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JAMA Network Open May 2024Unlike other surgical specialties, obstetrics and gynecology (OB-GYN) has been predominantly female for the last decade. The association of this with gender bias and...
IMPORTANCE
Unlike other surgical specialties, obstetrics and gynecology (OB-GYN) has been predominantly female for the last decade. The association of this with gender bias and sexual harassment is not known.
OBJECTIVE
To systematically review the prevalence of sexual harassment, bullying, abuse, and discrimination among OB-GYN clinicians and trainees and interventions aimed at reducing harassment in OB-GYN and other surgical specialties.
EVIDENCE REVIEW
A systematic search of PubMed, Embase, and ClinicalTrials.gov was conducted to identify studies published from inception through June 13, 2023.: For the prevalence of harassment, OB-GYN clinicians and trainees on OB-GYN rotations in all subspecialties in the US or Canada were included. Personal experiences of harassment (sexual harassment, bullying, abuse, and discrimination) by other health care personnel, event reporting, burnout and exit from medicine, fear of retaliation, and related outcomes were included. Interventions across all surgical specialties in any country to decrease incidence of harassment were also evaluated. Abstracts and potentially relevant full-text articles were double screened.: Eligible studies were extracted into standard forms. Risk of bias and certainty of evidence of included research were assessed. A meta-analysis was not performed owing to heterogeneity of outcomes.
FINDINGS
A total of 10 eligible studies among 5852 participants addressed prevalence and 12 eligible studies among 2906 participants addressed interventions. The prevalence of sexual harassment (range, 250 of 907 physicians [27.6%] to 181 of 255 female gynecologic oncologists [70.9%]), workplace discrimination (range, 142 of 249 gynecologic oncologists [57.0%] to 354 of 527 gynecologic oncologists [67.2%] among women; 138 of 358 gynecologic oncologists among males [38.5%]), and bullying (131 of 248 female gynecologic oncologists [52.8%]) was frequent among OB-GYN respondents. OB-GYN trainees commonly experienced sexual harassment (253 of 366 respondents [69.1%]), which included gender harassment, unwanted sexual attention, and sexual coercion. The proportion of OB-GYN clinicians who reported their sexual harassment to anyone ranged from 21 of 250 AAGL (formerly, the American Association of Gynecologic Laparoscopists) members (8.4%) to 32 of 256 gynecologic oncologists (12.5%) compared with 32.6% of OB-GYN trainees. Mistreatment during their OB-GYN rotation was indicated by 168 of 668 medical students surveyed (25.1%). Perpetrators of harassment included physicians (30.1%), other trainees (13.1%), and operating room staff (7.7%). Various interventions were used and studied, which were associated with improved recognition of bias and reporting (eg, implementation of a video- and discussion-based mistreatment program during a surgery clerkship was associated with a decrease in medical student mistreatment reports from 14 reports in previous year to 9 reports in the first year and 4 in the second year after implementation). However, no significant decrease in the frequency of sexual harassment was found with any intervention.
CONCLUSIONS AND RELEVANCE
This study found high rates of harassment behaviors within OB-GYN. Interventions to limit these behaviors were not adequately studied, were limited mostly to medical students, and typically did not specifically address sexual or other forms of harassment.
