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.

Multicenter analysis of stereotactic radiosurgery for multiple brain metastases from EGFR and ALK driven non-small cell lung cancer.

INTRODUCTION: Patients with brain metastases (BrMs) arising from EGFR and ALK driven non-small cell lung cancer (NSCLC) have favorable prognoses and evolving treatment options. We evaluated multicenter outcomes for stereotactic radiosurgery (SRS) to multiple (≥4) BrMs, where randomized data remain limited. METHODS: Data were collected retrospectively from 5 academic centers on EGFR and ALK NSCLC who received SRS to ≥4 BrMs with their first SRS treatment between 2008 and 2018. Analyzed endpoints included overall survival (OS), freedom from CNS progression (FFCNSP), and freedom from whole-brain radiotherapy (FFWBRT). RESULTS: Eighty-nine patients (50 EGFR, 39 ALK) received a total of 159 SRS treatments to 1,080 BrMs, with a median follow up of 51.3 months. The median number of BrMs treated with SRS treatment-1 was 6 (range 4-26) and median for all treatments was 9 (range 4-47). Sixteen patients (18 %) had received WBRT prior to SRS treatment-1. The median OS was 24.2, 21.2, and 33.2 months for all patients, EGFR, and ALK subsets, respectively. After multivariable adjustment, only receipt of a next-generation tyrosine kinase inhibitor was associated with OS (HR 0.40, p = 0.005). No differences in OS were observed based on number of BrMs treated. The median FFCNSP was 9.4, 11.6, and 7.5 months, for all patients, EGFR, and ALK subsets, respectively. After multivariable adjustment, the number of BrMs (continuous) treated during treatment-1 was the only negative prognostic factor associated with FFCNSP (HR 1.071, p = 0.045). The 5-year FFWBRT was 73.6 %. CONCLUSIONS: This multicenter analysis over a >10-year period demonstrated favorable OS, FFCNSP, and FFWBRT, in patients with EGFR and ALK driven NSCLC receiving SRS to ≥4 BrMs. These data support SRS as an option in the upfront and salvage setting for higher burden CNS disease in this population.

Co-occurring insomnia and anxiety: a randomized controlled trial of internet cognitive behavioral therapy for insomnia versus internet cognitive behavioral therapy for anxiety.

STUDY OBJECTIVES: Insomnia and anxiety are highly prevalent and frequently co-occur. Given limited therapeutic resources and time constraints, the aim of this study was to compare which treatment-internet cognitive behavioral therapy (CBT) for insomnia or internet CBT for anxiety-leads to the best outcomes in individuals with comorbid insomnia and anxiety. METHODS: 120 participants with comorbid insomnia and clinical anxiety (as defined by scores above the clinical cutoff on the insomnia severity index (ISI) and the generalized anxiety disorder 7-item scale (GAD-7)) were randomized to receive internet-based cognitive behavioral therapy (iCBT) for insomnia or iCBT for anxiety. The primary outcome measures were the ISI and the generalized anxiety disorder 7-item scale. Primary outcome measures were assessed before treatment, at mid-treatment, at post-treatment, and 3 months after treatment. Secondary outcome measures assessed depression symptoms, distress, and sleep diary parameters. RESULTS: Participants in both groups experienced large reductions in symptoms of insomnia, anxiety, depression, and distress, as well as improvements in sleep efficiency and total sleep time. Improvements were maintained at follow-up. Crucially, at the end of treatment, the insomnia treatment was more effective in reducing symptoms of insomnia than the anxiety treatment, and equally effective in reducing symptoms of anxiety. Treatment gains were maintained at 3-month follow-up, however, there were no differences between groups at that time point. CONCLUSIONS: These results suggest that in the common case of a patient presenting with comorbid insomnia and anxiety, treatment for insomnia may be the most efficient treatment strategy. TRIAL REGISTRATION: The trial was registered with the Australian and New Zealand Clinical Trials Registry, https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12618001141235. Trial ID: ACTRN12618001141235. Trial name: a comparison of internet-based CBT for insomnia versus internet-based CBT for anxiety in a comorbid sample.

Treatment-related pulmonary adverse events induced by chemoradiation and Durvalumab affect survival in locally advanced non-small cell lung cancer.

