Longitudinal quality of life after sublobar resection and stereotactic body radiation therapy for early-stage non-small cell lung cancer.

BACKGROUND: Many patients with early-stage lung cancer are not candidates for lobectomy because of various factors, with treatment options including sublobar resection or stereotactic body radiation therapy (SBRT). Limited information exists regarding patient-centered outcomes after these treatments. METHODS: Subjects with stage I-IIA non-small cell lung cancer (NSCLC) at high risk for lobectomy who underwent treatment with sublobar resection or SBRT were recruited from five medical centers. Quality of life (QOL) was compared with the Short Form 8 (SF-8) for physical and mental health and Functional Assessment of Cancer Therapy-Lung (FACT-L) surveys at baseline (pretreatment) and 7 days, 30 days, 6 months, and 12 months after treatment. Propensity score methods were used to control for confounders. RESULTS: Of 337 subjects enrolled before treatment, 63% received SBRT. Among patients undergoing resection, 89% underwent minimally invasive video-assisted thoracic surgery or robot-assisted resection. Adjusted analyses showed that SBRT-treated patients had both higher physical health SF-8 scores (difference in differences [DID], 6.42; p = .0008) and FACT-L scores (DID, 2.47; p = .004) at 7 days posttreatment. Mental health SF-8 scores were not different at 7 days (p = .06). There were no significant differences in QOL at other time points, and all QOL scores returned to baseline by 12 months for both groups. CONCLUSIONS: SBRT is associated with better QOL immediately posttreatment compared with sublobar resection. However, both treatment groups reported similar QOL at later time points, with a return to baseline QOL. These findings suggest that sublobar resection and SBRT have a similar impact on the QOL of patients with early-stage lung cancer deemed ineligible for lobectomy.

Prospective Cohort Study to Compare Long-Term Lung Cancer-Specific and All-Cause Survival of Clinical Early Stage (T1a-b; ≤20 mm) NSCLC Treated by Stereotactic Body Radiation Therapy and Surgery.

INTRODUCTION: We aimed to compare outcomes of patients with first primary clinical T1a-bN0M0 NSCLC treated with surgery or stereotactic body radiation therapy (SBRT). METHODS: We identified patients with first primary clinical T1a-bN0M0 NSCLCs on last pretreatment computed tomography treated by surgery or SBRT in the following two prospective cohorts: International Early Lung Cancer Action Program (I-ELCAP) and Initiative for Early Lung Cancer Research on Treatment (IELCART). Lung cancer-specific survival and all-cause survival after diagnosis were compared using Kaplan-Meier analysis. Propensity score matching was used to balance baseline demographics and comorbidities and analyzed using Cox proportional hazards regression. RESULTS: Of 1115 patients with NSCLC, 1003 had surgery and 112 had SBRT; 525 in I-ELCAP in 1992 to 2021 and 590 in IELCART in 2016 to 2021. Median follow-up was 57.6 months. Ten-year lung cancer-specific survival was not significantly different: 90% (95% confidence interval: 87%-92%) for surgery versus 88% (95% confidence interval: 77%-99%) for SBRT, p = 0.55. Cox regression revealed no significant difference in lung cancer-specific survival for the combined cohorts (p = 0.48) or separately for I-ELCAP (p = 1.00) and IELCART (p = 1.00). Although 10-year all-cause survival was significantly different (75% versus 45%, p < 0.0001), after propensity score matching, all-cause survival using Cox regression was no longer different for the combined cohorts (p = 0.74) or separately for I-ELCAP (p = 1.00) and IELCART (p = 0.62). CONCLUSIONS: This first prospectively collected cohort analysis of long-term survival of small, early NSCLCs revealed that lung cancer-specific survival was high for both treatments and not significantly different (p = 0.48) and that all-cause survival after propensity matching was not significantly different (p = 0.74). This supports SBRT as an alternative treatment option for small, early NSCLCs which is especially important with their increasing frequency owing to low-dose computed tomography screening. Furthermore, treatment decisions are influenced by many different factors and should be personalized on the basis of the unique circumstances of each patient.

The incorporation of cognitive-sparing techniques into prophylactic cranial irradiation in the management of small cell lung cancer.

