Latest Articles
If it’s your first time on this website, please read the disclaimer section.
Oct 19 – Oct 26, 2026
Association of Circulating Eosinophils With Systemic Immune Activation and Reduced Recurrence in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This study evaluated circulating eosinophil counts as a noninvasive biomarker for recurrence in HR+/HER2- breast cancer using a discovery cohort (N=472) and a large validation cohort (N=23,170). Higher preoperative eosinophil counts significantly correlated with improved recurrence-free survival and provided additive prognostic value beyond the 21-gene recurrence score in 2,973 patients. In high-risk patients (n=3,471), eosinophil levels predicted which individuals would derive greater benefit from adjuvant CDK4/6 inhibitors, reflecting systemic immune activation and antitumor CD8+ T-cell involvement. These findings establish circulating eosinophils as a clinically accessible liquid biopsy tool for prognosticating recurrence risk and tailoring targeted therapy in the most common breast cancer subtype.
10.1200/JCO-26-00261
Hypofractionated Versus Conventionally Fractionated Postmastectomy Radiotherapy With Internal Mammary Node Irradiation for High-Risk Breast Cancer (HypoMast-IMNI): A Randomized Phase III Trial.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This Phase III noninferiority trial compared hypofractionated radiotherapy (42.56 Gy in 16 fractions) to conventional fractionation (50 Gy in 25 fractions) in 1,494 patients with high-risk breast cancer requiring internal mammary node irradiation. At 58.1 months median follow-up, the 5-year locoregional recurrence rate was 1.7% for hypofractionation versus 2.2% for conventional treatment, successfully meeting noninferiority criteria (HR 0.69). Hypofractionation significantly reduced grade 3 acute skin toxicity (1.7% vs. 12.2%, p < .001) while maintaining comparable survival outcomes and low cardiopulmonary complications. These results support the 16-fraction regimen as a safe, effective, and more efficient standard of care for high-risk postmastectomy patients needing complex regional nodal irradiation.
10.1200/JCO-25-02843
Oct 12 – Oct 19, 2026
Efficacy and safety of camrelizumab plus docetaxel and carboplatin as neoadjuvant therapy for stage II-III triple-negative breast cancer: the HELEN-Trio 011 randomized clinical trial.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This phase 3 randomized clinical trial evaluated camrelizumab plus docetaxel-carboplatin as neoadjuvant therapy for stage II-III triple-negative breast cancer (TNBC), aiming to improve outcomes with an anthracycline-free regimen. Among 352 mITT patients, the camrelizumab-chemotherapy group achieved a significantly higher pathological complete response (pCR) rate of 57.5% compared to 45.4% with chemotherapy alone, an absolute difference of 12.2% (P=0.014). Grade 3-4 adverse events were manageable, occurring in 24.9% versus 21.8%, with no treatment-related deaths. This promising anthracycline-free regimen offers a clinically relevant strategy to enhance pCR in TNBC patients, warranting further comparison with existing standard chemoimmunotherapy.
10.1016/j.annonc.2026.10.102
Expert Histopathologic Evaluation and Molecular Analyses for Ambiguous Cutaneous Melanocytic Tumors.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This prospective cohort study evaluated a stepwise diagnostic approach combining expert histopathology and molecular analyses for ambiguous primary cutaneous melanocytic tumors. A definitive diagnosis was achieved in 97.2% of 994 patients, with 55.2% requiring molecular analyses. Nonmelanoma diagnoses (61.2%) showed no melanoma-related events over 5.4 years, while melanoma diagnoses (36.0%) had a 5.7% cumulative incidence of events over 5.0 years. This validated approach significantly improves accurate melanoma diagnosis, crucial for guiding appropriate patient management and ensuring timely cancer identification.
10.1200/JCO-26-00432
Nivolumab-Ipilimumab for Localized Microsatellite Instability-High Gastric/Gastroesophageal Junction Adenocarcinoma: The Phase 2 NEONIPIGA Nonrandomized Clinical Trial.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
This phase 2 nonrandomized clinical trial evaluated neoadjuvant nivolumab plus ipilimumab, followed by surgery and adjuvant nivolumab, for localized deficient mismatch repair/microsatellite instability-high gastric/gastroesophageal junction adenocarcinoma. Among 32 patients, the 4-year overall survival was 84.1% (95% CI, 65.8%-93.0%) and event-free survival was 83.5% (95% CI, 64.8%-92.8%), with 59% achieving pathological complete response. While associated with sustained long-term survival and high pCR rates, the study found no clear evidence of improved survival over surgery alone. These findings provide valuable data for designing future randomized trials, particularly those investigating organ-preserving strategies in this cancer population.
10.1001/jamaoncol.2026.4162
Talazoparib plus enzalutamide in high-volume metastatic hormone-naive prostate cancer: a randomized phase 2 trial.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This randomized phase 2 trial investigated talazoparib plus enzalutamide versus enzalutamide alone in 54 men with high-volume metastatic hormone-naive prostate cancer. The combination arm achieved a 73% PSA <0.2 ng/ml response rate at 12 months (95% CI=56-86%), meeting the primary endpoint, compared to 64.7% in the control arm. However, the combination did not establish clear additional clinical benefit over enzalutamide alone in this biomarker-unselected population and was associated with increased toxicity, including 68% Grade ≥3 adverse events versus 35% with enzalutamide alone, and two fatal myeloid neoplasms. These findings suggest that while active, the combination’s increased toxicity without clear additional benefit in unselected patients limits its immediate broad clinical applicability for metastatic hormone-naive prostate cancer.
10.1038/s41591-026-04671-5
Personalized neoantigen-targeting cancer vaccines in ovarian cancer: a phase 1 trial.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This phase 1 trial evaluated the feasibility and safety of personalized neoantigen-targeting cancer vaccines (“NeoVax”) combined with anti-PD-1 in ten patients with high-grade epithelial ovarian cancer. The study found the vaccine feasible, with 9 of 12 evaluable Cohort B patients (75%) vaccinated, and safe, reporting no unexpected toxicities or discontinuations. Biomarker analysis suggested biologic activity in 6 of 10 patients, associated with broader immune responses and immune-selective pressure on tumor clones. These findings support the continued development of personalized neoantigen vaccines as a promising therapeutic strategy for ovarian cancer.
10.1038/s41591-026-04717-8
Levetiracetam therapeutically targets GABAergic synapses in diffuse midline glioma.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This study investigated the therapeutic impact of levetiracetam on diffuse midline glioma (DMG) using retrospective clinical data and preclinical orthotopic xenograft models. Results demonstrated significantly longer overall survival in pediatric DMG patients taking levetiracetam, a benefit not observed in hemispheric high-grade glioma cohorts. Preclinical findings confirmed that levetiracetam reduces tumor proliferation and extends survival by selectively attenuating GABAergic synaptic transmission within DMG cells, independent of its standard SV2A mechanism. These results suggest that levetiracetam may serve as a targeted therapy for DMG, warranting prospective clinical trials to validate its anti-cancer efficacy in this specific pediatric population.
10.1038/s41591-026-04646-6
Emerging Therapeutic targets and Early-phase drug Development in Gynecological Malignancies.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This review examines emerging molecular targets and early-phase drug development strategies for gynecological malignancies, focusing on overcoming treatment resistance through biomarker-driven therapies. The authors highlight novel agents targeting DNA damage response pathways, such as WEE1 and PKMYT1, alongside specific alterations like TP53 Y220C and the rapid expansion of antibody-drug conjugates. For clinicians, these developments represent a significant shift toward precision oncology, offering potential alternatives to conventional chemotherapy for recurrent or treatment-resistant cancers. While tumor heterogeneity and resistance persist, the integration of these targeted therapies into clinical sequencing protocols is essential for improving patient outcomes in oncology practice.
10.1016/j.annonc.2026.10.101
Ponatinib-Blinatumomab or Imatinib-Chemotherapy for Adult Ph-Positive ALL.
NEW ENGL J MED · Q1 JOURNAL - RANK #2/332TOP-TIER
This phase 3 trial randomized 236 adults with Philadelphia-positive acute lymphoblastic leukemia to frontline ponatinib plus blinatumomab (chemotherapy-free) versus imatinib plus chemotherapy. At 23.7 months median follow-up, 24-month event-free survival was 86% versus 67% (P<0.001), with molecular response rates of 71% versus 49% after consolidation. The chemotherapy-free regimen significantly improved event-free and molecular response rates, though overall survival was similar (90% vs 85%). These findings support a frontline chemotherapy-free approach as a new standard for adult Ph-positive ALL.
10.1056/NEJMoa2606208
Neurodevelopmental Blueprint in Gliomas: Toward an Ontogenetic Multimodal Integrated Therapy.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This review synthesizes evidence proposing that neuroepithelial tumor biology, including gliomas, re-enacts brain ontogeny, offering a unifying framework for their cellular hierarchy and progression. It suggests neoplastic transformation mirrors physiological developmental trajectories, explaining hallmarks like intratumoral mosaicism and therapy resistance. The authors propose an “Ontogenetic multimodal integrated therapy,” an anatomy-guided strategy aligning neurosurgery, radiotherapy, and pharmacotherapy with tumor stage. This framework provides a clinically oriented paradigm for diagnosis, treatment planning, and monitoring in patients with neuroepithelial tumors.