PURPOSE: We compared treatment-related pulmonary adverse events (TRPAE), progression-free survival (PFS), and overall survival (OS) among locally advanced non-small cell lung cancer (NSCLC) patients who received concurrent chemoradiotherapy (CRT) versus CRT followed by immune check point inhibitor (ICI) immunotherapy (CRTI). MATERIALS AND METHODS: TRPAE was defined as any pulmonary events as defined in CTCAE v.5 occurring within 12 months after completion of radiotherapy. Outcomes were compared between CRT and CTRI by Cox proportional hazard regression and Kaplan-Meier analyses. We also assessed if TRPAE-induced discontinuation of ICI affected survival. RESULTS: We analyzed 326 patients treated between July 2010 and November 2019; 195 patients received CRT and 131 received CRTI. The incidences of severe grade ≥ 3 TRPAE were similar between the two groups, however, symptomatic TRPAE was almost doubled in CRTI group (65.7 % CTRI vs 35.9 % CRT, P < 0.0001). The rates of 4-year OS and PFS were 54.5 % vs 36.7 % (P = 0.0003) and 43.8 % vs 35.8 % (P = 0.038) in CRT + Durvalumab and CRT group, respectively. Receipt of ICI Durvalumab was associated with better 4-year OS (HR 0.53, 95 % CI 0.36-0.78, P = 0.001) and PFS (HR 0.55, 95 % CI 0.38-0.80, P = 0.002). Patients who discontinued ICI because of TRPAE had worse 4-year OS (P = 0.001) and higher rates of distant metastasis (P = 0.003) than those who completed planned ICI after developing TRPAE. CONCLUSION: CRT followed by adjuvant ICI led to improved 4-year OS and PFS consistent with published data. CRTI was associated with higher incidence of grade ≥ 2 TRPAE in both high and low mean lung dose groups without significant difference in grade ≥ 3 TRPAE. Discontinuation of ICI due to TRPAE was associated with poorer OS and distant disease control than completing ICI as planned after developing TRPAE.

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.

Pilot Randomized Controlled Trial in Women With Non-Small Cell Lung Cancer to Assess the Feasibility of Delivering Group-Based Psychosocial Care via Videoconference.

BACKGROUND: The goal of this pilot randomized controlled trial was to examine the feasibility and acceptability of delivering group-based psychosocial care via videoconference (ie, Zoom) to women with lung cancer undergoing treatment. METHODS: At baseline, women indicated their typical computer and internet use and were then randomized to a group-based intervention that either focused on mindfulness training or psychoeducation. Participants completed 1 Zoom "practice run" prior to starting the 5 group sessions (1 per week). After the last session, they evaluated their experiences with the intervention and its delivery. RESULTS: With a consent rate of 68%, 54 women (mean age = 66 years; 69% non-Hispanic White; 48% with stage IV disease) were equally randomized. Attendance was high in both arms (session mean, mindfulness = 4.38; education = 4.75; 85% attended all sessions). Across arms, all women rated the program as useful; most preferred group-based delivery (67%) and remote delivery (50%) or had no preference. Although the sample's typical computer use was relatively low (eg, 19% said that they rarely or never use a computer), most women (76%) indicated that Zoom was "very easy" or "easy" to use. After only 0 to 1 attempts, 56% felt comfortable but 26% stated that they never felt comfortable with the technology. CONCLUSIONS: It seems to be feasible to deliver group-based psychosocial interventions via videoconference in women with lung cancer undergoing treatment. Challenges regarding scheduling the group sessions and familiarizing older rather than infrequent computer users with the technology were encountered but resolved over the course of the trial.

Managing rumination and worry: A pilot study of an internet intervention targeting repetitive negative thinking in Australian adults.

BACKGROUND: Rumination and worry, both forms of repetitive negative thinking (RNT), have been implicated in the onset, maintenance, severity, and relapse risk of depression and anxiety disorders. Despite promising initial findings for internet-delivered interventions targeting both rumination and worry simultaneously, no studies have investigated treatment effects in an adult population or when delivered in a brief, unguided format. We developed a 3-lesson unguided online treatment program targeting both rumination and worry and evaluated the adherence and effectiveness in Australian adults using an open pilot trial. METHODS: Adult participants (N=26) experiencing elevated levels of RNT completed the online program over 6-weeks. Outcomes were assessed at baseline, post-treatment, and 1-month follow-up. Intention-to-treat linear mixed models were used to examine effects on RNT, anxiety, depression, and general psychological distress. RESULTS: Of the 26 participants who started the program, 18 completed all three lessons (69.2% completion rate). Large within-subject effect sizes were found between pre- and post-treatment for RNT (Hedges' g= 2.26) and symptoms of depression (g = 1.04), generalised anxiety (g = 1.82) and distress (g = 0.93). Treatment effects were maintained at 1-month follow-up. LIMITATIONS: No long-term follow-up, exclusion of severely depressed individuals. CONCLUSIONS: This is the first study to evaluate a brief, unguided internet intervention targeting both rumination and worry in adults. The results provide promising preliminary evidence for the feasibility and acceptability of the online program. Randomised controlled trials are needed to evaluate treatment efficacy compared to a control group and to investigate long-term outcomes.

