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To describe the post-transplant outcomes in patients with myelofibrosis stratified by the Dynamic International Prognostic Scoring System (DIPSS) risk at transplantation, and to identify clinical factors associated with overall survival (OS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively analyzed the data of 42 patients with myelofibrosis who underwent allo-HSCT at Samsung Medical Center between 2014 and 2023. OS was estimated using the Kaplan-Meier method and compared using the log-rank test. Exploratory Cox proportional-hazard regression analyses were performed to assess independent associations with OS. At transplantation, 28 patients (66.7%) had Intermediate (Int-1/2) and 14 (33.3%) had High DIPSS risk. OS differed significantly by DIPSS risk group (log-rank P = 0.0034): the median OS was 15.2 months (95% confidence interval [CI], 7.2-NR months) in the Intermediate-risk group versus 6.4 months (95% CI, 3.3-35.1 months) in the High-risk group. All 14 patients in the High-risk group (100%) and 14 of 28 patients in the Intermediate-risk group (50%) died during follow-up. The 1-, 2-, and 3-year OS rates in the Intermediate- and High-risk groups were 57.1% vs. 28.6%, 50.0% vs. 14.3%, and 50.0% vs. 7.1%, respectively. In an exploratory multivariable analysis adjusted for hematopoietic cell transplantation-specific comorbidity index and donor type, DIPSS High-risk disease remained independently associated with inferior OS (adjusted hazard ratio [HR], 2.91; 95% CI, 1.27-6.63; P = 0.011). No other clinical variable, including age (≥ 60 vs. < 60 years; P = 0.16 by log-rank), achieved statistical significance. DIPSS High-risk disease at transplantation was associated with uniformly poor post-transplant survival in this single-center cohort. These hypothesis-generating findings underscore the importance of transplant timing before progression to high-risk disease, and warrant validation in larger multicenter studies.
Ewing sarcoma is a malignant small round-cell sarcoma of bone or soft tissue that is highly responsive to modern multimodal therapy and considered a highly curable disease in developed countries. However, survival remains poor in developing countries. This study aims to assess treatment patterns and survival outcomes of Ewing sarcoma at Tikur Anbessa Hospital. We conducted a retrospective study on all patients diagnosed with Ewing sarcoma at Tikur Anbessa Hospital between November 15, 2018, and November 15, 2023. Descriptive statistics and Kaplan-Meier survival analysis were used to analyze the data. The median age at diagnosis was 19 years, with most of the patients (67.2%) in the age range of 8-25 years. The main modality of treatment for localized disease was chemotherapy combined with surgery, whereas chemotherapy alone was used for metastatic disease. The Kaplan-Meier estimated 1-year and 3-year overall survival (OS) rates for the entire cohort were 96% and 68%, respectively, and the corresponding 1-year and 3-year event-free survival (EFS) rates were 70% and 40%, respectively. A sensitivity analysis treating loss to follow-up as events reduced the 3-year overall survival from 68% to 55% and the 3-year event-free survival from 40 to 33%. The 3-year OS and EFS rates were 89% and 76% for localized disease versus 10% and 0% for metastatic disease. This difference was statistically significant (log-rank p < 0.001). Small tumor size (≤ 8 cm), surgical intervention, and localized stage were associated with statistically significant improvements in OS and EFS, whereas pelvic location was associated with a poorer prognosis. Ewing sarcoma at our institution mainly affects adolescents and young adults. Survival is poor, especially for metastatic disease, while localized tumors, smaller size, and surgery are associated with better survival. Therefore, early diagnosis and improved multimodal treatment are needed to improve survival.
A prior national survey of U.S. hematology/oncology (H/O) fellowship curricula demonstrated substantial heterogeneity and limited protected didactic time. Since then, artificial intelligence (AI), including large language models (LLM) and ambient tools, has become increasingly integrated into trainee education and clinical practice. We conducted a multi-center survey to assess the use of AI among H/O fellows. H/O fellows were recruited via program leadership to complete an anonymous survey adapted from our prior study, with added questions on AI education, attitudes, and clinical use. Responses were collected via REDCap and summarized using descriptive statistics. A total of 118 H/O fellows responded from 18 of 30 invited U.S. H/O fellowship programs (60%), primarily from academic centers (94%), with an even distribution across fellowship training years. Most fellows (74%) reported using AI tools. Other commonly used resources included NCCN guidelines (92%), UpToDate (86%). Only 8% reported receiving formal AI training. Most fellows viewed AI as useful for education (93%) and were confident using it for learning (74%); 92% anticipated increased use and 82% desired formal training. LLMs were most commonly used to clarify concepts (86%), summarize literature (83%), and explore emerging research (75%). AI-assisted documentation was the most frequent clinical application (51%). Reported barriers included (in order of highest concern) accuracy, lack of formal training, data privacy, and unclear ethical or institutional guidelines. AI is widely used and valued by current H/O fellows, yet formal training during fellowship remains limited. These findings highlight the need for structured education on effective, safe, and ethical AI use to support clinical integration.
