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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.

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.

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.

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: 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.

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.

Background There are limited data regarding the quality of patient‐reported outcome (PRO) data in immune checkpoint inhibitor (ICI) clinical trial publications. Methods A systematic search of citations from various databases was conducted to identify prospective clinical trials involving ICI in advanced tumors from 2003 to 2020. A 30‐point score was adapted from the CONSORT PRO extension statement to assess adherence to CONSORT PRO reporting. Linear regression was used to identify factors associated with quality reporting. Results After the review of 8058 articles, 33 trials were included with ICIs as either monotherapy (91%) or part of a combination regimen (9%). The median score was 23.5 points (range 15–29). In the majority of cases (82%), PROs were reported in a separate publication from the original study. Most of the trials were conducted in the metastatic setting and predominantly in melanoma, lung, and renal cell carcinoma (RCC) (73%). Univariate analysis revealed that trials with greater than 250 patients were associated with a higher score. The score was more likely to be lower in disease sites other than melanoma, lung, and RCC and was higher in the KEYNOTE than in the CHECKMATE trial series. There was no significant correlation between the score and whether a trial met its primary end‐point or if the trial improved or worsened the quality of life. In the multivariate analysis, the number of patients enrolled to the trial, disease site, and trial series remained significant. Conclusions The quality of reporting of PROs in ICI phase II and III clinical trials is heterogeneous across various cancer sites. As PRO data are increasingly used to counsel patients and complement clinical decision making, innovative and collaborative efforts are required to improve the reporting of these essential data., There are limited data regarding the quality of patient‐reported outcome data in immune checkpoint inhibitor clinical trial publications. A systematic review was conducted of published clinical trials to assess the quality of reporting.

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.

Background:Screening for problematic opioid use is increasingly recommended in patients receiving palliative care.Aim:To identify tools used to assess for the presence or risk of problematic opioid use in palliative care.Design:Scoping review.Data sources:Bibliographic databases (inception to January 31, 2020), reference lists, and grey literature were searched to find primary studies reporting on adults receiving palliative care and prescription opioids to manage symptoms from advanced cancer, neurodegenerative diseases, or end-stage organ diseases; and included tools to assess for problematic opioid use. There were no restrictions based on study design, location, or language.Results:We identified 42 observational studies (total 14,431 participants) published between 2009 and 2020 that used questionnaires ( n = 32) and urine drug tests ( n = 21) to assess for problematic opioid use in palliative care, primarily in US ( n = 38) and outpatient palliative care settings ( n = 36). The questionnaires were Cut down, Annoyed, Guilty, and Eye-opener (CAGE, n = 8), CAGE-Adapted to Include Drugs (CAGE-AID, n = 6), Opioid Risk Tool ( n = 9), Screener and Opioid Assessment for Patients with Pain (SOAPP; n = 3), SOAPP-Revised ( n = 2), and SOAPP-Short Form ( n = 5). Only two studies’ primary objectives were to evaluate a questionnaire’s psychometric properties in patients receiving palliative care. There was wide variation in how urine drug tests were incorporated into palliative care; frequency of abnormal urine drug test results ranged from 8.6% to 70%.Conclusion:Given the dearth of studies using tools developed or validated specifically for patients receiving palliative care, further research is needed to inform clinical practice and policy regarding problematic opioid use in palliative care.

