Search

Purpose: People of Culturally and Linguistically Diverse (CALD) backgrounds face disparities in cancer care. This scoping review aims to identify the breadth of international literature focused on cancer survivorship programs/interventions specific to CALD populations, and barriers and facilitators to program participation., Methods: Scoping review included studies focused on interventions for CALD cancer survivors after curative-intent treatment. Electronic databases: Medline, Embase, CINAHL, PsycInfo and Scopus were searched, for original research articles from database inception to April 2022., Results: 710 references were screened with 26 included: 14 randomized (54%), 6 mixed-method (23%), 4 non-randomized experimental (15%), 2 qualitative studies (8%). Most were United States-based (85%), in breast cancer survivors (88%; Table 1), of Hispanic/Latinx (54%) and Chinese (27%) backgrounds. Patient-reported outcome measures were frequently incorporated as primary endpoints (65%), or secondary endpoints (15%). 81% used multi-modal interventions with most encompassing domains of managing psychosocial (85%) or physical (77%) effects from cancer, and most were developed through community-based participatory methods (46%) or informed by earlier work by the same research groups (35%). Interventions were usually delivered by bilingual staff (88%). 17 studies (77%) met their primary endpoints, such as meeting feasibility targets or improvements in quality of life or psychological outcomes. Barriers and facilitators included cultural sensitivity, health literacy, socioeconomic status, acculturation, and access., Conclusions: Positive outcomes were associated with cancer survivorship programs/interventions for CALD populations. As we identified only 26 studies over the last 14 years in this field, gaps surrounding provision of cancer survivorship care in CALD populations remain., Implications for Cancer Survivors: Ensuring culturally sensitive and specific delivery of cancer survivorship programs and interventions is paramount in providing optimal care for survivors from CALD backgrounds., (© 2023. The Author(s).)

Objective: This systematic review aims to evaluate the proactive or real-time assessment of patient reported outcomes in studies involving patients with ovarian cancer undergoing systemic therapy., Methods: PubMed, Embase, and Cochrane databases were searched (from database inception until February 2022), and prospective ovarian cancer studies (experimental or observational) that incorporated patient reported outcomes, including quality of life, were included. The primary objective was to assess the ratio of studies incorporating real-time use of patient reported outcomes among those studies performing patient reported outcomes. A secondary objective was to describe the patient reported outcome reporting. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 checklist was followed. Descriptive statistics were used., Results: 3071 articles were screened, with 117 included in the final analysis. Studies were published between 1990 and 2022, and consisted of 35 735 patients (median 140 patients per study; interquartile range 58-415). Median time from patient enrollment initiation to study publication was 7 years (range 1-15). Most studies were experimental/clinical trials (n=93, 79%) followed by observational (n=23, 20%). Therapeutic strategies were assessed in 98% (91/93) of experimental studies, most frequently chemotherapy (n=53, 58%), followed by antiangiogenics or poly-ADP ribose polymerase (PARP) inhibitors (n=8, 9%, each). Patient reported outcomes were the primary endpoint in 7.5% (7/93) and 83% (19/23) of experimental and observational studies, respectively. The ratio of real-time patient reported outcomes assessment/evaluation was 0.9% (1/117)., Conclusions: Completion of patient reported outcome questionnaires involves time and effort for patients with ovarian cancer. Responses to these questionnaires were only assessed in real time in <1% of analyzed studies. Efforts should be made to incorporate proactive assessment of patient reported outcomes to optimize patient care and safety., Competing Interests: Competing interests: AM received honoraria from AstraZeneca, Clovis, GSK, MSD, PharmaMar. SL is principal investigator or co-investigator of different clinical trials with agents from AstraZeneca, Merck, Roche, GSK, Regeneron, Repare Therapeutics, Clovis. LK received honoraria from Eisai, Novartis, GSK. PT reports a consulting or advisory role with AstraZeneca, Daiichi-Sankyo, Adamed, Novartis and Seagen. Speakers’ bureaus for Pfizer, Novartis, Lilly, AstraZeneca, Daiichi-Sankyo, Esteve, Gilead, Reveal Genomics and Seagen. Travel grants from Pfizer, Novartis, AstraZeneca and Gilead. DV received honoraria from Abbie, Agios, Amgen, Astellas, BMS/Celgene, Gebro, Grifols, Janssen, Jazz Pharmaceuticals, Kite/Gilead, MSD, Novartis, Pfizer, Sanofi, Servier, Sobi and Takeda. AMO declared uncompensated consulting or advisory role in AstraZeneca and GSK. He has uncompensated relationships with AstraZeneca and Clovis and research funding from AstraZeneca, GSK. SL declared consulting fees from AstraZeneca, GSK, Merck, Eisai, Shattuck laboratories, Repare and Seagen. The remaining authors declare no other competing interests., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy, and despite advancements in therapeutics, most women unfortunately still succumb to their disease. Immunotherapies, in particular immune checkpoint inhibitors (ICI), have been therapeutically transformative in many tumour types, including gynaecological malignancies such as cervical and endometrial cancer. Unfortunately, these therapeutic successes have not been mirrored in ovarian cancer clinical studies. This review provides an overview of the ovarian tumour microenvironment (TME), particularly factors associated with survival, and explores current research into immunotherapeutic strategies in EOC, with an exploratory focus on novel therapeutics in navigating drug resistance., Competing Interests: ADeF declares receiving grant funding from AstraZeneca. All other authors declared that there are no conflicts of interest., (© The Author(s) 2023.)

