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The liver is a common site for metastatic spread for various primary tumor histologies. Stereotactic body radiation therapy (SBRT) is a non-invasive treatment technique with broad patient candidacy for the ablation of tumors in the liver and other organs. SBRT involves focused, high-dose radiation therapy delivered in one to several treatments, resulting in high rates of local control. Use of SBRT for ablation of oligometastatic disease has increased in recent years and emerging prospective data have demonstrated improvements in progression free and overall survival in some settings. When delivering SBRT to liver metastases, clinicians must balance the priorities of delivering ablative tumor dosing while respecting dose constraints to surrounding organs at risk (OARs). Motion management techniques are crucial for meeting dose constraints, ensuring low rates of toxicity, maintaining quality of life, and can allow for dose escalation. Advanced radiotherapy delivery approaches including proton therapy, robotic radiotherapy, and real-time MR-guided radiotherapy may further improve the accuracy of liver SBRT. In this article, we review the rationale for oligometastases ablation, the clinical outcomes with liver SBRT, tumor dose and OAR considerations, and evolving strategies to improve liver SBRT delivery. [ABSTRACT FROM AUTHOR]

This guideline provides updated evidence-based recommendations addressing recent developments in the management of patients with brain metastases, including advanced radiation therapy techniques such as stereotactic radiosurgery (SRS) and hippocampal avoidance whole brain radiation therapy and the emergence of systemic therapies with central nervous system activity. The American Society for Radiation Oncology convened a task force to address 4 key questions focused on the radiotherapeutic management of intact and resected brain metastases from nonhematologic solid tumors. The guideline is based on a systematic review provided by the Agency for Healthcare Research and Quality. Recommendations were created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. Strong recommendations are made for SRS for patients with limited brain metastases and Eastern Cooperative Oncology Group performance status 0 to 2. Multidisciplinary discussion with neurosurgery is conditionally recommended to consider surgical resection for all tumors causing mass effect and/or that are greater than 4 cm. For patients with symptomatic brain metastases, upfront local therapy is strongly recommended. For patients with asymptomatic brain metastases eligible for central nervous system–active systemic therapy, multidisciplinary and patient-centered decision-making to determine whether local therapy may be safely deferred is conditionally recommended. For patients with resected brain metastases, SRS is strongly recommended to improve local control. For patients with favorable prognosis and brain metastases receiving whole brain radiation therapy, hippocampal avoidance and memantine are strongly recommended. For patients with poor prognosis, early introduction of palliative care for symptom management and caregiver support are strongly recommended. The task force has proposed recommendations to inform best clinical practices on the use of radiation therapy for brain metastases with strong emphasis on multidisciplinary care. [ABSTRACT FROM AUTHOR]

Purpose: The significance of radiation dose to the host immune system during the treatment of stage III non-small cell lung cancer (NSCLC) is unknown, but higher doses were associated with worse tumor control and overall survival (OS) in a secondary analysis of RTOG 0617. In this study, we sought to assess the impact of the estimated dose of radiation to immune cells (EDRIC) on cancer-specific outcomes in an independent cohort of patients treated at our institution.Methods and Materials: We retrospectively identified 117 patients with stage III NSCLC treated with definitive fractionated radiation from 2004 to 2017 at a single academic center (median dose of 60 Gy; 60% underwent intensity modulated radiation therapy and 92% received concurrent platinum-based chemotherapy). EDRIC was calculated as a function of the number of radiation fractions and mean doses to the lung, heart, and remaining body based on a model developed by Jin et al.Results: Median follow-up was 16 months with 77% of patients followed until death. In the entire population, 5-year OS was 11.2% with a median survival of 17.3 months. Median EDRIC for the entire cohort was 6.1 Gy (range, 2.5-10.0 Gy). A higher EDRIC was correlated with greater risk of grade ≥3 lymphopenia (P = .004). On multivariate analysis including total prescription radiation dose, planning target volume, and chemotherapy utilization, EDRIC was independently associated with OS (hazard ratio [HR] 1.17, P = .03), local progression-free survival (HR 1.17, P = .02), and disease-free survival (HR 1.15, P = .04). The median OS for patients with an EDRIC above 7.3 Gy (fourth quartile) and below 5.1 Gy (first quartile) was 14.3 and 28.2 months, respectively.Conclusions: Higher doses of radiation to the immune system were associated with tumor progression and death after the definitive treatment of stage III NSCLC. Tailoring radiation therapy to spare the immune system may be an important future direction to improve outcomes in this population. [ABSTRACT FROM AUTHOR]

Highlights • Early stage non-small-cell lung cancer (NSCLC) often fails distantly post-SBRT. • Adjuvant chemotherapy associated with lower overall survival (OS) for T1-3N0 NSCLC. • Adjuvant chemotherapy did not associate with OS for T1-3N0 NSCLC ≥ 4 cm. • Adjuvant chemotherapy associated with lower OS after propensity-score matching. • Other strategies to lower distant failure and improve OS warrant investigation. Abstract Objectives Adjuvant chemotherapy is routinely offered post-surgical resection for early stage non-small-cell lung cancer (NSCLC) ≥4 cm; however, its role following definitive stereotactic body radiotherapy (SBRT) has not been well defined. We investigated the association between receipt of adjuvant chemotherapy post-SBRT and overall survival (OS) for patients with T1-T3N0M0 NSCLC in the National Cancer Database (NCDB). Materials and Methods The NCDB was queried for patients with T1-T3N0M0 NSCLC treated with definitive SBRT from 2004 to 2014. The association between non-randomized receipt of adjuvant chemotherapy and OS was analyzed for all patients (n = 24,011) and a propensity-matched cohort (n = 608) using Kaplan-Meier methods and Cox proportional hazard models. A subset analysis was performed for patients with tumors ≥4 cm (n = 2,323). Results There were 24,011 patients in the cohort with a median follow-up of 32.5 months. Of these, 322 (1.3%) received adjuvant chemotherapy. Three-year OS was 41.3% with adjuvant chemotherapy compared to 50.6% without adjuvant chemotherapy (p = 0.001). On multivariate analysis, adjuvant chemotherapy was independently associated with higher overall mortality (hazard ratio:1.22, 95% confidence interval:1.06–1.40, p = 0.005). For tumors ≥4 cm, 3-year OS was 38.2% with adjuvant chemotherapy (n = 80) compared to 33.0% without adjuvant chemotherapy (p = 0.81). After propensity-score matching, there was a persistent association between lower OS and adjuvant chemotherapy with those receiving adjuvant chemotherapy (n = 322) having 3-year OS of 41.3% compared to 60.9% without adjuvant chemotherapy (p < 0.0001). Conclusion Adjuvant chemotherapy following definitive SBRT for T1-3N0M0 NSCLC is associated with lower OS and is not associated with a survival benefit for patients with tumors ≥4 cm. [ABSTRACT FROM AUTHOR]

