Search

One year of adjuvant durvalumab following concurrent chemoradiotherapy significantly improves progression-free survival (PFS) and overall survival (OS) for patients with stage III non-small cell lung cancer (NSCLC). However, the optimal length of adjuvant therapy has not been determined.We identified patients with stage III NSCLC treated with definitive chemoradiation and adjuvant durvalumab from November 2017 to April 2021 from the United States Veterans Affairs system. Predictors of early durvalumab discontinuation were evaluated with Cox proportional hazards regression. The effect of differing durations of durvalumab treatment (up to 6, 9, and 12 months) on PFS and OS were compared with a marginal structural model and time-dependent Cox modelling.We included 1006 patients with stage III non-small cell lung cancer who received concurrent chemoradiotherapy and at least one dose of adjuvant durvalumab. The median duration of durvalumab treatment was 7 months (interquartile range 2.8-11.5) and 31% completed the intended durvalumab course. The most common reasons for early discontinuation were tumour progression (22%), immune-related adverse events (15%), and non-immune-related toxicity (6.0%), Marginal structural models suggested similar PFS for 9 months versus 12 months of durvalumab treatment and inferior PFS for 6 months versus 12 months.A substantial proportion of patients undergoing adjuvant durvalumab discontinue therapy early due to toxicity, and shorter durvalumab treatment durations may provide similar disease control to 12 months of therapy. Prospective randomised controlled studies are needed to characterise the optimal durvalumab treatment duration in locally advanced NSCLC patients.

IntroductionOsimertinib is an effective treatment for metastatic NSCLC. Occasionally, thoracic radiation therapy (TRT) is delivered to patients receiving osimertinib to treat residual or progressing pulmonary tumors. Anecdotal reports suggest that the delivery of TRT in combination with osimertinib may be associated with a high risk of severe pneumonitis.MethodsA retrospective study was performed at a single academic medical center in the United States to investigate the incidence of severe pneumonitis among patients treated with combined TRT and osimertinib between June 2016 and December 2021. Baseline patient characteristics, tumor size and location, and dosimetric parameters were evaluated. The highest grade of radiation pneumonitis that developed within 6 months of treatment was scored in accordance with the Common Terminology Criteria for Adverse Events version 5.0.ResultsA total of 16 patients were identified who were treated with combined TRT and osimertinib. All had a diagnosis of metastatic NSCLC. Treatment-related grade greater than or equal to 2 pneumonitis developed in 56%, grade greater than or equal to 3 in 37.5%, and grade 4 in 6.3%; no patient developed grade 5 pneumonitis. Median time to any-grade pneumonitis was 29 days (1-84 d); all patients had symptom resolution with expectant management or oral steroid therapies. All patients discovered to have grade greater than or equal to 3 pneumonitis (n= 6) received TRT to tumors located within 2 cm of the proximal bronchial tree, including tumors abutting the proximal bronchial tree (n= 2) and within the mediastinum (n= 1).ConclusionsThe combination of TRT with osimertinib was associated with a high rate of severe pneumonitis that required oral steroid medications. Larger studies are needed to validate these findings and to understand the clinical and treatment factors that influence this risk and how they can be mitigated.

Peroxisome proliferator-activated receptor agonists such as fibrates restore oxidative metabolism in cytotoxic T-lymphocytes, thereby enhancing response to immune checkpoint inhibitors (ICI) in preclinical models. However, there is no evidence in humans on the clinical impact of fibrates as an adjunct to ICI.In this cohort study of Veterans with non-small cell lung cancer (NSCLC) receiving ICI, fibrate exposure was defined as a prescription filled within 90 days of an ICI infusion. Overall survival (OS), measured from the start of ICI, was compared between exposed and unexposed Veterans. Cox multivariable analysis (MVA) was used to identify factors associated with OS. A sensitivity analysis of Veterans with stage IV NSCLC who received docetaxel without ICI was similarly performed.The ICI cohort included 3593 Veterans, of whom 301 (8.5%) coincidentally received a fibrate. Veterans receiving fibrates were more likely to be older, white, male, and married, and to have greater comorbidity burden, but less likely to receive chemotherapy. Coincidental fibrates were associated with improved OS both on MVA (HR 0.86, 95%CI 0.75-0.99) and in a matched subset (HR 0.75, 95%CI 0.63-0.90). In contrast, among the cohort of 968 Veterans treated with chemotherapy, fibrates did not have a significant impact on OS by MVA (HR 0.99, 95%CI 0.79-1.25) or in a matched subset (HR 1.02, 95%CI CI 0.75-1.39).Concomitant fibrates are associated with improved OS among NSCLC patients receiving ICI but not among those receiving chemotherapy. This hypothesis-generating observation supports a potential role for fibrates as an adjunct to immunotherapy.

MICROABSTRACT: We evaluated the association of operability status with early post-treatment mortality among patients with early-stage non-small cell lung cancer undergoing stereotactic body radiotherapy. In this cohort study of 80,108 patients from a large US cancer dataset, operable patients undergoing stereotactic body radiotherapy experienced

