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Objective: Pulmonary hypertension (PH) is a rare but severe manifestation of systemic lupus erythematosus (SLE) that can ultimately result in death. The identification of factors that prognosticate survival in SLE-PH is necessary for appropriate monitoring, timing of therapeutics and lung transplantation. The primary objective of this study was to identify prognostic factors for survival in SLE-PH through review of the literature. The methodological quality of the prognostic studies was also evaluated.Methods: A systematic review of the literature was performed to identify studies evaluating prognostic factors for survival in SLE-PH. Medline, EMBASE, CINAHL, and Cochrane Central Registry of Controlled Trials (inception – week 2 2010) were searched. A standardized abstraction form was used by two independent reviewers to extract prognostic factors. Methodological quality was evaluated using a validated quality index. Results: Twenty-three observational studies from 375 citations were evaluated. Elevated mean pulmonary artery pressure, Raynaud’s phenomenon, thrombocytopenia, plexiform lesion, infection, thrombosis, pregnancy, pulmonary vasculitis and anticardiolipin antibodies were associated with decreased survival. Lupus disease activity, nephritis and central nervous system disease were not associated with survival. The sample sizes were small and methodological quality of the studies was variable. Conclusion: This study summarizes factors that may be associated with decreased survival in SLE-PH. The small sample sizes and variable methodological quality preclude definitive conclusions. This study provides the groundwork for further research using large cohorts. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this systematic review and meta-analysis was to review evidence and pool outcomes to assess the effectiveness of stereotactic ablative radiotherapy (SABR) in patients treated for oligoprogressive metastases., Methods and Materials: A search was conducted January 2010 to January 2023 in five bibliographic databases for studies of patients with oligoprogressive disease treated with SABR to all lesions. Clinical outcomes included PFS (progression-free survival), OS (overall survival) and CST (change in systemic therapy). Descriptive statistics were used to summarize the data. Binary random effects model was used for pooled analyses., Results: 12,366 titles/abstracts screened, of which 25 met eligibility criteria and were included the review. All studies were published after 2017 with approximately 80% of the publications in 2021 and 2022. The primary tumour was prostate (n=8, 32%), kidney (n=6, 24%), colorectal (n=4, 16%) followed by breast (n=3, 12%), lung (n=2, 8%) and mixed (n=3, 12%). At 1 year, the pooled PFS was 44% (95% confidence interval [CI]: 34-53%, I 2 =91%); 53% (95% CI: 45-60%, I 2 =46%) in prostate, 49% (95% CI: 33-65%, I 2 =88%) in kidney, 62% (95% CI: 11-113%, I 2 =96%) in lung, 13% (95% CI: 3-24%, I 2 =39%) in breast and 30% (95% CI: 19-41%, I 2 =59%) in mixed., Discussion: There has been a surge in publications describing the use of SABR in oligoprogressive tumours. Published studies are mostly retrospective reported in prostate and kidney cancers, with limited evidence in other sites. Universal guidelines are recommended to ensure consistency in reporting and comparability of future studies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Palma reports clinician-scientist grant from the Ontario Institute for Cancer Research, royalties from Uptodate.com and a consultant role with equity at Need Inc, all unrelated to the current work. Dr. Barry reports honorarium from Eisai. Dr. Raphael reports advisory boards for AstraZenaca and Novartis. No other disclosures were reported., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: The aim of this systematic review was to summarize the current literature on wearable technologies in oncology patients for the purpose of prognostication, treatment monitoring, and rehabilitation planning., Methods: A search was conducted in Medline ALL, Cochrane Central Register of Controlled Trials, Embase, Emcare, CINAHL, Scopus, and Web of Science, up until February 2022. Articles were included if they reported on consumer grade and/or non-commercial wearable devices in the setting of either prognostication, treatment monitoring or rehabilitation., Results: We found 199 studies reporting on 18 513 patients suitable for inclusion. One hundred and eleven studies used wearable device data primarily for the purposes of rehabilitation, 68 for treatment monitoring, and 20 for prognostication. The most commonly-reported brands of wearable devices were ActiGraph (71 studies; 36%), Fitbit (37 studies; 19%), Garmin (13 studies; 7%), and ActivPAL (11 studies; 6%). Daily minutes of physical activity were measured in 121 studies (61%), and daily step counts were measured in 93 studies (47%). Adherence was reported in 86 studies, and ranged from 40% to 100%; of these, 63 (74%) reported adherence in excess of 80%., Conclusion: Wearable devices may provide valuable data for the purposes of treatment monitoring, prognostication, and rehabilitation. Future studies should investigate live-time monitoring of collected data, which may facilitate directed interventions., (© The Author(s) 2023. Published by Oxford University Press.)

Background: The intersection of race and older age compounds existing health disparities experienced by historically marginalised communities. Therefore, racialised older adults with cancer are more disadvantaged in their access to cancer clinical trials compared with age-matched counterparts. To determine what has already been published in this area, the rapid scoping review question are: what are the barriers, facilitators and potential solutions for enhancing access to cancer clinical trials among racialised older adults?, Methods: We will use a rapid scoping review methodology in which we follow the six-step framework of Arksey and O'Malley, including a systematic search of the literature with abstract and full-text screening to be conducted by two independent reviewers, data abstraction by one reviewer and verification by a second reviewer using an Excel data abstraction sheet. Articles focusing on persons aged 18 and over who identify as a racialised person with cancer, that describe therapies/therapeutic interventions/prevention/outcomes related to barriers, facilitators and solutions to enhancing access to and equity in cancer clinical trials will be eligible for inclusion in this rapid scoping review., Ethics and Dissemination: All data will be extracted from published literature. Hence, ethical approval and patient informed consent are not required. The findings of the scoping review will be submitted for publication in a peer-reviewed journal and presentation at international conferences., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: There is limited guidance on how to effectively promote safety culture in health care settings. We performed a systematic review to identify interventions to promote safety culture, specifically in oncology settings., Methods: Medical Subject Headings and text words for "safety culture" and "cancer care" were combined to conduct structured searches of MEDLINE, EMBASE, CDSR, CINAHL, Cochrane CENTRAL, PsycINFO, Scopus, and Web of Science for peer-reviewed articles published from 1999 to 2021. To be included, articles had to evaluate a safety culture intervention in an oncology setting using a randomized or nonrandomized, pre-post (controlled or uncontrolled), interrupted time series, or repeated-measures study design. The review followed PRISMA guidelines; quality of included citations was assessed using the ROBINS-I risk of bias tool., Results: Eighteen articles meeting the inclusion criteria were retained, reporting on interventions in radiation (14 of 18), medical (3 of 18), or general oncology (1 of 18) settings. Articles most commonly addressed incident learning systems (7 of 18), lean initiatives (4 of 18), or quality improvement programs (3 of 18). Although 72% of studies reported improvement in safety culture, there was substantial heterogeneity in the evaluation approach; rates of reporting of adverse events (9 of 18) or Agency for Healthcare Research and Quality Safety Culture survey results (9 of 18) were the most commonly used metrics. Most of the studies had moderate (28%) or severe (67%) risk of bias., Conclusions: Despite a growing evidence base describing interventions to promote safety culture in cancer care, definitive recommendations were difficult to make because of heterogeneity in study designs and outcomes. Implementation of incident learning systems seems to hold most promise., Competing Interests: The authors disclose no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Low-grade serous ovarian cancer (LGSC) represents 5% of all epithelial ovarian cancers. They are characterized by indolent growth and KRAS and BRAF mutations, differing from high-grade serous ovarian cancer both clinically and molecularly. LGSC has low response rates to traditional systemic therapies, including chemotherapy and hormonal therapy. The objective of this systematic review was to appraise the literature describing the efficacy of MEK inhibitors in the treatment of LGSC., Methods: A comprehensive search was conducted of the following databases: Medline ALL, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Sciences, ClinicalTrials.gov, International Clinical Trials Registry Platform (ICFRP), and International Standard Randomized Controlled Trials Number (ISRCTN) Registry. All studies investigating MEKi in the treatment of LGSC in the adjuvant or recurrent setting for patients 18 years of age or older were included. All titles/abstracts were then screened by 2 independent reviewers (A.K. and C.C.). The full-text articles were then screened. All disagreements were resolved by a third independent reviewer (T.Z.). Two independent reviewers (A.K. and C.C.) extracted data from the studies deemed eligible for final review., Results: A total of 2108 studies were identified in the initial search. Of these, a total of 4 studies met the eligibility criteria for systematic review. In these studies, 416 patients were treated with an MEKi alone. All patients included in the studies were being treated for LGSC in the recurrent setting. Varied results and efficacy of the MEKi were reported in each study., Conclusions: The results highlighted in this systematic review demonstrate varied responses to MEKi for recurrent LGSC. Further research is needed in this field comparing the efficacy to current therapies, as well as to further evaluate the safety and toxicity profile with long-term use of MEKi., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Health numeracy (numerical literacy) refers to an individual's ability to use numerical information to make effective health decisions. Numeracy is fundamental in the role of a health care provider, forming the basis of evidence-based medicine and effective patient-provider communication. Despite a high level of education, many health care providers struggle with numeracy. Numeracy is often integrated into training curricula; however, teaching modality, competencies covered, learner satisfaction, and effectiveness of these educational interventions varies., Method: A scoping review was conducted to explore and summarize what is known about numeracy skills education programs for health care providers. A comprehensive literature search was conducted from January 2010 to April 2021 in 10 databases. Controlled vocabulary terms and text words were used. The search was restricted to human studies, adults, and the English language. Articles were included if they were related to numeracy education for health care providers or trainees and provided details regarding methods, evaluation, and results., Results: The literature search retrieved 31,611 results and 71 met the inclusion criteria. Most interventions were conducted in a university setting, and targeted nursing students, medical students, resident physicians, and pharmacy students. Common numeracy concepts included statistics/biostatistics, medication calculations, evidence-based medicine, research methodology, and epidemiology. A variety of teaching modalities were used, which most often combined active approaches (eg, workshops, laboratories, small-group exercises, and discussion boards) with passive approaches (eg, traditional lectures and didactic teaching). Measured outcomes included knowledge and skills, self-efficacy, attitudes, and engagement., Discussion: Although efforts have been made to incorporate numeracy into training curricula, greater emphasis should be placed on developing strong numeracy skills in health care providers, particularly given the role numerical information plays in clinical decision making, evidence-based practices, and patient-provider communication., Competing Interests: Disclosures: The authors declare no conflict of interest., (Copyright © 2023 The Alliance for Continuing Education in the Health Professions, the Association for Hospital Medical Education, and the Society for Academic Continuing Medical Education.)

