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Introduction: High-risk prostate cancer is associated with poorer overall survival (OS) and biochemical control compared to more favorable risk groups. External beam radiation therapy (EBRT) is widely used; however, outcomes data are limited with respect to time elapsed between diagnosis and initiation of EBRT. Methods: The National Cancer Database was queried from 2004 to 2015 for patients diagnosed with high-risk adenocarcinoma of the prostate who received androgen deprivation therapy (ADT) and definitive EBRT. Logistic regression was utilized to determine covariates associated with missing EBRT treatments. OS was analyzed using multivariate cox proportional hazards models and propensity score matching. Results: 9,610 patients met inclusion criteria with median follow-up of 40.6 months and median age of 72 years. Median PSA was 8.7 and median EBRT dose was 78 Gy. ADT was initiated at a median of 36 days and EBRT at a median of 63 days post-diagnosis. Median number of prolonged treatment days was 2.2. Black race (OR: 1.40; p 74 days (HR: 1.20; p = 0.01) and prolonged treatment>3 days of EBRT (HR: 1.26; p = 0.005) were associated with an increased hazard of death. The 5-year OS was 79.6% and 82.9% for patients with prolonged treatment of 3 days or more of EBRT and those missing 3 days or less, respectively (p = 0.0006). Conclusion: In this hypothesis-generating study, prolonged treatment delays and missing three or more EBRT treatments was associated with poorer OS in patients with high-risk adenocarcinoma of the prostate.

Purpose: Spatially fractionated radiation therapy (SFRT), which delivers highly nonuniform dose distributions instead of conventionally practiced homogeneous tumor dose, has shown high rates of clinical response with minimal toxicities in large-volume primary or metastatic malignancies. However, prospective multi-institutional clinical trials in SFRT are lacking, and SFRT techniques and dose parameters remain variable. Agreement on dose prescription, technical administration, and clinical and translational design parameters for SFRT trials is essential to enable broad participation and successful accrual to rigorously test the SFRT approach. We aimed to develop a consensus for the design of multi-institutional clinical trials in SFRT, tailored to specific primary tumor sites, to help facilitate development and enhance the feasibility of such trials. Methods and Materials: Primary tumor sites with sufficient pilot experience in SFRT were identified, and fundamental trial design questions were determined. For each tumor site, a comprehensive consensus effort was established through disease-specific expert panels. Clinical trial design criteria included eligibility, SFRT technology and technique, dose and fractionation, target- and normal-tissue dose parameters, systemic therapies, clinical trial endpoints, and translational science considerations. Iterative appropriateness rank voting, expert panel consensus reviews and discussions, and public comment posting were used for consensus development. Results: Clinical trial criteria were developed for head and neck cancer and soft-tissue sarcoma. Final consensus among the 22 trial design categories each (a total of 163 criteria) was high to moderate overall. Uniform patient cohorts of advanced bulky disease, standardization of SFRT technologies and dosimetry and physics parameters, and collection of translational correlates were considered essential to trial design. Final guideline recommendations and the degree of agreement are presented and discussed. Conclusions: This consensus provides design guidelines for the development of prospective multi-institutional clinical trials testing SFRT in advanced head and neck cancer and soft-tissue sarcoma through in-advance harmonization of the fundamental clinical trial design among SFRT experts, potential investigators, and the SFRT community.

Purpose: Phantosmia, an underreported toxicity of brain radiation therapy (RT), is defined as an olfactory disorder resulting in a malodorous phantom smell. This study aimed to characterize the incidence of phantosmia in patients treated with intensity modulated proton therapy (IMPT). Methods and Materials: In this institutional review board–approved retrospective study, the electronic medical record of a pencil beam scanning-only proton center was queried for patients ≤39 years of age who received IMPT for primary intracranial, metastatic intracranial, skull base, nasopharyngeal or sinonasal neoplasms between August 2019 and December 2020. Patient, clinical, and phantosmia-related characteristics were collected. The olfactory region was defined to include the olfactory bulb and tract. Phantosmia severity was graded by intervention use (mild, no intervention; moderate, supportive treatment; severe, RT discontinuation). Results: Ninety-nine patients met the inclusion criteria. Twelve patients (12.1%) reported phantosmia. Patients described perceiving a “chlorine,” “broccoli,” “stale water,” “metallic,” or “noxious” smell. Of the patients who reported phantosmia, median age was 17 (12-33) years, 66.7% were male, and 91.7% had intracranial tumors. None of the patients had prior RT. Chemoradiotherapy treatment did not correlate with phantosmia development (odds ratio, 1.09; 95% confidence interval, 0.32-3.70; P = .90). Ten patients experienced accompanying toxicities, including taste changes (n = 3), vision disturbances (n = 5), and nausea/emesis (n = 7). Phantosmia was mild (n = 7) or moderate (n = 5). All patients completed their RT course. Sixty-seven percent received craniospinal irradiation (CSI) while 33% received focal brain RT, with the olfactory region receiving doses as low as 0.5 Gy. Notably, 8 of 27 patients who received CSI (30%) reported phantosmia (odds ratio, 7.66; 95% confidence interval, 2.07-28.34; P = .002). Conclusions: In the first-ever study examining radiation-induced phantosmia among children and young adults treated with IMPT, all affected patients received irradiation dose to the olfactory region. Physician awareness of phantosmia, especially in the context of CSI, may improve the patient experience and treatment compliance. A prospective study is needed to elucidate frequency, severity, and phantosmia mechanism.