BackgroundPatients undergoing surgery for early stage non-small cell lung cancer (NSCLC) may be at high risk for postoperative mortality. Access to stereotactic body radiation therapy (SBRT) may facilitate more appropriate patient selection for surgery.Research questionIs postoperative mortality associated with early stage NSCLC lower at facilities with higher use of SBRT?Study design and methodsPatients with early stage NSCLC reported to the National Cancer Database between 2004 and 2015 were included. Use of SBRT was defined by each facility's SBRT experience (in years) and SBRT to surgery volume ratios. Multivariate logistic regression was used to test for the associations between SBRT use and postoperative mortality.ResultsThe study cohort consisted of 202,542 patients who underwent surgical resection of cT1-T2N0M0 NSCLC tumors. The 90-day postoperative mortality rate declined during the study period from 4.6%to 2.6%(P< .001), the proportion of facilities that used SBRT increased from 4.6%to 77.5%(P< .001), and the proportion of patients treated with SBRT increased from 0.7%to 15.4%(P< .001). On multivariate analysis, lower 90-day postoperative mortality rates were observed at facilities with > 6 years of SBRT experience (OR, 0.84; 95% CI, 0.76-0.94; P= .003) and SBRT to surgery volume ratios of more than 17%(OR, 0.85; 95% CI, 0.79-0.92; P< .001). Ninety-day mortality also was associated with surgical volume, region, year, age, sex, and race, among other covariates. Interaction testing between these covariates showed negative results.InterpretationPatients who underwent resection for early stage NSCLC at facilities with higher SBRT use showed lower rates of postoperative mortality. These findings suggest that the availability and use of SBRT may improve the selection of patients for surgery who are predicted to be at high risk of postoperative mortality.

Background: Lung cancer screening includes identification of eligible individuals, shared decision-making inclusive of tobacco cessation, and management of screening results. Adaptations to the implemented processes for lung cancer screening in situ are understudied and underreported, with potential loss of important considerations for improved implementation. The Framework for Reporting Adaptations and Modifications-Expanded (FRAME) allows for systematic enumeration of adaptations to implementations of evidence-based practices. We used FRAME to study adaptations in lung cancer screening processes that were implemented as part of a Veterans Health Administration (VHA) Enterprise-Wide Initiative.Methods: We conducted semi-structured interviews at baseline and 1-year intervals with lung cancer screening program navigators at 10 Veterans Affairs Medical Centers (VAMC) between 2019-2021. Using this data, we developed baseline (1st) process maps for each program. In subsequent years (year 1 and year 2), each program navigator reviewed the process maps. Adaptations in screening processes were identified, recorded and mapped to FRAME categories. Results: A total of 14 program navigators across 10 VHA lung cancer screening programs participated in 20 interviews. In year 1 (2019-2020), seven programs were operational and of these, three reported adaptations to their screening process that were either planned and in response to COVID-19. In year 2 (2020-2021), all 10 programs were operational. Programs reported 14 adaptations in year 2. These adaptations were both planned and unplanned and often triggered by increased workload; 57% of year 2 adaptations were related to identification and eligibility of Veterans and 43% were related to follow-up with Veterans for screening results. Throughout the 2 years, adaptations related to data management and patient tracking occurred in 6 of 10 programs to improve the data collection and tracking of Veterans in the screening process. Conclusions: Using FRAME, we found that adaptations occurred throughout the lung cancer screening process but primarily in the areas of patient identification and communication of results. These findings highlight considerations for lung cancer screening implementation and potential areas for future intervention.

Rationale: Because of improvements in screening, there is an increasing number of patients with early-stage non-small-cell lung cancer (NSCLC) who are making treatment decisions.Objectives: Among patients with suspected stage I NSCLC, we evaluated longitudinal patient-centered outcomes (PCOs) and the association of changes in PCOs with treatment modality, stereotactic body radiotherapy (SBRT) compared with surgical resection.Methods: We conducted a multisite, prospective, observational cohort study at seven medical institutions. We evaluated minimum clinically important differences of PCOs at four time points (during treatment, 4-6 wk after treatment, 6 mo after treatment, and 12 mo after treatment) compared with pretreatment values using validated instruments. We used adjusted linear mixed models to examine whether the association between treatment and European Organization for Research and Treatment of Cancer global and physical quality-of-life (QOL) scales differed over time.Results: We included 127 individuals with stage I NSCLC (53 surgery, 74 SBRT). At 12 months, approximately 30% of patients remaining in each group demonstrated a clinical deterioration on global QOL from baseline. There was a significant difference in slopes between treatment groups on global QOL (-12.86; 95% confidence interval [CI], -13.34 to -12.37) and physical QOL (-28.71; 95% CI, -29.13 to -28.29) between baseline and during treatment, with the steeper decline observed among those who underwent surgery. Differences in slopes between treatment groups were not significant at all other time points.Conclusions: Approximately 30% of patients with stage I NSCLC have a clinically significant decrease in QOL 1 year after SBRT or surgical resection. Surgical resection was associated with steeper declines in QOL immediately after treatment compared with SBRT; however, these declines were not lasting and resolved within a year for most patients. Our results may facilitate treatment option discussions for patients receiving treatment for early-stage NSCLC.

We learned many unanticipated and valuable lessons since we started planning our study of low-dose computed tomography (CT) screening for lung cancer in 1991. The publication of the baseline results of the Early Lung Cancer Action Project (ELCAP) in Lancet 1999 showed that CT screening could identify a high proportion of early, curable lung cancers. This stimulated large national screening studies to be quickly started. The ELCAP design, which provided evidence about screening in the context of a clinical program, was able to rapidly expand to a 12-institution study in New York State (NY-ELCAP) and to many international institutions (International-ELCAP), ultimately working with 82 institutions, all using the common I-ELCAP protocol. This expansion was possible because the investigators had developed the ELCAP Management System for screening, capturing data and CT images, and providing for quality assurance. This advanced registry and its rapid accumulation of data and images allowed continual assessment and updating of the regimen of screening as advances in knowledge and new technology emerged. For example, in the initial ELCAP study, introduction of helical CT scanners had allowed imaging of the entire lungs in a single breath, but the images were obtained in 10 mm increments resulting in about 30 images per person. Today, images are obtained in submillimeter slice thickness, resulting in around 700 images per person, which are viewed on high-resolution monitors. The regimen provides the imaging acquisition parameters, imaging interpretation, definition of positive result, and the recommendations for further workup, which now include identification of emphysema and coronary artery calcifications. Continual updating is critical to maximize the benefit of screening and to minimize potential harms. Insights were gained about the natural history of lung cancers, identification and management of nodule subtypes, increased understanding of nodule imaging and pathologic features, and measurement variability inherent in CT scanners. The registry also provides the foundation for assessment of new statistical techniques, including artificial intelligence, and integration of effective genomic and blood-based biomarkers, as they are developed.