10.1200/JCO-25-02798
Dose-Escalated Focal Salvage High-Dose-Rate Brachytherapy and Genomic Classifier Risk Stratification in Radiorecurrent Prostate Cancer: The F-SHARP Phase I/II Clinical Trial.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This multi-institutional phase I/II trial (F-SHARP) evaluated the safety and efficacy of dose-escalated focal salvage high-dose-rate brachytherapy (DE-fsHDR) and genomic classifier (GC) risk stratification in 62 patients with radiorecurrent prostate cancer. Results demonstrated high safety with no acute grade 3 toxicities and only 3.2% late grade 3 toxicity, while 3-year biochemical progression-free survival reached 62.7% and metastasis-free survival was 85.9%. The study highlights that GC scores significantly correlate with outcomes, as all patients with scores above 0.85 experienced biochemical, local, and metastatic recurrence. DE-fsHDR offers a safe salvage option for intraprostatic recurrence, and genomic profiling provides a promising prognostic tool to guide treatment intensification in this oncological setting.
10.1200/JCO-25-02730
Treatment of Advanced Biliary Tract Cancer: ASCO Living Guideline, Version 2026.1.0.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This ASCO living guideline provides evidence-based recommendations for liquid biopsy and systemic treatment of advanced biliary tract cancer (BTC), developed by an Expert Panel conducting a systematic review of relevant studies including RCTs. It recommends broad-based tissue NGS testing at diagnosis, with liquid biopsy for unavailable tissue. First-line therapy for pMMR/MSS advanced BTC is ICIs plus chemotherapy, while pembrolizumab monotherapy is an option for dMMR/MSI-H BTC. The guideline offers specific, actionable treatment options for various BTC patient subgroups, including those with disease progression or specific biomarkers (e.g., FGFR2, IDH1, BRAF V600E, HER2, NTRK fusions), directly impacting clinical decision-making in oncology.
10.1200/JCO-26-02462
VERIFY: A Phase III Trial of Rusfertide Versus Placebo in Phlebotomy-Dependent Patients With Polycythemia Vera Receiving Standard-of-Care Therapy.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
The Phase III VERIFY trial evaluated rusfertide, a hepcidin mimetic, in 293 phlebotomy-dependent patients with polycythemia vera (PV), a myeloproliferative neoplasm. Patients were randomized (1:1, double-blind) to rusfertide or placebo alongside standard-of-care. Rusfertide significantly improved clinical response (77% vs 33%, p < .0001), reduced mean phlebotomies (0.5 vs 1.8, p < .0001), and maintained hematocrit <45% (63% vs 14%, p < .0001). It also improved patient-reported fatigue and symptom scores (p = .0252 and .0240). This suggests rusfertide offers a significant new treatment option for PV, improving hematocrit control and patient quality of life.
10.1200/JCO-26-00992
Development and Validation of a Blood Test Informed Risk Prediction Model for Lung Cancer-The Copenhagen Lung Cancer Risk Model (CPH-Lung).
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This study developed and validated CPH-Lung, a blood test-based model, to improve 6-year lung cancer risk stratification for screening. Utilizing two prospective cohorts of ever-smokers, the model was trained and validated against the PLCOm2012 model. CPH-Lung demonstrated superior discrimination (AUC 0.783 vs. 0.720, p=.0059) and higher sensitivity (e.g., 57.6% vs. 39.2% in women, p<.0001) for detecting lung cancer. This offers a more sensitive tool for identifying high-risk individuals, particularly women and younger patients, potentially enhancing early lung cancer detection in clinical practice.
10.1200/JCO-25-02326
Randomized Trial of Hypofractionated Postmastectomy Radiation Therapy in Women With Breast Reconstruction (RT CHARM, Alliance A221505).
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This randomized noninferiority trial compared hypofractionated postmastectomy radiation therapy (42.56 Gy in 16 fractions) to conventional treatment (50 Gy in 25 fractions) in 898 women with invasive breast cancer undergoing reconstruction. At 24 months, reconstruction complication rates were 12.3% for hypofractionated versus 10.2% for conventional therapy, confirming noninferiority with an estimated difference of -2.1% (95% CI, -6.5 to 2.2). Locoregional recurrence rates at 36 months remained low and statistically similar between groups (1.5% vs. 2.2%), while implant-only reconstructions showed higher complication risks than autologous methods. These findings support the clinical adoption of shorter radiation courses for breast cancer patients, offering comparable safety and oncologic control while significantly reducing treatment duration.
10.1200/JCO-26-00474
A health-system-scale, episode-resolved multimodal atlas of cancer cachexia.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This study analyzed longitudinal clinicogenomic data from 52,236 cancer patients to map trajectories of cancer cachexia and its association with clinical outcomes and tumor genotypes. Cachectic episodes were linked to inferior outcomes across nearly all cancer types and exhibited a consistent serologic signature of low albumin and hemoglobin alongside elevated liver enzymes. Somatic mutations, notably TP53, were associated with increased cachexia frequency, leading to the development of a predictive model for lung, colorectal, and prostate cancers. Validated in an external cohort of 5,785 patients, the findings demonstrate that routine clinicogenomic data can effectively predict impending cachectic weight loss to improve supportive care in oncology.
10.1038/s41591-026-04689-9
Oct 05 – Oct 12, 2026
Phase I/II Study of Bavdegalutamide, a Proteolysis-Targeting Chimera Androgen Receptor Degrader, in Metastatic Castration-Resistant Prostate Cancer.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This phase I/II study evaluated the safety and efficacy of bavdegalutamide, a novel AR degrader, in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with an AR pathway inhibitor. The study determined 420 mg once daily as the recommended phase II dose. Promising antitumor activity was observed, particularly in patients with AR T878/H875 mutations, where PSA50/PSA30 rates were 60.0%/70.0% and median radiographic progression-free survival was 11.1 months. With a manageable safety profile (17.4% grade 3 TRAEs), bavdegalutamide offers a potential new therapeutic option for mCRPC, especially for those with specific AR mutations, addressing a critical need in cancer treatment.
10.1200/JCO-25-02995
A modular framework for antibody-drug conjugate biomarkers.
NAT REV CLIN ONCOL · Q1 JOURNAL - RANK #2/326TOP-TIER
This review proposes a modular framework for antibody-drug conjugate (ADC) biomarker development to enhance patient selection, therapeutic sequencing, and toxicity management in oncology. It highlights the need to move beyond semi-quantitative target expression, advocating for a comprehensive approach considering antigen abundance, intracellular trafficking, linker cleavage, payload susceptibility, and toxicity. The framework aims to inform rational combinations, dose optimization, and regulatory strategies. This is highly relevant for improving the clinical utility and safety of ADCs, ultimately benefiting cancer patients by optimizing treatment outcomes.
10.1038/s41571-026-01213-3
Sofetabart mipitecan, an antibody drug conjugate targeting folate receptor alpha, in high grade ovarian cancer: Results from the first-in-human phase 1 study.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This phase 1 study evaluated Sofetabart mipitecan (Sofe-M), a novel FRα-targeting antibody-drug conjugate, in 105 heavily pretreated high-grade ovarian cancer (HGOC) patients. Sofe-M achieved an overall response rate of 50.5% (95% CI 40.5, 60.4) and median progression-free survival of 8.1 months (95% CI 6.4, 8.5), showing activity across FRα expression levels and prior MIRV exposure. The drug demonstrated a favorable tolerability profile, notably absent of keratopathy and high-grade neuropathy, addressing a critical need for well-tolerated treatments in advanced HGOC. These data support 3 mg/kg as the recommended phase 3 dose, positioning Sofe-M as a promising new therapeutic option for platinum-resistant and previously treated HGOC patients.
10.1016/j.annonc.2026.10.001
Prognostic Impact of Telomere Maintenance Mechanisms in Neuroblastoma.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This study investigated whether telomere maintenance mechanisms (TMM) improve neuroblastoma risk classification compared to current standards. Researchers examined TMM prognostic accuracy in 366 neuroblastoma patients, including 259 non-high-risk individuals, comparing it with standard-of-care variables and other molecular classifications. TMM-based classification accurately distinguished non-high-risk patients, remaining the only significant risk factor in multivariable analyses (EFS HR 6.4, OS HR 29.4, both p < .001), outperforming other molecular classifications. This research directly addresses a critical need in pediatric oncology by offering a more precise method for risk stratification in neuroblastoma, potentially optimizing treatment decisions and avoiding overtreatment.
10.1200/JCO-26-00742
Disitamab Vedotin Plus Tislelizumab in Transurethrally Unresectable, ERBB2-Positive, Non-Muscle-Invasive Bladder Cancer: A Nonrandomized Clinical Trial.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
This phase 2 trial evaluated the efficacy and safety of disitamab vedotin combined with tislelizumab in 28 patients with transurethrally unresectable, ERBB2-positive, very high-risk non-muscle-invasive bladder cancer. A complete response was achieved in 73.1% (19/26) of evaluable patients, with a 24-month sustained response rate of 83.5% among responders. The study directly addresses the clinician’s interest in cancer by investigating a novel antibody-drug conjugate and immunotherapy combination for a difficult-to-treat oncological population. These findings suggest a potent nonsurgical alternative for patients ineligible for radical cystectomy, warranting further validation in randomized clinical trials.
10.1001/jamaoncol.2026.3909
Right-sizing treatment for HER2-positive breast cancer: evolving algorithms across the disease continuum.
NAT REV CLIN ONCOL · Q1 JOURNAL - RANK #2/326TOP-TIER
This review examines evolving treatment algorithms for HER2-positive breast cancer, focusing on “right-sizing” therapy across early and metastatic disease stages. It highlights the impact of novel agents like trastuzumab deruxtecan and discusses strategies for de-escalating treatment in low-risk patients while intensifying therapy for those with residual disease. The analysis addresses critical evidence gaps in treatment sequencing, maintenance strategies using palbociclib or tucatinib, and the integration of tissue and plasma-based biomarkers. Clinicians can utilize these frameworks to optimize therapeutic selection, aiming to improve the 5-year survival rates already observed in a substantial proportion of metastatic patients.
10.1038/s41571-026-01211-5
Boosting CAR T cell efficacy in cancer with metabolic insights from design to diet.
