Case report: Molecular profiling facilitates the diagnosis of a challenging case of lung cancer with choriocarcinoma features.

Accurate diagnoses are crucial in determining the most effective treatment across different cancers. In challenging cases, morphology-based traditional pathology methods have important limitations, while molecular profiling can provide valuable information to guide clinical decisions. We present a 35-year female with lung cancer with choriocarcinoma features. Her disease involved the right lower lung, brain, and thoracic lymph nodes. The pathology from brain metastasis was reported as "metastatic choriocarcinoma" (a germ cell tumor) by local pathologists. She initiated carboplatin and etoposide, a regimen for choriocarcinoma. Subsequently, her case was assessed by pathologists from an academic cancer center, who gave the diagnosis of "adenocarcinoma with aberrant expression of ß-hCG" and finally pathologists at our hospital, who gave the diagnosis of "poorly differentiated carcinoma with choriocarcinoma features". Genomic profiling detected a KRAS G13R mutation and transcriptomics profiling was suggestive of lung origin. The patient was treated with carboplatin/paclitaxel/ipilimumab/nivolumab followed by consolidation radiation therapy. She had no evidence of progression to date, 16 months after the initial presentation. The molecular profiling could facilitate diagnosing of challenging cancer cases. In addition, chemoimmunotherapy and local consolidation radiation therapy may provide promising therapeutic options for patients with lung cancer exhibiting choriocarcinoma features.

American Radium Society Appropriate Use Criteria for Unresectable Locally Advanced Non-Small Cell Lung Cancer.

Importance: The treatment of locally advanced non-small cell lung cancer (LA-NSCLC) has been informed by more than 5 decades of clinical trials and other relevant literature. However, controversies remain regarding the application of various radiation and systemic therapies in commonly encountered clinical scenarios. Objective: To develop case-referenced consensus and evidence-based guidelines to inform clinical practice in unresectable LA-NSCLC. Evidence Review: The American Radium Society (ARS) Appropriate Use Criteria (AUC) Thoracic Committee guideline is an evidence-based consensus document assessing various clinical scenarios associated with LA-NSCLC. A systematic review of the literature with evidence ratings was conducted to inform the appropriateness of treatment recommendations by the ARS AUC Thoracic Committee for the management of unresectable LA-NSCLC. Findings: Treatment appropriateness of a variety of LA-NSCLC scenarios was assessed by a consensus-based modified Delphi approach using a range of 3 points to 9 points to denote consensus agreement. Committee recommendations were vetted by the ARS AUC Executive Committee and a 2-week public comment period before official approval and adoption. Standard of care management of good prognosis LA-NSCLC consists of combined concurrent radical (60-70 Gy) platinum-based chemoradiation followed by consolidation durvalumab immunotherapy (for patients without progression). Planning and delivery of locally advanced lung cancer radiotherapy usually should be performed using intensity-modulated radiotherapy techniques. A variety of palliative and radical fractionation schedules are available to treat patients with poor performance and/or pulmonary status. The salvage therapy for a local recurrence after successful primary management is complex and likely requires both multidisciplinary input and shared decision-making with the patient. Conclusions and Relevance: Evidence-based guidance on the management of various unresectable LA-NSCLC scenarios is provided by the ARS AUC to optimize multidisciplinary patient care for this challenging patient population.

Survival outcomes and toxicity of adjuvant immunotherapy after definitive concurrent chemotherapy with proton beam radiation therapy for patients with inoperable locally advanced non-small cell lung carcinoma.

