Strategic Operational Redesign Improves Prior Authorization Access: A Validation Study.

Purpose: Obtaining prior authorization (PA) before treatment is becoming increasingly burdensome in oncology, especially in radiation oncology. Here, we describe the impact of a strategic novel operational PA redesign to shorten authorization time and to improve patient access to cancer care at a large United States academic proton therapy center. We ask whether such a redesign may be replicable and adoptable across oncology centers. Materials and Methods: Our PA redesign strategy was based on a 3-tiered approach. Specifically, we (1) held payors accountable to legally backed timelines, (2) leveraged expertise on insurance policies and practices, and (3) updated the submission, appeal writing, and planning procedures for PA. Metrics were compared at the following 3 time points: 6 months before, at phase-in, and at 6 months after intervention. Results: In analyzing the impact of improving PA access to care, the percentage of approvals for commercial proton beam therapy improved by an absolute 30.6% postintervention (P < .001). The proportion of commercially insured patients treated with proton beam therapy also increased by 6.2%, and the number of new starts rose by 11.7 patients/mo. Overall patient census increased by 13 patients/d. Median authorization time was 1 week, and 90% of surveyed providers reported reduced PA burden and improved patient care. Conclusion: This is the first validated, comprehensive operational strategy to improve access to cancer therapy while reducing the burden of PA. This novel approach may be helpful for addressing barriers to PA in medical and surgical oncology because the redesign is predicated on laws that regulate PA across disciplines.

Proton Therapy in the Treatment of Men with Breast Cancer.

Purpose: Male breast cancer treatment involves multimodality therapy, including radiation therapy; nevertheless, few men have received proton therapy (PT) for it. Further, heart disease is an established leading cause of death in men, and radiation therapy heart dose correlates with cardiac toxicity, highlighting the need for cardiac-sparing radiation techniques. Thus, we provide a descriptive analysis of PT in a male breast cancer cohort. Patients and Methods: Men who received PT for localized breast cancer between 2012 and 2022 were identified from a prospective database. Toxicities were prospectively recorded by using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Results: Five male patients were identified. All had estrogen receptor (ER)-positive, Her2neu-negative disease and received adjuvant endocrine therapy. One had genetic testing positive for BRCA2, one had a variant of unknown significance (VUS) in the APC gene, and one had a VUS in MSH2. Median age was 73 years (range, 41-80). Baseline comorbidities included obesity (n = 1), diabetes (n = 1), hypertension (n = 4), history of deep vein thrombosis (n = 1), personal history of myocardial infarction (n = 3; 1 with a pacemaker), and a history of lung cancer (n = 1). All received PT to the left chest wall and comprehensive regional lymphatics. One received passive-scattering PT, and 4 received pencil beam scanning. One patient received a boost to the mastectomy incision via electrons. Median heart dose was 1 GyRBE (range, 0-1.0), median 0.1-cm3 dose to the left anterior descending artery was 7.5 GyRBE (range, 0-14.2), and median follow-up was 2 years (range, 0.75-6.5); no patient experienced a new cardiac event, and all remain free from breast cancer recurrence and progression. Conclusion: In a small case series for a rare diagnosis, PT to the chest wall and regional lymphatics, including internal mammary nodes, resulted in low cardiac exposure, high local regional disease control rates, and minimal toxicity. Proton therapy should be considered for treating men with breast cancer to achieve cardiac sparing.

Palliative care utilization and racial and ethnic disparities among women with de novo metastatic breast cancer in the United States.

