Tag: nevin manimala

JCO Glob Oncol. 2026 Jun;12(6):e2500574. doi: 10.1200/GO-25-00574. Epub 2026 Jun 24.

ABSTRACT

PURPOSE: There are now six anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) approved for first-line ALK-positive non-small cell lung cancer (NSCLC) therapy, improving survival and quality of life. However, real-world data on treatment outcomes, predictors of discontinuation, and sequencing strategies remain scarce, while direct comparisons between second- and third-generation TKIs are limited.

METHODS: This global longitudinal observational study evaluated patients with ALK-positive NSCLC, with data collected via online surveys from September 2022 to April 2025. Treatment patterns, outcomes, and factors associated with time to discontinuation (TTD) were assessed using descriptive statistics and univariable regression.

RESULTS: Overall, 1,111 patients from 71 countries were included (64% female; median age at diagnosis 53 years; 28% with a smoking history). Crizotinib was predominantly the first TKI administered, although prescribing patterns shifted over time (crizotinib before 2016, alectinib between 2017 and 2022, and lorlatinib thereafter). After the follow-up period (median of 20.7 months), 60% of patients remained on their initial TKI, with TTD varying significantly across agents. Factors associated with prolonged TTDs included radiotherapy, prior chemotherapy, delayed therapy initiation, and treatment in India (crizotinib) and retirement, prior chemotherapy, and treatment in the United Kingdom (alectinib). Gastroesophageal reflux disease, thyroid disease, TP53 mutations, and ALK V3a/b fusions were associated with a short TTD. Globally, alectinib to lorlatinib was the most common treatment sequence. Discontinuations because of toxicity were the highest with crizotinib and ceritinib and the lowest with lorlatinib and alectinib.

CONCLUSION: This multinational registry-based analysis highlights evolving global treatment patterns, supports newer TKIs’ effectiveness, and identifies clinical and molecular factors associated with treatment duration.

PMID:42341251 | DOI:10.1200/GO-25-00574

JCO Glob Oncol. 2026 Jun;12(6):e2600042. doi: 10.1200/GO-26-00042. Epub 2026 Jun 24.

ABSTRACT

PURPOSE: ALK rearrangements occur in 5.4% of Brazilian patients with non-small cell lung cancer (NSCLC). Data on treatment patterns, access to ALK inhibitors, and survival outcomes are scarce.

MATERIALS AND METHODS: LACOG/GBOT 1918 is a retrospective, observational study that included patients diagnosed with ALK-positive NSCLC between January 2015 and December 2020 in 12 Brazilian public and private centers. Data were extracted from patient records, including clinic-epidemiologic features, diagnosis, ALK testing methods, treatment patterns, and outcomes. Data were analyzed using descriptive statistical methods.

RESULTS: A total of 101 patients were enrolled. The median age was 55 years (range, 18-86), and 55.4% were female. Immunohistochemistry was the most frequently used method for ALK testing. The median time from the first symptom to diagnosis was 2 months, from diagnosis to ALK testing 1.7 months, and from diagnosis to treatment initiation 1.7 months. Among patients receiving first-line treatment, only 47.9% received ALK inhibitors (53.9% private v 22.2% public), with crizotinib being the most used. For second-line treatment, 66.0% of patients received ALK inhibitors, with alectinib being the most used (50%). Most treated patients had access to ALK inhibitors in some line of treatment (83.3% private v 72.2% public); however, in the public setting, targeted treatment was restricted to first-generation and second-generation ALK inhibitors. The 3-year overall survival (OS) rate was 82.6% (95% CI, 72.6 to 89.2), with a lower 3-year OS in the public setting (61.4% public v 87.2% private; P = .0279).

CONCLUSION: Access to targeted ALK therapy is limited in the public health care system, reflecting poor clinical outcomes. Public health measures are necessary to minimize the differences between these two systems.

PMID:42341249 | DOI:10.1200/GO-26-00042

JCO Glob Oncol. 2026 Jun;12(6):e2500361. doi: 10.1200/GO-25-00361. Epub 2026 Jun 24.

ABSTRACT

PURPOSE: In low- and middle-income countries (LMICs), access to traditional oncology education through conferences, journals, and in-person mentorship is often restricted. Social media has emerged as a potential tool to bridge this gap; however, its educational and clinical influence on oncology professionals remains underexplored.

