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Aims: During the COVID-19 public health emergency, we previously identified decreased rates of radiotherapy (RT) peer review (PR) discussion and plan changes in virtual versus in-person PR conferences. To expand on these findings, we continued to prospectively collect data on all PR conferences from 2021 to 2023 and performed a follow-up analysis before and after the transition back to in-person PR., Materials and Methods: A prospectively maintained database of weekly PR cases was queried for consecutive cases reviewed before and after the transition from virtual to in-person conferences. Rates of PR discussion and change recommendations were summarized and compared between the virtual and in-person groups. A survey was developed and administered to assess participants' perceived levels of engagement, opinions on optimal PR format, and preferences for future meetings before and 3 months after the transition back to in-person PR., Results: In total, 2,103 RT plans were reviewed: 1,590 virtually and 513 after the transition back to in-person. There was no difference in faculty attendance between groups. The proportion of cases with PR discussion increased from virtual (9.8%) to in-person (25.5%) format (p < 0.001). In the virtual group, 8.1% of cases had 1 topic and 1.7% had 2+ topics discussed. This increased to 15.8% and 9.7% during in-person PR, respectively (p < 0.001). The rate of change recommendation also increased from 1.5% (virtual) to 3.3% (in-person, p = 0.016). Among cases with at least 1 topic discussed, there was no difference in changes. Survey-reported distraction significantly decreased from virtual to in-person PR (p < 0.001)., Conclusion: Upon returning to in-person PR conferences, peer discussion and plan change recommendations significantly increased and returned to pre-pandemic levels, and participants' perceived levels of distraction were reduced. In an increasingly virtual world, additional efforts to develop best practices that maximize PR discussion and minimize distraction outside virtual conferences are warranted., (Copyright © 2024. Published by Elsevier Ltd.)

Importance: The impact of patient-specific, disease-related, and social factors on outcomes in limited-stage small cell lung cancer (LS-SCLC) is not well defined. A post hoc secondary analysis of such factors from the Cancer and Leukemia Group B (CALGB) 30610-Radiation Therapy Oncology Group (RTOG) 0538 trial may impact future trial design., Objective: To assess the comprehensive demographic, disease-related, treatment-related, and social factors for potential associations with survival outcomes and understand whether specific subpopulations may benefit from radiotherapy (RT) dose escalation in LS-SCLC., Design, Setting, and Participants: This post hoc secondary analysis of a randomized clinical trial included 638 adults with LS-SCLC treated at 186 unique treatment sites with at least 1 accrual for all patients from March 15, 2008, to December 1, 2019; 313 patients were randomized to receive RT twice daily to a dosage of 45 Gy for 3 weeks and 325 to receive RT once daily to a dosage of 70 Gy for 7 weeks. Data were locked February 28, 2022, and analyzed from November 28, 2022, to June 4, 2024., Interventions: Twice-daily RT or once-daily RT., Main Outcomes and Measures: Multivariable Cox proportional hazards models evaluated the association of treatment groups and other risk factors with progression-free survival (PFS) and overall survival (OS). Patient-specific factors included age, sex, and Eastern Cooperative Oncology Group performance status. Disease-related factors included tumor, nodal, and overall cancer stages. Treatment-related factors included type of chemotherapy, timing of concurrent RT, RT technique, and prophylactic cranial irradiation. Social factors included marital status and treatment center accrual volume., Results: Among 507 patients (260 [51.3%] female and 247 [48.7%] male; mean [SD] age, 62.6 [7.9] years) included in the multivariate survival analysis, with a median follow-up of 4.7 (IQR, 3.7-7.1) years, female sex was associated with improved OS (hazard ratio [HR], 0.73 [95% CI, 0.58-0.91]; P = .006), while being 70 years or older was associated with decreased OS (HR, 1.50 [95% CI, 1.14-1.98]; P = .004). Neither age nor sex was associated with PFS. When compared with those with N1 disease, OS and PFS were worse in patients with N2 (HRs, 1.64 [95% CI, 1.19-2.26]; P = .002 and 1.36 [95% CI, 1.02-1.81]; P = .04, respectively) and N3 (HRs, 2.03 [95% CI, 1.40-2.93]; P < .001 and 1.63 [95% CI, 1.17-2.26]; P = .004) disease. Compared with stage II cancer, OS was worse for stage IIIA (HR, 1.65 [95% CI, 1.17-2.31]; P = .004) and stage IIIB (HR, 1.94 [95% CI, 1.34-2.83]; P < .001). Compared with high-volume accrual centers, treatment at low- or middle-volume accrual centers was associated with worse PFS (HRs, 1.94 [95% CI, 1.33-2.82; P < .001] and 1.44 [95% CI, 1.15-1.82; P = .002], respectively) and worse OS (HRs, 1.55 [95% CI, 1.03-2.32; P = .03] and 1.33 [95% CI, 1.04-1.70; P = .02], respectively)., Conclusions and Relevance: This secondary analysis of the CALGB 30610-RTOG 0538 randomized clinical trial of patients with LS-SCLC found associations between female sex or being younger than 70 years and improved overall survival and between advanced nodal stage or treatment at low- or middle-volume accrual centers and worse outcomes. These findings suggest that stratification by nodal stage, clinical stage, and age should be considered in future randomized trials., Trial Registration: ClinicalTrials.gov Identifier: NCT00632853.

