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Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2024.3
No full textLiving guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in recommended clinical practice. Living guidelines are updated on a regular schedule by a standing expert panel that systematically reviews the health literature on a continuous basis, as described in the ASCO Guidelines Methodology Manual. ASCO Living Guidelines follow the ASCO Conflict of Interest Policy Implementation for Clinical Practice Guidelines. Living Guidelines and updates are not intended to substitute for independent professional judgment of the treating clinician and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix 1 and 2). Updates are published regularly and can be found at https://ascopubs.org/nsclc-da-living-guideline
A window-of-opportunity trial reveals mechanisms of response and resistance to navtemadlin in patients with recurrent glioblastoma
No full textInhibitors of murine double minute homolog 2 (MDM2) represent a promising therapeutic approach for the treatment of TP53 wild-type glioblastomas (GBMs), reactivating p53 signaling to induce cancer cell death. We conducted a surgical window-of-opportunity trial (NCT03107780) of the MDM2 inhibitor navtemadlin (KRT-232) in 21 patients with TP53 wild-type recurrent GBM to determine achievable drug concentrations within tumor tissues and biological mechanisms of response and resistance. Participants received navtemadlin at 120 mg (n = 10) or 240 mg (n = 11) for 2 days before surgical resection and after surgery until progression or unacceptable toxicity. Both 120 and 240 mg daily dosing achieved a pharmacodynamic impact, but median progression-free survival was 3.1 months. DNA sequencing of three recurrent tumors revealed an absence of TP53-inactivating mutations, indicating alternative mechanisms of resistance. To understand the mechanisms of response and resistance associated with navtemadlin, we conducted functional and spatial analyses of human tissue and patient-derived GBM neurosphere models. Navtemadlin induced partial tumor cell death as monotherapy, and combination with temozolomide enhanced apoptosis in GBM neurospheres while sparing normal bone marrow cells in vitro. We also observed up-regulation of oligodendrocyte differentiation genes with navtemadlin treatment and enrichment of oligodendrocyte transcription factor 2 (OLIG2)-positive cells at relapse, suggesting an unexplored mechanism of navtemadlin tolerance in GBM. Overall, these results indicated that clinically achievable doses of navtemadlin exert pharmacodynamic effects on GBM and suggest that combined treatment with temozolomide may be a route to more durable survival benefits
Association of systemic therapy with survival among adults with advanced non-small cell lung cancer
No full textBACKGROUND: Uptake of new systemic therapy treatments among patients with advanced non-small cell lung cancer (NSCLC) occurred rapidly after FDA approval. Few studies have characterized the association of these therapies on survival in community settings. We assessed survival by type of systemic therapy received among patients diagnosed with advanced NSCLC who were treated in community-based settings.
METHODS: In this retrospective cohort, patients diagnosed with de novo stage IV NSCLC between March 2012 and December 2020 were followed through December 31, 2021. Survival was ascertained with restricted mean survival time from treatment receipt through 12 and 60 months and compared by RMST differences adjusting for demographic and tumor characteristics. Trends in one-year survival probabilities were assessed using joinpoint regression.
RESULTS: Of 945 patients receiving systemic therapy, 46% received cytotoxic chemotherapy (Chemo-Only), 15% bevacizumab +/- Chemo, 22% immunotherapy +/- Chemo, and 16% targeted therapies. Median days from diagnosis to treatment ranged from 32 to 42. Compared to those receiving Chemo-Only, patients receiving immunotherapy +/- Chemo survived 1.4 months longer [95% confidence interval (CI): 0.5 to 2.3 months; P=0.002] and 3.2 months longer (95% CI: -1.4 to 7.9 months; P=0.18) through 12 and 60 months follow-up, respectively. Relative to those receiving Chemo-Only, patients receiving targeted therapies survived 1.6 months longer (95% CI: 0.7 to 2.5 months; P\u3c 0.001) and 5.5 months longer (95% CI: 0.7 to 10.4 months; P=0.02) through 12 and 60 months follow-up. One-year survival significantly increased from 30% to 59% between 2012 and 2020 (P=0.007).
CONCLUSIONS: We found patients receiving targeted therapies and immunotherapy +/- Chemo survived longer than those on Chemo-Only. One-year survival probabilities significantly increased between 2012 and 2020. Additional research is needed to better understand the potential benefits and harms, including patient adverse events and financial toxicity
Increasing Prostate Cancer Education and Screening for Black Men in Southeastern Michigan: Your Prostate, Your Health
No full textBlack Men (BM) have disproportionately higher mortality rates from prostate cancer (PCa) and present with more advanced disease. Early screening may improve outcomes. The aim of our project was to provide education, screening, and provider outreach with a long-term goal to decrease the disproportionate number of PCa deaths in BM. We conducted focus group discussions with BM to assess their perceptions and understanding of PCa and screening. Focus groups aided in the development of educational materials. Educational materials were distributed at community events. Screening was offered, at select events, using prostate-specific antigen (PSA) testing. Men with PSA levels of ≤ 4 ng/ml were contacted for follow-up. The project included training for Henry Ford Health (HFH) providers and an assessment of their PCa screening practice. We completed 4 focus groups and distributed ~ 1000 PCa educational brochures. We participated in 45 community events between March 2022 to June 30, 2023. 340 men were screened. 28 men had an elevated PSA, and 17 men did not complete follow-up. Multiple HFH provider educational sessions were conducted. Of 129 providers who completed a screening practice assessment, 78 (60%) routinely offered PSA screening to men between ages 55-69. Between 2018 to 2023 at HFH, the PSA screening rate overall increased from 8.2% to 12.7%. Although our outreach efforts were effective at increasing PSA screening, 60.7% of men screened in our community events with elevated PSA did not follow-up. Future efforts should further reduce barriers to PCa screening and follow-up
Comment on \u27Peri-operative and anaesthetic considerations for gender-affirming vocal surgery\u27
No full textEffect of Red Blood Cell Transfusion Strategy on Clinical Outcomes Among Patients With Acute Myocardial Infarction Undergoing Revascularization: A Prespecified Analysis of the MINT Trial
No full textBACKGROUND: The MINT trial (Myocardial Ischemia and Transfusion; N=3504) randomized patients with acute myocardial infarction (MI) and hemoglobin ≤10 g/dL to liberal (maintain hemoglobin ≥10 g/dL) or restrictive (maintain hemoglobin ≥8 g/dL) red blood cell transfusion. The results suggested a benefit on 30-day death or MI with a liberal transfusion strategy. The effect of transfusion in patients with acute MI undergoing revascularization is unclear.