Topics: Humans; Sexual Harassment; Gynecology; Female; Obstetrics; Male; Sexism; Bullying; Prevalence; Canada; United States
PubMed: 38717770
DOI: 10.1001/jamanetworkopen.2024.10706 -
Scientific Reports Aug 2023Cancer-related fatigue (CRF) affects therapeutic compliance and clinical outcomes including recurrence and mortality. This study aimed to comprehensively and... (Meta-Analysis)
Meta-Analysis
Cancer-related fatigue (CRF) affects therapeutic compliance and clinical outcomes including recurrence and mortality. This study aimed to comprehensively and comparatively assess the severity-based prevalence of CRF. From two public databases (PubMed and Cochrane Library), we extracted data containing information on both prevalence and severity of fatigue in cancer patients through December 2021. We conducted a meta-analysis to produce point estimates using random effects models. Subgroup analyses were used to assess the prevalence and severity by the organ/system tumor development, treatment phase, therapeutic type, sex and assessment method. A total of 151 data (57 studies, 34,310 participants, 11,805 males and 22,505 females) were selected, which indicated 43.0% (95% CI 39.2-47.2) of fatigue prevalence. The total CRF prevalence including 'mild' level of fatigue was 70.7% (95% CI 60.6-83.3 from 37 data). The prevalence of 'severe' fatigue significantly varied by organ/system types of cancer origin (highest in brain tumors 39.7% vs. lowest in gynecologic tumors 3.9%) and treatment phase likely 15.9% (95% CI 8.1-31.3) before treatment, 33.8% (95% CI 27.7-41.2) ongoing treatment, and 24.1% (95% CI 18.6-31.2) after treatment. Chemotherapy (33.1%) induced approximately 1.5-fold higher prevalence for 'severe' CRF than surgery (22.0%) and radiotherapy (24.2%). The self-reported data for 'severe' CRF was 20-fold higher than those assessed by physicians (23.6% vs. 1.6%). Female patients exhibited a 1.4-fold higher prevalence of 'severe' fatigue compared to males. The present data showed quantitative feature of the prevalence and severity of CRF based on the cancer- or treatment-related factors, sex, and perspective of patient versus physician. In the context of the medical impact of CRF, our results provide a comparative reference to oncologists or health care providers making patient-specific decision.
Topics: Male; Humans; Female; Prevalence; Neoplasms; Fatigue; Genital Neoplasms, Female; Self Report; Quality of Life
PubMed: 37550326
DOI: 10.1038/s41598-023-39046-0 -
JCO Precision Oncology Jan 2023With the growing number of available targeted therapeutics and molecular biomarkers, the optimal care of patients with cancer now depends on a comprehensive...
PURPOSE
With the growing number of available targeted therapeutics and molecular biomarkers, the optimal care of patients with cancer now depends on a comprehensive understanding of the rapidly evolving landscape of precision oncology, which can be challenging for oncologists to navigate alone.
METHODS
We developed and implemented a precision oncology decision support system, GI TARGET, (Gastrointestinal Treatment Assistance Regarding Genomic Evaluation of Tumors) within the Gastrointestinal Cancer Center at the Dana-Farber Cancer Institute. With a multidisciplinary team, we systematically reviewed tumor molecular profiling for GI tumors and provided molecularly informed clinical recommendations, which included identifying appropriate clinical trials aided by the computational matching platform MatchMiner, suggesting targeted therapy options on or off the US Food and Drug Administration-approved label, and consideration of additional or orthogonal molecular testing.
RESULTS
We reviewed genomic data and provided clinical recommendations for 506 patients with GI cancer who underwent tumor molecular profiling between January and June 2019 and determined follow-up using the electronic health record. Summary reports were provided to 19 medical oncologists for patients with colorectal (n = 198, 39%), pancreatic (n = 124, 24%), esophagogastric (n = 67, 13%), biliary (n = 40, 8%), and other GI cancers. We recommended ≥ 1 precision medicine clinical trial for 80% (406 of 506) of patients, leading to 24 enrollments. We recommended on-label and off-label targeted therapies for 6% (28 of 506) and 25% (125 of 506) of patients, respectively. Recommendations for additional or orthogonal testing were made for 42% (211 of 506) of patients.
CONCLUSION
The integration of precision medicine in routine cancer care through a dedicated multidisciplinary molecular tumor board is scalable and sustainable, and implementation of precision oncology recommendations has clinical utility for patients with cancer.
Topics: Humans; Precision Medicine; Medical Oncology; Gastrointestinal Neoplasms; Genomics; Molecular Diagnostic Techniques
PubMed: 36634297
DOI: 10.1200/PO.22.00342 -
The Cochrane Database of Systematic... Apr 2013High grade glioma (HGG) is an aggressive form of brain cancer. Treatment of HGG usually entails biopsy, or resection if safe, followed by radiotherapy. Temozolomide is a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
High grade glioma (HGG) is an aggressive form of brain cancer. Treatment of HGG usually entails biopsy, or resection if safe, followed by radiotherapy. Temozolomide is a novel oral chemotherapy drug that penetrates into the brain and purportedly has a low incidence of adverse events.
OBJECTIVES
To assess whether temozolomide has any advantage for treating HGG in either primary or recurrent disease settings.