Avatrombopag (AVA), an oral thrombopoietin receptor agonist (TPO-RA), has demonstrated favorable efficacy in the treatment of pediatric immune thrombocytopenia (ITP). However, treatment-related thrombocytosis represents a clinically relevant adverse event that may compromise treatment safety and continuity. Currently, no validated tools are available to predict the risk of AVA-induced thrombocytosis before treatment initiation. In this real-world study, we aimed to develop and validate a predictive model for AVA-associated thrombocytosis in children with ITP. A total of 74 pediatric patients treated with AVA at the Hematology-Oncology Center of Beijing Children's Hospital between July 2021 and January 2024 were included. We compared the proposed model with established classical machine learning baselines, including Logistic Regression (LR), Support Vector Machine (SVM), Multilayer Perceptron (MLP), Random Forest (RF), and XGBoost, as well as state-of-the-art deep learning models for tabular data, including TabPFN, FT-Transformer, and HyperTab. Among the evaluated models, the FT-Transformer achieved the best performance, with an accuracy of 0.785 ± 0.023 and an area under the receiver operating characteristic curve (AUC) of 0.851 ± 0.021. Model interpretability was enhanced using Shapley Additive Explanations (SHAP), enabling visualization of individual feature contributions to thrombocytosis risk. This AI-driven prediction model, grounded in real-world clinical data, demonstrates robust predictive performance and offers clinically interpretable insights. It provides a reliable reference for individualized risk assessment and supports safer, more precise use of AVA in pediatric ITP management.
Chronic obstructive pulmonary disease (COPD) is characterized by persistent inflammation, structural remodeling, and irreversible airflow limitation, but the cellular mechanisms that sustain chronic inflammatory remodeling remain poorly understood. We integrated newly generated single cell transcriptomic data with publicly available datasets, comprising 6 healthy controls and 10 patients with COPD. Gene expression programs, intercellular communication, pseudotime trajectories, and transcription factor regulatory networks were assessed to define fibroblast associated changes in COPD lung tissue. Fibroblasts exhibited the strongest outgoing signaling activity among lung parenchymal cells and showed the greatest increase in outgoing signaling in COPD. Across multiple fibroblast subpopulations, fibroblasts from COPD lungs acquired a shared proinflammatory and immunoregulatory state associated with inflammatory activation, tissue injury, and fibrotic remodeling. This state was characterized by increased expression of inflammatory mediators and enhanced potential to promote immune cell recruitment and activation. Regulatory analyses further suggested that this inflammatory program was accompanied by extensive remodeling of transcription factor networks in fibroblasts. These findings identify fibroblasts as key immunoregulatory cells in COPD lung tissue and suggest that fibroblast associated inflammatory programs may contribute to the maintenance of chronic inflammatory remodeling. Fibroblast centered inflammatory pathways may represent potential targets for future mechanistic and translational studies.
Liquid biopsy is an emerging non-invasive detection technology that diagnoses tumors and provides prognostic value by analyzing samples such as circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and exosomes. Exosomes are nanoscale extracellular vesicles (EVs) secreted by cells, encapsulating a diverse array of biomolecules, including proteins, nucleic acids (e.g., mRNA and miRNA), and lipids. Lymphoma cells secrete various exosomes, whose contents carry abundant tumor-associated information and serve as messengers in the tumor microenvironment (TME). Consequently, tumor-derived exosomes can provide a broader picture of lymphoma, serving as promising biomarkers for liquid biopsy. They contribute to diagnosis, prognosis and therapeutic response evaluation, and medication guidance in lymphoma precision medicine. With further research, exosome-based liquid biopsy has the potential to enhance patients' quality of life. This review summarizes the application of exosome-based liquid biopsy in lymphoma and its underlying mechanisms within the TME, emphasizing the promising opportunities this technique presents for medical research.