Purpose: We undertook a scoping review of the literature to synthesize what is known about lymphoma survivorship and develop a comprehensive set of lymphoma-specific survivorship recommendations., Methods: We searched the peer-reviewed literature from January 1995 to April 2022, focused on topics relevant to survivorship care in patients ≥ 18 years of age, treated curatively for non-Hodgkin's and Hodgkin's lymphoma, and in remission for at least 2 years., Results: We retained 92 articles; themes included late effects of treatment (53.3%, 49/92), particularly fatigue and sleep disturbances, and fertility, as well as psychosocial considerations of survivors (27.2%; 25/92), screening for secondary malignancies (22.8%; 21/92), outcomes of interventions to improve survivorship care (10.9%; 10/92), and best practices and elements for survivorship plans (8.7%; 8/92). While there were published guidelines for screening for recurrence and secondary malignancies, despite the considerable number of articles on the psychosocial aspects of survivorship care, there remains limited guidance on screening frequency and management strategies for anxiety and depression, sleep disturbances, and treatment-related fatigue within the lymphoma population., Conclusion: We have developed a comprehensive set of lymphoma-survivorship recommendations; however, work is needed to adapt them to local healthcare contexts., Implications for Survivors: While there is a focus in the literature on the long-term psychosocial impacts of cancer and its treatment on lymphoma survivors, there remains no concrete recommendations on effective screening and management of detriments to quality of life such as anxiety, depression, fatigue, and distress, and availability of local resources vary widely., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

With increasing reliance on technology in oncology, the impact of digital clinical decision support (CDS) tools needs to be examined. A systematic review update was conducted and peer-reviewed literature from 2016 to 2022 were included if CDS tools were used for live decision making and comparatively assessed quantitative outcomes. 3369 studies were screened and 19 were included in this updated review. Combined with a previous review of 24 studies, a total of 43 studies were analyzed. Improvements in outcomes were observed in 42 studies, and 34 of these were of statistical significance. Computerized physician order entry and clinical practice guideline systems comprise the greatest number of evaluated CDS tools (13 and 10 respectively), followed by those that utilize patient-reported outcomes (8), clinical pathway systems (8) and prescriber alerts for best-practice advisories (4). Our review indicates that CDS can improve guideline adherence, patient-centered care, and care delivery processes in oncology., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: A head and neck cancer (HNC) diagnosis significantly impacts a patient's quality of life (QOL). Palliative care potentially improves their QOL. We will conduct a scoping review to identify existing knowledge about palliative care interventions for patients with HNC., Methods and Analysis: This scoping review was designed in accordance with the JBI Manual for Evidence Synthesis: Scoping Reviews and will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Our eligibility criteria follow the Population, Intervention, Comparison or Control, Outcomes and Study characteristics framework. The population is adult patients with locally advanced, metastatic, unresectable and/or recurrent HNC. We include peer-reviewed journal articles and articles in the press, in English, reporting on palliative care interventions with at least two of the eight National Consensus Project on Clinical Practice Guidelines for Quality Palliative Care domains; studies with and without comparators will be included. The outcomes are patient QOL (primary) and symptom severity, patients' satisfaction with care, patients' mood, advance care planning and place of death (secondary). We developed a search strategy across ten databases, to be searched from the inception to 11 September 2023: Medline ALL (Medline and EPub Ahead of Print and In-Process, In-Data-Review & Other Non-Indexed Citations), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase Classic+Embase, Emcare and PsycINFO all from the OvidSP platform; CINAHL from EBSCOhost, Scopus from Elsevier, Web of Science from Clarivate and Global Index Medicus from WHO. We will extract data using a piloted data form and analyse the data through descriptive statistics and thematic analysis., Ethics and Dissemination: Ethics approval is not needed for a scoping review. We will disseminate the findings to healthcare providers and policy-makers by publishing the results in a scientific journal., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The prognosis of hepatocellular carcinoma (HCC) is influenced by both tumor and patient specific factors. Current therapies of advanced HCC target angiogenesis and immune evasion, however there are no clinically useful biomarkers to guide clinicians., Methods: Our aim in this retrospective cohort study was to validate single nucleotide polymorphisms (SNPs) prognostic of outcome in advanced HCC from the literature, and to analyze exploratory SNPs chosen from evaluation of the HCC tumor immune microenvironment. Using a database of patients with HCC treated with sorafenib, blood samples were genotyped, clinical variables were retrospectively collected, and SNPs were analyzed for association with progression-free survival (PFS) and overall survival (OS). A subsequent analysis was conducted to determine if identified SNPs were prognostic in trans arterial chemoembolization (TACE) treated patients., Results: Literature review identified 7 SNPs in vascular endothelial growth factor (VEGF), eNOS, angiopoietin 2 (ANGPT2) and vascular endothelial growth factor receptor 2 (VEGFR2), however none were externally validated in our dataset. Of the 35 exploratory immunomodulatory SNPs, the following were associated with PFS or OS: CCL2 C-C motif ligand 2 (CCL2) (rs1024611), interleukin-10 ( IL-10 ) (rs1800896), cytotoxic T-lymphocyte antigen-4 ( CTLA-4 ) (rs231775) and NFKB1 (rs28362491)., Conclusions: SNPs identified by literature review to be prognostic in sorafenib treated patients with advanced HCC were not validated in our dataset. Our findings suggest potentially important prognostic implications of SNPs in VEGFR2, CCL2, IL-10, CTLA-4 and NFKB1 that deserve further study., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tgh.amegroups.com/article/view/10.21037/tgh-23-22/coif). BHL reports grants, honoraria, and meeting support from Astrazeneca, and grants from Pfizer. DC reports grants, honoraria, or advisory board support from NCI, CIHR, CCSRI, Astrazeneca, Takeda, Boehringer Ingelheim, AMGEN, EMD Serono, Pfizer, Jazz, Merck, Abvie, Anheart, Roche, BMS, and Novartis. GL reports grants, honoraria, or advisory board support from NCI, CIHR, CCSRI, Astrazeneca, Takeda, Boehringer Ingelheim, AMGEN, EMD Serono, Pfizer, Jazz, Merck, Abvie, Anheart, Roche, BMS, and Novartis. The other authors have no conflicts of interest to declare., (2023 Translational Gastroenterology and Hepatology. All rights reserved.)