Background and Purpose: Radiation esophagitis is a clinically important toxicity seen with treatment for locally-advanced non-small cell lung cancer. There is considerable disagreement among prior studies in identifying predictors of radiation esophagitis. We apply machine learning algorithms to identify factors contributing to the development of radiation esophagitis to uncover previously unidentified criteria and more robust dosimetric factors. Materials and Methods: We used machine learning approaches to identify predictors of grade ≥ 3 radiation esophagitis in a cohort of 202 consecutive locally-advanced non-small cell lung cancer patients treated with definitive chemoradiation from 2008 to 2016. We evaluated 35 clinical features per patient grouped into risk factors, comorbidities, imaging, stage, histology, radiotherapy, chemotherapy and dosimetry. Univariate and multivariate analyses were performed using a panel of 11 machine learning algorithms combined with predictive power assessments. Results: All patients were treated to a median dose of 66.6 Gy at 1.8 Gy per fraction using photon (89.6%) and proton (10.4%) beam therapy, most often with concurrent chemotherapy (86.6%). 11.4% of patients developed grade ≥ 3 radiation esophagitis. On univariate analysis, no individual feature was found to predict radiation esophagitis (AUC range 0.45–0.55, p ≥ 0.07). In multivariate analysis, all machine learning algorithms exhibited poor predictive performance (AUC range 0.46–0.56, p ≥ 0.07). Conclusions: Contemporary machine learning algorithms applied to our modern, relatively large institutional cohort could not identify any reliable predictors of grade ≥ 3 radiation esophagitis. Additional patients are needed, and novel patient-specific and treatment characteristics should be investigated to develop clinically meaningful methods to mitigate this survival altering toxicity. Keywords: Radiation esophagitis, Machine learning, Non-small cell lung cancer, Chemoradiation, Radiation-induced toxicity, Intensity-modulated radiation therapy, Proton beam therapy

Introduction: Given the concern for cardiopulmonary toxicity in patients with NSCLC undergoing postoperative radiation therapy (PORT), the purpose of this study was to evaluate the association between heart dose and overall survival (OS) in patients undergoing PORT with modern techniques. Methods: This is a retrospective study of consecutive patients with NSCLC treated with PORT between May 2004 and January 2017. Clinical records were reviewed and radiation dose distributions were analyzed for association with OS. Results: A total of 284 patients were analyzed. At the time of surgery, most patients had pathologic American Joint Committee on Cancer seventh edition stage III disease (91.2 %) and received either preoperative or adjuvant chemotherapy (92.3 %). Most patients underwent a lobectomy (81.3 %) and had R0 (80.6 %) or R1 (19.4 %) resection. PORT was delivered with a median radiation dose of 54 Gy, and 70.4 % of patients were treated with intensity-modulated radiation therapy. Dosimetric variables across a large range of doses to the heart were highly significant (p < 0.05) for OS. The volume of the heart receiving 8 Gy (HV8) was the most significant dosimetric variable (p < 0.001), and the median HV8 was 35.5 %. The median OS was 33.2 versus 53.6 months (p < 0.005) for patients with HV8 above or below 35.5 %, respectively. On multivariable analysis accounting for other potential prognostic confounders, HV8 remained highly significant (p < 0.001). Conclusions: The data reveal a strong correlation between increasing heart dose and OS in patients with NSCLC undergoing PORT. Taken together with the recently presented LungART trial, lowering heart dose in PORT patients may help to decrease the risk of morbidity and mortality and improve the therapeutic ratio of PORT.