One year of durvalumab following concurrent chemoradiotherapy improves progression-free (PFS) and overall survival (OS) for patients with stage III non-small cell lung cancer (NSCLC). However, the real-world efficacy of durvalumab has not been determined. We conducted a multi-center observational cohort study across the Veterans Health Administration, including patients with stage III NSCLC who received concurrent chemoradiotherapy and durvalumab, compared to patients who received concurrent chemoradiotherapy alone. Kaplan–Meier and Cox regression approaches were used to identify factors associated with PFS and OS. We calculated a hazard ratio and efficacy-effectiveness factor to compare OS of veterans to the referenced clinical trial population. A total of 1006 patients with stage III NSCLC who received concurrent chemoradiotherapy and at least one dose of durvalumab from November 2017 to April 2021 were compared to 989 patients who received concurrent chemoradiotherapy alone from January 2015 to December 2016. Adjuvant durvalumab was associated with higher PFS (HR 0.62, 95% CI 0.55–0.70, p < 0.001) and OS (HR 0.57, 95% CI 0.50–0.66, p < 0.001). OS was shorter in veterans compared to PACIFIC (HR 1.24, 95% CI 1.03–1.48, p = 0.02: EE gap 0.73). OS of veterans with stage III NSCLC treated with adjuvant durvalumab is improved compared to a modern comparator but is reduced compared to the PACIFIC population.

Oligometastatic disease refers to a limited number of metastatic sites that are either “synchronous” when presenting at the time of initial diagnosis or “metachronous” when arising following therapy of the primary tumor. It is hypothesized that the biology of oligometastatic tumors may be different than that of tumors with more widespread metastases (1-3). As such, treatment of oligometastatic sites with local consolidative therapy (LCT) is a topic of interest, and has been increasingly offered in clinical practice. While there is no single definition of this state, it is commonly defined as up to 3–5 sites of metastases (excluding the primary lesion) following induction systemic therapy (1-6). In patients receiving chemotherapy for non-small cell lung cancer (NSCLC), it has been observed that the most common sites of progression are within the original disease sites (1-3,6). Patients with oligometastatic disease remaining after induction systemic therapy are believed to harbor treatment resistant clones in these sites which may not be effectively managed with subsequent systemic agents (7). In these cases, there is a widow of opportunity to eradicate radiographically visible disease sites with LCT and delay further progressive disease, and perhaps even help patients live longer (1,8,9). Initially, highly select patients with limited metastases were treated off trial with LCT to all visible disease sites, including to the primary tumor (10). Later, retrospective observational studies and single arm prospective trials suggested a potential survival benefit with this approach (11-14). In a meta-analysis of 757 NSCLC patients with or without prior chemotherapy, and having 1-5 sites of metastases, the delivery of LCT to all visible disease sites (62% surgery and 38% radiation) was associated with a 5-year overall survival (OS) rate of 29.4% (15). When considering the historical 5-year OS rate of 2% in stage IV NSCLC patients, this approach received widespread attention (16). However, this meta-analysis was subject to selection bias as it did not include randomized prospective data. Additionally, the historical rates included patients with any number of metastatic sites, and as such the patients treated with LCT for oligometastatic disease may have simply done better because their disease burden was lower. Subsequently, randomized clinical trials were initiated to more rigorously evaluate the role of LCT vs. standard systemic therapy/observation in patients with oligometastatic disease following induction chemotherapy (4-6).

There is a paucity of clinical data to support the hypothesis that external beam radiation therapy causes iatrogenic hypogonadism in prostate cancer patients. All prostate cancer patients treated at a single institution with radiation therapy between 2002 and 2010 were retrospectively evaluated. Patients treated with brachytherapy alone received 0 Gy of external beam radiation therapy and served as the control group. Patients treated with combination external beam radiation therapy + brachytherapy, or external beam radiation therapy alone were categorized into groups who received 45–54 Gy or > 60 Gy of external beam radiation therapy, respectively. Serum testosterone levels were routinely measured with prostate-specific antigen tests. The median follow-up periods for 149 evaluable patients in the control group (0 Gy), the 45–54 Gy group, and > 60 Gy group were 57, 62, and 55 months, respectively (p = 0.43). Among patients who underwent external beam radiation therapy, 53% were treated with intensity-modulated radiation therapy, 65% with pelvic lymph node coverage, and 78% with 18 megavoltage photons. There were no differences in serum testosterone level declines over time between the 45–54 Gy group (p = 0.32) or the > 60 Gy group (p = 0.14) when compared to the control group (0 Gy). While body mass index was associated with baseline testosterone levels in univariate analysis (p

