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Stage IV non-small cell lung cancer (NSCLC) denotes the presence of metastatic disease and is largely incurable using present-day therapies. Chemotherapy remains a therapeutic option in this patient population, and there are many pertinent issues surrounding its use in patients with stage IV NSCLC. Eleven questions were framed by the American College of Chest Physicians Lung Cancer Guidelines Committee, and these were addressed by a systematic search of the available literature. The issues addressed included the identification of prognostic factors in selecting patients for chemotherapy and a critical analysis of the survival benefit provided by chemotherapy. Given the development of several new chemotherapy agents over the past decade, the impact that these agents have made was addressed as well as the definition of a standard of care regarding chemotherapeutic regimens. Given the fact that chemotherapy does not represent a curative option, other issues addressed were the optimal duration of treatment as well as its impact on symptom relief and quality of life, the role of second-line therapy, and the outcomes expectations from both first-line and second-line chemotherapy. The question of what specialty delivered the chemotherapy also was addressed. Once the data were identified, a critical analysis was undertaken attempting to objectively portray the data in support of answers for each of the questions posed. We believe the data support the fact that properly selected patients benefit from chemotherapy with regard to survival and palliation in both first-line and second-line settings. It appears that in trials addressing the duration of first-line therapy, this survival and palliative benefit occurs early, and prolonged therapy is not indicated. Therapy in this setting is cost-effective, and there are several regimens that can be considered to be "standard-of-care" options. Physicians involved in the diagnosis of these patients should be aware of the potential benefits of chemotherapy, allowing them to give recommendations to patients that are based on data derived from clinical trials. In addition, this awareness will allow them to make referrals, when appropriate, to physicians who are trained in the administration of chemotherapy and the management of patients undergoing such therapy. [ABSTRACT FROM AUTHOR]

Importance: The impact of patient-specific, disease-related, and social factors on outcomes in limited-stage small cell lung cancer (LS-SCLC) is not well defined. A post hoc secondary analysis of such factors from the Cancer and Leukemia Group B (CALGB) 30610-Radiation Therapy Oncology Group (RTOG) 0538 trial may impact future trial design., Objective: To assess the comprehensive demographic, disease-related, treatment-related, and social factors for potential associations with survival outcomes and understand whether specific subpopulations may benefit from radiotherapy (RT) dose escalation in LS-SCLC., Design, Setting, and Participants: This post hoc secondary analysis of a randomized clinical trial included 638 adults with LS-SCLC treated at 186 unique treatment sites with at least 1 accrual for all patients from March 15, 2008, to December 1, 2019; 313 patients were randomized to receive RT twice daily to a dosage of 45 Gy for 3 weeks and 325 to receive RT once daily to a dosage of 70 Gy for 7 weeks. Data were locked February 28, 2022, and analyzed from November 28, 2022, to June 4, 2024., Interventions: Twice-daily RT or once-daily RT., Main Outcomes and Measures: Multivariable Cox proportional hazards models evaluated the association of treatment groups and other risk factors with progression-free survival (PFS) and overall survival (OS). Patient-specific factors included age, sex, and Eastern Cooperative Oncology Group performance status. Disease-related factors included tumor, nodal, and overall cancer stages. Treatment-related factors included type of chemotherapy, timing of concurrent RT, RT technique, and prophylactic cranial irradiation. Social factors included marital status and treatment center accrual volume., Results: Among 507 patients (260 [51.3%] female and 247 [48.7%] male; mean [SD] age, 62.6 [7.9] years) included in the multivariate survival analysis, with a median follow-up of 4.7 (IQR, 3.7-7.1) years, female sex was associated with improved OS (hazard ratio [HR], 0.73 [95% CI, 0.58-0.91]; P = .006), while being 70 years or older was associated with decreased OS (HR, 1.50 [95% CI, 1.14-1.98]; P = .004). Neither age nor sex was associated with PFS. When compared with those with N1 disease, OS and PFS were worse in patients with N2 (HRs, 1.64 [95% CI, 1.19-2.26]; P = .002 and 1.36 [95% CI, 1.02-1.81]; P = .04, respectively) and N3 (HRs, 2.03 [95% CI, 1.40-2.93]; P < .001 and 1.63 [95% CI, 1.17-2.26]; P = .004) disease. Compared with stage II cancer, OS was worse for stage IIIA (HR, 1.65 [95% CI, 1.17-2.31]; P = .004) and stage IIIB (HR, 1.94 [95% CI, 1.34-2.83]; P < .001). Compared with high-volume accrual centers, treatment at low- or middle-volume accrual centers was associated with worse PFS (HRs, 1.94 [95% CI, 1.33-2.82; P < .001] and 1.44 [95% CI, 1.15-1.82; P = .002], respectively) and worse OS (HRs, 1.55 [95% CI, 1.03-2.32; P = .03] and 1.33 [95% CI, 1.04-1.70; P = .02], respectively)., Conclusions and Relevance: This secondary analysis of the CALGB 30610-RTOG 0538 randomized clinical trial of patients with LS-SCLC found associations between female sex or being younger than 70 years and improved overall survival and between advanced nodal stage or treatment at low- or middle-volume accrual centers and worse outcomes. These findings suggest that stratification by nodal stage, clinical stage, and age should be considered in future randomized trials., Trial Registration: ClinicalTrials.gov Identifier: NCT00632853.

Objectives: Depression is common during pregnancy and the year following childbirth (the perinatal period). This study assessed the association of depressive symptoms and contraception decisions in perinatal individuals., Study Design: We conducted a secondary analysis using data from the PRogram in Support of Moms (PRISM) study, a cluster randomized controlled trial of active interventions which aimed to address perinatal depression. This analysis included 191 individuals aged 18-45 who screened positive for depression on the Edinburgh Postnatal Depression Scale (EPDS, score ≥10) during pregnancy or up to 3 months postpartum. We assessed contraception intent and method choice at 1-3 months postpartum. At 5-7 months postpartum, we assessed contraceptive method used and EPDS depression scores. We used logistic regressions to examine the relationship between depression and contraceptive use/method., Results: At 1-3 months postpartum, the majority of participants (76.4%) expressed an intention to use contraception. Of those, over half (53.4%) indicated a preference for higher effectiveness contraception methods. Participants with persistent depression symptoms (positive EPDS) at 5-7 months were significantly less likely to report using higher effectiveness contraceptive methods (aOR = 0.28, 95% CI = 0.11-0.70) compared to those without. Among participants with persistent depressive symptoms, 21.1% reported using a contraception method of lower effectiveness than had originally intended., Conclusion: Perinatal individuals with persistent depressive symptoms at 5-7 months postpartum reported greater use of less-effective contraception methods than originally planned., Implications: We found associations between perinatal depression and use of less effective contraception use. Provider discussions regarding contraception planning is important, particularly in those with perinatal depression symptoms., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: RTOG 0617 was a phase III randomized trial for patients with unresectable stage IIIA/IIIB non-small cell lung cancer comparing standard-dose (60 Gy) versus high-dose (74 Gy) radiotherapy and chemotherapy, plus or minus cetuximab. Although the study was negative, based on prior evidence that patients with the KRAS-variant, an inherited germline mutation, benefit from cetuximab, we evaluated KRAS-variant patients in RTOG 0617., Experimental Design: From RTOG 0617, 328 of 496 (66%) of patients were included in this analysis. For time-to-event outcomes, stratified log-rank tests and multivariable Cox regression models were used. For binary outcomes, Cochran-Mantel-Haenzel tests and multivariable logistic regression models were used. All statistical tests were two sided, and a P value <0.05 was considered significant., Results: A total of 17.1% (56/328) of patients had the KRAS-variant, and overall survival rates were similar between KRAS-variant and non-variant patients. However, there was a time-dependent effect of cetuximab seen only in KRAS-variant patients-while the hazard of death was higher in cetuximab-treated patients within year 1 [HR = 3.37, 95% confidence interval (CI): 1.13-10.10, P = 0.030], death was lower from year 1 to 4 (HR = 0.33, 95% CI: 0.11-0.97, P = 0.043). In contrast, in non-variant patients, the addition of cetuximab significantly increased local failure (HR = 1.59, 95% CI: 1.11-2.28, P = 0.012)., Conclusions/discussion: Although an overall survival advantage was not achieved in KRAS-variant patients, there is potential impact of cetuximab for this genetic subset of patients. In contrast, cetuximab seems to harm non-variant patients. These findings further support the importance of genetic patient selection in trials studying the addition of systemic agents to radiotherapy., Significance: The KRAS-variant is the first functional, inherited miRNA-disrupting variant identified in cancer. Our findings support that cetuximab has a potentially beneficial impact on KRAS-variant patients treated with radiation. The work confirms prior evidence that KRAS-variant patients are a subgroup who are especially sensitive to radiation. These findings further support the potential of this class of variants to enable true treatment personalization, considering the equally important endpoints of response and toxicity., (© 2023 The Authors; Published by the American Association for Cancer Research.)