Serous epithelial ovarian cancer, classified as either high-grade (90%) or low-grade (10%), varies in molecular, histological, and clinicopathological presentation. Low-grade serous ovarian cancer (LGSOC) is a rare histologic subtype that lacks disease-specific evidence-based treatment regimens. However, LGSOC is relatively chemo-resistant and has a poor response to traditional treatments. Alternative treatments, including biologic therapies such as bevacizumab, have shown some activity in LGSOC. Thus, the objective of this systematic review is to determine the effect and safety of bevacizumab in the treatment of LGSOC. Following PRISMA guidelines, Medline ALL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase all from the OvidSP platform, ClinicalTrials.gov, International Clinical Trials Registry Platform, International Standard Randomised Controlled Trial Number Registry were searched from inception to February 2022. Articles describing bevacizumab use in patients with LGSOC were included. Article screening, data extraction, and critical appraisal of included studies were completed by two independent reviewers. The effect of bevacizumab on the overall response rate, progression-free survival, overall survival, and adverse effects were summarized. The literature search identified 3064 articles, 6 of which were included in this study. A total of 153 patients were analyzed; the majority had stage IIIC cancer (56.2%). The overall median response rate reported in the studies was 47.5%. Overall, bevacizumab is a promising treatment for LGSOC, with response rates higher than traditional treatment modalities such as conventional chemotherapy, and is often overlooked as a treatment tool. A prospective clinical trial evaluating the use of bevacizumab in LGSOC is necessary to provide greater evidence and support these findings.

Introduction: With the COVID-19 pandemic, most continuing medical education activities became virtual (VCME). The authors conducted a scoping review to synthesize the advantages and disadvantages of VCME to establish the impact of this approach on inequities that physicians face along the intersections of gender, race, and location of practice., Methods: Guided by the methodological framework of Arksey and O'Malley, the search included six databases and was limited to studies published between January 1991 to April 2021. Eligible studies included those related to accredited/non-accredited post-certification medical education, conferences, or meetings in a virtual setting focused on physicians. Numeric and inductive thematic analyses were performed., Results: 282 studies were included in the review. Salient advantages identified were convenience, favourable learning formats, collaboration opportunities, effectiveness at improving knowledge and clinical practices, and cost-effectiveness. Prominent disadvantages included technological barriers, poor design, cost, lack of sufficient technological skill, and time. Analysis of the studies showed that VCME was most common in the general/family practice specialty, in suburban settings, and held by countries in the Global North. A minority of studies reported on gender (35%) and race (4%)., Discussion: Most studies report advantages of VCME, but disadvantages and barriers exist that are contextual to the location of practice and medical subspecialty. VCME events are largely organized by Global North countries with suboptimized accessibility for Global South attendees. A lack of reported data on gender and race reveals a limited understanding of how VCME affects vulnerable populations, prompting potential future considerations as it evolves., Competing Interests: The authors report no conflicts of interest., (© 2023 Cheng, Papadakos, Umakanthan, Fazelzad, Martimianakis, Ugas, Giuliani; licensee Synergies Partners.)

Purpose: Global increases in cancer, coupled with a shortage of cancer specialists, has led to an increasing role for primary care providers (PCP) in cancer care. This review aimed to examine all extant cancer curricula for PCPs and to analyze the motivations for curriculum development., Methods: A comprehensive literature search was conducted from inception to October 13, 2021, with no language restrictions. The initial search yielded 11,162 articles and 10,902 articles underwent title and abstract review. After full-text review, 139 articles were included. Numeric and thematic analyses were conducted and education programs were evaluated using Bloom's taxonomy., Results: Most curricula were developed in high-income countries (HICs), with 58% in the United States. Cancer-specific curricula focused on HIC priority cancers, such as skin/melanoma, and did not represent the global cancer burden. Most (80%) curricula were developed for staff physicians and 73% focused on cancer screening. More than half (57%) of programs were delivered in person, with a shift toward online delivery over time. Less than half (46%) of programs were codeveloped with PCPs and 34% did not involve PCPs in the program design and development. Curricula were primarily developed to improve cancer knowledge, and 72 studies assessed multiple outcome measures. No studies included the top two levels of Bloom's taxonomy of learning (evaluating; creating)., Conclusion: To our knowledge, this is the first review to assess the current state of cancer curricula for PCPs with a global focus. This review shows that extant curricula are primarily developed in HICs, do not represent the global cancer burden, and focus on cancer screening. This review lays a foundation to advance the cocreation of curricula that are aligned to the global cancer burden.

Background: Electronic prospective surveillance models (ePSMs) for cancer rehabilitation include routine monitoring of the development of treatment toxicities and impairments via electronic patient-reported outcomes. Implementing ePSMs to address the knowledge-to-practice gap between the high incidence of impairments and low uptake of rehabilitation services is a top priority in cancer care., Methods: We conducted a scoping review to understand the state of the evidence concerning the implementation of ePSMs in oncology. Seven electronic databases were searched from inception to February 2021. All articles were screened and extracted by two independent reviewers. Data regarding the implementation strategies, outcomes, and determinants were extracted. The Expert Recommendations for Implementing Change taxonomy and the implementation outcomes taxonomy guided the synthesis of the implementation strategies and outcomes, respectively. The Consolidated Framework for Implementation Research guided the synthesis of determinants based on five domains (intervention characteristics, individual characteristics, inner setting, outer setting, and process)., Results: Of the 5122 records identified, 46 interventions met inclusion criteria. The common implementation strategies employed were "conduct educational meetings," "distribute educational materials," "change record systems," and "intervene with patients to enhance uptake and adherence." Feasibility and acceptability were the prominent outcomes used to assess implementation. The complexity, relative advantage, design quality, and packaging were major implementation determinants at the intervention level. Knowledge was key at the individual level. At the inner setting level, major determinants were the implementation climate and readiness for implementation. At the outer setting level, meeting the needs of patients was the primary determinant. Engaging various stakeholders was key at the process level., Conclusions: This review provides a comprehensive summary of what is known concerning the implementation of ePSMs. The results can inform future implementation and evaluation of ePSMs, including planning for key determinants, selecting implementation strategies, and considering outcomes alongside local contextual factors to guide the implementation process., (© 2023. The Author(s).)

Objective: Medical care for cancer is increasingly directed by genomic laboratory testing for alterations in the tumor genome that are significant for diagnosis, prognosis and therapy. Uniquely in medicine, providers must search the biomedical literature for each patient to determine the clinical significance of these alterations. Access to published scientific literature is frequently subject to high fees, with access limited to institutional subscriptions. We sought to investigate the degree to which the scientific literature is accessible to clinical cancer genomics providers, and the potential role of university and hospital system libraries in information access for cancer care., Methods: We identified 265 journals that were accessed during the interpretation and reporting of clinical test results from 1,842 cancer patients at the University Health Network (Toronto, Canada). We determined the degree of open access for this set of clinically important literature, and for any journals not available through open access we surveyed subscription access at seven academic hospital systems and at their affiliated universities., Results: This study found that nearly half (116/265) of journals have open access mandates that make articles freely available within one year of release. For the remaining subscription access journals, universities provided a uniformly high level of access, but access available through hospital system collections varied widely., Conclusion: This study highlights the importance of different modes of access to the use of the scientific literature in clinical practice and points to challenges that must be overcome as genomic medicine grows in scale and complexity., (Copyright © 2023 Schnell D'Souza, Gregory Downs, Shawn Hendrikx, Rouhi Fazelzad, Gabriel Boldt, Karen Burns, Darlene Chapman, Declan Dawes, Antonia Giannarakos, Lori Anne Oja, Risa Schorr, Maureen Babb, Amada Hodgson, Jessica McEwan, Pamela Jacobs, Tracy Stockley, Tim Tripp, Ian King.)

This scoping review explored what is known about the experiences of informal cancer caregivers (CGs) who are newcomers with limited language proficiency. A literature search was performed in seven databases and the search yielded 11,289 articles. After duplicate removal and title and abstract screening, 216 articles underwent full text review and 57 articles and were synthesized. Most studies (n = 41, 72%) were qualitative and were published in North America (n = 35, 61%). Most CG participants were female (69%) and only 19 studies explicitly identified the CG country of origin. Of those that did, 26% originated from Asia, with most migrating from East Asia. Significant challenges were experienced by newcomer CGs and chief among these were related to communication challenges with HCPs that were exacerbated by a lack of availability of medical interpreters and the complexity of oncology health information. Efforts are needed to better integrate newcomer CGs into cancer care., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: People who use drugs with life-limiting illnesses experience substantial barriers to accessing palliative care. Demand for palliative care is expected to increase during communicable disease epidemics and pandemics. Understanding how epidemics and pandemics affect palliative care for people who use drugs is important from a service delivery perspective and for reducing population health inequities., Aim: To explore what is known about communicable disease epidemics and pandemics, palliative care, and people who use drugs., Design: Scoping review., Data Sources: We searched six bibliographic databases from inception to April 2021 as well as the grey literature. We included English and French records about palliative care access, programs, and policies and guidelines for people ⩾18 years old who use drugs during communicable disease epidemics and pandemics., Results: Forty-four articles were included in our analysis. We identified limited knowledge about palliative care for people who use drugs during epidemics and pandemics other than HIV/AIDS. Through our thematic synthesis of the records, we generated the following themes: enablers and barriers to access, organizational barriers, structural inequity, access to opioids and other psychoactive substances, and stigma., Conclusions: Our findings underscore the need for further research about how best to provide palliative care for people who use drugs during epidemics and pandemics. We suggest four ways that health systems can be better prepared to help alleviate the structural barriers that limit access as well as support the provision of high-quality palliative care during future epidemics and pandemics.

