specialty, in an effort to ensure public care needs are met in the future. Medical student-led oncology interest groups (OIGs) are a subset of specialty interest groups that supplement formal didactic and clinical learning to increase exposure to oncology and access to mentors. We conducted a survey of OIG leaders to ascertain their goals, activities, barriers, future directions, and perceptions about employment prospects. OIG leaders from 12/17 Canadian medical schools responded. Medical oncology was the most represented specialty in OIGs. Half of OIGs had faculty mentors. Self-reported goals were to increase exposure to oncology disciplines (n = 12), assist students with career selection (n = 11) and finding mentors (n = 7), and enhance oncology education (n = 10). OIGs held on average 5 events per year (range 1-12). Reported barriers were finding time to plan events, declining student interest over academic year, and limited funding. Many OIGs showed interest in more standardized resources about oncology disciplines (n = 9), access to presentations (n = 10), more funding (n = 7), and collaboration (n = 7). Employment in many oncology specialties was perceived poorly, and the most important career selection considerations were ease of employment, practice location, and partner/family preference. Our survey highlights common goals, barriers, and perceptions in OIG medical student leaders across Canada and provides guidance for future interventions.

Organ at Risk Dose Constraints in SABR: A Systematic Review of Active Clinical Trials.

PURPOSE: Organ at risk (OAR) dose constraints are a critical aspect of SABR treatment planning. There is limited evidence supporting preferred dose constraints for many OARs. We sought to evaluate OAR dose constraints used in ongoing clinical trials of SABR for oligometastatic disease. METHODS AND MATERIALS: Clinicaltrials.gov was searched from inception to February 2020 to capture actively accruing clinical trials using SABR in oligometastatic disease. Dose constraints were obtained by contacting principal investigators and abstracted by 2 authors. Variability of constraints was assessed by comparing the width of the interquartile range and difference between the maximum and minimum dose to a volume. RESULTS: Fifty-three of 85 eligible clinical trials contributed OAR constraints used in analysis. Dose constraints for 1 to 8 fractions of SABR were collected for 33 OARs. Variability was found in the absolute allowable OAR doses, use of planning OAR volumes, and whether constraints were optional versus mandatory. For many OARs, modal dose constraints often matched a pre-existing publication, but no single pre-existing publication matched the modes of all OAR dose constraints. Organs displaying the most variability were the rectum, penile bulb, and chest wall and ribs. The esophagus, stomach, duodenum, and small bowel also indicated high variability for at least 1 constraint. OARs previously evaluated by HyTEC appeared to have less variability among study protocols. CONCLUSIONS: We found substantial variability in OAR dose constraints used in current clinical trials evaluating SABR in oligometastatic disease. We are unable to comment on toxicity rates or acceptability of dose constraints used. Future research and recommendations for standardized OAR dose constraints, as well as consistency in implementing planning OAR volume margins, should be priorities for the field of radiation oncology.

A review of ongoing trials of stereotactic ablative radiotherapy for oligometastatic disease in the context of new consensus definitions.

The characterization and treatment of oligometastatic disease (OMD) are rapidly growing areas of research. Consensus statements have recently been developed by European Society for Radiotherapy and Oncology (ESTRO)/American Society for Radiation Oncology (ASTRO) and ESTRO/European Organization for Research and Treatment of Cancer (EORTC) in an effort to harmonize terminology describing OMD. The purpose of this study was to assess patient populations eligible for ongoing clinical trials evaluating stereotactic ablative radiotherapy (SABR) in OMD in the context of key definitions from both statements. Using the clinicaltrials.gov database, a search of ongoing OMD clinical trials evaluating the use of SABR was performed from inception to January 2020, using the keywords "oligometastasis", "stereotactic radiotherapy", and related terms. Results were independently reviewed by two investigators, with discrepancies settled by a third. Information from these trials including study design, population criteria, and primary endpoints were extracted. OMD was defined in general as a limited number of metastases that could be safely treated with metastasis-directed therapy. States of OMD were broadly categorized into de novo, repeat, and induced, with synchronous and metachronous being subsets of de novo. The initial search strategy identified 293 trials, of which 85 met our eligibility criteria. Phase II trials were by far the most common (n=46, 52%). Most trials had a single treatment arm (n=43, 51%), and 31 (36%) were randomized. The majority of trials (n=65, 76%) had populations that included all three subsets of OMD. Notably, 70 trials (82%) also included oligoprogressive disease, which is debatably a distinct entity from OMD. Progression-free survival was the most common primary endpoint (n=31, 36%), followed by local control (n=17, 20%), toxicity (n=14, 16%) and overall survival (n=7, 8%). Although the use of SABR for OMD is an active area of prospective clinical trial research, ongoing studies include mixed populations as defined by new consensus statements. Therefore, the applicability of results from these trials should be considered within relevant OMD scenarios.

