Estimates and measurements of radiofrequency exposures in smart-connected homes.

The aim of this research was to quantify the levels of radiofrequency electromagnetic energy (RF-EME) in a residential home/apartment equipped with a range of wireless devices, often referred to as internet of things (IoT) devices or smart devices and subsequently develop a tool that could be useful for estimating the levels of RF-EME in a domestic environment. Over the course of 3 years measurements were performed in peoples' homes on a total of 43 devices across 16 device categories. Another 12 devices were measured in detail in a laboratory setup. In all a total of 55 individual devices across 23 device categories were measured. Based on this measurement data we developed predictive software that showed that even with a single device in 23 device categories operating near maximum they would, in total, produce exposures at a distance of 1 m of 0.17% of the ICNIRP (2020) public exposure limits. Measurements were also made in two separate smart apartments-one contained over 50 IoT devices and a second with over 100 IoT devices with the devices driven as hard as could reasonably be achieved. The respective 6-min average exposure level recorded were 0.0077% and 0.44% of the ICNIRP (2020) 30-min average public exposure limit.

Target coverage and cardiopulmonary sparing with the updated ESTRO-ACROP contouring guidelines for postmastectomy radiation therapy after breast reconstruction: a treatment planning study using VMAT and proton PBS techniques.

BACKGROUND: The European Society for Therapeutic Radiology and Oncology Advisory Committee in Radiation Oncology Practice (ESTRO-ACROP) recently released new contouring guidelines for postmastectomy radiation therapy (PMRT) after implant-based reconstruction (IBR). As compared to prior ESTRO guidelines, the new guidelines primarily redefined the chest wall (CW) target to exclude the breast prosthesis. In this study, we assessed the impact of these changes on treatment planning and dosimetric outcomes using volumetric-modulated arc therapy (VMAT) and proton pencil-beam scanning (PBS) therapy. METHODS: We performed a treatment planning study of 10 women with left-sided breast cancer who underwent PMRT after IBR. All target structures were delineated first using standard (ESTRO) breast contouring guidelines and then separately using the new (ESTRO-ACROP) guidelines. Standard organs-at-risk (OARs) and cardiac substructures were contoured. Four sets of plans were generated: (1) VMAT using standard ESTRO contours, (2) VMAT using new ESTRO-ACROP contours, (3) PBS using standard contours, and (4) PBS using new contours. RESULTS: VMAT plans using the new ESTRO-ACROP guidelines resulted in modest sparing of the left anterior descending coronary artery (LAD) (mean dose: 6.99 Gy standard ESTRO vs. 6.08 Gy new ESTRO-ACROP, p = 0.010) and ipsilateral lung (V20: 21.66% vs 19.45%, p = 0.017), but similar exposure to the heart (mean dose: 4.6 Gy vs. 4.3 Gy, p = 0.513), with a trend toward higher contralateral lung (V5: 31.0% vs 35.3%, p = 0.331) and CW doses (V5: 31.9% vs 35.4%, p = 0.599). PBS plans using the new guidelines resulted in further sparing of the heart (mean dose: 1.05 Gy(RBE) vs. 0.54 Gy(RBE), p < 0.001), nearly all cardiac substructures (LAD mean dose: 2.01 Gy(RBE) vs. 0.66 Gy(RBE), p < 0.001), and ipsilateral lung (V20: 16.22% vs 6.02%, p < 0.001). CONCLUSIONS: PMRT after IBR using the new ESTRO-ACROP contouring guidelines with both VMAT and PBS therapy is associated with significant changes in exposure to several cardiopulmonary structures.

Treating the SARS-CoV-2-positive patient with cancer: A proposal for a pragmatic and transparent ethical process.

The treatment of patients with cancer who test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses unique challenges. In this commentary, the authors describe the ethical rationale and implementation details for the creation of a novel, multidisciplinary treatment prioritization committee, including physicians, frontline staff, an ethicist, and an infectious disease expert. Organizational obligations to health care workers also are discussed. The treatment prioritization committee sets a threshold of acceptable harm to patients from decreased cancer control that is justified to reduce risk to staff. The creation of an ethical, consistent, and transparent decision-making process involving such frontline stakeholders is essential as departments across the country are faced with decisions regarding the treatment of SARS-CoV-2-positive patients with cancer.

