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Background: The purpose of this study is to evaluate practice patterns and outcomes between intensity‐modulated radiation therapy (IMRT) and 3D‐conformal radiation (3D‐CRT) in early stage glottic cancer. Methods: The linked Surveillance, Epidemiology, and End Results (SEER)‐Medicare database was used to identify and compare patient and disease profiles, mortality, and toxicity in patients with T1‐2 larynx cancer undergoing definitive radiation (RT). Results: A total of 1520 patients underwent definitive radiation with 3D‐CRT (n = 1309) or IMRT (n = 211). Non‐white race, those with a Charlson Comorbidity Index ≥2, T2 disease, and those treated at community practices were more likely to undergo IMRT. Rates of IMRT increased from 2006 to 2015, while relative rates of 3D‐CRT decreased. Two‐year CSS was superior with 3D‐CRT (hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.22–0.65; p < 0.001). There was no difference in OS between 3D‐CRT and IMRT (p = 0.119). Conclusions: Patients receiving 3D‐CRT had improved CSS compared to IMRT with no difference in OS. [ABSTRACT FROM AUTHOR]

Background: Preclinical evidence suggests a link between the renin‐angiotensin system and oncogenesis. We aimed to explore the impact of angiotensin‐converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) in head and neck cancer (HNC). Methods: Over 5000 patients were identified from the Surveillance, Epidemiology, and End Results‐Medicare linked dataset and categorized according to ACEi and ARB and diagnoses of chronic kidney disease (CKD) or hypertension (HTN). Overall survival (OS) and cancer‐specific survival (CSS) were compared using Cox multivariable regression (MVA), expressed as hazard ratios (HR) with 95% confidence intervals (95%CI). Results: No significant MVA associations for OS or CSS were found for ACEi. Compared to patients with CKD/HTN taking ARB, those with CKD/HTN not taking ARB experienced worse OS (HR 1.28, 95%CI 1.09–1.51, p = 0.003) and CSS (HR 1.23, 95%CI 1.00–1.50, p = 0.050). Conclusions: ARB usage is associated with improved OS and CSS among HNC patients with CKD or HTN. [ABSTRACT FROM AUTHOR]

Positron emission tomography (PET) is typically performed in the supine position. However, breast magnetic resonance imaging (MRI) is performed in prone, as this improves visibility of deep breast tissues. With the emergence of hybrid scanners that integrate molecular information from PET and functional information from MRI, it is of great interest to determine if the prognostic utility of prone PET is equivalent to supine. We compared PERCIST (PET Response Criteria in Solid Tumors) measurements between prone and supine FDG-PET in patients with breast cancer and the effect of orientation on predicting pathologic complete response (pCR). In total, 47 patients were enrolled and received up to 6 cycles of neoadjuvant therapy. Prone and supine FDG-PET were performed at baseline (t0; n=46), after cycle 1 (t1; n=1) or 2 (t2; n=10), or after all neoadjuvant therapy (t3; n= 19). FDG uptake was quantified by maximum and peak standardized uptake value (SUV) with and without normalization to lean body mass; that is, SUVmax, SUVpeak, SULmax, and SULpeak. PERCIST measurements were performed for each paired baseline and post-treatment scan. Receiver operating characteristic analysis for the prediction of pCR was performed using logistic regression that included age and tumor size as covariates. SUV and SUL metrics were significantly different between orientation (P<.001), but were highly correlated (P>.98). Importantly, no differences were observed with the PERCIST measurements (P>.6). Overlapping 95% confidence intervals for the receiver operating characteristic analysis suggested no difference at predicting pCR. Therefore, prone and supine PERCIST in this data set were not statistically different. [ABSTRACT FROM AUTHOR]