NAT REV CANCER · Q1 JOURNAL - RANK #3/326TOP-TIER
This review explores how metabolic insights can boost CAR T cell efficacy in cancer, particularly for solid tumours. It examines the impact of CAR design, manufacturing platforms, and host metabolism on T cell fitness and antitumour activity. The abstract highlights that co-stimulatory domains induce distinct metabolic profiles and that manufacturing protocols lack standardization. It proposes leveraging diet-based interventions as a clinically accessible strategy to enhance CAR T cell therapy, aiming for more durable responses in cancer patients.
10.1038/s41568-026-00984-2
Exercise therapy in cancer prevention and treatment.
NAT REV CLIN ONCOL · Q1 JOURNAL - RANK #2/326TOP-TIER
This review synthesizes epidemiological and clinical trial evidence to evaluate exercise therapy as a strategy for cancer prevention and a therapeutic adjunct post-diagnosis. The analysis examines the link between exercise and primary cancer risk, disease outcomes, and changes in blood-based and tissue-based biomarkers across various oncology settings. Findings suggest that exercise modifies the host macroenvironment and tumor microenvironment, potentially enhancing the efficacy of conventional cancer therapies. The study establishes a translational framework for precision exercise oncology, positioning structured physical activity as a viable anticancer therapeutic modality for clinical practice.
10.1038/s41571-026-01201-7
Neoadjuvant niraparib monotherapy for unresectable, homologous recombination deficiency-positive, high-grade serous ovarian cancer (NANT): a multicentre, single-arm, phase 2 trial.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This phase 2 trial evaluated neoadjuvant niraparib monotherapy as a chemotherapy-free alternative for 67 patients with HRD-positive, unresectable high-grade serous ovarian cancer. Results demonstrated an investigator-assessed objective response rate of 63% and an R0 resection rate of 80% among the operated population. While effective in enabling surgery, grade 3-4 hematological toxicities were frequent, with thrombocytopenia occurring in 48% of participants. This strategy offers a potential targeted approach for molecularly selected patients, though randomized comparison against standard platinum-taxane chemotherapy is required before clinical adoption.
10.1016/S1470-2045(26)00387-6
Advances in Systemic Treatment of Breast Cancer.
NEW ENGL J MED · Q1 JOURNAL - RANK #2/332TOP-TIER
This review examines the rapid evolution of systemic breast cancer therapies since 2020, focusing on the integration of targeted agents, antibody-drug conjugates (ADCs), and immunotherapy guided by molecular profiling. Key developments include the foundational role of CDK4/6 inhibitors in HR+/HER2- disease and the transformative impact of trastuzumab deruxtecan in HER2-positive cases. For triple-negative breast cancer, immune checkpoint inhibitors have significantly improved outcomes in both early and metastatic stages, while risk-adapted strategies allow for treatment escalation or de-escalation. These advancements necessitate personalized, biomarker-driven approaches, though challenges remain regarding treatment sequencing, circulating tumor DNA integration, and equitable access to high-cost therapies.
10.1056/NEJMra2500695
Exploring the immunological effects of antibody-drug conjugates.
NAT REV CLIN ONCOL · Q1 JOURNAL - RANK #2/326TOP-TIER
This review examines the immunological mechanisms by which antibody-drug conjugates (ADCs) exert antitumor activity beyond direct cytotoxicity, including immunogenic cell death, antibody-dependent cellular cytotoxicity, dendritic cell activation, and tumor microenvironment reprogramming. It appraises clinical evidence for combining ADCs with immune checkpoint inhibitors and other immunostimulatory agents, and highlights novel ADC designs with enhanced immunogenic potential. Although no original numerical results are presented, the synthesis supports a paradigm shift positioning ADCs as modulators of tumor-immune interactions. For clinicians focused on cancer, this informs rationale for ADC–immunotherapy combinations and future trial design.
10.1038/s41571-026-01209-z
Sitagliptin for Acute Graft-Versus-Host Disease Prevention in Alternative Donor Transplantation: A Randomized Phase III Trial.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This Phase III randomized trial evaluated adding sitagliptin to standard ATG-based prophylaxis to prevent acute graft-versus-host disease (aGVHD) in 190 patients with hematologic malignancies undergoing stem-cell transplantation. Sitagliptin significantly reduced the incidence of grade II-IV aGVHD by day 100 (14.7% vs. 31.6%; p=0.005) and decreased severe grade III-IV cases (6.3% vs. 18.9%). The intervention improved day 180 GVHD-free, relapse-free survival (86.3% vs. 72.6%) without increasing relapse risk or adverse events. These findings suggest sitagliptin is a safe, effective adjunct for reducing early transplant-related morbidity in cancer patients, though long-term overall survival benefits were not observed.
10.1200/JCO-26-00670
Sep 28 – Oct 05, 2026
Clinical Practice Guideline for Systemic Antibacterial and Antifungal Prophylaxis in Pediatric Patients With Cancer and Hematopoietic Cell Transplant Recipients: 2026 Update.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This updated clinical practice guideline (CPG) provides harmonized recommendations for systemic antibacterial and antifungal prophylaxis in pediatric cancer and hematopoietic cell transplant (HCT) recipients, based on systematic reviews of 195 randomized trials. Key recommendations include conditional antibacterial prophylaxis for pediatric AML/relapsed ALL (strong for levofloxacin) and strong antifungal prophylaxis for pediatric AML/allogeneic HCT (echinocandin or mold-active azole). A new conditional recommendation suggests considering no antibacterial prophylaxis if levofloxacin is unavailable, directly impacting infection prevention for vulnerable pediatric cancer patients. This update consolidates CPGs, emphasizing practical considerations like drug interactions and infection monitoring, with future research needed for subgroup refinement.
10.1200/JCO-26-00720
Urine cell-free RNA for bladder cancer detection and treatment response prediction.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This study evaluated uRARE-seq, a novel liquid biopsy method for profiling urine cell-free RNA (cfRNA), across 683 samples to detect and characterize bladder cancer. The method demonstrated 95% sensitivity and 90% specificity for localized bladder cancer detection, outperforming traditional urine tumor DNA analysis. Analysis successfully identified minimal residual disease and predicted BCG treatment response versus chemotherapy with an area under the curve of 0.93 based on immune and proliferation signatures. These findings suggest urine cfRNA is a highly effective non-invasive tool for cancer diagnosis and personalized treatment selection, pending prospective clinical validation.
10.1038/s41591-026-04673-3
Rethinking Treatment Intensification in Poorly Chemosensitive Ovarian Cancer: A Review.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
This review evaluates treatment intensification strategies for patients with poorly chemosensitive, high-grade serous ovarian cancer who often fail to achieve complete cytoreductive surgery. Analysis of phase 3 trials like ICON-8 indicates that weekly dose-dense paclitaxel and bevacizumab provide significant survival benefits specifically within this high-risk “2 red flags” subgroup. The study emphasizes using pragmatic indicators like the KELIM score and pathological chemotherapy response to identify patients for response-adapted first-line therapies. These findings offer a clinically actionable framework to improve interval cytoreduction rates and long-term outcomes in a population with historically limited treatment options.
10.1001/jamaoncol.2026.3875
Immune Checkpoint Inhibitor-Based Downstaging Therapy for Hepatocellular Carcinoma.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
This multicenter, retrospective matched cohort study investigated an immune checkpoint inhibitor (ICI)-based multimodal pretransplant strategy for hepatocellular carcinoma (HCC) initially beyond Milan criteria, evaluating posttransplant oncologic outcomes. Among 416 recipients, the ICI group demonstrated significantly better median overall survival (4.57 vs 2.53 years, P<.001) and recurrence-free survival (1.47 vs 0.89 years, P=.02), with lower recurrence risk (HR 0.54). These findings are highly relevant for cancer clinicians, suggesting improved survival and reduced recurrence in advanced HCC patients receiving ICI-based downstaging before liver transplant. The study implies that this strategy could be valuable for selected HCC patients, despite an increased acute rejection rate (16.3% vs 8.2%).
10.1001/jamaoncol.2026.3901
Five-year survival with neoadjuvant therapy in melanoma: updated pooled analysis from the International Neoadjuvant Melanoma Consortium (INMC).
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This pooled analysis of 1,038 patients with stage IIIB-D melanoma evaluated the five-year efficacy of neoadjuvant immune checkpoint inhibitors (ICIs) and targeted therapies across 26 international sites. Results showed that PD-1 plus immuno-oncology combinations achieved higher major pathological response (MPR) rates (61.4%) and superior five-year recurrence-free survival (73.9%) compared to PD-1 monotherapy or BRAF/MEK inhibitors. Notably, ICI-treated patients achieving MPR demonstrated exceptional five-year overall survival rates exceeding 97%, suggesting that adjuvant therapy may be unnecessary for this specific subgroup. These findings establish neoadjuvant ICI combinations as a highly effective standard for resectable melanoma, though poor outcomes with targeted therapies alone highlight the need for biomarker-driven treatment selection.
10.1038/s41591-026-04677-z
Treatment of Multiple Myeloma: ASCO Living Guideline, Version 2026.1.3.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This ASCO living guideline provides updated, evidence-based recommendations for the systemic treatment of patients with multiple myeloma. The methodology involves a systematic review of clinical trials to evaluate the efficacy of induction, consolidation, and maintenance therapies. Key findings emphasize the use of quadruplet regimens and proteasome inhibitors, which have significantly improved progression-free survival and minimal residual disease (MRD) negativity rates in recent trials. These recommendations are directly relevant to oncology practice, offering a definitive framework for managing this hematologic malignancy through various stages of disease progression.
10.1200/JCO-26-02399
Giredestrant plus Everolimus in Advanced Breast Cancer.