Overuse of Diagnostic Brain Imaging Among Patients With Stage IA Non-Small Cell Lung Cancer.

BACKGROUND: Among patients diagnosed with stage IA non-small cell lung cancer (NSCLC), the incidence of occult brain metastasis is low, and several professional societies recommend against brain imaging for staging purposes. The goal of this study was to characterize the use of brain imaging among Medicare patients diagnosed with stage IA NSCLC. METHODS: Using data from linked SEER-Medicare claims, we identified patients diagnosed with AJCC 8th edition stage IA NSCLC in 2004 through 2013. Patients were classified as having received brain imaging if they underwent head CT or brain MRI from 1 month before to 3 months after diagnosis. We identified factors associated with receipt of brain imaging using multivariable logistic regression. RESULTS: Among 13,809 patients with stage IA NSCLC, 3,417 (25%) underwent brain imaging at time of diagnosis. The rate of brain imaging increased over time, from 23.5% in 2004 to 28.7% in 2013 (P=.0006). There was significant variation in the use of brain imaging across hospital service areas, with rates ranging from 0% to 64.0%. Factors associated with a greater likelihood of brain imaging included older age (odds ratios [ORs] of 1.16 for 70-74 years, 1.13 for 75-79 years, 1.31 for 80-84 years, and 1.46 for ≥85 years compared with 65-69 years; all P<.05), female sex (OR, 1.09; P<.05), black race (OR 1.23; P<.05), larger tumor size (ORs of 1.23 for 11-20 mm and 1.28 for 21-30 mm tumors vs 1-10 mm tumors; all P<.05), and higher modified Charlson-Deyo comorbidity score (OR, 1.28 for score >1 vs score of 0; P<.05). CONCLUSIONS: Roughly 1 in 4 patients with stage IA NSCLC received brain imaging at the time of diagnosis despite national recommendations against the practice. Although several patient factors are associated with receipt of brain imaging, there is significant geographic variation across the United States. Closer adherence to clinical guidelines is likely to result in more cost-effective care.

Legacy Polybrominated Diphenyl Ethers (PBDEs) Trends in Top Predator Fish of the Laurentian Great Lakes (GL) from 1979 to 2016: Will Concentrations Continue to Decrease?

Polybrominated diphenyl ethers (PBDEs) were widely used as fire retardants and have been detected throughout the Great Lakes (GL) ecosystem. The concentration trends (after fish age normalization) of PBDEs in top predator fish (lake trout and walleye) of the GLs were determined from 1979 to 2016, which includes most of the period when PBDEs were manufactured and used in this region. The fish samples were collected by two national (U.S. and Canada) long-term monitoring and surveillance programs. Trends in total concentrations (age-normalized) of the five major PBDE congeners (BDE-47, 99, 100, 153, and 154) found in fish across all five lakes have varied over time. Significant increases were observed from 1990 to 2000 (16.3% per year). Rapidly decreasing concentrations (-19.5% per year) were found from 2000 to 2007. Since 2007, the decreasing trend has become smaller (less than -5.5% per year) and relatively unchanged from 2011 to 2015. BDE-47, the congener with the highest concentrations in lake trout, has decreased continuously (ranging from -6.7% to -16.2% per year) in all lakes except Lake Erie. This decrease can be associated with the voluntary and regulatory phase out of production and/or usage of PBDEs since 2000. However, it has been offset by recent (since 2007) increasing trends of the other four higher brominated BDE congeners, especially BDE-100 and 154. Production and usage of commercial penta- and octa- BDE mixtures containing primarily the five major PBDE congeners was discontinued in 2004 in the U.S.A. and 2008 in Canada. These results indicate increasing fish uptake and bioaccumulation of higher brominated BDE congeners may be related to the transformation of BDE-209 to lower brominated BDE compounds in the GL environment or food web. Considering the abundance of BDE-209 in existing products and sediment in GL region, the duration of the unchanging total PBDE concentration trend in GL fish could be longer than expected.

