Search

Introduction: Although menstruation is a natural biological process, many people feel embarrassed of their menses and struggle to discuss it. To mitigate menstrual communication stigma, it is necessary to first elucidate communication experiences and perceptions. Thus, we qualitatively explore menstrual communication among cisgender women who menstruate and their family, friends, healthcare providers, and community., Methodology: In partnership with No More Secrets (NMS), a Philadelphia menstrual health non-profit, we conducted a community-based participatory research (CBPR) project in Fall 2020. Cisgender, menstruating individuals ages 18-45 recruited from NMS' catchment in Philadelphia participated in semi-structured interviews about their menstrual experiences and communication (N = 20). A deductive, theory-driven approached based on the social-ecological model was used to analyze the data., Results: Varying emotional responses arose across social-ecological levels: communication was awkward and simplistic with family; positive and supportive with friends and community members; and uncomfortable and frustrating with healthcare providers. Participants echoed the importance of menstrual communication as a means of sharing information, feeling less alone, and decreasing menstrual stigma., Discussion: Findings can inform future CBPR workshops that address stigma in familial, healthcare, and community-based discussions to improve menstrual health and experiences for cisgender girls and women, transgender men, and gender non-binary individuals who menstruate., (© 2024 The Author(s). Perspectives on Sexual and Reproductive Health published by Wiley Periodicals LLC on behalf of University of Ottawa.)

Importance: The timing of adjuvant chemotherapy after surgery for colorectal cancer and its association with long-term outcomes have been investigated in national cohort studies, with no consensus on the optimal time from surgery to adjuvant chemotherapy., Objective: To analyze the association between the timing of adjuvant chemotherapy after surgery for colorectal cancer and disease-free survival., Design, Setting, and Participants: This is a post hoc analysis of the phase 3 SCOT randomized clinical trial, from 244 centers in 6 countries, investigating the noninferiority of 3 vs 6 months of adjuvant chemotherapy. Patients with high-risk stage II or stage III nonmetastatic colorectal cancer who underwent curative-intended surgery were randomized to either 3 or 6 months of adjuvant chemotherapy consisting of fluoropyrimidine and oxaliplatin regimens. Those with complete information on the date of surgery, treatment type, and long-term follow-up were investigated for the primary and secondary end points. Data were analyzed from May 2022 to February 2024., Intervention: In the post hoc analysis, patients were grouped according to the start of adjuvant chemotherapy being less than 6 weeks vs greater than 6 weeks after surgery., Main Outcomes and Measures: The primary end point was disease-free survival. The secondary end points were adverse events in the total treatment period or the first cycle of adjuvant chemotherapy., Results: A total of 5719 patients (2251 [39.4%] female; mean [SD] age, 63.4 [9.3] years) were included in the primary analysis after data curation; among them, 914 were in the early-start group and 4805 were in the late-start group. Median (IQR) follow-up was 72.0 (47.3-88.1) months, with a median (IQR) of 56 (41-66) days from surgery to chemotherapy. Five-year disease-free survival was 78.0% (95% CI, 75.3%-80.8%) in the early-start group and 73.2% (95% CI, 72.0%-74.5%) in the late-start group. In an adjusted Cox regression analysis, the start of adjuvant chemotherapy greater than 6 weeks after surgery was associated with worse disease-free survival (hazard ratio, 1.24; 95% CI, 1.06-1.46; P = .01). In adjusted logistic regression models, there was no association with adverse events in the total treatment period (odds ratio, 0.82; 95% CI, 0.65-1.04; P = .09) or adverse events in the first cycle of treatment (odds ratio, 0.77; 95% CI, 0.56-1.09; P = .13)., Conclusions and Relevance: In this international population of patients with high-risk stage II and stage III colorectal cancer, starting adjuvant chemotherapy more than 6 weeks after surgery was associated with worse disease-free survival, with no difference in adverse events between the groups., Trial Registration: isrctn.org Identifier: ISRCTN59757862.