PURPOSE: The potential disparities in palliative care delivery for underrepresented minorities with breast cancer are not well known. We sought to determine whether race and ethnicity impact the receipt of palliative care for patients with metastatic breast cancer (MBC). METHODS: We retrospectively reviewed the National Cancer Database for female patients diagnosed with stage IV breast cancer between 2010 and 2017 who received palliative care following diagnosis of MBC to assess the proportion of patients who received palliative care, including non-curative-intent local-regional or systemic therapy. Multivariable logistic regression analysis was performed to identify variables associated with receiving palliative care. RESULTS: 60,685 patients were diagnosed with de novo MBC. Of these, only 21.4% (n = 12,963) received a palliative care service. Overall, there was a positive trend in palliative care receipt from 18.2% in 2010 to 23.0% in 2017 (P < 0.001), which persisted when stratified by race and ethnicity. Relative to non-Hispanic White women, Asian/Pacific Islander women (aOR 0.80, 95% CI 0.71-0.90, P < 0.001), Hispanic women (adjusted odds ratio [aOR] 0.69, 95% CI 0.63-0.76, P < 0.001), and non-Hispanic Black women (aOR 0.94, 95% CI 0.88-0.99, P = 0.03) were less likely to receive palliative care. CONCLUSIONS: Fewer than 25% of women with MBC received palliative care between 2010 and 2017. While palliative care has significantly increased for all racial/ethnic groups, Hispanic White, Black, and Asian/Pacific Islander women with MBC still receive significantly less palliative care than non-Hispanic White women. Further research is needed to identify the socioeconomic and cultural barriers to palliative care utilization.

Incidence of Rib Fracture following Treatment with Proton Therapy for Breast Cancer.

Purpose: To determine the rib fracture rate in a cohort of patients with breast cancer treated with proton therapy. Patient and Methods: From a prospective database, we identified 225 patients treated with proton therapy between 2012 and 2020 (223 women; 2 men). Clinical and dosimetric data were extracted, the cumulative incidence method assessed rib fracture rate, and Fine-Gray tests assessed prognostic significance of select variables. In-field rib fracture was defined as a fracture that occurred in a rib located within the 10% isodose line. Out-of-field rib fracture was defined as a fracture occurring in a rib location outside of the 10% isodose line. Results: Of the patients, 74% had left-sided breast cancer; 5%, bilateral; and 21%, right-sided. Dual-energy x-ray absorptiometry scans showed normality in 20%, osteopenia in 34%, and osteoporosis in 6% (test not performed in 40%). Additionally, 57% received an aromatase inhibitor. Target volumes were breast ± internal mammary nodes (IMNs) (16%), breast and comprehensive regional lymphatics (32%), chest wall ± IMNs (1%), and chest wall/comprehensive regional lymphatics (51%). Passive-scattered proton therapy was used for 41% of patients, 58% underwent pencil-beam scanning (PBS), and 1% underwent a combination (passive scattering/PBS), with 85% of patients receiving a boost. Median follow-up was 3.1 years, with 97% having >12-month follow-up. The 3-year cumulative in-field rib fracture incidence was 3.7%. Eight patients developed in-field rib fractures (1 symptomatic, 7 imaging identified) for a 0.4% symptomatic rib fracture rate. Median time from radiation completion to rib fracture identification was 1.8 years (fractures were identified within 2.2 years for 7 of 8 patients). No variables were associated with rib fracture on univariate analysis. Three fractures developed outside the radiation field (0.9% cumulative incidence of out-of-field rib fracture). Conclusion: In this series of patients with breast cancer treated with proton therapy, the 3-year rib fracture rates remain low (in-field 3.7%; symptomatic 0.4%). As in photon therapy, the asymptomatic rate may be underestimated owing to a lack of routine surveillance imaging. However, patients experiencing symptomatic rib fractures after proton therapy for breast cancer are rare.

Proton Therapy for Bilateral Breast Cancer Maximizes Normal-Tissue Sparing.