The use of prophylactic cranial irradiation (PCI) remains an important component in the management of small cell lung cancer (SCLC). This is due to the high rates of subclinical brain metastases at the time of diagnosis. Following a response to initial treatment, PCI historically has been associated with improvements in overall survival and decreased development of brain metastases in patients with limited stage (LS-SCLC) and extensive stage (ES-SCLC) SCLC. However, PCI is commonly withheld in these settings in favor of observation, largely due to its association with cognitive sequelae following treatment. While randomized data has demonstrated that in patients with ES-SCLC, PCI may be withheld in favor of close MRI surveillance without a detriment in overall survival or cognitive functioning, these patients did not undergo formal neuropsychological assessments. In recent years, cognitive sparing techniques incorporated into whole brain radiation therapy and PCI, such as the addition of memantine and hippocampal avoidance, have demonstrated significant improvements in cognitive outcomes. As the overall survival in patients with SCLC continues to improve due to the incorporation of novel systemic therapies (e.g., immune checkpoint inhibitors), the role of PCI and maximizing quality of life remains a highly relevant topic. This article reviews the role of PCI and cognitive-sparing techniques in the management of SCLC.

Radiotherapy and Immunotherapy in Lung Cancer.

The emergence of immune checkpoint inhibitors (ICIs) as a pillar of cancer treatment has emphasized the immune system's integral role in tumor control and progression through cancer immune surveillance. ICIs are being investigated and incorporated into the treatment paradigm for lung cancers across stages and histology. To date, definitive concurrent chemoradiotherapy followed by consolidative durvalumab is the only National Comprehensive Cancer Network's recommended treatment paradigm including radiotherapy with ICI in lung cancers, although there are other recommendations for ICI with chemotherapy and/or surgery. This narrative review provides an overall view of the evolving integration and synergistic role of immunotherapy and radiotherapy and outlines the use of immunotherapy with radiotherapy for the management of small cell lung cancer and non-small cell lung cancer. It also reviews selected, practice-changing clinical trials that led to the current standard of care for lung cancers.

First clinical implementation of Yttrium-90 Disc Brachytherapy after FDA clearance.

PURPOSE: Herein, we study if high-dose-rate (HDR) yttrium-90 (90Y) brachytherapy could be utilized by medical physicists, radiation oncologists, and ophthalmic surgeons. METHODS AND MATERIALS: Yttrium-90 (90Y) beta-emitting brachytherapy sources received United States Food and Drug Administration clearance for episcleral treatment of ocular tumors and benign growths. Dose calibration traceable to the National Institute of Standards and Technology as well as treatment planning and target delineation methods were established. Single-use systems included a 90Y-disc affixed within specialized, multifunction, handheld applicator. Low-dose-rate to high-dose-rate prescription conversions and depth-dose determinations were performed. Radiation safety was evaluated based on live exposure rates during assembly and surgeries. Clinical data for radiation safety, treatment tolerability, and local control was collected. RESULTS: Practice parameters for the medical physicist, radiation oncologist, and ophthalmic surgeon were defined. Device sterilizations, calibrations, assemblies, surgical methods, and disposals were reproducible and effective. Treated tumors included iris melanoma, iridociliary melanoma, choroidal melanoma, and a locally invasive squamous carcinoma. Mean calculated 90Y disc activity was 14.33 mCi (range 8.8-16.6), prescription dose 27.8 Gy (range 22-30), delivered to depth of 2.3 mm (range 1.6-2.6), at treatment durations of 420 s (7.0 min, range 219 s-773 s). Both insertion and removal were performed during one surgical session. After surgery, each disc-applicator- system was contained for decay in storage. Treatments were well-tolerated. CONCLUSIONS: HDR 90Y episcleral brachytherapy devices were created, implementation methods developed, and treatments performed on 6 patients. Treatments were single-surgery, rapid, and well-tolerated with short-term follow up.

Outcomes Following SBRT vs. IMRT and 3DCRT for Older Patients with Stage IIA Node-Negative Non-Small Cell Lung Cancer > 5 cm.

