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.

Stereotactic ablative radiotherapy with or without immunotherapy for early-stage or isolated lung parenchymal recurrent node-negative non-small-cell lung cancer: an open-label, randomised, phase 2 trial.

BACKGROUND: Stereotactic ablative radiotherapy (SABR) is the standard treatment for medically inoperable early-stage non-small-cell lung cancer (NSCLC), but regional or distant relapses, or both, are common. Immunotherapy reduces recurrence and improves survival in people with stage III NSCLC after chemoradiotherapy, but its utility in stage I and II cases is unclear. We therefore conducted a randomised phase 2 trial of SABR alone compared with SABR with immunotherapy (I-SABR) for people with early-stage NSCLC. METHODS: We did an open-label, randomised, phase 2 trial comparing SABR to I-SABR, conducted at three different hospitals in TX, USA. People aged 18 years or older with histologically proven treatment-naive stage IA-IB (tumour size ≤4 cm, N0M0), stage IIA (tumour size ≤5 cm, N0M0), or stage IIB (tumour size >5 cm and ≤7 cm, N0M0) as per the American Joint Committee on Cancer version 8 staging system or isolated parenchymal recurrences (tumour size ≤7 cm) NSCLC (TanyNanyM0 before definitive surgery or chemoradiotherapy) were included in this trial. Participants were randomly assigned (1:1; using the Pocock & Simon method) to receive SABR with or without four cycles of nivolumab (480 mg, once every 4 weeks, with the first dose on the same day as, or within 36 h after, the first SABR fraction). This trial was unmasked. The primary endpoint was 4-year event-free survival (local, regional, or distant recurrence; second primary lung cancer; or death). Analyses were both intention to treat (ITT) and per protocol. This trial is registered with ClinicalTrials.gov (NCT03110978) and is closed to enrolment. FINDINGS: From June 30, 2017, to March 22, 2022, 156 participants were randomly assigned, and 141 participants received assigned therapy. At a median 33 months' follow-up, I-SABR significantly improved 4-year event-free survival from 53% (95% CI 42-67%) with SABR to 77% (66-91%; per-protocol population, hazard ratio [HR] 0·38; 95% CI 0·19-0·75; p=0·0056; ITT population, HR 0·42; 95% CI 0·22-0·80; p=0·0080). There were no grade 3 or higher adverse events associated with SABR. In the I-SABR group, ten participants (15%) had grade 3 immunologial adverse events related to nivolumab; none had grade 3 pneumonitis or grade 4 or higher toxicity. INTERPRETATION: Compared with SABR alone, I-SABR significantly improved event-free survival at 4 years in people with early-stage treatment-naive or lung parenchymal recurrent node-negative NSCLC, with tolerable toxicity. I-SABR could be a treatment option in these participants, but further confirmation from a number of currently accruing phase 3 trials is required. FUNDING: Bristol-Myers Squibb and MD Anderson Cancer Center Alliance, National Cancer Institute at the National Institutes of Health through Cancer Center Core Support Grant and Clinical and Translational Science Award to The University of Texas MD Anderson Cancer Center.

ASTRO Radiation Therapy Summary of the ASCO Guideline on Management of Stage III Non-Small Cell Lung Cancer.

PURPOSE: To develop a radiation therapy summary of recommendations on the management of locally advanced non-small cell lung cancer (NSCLC) based on the Management of Stage III Non-Small Cell Lung Cancer: American Society of Clinical Oncology Guideline, which was endorsed by the American Society for Radiation Oncology (ASTRO). METHODS: The American Society of Clinical Oncology, ASTRO, and the American College of Chest Physicians convened a multidisciplinary panel to develop a guideline based on a systematic review of the literature and a formal consensus process, that has been separately published. A new panel consisting of radiation oncologists from the original guideline as well as additional ASTRO members was formed to provide further guidance to the radiation oncology community. A total of 127 articles met the eligibility criteria to answer 5 clinical questions. This summary focuses on the 3 radiation therapy questions (neoadjuvant, adjuvant, and unresectable settings). RESULTS: Radiation-specific recommendations are summarized with additional relevant commentary on specific questions regarding the management of preoperative radiation, postoperative radiation, and combined chemoradiation. CONCLUSIONS: Patients with stage III NSCLC who are planned for surgical resection, should receive either neoadjuvant chemotherapy or chemoradiation. The addition of neoadjuvant treatment is particularly important in patients planned for surgery in the N2 or superior sulcus settings. Postoperatively, patients who did not receive neoadjuvant chemotherapy should be offered adjuvant chemotherapy. The use of postoperative radiation for completely resected N2 disease is not routinely recommended. Unresectable patients with stage III NSCLC should ideally be managed with combined concurrent chemoradiation using a platinum-based doublet with a standard radiation dose of 60 Gy followed by consolidation durvalumab in patients without progression after initial therapy. Patients who cannot tolerate a concurrent chemoradiation approach can be managed either by sequential chemotherapy followed by radiation or by dose-escalated or hypofractionated radiation alone.