NEW ENGL J MED · Q1 JOURNAL - RANK #2/332TOP-TIER
This phase 3 randomized trial investigated giredestrant plus everolimus versus standard endocrine therapy plus everolimus in 373 patients with ER-positive, HER2-negative advanced breast cancer progressing after CDK4/6 inhibitors. The giredestrant-everolimus regimen significantly extended median progression-free survival to 10.0 months (vs 5.5 months) in ESR1-mutated tumors (HR 0.38; P<0.001) and to 8.8 months (vs 5.5 months) in the overall population (HR 0.56; P<0.001). This all-oral combination offers a clinically relevant new treatment option for this challenging patient group, particularly those with ESR1 mutations, with a comparable safety profile. It provides a significant improvement in disease control for advanced breast cancer.
10.1056/NEJMoa2602457
Intravenous hyaluronidase-expressing oncolytic adenovirus with chemotherapy in metastatic pancreatic cancer: a randomized phase 2b trial.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This randomized phase 2b trial evaluated intravenous VCN-01 (oncolytic adenovirus) plus gemcitabine and nab-paclitaxel (GnP) versus GnP alone as first-line therapy for metastatic pancreatic ductal adenocarcinoma. In the full analysis set, VCN-01+GnP significantly improved median progression-free survival (7.0 vs 4.6 months, HR=0.55, P=0.011) and duration of response (11.2 vs 5.4 months, HR=0.22, P=0.004). Median overall survival was 10.8 vs 8.6 months (HR=0.57, P=0.055), with 18-month survival rates of 31.1% vs 8.5%. These findings suggest a potential new first-line treatment option for a challenging cancer, warranting further investigation in a phase 3 trial.
10.1038/s41591-026-04705-y
Final results and predictive biomarkers of response and long-term outcomes with first-line pembrolizumab monotherapy in advanced renal cell carcinoma in the phase II KEYNOTE-427 study.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This phase II KEYNOTE-427 study evaluated first-line pembrolizumab monotherapy in advanced renal cell carcinoma, reporting final efficacy, safety, and predictive biomarkers after ~5 years of follow-up. In cohort A (clear cell RCC), the objective response rate was 36.4%; in cohort B (non-clear cell RCC), it was 26.7%. T-cell-inflamed gene expression profile and PD-L1 combined positive score were positively associated with response, while detectable circulating tumor DNA at baseline predicted shorter overall survival (30.5 vs 53.7 months). These findings support pembrolizumab as active in advanced RCC and suggest molecular biomarkers may guide precision treatment.
10.1016/j.annonc.2026.09.011
Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Patients Presenting With Locally Advanced Breast Cancer.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This prospective study evaluated the false-negative rate (FNR) of sentinel lymph node biopsy (SLNB) in 145 patients with locally advanced breast cancer who achieved a clinical nodal response after neoadjuvant chemotherapy. While the SLN identification rate was 74%, the FNR among patients with adequate mapping was only 2.1% (95% CI, 0.1–12.7), with a nodal pathologic complete response rate of 46%. These findings directly address the clinician’s interest in oncology by demonstrating that SLNB can accurately stage the axilla in high-risk breast cancer patients downstaged by systemic therapy. The low FNR suggests that SLNB is a viable alternative to completion axillary lymph node dissection in this specific cancer population, potentially reducing surgical morbidity.
10.1200/JCO-26-01114
Cancer and the microbiome: from association to intervention.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This review synthesizes evidence regarding the gut microbiome’s role as a modifiable determinant of efficacy and toxicity in systemic cancer therapies, particularly immune checkpoint inhibitors (ICIs). Research indicates that higher microbial diversity and specific immunostimulatory pathways correlate with improved survival and treatment response in melanoma, non-small-cell lung cancer, and renal cell carcinoma. Conversely, the use of antibiotics and proton pump inhibitors is linked to inferior clinical outcomes due to microbiome disruption, while interventions like fecal microbiota transplantation are currently under investigation. These findings suggest that modulating the intestinal microbiome could optimize anticancer treatment responses, though therapeutic strategies remain in the investigational phase.
10.1016/S1470-2045(26)00326-8
Hypofractionated versus conventional fractionated postmastectomy radiotherapy for patients with high-risk breast cancer (CHN HYPOPMRT): 10-year outcomes from a randomised, non-inferiority, open-label, phase 3 trial.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This phase 3 randomized trial (CHN HYPOPMRT) compared hypofractionated (43.5 Gy in 15 fractions) versus conventional (50 Gy in 25 fractions) postmastectomy radiotherapy in 810 high-risk breast cancer patients, with a median follow-up of 11.5 years. At 10 years, cumulative locoregional recurrence was 10.3% with conventional and 12.0% with hypofractionated radiotherapy (HR 1.19, 95% CI 0.79-1.82), showing comparable control. Grade 3 adverse events, such as ischemic heart disease, were similar (1% in both groups), with no grade 4-5 events. This supports hypofractionated PMRT as a time-efficient and safe alternative for durable locoregional control in high-risk breast cancer.
10.1016/S1470-2045(26)00297-4
Global burden of cancer attributable to infections in 2024: a worldwide incidence analysis.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This worldwide incidence analysis utilized GLOBOCAN 2024 data to quantify the global burden of cancer attributable to 12 Group 1 carcinogenic infectious agents, aiming to inform prevention efforts. Findings revealed an estimated 2.3 million new cancer cases globally in 2024 (12% of all cancers) were infection-attributable, with H. pylori (760,000 cases, 4%) and HPV (750,000 cases, 4%) being the leading causes. The highest burden was observed in eastern Asia, accounting for 990,000 cases (42%). This research highlights the critical importance of infection control for cancer prevention, reinforcing the value of vaccination, screening, and treatment strategies in clinical practice.
10.1016/S1470-2045(26)00307-4
Surgery and tile-based radiation therapy versus surgery and stereotactic radiation for newly diagnosed brain metastases (ROADS): a randomized, open-label, phase 3 trial.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This phase 3 randomized trial (ROADS) compared resection with tile-based radiation therapy (R+TBRT) to resection with stereotactic radiation (R+SRT) for newly diagnosed brain metastases. R+TBRT significantly improved time-to-surgical bed recurrence (HR: 0.06; 95% CI: 0.01-0.46; p=0.0070) and surgical bed recurrence-free survival (HR: 0.48; 95% CI: 0.30-0.76; p=0.0021). Overall adverse events were similar between groups. This study demonstrates that R+TBRT offers superior local control for resected brain metastases, providing a potentially improved treatment strategy for cancer patients.
10.1200/JCO-26-01894
Sep 21 – Sep 28, 2026
Radiotherapy versus observation following surgical resection of WHO grade 2 atypical meningioma (ROAM/EORTC-1308): an international, multicentre, open-label, phase 3, randomised controlled trial.
LANCET · Q1 JOURNAL - RANK #1/332TOP-TIER
This phase 3 randomized controlled trial (ROAM/EORTC-1308) evaluated whether adjuvant radiotherapy (60 Gy) improves disease-free survival compared to observation in 157 patients with WHO grade 2 atypical meningioma following complete surgical resection. At a median follow-up of 64 months, the radiotherapy group demonstrated a significantly higher 5-year disease-free survival rate of 79.9% compared to 64.3% in the observation group (HR 0.51, p=0.0396). Recurrence occurred in only 14% of the radiotherapy group versus 30% of the observation group, though 8% of radiotherapy patients experienced grade 2 or 3 serious adverse events. These findings suggest that adjuvant radiotherapy should be considered post-resection to reduce recurrence risk, provided the clinical benefit outweighs potential delayed radiation-related toxicities.
10.1016/S0140-6736(26)01804-0
Global uptake of essential cancer medicines with and without complex genomic diagnostics: a retrospective observational study.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This retrospective observational study analyzed the global uptake of 41 essential cancer medicines in 71 countries from 2002-2023, categorizing them by diagnostic requirements. Key findings revealed that medicines requiring complex genomic diagnostics had 65% (regression coefficient -0·453) lower standard-unit uptake than those without, with the lowest uptake observed in lower-GDP countries. Overall, lower-GDP countries showed less uptake across all medicine types compared to middle and high-GDP countries. These results highlight significant disparities in access to essential cancer medicines, particularly precision oncology, suggesting that EML inclusion alone is insufficient to ensure patient access and impacting global cancer care delivery.
10.1016/S1470-2045(26)00432-8
Accelerating equitable cancer genomics and precision oncology in health care and research: a Lancet Oncology Commission.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This Lancet Oncology Commission defines the global precision oncology landscape, analyzing scientific, structural, and health-system challenges to equitable implementation in cancer care. Findings indicate profoundly unequal access to cancer genomics, leaving millions of patients without guideline-indicated interventions annually, and research concentrated in high-income settings. While precision oncology offers heterogeneous benefits, significant gains are confined to a few well-validated biomarker-treatment pairings, with broader approaches benefiting only a few patients. The Commission offers frameworks for value-based, resource-stratified implementation, workforce competency, and monitoring to integrate cancer genomics effectively, equitably, and sustainably, aiming to improve cancer outcomes.
10.1016/S1470-2045(26)00302-5
Iberdomide plus daratumumab and dexamethasone versus daratumumab, bortezomib, and dexamethasone in patients with relapsed or refractory multiple myeloma (EXCALIBER-RRMM): an open-label, randomised, controlled, phase 3 trial.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
The EXCALIBER-RRMM phase 3 trial compared iberdomide, daratumumab, and dexamethasone (IDd) with daratumumab, bortezomib, and dexamethasone (DVd) in 420 patients with relapsed or refractory multiple myeloma. IDd significantly improved minimal residual disease (MRD)-negative complete response, achieved in 41% (85/207) of patients versus 21% (44/213) with DVd (proportion difference 20.1%, p<0.0001). This demonstrates a superior treatment option for a specific cancer, directly addressing the clinician’s interest in cancer research. IDd represents an efficacious new regimen for relapsed or refractory multiple myeloma, potentially improving outcomes for these cancer patients.