METHODS: We conducted a cross-sectional, anonymized, web-based survey of 202 oncology professionals from 13 countries. A 30-item questionnaire was used for the survey. Data were analyzed using descriptive statistics and chi-square tests.

RESULTS: Among the respondents, 93% practiced in India, with 61% identifying Twitter (X) as their primary oncology information source. Daily engagement was reported by 53% of the respondents. The most valued benefits were early access to emerging research (30%) and trial updates (29%). Social media discussions atleast moderately influenced clinical decision making in 75% of respondents, with 29% reporting a substantial impact, which was a subjective assessment of the participants. Virtual tumor boards engaged 58% of the participants and prompted practice changes in 21%. Sixty-eight percent credited social media, with expanding their professional networks, and 25% initiated research collaborations through these platforms. Structured digital literacy training and tools, such as automated fact-checking and professional credential verification, were supported by over two thirds of the participants.

CONCLUSION: Social media has become an essential educational and collaborative platform for oncology professionals, particularly in LMICs. By enabling timely access to research and supporting peer learning, it complements the traditional modes of oncology education. The formal integration of digital literacy training and content-verification mechanisms may enhance its safe and equitable use.

PMID:42341248 | DOI:10.1200/GO-25-00361

JCO Glob Oncol. 2026 Jun;12(6):e2500148. doi: 10.1200/GO-25-00148. Epub 2026 Jun 24.

ABSTRACT

PURPOSE: The emergence of targeted therapy for patients with human epidermal growth factor receptor 2 (HER2)-low tumors has transformed treatment paradigms, increasing the relevance of assessing this biomarker. Approximately 60% of patients with breast cancer have HER2-low tumors. This study aims to describe the clinicopathologic characteristics and prognosis of patients with HER2-low.

METHODS: We conducted a multicenter, retrospective cohort study including patients with breast cancer previously classified as HER2-negative between January 2018 and December 2022. Tumors were reclassified as HER2-0 (immunohistochemistry [IHC] score 0) or HER2-low (IHC score 1+ or 2+ with negative in situ hybridization). Survival outcomes were analyzed using the Kaplan-Meier method with log-rank tests for group comparisons. Univariable and multivariable Cox proportional hazards models were constructed to assess independent prognostic factors. Statistical analyses were performed using STATA version 19.5, and two-sided P values <.05 were considered statistically significant.

RESULTS: A total of 704 patients were included with a median follow-up of 63.1 months. No significant differences in event-free survival (EFS) were observed between HER2-0 and HER2-low patients (P = .139). Overall survival (OS) favored HER2-low over HER2-0 patients (P = .050). HER2-low and estrogen receptor had a marked prognostic impact in EFS (P = .002) and OS (P < .0001).

CONCLUSION: HER2-low was associated with a modest difference in OS compared with HER2-0 tumors; the borderline statistical significance of this finding should be interpreted cautiously and may not reflect a clinically meaningful effect. Further prospective studies are warranted to validate this observation and explore the potential predictive value of HER2-low status for response to novel directed agents.

PMID:42341245 | DOI:10.1200/GO-25-00148

Sex Med Rev. 2026 Apr 2;14(2):qeag038. doi: 10.1093/sxmrev/qeag038.

ABSTRACT

INTRODUCTION: Very little research exists on genitopelvic pain in racially/ethnically, sexually, and gender/sex minoritized samples despite its high prevalence among these groups. Existing frameworks of genitopelvic pain are based largely on White, heterosexual, cisgender women samples; applying these frameworks to minoritized samples may be prone to inaccuracies, as they do not account for minority stress and strength, social safety, and broader social determinants of health that structure exposure to pain, access to care, and health outcomes among marginalized populations.

OBJECTIVE: The main purpose of this scoping review was to synthesize findings of genitopelvic pain research published on racially/ethnically, sexually, and gender/sex minoritized samples in Canada and the United States.