INTRODUCTION: Adjuvant immunotherapy (IO) following concurrent chemotherapy and photon radiation therapy confers an overall survival (OS) benefit for patients with inoperable locally advanced non-small cell lung carcinoma (LA-NSCLC); however, outcomes of adjuvant IO after concurrent chemotherapy with proton beam therapy (CPBT) are unknown. We investigated OS and toxicity after CPBT with adjuvant IO versus CPBT alone for inoperable LA-NSCLC. MATERIALS AND METHODS: We analyzed 354 patients with LA-NSCLC who were prospectively treated with CPBT with or without adjuvant IO from 2009 to 2021. Optimal variable ratio propensity score matching (PSM) matched CPBT with CPBT + IO patients. Survival was estimated with the Kaplan-Meier method and compared with log-rank tests. Multivariable Cox proportional hazards regression evaluated the effect of IO on disease outcomes. RESULTS: Median age was 70 years; 71 (20%) received CPBT + IO and 283 (80%) received CPBT only. After PSM, 71 CPBT patients were matched with 71 CPBT + IO patients. Three-year survival rates for CPBT + IO vs CPBT were: OS 67% vs 30% (P < 0.001) and PFS 59% vs 35% (P = 0.017). Three-year LRFS (P = 0.137) and DMFS (P = 0.086) did not differ. Receipt of adjuvant IO was a strong predictor of OS (HR 0.40, P = 0.001) and PFS (HR 0.56, P = 0.030), but not LRFS (HR 0.61, P = 0.121) or DMFS (HR 0.61, P = 0.136). There was an increased incidence of grade ≥3 esophagitis in the CPBT-only group (6% CPBT + IO vs 17% CPBT, P = 0.037). CONCLUSION: This study, one of the first to investigate CPBT followed by IO for inoperable LA-NSCLC, showed that IO conferred survival benefits with no increased rates of toxicity.

Optimizing Outpatient Radiation Oncology Consult Workflow by Using Time-Driven Activity-Based Costing: Efficiency and Financial Impacts.

PURPOSE: Clinical efficiency is a key component of value-based health care. Our objective here was to identify workflow inefficiencies by using time-driven activity-based costing (TDABC) and evaluate the implementation of a new clinical workflow in high-volume outpatient radiation oncology clinics. METHODS: Our quality improvement study was conducted with the Departments of GI, Genitourinary (GU), and Thoracic Radiation Oncology at a large academic cancer center and four community network sites. TDABC was used to create process maps and optimize workflow for outpatient consults. Patient encounter metrics were captured with a real-time status function in the electronic medical record. Time metrics were compared using Mann-Whitney U tests. RESULTS: Individual patient encounter data for 1,328 consults before the intervention and 1,234 afterward across all sections were included. The median overall cycle time was reduced by 21% in GI (19 minutes), 18% in GU (16 minutes), and 12% at the community sites (9 minutes). The median financial savings per consult were $52 in US dollars (USD) for the GI, $33 USD for GU, $30 USD for thoracic, and $42 USD for the community sites. Patient satisfaction surveys (from 127 of 228 patients) showed that 99% of patients reported that their providers spent adequate time with them and 91% reported being seen by a care provider in a timely manner. CONCLUSION: TDABC can effectively identify opportunities to improve clinical efficiency. Implementing workflow changes on the basis of our findings led to substantial reductions in overall encounter cycle times across several departments, as well as high patient satisfaction and significant financial savings.

Implementation and Efficacy of a Large-Scale Radiation Oncology Case-Based Peer-Review Quality Program across a Multinational Cancer Network.

