BACKGROUND: Operability is both a crucial determinant in treatment selection and a potential confounder in analyses comparing surgery with non-surgical approaches such as stereotactic body radiotherapy (SBRT). We aimed to assess the association between operability status and intervention with post-treatment mortality in early-stage non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: We defined four groups of patients with cT1-T2N0M0 NSCLC diagnosed 2010 to 2014 from the National Cancer Database: SBRT patients deemed operable vs. inoperable and surgery patients receiving open vs. minimally-invasive approaches. Mortality rates at 30, 60, and 90 days post-treatment were calculated and compared. RESULTS: We abstracted 80,108 patients, 0.8% undergoing SBRT and operable, 13.2% undergoing SBRT and inoperable, 52.4% undergoing open surgery, and 33.7% undergoing minimally-invasive surgery. Mortality rates were highest among open surgery patients and lowest among operable SBRT patients (2.0% vs. 0.2% at 30 days and 3.7% vs. 0.7% at 90 days), with intermediate results in the other two groups. These findings persisted on multivariate Cox regression: compared to patients undergoing minimally-invasive surgery, mortality risk was highest among open surgery patients (30 days HR 1.32, 95%CI 1.16-1.51; 90 days HR 1.36, 95%CI 1.24-1.50; both P < .001) and lowest among operable SBRT patients (30 days HR 0.09, 95%CI 0.01-0.64; 90 days HR 0.15, 95%CI 0.05-0.46; both P ≤ .016). These associations were maintained in a propensity score-matched subset. CONCLUSION: Operable patients undergoing SBRT experience minimal post-treatment mortality compared to their inoperable counterparts. These findings illustrate the potential for confounding by operability to bias results in cohort studies that compare surgical vs. non-surgical approaches in early-stage NSCLC.

Patients with primary tumor progression after stereotactic body radiation therapy (SBRT) for stage I non-small cell lung cancer (NSCLC) have a second chance at complete tumor eradication with salvage local therapies, including lung resection, repeat course of SBRT, and percutaneous ablative therapies. In this paper, we presented our institutions initial experience with percutaneous high-dose-rate (HDR) brachyablation for a relapsed stage I NSCLC that had been treated with SBRT 4.3 years earlier. Lung tumor measuring approximately 5 cm in maximum tumor dimension at the time of relapse was histopathologically confirmed to be persistent squamous cell carcinoma, and successfully treated with a single fraction of 24 Gy with HDR brachyablation. Treatment was delivered via two percutaneous catheters inserted under CT-guidance, and treated in less than 20 minutes. The patient was discharged home later the same day without the need for a chest tube, and has been monitored with serial surveillance scans every 3 to 6 months without evidence of further lung cancer progression or complications at 2.8 years post-HDR brachyablation procedure and 7.8 years after initial SBRT.

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.

PURPOSE/OBJECTIVES: Malignant pleural mesothelioma (MPM) is a rare but aggressive cancer arising from the cells of the thoracic pleura with a poor prognosis. We aimed to develop a model, via interpretable machine learning (ML) methods, predicting overall survival for MPM following radiotherapy based on dosimetric metrics as well as patient characteristics. MATERIALS/METHODS: Sixty MPM (37 right, 23 left) patients treated on a Tomotherapy unit between 2013 and 2018 were retrospectively analyzed. All patients received 45 Gy (25 fractions). The multivariable Cox regression (Cox PH) model and Survival Support Vector Machine (sSVM) were applied to build predictive models of overall survival (OS) based on clinical, dosimetric, and combined variables. RESULTS: Significant differences in dosimetric endpoints for critical structures, i.e., the lung, heart, liver, kidney, and stomach, were observed according to target laterality. The OS was found to be insignificantly different (p = 0.18) between MPM patients who tested left- and right-sided, with 1-year OS of 77.3% and 75.0%, respectively. With Cox PH regression, considering dosimetric variables for right-sided patients alone, an increase in PTV_Min, Total_Lung_PTV_Mean, Contra_Lung_Volume, Contra_Lung_V20, Esophagus_Mean, and Heart_Volume had a greater hazard to all-cause death, while an increase in Total_Lung_PTV_V20, Contra_Lung_V5, and Esophagus_Max had a lower hazard to all-cause death. Considering clinical variables alone, males and increases in N stage had greater hazard to all-cause death; considering both clinical and dosimetric variables, increases in N stage, PTV_Mean, PTV_Min, and esophagus_Mean had greater hazard to all-cause death, while increases in T stage and Heart_V30 had lower hazard to all-cause-death. In terms of C-index, the Cox PH model and sSVM performed similarly and fairly well when considering clinical and dosimetric variables independently or jointly. CONCLUSIONS: Clinical and dosimetric variables may predict the overall survival of mesothelioma patients, which could guide personalized treatment planning towards a better treatment response. The identified predictors and their impact on survival offered additional value for translational application in clinical practice.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Purpose

Both the superstructures of virtual discourse in radiation oncology and the entities occupying influential positions in the social media landscape of radiation oncology remain poorly characterized.