METHODS: After removal of duplicates, the abstracts of 1330 articles were independently screened for eligibility for full-text review, of which 974 were excluded. Of the remaining 356, 59 studies were included for data extraction and synthesis. Results were organized according to the underrepresented sample of interest (racially/ethnically, sexually, or gender/sex minoritized) and subcategorized according to study aims focusing on prevalence, pain characteristics and experiences, minority stressors and strengths (eg, stigma, coping, resilience), social safety (eg, relational and healthcare contexts), and social determinants of health.

RESULTS: Results indicated that genitopelvic pain is prevalent, there are similarities and differences in pain characteristics and experiences, and variables related to minority stress and strength, social safety, and social determinants of health-when examined-were associated with pain prevalence, severity, coping, and care trajectories in racially/ethnically, sexually, and gender/sex minoritized samples.

CONCLUSION: Genitopelvic pain is common in racially/ethnically, sexually, and gender/sex minoritized individuals and is meaningfully shaped by minority stress processes, minority strength adaptations, social safety, and social determinants of health, underscoring the need for theory-informed and equity-oriented pain frameworks.

PMID:42341242 | DOI:10.1093/sxmrev/qeag038

BJS Open. 2026 May 12;10(3):zrag074. doi: 10.1093/bjsopen/zrag074.

ABSTRACT

BACKGROUND: An inverse relationship between surgical volume and outcomes has been suggested, with higher-volume hospitals and surgeons achieving better results, prompting debate over the centralization of surgical services. However, minimum volume thresholds are unclear, and volume is a poor proxy for quality. Despite the significant global burden of colorectal cancer, the benefits of high-volume care remain uncertain. This umbrella review synthesized the evidence on volume-outcome associations in colorectal surgery.

METHODS: An umbrella review (PRISMA 2020) was conducted to evaluate systematic reviews and meta-analyses of the hospital/surgeon volume-outcome relationship in colorectal cancer. The Cochrane Library, PubMed, Embase, and MEDLINE were searched to 1 October 2025. Volume definitions and outcomes were extracted and meta-analysed by subgroup. A MeaSurement Tool to Assess Systematic Reviews 2 and Risk of Bias in Systematic Reviews were used for analysis of bias.

RESULTS: A total of 150 unique records was identified, with 10 systematic reviews meeting the inclusion criteria. High- versus low-volume hospitals demonstrated an inverse relationship in terms of postoperative mortality following resection for rectal cancer (fixed- and random-effects models: odds ratio 0.73, 95 per cent confidence interval 0.64 to 0.82), colon cancer (fixed-effect model: odds ratio 0.74, 0.70 to 0.78; random-effects model: odds ratio 0.75, 0.69 to 0.81), and colorectal cancer (fixed- and random-effects models: odds ratio 0.77, 0.67 to 0.88). High- versus low-volume surgeons demonstrated an inverse relationship with respect to postoperative mortality following resection for rectal cancer (fixed- and random-effects models: odds ratio 0.69, 0.59 to 0.81), colon cancer (fixed-effect model: odds ratio 0.70, 0.63 to 0.77; random-effects model: odds ratio 0.68, 0.55 to 0.85), and colorectal cancer (fixed- and random-effects models: odds ratio 0.67, 0.60 to 0.74). There were no consistent significant differences in rates of the secondary outcomes (anastomotic leak rate, permanent stoma formation, local recurrence rate, rate of abdominoperineal excision of the rectum).

CONCLUSION: High-volume hospitals and surgeons are associated with both improved short- and long-term outcomes for patients undergoing colorectal cancer surgery. However, a specific cut-off definition for high- versus low-volume hospitals and surgeons is yet to be elucidated owing to the heterogeneity of existing volume definitions. Future studies are required to confirm a threshold for this dose-response relationship.

PMID:42341213 | DOI:10.1093/bjsopen/zrag074

Am J Speech Lang Pathol. 2026 Jun 24:1-15. doi: 10.1044/2026_AJSLP-25-00087. Online ahead of print.

ABSTRACT

PURPOSE: Dysarthria, drooling, and swallowing disorders are common motor problems in people with Parkinson’s disease (PwP), leading to significant physical, emotional, and functional impairments that compromise quality of life. However, evidence on the progression of these disorders and their relationship with other features of Parkinson’s disease (PD) remains scarce. This study aimed to investigate the progression of dysarthria, drooling, and swallowing disorders in PwP and identify predictors of progression.