PURPOSE: With expansion of academic cancer center networks across geographically-dispersed sites, ensuring high-quality delivery of care across all network affiliates is essential. We report on the characteristics and efficacy of a radiation oncology peer-review quality assurance (QA) system implemented across a large-scale multinational cancer network. METHODS AND MATERIALS: Since 2014, weekly case-based peer-review QA meetings have been standard for network radiation oncologists with radiation oncology faculty at a major academic center. This radiotherapy (RT) QA program involves pre-treatment peer-review of cases by disease site, with disease-site subspecialized main campus faculty members. This virtual QA platform involves direct review of the proposed RT plan as well as supporting data, including relevant pathology and imaging studies for each patient. Network RT plans were scored as being concordant or nonconcordant based on national guidelines, institutional recommendations, and/or expert judgment when considering individual patient-specific factors for a given case. Data from January 1, 2014, through December 31, 2019, were aggregated for analysis. RESULTS: Between 2014 and 2019, across 8 network centers, a total of 16,601 RT plans underwent peer-review. The network-based peer-review case volume increased over the study period, from 958 cases in 2014 to 4,487 in 2019. A combined global nonconcordance rate of 4.5% was noted, with the highest nonconcordance rates among head-and-neck cases (11.0%). For centers that joined the network during the study period, we observed a significant decrease in the nonconcordance rate over time (3.1% average annual decrease in nonconcordance, P = 0.01); among centers that joined the network prior to the study period, nonconcordance rates remained stable over time. CONCLUSIONS: Through a standardized QA platform, network-based multinational peer-review of RT plans can be achieved. Improved concordance rates among newly added network affiliates over time are noted, suggesting a positive impact of network membership on the quality of delivered cancer care.

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.

The American Brachytherapy Society and Indian Brachytherapy Society consensus statement for the establishment of high-dose-rate brachytherapy programs for gynecological malignancies in low- and middle-income countries.

PURPOSE: The global cervical cancer burden is disproportionately high in low- and middle-income countries (LMICs), and outcomes can be governed by the accessibility of appropriate screening and treatment. High-dose-rate (HDR) brachytherapy plays a central role in cervical cancer treatment, improving local control and overall survival. The American Brachytherapy Society (ABS) and Indian Brachytherapy Society (IBS) collaborated to provide this succinct consensus statement guiding the establishment of brachytherapy programs for gynecological malignancies in resource-limited settings. METHODS AND MATERIALS: ABS and IBS members with expertise in brachytherapy formulated this consensus statement based on their collective clinical experience in LMICs with varying levels of resources. RESULTS: The ABS and IBS strongly encourage the establishment of HDR brachytherapy programs for the treatment of gynecological malignancies. With the consideration of resource variability in LMICs, we present 15 minimum component requirements for the establishment of such programs. Guidance on these components, including discussion of what is considered to be essential and what is considered to be optimal, is provided. CONCLUSIONS: This ABS/IBS consensus statement can guide the successful and safe establishment of HDR brachytherapy programs for gynecological malignancies in LMICs with varying levels of resources.

Feasibility of quantitative diffusion-weighted imaging during intra-procedural MRI-guided brachytherapy of locally advanced cervical and vaginal cancers.

PURPOSE: To determine the feasibility of quantitative apparent diffusion coefficient (ADC) acquisition during magnetic resonance imaging-guided brachytherapy (MRgBT) using reduced field-of-view (rFOV) diffusion-weighted imaging (DWI). METHODS AND MATERIALS: T2-weighted (T2w) MR and full-FOV single-shot echo planar (ssEPI) DWI were acquired in 7 patients with cervical or vaginal malignancy at baseline and prior to brachytherapy, while rFOV-DWI was acquired during MRgBT following brachytherapy applicator placement. The gross target volume (GTV) was contoured on the T2w images and registered to the ADC map. Voxels at the GTV's maximum Maurer distance comprised a central sub-volume (GTVcenter). Contour ADC mean and standard deviation were compared between timepoints using repeated measures ANOVA. RESULTS: ssEPI-DWI mean ADC increased between baseline and prebrachytherapy from 1.03 ± 0.18 10-3 mm2/s to 1.34 ± 0.28 10-3 mm2/s for the GTV (p = 0.06) and from 0.84 ± 0.13 10-3 mm2/s to 1.26 ± 0.25 10-3 mm2/s at the level of the GTVcenter (p = 0.03), consistent with early treatment response. rFOV-DWI during MRgBT demonstrated mean ADC values of 1.28 ± 0.14 10-3 mm2/s and 1.28 ± 0.19 10-3 mm2/s for the GTV and GTVcenter, respectively (p = 0.02 and p = 0.03 relative to baseline). No significant differences were observed between ssEPI-DWI and rFOV-DWI ADC measurements. CONCLUSIONS: Quantitative ADC measurement in the setting of MRI guided brachytherapy implant placement for cervical and vaginal cancers is feasible using rFOV-DWI, with comparable mean ADC comparable to prebrachytherapy ssEPI-DWI, and may enable MRI-guided radiotherapy targeting of low ADC, radiation resistant sub-volumes of tumor.