Objectives: Few studies have elucidated the impact of work-related trauma on labor and delivery clinician or considered whether it may be a cause of burnout. This study aims to elicit labor and delivery clinician perspectives on the impact of exposure to traumatic births on their professional quality of life., Methods: Labor and delivery clinicians (physicians, midwives, nurse practitioners, and nurses; n = 165) were recruited to complete an online questionnaire on experiences with traumatic births. The questionnaire contained measures from the Maslach Burnout Inventory and the professional quality of life scale version 5. Some participants completed an optional free-text prompt to recommend ways to support clinicians after traumatic births (n = 115). Others opted into a semi-structured phone interview (n = 8). Qualitative data was analyzed using a modified grounded theory approach., Results: Self-reported adequate institutional support for clinicians after a traumatic birth was positively correlated with compassion satisfaction (r = 0.21, p < 0.01) and negatively correlated with secondary traumatic stress (r = - 0.27, p < 0.01), and burnout (r = - 0.26, p < 0.01). Qualitative themes included lack of system-wide and leadership support, lack of access to mental health resources, and suboptimal workplace culture as contributors toward secondary traumatic stress and burnout. Participants recommended proactive leadership, consistent debriefing protocols, trauma education, and improved access to counseling., Conclusions for Practice: Multi-level barriers prevented labor and delivery clinicians from accessing needed mental health support after exposure to traumatic births. Proactive investment in healthcare system supports for clinicians may improve clinician professional quality of life., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Immunotherapy response score (IRS) integrates tumor mutation burden (TMB) and quantitative expression biomarkers to predict anti-PD-1/PD-L1 [PD-(L)1] monotherapy benefit. Here, we evaluated IRS in additional cohorts. Patients from an observational trial (NCT03061305) treated with anti-PD-(L)1 monotherapy were included and assigned to IRS-High (-H) versus -Low (-L) groups. Associations with real-world progression-free survival (rwPFS) and overall survival (OS) were determined by Cox proportional hazards (CPH) modeling. Those with available PD-L1 IHC treated with anti-PD-(L)1 with or without chemotherapy were separately assessed. Patients treated with PD-(L)1 and/or chemotherapy (five relevant tumor types) were assigned to three IRS groups [IRS-L divided into IRS-Ultra-Low (-UL) and Intermediate-Low (-IL), and similarly assessed]. In the 352 patient anti-PD-(L)1 monotherapy validation cohort (31 tumor types), IRS-H versus IRS-L patients had significantly longer rwPFS and OS. IRS significantly improved CPH associations with rwPFS and OS beyond microsatellite instability (MSI)/TMB alone. In a 189 patient (10 tumor types) PD-L1 IHC comparison cohort, IRS, but not PD-L1 IHC nor TMB, was significantly associated with anti-PD-L1 rwPFS. In a 1,103-patient cohort (from five relevant tumor types), rwPFS did not significantly differ in IRS-UL patients treated with chemotherapy versus chemotherapy plus anti-PD-(L)1, nor in IRS-H patients treated with anti-PD-(L)1 versus anti-PD-(L)1 + chemotherapy. IRS associations were consistent across subgroups, including both Europeans and non-Europeans. These results confirm the utility of IRS utility for predicting pan-solid tumor PD-(L)1 monotherapy benefit beyond available biomarkers and demonstrate utility for informing on anti-PD-(L)1 and/or chemotherapy treatment., Significance: This study confirms the utility of the integrative IRS biomarker for predicting anti-PD-L1/PD-1 benefit. IRS significantly improved upon currently available biomarkers, including PD-L1 IHC, TMB, and MSI status. Additional utility for informing on chemotherapy, anti-PD-L1/PD-1, and anti-PD-L1/PD-1 plus chemotherapy treatments decisions is shown., (© 2023 The Authors; Published by the American Association for Cancer Research.)

Perinatal mood disorders (PMDs) are common, yet many patients are undertreated. The Massachusetts Child Psychiatry Access Program (MCPAP) for Moms is designed to increase clinicians' willingness to address PMDs. We examined utilization of MCPAP for Moms and associations with PMDs treatment, including the more complex bipolar disorder (BD). Analyses of MCPAP for Moms data examined utilization from 7/2014 to 6/2020 and associated treatment outcomes. Participants were clinicians (n = 1006) in obstetrics/gynecology, family medicine, and pediatrics. Encounters included (1) resource and referrals and (2) psychiatric consultations (program psychiatrist consultation with clinicians or patients). Utilization sub-groups were identified using group-based trajectory modeling. Higher utilization of MCPAP for Moms was associated with increased rates of treating PMDs (incidence rate ratio [IRR] = 1.07, 95% CI: 1.06-1.07). Examining by encounter type, psychiatric consultations resulted in more frequent rates of clinicians treating PMDs than resource and referral encounters. Utilization of direct patient consultation was associated with the greatest increase in rates of clinicians treating BD (IRR = 2.12, 95% CI: 1.82-2.41). Clinicians with highest utilization rates of psychiatric consultations longitudinally had strongest predictive associations with providing direct mental healthcare to patients with BD (IRR = 13.5, 95% CI: 4.2-43.2). Utilization of MCPAP for Moms facilitates clinicians' ability to provide mental health treatment to patients., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Upwards of one in seven individuals experience perinatal depression and many individuals cannot access treatment. In response, perinatal depression is increasingly being managed in the obstetric setting. This study aimed to characterize the experiences of clinicians and clinician assistants to inform the extent to which clinician assistants can help address depression in obstetric settings., Methods: This cross-sectional analysis used data from an ongoing cluster randomized control trial: The PRogram In Support of Moms (PRISM). Participants included clinicians (physicians, certified nurse midwives, nurse practitioners) and clinician assistants (medical assistants, nursing assistants). Baseline data regarding practices and attitudes of clinicians and clinician assistants toward addressing depression in the obstetric setting were described. Logistic regressions were used to examine the association of clinician time to complete work and depression management., Results: Clinician assistants experienced significantly fewer time constraints than did clinicians. However, having adequate time to complete work was not significantly associated with increased depression management in clinicians. Clinician assistants reported feeling that addressing depression is an important part of their job, despite variation in doing so., Conclusion: Clinician assistants are interacting with perinatal women extensively and are a vital part of obstetric care workflows. Clinician assistants report that they want to address depression and have time to do so. Thus, clinician assistants may be poised to help address the mental health needs of perinatal individuals.

Background: The American Society of Clinical Oncology (ASCO) surveyed cancer patients to assess practice patterns related to weight, diet, and exercise as a part of cancer care., Methods: An online survey was distributed between March and June 2020 through ASCO channels and patient advocacy organizations. Direct email communication was sent to more than 25,000 contacts, and information about the survey was posted on Cancer.Net. Eligibility criteria included being aged at least 18 years, living in the United States, and having been diagnosed with cancer. Logistic regression was used to determine factors associated with recommendation and referral patterns., Results: In total, 2419 individuals responded to the survey. Most respondents were female (60.1%), 61.1% had an early-stage malignancy, and 48.4% were currently receiving treatment. Breast cancer was the most common cancer (35.7%). The majority of respondents consumed ≤2 servings of fruits and vegetables/d (50.5%) and exercised ≤2 times/wk (50.1%). Exercise was addressed at most or some oncology visits in 56.8% of respondents, diet in 50.1%, and weight in 28.0%. Respondents whose oncology provider provided diet and/or exercise recommendations were more likely to report changes in these behaviors vs. those whose oncology provider did not (exercise: 79.6% vs 69.0%, P < .001; diet 81.1% vs 71.3%, P < .001; weight 81.0% vs 73.3%, P = .003)., Conclusions: In a national survey of oncology patients, slightly more than one-half reported attention to diet and exercise during oncology visits. Provider recommendations for diet, exercise, and weight were associated with positive changes in these behaviors, reinforcing the importance of attention to these topics as a part of oncology care., (© 2022 American Cancer Society.)

Objective: To estimate overall prevalence of bipolar disorder (BD) and the prevalence and timing of bipolar-spectrum mood episodes in perinatal women., Data Sources: Databases (PubMed, Scopus, PsycINFO, CINAHL, Cochrane, ClincalTrials.gov) were searched from inception to March 2020., Study Selection: Included studies were original research in English that had (1) populations of perinatal participants (pregnant or within 12 months postpartum), aged ≥ 18 years, and (2) a screening/diagnostic tool for BD. Search terms described the population (eg, perinatal ), illness (eg, bipolar disorder ), and detection (eg, screen , identify )., Data Extraction: Study design data, rates, and timing of positive screens/diagnoses and mood episodes were extracted by 3 independent reviewers. Pooled prevalences were estimated using random-effects meta-analyses., Results: Twenty-two articles were included in qualitative review and 12 in the meta-analysis. In women with no known psychiatric illness preceding the perinatal period, pooled prevalence of BD was 2.6% (95% CI, 1.2%-4.5%) and prevalence of bipolar-spectrum mood episodes (including depressed, hypomanic/manic, mixed) during pregnancy and the postpartum period was 20.1% (95% CI, 16.0%-24.5%). In women with a prior BD diagnosis, 54.9% (95% CI, 39.2%-70.2%) were found to have at least one bipolar-spectrum mood episode occurrence in the perinatal period., Conclusions: Our review suggests that the perinatal period is associated with high rates of bipolar-spectrum mood episodes and that pregnant and postpartum women represent a special risk population. This review may help to inform clinical care recommendations, thus helping to identify those who may have., (© Copyright 2022 Physicians Postgraduate Press, Inc.)