METHOD: A 1-year prospective cohort study was conducted with 73 PwP. Dysarthria was assessed using the Frenchay Dysarthria Assessment-Second Edition (FDA-2), drooling with Item 2.2 (Saliva and drooling) of the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), and swallowing with the Swallowing Clinical Assessment Score in Parkinson’s Disease (SCAS-PD). The FDA-2 and SCAS-PD rely on clinician assessment, whereas MDS-UPDRS Item 2.2 (Saliva and drooling) assesses patient-reported problems with saliva control. The Wilcoxon signed-ranks test for paired samples was used to compare baseline and 1-year follow-up scores, and linear regression was used to identify predictors of progression.

RESULTS: Dysarthria worsened significantly (p < .001) after 1 year and was predicted by poorer cognitive (β = -.02; SE = 0.01; p = .02) and motor performance (β = .48; SE = 0.21; p = .03). Drooling and swallowing showed a trend toward deterioration, although these changes were not statistically significant (p > .05).

CONCLUSIONS: After 1 year, dysarthria worsened significantly, while drooling and swallowing showed a tendency to decline, but did not reach statistical significance. Assessments based on clinician and patient reports may have limited sensitivity to subtle changes. Dysarthria progression reflected overall PD severity, with poorer cognitive and motor performance emerging as key predictors. These findings highlight the importance of routine clinical monitoring of these domains and support future studies using instrumental assessments (e.g., acoustic analysis and videofluoroscopic swallow studies) to better capture progression in dysarthria, drooling, and swallowing disorders.

SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.32764596.

PMID:42340753 | DOI:10.1044/2026_AJSLP-25-00087

JAMA Netw Open. 2026 Jun 1;9(6):e2621632. doi: 10.1001/jamanetworkopen.2026.21632.

ABSTRACT

IMPORTANCE: Suicide is a leading cause of death among US adolescents, and restrictive abortion policies may influence suicide risk by increasing uncertainty and reducing perceived control over life trajectories, particularly among female adolescents who face disproportionate barriers to abortion access. Following the 2022 US Supreme Court decision in Dobbs v Jackson Women’s Health Organization, multiple states implemented total abortion bans. Their association with adolescent suicidality has not been quantitatively assessed.

OBJECTIVE: To evaluate whether implementation of total abortion bans was associated with suicidal ideation and suicide attempts among female high school students.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used difference-in-differences and event-study analyses of data from the Centers for Disease Control and Prevention Youth Risk Behavior Surveys (2017, 2019, 2021, and 2023) conducted among female and male students in grades 9 to 12 at public high schools in 15 participating states. Analyses were conducted between January 2025 and February 2026 and stratified by sex.

EXPOSURE: State-level implementation of a total abortion ban during the 12 months preceding survey administration.

MAIN OUTCOMES AND MEASURES: Outcomes of interest were self-reported suicidal ideation (serious consideration or planning) and suicide attempts (≥1) in the past 12 months, measured using Youth Risk Behavior Survey items.

RESULTS: The analytic sample included 338 324 students (median [IQR] age, 16 [15-17] years), of whom 169 967 (50%) were female. Among female students, increases in suicidal ideation were greater in states that implemented abortion bans than in states that did not (adjusted difference-in-differences estimate, 4.3 [95% CI, 1.6 to 6.5] percentage points). For suicide attempts, the corresponding estimate was similar but less precise and did not reach statistical significance (adjusted difference-in-differences estimate, 3.2 [95% CI, -0.4 to 6.1] percentage points). Among male students, estimates were smaller and not statistically significant (adjusted difference-in-differences estimate: ideation, 1.1 [95% CI, -0.9 to 4.4] percentage points; attempts, -0.3 [95% CI, -3.2 to 6.6] percentage points). For both sexes, event-study estimates reinforced the difference-in-differences findings and showed no evidence of differential prepolicy trends.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of high school students, implementation of total abortion bans was associated with increased suicidal ideation among female students, with similar but less precise estimates observed for suicide attempts. These findings suggest that the policies in these states may adversely influence female adolescents’ mental health and underscore the importance of accessible suicide prevention and mental health services in affected states.

PMID:42340717 | DOI:10.1001/jamanetworkopen.2026.21632

JAMA Psychiatry. 2026 Jun 24. doi: 10.1001/jamapsychiatry.2026.1438. Online ahead of print.