American Radium Society Appropriate Use Criteria for Radiation Therapy in the Multidisciplinary Management of Thymic Carcinoma.

Importance: Thymic carcinoma is rare, and its oncologic management is controversial due to a paucity of prospective data. For this reason, multidisciplinary consensus guidelines are crucial to guide oncologic management. Objective: To develop expert multidisciplinary consensus guidelines on the management of common presentations of thymic carcinoma. Evidence Review: Case variants spanning the spectrum of stage I to IV thymic carcinoma were developed by the 15-member multidisciplinary American Radium Society (ARS) Thoracic Appropriate Use Criteria (AUC) expert panel to address management controversies. A comprehensive review of the English-language medical literature from 1980 to 2021 was performed to inform consensus guidelines. Variants and procedures were evaluated by the panel using modified Delphi methodology. Agreement/consensus was defined as less than or equal to 3 rating points from median. Consensus recommendations were then approved by the ARS Executive Committee and subject to public comment per established ARS procedures. Findings: The ARS Thoracic AUC panel identified 89 relevant references and obtained consensus for all procedures evaluated for thymic carcinoma. Minimally invasive thymectomy was rated as usually inappropriate (regardless of stage) due to the infiltrative nature of thymic carcinomas. There was consensus that conventionally fractionated radiation (1.8-2 Gy daily) to a dose of 45 to 60 Gy adjuvantly and 60 to 66 Gy in the definitive setting is appropriate and that elective nodal irradiation is inappropriate. For radiation technique, the panel recommended use of intensity-modulated radiation therapy or proton therapy (rather than 3-dimensional conformal radiotherapy) to reduce radiation exposure to the heart and lungs. Conclusions and Relevance: The ARS Thoracic AUC panel has developed multidisciplinary consensus guidelines for various presentations of thymic carcinoma, perhaps the most well referenced on the topic.

Benchmarking Outcomes for Molecularly Characterized Synchronous Oligometastatic Non-Small-Cell Lung Cancer Reveals EGFR Mutations to Be Associated With Longer Overall Survival.

PURPOSE: Local consolidative therapy (LCT) for patients with synchronous oligometastatic non-small-cell lung cancer is an evolving treatment strategy, but outcomes following LCT stratified by genetic mutations have not been reported. We sought to identify genomic associations with overall survival (OS) and progression-free survival (PFS) for these patients. METHODS: We identified all patients presenting between 2000 and 2017 with stage IV non-small-cell lung cancer and ≤ 3 synchronous metastatic sites. Patients were grouped according to mutational statuses. Primary outcomes included OS and PFS following initial diagnosis. RESULTS: Of 194 included patients, 121 received comprehensive LCT to all sites of disease with either surgery or radiation. TP53 mutations were identified in 40 of 78 (55%), KRAS in 32 of 95 (34%), EGFR in 24 of 109 (22%), and STK11 in nine of 77 (12%). At median follow-up of 96 months, median OS and PFS were 26 (95% CI, 23 to 31) months and 11 (95% CI, 9 to 13) months, respectively. On multivariable analysis, patients with EGFR mutations had lower mortality risk (hazard ratio [HR], 0.53; 95% CI, 0.29 to 0.98; P = .044) compared with wild-type patients, and patients with STK11 mutations had higher risk of progression or mortality (HR, 2.32; 95% CI, 1.12 to 4.79; P = .023) compared with wild-type patients. TP53 and KRAS mutations were not associated with OS or PFS. Among 71 patients with known EGFR mutational status who received comprehensive LCT, EGFR mutations were associated with lower mortality compared with wild-type (HR, 0.45; 95% CI, 0.22 to 0.94; P = .032). CONCLUSION: When compared with wild-type patients, those with EGFR and STK11 mutations had longer OS and shorter PFS, respectively. EGFR mutations were associated with longer OS among oligometastatic patients treated with comprehensive LCT in addition to systemic therapy.