BACKGROUND: To describe outcomes and compare the effectiveness of stereotactic body radiotherapy (SBRT) versus 3-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT) in patients with stage IIA lymph node-negative (N0) non-small cell lung cancer (NSCLC) tumors > 5 cm. METHODS: We used the SEER-Medicare database (2005-2015) to identify patients > 65 years with stage IIA (AJCC TNM7) N0 NSCLC > 5 cm tumors who were treated with SBRT, IMRT, and 3DCRT. We used propensity score methods with inverse probability weighting to compare lung cancer-specific survival (LCSS), overall survival (OS), and toxicity. RESULTS: Of 584 patients, 88 (15%), 140 (24%), and 356 (61%) underwent SBRT, IMRT, and 3DCRT, respectively. The SBRT group was older (P = .004), had more comorbidities (P = .02), smaller tumors (P = .03), and more adenocarcinomas (P < .0001). We found a trend towards higher median unadjusted OS with SBRT compared to IMRT and 3DCRT (19 vs. 13 and 14 months, respectively, P = .37). In our propensity score-adjusted analyses, SBRT was significantly associated with better OS and LCSS compared to IMRT (HROS: 0.78, 95% CI: 0.68-0.89, HRLCSS: 0.70, 95% CI: 0.60-0.81) and 3DCRT (HROS: 0.81, 95% CI: 0.72-0.93, HRLCSS: 0.80, 95% CI: 0.68-0.93). SBRT-treated patients also had lower overall adjusted complication rates compared to IMRT (OR: 0.74, 95% CI: 0.55-0.99) and 3DCRT (OR: 0.53, 95% CI: 0.40-0.71). CONCLUSION: For patients with NSCLC tumors > 5 cm, SBRT trends towards fewer toxicities and improved survival compared to other forms of radiotherapy. Our findings support SBRT as an appropriate treatment strategy for older patients with larger inoperable NSCLC tumors.

The Rise of Open Access Journals in Radiation Oncology: Influence on Resident Research, 2015 to 2019.

Purpose: While a rising share of scientific research articles are being published in open access (OA) journals, their impact on resident research in radiation oncology is unknown. Thus, we sought to determine the number, content, and costs of first-author, PubMed-searchable articles radiation oncology residents in the United States (US) published in OA journals in recent years. Methods and Materials: We built a database of first-author, PubMed-searchable articles published by US radiation oncology residents who graduated between 2015 and 2019. We then classified each journal in which these articles appeared as either OA or non-OA and obtained the current article-processing charge (APC) for each publication that appeared in an OA journal. Results: The residents in this study published 2637 first-author, PubMed-searchable articles, 555 of which (21.0%) appeared in 138 OA journals. The number of publications in OA journals per resident increased from 0.47 for the class of 2015 to 0.79 for the class of 2019. Publications in OA journals garnered fewer citations than those in non-OA journals (8.9 vs 14.9, P < .01). Furthermore, 90.6% of OA journals levy an APC for original research reports (median, $1896), which is positively correlated with their 2019 impact factor (r = 0.63, P < .01). Aggregate APCs totaled $900,319.21 and appeared to increase over the study period. Conclusions: The number of first-author, PubMed-searchable articles published by graduating US radiation oncology residents in OA journals rose significantly between 2015 and 2019. To maximize the benefits of OA publishing in the future, US radiation oncology residents will need to ensure that they use vetted OA journals to publish their research findings and avoid predatory journals.

Characterization of rib fracture development following liver directed stereotactic body radiation therapy.

Purpose: Rib fractures are a well-described complication following thoracic stereotactic body radiation therapy (SBRT). However, there are limited data in the setting of liver-directed SBRT. Methods: Patients who underwent liver SBRT from 2014 to 2019 were analyzed. Logistic regression models were used to identify the demographic, clinical, and dosimetric factors associated with the development of rib fractures. Results: Three hundred and forty-three consecutive patients were reviewed with median follow-up of 9.3 months (interquartile range [IQR]: 4.7-17.4 months); 81% of patients had primary liver tumors and 19% had liver metastases. Twenty-one patients (6.2%) developed rib fractures with a median time to diagnosis of 7 months following SBRT (IQR: 5-19 months). Of those patients, 11 experienced concomitant chest wall pain, while 10 patients had an incidental finding of a rib fracture on imaging. On univariate analysis, female gender (odds ratio [OR]: 2.29; p = 0.05), V30 Gy (OR: 1.02; p < 0.001), V40 Gy (OR: 1.08; p < 0.001), maximum chest wall dose (OR: 1.1; p < 0.001), and chest wall D30 cm3 (OR: 1.09; p < 0.001) were associated with an increased probability of developing a rib fracture. On multivariate analysis, maximum chest wall dose (OR: 1.1; p < 0.001) was associated with developing a rib fracture. Receipt of more than one course of SBRT (p = 0.34), left versus right sided lesion (p = 0.69), osteoporosis (p = 0.54), age (p = 0.82), and PTV volume (p = 0.55) were not significant. Conclusions: Rib fractures following liver SBRT were observed in 6.2% of patients with the majority being asymptomatic. To mitigate this risk, clinicians should minimize dose delivery to the chest wall. Female patients may be at increased risk.