SEARCH METHODS
The following databases were searched: CENTRAL (Issue 10, 2012), MEDLINE, EMBASE, Science Citation Index, Physician Data Query and the Meta-Register of Controlled Trials in October, 2012. Reference lists of identified studies were searched. The Journal of Neuro-Oncology and Neuro-oncology were handsearched from 1999 to 2012 including conference abstracts. We contacted neuro-oncologists regarding ongoing and unpublished trials.
SELECTION CRITERIA
Randomised controlled trials (RCTs) where the interventions were the use of temozolomide during primary therapy or for recurrent disease. Comparisons included no chemotherapy, non-temozolomide chemotherapy or different dosing schedules of temozolomide. Patients included those of all ages with histologically proven HGG.
DATA COLLECTION AND ANALYSIS
Two review authors undertook the quality assessment and data extraction. Outcome measures included: overall survival (OS); progression-free survival (PFS); quality of life (QoL); and adverse events.
MAIN RESULTS
For primary therapy three RCTs were identified, enrolling a total of 745 patients, that investigated temozolomide in combination with radiotherapy versus radiotherapy alone for glioblastoma multiforme (GBM). Temozolomide increased OS (hazard ratio (HR) 0.60, 95% confidence interval (CI) 0.46 to 0.79, P value 0.0003) and increased PFS (HR 0.63, 95% CI 0.43 to 0.92, P value 0.02), when compared with radiotherapy alone, although these benefits only appear to emerge when therapy is given in both concomitant and adjuvant phases of treatment. A single RCT found that temozolomide did not have a statistically significant effect on QoL. Risk of haematological complications, fatigue and infections were increased with temozolomide.In recurrent HGG, two RCTs enrolling 672 patients in total found that temozolomide did not increase OS compared to standard chemotherapy (HR 0.9, 95% CI 0.76 to 1.06, P value 0.2) but it did increase PFS in a subgroup analysis of grade IV GBM tumours (HR 0.68, 95% CI 0.51 to 0.90, P value 0.008). Adverse events were similar between arms.In the elderly, 2 RCTs of 664 patients found OS and PFS was similar with temozolomide alone versus radiotherapy alone. QoL did not appear to differ between arms in a single trial but certain adverse events were significantly more common with temozolomide.
AUTHORS' CONCLUSIONS
Temozolomide when given in both concomitant and adjuvant phases is an effective primary therapy in GBM compared to radiotherapy alone. It prolongs survival and delays progression without impacting on QoL but it does increase early adverse events. In recurrent GBM, temozolomide compared with standard chemotherapy improves time-to-progression (TTP) and may have benefits on QoL without increasing adverse events but it does not improve overall. In the elderly, temozolomide alone appears comparable to radiotherapy in terms of OS and PFS but with a higher instance of adverse events.
Topics: Age Factors; Antineoplastic Agents, Alkylating; Brain Neoplasms; Dacarbazine; Glioblastoma; Humans; Neoplasm Grading; Neoplasm Recurrence, Local; Randomized Controlled Trials as Topic; Survival Analysis; Temozolomide
PubMed: 23633341
DOI: 10.1002/14651858.CD007415.pub2 -
Systematic Review of PD-1/PD-L1 Inhibitors in Oncology: From Personalized Medicine to Public Health.The Oncologist Oct 2021To review and summarize all U.S. Food and Drug Administration (FDA) approvals of programmed death (PD)-1 and PD-ligand 1 blocking antibodies (collectively referred to as... (Review)
Review
BACKGROUND
To review and summarize all U.S. Food and Drug Administration (FDA) approvals of programmed death (PD)-1 and PD-ligand 1 blocking antibodies (collectively referred to as PD-[L]1 inhibitors) over a 6-year period and corresponding companion/complementary diagnostic assays.
MATERIALS AND METHODS
To determine the indications and pivotal trials eligible for inclusion, approval letters and package inserts available on Drugs@FDA were evaluated for approved PD-[L]1 inhibitors to identify all new indications granted from the first approval of a PD-[L]1 inhibitor on September 4, 2014, through September 3, 2020. The corresponding FDA drug and device reviews from the marketing applications for the approved indications were identified through FDA internal records. Two reviewers independently extracted information for the endpoints, efficacy data, basis for approval, type of regulatory approval, and corresponding in vitro diagnostic device test. The results were organized by organ system and tumor type.