Patients with prostate cancer (PC) face elevated cardiovascular (CV) risk. Conventional CV risk scores are often poorly calibrated for PC and require laboratory tests that are not routinely available in PC clinics, limiting oncology use. The development cohort (DC) included men with PC (age ≥18 years) diagnosed in 2010-2014. Validation cohort 1 (V1) included men age 45 years and older within 1 year of PC diagnosis or near initiation of androgen deprivation therapy. Validation cohort 2 (V2) included men with PC diagnosed in 2006-2019. Outcomes were cardiovascular disease (CVD), atherosclerotic CVD (ASCVD), and heart failure (HF). Predictors were selected with XGBoost and LASSO, modeled with Fine-Gray and penalized Cox regression, and scaled to additive point scores (low/intermediate/high risk). Performance was assessed using time-dependent AUC (TDAUC), which quantifies the model's ability to correctly rank patients by risk at each time point, and compared with conventional scores. The DC included 1,815 patients, and V1 and V2 included 4,022 and 1,729 patients, respectively (median follow-up 10.3 years). At 10 years, cumulative incidence was 15.0% for composite CVD, 9.4% for ASCVD, and 10.1% for HF. The composite CVD score (age, race, smoking history, high-risk Gleason score, and household members) achieved a 10-year TDAUC of 0.71 (95% CI, 0.64 to 0.78) in the DC and 0.59 (95% CI, 0.52 to 0.65) in V2, with a 2-year TDAUC of 0.66 (95% CI, 0.56 to 0.75) in V1. In the DC, ASCVD and HF scores achieved 10-year TDAUCs of 0.66 (95% CI, 0.58 to 0.75) and 0.70 (95% CI, 0.62 to 0.79), respectively, and retained discrimination in validation. To our knowledge, these are the first PC-specific CV risk scores derived from oncology-available variables, supporting pragmatic CV risk stratification in PC clinics and motivating further validation and implementation studies.
This study aimed to investigate the real-world profiles of 6-mercaptopurine (6-MP) treatment in various TPMT/NUDT15 phenotype groups among paediatric patients with ALL. We conducted a prospective cohort study of 104 paediatric patients with ALL during the maintenance phase, collecting baseline data and following up monthly for 5 months. Patients were genotyped and classified as normal (NM), intermediate (IM) or poor (PM) metabolizers based on the TPMT and NUDT15 genetic variations. Additionally, TPMT activity and metabolite concentrations (6-thioguanine nucleotides; 6-TGN and 6-methylmercaptopurine nucleotides; 6-MMPN) were also quantified. The patients were categorized into five TPMT/NUDT15 phenotype groups: NM/NM (73.08%), NM/IM (17.31%), NM/PM (1.92%), IM/NM (3.85%) and IM/IM (3.85%). The tolerated 6-MP dose was lowest in the NM/PM group (18 mg/m2, IQR = 8-29 mg/m2) and IM/IM group (25 mg/m2, IQR = 8-26 mg/m2). The IM/IM had the highest rate of early neutropenia (75%). TPMT activity remained stable throughout the study except in the NM/PM group, which showed significant fluctuations. Patients with NM/PM had the lowest 6-TGN level, and patients with IM/NM showed high 6-TGN levels. Patients with NM/NM and NM/IM exhibited elevated levels of 6-MMPN, which were associated with the occurrence of hepatotoxicity. The TPMT and NUDT15 genes influence the side effects of 6-MP medications. Patients who have variations in both genes are at a higher risk of experiencing toxicity. High levels of 6-TGN are associated with TPMT variants, whereas low levels are linked to NUDT15 variants. This could facilitate more precise monitoring of toxicity.