Objective: Perinatal Psychiatry Access Programs have emerged to help obstetric professionals meet the needs of perinatal individuals with mental health conditions, including bipolar disorder (BD). We elucidate obstetric professionals' perspectives on barriers and facilitators to managing BD in perinatal patients, and how Access Programs may affect these processes., Methods: We conducted three focus groups with obstetric professionals, two with- and one without-exposure to an Access Program, the Massachusetts Child Psychiatry Access Program (MCPAP) for Moms. Focus groups discussed experiences, barriers, facilitators, and solutions to caring for perinatal individuals with BD. Qualitative data were coded and analyzed by two independent coders; emergent themes were examined across exposure groups., Results: Thirty-one obstetric professionals (7 without-exposure, 24 with-exposure) participated. Identified themes included: (1) gaps in perinatal BD education; (2) challenges in patient assessment; (3) MCPAP for Moms as a facilitator for addressing BD; and (4) importance of continued outreach and destigmaization to increase care collaboration., Conclusions: Barriers to obstetric professionals accessing adequate mental healthcare for their patients with BD abound. With psychiatric supports in place, it is possible to build obstetric professionals' capacity to address BD. Perinatal Psychiatry Access Programs can facilitate obstetric professionals bridging these gaps in mental health care., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Breastfeeding has many positive effects on the health of infants and mothers, however, the effect of breastfeeding on maternal mental health is largely unknown. The goal of this systematic review was to (1) synthesize the existing literature on the effects of breastfeeding on maternal mental health, and (2) inform breastfeeding recommendations. Materials and Methods: A literature search was conducted in electronic databases using search terms related to breastfeeding ( e.g., breastfeeding, infant feeding practices) and mental health conditions ( e.g., mental illness, anxiety, depression), resulting in 1,110 records. After reviewing article titles and abstracts, 339 articles were advanced to full-text review. Fifty-five articles were included in the final analysis. Results: Thirty-six studies reported significant relationships between breastfeeding and maternal mental health outcomes, namely symptoms of postpartum depression and anxiety: 29 found that breastfeeding is associated with fewer mental health symptoms, one found it was associated with more, and six reported a mixed association between breastfeeding and mental health. Five studies found that breastfeeding challenges were associated with a higher risk of negative mental health symptoms. Conclusions: Overall, breastfeeding was associated with improved maternal mental health outcomes. However, with challenges or a discordance between breastfeeding expectations and actual experience, breastfeeding was associated with negative mental health outcomes. Breastfeeding recommendations should be individualized to take this into account. Further research, specifically examining the breastfeeding experiences of women who experienced mental health conditions, is warranted to help clinicians better personalize breastfeeding and mental health counseling.

Background: About 7 million people, 2.8% of US adults, have bipolar disorder (BD). While second-generation antipsychotics (SGA) are indicated as acute and maintenance treatments for BD, therapeutic success requires medication adherence and reported nonadherence estimates to range as high as 60%. Identifying patient risk factors for nonadherence is important for reducing it., Objective: The objective of this study was to quantify the associations of risk factors, including social determinants of health, with SGA nonadherence among patients with BD., Methods: In this cross-sectional study of 2015-2017 MassHealth Medicaid data, we examined several definitions of adherence and used logistic regression to identify risk factors for nonadherence (medication possession ratio <0.8) among all adults aged 18-64 diagnosed with BD who could be followed for 12 months following SGA initiation., Results: Among 5197 patients, the mean (±SD) age was 37.7 (±11.4) years, and 42.3% were men. Almost half (47.7%) of patients were nonadherent to SGAs when measured by medication possession ratio. The prevalence of nonadherence peaked at middle age for men and younger for women. Nonadherence was less common among Massachusetts' Department of Mental Health clients (odds ratio=0.60, 95% confidence limit: 0.48-0.74) and among those who used other psychotropic medications (odds ratios between 0.45 and 0.81); in contrast, increase in neighborhood socioeconomic stress was associated with increased odds of nonadherence., Conclusions/implications: Adherence to SGA treatment is suboptimal among people with BD. Recognizing risk factors, including those related to social determinants of health, can help target interventions to improve adherence for people at high risk and has implications for adherence-based quality measures., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To elicit the perspectives of individuals with a traumatic birth experience on barriers and facilitators to receiving mental health support in the postpartum period., Methods: Individuals who experienced a traumatic birth within the last three years (n = 32) completed semi-structured phone interviews about their birth and postpartum experience. The Post-traumatic Stress Disorder Checklist for DSM-V (PCL-5), Patient Health Questionnaire (PHQ-8), and Generalized Anxiety Disorder scale (GAD-7) were administered. Qualitative data was analyzed using a modified grounded theory by three independent coders., Results: Among participants, 34.4% screened positive for PTSD, 18.8% for depression, and 34.4% for anxiety. Participants described multi-level barriers that prevented clinicians from recognizing and supporting patients' postpartum mental health needs; those involved lack of communication, education, and resources. Recommendations from participants included that 1) obstetric professionals should acknowledge birth-related trauma experienced by any individual, 2) providers of multiple disciplines need to be integrated into postpartum care, and 3) mental health support may be needed before the ambulatory postpartum visit., Conclusions: There are multi-level barriers towards detecting and responding to individuals' mental health needs after a traumatic birth. Obstetric professionals need to use a trauma-informed approach and proactively assess mental health throughout the postpartum period., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Perinatal depression is common, underdiagnosed, and undertreated. Obstetric providers often do not receive training in perinatal depression, despite being the frontline providers for perinatal individuals. The objective of this study was to develop and pilot test an online training module to assess feasibility, efficacy, and acceptance in improving obstetric providers' knowledge, skills, and practices regarding perinatal depression. Materials and Methods: We designed, developed, and implemented an online, asynchronous, interactive educational module that trains obstetric providers to: (1) know the prevalence and impact of perinatal depression; (2) use validated tools for depression screening; (3) assess for depression; and (4) start and/or refer for treatment. Formative evaluation with five providers, iterative module and question refinement, and a pilot test with pre- and post-test knowledge and self-efficacy questions were conducted. Results: Sixteen obstetric providers averaged a 32% improvement in their pre- to post-test scores ( p  < 0.01). The average pretest score was 49% (range 20%-70%), and the average post-test score was 81% (range 70%-95%). Provider beliefs ( p  = 0.01), self-efficacy ( p  < 0.01), and confidence ( p  < 0.01) in treating perinatal depression were also significantly increased between pre- and post-test. Average Likert scores on overall training satisfaction were very high post-training completion (4.44 out of 5, with 5 being most positive). Conclusions: The module was feasible and effective at improving provider knowledge of perinatal depression, self-rated confidence, and self-efficacy. Improving the knowledge and skills of obstetric providers regarding depression is a critical part of any intervention aimed to close gaps in care and help ensure that patients receive optimal treatment.