Comprehensive Analysis of the Great Lakes Top Predator Fish for Novel Halogenated Organic Contaminants by GC×GC-HR-ToF Mass Spectrometry.

The U.S. Environmental Protection Agency's Great Lakes Fish Monitoring and Surveillance Program (GLFMSP) has traced the fate and transport of anthropogenic chemicals in the Great Lakes region for decades. Isolating and identifying halogenated species in fish is a major challenge due to the complexity of the biological matrix. A nontargeted screening methodology was developed and applied to lake trout using a 2-dimensional gas chromatograph coupled to a high resolution time-of-flight mass spectrometer (GC×GC-HR-ToF MS). Halogenated chemicals were identified using a combination of authentic standards and library spectral matching, with molecular formula estimations provided by exact mass spectral interpretation. In addition to the halogenated chemicals currently being targeted by the GLFMSP, more than 60 nontargeted halogenated species were identified. Most appear to be metabolites or breakdown products of larger halogenated organics. The most abundant compound class was halomethoxyphenols accounting for more than 60% of the total concentration of halogenated compounds in top predator fish from all five Great Lakes illustrating the need and utility of nontargeted halogenated screening of aquatic systems using this platform.

Age-Corrected Trends and Toxic Equivalence of PCDD/F and CP-PCBs in Lake Trout and Walleye from the Great Lakes: 2004-2014.

Our research reports polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (CP-PCBs) concentrations and age-corrected trends for lake trout and walleye in the Great Lakes over the 2004-2014 period. We determined that age-contaminant corrections are required to accurately report contaminant trends due to significant lake trout age structure changes. The age-trend model (ATM) described here uses a lake-specific age-contaminant regression to mitigate the effect of a fluctuating lake trout age structure to directly improve the log-linear regression model. ATM results indicate that half-life (t1/2) and percent decreases for PCDD/Fs, CP-PCBs, and toxic equivalence (TEQ) (average -56 to 70%) were fairly uniform and consistent across the Great Lakes over the 2004-2014 period. The vast majority of TEQ associated with all Great Lakes lake trout and walleye samples is due to the nonortho CP-PCBs (average = 79%) as compared with PCDD/Fs (average = 21%). On average, CP-PCB_126 individually accounted for over 95% of the total CP-PCB TEQ. A retrospective analysis (1977-2014) of 2378-TCDF and 2378-TCDD raw concentrations in Lake Ontario lake trout revealed decreases of 94% and 96%, respectively. Tissue residue guidelines for wildlife protection based on lake trout and walleye total TEQ were uniformly exceeded in all the Great Lakes.

Polychlorinated biphenyls and organochlorine pesticides concentration patterns and trends in top predator fish of Laurentian Great Lakes from 1999 to 2014.

Concentration patterns and temporal trends of legacy persistent, bioaccumulative and toxic (PBT) contaminants were determined using the Great Lake Fish Monitoring and Surveillance Program (GLFMSP) top predator fish data from 1999 to 2014 and applying Kendall-Theil robust regression after cluster-based age normalization. For most Great Lakes sites, significant decreasing concentration trends ranging from -4.1% to -21.6% per year (with the only exception being mirex in Lake Erie walleye) were found for PBTs including polychlorinated biphenyls (PCBs), dichloro-diphenyl-trichlorethane (DDTs), dieldrin, endrin, chlordane, oxychlordane, nonachlor, mirex, and hexachlorobenzene (HCB) reflecting the successful historical and ongoing reduction of fugitive releases and remediation efforts in the U.S. and Canada including physical removal (dredging) coupled with sediment sequestration. Generally, lower concentrations and faster decreasing trends are observed in western/northern sampling sites compared to eastern/southern sites as the former sites are generally more remote from population centers and industrial activities. PCBs, which can be released from ongoing sources, have the highest concentration, the second slowest decreasing trend, and increasing mass fractions of the contaminants studied suggesting that they will continue to be the legacy contaminant of greatest concern into the future.