Purpose: Treatment for bilateral breast cancer with radiation therapy is technically challenging. We evaluated the clinical and dosimetric outcomes of a small series of patients with synchronous bilateral breast cancer, including a photon dosimetric comparison, to identify optimal treatment planning approaches. Materials and Methods: We reviewed a registry of patients (simultaneously) diagnosed with synchronous bilateral breast cancers who underwent postoperative definitive adjuvant proton therapy at our institution between 2012 and 2021. All patients were treated with double-scattered proton or pencil-beam scanning therapies. For comparison, intensity-modulated radiation therapy photon plans optimized for organ sparing and coverage were generated after treatment. Results: Six patients were included. The median patient age was 66 years; all were female with no history of breast cancer or radiation therapy. Two (33%) patients received breast/chest wall-only treatments, 1 (17%) required breast plus level I axillary treatment to one side and breast plus regional nodal irradiation (RNI) to the other, and 3 (50%) received bilateral breast/chest plus RNI; dosimetric results are reported for each group's median. Analysis showed clinical target coverage was comparable between proton and photon techniques (V95% of 96.4% with proton, 97.8% with photon). However, protons could deliver superior organ sparing at clinically relevant dose metrics for virtually all structures: a 6.7 Gy absolute reduction in the mean heart dose (7.5 Gy with photons to 0.7 Gy with protons), a 47% to 57% relative reduction in D0.1cm3 to coronary arteries, a 54% relative reduction in lung V20 Gy, and an absolute 7.6 Gy reduction to the brachial plexus. There was also greater esophagus and spinal cord sparing. The overall survival rate was 100% at 1.5 years of median follow-up (0.5-4.9), and all patients were free of disease. For toxicity, all patients had some form of acute side effects: 66% experienced grade 2 breast/chest pain or soreness; 100% had grade 2 radiation dermatitis or skin induration; 33% had grade 2 fatigue; and 17% had grade 2 esophagitis (per the Common Terminology Criteria for Adverse Events [CTCAE] version 5.0; US National Cancer Institute, Bethesda, Maryland). Subacute toxicity (within 6 months) was observed for 17% of patients with delayed onset of grade 3 dermatitis in the setting of preexisting lupus, 17% with a delayed surgical wound complication, and 17% with grade 2 soft tissue fibrosis. No grade 4 or 5 events were observed. Conclusions: Substantial dose reductions to multiple organs at risk while maintaining target coverage make proton the preferred modality for bilateral breast cancer treatment when available.

Hyperfractionated-Accelerated Reirradiation with Proton Therapy for Radiation-Associated Breast Angiosarcoma.

Purpose: Radiation-associated angiosarcoma (RAAS) is a rare complication among patients treated with radiation therapy for breast cancer. Hyperfractionated-accelerated reirradiation (HART) improves local control after surgery. Proton therapy may further improve the therapeutic ratio by mitigating potential toxicity. Materials and Methods: Six patients enrolled in a prospective registry with localized RAAS received HART with proton therapy between 2015 and 2021. HART was delivered twice or thrice daily in fraction sizes of 1.5 or 1.0 Gy, respectively. All patients received 45 Gy to a large elective volume followed by boosts to a median dose of 65 (range, 60-75) Gy. Toxicity was recorded prospectively by using the Common Terminology Criteria for Adverse Events, version 4.0. Results: The median follow-up duration was 1.5 (range, 0.25-2.9) years. The median age at RAAS diagnosis was 73 (range, 60-83) years with a median latency of 8.9 (range, 5-14) years between radiation therapy completion and RAAS diagnosis. The median mean heart dose was 2.2 (range, 0.1-4.96) Gy. HART was delivered postoperatively (n = 1), preoperatively (n = 3), preoperatively for local recurrence after initial management with mastectomy (n = 1), and as definitive treatment (n = 1). All patients had local control of disease throughout follow-up. Three of 4 patients treated preoperatively had a pathologic complete response. The patient treated definitively had a complete metabolic response on her posttreatment PET/CT (positron emission tomography-computed tomography) scan. Two patients developed distant metastatic disease despite local control and died of their disease. Acute grade 3 toxicity occurred in 3 patients: 2 patients undergoing preoperative HART experienced wound dehiscence and 1 postoperatively developed grade 3 wound infection, which resolved. Conclusion: HART with proton therapy appears effective for local control of RAAS with a high rate of pathologic complete response and no local recurrences to date. However, vigilant surveillance for distant metastasis should occur. Toxicity is comparable to that in photon/electron series. Proton therapy for RAAS may maximize normal tissue sparing in this large-volume reirradiation setting.

Evaluating Regional Nodal Irradiation Allocation and Association with Oncologic Outcomes in NSABP B-18, B-27, B-40, and B-41.

