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Jun 01 – Jun 08, 2026
MAGE-A4/MAGE-A8-targeted TCR-based bispecific T cell engager in recurrent and/or refractory solid tumors: a phase 1 trial.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This phase 1 first-in-human trial evaluated IMA401, a TCR-based bispecific T cell engager targeting MAGE-A4/MAGE-A8, in 61 patients with recurrent or refractory solid tumors. The recommended phase 2 dose was established at 1-2 mg biweekly, with a manageable safety profile featuring 38% grade 1-2 cytokine release syndrome and no maximum tolerated dose reached. Efficacy results showed a 20% objective response rate at the recommended dose across multiple indications, notably reaching 29% in head and neck cancer patients. These findings demonstrate the clinical potential of the bispecific TCER platform as a promising immunotherapy for advanced malignancies.
10.1038/s41591-026-04455-x
A randomised study of encorafenib, cetuximab, and FOLFIRI versus FOLFIRI with or without bevacizumab in BRAF V600E-mutant colorectal cancer: BREAKWATER Cohort 3.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This randomized study (BREAKWATER Cohort 3) evaluated encorafenib, cetuximab, and FOLFIRI (EC+FOLFIRI) versus FOLFIRI with or without bevacizumab in 147 previously untreated BRAF V600E-mutant metastatic colorectal cancer patients. EC+FOLFIRI significantly improved objective response rate (64.4% vs 39.2%, P=0.0011) and progression-free survival (15.2 vs 8.3 months, HR=0.44, P=0.0002). Prolonged overall survival (HR=0.56) was also observed, with a manageable safety profile. These findings support EC+FOLFIRI as a new standard of care, enabling personalized treatment for this specific cancer subtype.
10.1016/j.annonc.2026.04.017
PARP and Androgen-Signaling Inhibition plus ADT in Metastatic Prostate Cancer.
NEW ENGL J MED · Q1 JOURNAL - RANK #2/332TOP-TIER
This Phase 3 trial (TALAPRO-3) evaluated the efficacy of adding the PARP inhibitor talazoparib to enzalutamide in 599 patients with metastatic androgen pathway modulation-sensitive prostate cancer harboring homologous recombination repair gene alterations. At three years, imaging-based progression-free survival was significantly higher in the talazoparib group at 77% compared to 56% in the control group (HR 0.48; 95% CI, 0.36 to 0.65; P<0.001). While overall survival showed a positive trend (78% vs. 72%), clinicians must manage increased toxicity, as 51% of patients receiving talazoparib experienced grade 3 or higher anemia. These results support the use of combination PARP and androgen-signaling inhibition as a potent first-line strategy for this specific molecular subset of metastatic prostate cancer.
10.1056/NEJMoa2604126
Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer.
NEW ENGL J MED · Q1 JOURNAL - RANK #2/332TOP-TIER
This phase 3, international, open-label, randomized trial investigated daraxonrasib versus chemotherapy in 500 patients with previously treated metastatic pancreatic ductal adenocarcinoma (mPDAC). Daraxonrasib, an oral RAS(ON) inhibitor, significantly improved median overall survival to 13.2 months compared to 6.6 months with chemotherapy in the KRAS G12 population (HR 0.40, P<0.001). Similarly, median progression-free survival was 7.3 months versus 3.5 months (HR 0.45, P<0.001). These findings demonstrate daraxonrasib’s superior efficacy, offering a promising new therapeutic option for clinicians managing advanced pancreatic cancer.
10.1056/NEJMoa2605555
Perioperative Apalutamide in High-Risk Localized Prostate Cancer.