Background The best supplemental breast cancer screening modality in women at average risk or intermediate risk for breast cancer with dense breast and negative mammogram remains to be determined. Purpose To conduct systematic review and meta-analysis comparing clinical outcomes of the most common available supplemental screening modalities in women at average risk or intermediate risk for breast cancer in patients with dense breasts and mammography with negative findings. Materials and Methods A comprehensive search was conducted until March 12, 2020, in Medline, Epub Ahead of Print and In-Process and Other Non-Indexed Citations; Embase Classic and Embase; Cochrane Central Register of Controlled Trials; and Cochrane Database of Systematic Reviews, for Randomized Controlled Trials and Prospective Observational Studies. Incremental cancer detection rate (CDR); positive predictive value of recall (PPV1); positive predictive value of biopsies performed (PPV3); and interval CDRs of supplemental imaging modalities, digital breast tomosynthesis, handheld US, automated breast US, and MRI in non-high-risk patients with dense breasts and mammography negative for cancer were reviewed. Data metrics and risk of bias were assessed. Random-effects meta-analysis and two-sided metaregression analyses comparing each imaging modality metrics were performed (PROSPERO; CRD42018080402). Results Twenty-two studies reporting 261 233 screened patients were included. Of 132 166 screened patients with dense breast and mammography negative for cancer who met inclusion criteria, a total of 541 cancers missed at mammography were detected with these supplemental modalities. Metaregression models showed that MRI was superior to other supplemental modalities in CDR (incremental CDR, 1.52 per 1000 screenings; 95% CI: 0.74, 2.33; P < .001), including invasive CDR (invasive CDR, 1.31 per 1000 screenings; 95% CI: 0.57, 2.06; P < .001), and in situ disease (rate of ductal carcinoma in situ, 1.91 per 1000 screenings; 95% CI: 0.10, 3.72; P < .04). No differences in PPV1 and PPV3 were identified. The limited number of studies prevented assessment of interval cancer metrics. Excluding MRI, no statistically significant difference in any metrics were identified among the remaining imaging modalities. Conclusion The pooled data showed that MRI was the best supplemental imaging modality in women at average risk or intermediate risk for breast cancer with dense breasts and mammography negative for cancer. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Hooley and Butler in this issue.

Introduction: Antimicrobial resistance (AMR) is a growing global public health concern and is becoming a significant challenge in the management of patients with cancer. Due to the immunosuppressive nature of cancer treatment, infection is a common complication and the necessary high usage of antibiotics increases the risk of AMR. Failure to adequately prevent and treat infection in patients with cancer as a result of AMR can increase the morbidity and mortality of the disease. The objective of this scoping review is to understand the relationship between AMR and cancer in order to develop effective antimicrobial stewardship in this patient population and minimise the detrimental effects of AMR on cancer outcomes., Methods and Analysis: This scoping review will follow the Arksey and O'Malley methodology framework. An exploratory review of the literature on antibiotic resistance in cancer care will help to define the research questions (stage 1). A broad range of electronic databases (MEDLINE ALL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and Embase) and search terms will be used to retrieve relevant articles published between 2000 and 2021 (stage 2). Studies will be systematically selected based on the eligibility criteria by two independent reviewers (stage 3). The titles and abstracts will be appraised to determine whether articles meet the eligibility criteria. This will be followed by screening of the full texts and only relevant publications will be retrieved. Data will then be extracted, collated and charted (stage 4); and the summary of aggregated results will be presented (stage 5)., Ethics and Dissemination: As this scoping review will collect and synthesise data from publicly available sources, no ethics review is required. When data collection and summarisation is completed, results will be disseminated through peer-reviewed publication and the key findings of the review will be presented at relevant conferences., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Populations with limited language proficiency (LLP) experience difficulties understanding health information and accessing care. This study aimed to explore health literacy and LLP by examining the published literature on the barriers and facilitators to health care., Methods: A scoping review of studies with populations in countries and regions where they have LLP in the locally dominant language was conducted., Results: One-hundred and forty-three (143) articles met eligibility criteria. Most studies were conducted in North America (n = 99, 69.2%) and the primary language of study participants was Spanish (n = 32; 22.4%). Limited language proficiency was associated with low health literacy. Age was a consistent predictor of LLP, while education was predictive of low health literacy. Low health literacy was associated with poorer health outcomes., Discussion: This review synthesizes the existing research regarding populations with LLP and their health literacy, demonstrating the importance that the intersection between the two has on patient experiences and behaviors.

Background: Age-related complex medical conditions have been commonly reported among adolescents and young adults with advanced life-limiting illness. There is increasing interest in exploring their palliative care needs and end-of-life experiences., Aim: This scoping review aimed to explore the available literature about providing palliative and end-of-life care to adolescents and young adults with advanced life-limiting illnesses., Design: Scoping review. This review was registered on Open Science Framework (https://doi.org/10.17605/OSF.IO/SPTD7)., Data Sources: Electronic databases (MEDLINEALL, Embase, Emcare, Cochrane Central Register of Controlled Trial CENTRAL, Scopus, PsycINFO, Cochrane Database of Systematic Reviews), Google Scholar and reference lists were searched up to October 2021. We included studies reporting on adolescents and/or young adults with advanced life-limiting illnesses. There were no limitations concerning location, type of illness or study design., Results: We identified 51 studies published between 2002 and 2021. Most studies were published in the United States ( n  = 34, 67%), and nine studies (18%) reported exclusively on patients with non-malignant illnesses. Two thirds of the identified studies were case reports and retrospective chart reviews ( n  = 33). Three main topics were identified: Physical symptom burden ( n  = 26, 51%), Psychological and social needs ( n  = 33, 65%), and end-of-life care ( n  = 30, 59%). Twenty-six studies (51%) were focused only on one topic, and the age range used to identify adolescents and young adults varied based on the study location., Conclusion: The findings of this review shed light on the different palliative care experiences and knowledge gaps related to adolescents and young adults as an underserved and vulnerable patient population. Further research needs to be dedicated toward palliative care programs tailored for adolescents and young adults.

Importance: Epidemiological evidence supports a role for statins in improving survival in advanced prostate cancer, particularly among men receiving androgen-ablative therapies., Objective: To study the association between statin use and survival among men with prostate cancer receiving androgen deprivation therapy (ADT) or androgen receptor axis-targeted therapies (ARATs)., Data Sources: This systemic review and meta-analysis used sources from MEDLINE, EMBASE, Epub Ahead of Print, Cochrane Clinical Trials, Cochrane Systematic Reviews, and Web of Science from inception to September 6, 2022., Study Selection: Observational studies reporting associations of concurrent statin use and survival outcomes (in hazard ratios [HRs])., Data Extraction and Synthesis: Two authors independently abstracted all data. Summary estimates pooled multivariable HRs with 95% CIs using the generic inverse variance method with random-effects modeling. A priori specified subgroup and sensitivity analyses were undertaken, and heterogeneity, study quality, and publication bias were evaluated. Confidence in the evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach., Main Outcomes and Measures: Overall mortality and prostate cancer-specific mortality (PCSM)., Results: Twenty-five cohorts of 119 878 men (65 488 statin users [55%]) with more than 74 416 deaths were included. Concurrent statin use was associated with a 27% reduction in the risk of overall mortality (HR, 0.73 [95% CI, 0.66-0.82]; I2 = 83%) and a 35% reduction in the risk of PCSM (HR, 0.65 [95% CI, 0.58-0.73]; I2 = 74%), with substantial heterogeneity in both estimates. Subgroup analyses identified a PCSM advantage associated with statins for men receiving ARATs compared with ADT alone (HR, 0.40 [95% CI, 0.30-0.55] vs 0.68 [95% CI, 0.60-0.76]; P = .002 for difference). Confidence in the evidence was rated low for both outcomes., Conclusions and Relevance: The findings of this meta-analysis show that concurrent statin use was associated with reduced overall mortality and PCSM among men receiving androgen-ablative therapies for advanced prostate cancer. These findings are limited by the observational nature of the data and residual unexplained interstudy heterogeneity. Randomized clinical trials are warranted to validate these results.