10.1016/S1470-2045(26)00450-X
Balancing benefits, costs, and harms: policy implications of expanding cancer susceptibility testing from genetics clinics to the general population.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This policy review examines the clinical and health-system challenges of expanding cancer susceptibility testing from specialized clinics to the general population for precision prevention. While risks for first-wave genes like BRCA1 and BRCA2 are well-established, the review highlights that evidence for newer multigene panels and polygenic risk scores remains scarce regarding mortality reduction and cost-effectiveness. Clinicians must navigate uncertain penetrance estimates and ancestry-dependent performance of risk scores when implementing these tools in routine oncology. The authors propose a tiered, context-specific implementation framework to ensure testing provides a net benefit rather than harm in diverse clinical and public health settings.
10.1016/S1470-2045(26)00390-6
Daratumumab Plus Bortezomib, Lenalidomide, and Dexamethasone in Newly Diagnosed Multiple Myeloma: Transplant-Ineligible Subgroup Analysis of CEPHEUS.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This Phase III CEPHEUS subgroup analysis evaluated the efficacy and safety of adding daratumumab to bortezomib, lenalidomide, and dexamethasone (DVRd) versus VRd alone in 289 transplant-ineligible patients with newly diagnosed multiple myeloma. At 58.7 months follow-up, DVRd significantly increased MRD negativity rates to 60.4% compared to 39.3% for VRd (p=.0004) and reduced the risk of disease progression or death by 49% (HR 0.51). The quadruplet regimen also demonstrated superior sustained MRD negativity for ≥24 months (40.3% vs 22.8%), indicating deeper and more durable responses in this older or comorbid population. These findings reinforce DVRd as a potent standard of care for transplant-ineligible patients, offering substantial progression-free survival benefits with a manageable safety profile.
10.1200/JCO-26-00401
Evorpacept plus trastuzumab, ramucirumab and paclitaxel in HER2-positive gastric cancer: a randomized phase 2 trial.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This randomized phase 2 trial (ASPEN-06) investigated evorpacept plus trastuzumab, ramucirumab, and paclitaxel (evo+TRP) versus TRP alone in 127 pretreated HER2-overexpressing advanced gastric/gastroesophageal junction cancer patients. The primary endpoint, investigator-assessed objective response rate (ORR), was 40.3% for evo+TRP versus 26.6% for TRP in the ITT population, and 54.8% versus 23.1% in the fresh biopsy HER2+ subgroup. While ORR differences exceeded prespecified thresholds (13.7% and 31.7%), ORRs did not meet the statistical criterion against the 30% historical benchmark. Evo+TRP demonstrated encouraging efficacy with manageable safety, suggesting a potential new treatment option for this challenging cancer.
10.1038/s41591-026-04700-3
First-Line Retlirafusp Alfa Plus Chemotherapy for Human Epidermal Growth Factor Receptor 2-Negative Gastric or Gastroesophageal Junction Adenocarcinoma: A Randomized, Double-Blind, Phase III Study (RELIGHT).
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
The RELIGHT phase III study evaluated retlirafusp alfa plus CAPOX as first-line treatment for 731 patients with HER2-negative gastric or GEJ adenocarcinoma. It significantly prolonged overall survival in PD-L1 CPS ≥5 patients (median 16.8 vs 10.4 months; HR 0.53) and the intention-to-treat population (median 15.8 vs 11.2 months; HR 0.66). Progression-free survival also improved, with comparable grade ≥3 adverse events (62.6% vs 59.0%). This regimen represents a new first-line treatment option for this specific cancer, offering improved survival outcomes.
10.1200/JCO-25-02933
Disparities in Cancer Incidence by Sex and Associated Lifestyle Factors and Health Conditions.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
This cohort study analyzed 589,766 participants from China and the UK to quantify how 11 modifiable lifestyle factors and health conditions contribute to sex disparities in the incidence of 34 non-sex-specific cancers. In the Chinese population, modifiable factors accounted for 84.44% of the male-female incidence gap, primarily driven by smoking (51.75%) and heavy alcohol consumption (15.10%). Conversely, these factors explained only 26.21% of the disparity in the UK population, with obesity (7.68%) and smoking (6.26%) identified as the leading individual contributors. These results demonstrate that while lifestyle interventions can significantly reduce cancer sex disparities, prevention strategies must be tailored to specific population contexts to address varying risk profiles effectively.
10.1001/jamaoncol.2026.3747
Chemotherapy and Surgical Outcomes for Ovarian Metastases From Colorectal Cancer: A Narrative Review.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
This narrative review evaluated 24 retrospective studies (2705 patients) on ovarian metastases from colorectal cancer to assess chemotherapy efficacy and surgical outcomes. It found that ovarian metastases exhibited lower chemotherapy response rates and shrinkage compared to extraovarian sites, suggesting the ovary as a chemotherapy-resistant sanctuary. The most favorable outcomes and improved survival were associated with complete surgical resection and negative margins. Therefore, optimal management should prioritize comprehensive surgical clearance of macroscopic disease, with systemic therapy playing a complementary role to improve candidacy for resection.
10.1001/jamaoncol.2026.3634
Optimizing the delivery of radiotherapy with artificial intelligence.
NAT REV CLIN ONCOL · Q1 JOURNAL - RANK #2/326TOP-TIER
This review examines the integration of artificial intelligence and machine learning to optimize radiation oncology through tasks like auto-contouring, dose calculation, and outcome prediction. The authors highlight how generative AI and foundation models now enable automated treatment planning and synthetic CT generation to improve individual patient care. While clinical deployment currently lags due to ethical and technical challenges, the study emphasizes that innovations like digital twins and multimodal AI can significantly enhance radiotherapy efficacy. Ultimately, these tools aim to optimize treatment outcomes and the quality of care for patients undergoing oncological interventions.
10.1038/s41571-026-01204-4
Phase 1 Study of Anito-cel, a d-Domain BCMA CAR T Cell for Refractory or Recurrent Myeloma.
NEW ENGL J MED · Q1 JOURNAL - RANK #2/332TOP-TIER
This Phase 1 study investigated the safety and efficacy of anito-cel, a novel BCMA CAR T-cell therapy, in 38 patients with relapsed or refractory multiple myeloma. At a median follow-up of 38.1 months, the therapy achieved a 100% overall response rate, with 79% complete responses. Notably, grade 3 or higher cytokine release syndrome and ICANS were rare (0% and 3% respectively at the recommended phase 2 dose). With a 24-month progression-free survival of 57% and 36-month overall survival of 65%, anito-cel offers a promising, durable treatment option for this challenging cancer.
10.1056/NEJMoa2603527
Five-Year Follow-Up of the Phase III ASCOT Trial of Adjuvant S-1 After Resection for Biliary Tract Cancer.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This phase III multicenter trial evaluated the long-term efficacy of adjuvant S-1 versus observation in 440 Japanese patients with resected biliary tract cancer. At a median follow-up of 61.5 months, the S-1 group demonstrated a significantly higher 5-year overall survival rate of 64% compared to 52% in the observation group (HR 0.72). Median overall survival was extended to 8.2 years with S-1 treatment, while stratified relapse-free survival also showed improvement (HR 0.76). These findings confirm that adjuvant S-1 provides a sustained survival benefit, establishing it as a standard treatment option for patients following biliary tract cancer resection.
10.1200/JCO-26-00017
Effect of Screening with Multicancer Early-Detection Test on Late-Stage Cancer Diagnosis.
NEW ENGL J MED · Q1 JOURNAL - RANK #2/332TOP-TIER
This randomized controlled trial evaluated whether adding multicancer early-detection (MCED) blood tests to usual care reduces late-stage cancer diagnoses among 142,250 participants aged 50–77. Results showed no significant difference in the incidence of stage III or IV cancers between the intervention and control groups (IRR 1.03; 95% CI, 0.92–1.14; P=0.63). While the incidence of stage IV cancer alone showed a non-significant trend toward reduction (IRR 0.86; 95% CI, 0.74–1.00), the primary endpoint was not met. These findings suggest that current MCED screening does not yet provide a measurable reduction in late-stage cancer burden, though long-term follow-up is necessary to assess evolving diagnostic trends.
10.1056/NEJMoa2505723
Transcriptomic Plasticity and Its Spatial Architecture Shape Melanoma Response to Immunotherapy and Its Combination With BRAF/MEKi.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This study aimed to define tumor biology and identify biomarkers guiding treatment strategies for BRAF-mutant melanoma, integrating multi-omics data from large clinical cohorts and functional assays. Researchers identified two distinct ICB-resistant states: differentiated tumors, which benefited from BRAF/MEK inhibition combined with ICB, and undifferentiated tumors, less responsive to these combinations but showing sensitivity to anti-VEGF therapy retrospectively and CDK7 inhibition preclinically. These findings establish a transcriptional classification framework for melanoma, supporting biomarker-driven approaches to optimize therapeutic escalation by adding MAPK inhibition to ICB for specific patient subgroups. This has significant implications for personalized cancer treatment, addressing persistent unmet needs in melanoma management.
10.1200/JCO-25-02766
Large-scale esophageal cancer screening through noncontrast computed tomography and artificial intelligence.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This study developed the EAGLE artificial intelligence model to detect esophageal cancer and precancerous lesions from noncontrast chest CT, historically considered infeasible. Trained on 6,813 patients and validated across 12 centers involving 80,612 patients, EAGLE achieved 98.5% specificity and 90.0% sensitivity for cancer in opportunistic screening, with 52.5% sensitivity for precancerous lesions. Real-world calibration reduced false positives by 72.7% while preserving sensitivity; prospective validation reached 42.2% PPV and low-dose screening achieved 99.94% specificity. EAGLE offers a scalable, noninvasive tool for early esophageal cancer screening, potentially integrating with lung cancer screening programs to improve detection and referral efficiency.