Objective: Perinatal depression is a common pregnancy complication and universal screening is recommended. The Practice Readiness to Evaluate and address Perinatal Depression (PREPD) was developed to measure obstetric practice readiness to integrate depression care into workflows. Objectives were to describe: (1) the PREPD; (2) associated characteristics by readiness level; and (3) use of the assessment to measure change., Method: The PREPD has four components, each scored to a 16-point maximum: (1) Environmental Scan (10% of PREPD); (2) Depression Detection, Assessment, and Treatment Questionnaire (30%); (3) Depression-related Policies Questionnaire (10%); and (4) Chart Abstraction (50%). Components were weighted and summed for an overall score. Summary and component scores were calculated by patient, practice, and provider., Results: Average overall PREPD score was 7.3/16 (range: 4.8-9.9); scores varied between practices. The Environmental Scan averaged 2.0/16 (range: 0-5.2); Detection, Assessment, and Treatment averaged 8.3/16 (range: 3.0-11.5); Chart Abstraction averaged 7.2/16 (range: 5.1-9.6); and Depression-related Policies averaged 10.4/16 (range: 7.5-15)., Conclusion: We found wide variation in obstetric practices' readiness to implement interventions for depression; most were minimally prepared. These data may be used to tailor practice intervention goals and as benchmarks with which to measure changes in integration of depression care over time., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Immune checkpoint inhibitors (ICIs) are the standard of care for the treatment of several cancers. While these immunotherapies have improved patient outcomes in many clinical settings, they bring accompanying risks of toxicity, specifically immune-related adverse events (irAEs). There is a need for clear, effective guidelines for the management of irAEs during ICI treatment, motivating the Society for Immunotherapy of Cancer (SITC) to convene an expert panel to develop a clinical practice guideline. The panel discussed the recognition and management of single and combination ICI irAEs and ultimately developed evidence- and consensus-based recommendations to assist medical professionals in clinical decision-making and to improve outcomes for patients., Competing Interests: Competing interests: PAA—Contracted research: Bristol-Myers Squibb, Roche, Array; Consulting fees: Bristol-Myers Squibb, Roche, Array, Novartis, Merck Serono, Pierre Fabre, Incyte, Medimmune, Sindax, AstraZeneca, Sun Pharma, Sanofy, Idera, Ultimovacs, Sandox, Immunocore, 4sc, Alkermes, Italfarmaco, Nektar, Boehringer-Ingelheim, Eisai, Regeneron; Travel support: MSD. JRB—Contracted research: AstraZeneca, Bristol-Myers Squibb, Genentech/Roche, Merck, RAPT Therapeutics, Inc, Revolution Medicines; Consulting fees: Amgen, Bristol-Myers Squibb, Genentech/Roche, Eli Lilly, GlaxoSmithKline, Merck, Sanofi, Regeneron; Data and safety monitoring board/committees: GlaxoSmithKline, Sanofi. JB—Partner consulting fees: AstraZeneca, Merck, Roche, Pfizer, Lilly, Daiichi, Seattle Genetics, Novartis. LCC—Consulting fees: AbbVie; Contracted research: Bristol-Myers Squibb, Merck, EMD Serono, Alkermes, Iovance, Merrimack, National Cancer Institute. DEG—Consulting fees: Samsung Bioepis, Catalyst Pharmaceuticals, Bristol-Myers Squibb Steering Committee, G1 Therapeutics; Contracted research: AstraZeneca, BerGenBio, Karyopharm, Bristol-Myers Squibb Steering Committee; Ownership interest: Gilead. DBJ—Consulting fees: Bristol-Myers Squibb, Catalyst Biopharma, Iovance, Jansen, Merck, Novartis, Oncosec; Contracted research: Bristol-Myers Squibb, Incyte. MEL—Contracted research: Veloce, US Biotest, Lutris, Paxman, Novocure Inc; Grant funding: National Cancer Institute Cancer Center support grant P30 CA008748, National Institute of Arthritis and Musculoskeletal and Skin Diseases grant U01AR0775; Royalty: Legacy Healthcare Services, Apricity Health, Azitra, Inc, Deciphera, Galderma Research and Development, Johnson and Johnson, NCODA, Novocure Inc, Kyowa Kirin Inc, Loxo, Merck Sharp and Dohme Corporation, Janssen Research & Development, Menlo Therapeutics, Novartis Pharmaceuticals Corporation, QED Therapeutics, F. Hoffmann-La Roche AG, Amgen Inc, AstraZeneca Pharmceuticals, Genentech Inc, Seattle Genetics, Lutris, Paxman Coolers, OnQuality Pharmaceuticals Ltd, Takeda Millenium. JN—Consulting fees: AstraZeneca, Bristol-Myers Squibb, Merck, Roche/Genentech; Contracted research: AstraZeneca, Merck; Non-CME services: Merck, Bristol-Myers Squibb, AstraZeneca. M-AP—Consulting fees: AbbVie, Bellicum, Celgene, Bristol-Myers Squibb, Incyte, Kite/Gilead, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda; Contracted research: Incyte, Kite/Gilead and Miltenyi Biotec; Ownership interest: NexImmune Member, DSMBs for Cidara Therapeutics, Servier and Medigene. IP—Consulting fees: Merck, Amgen; Ownership interest: Celldex; Partner ownership: Celldex. BDS—Consulting fees: Kite/Gilead, Juno/Celgene; Contracted research: ADC Therapeutics; NPI: 1215164884. SPS—Consulting fees: Takeda, GSK, Kura, Celgene, Daiichi-Sankyo. DS—Scientific advisory board: Allergan, Alimera, Biogen. JAS—Consulting fees: Array, Nektar, Bristol-Myers Squibb, Iovance, Curis; Contracted research: Bristol-Myers Squibb, Corvus, Caltera. HA-S, FBC, MSE, LH, EH, GAM, MN, RS, MT—Nothing to disclose. SITC staff: SMW—Shares owned: Pacific Biosciences of California Inc, Editas Medicine. EG, AK, BL, LL—Nothing to disclose., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The CALGB 30610/RTOG 0538 randomized trial was designed to test whether high-dose thoracic radiotherapy (TRT) would improve survival compared with 45 Gy twice-daily (BID) TRT in limited stage small cell lung cancer (LSCLC). Two piloted experimental TRT regimens were of interest to study, 70 Gy daily (QD) and 61.2 Gy concomitant boost (CB). Driven by concerns about adequate patient accrual, a study design was employed that eliminated one experimental TRT arm based on early interim toxicity and tolerability, with the study then continuing as a traditional 2-arm phase III study., Methods: Patients with LSCLC were assigned to receive four cycles of cisplatin and etoposide chemotherapy with one of 3 TRT regimens starting with either the first or second cycle of chemotherapy. The interim endpoint was the cumulative highest toxicity calculated from a scoring system based on treatment-related grade 3 and higher toxicity and the ability to complete therapy in the experimental arms., Results: The final interim analysis was performed after 70 patients accrued to each experimental cohort, and a difference in treatment related toxicity scoring was not found (p = 0.739). Severe esophageal toxicity was comparable in both cohorts. Pulmonary toxicity was low overall, though 4 patients (5.7 %) on the 61.2 Gy arm developed grade 4 dyspnea, which was not observed in the 70 Gy arm. A protocol mandated decision was made to discontinue the 61.2 Gy arm following review of toxicity with the Data and Safety Monitoring Board., Conclusion: A randomized trial design using a planned early interim toxicity analysis to discriminate between experimental treatment arms is feasible in a phase III setting. Refinement of the design could increase the likelihood of detecting clinically meaningful differences in toxicity in future studies., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Sacituzumab govitecan (SG), a trophoblast cell surface antigen-2 (Trop-2)-directed antibody-drug conjugate, has demonstrated antitumor efficacy and acceptable tolerability in a phase I/II multicenter trial (NCT01631552) in patients with advanced epithelial cancers. This report summarizes the safety data from the overall safety population (OSP) and efficacy data, including additional disease cohorts not published previously., Patients and Methods: Patients with refractory metastatic epithelial cancers received intravenous SG (8, 10, 12, or 18 mg/kg) on days 1 and 8 of 21-day cycles until disease progression or unacceptable toxicity. Endpoints for the OSP included safety and pharmacokinetic parameters with investigator-evaluated objective response rate (ORR per RECIST 1.1), duration of response, clinical benefit rate, progression-free survival, and overall survival evaluated for cohorts (n > 10 patients) of small-cell lung, colorectal, esophageal, endometrial, pancreatic ductal adenocarcinoma, and castrate-resistant prostate cancer., Results: In the OSP (n = 495, median age 61 years, 68% female; UGT1A1∗28 homozygous, n = 46; 9.3%), 41 (8.3%) permanently discontinued treatment due to adverse events (AEs). Most common treatment-related AEs were nausea (62.6%), diarrhea (56.2%), fatigue (48.3%), alopecia (40.4%), and neutropenia (57.8%). Most common treatment-related serious AEs (n = 75; 15.2%) were febrile neutropenia (4.0%) and diarrhea (2.8%). Grade ≥3 neutropenia and febrile neutropenia occurred in 42.4% and 5.3% of patients, respectively. Neutropenia (all grades) was numerically more frequent in UGT1A1∗28 homozygotes (28/46; 60.9%) than heterozygotes (69/180; 38.3%) or UGT1A1∗1 wild type (59/177; 33.3%). There was one treatment-related death due to an AE of aspiration pneumonia. Partial responses were seen in endometrial cancer (4/18, 22.2% ORR) and small-cell lung cancer (11/62, 17.7% ORR), and one castrate-resistant prostate cancer patient had a complete response (n = 1/11; 9.1% ORR)., Conclusions: SG demonstrated a toxicity profile consistent with previous published reports. Efficacy was seen in several cancer cohorts, which validates Trop-2 as a broad target in solid tumors., Competing Interests: Disclosure AB has received research support (paid to institution) from Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics, Inc., Mersana, Innocrin, and Biotheranostics Inc.; has served as a consultant to Biotheranostics Inc., Pfizer, Novartis, Genentech, Merck, Radius Health, Immunomedics, Inc., Spectrum Pharma, Taiho, Sanofi, Daiichi Pharma/AstraZeneca, Puma, Philipps, and Eli Lilly; and has received travel support from Biotheranostics Inc., Pfizer, Novartis, Genentech, Merck, Radius Health, Immunomedics, Inc., Spectrum Pharma, Taiho, Sanofi, and Philipps. WM has received research support (paid to institution) from Immunomedics, Inc. EAK is a stockholder of Immunomedics, Inc. JDB has received research support (paid to institution) from AbbVie/Pharmacyclics, Beigene, EMD Serono, Immunomedics, Inc., Symphogen, Pfizer, Taiho, Novartis, Genentech/Roche, Bayer, Lilly/Loxo, Incyte, Boston Biomedical, Macrogenics, and I-Mab Biopharma; has served as a consultant to Ipsen, Clovis, and QED Therapeutics, EMD Serono, Seattle Genetics, Bayer, Celgene, LSK Biopharma, Eisai, AstraZeneca, Five Prime, Armo, AbbVie, Symphogen, Erytech, and Gritstone; participates in a Data Safety Monitoring Board for the Pancreatic Cancer Action Network; and receives compensation from the National Cancer Institute for study sections and work on an Investigational Drug Steering Committee. LV has received research support from Weill Cornell Medicine, serves on advisory boards for Immunomedics, Inc., Berg Pharma, and Seattle Genetics, and has served as a consultant to Osmol Therapeutics. RM has received research support from the Orlando Health UF Health Cancer Center and has received honorarium from Eli Lilly, Pfizer, Genentech, Immunomedics, Inc., Seattle Genetics, and Bristol-Myers Squibb (BMS). ADS has served as a consultant to Puma and Merck, and has received research support from Gilead, Puma, Immunomedics, Inc., Synthon, Boehringer-Ingelheim, Genentech, and Tesaro. KK has received research support from Immunomedics, Inc., Novartis, Incyte, Genentech/Roche, Eli Lilly, Pfizer, Calithera Biosciences, Acetylon, Seattle Genetics, Amgen, Zentalis Pharmaceuticals, and CytomX Therapeutics; has served as a consultant to Immunomedics, Inc., Merck, Seattle Genetics, Pfizer, Novartis, Eisai, Eli Lilly, Amgen, and AstraZeneca. His spouse is currently employed by Grail and was previously employed at Array and Pfizer. JO has served as a consultant to AbbVie, Agendia, AstraZeneca, BMS, Celgene, Eisai, Genentech, Immunomedics, Inc., Jounce Therapeutics, Lilly, Merck, Novartis, Pfizer, Puma, Roche, and Seattle Genetics. JEG has received research support from BMS, Merck, AstraZeneca, Array, Boehringer Ingelheim, and Genentech, and has served as a consultant to BMS, Merck, Inivata, EMD Serono/Merck KGaA, AstraZeneca, Celgene, and Novartis. TK has received travel support from Merck and has received honoraria from Boehringer Ingelheim. JML holds equity interest in Salus Discovery, LLC. He has served as a consultant to Janssen, Sanofi, Astellas, Pfizer, and Immunomedics, Inc. AS has served as a consultant to Sandoz and Bayer and has received speaking honoraria from BMS. DMG reports previous employment by Immunomedics, Inc. and status as company founder; serving as Chairman of the Board and Chief Scientific Officer of Immunomedics, Inc.; and was a stockholder. He is an inventor and co-inventor of patents pertaining to sacituzumab govitecan, with potential royalties from product sales. RMS was previously employed by Immunomedics, Inc., at the time this study was conducted; has served as a consultant to Immunomedics, Inc.; and was a stockholder of Immunomedics, Inc. PM reports previous employment by Immunomedics, Inc., while study was performed and being a stockholder in Immunomedics, Inc. QH was an employee and stock shareholder of Immunomedics, Inc., a subsidiary of Gilead Sciences, Inc. and has received travel support from Advaxis; spouse is an employee and stock shareholder of Merck. WW reports previous employment by Immunomedics, Inc., while study was performed; served as a consultant to Immunomedics, Inc., and was a stockholder in Immunomedics, Inc. TG was an employee and stockholder of Immunomedics, Inc. a subsidiary of Gilead Sciences, Inc. AJO has served in a consulting or advisory role for Immunomedics, Inc., Celgene, Tyme Therapeutics, Array, Merck, BMS, ProStrakan, Novartis, Pfizer, Eli Lilly, and Genentech; has served in Speaker's Bureau for Daiichi Sankyo; and has received travel, accommodations, expenses from Daiichi Sankyo. All other authors have declared no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The COVID-19 pandemic has affected mental health and created barriers to healthcare. In this study, we sought to elucidate the pandemic's effects on mental health and access to care for perinatal individuals., Methods: This cross-sectional study of individuals in Massachusetts who were pregnant or up to three months postpartum with a history of depressive symptoms examined associations between demographics and psychiatric symptoms (via validated mental health screening instruments) and the COVID-19 pandemic's effects on mental health and access to care. Chi-square associations and multivariate regression models were used., Results: Of 163 participants, 80.8% perceived increased symptoms of depression and 88.8% of anxiety due to the pandemic. Positive screens for depression, anxiety, and/or PTSD at time of interview, higher education, and income were associated with increased symptoms of depression and anxiety due to the pandemic. Positive screens for depression, anxiety, and/or PTSD were also associated with perceived changes in access to mental healthcare. Compared to non-Hispanic White participants, participants of color (Black, Asian, Multiracial, and/or Hispanic/Latinx) were more likely to report that the pandemic changed their mental healthcare access (aOR:3.25, 95%CI:1.23, 8.59)., Limitations: Limitations included study generalizability, given that participants have a history of depressive symptoms, and cross-sectional design., Conclusions: The pandemic has increased symptoms of perinatal depression and anxiety and impacted perceived access to care. Self-reported increases in depression and anxiety and changes to healthcare access varied by education, race/ethnicity, income, and positive screens. Understanding these differences is important to address perinatal mental health and provide equitable care., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose of Review: The objective of this review is to describe the extent to which (1) obstetric settings are currently screening for mental health and substance use disorders and social determinants of health (SDoH), and (2) screening is followed by systematic approaches for ensuring an adequate response to positive screens. Additionally, clinical and policy implications of current screening practices and recommendations are discussed., Recent Findings: Screening for perinatal depression in obstetric settings has increased. Despite their prevalence and negative impact, screening for other mental health and substance use disorders and SDoH is much less common and professional society recommendations are either nonexistent, less consistent, or less prescriptive. To truly address maternal mental health, we need to move beyond focusing solely on depression and address other mental health and substance use disorders and the contextual social determinants in which they occur.