Purpose: Functional imaging has been proposed that uses 4DCT images to calculate 4DCT-based lung ventilation (4DCT-ventilation). We have started a 2-institution, phase 2 prospective trial evaluating the feasibility, safety, and preliminary efficacy of 4DCT-ventilation functional avoidance. The trial hypothesis is that the rate of grade ≥2 radiation pneumonitis could be reduced to 12% with functional avoidance, compared with a 25% rate of pneumonitis with a historical control. The trial employed a Simon 2-stage design with a planned futility analysis after 17 evaluable patients. The purpose of this work is to present the trial design and implementation, dosimetric data, and clinical results for the planned futility analysis.Methods and Materials: Eligible patients were patients with lung cancer who were prescribed doses of 45 to 75 Gy. For each patient, the 4DCT data were used to generate a 4DCT-ventilation image using the Hounsfield unit technique along with a compressible flow-based image registration algorithm. Two intensity modulated radiation therapy treatment plans were generated: (1) a standard lung plan and (2) a functional avoidance treatment plan that aimed to reduce dose to functional lung while meeting target and normal tissue constraints. Patients were treated with the functional avoidance plan and evaluated for thoracic toxicity (presented as rate and 95% confidence intervals [CI]) with a 1-year follow-up.Results: The V20 to functional lung was 21.6% ± 9.5% (mean ± standard deviation) with functional avoidance, representing a decrease of 3.2% (P < .01) relative to standard, nonfunctional treatment plans. The rates of grade ≥2 and grade ≥3 radiation pneumonitis were 17.6% (95% CI, 3.8%-43.4%) and 5.9% (95% CI, 0.1%-28.7%), respectively.Conclusions: Dosimetrically, functional avoidance achieved reduction in doses to functional lung while meeting target and organ at risk constraints. On the basis of Simon's 2-stage design and the 17.6% grade ≥2 pneumonitis rate, the trial met its futility criteria and has continued accrual. [ABSTRACT FROM AUTHOR]

Background To analyze the national trends of patients treated radiotherapy for brain metastases from non-small cell lung cancer (NSCLC) that were found at diagnosis. Methods The National Cancer Database was queried for patients with NSCLC diagnosed from 2004 to 2013 that received brain irradiation for metastases and patients grouped into having had received fractionated brain radiotherapy (5–15 fractions with or without radiosurgery) or intracranial radiosurgery alone (1–5 fractions). Univariable and multivariable (MVA) analyses were performed to investigate factors associated with the receipt of SRS alone, and temporal/regional trends. Results 47,746 patients met inclusion criteria, of which 42,148 received fractionated brain irradiation (88%) and 5,598 received radiosurgery (12%). 345 patients received fractioned brain irradiation with a radiosurgical boost (0.8%). The utilization of radiosurgery-alone increased over time owing to increases in each radiosurgery modality. On MVA, several factors were associated with increased odds of receiving intracranial radiosurgery-alone over fractionated brain radiotherapy including more recent year of diagnosis, increased median income, eastern U.S. regions, further distance to the hospital, and the receipt of chemotherapy (each p < 0.001). Patients of Asian descent were less likely to receive radiosurgery alone ( p = 0.044). Conclusions In the management of brain metastases from NSCLC, overall utilization of an intracranial radiosurgery alone treatment strategy has increased over the past decade. Despite this, there appear to be significant geographic variations and disparities remain based on patient income level and race. Further study is needed to define the reasons for these disparities and appropriate actions to mitigate them. [ABSTRACT FROM AUTHOR]

Background: Studies evaluating insurance status and melanoma outcomes are limited.Objective: We investigated whether health insurance correlates with more advanced disease, receipt of treatment, and survival in melanoma.Methods: This was a cross-sectional analysis of 61,650 patients with cutaneous melanoma using the Surveillance, Epidemiology, and End Results database.Results: Under multivariate analysis, patients with either Medicaid insurance (hazard ratio, 1.83; 95% confidence interval [CI], 1.65-2.04; P < .001) or uninsured status (hazard ratio, 1.63; 95% CI, 1.44-1.85; P < .001) were more likely to die of any cause, including melanoma. Uninsured compared with non-Medicaid insured cases more often presented with increasing tumor thickness (odds ratio [OR], 2.19; 95% CI, 1.76-2.73; P < .001) and presence of ulceration (OR, 1.64; 95% CI, 1.40-1.92; P < .001), and less often received treatment (OR, 1.87; 95% CI, 1.60-2.19; P < .001). Compared with non-Medicaid insured, Medicaid cases more often had increasing tumor thickness (OR, 2.36; 95% CI, 1.91-2.91; P < .001), advanced stage (OR, 1.59; 95% CI, 1.37-1.85; P < .001), and presence of ulceration (OR, 1.40; 95% CI, 1.19-1.63; P < .001), and less often received treatment (OR, 1.61; 95% CI, 1.37-1.89; P < .001).Limitations: This was a retrospective study.Conclusion: Patients with melanoma and Medicaid or uninsured status were more likely to present with advanced disease and were less likely to receive treatment, likely contributing to an overall and cause-specific survival detriment. Addressing access to care may help improve these outcomes. [ABSTRACT FROM AUTHOR]