10.1038/s41591-026-04656-4
Trastuzumab plus nivolumab with gemcitabine and cisplatin as first-line therapy for HER2-positive unresectable biliary tract cancer: a phase 1b/2 trial.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This phase 1b/2 HERBOT study evaluated a first-line HER2-targeted quadruplet regimen (trastuzumab, nivolumab, gemcitabine, cisplatin) for HER2-positive advanced unresectable biliary tract cancer (BTC). The primary endpoint was met with an objective response rate of 55% (95% CI 38.5-70.7) and a disease control rate of 95% among 40 participants. Median progression-free survival was 10.6 months (95% CI 7.8-17.4), and median overall survival was not reached, with 5% undergoing conversion surgery. These findings suggest upfront HER2-targeted therapeutic intensification is a promising first-line strategy for HER2-positive BTC, relevant to ongoing phase 3 studies.
10.1038/s41591-026-04679-x
Performance of a multi-cancer early detection test in the randomized controlled NHS-Galleri trial.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This randomized trial evaluated a multi-cancer early detection (MCED) test added to usual care in 142,250 participants aged 50-77. Across three annual rounds, positive test rates were 1.03%, 0.80%, and 0.90%, with positive predictive values of 58.0%, 50.4%, and 45.8%, and negative predictive values above 98.8%. Specificity exceeded 99.5%, but episode sensitivity was low (26.7-37.2% for all cancers; 47.6-63.4% for 12 prespecified types), and cancer signal origin accuracy was 91.1-93.6%. Although the primary endpoint of reducing stage III/IV diagnoses was not met, the test showed high specificity and moderate PPV, informing its potential role in population screening.
10.1038/s41591-026-04652-8
Performance and safety of a multi-cancer early detection test: the PATHFINDER 2 study.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This prospective, interventional PATHFINDER 2 study evaluated the performance and safety of a blood-based multi-cancer early detection (MCED) test in 32,007 participants aged 50 or older without cancer suspicion. Key findings included a cancer detection rate of 0.54%, a positive predictive value of 60.3%, and a specificity of 99.64%. Episode sensitivity was 39.3% for all cancers and 69.8% for a prespecified 12-cancer subgroup, with 91.3% accuracy in predicting cancer signal origin. These results offer crucial insights into the MCED test’s potential for early cancer detection and guiding diagnostic workup, with a number needed to screen of 185 and minimal invasive procedures (0.6%) after positive results.
10.1038/s41591-026-04618-w
Replication stress in cancer: origins, consequences and therapeutic opportunities.
NAT REV CANCER · Q1 JOURNAL - RANK #3/326TOP-TIER
This review article explores replication stress as a fundamental driver of tumor development and a key target for precision oncology. It details how impaired DNA replication, stemming from oncogene activation and other factors, leads to genomic instability in cancer cells. The study highlights the essential role of pathways like ATR-CHK1 in managing this stress and identifies therapeutic vulnerabilities. Inhibitors targeting ATR, CHK1, and WEE1 are in clinical development, alongside synthetic lethal strategies such as PARP inhibition in BRCA1/2-deficient tumors and WRN inhibition in microsatellite-unstable cancers. This framework offers significant implications for developing targeted cancer therapies.
10.1038/s41568-026-00979-z
Patient-Level Evaluation of Optimal Margin Width for Lumpectomy in Ductal Carcinoma In Situ: An Analysis of Patients in the National Cancer Database Special Study.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This retrospective cohort study of 11,156 women from the National Cancer Database evaluated whether surgical margin widths <2 mm increase recurrence risk in ductal carcinoma in situ (DCIS) compared to the standard ≥2 mm threshold. Over a median follow-up of 66.6 months, 445 patients (4%) experienced ipsilateral recurrence, with multivariable analysis showing no significant difference in recurrence risk between negative margin groups (0.01-1.9 mm vs. ≥2 mm) for the overall cohort. However, subgroup analysis revealed that patients younger than 50 years did experience a significantly higher recurrence risk with narrow margins compared to wider margins. These findings suggest that the 2 mm margin guideline may be unnecessarily restrictive for most DCIS patients, though wider margins remain clinically prudent for younger women to minimize local recurrence.
10.1200/JCO-25-02476
Understanding and targeting the tumour matrisome.
NAT REV CLIN ONCOL · Q1 JOURNAL - RANK #2/326TOP-TIER
This review examines the composition and signaling functions of the tumor extracellular matrix (ECM), or matrisome, utilizing recent advances in proteomics and imaging to define its role in cancer progression. While specific numerical trial data are not provided in this overview, it highlights that ECM accumulation serves as a universal hallmark of cancer that correlates directly with increased tumor aggressiveness and decreased patient survival. The study evaluates the clinical utility of the ECM as a reservoir for prognostic biomarkers and a scaffold for targeted therapeutic delivery systems. Practitioners can anticipate novel ‘matritherapies’ designed to normalize the tumor microenvironment or modulate ECM signaling pathways to improve clinical outcomes in oncology.
10.1038/s41571-026-01203-5
Sep 14 – Sep 21, 2026
Navigating uncertainties and evidence gaps in adjuvant therapy for premenopausal women with HR+/HER2- breast cancer.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This review synthesizes current evidence to address management uncertainties in premenopausal women with HR+/HER2-negative early breast cancer, a population characterized by aggressive tumor biology. The authors evaluate the roles of adjuvant endocrine therapy, CDK4/6 inhibitors, ovarian function suppression, and genomic assays in guiding chemotherapy and extended therapy choices. While specific numerical trial data are not detailed in the abstract, the work focuses on optimizing individualized care and managing treatment-related toxicities and survivorship. The study provides a pragmatic clinical framework to bridge evidence gaps, directly supporting clinical decision-making for this specific oncological population.
10.1016/j.annonc.2026.09.005
Immunotherapy in Head and Neck Squamous Cell Carcinoma With PD-L1 Combined Positive Score Less Than 1: A Bayesian Meta-Analysis.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
This Bayesian meta-analysis evaluated the efficacy of immune checkpoint inhibitors (ICIs) in 630 patients with recurrent/metastatic or locally advanced Head and Neck Squamous Cell Carcinoma (HNSCC) with PD-L1 Combined Positive Score less than 1, comparing ICI-based regimens to standard non-ICI therapy across 7 randomized trials. Key findings indicate a high probability that ICIs were associated with reduced overall survival (OS) in this subgroup, with a Bayesian HR for OS of 1.43 (95% CrI, 0.97-2.07) and a 96.2% posterior probability of HR exceeding 1.0. For recurrent/metastatic HNSCC, the Bayesian HR for OS was 1.42 (95% CrI, 0.93-2.06), with a 95.6% probability of HR > 1.0. These results suggest that ICIs may be detrimental in this specific HNSCC population, warranting cautious use and further validation.
10.1001/jamaoncol.2026.3626
PDS0101 With Pembrolizumab in HPV16-Positive Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma: A Phase 2 Nonrandomized Clinical Trial.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
This phase 2 nonrandomized trial evaluated PDS0101, an HPV16-targeted immunotherapy, plus pembrolizumab in 75 evaluable patients with HPV16-positive recurrent/metastatic head and neck squamous cell carcinoma. In 53 immune checkpoint inhibitor-naive patients, the objective response rate was 34.0%, median progression-free survival 5.3 months, and median overall survival 39.3 months; no responses occurred in 22 ICI-resistant patients, though median overall survival was 14.8 months. Grade 3 or higher treatment-related adverse events occurred in 13.8%. These findings support further evaluation of this combination in the first-line setting for HPV16-positive disease.
10.1001/jamaoncol.2026.3492
Advances in therapeutic approaches to gastric cancer.
CA-CANCER J CLIN · Q1 JOURNAL - RANK #1/326TOP-TIER
This abstract reviews advances in therapeutic approaches for gastric cancer, a leading cause of cancer-related mortality, covering various stages and treatment modalities. Key findings include improved survival with perioperative oxaliplatin-based chemotherapy for locally advanced disease and significant improvements in pathologic complete response and overall survival with immunotherapy (PD-1/PD-L1 inhibitors + chemotherapy) in specific biomarker-positive tumors. Targeted agents like zolbetuximab for Claudin 18.2-positive disease and trastuzumab deruxtecan for HER2-positive disease have revolutionized treatment paradigms. The field is progressing towards personalized, biomarker-driven approaches, offering enhanced outcomes and emphasizing multidisciplinary care for cancer patients.
10.3322/caac.70103
Liquid biopsy for early detection of pancreatic ductal adenocarcinoma.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This international, multicenter study developed and validated PANXEON, a blood-based assay combining a 10-miRNA signature with CA 19-9 for early-stage pancreatic ductal adenocarcinoma (PDAC) detection in 1,785 individuals. The miRNA signature achieved an 88.6% AUC and 83.8% sensitivity for early-stage PDAC, while the composite PANXEON score reached 86.8% sensitivity for stage I-II disease. Biomarker levels correlated with clinical status, decreasing after surgery or chemotherapy and increasing prior to disease recurrence, while also identifying 64.3% of high-grade dysplasia in high-risk cysts. This liquid biopsy approach offers a promising non-invasive tool for early cancer detection and longitudinal monitoring, warranting further large-scale prospective validation in clinical practice.
10.1038/s41591-026-04625-x
Blinatumomab for Replacing Chemotherapy in Pediatric Acute Lymphoblastic Leukemia.