End-of-Life Care, Symptom Burden, and Quality of Life in Couples Facing Stage IV Lung Cancer: The Role of Patient and Spousal Psychospirituality and Discussions Around Fear of Death and Disease Progression.

Background: As patients live longer with stage IV nonsmall cell lung cancer, correlates of end-of-life (EOL) care and experience are increasingly relevant. Methods: We, therefore, prospectively examined associations among psychospirituality (Center for Epidemiologic Studies Depression Scale, Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being), discussions around fear of death and disease progression, and hospital-based EOL care in patients and caregivers. Patients additionally reported symptom burden (MD Anderson Symptom Inventory-Lung Cancer total) and quality of life (QOL) (quality-of-life at EOL). Results: Of the baseline patients (n = 75), 32% were alive at time of the analyses (mean = 4.6 years postbaseline). Deceased patients (n = 51) were middle aged (mean = 65.3 years) and non-Hispanic White (81%). Caregiver spiritual well-being (r = 0.34, p = 0.02) and depression (r = -0.31, p = 0.03) were associated with EOL care metrics. Patients who "held back" more of their fear of death or disease progression experienced greater symptom burden (r = 0.41, p < 0.001) and poorer QOL (r = -0.44, p < 0.001). Conclusion: For couples facing prolonged metastatic disease, psychospirituality is highly relevant to EOL care with potential sequelae of withholding one's fear regarding death or disease progression.

Prognostic Understanding and Goals of Palliative Radiotherapy: A Qualitative Study.

CONTEXT: There is a paucity of data describing patients' expectations of goals of palliative radiotherapy (RT) and overall prognosis. OBJECTIVES: To explore patients' perceptions of and preferences for communication surrounding goals of palliative RT and cancer prognosis. METHODS: We conducted a qualitative study utilizing semi-structured interviews with seventeen patients with either bone or lung metastases receiving their first course of palliative RT at a comprehensive cancer center. All patient interviews were recorded, transcribed verbatim, and thematically analyzed. RESULTS: Themes of goals of palliative RT centered on either restoration, such as through improving quality of life or minimizing pain, or on a desire to combat cancer by eliminating tumor. While most patients perceived that palliative RT would palliate symptoms but not cure their cancer, some patients believed that the goal of palliative RT was to cure. Themes that emerged surrounding patients' understanding of prognosis and what lies ahead included uncertainty and apprehension about the future, a focus on additional treatment, and confronting mortality. Most patients preferred to receive information about goals of treatment and prognosis from their doctors, including radiation oncologists, rather than other members of the medical team. Patients also expressed a desire for written patient education materials on palliative RT. CONCLUSION: Unclear perceptions of goals of treatment and prognosis may motivate some patients to pursue unnecessarily aggressive cancer treatments. Patients desire prognostic information from their doctors, including radiation oncologists, who are important contributors to goals of care discussions and may improve patient understanding and well-being by using restorative rather than combat-oriented language.

Health Care Resource Utilization for Esophageal Cancer Using Proton versus Photon Radiation Therapy.