Objectives The optimal systemic therapy strategy for advanced epithelial ovarian cancer (EOC) remains unclear. We performed a systematic review and meta-analysis to assess oncologic outcomes and toxicity of bevacizumab combination treatment in advanced EOC. Methods We conducted an electronic search of all phase 2 and 3 clinical trials involving bevacizumab combination therapy in advanced-stage EOC between 2010 and March 2020, using Embase, Medline, Epub Ahead of Print, Cochrane for clinical trials, Cochrane Database of Systematic Reviews, Web of Science and clinicaltrials.gov databases. Progression-free survival (PFS), overall survival (OS), and their hazard ratios (HR) when available were extracted. Pooled HR were calculated for each efficacy endpoint in the meta-analysis using inverse variance weighted method. Bias was assessed using the Cochrane Collaboration Risk of Bias I (ROB1) tool for randomized controlled trials. Results Thirty-five studies were included in the qualitative analysis and eight studies in the quantitative synthesis. In the first-line setting, bevacizumab combined with chemotherapy revealed a significant improvement in PFS (pooled HR = 0.72, 95% CI 0.65–0.81) when compared to chemotherapy alone but no significant OS benefit (pooled HR = 0.88, 95% CI 0.72–1.06). In the recurrent setting, bevacizumab combinations showed significant PFS (pooled HR = 0.52, 95% CI 0.47–0.58) and OS benefits (pooled HR = 0.88, 95% CI 0.79–0.99) compared with non-bevacizumab regimens. Rate of bowel perforation was low at 1.24% (range 0–4.2%). Conclusions Bevacizumab-containing regimens are associated with significant PFS benefit in advanced and recurrent epithelial ovarian cancer. While the difference in OS did not reach statistical significance in the first-line setting, bevacizumab was associated with improved survival in the recurrent setting.

Serious concerns regarding quality of conduct and reporting of noninferiority trials (NITs) have been raised. Systematic analysis of the quality of the surgical NITs is lacking. Assessing the quality of conduct, reporting, and interpretation of surgical NITs in cancer patients is critical given their potential clinical impact. We aim to assess the quality of conduct, reporting, and interpretation of NITs that investigate the effects of surgical management in cancer patients. A cross-sectional analysis of papers identified through a comprehensive literature database search was performed. Forty papers employing a phase III noninferiority (NI) randomized trial design to study effects of surgical methodology or sequencing of surgery in patients with solid cancers were included. Papers were assessed for type of analysis, justification of the noninferiority margin (NIM), consistency of type I error with confidence intervals (CIs), ability to achieve the predefined sample size, and interpretations regarding NI. Only half of the papers used both intention-to-treat and per protocol analyses; 62.5% provided no or poor justification for the NIM; 42.5% showed inconsistency of the type I error rate with CIs; 52.5% were deemed poor or fair quality, and 60.0% did not achieve the predefined sample size. One-fifth of the papers provided interpretation of the NI hypothesis that was not in concordance with the CONSORT guidelines. The quality of conduct, reporting, and interpretation of surgical NITs is suboptimal, requiring further improvements through adherence to guidelines and rigorous assessment at the stages of the study approval, funding, and the peer-review process.

Supplemental Digital Content is available in the text., Purpose The aim of this scoping review is to understand the motivations for the creation of global medical curricula, summarize methods that have been used to create these curricula, and understand the perceived premises for the creation of these curricula. Method In 2018, the authors used a comprehensive search strategy to identify papers on existing efforts to create global medical curricula published from 1998 to March 29, 2018, in the following databases: MEDLINE; MEDLINE Epub Ahead of Print, In-Process, and Other Non-Indexed Citations; Embase; Cochrane Central Register of Controlled Trials; Cochrane Database of Systematic Reviews; PsycINFO; CINAHL; ERIC; Scopus; African Index Medicus; and LILACS. There were no language restrictions. Two independent researchers applied the inclusion and exclusion criteria. Demographic data were abstracted from publications and summarized. The stated purposes, methods used for the development, stated motivations, and reported challenges of curricula were coded. Results Of the 18,684 publications initially identified, 137 met inclusion criteria. The most common stated purposes for creating curricula were to define speciality-specific standards (50, 30%), to harmonize training standards (38, 23%), and to improve the quality or safety of training (31, 19%). The most common challenges were intercountry variation (including differences in health care systems, the operationalization of medical training, and sociocultural differences; 27, 20%), curricular implementation (20, 15%), and the need for a multistakeholder approach (6, 4%). Most curricula were developed by a social group (e.g., committee; 30, 45%) or Delphi or modified Delphi process (22, 33%). Conclusions The challenges of intercountry variation, the need for a multistakeholder approach, and curricular implementation need to be considered if concerns about curricular relevance are to be addressed. These challenges undoubtedly impact the uptake of global medical curricula and can only be addressed by explicit efforts to make curricula applicable to the realities of diverse health care settings.