KRAS G12C mutations occur in approximately 3-4% of metastatic colorectal cancer (mCRC) cases. While the introduction of KRAS G12C inhibitors has transformed the therapeutic landscape for this molecular subset, conflicting evidence exists regarding the independent prognostic impact of this mutation in inhibitor-naïve settings. Small sample sizes and methodological heterogeneity have limited individual studies, precluding definitive conclusions. To address this knowledge gap, we conducted a systematic review and meta-analysis to establish the prognostic significance of KRAS G12C mutations in mCRC. A comprehensive systematic literature search was conducted across PubMed, Google Scholar, and Cochrane Library through August 2025. Studies comparing overall survival between KRAS G12C and non-G12C RAS-mutant mCRC were included. Hazard ratios (HR) were extracted or calculated from reconstructed individual patient data. Pooled analyses employed random-effects models. Quality assessment utilized the Newcastle-Ottawa Scale. Fourteen retrospective studies encompassing 9,308 patients (903 KRAS G12C, 8,405 non-G12C RAS) were included. The pooled analysis demonstrated that KRAS G12C mutations confer significantly worse prognosis, with a 28% increased risk of mortality compared to non-G12C RAS mutations (HR 1.28, 95% CI 1.10-1.48; p = 0.0015). A meta-analysis of difference in medians showed a pooled mOS difference of - 4.5 months (95% CI, -9.1 to 0.0; p = 0.05) and a pooled mPFS difference of - 1.3 months (95% CI, -2.4 to - 0.1; p = 0.03) for KRAS G12C versus non-G12C patients. Moderate heterogeneity was observed (I2=54.3%). Sensitivity analysis restricted to high-quality studies confirmed these findings (HR 1.31, 95% CI 1.11-1.54). No publication bias was detected. KRAS G12C mutations represent an independent adverse prognostic biomarker in mCRC, with a statistically significant 28% increased risk of mortality compared to other RAS mutations. The consistent hazard ratio across multiple sensitivity analyses supports a true prognostic effect. These findings have important implications for patient counseling and risk stratification. While the poor prognosis may provide rationale for prioritizing trial enrollment, translation into therapeutic decision-making requires caution, as prospective data demonstrating benefit from earlier use of KRAS G12C inhibitors are lacking.
Cancer care in conflict-affected settings represents a growing yet underrecognized global health crisis, disproportionately affecting populations in low- and middle-income countries, particularly in Africa. With over 130 million people forcibly displaced worldwide, conflict-driven disruptions to health systems have created profound gaps across the cancer care continuum, from prevention and diagnosis to treatment and palliative care. In these settings, cancer is often deprioritized in favor of acute and communicable diseases, resulting in delayed diagnosis, treatment interruptions, and poor outcomes. This review examines the impact of conflict on cancer care delivery, highlighting structural disruptions, including infrastructure destruction, workforce displacement, and supply chain collapse. Drawing on case studies from Sudan, Somalia, Burkina Faso, and Kenya, it presents exploratory, field-informed strategies to sustain care. In Sudan, telehealth, primarily through WhatsApp and mobile communication, has enabled continuity of care, real-time triage, and cross-border clinical collaboration despite severe connectivity challenges, supported by emerging hybrid digital platforms. In Burkina Faso, the collapse of surgical oncology capacity has led to predominantly late-stage, palliative interventions; however, adaptive responses such as mobile clinics, tele-oncology, and decentralized service delivery have partially mitigated these gaps. The manuscript further emphasizes the potential role of mobile oncology units in delivering cancer medicines, basic surgical care, and palliative services, alongside context-adapted training for health care workers in crisis settings. It highlights the need for coordinated safe cross-border referral systems, interoperable digital health platforms, and the establishment of safe humanitarian corridors for patient transfer. Addressing cancer care in conflict settings requires integrating oncology into humanitarian responses, strengthening decentralized and resilient systems, and fostering regional collaboration to ensure equitable access for vulnerable populations.
Cancer survivorship is increasingly characterized by long-term treatment sequelae, including cardiometabolic disease, fatigue, sleep disturbance, psychological distress, and risk of second malignancies. As survivorship populations expand, there is growing recognition that traditional symptom-focused follow-up does not adequately address modifiable drivers of long-term morbidity. This review evaluates lifestyle medicine as a structured framework integrating physical activity, nutrition, sleep health, psychological well being, and substance cessation to improve survivorship outcomes across solid tumors and hematologic malignancies. Evidence from randomized trials, cohort studies, and consensus guidelines demonstrates that lifestyle interventions influence systemic inflammation, immune function, metabolic regulation, and functional capacity. Physical activity improves fatigue, cardiorespiratory fitness, and quality of life, while plant-forward dietary patterns are associated with improved survival outcomes. Sleep optimization and stress reduction interventions improve inflammatory signaling and psychological outcomes. Tobacco cessation and alcohol reduction reduce recurrence risk and mortality. Emerging literature highlights the relevance of cardiometabolic pathways and behavioral interventions as modifiable determinants of survivorship trajectories. Lifestyle medicine provides a biologically plausible and clinically actionable framework to address shared mechanisms underlying cancer recurrence, treatment toxicity, and chronic disease risk. Integration of multidisciplinary interventions and digital health tools may enable scalable survivorship models focused on prevention, functional recovery, and long-term health optimization. Future research should prioritize mechanistic studies and pragmatic trials evaluating multimodal interventions across diverse cancer populations.
