Lung cancer screening via annual low-dose computed tomography has poor adoption. We conducted a prospective case–control study among 958 individuals eligible for lung cancer screening to develop a blood-based lung cancer detection test that when positive is followed by a low-dose computed tomography. Changes in genome-wide cell-free DNA fragmentation profiles (fragmentomes) in peripheral blood reflected genomic and chromatin characteristics of lung cancer. We applied machine learning to fragmentome features to identify individuals who were more or less likely to have lung cancer. We trained the classifier using 576 cases and controls from study samples and validated it in a held-out group of 382 cases and controls. The validation demonstrated high sensitivity for lung cancer and consistency across demographic groups and comorbid conditions. Applying test performance to the screening eligible population in a 5-year model with modest utilization assumptions suggested the potential to prevent thousands of lung cancer deaths. Significance: Lung cancer screening has poor adoption. Our study describes the development and validation of a novel blood-based lung cancer screening test utilizing a highly affordable, low-coverage genome-wide sequencing platform to analyze cell-free DNA fragmentation patterns. The test could improve lung cancer screening rates leading to substantial public health benefits. See related commentary by Haber and Skates, p. 2025

Background: Bone-modifying agent (BMA) therapy is recommended for metastatic castration-resistant prostate cancer but not metastatic castration-sensitive prostate cancer (mCSPC). BMA treatment in mCSPC may therefore constitute overuse. Methods: In this retrospective cohort study using linked Surveillance, Epidemiology, and End Results–Medicare data, we included patients diagnosed with stage IV prostate adenocarcinoma from 2007 to 2015 who were 66 years of age or older at diagnosis and had received androgen-deprivation or antiandrogen therapy. We excluded patients who had previously received BMAs or had existing osteoporosis, osteopenia, hypercalcemia, or prior bone fracture. The primary outcome was receipt of BMA (zoledronic acid or denosumab) within 180 days of diagnosis (emergence of CRPC within this time frame is unlikely). The secondary outcome was receipt of a BMA within 90 days. Exposures of interest included practice location (physician office vs hospital outpatient) and the specialty (medical oncologist vs urologist) of the treating physician. Results: Our sample included 2627 patients, of whom 52.9% were treated by medical oncologists and 47.1% by urologists; 77.7% and 22.3% received care in physician office and hospital outpatient locations, respectively. Overall, 23.6% received a BMA within 180 days; 18.4% did within 90 days. BMA therapy was more common among patients treated by oncologists (odds ratio = 8.23, 95% confidence interval = 6.41 to 10.57) and in physician office locations (odds ratio = 1.33, 95% confidence interval = 1.06 to 1.69). Utilization has increased: 17.3% of patients received BMAs from 2007 to 2009 (17.3% zoledronic acid, 0% denosumab) and 28.1% from 2012 to 2015 (8.4% zoledronic acid, 20.3% denosumab). Conclusions: Among patients with mCSPC who had no evidence of high osteoporotic fracture risk, more than one-quarter have received BMAs in recent years. This overuse may lead to excess costs and toxicity.

PURPOSE: The Medicare part D Low-Income Subsidy (LIS) improves access to oral cancer drugs, but provides no assistance for clinician-administered/part B drugs. This analysis assessed the association between LIS participation and receipt of optimal cancer treatment. METHODS: We investigated initial systemic therapy using SEER-Medicare data (2015-2017) and National Comprehensive Cancer Network (NCCN) Evidence Blocks (EB) as the standard for treatment recommendations. We included cancer clinical scenarios wherein (1) ≥one treatment was optimal (higher efficacy and safety scores) versus other treatments; (2) identifiable in SEER-Medicare (eg, not defined by clinical data unavailable in registry data or claims); and (3) both EB and ASCO Value Framework agreed regarding optimal treatment. We fit logistic regression models to assess the association between receipt of systemic therapy ( v no therapy) and patient and provider characteristics. Contingent on receipt of treatment, we modeled the likelihood of receiving a treatment ranked (by EB scores) within the highest or lowest quartile for that cancer type. RESULTS: Nine thousand two hundred and ninety patients were included across 11 clinical scenarios. Fifty-seven percent (5,336) of patients received any systemic therapy and 43% (3,954) received no systemic therapy. Compared with non-LIS participants, LIS participants were less likely to receive any systemic therapy versus no systemic therapy (odds ratio, 0.64 [95% CI, 0.57 to 0.72]). Contingent on receiving systemic therapy, LIS participants received treatment ranked within the worst quartile 24.8% of the time, compared with 21.9% of non-LIS patients (adjusted prevalence difference, 4.3% [95% CI, 0.5 to 8.2]). CONCLUSION: LIS participants were less likely to receive systemic therapy at all and were more likely to receive treatments that receive low NCCN EB scores.

Lung cancer mortality rates, particularly non-small cell lung cancer (NSCLC), continue to present a significant global health challenge, and the adoption of lung cancer screening remains limited, often influenced by inequities in access to healthcare. Despite clinical evidence demonstrating the efficacy of annual screening with low-dose computed tomography (LDCT) and recommendations from medical organizations including the U.S. Preventive Services Task Force (USPSTF), the national lung cancer screening uptake remains around 5% among eligible individuals. Advancements in the clinical management of NSCLC have recently become more personalized with the implementation of blood-based biomarker testing. Extensive research into tumor-derived cell-free DNA (cfDNA) through fragmentation offers a novel method for improving early lung cancer detection. This review assesses the screening landscape, explores obstacles to lung cancer screening, and discusses how a plasma whole genome fragmentome test (pWGFrag-Lung) can improve lung cancer screening participation and adherence.

Background: While public reporting of surgical outcomes for noncancer conditions is common, cancer surgeries have generally been excluded. This is true despite numerous studies showing outcomes to differ between hospitals based on their characteristics. Our objective was to assess whether three prerequisites for quality assessment and reporting are present for 30‐day mortality after cancer surgery: low burden for timely reporting, hospital variation, and potential for public health gains.Study Design: We used Fee‐for‐Service (FFS) Medicare claims to examine the extent of variation in 30‐day cancer surgical mortality between 3860 US hospitals. We included 340 489 surgeries for 12 cancer types for FFS Medicare beneficiaries aged ≥66 years, 2011‐2013. Hierarchical mixed‐effects logistic regression models adjusted for patient and hospital characteristics and with a random hospital effect were fit to obtain hospital‐specific risk‐standardized mortality rates (RSMRs) and 99% confidence intervals (CI). We calculated a hospital odds ratio to describe the difference in mortality risk for a hospital above vs below average quality and estimated the potential mortality reduction.Results: The median number of cancer surgeries per hospital was 34. The median RSMR overall was 2.41% (99% CI 2.28%, 2.66%). In aggregate and for most cancers, variation between hospitals exceeded that due to differences in patient and hospital characteristics. For individual cancers, relative differences exceeded 20% in mortality risk between patients undergoing surgery at a hospital below vs above average quality, with the potential for an estimated 500 deaths prevented annually given hypothetical improvements.Conclusion: Quality measurement and reporting of 30‐day mortality for cancer surgery is worthy of consideration.

The author expresses concerns regarding possible errors in a recent article published in The Oncologist by the International Early Lung Cancer Action Project group.