Background: 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 (neoadjuvant vs. adjuvant) and study design (retrospective vs. randomized controlled trials). When available, odds ratios (OR) for commonly reported safety and tolerability measures such as treatment-related death, treatment discontinuation without progression, dose reduction, neuropathy, renal impairment and hematological toxicity were calculated. Results: Seven studies comprising 1699 patients met the inclusion criteria. Median follow up was 54.5 months. All studies reported DFS and 4 studies reported OS. DFS was significantly better in platinum-based treatment (HR 0.71, 95% confidence interval (CI) 0.53-0.96; P = 0.03). However, OS was no different with a higher number of events in the platinum-based treatment arm (HR 1.17, 95% CI 0.81-1.69; P = 0.42). There was no significant difference between treatment settings (p = 0.74) or between study designs (p = 0.74), although a higher HR for OS was observed for studies in the adjuvant (HR 1.34, 95% CI 0.54-3.35) compared to neoadjuvant setting (HR 1.14, 95% CI 0.76-1.70). The reporting of toxicity was suboptimal with most studies not reporting safety and tolerability metrics clearly. Platinum-based treatment was associated with more neutropenia and thrombocytopenia and treatment discontinuation, however, the magnitude of this effect could not be estimated accurately. Conclusions: Platinum-based treatment improves DFS but has no effect on OS and increases toxicity. The discordant effect of platinum-based treatment on DFS and OS suggest the potential development of platinum resistance and worse outcomes after recurrence. The higher magnitude of discordance in adjuvant compared to neoadjuvant studies suggests an effect of platinum-based therapy on loco-regional control prior to surgery rather than prevention of distant metastatic disease. Platinum-based chemotherapy cannot be recommended in unselected patients with TNBC. Citation Format: Ramy Saleh, Michelle B Nadler, Alexandra Desnoyers, Rouhi Fazelzad, Eitan Amir. Platinum-based chemotherapy in early-stage triple negative breast cancer: A meta-analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-14-09.

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.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).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.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.

PurposeNon-V600 mutations comprise approximately 35% of all BRAF mutations in cancer. Many of these mutations have been identified as oncogenic drivers in a wide array of cancer types 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.MethodsWe performed a systematic review and meta-analysis of individual patient data to assess treatment outcomes with FDA-approved mitogen activated protein kinase pathway (MAPK) targeted therapy according to BRAF Class, cancer type and MAPK targeted therapy type. A search was conducted on literature from 2010-2021. Individual patient data was collected and analyzed from published reports of patients with cancer harboring Class 2 or 3 BRAF mutations and who received MAPK targeted therapy with available treatment response data. Co-primary outcomes were response rate (RR) and progression-free survival (PFS).Results18167 studies were screened, identifying 80 studies with 238 patients that 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, RR and PFS were higher among patients with Class 2 compared to 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 to Class 3 BRAF mutant tumors than BRAF or EGFR inhibitors.ConclusionsThis meta-analysis suggests that MAPK targeted therapies 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 metastatic melanoma and lung cancers. Together, this analysis provides clinical validation of predictions made based on a mutation classification system established in the preclinical literature. Further evaluation with prospective clinical trials is needed for this population.

© 2022 British Society for Haematology and John Wiley & Sons Ltd., 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, I2 = 6%] in women with COC-associated VTE, 3.89/100 PY (95% CI 2.93-5.17, I2 = 74%) in women with unprovoked VTE and the unadjusted incidence rate ratio was 0.34 (95% CI 0.26-0.46, I2 = 3%). The recurrence risk in women after COC-associated VTE is low and lower than after an unprovoked VTE.