Background: Primary mediastinal B cell lymphoma (PMBCL) is an uncommon lymphoma for which trials are few with small patient numbers. The role of radiation therapy (RT) after standard immunochemotherapy for early-stage disease has never been studied prospectively. We used the Surveillance, Epidemiology, and End Results (SEER) database to evaluate PMBCL and the impact of RT on outcomes.Methods and Materials: We queried the SEER database for patients with stage I-II PMBCL diagnosed from 2001 to 2011. Retrievable data included age, gender, race (white/nonwhite), stage, extranodal disease, year of diagnosis, and use of RT as a component of definitive therapy. Kaplan-Meier overall survival (OS) estimates, univariate (UVA) log-rank and multivariate (MVA) Cox proportional hazards regression analyses were performed.Results: Two hundred fifty patients with stage I-II disease were identified, with a median follow-up time of 39 months (range, 3-125 months). The median age was 36 years (range, 18-89 years); 61% were female; 76% were white; 45% had stage I disease, 60% had extranodal disease, and 55% were given RT. The 5-year OS for the entire cohort was 86%. On UVA, OS was improved with RT (hazard ratio [HR] 0.446, P=.029) and decreased in association with nonwhite race (HR 2.70, P=.006). The 5-year OS was 79% (no RT) and 90% (RT). On MVA, white race and RT remained significantly associated with improved OS (P=.007 and .018, respectively). The use of RT decreased over time: 61% for the 67 patients whose disease was diagnosed from 2001 to 2005 and 53% in the 138 patients treated from 2006 to 2010.Conclusion: This retrospective population-based analysis is the largest PMBCL dataset to date and demonstrates a significant survival benefit associated with RT. Nearly half of patients treated in the United States do not receive RT, and its use appears to be declining. In the absence of phase 3 data, the use of RT should be strongly considered for its survival benefit in early-stage disease. [ABSTRACT FROM AUTHOR]

Purpose We aimed to determine the comparative effectiveness of radiation dose escalation and concurrent chemoradiation therapy (CCRT) in a population-based cohort of patients with stage IV non-small cell lung cancer who underwent palliative thoracic radiation therapy (RT). Methods and materials The cohort consisted of 27,063 patients in the National Cancer Database with stage IV non-small cell lung cancer treated with thoracic RT between 20 and 55 Gy in 2004 to 2011. High- versus intermediate- vs low-dose (HD vs ID vs LD, respectively) RT was defined as biologically effective dose above 50 Gy, between 35 and 50 Gy, and below 35 Gy, respectively. Among patients who received any chemotherapy, separate analyses were performed to examine the impact of CCRT on overall survival (OS). Results The median follow-up was 3.9 months for the entire cohort and 18 months for surviving patients. The 5 most common treatment schemes were 30/10 (Gy/fraction, 23% of entire cohort), 35/14 (8%), 37.5/15 (7%), 40/20 (3%), and 50/20 (3%). On multivariable analysis, the survival hazard ratios (HRs) for HD and ID compared with LD RT were 0.37 and 0.51, respectively ( P < .0001). Propensity score matching found a superior survival benefit for ID and HD (HR, 0.41 and 0.57 for HD and ID RT, respectively, vs LD, P < .0001). Among those who received any chemotherapy (59% of total), the median OS for patients treated with CCRT (19% of total) was 5.3 versus 5.6 months ( P = .667). On multivariable analysis, the HR for CCRT was 1.01 ( P = .46). Conclusions The delivery of higher-dose RT but not concurrent chemotherapy was associated with a significant improvement of OS. This population-based study supports higher-dose palliative regimens and motivates prospective study of escalation beyond a biologically effective dose of 35 Gy. [ABSTRACT FROM AUTHOR]

Purpose Non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) are a heterogeneous group of sarcomas that encompass over 35 histologies. With an incidence of ∼500 cases per year in the United States in those <20 years of age, NRSTS are rare and therefore difficult to study in pediatric populations. We used the large Surveillance, Epidemiology, and End Results (SEER) database to validate the prognostic ability of the Children's Oncology Group (COG) risk classification system and to define patient, tumor, and treatment characteristics. Methods and Materials From SEER data from 1988 to 2007, we identified patients ≤18 years of age with NRSTS. Data for age, sex, year of diagnosis, race, registry, histology, grade, primary size, primary site, stage, radiation therapy, and survival outcomes were analyzed. Patients with nonmetastatic grossly resected low-grade tumors of any size or high-grade tumors ≤5 cm were considered low risk. Cases of nonmetastatic tumors that were high grade, >5 cm, or unresectable were considered intermediate risk. Patients with nodal or distant metastases were considered high risk. Results A total of 941 patients met the review criteria. On univariate analysis, black race, malignant peripheral nerve sheath (MPNST) histology, tumors >5 cm, nonextremity primary, lymph node involvement, radiation therapy, and higher risk group were associated with significantly worse overall survival (OS) and cancer-specific survival (CSS). On multivariate analysis, MPNST histology, chemotherapy-resistant histology, and higher risk group were significantly poor prognostic factors for OS and CSS. Compared to low-risk patients, intermediate patients showed poorer OS (hazard ratio [HR]: 6.08, 95% confidence interval [CI]: 3.53-10.47, P <.001) and CSS (HR: 6.27; 95% CI: 3.44-11.43, P <.001), and high-risk patients had the worst OS (HR: 13.35, 95% CI: 8.18-21.76, P <.001) and CSS (HR: 14.65, 95% CI: 8.49-25.28, P <.001). Conclusions The current COG risk group stratification for children with NRSTS has been validated with a large number of children in the SEER database. [ABSTRACT FROM AUTHOR]