Combination Transarterial Chemoembolization and Stereotactic Body Radiation Therapy for Unresectable Single Large Hepatocellular Carcinoma: Results From a Prospective Phase 2 Trial.

PURPOSE: Patients with hepatocellular carcinoma (HCC) at Barcelona Clinic Liver Cancer (BCLC) early-stage A (BCLC A) not suitable for surgery are first considered for ablation. Nonetheless, objective responses and long-term results for ablation in tumors larger than 3 to 4 cm are suboptimal, creating an unmet clinical need. This phase 2 trial studied combination of transarterial chemoembolization (TACE) and stereotactic body radiation therapy (SBRT) for BCLC A patients with a solitary HCC from 4 to 7 cm. METHODS AND MATERIALS: Eligible patients were BCLC A, Child-Pugh score ≤7, Eastern Cooperative Oncology Group performance status 0 presenting with a single HCC from 4 to 7 cm not suitable for resection or liver transplantation. Treatment consisted of 2 sessions of drug-eluting bead-TACE within 1 month followed by immediate SBRT. SBRT delivered 35 to 50 Gy in 5 fractions. The primary endpoint was best objective response rate (ORR) by modified Response Evaluation Criteria in Solid Tumours (mRECIST). Secondary endpoints were overall survival (OS), progression-free survival (PFS), and toxic effects. RESULTS: From 2014 to 2020, 32 were enrolled in a single institution with median follow-up of 37 months. Thirty patients had at least 1 posttreatment scan to assess response. ORR in the target lesion was 91%: 63% complete response (CR; n = 20), 28% partial response (n = 9), and 3% progression of disease (n = 1). Median time to CR was 10.1 months. Median OS was not yet reached and median PFS was 35 months. Patients achieving CR had a trend toward improved PFS (P = .09). Toxic effects were low. CONCLUSIONS: This phase 2 trial showed very promising ORR when combining TACE + SBRT in large, unresectable HCC, which translates into excellent OS and PFS. These results provide the rationale for exploring this combination in larger phase 2 and 3 clinical trials and a space where SBRT might offer unique clinical advantage.

Risk of Cardiovascular Toxicity According to Tumor Laterality Among Older Patients With Early Stage Non-small Cell Lung Cancer Treated With Radiation Therapy.

BACKGROUND: The long-term risk of cardiovascular outcomes from either stereotactic body radiation therapy (SBRT) or three-dimensional conformal radiation therapy (3DCRT) plus intensity-modulated radiation therapy (IMRT) to treat early stage non-small cell lung cancer (NSCLC) is largely unknown. As continued adoption of SBRT accelerates, it is important to delineate unforeseen cardiovascular risks associated with treatment. RESEARCH QUESTION: Does the long-term risk of cardiovascular outcomes for patients with early stage NSCLC treated with either SBRT or 3DCRT plus IMRT differ by tumor laterality? STUDY DESIGN AND METHODS: Data from the Surveillance, Epidemiology, and End Results registry linked to Medicare was analyzed to identify a sample of 3,256 patients (1,506 treated with SBRT and 1,750 treated with 3DCRT plus IMRT) with node-negative stage I or IIA NSCLC. Cardiovascular events were identified using diagnosis codes, and outcomes were compared between left- and right-sided tumors. We assumed that tumor laterality was random and that the radiation field for left-sided tumors likely would result in greater dose to cardiac tissues. Cox regression models were fit to quantify the association of laterality on outcomes. RESULTS: Patients were followed up for a median of 2 years. Those treated with SBRT showed no difference in hazard of any cardiovascular outcomes by tumor laterality, including the cardiovascular composite (hazard ratio [HR] comparing left- vs right-sided tumors, 0.98; 95% CI, 0.84-1.15). In contrast, patients treated with 3DCRT plus IMRT showed a greater risk of congestive heart failure (HR, 1.23; 95% CI, 1.01-1.48) and percutaneous coronary artery intervention (HR, 2.24; 95% CI, 1.12-4.47). INTERPRETATION: Patients with left- vs right-sided early stage NSCLC showed similar rates of cardiovascular events when treated with SBRT. However, these patients also showed higher rates of select cardiac events when they were treated with 3DCRT plus IMRT. This study provides evidence that SBRT may provide a safer option over 3DCRT plus IMRT for patients with left-sided early stage NSCLC and underscores the need for long-term follow-up for patients treated with radiation therapy.