ABSTRACT

IMPORTANCE: Surveys have indicated that patients and clinicians can overestimate the efficacy and safety of drugs approved by the US Food and Drug Administration (FDA). In recent years, only approximately half of new drug approvals have been based on 2 or more adequate and well-controlled trials; furthermore, regulations do not limit how many trials can be conducted or provide clear guidance on how the FDA should consider a drug with conflicting evidence of benefit from multiple trials.

OBJECTIVE: To understand how the FDA evaluated a single investigational drug with positive and negative preapproval trials.

FINDINGS: The case of gepirone extended release (ER), approved for major depressive disorder, was reviewed. The FDA based its efficacy evaluation of gepirone ER on 13 trials: 12 acute treatment trials and 1 maintenance or relapse prevention trial. The FDA judged 2 acute treatment trials as positive. In the others, gepirone ER did not demonstrate superiority to placebo; and for 3, the FDA found evidence of statistical inferiority to an active comparator. Concerned that the positive trials might have occurred by chance and the amount of countervailing evidence, the FDA rejected the New Drug Application from the sponsor 4 times (Organon in 1999, 2002, and 2004, and Fabre-Kramer Pharmaceuticals, Inc in 2007). In 2014, the sponsor filed a dispute resolution request, leading to intervention by senior FDA leaders. In 2015, an FDA Advisory Committee voted that drug efficacy had not been demonstrated. Nevertheless, FDA leaders came to agree with the sponsor’s arguments that the 2 positive trials had not occurred by chance and that the drug satisfied the FDA statutory standard for efficacy, and the drug was approved.

CONCLUSIONS AND RELEVANCE: The case of gepirone shows how the FDA evaluated an investigational drug with conflicting evidence. The FDA sometimes exercises “regulatory flexibility” and focuses on statistical (as opposed to clinical) significance in a few trials, allowing the approval of drugs with scant benefits. Product labeling should transparently report on all adequate and well-controlled trials relating to an FDA-approved indication, not just those with positive outcomes, so that clinicians can make better-informed prescribing decisions.

PMID:42340691 | DOI:10.1001/jamapsychiatry.2026.1438

Cutan Ocul Toxicol. 2026 Jun 24:1-10. doi: 10.1080/15569527.2026.2692370. Online ahead of print.

ABSTRACT

BACKGROUND: Multimodal Large Language Models (LLMs) are increasingly positioned as diagnostic assistants in dermatology. However, current research often relies on clear-cut cases, leaving their performance in clinically ambiguous, gray zone scenarios insufficiently explored. Specifically, whether integrating visual data helps LLMs correct initial human misdiagnoses or reinforces cognitive biases remains unknown.

OBJECTIVES: To evaluate the diagnostic accuracy of three recent multimodal large language models all queried through their default web interfaces on 5 February 2026, using standardized single-turn prompts in biopsy-confirmed dermatologic cases initially misdiagnosed by clinicians, and to assess the impact of visual integration on human error replication rates.

METHODS: A cross-sectional analysis was conducted on 30 diagnostic dilemmas confirmed by histopathology. Models were queried using a two-stage protocol: (1) Text-Only and (2) Multimodal. Primary outcomes were Top-1 accuracy, visual gain, and the rate of replicating the clinician’s initial error.

RESULTS: Gemini 3 achieved the highest multimodal Top-1 accuracy (60.0% (18/30), followed by ChatGPT-5.2 at 56.7% (17/30) and Claude 4.5 Sonnet at 33.3% (10/30). In the inflammatory subgroup, Gemini 3 accuracy increased from 45.5% (5/11) in text-only to 72.7% (8/11) in multimodal mode; this difference was not statistically significant (McNemar’s test, p = 0.248). All models showed limited accuracy for malignant lesions using macro-images.

CONCLUSIONS: While Gemini 3 shows promise as a de-biasing tool in complex inflammatory dermatoses, multimodal LLMs currently lack the granular precision required for malignancy detection without dermoscopic data. These findings underscore the need for cautious integration of AI in high-stakes diagnostic scenarios.

PMID:42340682 | DOI:10.1080/15569527.2026.2692370