Purpose To compare the survival impact of adjuvant external beam radiation therapy (RT) for malignant gliomas of glioblastoma (GBM), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), and mixed anaplastic oligoastrocytoma (AOA) histology. Methods and Materials The Surveillance, Epidemiology, and End Results (SEER) database was queried from 1998 to 2007 for patients aged ≥18 years with high-grade gliomas managed with upfront surgical resection, treated with and without adjuvant RT. Results The primary analysis totaled 14,461 patients, with 12,115 cases of GBM (83.8%), 1312 AA (9.1%), 718 AO (4.9%), and 316 AOA (2.2%). On univariate analyses, adjuvant RT was associated with significantly improved overall survival (OS) for GBMs (2-year OS, 17% vs 7%, p<.001), AAs (5-year OS, 38% vs 24%, p<.001), and AOAs (5-year OS, 55% vs 44%, p=.026). No significant differences in OS were observed for AOs (5-year OS, with RT 50% vs 56% without RT, p=.277). In multivariate Cox proportional hazards models accounting for extent of resection, age, sex, race, year, marital status, and tumor registry, RT was associated with significantly improved OS for both GBMs (HR, 0.52; 95% CI, 0.50-0.55; P <.001) and AAs (HR, 0.57; 95% CI, 0.48-0.68; P <.001) but only a trend toward improved OS for AOAs (HR, 0.70; 95% CI, 0.45-1.09; P =.110). Due to the observation of nonproportional hazards, Cox regressions were not performed for AOs. A significant interaction was observed between the survival impact of RT and histology overall (interaction P<.001) and in a model limited to the anaplastic (WHO grade 3) histologies. (interaction P=.024), characterizing histology as a significant predictive factor for the impact of RT. Subgroup analyses demonstrated greater hazard reductions with RT among patients older than median age for both GBMs and AAs (all interaction P≤.001). No significant interactions were observed between RT and extent of resection. Identical patterns of significance were observed for cause-specific survival and OS across analyses. Conclusions In this large population-based cohort, glioma histology represented a significant predictor for the survival impact of RT. Adjuvant RT was associated with improved survival for AAs, with benefits comparable to those observed for GBMs over the same 10-year interval. No survival advantage was observed with adjuvant RT for AOs. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Although the majority of metastatic prostate cancer (mPCa) will arise from tumors with Gleason scores (GS) of 8 to 10 existing tumor grade analyses for mPCa have been almost uniformly limited to comparisons of≤7 vs.≥8. In this analysis, we comprehensively evaluate the GS as a prognostic factor for mPCa in the era of the updated Gleason grading system. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried for patients with mPCa, GS 6 to 10, diagnosed from 2006 to 2008. GS and primary-secondary Gleason pattern variations were analyzed for overall survival and prostate cancer–specific survival (PCSS). Results: A total of 4,654 patients were evaluable. At 4 years, the overall survival rates were 51%, 45%, 34%, 25%, and 15% and PCSS rates were 69%, 57%, 44%, 33%, and 21% for GS 6, 7, 8, 9, and 10, respectively. Survival differences for GS 7 vs. 8, 8 vs. 9, and 9 vs. 10 were highly significant on both univariate and multivariate analyses accounting for age, prostate-specific antigen level, and T stage (all P<0.001). Gleason pattern 5 was an independent prognostic factor, both overall for patients with GS 6 to 10 and on primary-secondary Gleason pattern comparisons within the GS 8 (4+4 vs. 3+5 and 5+3) and GS 9 (4+5 vs. 5+4) subgroups. No survival differences were observed between 3+4 vs. 4+3. Overall, lower prostate-specific antigen level, younger age, and lower GS were associated with improved survival, with GS being the strongest prognostic factor for PCSS. Conclusions: In this large population-based cohort, stratified survival outcomes were observed for GS 6 to 10, with sequential comparisons of GS 7 to 10, and the presence and extent of Gleason pattern 5 representing independent prognostic factors in the metastatic setting. [Copyright &y& Elsevier]

Purpose: To evaluate the survival outcomes for patients with lymph node-positive, nonmetastatic prostate cancer undergoing definitive local therapy (radical prostatectomy [RP], external beam radiation therapy [EBRT], or both) versus no local therapy (NLT) in the US population in the modern prostate specific antigen (PSA) era. Methods and Materials: The Surveillance, Epidemiology, and End Results database was queried for patients with T1-4N1M0 prostate cancer diagnosed from 1995 through 2005. To allow comparisons of equivalent datasets, patients were analyzed in separate clinical (cN+) and pathologically confirmed (pN+) lymph node-positive cohorts. Kaplan-Meier overall survival (OS) and prostate cancer-specific survival (PCSS) estimates were generated, with accompanying univariate log-rank and multivariate Cox proportional hazards comparisons. Results: A total of 796 cN+ and 2991 pN+ patients were evaluable. Among cN+ patients, 43% underwent EBRT and 57% had NLT. Outcomes for cN+ patients favored EBRT, with 10-year OS rates of 45% versus 29% (P<.001) and PCSS rates of 67% versus 53% (P<.001). Among pN+ patients, 78% underwent local therapy (RP 57%, EBRT 10%, or both 11%) and 22% had NLT. Outcomes for pN+ also favored local therapy, with 10-year OS rates of 65% versus 42% (P<.001) and PCSS rates of 78% versus 56% (P<.001). On multivariate analysis, local therapy in both the cN+ and pN+ cohorts remained independently associated with improved OS and PCSS (all P<.001). Local therapy was associated with favorable hazard ratios across subgroups, including patients aged ≥70 years and those with multiple positive lymph nodes. Among pN+ patients, no significant differences in survival were observed between RP versus EBRT and RP with or without adjuvant EBRT. Conclusions: In this large, population-based cohort, definitive local therapy was associated with significantly improved survival in patients with lymph node-positive prostate cancer. [Copyright &y& Elsevier]