Purpose: In patients treated with chemoradiation for esophageal cancer (EC), randomized trial data demonstrate that proton beam therapy (PBT) reduces toxicities and postoperative complications (POCs) compared with intensity-modulated radiation therapy (IMRT). However, whether radiation therapy modality affects postoperative health care resource utilization remains unknown. Materials and Methods: We examined 287 patients with EC who received chemoradiation (prescribed 50.4 Gy/GyE) followed by esophagectomy, including a real-world observational cohort of 237 consecutive patients treated from 2007 to 2013 with PBT (n = 81) versus IMRT (n = 156); and an independent, contemporary comparison cohort of 50 patients from a randomized trial treated from 2012 to 2019 with PBT (n = 21) versus IMRT (n = 29). Postoperative complications were abstracted from medical records. Health care charges were obtained from institutional claims and adjusted for inflation (2021 dollars). Charge differences (Δ = $PBT - $IMRT) were compared by treatment using adjusted generalized linear models with the gamma distribution. Results: Baseline PBT versus IMRT characteristics were not significantly different. In the observational cohort, during the neoadjuvant chemoradiation phase, health care charges were higher for PBT versus IMRT (Δ = +$71,959; 95% confidence interval [CI], $62,274-$82,138; P < .001). There was no difference in surgical charges (Δ = -$2234; 95% CI, -$6003 to $1695; P = .26). However, during postoperative hospitalization following esophagectomy, health care charges were lower for PBT versus IMRT (Δ = -$25,115; 95% CI, -$37,625 to -$9776; P = .003). In the comparison cohort, findings were analogous: Charges were higher for PBT versus IMRT during chemoradiation (Δ = +$61,818; 95% CI, $49,435-$75,069; P < .001), not different for surgery (Δ = -$4784; 95% CI, -$6439 to $3487; P = .25), and lower for PBT postoperatively (Δ = -$27,048; 95% CI, -$41,974 to -$5300; P = .02). Lower postoperative charges for PBT were especially seen among patients with any POCs in the contemporary comparison (Δ = -$176,448; 95% CI, -$209,782 to -$78,813; P = .02). Conclusion: Higher up-front chemoradiation resource utilization for PBT in patients with EC was partially offset postoperatively, moderated by reduction in POC risks. Results extend existing clinical evidence of toxicity reduction with PBT.

Moderators of the association between stigma and psychological and cancer-related symptoms in women with non-small cell lung cancer.

OBJECTIVE: Lung cancer patients, particularly women, are vulnerable to experience disease-related stigma, which is linked to greater psychological distress and worse treatment outcomes. To inform future stigma-resilience interventions, we examined if mindfulness, self-compassion, and social support might buffer the associations between perceived lung cancer stigma and psychological and cancer-related symptoms. METHODS: In this cross-sectional study, women with recently diagnosed non-small cell lung cancer undergoing cancer treatment completed measures of Cataldo Lung Cancer Stigma Scale, depressive (Center for Epidemiologic Studies Depression Scale), stress (Impact of Events Scale) and cancer-related (MD Anderson Symptom Inventory-Lung Cancer) symptoms, mindfulness (Mindful Attention Awareness Scale), self-compassion (Self-Compassion Scale), and social support (Social Provisions Scale). RESULTS: The sample included 56 women (mean age = 65 years; 71% non-Hispanic White; 50% college educated; 74% advanced stage) who had consented to participate in an online support group study. Most (70%) had a smoking history and reported moderate levels of stigma (M = 36.28, SD = 10.51). Based on general linear modeling, mindfulness moderated the associations between stigma and depressive symptoms (F = 5.78, p = 0.02), cancer-related stress (F = 12.21, p = 0.002), and cancer-related symptom severity (F = 4.61, p = 0.04), such that, only for women scoring low in mindfulness, the associations between stigma and symptoms were significant. For those scoring high in mindfulness, the associations between stigma and symptoms were not significant supporting a buffering effect. Self-compassion and social support did not significantly moderate the stigma and symptom associations. CONCLUSIONS: Higher levels of mindfulness may protect women from psychological and cancer-related symptoms typically associated with the stigmatizing experience of a lung cancer diagnosis. Yet, longitudinal studies and randomized controlled designs are needed to identify mindfulness as a causal protective factor.

Patient, physician, and policy factors underlying variation in use of telemedicine for radiation oncology cancer care.