IntroductionAntimicrobial 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 analysisThis 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 disseminationAs 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.

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.

ImportanceEpidemiological evidence supports a role for statins in improving survival in advanced prostate cancer, particularly among men receiving androgen-ablative therapies.ObjectiveTo 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 SourcesThis 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 SelectionObservational studies reporting associations of concurrent statin use and survival outcomes (in hazard ratios [HRs]).Data Extraction and SynthesisTwo 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 MeasuresOverall mortality and prostate cancer–specific mortality (PCSM).ResultsTwenty-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 RelevanceThe 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.

ObjectivesIn response to the COVID-19 pandemic there have been significant developments in research, its conduct and the supporting ethical framework. While many protocols have been delayed, halted or modified, other research efforts have been accelerated, generating controversy. The goal of this paper is to determine the rates of references surrounding the ethical oversight of research as reported in current COVID-19-related research publications.DesignScoping review.SettingPopulation-based observational or interventional studies from December 2019 to May 2020 with sample size of two or more. Studies were searched through electronic databases including Medline, EMBASE, and Cochrane CENTRAL Register of Controlled Trials.ParticipantsEligibility criteria included participants within published studies who tested positive for COVID-19.Main outcomes and measuresData were extracted and charting methods included taking note of references to ethical frameworks, institutional review board (IRB), ethics committee (EC) or research ethics board (REB) involvement, consent processes, and other variables.Results11 556 articles were screened, with 656 included in the final analysis. References to ethics were present in 530 (80.8%) studies, with 491 (74.8%) involving IRB/ECs/REBs and 126 (19.2%) not referencing ethics. Consent processes were outlined in 201 (30.6%) studies, with 198 (30.2%) reporting that they obtained consent waivers, however, 257 (39.2%) did not mention consent at all. Differences (pConclusionsThe majority of published articles pertaining to COVID-19 research made mention of ethical considerations, however, national and regional variations in research ethics review requirements introduce heterogeneity between studies and raise important questions about the conduct of scientific research during global public emergencies.Trial registration numberOpen Science Framework: https://osfio/z67wb.

Some thyroid cancer (TC) survivors experience cognitive symptoms. The purpose of this study is to perform a systematic literature review and meta-analysis comparing cognitive performance in TC survivors to controls. We performed a seven-database electronic search and hand-search. We performed duplicate independent reviews and data abstraction. Random effects meta-analyses reported standardized mean differences (SMDs) with 95% confidence intervals (CIs), where a negative value implies worse performance in the TC group. We reviewed 1174 unique citations and 10 full-text papers. We included seven studies of 241 treated TC survivors and 273 controls. Cognitive function was statistically significantly worse in TC survivors in the following domains: Attention and Concentration (Digit Span Forwards) SMD − 0.37 (95% CI − 0.62, − 0.13, p = 0.003, four studies), Speed of Processing (Trail Making A) SMD − 0.36 (95% CI − 0.66, − 0.05, p = 0.022, four studies), and Language (Controlled Oral Word Association [COWAT]-Categories) SMD − 0.97 (95% − 1.31, − 0.64, p