RESULTS
Of 70 Biologic Licensing Application or supplement approvals that resulted in new indications, 32 (46%) were granted based on response rate (ORR) and durability of response, 26 (37%) on overall survival, 9 (13%) on progression-free survival, 2 (3%) on recurrence-free survival, and 1 (1%) on complete response rate. Most ORR-based approvals were granted under the accelerated approval provisions and were supported with prolonged duration of response. Overall, 21% of approvals were granted with a companion diagnostic. Efficacy results according to tumor type are discussed.
CONCLUSION
PD-[L]1 inhibitors are an effective anticancer therapy in a subset of patients. This class of drugs has provided new treatment options for patients with unmet need across a wide variety of cancer types. Yet, the modest response rates in several tumor types signal a lack of understanding of the biology of these diseases. Further preclinical and clinical investigation may be required to identify a more appropriate patient population, particularly as drug development continues and additional treatment alternatives become available.
IMPLICATIONS FOR PRACTICE
The number of PD-[L]1 inhibitors in drug development and the associated companion and complementary diagnostics have led to regulatory challenges and questions regarding generalizability of trial results. The interchangeability of PD-L1 immunohistochemical assays between PD-1/PD-L1 drugs is unclear. Furthermore, robust responses in some patients with low levels of PD-L1 expression have limited the use of PD-L1 as a predictive biomarker across all cancers, particularly in the setting of diseases with few alternative treatment options. This review summarizes the biomarker thresholds and assays approved as complementary and companion diagnostics and provides regulatory perspective on the role of biomarkers in oncology drug development.
Topics: B7-H1 Antigen; Humans; Immune Checkpoint Inhibitors; Neoplasms; Precision Medicine; Programmed Cell Death 1 Receptor; Public Health
PubMed: 34196068
DOI: 10.1002/onco.13887 -
Journal of Thoracic Oncology : Official... Aug 2011Greater understanding of molecular pathways important in cell growth and proliferation of thoracic malignancies, particularly non-small cell lung cancer (NSCLC), has... (Review)
Review
INTRODUCTION
Greater understanding of molecular pathways important in cell growth and proliferation of thoracic malignancies, particularly non-small cell lung cancer (NSCLC), has resulted in intense clinical and translational research. There is now considerable interest in personalizing treatment based on an understanding of tumor histology and molecular abnormalities. However, there is a multiplicity of data, often with discordant results resulting in confusion and uncertainty among clinicians.
METHODS
We conducted a systematic review and a consensus meeting of Canadian lung cancer oncologists and pathologists to make recommendations on the use of biomarkers in NSCLC. PubMed covering 2005 to March 2010 was searched using MESH terms for NSCLC and randomized trials, plus text words for the biomarkers of interest. Conference proceedings from 2005 to 2009 ASCO, ESMO, IASLC, and USCAP were also searched. The articles were reviewed by pairs of oncologists and pathologists to determine eligibility for inclusion.
RESULTS
Ten oncologists and pathologists reviewed and summarized the literature at a meeting attended by 37 individuals. Draft recommendations were formulated and agreed upon by consensus process. There is some evidence that histology is prognostic for survival. There is evidence from multiple randomized clinical trials to recommend the following: histologic subtype is predictive of treatment efficacy and for some agents toxicity. Immunohistochemistry testing should be performed on NSCLC specimens that cannot be classified accurately with conventional H&E staining. As EGFR mutations are predictive of benefit from tyrosine kinase inhibitors, diagnostic NSCLC samples should be routinely tested for EGFR-activating mutations. Clinical data on K-RAS mutations are inconsistent, therefore testing is not recommended. There is insufficient evidence to recommend other biomarker testing. No biomarkers to date reliably predict improved efficacy for anti-VEGF therapy. Routine assessment for EML4/ALK mutations is not recommended at present, although emerging data suggest that it may become valuable in the near future.
CONCLUSIONS
Assessment of NSCLC biomarkers is becoming increasingly important. Therefore, adequate diagnostic material must be obtained for accurate histologic subtyping and relevant molecular biology assays.