Angiogenesis inhibitors have been adopted into the standard armamentarium of therapies for advanced-stage renal cell carcinomas (RCC), but more recently, combination regimens with immune checkpoint inhibitors have demonstrated better outcomes. Despite this, the majority of affected patients still eventually experience progressive disease due to therapeutic resistance mechanisms, and there remains a need to develop novel therapeutic strategies. This article will review the synergistic mechanisms behind angiogenesis and immunomodulation in the tumor microenvironment and discuss the pre-clinical and clinical evidence for both clear-cell and non-clear-cell RCC, exploring opportunities for future growth in this exciting area of drug development.

Since the discovery of angiogenesis and its relevance to the tumorigenesis of gynecologic malignancies, a number of therapeutic agents have been developed over the last decade, some of which have become standard treatments in combination with other therapies. Limited clinical activity has been demonstrated with anti-angiogenic monotherapies, and ongoing trials are focused on combination strategies with cytotoxic agents, immunotherapies and other targeted treatments. This article reviews the science behind angiogenesis within the context of gynecologic cancers, the evidence supporting the targeting of these pathways and future directions in clinical trials.

Background: Despite the growing integration of mandatory biopsies for correlative endpoints within oncology clinical trials, there are sparse data on patient-reported outcomes, perceptions, and preferences., Objective: This study aimed to prospectively assess the impact of research biopsies on the quality of life in patients with gynecologic cancer, evaluate patient-reported outcomes, and determine factors associated with patients' willingness to undergo sequential biopsies., Study Design: We conducted a prospective study in patients with gynecologic malignancies undergoing research biopsies between 2015 and 2019 at Princess Margaret Cancer Centre (ClinicalTrials.gov Identifier: NCT02334761). Here, we report the results of the paper-based surveys performed before and 1 week after biopsy. Although the questionnaires each assessed the impact of anxiety using a modified version of the Hospital Anxiety and Depression Scale, the postbiopsy questionnaire specifically assessed the likelihood of future biopsies, postbiopsy symptoms, complications, and perceptions., Results: A total of 129 patients were enrolled, of which 91 (70.5%) completed at least 1 questionnaire. These patients had either ovarian (89%; 81 of 91) or endometrial cancer (11%; 10 of 91). Of all biopsies taken, 75% were from the abdomen or pelvis (67 of 89). There was 1 clinician-reported complication, a perihepatic hematoma (1%). Pain during the biopsy and physical discomfort were experienced by 60.3% (41 of 68) and 61.8% (42 of 68), respectively. Embarrassment and loss of dignity were experienced by 13.2% (9 of 68) and 11.8% (8 of 68), respectively. Although the mean Hospital Anxiety and Depression Scale score was in the normal range before and after biopsy, there was a significant decline in the total score after the biopsy (prebiopsy, 5.3 [standard deviation, 4.7] vs postbiopsy, 3.7 [standard deviation, 4.5]; P=.005); 84% of subjects (58 of 69) stated that they would definitely or likely consent to another biopsy. There was no impact on patients' willingness for future biopsies based on Eastern Cooperative Oncology Group status, biopsy site, age, number of cores, and pain during the biopsy; however, subjects who reported feeling physically uncomfortable (odds ratio, 0.14; P=.005), embarrassed (odds ratio, 0.03; P=.004) or experienced loss of dignity (odds ratio, 0.05; P=.01) during the biopsy and those who experienced flu-like symptoms (odds ratio, 0.2; P=.018) or felt feverish (odds ratio, 0.2; P=.035) 1 week after biopsy, were less likely to undergo a