Purpose: To report the outcomes of sinonasal tumors treated with proton beam therapy (PBT) on the Proton Collaborative Group registry study. Methods and Materials: Sixty-nine patients with sinonasal tumors underwent curative intent PBT between 2010 and 2016. Patients who received de novo irradiation (42 patients) were analyzed separately from those who received reirradiation (27 patients) (re-RT). Median age was 53.1 years (range, 15.7-82.1; de novo) and 57.4 years (range, 31.3-88.0; re-RT). The most common histology was squamous cell carcinoma in both groups. Median PBT dose was 58.5 Gy (RBE) (range, 12-78.3; de novo) and 60.0 Gy (RBE) (range 18.2-72.3; re-RT), and median dose per fraction was 2.0 Gy (RBE) for both cohorts. Survival estimates for patients who received de novo irradiation and those who received re-RT were calculated using the Kaplan-Meier method. Results: Median follow-up for surviving patients was 26.4 months (range, 3.5-220.5). The 3-year overall survival (OS), freedom from distant metastasis, freedom from disease progression, and freedom from locoregional recurrence (FFLR) for de novo irradiation were 100%, 84.0%, 77.3%, and 92.9%, respectively. With re-RT, the 3-year OS, freedom from distant metastasis, FFDP, and FFLR were 76.2%, 47.4%, 32.1%, and 33.8%, respectively. In addition, 12 patients (17.4%) experienced recurrent disease. Re-RT was associated with inferior FFLR (P = .04). On univariate analysis, squamous cell carcinoma was associated with inferior OS (P

Purpose: The emergence of the coronavirus disease (COVID-19) global pandemic has led to a significant shift in the delivery of health care, including an explosive growth of telemedicine services. This reverberated in the field of radiation oncology, with a recent American Society for Radiation Oncology (ASTRO) nationwide survey reporting 89% of surveyed clinics began to offer telemedicine programs to patients because of the pandemic. However, this survey did not study the perceptions and experiences of those clinicians delivering telemedicine services. Methods and Materials: We investigated through a national physician survey the merits and limitations of radiation oncology tele-consultations. An anonymous web-based survey was distributed using SurveyMonkey (www.surveymonkey.com) via email. Results: Seventy six respondents (16.1% overall response rate) completed the survey, with broad representation from both academic and community-based practices. Many respondents agreed that transitioning to tele-consultations was a needed step given the emergence of the pandemic, despite most having never previously offered this service. Despite many radiation oncologists having little prior experience with tele-consultations, a majority were satisfied in being able to explain the details of a medical diagnosis, provide results of imaging and bloodwork, and discuss recommendations around radiation treatments through this format. Nearly half of the respondents agreed that tele-consultations felt impersonal, with the inability to complete physical examinations noted as a contributor to the impersonality. Nevertheless, respondents still agreed that telemedicine will play an important role going forward, and almost 90% agreed that they would offer tele-consultations even after the pandemic has resolved.

Purpose: Guidelines for locally advanced non-small cell lung cancer (LA-NSCLC) recommend definitive chemoradiation therapy (CRT) for cN2-N3 disease, reserving surgery for patients with minimal nodal involvement at presentation. The current literature suggests that surgery after CRT for stage III NSCLC can improve freedom-from-recurrence (FFR) but has not consistently demonstrated an improvement in overall survival, perhaps partly due to the low (45-50.4 Gy) preoperative doses delivered that result in low rates of mediastinal nodal clearance. We therefore analyzed factors associated with trimodality therapy receipt and determined outcomes in patients with LA-NSCLC who were treated with definitive doses (≥60 Gy) of neoadjuvant CRT prior to surgery. Methods and materials: We retrospectively analyzed 355 consecutive patients with LA-NSCLC who were treated with curative intent between January 2000 and December 2013. The Kaplan-Meier method was used to estimate the overall survival and FFR of patients who were initially planned to receive trimodality treatment but never underwent surgery (unplanned bimodality) compared with those who were never considered to be surgical candidates (planned bimodality) and those who underwent surgical resection after CRT (trimodality). Cox proportional hazards regression with forward selection was used for multivariate analyses, and the Fisher exact test was used to test contingency tables. Results: Patients who received trimodality therapy had a longer median survival than those with unplanned or planned bimodality therapy at 59.9, 20.1, and 17.3 months, respectively (P < .001). The survival benefit with surgery persisted in patients with stage IIIB (P < .001) and N3 (P = .010) nodal disease when mediastinal nodal clearance was achieved. FFR was also improved with surgical resection (P = .001). Race (P < .001), stage (P < .001), performance status (P < .001), age (P < .001), and diagnosis of chronic obstructive pulmonary disease (P = .009) were significant indicators that influenced both the decision to initially choose trimodality therapy at consultation and to actually perform surgical resection. Conclusions: Trimodality treatment significantly improves survival and FFR in patients with LA-NSCLC when definitive doses of radiation with neoadjuvant chemotherapy are employed. We identified important demographic features that predict the use of surgical intervention in patients with stage III NSCLC.