PURPOSE: There is a lack of level I evidence to guide radiation therapy recommendations for patients receiving neoadjuvant chemotherapy for breast cancer. We used 4 neoadjuvant chemotherapy trials to determine which patients benefit from regional nodal irradiation (RNI). METHODS AND MATERIALS: We obtained data from the NSABP (National Surgical Adjuvant Breast and Bowel Project) B-18, B-27, B-40, and B-41 clinical trials. B-40 and B-41 allowed RNI at physician's discretion. We evaluated locoregional recurrence (LRR), distant recurrence, disease-free survival, and overall survival (OS). Kaplan-Meier, Peto-Peto, χ2, Fisher exact, and Wilcoxon rank-sum tests were used for survival estimates and comparison. RESULTS: Median follow-up for B-18, B-27, B-40, and B-41 was 13.7, 9.7, 4.5, and 5.1 years, respectively, including 742, 2254, 1154, and 504 patients for analysis. On multivariable analysis, factors significantly associated with RNI included tumor size, ypN status, and tumor subtype; Hispanic patients were less likely to receive RNI. Patients with ypN+HER2+ disease who received RNI had improved OS. B-40 patients with ypN+HR+ disease had improved LRR. On multivariable analysis for the B-40 and B-41 study population, RNI was not associated with significantly improved OS, disease-free survival, distant recurrence, or LRR. CONCLUSIONS: RNI was associated with a clinical benefit for patients with ypN+HER2+ and ypN+HR+ disease. RNI was not significantly associated with a clinically beneficial outcome for the entire cohort. Prospective phase 3 clinical trials are needed to establish guidelines for patients who should receive RNI after neoadjuvant treatment, and action is necessary to eliminate the disparity in care delivery shown for Hispanic women.

Insurance Approval for Definitive Proton Therapy for Prostate Cancer.

PURPOSE: To determine factors that influence insurance approval for definitive proton therapy (PT) for prostate cancer. MATERIALS AND METHODS: Between 2014 and 2018, 1592 insured patients with localized prostate cancer were evaluated and recommended to undergo definitive PT; 547 patients (34.4%) had commercial insurance, whereas 1045 patients (65.6%) had Medicare/Medicaid. Of those with Medicare, 164 patients (15.7%) had Medicare alone; 677 (64.8%) had supplemental plans; and 204 (19.5%) had secondary commercial insurance. Insurance that "covered" PT for prostate cancer implied that it was an indication designated in the coverage policy. "Not covered" means that the insurance policy did not list prostate cancer as an indication for PT. Of all 1592 patients, 1263 (79.3%) belonged to plans that covered PT per policy. However, approval for PT was still required via medical review for 619 patients (38.9%), comparative dosimetry for 56 patients (3.5%), peer-to-peer discussion for 234 patients (14.7%), and administrative law judge hearings for 3 patients (<0.1%). Multivariate analyses of factors affecting approval were conducted, including risk group (low/intermediate versus high), insurance type (commercial versus Medicare/Medicaid), whether PT was included as a covered benefit under the plan (covered versus not covered), and time period (2014-16 versus 2017 versus 2018). RESULTS: On multivariate analysis, factors affecting PT approval for prostate treatment included coverage of PT per policy (97.1% had approval with insurance that covered PT versus 48.6% whose insurance did not cover PT; P < .001); insurance type (32.5% had approval with commercial insurance versus 97.4% with Medicare; P < .001); and time, with 877/987 patients (88.9%) approved between 2014 and 2016, 255/312 patients (81.7%) approved during 2017, and 255/293 patients (87.0%) approved thereafter (P = .02). Clinical factors, including risk group, had no bearing on insurance approval (P = .44). CONCLUSION: Proton insurance approval for prostate cancer has decreased, is most influenced by the type of insurance a patient belongs to, and is unrelated to clinical factors (risk group) in this study. More work is needed to help navigate appropriate access to care and to assist patients seeking definitive PT for prostate cancer treatment.

How 3 Academic Centers Prescribe Stereotactic Body Radiation Therapy for Primary Lung Cancer.

Stereotactic body radiation therapy (SBRT) is commonly used to treat early-stage, node-negative primary lung cancer, but society guidelines provide limited information regarding several technical aspects of SBRT, leading to potential variation in practice. In this report, we present the technical details used by 3 academic institutions when treating a solitary primary lung tumor up to 5 cm in dimension with curative-intent SBRT. We provide specifications outlined in major active or recently completed clinical trials. Among the participating institutions, we discovered multiple divergences in treatment parameters, including, but not limited to, prescription dose and desired degree of heterogeneity within the target volume. It is unclear to what extent these differences in parameters might affect tumor control or toxicity, but updated consensus guidelines addressing the relevant SBRT prescription details may help standardize practice patterns.