The Choosing Wisely (CW) campaign, launched in 2012, includes oncology-specific recommendations to promote evidence-based care and deimplementation of low-value practices. However, it is unclear to what extent the campaign has prompted practice change. We systematically reviewed the literature to evaluate the uptake of cancer-specific CW recommendations focusing on the period before the declaration of the COVID-19 pandemic. We used Grimshaw's deimplementation framework to thematically group the findings and extracted information on implementation strategies, barriers, and facilitators from articles reporting on active implementation. In the 98 articles addressing 32 unique recommendations, most reported on passive changes in adherence pre-post publication of CW recommendations. Use of active surveillance for low-risk prostate cancer and reduction in staging imaging for early breast cancer were the most commonly evaluated recommendations. Most articles assessing passive changes in adherence pre-post CW publication reported improvement. All articles evaluating active implementation (10 of 98) reported improved compliance (range: 3%-73% improvement). Most common implementation strategies included provider education and/or stakeholder engagement. Preconceived views and reluctance to adopt new practices were common barriers; common facilitators included the use of technology and provider education to increase provider buy-in. Given the limited uptake of oncology-specific CW recommendations thus far, more attention toward supporting active implementation is needed. Effective adoption of CW likely requires a multipronged approach that includes building stakeholder buy-in through engagement and education, using technology-enabled forced functions to facilitate change along with policy and reimbursement models that disincentivize low-value care. Professional societies have a role to play in supporting this next phase of CW., Competing Interests: Monika K. KrzyzanowskaThis author is an Editor for JCO Oncology Practice. Journal policy recused the author from having any role in the peer review of this manuscript.Consulting or Advisory Role: Eisai, Lilly, IpsenResearch Funding: Eisai (Inst), Exelixis (Inst), Lilly (Inst) Vishal KukretiHonoraria: Celgene, Takeda, Amgen, Kirin Kyoto, Eusa PharmaceuticalConsulting or Advisory Role: AmgenNo other potential conflicts of interest were reported.

The risk of recurrence after discontinuation of anticoagulation for a combined oral contraceptive (COC)-associated venous thromboembolism (VTE) is unclear. Therefore, we conducted a systematic review and meta-analysis to estimate the incidence of recurrent VTE among women with COC-associated VTE, unprovoked VTE and to compare the incidence of recurrent VTE between the two groups. The Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase Classic +Embase and Medline ALL to July 2020 and citations from included studies were searched. Randomized controlled trials, prospective cohort studies and meta-analyses of these study types were selected. The analysis was conducted by random-effects model. Nineteen studies were identified including 1537 women [5828 person-years (PY)] with COC-associated VTE and 1974 women (7798 PY) with unprovoked VTE. Studies were at low risk of bias. The incidence rate of VTE recurrence was 1.22/100 PY [95% confidence interval (CI) 0.92-1.62, I 2  = 6%] in women with COC-associated VTE, 3.89/100 PY (95% CI 2.93-5.17, I 2  = 74%) in women with unprovoked VTE and the unadjusted incidence rate ratio was 0.34 (95% CI 0.26-0.46, I 2  = 3%). The recurrence risk in women after COC-associated VTE is low and lower than after an unprovoked VTE., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)