Topics: Biomarkers, Tumor; Canada; Carcinoma, Non-Small-Cell Lung; Clinical Trials as Topic; Consensus; Humans; Lung Neoplasms; Practice Guidelines as Topic
PubMed: 21709590
DOI: 10.1097/JTO.0b013e318220cb8e -
Biomedicines Aug 2022Trastuzumab is a monoclonal antibody used in the treatment of breast cancer in cases where the tumor overexpresses the HER2 receptor, a cell membrane receptor activated... (Review)
Review
Trastuzumab is a monoclonal antibody used in the treatment of breast cancer in cases where the tumor overexpresses the HER2 receptor, a cell membrane receptor activated by the epidermal growth factor. Intravenous and subcutaneous administration of trastuzumab have comparable clinical and pharmacological characteristics, but trastuzumab biosimilars are currently only available in intravenous form. Trastuzumab biosimilars are ultimately preferred by a proportion of patients, especially in cases where co-administration of other chemotherapeutic agents, such as trastuzumab and tucatinib, a small molecule of tyrosine kinase inhibitor, is required in patients with HER-positive metastatic breast cancer. Oncologists should be well-aware of the advantages of intravenously administered trastuzumab biosimilars over subcutaneous administration, certainly also taking into account the patient's preferences. Further cost-effectiveness analyses will be very important, along with expectations regarding successful concomitant subcutaneous administration of trastuzumab with other anticancer drugs, such as pertuzumab. This systematic review describes and analyzes the so-far published studies concerning the use of the available trastuzumab biosimilars in HER-positive early and metastatic breast cancer in terms of efficacy, safety, and cost-benefit ratio. An attempt was also made to draw some conclusions and to comment on future needs and perspectives.
PubMed: 36009592
DOI: 10.3390/biomedicines10082045 -
JCO Clinical Cancer Informatics Aug 2023Selection of appropriate adjuvant therapy to ultimately reduce the risk of breast cancer (BC) recurrence is a challenge for medical oncologists. Several automated risk... (Review)
Review
PURPOSE
Selection of appropriate adjuvant therapy to ultimately reduce the risk of breast cancer (BC) recurrence is a challenge for medical oncologists. Several automated risk prediction models have been developed using retrospective clinical data and have evolved significantly over the years in terms of predictors of recurrence, data usage, and predictive techniques (statistical/machine learning [ML]).
METHODS
Following PRISMA guidelines, we performed a systematic literature review of the aforementioned statistical and ML models published between January 2008 and December 2022 through searching five digital databases-PubMed, ScienceDirect, Scopus, Cochrane, and Web of Science. The comprehensive search yielded a total of 163 papers and after a screening process focusing on papers that dealt exclusively with statistical/ML methods, only 23 papers were deemed appropriate for further analysis. We benchmarked the studies on the basis of development, evaluation metrics, and validation strategy with an added emphasis on racial diversity of patients included in the studies.
RESULTS
In total, 30.4% of the included studies use statistical techniques, while 69.6% are ML-based. Among these, traditional ML models (support vector machines, decision tree, logistic regression, and naïve Bayes) are the most frequently used (26.1%) along with deep learning (26.1%). Deep learning and ensemble learning provide the most accurate predictions (AUC = 0.94 each).
CONCLUSION
ML-based prediction models exhibit outstanding performance, yet their practical applicability might be hindered by limited interpretability and reduced generalization. Moreover, predictive models for BC recurrence often focus on limited variables related to tumor, treatment, molecular, and clinical features. Imbalanced classes and the lack of open-source data sets impede model development and validation. Furthermore, existing models predominantly overlook African and Middle Eastern populations, as they are trained and validated mainly on Caucasian and Asian patients.
Topics: Humans; Female; Breast Neoplasms; Retrospective Studies; Bayes Theorem; Neoplasm Recurrence, Local; Machine Learning
PubMed: 37566789
DOI: 10.1200/CCI.23.00049 -
Cancer Control : Journal of the Moffitt... 2018Obtaining informed consent in pediatric cancer research can be subject to important ethical challenges because of the difficulty in distinguishing between care and... (Review)
Review
OBJECTIVE
Obtaining informed consent in pediatric cancer research can be subject to important ethical challenges because of the difficulty in distinguishing between care and research, which are interrelated. Pediatric oncologists also often conduct research, such as clinical trials, on their own patients, which may influence voluntary informed consent. This review aims to determine the ethical issues encountered in obtaining informed consent in pediatric oncology by identifying and summarizing the findings of existing qualitative studies on this topic.