Objective: In a cohort of patients who were treated with resection and adjuvant radiotherapy (RT) for adamantinomatous craniopharyngioma (ACP), the authors aimed to determine whether gross tumor volume (GTV) at the initiation of RT was associated with the risk of progressive disease (PD) following treatment., Methods: Pediatric and adolescent patients who received surgery and RT for ACP at a single institution from 1998 to 2021 were identified. Univariable Cox regression analyses (UVAs) were performed to assess the association between pre-RT GTV and PD after RT. Multivariable analyses (MVAs) were used to control for potential confounders. Two different endpoints were used to define PD. The first definition was based on radiographic tumor growth, with or without progression of clinical symptoms. The second definition was the requirement for an additional tumor-directed intervention following the completion of RT., Results: Forty-eight patients were eligible for inclusion. The median age at diagnosis was 7.9 years (range 2.1-17.4 years). All patients were treated with surgery and RT with a median dose of 52.2 Gy (range 45-55.8 Gy) and median GTV of 9.86 cm3 (range 0.7-117.7 cm3). After a median follow-up of 66.4 months, 8 patients experienced PD based on both definitions. The 5-year event-free survival rate was 85.4% (95% CI 74.1%-98.3%). On both UVA and MVA, GTV was significantly associated with an increased likelihood of PD (UVA: HR 1.02, 95% CI 1.00-1.04, p = 0.02; MVA: HR 1.10, 95% CI 1.02-1.19, p = 0.01). However, after exclusion of a single outlier with a GTV of 117.7 cm3 prior to RT (remainder of the cohort: range 0.7-37.3 cm3), a second analysis identified no significant association between GTV and PD (UVA: HR 1.03, 95% CI 0.96-1.10, p = 0.4; MVA: HR 1.06, 95% CI 0.96-1.17, p = 0.24)., Conclusions: The authors conclude that for most children and adolescents with ACP, the GTV at the initiation of RT is not associated with the risk of PD. This finding may influence surgical practice, because it suggests that aggressive tumor debulking for the purpose of improving the efficacy of RT may not be necessary. In the case of giant tumors, however, novel strategies may be needed for tumor control.

Background: Bone metastasis is the most common cause of cancer-related pain. Radiation therapy (RT) can provide successful palliation but there is currently no consensus for surveillance after palliative radiation. This study aimed to assess the feasibility of surveillance after RT for painful bone metastases., Methods: The study took place in an academic cancer center. Patient feasibility measures included % of calls answered, ease of recruitment and study retention. Clinician measures included % of calls made within 3 days, call time and qualitative feedback. Patients were identified with a painful bone metastasis treated with RT. The bone metastasis had a worst pain score of at least 4 (0-10 scale), with pain localized to a radiographically confirmed lesion. Patients were called at weeks 1, 4 and 8 following RT. Pain response and opioid use were assessed. Quality of life was assessed using a validated questionnaire. Descriptive statistics were used to assess if these metrics were met for patients and clinicians over 8 weeks post-RT., Results: Twenty patients were consented: 14 participants completed treatment and were not hospitalized or deceased prior to week 1. The patients were 50% male and 50% female. Recruitment was completed quickly, with no patients withdrawing. Response rate was week 1: 85% week 4: 83% and week 8: 83%. Six patients were referred back to their provider for pain management. Calls were made to patients within 3 days a median of 63% of the time (range, 40-82%), with a median call time of 16 (range, 8-42) minutes. Call lengths were longer for patients who required interpretation. Nurse feedback highlighted length of call and nursing time available as limitations., Conclusions: All patient feasibility measures were met. Six patients required further pain management, highlighting a need for improved follow up post-RT for bone metastases. Staffing challenges for this intervention must be overcome.

Purpose: Complementary health approaches (CHAs) equip patients to self-manage radiation therapy (RT)-related symptoms and fulfill unmet needs, but few disclose CHA use to their radiation oncologist. An integrative medicine educational program (IMEP) was developed to assess its ability to improve patient self-efficacy for symptom management and CHA use disclosure., Methods and Materials: The IMEP included 4 1-hour sessions covering topics of (1) meditation, (2) yoga, (3) massage therapy, and (4) nutrition. Individuals over age 18 years and actively receiving RT were administered presession and postsession surveys. The primary outcomes were intention to disclose CHA use and self-efficacy. Qualitative data were assessed with a thematic approach., Results: Overall, 23 patients attended 1 or more sessions, yielding 43 completed surveys. Compared with 35.9% of participants who had disclosed CHA use before the session, 67.4% intended to disclose after the session. Of the 5 self-efficacy statements, there were significant improvements in "I have ownership over my health" (increase of 0.42; 95% CI, 0.07-0.77; P = .01), "I have tools to manage my disease on my own" (1.14; 95% CI, 0.42-1.87; P = .001), and "I have control over my cancer" (0.96; 95% CI, 0.39-1.53; P < .001). Barriers to involvement included transportation, timing relative to RT appointment, and poor performance status., Conclusions: A radiation-specific IMEP resulted in a high rate of intention to disclose CHA use and improvements in patients' reported self-efficacy to manage radiation-related symptoms. However, substantial resources were needed to deliver the IMEP. Future work must focus on increasing accessibility through telehealth and flexible timing., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