BACKGROUND: Oncology telemedicine was implemented rapidly after COVID-19. We examined multilevel correlates and outcomes of telemedicine use for patients undergoing radiotherapy (RT) for cancer. METHODS: Upon implementation of a telemedicine platform at a comprehensive cancer center, we analyzed 468 consecutive patient RT courses from March 16, 2020 to June 1, 2020. Patients were categorized as using telemedicine during ≥1 weekly oncologist visits versus in-person oncologist management only. Temporal trends were evaluated with Cochran-Armitage tests; chi-squared test and multilevel multivariable logistic models identified correlates of use and outcomes. RESULTS: Overall, 33% used telemedicine versus 67% in-person only oncologist management. Temporal trends (ptrend  < 0.001) correlated with policy changes: uptake was rapid after local social-distancing restrictions, reaching peak use (35% of visits) within 4 weeks of implementation. Use declined to 15% after national "Opening Up America Again" guidelines. In the multilevel model, patients more likely to use telemedicine were White non-Hispanic versus Black or Hispanic (odds ratio [OR] = 2.20, 95% confidence interval [CI] 1.03-4.72; p = 0.04) or receiving ≥6 fractions of RT versus 1-5 fractions (OR = 4.49, 95% CI 2.29-8.80; p < 0.001). Model intraclass correlation coefficient demonstrated 43% utilization variation was physician-level driven. Treatment toxicities and 30-day emergency visits or unplanned hospitalizations did not differ for patients using versus not using telemedicine (p > 0.05, all comparisons). CONCLUSION: Though toxicities were similar with telemedicine oncology management, there remained lower uptake among non-White patients. Continuing strategies for oncology telemedicine implementation should address multilevel patient, physician, and policy factors to optimize telemedicine's potential to surmount-and not exacerbate-barriers to quality cancer care.

Financial distress and its associated burden in couples coping with an advanced cancer.

PURPOSE: In efforts to understand financial distress (FD) associated with advanced cancer care from the perspective of both patients with incurable disease and their spousal caregivers, we assessed FD in both members of the couple, identified symptom and quality of life (QOL) correlates, and examined the potential role of illness communication. METHODS: Patients undergoing treatment for stage III/IV lung cancer or a grade III/IV primary brain tumor and their spousal caregivers (n = 76 dyads) completed measures of somatic and affective symptoms including FD, physical and mental QOL, and ease of engaging in illness communication. Patients and caregivers additionally rated their perception of each other's symptoms, including FD. RESULTS: FD was endorsed by both patients (any FD 62.7%; high FD 24%) and spousal caregivers (any FD 64.7%; high FD 32.3%). Self-reported FD was significantly correlated (partial r = .52, p < .001) within couples. FD was associated with greater symptoms of anxiety (r = .29, p = .01; r = .31, p = .01), depression (r = 29, p = 01; r = .39, p = .001), and poorer physical QOL(r = - .25, p = .03; r = - .25, p = .001) for patients and caregivers, respectively. For patients, FD was additionally associated with poorer mental QOL(r = - .44, p < .001). Caregivers accurately perceived patient FD, yet patients tended to underreport their caregiver's FD by almost an entire point (t = 2.8, p = .007). A 3-way interaction (FD X role X illness communication) revealed (b = .40, p = .041) that illness communication moderated the association between FD and physical QOL for spouses so that spouses who reported less ease of illness communication demonstrated a stronger association between financial distress and physical QOL (b = - 2.08, p < .001) than those reporting greater ease of engaging in illness communication (b = .49, p = .508). CONCLUSION: In the advanced cancer setting, FD is prevalent in both patients and their spousal caregivers and associated with psychological distress and poor physical QOL. Results suggest that optimal FD assessment should include patients and spouses, and spouse's ease of engaging with illness communication may be a potential target for future intervention studies.

National Quality Measure Compliance for Palliative Bone Radiation Among Patients With Metastatic Non-Small Cell Lung Cancer.