Purpose/objectives: Biomarkers for extracranial oligometastatic disease remain elusive and few studies have attempted to correlate genomic data to the presence of true oligometastatic disease., Methods: Patients with non-small cell lung cancer (NSCLC) and brain metastases were identified in our departmental database. Electronic medical records were used to identify patients for whom liquid biopsy-based comprehensive genomic profiling (Guardant Health) was available. Extracranial oligometastatic disease was defined as patients having ≤5 non-brain metastases without diffuse involvement of a single organ. Widespread disease was any spread beyond oligometastatic. Fisher's exact tests were used to screen for mutations statistically associated (p<0.1) with either oligometastatic or widespread extracranial disease. A risk score for the likelihood of oligometastatic disease was generated and correlated to the likelihood of having oligometastatic disease vs widespread disease. For oligometastatic patients, a competing risk analysis was done to assess for cumulative incidence of oligometastatic progression. Cox regression was used to determine association between oligometastatic risk score and oligoprogression., Results: 130 patients met study criteria and were included in the analysis. 51 patients (39%) had extracranial oligometastatic disease. Genetic mutations included in the Guardant panel that were associated (p<0.1) with the presence of oligometastatic disease included ATM, JAK2, MAP2K2, and NTRK1, while ARID1A and CCNE1 were associated with widespread disease. Patients with a positive, neutral and negative risk score for oligometastatic disease had a 78%, 41% and 11.5% likelihood of having oligometastatic disease, respectively (p<0.0001). Overall survival for patients with positive, neutral and negative risk scores for oligometastatic disease was 86% vs 82% vs 64% at 6 months (p=0.2). Oligometastatic risk score was significantly associated with the likelihood of oligoprogression based on the Wald chi-square test. Patients with positive, neutral and negative risk scores for oligometastatic disease had a cumulative incidence of oligometastatic progression of 77% vs 35% vs 33% at 6 months (p=0.03)., Conclusions: Elucidation of a genomic signature for extracranial oligometastatic disease derived from non-invasive liquid biopsy appears feasible for NSCLC patients. Patients with this signature exhibited higher rates of early oligoprogression. External validation could lead to a biomarker that has the potential to direct local therapies in oligometastatic patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Choi, D’Agostino, Farris, Abdulhaleem, Hunting, Wang, Smith, Ruiz, Lycan, Petty, Cramer, Tatter, Laxton, White, Li, Su, Whitlow, Xing and Chan.)

Stereotactic Body Radiation Therapy for lung tumors near the chest wall often causes significant chest wall pain (CWP), negatively impacting patients' quality of life. The mechanisms behind SBRT-induced CWP remain unclear and may involve multiple factors. We investigated the potential crosstalk between radiation-activated osteoclasts and sensory neurons, focusing on osteoclast-derived factors in CWP. Using the murine pre-osteoclast cell line Raw264.7, we induced differentiation with RANKL, followed by 10Gy gamma-irradiation. Conditioned media from these irradiated osteoclasts was used to treat sensory neuronal cultures from mouse dorsal root ganglia. Neuronal cultures were also directly exposed to 10Gy radiation, with and without osteoclast co-culture. Analysis of osteoclast markers and pain-associated neuropeptides was conducted using RT-qPCR and histochemical staining. Osteoclast differentiation and activity were inhibited using Osteoprotegerin and risedronate. Results showed that high-dose radiation significantly increased osteoclast size, resorption pit size, and activity biomarkers. Neurons treated with CM from irradiated osteoclasts showed increased expression of pain-associated neuropeptides CGRP and Substance P, which was mitigated by osteoprotegerin and risedronate. This study suggests that high-dose radiation enhances osteoclast activity, upregulating pain-associated neuropeptides in sensory neurons, and that inhibitors like osteoprotegerin and risedronate may offer therapeutic strategies for managing radiation-induced pain., Competing Interests: Declarations CONFLICT OF INTEREST The authors have no conflicts of interest to declare