Background: Individuals with depression have increased nonpsychiatric health care utilization. Associations between depression and utilization have not been studied in perinatal women, despite their heightened depression risk. We examined patterns of nonpsychiatric health care utilization by symptoms of perinatal depression, expecting more frequent use of acute services while being less likely to have routine medical care. Materials and Methods: We identified 1,103 perinatal participants from the 2005 to 2016 National Health and Nutrition Examination Surveys. The Patient Health Questionnaire was used to identify depression (score ≥10). We evaluated associations between perinatal depressive symptoms and health care utilization using logistic models and relative excess risk due to interaction (RERI) using adjusted models with appropriate weighting to provide national estimates. Results: Among perinatal U.S. women, 7.3% had depressive symptoms. Relative to those without these symptoms, women experiencing depressive symptoms were younger, more impoverished, and uninsured ( p  < 0.05). Women with depressive symptoms, compared with those without them, had twice the odds of being without routine medical care (21.6% vs. 12.5%, adjusted odds ratio [aOR]: 2.1, 95% confidence interval [CI]: 1.1 to 4.1) and of using urgent care more frequently (26.5% vs. 15.1%, aOR: 1.9, 95% CI: 1.0 to 3.9). Depressive symptoms combined with lack of insurance generally increased the odds of not having routine care (RERI: 8.4, 95% CI: -0.5 to 17.3) and more frequent use of urgent care (RERI: 7.1, 95% CI: -2.7 to 17.0). Conclusions: Perinatal depression is a prevalent, high-risk illness that requires more nonpsychiatric services and increased psychiatric care. Approaches that facilitate establishing a place for routine care and decreasing acute care use are necessary.

Purpose: RTOG 0617 compared standard-dose (SD; 60 Gy) versus high-dose (HD; 74 Gy) radiation with concurrent chemotherapy and determined the efficacy of cetuximab for stage III non-small-cell lung cancer (NSCLC)., Methods: The study used a 2 × 2 factorial design with radiation dose as 1 factor and cetuximab as the other, with a primary end point of overall survival (OS)., Results: Median follow-up was 5.1 years. There were 3 grade 5 adverse events (AEs) in the SD arm and 9 in the HD arm. Treatment-related grade ≥3 dysphagia and esophagitis occurred in 3.2% and 5.0% of patients in the SD arm v 12.1% and 17.4% in the HD arm, respectively ( P = .0005 and < .0001). There was no difference in pulmonary toxicity, with grade ≥3 AEs in 20.6% and 19.3%. Median OS was 28.7 v 20.3 months ( P = .0072) in the SD and HD arms, respectively, 5-year OS and progression-free survival (PFS) rates were 32.1% and 23% and 18.3% and 13% ( P = .055), respectively. Factors associated with improved OS on multivariable analysis were standard radiation dose, tumor location, institution accrual volume, esophagitis/dysphagia, planning target volume and heart V5. The use of cetuximab conferred no survival benefit at the expense of increased toxicity. The prior signal of benefit in patients with higher H scores was no longer apparent. The progression rate within 1 month of treatment completion in the SD arm was 4.6%. For comparison purposes, the resultant 2-year OS and PFS rates allowing for that dropout rate were 59.6% and 30.7%, respectively, in the SD arms., Conclusion: A 60-Gy radiation dose with concurrent chemotherapy should remain the standard of care, with the OS rate being among the highest reported in the literature for stage III NSCLC. Cetuximab had no effect on OS. The 2-year OS rates in the control arm are similar to the PACIFIC trial.