While transitions occur multiple times over the course of medical training, there is limited research focused on fellows' experiences and challenges during their transition from residency into subspecialty training, specifically hematology-oncology fellowship. We aimed to explore the lived experiences of hematology-oncology fellows, with a focus on the transition to fellowship. We conducted a qualitative study using one-on-one semi-structured interviews with 13 hematology-oncology fellows across all three fellowship years at the University of Colorado from September 2024 to May 2025. The authors used a combined interpretive phenomenological analysis approach and practical thematic analysis to describe hematology-oncology fellows' experiences of the fellowship transition. Fellows describe three distinct transitional phases including 1) pre-fellowship, 2) initial transition, and 3) extended transition. The end of the transition is followed by a plateau/stabilization phase. These phases are characterized by different levels of autonomy, support needs, and learning, and are influenced by fellows' self-imposed expectations and program and attending expectations. This qualitative study exploring fellows' experiences during their first year of hematology-oncology fellowship provides insight into the challenges of adapting to new roles in subspecialty training.
Sickle cell disease (SCD) is characterized by chronic hemolysis, ischemia-reperfusion injury, and progressive end organ damage. Although survival for children with SCD in the United States (US) is excellent the life expectancy for adults is approximately two decades shorter compared to those without SCD. Consequently, those with severe SCD, estimated to be about 20% of individuals with SCD in the US deserve to be offered treatment choices with the potential for cure. Two treatment options with curative intent are available. The first, hematopoietic cell transplantation is limited by donor availability and complicated by graft failure, graft versus host disease and prolonged immune suppression. The second, gene therapy and gene editing offered in clinical trials and in 2023, the US Food and Drug Administration approved two of these therapies. Gene therapy and gene editing obviate the need for a donor, and have shown efficacy, yet challenges include difficulty in obtaining sufficient numbers of autologous hematopoietic stem cell progenitors for genetic manipulation and loss of cells during the manufacturing process. Long term follow up is only available for recipients of matched sibling transplantation as all other potentially curative treatment modalities are relatively recent. We recommend transplantation be reserved for those with neurologic injury as gene therapy/editing trials have not systematically studied their effect to stabilize cerebral hemodynamic stress. When the indication for curative treatment is frequent pain or recurrent acute chest syndrome for those aged 12 years and older and a matched sibling is not available, we recommend a treatment algorithm that prioritize gene therapy or gene editing therapies over alternative donor transplantation.
Our study aimed to investigate the experiences of adolescents and young adults (AYAs) with cancer from racially/ethnically diverse and/or 2SLGBTQIA + communities within the Canadian healthcare system to identify areas for improvement in their cancer care experience. The study included participants who self-identified as racially/ethnically diverse and/or 2SLGBTQIA + , diagnosed with cancer between ages 15 and 39 years, currently aged 18 years or older, and received or were receiving cancer care in Canada. Patient partners with lived experience of cancer were recruited as collaborators. Semi-structured virtual interviews were conducted using an interview guide, and transcripts were analyzed using framework analysis. Twenty-three participants (17 racially/ethnically diverse; 1 sexual/gender diverse; 5 both racially and sexually diverse) were interviewed. Positive experiences reported by participants included being able to identify with healthcare providers (HCPs), effective communication, comprehensive information sharing, and access to support services tailored for younger patients. Negative experiences were characterized by perceptions of judgmental attitudes and racialization from HCPs, the necessity of self-advocacy to obtain resources, systemic barriers to care, and psychosocial difficulties. Participants' recommendations for improving cancer care included increasing the diversity of HCPs, implementing equity, diversity, and inclusion training, and enhancing both communication and information dissemination practices. The experiences of diverse AYAs revealed both facilitators and barriers to equitable cancer care. Findings emphasize the need for workforce diversity and equity-informed practices to advance culturally responsive oncology care. Précis: This study examined the cancer care experiences of racially/ethnically diverse and/or 2SLGBTQIA + adolescents and young adults in Canada, revealing both supportive interactions and significant barriers such as discrimination and systemic inequities. Participants recommended increasing provider diversity, equity-focused training, and improved communication to create more inclusive and responsive cancer care.