The prevalence of human papillomavirus (HPV) in squamous cell carcinoma of unknown primary in the head and neck (SCCUPHN), and prognosis by HPV status of SCCUPHN patients has been difficult to estimate because of the rarity of this subtype. In MEDLINE, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, EMBASE, Cochrane library and Web of Science searches, observational studies and clinical trials that reported survival rates of patients with SCCUPHN by HPV status were identified. Meta-analysis estimated the prevalence and prognosis (overall survival, OS; progression-free survival, PFS) of SCCUPHN by HPV status, and compared them to studies of oropharyngeal squamous cell carcinoma (OPSCC) from the same institutions and across continents. In 17 SCCUPHN studies (n = 1,149) and 17 institution-matched OPSCC studies (n = 6,522), the pooled HPV prevalence of SCCUPHN was 49%, which was only 10% (95%CI: 1-19%) lower than OPSCC prevalence in the underlying population. Estimated 5-year OS for HPV-negative SCCUPHN was 44% (95%CI: 36-51%) vs. HPV-positive SCCUPHN of 91% (95%CI: 86-96%); hazard ratio (HR) for OS was 3.25 (95%CI: 2.45-4.31) and PFS was 4.49 (95%CI: 2.88-7.02). HRs by HPV status for OPSCC were similar to that in SCCUPHN. While North American SCCUPHNs had higher HPV prevalence than European SCCUPHNs (OR = 2.68 (95%CI: 1.3-5.6)), HR of OS for HPV-negative vs. HPV-positive patients were similar in both continents (HRs of 3.78-4.09). Prevalence of HPV among SCCUPHN patients were lower than in OPSCC. The survival benefit conferred by being HPV-positive was similar in SCCUPHN as in OPSCCs, independent of continent.

ObjectivesWhen resources are strained during communicable disease outbreaks, novel palliative care interventions may be required to optimally support people who use substances with life-limiting illnesses. Therefore, we asked the question, ‘what is known about communicable disease outbreaks, palliative care and people who use substances?’, such as palliative care interventions that can improve the quality of life of patients with life-limiting illnesses.DesignWe conducted a scoping review that involved comprehensive searches in six bibliographic databases from inception to April 2021 (Medline ALL (Medline and Epub Ahead of Print and In-Process and Other Non-Indexed Citations), Embase Classic+Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trial, PsycInfo all from the OvidSP platform, Scopus from Elsevier) and grey literature searches. We included English and French records about people ≥18 years old with life-limiting illnesses who use substances during communicable disease outbreaks. We identified, summarised and presented the findings about palliative care interventions in figures, tables and narrative descriptions.ResultsWe identified 32 records about palliative care interventions for people who use substances during communicable disease outbreaks. The majority focused on palliative care for people who use substances with AIDS during HIV epidemics (n=27, 84.4%), and approximately half were published in the USA (n=15, 46.9%). Most common substances used were alcohol (n=18, 56.3%), opioids (n=14, 43.8%) and cocaine (n=10, 31.3%). Four groups of palliative care interventions were identified: (1) symptom management (n=20, 62.5%), (2) psychosocial support (n=15, 46.9%), (3) advance care planning (n=8, 25.0%) and (4) healthcare provider training (n=6, 18.8%).ConclusionsBeyond studies on HIV epidemics, there is limited knowledge about palliative care interventions for people who use substances during communicable disease outbreaks. Research and guidance are needed about how best to provide palliative care to this population with complex needs including in resource-limited countries.ProtocolBuchman DZ, Ding P, Lo S, et al. Palliative care for people who use substances during communicable disease epidemics and pandemics. BMJ Open 2021; 11: e053124