Association of Driver Oncogene Variations With Outcomes in Patients With Locally Advanced Non-Small Cell Lung Cancer Treated With Chemoradiation and Consolidative Durvalumab.

Importance: Consolidative durvalumab after definitive chemoradiation for unresectable locally advanced non-small cell lung cancer (NSCLC) can significantly improve progression-free survival (PFS) and overall survival (OS), as shown in the PACIFIC trial. However, whether patients with driver variations derive equal benefit from this regimen remains unclear. Objectives: To compare outcomes of patients with locally advanced NSCLC with and without driver variations treated with the PACIFIC regimen. Design, Setting, and Participants: This cohort study examined 104 patients with unresectable locally advanced NSCLC with mutational profiling treated at a tertiary cancer center with definitive chemoradiation and consolidative durvalumab from June 2017 through May 2020. Patients with recurrent disease or those receiving postoperative therapy were excluded. Outcomes were analyzed with Kaplan-Meier and multivariate regression analyses. Exposures: Patients were grouped according to the presence of non-KRAS driver variations (EGFR exon 19 deletion, EGFR exon 20 insertion, EGFR exon 21 mutation [L858R], ERBB2 exon 20 insertion, EML4-ALK fusion, MET exon 14 skipping, NTRK2 fusion), KRAS driver variations, or no driver variations. Main Outcomes and Measures: The primary outcomes were PFS, OS, and second progression-free survival (PFS2) times. Results: The 104 patients had a median (IQR) age of 65.1 (9.8) years, with 55 females (53%) and 85 former or current smokers (88%). There were 43 patients (41%) with driver variations with a median PFS time of 8.4 months vs 40.1 months for patients without driver variations (hazard ratio [HR], 2.75; 95% CI, 1.64-4.62; log-rank P < .001). Both patients with non-KRAS and KRAS driver variations had worse PFS. No difference in OS was found between patients with and without driver variations (log rank P = .24). Among the 63 patients who developed progressive disease, those with non-KRAS driver variations had a median PFS2 time of 13.7 months vs 4.4 months for all other patients (HR, 0.37; 95% CI, 0.21-0.64; log-rank P = .001). Rates of overall grade 2 toxic effects or higher did not differ by driver mutation status. Conclusions and Relevance: In this cohort study, driver variations in patients with unresectable locally advanced NSCLC were associated with significantly shorter PFS time after definitive chemoradiation and consolidative durvalumab. These findings suggest the need to consider additional or alternative treatment options to the PACIFIC regimen for patients with driver variations.

Barriers and Facilitators of Implementing Automated Radiotherapy Planning: A Multisite Survey of Low- and Middle-Income Country Radiation Oncology Providers.