An algorithm for thoracic re-irradiation using biologically effective dose: a common language on how to treat in a "no-treat zone".

BACKGROUND: Re-irradiation (re-RT) is a technically challenging task for which few standardized approaches exist. This is in part due to the lack of a common platform to assess dose tolerance in relation to toxicity in the re-RT setting. To better address this knowledge gap and provide new tools for studying and developing thresholds for re-RT, we developed a novel algorithm that allows for anatomically accurate three-dimensional mapping of composite biological effective dose (BED) distributions from nominal doses (Gy). METHODS: The algorithm was designed to automatically convert nominal dose from prior treatment plans to corresponding BED value maps (voxel size 2.5 mm3 and α/ß of 3 for normal tissue, BED3). Following the conversion of each plan to a BED3 dose distribution, deformable registration was used to create a summed composite re-irradiation BED3 plan for each patient who received two treatments. A proof-of-principle analysis was performed on 38 re-irradiation cases of initial stereotactic ablative radiotherapy (SABR) followed by either re-SABR or chemoradiation for isolated locoregional recurrence of early-stage non-small cell lung cancer. RESULTS: Evaluation of the algorithm-generated maps revealed appropriate conversion of physical dose to BED at each voxel. Of 14 patients receiving repeat SABR, there was one case each of grade 3 chest wall pain (7%), pneumonitis (7%), and dyspnea (7%). Of 24 patients undergoing repeat fractionated radiotherapy, grade 3 events were limited to two cases each of pneumonitis and dyspnea (8%). Composite BED3 dosimetry for each patient who experienced grade 2-3 events is provided and may help guide development of precise cumulative dose thresholds for organs at risk in the re-RT setting. CONCLUSIONS: This novel algorithm successfully created a voxel-by-voxel composite treatment plan using BED values. This approach may be used to more precisely examine dosimetric predictors of toxicities and to establish more accurate normal tissue constraints for re-irradiation.

Salvage radiotherapy for primary refractory and relapsed diffuse large B-Cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, accounting for 30-40% of all non-Hodgkin lymphoma cases and presenting later in life, most often in the sixth decade. Although DLBCL is curable, long-term remission rates are only 60-80%. The most recent major advance in upfront therapy for DLBCL was the monoclonal anti-CD20 antibody rituximab, which was approved in the late 1990s; now, 25 years later, up to 40% of patients will experience primary refractory or relapsed disease, thereby underscoring the importance of salvage therapy. Radiation therapy can be highly effective in DLBCL, both initially as consolidation therapy and later as salvage therapy and is currently being explored in the context of immune and cellular therapies. The aim of this review is to examine the therapeutic approaches for relapsed or refractory DLBCL, with a focus on whether using radiation therapy as salvage therapy can improve the likelihood of cure.

Cost-Effectiveness Models of Proton Therapy for Head and Neck: Evaluating Quality and Methods to Date.

PURPOSE: Proton beam therapy (PBT) is associated with less toxicity relative to conventional photon radiotherapy for head-and-neck cancer (HNC). Upfront delivery costs are greater, but PBT can provide superior long-term value by minimizing treatment-related complications. Cost-effectiveness models (CEMs) estimate the relative value of novel technologies (such as PBT) as compared with the established standard of care. However, the uncertainties of CEMs can limit interpretation and applicability. This review serves to (1) assess the methodology and quality of pertinent CEMs in the existing literature, (2) evaluate their suitability for guiding clinical and economic strategies, and (3) discuss areas for improvement among future analyses. MATERIALS AND METHODS: PubMed was queried for CEMs specific to PBT for HNC. General characteristics, modeling information, and methodological approaches were extracted for each identified study. Reporting quality was assessed via the Consolidated Health Economic Evaluation Reporting Standards 24-item checklist, whereas methodologic quality was evaluated via the Philips checklist. The Cooper evidence hierarchy scale was employed to analyze parameter inputs referenced within each model. RESULTS: At the time of study, only 4 formal CEMs specific to PBT for HNC had been published (2005, 2013, 2018, 2020). The parameter inputs among these various Markov cohort models generally referenced older literature, excluding many clinically relevant complications and applying numerous hypothetical assumptions for toxicity states, incorporating inputs from theoretical complication-probability models because of limited availability of direct clinical evidence. Case numbers among study cohorts were low, and the structural design of some models inadequately reflected the natural history of HNC. Furthermore, cost inputs were incomplete and referenced historic figures. CONCLUSION: Contemporary CEMs are needed to incorporate modern estimates for toxicity risks and costs associated with PBT delivery, to provide a more accurate estimate of value, and to improve their clinical applicability with respect to PBT for HNC.