BACKGROUND: There exists wide practice variability in palliative treatment schedules for bone metastases. In an effort to reduce variation and promote high-quality, cost-conscious care, the National Quality Forum (NQF) endorsed measure 1822 in 2012. This measure recommends the use of 30 Gy in 10 fractions, 24 Gy in 6 fractions, 20 Gy in 5 fractions, or 8 Gy in a single fraction for palliative radiation for bone metastases. We report on longitudinal compliance with this measure. METHODS: Using the National Cancer Database, patients with metastatic thoracic non-small cell lung cancer diagnosed between 2004 and 2016 who received radiation therapy for bony sites of metastatic disease were identified. Treatment courses fitting 1 of the 4 recommended schedules under NQF 1822 were coded as compliant. Rates of compliance by patient, tumor, and treatment characteristics were analyzed. RESULTS: A total of 42,685 patients met the criteria for inclusion. Among all patients, 60.2% of treatment courses were compliant according to NQF 1822. Compliance increased over time and was highest for treatments to the extremity (69.8%), lowest for treatments to the skull or head (48.8%), and higher for academic practice (67.1%) compared with community (56.0%) or integrated network facilities (61.2%). On multivariable analysis, predictors of NQF 1822 compliance included year of diagnosis after 2011, treatment to an extremity, or treatment at an academic facility. Of noncompliant treatment courses, extended fractionation (≥11 fractions) occurred in 62.6% and was more common before 2012, in community practice, and for treatments of the skull or head. CONCLUSIONS: Among patients treated for metastatic non-small cell lung cancer, compliance with NQF 1822 increased over time. Although extended fractionation constituted a majority of noncompliant treatment courses, a substantial proportion also involved shorter courses.

Prognosis of severe lymphopenia after postoperative radiotherapy in non-small cell lung cancer: Results of a long-term follow up study.

PURPOSE: To investigate the incidence and prognosis of severe radiation-induced lymphopenia (sRIL) after postoperative radiotherapy (PORT) for resected NSCLC. PATIENTS AND METHODS: Between 1998 and 2017, 170 patients treated with PORT for NSCLC were retrospectively reviewed. Lymphopenia was divided into tertiles with severe lymphopenia defined as absolute lymphocyte counts (ALC) < 0.37 × 103/ul. RESULTS: sRIL was observed in 32.3% of patients. Multivariable logistic regression analysis indicated sRIL was associated with planning target volume radiation fraction numbers (OR 1.09, p = 0.005) and total lung mean dose (OR 1.12, p = 0.006). With a median follow-up time of 12.2 years, the median progression-free survival and overall survival were 14.8 months and 28.4 months respectively in patients with sRIL, vs. 21.7 months (p = 0.008) and 48.3 months (p = 0.01) respectively in patients without sRIL. Multivariable analyses indicated sRIL significantly decreased OS (HR 1.95, p < 0.01). Since PORT for stage I-II NSCLC was done largely for positive margins, which may confound the contribution of severe RIL, we analyzed stage III separately and found that sRIL also significantly decreased OS (HR 1.88, p = 0.004) in multivariable analysis. CONCLUSION: For this long-term outcome study, severe RIL correlated with total lung mean dose and radiation fractionation numbers, and was a strong prognostic factor for poor survival in PORT patients, particularly in patients with stage III NSCLC, highlighting the importance of an intact immune system for post-radiation immunologic disease surveillance.

Patient-Provider Communication, Decision-Making, and Psychosocial Burdens in Palliative Radiotherapy: A Qualitative Study on Patients' Perspectives.

CONTEXT: Patient-provider communication impacts how patients with cancer make decisions about treatment. OBJECTIVES: To examine patient perceptions of discussions, decision-making, and psychosocial burdens related to receiving palliative radiotherapy (RT), in order to inform best practices for communication about palliative RT. METHODS: We conducted an exploratory qualitative study using oral questionnaires and semi-structured interviews. Seventeen patients receiving their first course of palliative RT for lung or bone metastases at a comprehensive cancer center were interviewed. Patient interviews were transcribed verbatim and thematically analyzed using NVivo software. RESULTS: Themes that impacted patients' decisions to initiate RT included a desire to minimize pain, optimism about what RT could provide for the future, perception of having "no other choice," disappointment about cancer progression, and unfamiliarity with RT. Most patients preferred shared decision-making regarding RT initiation and reported patient empowerment, effective communication, and team collaboration as contributing to shared decision-making. Most patients preferred their physicians to make decisions about RT treatment intensity and described trust in their physicians, institutional reputation, and RT expertise as motivators for this preference. Patients who possessed a proactive decisional mindset about initiating RT as opposed to having "no other choice" were less likely to report experiencing psychosocial burdens. CONCLUSION: Most patients prefer shared decision-making regarding RT initiation but prefer their radiation oncologists to make decisions regarding treatment intensity. Communication that empowers patients in their desired level of engagement for RT decision-making may help patients make informed decisions, contribute toward a proactive decisional mindset, and reduce their perception of psychosocial burdens.