PURPOSE/OBJECTIVE(S) The management of oligo-metastatic disease (OMD) is evolving, with increasing data supporting the use of stereotactic body radiotherapy. The aim of this systematic review and meta-analysis is to analyses health related quality of life (HRQOL) outcomes and the side-effects of SBRT in patients with OMD. MATERIALS/METHODS We searched MEDLINE, Epub Ahead of Print, EMBASE, Cochrane CT, Cochrane SR, Emcare, and PsycInfo databases (from inception to March 2020). Randomized clinical trials (RCTs) or observational studies were included if HRQOL outcomes were reported from patients with defined OMD (£5 metastases) who received SBRT as metastasis-directed therapy, and who completed validated HRQOL questionnaires at baseline and 12-months. Meta-analysis using weighted mean difference was performed to estimate a difference between baseline and 12-month scores. Secondary outcome, calculated by the pooled incidence rate approach using the inverse variance method, was the estimated event rate of clinically significant Common Terminology Criteria for Adverse Events (CTCAE) grade 2-4 and grade 5 toxicity, expressed per person-time of follow-up. Authors of studies included were contacted to obtain additional information. Methods adhered to PRISMA guidelines. RESULTS Four of 7,545 studies screened were eligible for inclusion. Two studies were phase II RCTs and two were prospective single arm studies. Among 277 patients who received SBRT, median follow-up was 31 months (range 24-41 months). Two studies included only prostate cancer patients and two studies included mixed histologies. Two studies measured European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and two measured Functional Assessment of Cancer Therapy - General (FACT-G) scores. Using a fixed effects model, the mean change in 12-month EORTC QLQ-C30 global health QOL score from baseline demonstrated a statistically significant decline (pooled weighted mean difference -5.2, 95% CI -9.3 to -1.2, both prostate cancer studies, 57 patients total). Meta-analysis of total FACT-G scores in the other two studies was not possible as mean difference results for one study were unavailable. For the available multi-histology study, no statistically significant difference was seen in baseline to 12-month mean FACT-G total scores in the SBRT arm. We estimated an event rate of 0.06 (95% CI: 0.024, 0.15) CTCAE grade 2-4 toxicities per person-year and 0.008 (95% CI: 0.002, 0.031) grade 5 toxicities per person-year. CONCLUSION Although a statistically significant decline in the EORTC QLQ C30 global health/QOL measure was seen, it was small and unlikely to be of clinical importance. Rates of SBRT-related clinical toxicities are low. There is limited QOL data published for patients with OMD, with varying HRQOL tools used.

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/m2 (range, 19.4–43.7 kg/m2). The pooled detection rates were 91% per patient (95% confidence interval, 85%–95%; I2=59%) and 64% bilaterally (95% confidence interval, 53%–73%; I2=69%). The overall node positivity rate was 26% (95% confidence interval, 19%–34%; I2=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%; I2=0%), a false negative rate of 8% (95% confidence interval, 4%–16%; I2=0%), and a negative predictive value of 97% (95% confidence interval, 95%–99%; I2=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.

Importance Active surveillance is sometimes considered as a disease management option for individuals with small, low-risk papillary thyroid carcinoma. Objective To assess whether patient age is associated with progression of low-risk papillary thyroid carcinoma (tumor growth or incident metastatic disease) in adults under active surveillance. Evidence Review Eight electronic databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Emcare, PsycINFO, Web of Science, and ClincalTrials.gov) were searched from inception to March 2019, supplemented with a hand search. Two investigators independently screened citations, reviewed full-text articles, and abstracted data. Additional data were sought from authors. Random-effects meta-analyses were performed using incidence data (statistically adjusted for confounders and crude rates). Findings A total of 1658 unique citations were screened, and 62 full-text articles were reviewed, including 5 studies. Three studies included exclusively microcarcinomas and 2 included tumors up to 2 cm in maximal diameter. The mean age of participants was 51.0 to 55.2 years in 4 studies reporting this value. The mean or median follow-up was 5 years or more in 3 studies and approximately 2 years in 2 studies. The pooled risk ratio for tumor growth of 3 mm or more in maximal diameter in individuals aged 40 to 50 years or older compared with younger individuals was 0.51 when adjusted for confounders (95% CI, 0.29-0.89; 1619 patients, 2 studies), and the unadjusted risk ratio of this outcome for individuals 40 years or older was 0.55 (95% CI, 0.36-0.82; 2097 patients, 4 studies). In adults aged 40 to 45 years or older, the unadjusted risk ratio for any tumor volume increase compared with younger individuals was 0.65 (95% CI, 0.51-0.83; 1232 patients, 4 studies). The pooled risk ratio for incident nodal metastases in individuals 40 years or older was 0.22 (95% CI, 0.10-0.47; 1806 patients, 3 studies); however, in a secondary analysis, the risk difference was not significantly different. There was no statistically significant heterogeneity in any of the meta-analyses. There were no thyroid cancer–related deaths nor incident distant metastases. Conclusions and Relevance This study suggests that older age may be associated with a reduced risk of primary papillary thyroid carcinoma tumor growth under active surveillance. Incident metastatic disease is uncommon during active surveillance.