PURPOSE: Global access to radiotherapy (RT) is inequitable, with obstacles to implementing modern technologies in low- and middle- income countries (LMICs). The Radiation Planning Assistant (RPA) is a web-based automated RT planning software package intended to increase accessibility of high-quality RT planning. We surveyed LMIC RT providers to identify barriers and facilitators of future RPA deployment and uptake. METHODS: RT providers underwent a pilot RPA teaching session in sub-Saharan Africa (Botswana, South Africa, and Tanzania) and Central America (Guatemala). Thirty providers (30 of 33, 90.9% response rate) participated in a postsession survey. RESULTS: Respondents included physicians (n = 10, 33%), physicists (n = 9, 30%), dosimetrists (n = 8, 27%), residents/registrars (n = 1, 3.3%), radiation therapists (n = 1, 3.3%), and administrators (n = 1, 3.3%). Overall, 86.7% expressed interest in RPA; more respondents expected that RPA would be usable in 2 years (80%) compared with now (60%). Anticipated barriers were lack of reliable internet (80%), potential subscription fees (60%), and need for functionality in additional disease sites (48%). Expected facilitators included decreased workload (80%), decreased planning time (72%), and ability to treat more patients (64%). Forty-four percent anticipated that RPA would help transition from 2-dimensional to 3-dimensional techniques and 48% from 3-dimensional to intensity-modulated radiation treatment. Of a maximum acceptability/feasibility score of 60, physicians (45.6, standard deviation [SD] = 7.5) and dosimetrists (44.3, SD = 9.1) had lower scores than the mean for all respondents (48.3, SD = 7.7) although variation in scores by roles was not significantly different (P = .21). CONCLUSION: These data provide an early assessment and create an initial framework to identify stakeholder needs and establish priorities to address barriers and promote facilitators of RPA deployment and uptake across global sites, as well as to tailor to needs in LMICs.

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.

Care Patterns for Stereotactic Radiosurgery in Small Cell Lung Cancer Brain Metastases.

INTRODUCTION: The historical standard of care for brain metastases (BMs) from small cell lung cancer (SCLC) has been whole-brain radiotherapy (WBRT). However, there is growing interest in upfront stereotactic radiosurgery (SRS) for select SCLC patients. MATERIALS AND METHODS: We invited United State-based Radiation Oncologists (ROs) via email to answer an anonymous survey using a branching logic system addressing their use of SRS and WBRT for SCLC BMs. Wilcoxon rank-sum test and Fisher's exact test were used to compare differences in continuous and categorical variables, respectively. Multivariable logistic regression analyses were fitted for outcome variables including covariates with P < .10 obtained on univariable analysis. RESULTS: In total, 309 ROs completed the survey and 290 (95.7%) reported that they would consider SRS for SCLC BMs under certain clinical circumstances. Across patient characteristics, the number of BMs was the most heavily weighted factor (mean 4.3/5 in importance), followed by performance status, cognitive function, and response to prior therapy. Fewer BMs were correlated with increased SRS use (55.8% offered SRS "very frequently" [>75% of cases] or "often" [51%-75% of cases] for 1 BM vs. 1.1% for >10 BM, P < .001). In situations where WBRT was preferred, concern for rapid intracranial progression (45.3%) and lack of high-level data (36.9%) were the most important factors. The majority (60.6%) were aware of a large recent international retrospective analysis (the FIRE-SCLC study) reporting similar OS between upfront SRS and WBRT; awareness of this study was the only respondent variable predictive of SRS use for limited BMs (19.2% of those aware of the study preferring SRS for limited [≤4] BMs before vs. 61% preferring SRS after the publication, P < .001). The majority of respondents (88.2%) expressed a willingness to enroll patients on a recently opened recently opened randomized trial, NRG-CC009, comparing SRS versus hippocampal-avoidance WBRT. CONCLUSIONS: In the first survey of SRS for SCLC BMs, we observed a high level of physician openness to upfront SRS in SCLC, particularly for patients with limited numbers of BMs, as well as significant interest in generating prospective randomized data to clarify the role of SRS in this population.

High-dose irradiation in combination with non-ablative low-dose radiation to treat metastatic disease after progression on immunotherapy: Results of a phase II trial.