Background: While menstruation is a physiologic process, it remains highly stigmatized. Despite the sheer number of menstruators, menstruation is a highly individualized experience, with wide variation in duration, symptoms, and management. This wide variability lends itself to large disparities in access to menstruation management products and subsequently the lived experience of menstruators., Objectives: The research team sought to understand lived menstrual experiences, symptoms, management tactics, and commonly used and desired resources among 20 cisgendered women aged 18-45 years in Philadelphia., Design: This project was a qualitative research study., Methods: We used a collaborative, community-based participatory research approach with No More Secrets, a Philadelphia-based grassroots sexuality awareness and menstrual health hub. Semi-structured telephone interviews were used to gain insight into general menstruation-related experiences, communication, worries, and concerns, with subsequent thematic analysis via Key Words in Context approach., Results: Four themes emerged following analysis: cycle characteristics, menstruation management, coping resources, and future resources. Participants largely spoke about their menses as a negative experience, asked for more comprehensive, verified sources of information and needed greater access to menstrual management supplies., Conclusion: Menstruation is a highly individualized experience with a large variety in knowledge, menstrual product use, and individual needs. Despite the individuality of menstruation, our community-based research shows that there is a dire need for interventions that promotes knowledge and access to menstrual care.

Background: Analysis of circulating tumour DNA could stratify cancer risk in symptomatic patients. We aimed to evaluate the performance of a methylation-based multicancer early detection (MCED) diagnostic test in symptomatic patients referred from primary care., Methods: We did a multicentre, prospective, observational study at National Health Service (NHS) hospital sites in England and Wales. Participants aged 18 or older referred with non-specific symptoms or symptoms potentially due to gynaecological, lung, or upper or lower gastrointestinal cancers were included and gave a blood sample when they attended for urgent investigation. Participants were excluded if they had a history of or had received treatment for an invasive or haematological malignancy diagnosed within the preceding 3 years, were taking cytotoxic or demethylating agents that might interfere with the test, or had participated in another study of a GRAIL MCED test. Patients were followed until diagnostic resolution or up to 9 months. Cell-free DNA was isolated and the MCED test performed blinded to the clinical outcome. MCED predictions were compared with the diagnosis obtained by standard care to establish the primary outcomes of overall positive and negative predictive value, sensitivity, and specificity. Outcomes were assessed in participants with a valid MCED test result and diagnostic resolution. SYMPLIFY is registered with ISRCTN (ISRCTN10226380) and has completed follow-up at all sites., Findings: 6238 participants were recruited between July 7 and Nov 30, 2021, across 44 hospital sites. 387 were excluded due to staff being unable to draw blood, sample errors, participant withdrawal, or identification of ineligibility after enrolment. Of 5851 clinically evaluable participants, 376 had no MCED test result and 14 had no information as to final diagnosis, resulting in 5461 included in the final cohort for analysis with an evaluable MCED test result and diagnostic outcome (368 [6·7%] with a cancer diagnosis and 5093 [93·3%] without a cancer diagnosis). The median age of participants was 61·9 years (IQR 53·4-73·0), 3609 (66·1%) were female and 1852 (33·9%) were male. The MCED test detected a cancer signal in 323 cases, in whom 244 cancer was diagnosed, yielding a positive predictive value of 75·5% (95% CI 70·5-80·1), negative predictive value of 97·6% (97·1-98·0), sensitivity of 66·3% (61·2-71·1), and specificity of 98·4% (98·1-98·8). Sensitivity increased with increasing age and cancer stage, from 24·2% (95% CI 16·0-34·1) in stage I to 95·3% (88·5-98·7) in stage IV. For cases in which a cancer signal was detected among patients with cancer, the MCED test's prediction of the site of origin was accurate in 85·2% (95% CI 79·8-89·3) of cases. Sensitivity 80·4% (95% CI 66·1-90·6) and negative predictive value 99·1% (98·2-99·6) were highest for patients with symptoms mandating investigation for upper gastrointestinal cancer., Interpretation: This first large-scale prospective evaluation of an MCED diagnostic test in a symptomatic population demonstrates the feasibility of using an MCED test to assist clinicians with decisions regarding urgency and route of referral from primary care. Our data provide the basis for a prospective, interventional study in patients presenting to primary care with non-specific signs and symptoms., Funding: GRAIL Bio UK., Competing Interests: Declaration of interests BDN and MRM receive institutional research funding from GRAIL. MRM reports grants from Roche, Astrazeneca, BMS, Infinitopes, Immunocore, and study fees from BMS, Pfizer, MSD, Regeneron, BiolineRx, Replimune and Novartis outside of the submitted work. HK, KNK, SH, KR, YL, and HN are employees of GRAIL. HK, KNK, SH, KR, and YL hold stock in Illumina. HK reports a leadership position with GRAIL. DH reports a leadership role with CanSense, outside of the submitted work. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Menstrual health is a secretive, stigmatized, and understudied topic in the United States. To begin addressing this stigma requires understanding menstrual communication patterns in the community; however, few studies have applied community-based participatory research to explore menstrual health stigma., Objectives: To describe the team and lessons learned building a community-academic partnership aimed to explore menstrual health stigma and communication in Philadelphia, Pennsylvania.Partnership: A menstrual health non-profit and a social-reproductive epidemiologist forged a community-academic partnership using a unique program that encourages partnerships between researchers and community organizations., Lessons Learned: Three lessons are described: 1) take time to build trust, 2) be patient and respectful navigating challenges and unforeseen difficulties, and 3) ensure equitable distribution of project resources and benefits., Conclusions: Our partnership accomplished impactful work by acknowledging the unique resources, skills, and networks that each partner possessed.