Semisynthetic model calibration for monitoring glucose in mammalian cell culture with in situ near infrared spectroscopy.

Near infrared (NIR) spectroscopy has the capability of providing real-time, multi-analyte monitoring of the complex reaction mixture associated with cell culture processes. However, the development of robust models to predict the concentration of key analytes has proven difficult. In this study, a modeling methodology using semisynthetic process samples was used to predict glucose concentrations in Chinese Hamster Ovary (CHO) cell culture processes. Partial Least Squares (PLS) regression models were built from in situ NIR spectra, and glucose levels between 4.0 and 14.0 g/L. Two models were constructed. The "standard model" used data provided by cell culture production process samples. The "full model" included the data provided from both cell culture production process samples and semisynthetic samples. The semisynthetic samples were generated by titrating cell culture samples with target viable cell density (VCD) and lactate levels to defined glucose concentrations. The robustness of each model was gauged by predicting glucose in a subsequent cell culture process utilizing a media formulation and cell line not contained in the calibration data sets. The "full model" generated glucose predictions with a root mean square error of prediction (RMSEP) of 0.99 g/L while the "standard model" provided glucose predictions with a RMSEP of 2.26 g/L. The modeling approach utilizing semisynthetic samples proved to be faster development and more effective than using just standard cell culture processes.

Practice Consolidation Among US Medical Oncologists, 2015-2022.

PURPOSE: Health care consolidation has significantly affected cancer care delivery, with oncology practices undergoing substantial consolidation over the past two decades. This study investigates practice consolidation trends among medical oncologists (MOs), factors associated with consolidation, and changes in MO geographic distribution. METHODS: Medicare data from 2015 to 2022 were used to assess MO practice consolidation in hospital referral regions (HRRs), linked with regional health care market data and physician demographics. The Herfindahl-Hirschman Index (HHI) was used to measure consolidation, and the Gini coefficient was used to measure MO distribution across counties. Multivariable linear regression explored factors associated with MO practice consolidation. RESULTS: Between 2015 and 2022, the number of MOs increased by 14.5% (11,727-13,433), whereas the number of MO practices decreased by 18.0% (2,774-2,276). The mean number of MOs per practice increased by 40% (4.26-5.95; P < .001). The percentage of MOs in small practices decreased, whereas larger practices saw an increase. MO consolidation, as indicated by the HHI, increased by 9% (median HHI, 0.3204-0.3480). HRRs with higher baseline hospital consolidation and more hospital beds per capita were more likely to have MO practice consolidation. Despite MO practice consolidation, the county-level distribution of MOs did not change substantially. CONCLUSION: On the basis of Federal Trade Commission classifications, MO practices were highly concentrated in 2015 and consolidated even further by 2022. While distribution of MOs at the county level remained stable, further research is needed to assess the effects of rapid consolidation on cancer care cost, quality, and access. These data have important implications for policymakers and payers as they design programs that ensure high-quality, affordable cancer care.

Assessment of Price Variation in Coronary Artery Bypass Surgery at US Hospitals.

BACKGROUND: Little is known about hospital pricing for coronary artery bypass grafting (CABG). Using new price transparency data, we assessed variation in CABG prices across US hospitals and the association between higher prices and hospital characteristics, including quality of care. METHODS AND RESULTS: Prices for diagnosis related group code 236 were obtained from the Turquoise database and linked by Medicare Facility ID to publicly available hospital characteristics. Univariate and multivariable analyses were performed to assess factors predictive of higher prices. Across 544 hospitals, median commercial and self-pay rates were 2.01 and 2.64 times the Medicare rate ($57 240 and $75 047, respectively, versus $28 398). Within hospitals, the 90th percentile insurer-negotiated price was 1.83 times the 10th percentile price. Across hospitals, the 90th percentile commercial rate was 2.91 times the 10th percentile hospital rate. Regional median hospital prices ranged from $35 624 in the East South Central to $84 080 in the Pacific. In univariate analysis, higher inpatient revenue, greater annual discharges, and major teaching status were significantly associated with higher prices. In multivariable analysis, major teaching and investor-owned status were associated with significantly higher prices (+$8653 and +$12 200, respectively). CABG prices were not related to death, readmissions, patient ratings, or overall Centers for Medicare and Medicaid Services hospital rating. CONCLUSIONS: There is significant variation in CABG pricing, with certain characteristics associated with higher rates, including major teaching status and investor ownership. Notably, higher CABG prices were not associated with better-quality care, suggesting a need for further investigation into drivers of pricing variation and the implications for health care spending and access.