Objectives Heated intraperitoneal chemotherapy (HIPEC) has not been universally adopted at the time of interval cytoreductive surgery for primary epithelial ovarian cancer (EOC) despite evidence of a 12-month overall survival (OS) benefit in a recent landmark randomized trial. We performed a systematic review and meta-analysis to assess oncologic outcomes and perioperative morbidity following HIPEC among primary EOC patients. Methods We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews, from inception to August 2019, for observational and randomized studies of primary EOC patients undergoing HIPEC. We assessed risk of bias using the Institute of Health Economics Quality Appraisal Checklist for single-arm cohort studies, Newcastle-Ottawa Scale for comparative cohort studies, and Cochrane Collaboration's Tool for randomized trials. We qualitatively summarized survival outcomes and calculated the pooled proportion of 30-day grade III-IV morbidity and postoperative death. Results: We identified 35 articles including 2252 primary EOC patients; one study was a randomized trial, and only six studies included a comparator group of surgery alone. The timing, temperature, and chemotherapeutic agents used for HIPEC differed across studies. Reported OS was highly variable (3-year OS range: 46–77%); three comparative cohort studies and the sole randomized trial reported statistically significant survival benefits for HIPEC over surgery alone, while two comparative cohort studies did not. The pooled proportions for grade III-IV morbidity and postoperative death at 30 days were 34% (95% CI 20–52) and 0% (95% CI 0–5) respectively. Conclusion One randomized trial suggests that HIPEC at time of interval cytoreductive surgery should be considered in patients with primary EOC. However, there is significant heterogeneity in literature with respect to an appropriate HIPEC regimen, short- and long-term outcomes. High-quality prospective randomized trials are urgently needed to clarify the role of HIPEC in the first-line treatment of primary EOC.

Background: The potential risk of subsequent malignant neoplasms (SMNs) after radioactive iodine (RAI) treatment of thyroid cancer (TC) is an important concern. Methods: A systematic review was upd...

PURPOSE To evaluate the performance of 18 F-fluorodeoxy-d-glucose positron emission tomography-computed tomography (18 F-FDG PET/CT) in identifying local failure and regional failure following curative radiotherapy or surgery for head and neck squamous cell carcinoma. METHODS A comprehensive literature search identified studies published between January 2010 and August 2016. Diagnostic performance of 18 F-FDG PET/CT was evaluated for local failure/regional failure stratified by treatment-to-scan time interval of ≤3 versus >3 months. RESULTS Twenty-four studies (2627 patients) were included. Compared to ≤3 months, 18 F-FDG PET/CT performed >3 months showed significantly improved sensitivity (87% vs 60%, P = 0.020) and specificity (93% vs 84%, P 3 versus ≤3 months. CONCLUSIONS This meta-analysis confirms high specificity but modest sensitivity of posttreatment 18 F-FDG PET/CT for local failure and regional failure. Sensitivity and specificity are significantly improved when 18 F-FDG PET/CT is performed >3 months for local failure.