Referral Patterns and Treatment Delays in Medulloblastoma: A Large Academic Proton Center Experience.

PURPOSE: Patient travel time can cause treatment delays when providers and families decide to seek proton therapy. We examined whether travel distance or referral pattern (domestic versus international) affects time to radiation therapy and subsequent disease outcomes in patients with medulloblastoma at a large academic proton center. PATIENTS AND METHODS: Children with medulloblastoma treated at MD Anderson (MDA) with a protocol of proton beam therapy (PBT) between January 4, 2007, and June 25, 2014, were included in the analysis. The Wilcoxon rank-sum test was used to study the association between time to start of radiation and distance. Classification- and regression-tree analyses were used to explore binary thresholds for continuous covariates (ie, distance). Failure-free survival was defined as the time interval between end of radiation and failure or death. RESULTS: 96 patients were included in the analysis: 17 were international (18%); 19 (20%) were from Houston, Texas; 21 were from other cities inside Texas (21%); and 39 (41%) were from other US states. The median time from surgery to start of radiation was not significantly different for international patients (median = 1.45 months) compared with US patients (median = 1.15 months; P = .13). However, time from surgery to start of radiation was significantly longer for patients residing > 1716 km (> 1066 miles) from MDA (median = 1.31 months) than for patients residing ≤ 1716 km (≤ 1066 miles) from MDA (median = 1.05 months; P = .01). This 1- to 2-week delay (median = 7.8 days) did not affect failure-free survival (hazard ratio = 1.34; P = .43). CONCLUSION: We found that short delays in proton access can exist for patients traveling long distances to proton centers. However, in this study, treatment delays did not affect outcomes. This highlights the appropriateness of PBT in the face of travel coordination. Investment by proton centers in a rigorous intake process is justified to offer timely access to curative PBT.

Strategic Operational Redesign for Successfully Navigating Prior Authorization Barriers at a Large-Volume Proton Therapy Center.

PURPOSE: Prior authorization (PA) can be a resource-intensive barrier to oncologic care. To improve patient access and reduce delays at our large, academic proton therapy center, we implemented a novel payor-focused strategy to efficiently navigate the PA process while eliminating physician burden and reducing inappropriate denials. METHODS: In 2017, business operations were redesigned to better reflect the insurance process: (1) certified medical dosimetrists (CMDs), with their unique treatment expertise, replaced our historical PA team to function as an effective interface among physicians, patients, and payors; (2) a structured, tiered timeline was implemented to hold payors accountable to PA deadlines; and (3) our PA team provided administrative leadership with requisite insurance knowledge. PA outcomes were compared 6 months before and after the intervention. RESULTS: After implementation of this multifaceted strategy, the median time to successful appeal (after initial denial of coverage) decreased from 30 to 18 days (P < .001), and the total number of overturned denials increased by 56%. Because of the efficiency of the CMDs, full-time equivalents on the PA team actually decreased by 44%, translating to a 34% reduction in team personnel expenses. Internal referrals increased by 29%, attributable to optimized communication and diminished administrative burden for providers. New treatment starts also increased, resulting in a 37% larger patient census on treatment. CONCLUSION: Incorporating payor-focused strategies can improve patient access in a cost-effective manner while decreasing time and administrative burden associated with the PA process. These operational concepts can be adapted for other oncologic practice settings facing analogous PA-related obstacles.

An improved method for analyzing and reporting patterns of in-field recurrence after stereotactic ablative radiotherapy in early-stage non-small cell lung cancer.