TPS5112 Background: Two diverging paradigms have been studied in recent years to improve the survival of men with recurrent metastatic prostate cancer (PCa). First, multiple recent phase II randomized trials have demonstrated improved long-term progression-free survival (PFS) with metastasis-directed therapy (MDT) in men with oligorecurrent PCa in the absence of systemic therapy. Yet, most patients receiving MDT for oligorecurrent PCa develop progression in new areas, arguing that systemic therapy is needed to treat occult metastases. The second approach that has recently been studied is whether escalating systemic therapy by adding novel androgen receptor axis targeted agents or chemotherapy improves outcomes in men with metastatic PCa. Multiple phase III randomized trials demonstrate that enhancing hormonal therapy with these therapeutic agents improves progression-free survival (PFS) and overall survival. Therefore, these agents have been integrated into today’s standard systemic therapy (SST) for metastatic recurrence, and SST is the current NCCN guidelines standard of care for recurrent metastatic PCa. The primary goal of our study is to determine if adding PET-directed local therapy (PDLT) to SST improves disease control compared to SST alone in Veterans with oligorecurrent PCa. Methods: VA STARPORT is a phase II/III randomized trial open at 16 VA medical centers comparing SST with or without PDLT in Veterans with oligorecurrent PCa. Key eligibility criteria include prior localized PCa with biochemical recurrence after initial curative-intent local therapy and workup including any FDA-approved PCa PET/CT that reveals oligorecurrence in 1-5 metastatic lesions. The primary endpoint is castration-resistant prostate cancer-free survival (CRPC-free survival). Secondary endpoints include radiographic PFS, clinical PFS, freedom from index lesion progression, toxicity, quality of life, and prostate cancer-specific and overall survival. SST is delivered with an intent for indefinite SST using any NCCN guideline-concordant regimen in both arms. PDLT (Arm 2) consists of surgery or radiation to metastases and any present prostate/prostate bed local recurrence. Metastasis-directed radiation can consist of stereotactic body radiotherapy or elective nodal radiotherapy per clinician discretion from dose/fractionation options defined in the protocol. All participants undergo somatic tumor sequencing using the VA National Precision Oncology Program. Germline sequencing and tumor banking in a separate biorepository study is recommended. Assuming a hazard ratio of 0.60 for SST + PDLT vs SST, two-sided alpha = 0.05 and 90% power, a total of 464 participants will be randomized to generate 166 primary events (CRPC-free survival) by the end of the 48-month active study phase. The study began enrollment in August 2021. Clinical trial information: NCT04787744.

Approximately 20,000 US veterans receive radiation oncology services at a Veterans Healthcare Administration (VHA) medical facility each year. They currently have access to advanced technologies, which include image-guided intensity-modulated radiotherapy, stereotactic radiosurgery, and stereotactic body radiation therapy. Although this provides access to cancer therapies that are modern, safe, and efficient, the technical complexities of these treatments and clinical decision making that goes into the patient selection and prescriptions demand quality assurances at each VHA practice. To meet the challenges of this need, the VHA established a partnership in 2008 with the ACR’s Radiation Oncology Practice Accreditation Program (ACR-ROPA). This report summarizes the experience of this ongoing partnership and demonstrates the combined impact of the VHA’s mandate for ACR-ROPA accreditation and internal monitoring of all identified corrective actions at each of its radiation oncology practices.

Addition of a brachytherapy boost to external beam radiation therapy (EBRT) reduces prostate cancer (PCa) recurrence at the expense of genitourinary (GU) toxicity. Whether brachytherapy boost technique, specifically low-dose-rate (LDR-BT) versus high-dose-rate (HDR-BT), impacts treatment-related toxicity is unclear.Between 2012-2018, 106 men with intermediate/high risk PCa underwent EBRT (37.5-45 Gy in 1.8-2.5 Gy/fraction) plus brachytherapy boost, either with LDR-BT (110 Gy I-125 or 100 Gy Pd-103; n = 51) or HDR-BT (15 Gy x1 Ir-192; n = 55). Patient-reported outcomes (PRO) were assessed by International Prostate Symptom Score (IPSS) and Expanded Prostate Cancer Index Composite (EPIC-CP) surveys at 3-6-month intervals for up to three years following treatment, with higher scores indicating more severe toxicity. Provider-reported GU and gastrointestinal (GI) toxicity was graded per CTCAE v5.0 at each follow-up. Linear mixed models comparing PROs between LDR-BT versus HDR-BT were fitted. Stepwise multivariable analysis (MVA) was performed to account for age, gland size, androgen deprivation therapy use, and alpha-blocker medication use. Incidence rates of grade 2+ GU/GI toxicity was compared using Fisher's exact test.Use of LDR-BT was associated with greater change in IPSS (p=0.003) and EPIC-CP urinary irritative score (p = 0.002) compared with HDR-BT, but effect size diminished over time (LDR-BT versus HDR-BT: baseline to 6-/24-month mean IPSS change, +6.4/+1.4 versus +2.7/-3.0, respectively; mean EPIC-CP irritative/obstructive change, +2.5/+0.1 versus +0.9/+0.1, respectively). Results remained significant on MVA. Post-treatment grade 2+ GU toxicity was significantly higher in the LDR-BT group (67.5% versus 42.9% for LDR-BT and HDR-BT, respectively; p0.001). There were no differences between groups in incontinence, bowel function, and erectile function, or grade 2+ GI toxicity.Compared with LDR-BT, HDR-BT was associated with lower acute patient- and provider-reported GU toxicity.

Purpose: Thoracic reirradiation for non-small cell lung cancer with curative intent is potentially associated with severe toxicity. There are limited prospective data on the best method to deliver this treatment. We sought to develop expert consensus guidance on the safe practice of treating non-small cell lung cancer with radiation therapy in the setting of prior thoracic irradiation.Methods and Materials: Twenty-one thoracic radiation oncologists were invited to participate in an international Delphi consensus process. Guideline statements were developed and refined during 4 rounds on the definition of reirradiation, selection of appropriate patients, pretreatment assessments, planning of radiation therapy, and cumulative dose constraints. Consensus was achieved once >75% of respondents agreed with a statement. Statements that did not reach consensus in the initial survey rounds were revised based on respondents' comments and re-presented in subsequent rounds.Results: Fifteen radiation oncologists participated in the 4 surveys between September 2019 and March 2020. The first 3 rounds had a 100% response rate, and the final round was completed by 93% of participants. Thirty-three out of 77 statements across all rounds achieved consensus. Key recommendations are as follows: (1) appropriate patients should have a good performance status and can have locally relapsed disease or second primary cancers, and there are no absolute lung function values that preclude reirradiation; (2) a full diagnostic workup should be performed in patients with suspected local recurrence and; (3) any reirradiation should be delivered using optimal image guidance and highly conformal techniques. In addition, consensus cumulative dose for the organs at risk in the thorax are described.Conclusions: These consensus statements provide practical guidance on appropriate patient selection for reirradiation, appropriate radiation therapy techniques, and cumulative dose constraints. (C) 2021 The Authors. Published by Elsevier Inc. on behalf of American Society for Radiation Oncology.