Introduction: Published health-related quality of life (HRQOL) outcomes are lacking in patients treated for oligo-metastatic disease (OMD). The aim of this systematic review and individual patient data meta-analysis is to determine the effect of stereotactic body radiotherapy (SBRT) on HRQOL outcomes of patients with OMD., Methods: Studies screened included adults with extra-cranial OMD, defined as ≤ 5 metastases, SBRT intended as definitive treatment, and HRQOL as primary or secondary outcome. Primary outcome was change in HRQOL at 12-months from baseline in patients with OMD who received SBRT (versus not), reported as standardized mean difference (SMD)., Results: A total of 7556 publications were identified, four studies met inclusion criteria (2 single arm interventional studies and 2 randomised controlled trials [RCTs]), and individual patient data was available from 3 studies (175 patients). In the two RCTs, there was no SS difference in the SMD between patients who received SBRT and those that did not (0.09 [95 % CI -0.32, 0.5], P = 0.66). On meta-analysis of patients (N = 107) who received SBRT the SMDwas -0.23 (95 % CI [-0.42, -0.04], versus -0.25 (95 % CI [-0.57, 0.07]) in those who did not (N = 37) receive SBRT, demonstrating a small deterioration from baseline., Conclusion: In patients with OMD, there is no difference in HRQOL at 12-months from baseline between patients who received SBRT and those that did not. However, a small HRQOL deterioration was found in both groups of patients. More in-depth analysis of relevant HRQOL domains, in the setting of OMD, is required to better understand the potential impact of SBRT., Competing Interests: Declaration of Competing Interest RO – reports Varian Medical Systems Research Grant. PO – reports grant support from Varian and Bayer. Consultancies for AAA, Astella, Bayer, Curium, Janssen and Telix. LAD – reports current activity on Merck ITT clinical trial - ongoing. DP - reports research funding from the Ontario Insitute for Cancer Research, and a consultant role with Need Inc (digital oncology startup). SS – reports grant support from Varian. No conflicts of interest are reported by - ASB, JH, AB, RW, JR, RF, ZL, RP, NA., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: Non-V600 mutations comprise approximately 35% of all BRAF mutations in cancer. Many of these mutations have been identified as oncogenic drivers and can be classified into three classes according to molecular characteristics. Consensus treatment strategies for class 2 and 3 BRAF mutations have not yet been established., Methods: We performed a systematic review and meta-analysis with published reports of individual patients with cancer harboring class 2 or 3 BRAF mutations from 2010 to 2021, to assess treatment outcomes with US Food and Drug Administration-approved mitogen-activated protein kinase (MAPK) pathway targeted therapy (MAPK TT) according to BRAF class, cancer type, and MAPK TT type. Coprimary outcomes were response rate and progression-free survival., Results: A total of 18,167 studies were screened, identifying 80 studies with 238 patients who met inclusion criteria. This included 167 patients with class 2 and 71 patients with class 3 BRAF mutations. Overall, 77 patients achieved a treatment response. In both univariate and multivariable analyses, response rate and progression-free survival were higher among patients with class 2 compared with class 3 mutations, findings that remain when analyses are restricted to patients with melanoma or lung primary cancers. MEK ± BRAF inhibitors demonstrated greater clinical activity in class 2 compared with class 3 BRAF-mutant tumors than BRAF or EGFR inhibitors., Conclusion: This meta-analysis suggests that MAPK TTs have clinical activity in some class 2 and 3 BRAF-mutant cancers. BRAF class may dictate responsiveness to current and emerging treatment strategies, particularly in melanoma and lung cancers. Together, this analysis provides clinical validation of predictions made on the basis of a mutation classification system established in the preclinical literature. Further evaluation with prospective clinical trials is needed for this population., Competing Interests: Benny JohnsonConsulting or Advisory Role: Gritstone Bio, Incyte, Taiho Oncology, InsmedResearch Funding: Bristol Myers Squibb (Inst), Syntrix Biosystems (Inst) Ibiayi Dagogo-JackHonoraria: American Academic Health System, Total Health Conferencing, DAVA Oncology, Creative Educational Concepts, Medscape, ASCO Post, OncLive/MJH Life SciencesConsulting or Advisory Role: Boehringer Ingelheim, AstraZeneca, Xcovery, Catalyst Pharmaceuticals, Pfizer, Syros Pharmaceuticals, Novocure, BostonGene, Bayer, Genentech, Sanofi, JanssenResearch Funding: Pfizer (Inst), Array BioPharma (Inst), Novartis (Inst), Genentech (Inst), Calithera Biosciences (Inst), Vivace Therapeutics (Inst)Travel, Accommodations, Expenses: Pfizer, Array BioPharma Nathaniel J. MyallHonoraria: Patient Power Georg RichtigTravel, Accommodations, Expenses: Ipsen Marco GerlingerStock and Other Ownership Interests: VertexResearch Funding: Bristol Myers Squibb, Merck KGaA, Roche/Genentech Eiji ShinozakiHonoraria: Yakult Honsha, Merck Serono, Chugai Pharma, Takeda, Sanofi, Lilly, Taiho Pharmaceutical, Daiichi Sankyo/UCB Japan Takayuki YoshinoHonoraria: Chugai Pharma, Merck, Bayer Yakuhin, Ono Pharmaceutical, MSD K.K.Research Funding: MSD (Inst), Daiichi Sankyo Company, Limited (Inst), Ono Pharmaceutical (Inst), Taiho Pharmaceutical (Inst), Amgen (Inst), Sanofi (Inst), Pfizer (Inst), Genomedia (Inst), Sysmex (Inst), Nippon Boehringer Ingelheim (Inst), Chugai Pharma (Inst) Daisuke KotaniHonoraria: Takeda, Chugai Pharma, Lilly Japan, Merck Serono, Sysmex, Taiho Pharmaceutical, Ono Pharmaceutical, Bristol Myers Squibb Japan, MSD, Daiichi Sankyo/UCB JapanResearch Funding: Ono Pharmaceutical (Inst), MSD (Inst), Novartis (Inst), Janssen (Inst), IQvia (Inst), Syneos Health (Inst), CMIC (Inst) Jason R. FangusaroHonoraria: AstraZeneca, Pyramid BiosciencesConsulting or Advisory Role: Celgene, AstraZeneca Oliver GautschiConsulting or Advisory Role: Amgen (Inst), Lilly (Inst)Other Relationship: Bayer (Inst), Pfizer (Inst), Roche (Inst), Merck, Lilly Julien MazieresConsulting or Advisory Role: Novartis, Roche/Genentech, Pfizer, Bristol Myers Squibb, Lilly/ImClone, MSD, AstraZeneca, Pierre Fabre, Blueprint Medicines, Hengrui TherapeuticsResearch Funding: Roche (Inst), Bristol Myers Squibb (Inst), AstraZeneca (Inst), Pierre Fabre (Inst)Travel, Accommodations, Expenses: Pfizer, Roche, Bristol Myers Squibb Jeffrey A. SosmanHonoraria: Jazz Pharmaceuticals, Apexian Pharmaceuticals, Iovance BiotherapeuticsConsulting or Advisory Role: Apexigen, Jazz Pharmaceuticals, Iovance Biotherapeutics Scott KopetzThis author is a member of the JCO Precision Oncology Editorial Board. Journal policy recused the author from having any role in the peer review of this manuscript.Stock and Other Ownership Interests: MolecularMatch, Lutris, Iylon, Frontier MedicinesConsulting or Advisory Role: Genentech, EMD Serono, Merck, Holy Stone Healthcare, Novartis, Lilly, Boehringer Ingelheim, Boston Biomedical, AstraZeneca/MedImmune, Bayer Health, Pierre Fabre, Redx Pharma, Ipsen, Daiichi Sankyo, Natera, HalioDx, Lutris, Jacobio, Pfizer, Repare Therapeutics, Inivata, GlaxoSmithKline, Jazz Pharmaceuticals, Iylon, Xilis, AbbVie, Amal Therapeutics, Gilead Sciences, Mirati Therapeutics, Flame Biosciences, Servier, Carina Biotech, Bicara Therapeutics, Endeavor BioMedicines, Numab, Johnson & Johnson/Janssen, Genomic Health, Frontier Medicines, Replimune, Taiho PharmaceuticalResearch Funding: Sanofi, Biocartis, Guardant Health, Array BioPharma, Genentech/Roche, EMD Serono, MedImmune, Novartis, Amgen, Lilly, Daiichi Sankyo Vivek SubbiahConsulting or Advisory Role: MedImmune, Helsinn Therapeutics, Loxo, R-Pharm, QED TherapeuticsResearch Funding: Novartis (Inst), GlaxoSmithKline (Inst), NanoCarrier (Inst), Northwest Biotherapeutics (Inst), Genentech/Roche (Inst), Berg Pharma (Inst), Bayer (Inst), Incyte (Inst), Fujifilm (Inst), PharmaMar (Inst), D3 Oncology Solutions (Inst), Pfizer (Inst), Amgen (Inst), AbbVie (Inst), Multivir (Inst), Blueprint Medicines (Inst), LOXO (Inst), Vegenics (Inst), Takeda (Inst), Alfasigma (Inst), Agensys (Inst), Idera (Inst), Boston Biomedical (Inst), Inhibrx (Inst), Exelixis (Inst), Turning Point Therapeutics (Inst)Travel, Accommodations, Expenses: PharmaMar, Bayer, Novartis, Helsinn TherapeuticsOther Relationship: Medscape Michael A. DaviesConsulting or Advisory Role: Genentech/Roche, Novartis, Bristol Myers Squibb, NanoString Technologies, Array BioPharma, Apexigen, Pfizer, Eisai, ABM, Iovance BiotherapeuticsResearch Funding: GlaxoSmithKline (Inst), Genentech/Roche (Inst), AstraZeneca (Inst), Merck (Inst), Oncothyreon (Inst), Myriad Genetics (Inst), Sanofi (Inst), Pfizer (Inst), ABM (Inst), LEAD (Inst) Anna L. GrooverEmployment: BioMed Valley Discoveries Ryan J. SullivanConsulting or Advisory Role: Novartis, Merck, Replimune, Asana Biosciences, Alkermes, Eisai, Pfizer, Iovance Biotherapeutics, OncoSec, AstraZeneca, Bristol Myers SquibbResearch Funding: Amgen (Inst), Lilly (Inst), BioMed Valley Discoveries (Inst), Merck (Inst), Deciphera (Inst), Roche/Genentech (Inst), Moderna Therapeutics (Inst), Sanofi (Inst), Aeglea Biotherapeutics (Inst), Asana Biosciences (Inst), Viralytics (Inst), Compugen (Inst), Neon Therapeutics (Inst), Pfizer (Inst), BeiGene (Inst), Rubius Therapeutics (Inst), Strategia (Inst) Keith T. FlahertyStock and Other Ownership Interests: Clovis Oncology, Loxo, X4 Pharma, Strata Oncology, PIC Therapeutics, Apricity Health, Oncoceutics, FOGPharma, Tvardi Therapeutics, Checkmate Pharmaceuticals, Kinnate Biopharma, Scorpion Therapeutics, ALX Oncology, xCures, Monopteros Therapeutics, Vibliome Therapeutics, Transcode Therapeutics, Soley Therapeutics, Nextech InvestConsulting or Advisory Role: Novartis, Lilly, Oncoceutics, Tvardi Therapeutics, Takeda, Debiopharm Group, OmRx Douglas B. JohnsonConsulting or Advisory Role: Bristol Myers Squibb, Merck, Novartis, Iovance Biotherapeutics, Catalyst Pharmaceuticals, Oncosec, Pfizer, Mosaic ImmunoEngineering, Targovax, MallinckrodtResearch Funding: Incyte, Bristol Myers SquibbPatents, Royalties, Other Intellectual Property: Intellectual property and patents pending surrounding use of MHC-II and response to immune therapy David W. CesconConsulting or Advisory Role: Pfizer, AstraZeneca, Novartis, GlaxoSmithKline, Merck, Roche/Genentech, Exact Sciences, Gilead Sciences, EisaiResearch Funding: Merck (Inst), Roche/Genentech (Inst), GlaxoSmithKline (Inst), Pfizer (Inst), Inivata (Inst), AstraZeneca (Inst), Gilead Sciences (Inst)Patents, Royalties, Other Intellectual Property: Patent (US62/675,228) for methods of treating cancers characterized by a high expression level of spindle and kinetochore-associated complex subunit 3 (ska3) geneUncompensated Relationships: Inivata Anna SpreaficoHonoraria: Bristol Myers Squibb, Medison & ImmunocoreConsulting or Advisory Role: Novartis, Merck, Bristol Myers Squibb, Oncorus, Medison & ImmunocoreResearch Funding: Bristol Myers Squibb, Novartis, Merck, Symphogen, AstraZeneca/MedImmune, Bayer, Surface Oncology, Janssen Oncology, Northern Biologics, Replimune, Roche, Alkermes, Array BioPharma, GlaxoSmithKline, Treadwell Therapeutics (Inst), Amgen (Inst)Travel, Accommodations, Expenses: Merck, Bristol Myers Squibb, Idera, Bayer, Janssen Oncology, Roche George ZogopoulosPatents, Royalties, Other Intellectual Property: TC-PTP inhibitors as APC activators for immunotherapyTravel, Accommodations, Expenses: Baxalta April A.N. RoseEmployment: Merck (I)Stock and Other Ownership Interests: Merck (I)Consulting or Advisory Role: PfizerNo other potential conflicts of interest were reported.

Purpose: To provide evidence-based recommendations on the management of malignant bowel obstruction (MBO) for patients with advanced cancer., Methods: The Multinational Association for Supportive Care in Cancer (MASCC) MBO study group conducted a systematic review of databases (inception to March 2021) to identify studies about patients with advanced cancer and MBO that reported on the following outcomes: symptom management, bowel obstruction resolution, prognosis, overall survival, and quality of life. The review was restricted to studies published in English, but no restrictions were placed on publication year, country, and study type. As per the MASCC Guidelines Policy, the findings were synthesized to determine the levels of evidence to support each MBO intervention and, ultimately, the graded recommendations and suggestions., Results: The systematic review identified 17,656 published studies and 397 selected for the guidelines. The MASCC study group developed a total of 25 evidence-based suggestions and recommendations about the management of MBO-related nausea and vomiting, bowel movements, pain, inflammation, bowel decompression, and nutrition. Expert consensus-based guidance about advanced care planning and psychosocial support is also provided., Conclusion: This MASCC Guideline provides comprehensive, evidence-based recommendations about MBO management for patients with advanced cancer., (© 2022. The Author(s).)