A novel form of lung function imaging has been developed that uses 4-dimensional computed tomography (4DCT) data to generate lung ventilation images (4DCT-ventilation). Functional avoidance uses 4DCT-ventilation to reduce doses to functional lung with the aim of reducing pulmonary side effects. A phase 2, multicenter 4DCT-ventilation functional avoidance clinical trial was completed. The purpose of this work was to quantify changes in patient-reported outcomes (PROs) for patients treated with functional avoidance and determine which metrics are predictive of PRO changes. Patients with locally advanced lung cancer receiving curative-intent radiation therapy were accrued. Each patient had a 4DCT-ventilation image generated using 4DCT data and image processing. PRO instruments included the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire administered pretreatment; at the end of treatment; and at 3, 6, and 12 months posttreatment. Using the FACT-Trial Outcome Index and the FACT-Lung Cancer Subscale results, the percentage of clinically meaningful declines (CMDs) were determined. A linear mixed-effects model was used to determine which patient, clinical, dose, and dose-function metrics were predictive of PRO decline. Of the 59 patients who completed baseline PRO surveys. 83% had non-small cell lung cancer, with 75% having stage 3 disease. The median dose was 60 Gy in 30 fractions. CMD FACT-Trial Outcome Index decline was 46.3%, 38.5%, and 26.8%, at 3, 6, and 12 months, respectively. CMD FACT-Lung Cancer Subscale decline was 33.3%, 33.3%, and 29.3%, at 3, 6, and 12 months, respectively. Although an increase in most dose and dose-function parameters was associated with a modest decline in PROs, none of the results were significant (all P >.053). The current work presents an innovative combination of use of functional avoidance and PRO assessment and is the first report of PROs for patients treated with prospective 4DCT-ventilation functional avoidance. Approximately 30% of patients had clinically significant decline in PROs at 12 months posttreatment. The study provides additional data on outcomes with 4DCT-ventilation functional avoidance. [ABSTRACT FROM AUTHOR]

The role of stereotactic radiosurgery (SRS) in the management of grade 2 and 3 meningiomas is not well elucidated. Unfortunately, local recurrence rates are high, and guidelines for management of recurrent disease are lacking. To address this knowledge gap, we conducted STORM (Salvage Stereotactic Radiosurgery for Recurrent WHO Grade 2 and 3 Meningiomas), a multicenter retrospective cohort study of patients treated with primary SRS for recurrent grade 2 and 3 meningiomas. Data on patients with recurrent grade 2 and 3 meningioma treated with SRS at first recurrence were retrospectively collected from 8 academic centers in the United States. Patients with multiple lesions at the time of initial diagnosis or more than 2 lesions at the time of first recurrence were excluded from this analysis. Patient demographics and treatment parameters were extracted at time of diagnosis, first recurrence, and second recurrence. Oncologic outcomes, including progression-free survival (PFS) and overall survival, as well as toxicity outcomes, were reported at the patient level. From 2000 to 2022, 108 patients were identified (94% grade 2, 6.0% grade 3). A total of 106 patients (98%) had upfront surgical resection (60% gross-total resection) with 18% receiving adjuvant radiation therapy (RT). Median time to first progression was 2.5 years (IQR, 1.34-4.30). At first recurrence, patients were treated with single or fractionated SRS to a median marginal dose of 16 Gy to a maximum of 2 lesions (87% received single-fraction SRS). The median follow-up time after SRS was 2.6 years. The 1-, 2-, and 3-year PFS was 90%, 75%, and 57%, respectively, after treatment with SRS. The 1-, 2-, and 3-year overall survival was 97%, 94%, and 92%, respectively. In the multivariable analysis, grade 3 disease (HR, 6.80; 95% CI, 1.61-28.6), male gender (HR, 3.48; 95% CI, 1.47-8.26), and receipt of prior RT (HR, 2.69; 95% CI, 1.23-5.86) were associated with worse PFS. SRS dose and tumor volume were not correlated with progression. Treatment was well tolerated, with a 3.0% incidence of grade 2+ radiation necrosis. This is the largest multicenter study to evaluate salvage SRS in recurrent grade 2 and 3 meningiomas. In this select cohort of patients with primarily grade 2 meningioma with a potentially more favorable natural history of delayed, localized first recurrence amenable to salvage SRS, local control rates and toxicity profiles were favorable, warranting further prospective validation. [ABSTRACT FROM AUTHOR]