sequential biopsy. Similarly, those with higher Hospital Anxiety and Depression Scale scores before biopsy (odds ratio, 0.83; P=.008) and after biopsy (odds ratio, 0.8; P=.003) were less likely to consent for another biopsy., Conclusion: Research biopsies were generally well accepted. Most patients (83%) were willing to undergo serial biopsies if necessary. Addressing the potentially modifiable psychosocial aspects of the procedure may improve the experience with research biopsies for patients with gynecologic cancers., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Abstract: The use of poly(ADP-ribose) polymerase inhibitors and immune checkpoint inhibitor therapies has seen substantial clinical success in oncology therapeutic development. Although multiple agents within these classes have achieved regulatory approval globally-in several malignancies in early and advanced stages-drug resistance remains an issue. Building on preclinical evidence, several early trials and late-phase studies are underway. This review explores the therapeutic potential of combination poly(ADP-ribose) polymerase inhibitors and immune checkpoint inhibitor therapy in solid tumors, including the scientific and therapeutic rationale, available clinical evidence, and considerations for future trial and biomarker development across different malignancies using ovarian and other solid cancer subtypes as key examples., Competing Interests: Conflicts of Interest and Source of Funding: A.M.O. is on the steering committee of GlaxoSmithKline, AstraZeneca, Clovis, Tesaro, and Merck (uncompensated) and is principal investigator on clinical trials for AstraZeneca, GlaxoSmithKline, and Clovis. For the remaining authors, none were declared. No funding support was received for this work., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Disseminated intravascular coagulation (DIC) is a rare paraneoplastic complication in advanced solid malignancies, with success of treatment and survival dependent on treatment of the underlying malignancy. Best estimates suggest an incidence of 1.6-6.8% in cancer, with risk factors being advanced disease, older age, and adenocarcinoma, especially of lung origin. Few cases, however, have reported on an association between DIC and oncogene-addicted lung cancers, especially those containing ROS proto-oncogene 1 (ROS1) mutations, however precedent exists to suggest increased prothrombotic rates in tumors harboring this mutation. We present a young woman with ROS1-mutant non-small-cell lung cancer who presented in DIC and subsequently developed complications of both hemorrhage and thrombosis. Following initiation of targeted treatment, rapid resolution of laboratory coagulation derangement was observed and clinical improvement quickly followed. This event underscores the need for rapid evaluation of lung molecular panels and the dramatic resolution of life-threatening illness that can occur with institution of appropriate therapy. This case contributes to growing evidence for a possible underlying link between oncogene addicted tumors and abnormalities of coagulation., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Objectives: In 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., Design: Scoping review., Setting: Population-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., Participants: Eligibility criteria included participants within published studies who tested positive for COVID-19., Main Outcomes and Measures: Data 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., Results: 11 556 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 (p<0.001) in ethics-related references were apparent when analysed by continent, publication type, sample size and IF., Conclusions: The 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 Number: Open Science Framework: https://osfio/z67wb., Competing Interests: Competing interests: None declared., (© 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.)