Purpose: Many individuals with advanced cancer have unmet psychological needs and often lack access to supportive care. Psychotherapy for adults with advanced cancer is a promising way to address some of the challenges in meeting these care needs. Nurses are the largest cohort of healthcare workers who can practice as psychotherapists and are positioned ideally to integrate these interventions as part of routine care. The purpose of this scoping review is to map the literature on psychotherapeutic interventions among adults with advanced cancer and to explore the nursing role in this body of evidence., Methods: We conducted a scoping review for relevant quantitative, qualitative, and mixed methods studies. The content of included studies was analyzed and grouped based on two broad categories that describe how nursing's role was mentioned, described, and utilized: 1. Nurses are not the interventionist/psychotherapist and, 2. Nurses are mentioned as the interventionist/psychotherapist., Results: Eighty-six studies were included. Overall, majority of studies did not mention a role for nursing in any capacity. Some studies mentioned a non-interventionist role for nursing in the research study. Fourteen studies mentioned nurses as interventionists/psychotherapists. These studies focused on feasibility, acceptability and patient related outcomes of brief psychotherapies. Dignity therapy was the most common psychotherapy in studies where nurses were utilized as interventionists, followed by life review and supportive expressive therapies. Very few studies discussed nursing's role in this area and nursing's capacity to deliver this form of care., Conclusion: There is paucity in nursing research focused on psychotherapy for adults with advanced cancer. It is feasible and acceptable for nurses to deliver brief psychotherapies to adults with advanced cancer, and the integration of these techniques in everyday practice has great potential that must be explored. The development of this knowledge base is needed to support future education, research, and practice policy agendas., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: Low-grade serous ovarian cancer (LGSC) is a relatively chemo-resistant disease with limited effective treatment options for patients with recurrence. Secondary cytoreductive surgery (SCS) is commonly offered at recurrence, although any benefit this has on survival is not fully determined. This review evaluates the impact of SCS, including residual disease, on progression-free survival (PFS) and overall survival (OS) in recurrent LGSC., Methods: A comprehensive search of Medline ALL, Embase Classic + Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science was conducted to obtain studies evaluating optimal or complete SCS versus suboptimal SCS and the amount of residual disease in recurrent LGSC. Meta-analysis was performed and PFS and OS outcomes were calculated., Results: 1Of 5296 studies screened, 350 progressed to full-text review, with 9 ultimately selected for inclusion in the systematic review. Two studies met criteria for meta-analysis of PFS and of OS. The presence of visible residual disease at the conclusion of SCS negatively impacted PFS (HR = 3.51, 95% CI = 1.72-7.14), whereas SCS with no residual disease significantly improved OS (HR = 0.4, 95% CI = 0.23-0.7) in patients with recurrent LGSC. Diffuse and extensive disease distribution was inversely linked to survival. In addition, SCS as an initial treatment for recurrent LGSC was associated with superior survival in comparison to chemotherapy. A short platinum-free interval was not associated with worse survival in this cohort., Conclusions: Complete SCS, and to a lesser extent optimal SCS, are associated with improved PFS and OS in patients with recurrent LGSC. SCS may be a better initial treatment strategy than systemic chemotherapy for recurrent disease. Patients with recurrent LGSC should be evaluated for the role of SCS based on disease distribution and functional status, irrespective of the platinum-free interval. Prospective studies are needed to further study the role of SCS in patients with recurrent LGSC., Competing Interests: Declaration of Competing Interest The authors have no conflict of interests to declare., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Current guidelines recommend somatic genomic sequencing for patients with advanced pancreatic cancer to identify targetable alterations amenable to targeted therapy. The benefit of somatic genomic sequencing in pancreatic cancer remains unclear. This study aims to assess the evidence supporting genomic sequencing to inform treatment selection for patients with advanced pancreatic cancer., Methods: A systematic review identified prospective studies of exocrine pancreatic cancer patients published before August 2020 which conducted genomic sequencing to inform treatment selection. Outcomes of interest included the proportion of patients with targetable alterations, the proportion that received targeted treatments, and the impact of targeted treatments on overall survival. Meta-analysis for proportions and hazard ratios was performed using Dersimonian and Laird random effect models., Results: 19 studies (representing 2048 pancreatic cancer patients) were included. Sequencing methodologies, definitions of targetable alterations, and approaches treatment selection varied across studies and were incompletely reported. 590 of 1382 sequenced patients harboured a targetable alteration (random effects meta-analysis estimate of the proportion 0.46, 95% confidence interval 0.32-0.61). The proportion of patients with targetable alterations was highly heterogenous between studies (I 2 93%, P < 0.001). 91 of 1390 patients received a matched therapy based on their targetable alterations (random effects meta-analysis estimate of the proportion 0.12, 95% CI 0.06-0.23). One observational study reported an overall survival benefit of matched therapy., Conclusions: Genomic sequencing frequently identifies targetable alterations in pancreatic cancers. Further research is required to standardize the definitions of targetable alterations, the approach to treatment matching, and quantify the benefit of targeted therapy., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: The addition of platinum agents to anthracycline and taxane-based chemotherapy in early-stage triple negative breast cancer (TNBC) patients improves pathological complete response (pCR). Long-term outcomes, such as disease-free survival (DFS) and overall survival (OS), have not been well-established., Methods: A systematic literature review identified studies using platinum-based treatment in TNBC patients in the neoadjuvant or adjuvant setting with reportable long-term outcomes. Hazard ratios (HR) from collected data were pooled in a meta-analysis using generic inverse-variance and random effects modeling. Subgroup analyses were conducted based on treatment setting and study design., Results: Fourteen studies comprising 3518 patients met the inclusion criteria. Median follow up was 56.2 months. All studies reported DFS and 9 studies (64%) reported OS. DFS was significantly better in platinum-based treatment (HR 0.71, 95% confidence interval (CI) 0.56-0.89; p = 0.03). However, OS was no different (HR 0.98, 95% CI 0.75-1.27; p = 0.87). There was a non-significant difference between platinum exposure in the adjuvant compared to neoadjuvant setting for both DFS (HR 0.75 vs 0.62, p = 0.43) and for OS (HR 0.90 vs 1.10, p = 0.58). The addition of platinum was associated with more thrombocytopenia and all-grade neuropathy and non-significant increases in neutropenia and grade 3-4 neuropathy., Conclusions: Platinum-based treatment improves DFS but not OS. The reporting of toxicity was suboptimal, but in general adding platinum increased toxicity. The discordant effect of platinum-based treatment on DFS and OS suggest the potential development of platinum resistance and worse outcomes after recurrence. Platinum-based chemotherapy cannot be recommended in unselected patients with early TNBC., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Communicable disease epidemics and pandemics magnify the health inequities experienced by marginalised populations. People who use substances suffer from high rates of morbidity and mortality and should be a priority to receive palliative care, yet they encounter many barriers to palliative care access. Given the pre-existing inequities to palliative care access for people with life-limiting illnesses who use substances, it is important to understand the impact of communicable disease epidemics and pandemics such as COVID-19 on this population., Methods and Analysis: We will conduct a scoping review and report according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews reporting guidelines. We conducted a comprehensive literature search in seven bibliographical databases from the inception of each database to August 2020. We also performed a grey literature search to identify the publications not indexed in the bibliographical databases. All the searches will be rerun in April 2021 to retrieve recently published information because the COVID-19 pandemic is ongoing at the time of this writing. We will extract the quantitative data using a standardised data extraction form and summarise it using descriptive statistics. Additionally, we will conduct thematic qualitative analyses and present our findings as narrative summaries., Ethics and Dissemination: Ethics approval is not required for a scoping review. We will disseminate our findings to healthcare providers and policymakers through professional networks, digital communications through social media platforms, conference presentations and publication in a scientific journal., Competing Interests: Competing interests: AF receives an unrestricted educational grant to maintain the online opioid self-assessment programme from the Canadian Generic Pharmaceutical Association (CGPA). AF is the inventor of the App Opioid Manager, which is sold in iTunes. The app is owned by UHN, the hospital where AF works and AF does not receive any profits from the app sales. AF has a YouTube monetised channel and receives payment for advertisements on the channel. There are some videos related to opioids in her channel. All other authors report no competing interests., (© 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.)