Background Centrally located lung tumors present treatment challenges given their proximity to mediastinal structures including the central airway, esophagus, major vessels, and heart. Therapeutic options can be limited for medically inoperable patients, particularly if they have received previous thoracic radiotherapy. High dose rate (HDR) brachyablation was developed to improve the therapeutic ratio for patients with central lung tumors. The purpose of this study is to report initial safety and efficacy outcomes with this treatment for central lung malignancies. Methods From September 2015 to August 2019, a total of 25 patients with 37 pulmonary tumors were treated with percutaneous HDR brachyablation. Treatment was delivered by a multi-disciplinary team of interventional radiologists, pulmonologists, and radiation oncologists. Twenty-three patients received a median dose of 21.5 Gy (range 15–27.5) in a single fraction, whereas two patients received median dose of 24.75 Gy (range 24–25.5) over 2–3 fractions. Tumor local control (LC) was evaluated by Response Evaluation Criteria in Solid Tumors v1.1. Treatment-related toxicities were graded by Common Terminology Criteria for Adverse Events v5.0, with adverse events less than 90 days defined as acute, and those occurring later were defined as late. LC, progression-free survival (PFS), and overall survival (OS) rates were estimated by the Kaplan–Meier method. Results Of 37 treated tumors, 88% were metastatic. Tumor location was central and ultra-central in 24.3% and 54.1%, respectively. Average tumor volume was 11.6 cm3 (SD 12.4, range 0.57–62.8). Median follow-up was 19 months (range 3–48). Two–year LC, PFS, and OS were 96.2%, 29.7%, and 65.5%, respectively. Thirteen of 39 (33.3%) catheter implantation procedures were associated with trace minor pneumothorax requiring no intervention, 1 (2.5%) procedure with minor radiographic pulmonary hemorrhage, and 4 (10.3%) with major pneumothorax requiring chest tube insertions. All procedural complications resolved within 24 h from treatment. Acute grade 1–2 toxicity was identified in 4 patients, whereas none developed late toxicity beyond 90 days of follow-up. Conclusion Percutaneous HDR brachyablation is a safe and promising treatment option for centrally located primary and metastatic lung tumors. Future comparisons with stereotactic body radiotherapy and other ablative techniques are warranted to expand multi-disciplinary management options.

The treatment paradigm for extensive stage small cell lung cancer (ES-SCLC) is evolving. Prophylactic cranial irradiation (PCI) has long been considered a component of standard treatment in patients with extensive stage disease who respond to chemotherapy. However, in the modern era of magnetic resonance imaging, the role of PCI has become an area of controversy following conflicting level I evidence. Due to conflicting data and toxicity concerns, the routine use of PCI has declined. Recent improvements in systemic disease control with the use of immunotherapy and reductions in the toxicity attributable to PCI with hippocampal avoidance and memantine have reignited the discussion. As such, we present here a narrative review of PCI with a focus on historical milestones, randomized data, risk mitigation and future directions.

Introduction The Veterans Affairs Partnership to increase Access to Lung Screening (VA-PALS) is an enterprise-wide initiative to implement lung cancer screening programs at VA medical centers (VAMCs). VA-PALS will be using implementation strategies that include program navigators to coordinate screening activities, trainings for navigators and radiologists, an open-source software management system, tools to standardize low-dose computed tomography image quality, and access to a support network. VAMCs can utilize strategies according to their local needs. In this protocol, we describe the planned program evaluation for the initial 10 VAMCs participating in VA-PALS. Materials and methods The implementation of programs will be evaluated using the Consolidated Framework for Implementation Research to ensure broad contextual guidance. Program evaluation measures have been developed using the Reach, Effectiveness, Adoption, Implementation and Maintenance framework. Adaptations of screening processes will be assessed using the Framework for Reporting Adaptations and Modifications to Evidence Based Interventions. Measures collected will reflect the inner settings, estimate and describe the population reached, adoption by providers, implementation of the programs, report clinical outcomes and maintenance of programs. Analyses will include descriptive statistics and regression to evaluate predictors and assess implementation over time. Discussion This theory-based protocol will evaluate the implementation of lung cancer screening programs across the Veterans Health Administration using scientific frameworks. The findings will inform plans to expand the VA-PALS initiative beyond the original sites and can guide implementation of lung cancer screening programs more broadly.

Background The Veterans Affairs Partnership to increase Access to Lung Screening (VA-PALS) is an enterprise-wide initiative to implement high quality lung cancer screening programs at VA medical centers (VAMCs). VA-PALS will be using implementation strategies that include program navigators to coordinate screening activities, trainings for navigators and radiologists, an open-source software management system, tools to standardize low-dose computed tomography (LDCT) image quality, and access to a support network. Individual VAMCs can utilize strategies according to their local contextual factors. In this protocol, we describe the planned program evaluation for the initial 10 VAMCs participating in VA-PALS. Methods The implementation of programs will be evaluated using the Consolidated Framework for Implementation Research to ensure broad contextual guidance. Program evaluation measures have been developed using the Reach, Effectiveness, Adoption, Implementation and Maintenance framework. Adaptations of screening processes will be assessed every six months using the Framework for Reporting Adaptations and Modifications to Evidence Based Interventions. Measures collected will reflect the inner setting at each VAMC, estimate and describe the population reached, adoption by providers, implementation of the programs, report patient clinical outcomes and maintenance of screening programs. Analyses will primarily use descriptive statistics with means, medians, and frequencies. Outcomes will be compared over time and among VA-PALS VAMCs and non-VA-PALS VAMCs in interrupted time series analyses. Assessment of contextual factors and the relationship between predictors, such as organizational readiness and improved implementation, will be evaluated. Adaptations of processes to overcome barriers will be identified and evaluated for association with implementation. Conclusion This theory-based protocol will evaluate the implementation of lung cancer screening programs across the Veterans Health Administration (VHA) using scientific frameworks. The findings will inform plans to expand the VA-PALS initiative beyond the original sites and can guide implementation of lung cancer screening programs more broadly within and outside VHA.