Lung cancer remains second most common cancer in men and women in the United States. More than 50% of patients are diagnosed in the advanced stage. Traditionally, chemotherapy has been the backbone of management of stage IV lung cancer. A better understanding of the molecular pathogenesis has led to rapid development of targeted therapy and immunotherapy. This has led to significant improvement in survival of patients with lung cancer stages III to IV. These drugs are being studied in early stage lung cancer. Several trials are ongoing to improve the survival and quality of life of our patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Bipolar disorder affects 2-8% of pregnant and postpartum women; untreated illness is associated with poor outcomes. This study aimed to describe bipolar disorder screening rates in obstetric settings and associated characteristics., Method: Women were recruited during pregnancy through three months postpartum from 14 obstetric clinics in Massachusetts. The Mood Disorder Questionnaire (MDQ) was used to screen for bipolar disorder; a subset previously diagnosed with bipolar was also examined. Differences in characteristics by screening outcome were tested using chi-square and t-tests., Results: Of 574 participating women, 18.8% screened positive for bipolar disorder. Compared to those with negative, those with positive bipolar screens had 18.5-times the prevalence of positive substance use screens (11.1% vs. 0.6%, p < 0.001) and 3.4-times reported feeling they were not receiving adequate psychiatric help (24.0 vs. 7.0%, p < 0.001). Less than half of those with positive bipolar screens (42.0%) and 61.3% with pre-existing bipolar reported receiving current psychiatric care., Conclusions: Almost one in five perinatal women screened positive for bipolar disorder. Positive screenings were associated with comorbid substance use and low treatment rates. This study highlights the importance of screening for bipolar disorder during the perinatal period and the need for systematic approaches to ensure adequate assessment and follow-up., Clinical Trials Registration: ClinicalTrials.gov identifier: NCT02760004., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Perinatal depression, the most common pregnancy complication, is associated with negative maternal-offspring outcomes. Despite existence of effective treatments, it is under-recognized and under-treated. Professional organizations recommend universal screening, yet multi-level barriers exist to ensuring effective diagnosis, treatment, and follow-up. Integrating mental health and obstetric care holds significant promise for addressing perinatal depression. The overall study goal is to compare the effectiveness of two active interventions: (1) the Massachusetts Child Psychiatry Access Program (MCPAP) for Moms, a state-wide, population-based program, and (2) the PRogram In Support of Moms (PRISM) which includes MCPAP for Moms plus a proactive, multifaceted, practice-level intervention with intensive implementation support., Methods: This study is conducted in two phases: (1) a run-in phase which has been completed and involved practice and patient participant recruitment to demonstrate feasibility for the second phase, and (2) a cluster randomized controlled trial (RCT), which is ongoing, and will compare two active interventions 1:1 with ten Ob/Gyn practices as the unit of randomization. In phase 1, rates of depressive symptoms and other demographic and clinical features among patients were examined to inform practice randomization. Patient participants to be recruited in phase 2 will be followed longitudinally until 13 months postpartum; they will have 3-5 total study visits depending on whether their initial recruitment and interview was at 4-24 or 32-40 weeks gestation, or 1-3 months postpartum. Sampling throughout pregnancy and postpartum will ensure participants with different depressive symptom onset times. Differences in depression symptomatology and treatment participation will be compared between patient participants by intervention arm., Discussion: This manuscript describes the full two-phase study protocol. The study design is innovative because it combines effectiveness with implementation research designs and integrates critical components of participatory action research. Our approach assesses the feasibility, acceptance, efficacy, and sustainability of integrating a stepped-care approach to perinatal depression care into ambulatory obstetric settings; an approach that is flexible and can be tailored and adapted to fit unique workflows of real-world practices., Trial Registration: ClinicalTrials.gov Identifier: NCT02760004, registered prospectively on May 3, 2016.

Lung cancer remains the leading cause of cancer death throughout the world. Despite new chemotherapeutic, immunomodulating and molecularly targeted agents, patients with locally advanced or metastatic disease still have a poor prognosis. This trial looked to combine antiangiogenic therapy with a first-line cytotoxic chemotherapy doublet, hoping to extend median progression-free survival (PFS) while minimizing toxicity in patients with advanced nonsquamous non-small-cell lung cancer (NSCLC). In this single institution, single-arm study, 51 patients (age >18 yo) were followed from 2007 to 2012. Patients with stage IV nonsquamous NSCLC and patients with recurrent unresectable disease (nonradiation candidates) were eligible. Treatment consisted of carboplatin AUC 5 IV 30-60 minutes, pemetrexed 500/mg 2 IV 10 minutes, bevacizumab 15 mg/kg IV (90 minutes 1st dose, 60 minutes 2nd dose, 30 minutes subsequent doses). Treatment was administered every 21 days and planned for 6 cycles, in the absence of disease progression or unacceptable toxicities. Growth factor support was not permitted prophylactically but allowed for toxicities, as were dose reductions. Maintenance treatment for those with stable disease or better consisted of Bevacizumab 15 mg/kg every 3 weeks for up to 1 year. Between November 2007 and March 2012, 51 patients were followed in the phase II trial of carboplatin, pemetrexed, and bevacizumab. Patients were enrolled over a 24-month period. After the end of treatment visits, subjects were followed at least every 3 months for survival data. The median follow-up period was 49 weeks (6 weeks to 178), and the median number of treatment cycles was 6 (range, 1-6). Among the 50 patients assessable for response, median overall survival was 49 weeks (95% CI, 0-62.7) with median PFS of 28 weeks (95% CI, 0-132.4). A complete or partial response was seen in 28 (59.5%) patients. Grade 3-4 treatment-related adverse events occurred in 9 (17.6%) of 51 patients; the most common were thrombocytopenia (4 [7.8%]) and neutropenia (3 [5.9%]). Three (5.8%) of 51 patients were discontinued because of treatment-related adverse events (grade 3 diarrhea, thrombocytopenia, dehydration, fatigue, and grade 4 respiratory distress), and 1 patient (1.9%) was found to be ineligible due to anticoagulation use. A novel 3-drug combination for advanced nonsquamous NSCLC shows promising efficacy with modest toxicity., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: We evaluated a Trop-2-targeting antibody conjugated with SN-38 in metastatic small cell lung cancer (mSCLC) patients. Experimental Design: Sacituzumab govitecan was studied in patients with pretreated (median, 2; range, 1-7) mSCLC who received either 8 or 10 mg/kg i.v. on days 1 and 8 of 21-day cycles. The primary endpoints were safety and objective response rate (ORR); duration of response, progression-free survival (PFS), and overall survival (OS) were secondary endpoints. Results: Sixty percent of patients showed tumor shrinkage from baseline CTs. On an intention-to-treat basis ( N = 50), the ORR was 14% (17% for the 10-mg/kg group); the median response duration, 5.7 months; the clinical benefit rate (CBR ≥4 months), 34%; median PFS, 3.7 months; and median OS, 7.5 months. There was a suggested improvement in PR, CBR, and PFS with sacituzumab govitecan in second-line patients who were sensitive to first-line therapy, but no difference between first-line chemosensitive versus chemoresistant patients in the overall population. There was a statistically significant higher OS in those patients who received prior topotecan versus no topotecan therapy in a small subgroup. Grade ≥3 adverse events included neutropenia (34%), fatigue (13%), diarrhea (9%), and anemia (6%). Trop-2 tumor staining was not required for patient selection. No antibodies to the drug conjugate or its components were detected on serial blood collections. Conclusions: Sacituzumab govitecan appears to have a safe and effective therapeutic profile in heavily pretreated mSCLC patients, including those who are chemosensitive or chemoresistant to first-line chemotherapy. Additional studies as a monotherapy or combination therapy are warranted. Clin Cancer Res; 23(19); 5711-9. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Objectives: Relapsed small cell lung cancer (SCLC) has limited treatment options. Anthracyclines and cyclophosphamide have shown synergy in many tumors. Amrubicin (AMR) and cyclophosphamide both have single-agent activity in SCLC. This phase I trial evaluated the combination of AMR and cyclophosphamide in refractory solid organ malignancies and in relapsed SCLC., Materials and Methods: The primary endpoint was to determine maximum-tolerated dose and dose-limiting toxicities of the combination. Eligible patients were enrolled in sequential dose escalation cohorts in a standard 3+3 design. Treatment consisted of cyclophosphamide IV at 500 mg/m on day 1 with escalating doses of AMR IV on days 1 to 3 (25 to 40 mg/m with increments of 5 mg/m per cohort). Cycles were repeated every 21 days. Exploratory objectives analyzed the presence of NQO1 polymorphisms and topoisomerase IIA amplification and correlation with response., Results: Thirty-six patients were enrolled, of whom 18 patients had SCLC (50%). Maximum-tolerated dose was determined to be dose level 2 (cyclophosphamide 500 mg/m, AMR 30 mg/m) due to grade 4 thrombocytopenia. The main grade 3 to 4 toxicities were hematologic. Efficacy results are available for 34 patients. Partial responses, stable disease, and progressive disease rates in the overall study population were 20.6% (n=7), 38.2% (n=13), and 41.2% (n=14), respectively. Partial response, stable disease, and progressive disease rates in the SCLC patients and 1 patient with extrathoracic small cell were 36.8% (n=7), 26.3% (n=5), and 36.8% (n=7), respectively. There was no correlation between topoisomerase IIA amplification or NQO1 polymorphisms and response., Conclusions: AMR and cyclophosphamide can be safely combined with little activity observed in heavily pretreated SCLC patients.