Variation in Use of High-Cost Technologies for Palliative Radiation Therapy by Radiation Oncologists.

BACKGROUND: Understanding the sources of variation in the use of high-cost technologies is important for developing effective strategies to control costs of care. Palliative radiation therapy (RT) is a discretionary treatment and its use may vary based on patient and clinician factors. METHODS: Using data from the SEER-Medicare linked database, we identified patients diagnosed with metastatic lung, prostate, breast, and colorectal cancers in 2010 through 2015 who received RT, and the radiation oncologists who treated them. The costs of radiation services for each patient over a 90-day episode were calculated, and radiation oncologists were assigned to cost quintiles. The use of advanced technologies (eg, intensity-modulated radiation, stereotactic RT) and the number of RT treatments (eg, any site, bone only) were identified. Multivariable random-effects models were constructed to estimate the proportion of variation in the use of advanced technologies and extended fractionation (>10 fractions) that could be explained by patient fixed effects versus physician random effects. RESULTS: We identified 37,361 patients with metastatic lung cancer, 3,684 with metastatic breast cancer, 5,323 with metastatic prostate cancer, and 8,726 with metastatic colorectal cancer, with 34%, 27%, 22%, and 9% receiving RT within the first year, respectively. The use of advanced technologies and extended fractionation was associated with higher costs of care. Compared with the patient case-mix, physician variation accounted for a larger proportion of the variation in the use of advanced technologies for palliative RT and the use of extended fractionation. CONCLUSIONS: Differences in radiation oncologists' practice and choices, rather than differences in patient case-mix, accounted for a greater proportion of the variation in the use of advanced technologies and high-cost radiation services.

Toxicity and Survival After Intensity-Modulated Proton Therapy Versus Passive Scattering Proton Therapy for NSCLC.

OBJECTIVE: Although intensity-modulated radiation therapy (IMPT) is dosimetrically superior to passive scattering proton therapy (PSPT) for locally advanced NSCLC (LA-NSCLC), direct comparisons of clinical outcomes are lacking. Here, we compare toxicity profiles and clinical outcomes after IMPT versus PSPT for LA-NSCLC. METHODS: This is a nonrandomized, comparative study of two independent cohorts with LA-NSCLC (stage II-IIIB, stage IV with solitary brain metastasis) treated with concurrent chemotherapy and proton beam therapy. Toxicity (Common Terminology Criteria for Adverse Events version 4.0) and outcomes were prospectively collected as part of a clinical trial (ClinicalTrials.gov identifier NCT00915005) or prospective registry (ClinicalTrials.gov identifier NCT00991094). RESULTS: Of 139 patients, 86 (62%) received PSPT and 53 (38%) IMPT; median follow-up times were 23.9 and 29.0 months, respectively. IMPT delivered lower mean radiation doses to the lungs (PSPT 16.0 Gy versus IMPT 13.0 Gy, p < 0.001), heart (10.7 Gy versus 6.6 Gy, p = 0.004), and esophagus (27.4 Gy versus 21.8 Gy, p = 0.005). Consequently, the IMPT cohort had lower rates of grade 3 or higher pulmonary (17% versus 2%, p = 0.005) and cardiac (11% versus 0%, p = 0.01) toxicities. Six patients (7%) with PSPT and zero patients (0%) with IMPT experienced grade 4 or 5 toxicity. Lower rates of pulmonary (28% versus 3%, p = 0.006) and cardiac (14% versus 0%, p = 0.05) toxicities were observed in the IMPT cohort even after propensity score matching for baseline imbalances. There was also a trend toward longer median overall survival in the IMPT group (23.9 mo versus 36.2 mo, p = 0.09). No difference was found in the 3-year rates of local (25% versus 20%, p = 0.44), local-regional (29% versus 36%, p = 0.56) and distant (52% versus 51%, p = 0.71) recurrences. CONCLUSIONS: IMPT is associated with lower radiation doses to the lung, heart, and esophagus, and lower rates of grade 3 or higher cardiopulmonary toxicity; additional clinical studies will be needed to assess the potential differences in survival between the two techniques.