American Radium Society Appropriate Use Criteria for Radiation Therapy in Oligometastatic or Oligoprogressive Non-Small Cell Lung Cancer.

PURPOSE: Recent randomized studies have suggested improvements in progression-free and overall survival with the addition of stereotactic body radiation therapy (SBRT, also known as SABR) in patients with oligometastatic non-small cell lung cancer. Given the novelty and complexity of incorporating SBRT in the oligometastatic setting, the multidisciplinary American Radium Society Lung Cancer Panel was assigned to create appropriate use criteria on SBRT as part of consolidative local therapy for patients with oligometastatic and oligoprogressive non-small cell lung cancer. METHODS AND MATERIALS: A review of the current literature was conducted from January 1, 2008, to December 25, 2020, using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines to systematically search the PubMed database to retrieve a comprehensive set of relevant articles. RESULTS: Based on representation in existing randomized trials, the panel defined the term "oligometastasis" as ≤3 metastatic deposits (not including the primary tumor) in the previously untreated setting or after first-line systemic therapy after the initial diagnosis. "Oligoprogression" also referred to ≤3 discrete areas of progression in the setting of prior or ongoing receipt of systemic therapy. In all appropriate patients, the panel strongly recommends enrollment in a clinical trial whenever available. For oligometastatic disease, administering first-line systemic therapy followed by consolidative radiation therapy (to all sites plus the primary/nodal disease) is preferred over up-front radiation therapy. Owing to a dearth of data, the panel recommended that consolidative radiation therapy be considered on a case-by-case basis for 4 to 5 sites of oligometastatic disease, driver mutation-positive oligometastatic disease without progression on up-front targeted therapy, and oligoprogressive cases. CONCLUSIONS: Although SBRT/SABR appears to be both safe and effective in treating patients with limited metastatic sites of disease, many clinical circumstances require individualized management and strong multidisciplinary discussion on account of the limited existing data.

Comparison of Pathologic Complete Response Rates and Oncologic Outcomes in Patients With Surgically Resectable Esophageal Cancer Treated With Neoadjuvant Chemoradiation to 50.4 Gy vs 41.4 Gy.

Background Excellent outcomes and high rates of pathologic complete response (pCR) have been reported in patients with operable esophageal carcinoma using 41.4 Gy of radiation with concurrent carboplatin and paclitaxel. With pCR rates similar to studies using higher doses, it remains unclear whether doses greater than 41.4 Gy result in improved outcomes. This study aims to compare pCR rates and oncologic outcomes in patients treated with neoadjuvant chemoradiation to 50.4 Gy vs 41.4 Gy. Methods We reviewed the charts of patients with operable esophageal carcinoma who were treated with neoadjuvant chemoradiation followed by oncologic resection. Our primary endpoint was the pCR rate. Secondary endpoints were overall survival, progression-free survival (PFS), and toxicity.  Results We identified 43 patients meeting inclusion criteria. Nineteen patients were treated with 41.4 Gy and 24 were treated with 50.4 Gy. Cohorts were well-matched, except for a significantly higher percentage of patients with adenocarcinoma (AC) (89.5% vs 54.2%, p = 0.02), usage of intensity-modulated radiation therapy (IMRT) (100% vs 47.6%; p = 0.002), and usage of carboplatin, plus paclitaxel (100% vs 75%; p = 0.003) in the 41.4 Gy group. The pCR rate for the cohort was 44.2%. No differences in the pCR rate (41.7% vs 47.4%), three-year overall survival (OS) (73.7% vs 77.5%), or three-year PFS (52.8% vs 43.7%) were observed. Late toxicity rates also did not vary significantly (p = 0.2). No grade 4 or 5 events were observed. Conclusion In this small series, there were no differences in the pCR rate, PFS, or OS between those treated with 50.4 Gy and 41.4 Gy. Larger, multi-institutional series are needed to validate these findings.

The Holman Research Pathway in Radiation Oncology: 2010 to 2019.