Background and Purpose: Histology was found to be an important prognostic factor for local tumor control probability (TCP) after stereotactic body radiotherapy (SBRT) of early-stage non-small-cell lung cancer (NSCLC). A histology-driven SBRT approach has not been explored in routine clinical practice and histology-dependent fractionation schemes remain unknown. Here, we analyzed pooled histologic TCP data as a function of biologically effective dose (BED) to determine histology-driven fractionation schemes for SBRT and hypofractionated radiotherapy of two predominant early-stage NSCLC histologic subtypes adenocarcinoma (ADC) and squamous cell carcinoma (SCC)., Material and Methods: The least-χ 2 method was used to fit the collected histologic TCP data of 8510 early-stage NSCLC patients to determine parameters for a well-developed radiobiological model per the Hypofractionated Treatment Effects in the Clinic (HyTEC) initiative., Results: A fit to the histologic TCP data yielded independent radiobiological parameter sets for radiotherapy of early-stage lung ADC and SCC. TCP increases steeply with BED and reaches an asymptotic maximal plateau, allowing us to determine model-independent optimal fractionation schemes of least doses in 1-30 fractions to achieve maximal tumor control for early-stage lung ADC and SCC, e.g., 30, 44, 48, and 51 Gy for ADC, and 32, 48, 54, and 58 Gy for SCC in 1, 3, 4, and 5 fractions, respectively., Conclusion: We presented the first determination of histology-dependent radiobiological parameters and model-independent histology-driven optimal SBRT and hypofractionated radiation therapy schemes for early-stage lung ADC and SCC. SCC requires substantially higher radiation doses to maximize tumor control than ADC, plausibly attributed to tumor genetic diversity and microenvironment. The determined optimal SBRT schemes agree well with clinical practice for early-stage lung ADC. These proposed optimal fractionation schemes provide first insights for histology-based personalized radiotherapy of two predominant early-stage NSCLC subtypes ADC and SCC, which require further validation with large-scale histologic TCP data., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: A series of radiobiological models were developed to study tumor control probability (TCP) for stereotactic body radiation therapy (SBRT) of early-stage non-small cell lung cancer (NSCLC) per the Hypofractionated Treatment Effects in the Clinic (HyTEC) working group. This study was conducted to further validate 3 representative models with the recent clinical TCP data ranging from conventional radiation therapy to SBRT of early-stage NSCLC and to determine systematic optimal fractionation regimens in 1 to 30 fractions for radiation therapy of early-stage NSCLC that were found to be model-independent., Methods and Materials: Recent clinical 1-, 2-, 3-, and 5-year actuarial or Kaplan-Meier TCP data of 9808 patients from 56 published papers were collected for radiation therapy of 2 to 4 Gy per fraction and SBRT of early-stage NSCLC. This data set nearly triples the original HyTEC sample, which was used to further validate the HyTEC model parameters determined from a fit to the clinical TCP data., Results: TCP data from the expanded data set are well described by the HyTEC models with α/β ratios of about 20 Gy. TCP increases sharply with biologically effective dose and reaches an asymptotic maximal plateau, which allows us to determine optimal fractionation schemes for radiation therapy of early-stage NSCLC., Conclusions: The HyTEC radiobiological models with α/β ratios of about 20 Gy determined from the fits to the clinical TCP data for SBRT of early-stage NSCLC describe the recent TCP data well for both radiation therapy of 2 to 4 Gy per fraction and SBRT dose and fractionation schemes of early-stage NSCLC. A steep dose response exists between TCP and biologically effective dose, and TCP reaches an asymptotic maximum. This feature results in model-independent optimal fractionation regimens determined whenever safe for SBRT and hypofractionated radiation therapy of early-stage NSCLC in 1 to 30 fractions to achieve asymptotic maximal tumor control, and T2 tumors require slightly higher optimal doses than T1 tumors. The proposed optimal fractionation schemes are consistent with clinical practice for SBRT of early-stage NSCLC., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Clinical biomarkers for brain metastases remain elusive. Increased availability of genomic profiling has brought discovery of these biomarkers to the forefront of research interests., Method: In this single institution retrospective series, 130 patients presenting with brain metastasis secondary to Non-Small Cell Lung Cancer (NSCLC) underwent comprehensive genomic profiling conducted using next generation circulating tumor deoxyribonucleic acid (DNA) (Guardant Health, Redwood City, CA). A total of 77 genetic mutation identified and correlated with nine clinical outcomes using appropriate statistical tests (general linear models, Mantel-Haenzel Chi Square test, and Cox proportional hazard regression models). For each outcome, a genetic signature composite score was created by summing the total genes wherein genes predictive of a clinically unfavorable outcome assigned a positive score, and genes with favorable clinical outcome assigned negative score., Results: Seventy-two genes appeared in at least one gene signature including: 14 genes had only unfavorable associations, 36 genes had only favorable associations, and 22 genes had mixed effects. Statistically significant associated signatures were found for the clinical endpoints of brain metastasis velocity, time to distant brain failure, lowest radiosurgery dose, extent of extracranial metastatic disease, concurrent diagnosis of brain metastasis and NSCLC, number of brain metastases at diagnosis as well as distant brain failure. Some genes were solely associated with multiple favorable or unfavorable outcomes., Conclusion: Genetic signatures were derived that showed strong associations with different clinical outcomes in NSCLC brain metastases patients. While these data remain to be validated, they may have prognostic and/or therapeutic impact in the future., Statement of Translation Relevance: Using Liquid biopsy in NSCLC brain metastases patients, the genetic signatures identified in this series are associated with multiple clinical outcomes particularly these ones that lead to early or more numerous metastases. These findings can be reverse-translated in laboratory studies to determine if they are part of the genetic pathway leading to brain metastasis formation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Abdulhaleem, Hunting, Wang, Smith, Agostino, Lycan, Farris, Ververs, Lo, Watabe, Topaloglu, Li, Whitlow, Su, Wang, Chan, Xing and Ruiz.)