AIM: To report early findings from a phase II trial of high-dose radiotherapy (HD-RT) with or without low-dose RT (LD-RT) for metastatic cancer. METHODS: Eligible patients had metastatic disease that progressed on immunotherapy within 6 months. Patients were given either HD-RT (20-70 Gy total; 3-12.5 Gy/f), or HD-RT + LD-RT (0.5-2 Gy/f up to 1-10 Gy total) to separate lesions, with continued immunotherapy. Radiographic response was assessed per RECIST 1.1 and Immune-Related Response Criteria (irRC). Primary endpoints: (1) 4-month disease control (DCR, complete/partial response [CR/PR] or stable disease [SD]) or an overall response (ORR, CR/PR) at any point in ≥10% of patients, per RECIST 1.1; (2) dose-limiting toxicity within 3 months not exceeding 30%. Secondary endpoint was lesion-specific response. RESULTS: Seventy-four patients (NSCLC, n = 38; melanoma n = 21) were analyzed (39 HD-RT and 35 HD-RT + LD-RT). The median follow-up time was 13.6 months. The primary endpoint was met for 72 evaluable patients, with a 4-month DCR of 42% (47% [16/34] vs. 37% [14/38] in HD-RT + LD-RT vs. HD-RT, P = 0.38), and 19% ORR at any time (26% [9/34] vs. 13% [5/38] in HD-RT + LD-RT vs. HD-RT, P = 0.27). Three patients had toxicity ≥grade 3. LD-RT lesion response (53%) was improved compared to nonirradiated lesions in HD-RT + LD-RT (23%, P = 0.002) and HD-RT (11%, P < 0.001). T- and NK cell infiltration was enhanced in lesions treated with LD-RT. CONCLUSIONS: HD-RT plus LD-RT safely improved lesion-specific response in patients with immune resistant solid tumors by promoting infiltration of effector immune cells into the tumor microenvironment.

Work Outcomes after Intensity-Modulated Proton Therapy (IMPT) versus Intensity-Modulated Photon Therapy (IMRT) for Oropharyngeal Cancer.

PURPOSE: We compared work outcomes in patients with oropharyngeal cancer (OPC), randomized to intensity-modulated proton (IMPT) versus intensity-modulated photon therapy (IMRT) for chemoradiation therapy (CRT). PATIENTS AND METHODS: In 147 patients with stage II-IVB squamous cell OPC participating in patient-reported outcomes assessments, a prespecified secondary aim of a randomized phase II/III trial of IMPT (n = 69) versus IMRT (n = 78), we compared absenteeism, presenteeism (i.e., the extent to which an employee is not fully functional at work), and work productivity losses. We used the work productivity and activity impairment questionnaire at baseline (pre-CRT), at the end of CRT, and at 6 months, 1 year, and 2 years. A one-sided Cochran-Armitage test was used to analyze within-arm temporal trends, and a χ2 test was used to compare between-arm differences. Among working patients, at each follow-up point, a 1-sided Wilcoxon rank-sum test was used to compare work-productivity scores. RESULTS: Patient characteristics in IMPT versus IMRT arms were similar. In the IMPT arm, within-arm analysis demonstrated that an increasing proportion of patients resumed working after IMPT, from 60% (40 of 67) pre-CRT and 71% (30 of 42) at 1 year to 78% (18 of 23) at 2 years (P = 0.025). In the IMRT arm, the proportion remained stable, with 57% (43 of 76) pre-CRT, 54% (21 of 39) at 1 year, and 52% (13 of 25) working at 2 years (P = 0.47). By 2 years after CRT, the between-arm difference between patients who had IMPT and those who had IMRT trended toward significance (P = 0.06). Regardless of treatment arm, among working patients, the most severe work impairments occurred from treatment initiation to the end of CRT, with significant recovery from absenteeism, presenteeism, and productivity impairments by the 2-year follow-up (P < 0.001 for all). Higher magnitudes of recovery from absenteeism (at 1 year, P = 0.05; and at 2 years, P = 0.04) and composite work impairment scores (at 1 year, P = 0.04; and at 2 years, P = 0.04) were seen in patients treated with IMPT versus those treated with IMRT. CONCLUSION: In patients with OPC receiving curative CRT, patients randomized to IMPT demonstrated increasing work and productivity recovery trends. Studies are needed to identify mechanisms underlying head and neck CRT treatment causing work disability and impairment.