The purpose of this report is to present the implementation of a process for after-hours radiation treatment (RT) utilizing remote treatment planning based on optimized diagnostic computed tomography (CT) scans for the urgent palliative treatment of inpatients. A standardized operating procedure was developed by an interprofessional panel to improve the quality of after-hours RT and minimize the risk of treatment errors. A new diagnostic CT protocol was created that could be performed after-hours on hospital scanners and would ensure a reproducible patient position and adequate field of view. An on-call structure for dosimetry staff was created utilizing remote treatment planning. The optimized CT protocol was developed in collaboration with the radiology department, and a novel order set was created in the electronic health system. The clinical workflow begins with the radiation oncologist notifying the on-call team (therapist, dosimetrist, and physicist) and obtaining an optimized diagnostic CT scan on a hospital-based scanner. The dosimetrist remotely creates a plan; the physicist checks the plan; and the patient is treated. Plans are intentionally simple (parallel opposed fields, symmetric jaws) to expedite care and reduce the risk of error. Education on the new process was provided for all relevant staff. Our process was successfully implemented with the use of an optimized CT protocol and remote treatment planning. This approach has the potential to improve the quality and safety of emergent after-hours RT by better approximating the normal process of care., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Fakhoury et al.)

Objective: Immune checkpoint inhibitors (ICIs) and stereotactic radiosurgery (SRS) are commonly utilized in the management of brain metastases. Treatment-related imaging changes (TRICs) are a frequently observed clinical manifestation and are commonly classified as imaging-defined radiation necrosis. However, these findings are not well characterized and may predict a response to SRS and ICIs. The objective of this study was to investigate predictors of TRICs and their impact on patient survival., Methods: This retrospective multicenter cohort study was conducted through the International Radiosurgery Research Foundation. Member institutions submitted de-identified clinical and dosimetric data for patients with non-small cell lung cancer (NSCLC), melanoma, and renal cell carcinoma (RCC) brain metastases that had been treated with SRS and ICIs. Data were collected from March 2020 to February 2021. Univariable and multivariable Cox and logistic regression analyses were performed. The Kaplan-Meier method was used to evaluate overall survival (OS). The diagnosis-specific graded prognostic assessment was used to guide variable selection. TRICs were determined on the basis of MRI, PET/CT, or MR spectroscopy, and consensus by local clinical providers was required., Results: The analysis included 697 patients with 4536 brain metastases across 11 international institutions in 4 countries. The median follow-up after SRS was 13.6 months. The median age was 66 years (IQR 58-73 years), 54.1% of patients were male, and 57.3%, 36.3%, and 6.4% of tumors were NSCLC, melanoma, and RCC, respectively. All patients had undergone single-fraction radiosurgery to a median margin dose of 20 Gy (IQR 18-20 Gy). TRICs were observed in 9.8% of patients. The median OS for all patients was 24.5 months. On univariable analysis, Karnofsky Performance Status (KPS; HR 0.98, p < 0.001), TRICs (HR 0.67, p = 0.03), female sex (HR 0.67, p < 0.001), and prior resection (HR 0.60, p = 0.03) were associated with improved OS. On multivariable analysis, KPS (HR 0.98, p < 0.001) and TRICs (HR 0.66, p = 0.03) were associated with improved OS. A brain volume receiving ≥ 12 Gy of radiation (V12Gy) ≥ 10 cm3 (OR 2.78, p < 0.001), prior whole-brain radiation therapy (OR 3.46, p = 0.006), and RCC histology (OR 3.10, p = 0.01) were associated with an increased probability of developing TRICs. The median OS rates in patients with and without TRICs were 29.0 and 23.1 months, respectively (p = 0.03, log-rank test)., Conclusions: TRICs following ICI and SRS were associated with a median OS benefit of approximately 6 months in this retrospective multicenter study. Further prospective study and additional stratification are needed to validate these findings and further elucidate the role and etiology of this common clinical scenario.