Imatinib in children with chronic myeloid leukemia (CML) is associated with growth deceleration. However, the long-term impact on final height remains less clear. The aim was to evaluate the effect of prolonged imatinib on linear growth at skeletal maturity. A cross-sectional study was conducted at a single center (2020-2021). Patients with chronic-phase CML on imatinib, diagnosed before 13 years and who had attained skeletal maturity at enrollment, were included. Anthropometry, sexual maturity rating, bone age, and evaluation for causes of short stature were performed. Longitudinal height data were retrieved from clinic records and compared with population-specific growth charts. Of 46 screened patients, 13 fulfilled the inclusion criteria. Mean age at diagnosis and enrollment was 9.3 ± 2.3 and 23.7 ± 2.6 years. The median duration of imatinib therapy was 14.3 years (IQR: 14.2-16), with 184.4 patient-years of follow-up. Mean height z-score declined from -0.6 ± 1.2 at diagnosis to -1.1 ± 0.9 at maturity (p = 0.04). In those administered imatinib before the onset of pubertal growth spurt, the decline was significant (-0.5 ± 0.6 to -1.3 ± 0.6, p = 0.03), compared to those administered after the pubertal growth spurt (p = 0.60). In one of the longest follow-up cohorts of children with CML reported to date, imatinib resulted in growth deceleration, particularly when initiated before the onset of pubertal growth spurt. Despite catch-up growth during adolescence, final height z-scores remained reduced at skeletal maturity.
Cancer care is often complicated by coagulopathy leading to thrombosis and bleeding. While venous thromboembolism (VTE) has been extensively studied, bleeding remains an underestimated threat. To address this knowledge gap, we leveraged the Epic Cosmos database to determine the impact of cancer-associated clinically relevant bleeding (CRB) in 2 455 332 individuals with incident cancer encounters from 215 US health systems between 2018 and 2024. In the 12 months leading up to the cancer diagnosis, the period prevalence of CRB was 5.3% in the overall cohort, highlighting CRB as a common early presentation preceding cancer diagnosis. In the 12-month window after cancer diagnosis, the cumulative incidence of CRB was 6.3% in the overall cohort, 7.0% in those receiving systemic antineoplastic therapy, and up to 15.0% among individuals on certain baseline anticoagulants. In addition to age, sex, and race, factors appreciably associated with CRB on multivariable analysis included cancer types, metastatic disease, systemic therapy, anticoagulant or antiplatelet use, higher comorbidity index, recent hospitalization, recent history of bleeding or VTE, and selective laboratory features (hemoglobin, platelets, albumin, eGFR). Furthermore, the onset of CRB as a time varying covariate was independently associated with mortality in multivariable adjusted analysis: intracranial hemorrhage (HR 4.17, 95% CI 4.11-4.24); gastrointestinal bleeding (HR 2.52, 95% CI 2.50-2.55); other bleeding (HR 2.46, 95% CI 2.44-2.49). Together, these findings reveal a substantial and overlooked risk of bleeding in cancer care and underscore a need for validated bleeding risk models that can be integrated alongside VTE prediction tools to guide personalized thromboprophylaxis decisions.
Single-agent paclitaxel or cetuximab after immune checkpoint inhibitor (ICI) and chemotherapy demonstrated objective response rates (ORRs) of 21%-24% in recurrent/metastatic (R/M) head/neck squamous cell cancer (HNSCC). EGFR and MET are overexpressed in R/M HNSCC. Amivantamab, an EGFR-MET bispecific antibody, may be a rational treatment. Cohort 1 of OrigAMI-4 (NCT06385080) evaluated subcutaneous amivantamab administered every three weeks in participants with R/M HNSCC after PD-(L)1 inhibitor and platinum-based chemotherapy. Prior anti-EGFR was exclusionary. The primary endpoint was RECIST v1.1 ORR. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. In 102 participants, blinded independent central review-assessed ORR was 42% (95% CI, 32-52); the complete response rate was 15%. Median DoR was not reached (NR; 95% CI, 6.9-NR); 56% of responses lasted ≥6 months. Investigator-assessed ORR was 47% (95% CI, 37-57). At a median follow-up of 11.8 months (range, 1.1-21.9), median PFS and OS were 6.8 months (95% CI, 5.2-8.3) and 12.5 months (95% CI, 10.2-16.8), respectively. Adverse events were consistent with previous experience with no new safety signals. Treatment-related discontinuations were low (8%). Amivantamab demonstrated greater antitumor activity in participants previously exposed to ICI and chemotherapy than what has been reported for paclitaxel or cetuximab.