Methods and materials

NodeXL Pro was used to prospectively sample all tweets with the hashtag #radonc every 8 to 10 days during the course of 1 year (December 4, 2018, to November 29, 2019). Twitter handles were grouped into conversational clusters using the Clauset-Newman-Moore community detection algorithm. For each sample period, the top 10 #radonc Twitter influencers, defined using betweenness centrality, were categorized. Influencers were scored in each sample period according to their top 10 influence rank and summarized with descriptive statistics. Linear regression assessed for characteristics that predicted higher influence scores among top influencers.

Results

In the study, 684,000 tweets were sampled over 38 periods. #radonc tweets took on the crowd superstructure of a hub-and-spoke broadcast network formed when prominent individuals are widely repeated by many audience members. Professional societies were the most influential category of Twitter handles with an average influence score of 7.63 out of 10 (standard deviation [SD] = 1.94). When industry handles were present among top 10 influencers, they exhibited the second highest average influence scores (6.75, SD = 1.06), followed by individuals with scores of 5.28 (SD = 0.43). The categories of influencers were stable during the course of 1 year. The role of attending physician, radiation oncology specialty, male sex, academic practice, and US-based handles in North America were predictors of higher influence score.

Conclusions

Twitter influencers in radiation oncology represent a diverse group of people and organizations, but male academic radiation oncologists based in North America occupy particularly influential positions in virtual communities broadly characterized as "hub and spoke" broadcast networks. Periodic network-based analyses of the social media discourse in radiation oncology are warranted to maintain an awareness of the handles that are influencing discussions on Twitter and ensure that social media utilization continues to contribute to the field of radiation oncology in a meaningful way.

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.

BACKGROUND: The optimal upfront treatment modality for patients with nonmetastatic Gleason Score 9 and 10 prostate cancer (GS 9-10 PCa) is unknown. METHODS: We conducted a retrospective cohort study of patients in the Veterans Health Administration (VHA) with GS 9-10 PCa treated with radical prostatectomy (RP) or external beam radiation therapy with androgen deprivation therapy (EBRT+ADT) from 1/2000 to 12/2010. Outcomes included overall survival (OS), distant metastasis-free survival (DMFS), and salvage/adjuvant therapy-free survival (SAFS), as assessed by Kaplan-Meier analysis. RESULTS: We identified 1220 veterans with GS 9-10 PCa; 335 were treated with RP, and 885 were treated with EBRT+ADT. With a median follow-up of 9.9 years, propensity score-matched analyses demonstrated that RP had superior 10-year OS (70.8% [RP] vs. 61.2% [EBRT+ADT], p < 0.001), 10-year DMFS rates were similar between RP (76.7%) and EBRT+ADT (81.0%), and 10-year SAFS rates were lower for RP vs EBRT + ADT (35.2% [RP] vs. 75.2% [EBRT+ADT], p < 0.001). The receipt of salvage ADT was higher with upfront RP (51.9% vs. 26.1%, p < 0.001), despite receipt of adjuvant/salvage EBRT in 41.8% of RP patients. Among patients treated with RP, there were no differences in outcomes by race. However, higher survival rates were noted among Black patients treated with EBRT+ADT compared with White patients. CONCLUSIONS: This analysis demonstrated higher 10-year OS rates among men treated with upfront RP versus EBRT+ADT, though missing confounders and similar DMFS rates suggest the long-term cause-specific OS rates may be similar. We also highlight real-world outcomes of a diverse patient population in the VHA and improved outcomes for Black patients receiving EBRT+ADT.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Background

The National Death Index (NDI) is a centralized database containing information from death certificates that are frequently referenced by health and medical investigators to ascertain vital statistics. Yet, it commonly includes misclassified causes of death. Since the NDI is frequently relied upon in studies that evaluate outcomes following radical prostatectomy (RP) for prostate cancer (PC), we evaluated its validity by referencing mortality data from the Shared Equal Access Regional Cancer Hospital (SEARCH) database which is a prospectively managed database of 5009 Veterans who underwent a RP at eight Veterans Affairs medical centers between 1982 and 2016.

Methods

We compared vital status, cause of death and date of death from the SEARCH database with the NDI.

Results

A total of 1312 men in SEARCH were deceased, yet the NDI reported 17% (219) of those men as still alive. Among the 1093 men who had concordant vital status in both SEARCH and NDI, the date of death was an exact match within one day, a week, or 31 days in 94%, 97%, 99%, and 100%, respectively. Of those men coded as dying from prostate cancer in the SEARCH database (n = 105), 12% were coded as having died from non-PC causes in the NDI. Meanwhile, among patients coded by the NDI as having died of PC (n = 139), 34% were coded in SEARCH as having died of non-PC causes.

Conclusions

These findings demonstrate that the NDI provides accurate dates of death, but frequently misclassifies whether a death was due to prostate cancer. Studies that rely upon death certificates, as captured in the NDI, may be unreliable to report prostate cancer-specific mortality rates after prostatectomy.