Background: Oxaliplatin and fluoropyrimidine chemotherapy administered over 6 months is the standard adjuvant regimen for patients with high-risk stage II or III colorectal cancer. However, the regimen is associated with cumulative toxicity, characterised by chronic and often irreversible neuropathy., Objectives: To assess the efficacy of 3-month versus 6-month adjuvant chemotherapy for colorectal cancer and to compare the toxicity, health-related quality of life and cost-effectiveness of the durations., Design: An international, randomised, open-label, non-inferiority, Phase III, parallel-group trial., Setting: A total of 244 oncology clinics from six countries: UK (England, Scotland, Wales and Northern Ireland), Denmark, Spain, Sweden, Australia and New Zealand., Participants: Adults aged ≥ 18 years who had undergone curative resection for high-risk stage II or III adenocarcinoma of the colon or rectum., Interventions: The adjuvant treatment regimen was either oxaliplatin and 5-fluorouracil or oxaliplatin and capecitabine, randomised to be administered over 3 or 6 months., Main Outcome Measures: The primary outcome was disease-free survival. Overall survival, adverse events, neuropathy and health-related quality of life were also assessed. The main cost categories were chemotherapy treatment and hospitalisation. Cost-effectiveness was assessed through incremental cost comparisons and quality-adjusted life-year gains between the options and was reported as net monetary benefit using a willingness-to-pay threshold of £30,000 per quality-adjusted life-year per patient., Results: Recruitment is closed. In total, 6088 patients were randomised (3044 per group) between 27 March 2008 and 29 November 2013, with 6065 included in the intention-to-treat analyses (3-month analysis, n  = 3035; 6-month analysis, n  = 3030). Follow-up for the primary analysis is complete. The 3-year disease-free survival rate in the 3-month treatment group was 76.7% (standard error 0.8%) and in the 6-month treatment group was 77.1% (standard error 0.8%), equating to a hazard ratio of 1.006 (95% confidence interval 0.909 to 1.114; p -value for non-inferiority = 0.012), confirming non-inferiority for 3-month adjuvant chemotherapy. Frequent adverse events (alopecia, anaemia, anorexia, diarrhoea, fatigue, hand-foot syndrome, mucositis, sensory neuropathy, neutropenia, pain, rash, altered taste, thrombocytopenia and watery eye) showed a significant increase in grade with 6-month duration; the greatest difference was for sensory neuropathy (grade ≥ 3 was 4% for 3-month vs.16% for 6-month duration), for which a higher rate of neuropathy was seen for the 6-month treatment group from month 4 to ≥ 5 years ( p  < 0.001). Quality-of-life scores were better in the 3-month treatment group over months 4-6. A cost-effectiveness analysis showed 3-month treatment to cost £4881 less over the 8-year analysis period, with an incremental net monetary benefit of £7246 per patient., Conclusions: The study achieved its primary end point, showing that 3-month oxaliplatin-containing adjuvant chemotherapy is non-inferior to 6 months of the same regimen; 3-month treatment showed a better safety profile and cost less. For future work, further follow-up will refine long-term estimates of the duration effect on disease-free survival and overall survival. The health economic analysis will be updated to include long-term extrapolation for subgroups. We expect these analyses to be available in 2019-20. The Short Course Oncology Therapy (SCOT) study translational samples may allow the identification of patients who would benefit from longer treatment based on the molecular characteristics of their disease., Trial Registration: Current Controlled Trials ISRCTN59757862 and EudraCT 2007-003957-10., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 23, No. 64. See the NIHR Journals Library website for further project information. This research was supported by the Medical Research Council (transferred to NIHR Evaluation, Trials and Studies Coordinating Centre - Efficacy and Mechanism Evaluation; grant reference G0601705), the Swedish Cancer Society and Cancer Research UK Core Clinical Trials Unit Funding (funding reference C6716/A9894)., Competing Interests: Timothy Iveson reports honoraria from Amgen Inc. (Thousand Oaks, CA, USA), Bayer AG (Leverkusen, Germany), Bristol-Myers Squibb (New York, NY, USA), Celgene Corporation (Summit, NJ, USA), Pierre-Fabre (Paris, France), Roche (Roche Holding AG, Basel, Switzerland) and Servier (Laboratories Servier, Suresnes, France). Kathleen A Boyd reports grants from the Medical Research Council during the conduct of the study. Mark P Saunders reports personal fees from Servier, Amgen, Merck (Merck and Co., Kenilworth, New Jersey, USA), Eisai (Eisai Co., Ltd., Tokyo, Japan) and Roche outside the submitted work. Jim Cassidy reports grants from the Medical Research Council during the conduct of the study and is currently an employee of Celgene Corporation. Josep Tabernero reports personal fees from Array Biopharma (Boulder, CO, USA), AstraZeneca (Cambridge, UK), Bayer AG (Leverkusen, Germany), BeiGene (Beijing, China), Boehringer Ingelheim (Ingelheim am Rhein, Germany), Chugai (Chugai Pharmaceutical Co., Tokyo, Japan), Genentech, Inc. (South San Francisco, CA, USA), Genmab A/S (Copenhagen, Denmark), Halozyme (Halozyme Therapeutics, San Diego, CA, USA), Imugene Limited (Sydney, NSW, Australia), Inflection Biosciences Limited (Blackrock, Dublin), Ipsen (Paris, France), Kura Oncology (San Diego, CA, USA), Eli Lilly and Company (Indianapolis, IN, USA), Merck, Menarini (The Menarini Group, Florence, Italy), Merck Serono (Rockland, MA, USA), Merrimack Pharmaceuticals (MA, USA), Merus (Utrecht, the Netherlands), Molecular Partners (Molecular Partners AG, Zurich, Switzerland), Novartis (Novartis International AG, Basel, Switzerland), Peptomyc, Pfizer Inc. (New York, NY, USA), Pharmacyclics (Pharmacyclics LLC, Sunnyvale, CA, USA), ProteoDesign SL (Barcelona, Spain), Rafael Pharmaceuticals (Stony Brook, NY, USA), F. Hoffmann-La Roche Ltd, Sanofi (Sanofi S. A., Paris, France), Seattle Genetics (Bothwell, WA, USA), Servier, Symphogen (Symphogen A/S, Ballerup, Denmark), Taiho Pharmaceutical (Tokyo, Japan), VCN Biosciences (Barcelona, Spain), Biocartis (Biocartis Group, Mechelen, Belgium), Foundation Medicine (Cambridge, MA, USA), HalioDX (Marseille, France), SAS Pharmaceuticals (Delhi, India) and Roche Diagnostics outside the submitted work. Bengt Glimelius reports support from PledPharma AB for being on advisory boards. Sherif Raouf reports grants, personal fees and non-financial support from Roche, grants and personal fees from Amgen, and grants and personal fees from Merck outside the submitted work. David Farrugia reports that he received honoraria for speaking in educational events and support for meeting attendance from Bristol-Myers Squibb, Novartis, Ipsen, Amgen, AstraZeneca and Merck. David Cunningham reports grants from 4SC (4SC AG, Planegg, Germany), AstraZeneca, Bayer, Amgen, Celgene, Clovis Oncology (Boulder, CO, USA), Eli Lilly and Company, Janssen Pharmaceuticals (Beerse, Belgium), MedImmune (Gaithersburg, MD, USA), Merck, Merrimack and Sanofi, outside the submitted work. Tamish Hickish reports grants from Pfizer, Roche, Pierre Fabre (Paris, France) and personal fees from Eli Lilly and Company during the conduct of the study. John Bridgewater reports funding from the University College London Hospitals NHS Foundation Trust/University College London Biomedical Research Centre. David Cunningham reports funding from the National Institute for Health Research Biomedical Research Centres at the Royal Marsden.