BACKGROUND: Radiotherapy plays an important role in the palliation of lung cancer, which is the second most common cancer diagnosed in the Veterans Health Administration (VHA). The American Society for Radiation Oncology (ASTRO) developed evidenced-based treatment guidelines for the management of patients with metastatic lung cancer. METHODS: In May 2016, an electronic survey of 88 VHA radiation oncologists (ROs) was conducted to assess metastatic lung cancer management. Demographic information was obtained and 2 clinical scenarios were presented to glean opinions on dose/fractionation schemes preferred, preferences for/against concurrent chemotherapy, and use of endobronchial brachytherapy (EBB) and/or yttrium aluminum garnet (YAG) laser technology. Survey results were assessed for concordance with published ASTRO guidelines. RESULTS: The survey response rate was 61%, with 93% of the 40 VHA radiation departments represented. Among respondents, 96% were board certified, and 90% held academic appointments. 88% were familiar with ASTRO guidelines. Preferred fractionation schemes were 20 Gy in 5 fractions (69%) and 30 Gy in 10 fractions (22%). The vast majority (98%) did not recommend concurrent chemotherapy for palliation. In the setting of bronchial obstruction with lung collapse, about half (49%) recommended EBB or YAG lung reexpansion before external beam radiotherapy. A minority of respondents use stereotactic body radiotherapy or EBB for palliation. CONCLUSION: Most respondents demonstrated up-to-date knowledge of current evidence-based treatment guidelines. We found no distinction in clinical decisions based on demographic profiles.

Background Lung cancer is a leading cause of cancer-related mortality among veterans-as well as the US population-despite veterans' access to advanced medical technologies within the Veterans Health Administration (VHA). To improve outcomes, the VHA launched 3 lung cancer treatment initiatives in 2016 and 2017. Observations This article summarizes the VHA lung cancer initiatives and discusses future programs aimed to improve care for veterans. The US Department of Veterans Affairs (VA) Partnership to Increase Access to Lung Screening aims to reduce lung cancer mortality among veterans at risk by increasing access to low-dose computed tomography lung screening scans. The VALOR study is a randomized phase 3 clinical trial that evaluates optimal treatment for participants with operable early stage non-small cell lung cancer (NSCLC). This trial plans to enroll veterans with stage I NSCLC who will be randomly assigned to treatment with either surgical lobectomy or stereotactic body radiation therapy. Researchers will follow each participant for at least 5 years to evaluate which treatment, if either, results in a higher overall survival rate. The VA Radiation Oncology Quality Surveillance program compares treatment of veterans with lung cancer in the VHA with quality standards recommended by nationally recognized experts in lung cancer care. Conclusions The VHA continues to prioritize resources to improve and assure optimal outcomes for veterans with lung cancer. Future efforts include creating a national network of lung cancer centers of excellence to ensure that treatment decisions for veterans with lung cancer are based on all available molecular information, including data on pharmacogenomic profiles.

Objectives Lung cancer has the highest cancer-related mortality in the United States and among Veterans. Screening of high-risk individuals with low-dose CT (LDCT) can improve survival through detection of early-stage lung cancer. Organizational factors that aid or impede implementation of this evidence-based practice in diverse populations are not well described. We evaluated organizational readiness for change and change valence (belief that change is beneficial and valuable) for implementation of LDCT screening. Methods We performed a cross-sectional survey of providers, staff, and administrators in radiology and primary care at a single Veterans Affairs Medical Center. Survey measures included Shea’s validated Organizational Readiness for Implementing Change (ORIC) scale and Shea’s 10 items to assess change valence. ORIC and change valence were scored on a scale from 1 to 7 (higher scores representing higher readiness for change or valence). Multivariable linear regressions were conducted to determine predictors of ORIC and change valence. Results Of 523 employees contacted, 282 completed survey items (53.9% overall response rate). Higher ORIC scores were associated with radiology versus primary care (mean 5.48, SD 1.42 versus 5.07, SD 1.22, β = 0.37, P = .039). Self-identified leaders in lung cancer screening had both higher ORIC (5.56, SD 1.39 versus 5.11, SD 1.26, β = 0.43, P = .050) and change valence scores (5.89, SD 1.21 versus 5.36, SD 1.19, β = 0.51, P = .012). Discussion Radiology health professionals have higher levels of readiness for change for implementation of LDCT screening than those in primary care. Understanding health professionals’ behavioral determinants for change can inform future lung cancer screening implementation strategies.