INTRODUCTION: Patterns of local, regional, and distant failure after stereotactic ablative radiotherapy (SABR) for early-stage non-small cell lung cancer (NSCLC) have been widely reported. However, reliable methods for analyzing causes of local failure are lacking. We describe a method for analyzing and reporting patterns of in-field recurrence after SABR, incorporating dosimetric parameters from initial treatment plan as well as geometric information from diagnostic images at recurrence. MATERIAL AND METHODS: Diagnostic CT images at recurrence were registered with initial treatment planning images and radiation dose by deformable image registration. Recurrent gross tumor volume (rGTV) and centroid (geometric center of rGTV) were delineated. In-field failure was classified as centroids originating within the original planning target volume. Dose-volume histograms for each rGTV were used to further classify in-field recurrences as central high-dose (dose to 95% of rGTV [rGTVD95%] ≥95% of dose prescribed to PTV) or peripheral high-dose (rGTVD95% <95% of dose prescribed to PTV). RESULTS: 634 patients received SABR from 2004 to 2014 with 48 local recurrences. 35 of these had evaluable images with 16 in-field recurrences: 9 central high-dose, 6 peripheral high-dose, and 1 had both. Time to and volume of recurrence were not statistically different between central versus peripheral high-dose recurrences. However mean rGTV dose, mean centroid dose, and rGTVD95% were higher for central versus peripheral high-dose recurrences. CONCLUSION: We report a standardized method for analysis and classification of in-field recurrence after SABR. There were more central as opposed to peripheral high-dose recurrences, suggesting biological rather than technical issues underlying majority of in-field failures.

Definitive Management of Presumed Synchronous Early Stage Non-Small Cell Lung Cancers: Outcomes and Utility of Stereotactic Ablative Radiation Therapy.

PURPOSE: Management of synchronous early-stage non-small cell lung cancer (NSCLC) remains controversial because resection is not always feasible. This study evaluates efficacy and patterns of failure after SABR for synchronous early-stage NSCLC. METHODS AND MATERIALS: From 2005 to 2015, patients presenting with ≥2 synchronous NSCLC tumors (T1a-T2b) and receiving SABR to ≥1 lesion were reviewed. The most common prescriptions were 50 Gy in 4 or 70 Gy in 10 fractions. Patients underwent multidisciplinary management with workup including chest computed tomography and positron emission tomography/computed tomography, plus brain imaging and endoscopic bronchial ultrasound for most patients to rule out mediastinal and distant disease. Synchronous lesions were defined as multiple ipsilateral or contralateral intrapulmonary lesions diagnosed within 6 months. RESULTS: Of 912 patients treated with SABR for early-stage NSCLC at our institution, 82 (9%) presented with synchronous disease, with a total of 169 lesions. SABR was delivered to 142 lesions (84%), with 57 patients (69.5%) receiving SABR for all sites. Median overall survival (OS) and progression-free survival (PFS) were 5.1 and 2.7 years, respectively. At a median follow-up of 58 months, OS was 67% and 52% at 3 and 5 years, and corresponding PFS was 47% and 29%. Thirty-nine patients (48%) had progression, with 21 (26%) experiencing distant failure, and intralobar recurrence was among the first failure for 15 patients (18%). Of the 142 SABR-treated sites, these included 6 in-field (4%) and 4 marginal (3%) recurrences. There were no grade ≥3 adverse events. Among patients receiving SABR for all sites, there were no differences in OS (P = .946), PFS (P = .980), local control (P = .683), regional and distant control (P = .656), or toxicity (P = .791). On multivariable analysis, ipsilateral synchronous disease was associated with greater regional and distant failure (hazard ratio, 2.691; P = .025). CONCLUSIONS: Synchronous NSCLC can be managed with definitive local therapy. With high control rates and favorable outcomes, SABR is an effective and feasible treatment for synchronous early-stage NSCLC.

Predicting 5-Year Progression and Survival Outcomes for Early Stage Non-small Cell Lung Cancer Treated with Stereotactic Ablative Radiation Therapy: Development and Validation of Robust Prognostic Nomograms.