Current Management and Progress in Radiotherapy for Small Cell Lung Cancer.

Radiotherapy (RT) and chemotherapy continue to be widely utilized in small cell lung cancer (SCLC) management. In most limited stage (LS)-SCLC cases, the standard initial therapy remains concurrent chemoradiotherapy (CRT), typically with an etoposide and platinum-based regimen. Hyperfractionated twice daily (BID) RT remains the standard of care, though conventional daily (QD) RT is now a viable alternative supported by randomized evidence. In LS-SCLC patients who experienced good response to CRT, prophylactic cranial irradiation (PCI) remains the standard of care. Brain imaging, ideally with MRI, should be performed prior to PCI to screen for clinically apparent brain metastases that may require a higher dose of cranial irradiation. Platinum doublet chemotherapy alone is the historic standard initial therapy in extensive stage (ES)-SCLC. Addition of immunotherapy such as atezolizumab and durvalumab to chemotherapy is now recommended after their benefits were demonstrated in recent trials. In patients with response to chemotherapy, consolidation thoracic RT and PCI could be considered, though with caveats. Emergence of hippocampal avoidance cranial irradiation and SRS in SCLC patients may supplant whole cranial irradiation as future standards of care. Incorporation of novel systemic therapies such as immunotherapies has changed the treatment paradigm and overall outlook of patients with SCLC. This narrative review summarizes the current state, ongoing trials, and future directions of radiotherapy in management of SCLC.

Incidence, Risk Factors, and Outcomes of Clostridium difficile Infections in Kidney Transplant Recipients.

BACKGROUND: Kidney transplant recipients (KTR) may be at increased risk for Clostridium difficile infections (CDI) but risk factors and outcomes in this population have not been well studied. METHODS: An observational cohort study was conducted to determine the incidence, risk factors, and outcomes of CDI in KTR. A total of 1816 KTR transplanted between 2000 and 2013 at the Toronto General Hospital were included. Sixty-eight patients developed CDI. Controls were selected at a 4:1 ratio using risk-set sampling, and risk factors were explored using conditional logistic regression models. The impact of CDI on graft outcomes was evaluated using Cox proportional hazards models. RESULTS: The incidence rate of CDI was 0.64 cases/100 person-years. Independent predictors of CDI included antibiotic use (odds ratio [OR], 2.88; 95% confidence interval [CI], 1.35-6.15), increased duration of hospitalization posttransplant (OR, 1.04; 95% CI, 1.02-1.06]), receiving a deceased donor kidney (OR, 2.98; 95% CI, 1.47-6.05), and a history of biopsy-proven acute rejection (OR, 5.82; 95% CI, 2.22-15.26). In the Cox proportional hazards model, CDI was found to be an independent risk factor for the subsequent development of biopsy-proven acute rejection (hazard ratio, 2.18; 95% CI, 1.34-3.55). CONCLUSIONS: Our results confirm that transplant-specific factors place KTR at a higher risk for CDI. Clostridium difficile infections may increase the risk of adverse outcomes, such as biopsy-proven acute rejection. These findings emphasize the importance of preventive strategies to reduce the morbidity associated with CDI in KTR.