Phase 1 dose-escalation trials are crucial to drug development by providing a framework to assess the toxicity of novel agents in a stepwise and monitored fashion. Despite widely adopted, rule-based dose-escalation methods (such as 3 + 3) are limited in finding the maximum tolerated dose (MTD) and tend to treat a significant number of patients at subtherapeutic doses. Newer methods of dose escalation, such as model-based and model-assisted designs, have emerged and are more accurate in finding MTD. However, these designs have not yet been broadly embraced by investigators. In this review, we summarise the advantages and disadvantages of contemporary dose-escalation methods, with emphasis on model-assisted designs, including time-to-event designs and hybrid methods involving optimal biological dose (OBD). The methods reviewed include mTPI, keyboard, BOIN, and their variations. In addition, the challenges of drug development (and dose-escalation) in the era of immunotherapeutics are discussed, where many of these agents typically have a wide therapeutic window. Fictional examples of how the dose-escalation method chosen can alter the outcomes of a phase 1 study are described, including the number of patients enrolled, the trial's timeframe, and the dose level chosen as MTD. Finally, the recent trends in dose-escalation methods applied in phase 1 trials in the immunotherapeutics era are reviewed. Among 856 phase I trials from 2014 to 2019, a trend towards the increased use of model-based and model-assisted designs over time (OR = 1.24) was detected. However, only 8% of the studies used non-rule-based dose-escalation methods. Increasing familiarity with such dose-escalation methods will likely facilitate their uptake in clinical trials., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships that may be considered as potential competing interests: DVA: Honoraria from MSD, Pfizer, Novartis, and GSK. MO: Honoraria from Bristol-Myers Squibb, MSD and Merck. Advisory role for BMS Canada. Research funding (Clinical Trials) from Abbvie, Ayala Pharmaceuticals, MSD, ALX Oncology, Debiopharm International, ISA Pharmaceuticals, Roche Pharmaceuticals. LLS has consulting/advisory arrangements with Merck, Pfizer, Celgene, AstraZeneca, Morphosys, Roche, Oncorus, Symphogen, Seattle Genetics, GlaxoSmithKline, Voronoi, Arvinas, Tessa, Navire, Relay, Rubius, Janpix, Daiichi Sanyko; stock ownership of Agios (spouse); leadership position in Treadwell Therapeutics (spouse); and institution receives clinical trials support from Novartis, Bristol-Myers Squibb, Pfizer, Boerhinger-Ingelheim, GlaxoSmithKline, Roche/Genentech, Karyopharm, AstraZeneca, Merck, Celgene, Astellas, Bayer, Abbvie, Amgen, Symphogen, Intensity Therapeutics, Mirati Therapeutics, Shattucks, Avid. KL, RF and ZL have no conflicts to disclose., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: A sentinel lymph node biopsy is widely accepted as the standard of care for surgical staging in low-grade endometrial cancer, but its value in high-grade endometrial cancer remains controversial. The aim of this systematic review and meta-analysis was to evaluate the performance characteristics of sentinel lymph node biopsy in patients with endometrial cancer with high-grade histology (registered in the International Prospective Register of Systematic Reviews with identifying number CRD42020160280)., Data Sources: We systematically searched the MEDLINE, Epub Ahead of Print, MEDLINE In-Process & Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Embase databases all through the OvidSP platform. The search was performed between January 1, 2000, and January 26, 2021. ClinicalTrials.gov was searched to identify ongoing registered clinical trials., Study Eligibility Criteria: We included prospective cohort studies in which sentinel lymph node biopsy were evaluated in clinical stage I patients with high-grade endometrial cancer (grade 3 endometrioid, serous, clear cell, carcinosarcoma, mixed, undifferentiated or dedifferentiated, and high-grade not otherwise specified) with a cervical injection of indocyanine green for sentinel lymph node detection and at least a bilateral pelvic lymphadenectomy as a reference standard. If the data were not reported specifically for patients with high-grade histology, the authors were contacted for aggregate data., Methods: We pooled the detection rates and measures of diagnostic accuracy using a generalized linear mixed-effects model with a logit and assessed the risk of bias using the Quality Assessment of Diagnostic Accuracy Studies 2 tool., Results: We identified 16 eligible studies of which the authors for 9 of the studies provided data on 429 patients with high-grade endometrial cancer specifically. The study-level median age was 66 years (range, 44-82.5 years) and the study-level median body mass index was 28.6 kg/m 2 (range, 19.4-43.7 kg/m 2 ). The pooled detection rates were 91% per patient (95% confidence interval, 85%-95%; I 2 =59%) and 64% bilaterally (95% confidence interval, 53%-73%; I 2 =69%). The overall node positivity rate was 26% (95% confidence interval, 19%-34%; I 2 =44%). Of the 87 patients with positive node results, a sentinel lymph node biopsy correctly identified 80, yielding a pooled sensitivity of 92% per patient (95% confidence interval, 84%-96%; I 2 =0%), a false negative rate of 8% (95% confidence interval, 4%-16%; I 2 =0%), and a negative predictive value of 97% (95% confidence interval, 95%-99%; I 2 =0%)., Conclusion: Sentinel lymph node biopsy accurately detect lymph node metastases in patients with high-grade endometrial cancer with a false negative rate comparable with that observed in low-grade endometrial cancer, melanoma, vulvar cancer, and breast cancer. These findings suggest that sentinel lymph node biopsy can replace complete lymphadenectomies as the standard of care for surgical staging in patients with high-grade endometrial cancer., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Low-grade serous ovarian cancer (LGSOC) is a rare form of ovarian cancer that accounts for 5-10% of epithelial ovarian cancers. LGSOCs are difficult to treat as they respond poorly to traditional chemotherapy treatments. This systematic review aims to appraise the literature describing the efficacy of hormone maintenance therapy (HMT) in patients with LGSOC given after cytoreductive surgery., Methods: Medline, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews were searched from inception to November 2020. No language restrictions were applied. Publications describing HMT in the primary setting following cytoreductive surgery with or without chemotherapy in women with LGSOC were included. Publications describing HMT in recurrence, non-LGSOC carcinomas, and in-vitro or animal studies were excluded along with case reports, case series, and conference proceedings. We summarized oncologic outcomes, HMT used, and hormone receptor status where reported. Studies were assessed for risk of bias and quality of evidence., Results: The literature search identified 14,799 records. Four cohort studies met eligibility criteria. A total of 558 patients were included, of which 127 were treated with HMT. There was significant heterogeneity between studies demonstrated by differences in HMT regimens used, dosing, and study population, leading to various outcomes following treatment with HMT., Conclusions: Treatment of LGSOC remains a challenge. One retrospective study demonstrated improved progression-free survival following HMT for LGSOC, while two others failed to show significant improvements. However, there is limited data available in the literature which restricts the generalizability of these results. Therefore, well-designed, prospective, and randomized trials are needed to confirm the benefit of HMT in patients with this rare subgroup of ovarian cancer., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Systemic inflammatory response (SIR) may influence prognosis in epidermal growth factor receptor (EGFR)-mutated (m) non-small-cell lung cancer (NSCLC). Pretreatment SIR markers (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio [LMR], lactate dehydrogenase [LDH], and lung immune prognostic index [LIPI]) were assessed as prognostic factors in NSCLC survival., Patients and Methods: Retrospective survival analysis (overall survival [OS] and progression-free survival [PFS]) of EGFR-mutated NSCLC patients at Princess Margaret Cancer Centre were performed separately for early (I-IIIa) and late (IIIb-IV) stage disease for individual SIR variables, dichotomized by optimal cutoff points by Kaplan-Meier survival analysis and multivariable Cox proportional hazard modeling. A systematic review and meta-analysis of known SIR studies in patients with late-stage EGFR-mutated were also performed., Results: From 2012 to 2019, in 530 patients, significant adjusted hazard ratios (aHR) for OS comparing high versus low NLR were 2.12 for early stage and 1.79 for late stage disease. Additionally, late stage cohorts had significant associations, as follows: high versus low derived NLR, aHR = 1.53; LMR, aHR = 0.62; LDH, aHR = 2.04; and LIPI, aHR = 2.04. Similar patterns were found for PFS in early stage NLR (aHR = 1.96) and late stage NLR (aHR = 1.46), while for PFS, only late stage derived NLR (aHR = 1.34), LDH (aHR = 1.75), and LIPI (aHR = 1.66) were significant. A meta-analysis confirmed that NLR, LMR, LDH, and LIPI were all significantly associated with OS and PFS in the late stage., Conclusion: This primary study and meta-analysis demonstrated that LMR and LDH were significantly associated with late stage EGFR-mutated NSCLC outcomes, and the LIPI scoring system was prognostic. NLR remained an independent prognostic factor across all stages and could represent an early marker of immuno-oncology interactions., (Copyright © 2021 Elsevier Inc. All rights reserved.)