NEW ENGL J MED · Q1 JOURNAL - RANK #2/332TOP-TIER
This phase 3 trial evaluated the efficacy of perioperative androgen-deprivation therapy (ADT) plus apalutamide versus ADT plus placebo in 2,109 patients undergoing radical prostatectomy for high-risk localized prostate cancer. Apalutamide significantly improved pathological complete response or minimal residual disease rates (8.9% vs. 1.0%; OR 10.17) and 5-year metastasis-free survival (78.2% vs. 73.5%; HR 0.80). The treatment also showed superior event-free survival and delayed subsequent therapy, though it was associated with higher rates of grade 3/4 adverse events, particularly rash (39.6% vs. 31.0%). These results suggest that adding apalutamide to perioperative ADT provides a significant oncologic benefit for patients with high-risk localized prostate cancer, potentially redefining the standard of care.
10.1056/NEJMoa2603878
EP4 Antagonist ONO-4578 Plus Nivolumab and Chemotherapy in HER2-Negative Unresectable Advanced or Recurrent Gastric or Gastroesophageal Junction Cancer.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This multicenter, randomized phase 2 study evaluated the efficacy of adding ONO-4578, an EP4 antagonist, to nivolumab and chemotherapy as first-line treatment for 226 patients with HER2-negative advanced gastric or gastroesophageal junction cancer. The ONO-4578 group demonstrated a significant improvement in progression-free survival (HR 0.67; p=0.040) and a higher objective response rate of 62.0% compared to 48.7% in the placebo group. Exploratory analyses indicated that clinical benefits were most pronounced in patients with PD-L1 CPS ≥1, while safety profiles remained manageable despite increased rates of diarrhea and anemia. These results suggest that targeting the PGE2-EP4 axis may overcome tumor immunosuppression, providing a promising therapeutic strategy that warrants further validation in phase 3 clinical trials.
10.1200/JCO-26-01072
Intismeran Autogene Plus Pembrolizumab Versus Pembrolizumab Alone in High-Risk Resected Melanoma: 5-Year Update of the Randomized Phase 2b KEYNOTE-942 Study.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This phase 2b randomized study evaluated the 5-year efficacy of intismeran, an individualized mRNA neoantigen therapy, combined with pembrolizumab versus pembrolizumab alone in 157 patients with resected high-risk melanoma. The combination therapy significantly prolonged recurrence-free survival (HR 0.510; 95% CI, 0.294–0.887) and distant metastasis-free survival (HR 0.411; 95% CI, 0.200–0.843) compared to monotherapy. These findings demonstrate sustained clinical benefit and a manageable safety profile, supported by increased T-cell receptor clonality in the combination arm. For clinicians, this suggests that personalized mRNA vaccines may provide durable long-term protection against recurrence in advanced melanoma patients.
10.1200/JCO-26-00835
Pemigatinib for Unresectable or Metastatic Cholangiocarcinoma With Fibroblast Growth Factor Receptor-2 Rearrangement: Results From the Phase 3 FIGHT-302 Trial.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This phase 3 randomized trial (FIGHT-302) evaluated the efficacy and safety of first-line pemigatinib compared to gemcitabine plus cisplatin chemotherapy in 167 adults with advanced FGFR2-rearranged cholangiocarcinoma. Pemigatinib significantly improved median progression-free survival to 8.3 months compared to 6.8 months for chemotherapy (HR 0.58; p=0.0078), with a notably higher objective response rate of 47% versus 15%. Although median overall survival was similar between groups (24.4 vs. 25.0 months), pemigatinib demonstrated a superior duration of response (14.2 vs. 6.3 months) with a safety profile consistent with previous findings. These results support pemigatinib as a potent first-line targeted therapy option for patients with this specific genetic rearrangement, offering a non-chemotherapeutic alternative with improved progression control.
10.1200/JCO-26-00788
Cost-Effectiveness of Fecal Immunochemical Testing Alone vs Co-Testing With Helicobacter pylori Stool Antigen.