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.

Activity-Based Costing of Intensity-Modulated Proton versus Photon Therapy for Oropharyngeal Cancer.

PURPOSE: In value-based health care delivery, radiation oncologists need to compare empiric costs of care delivery with advanced technologies, such as intensity-modulated proton therapy (IMPT) and intensity-modulated radiation therapy (IMRT). We used time-driven activity-based costing (TDABC) to compare the costs of delivering IMPT and IMRT in a case-matched pilot study of patients with newly diagnosed oropharyngeal (OPC) cancer. MATERIALS AND METHODS: We used clinicopathologic factors to match 25 patients with OPC who received IMPT in 2011-12 with 25 patients with OPC treated with IMRT in 2000-09. Process maps were created for each multidisciplinary clinical activity (including chemotherapy and ancillary services) from initial consultation through 1 month of follow-up. Resource costs and times were determined for each activity. Each patient-specific activity was linked with a process map and TDABC over the full cycle of care. All calculated costs were normalized to the lowest-cost IMRT patient. RESULTS: TDABC costs for IMRT were 1.00 to 3.33 times that of the lowest-cost IMRT patient (mean ± SD: 1.65 ± 0.56), while costs for IMPT were 1.88 to 4.32 times that of the lowest-cost IMRT patient (2.58 ± 0.39) (P < .05). Although single-fraction costs were 2.79 times higher for IMPT than for IMRT (owing to higher equipment costs), average full cycle cost of IMPT was 1.53 times higher than IMRT, suggesting that the initial cost increase is partly mitigated by reductions in costs for other, non-RT supportive health care services. CONCLUSIONS: In this matched sample, although IMPT was on average more costly than IMRT primarily owing to higher equipment costs, a subset of IMRT patients had similar costs to IMPT patients, owing to greater use of supportive care resources. Multidimensional patient outcomes and TDABC provide vital methodology for defining the value of radiation therapy modalities.

Chemoradiation versus radiation alone in stage IIIB cervical cancer patients with or without human immunodeficiency virus.

OBJECTIVE: Cervical cancer remains the most common cancer among women in sub-Saharan Africa and is also a leading cause of cancer related deaths among these women. The benefit of chemoradiation in comparison with radiation alone for patients with stage IIIB disease has not been evaluated prospectively in women living with human immunodeficiency virus (HIV). We assessed the survival of chemoradiation versus radiation alone among stage IIIB cervical cancer patients based on HIV status. METHODS: Between February 2013 and June 2018, patients with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IIIB cervical cancer with or without HIV and treated with chemoradiation or radiation alone, were prospectively enrolled in an observational cohort study. Overall survival was evaluated using the Kaplan-Meier method. Cox proportional hazards modeling was used to analyze associations with survival. RESULTS: Among 187 patients, 63% (n=118) of women had co-infection with HIV, and 48% (n=69) received chemoradiation. Regardless of HIV status, patients who received chemoradiation had improved 2 year overall survival compared with those receiving radiation alone (59% vs 41%, p<0.01), even among women living with HIV (60% vs 38%, p=0.02). On multivariable Cox regression analysis, including all patients regardless of HIV status, 2 year overall survival was associated with receipt of chemoradiation (hazard ratio (HR) 0.63, p=0.04) and total radiation dose ≥80 Gy (HR 0.57, p=0.02). Among patients who received an adequate radiation dose of ≥80 Gy, adjusted overall survival rates were similar between chemoradiation versus radiation alone groups (HR 1.07; p=0.90). However, patients who received an inadequate radiation dose of <80 Gy, adjusted survival was significantly higher in chemoradiation versus radiation alone group (HR 0.45, p=0.01). CONCLUSIONS: Addition of chemotherapy to standard radiation improved overall survival, regardless of HIV status, and is even more essential in women who cannot receive full doses of radiation.