Rationale and Objectives: The treatment of locally advanced lung cancer (LALC) with radiotherapy (RT) can be challenging. Multidisciplinary collaboration between radiologists and radiation oncologists (ROs) may optimize RT planning, reduce uncertainty in follow-up imaging interpretation, and improve outcomes., Materials and Methods: In this prospective clinical treatment trial (clinicaltrials.gov NCT04844736), 37 patients receiving definitive RT for LALC, six attending ROs, and three thoracic radiologists were consented and enrolled across four treatment centers. Prior to RT plan finalization, representative computed tomography (CT) slices with overlaid outlines of preliminary irradiation targets were shared with the team of radiologists. The primary endpoint was to assess feasibility of receiving feedback no later than 4 business days of RT simulation on at least 50% of plans., Results: Thirty-seven patients with lung cancer were enrolled, and 35 of 37 RT plans were reviewed. Of the 35 patients reviewed, mean age was 69 years. For 27 of 37 plans (73%), feedback was received within 4 or fewer days (interquartile range 3-4 days). Thirteen of 35 cases (37%) received feedback that the delineated target potentially did not include all sites suspicious for tumor involvement. In total, changes to the RT plan were recommended for over- or undercoverage in 16 of 35 cases (46%) and implemented in all cases. Radiology review resulted in no treatment delays and substantial changes to irradiated volumes: gross tumor volume, -1.9 to +96.1%; planning target volume, -37.5 to +116.5%., Conclusion: Interdisciplinary collaborative RT planning using a simplified workflow was feasible, produced no treatment delays, and prompted substantial changes in RT targets., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Aims: Clinical equipoise exists regarding early-stage lung cancer treatment among patients as trials comparing stereotactic body radiation therapy (SBRT) and surgical resection are unavailable. Given the potential differences in treatment effectiveness and side-effects, we sought to determine the associations between treatment type, decision regret and depression., Materials and Methods: A multicentre, prospective study of patients with stage IA-IIA non-small cell lung cancer (NSCLC) with planned treatment with SBRT or surgical resection was conducted. Decision regret and depression were measured using the Decision Regret Scale (DRS) and Patient Health Questionnaire-4 (PHQ-4) at 3, 6 and 12 months post-treatment, respectively. Mixed linear regression modelling examined associations between treatment and decision regret adjusting for patient sociodemographics., Results: Among 211 study participants with early-stage lung cancer, 128 (61%) patients received SBRT and 83 (39%) received surgical resection. The mean age was 73 years (standard deviation = 8); 57% were female; 79% were White non-Hispanic. In the entire cohort at 3 months post-treatment, 72 (34%) and 57 (27%) patients had mild and severe decision regret, respectively. Among patients who received SBRT or surgery, 71% and 46% of patients experienced at least mild decision regret at 3 months, respectively. DRS scores increased at 6 months and decreased slightly at 12 months of follow-up in both groups. Higher DRS scores were associated with SBRT treatment (adjusted mean difference = 4.18, 95% confidence interval 0.82 to 7.54) and depression (adjusted mean difference = 3.49, 95% confidence interval 0.52 to 6.47). Neither patient satisfaction with their provider nor decision-making role concordance was associated with DRS scores., Conclusions: Most early-stage lung cancer patients experienced at least mild decision regret, which was associated with SBRT treatment and depression symptoms. Findings suggest patients with early-stage lung cancer may not be receiving optimal treatment decision-making support. Therefore, opportunities for improved patient-clinician communication probably exist., (Copyright © 2023. Published by Elsevier Ltd.)

Purpose: To describe a novel metric to aid clinical decision making between shorter versus longer palliative radiotherapy (PRT) regimens using objective patient factors. Materials and Methods: Patients receiving PRT at a single institution between 2014 and 2018 were reviewed. The time between PRT start and finish was calculated and divided by overall survival (in days from start of PRT) to generate the percent of remaining life (PRL). This value was compared across various clinical factors using the Kruskal-Wallis test. Factors identified with a significance level p  < 0.01 were included in a novel Palliative Appropriateness Criteria Score (PACS) and were included in an online risk assessment tool to assist clinicians in patient-specific fractionation decisions. Results: Totally 1027 courses of PRT were analyzed. Median age was 64 years; Eastern Cooperative Oncology Group (ECOG) performance status was 3-4 in 22%. Primary malignancies included were lung (38%), breast (13.8%), prostate (9.3%), and other (39%). The indication for PRT was pain (61%), neurological (21%), or other (18%). Palliative regimens included 199 (19.4%) receiving single fraction, 176 (17.1%) receiving 2-5 fractions, and 652 (63.5%) receiving 10 fractions. Median follow-up was 83 days overall and 437 days for patients alive at last follow-up. Factors significantly associated with increased PRL (and included in the PACS) were male gender, ECOG 3-4, lung or "other" primary diagnosis (vs. breast or prostate), PRT indication (neurological dysfunction vs. pain/other), inpatient status, and extraosseous sites treatment. Death within 30 days was significantly associated with high-risk PACS categorization, regardless of fractionation scheme ( p  < 0.001). Conclusions: The PACS is a novel metric for evaluating the utility of PRT regimens to improve clinical decision making. Single fraction is associated with low PRL. When considering multifraction PRT regimens, the PACS identifies patients who may benefit from shorter courses of PRT and alternatively, low-risk patients for whom a more protracted course is reasonable. Prospective external validation is warranted.