Background: Patients with renal cell carcinoma (RCC) brain metastases are frequently treated with immune checkpoint inhibitors (ICIs) and stereotactic radiosurgery (SRS). However, data reporting on the risk of developing radiation necrosis (RN) are limited., Methods: RN rates were compared for concurrent therapy (ICI/SRS administration within 4 weeks of one another) and nonconcurrent therapy with the χ 2 test. Univariable logistic regression was used to identify factors associated with developing RN., Results: Fifty patients (23 concurrent and 27 nonconcurrent) with 395 brain metastases were analyzed. The median follow-up was 12.1 months; the median age was 65 years. The median margin dose was 20 Gy, and 4% underwent prior whole-brain radiation therapy (WBRT). The median treated tumor volume was 3.32 cm 3 (range, 0.06-42.38 cm 3 ); the median volume of normal brain tissue receiving a dose of 12 Gy or higher (V12 Gy) was 8.42 cm 3 (range, 0.27-111.22 cm 3 ). Any-grade RN occurred in 17.4% and 22.2% in the concurrent and nonconcurrent groups, respectively (P = .67). Symptomatic RN occurred in 4.3% and 14.8% in the concurrent and nonconcurrent groups, respectively (P = .23). Increased tumor volume during SRS (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.01-1.19; P = .04) was associated with developing RN, although V12 Gy (OR, 1.03; 95% CI, 0.99-1.06; P = .06), concurrent therapy (OR, 0.74; 95% CI, 0.17-2.30; P = .76), prior WBRT, and ICI agents were not statistically significant., Conclusions: Symptomatic RN occurs in a minority of patients with RCC brain metastases treated with ICI/SRS. The majority of events were grade 1 to 3 and were managed medically. Concurrent ICI/SRS does not appear to increase this risk. Attempts to improve dose conformality (reduce V12) may be the most successful mitigation strategy in single-fraction SRS., (© 2022 American Cancer Society.)

Objective: Resection of meningiomas in direct contact with the anterior optic apparatus carries risk of injury to the visual pathway. Stereotactic radiosurgery (SRS) offers a minimally invasive alternative. However, its use is limited owing to the risk of radiation-induced optic neuropathy. Few SRS studies have specifically assessed the risks and benefits of treating meningiomas in direct contact with the optic nerve, chiasm, or optic tract. The authors hypothesized that SRS is safe for select patients with meningiomas in direct contact with the anterior optic apparatus., Methods: The authors performed an international multicenter retrospective analysis of 328 patients across 11 institutions. All patients had meningiomas in direct contract with the optic apparatus. Patients were followed for a median duration of 56 months after SRS. Neurological examinations, including visual function evaluations, were performed at follow-up visits. Clinical and treatment variables were collected at each site according to protocol. Tumor volumes were assessed with serial MR imaging. Variables predictive of visual deficit were identified using univariable and multivariable logistic regression., Results: SRS was the initial treatment modality for 64.6% of patients, and 93% of patients received SRS as a single fraction. Visual information was available for 302 patients. Of these patients, visual decline occurred in 29 patients (9.6%), of whom 12 (41.4%) had evidence of tumor progression. Visual decline in the remaining 17 patients (5.6%) was not associated with tumor progression. Pre-SRS Karnofsky Performance Status predicted visual decline in adjusted analysis (adjusted OR 0.9, 95% CI 0.9-1.0, p < 0.01). Follow-up imaging data were available for 322 patients. Of these patients, 294 patients (91.3%) had radiographic evidence of stability or tumor regression at last follow up. Symptom duration was associated with tumor progression in adjusted analysis (adjusted OR 1.01, adjusted 95% CI 1.0-1.02, adjusted p = 0.02)., Conclusions: In this international multicenter study, the vast majority of patients exhibited tumor control and preservation of visual function when SRS was used to treat meningioma in direct contact with the anterior optic pathways. SRS is a relatively safe treatment modality for select patients with perioptic meningiomas in direct contact with the optic apparatus.