METHODS: In this prespecified analysis of the MINT trial, patients who underwent revascularization (n=1002) before randomization but during index hospitalization were compared with those who did not (n=2442). The primary outcome was 30-day death or MI; secondary outcomes included 30-day death, recurrent MI, the composite of death, recurrent MI, ischemia-driven unscheduled revascularization, or readmission for ischemic cardiac diagnosis, heart failure, and cardiac death. Multivariable log-binomial regression was used to determine the relative risks of the primary and secondary outcomes by transfusion strategy for revascularized and nonrevascularized patients with interaction terms.
RESULTS: Patients undergoing revascularization were younger, more often female, and had fewer comorbidities than those who did not. There was no significant interaction between revascularization and assigned transfusion strategy for any outcome except cardiac death. Compared with liberal transfusion, restrictive transfusion increased the risk of 30-day cardiac death among non-revascularized patients [RR 2.45 (1.58, 3.81)] but not among revascularized patients [(RR 0.97 (0.59, 1.60), interaction p 0.006].
CONCLUSIONS: In this analysis of the MINT trial, revascularization did not alter the effect of the randomized transfusion strategy on 30-day death or MI. The hypothesis-generating finding that a restrictive transfusion strategy was associated with an increased risk of cardiac death among patients with anemia and acute MI who do not undergo revascularization requires confirmation.
REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02981407
Donor Selection for Heart Transplantation in 2025
No full textThe number of candidates on the waiting list for heart transplantation (HT) continues to far outweigh the number of available organs, and the donor heart nonuse rate in the United States remains significantly higher than that of other regions such as Europe. Although predicting outcomes in HT remains challenging, our overall understanding of the factors that play a role in post-HT outcomes continues to grow. We observe that many donor risk factors that are deemed high-risk do not necessarily always adversely affect post-HT outcomes, but are in fact nuanced and interact with other donor and recipient risk factors. The field of HT continues to evolve, with ongoing development of technologies for organ preservation during transport, expansion of the practice of donation after circulatory death, and proposed changes to organ allocation policy. As such, the field must continue to refine its processes for donor selection and risk prediction in HT
Multicenter, retrospective cohort study of antimycobacterial treatment-related harms among patients with non-tuberculosis
No full textNon-tuberculosis mycobacteria (NTM) are extensively drug-resistant organisms that require long-term therapy. The study purpose was to quantify the incidence of and risk factors for antimycobacterial-associated adverse drug events (ADEs) in persons with NTM infections receiving outpatient therapy. A multicenter, retrospective cohort was performed of persons with NTM infections who received antimycobacterial treatment from 2013 to 2024. Inclusion criteria were age ≥18 years, ≥1 month of outpatient treatment, and ≥1 follow-up outpatient visit within 3 months of index encounter
Cryoneurolysis: A Comprehensive Review of Applications in Pain Management
No full textPain management is an integral part of healthcare, and cryoneurolysis, a technique that uses extreme cold to disrupt nerve conduction, has demonstrated potential in managing both acute and chronic pain. It is an alternative for patients who do not respond to traditional pain management therapies. This review examines the efficacy, application, mechanism, limitations, challenges, and advancements in cryoneurolysis. Cryoneurolysis has broad applications, including acute pain management, reducing opioid dependency, and shortening hospital stays. It effectively treats chronic pain conditions like lumbar facet syndrome, phantom limb pain, occipital neuralgia, and, in some cases, unresponsiveness to traditional therapies. Furthermore, it offers values in tumor-induced neuropathies and postoperative pain. Cryoneurolysis has a favorable safety profile, presenting a low risk of minor complications such as infection and bruising, which resolve with proper care. Comparative studies indicate that cryoneurolysis, which induces Wallerian degeneration, is as effective as cooled radiofrequency ablation (CRFA), which achieves thermal nerve degradation to block pain transmission, particularly in knee osteoarthritis. However, its potential limitations impede widespread adoption, including small sample sizes, study heterogeneity, and the lack of standardized protocols. Future research should focus on large-scale trials, comparative studies with other pain management modalities, and developing standardized guidelines to enhance clinical outcomes
Colonic malakoplakia
No full textColonic malakoplakia is a rare granulomatous inflammatory condition that can cause abdominal pain, diarrhoea and rectal bleeding and be associated with colon adenocarcinoma. Chronic bacterial infections with defective lysosomal activity in macrophages are possible causes for malakoplakia. We present a case report of asymptomatic colonic malakoplakia in an otherwise healthy woman undergoing a screening colonoscopy for colorectal cancer. Limited case reports and treatment guidance are available for colonic malakoplakia with only a few dozen cases in the literature. Given the potential morbidity and mortality associated with this condition, we emphasise the importance of thorough diagnostic and therapeutic evaluation even in asymptomatic patients