Purpose: Head and neck (HN) radiotherapy (RT) is complex, involving multiple target and organ at risk (OAR) structures delineated by the radiation oncologist. Site-agnostic peer review after RT plan completion is often inadequate for thorough review of these structures. In-depth review of RT contours is critical to maintain high-quality RT and optimal patient outcomes., Materials and Methods: In August 2020, the HN RT Quality Assurance Conference, a weekly teleconference that included at least one radiation oncology HN specialist, was activated at our institution. Targets and OARs were reviewed in detail prior to RT plan creation. A parallel implementation study recorded patient factors and outcomes of these reviews. A major change was any modification to the high-dose planning target volume (PTV) or the prescription dose/fractionation; a minor change was modification to the intermediate-dose PTV, low-dose PTV, or any OAR. We analysed the results of consecutive RT contour review in the first 20 months since its initiation., Results: A total of 208 patients treated by 8 providers were reviewed: 86·5% from the primary tertiary care hospital and 13·5% from regional practices. A major change was recommended in 14·4% and implemented in 25 of 30 cases (83·3%). A minor change was recommended in 17·3% and implemented in 32 of 36 cases (88·9%). A survey of participants found that all ( n = 11) strongly agreed or agreed that the conference was useful., Conclusion: Dedicated review of RT targets/OARs with a HN subspecialist is associated with substantial rates of suggested and implemented modifications to the contours., Competing Interests: Competing Interests. The author(s) declare none

Purpose: Brain metastases (BMs) are a common source of morbidity and mortality. Guidelines do not advise brain surveillance for locally advanced non-small cell lung cancer (LA-NSCLC). We describe the incidence, time to development, presentation, and management of BMs after definitive chemoradiotherapy (CRT)., Methods and Materials: We reviewed records of patients with LA-NSCLC treated with CRT within the period from 2013 to 2020. Descriptive statistics were used to characterize the population and the Kaplan-Meier method was used to estimate time to BM. Fisher exact tests and Wilcoxon rank-sum tests were used to compare outcomes between symptomatic and asymptomatic patients., Results: A total of 219 patients were reviewed including 96 with squamous cell carcinoma, 88 with adenocarcinoma, and 35 with large cell/not otherwise specified (LC/NOS). Thirty-nine patients (17.8%) developed BMs: 35 (90%) symptomatic and 4 (10%) asymptomatic. The rate of BM was highest in LC/NOS (34.3%) and adenocarcinoma (23.9%). Ninety percent of BMs occurred within 2 years. All asymptomatic patients underwent stereotactic radiosurgery alone, compared with 40% of symptomatic patients ( P  = .04). Symptomatic patients were more likely to require hospitalization (65.7% vs 0%, P  = .02), craniotomy (25.7% vs 0%, not significant), and steroids (91.4% vs 0%, P < .001). Cumulative BM volume was higher for symptomatic patients (4 vs 0.24 cm 3 , P < .001) as was median greatest axial dimension (2.18 vs 0.52 cm, P < .001)., Conclusions: We identified a high rate of BMs, particularly in LC/NOS and adenocarcinoma histology NSCLC. The majority were symptomatic. These results provide rationale for post-CRT magnetic resonance imaging brain surveillance for patients at high risk of BM., (© 2022 The Authors.)

Introduction: The purpose of this study was to determine the efficacy of palliative radiotherapy (PRT) for patients with pulmonary obstruction from advanced malignancy and identify factors associated with lung re-expansion and survival. Materials and Methods: We reviewed all patients treated with PRT for malignant pulmonary obstruction ( n  = 108) at our institution between 2010 and 2018. Radiographic evidence of lung re-expansion was determined through review of follow-up CT or chest X-ray. Cumulative incidence of re-expansion and overall survival (OS) were estimated using competing risk methodology. Clinical characteristics were evaluated for association with re-expansion, OS, and early mortality. Treatment time to remaining life ratio (TT:RL) was evaluated as a novel metric for palliative treatment. Results: Eighty-one percent of patients had collapse of an entire lung lobe, 46% had Eastern Cooperative Oncology Group (ECOG) performance status 3-4, and 64% were inpatient at consultation. Eighty-four patients had follow-up imaging available, and 25 (23%) of all patients had lung re-expansion at median time of 35 days. Rates of death without re-expansion were 38% and 65% at 30 and 90 days, respectively. Median OS was 56 days. Death within 30 days of PRT occurred in 38%. Inpatients and larger tumors trended toward lower rates of re-expansion. Notable factors associated with OS were re-expansion, nonlung histology, tumor size, and performance status. Median TT:RL was 0.11 and significantly higher for subgroups: ECOG 3-4 (0.19), inpatients (0.16), patients with larger tumors (0.14), those unfit for systemic therapy (0.17), and with 10-fraction PRT (0.14). Conclusion: One-fourth of patients experienced re-expansion after PRT for malignant pulmonary obstruction. Survival is poor and a significant proportion of remaining life may be spent on treatment. Careful consideration of these clinical factors is recommended when considering PRT fractionation.