Determinants of Commercial Prices for Common Radiation Therapy Procedures.

PURPOSE: Using hospital-reported price data, we analyzed whether various market factors including radiation oncology practice consolidation were associated with higher commercial prices for radiation therapy (RT). METHODS AND MATERIALS: We evaluated commercial prices paid by private insurers for 4 common RT procedures-intensity modulated RT (IMRT) planning, IMRT delivery, 3-dimensional RT (3D-RT) planning, and 3D-RT delivery-reported among the 2096 hospitals in the United States that deliver RT according to the Medicare Provider of Service file. To assess price variation within hospitals, we evaluated the ratio of the 90th percentile price to the 10th percentile price among different private insurers. To assess regional variation, we similarly compared median commercial prices at the 90th and 10th percentile hospitals in each Hospital Referral Region. We generated multivariable models to test the association of various hospital, health system, regional, and market factors on median hospital commercial prices. RESULTS: A total of 1004 hospitals (47.9%) reported at least 1 commercial price for any of the 4 RT procedures considered in this study. National median commercial prices for IMRT planning and IMRT delivery were $4073 (interquartile ratio [IQR], $2242-$6305) and $1666 (IQR, $1014-$2619), respectively. Prices for 3D-RT planning and 3D-RT delivery were $2824 (IQR, $1339-$4738) and $616 (IQR, $419-877), respectively. Within hospitals, the 90th percentile price paid by a private insurer was 2.3 to 2.5 times higher on average than the 10th percentile price, depending on the procedure. Within each Hospital Referral Region, the median price at the 90th percentile hospital was between 2.4 and 3.2 times higher than at the 10th percentile hospital. On multivariable analysis, higher prices were generally observed at hospitals with for-profit ownership, teaching status, and affiliation with large health systems. Levels of radiation oncology practice consolidation were not significantly associated with any prices. CONCLUSIONS: Commercial prices for common RT procedures vary by more than a factor of 2 depending on a patient's private insurer and hospital of choice. Higher prices were more likely to be found at for-profit hospitals, teaching hospitals, and hospitals affiliated with large health systems.

Variation in Cost of Echocardiography Within and Across United States Hospitals.

BACKGROUND: While transthoracic echocardiography (TTE) is responsible for more Medicare spending than any other cardiovascular imaging procedure, little is known about its commercial cost footprint. The 2021 Hospital Price Transparency Final Rule mandated that U.S. hospitals publish their insurer-negotiated and self-pay prices for services. This study sought to characterize and assess factors contributing to variation in TTE prices. METHODS: We used a commercial database containing hospital-disclosed prices to characterize variation in TTE prices within and across hospitals. We linked these price data to hospital and regional characteristics using Medicare Facility IDs. RESULTS: A total of 1,949 hospitals reported commercial prices. Among reporting hospitals, median commercial and self-pay prices were 2.93 and 3.06 times greater than the median Medicare price ($1,313 and $1,422, respectively, vs $464). Within hospitals, the 90th percentile payer-negotiated rate was 2.78 (interquartile range, 1.80-5.09) times the 10th percentile rate (within-center ratio). Across hospitals within the same hospital referral region, the median price at the 90th percentile hospital was 2.47 (interquartile range, 1.69-3.75) times that at the 10th percentile hospital (across-center ratio). On univariate analysis, for-profit (P = .04), teaching (P < .01), investor-owned (P < .01), and higher-rated hospitals (P < .01) charged higher prices, whereas rural referral centers (P = .01) and disproportionate share hospitals (P < .01) charged less. On multivariate analysis, the association between these characteristics and TTE prices persisted, except for investor ownership and rural referral centers. CONCLUSIONS: Self-pay and commercial TTE prices were higher than Medicare prices and varied significantly within and across hospitals. For-profit, teaching, and higher-rated hospitals had higher prices, in contrast to DSH hospitals. A better understanding of the relationship between this cost variation and quality of care is critical given the impact of cost on health care access and affordability.