PURPOSE: Our purpose was to develop predictive nomograms for overall survival (OS), progression-free survival (PFS), and time-to-progression (TTP) at 5 years in patients with early-stage non-small cell lung cancer (ES-NSCLC) treated with stereotactic ablative radiation therapy (SABR). METHODS AND MATERIALS: The study cohort included 714 ES-NSCLC patients treated with SABR from 2004-2015 with median follow-up of 59 months, divided into training and testing sets (8:2), with the former used for nomogram development. The least absolute shrinkage and selection operator were initially employed to screen for predictors of OS, PFS, and TTP, and identified predictors were subsequently applied toward Cox proportional hazards regression modeling. Significant predictors (P < .05) on multivariable regression were then used to develop nomograms, which were validated via evaluation of concordance indexes (C-index) and calibration plots. Finally, Kaplan-Meier method and Gray's test were employed to compare and confirm differences in outcomes among various groups and explore prognostic factors associated with local versus distant disease progression. RESULTS: Significant predictors of both OS and PFS at 5 years included age, sex, Charlson comorbidity index, diffusing capacity of carbon monoxide, systemic immune-inflammation index, and tumor size (P ≤ .01 for all). Eastern Cooperative Oncology Group performance status predicted for OS as well (P = .01), and both tumor size (P < .01) and minimum biological equivalent dose to 95% of planning target volume (PTV D95 BED10; P < .01) were predictive of TTP. The C-indexes for the OS, PFS, and TTP nomograms were 0.73, 0.68, and 0.60 in the training data set and 0.72, 0.66, and 0.59 in the testing data set, respectively. Tumor size > 2.45 cm and PTV D95 BED10 < 113 Gy were significantly associated with both local and distant progression. CONCLUSIONS: These prognostic nomograms can accurately predict for OS, PFS, and TTP at 5 years after SABR for ES-NSCLC and may thus help identify high-risk patients who could benefit from additional systemic therapy.

Commercial Insurance Coverage of Advanced Radiation Therapy Techniques Compared With American Society for Radiation Oncology Model Policies.

PURPOSE: This study aimed to compare and contrast the American Society for Radiation Oncology (ASTRO) model policies (MPs) for intensity modulated radiation therapy (IMRT), stereotactic radiosurgery (SRS), stereotactic ablative radiation therapy (SABR), and proton beam therapy (PBT) with the coverage policies constructed by 5 of the largest publicly available commercial insurers throughout the United States (ie, Aetna, Anthem, Cigna, Humana, and United Healthcare). METHODS AND MATERIALS: Appropriate indications for IMRT, SRS, SABR, and PBT by disease site (and particular clinical setting thereof) were extracted from the most recently published ASTRO MPs and published coverage policies (2019 editions) of the 5 carriers. After tabulation, concordance between ASTRO MPs and insurance policies were calculated for each modality. RESULTS: All 5 insurer policies supported IMRT for neoplasms of the central nervous system, head/neck, hepatopancreaticobiliary, anal, and prostate cancers. The least covered diseases were retroperitoneal tumors (n = 0 carriers) and bladder cancer (n = 1). For SRS, all carriers covered benign brain tumors, brain metastases, arteriovenous malformations, and trigeminal neuralgia. None of the insurance carriers covered SRS for medically refractory epilepsy. For SABR, primary liver, lung, and low- or intermediate-risk prostate cancer were covered by all insurers, and none allowed SABR for primary biliary neoplasms. Only one insurance carrier each covered SABR for primary/metastatic adrenal disease and primary renal cancer. All carriers approved PBT for ocular melanoma, skull base tumors, and pediatric malignancies. The ASTRO MPs listed 4 PBT scenarios (ie, spinal disease, retroperitoneal sarcoma, head/neck neoplasms, and patients with genetic radiosensitivity syndromes) not covered by any insurer. Concordance between insurance carriers and ASTRO MPs was 67.8% for IMRT, 72.0% for SRS, 58.4% for SABR, and 41.8% for PBT (P = .005). CONCLUSIONS: Coverage guidelines for IMRT, SRS, SABR, and PBT vary across 5 major insurance providers and may be substantially discordant compared with ASTRO coverage guidelines. There remain several specific areas where ongoing and future dialogues between ASTRO members, payers, and policymakers remain essential.