Purpose: Long-term outcomes after external beam radiation therapy (EBRT) and radiofrequency ablation (RFA) for medically inoperable early-stage non-small cell lung cancer (NSCLC) are not well known., Methods and Materials: Patients with medically inoperable early-stage NSCLC were enrolled in a prospective single-arm, phase 2 study between June 2007 and October 2008 and were treated with RFA followed by EBRT. Radiation was delivered using hypofractionated radiation therapy (HFRT; 70.2 Gy in 26 fractions) or stereotactic body radiation therapy (54 Gy in 3 fractions)., Results: Twelve patients were evaluable; 10 patients were treated with HFRT. The cumulative incidence of local progression at 5 years was 16.7% (95% confidence interval [CI], 0-37.8). Median progression-free survival was 37.8 months (95% CI, 11.1 to not reached) and median overall survival was 53.6 months (95% CI, 21.0 to not reached). There were no mortalities within 30 days after RFA and no grade ≥4 toxicity., Conclusions: The combination of RFA with EBRT appears feasible with favorable long-term local control. However, because SBRT alone has similar or better rates of control, we do not recommend routine combined RFA and EBRT., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Mean dose (EQD2) to 3-cm shell of lung surrounding the PTV was evaluated for association with distant metastasis and PFS after SBRT for stage I NSCLC. Dose was uniformly above previously determined threshold and metastasis was uncommon. An association between outcomes and mean EQD2 could not be confirmed or refuted., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: In patients with non-small cell lung cancer (NSCLC) who present with multiple pulmonary nodules, it is often difficult to distinguish metastatic disease from synchronous primary lung cancers (SPLC). We sought to evaluate clinical outcomes after stereotactic body radiotherapy (SBRT) alone to synchronous primary lesions., Material and Methods: Patients with synchronous AJCC 8 th Edition Stage IA-IIA NSCLC and treated with stereotactic body radiation therapy (SBRT) to all lesions between 2009-2018 were reviewed. SPLC was defined as patients having received two courses of SBRT within 180 days for treatment of separate early stage tumors. In total, 36 patients with 73 lesions were included. Overall survival (OS), progression-free survival (PFS), cumulative incidence of local failure (LF), and regional/distant failure (R/DF) were estimated and compared with a control cohort of solitary early stage NSCLC patients., Results: Median PFS was 38.8 months (95% CI 14.3-not reached [NR]); 3-year PFS rates were 50.6% (35.6-72.1). Median OS was 45.9 months (95% CI: 35.9-NR); 3-year OS was 63.0% (47.4-83.8). Three-year cumulative incidence of LF and R/DF was 6.6% (3.7-13.9) and 35.7% (19.3-52.1), respectively. Patients with SPLC were compared to a control group ( n  = 272) of patients treated for a solitary early stage NSCLC. There was no statistically significant difference in PFS ( p  = .91) or OS ( p  = .43). Evaluation of the patterns of failure showed a trend for worse cumulative incidence of R/DF in SPLC patients as compared to solitary early stage NSCLC ( p  = .06)., Conclusion: SBRT alone to multiple lung tumors with SPLC results in comparable PFS, OS, and LF rates to a cohort of patients treated for solitary early stage NSCLC. Those with SPLC had non-significantly higher R/DF. Patients with SPLC should be followed closely for failure and possible salvage therapy.

Introduction: At our institution, stereotactic body radiotherapy (SBRT) has commonly been prescribed with 50 Gy in 5 fractions and in select cases, 50 Gy in 10 fractions. We sought to evaluate the impact of these 2 fractionation schedules on local control and survival outcomes., Methods: We reviewed patients treated with SBRT with 50 Gy/5 fraction or 50 Gy/10 fraction for early-stage non-small cell lung cancer (NSCLC) and metastatic NSCLC. Cumulative incidence of local failure (LF) was estimated using competing risk methodology. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method only for patients with stage I disease., Results: Of the 353 lesions, 300 (85%) were treated with 50 Gy in 5 fractions and 53 (15%) with 10 fractions. LFs at 3 years were 6.5% and 23.9% and Kaplan-Meier estimate of median time to LF was 17.5 months and 26.2 months, respectively. Multivariable analysis revealed increasing planning target volume (hazard ratio 1.01, P = .04) as an independent predictor of increased LF, but tumor size, ultracentral location, and 10 fractions were not. Among patients with stage I NSCLC (n = 298), overall median PFS was 35.6 months and median OS was 42.4 months. There was no difference in PFS or OS between the 2 treatment regimens for patients with stage I NSCLC. Low rates of grade 3+ toxicity were observed, with 1 patient experiencing grade 3 pneumonitis after a 5-fraction regimen of SBRT., Conclusion: Dose-fractionation schemes with BED 10  ≥ 100 Gy provide superior local control and should be offered when meeting commonly accepted constraints. If those regimens appear unsafe, 50 Gy in 10 fractions may provide acceptable compromise between tumor control and safety with relatively durable control, and minimal negative impact on long-term survival., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The adrenal glands are a common site of metastatic disease. Definitive treatment for oligometastatic disease using ablative radiotherapy is becoming common in modern radiation oncology practice. However, most data on the treatment of adrenal metastases are limited to single institution reports. Furthermore, delivering ablative radiotherapy doses to intra-abdominal lesions can be challenging due to the proximity of the gastrointestinal tract. We report the outcomes of a multi-institutional cohort of patients treated with definitive radiotherapy for adrenal metastases, primarily using 10 fraction regimens. Retrospective review of institutional databases revealed 29 lesions in 27 patients were treated from 2005 to 2018 at two institutions. Outcome data, including local control, disease-free, and overall survival were abstracted from the medical record system. Toxicity was graded using CTCAE v5.0. Detailed radiotherapy data was abstracted from the treatment planning systems. The median dose was 50 Gy in 10 fractions. Actuarial 1 and 2 year local control was 86% and 76% respectively. The median overall and disease-free survival were 22.8 and 5.6 months respectively. There were no associations identified between local failure and GTV and PTV physical or biologic effective dose. Two patients developed late Grade 3 gastrointestinal toxicity. High dose radiotherapy to adrenal metastases is a feasible treatment with excellent local control and a reasonable safety profile. For lesions in close proximity to gastrointestinal structures, moderately hypofractionated 10 fraction regimens may be a reasonable compromise between local control and toxicity.