Observer preference of artificial intelligence-generated versus clinical prostate contours for ultrasound-based high dose rate brachytherapy.

BACKGROUND: For trans-rectal ultrasound (TRUS)-based high dose rate (HDR) prostate brachytherapy, prostate contouring can be challenging due to artifacts from implanted needles, bleeding, and calcifications. PURPOSE: To evaluate the geometric accuracy and observer preference of an artificial intelligence (AI) algorithm for generating prostate contours on TRUS images with implanted needles. METHODS: We conducted a retrospective study of 150 patients, who underwent HDR brachytherapy. These patients were randomly divided into training (104), validation (26) and testing (20) sets. An AI algorithm was trained/validated utilizing the TRUS image and reference (clinical) contours. The algorithm then provided contours for the test set. For evaluation, we calculated the Dice coefficient between AI and reference prostate contours. We then presented AI and reference contours to eight clinician observers, and asked observers to select their preference. Observers were blinded to the source of contours. We calculated the percentage of cases in which observers preferred AI contours. Lastly, we evaluate whether the presence of AI contours improved the geometric accuracy of prostate contours provided by five resident observers for a 10-patient subset. RESULTS: The median Dice coefficient between AI and reference contours was 0.92 (IQR: 0.90-0.94). Observers preferred AI contours for a median of 57.5% (IQR: 47.5, 65.0) of the test cases. For resident observers, the presence of AI contours was associated with a 0.107 (95% CI: 0.086, 0.128; p < 0.001) improvement in Dice coefficient for the 10-patient subset. CONCLUSION: The AI algorithm provided high-quality prostate contours on TRUS with implanted needles. Further prospective study is needed to better understand how to incorporate AI prostate contours into the TRUS-based HDR brachytherapy workflow.

Polybrominated diphenyl ethers (PBDEs): turning the corner in Great Lakes trout 1980-2009.

Lake trout and walleye composites were collected between 2004 and 2009 as part of the Great Lakes Fish Monitoring and Surveillance Program (GLFMSP) and analyzed for polybrominated diphenyl ethers (PBDEs). Yearly mean total PBDE concentrations (sum of congeners BDE-47, BDE-99, BDE-100, BDE-153, BDE-154) ranged from 44-192, 28-113, 50-107, 37-111, and 11-22 ng/g wet wt. for Lakes Michigan, Huron, Ontario, and Superior lake trout, and Lake Erie walleye, respectively. A 1980-2009 temporal record of PBDE concentrations in the Great Lakes' top predator fish (lake trout and walleye) was assembled by integrating previous GLFMSP data (1980-2003) with current results (2004-2009). Temporal profiles show obvious breakpoints between periods of PBDE accumulation and decline in trout for Lakes Huron, Michigan and Ontario with a significant (p < 0.0001 and r = 0.55, 0.72, and 0.51, respectively) decrease in concentration after 2000-2001. A similar transition was observed in Lake Superior for the nearshore site accompanied by a less significant decreasing trend (p = 0.016, r = 0.33), suggesting concentrations are declining very slowly or have leveled off. In contrast, Lake Erie walleye concentrations began leveling off in the late 1990s and no statistically significant trend (increasing or decreasing) has been observed in recent years. A decrease in the BDE-47/BDE-153 ratio was also recently observed, suggesting a transition to more highly brominated PBDEs is occurring in Great Lakes trout. This study provides region-wide evidence that PBDE concentrations are generally declining in Great Lakes trout, although there are clear exceptions to this trend. Results from this study reflect the positive impact of the 2004 PentaBDE ban on macro-scale aquatic freshwater ecosystems.