Background In this phase I/II trial, 5-year physician-assessed toxicity and patient reported quality of life data is reported for patients undergoing moderately hypofractionated intensity modulated radiation therapy (IMRT) for prostate cancer using a simultaneous integrated boost (SIB) and pelvic lymph node (LN) coverage. Materials and methods Patients with T1-T2 localized prostate cancer were prospectively enrolled, receiving risk group based coverage of prostate ± seminal vesicles (SVs) ± pelvic lymph nodes (LNs). Low risk (LR) received 69.6 Gy/29 fractions to the prostate, while intermediate risk (IR) and high risk (HR) patients received 72 Gy/30fx to the prostate and 54Gy/30fx to the SVs. If predicted risk of LN involvement >15%, 50.4 Gy/30fx was delivered to pelvic LNs. Androgen deprivation therapy was given to IR and HR patients. Results There were 55 patients enrolled and 49 patients evaluable at a median follow up of 60 months. Included were 11 (20%) LR, 23 (41.8%) IR, and 21 (38.2%) HR patients. Pelvic LN treatment was given in 25 patients (51%). Prevalence rates of late grade 2 GI toxicity at 1, 3, and 5 years was 5.8, 3.9, and 5.8%, respectively, with no permanent grade 3 events. Prevalence rates of late grade 2 GU toxicity at 1, 3, and 5 years rates were 15.4, 7.7, and 13.5%, respectively, with three grade 3 events (5.8%). The biochemical relapse free survival at 5 years was 88.3%. There were no local, regional, or distant failures, with all patients still alive at last follow up. Conclusion Moderate hypofractionation of localized prostate cancer utilizing a SIB technique and LN coverage produces tolerable acute/late toxicity. Given equivalent efficacy between moderate hypofractionation schedules, the optimal regimen will be determined by long-term toxicity reported from both the physician and patient perspective. Clinical trial registration www.ClinicalTrials.gov, identifier NCT01117935, Date of Registration: 5/6/2010.

Purpose The quality of stereotactic body radiation therapy (SBRT) treatment plans for early stage lung cancer are unknown outside of peer-reviewed publications. Thus, a study was conducted to crowdsource and analyze a variety of lung SBRT treatment plans from around the world. Methods and Materials This study had 2 parts, planning and contouring, and each was facilitated by a web-based technology platform. For planning, lung SBRT planners were invited to design, score, and submit their treatment plans (prescription of 11 Gy × 5) for a centralized stage I lung cancer case using standardized images and predefined contours. Each plan was scored with 20 weighted metrics adapted from currently recruiting phase 3 lung SBRT trials. For contouring, a separate image set was used to evaluate organ-at-risk contour accuracy using Dice coefficients and a StructSure score. Results For planning 227 plans were submitted in total with 7 different treatment planning systems and 7 different delivery methods represented. Variability was primarily user driven and not associated with the treatment planning system, delivery modality, total monitor units, or estimated beam-on time. Many of the highest-quality plans required the shortest amount of time to deliver, independent of the delivery technique. For contouring, organ-at-risk contours were frequently over- or undercontoured and often included only the luminal air of the trachea, proximal bronchial tree, and esophagus, even when the mucosal linings were within a few centimeters of the target tumor. Conclusions These findings demonstrate the importance of quality assurance to help improve planning and contouring and the value of peer review and comparison. More readily accessible quality evaluation software solutions, such as the one used herein, may help meet this growing need.

Importance: The COVID-19 pandemic is currently accelerating. Patients with locally advanced non-small cell lung cancer (LA-NSCLC) may require treatment in locations where resources are limited and the prevalence of infection is high. Patients with LA-NSCLC frequently present with comorbidities that increase the risk for severe morbidity and mortality from COVID-19. These risks may be further increased by treatments for LA-NSCLC. Observation: We present expert thoracic oncology multidisciplinary (radiation oncology, medical oncology, surgical oncology) consensus of alternative strategies for the treatment of LA-NSCLC during a pandemic. The overarching goals of these approaches are to reduce the number of visits to a healthcare facility, reduce the risk of SARS-CoV-2 exposure, and attenuate the immunocompromising effects of lung cancer therapies. Patients with resectable disease can be treated with definitive non-operative management if surgical resources are limited or the risks of perioperative care are high. Non-operative options include chemotherapy, chemoimmunotherapy, and radiation therapy with sequential schedules. The order of treatments may be based on patient factors and clinical resources. Whenever radiation therapy is delivered without concurrent chemotherapy, hypofractionated schedules are appropriate. For patients who are confirmed to have COVID-19, usually cancer therapies may be withheld until symptoms have resolved with negative viral test results. Conclusions and Relevance: The risk of severe treatment-related morbidity and mortality is significantly elevated for patients undergoing treatment for LA-NSCLC during the COVID-19 pandemic. Adapting alternative treatment strategies as quickly as possible may save lives and should be implemented through communication with the multidisciplinary cancer team.

The coronavirus disease 2019 (COVID-19) pandemic is currently accelerating. Patients with locally advanced NSCLC (LA-NSCLC) may require treatment in locations where resources are limited, and the prevalence of infection is high. Patients with LA-NSCLC frequently present with comorbidities that increase the risk of severe morbidity and mortality from COVID-19. These risks may be further increased by treatments for LA-NSCLC. Although guiding data is scarce, we present an expert thoracic oncology multidisciplinary (radiation oncology, medical oncology, surgical oncology) consensus of alternative strategies for the treatment of LA-NSCLC during a pandemic. The overarching goals of these approaches are the following: (1) reduce the number of visits to a health care facility, (2) reduce the risk of exposure to severe acute respiratory syndrome-coronavirus-2, (3) attenuate the immunocompromising effects of lung cancer therapies, and (4) provide effective oncologic therapy. Patients with resectable disease can be treated with definitive nonoperative management if surgical resources are limited or the risks of perioperative care are high. Nonoperative options include chemotherapy, chemoimmunotherapy, and radiation therapy with sequential schedules that may or may not affect long-term outcomes in an era in which immunotherapy is available. The order of treatments may be on the basis of patient factors and clinical resources. Whenever radiation therapy is delivered without concurrent chemotherapy, hypofractionated schedules are appropriate. For patients who are confirmed to have COVID-19, usually, cancer therapies may be withheld until symptoms have resolved with negative viral test results. The risk of severe treatment-related morbidity and mortality is increased for patients undergoing treatment for LA-NSCLC during the COVID-19 pandemic. Adapting alternative treatment strategies as quickly as possible may save lives and should be implemented through communication with the multidisciplinary cancer team.