Background: The Short Course Oncology Therapy (SCOT) study is an international, multicentre, non-inferiority randomised controlled trial assessing the efficacy, toxicity, and cost-effectiveness of 3 months (3 M) versus the usually given 6 months (6 M) of adjuvant chemotherapy in colorectal cancer., Methods: In total, 6088 patients with fully resected high-risk stage II or stage III colorectal cancer were randomised and followed up for 3-8 years. The within-trial cost-effectiveness analysis from a UK health-care perspective is presented using the resource use data, quality of life (EQ-5D-3L), time on treatment (ToT), disease-free survival after treatment (DFS) and overall survival (OS) data. Quality-adjusted partitioned survival analysis and Kaplan-Meier Sample Average Estimator estimated QALYs and costs. Probabilistic sensitivity and subgroup analysis was undertaken., Results: The 3 M arm is less costly (-£4881; 95% CI: -£6269; -£3492) and entails (non-significant) QALY gains (0.08; 95% CI: -0.086; 0.230) due to a better significant quality of life. The net monetary benefit was significantly higher in 3 M under a wide range of monetary values of a QALY. The subgroup analysis found similar results for patients in the CAPOX regimen. However, for the FOLFOX regimen, 3 M had lower QALYs than 6 M (not statistically significant)., Conclusions: Overall, 3 M dominates 6 M with no significant detrimental impact on QALYs. The results provide the economic case that a 3 M treatment strategy should be considered a new standard of care.