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., Competing Interests: Declaration of Competing Interest The authors have no personal nor financial conflict of interests to disclose. Several of the clinical trials included in this systematic review were conducted at the Princess Margaret Cancer Centre., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Public Health Emergencies of International Concern, such as the coronavirus disease 2019 pandemic, have a devastating impact on an individual and societal level, and there is an urgent need to learn, understand and bridge the therapeutic gap at a time of extreme stress on the patient, health care systems and staff. Well-designed, controlled clinical trials play a crucial role in the discovery of novel diagnostic and management strategies; however, these catastrophic circumstances pose unique challenges in initiating research studies at institutional, national, and international levels, highlighting the importance of a coordinated, collaborative approach. This review discusses key elements necessary to consider for developing clinical trials within a Public Health Emergency setting., (© 2020 Wiley Periodicals LLC.)

Immune checkpoint inhibitors have demonstrated significant clinical activity across various tumor subtypes; however, their utility in gynecologic malignancies has thus far proven modest. Since the identification of a molecular subclassification system for endometrial cancer (EC), research in immune checkpoint inhibitor therapies has been focusing on certain subgroups predictive for response, particularly microsatellite instability hypermutated/DNA mismatch repair-deficient subtype. Dostarlimab, a PD-1 inhibitor, has demonstrated preliminary evidence of clinical activity and acceptable safety profile in patients with across recurrent EC, particularly microsatellite instability-hypermutated/DNA mismatch repair-deficient EC. This review outlines existing data for the efficacy and safety of dostarlimab in recurrent or advanced-stage EC.

Competing Interests: Competing interests: AMO is on the steering committee of GlaxoSmithKline, AstraZeneca, Clovis, Tesaro and Merck (uncompensated), and is PI on clinical trials for AstraZeneca, GlaxoSmithKline, and Clovis.

Competing Interests: Competing interests: SL is principal investigator of cervical cancer studies of Regeneron and Merck. She reports grants and personal fees from Astra-Zeneca and GSK, and personal fees from Merck and Roche, outside the submitted work.

Objectives: There is uncertainty whether older patients derive a similar benefit from immune checkpoint inhibitors (ICI) as younger patients. We performed a meta-analysis of ICI trials in advanced cancers to better estimate treatment benefit in the older population., Materials and Methods: We performed an electronic search for randomized trials of ICI, either as monotherapy or in combination with other agents. Hazard ratios (HR) for subgroups defined by different age cut-offs were extracted. Pooled overall survival (OS) treatment estimates were calculated using the inverse variance weighted method., Results: In nineteen trials comparing ICI monotherapy versus non-ICI treatment, there was no significant treatment-age interaction (age ≥ 65 years: N = 6064, HR 0.73; age < 65 years: N = 7250, HR 0.79; P-interaction = 0.27). Findings were similar at older age cut-offs of 70 years (age ≥ 70 years: N = 433, HR = 0.93; age < 70 years: N = 169, HR = 0.95; P-interaction = 0.91) and 75 years (age ≥ 75 years: N = 139, HR = 0.75; age < 75 years: N = 1133, HR = 0.61; P-interaction = 0.72) respectively, and for trials of ICI combination therapy., Conclusion: ICI therapy improves OS in both younger and older patients with advanced cancers, and the magnitude of improvement does not depend on age. Patient selection for ICI therapy should be done based on performance status and adequate organ function independently of age., (Copyright © 2019. Published by Elsevier Ltd.)