Glioblastoma and other high-grade gliomas (HGGs) are the most common and deadly primary brain tumors. Due to recent advances in immunotherapy and improved clinical outcomes in other disease sites, the study of immunotherapy in HGG has increased significantly. Herein, we summarize and evaluate existing evidence and ongoing clinical trials investigating the use of immunotherapy in the treatment of HGG, including therapeutic vaccination, immune checkpoint inhibition, adoptive lymphocyte transfer, and combinatorial approaches utilizing radiation and multiple modalities of immunotherapy. Special attention is given to the mechanisms by which radiation may improve immunogenicity in HGG, why this motivates the study of radiation in combination with immunotherapy, and how to determine optimal dosing and scheduling of radiation. Though larger randomized controlled trials have not consistently shown improvements in clinical outcomes, this area of research is still in its early stages and a number of important lessons can be taken away from the studies that have been completed to date. Many studies found a subset of patients who experienced durable responses, and analysis of their immune cells and tumor cells can be used to identify biomarkers that predict therapeutic response, as well as additional glioma-specific targets that can enhance therapeutic efficacy in a challenging tumor type., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr-20-1933). The series “Synergy in Action: Novel Approaches to Combining Radiation Therapy and Immunotherapy” was commissioned by the editorial office without any funding or sponsorship. DEN reports personal fees from DNAtrix, outside the submitted work. DRO reports grants from American Heart Association, grants from American Cancer Society, grants from Medtronic, grants from Agios, outside the submitted work. CGR reports grants from Takeda, personal fees from Genentech, and personal fees from AstraZeneca, outside the submitted work. The authors have no other conflicts of interest to declare., (2021 Translational Cancer Research. All rights reserved.)

Background: Stereotactic radiosurgery (SRS) is increasingly used for management of perioptic meningiomas., Objective: To study the safety and effectiveness of SRS for perioptic meningiomas., Methods: From 12 institutions participating in the International Radiosurgery Research Foundation (IRRF), we retrospectively assessed treatment parameters and outcomes following SRS for meningiomas located within 3 mm of the optic apparatus., Results: A total of 438 patients (median age 51 yr) underwent SRS for histologically confirmed (29%) or radiologically suspected (71%) perioptic meningiomas. Median treatment volume was 8.01 cm3. Median prescription dose was 12 Gy, and median dose to the optic apparatus was 8.50 Gy. A total of 405 patients (93%) underwent single-fraction SRS and 33 patients (7%) underwent hypofractionated SRS. During median imaging follow-up of 55.6 mo (range: 3.15-239 mo), 33 (8%) patients experienced tumor progression. Actuarial 5-yr and 10-yr progression-free survival was 96% and 89%, respectively. Prescription dose of ≥12 Gy (HR: 0.310; 95% CI [0.141-0.679], P = .003) and single-fraction SRS (HR: 0.078; 95% CI [0.016-0.395], P = .002) were associated with improved tumor control. A total of 31 (10%) patients experienced visual decline, with actuarial 5-yr and 10-yr post-SRS visual decline rates of 9% and 21%, respectively. Maximum dose to the optic apparatus ≥10 Gy (HR = 2.370; 95% CI [1.086-5.172], P = .03) and tumor progression (HR = 4.340; 95% CI [2.070-9.097], P < .001) were independent predictors of post-SRS visual decline., Conclusion: SRS provides durable tumor control and quite acceptable rates of vision preservation in perioptic meningiomas. Margin dose of ≥12 Gy is associated with improved tumor control, while a dose to the optic apparatus of ≥10 Gy and tumor progression are associated with post-SRS visual decline., (© Congress of Neurological Surgeons 2021.)