Characterization of clinical outcomes after shorter course hypofractionated and standard-course radiotherapy for stage I-III curatively-treated Merkel cell carcinoma.

BACKGROUND: Limited data exists regarding the efficacy of curative hypofractionated radiotherapy (hypo-RT) regimens compared to conventionally-fractionated radiotherapy (conv-RT) for Merkel cell carcinoma (MCC). METHODS: A retrospective analysis of 241 patients diagnosed with non-metastatic MCC from 2005-2021 and who received RT at Dana-Farber/Brigham & Women's Cancer Center. The primary outcome was cumulative incidence of in-field locoregional relapse using Gray's test with competing risks of death and isolated out-of-field recurrence. Secondary outcomes included overall survival (OS) and MCC-specific survival using log-rank tests, and risk factors of recurrence using Cox-proportional hazards regression. RESULTS: There were 50 (20.6 %) and 193 (79.4 %) courses of hypo-RT and conv-RT, respectively. The hypo-RT cohort was older (≥73 years at diagnosis: 78.0 % vs 41.5 %, p < 0.01), and received a lower equivalent total RT dose in 2 Gy per fraction (<50 Gy: 58.0 % vs 5.2 %, p < 0.01). Median follow-up was 65.1 months (range: 1.2-194.5) for conv-RT and 25.0 months (range: 1.6-131.3) for hypo-RT cohorts. Two-year cumulative incidence of in-field locoregional relapse was low in both groups (1.1 % conv-RT vs 4.1 % hypo-RT, p = 0.114). While two-year OS was lower for the hypo-RT group (62.6 % vs 84.4 %, p = 0.0008), two-year MCC-specific survival was similar (84.7 % vs 86.6 %, p = 0.743). On multivariable analysis, immunosuppression, clinical stage III disease, and lymphovascular invasion were associated with any-recurrence when controlling for sex, age, and hypo-RT. CONCLUSIONS AND RELEVANCE: There was no difference in cumulative incidence of in-field locoregional relapse or MCC-specific survival between hypo-RT and conv-RT. Prospective studies are needed to confirm hypo-RT as an efficacious treatment option for MCC.

Incidence of Radiation Therapy Among Patients Enrolled in a Multidisciplinary Pulmonary Nodule and Lung Cancer Screening Clinic.

Importance: The number of pulmonary nodules discovered incidentally or through screening programs has increased markedly. Multidisciplinary review and management are recommended, but the involvement of radiation oncologists in this context has not been defined. Objective: To assess the role of stereotactic body radiation therapy among patients enrolled in a lung cancer screening program. Design, Setting, and Participants: This prospective cohort study was performed at a pulmonary nodule and lung cancer screening clinic from October 1, 2012, to September 31, 2019. Referrals were based on chest computed tomography with Lung Imaging Reporting and Data System category 4 finding or an incidental nodule 6 mm or larger. A multidisciplinary team of practitioners from radiology, thoracic surgery, pulmonology, medical oncology, and radiation oncology reviewed all nodules and coordinated workup and treatment as indicated. Exposures: Patients referred to the pulmonary nodule and lung cancer screening clinic with an incidental or screen-detected pulmonary nodule. Main Outcomes and Measures: The primary outcome was the proportion of patients undergoing therapeutic intervention with radiation therapy, stratified by the route of detection of their pulmonary nodules (incidental vs screen detected). Secondary outcomes were 2-year local control and metastasis-free survival. Results: Among 1150 total patients (median [IQR] age, 66.5 [59.3-73.7] years; 665 [57.8%] female; 1024 [89.0%] non-Hispanic White; 841 [73.1%] current or former smokers), 234 (20.3%) presented with screen-detected nodules and 916 (79.7%) with incidental nodules. For patients with screen-detected nodules requiring treatment, 41 (17.5%) received treatment, with 31 (75.6%) undergoing surgery and 10 (24.4%) receiving radiation therapy. Patients treated with radiation therapy were older (median [IQR] age, 73.8 [67.1 to 82.1] vs 67.6 [61.0 to 72.9] years; P < .001) and more likely to have history of tobacco use (67 [95.7%] vs 128 [76.6%]; P = .001) than those treated with surgery. Fifty-eight patients treated with radiation therapy (82.9%) were considered high risk for biopsy, and treatment recommendations were based on a clinical diagnosis of lung cancer after multidisciplinary review. All screened patients who received radiation therapy had stage I disease and were treated with stereotactic body radiation therapy. For all patients receiving stereotactic body radiation therapy, 2-year local control was 96.3% (95% CI, 91.1%-100%) and metastasis-free survival was 94.2% (95% CI, 87.7%-100%). Conclusions and Relevance: In this unique prospective cohort, 1 in 4 patients with screen-detected pulmonary nodules requiring intervention were treated with stereotactic body radiation therapy. This finding highlights the role of radiation therapy in a lung cancer screening population and the importance of including radiation oncologists in the multidisciplinary management of pulmonary nodules.