The peer-reviewed literature is often referenced to generalize outcomes for lung cancer surgeries performed within the Veterans Health Administration (VHA) and include assessments following resection of early stage non–small-cell lung cancer (NSCLC). We sought to determine the reliability of these reports that are publicly available. A systematic review was undertaken to identify PubMed indexed articles that report postoperative outcomes following surgical resections for stage I NSCLC within the VHA. Only studies that reported American Joint Committee on Cancer staging were included. Eleven studies spanning 49 years (1966–2015) met the inclusion criteria. Two reported findings from national VHA databases while 9 reported outcomes from single institutions. Reporting of outcomes and prognostic factors varied widely between studies and were frequently omitted. This made it difficult to evaluate prognostic factors that may be associated with a wide range of 30- and 90-day perioperative mortality (0–3.8% and 0–6.4%), 3- and 5-year cause-specific survival (72–92% and 32–84%), and 3- and 5- year overall survival (47–85.7% and 24–74%). The quality of peer-reviewed literature that reports outcomes following thoracic surgery for stage I NSCLC in the VHA is inconsistent and precludes accurate assessments for generalizations about the quality of care in this healthcare system. Efforts to develop a dedicated outcome tracking and registry system can provide more meaningful evidence to identify areas for improvement for this often-curable malignancy.

PURPOSE Physician reported symptomatic late rectal injury occurs in about 5% to 25% of patients treated with radiation therapy for prostate cancer, depending on the treatment technique. Patients, however, report clinically meaningful declines in bowel/rectal function regardless of the technique used. Lovastatin has been shown to protect mice from late radiation injury. This study was designed to determine if lovastatin might reduce the incidence of late rectal injury in patients receiving radiation therapy for prostate cancer. MATERIALS AND METHODS Patients with adenocarcinoma of the prostate receiving radiotherapy with curative intent were eligible. A portion of the rectum had to receive at least 60 Gy. Gastrointestinal functioning was assessed using both physician-reported and patient-reported instruments at baseline and at prescribed intervals during and after treatment. Lovastatin (20 to 80 mg/d) was started on day 1 of radiation and continued for 12 months. Patients were followed for an additional 12 months. The primary endpoint was physician-reported rectal toxicity ≥grade 2 during the first 2 years after treatment. RESULTS A total of 20/53 (38%) patients developed grade 2 or higher toxicity during the 2-year follow-up period. Seventeen patients had 1 or more unresolved gastrointestinal symptom at the end of 2 years, 3 (6%) of which were grade 2 and none were of higher grade. CONCLUSIONS The primary endpoint of the study was not met. Lovastatin, as administered in this trial, did not reduce the incidence of grade 2 or higher rectal toxicity compared with historical controls.

Purpose: The current standard of care for surgically eligible stage I non-small cell lung cancer (NSCLC) is surgical resection, but emerging data suggest that stereotactic body radiation therapy (SBRT) is potentially as effective as surgery. However, specialist views of the current evidence about SBRT and how they would incorporate a randomized controlled trial (RCT) into practice is unclear. We sought to understand specialist opinions about evidence regarding treatment of stage I NSCLC and how this translates into practice and clinical trial implementation. Methods and materials: We used a 28-item, web-based survey that invited all participating providers from the American Society for Radiation Oncology, American Thoracic Society Thoracic Oncology Assembly, and the International Association for the Study of Lung Cancer to share opinions regarding practice beliefs, treatment of stage I NSCLC, and a clinical trial scenario. Results: A total of 959 surveys were completed; 64% were from radiation oncologists (ROs) and 49% were from outside the United States. The majority of ROs (80%) reported that current evidence indicates that SBRT has the same or a better benefit compared with surgery for surgically eligible patients with stage I NSCLC; 28% of non–radiation oncologists (NROs) indicated the same (P

Objective Stereotactic body radiotherapy is the standard treatment for medically inoperable early-stage non–small cell lung cancer. Recent data suggest that in operable patients, stereotactic body radiotherapy produces outcomes comparable to those of surgical resection. In veterans with early non–small cell lung cancer, we compared the outcomes of stereotactic body radiotherapy and video-assisted thoracoscopic lobectomy. Methods We retrospectively reviewed data from 183 patients (94.0% male) with clinical stage I non–small cell lung cancer who underwent stereotactic body radiotherapy (n = 56) or video-assisted thoracoscopic lobectomy (n = 127) from 2009 to 2014. Propensity matching was used to produce more comparable groups. Primary end points were tumor control and overall, recurrence-free, and lung-cancer–specific survival, as estimated by Kaplan–Meier actuarial analysis. Multivariable analysis was used to identify independent predictors. Results In the overall cohort, the patients who received stereotactic body radiotherapy were older than the patients who received video-assisted thoracoscopic lobectomy (median age, 79.5 vs 64 years) and had more comorbidities. In the 37 propensity-matched pairs, the 3-year actuarial tumor control rate was 54.3% after stereotactic body radiotherapy and 90.6% after video-assisted thoracoscopic lobectomy ( P = .0038). Actuarial lung cancer–specific 3-year survival was 78.1% (stereotactic body radiotherapy) versus 93.6% (video-assisted thoracoscopic lobectomy) ( P = .055). One-year overall, 3-year overall, and 3-year recurrence-free survivals were 89.2%, 52.9%, and 38.5% after stereotactic body radiotherapy and 94.6%, 85.7%, and 82.8% after video-assisted thoracoscopic lobectomy ( P Conclusions In veteran patients with early-stage non–small cell lung cancer, video-assisted thoracoscopic lobectomy resulted in better disease control and survival than stereotactic body radiotherapy. Although prior reports suggest that stereotactic body radiotherapy is a suitable alternative to surgery in early-stage lung cancer, a prospective randomized trial is needed. Nevertheless, stereotactic body radiotherapy remains a suitable option for medically inoperable patients.