JAMA-J AM MED ASSOC · Q1 JOURNAL - RANK #4/332TOP-TIER
This Markov model cost-effectiveness analysis, based on a Taiwanese pragmatic trial, evaluated adding one-time Helicobacter pylori stool antigen testing to biennial FIT screening for colorectal cancer. Compared to FIT alone, co-testing was dominant (cost-saving) in Taiwan, with an incremental cost-effectiveness ratio of -$2,094 per QALY gained and a 5-fold return on investment. Co-testing remained cost-effective in US settings when H pylori prevalence exceeded 21.9%, preventing gastric and colorectal cancer mortality. For a clinician focused on cancer, this provides strong evidence that combined screening improves cancer outcomes and is economically favorable, particularly in populations with moderate H pylori prevalence.
10.1001/jama.2026.6908
Adjuvant Nivolumab vs Observation in Resected Non-Small Cell Lung Cancer: A Randomized Clinical Trial.
JAMA-J AM MED ASSOC · Q1 JOURNAL - RANK #4/332TOP-TIER
This randomized phase 3 study investigated if adjuvant nivolumab improved disease-free survival (DFS) and overall survival in 935 patients with resected non-small cell lung cancer (NSCLC) without EGFR/ALK alterations, comparing nivolumab to observation after standard adjuvant therapy. After a median follow-up of 72.6 months, median DFS was 71.3 months with nivolumab versus 68.8 months with observation (HR 0.97; P=.39), showing no significant improvement. In patients with PD-L1 ≥50%, median DFS was 89.8 months with nivolumab versus 78.5 months with observation (HR 0.86; P=.22), also without significant benefit. The study concludes that adjuvant nivolumab, in this specific post-adjuvant chemotherapy/radiotherapy setting, does not improve DFS in resected NSCLC, guiding against its use in this context.
10.1001/jama.2026.8992
Tumor-Agnostic Therapies: Translating Scientific Breakthroughs Into Global Implementation.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This review investigates the global landscape of tumor-agnostic cancer therapies, their regulatory approvals, and implementation challenges across diverse regions. It identifies significant barriers in regulatory, reimbursement, infrastructure, and workforce domains, revealing that fewer than 50% of eligible patients receive matched therapies. The study is highly relevant to cancer care, highlighting practical issues affecting patient access to advanced treatments. It proposes a four-pillar framework for equitable implementation, focusing on biomarker testing, innovative trials, harmonized regulations, and workforce development to bridge the gap between innovation and accessibility for cancer patients.
10.1200/JCO-26-00034
Fovinaciclib for First-Line Therapy of Advanced Breast Cancer: A Randomized Clinical Trial.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
This phase 3 randomized clinical trial evaluated fovinaciclib plus an aromatase inhibitor as first-line therapy for 417 patients with hormone receptor-positive, ERBB2-negative advanced breast cancer. The fovinaciclib group demonstrated a significantly prolonged median progression-free survival compared to the placebo group (not reached vs 20.2 months; HR 0.55; P < .001). Clinically, the addition of fovinaciclib provides a meaningful efficacy benefit with a manageable safety profile and no detrimental impact on patient quality of life. These findings suggest fovinaciclib is a potent first-line treatment option for this specific oncological population.
10.1001/jamaoncol.2026.1938
Aglatimagene besadenovec (CAN-2409) with radiotherapy for patients with localised prostate cancer: a phase 3, multicentre, randomised, double-blind, placebo-controlled trial.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This phase 3 randomized trial evaluated the efficacy of adding aglatimagene besadenovec (CAN-2409) plus valacyclovir to standard external beam radiation therapy in 745 patients with intermediate or high-risk localized prostate cancer. After a median follow-up of 50.3 months, the treatment group demonstrated significantly improved disease-free survival compared to placebo (HR 0.70, 95% CI 0.52-0.94; p=0.016), with the median DFS not yet reached in the intervention arm. The intervention showed a manageable safety profile, with grade 3 or worse adverse events occurring in 8% of the aglatimagene group versus 7% in the placebo group. These results suggest that aglatimagene provides a meaningful clinical benefit for localized prostate cancer patients by enhancing the effects of radiotherapy without increasing significant toxicity.