Proceedings of the ASTRO-RSNA Oligometastatic Disease Research Workshop.

PURPOSE: On June 13 to 14, 2019, the American Society for Radiation Oncology and the Radiological Society of North America convened a workshop on the treatment of oligometastatic disease in Washington, DC. The workshop was initiated for several reasons. First, oligometastatic disease is of increasing academic and community interest and has been identified by the American Society for Radiation Oncology membership as a top research priority. Second, emerging imaging and diagnostic technologies are more readily defining and detecting oligometastatic disease, making contemporary discussion of oligometastatic disease especially relevant. Third, radiosurgery and radiation in general are theorized to be ideal noninvasive therapy for the treatment of oligometastatic disease. Finally, innovations in targeted therapy and immune therapy have the potential to reverse widely disseminating disease into an oligometastatic state. METHODS AND MATERIALS: The workshop was organized into 2 keynote addresses, 6 scientific sessions, and 3 group discussions during an end-of-workshop breakout session. New scientific work was presented in the form of 4 oral presentations and a poster session. Workshop participants were charged with attempting to answer 3 critical questions: (1) Can we refine the clinical and biological definitions of oligometastatic disease; (2) how can we better treat oligometastatic disease; and (3) what clinical trials are needed? RESULTS: Here, we present the proceedings of the workshop. CONCLUSIONS: The clinical implications of improved treatment of oligometastatic disease are enormous and immediate. Radiation oncology and diagnostic radiology should rightly be at the forefront of the characterization and treatment of oligometastatic disease. Focused effort is required so that we can translate current efforts of large numbers of studies with few patients to larger studies of larger impact.

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

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

Thoracic Radiation Oncology Clinical Trial Accrual and Reasons for Nonenrollment: Results of a Large, Prospective, Multiyear Analysis.

PURPOSE: Clinical trials are considered the gold standard in evidence-based medicine, yet few patients with cancer ultimately enroll. Here we examine patients screened for thoracic radiation oncology clinical trials to better understand enrollment trends. METHODS AND MATERIALS: A prospective database tracking screening and enrollment for patients referred for thoracic radiation oncology consultation at our institution from 2016 to 2019 was evaluated. Proportional enrollment rates, patient and disease characteristics, self-reported socioeconomic factors, and reasons for ineligibility or nonenrollment across 17 radiation therapy trials were compared. RESULTS: Enrollment data on 2372 patients were available for analysis. Of these patients, 40.0% (949) were deemed "not eligible" (NE) for any trial or were unwilling to be further screened. Reasons for ineligibility included stage (44%), histology (13%), radiation therapy not indicated (12%), patient decision (7%), and enrollment in a competing medical or surgical oncology trial (5%). The remaining 60.0% (1423) were "potentially eligible" (PE) for one or more trials. Most had non-small cell lung cancer (71%) or esophageal cancer (16%), and there were significantly fewer stage IV PE (29%) versus NE (49%) patients (P < .0001). Of 2372 patients, 281 (11.9%) enrolled. Notable reasons for nonenrollment were inclusion and exclusion criteria (58%), patients declining enrollment (14%), and physician decision (5%). The proportion of white patients was higher in the PE versus NE group (82.5% vs 75.8%; P < .001). Additionally, white race (87.9% vs 81.2%; P = .008), English language preference (96.4% vs 92.9%; P = .032), and non-Hispanic/Latino ethnicity (94.0% vs 90.1%; P = .042) were significantly different in enrolled versus nonenrolled PE patients. CONCLUSIONS: Only 12% of patients screened for radiation therapy trials ultimately enrolled, and more than two-thirds had no trial available or were found ineligible. In addition, 19% of potential eligible patients did not enroll because the patient or physician declined. Future trials may benefit from pragmatic designs with more inclusive enrollment criteria and multidisciplinary engagement of referring providers.

Cost Effectiveness of DCISionRT for Guiding Treatment of Ductal Carcinoma in Situ.