Graded Prognostic Assessment (GPA) for Patients With Lung Cancer and Brain Metastases: Initial Report of the Small Cell Lung Cancer GPA and Update of the Non-Small Cell Lung Cancer GPA Including the Effect of Programmed Death Ligand 1 and Other Prognostic Factors.

PURPOSE: Patients with lung cancer and brain metastases represent a markedly heterogeneous population. Accurate prognosis is essential to optimally individualize care. In prior publications, we described the graded prognostic assessment (GPA), but a GPA for patients with small cell lung cancer (SCLC) has never been reported, and in non-small cell lung cancer (NSCLC), the effect of programmed death ligand 1 (PD-L1) was unknown. The 3-fold purpose of this work is to provide the initial report of an SCLC GPA, to evaluate the effect of PD-L1 on survival in patients with NSCLC, and to update the Lung GPA accordingly. METHODS AND MATERIALS: A multivariable analysis of prognostic factors and treatments associated with survival was performed on 4183 patients with lung cancer (3002 adenocarcinoma, 611 nonadenocarcinoma, 570 SCLC) with newly diagnosed brain metastases between January 1, 2015, and December 31, 2020, using a multi-institutional retrospective database. Significant variables were used to update the Lung GPA. RESULTS: Overall median survival for lung adenocarcinoma, SCLC, and nonadenocarcinoma was 17, 10, and 8 months, respectively, but varied widely by GPA from 2 to 52 months. In SCLC, the significant prognostic factors were age, performance status, extracranial metastases, and number of brain metastases. In NSCLC, the distribution of molecular markers among patients with lung adenocarcinoma and known primary tumor molecular status revealed alterations/expression in PD-L1 50% to 100%, PD-L1 1% to 49%, epidermal growth factor receptor, and anaplastic lymphoma kinase in 32%, 31%, 30%, and 7%, respectively. Median survival of patients with lung adenocarcinoma and brain metastases with 0, 1% to 49%, and ≥50% PD-L1 expression was 17, 19, and 24 months, respectively (P < .01), confirming PD-L1 is a prognostic factor. Previously identified prognostic factors for NSCLC (epidermal growth factor receptor and anaplastic lymphoma kinase status, performance status, age, number of brain metastases, and extracranial metastases) were reaffirmed. These factors were incorporated into the updated Lung GPA with robust separation between subgroups for all histologies. CONCLUSIONS: Survival for patients with lung cancer and brain metastases has improved but varies widely. The initial report of a GPA for SCLC is presented. For patients with NSCLC-adenocarcinoma and brain metastases, PD-L1 is a newly identified significant prognostic factor, and the previously identified factors were reaffirmed. The updated indices establish unique criteria for SCLC, NSCLC-nonadenocarcinoma, and NSCLC-adenocarcinoma (incorporating PD-L1). The updated Lung GPA, available for free at brainmetgpa.com, provides an accurate tool to estimate survival, individualize treatment, and stratify clinical trials.