10.1016/S1470-2045(26)00071-9
International disruptions to cancer diagnosis and stage at presentation during the COVID-19 pandemic in 2020: an International Cancer Benchmarking Partnership (ICBP) population-based study.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This population-based study analyzed 2.6 million patients across seven countries to evaluate how the COVID-19 pandemic disrupted the incidence and staging of seven major cancer types in 2020. Researchers found that 16% (55,713) of expected cancer cases were missing between April and December 2020, with the highest deficits occurring in prostate (24%), breast (18%), and melanoma (18%) diagnoses. The data reveals significant regional variations, such as a 54% deficit in UK prostate cancer cases, highlighting critical gaps in screening and diagnostic access during lockdowns. These findings underscore a pressing clinical need to address diagnostic backlogs and monitor for potential stage shifts in patients whose diagnoses were delayed by pandemic-related healthcare barriers.
10.1016/S1470-2045(26)00089-6
Perioperative serplulimab with neoadjuvant chemotherapy versus perioperative chemotherapy in PD-L1-positive gastric cancer (ASTRUM-006): a randomised, double-blind, multicentre, phase 3 study.
LANCET · Q1 JOURNAL - RANK #1/332TOP-TIER
This phase 3 randomized trial evaluated the efficacy of perioperative serplulimab combined with neoadjuvant SOX chemotherapy followed by adjuvant serplulimab versus chemotherapy alone in 588 patients with PD-L1-positive resectable gastric or gastro-oesophageal junction adenocarcinoma. In the PD-L1 CPS ≥10 population, median event-free survival was significantly longer with serplulimab (not reached vs 42.0 months; HR 0.65; p=0.0082), a benefit also observed in the intention-to-treat population (HR 0.73; p=0.015). The serplulimab regimen demonstrated a superior safety profile, with grade 3 or worse treatment-related adverse events occurring in 47% of patients compared to 59% in the chemotherapy-only group. These results support perioperative serplulimab as a potent treatment strategy for PD-L1-positive gastric cancer, though long-term overall survival data are still required to confirm definitive clinical advantage.
10.1016/S0140-6736(26)00974-8
Chemotherapy for patients with circulating tumour DNA positive, stage II colon cancer (CIRCULATE) - an AIO / ABCSG trial.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This randomized trial (CIRCULATE) evaluated the efficacy of adjuvant chemotherapy versus observation in patients with stage II, pMMR/MSS colon cancer who tested positive for postoperative circulating tumor DNA (ctDNA). Results confirmed ctDNA as a potent prognostic marker, with ctDNA-positive patients showing significantly lower 3-year disease-free survival (DFS) compared to ctDNA-negative patients (52% versus 87%, HR 4.28). While the intention-to-treat analysis was underpowered due to early trial closure, per-protocol analysis demonstrated that chemotherapy significantly improved 3-year DFS (77% versus 38%, HR 0.31, P=0.021) in ctDNA-positive individuals. These findings suggest that ctDNA-guided adjuvant therapy decisions can identify high-risk stage II patients who benefit from chemotherapy, potentially refining current treatment paradigms in oncology.
10.1016/j.annonc.2026.05.001
SEZ6-targeting antibody-drug conjugate ABBV-706 in advanced small cell lung cancer and solid tumors: a phase 1 trial.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This phase 1 trial evaluated ABBV-706, a SEZ6-targeting antibody-drug conjugate, in 288 patients with advanced solid tumors, specifically focusing on relapsed/refractory small cell lung cancer (R/R SCLC). In the R/R SCLC cohort, the objective response rate was 52%, with a median overall survival of 12.4 months at the 1.8 mg/kg dose. Safety data showed grade 3 or higher treatment-related adverse events in 61% of patients, primarily anemia and fatigue, which were dose-dependent. These findings establish 1.8 mg/kg every three weeks as the recommended phase 2 dose, offering a promising new therapeutic strategy for neuroendocrine-derived cancers.