NEW ENGL J MED · Q1 JOURNAL - RANK #2/332TOP-TIER
This randomized controlled trial evaluated blinatumomab as a replacement for two cycles of chemotherapy in pediatric high-risk B-cell ALL after consolidation. Blinatumomab significantly improved 4-year event-free survival to 83.0% compared to 70.3% with chemotherapy (P=0.0002), with a hazard ratio of 0.51. Infections were significantly lower in the blinatumomab group (23.9% vs. 69.4%), though neurotoxic events were higher (12.0% vs. 3.2%). This offers a promising alternative to conventional chemotherapy, potentially improving outcomes and reducing treatment-related infections for children with high-risk B-cell ALL.
10.1056/NEJMoa2604166
Colonoscopy Intervals and Colorectal Cancer Incidence after Adenoma Removal.
NEW ENGL J MED · Q1 JOURNAL - RANK #2/332TOP-TIER
This interim analysis of a large-scale European noninferiority trial randomized 10,799 patients with high-risk adenomas to compare 5-year versus 3-year colonoscopy surveillance intervals. Results showed a 5-year cumulative colorectal cancer incidence of 0.77% in the 5-year group compared to 0.82% in the 3-year group, meeting the noninferiority criterion with a difference of -0.05 percentage points. The study demonstrates that extending the surveillance interval to 5 years does not significantly increase cancer risk or alter the stage of cancer at diagnosis for high-risk patients. These findings suggest that current guidelines recommending 3-year intervals may be safely extended, potentially reducing the procedural burden on patients and healthcare systems without compromising oncological safety.
10.1056/NEJMoa2603816
Viral mimicry escape as a necessary feature of malignant transformation.
NAT REV CANCER · Q1 JOURNAL - RANK #3/326TOP-TIER
This review article proposes a unifying conceptual model for viral mimicry escape as a necessary feature of malignant transformation and a therapeutic target. It outlines how cancer-associated changes lead to immunogenic nucleic acids, triggering viral mimicry as an intrinsic tumor-suppressive mechanism. Cancer cells suppress this response through epigenetic repression, RNA editing, and dampening interferon signaling, enabling their growth. Escaping viral mimicry is fundamental for cancer initiation and progression, suggesting it as a promising therapeutic target, particularly in combination with immunotherapies.
10.1038/s41568-026-00977-1
Financial Payments From Drug Manufacturers to Oncologists and Use of Guideline-Preferred Cancer Treatments.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This study investigated the influence of drug industry payments to oncologists on the likelihood of patients receiving guideline-preferred cancer treatments, analyzing Medicare claims data from 2014-2020 for 15,607 patients across 14 cancer scenarios. Oncologists receiving payments for guideline-preferred treatment showed a 6% increased likelihood of prescribing preferred treatment (RR=1.06), while payments for nonpreferred treatment were associated with a 7% decreased likelihood (RR=0.93). These findings are highly relevant to cancer care, demonstrating how financial ties can influence treatment decisions for cancer patients and adherence to NCCN guidelines. This highlights that industry payments are associated with increased use of promoted cancer treatments, regardless of guideline preference, impacting clinical practice and patient outcomes in oncology.
10.1200/JCO-26-00785
Circulating Tumor DNA Profiling Defines Risk Classification in Patients With Ewing Sarcoma: A Report From the Children’s Oncology Group and the LEOPARD Study.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This study prospectively validated circulating tumor DNA (ctDNA) as a prognostic factor and developed clinical-molecular risk groups in patients with Ewing sarcoma (EWS). Utilizing ultralow-pass whole-genome and hybrid capture panel sequencing on 395 patients, elevated baseline ctDNA was associated with inferior outcomes in localized (HR=2.36, p=.032) and metastatic disease (HR=2.15, p=.001). The research identified novel low-risk groups and differentiated patients into low-, intermediate-, and high-risk categories by integrating ctDNA burden with clinical-molecular features. These findings offer a crucial tool for risk stratification in EWS, directly impacting treatment planning and patient management in oncology.
10.1200/JCO-26-00285
Tambotatug Pelitecan in Small-Cell Lung Cancer after Platinum-Based Therapy.
NEW ENGL J MED · Q1 JOURNAL - RANK #2/332TOP-TIER
This phase 3 randomized trial evaluated tambotatug pelitecan versus topotecan in 451 patients with relapsed extensive-stage small-cell lung cancer after platinum-based therapy. Tambotatug pelitecan significantly improved median overall survival (13.3 vs. 9.4 months; HR 0.46, P<0.001) and progression-free survival (7.4 vs. 2.8 months; HR 0.29, P<0.001), with objective response rates of 59.1% versus 9.7%. Grade 3 or higher adverse events were lower with tambotatug pelitecan (55.4% vs. 77.9%). These findings support tambotatug pelitecan as a more effective and safer second-line option for this aggressive cancer.
10.1056/NEJMoa2610229
Clinical usability of an explainable AI decision support tool and evaluation of multimodal models in NSCLC.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
The I LUNG project (NCT05537922) evaluated AI-based decision support tools for immunotherapy selection in 2,396 NSCLC patients using real-world multimodal data. Machine learning (ML) and deep learning (DL) clinical and blood (CB)-only models achieved consistent performance (AUC up to 0.77 in the test set), significantly outperforming existing scores like PD-L1. An explainable AI tool improved physician prediction, demonstrating the clinical usefulness of AI in oncology. This pioneering framework, with ongoing prospective validation, holds significant implications for improving NSCLC treatment decisions.
10.1038/s41591-026-04488-2
Sep 07 – Sep 14, 2026
Patient-reported symptom monitoring in patients with lung cancer (SYMPRO-Lung trial): long-term, post-hoc survival results of a multicentre, stepped-wedged, cluster-randomised clinical trial.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This post-hoc analysis of the multicentre SYMPRO-Lung trial evaluated the impact of weekly online patient-reported outcome (PRO) symptom monitoring on long-term survival in 446 patients with stage I-IV lung cancer. At a median follow-up of 50 months, the intervention group achieved a median overall survival of 26 months compared to 21 months in the control group. Adjusted analysis indicated that PRO monitoring was associated with improved overall survival (HR 0.80, p=0.049), although no significant difference was observed in progression-free survival. These findings suggest that integrating routine digital symptom monitoring into oncology practice can provide a clinically meaningful 5-month survival advantage for lung cancer patients across all stages.
10.1016/S1470-2045(26)00305-0
Trastuzumab Botidotin Versus Trastuzumab Emtansine in Human Epidermal Growth Factor Receptor 2-Positive Advanced Breast Cancer: A Phase III, Open-Label, Randomized Controlled Trial.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This phase III trial randomized 365 patients with HER2-positive advanced breast cancer who had prior trastuzumab and taxane to trastuzumab botidotin or trastuzumab emtansine. Trastuzumab botidotin significantly improved median progression-free survival (11.1 vs 4.4 months; HR 0.39, 95% CI 0.30-0.51; p<0.0001) and objective response rate (76.9% vs 53.0%). Overall survival data were immature but favored the novel agent (HR 0.62). Grade ≥3 adverse events occurred in 69.8% vs 63.7%, with higher ocular toxicity for trastuzumab botidotin, though most resolved with a management algorithm.
10.1200/JCO-26-00602
COVID-19 vaccination around immune checkpoint inhibitor start and survival in a nationwide cohort of patients with cancer.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This nationwide cohort study investigated the association between COVID-19 mRNA vaccination timing (pre- or post-ICI initiation) and survival in 95,015 adults with cancer receiving immune checkpoint inhibitors. Both pre-ICI and post-ICI mRNA vaccination were associated with lower early all-cause mortality (e.g., pre-ICI HR 0.90 at 1-3 months; post-ICI HR 0.84 at 3 months), with similar patterns for cancer-specific mortality. These associations were transient, disappearing after 12 months, and potentially reflect healthy-vaccinee effects rather than a specific mRNA vaccine interaction. The findings suggest a modest, short-term survival benefit or healthy-vaccinee effect in vaccinated cancer patients on ICI therapy.
10.1038/s41591-026-04640-y
Management of Soft Tissue and Visceral Leiomyosarcomas.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
This international consensus review synthesizes evidence on diagnosing and managing soft tissue and visceral leiomyosarcomas, a rare mesenchymal cancer, using literature searches and expert panel input. Complete surgical resection remains the cornerstone for localized disease, while advanced disease benefits from anthracycline- or gemcitabine-based combinations, trabectedin, and tyrosine kinase inhibitors, though optimal sequencing is undefined. Molecular heterogeneity is recognized but not yet integrated into routine care, and prospective perioperative chemotherapy data are lacking. Clinically, the findings support multidisciplinary, site-specific management but highlight persistent uncertainties requiring leiomyosarcoma-specific trials.
10.1001/jamaoncol.2026.3366
Pembrolizumab Plus Chemotherapy for Cervical Cancer: An Exploratory Analysis of the KEYNOTE-826 Randomized Clinical Trial.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
This exploratory analysis of the phase 3 KEYNOTE-826 trial evaluated 5-year efficacy and safety of pembrolizumab plus platinum-based chemotherapy (with or without bevacizumab) in 617 patients with previously untreated persistent, recurrent, or metastatic cervical cancer. At median follow-up of 59.1 months, overall survival remained significantly improved with pembrolizumab in PD-L1 CPS ≥1 (median 28.6 vs 16.5 months; HR 0.62) and intention-to-treat (26.4 vs 16.8 months; HR 0.64) populations, with sustained progression-free survival benefit (median 10.5 vs 8.2 months; HR 0.58). No new safety signals emerged. These long-term data confirm pembrolizumab plus chemotherapy as a first-line standard-of-care option for recurrent/metastatic cervical cancer.