Association of Opioid Agonist Treatment With All-Cause Mortality and Specific Causes of Death Among People With Opioid Dependence: A Systematic Review and Meta-analysis.

Importance: Mortality among people with opioid dependence is higher than that of the general population. Opioid agonist treatment (OAT) is an effective treatment for opioid dependence; however, there has not yet been a systematic review on the relationship between OAT and specific causes of mortality. Objective: To estimate the association of time receiving OAT with mortality. Data Sources: The Embase, MEDLINE, and PsycINFO databases were searched through February 18, 2020, including clinical trial registries and previous Cochrane reviews. Study Selection: All observational studies that collected data on all-cause or cause-specific mortality among people with opioid dependence while receiving and not receiving OAT were included. Randomized clinical trials (RCTs) were also included. Data Extraction and Synthesis: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Data on study, participant, and treatment characteristics were extracted; person-years, all-cause mortality, and cause-specific mortality were calculated. Crude mortality rates and rate ratios (RRs) were pooled using random-effects meta-analyses. Main Outcomes and Measures: Overall all-cause and cause-specific mortality both by setting and by participant characteristics. Methadone and buprenorphine OAT were evaluated specifically. Results: Fifteen RCTs including 3852 participants and 36 primary cohort studies including 749 634 participants were analyzed. Among the cohort studies, the rate of all-cause mortality during OAT was more than half of the rate seen during time out of OAT (RR, 0.47; 95% CI, 0.42-0.53). This association was consistent regardless of patient sex, age, geographic location, HIV status, and hepatitis C virus status and whether drugs were taken through injection. Associations were not different for methadone (RR, 0.47; 95% CI, 0.41-0.54) vs buprenorphine (RR, 0.34; 95% CI, 0.26-0.45). There was lower risk of suicide (RR, 0.48; 95% CI, 0.37-0.61), cancer (RR, 0.72; 95% CI, 0.52-0.98), drug-related (RR, 0.41; 95% CI, 0.33-0.52), alcohol-related (RR, 0.59; 95% CI, 0.49-0.72), and cardiovascular-related (RR, 0.69; 95% CI, 0.60-0.79) mortality during OAT. In the first 4 weeks of methadone treatment, rates of all-cause mortality and drug-related poisoning were almost double the rates during the remainder of OAT (RR, 2.01; 95% CI, 1.55-5.09) but not for buprenorphine (RR, 0.58; 95% CI, 0.18-1.85). All-cause mortality was 6 times higher in the 4 weeks after OAT cessation (RR, 6.01; 95% CI, 4.32-8.36), remaining double the rate for the remainder of time not receiving OAT (RR, 1.81; 95% CI, 1.50-2.18). Opioid agonist treatment was associated with a lower risk of mortality during incarceration (RR, 0.06; 95% CI, 0.01-0.46) and after release from incarceration (RR, 0.09; 95% CI, 0.02-0.56). Conclusions and Relevance: This systematic review and meta-analysis found that OAT was associated with lower rates of mortality. However, access to OAT remains limited, and coverage of OAT remains low. Work to improve access globally may have important population-level benefits.

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.

Internet-delivered exposure therapy versus internet-delivered cognitive behavioral therapy for panic disorder: A pilot randomized controlled trial.

AIM: To compare the efficacy and acceptability of internet-delivered exposure therapy for panic disorder, to multi-component internet-delivered cognitive behavioral therapy (iCBT) that included controlled breathing, cognitive restructuring and exposure. METHODS: Participants with panic disorder, with or without agoraphobia, were randomized to internet-delivered exposure therapy (n = 35) or iCBT (n = 34). Both programs were clinician guided, with six lessons delivered over eight weeks. Outcomes included panic disorder and agoraphobia symptom severity, as well as depression symptom severity, functional impairment and days out of role. RESULTS: Participants in both conditions displayed a large reduction in panic disorder symptom severity (ds >1.30) from pre- to post-treatment. Participants in both conditions displayed medium to large reduction in agoraphobia and depression symptom severity, functional impairment and days out of role. Effects were maintained at three- and six-month follow-up. There was no significant difference between the interventions in clinical outcomes, adherence or treatment satisfaction. CONCLUSIONS: Internet-delivered exposure therapy appeared to be as acceptable and efficacious as more established iCBT, despite including less strategies. However, a fully powered replication is now needed to compare the two approaches.

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.