10.1038/s41591-026-04452-0
Savolitinib in MET-amplified gastric or gastroesophageal junction adenocarcinoma: a phase 2 trial.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This phase 2 multicenter trial evaluated the efficacy and safety of savolitinib, an oral MET inhibitor, in 110 patients with MET-amplified, locally advanced or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma who had progressed on prior systemic therapies. In the pivotal phase cohort of 65 patients, the independent review committee-assessed objective response rate was 32.3% (95% CI: 21.2–45.1%), successfully meeting the predefined efficacy threshold. Regarding safety, grade 3 or higher treatment-related adverse events occurred in 34.5% of the total cohort, with one treatment-related death reported. These results demonstrate that savolitinib provides encouraging antitumor activity and a manageable safety profile for heavily pretreated patients with MET-amplified G/GEJ cancer, warranting further validation in randomized controlled trials.
10.1038/s41591-026-04459-7
A Randomized Phase III Trial of Anthracyclines Followed by Taxane versus Taxane Plus Carboplatin as (Neo)Adjuvant Therapy in Patients with Triple-Negative Breast Cancer: KCSG BR 15-1 PEARLY Trial.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This multicenter, randomized phase III trial evaluated the efficacy of adding carboplatin to standard anthracycline-taxane chemotherapy in 868 patients with early-stage triple-negative breast cancer (TNBC). At a 57.2-month median follow-up, the carboplatin arm significantly improved 5-year event-free survival from 75.1% to 82.3% (HR 0.67; 95% CI: 0.49-0.92; P=0.012). While grade 3 or higher adverse events were more frequent with carboplatin (74.7% vs. 56.7%), secondary endpoints like overall survival showed positive trends without compromising quality of life. These results support incorporating carboplatin into (neo)adjuvant regimens for early TNBC to improve long-term clinical outcomes despite increased hematological toxicity.
10.1016/j.annonc.2026.05.703
Lorlatinib versus crizotinib as first-line treatment for advanced ALK-positive non-small cell lung cancer: 7-year update from the phase 3 CROWN study.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This 7-year update of the phase 3 CROWN study evaluated lorlatinib versus crizotinib as first-line treatment for 296 treatment-naive patients with advanced ALK-positive NSCLC. Lorlatinib demonstrated unprecedented long-term benefit, with median PFS not reached (NR) versus 9.1 months for crizotinib (HR, 0.19), and a 7-year PFS of 55% versus 3%. No new intracranial progression events occurred after 30 months on lorlatinib. These findings are highly relevant for cancer clinicians, indicating that lorlatinib provides superior, durable disease control, potentially transforming advanced ALK-positive NSCLC into a chronic condition.
10.1016/j.annonc.2026.05.692
Structured exercise program following adjuvant chemotherapy for colon cancer: A cost-utility analysis of the CHALLENGE trial.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This economic evaluation of the phase III CHALLENGE trial assessed the cost-utility of a three-year structured exercise program (SEP) versus health education materials in 889 patients with stage II/III colon cancer. Results demonstrated that the SEP was dominant over education, being less costly (-$1,589 CAD) and more effective (+0.05 life-years; +0.10 QALYs) over a five-year horizon. For clinicians treating colon cancer, these findings provide robust evidence that exercise interventions not only improve survival but also reduce overall healthcare costs by potentially mitigating cancer recurrence. The study supports the integration of structured exercise into routine post-chemotherapy oncology care as a high-value, cost-saving strategy for health systems.
10.1200/JCO-26-00765
Low-Dose Tamoxifen in Noninvasive Breast Neoplasia: Long-Term Results From an Individual-Participant Data Pooled Analysis.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This pooled analysis evaluated low-dose tamoxifen (5 mg daily or 10 mg every other day) versus control for preventing breast cancer events in 1,545 women with ER-positive/unknown DCIS, microinvasive carcinoma, or high-risk lesions over a median 9.4 years. Low-dose tamoxifen significantly reduced overall breast cancer events, particularly in postmenopausal women (HR, 0.51; 10-year absolute reduction of 11.2%). Although no overall reduction was seen in premenopausal women, contralateral breast cancer was reduced (HR, 0.45), with infrequent serious adverse events. These findings are highly relevant for clinicians managing breast cancer risk, supporting endocrine dose de-escalation to improve the benefit-risk profile for prevention in DCIS and high-risk lesions.