Background: 6 months of oxaliplatin-containing chemotherapy is usually given as adjuvant treatment for stage 3 colorectal cancer. We investigated whether 3 months of oxaliplatin-containing chemotherapy would be non-inferior to the usual 6 months of treatment., Methods: The SCOT study was an international, randomised, phase 3, non-inferiority trial done at 244 centres. Patients aged 18 years or older with high-risk stage II and stage III colorectal cancer underwent central randomisation with minimisation for centre, choice of regimen, sex, disease site, N stage, T stage, and the starting dose of capecitabine. Patients were assigned (1:1) to receive 3 months or 6 months of adjuvant oxaliplatin-containing chemotherapy. The chemotherapy regimens could consist of CAPOX (capecitabine and oxaliplatin) or FOLFOX (bolus and infused fluorouracil with oxaliplatin). The regimen was selected before randomisation in accordance with choices of the patient and treating physician. The primary study endpoint was disease-free survival and the non-inferiority margin was a hazard ratio of 1·13. The primary analysis was done in the intention-to-treat population and safety was assessed in patients who started study treatment. This trial is registered with ISRCTN, number ISRCTN59757862, and follow-up is continuing., Findings: 6088 patients underwent randomisation between March 27, 2008, and Nov 29, 2013. The intended treatment was FOLFOX in 1981 patients and CAPOX in 4107 patients. 3044 patients were assigned to 3 month group and 3044 were assigned to 6 month group. Nine patients in the 3 month group and 14 patients in the 6 month group did not consent for their data to be used, leaving 3035 patients in the 3 month group and 3030 patients in the 6 month group for the intention-to-treat analyses. At the cutoff date for analysis, there had been 1482 disease-free survival events, with 740 in the 3 month group and 742 in the 6 month group. 3 year disease-free survival was 76·7% (95% CI 75·1-78·2) for the 3 month group and 77·1% (75·6-78·6) for the 6 month group, giving a hazard ratio of 1·006 (0·909-1·114, test for non-inferiority p=0·012), significantly below the non-inferiority margin. Peripheral neuropathy of grade 2 or worse was more common in the 6 month group (237 [58%] of 409 patients for the subset with safety data) than in the 3 month group (103 [25%] of 420) and was long-lasting and associated with worse quality of life. 1098 serious adverse events were reported (492 reports in the 3 month group and 606 reports in the 6 month group) and 32 treatment-related deaths occurred (16 in each group)., Interpretation: In the whole study population, 3 months of oxaliplatin-containing adjuvant chemotherapy was non-inferior to 6 months of the same therapy for patients with high-risk stage II and stage III colorectal cancer and was associated with reduced toxicity and improved quality of life. Despite the fact the study was underpowered, these data suggest that a shorter duration leads to similar survival outcomes with better quality of life and thus might represent a new standard of care., Funding: Medical Research Council, Swedish Cancer Society, NETSCC, and Cancer Research UK., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