Broad genomic profiling (BGP) is recommended for several types of metastatic cancer but remains underused. Over half of Medicare beneficiaries are enrolled in Medicare Advantage (MA), where cost-containment strategies may limit access to BGP. Whether Medicare payer type and geographic region are associated with BGP use is not well established. To evaluate whether BGP use differs by Medicare payer type (MA vs fee-for-service Medicare [FFS]) and to characterize geographic variation in BGP use across hospital referral regions (HRRs). This nationwide retrospective cohort study used Medicare Chronic Conditions Data Warehouse claims and service records to identify beneficiaries aged 66 years or older with a new diagnosis of metastatic cancer, including bladder, breast, colorectal, endometrial, kidney, lung, melanoma, pancreatic, prostate, or thyroid, from January 1, 2020, to June 30, 2022. Data analysis was conducted from October 2024 to March 2026. Medicare type (FFS vs MA) and HRR. The primary outcome was receipt of BGP within 2 months before through 6 months after diagnosis. Mixed-effects logistic regression models were used to estimate adjusted odds ratios (AORs) for the association between Medicare type and BGP use, controlling for demographic, clinical, and geographic factors. HRR-level variation was summarized using the median odds ratio (MOR). Subgroup analyses stratified cancers by the strength of guideline recommendations for BGP. Of 254 720 Medicare beneficiaries with metastatic cancer (median age, 74 years [IQR, 70-79 years]; 141 964 female [55.7%]), 112 637 (44.2%) were enrolled in MA and 142 083 (55.8%) in FFS. Overall, 64 351 (25.3%) received BGP. FFS beneficiaries had higher BGP use than MA beneficiaries (36 633 of 142 083 [25.8%] vs 27 718 of 112 637 [24.6%]; AOR, 1.08 [95% CI, 1.06-1.10]). BGP use was more frequent among FFS vs MA beneficiaries for cancers with equivocal BGP recommendations (AOR, 1.15 [95% CI, 1.11-1.19]) and, to a lesser extent, cancers with explicit recommendations (AOR, 1.04 [95% CI, 1.02-1.07]). Adjusted BGP use varied widely across HRRs (range, 13.8%-35.9%; median, 24.5% [IQR, 21.8%-27.6%]; MOR, 1.28 [95% CI, 1.25-1.31]). In this cohort study of Medicare beneficiaries with metastatic cancer, BGP use differed by Medicare payer type and showed substantial regional variation. These findings highlight opportunities to improve guideline-concordant molecular testing.
Patients (pts) with Myeloproliferative Neoplasms evolved in blastic phase (MPN-BP) have a dismal overall survival (OS). Very few data on the association of hypomethylating agents (HMA) and venetoclax (VEN) are available at present in homogeneous cohort of MPN-BP pts. Data of 61 pts with MPN-BP treated frontline with HMA + VEN in 21 hematologic Centers in Italy outside clinical trials from 11/2018 to 8/2024 were retrospectively collected and analysed. Pts were treated for a median of 4 courses (IQR 2-8). Overall, 56 pts (91.8%) had at least one hematologic toxicity of grade 3-4: in particular, severe neutropenia (PMN < 0.5 × 109/l) was reported in 50 pts (81.9%). Thirty-two pts (52.4%) had at least one infective episode during the treatment: pulmonary infections were reported in 13 pts (21.3%). Overall Response Rate (ORR) was 60.6%, with a median response duration of 9.4 months (95%CI 4.3-18.3): in particular, 26 patients (42.6%) achieved ALR-C/Ci, with a median response duration of 18.3 months (95%CI 1.2-35.3). Median OS of the whole cohort was 10.5 months (95%CI 7.7-13.3). Pts with any type of response had a significantly longer OS compared to pts with progressive/stable disease [13.6 (95%CI 10.3-21.9) versus 7.1 (95%CI 4.4-11.7) months, respectively (p < 0.001)]. Our real-life data confirm that HMA + VEN combination could have a role in MPN-BP: however, response duration is still very short, with a persistently poor median OS. As a consequence, addition of other targeted therapies should be explored.