Background: Using resting-state functional magnetic resonance imaging (rsfMRI), we previously compared cohorts of bipolar I subjects in a manic state to those in a euthymic state to identify mood state-specific patterns of cortico-amygdala connectivity. Our results suggested that mania is reflected in the disruption of emotion regulation circuits. We sought to replicate this finding in a group of subjects with bipolar disorder imaged longitudinally across states of mania and euthymia METHODS: We divided our subjects into three groups: 26 subjects imaged in a manic state, 21 subjects imaged in a euthymic state, and 10 subjects imaged longitudinally across both mood states. We measured differences in amygdala connectivity between the mania and euthymia cohorts. We then used these regions of altered connectivity to examine connectivity in the longitudinal bipolar group using a within-subjects design., Results: Our findings in the mania vs euthymia cohort comparison were replicated in the longitudinal analysis. Bipolar mania was differentiated from euthymia by decreased connectivity between the amygdala and pre-genual anterior cingulate cortex. Mania was also characterized by increased connectivity between amygdala and the supplemental motor area, a region normally anti-correlated to the amygdala in emotion regulation tasks., Limitations: Stringent controls for movement effects limited the number of subjects in the longitudinal sample., Conclusions: In this first report of rsfMRI conducted longitudinally across mood states, we find that previously observed between-group differences in amygdala connectivity are also found longitudinally within subjects. These results suggest resting state cortico-amygdala connectivity is a biomarker of mood state in bipolar disorder., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: This randomized, double-blind, phase 2 trial evaluated whether the addition of vandetanib to platinum plus etoposide for previously untreated extensive-stage small cell lung cancer (SCLC) prolonged the time to disease progression in comparison with chemotherapy alone., Methods: Patients with previously untreated extensive-stage SCLC received platinum (cisplatin or carboplatin) with etoposide in combination with vandetanib (100 mg daily) or a placebo for up to 4 total cycles (no maintenance therapy). An initial safety run-in phase was conducted with the first 6 patients enrolled; all these patients received vandetanib with cisplatin and etoposide. With an overall sample size of 68 patients, the study had 80% power to detect a 3-month difference in the time to progression (TTP) from 4 to 7 months (significance level,.10 [1-sided log-rank test])., Results: Seventy-four patients were enrolled between April 2008 and May 2013. Thirty-three patients were ultimately randomized to each arm. The baseline characteristics were well balanced, and the median number of treatment cycles was 4 for each arm. Thirty-one patients in each arm were evaluable for TTP; the median TTP was 5.62 months with vandetanib and 5.68 months with the placebo (P = .9518). The median overall survival was 13.24 months with vandetanib and 9.23 months with the placebo (P = .4577; 33 evaluable patients in each arm). Nonhematologic toxicity was increased with vandetanib versus the placebo. No correlation was seen between vascular endothelial growth factor polymorphisms and outcomes., Conclusions: The addition of vandetanib to platinum and etoposide did not improve outcomes for patients with newly diagnosed extensive-stage SCLC. Toxicity was increased in comparison with chemotherapy alone. Cancer 2017;123:303-311. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

Renal cell carcinoma (RCC) is responsible for 80 to 85 percent of all primary renal malignancies. In the United State%, there are about 63,000 new cases and almost :14,000 deaths per year from RCC. Surgical resection of localized RCC can be curative but many patients eventually recur. Immunotherapy appears to be a promising new modality for many malignancies, including RCC. Nivolumab, a specific immunotherapy agent indicated for advanced RCC, may restore antitumor immunity and allow for greater progression-free survival by targeting proteins that negatively regulate T cell immunity. This case study aims to demonstrate the integration of nivolumab into the management of a patient with advanced RCC and provide a stimulus for further investigation and research into this treatment modality.