Ionizing radiation is a critical aspect of current cancer therapy. While classically mature bone was thought to be relatively radio-resistant, more recent data have shown this to not be the case. Radiation therapy (RT)-induced bone loss leading to fracture is a source of substantial morbidity. The mechanisms of RT likely involve multiple pathways, including changes in angiogenesis and bone vasculature, osteoblast damage/suppression, and increased osteoclast activity. The majority of bone loss appears to occur rapidly after exposure to ionizing RT, with significant changes in cortical thickness being detectable on computed tomography (CT) within three to four months. Additionally, there is a dose-response relationship. Cortical thinning is especially notable in areas of bone that receive >40 gray (Gy). Methods to mitigate toxicity due to RT-induced bone loss is an area of active investigation. There is an accruing clinical trial investigating the use of risderonate, a bisphosphonate, to prevent rib bone loss in patients undergoing lung stereotactic body radiation therapy (SBRT). Additionally, several other promising therapeutic/preventative approaches are being explored in preclinical studies, including parathyroid hormone (PTH), amifostine, and mechanical loading of irradiated bones., Competing Interests: The authors declare no conflict of interest.

Purpose: Prophylactic cranial irradiation (PCI) reduces the incidence of brain metastases in patients with limited stage small cell lung cancer (LS-SCLC). However, PCI is associated with neurotoxicity. Previous studies have not consistently used pretreatment magnetic resonance imaging. Modern imaging improvements continue to enhance early metastasis detection, potentially decreasing the utility of PCI. We sought to determine whether PCI was associated with improved outcomes in LS-SCLC patients with modern imaging., Methods and Materials: We identified LS-SCLC patients with no intracranial disease who were treated between 2007 and 2018. Kaplan-Meier estimates of overall survival (OS) and progression-free survival (PFS) were calculated and multivariate Cox proportional hazards models were generated. The cumulative incidence of brain metastases was estimated using competing risks methodology., Results: Ninety-two patients were identified without intracranial disease at initial staging, 39 of whom received PCI. Median follow-up was 56.7 months. The median OS for the cohort was 35.5 months (95% CI, 25.8-49.3), and median PFS was 19.1 months (95% CI, 12.3-30.5). Median OS with PCI versus observation was 37.9 months (95% CI, 31.8-not reached) versus 30.5 months (95% CI, 14.6-56.1; P = .07), whereas median PFS was 26.3 months (95% CI 19.1-not reached) versus 12.3 months (95% CI, 8.5-30.5; P = .02), respectively. Overall, at 2 years, the cumulative incidence of brain metastases was 10% with PCI and 29% without; this increased to 32% and 29% by 4 years (P = .66). In those patients who had negative magnetic resonance imaging of the brain after completing initial treatment, the 1-year cumulative incidence of brain metastasis was not significantly different at 8% versus 11% (P = .46) respectively. Both PCI and treatment response were independent predictors for PFS on multivariate analysis. Stratified by disease response, patients with a complete response did not benefit from PCI (P = .50), whereas those with partial response or stable disease experienced improved PFS (P = .01)., Conclusions: Overall, PCI was associated with improved PFS and reduced early incidence of brain metastases. Patients achieving a complete response to initial therapy did not experience a PFS benefit with PCI. This may indicate that subsets of LS-SCLC patients can potentially be spared from PCI in the era of modern imaging., (Copyright © 2019 American Society for Radiation Oncology. All rights reserved.)