METHODS
A systematic review of qualitative studies was conducted. Medline, Embase, CINAHL, and PubMed were searched using the following terms: (oncolog* or cancer or hematol* or haematol* or leuk* or malign* or neoplasm*) and (child* or adolescent* or minor* or young people or pediatr* or paediatr*) and ethic* or moral*) and (qualitative or interview). Other sources were also mined to identify all relevant studies. The data analysis method used was thematic analysis.
RESULTS
At the end of the search process, 2361 studies were identified. Duplicates were removed and irrelevant studies were excluded. After screening the full text of the remaining studies against our inclusion and exclusion criteria, 13 studies were included in the qualitative analysis. All studies were qualitative studies using semistructured and structured interviews, qualitative analysis of open-ended questions, and observation of informed consent conferences. Four themes were identified: parental comprehension of the trial and medical terms, influence of parental distress on decision-making, no offer of an alternative treatment, and influence of the doctor-parent relationship.
CONCLUSION
Many ethical challenges affect the informed consent process. These challenges may include a lack of parental understanding, the potential influence of treating doctors, and vulnerability because of psychological status. All of these result in parents being unable to give well-informed and voluntary consent. Researchers are encouraged to adopt a stepwise approach during the informed consent process.
Topics: Adolescent; Child; Female; Humans; Informed Consent; Male; Medical Oncology; Research Design
PubMed: 29716399
DOI: 10.1177/1073274818773720 -
Pediatric Blood & Cancer Aug 2017A marginal interaction between sex and the type of alkylating agent was observed for event-free survival in the Euro-EWING99-R1 randomized controlled trial (RCT)... (Meta-Analysis)
Meta-Analysis Review
Investigating the heterogeneity of alkylating agents' efficacy and toxicity between sexes: A systematic review and meta-analysis of randomized trials comparing cyclophosphamide and ifosfamide (MAIAGE study).
BACKGROUND
A marginal interaction between sex and the type of alkylating agent was observed for event-free survival in the Euro-EWING99-R1 randomized controlled trial (RCT) comparing cyclophosphamide and ifosfamide in Ewing sarcoma. To further evaluate this interaction, we performed an individual patient data meta-analysis of RCTs assessing cyclophosphamide versus ifosfamide in any type of cancer.
METHODS
A literature search produced two more eligible RCTs (EICESS92 and IRS-IV). The endpoints were progression-free survival (PFS, main endpoint) and overall survival (OS). The hazard ratios (HRs) of the treatment-by-sex interaction and their 95% confidence interval (95% CI) were assessed using stratified multivariable Cox models. Heterogeneity of the interaction across age categories and trials was explored. We also assessed this interaction for severe acute toxicity using logistic models.
RESULTS
The meta-analysis comprised 1,528 pediatric and young adult sarcoma patients from three RCTs: Euro-EWING99-R1 (n = 856), EICESS92 (n = 155), and IRS-IV (n = 517). There were 224 PFS events in Euro-EWING99-R1 and 200 in the validation set (EICESS92 + IRS-IV), and 171 and 154 deaths in each dataset, respectively. The estimated treatment-by-sex interaction for PFS in Euro-EWING99-R1 (HR = 1.73, 95% CI = 1.00-3.00) was not replicated in the validation set (HR = 0.97, 95% CI = 0.55-1.72), without heterogeneity across trials (P = 0.62). In the pooled analysis, the treatment-by-sex interaction was not significant (HR = 1.31, 95% CI = 0.89-1.95, P = 0.17), without heterogeneity across age categories (P = 0.88) and trials (P = 0.36). Similar results were observed for OS. No significant treatment-by-sex interaction was observed for leucopenia/neutropenia (P = 0.45), infection (P = 0.64), or renal toxicity (P = 0.20).
CONCLUSION
Our meta-analysis did not confirm the hypothesis of a treatment-by-sex interaction on efficacy or toxicity outcomes.
Topics: Alkylating Agents; Antineoplastic Agents; Cyclophosphamide; Female; Humans; Ifosfamide; Male; Randomized Controlled Trials as Topic; Sarcoma; Sex Characteristics
PubMed: 28111876
DOI: 10.1002/pbc.26457