Background: This study aimed to identify how the activity of large-scale brain networks differs between mood states in bipolar disorder. The authors measured spontaneous brain activity in subjects with bipolar disorder in mania and euthymia and compared these states to a healthy comparison population., Methods: 23 subjects with bipolar disorder type I in a manic episode, 24 euthymic bipolar I subjects, and 23 matched healthy comparison (HC) subjects underwent resting state fMRI scans. Using an existing parcellation of the whole brain, we measured functional connectivity between brain regions and identified significant differences between groups., Results: In unbiased whole-brain analyses, functional connectivity between parietal, occipital, and frontal nodes within the dorsal attention network (DAN) were significantly greater in mania than euthymia or HC subjects. In the default mode network (DMN), connectivity between dorsal frontal nodes and the rest of the DMN differentiated both mood state and diagnosis., Limitations: The bipolar groups were separate cohorts rather than subjects imaged longitudinally across mood states., Conclusions: Bipolar mood states are associated with highly significant alterations in connectivity in two large-scale brain networks. These same networks also differentiate bipolar mania and euthymia from a HC population. State related changes in DAN and DMN connectivity suggest a circuit based pathology underlying cognitive dysfunction as well as activity/reactivity in bipolar mania. Altered activities in neural networks may be biomarkers of bipolar disorder diagnosis and mood state that are accessible to neuromodulation and are promising novel targets for scientific investigation and possible clinical intervention., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Introduction: Adjuvant platinum-based chemotherapy is standard treatment for surgically resected stage II to IIIA NSCLC, but the relapse rate is high. The preferentially expressed antigen of melanoma (PRAME) tumor antigen is expressed in two-thirds of NSCLC and offers an attractive target for antigen-specific immunization. A phase I dose escalation study assessed the safety and immunogenicity of a PRAME immunotherapeutic consisting of recombinant PRAME plus proprietary immunostimulant AS15 in patients with surgically resected NSCLC (NCT01159964)., Methods: Patients with PRAME-positive resected stage IB to IIIA NSCLC were enrolled in three consecutive cohorts to receive up to 13 injections of PRAME immunotherapeutic (recombinant PRAME protein dose of 20 μg, 100 μg, or 500 μg, with a fixed dose of AS15). Adverse events, predefined dose-limiting toxicity, and the anti-PRAME humoral response (measured by enzyme-linked immunosorbent assay) were coprimary end points. Anti-PRAME cellular responses were assessed., Results: A total of 60 patients were treated (18 received 20 μg of PRAME, 18 received 100 μg of PRAME, and 24 received 500 μg of PRAME). No dose-limiting toxicity was reported. Adverse events considered by the investigator to be causally related to treatment were grade 1 or 2, and most were injection site reactions or fever. All patients had detectable anti-PRAME antibodies after four immunizations. The percentages of patients with PRAME-specific CD4-positive T cells were higher at the dose of 500 μg compared with lower doses. No predefined CD8-positive T-cell responses were detected., Conclusion: The PRAME immunotherapeutic had an acceptable safety profile. All patients had anti-PRAME humoral responses that were not dose related, and 80% of those treated at the highest dose showed a cellular immune response. The dose of 500 μg was selected. However, further development was stopped after negative results with a similar immunotherapeutic in patients with NSCLC., (Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: Existing models of the pathophysiology of bipolar disorder posit disruption in neural circuits of emotion regulation and reward processing. However, few fMRI studies have compared regional brain activity and connectivity in different mood states in bipolar disorder to determine if manic symptomatology is reflected in specific circuit abnormalities. The purpose of this study was to test the hypothesis that bipolar mania is associated with altered connectivity between cortical regions thought to regulate subcortical structures such as the amygdala and striatum., Methods: 28 subjects with bipolar disorder in a manic state, 24 different bipolar subjects in a euthymic state, and 23 matched healthy comparison subjects underwent resting state fMRI scans. Several cortical and sub-cortical structures implicated in the pathogenesis of bipolar disorder were selected for study. We conducted a whole-brain analysis of functional connectivity of these regions., Results: Bipolar mania was differentiated from euthymia by decreased functional connectivity between the amygdala and anterior cingulate cortex (ACC). Mania was also characterized by increased connectivity between amygdala and dorsal frontal cortical structures that are normally anti-correlated in emotion regulation tasks., Limitations: Both groups of bipolar subjects were prescribed medications. The study was not longitudinal in design., Conclusions: Compared to bipolar subjects in a euthymic state, subjects in the manic state demonstrate disrupted functional connectivity between brain regions involved in the regulation of emotion and the amygdala. This disruption of activity in neural circuits involved in emotion may underlie the emotional dysregulation inherent to a bipolar manic episode., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A childhood history of attention deficit hyperactivity disorder (ADHD) is common in psychotic disorders, yet prescription stimulants may interact adversely with the physiology of these disorders. Specifically, exposure to stimulants leads to long-term increases in dopamine release. We therefore hypothesized that individuals with psychotic disorders previously exposed to prescription stimulants will have an earlier onset of psychosis. Age of onset of psychosis (AOP) was compared in individuals with and without prior exposure to prescription stimulants while controlling for potential confounding factors. In a sample of 205 patients recruited from an inpatient psychiatric unit, 40% (n = 82) reported use of stimulants prior to the onset of psychosis. Most participants were prescribed stimulants during childhood or adolescence for a diagnosis of ADHD. AOP was significantly earlier in those exposed to stimulants (20.5 vs. 24.6 years stimulants vs. no stimulants, p < 0.001). After controlling for gender, IQ, educational attainment, lifetime history of a cannabis use disorder or other drugs of abuse, and family history of a first-degree relative with psychosis, the association between stimulant exposure and earlier AOP remained significant. There was a significant gender × stimulant interaction with a greater reduction in AOP for females, whereas the smaller effect of stimulant use on AOP in males did not reach statistical significance. In conclusion, individuals with psychotic disorders exposed to prescription stimulants had an earlier onset of psychosis, and this relationship did not appear to be mediated by IQ or cannabis., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: To provide evidence-based recommendations to update the American Society of Clinical Oncology guideline on systemic therapy for stage IV non-small-cell lung cancer (NSCLC)., Methods: An Update Committee of the American Society of Clinical Oncology NSCLC Expert Panel based recommendations on a systematic review of randomized controlled trials from January 2007 to February 2014., Results: This guideline update reflects changes in evidence since the previous guideline., Recommendations: There is no cure for patients with stage IV NSCLC. For patients with performance status (PS) 0 to 1 (and appropriate patient cases with PS 2) and without an EGFR-sensitizing mutation or ALK gene rearrangement, combination cytotoxic chemotherapy is recommended, guided by histology, with early concurrent palliative care. Recommendations for patients in the first-line setting include platinum-doublet therapy for those with PS 0 to 1 (bevacizumab may be added to carboplatin plus paclitaxel if no contraindications); combination or single-agent chemotherapy or palliative care alone for those with PS 2; afatinib, erlotinib, or gefitinib for those with sensitizing EGFR mutations; crizotinib for those with ALK or ROS1 gene rearrangement; and following first-line recommendations or using platinum plus etoposide for those with large-cell neuroendocrine carcinoma. Maintenance therapy includes pemetrexed continuation for patients with stable disease or response to first-line pemetrexed-containing regimens, alternative chemotherapy, or a chemotherapy break. In the second-line setting, recommendations include docetaxel, erlotinib, gefitinib, or pemetrexed for patients with nonsquamous cell carcinoma; docetaxel, erlotinib, or gefitinib for those with squamous cell carcinoma; and chemotherapy or ceritinib for those with ALK rearrangement who experience progression after crizotinib. In the third-line setting, for patients who have not received erlotinib or gefitinib, treatment with erlotinib is recommended. There are insufficient data to recommend routine third-line cytotoxic therapy. Decisions regarding systemic therapy should not be made based on age alone. Additional information can be found at http://www.asco.org/guidelines/nsclc and http://www.asco.org/guidelineswiki., Competing Interests: Authors' disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article., (© 2015 by American Society of Clinical Oncology.)

Purpose: To evaluate the efficacy of maintenance sunitinib after chemotherapy for small-cell lung cancer (SCLC)., Patients and Methods: The Cancer and Leukemia Group B 30504 trial was a randomized, placebo-controlled, phase II study that enrolled patients before chemotherapy (cisplatin 80 mg/m(2) or carboplatin area under the curve of 5 on day 1 plus etoposide 100 mg/m(2) per day on days 1 to 3 every 21 days for four to six cycles). Patients without progression were randomly assigned 1:1 to placebo or sunitinib 37.5 mg per day until progression. Cross-over after progression was allowed. The primary end point was progression-free survival (PFS) from random assignment for maintenance placebo versus sunitinib using a one-sided log-rank test with α = .15; 80 randomly assigned patients provided 89% power to detect a hazard ratio (HR) of 1.67., Results: One hundred forty-four patients were enrolled; 138 patients received chemotherapy. Ninety-five patients were randomly assigned; 10 patients did not receive maintenance therapy (five on each arm). Eighty-five patients received maintenance therapy (placebo, n = 41; sunitinib, n = 44). Grade 3 adverse events with more than 5% incidence were fatigue (19%), decreased neutrophils (14%), decreased leukocytes (7%), and decreased platelets (7%) for sunitinib and fatigue (10%) for placebo; grade 4 adverse events were GI hemorrhage (n = 1) and pancreatitis, hypocalcemia, and elevated lipase (n = 1; all in same patient) for sunitinib and thrombocytopenia (n = 1) and hypernatremia (n = 1) for placebo. Median PFS on maintenance was 2.1 months for placebo and 3.7 months for sunitinib (HR, 1.62; 70% CI, 1.27 to 2.08; 95% CI, 1.02 to 2.60; one-sided P = .02). Median overall survival from random assignment was 6.9 months for placebo and 9.0 months for sunitinib (HR, 1.28; 95% CI, 0.79 to 2.10; one-sided P = .16). Three sunitinib and no placebo patients achieved complete response during maintenance. Ten (77%) of 13 patients evaluable after cross-over had stable disease on sunitinib (6 to 27 weeks)., Conclusion: Maintenance sunitinib was safe and improved PFS in extensive-stage SCLC., (© 2015 by American Society of Clinical Oncology.)

The aim of this study is to demonstrate the validity of the Rorschach Perceptual Thinking Index (PTI) in the assessment of reality testing in patients with psychosis. We evaluated the relationship between the PTI criteria and the Positive and Negative Syndrome Scale (PANSS) scores in 98 psychotic disorder affected patients. Thirty four were evaluated during the acute episode (AP) and 64 were chronically treated and stable (CP). The PANSS positive score resulted significantly higher in AP than in CP group, but no significant difference was found in the PTI score. The PTI positively correlated with the PANSS total score. The PTI1 and PTI2 criteria significantly correlated with the PANSS negative score, the PTI4 and PTI5 with the positive. The Rorschach variable X-% significantly correlated with the negative symptoms; the WSum6 with thought disorders; and the M- with delusions. PTI score, X-% and WSum6 predicted impaired judgment and insight. These results suggest that PTI is a valid instrument to assess impairment in reality testing, regardless of the patient׳s current psychiatric presentation. The presence of conceptual disorganization, delusions, lack of judgment and insight don׳t have effects on the PTI, supporting its strength as an assessment tool for psychotic disorders., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: Criteria for psychiatric hospitalization have undergone marked changes. Efforts to limit length-of-hospitalization risk greater morbidity at discharge and increased needs for appropriate aftercare. Accordingly, we evaluated factors associated with length of psychiatric hospitalization and aftercare-types., Methods: We reviewed medical records of 589 patients with major psychiatric disorders hospitalized in a university-affiliated, not-for-profit psychiatric hospital to identify characteristics associated with length of hospitalization, types of aftercare and insurance coverage, using standard bivariate and multivariate analytical methods., Results: Notable factors associated with longer hospitalization included: more highly supervised aftercare, diagnosis of schizophrenia or schizoaffective>affective disorders, longer illnesses, higher antipsychotic doses and more complex drug-treatments at discharge, lower GAF functional status, unemployment, being unmarried, as well as public vs. private insurance. Multivariate modeling sustained association of longer hospitalization with higher antipsychotic doses, more structured aftercare, public insurance, lower GAF scores, and diagnoses of chronic psychotic disorders. Structured aftercare was associated with younger age, fewer years ill, and private insurance, but varied little by diagnosis and was unrelated to ethnicity. Public insurance was associated notably with being unemployed, unmarried, less functional, having a chronic psychotic disorder for more years, and lack of structured aftercare., Conclusions: Illness severity and functional impairment may modulate efforts to limit psychiatric hospitalization. Higher-level aftercare was associated with illness and disability factors as well as with private insurance; public insurance was associated with dysfunction, unemployment and chronic illness, as well as longer hospitalization., (Copyright © 2014 Elsevier Inc. All rights reserved.)