10.1001/jamaoncol.2026.3547
Development and external validation of a new prognostic model for metastatic clear cell renal cell carcinoma: a preregistered analysis using data from randomised clinical trials in the checkpoint inhibitor era.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This study developed and externally validated the new Clinical Prognostic Index in the Checkpoint Inhibitor era (CPI2) model for metastatic clear cell renal cell carcinoma (mccRCC), utilizing individual patient data from CheckMate-214 and CheckMate-9ER clinical trials. The CPI2 model, incorporating 14 readily available clinical parameters, showed improved discriminative accuracy at 36 months (0.72 in both cohorts) compared to the IMDC model (0.65 and 0.61). This enhanced prognostic tool directly aids clinicians in risk stratification and treatment decisions for cancer patients, particularly in the immune checkpoint inhibitor era. The model’s improved precision can inform clinical trial design and optimize personalized cancer therapy.
10.1016/S1470-2045(26)00338-4
Perioperative durvalumab plus fluorouracil, leucovorin, oxaliplatin, and docetaxel for resectable gastric and gastro-oesophageal junction adenocarcinoma (MATTERHORN): final results of overall survival and event-free survival by pathological response in a global, randomised, double-blind, placebo-controlled, multicentre, phase 3 trial.
LANCET · Q1 JOURNAL - RANK #1/332TOP-TIER
MATTERHORN is a global phase 3 trial evaluating perioperative durvalumab plus FLOT versus placebo plus FLOT in 948 patients with resectable gastric or gastro-oesophageal junction adenocarcinoma. Overall survival significantly improved with durvalumab (HR 0.78, 95% CI 0.63-0.96; p=0.021), meeting the prespecified significance threshold. Adverse events with fatal outcome possibly related to treatment occurred in 1% versus <1% of patients. Perioperative durvalumab plus FLOT represents a new standard treatment option for this cancer population.
10.1016/S0140-6736(26)01254-7
Treatment Decisions in Multiple Myeloma.
NEW ENGL J MED · Q1 JOURNAL - RANK #2/332TOP-TIER
This abstract provides a practical framework for navigating treatment decisions in multiple myeloma, a hematological cancer. It outlines how cytogenetic and genomic risk stratification, functional fitness, and measurable residual disease status individualize therapy in newly diagnosed disease, where quadruplet induction is standard and autologous transplantation is reevaluated. For relapse, it addresses sequencing of B-cell maturation antigen-directed CAR T cells, bispecific antibodies, and antibody-drug conjugates, emphasizing T-cell fitness and multiantigen targeting. The primary implication is to guide clinicians in personalizing therapy across the disease spectrum and encourage clinical trial enrollment for continued progress in cancer treatment.
10.1056/NEJMra2605253
LymphGen-Sig: Integrating Genetic and Transcriptional States to Predict Therapeutic Response in Diffuse Large B-Cell Lymphoma.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This study developed LymphGen-Sig (LGsig), a 294-gene expression-based platform designed to classify diffuse large B-cell lymphoma (DLBCL) by integrating genetic and transcriptional data from 764 patients. Validated using 678 samples from the POLARIX trial, LGsig successfully reclassified previously unassigned cases and TP53-altered tumors into biologically relevant clusters. The tool identified specific DLBCL subtypes that achieved superior survival outcomes with polatuzumab vedotin-R-CHP compared to standard R-CHOP therapy. By expanding molecular classification beyond traditional genetic markers, LGsig provides a robust framework for precision oncology and subtype-specific therapeutic decision-making in clinical practice.
10.1200/JCO-26-00451
Risk-Adapted Optimization of Neoadjuvant Therapy in Human Epidermal Growth Factor Receptor 2-Positive Early-Stage Breast Cancer.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This review article aims to optimize risk-adapted neoadjuvant therapy for HER2-positive early-stage breast cancer by examining de-escalation strategies and new treatment options. Randomized trial data indicate carboplatin can be safely omitted for most patients, achieving comparable pathological complete response rates with reduced toxicity. DESTINY-Breast11 and DESTINY-Breast05 trials established fam-trastuzumab deruxtecan-nxki as new FDA-approved options for high-risk disease, directly informing oncology practice. This supports a more precise, individualized approach to caring for patients, highlighting circulating tumor DNA monitoring and functional imaging for future investigation.
10.1200/JCO-26-01423
Personalized Circulating Tumor DNA Analysis for Predicting Outcomes and Tracking Response to Radiotherapy and Pembrolizumab in Localized Sarcomas: Analysis of the SU2C-SARC032 Trial.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This phase II randomized trial investigated personalized circulating tumor DNA (ctDNA) analysis to predict outcomes and track response to radiotherapy and pembrolizumab in 106 patients with high-risk, localized soft tissue sarcomas (STS). Personalized ctDNA profiling detected baseline ctDNA in 85% of patients, correlating with tumor size and grade, and levels across the perioperative course were strongly associated with disease-free and overall survival. Patients receiving pembrolizumab, who had significantly better disease-free survival, exhibited a greater decrease in ctDNA levels after neoadjuvant therapy. These findings demonstrate ctDNA’s utility as an independent prognostic and monitoring tool in STS, supporting future ctDNA-guided interventional trials in cancer management.
10.1200/JCO-26-00769
Early stage nonsmall cell lung cancer: Toward a risk-adaptive paradigm in the era of biologic precision.
CA-CANCER J CLIN · Q1 JOURNAL - RANK #1/326TOP-TIER
This review examines the evolving landscape of early stage nonsmall cell lung cancer, driven by low-dose CT screening and rising never-smoker incidence. It highlights therapeutic advances including parenchyma-sparing surgery, perioperative immunotherapy, and liquid biopsy monitoring. The authors propose a risk-adaptive paradigm using artificial intelligence and multi-omics to tailor treatment intensity. This approach aims to escalate therapy for high-risk patients while safely de-escalating for low-risk individuals, addressing TNM staging limitations and global disparities.
10.3322/caac.70100
Induction and extended consolidation with daratumumab, cyclophosphamide, bortezomib, lenalidomide, and dexamethasone in patients with high-risk multiple myeloma (OPTIMUM/MUKnine): 5-year follow-up of a multicentre, externally controlled, phase 2 trial.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This phase 2 externally controlled trial evaluated intensified induction and extended consolidation with daratumumab, cyclophosphamide, bortezomib, lenalidomide, and dexamethasone in 107 patients with high-risk multiple myeloma, compared to 120 genetically matched controls from the Myeloma XI trial. At a median follow-up of 71.1 months, progression-free survival was not reached versus 24.4 months (HR 0.32, 95% CI 0.22-0.45), and overall survival was not reached versus 57.4 months (HR 0.43, 95% CI 0.28-0.65). The survival benefit was consistent across molecular subgroups except for patients with three or more high-risk cytogenetic abnormalities. This study supports the use of risk-stratified, intensified therapy with molecular diagnostics to improve long-term outcomes in high-risk multiple myeloma, a form of blood cancer.
10.1016/S1470-2045(26)00286-X
Chemotherapy with or without pembrolizumab followed by maintenance pembrolizumab with or without olaparib as first-line treatment of patients with advanced BRCA non-mutated epithelial ovarian cancer (ENGOT-OV43/GOG-3036/KEYLYNK-001): a randomised, double-blind, placebo-controlled, phase 3 trial.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This phase 3, randomized, double-blind trial evaluated pembrolizumab plus chemotherapy followed by pembrolizumab-olaparib maintenance as first-line treatment for advanced BRCA non-mutated epithelial ovarian cancer. The pembrolizumab-olaparib regimen significantly improved progression-free survival (PFS) versus control in the intention-to-treat population (HR 0·68 [95% CI 0·58-0·81]; p<0·0001), with the benefit maintained at final analysis (HR 0·71). Pembrolizumab alone did not show significant PFS improvement, but the combination directly addresses a critical need for improved first-line therapies in this specific cancer subtype. This regimen could represent a clinically meaningful advancement for newly diagnosed stage III-IV BRCA non-mutated epithelial ovarian cancer patients.
10.1016/S1470-2045(26)00223-8
Induction and consolidation atezolizumab with stereotactic body radiation therapy versus radiation alone in high-risk, early-stage non-small-cell lung cancer (SWOG/NRG S1914): a multicentre, open-label, superiority, phase 3, randomised controlled trial.
LANCET · Q1 JOURNAL - RANK #1/332TOP-TIER
This phase 3 randomized controlled trial (SWOG/NRG S1914) investigated adding atezolizumab to stereotactic body radiation therapy (SBRT) for high-risk, early-stage, medically inoperable non-small-cell lung cancer (NSCLC), with overall survival as the primary objective. The trial, enrolling 402 eligible patients, closed early for futility, finding no improvement in overall survival (HR 1.04, 95% CI 0.69-1.58; 2-year OS 82% in both groups) with the combination. Importantly, grade 3 or higher adverse events were significantly higher with atezolizumab plus SBRT (12% vs 3% with SBRT alone), including two grade 5 respiratory events. These results directly inform cancer treatment, indicating that adding atezolizumab to SBRT does not improve outcomes and increases toxicity for this specific NSCLC patient population.
10.1016/S0140-6736(26)01655-7
The changing therapeutic landscape of small-cell lung cancer.
LANCET · Q1 JOURNAL - RANK #1/332TOP-TIER
This Series paper summarizes the evolving therapeutic landscape for small-cell lung cancer (SCLC), an exceptionally aggressive malignancy, by reviewing current standards of care, recent biological advances, and emerging novel approaches. Advances in understanding SCLC biology, particularly defining cell-surface proteins, have led to targeted therapies like T-cell engagers, antibody-drug conjugates, radioconjugates, and cell therapies, showing substantial preliminary efficacy. These novel approaches offer new hope for improved management of SCLC, a disease historically refractory to standard treatments after recurrence. The paper highlights promising strategies that could transform clinical practice for this lethal cancer.
10.1016/S0140-6736(26)01244-4