RNA-directed antisense and interference therapeutics are a promising treatment option for cancer. The demonstration of depletion of target proteins within human tumors in vivo using validated methodology will be a key to the application of this technology. Here, we present a flow cytometric-based approach to quantitatively determine protein levels in solid tumor material derived by fiber optic brushing (FOB) of non-small cell lung cancer (NSCLC) patients. Focusing upon the survivin protein, and its depletion by an antisense oligonucleotide (ASO) (LY2181308), we show that we can robustly identify a subpopulation of survivin positive tumor cells in FOB samples, and, moreover, detect survivin depletion in tumor samples from a patient treated with LY2181308. Survivin depletion appears to be a result of treatment with this ASO, because a tumor treated with conventional cytotoxic chemotherapy did not exhibit a decreased percentage of survivin positive cells. Our approach is likely to be broadly applicable to, and useful for, the quantification of protein levels in tumor samples obtained as part of clinical trials and studies, facilitating the proof-of-principle testing of novel targeted therapies.

The incidence of lung cancer continues to rise. The need and demand for more effective treatment to improve survival and palliate symptoms increases at a great rate. The most recent evidence for the use of chemotherapy in the palliative setting is summarized in this review of the literature from the last few years. It indicates that in advanced nonsmall-cell lung cancer survival, symptom control and physical functioning can be improved with the use of chemotherapy not only in the first-line but also in the second-line setting, in the elderly, and at disease relapse.

The purpose of this single-subject pilot study was to examine the efficacy of FM amplification for enhancing the discourse skills of a 4-year-old girl with a history of speech-language impairments, otitis media with effusion (OME), and motoric delays. Over a period of several weeks, language treatment sessions were conducted with and without FM amplification, in a classroom setting. Sessions were videotaped and analyzed for the appropriateness and effectiveness of the subject's conversational turns during sessions with amplification and with no amplification. Although the number of sessions was small, more appropriate and effective conversational turns occurred during sessions with amplification.

The relation of otitis media with effusion (OME) and associated hearing loss to language and cognitive skills at 1 year of age was studied to determine whether OME-related hearing loss had a direct association with language and cognitive outcomes at 1 year of age or an indirect association with these outcomes, as mediated by the child-rearing environment. Subjects were 61 black infants attending community-based child care programs. The presence of OME was assessed biweekly from 6 to 12 months of age by otoscopy and tympanometry. Hearing was assessed with visual reinforcement audiometry when children were well and when ill with OME. Language and cognitive skills and the child-rearing environment at home and in child care were examined. The results indicated a modest correlation between hearing loss associated with OME and receptive language. However, the direct association between OME-related hearing loss and all the language and cognitive measures was negligible. Hearing loss had an indirect association with receptive and expressive language, cognitive development, and overall communication as mediated by child-rearing factors. That is, children with more frequent hearing loss tended to have less responsive mothers and home environments, and this association was linked to lower performance on the infant assessments.