Background Increasing demands on health care systems require patients to take on more active roles in their health. Effective self-management has been linked to improved health outcomes, and evidence shows that effective self-management is linked to health literacy (HL). HL is an important predictor of successful self-management in other chronic diseases but has had minimal testing in cancer. Methods A scoping review was conducted to examine and summarize what is known about the association between HL and self-management behaviors and health service utilization in the cancer setting. The methodological framework articulated by Arksey and O'Malley was used and was further refined with the Joanna Briggs Institute methodology. Inclusion criteria included the following: peer review; publication in English; and adult patients and caregivers of all races, ethnicities, and cultural groups. Use of a validated instrument to measure HL was required. Results The search yielded 2414 articles. After the removal of duplicates and the performance of title scans and abstract reviews, the number was reduced to 44. Of the 44 full-text articles reviewed, 17 met the inclusion criteria. A number of important self-management behaviors and related outcomes were found to be associated with HL. These included the uptake of cancer screening, the receipt of prescribed chemotherapy, and a greater risk of postoperative complications. Conclusions This literature review shows that HL is associated with important self-management behaviors in cancer. The implications of these associations for individuals with inadequate HL and for the health care system are significant. More research is needed to explore these associations.

Background: Progression free-survival (PFS) is the dominant endpoint in phase 3 randomized controlled trials (RCTs) in women with metastatic breast cancer (MBC), and requires the ability to measure target lesions. It is unknown whether treatment effect on PFS is consistent among patients with measurable and non-measurable disease. Methods: We searched MEDLINE, EMBASE and COCHRANE for phase 3 RCTs in MBC that reported outcomes in subgroups with non-measurable (or bone only disease, if not reported explicitly) and measurable disease. Data were extracted and a single hazard ratio (HR) and 95% confidence intervals (CI) were computed to compare the individual trial treatment effect in non-measurable versus measurable disease. Data were then pooled in a meta-analysis. We repeated the analysis comparing bone only to non-bone only disease and performed subgroup analyses based on drug mechanism of action. Results: Of 82 RCTs that enrolled patients with non-measurable disease, 16 trials comprising 8516 patients were eligible for analysis. All included RCTs used PFS or time to progression as primary endpoints. There was no difference in pooled treatment effect between patients with non-measurable and measurable disease (HR 1.01, 95% CI 0.89-1.15, p=0.82). However, compared to non-bone only disease, a significantly greater effect on PFS was seen in those with bone only disease (HR 0.82, 95% CI 0.70-0.98, p=0.03). Subgroups analyses according to drug mechanism are shown in Table 1 Intra-study comparison, according to evaluated drug mechanismCohort/ Investigational drugNo. studies includedMeasurable HR (95% CI)Non measurable HR (95% CI)Intra- study comparison HR (95% CI)P – for intra-study comparisonAll160.69 (0.65-0.73)0.72 (0.64-0.80)1.01 (0.89-1.15)0.82Chemotherapy30.99 (0.87-1.13)0.67 (0.44-1.02)0.73 (0.44-1.21)0.22Endocrine treatment40.86 (0.77-0.96)0.94 (0.80-1.10)1.13 (0.92-1.40)0.23Signal transduction inhibitors40.52 (0.48-0.57)0.41 (0.33-0.50)0.74 (0.59-0.94)0.01Anti-angiogenetic agents50.66 (0.59-0.73)0.84 (0.67-1.04)1.34 (1.05-1.71)0.02CI- confidence interval, HR- hazard ratio . Compared to patients with measurable disease, there was a greater effect on PFS in those with non-measurable disease in RCTs of signal transduction inhibitors and endocrine therapy (HR 0.74, 95% CI 0.59-0.94, p=0.01). There was a lesser effect on PFS in patients with non-measurable disease in RCTs of antiangiogenic drugs (HR 1.34, 95% CI 1.05-1.71, p=0.02). Comparable effect on PFS was shown in RCTs evaluating endocrine therapy and chemotherapy. Conclusions: There is variability in treatment effect on PFS in patients with measurable and non-measurable disease. There is greater effect on PFS in RCTs of endocrine therapy and signal transduction inhibitors and in patients with bone only disease. Standardization of PFS determination in patients with non-measurable and bone only disease is warranted. Citation Format: Goldvaser H, Ribnikar D, Fazelzad R, Seruga B, Templeton AJ, Ocana A, Amir E. Influence of non-measurable disease on progression-free survival in patients with metastatic breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-17-02.

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 (I2 93%, P 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.