PURPOSE: There has not been an assessment of the Holman Research Pathway (HRP) in radiation oncology (RO) in nearly 10 years. In this study, we sought to review the demographic characteristics, research productivity during and after residency, job placements, and National Institutes of Health (NIH) grant funding of RO residents who completed the HRP in the modern era. METHODS AND MATERIALS: We created a comprehensive database of RO residents who completed the HRP between 2010 and 2019. Using a variety of data sources, we obtained demographic information, first-author manuscripts published in residency, and first- and last-author manuscripts published in the first 30 months after residency for each resident. In addition, we identified the first and current job and NIH grant funding for each resident. RESULTS: Ninety-seven RO residents who graduated from 50 medical schools and 25 residency programs were included. The majority were male (82.5%), had a PhD (92.8%), and identified as white (64.9%). Collectively, these residents published 212 first-author, PubMed-searchable manuscripts during residency (mean: 2.2) and 142 first- or last-author, PubMed-searchable manuscripts in the first 30 months after completion of residency (mean: 1.5). The number of first-author publications authored by HRP graduates during residency was highly correlated (r = 0.62; P < .01) with the number of first- and last-author publications they authored during the first 30 months after completing residency. Ninety-six of the 97 residents (99.0%) were employed in full-time clinical positions after completing residency. Seventy-six HRP residents (78.4%) obtained an academic position as their first job after residency, only 4 of whom have since left academia, and 20 (20.6%) obtained a nonacademic position. Of the 75 HRP graduates currently employed in an academic position, 39 (52.0%) have their own laboratories. Twenty-three of the 96 HRP residents (24.0%) who secured employment in full-time clinical positions after residency switched jobs over the study period. Lastly, 33 of the 97 HRP residents (34.0%) have thus far received 47 extramural NIH research grants, 15 of which were R-01 grants. CONCLUSIONS: Over the past decade, the HRP has proven successful in training a new cohort of physician investigators in RO. Although productive, HRP residents have had relatively homogenous sex, educational, and racial backgrounds. Ensuring sufficient representation of residents from a variety of backgrounds in the HRP in the future will be crucial.

Palliating Symptoms in Patients With Hepatocellular Carcinoma Involving the Inferior Vena Cava With External Beam Radiation Therapy.

Introduction Patients with hepatocellular carcinoma (HCC) involving the inferior vena cava (IVC) and/or right atrium (RA) often experience debilitating symptoms, including lower extremity edema, dyspnea on exertion, shortness of breath at rest, chest pain, and ascites, that impact quality of life. The efficacy of external beam radiation therapy (EBRT) in palliating these symptoms is unclear. Thus, we sought to assess the effectiveness of EBRT in the palliation of symptoms and treatment outcomes in this patient population. Materials and methods All patients with HCC that compressed or invaded the IVC, received EBRT, and had a two-month follow-up visit to assess clinical response at our institution between 2010 and 2018 were analyzed. Patient demographics and clinical features were retrieved from the electronic medical record. Local control, local progression-free survival, and overall survival (OS) were measured from the last day of EBRT and calculated using the Kaplan-Meier method. Results Twenty-six patients with invasion or compression of the IVC were identified, 11 of whom (42%) had involvement of the RA. The median follow-up was 3.6 months. Five patients (19%) were treated with stereotactic body radiation therapy (SBRT) (all with five fractions) and 21 patients (81%) were treated with fractionated radiation therapy (range 10-16 fractions), both to a median dose of 3,000 cGy (range 2500-4000 cGy for SBRT, 2500-3750 cGy for fractionated radiation therapy). Significant proportions of patients experienced symptomatic relief from peripheral edema (54%), dyspnea on exertion (57%), shortness of breath (83%), chest pain (67%), and ascites (25%) after receiving EBRT. Additionally, they experienced few toxicities, with zero experiencing grade three or higher toxicities. One-year and two-year local control rates were 11.5% and 7.7%, respectively, and the median local progression-free survival was 4.8 months. One-year and two-year OS rates were 38.4% and 38.4%, respectively. Conclusions Our results suggest that EBRT should be considered as a potential treatment option for patients with HCC invading or compressing the IVC with or without involvement of the RA. EBRT was very well-tolerated and effectively palliated a variety of symptoms in patients with advanced disease.

Where are we with proton beam therapy for thoracic malignancies? Current status and future perspectives.