Positron emission tomography (PET) is typically performed in the supine position. However, breast magnetic resonance imaging (MRI) is performed in prone, as this improves visibility of deep breast tissues. With the emergence of hybrid scanners that integrate molecular information from PET and functional information from MRI, it is of great interest to determine if the prognostic utility of prone PET is equivalent to supine. We compared PERCIST (PET Response Criteria in Solid Tumors) measurements between prone and supine FDG-PET in patients with breast cancer and the effect of orientation on predicting pathologic complete response (pCR). In total, 47 patients were enrolled and received up to 6 cycles of neoadjuvant therapy. Prone and supine FDG-PET were performed at baseline ( t 0 ; n = 46), after cycle 1 ( t 1 ; n = 1) or 2 ( t 2 ; n = 10), or after all neoadjuvant therapy ( t 3 ; n = 19). FDG uptake was quantified by maximum and peak standardized uptake value ( SUV ) with and without normalization to lean body mass; that is, SUV max , SUV peak , SUL max , and SUL peak . PERCIST measurements were performed for each paired baseline and post-treatment scan. Receiver operating characteristic analysis for the prediction of pCR was performed using logistic regression that included age and tumor size as covariates. SUV and SUL metrics were significantly different between orientation ( P < .001), but were highly correlated ( P > .98). Importantly, no differences were observed with the PERCIST measurements ( P > .6). Overlapping 95% confidence intervals for the receiver operating characteristic analysis suggested no difference at predicting pCR. Therefore, prone and supine PERCIST in this data set were not statistically different., Competing Interests: Conflict of Interest: None reported., (© 2020 The Authors. Published by Grapho Publications, LLC.)

Purpose: We designed a prospective randomized, controlled pilot trial to investigate the effects of an enriched oral nutrition supplement on body composition and clinical outcomes following radical cystectomy., Materials and Methods: A total of 61 patients were randomized to an oral nutrition supplement or a multivitamin multimineral supplement twice daily during an 8-week perioperative period. Body composition was determined by analyzing abdominal computerized tomography images at the L3 vertebra. Sarcopenia was defined as a skeletal muscle index of less than 55 cm/m in males and less than 39 cm/m in females. The primary outcome was the difference in 30-day hospital free days. Secondary outcomes included hospital length of stay, complications, readmissions and mortality., Results: The oral nutrition supplement group lost less weight (-5 vs -6.5 kg, p = 0.04) compared to the multivitamin multimineral supplement group. The proportion of patients with sarcopenia did not change in the oral nutrition supplement group but increased 20% in the multivitamin multimineral supplement group (p = 0.01). Mean length of stay and 30-day hospital free days were similar in the groups. The oral nutrition supplement group had a lower rate of overall and major (Clavien grade 3 or greater) complications (48% vs 67% and 19% vs 25%, respectively) and a lower readmission rate (7% vs 17%) but the differences did not reach statistical significance., Conclusions: Patients who undergo radical cystectomy after consuming an oral nutrition supplement perioperatively have a reduced prevalence of sarcopenia and may also experience fewer and less severe complications and readmissions. A larger blinded, randomized, controlled trial is necessary to determine whether oral nutrition supplement interventions can improve outcomes following radical cystectomy.

Pathologic complete response following neoadjuvant therapy (NAT) is used as a short-term surrogate marker of eventual outcome in patients with breast cancer. Analyzing voxel-level heterogeneity in MRI-derived parametric maps, obtained before and after the first cycle of NAT ([Formula: see text]), in conjunction with receptor status, may improve the predictive accuracy of tumor response to NAT. Toward that end, we incorporated two MRI-derived parameters, the apparent diffusion coefficient and efflux rate constant, with receptor status in a logistic ridge-regression model. The area under the curve (AUC) and Brier score of the model computed via 10-fold cross validation were 0.94 (95% CI: 0.85, 0.99) and 0.11 (95% CI: 0.06, 0.16), respectively. These two statistics strongly support the hypothesis that our proposed model outperforms the other models that we investigated (namely, models without either receptor information or voxel-level information). The contribution of the receptor information was manifested by an 8% to 15% increase in AUC and a 14% to 21% decrease in Brier score. These data indicate that combining multiparametric MRI with hormone receptor status has a high likelihood of improved prediction of pathologic response to NAT in breast cancer.