Purpose: Presently no reported prospective, randomized trials have clearly defined the role of androgen-deprivation therapy (ADT) for patients with intermediate-risk prostate cancer in the setting of radiation therapy (RT) dose escalation. This study׳s objective was to evaluate the survival benefit of adding ADT to high-dose RT for patients with intermediate-risk prostate cancer using the National Cancer Data Base.Materials and Methods: The National Cancer Data Base was queried for patients with intermediate-risk prostate cancer treated from 2004 to 2006, with available data for Gleason Score, prostate-specific antigen, TNM staging, and receipt of radiation and ADT. Start of RT was within 1 to 180 days of ADT; radiation included external beam alone (≥70Gy) or external beam RT plus brachytherapy boost. Overall survival was evaluated using multivariate (MVA) Cox regression and propensity score-matched (PSM) analyses.Results: A total of 14,126 patients were included of which 7,568 (53.6%) received no ADT and 6,558 (46.4%) received ADT. Median follow-up was 85.8 months (6.0-119.9mo). Median RT dose was 75.6Gy in 42 fractions. Under MVA, the addition of ADT for patients with intermediate-risk prostate cancer had no overall survival benefit compared with RT alone (hazard ratio [HR] = 0.97, P = 0.316). PSM also confirmed no survival benefit with the addition of ADT for the entire intermediate-risk cohort (HR = 0.98, P = 0.560). On subset analysis, those with 3 intermediate-risk factors had a survival benefit with the addition of ADT on both MVA (HR = 0.69, P = 0.037) and PSM (HR = 0.61, P = 0.026). Limitations include retrospective design and incomplete data on the type of ADT and duration.Conclusions: With the exception of men who present with all 3 intermediate-risk factors, a significant association with decreased all-cause mortality risk and ADT was not observed for patients with intermediate-risk prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose Histologic grade analyses for prostate cancer (PCa) have traditionally included Gleason scores (GS) of ≤6, 7, and 8-10. Stratified biochemical progression-free survival has increasingly been reported within these groups on analyses of primary-secondary patterns (PSPs) (e.g., 3+4 vs. 4+3) and overall GS (e.g., 8 vs. 9 vs. 10) but with limited data regarding stratified survival outcomes. In this analysis, outcomes for biopsy-assigned GS 6 to 10 were comprehensively evaluated to identify stratifications prognostic for survival in patients undergoing external beam radiation therapy (EBRT). Methods The Surveillance, Epidemiology, and End Results database was examined for T1–4 N0 M0, GS 6 to 10 PCa managed with EBRT alone from 2004 to 2006. GS and PSP variations were analyzed for PCa-specific survival (PCSS) and overall survival (OS). Results Overall, 26,885 patients were evaluated. Preliminary PSP analyses identified stratifications for 3+4 vs. 4+3 = 7 and 4+4 = 8 vs. GS 8 with pattern 5 (P5) (i.e., 3+5 and 5+3) as significant; however, no differences were observed for 4+5 vs. 5+4 = 9. The primary analysis included stratifications for GS 6, 3+4, 4+3, 4+4, 8 w/P5, 9, and 10, where the 7.5-year PCSS rates were 99%, 97%, 95%, 91%, 86%, 81%, and 78% and 7.5-year OS rates were 83%, 76%, 72%, 67%, 66%, 58%, and 54%, respectively. PCSS differences for sequential score increases were all significant on univariate analyses (all P <0.05). In sequential multivariate analyses of PCSS accounting for age, prostate-specific antigen, T stage, year, marital status, race, and tumor registry, the identified GS stratifications remained significant (all P <0.05), with the exception of GS 8 w/P5 vs. 9 ( P = 0.11). In overall multivariate analyses, the identified GS stratifications represented the strongest prognostic factor for survival. Subgroup analyses demonstrated that presence of any P5 was an independent prognostic factor for survival. Conclusion In the largest reported survival analysis of Gleason stratifications, biopsy-assigned GS 6, 3+4, 4+3, 4+4, 8 w/P5, 9, and 10 represented sequential prognostic factors for survival in patients managed with definitive EBRT. [ABSTRACT FROM AUTHOR]

Stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICI) are highly effective treatments for brain metastases, particularly when these therapies are administered concurrently. However, there are limited data reporting the risk of radiation necrosis (RN) in this setting. Patients with brain metastases from primary non-small cell lung cancer, renal cell carcinoma, or melanoma treated with SRS and ICI were considered. Time-to-event analyses were conducted for any grade RN and symptomatic RN (SRN) with death incorporated as a competing risk. As a secondary analysis, recursive partitioning analysis (RPA) was used for model development, and a loop of potential models was analyzed, with the highest-fidelity model selected. Brain V12 Gy thresholds identified on RPA were then incorporated into the competing risks analysis. Concurrent SRS and ICI administration. Six hundred fifty-seven patients with 4182 brain metastases across 11 international institutions were analyzed. The median follow-up for all patients was 13.4 months. The median follow-up was 12.8 months and 14.1 months for the concurrent and nonconcurrent groups, respectively (P =.03). The median patient age was 66 years, and the median Karnofsky Performance Status was 90. In patients with any grade RN, 1- and 2-year rates were 6.4% and 9.9%, respectively. In patients with SRN, 1- and 2-year rates were 4.8% and 7.2%, respectively. On RPA, the highest-fidelity models consistently identified V12 Gy as the dominant variable predictive of RN. Three risk groups were identified by V12 Gy: (1) < 12 cm3; (2) 20 cm3 ≥ V12 Gy ≥ 12 cm3; (3) V12 Gy > 20 cm3. In patients with any grade RN, 1-year rates were 3.7% (V12 Gy < 12 cm3), 10.3% (20 cm3 ≥ V12 Gy ≥ 12 cm3), and 12.6% (V12 Gy > 20 cm3); the 2-year rates were 7.5% (V12 Gy < 12 cm3), 13.8% (20 cm3 ≥ V12 Gy ≥ 12 cm3), and 15.4% (V12 Gy > 20 cm3) (P < 0.001). In patients with any SRN, 1-year rates were 2.4% (V12 Gy < 12 cm3), 8.9% (20 cm3 ≥ V12 Gy ≥ 12 cm3), and 10.3% (V12 Gy > 20 cm3); the 2-year rates were 4.4% (V12 Gy < 12 cm3), 12.4% (20 cm3 ≥ V12 Gy ≥ 12 cm3), and 13.1% (V12 Gy > 20 cm3; P < 0.001). There were no statistically significant differences in rates of any grade RN or SRN when accounting for therapy timing for all patients and by V12 risk group identified on RPA. The use of SRS and ICI results in a low risk of any grade RN and SRN. This risk is not increased with concurrent administration. Therefore, ICI can safely be administered within 4-weeks of SRS. Three risk groups based on V12 Gy were identified, which clinicians may consider to further reduce rates of RN. [ABSTRACT FROM AUTHOR]