Radiation therapy (RT) plays an important role in the curative treatment of a variety of thoracic malignancies. However, delivery of tumoricidal doses with conventional photon-based RT to thoracic tumors often presents unique challenges. Extraneous dose deposited along the entrance and exit paths of the photon beam increases the likelihood of significant acute and delayed toxicities in cardiac, pulmonary, and gastrointestinal structures. Furthermore, safe dose-escalation, delivery of concomitant systemic therapy, or reirradiation of a recurrent disease are frequently not feasible with photon RT. In contrast, protons have distinct physical properties that allow them to deposit a high irradiation dose in the target, while leaving a negligible exit dose in the adjacent organs at risk. Proton beam therapy (PBT), therefore, can reduce toxicities with similar antitumor effect or allow for dose escalation and enhanced antitumor effect with the same or even lower risk of adverse events, thus potentially improving the therapeutic ratio of the treatment. For thoracic malignancies, this favorable dose distribution can translate to decreases in treatment-related morbidities, provide more durable disease control, and potentially prolong survival. This review examines the evolving role of PBT in the treatment of thoracic malignancies and evaluates the data supporting its use.

RapidPlan for Knowledge-Based Planning of Malignant Pleural Mesothelioma.

PURPOSE: Treatment planning for malignant pleural mesothelioma is a challenging task due to the relatively large size of the target and the need to spare critical organs that overlap with or are within the target volume. We aimed to develop a knowledge-based model using RapidPlan (RP) for patients with 2 intact lungs. METHODS AND MATERIALS: Data from 57 patients treated with volumetric modulated arc therapy were chosen for training the dose estimation model at a single dose level. The prescription dose was 50.4 Gy in 1.8 Gy fractions. The model was validated on 23 new patients by comparing the clinical plan to the RP. Time taken to plan the RP was compared with that for the clinical plan. RESULTS: For similar target coverage and plan inhomogeneity, RP significantly improved the sparing of the contralateral lung, heart, stomach, esophagus, and ipsilateral kidney. On average, the contralateral lung V5 Gy and V10 Gy were reduced by 13.9% (P < .001) and 7.9% (P < .001), respectively. The mean heart dose was reduced by 5 Gy (P < .001) and V30 Gy by 9.1% (P < .001). Mean dose to the stomach and esophagus were both reduced by 5 Gy (P < .001), and the ipsilateral kidney V18 Gy by 4.1% (P < .001). Mean total lung dose was reduced by 0.8 Gy with RP, which enabled an increase in prescription dose by 1 fraction Absolute volume of ipsilateral lung was adequately spared by both techniques, while sparing of all other organs, namely the cord, liver, and bowel, was not compromised with RP. Time taken with RP was 20 minutes, 45 seconds versus at least 4 hours for an experienced treatment planner. CONCLUSIONS: The RP model for malignant pleural mesothelioma showed improved sparing of critical organs with a reduced treatment planning time and increased prescription dose.

Potential Significant Changes in Nuclear Regulatory Commission Policies Regarding Training and Experience Requirements for the Use of Radiopharmaceuticals.

The Code of Federal Regulations is a single-source repository of all rules and regulations promulgated by federal departments and agencies. In Title 10, Chapter 1, Part 35, Subpart D, §§35.100 to 35.290 detail regulations for the use of unsealed by product material not requiring a written directive (ie, diagnostic radiopharmaceuticals), and in Subpart E, §§35.300 to 35.396 detail regulations for the use of unsealed by product material requiring a written directive (ie, therapeutic radionuclides). Currently proposed changes for both Subparts D and E could have profound effects on patient care, public safety, and the practice of nuclear medicine, diagnostic radiology, and radiation oncology. This article details those proposed changes and actions under way to prevent promulgation of proposals that could negatively affect patient care and public safety.

Trends in Financial Relationships Between Industry and Radiation Oncologists Versus Other Physicians in the United States from 2014 to 2018.