Purpose: Several studies evaluating stereotactic radiosurgery (SRS) for patients with >4 brain metastases (BM) demonstrated similar outcomes after treatment of 1, 2 to 4, and 5 to 15 BM; others found clinically significant survival decrements in the latter group. In this review of 8 academic centers, we compared outcomes of patients undergoing initial SRS for 1, 2 to 4, and 5 to 15 BM., Methods and Materials: A total of 2089 patients treated with initial SRS for BM were included. Overall survival (OS) was estimated using the Kaplan-Meier method and compared using the log-rank test. Patient and disease characteristics were evaluated for association with OS and cumulative incidence of distant brain failure (DBF) using stepwise multivariable Cox proportional hazards and competing risk regression modeling., Results: In this series, 989 (47%) patients had 1 metastasis, 882 (42%) had 2 to 4 metastases, and 212 (10%) had 5 to 15 metastases treated. Median OS for the 1, 2 to 4, and 5 to 15 BM groups was 14.6, 9.5, and 7.5 months, respectively (log-rank P < .01). Univariate and multivariable analyses revealed no difference in survival between 2 to 4 and 5 to 15 BM. DBF at 1 year was 30%, 41%, and 50%, respectively (Gray's P < .01). Two-year cumulative incidence of salvage SRS decreased with increasing number of BM (1: 21% vs 2-4: 19% vs 5-15: 13%; P < .01), but no difference in salvage whole brain radiation therapy was observed (1: 12% vs 2-4: 15% vs 5-15: 16%, P = .10). At the time of DBF, median brain metastasis velocity was 3.9, 6.1, and 11.7 new metastases per year in the 1, 2 to 4, and 5 to 15 BM groups, respectively (P < .01)., Conclusions: Patients treated with initial SRS for 5 to 15 BM experienced survival similar to that in patients with 2 to 4 BM. Lower rates of salvage SRS were observed in the 5 to 15 BM group, with no difference in rates of salvage whole brain radiation therapy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Three-dimensional printing has produced customized bolus during radiation therapy for superficial tumors along irregular skin surfaces. In comparison, traditional bolus materials are often difficult to manipulate for a proper fit. Current 3-dimensional printed boluses are made from either preexisting computed tomography scans or complex surface scanning methods. Herein, we introduce an inexpensive, convenient approach to generate a 3-dimensional printed bolus from surface scanning technology available in common smartphones., Methods and Materials: A three-dimensional printed bolus was designed using surface scans from iPhone X true depth cameras and a low-cost 3-dimensional printer. The percentage density infill was adjusted to achieve tissue equivalence. To evaluate the clinical feasibility, fit against the skin surface and radiation dose distribution were compared with those of the traditional bolus., Results: We fabricated a customized 3-dimensional printed bolus for different areas of the face using an iPhone X camera and inexpensive commercially available 3-dimensional printer. When printed at 100% density, the bolus material approximated soft tissue/water and provided an equivalent dose distribution to that found with standard bolus materials on direct comparison. The bolus material is inexpensive and produces an ideal fit with the scanned anatomy., Conclusions: We present a simplified method of highly customized bolus production that requires minimal experience with computer modeling programs and can be accomplished with an iPhone true depth camera., (Copyright © 2019 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Splenic metastases from oligometastatic ovarian carcinoma are a rare occurrence. Usual treatment for splenic metastases includes splenectomy, but some patients are either unable or unwilling to undergo surgery. Stereotactic body radiotherapy (SBRT) is an effective ablative modality for treating metastatic disease. SBRT to abdominopelvic tumors has been shown to be safe and effective for properly-selected patients and is particularly attractive in the oligometastatic setting as an alternative to radical resection. In this case study, we report a patient with an isolated splenic metastasis from ovarian carcinoma treated with 50 Gy in 10 fractions., Competing Interests: Authors’ disclosure of potential conflicts of interest The authors have nothing to disclose. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Army, Department of Defense, or the U.S. Government., (© 2019 Old City Publishing, Inc.)

Purpose: The purpose of this study was to measure the daily prevalence of adhesive product use and related skin injuries in adult patients in a non-intensive care unit setting., Design: Prospective, descriptive study., Subjects and Setting: The study sample consisted of patients cared for on 2 inpatient care units in a university-based acute care facility in the Midwestern United States. One was a 30-bed medical/surgical unit and the second was a 35-bed cardiac/telemetry unit. Their median age was 58 years; the average daily proportion of males and females was 56% and 42%, respectively., Methods: Medical adhesive-related skin injury (MARSI) prevalence was calculated using 3 methods: (1) the proportion of subjects who had any MARSI injury (subject prevalence), (2) the prevalence of MARSI by injury type and severity (severity prevalence), and (3) the proportion of medical adhesive products that had any associated MARSI (product prevalence)., Results: The daily subject prevalence of any MARSI injury ranged from 3.4% to 25.0% with a mean and median of 13.0% and 12.7%, respectively. The severity prevalence of MARSI injury ranged from 8 to 149 per 1000 product-days with a mean and median of 63 and 56 MARSIs per 1000 product-days, respectively. The median (range) product prevalence among all adhesive products varied from a high of 70 injuries per 1000 product-days for surgical closure to a low of 0 injuries per 1000 product-days for peripheral intravenous line dressing., Conclusions: Medical adhesive-related skin injury is a prevalent event in the acute care setting. Preventing skin injury has the potential to reduce complications, increase patient satisfaction, and improve clinical outcomes.

Radiotherapy for prophylaxis of heterotopic ossification (HO) is commonly used in high risk patients following orthopedic surgery. While treatment is effective and can prevent morbidity associated with HO, with any dose of radiation there is a concern of a radiation induced malignancy. Here we a report a case of radiation induced osteosarcoma which developed 11 years after a single fraction of 700 cGy. We performed dosimetric analysis by superimposing the patient's original treatment field on a CT scan performed after the diagnosis. The radiotherapy dose for this patient is lower than classically reported for radiation induced sarcomas. We identified greatest bony destruction that was thought to be the epicenter of the tumor, and this was specially contoured on the diagnostic CT scan. This volume appears to be located at the edge of the radiotherapy field. Fifty percent of the treated volume received 240 cGy, the mean dose was 333 cGy. There was a variation across the treatment volume, between 21.8 cGy and 717 cGy. While a rare complication, we stress the importance of informing regarding the risk of a radiation induced malignancy following HO prophylaxis.