Purpose: Radiation pneumonitis remains a major limitation in the radiation therapy treatment of patients with lung cancer. Functional avoidance radiation therapy uses functional imaging to reduce pulmonary toxic effects by designing radiation therapy plans that reduce doses to functional regions of the lung. Lung functional imaging has been developed that uses 4-dimensional computed tomography (4DCT) imaging to calculate 4DCT-based lung ventilation (4DCT-ventilation). A phase 2 multicenter study was initiated to evaluate 4DCT-ventilation functional avoidance radiation therapy. The study hypothesis was that functional avoidance radiation therapy could reduce the rate of grade ≥2 radiation pneumonitis to 12% compared with a 25% historical rate, with the trial being positive if ≤16.4% of patients experienced grade ≥2 pneumonitis.Methods and Materials: Lung cancer patients receiving curative-intent radiation therapy (prescription doses of 45-75 Gy) and chemotherapy were accrued. Patient 4DCT scans were used to generate 4DCT-ventilation images. The 4DCT-ventilation images were used to generate functional avoidance plans that reduced doses to functional portions of the lung while delivering the prescribed tumor dose. Pneumonitis was evaluated by a clinician at 3, 6, and 12 months after radiation therapy.Results: Sixty-seven evaluable patients were accrued between April 2015 and December 2019. The median prescription dose was 60 Gy (range, 45-66 Gy) delivered in 30 fractions (range, 15-33 fractions). The average reduction in the functional volume of lung receiving ≥20 Gy with functional avoidance was 3.5% (range, 0%-12.8%). The median follow-up was 312 days. The rate of grade ≥2 radiation pneumonitis was 10 of 67 patients (14.9%; 95% upper CI, 24.0%), meeting the phase 2 criteria.Conclusions: 4DCT-ventilation offers an imaging modality that is convenient and provides functional imaging without an extra procedure necessary. This first report of a multicenter study of 4DCT-ventilation functional avoidance radiation therapy provided data showing that the trial met phase 2 criteria and that evaluation in a phase 3 study is warranted. [ABSTRACT FROM AUTHOR]

• Survival prediction models are still evolving and imperfect. • Some components of these models carry the risk of inter-observer inconsistency and time-dependent variation. • Opportunities exist to enhance the assessment of extracranial metastases and potential surrogates. Survival prediction models may serve as decision-support tools for clinicians who have to assign the right treatment to each patient, in a manner whereby harmful over- or undertreatment is avoided as much as possible. Current models differ regarding their components, the overall number of components and the weighting of individual components. Some of the components are easy to assess, such as age or primary tumor type. Others carry the risk of inter-assessor inconsistency and time-dependent variation. The present publication focuses on issues related to assessment of extracranial metastases and potential surrogates, e.g. blood biomarkers. It identifies areas of controversy and provides recommendations for future research projects, which may contribute to prognostic models with improved accuracy. [ABSTRACT FROM AUTHOR]

Highlights • Definitive chemoradiation associated with lower post-treatment mortality. • Larger differences were observed in 30-day post-treatment mortality. • Pneumonectomy associated with the worst surgical mortality. Abstract Purpose Locally advanced non-small cell lung cancer (NSCLC) is commonly managed with either definitive chemoradiation (dCRT) or neoadjuvant chemoradiation followed by surgery (nCRT + S). This study sought to compare 30- and 90-day mortality between nCRT + S and dCRT for these patients. Methods The National Cancer Database was queried (2004–2014) for clinicall staged T1-3N2 or T3-4N0-1 (except T3N0) NSCLC that received nCRT + S or dCRT. Statistics included cumulative incidence analysis of 30- and 90-day mortality (before and following propensity score matching) and Cox proportional hazards regressions. Results Of 28,379 patients, 4063 (14.3%) underwent nCRT-S, and 24,316 (85.6%) dCRT. Of the trimodality patients, 79.2% received lobectomy, 8.2% sublobar resection, and 12.5% pneumonectomy. Trimodality therapy and age, in addition to several soceiodempographic and oncologic variables, were associated with 30- and 90-day mortality. Short-term mortality was significantly higher with nCRT + S compared to dCRT at both 30 (3.4% vs. 0.8%, p < 0.001) and 90days (7.5% vs. 6.6%, p = 0.017), which persisted following propensity matching (3.4% vs. 0.4% and 7.5% vs. 5.3% respectively, both p < 0.001). At both 30 and 90 days, pneumonectomy was associated with higher mortality than lobectomy (6.1% vs. 2.9% and 11.1% vs. 6.9% respectively, both p < 0.001). Conclusions Treatment with nCRT + S was associated with greater 30- and 90- day post-treatment mortality when compared to treatment with dCRT, with larger differences in observed in 30-day post-treatment mortality. These data may inform shared-decsion making among patients eligible for both aproaches. [ABSTRACT FROM AUTHOR]

Purpose To determine the effect of radiotherapy (RT) technique on treatment compliance and overall survival (OS) in patients with stage III non-small lung cancer (NSCLC) treated with definitive chemoradiotherapy (CRT). Methods and Materials This study included patients with stage III NSCLC in the National Cancer Database treated between 2003 and 2011 with definitive CRT to 60–63 Gray (Gy). Radiation treatment interruption (RTI) was defined as a break of ≥4 days. Treatment technique was dichotomized as intensity modulated (IMRT) or non-IMRT techniques. Results Out of the cohort of 7492, 35% had a RTI and 10% received IMRT. With a median follow-up of surviving patients of 32 months, the median survival for those with non-IMRT vs. IMRT was 18.2 months vs. 20 months ( p < 0.0001). Median survival for those with and without an RTI ≥ 4 days was 16.1 months vs. 19.8 months ( p < 0.0001). Use of IMRT predicted for a decreased likelihood of RTI (odds ratio, 0.84, p = 0.04). On multivariable analysis for OS, IMRT had a HR of 0.89 (95% CI: 0.80–0.98, p = 0.01) and RTI had a HR of 1.2 (95% confidence interval (CI): 1.14–1.27, p = 0.001). Conclusions IMRT was associated with small but significant survival advantage for patients with stage III NSCLC treated with CRT. A RTI led to inferior survival, and both IMRT and RTI were independently associated with OS. Additional research should investigate whether improved tolerability, reduced normal tissue exposure, or superior coverage drives the association between IMRT and improved survival. [ABSTRACT FROM AUTHOR]