PURPOSE: The Open Payments transparency program publishes data on industry-physician payments, in part to discourage relationships considered inappropriate including gifts, meals, and speaker's bureau fees. We evaluated trends in physician-level payments to test whether implementation of Open Payments resulted in fewer industry-radiation oncologist (RO) interactions or shifted interactions toward those considered more appropriate compared with medical oncologists (MOs) and other hospital-based physicians (HBPs). METHODS AND MATERIALS: We performed a retrospective, population-based cohort study of practicing US ROs versus MOs and HBPs in 2014 matched to general (nonresearch) payments between 2014 and 2018. Trends in payments were analyzed and reported by nature of payment. Values of payments to ROs from the top 10 companies were identified. RESULTS: From 2014 to 2018, 3379 (90.3%) ROs accepted 106,930 payments totaling $40.8 million. The per-physician number and value of payments was lower in radiation oncology than in medical oncology and higher than HBPs. The proportion of ROs accepting payments increased from 61.8% in 2014 to 64.2% in 2018; the proportion of MOs accepting payments decreased from 78.7% to 77.7%; and the proportion of HBPs decreased from 40.8% to 37.5%, respectively. The annual per-physician value and number of payments accepted by ROs and MOs increased. Payments in entertainment, meals, travel and lodging, and gifts increased among ROs and remained stable or decreased among MOs and HBPs. Consulting payments increased across all groups. Top RO payors produced novel cancer therapeutics, hydrogel spacers, radiation treatment machines, and opioids. CONCLUSIONS: Industry payments to ROs have become more common since OP's inception, while becoming less common for MOs and HBPs. Payments to ROs and MOs have become more frequent and of modestly increasing value compared with other HBPs, for whom the value is decreasing. No large changes in the nature of relationships were seen in ROs. Increased engagement with financial conflicts of interest is needed in radiation oncology.

American Radium Society Appropriate Use Criteria on Radiation Therapy for Extensive-Stage SCLC.

INTRODUCTION: The standard-of-care therapy for extensive-stage SCLC has recently changed with the results of two large randomized trials revealing improved survival with the addition of immunotherapy to first-line platinum or etoposide chemotherapy. This has led to a lack of clarity around the role of consolidative thoracic radiation and prophylactic cranial irradiation in the setting of chemoimmunotherapy. METHODS: The American Radium Society Appropriate Use Criteria are evidence-based guidelines for specific clinical conditions that are reviewed by a multidisciplinary expert panel. The guidelines include a review and analysis of current evidence with the application of consensus methodology (modified Delphi) to rate the appropriateness of treatments recommended by the panel for extensive-stage SCLC. RESULTS: Current evidence supports either prophylactic cranial irradiation or surveillance with magnetic resonance imaging every 3 months for patients without evidence of brain metastases. Patients with brain metastases should receive whole-brain radiation with a recommended dose of 30 Gy in 10 fractions. Consolidative thoracic radiation can be considered in selected cases with the recommended dose ranging from 30 to 54 Gy; this recommendation was driven by expert opinion owing to the limited strength of evidence, as clinical trials addressing this question remain ongoing. CONCLUSIONS: Radiation therapy remains an integral component in the treatment paradigm for ES-SCLC.

Trends in Industry Payments to Medical Oncologists in the United States Since the Inception of the Open Payments Program, 2014 to 2019.

IMPORTANCE: Given the potential for undue influence of industry-physician payments on oncology care, it is important to understand how a national transparency program may be associated with financial interactions between industry and medical oncologists. OBJECTIVE: To identify trends in industry payments to medical oncologists from 2014 to 2019 and determine if the implementation of the Open Payments program is associated with changes in the frequency or value of payments or any shift in the nature of industry-oncologist financial interactions. DESIGN, SETTING, AND PARTICIPANTS: This retrospective, population-based, observational cohort study analyzed Open Payments reports of industry payments made in 2014 to 2019 to a cohort of licensed medical oncologists practicing in the US in 2014, using data from the National Plan and Provider Enumeration System. EXPOSURES: Receipt of an industry payment from January 1, 2014, to December 31, 2019. MAIN OUTCOMES AND MEASURES: General industry payments to medical oncologists, including the proportion receiving payments, total annual value and number of payments, and average annual trends over time, by aggregate value and by nature-of-payment category. Trends over time were analyzed using linear regression and generalized estimating equations. RESULTS: In 2014 to 2019, there were 15 585 medical oncologists who received a total of 2.2 million industry payments with a total value of $509 million. The absolute number of oncologists receiving payments decreased from 10 498 in 2014 to 8918 in 2019 (-15.1%). The annual per-physician payment value decreased among those receiving less than $10 000 in aggregate by -3.2% yearly (95% CI, -4.1% to -2.3%; P < .001), but increased for those receiving more than $10 000. Payments increased for consulting (13.7%; 95% CI, 12.4%-15.0%; P < .001) and for entertainment, meals, travel or lodging, and gifts (0.8%; 95% CI, 0.1%-1.5%; P = .03). CONCLUSIONS AND RELEVANCE: The number of medical oncologists accepting industry payments has decreased; however, high-value industry payments have been consolidated in a relatively small number of medical oncologists accepting higher payment values over time. The nature of payments has shifted toward consulting. These findings highlight the limitations of transparency without accountability.