The DCISionRT test estimates the risk of an ipsilateral breast event (IBE) in patients with ductal carcinoma in situ (DCIS) as well as the benefit of adjuvant radiation therapy (RT). We determined the cost-effectiveness of DCISionRT using a Markov model simulating 10-year outcomes for 60-year-old women with DCIS based on nonrandomized data. Three strategies were compared: no testing, no RT (strategy 1); test all, RT for elevated risk only (strategy 2); and no testing, RT for all (strategy 3). We used utilities and costs from the literature and Medicare claims to determine incremental cost-effectiveness ratios and examined the number of women irradiated per IBE prevented. In the base-case scenario, strategy 1 was the cost-effective strategy. Strategy 2 was cost-effective compared with strategy 3 when the cost of DCISionRT was less than $4588. The number irradiated per IBE prevented were 8.37 and 15.46 for strategies 2 and 3, respectively, relative to strategy 1.

The impact of quantitative CT-based tumor volumetric features on the outcomes of patients with limited stage small cell lung cancer.

INTRODUCTION: Limited stage small cell lung cancer (LS-SCLC) has a poor prognosis. Additional prognostic markers are needed for risk-stratification and treatment intensification. This study compares quantitative CT-based volumetric tumor measurements versus International Association for the Study of Lung Cancer (IASLC) TNM staging to predict outcomes. MATERIALS & METHODS: A cohort of 105 patients diagnosed with LS-SCLC and treated with chemoradiation (CRT) from 2000 to 2013 were analyzed retrospectively. Patients were staged by the Union for International Cancer Control (UICC) TNM Classification, 8th edition. Tumor volumes and diameters were extracted from radiation planning CT imaging. Univariable and multivariable models were used to analyze relationships between CT features and overall survival (OS), locoregional recurrence (LRR), in-field LRR, any progression, and distant metastasis (DM). RESULTS: Median follow-up was 21.3 months. Two-year outcomes were as follows: 38% LRR, 31% in-field LRR, 52% DM, 62% any progression, and 47% OS (median survival 16.5 months). On univariable analysis, UICC T-stage and N-stage were not associated with any clinical outcome. UICC overall stage was only statistically associated with in-field LRR. One imaging feature (3D maximum tumor diameter) was found to be significantly associated with LRR (HR 1.10, p = 0.003), in-field LRR (HR 1.10, p = 0.007), DM (HR 1.10, p = 0.02), any progression (HR 1.10, p = 0.008), and OS (HR 1.10, p = 0.03). On multivariable analysis, this feature remained significantly associated with all outcomes. CONCLUSION: For LS-SCLC, quantitative CT-based volumetric tumor measurements were significantly associated with outcomes after CRT and may be better predictors of outcome than TNM stage.

Veterans Affairs Insurance Disparities for Metastatic Lung Cancer in the Hawaiian Islands.

INTRODUCTION: The highest concentration of military personnel in the United States is located in Hawaii where occupational exposures, such as to asbestos in the Pacific Fleet shipyards, predispose them to thoracic malignancies. For this reason, Veterans Affairs (VA) insurance outcomes for lung cancer in Hawaii are of interest. METHODS: All cases of lung cancer in the Hawaii Tumor Registry from 2000 to 2015 were evaluated. The selection criterion included evidence of extensive-stage SCLC (ES-SCLC) or metastatic NSCLC. Overall survival was compared using the Kaplan-Meier log-rank method. Univariate analysis and multivariable analysis (MVA) were carried out to understand the variables associated with overall survival. RESULTS: There were 434 cases of ES-SCLC and 2139 cases of metastatic NSCLC identified. VA insurance (median survival [MS], 2 mo), Medicaid (MS, 4 mo), and Medicare (MS, 4 mo) had worse survival (log-rank p < 0.001) than private insurance (MS, 8 mo). In ES-SCLC, VA insurance (hazard ratio [HR], 2.74; 95% confidence interval [CI]: 1.50-5.01; p = 0.001) and Medicaid (HR, 1.46; 95% CI: 1.04-2.03; p = 0.027) had significantly worse survival compared with private insurance on MVA. VA insurance (HR, 1.84; 95% CI: 1.34-2.53; p < 0.001) and Medicaid (HR, 1.40; 95% CI: 1.20-1.63; p < 0.001) also had worse survival compared with private insurance in metastatic NSCLC on MVA. CONCLUSIONS: VA insurance coverage was associated with dismal survival for metastatic lung cancer that was effectively similar to hospice or supportive care, compelling further investigation to identify reasons for this disparity.