Purpose The purpose was to evaluate survival outcomes between external beam radiotherapy (EBRT) plus brachytherapy and brachytherapy alone for intermediate-risk prostate cancer, using the National Cancer Data Base. Methods and Materials The National Cancer Data Base was queried for cN0M0 intermediate-risk patients treated from 2004 to 2006, with available data for Gleason score (GS), prostate-specific antigen (PSA), tumor stage, and receipt of radiation therapy (RT) and androgen deprivation therapy. RT comparison groups were the following: EBRT (40–50.4 Gy) plus brachytherapy and brachytherapy alone. Results A total of 10,571 patients were included: 3,148 received EBRT plus brachytherapy and 7,423 received brachytherapy alone. Median followup was 84 months (2–122 months); median age was 68 years (40–90 years). Unadjusted 5- and 7-year overall survival (OS) rates between EBRT plus brachytherapy vs. brachytherapy alone were 91.4% vs. 90.2% and 85.7% vs. 82.9%, respectively ( p < 0.001). EBRT plus brachytherapy was associated with longer OS compared with brachytherapy alone under multivariate (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.75–0.93; p = 0.001) and propensity score-matched analyses (HR, 0.85; 95% CI, 0.75–0.97; p = 0.006). Further subset analysis performed based on the Radiation Therapy Oncology Group 0232 inclusion criteria (GS 7 if PSA < 10 or GS < 7 if PSA 10–20) also demonstrated longer OS with EBRT plus brachytherapy (HR, 0.87; 95% CI, 0.77–0.98; p = 0.026). Conclusions EBRT plus brachytherapy is associated with a modest OS improvement compared with brachytherapy alone in this population-based analysis. Although this benefit appears statistically significant, the relatively small difference in OS raises the question of overall clinical benefit with combined modality RT for intermediate-risk prostate cancer, given the potential increased risk for toxicities. Future results from Radiation Therapy Oncology Group 0232 should provide further insight on this topic. [ABSTRACT FROM AUTHOR]

Purpose/objectives: The addition of whole pelvic (WP) compared with prostate-only (PO) radiation therapy (RT) for clinically node-negative prostate cancer remains controversial. The purpose of our study was to evaluate the survival benefit of adding WPRT versus PO-RT for high-risk, node-negative prostate cancer, using the National Cancer Data Base (NCDB).Methods and Materials: Patients with high-risk prostate cancer treated from 2004 to 2006, with available data for RT volume, coded as prostate and pelvis (WPRT) or prostate alone (PO-RT) were included. Multivariate analysis (MVA) and propensity-score matched analysis (PSM) were performed. Recursive partitioning analysis (RPA) based on overall survival (OS) using Gleason score (GS), T stage, and pretreatment prostate-specific antigen (PSA) was also conducted.Results: A total of 14,817 patients were included: 7606 (51.3%) received WPRT, and 7211 (48.7%) received PO-RT. The median follow-up time was 81 months (range, 2-122 months). Under MVA, the addition of WPRT for high-risk patients had no OS benefit compared with PO-RT (HR 1.05; P=.100). On subset analysis, patients receiving dose-escalated RT also did not benefit from WPRT (HR 1.01; P=.908). PSM confirmed no survival benefit with the addition of WPRT for high-risk patients (HR 1.05; P=.141). In addition, RPA was unable to demonstrate a survival benefit of WPRT for any subset. Other prognostic factors for inferior OS under MVA included older age (HR 1.25; P<.001), increasing comorbidity scores (HR 1.46; P<.001), higher T stage (HR 1.17; P<.001), PSA (HR 1.81; P<.001), and GS (HR 1.29; P<.001), and decreasing median county household income (HR 1.15; P=.011). Factors improving OS included the addition of androgen deprivation therapy (HR 0.92; P=.033), combination external beam RT plus brachytherapy boost (HR 0.71; P<.001), and treatment at an academic/research institution (HR 0.84; P=.002).Conclusion: In the largest reported analysis of WPRT for patients with high-risk prostate cancer treated in the dose-escalated era, the addition of WPRT demonstrated no survival advantage compared with PO-RT. [ABSTRACT FROM AUTHOR]

Introduction Whole-brain radiation therapy (WBRT) is the standard approach for brain metastases (BM) arising in patients with small-cell lung cancer (SCLC), but the neurocognitive toxicities of WBRT are well documented. For this reason, stereotactic radiosurgery (SRS) alone is the preferred modality for limited BM in most histologies, but in SCLC there are few data exploring this approach. Methods We queried the National Cancer Database (NCDB) for patients with SCLC with BM at diagnosis and stratified by upfront SRS compared with upfront WBRT ± SRS. We utilized multivariate Cox regression and propensity score matching (PSM) to determine the impact on overall survival (OS) of each approach. Results 5952 eligible patients (WBRT: 5752; SRS: 200) were identified from 2010 to 2014 with a median follow-up of 40.0 months. Upfront SRS was associated with superior OS (median 10.8 vs 7.1 months, HR 0.65, 95% CI 0.55–0.75, p < 0.001), which persisted on multivariate analysis controlling for comorbidities, extracranial metastases, age, race/ethnicity, and gender (HR 0.70, 95% CI 0.60–0.81, p < 0.001). These results were confirmed in PSM analysis. A subset analysis comparing outcomes after SRS vs SRS + WBRT showed no differences in OS (p = .601). Conclusions To our knowledge, this is the largest dataset of patients treated with SRS alone for SCLC. The observation of favorable OS with SRS alone in this contemporary dataset suggests that SRS alone may be appropriate for some patients with SCLC. Prospective investigations of SRS in SCLC are warranted. [ABSTRACT FROM AUTHOR]