10.1200/JCO-26-00841
Neoadjuvant Sacituzumab Govitecan in Patients With Muscle-Invasive Bladder Cancer: Primary Results of the SURE-01 Trial.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
The phase II SURE-01 trial investigated neoadjuvant sacituzumab govitecan (SG) followed by radical cystectomy in 44 patients with muscle-invasive bladder cancer (MIBC) ineligible for or refusing standard chemotherapy. The study reported an overall ypT0N0-x rate of 29.5% (95% CI, 16.7 to 45.2), with enrichment in nonluminal subtypes (46% vs 14% in luminal), and a 24-month event-free survival rate of 71.4% (95% CI, 58 to 87.8). SG, at a reduced dose of 7.5 mg/kg, demonstrated activity and a manageable safety profile, corroborating TROP2 as a suitable target for MIBC treatment. This offers a promising neoadjuvant option for MIBC patients who cannot receive standard chemotherapy, potentially improving outcomes in a high-risk population.
10.1200/JCO-26-00142
Impact of Population-Based Pathogenic Variant Testing on Risk-Based Breast Screening Recommendations: A Secondary Analysis of the WISDOM Study.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
This cohort study, a secondary analysis of the WISDOM trial, evaluated how many pathogenic variant (PV) carriers in breast cancer genes would be recommended for high-risk screening based on clinical risk or clinical plus polygenic risk models. Among 712 women with PVs, including 232 high-penetrance carriers, only 0.9% of high-penetrance PV carriers would have received the same high-risk screening assignment based on clinical plus polygenic risk. Furthermore, 63.8% of PV carriers aged 40-49 and 88.9% aged 50-74 would have been recommended less intensive screening. These findings highlight that population-based PV testing identifies a distinct subset of high-risk women for breast cancer, underscoring its importance in risk-based screening strategies.
10.1001/jamaoncol.2026.2091
Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy in advanced squamous non-small-cell lung cancer (HARMONi-6): interim overall survival analysis of a randomised, double-blind, phase 3 trial in China.
LANCET · Q1 JOURNAL - RANK #1/332TOP-TIER
This phase 3 randomized trial (HARMONi-6) compared ivonescimab, a PD-1/VEGF bispecific antibody, plus chemotherapy against tislelizumab plus chemotherapy as first-line treatment for 532 patients with advanced squamous non-small-cell lung cancer. At a median follow-up of 21.4 months, ivonescimab significantly improved median overall survival to 27.9 months compared to 23.7 months with tislelizumab (HR 0.66; p=0.0017). While grade 3 or higher treatment-related adverse events were more frequent in the ivonescimab group (69% vs 59%), the survival benefit remained consistent across key patient subgroups. These results establish ivonescimab plus chemotherapy as a superior first-line therapeutic option, offering a clinically meaningful survival advantage for patients with advanced squamous lung cancer.
10.1016/S0140-6736(26)00966-9
May 25 – Jun 01, 2026
Cancer Diagnostic Delay Rates Associated With a Population-Based Screening Trial Evaluating a Cell-Free DNA Multicancer Early Detection Test.
JAMA-J AM MED ASSOC · Q1 JOURNAL - RANK #4/332TOP-TIER
This cross-sectional study used a difference-in-differences design to evaluate whether regional participation in the NHS-Galleri multicancer early detection (MCED) trial affected cancer diagnostic delay rates across 21 regions in England. In the first six months, participating regions saw diagnostic delay rates rise from 28.6% to 29.6%, while non-participating regions decreased from 28.9% to 26.3%, representing a 3.4 percentage point adjusted difference (P < .001). The study highlights that large-scale cancer screening trials can increase system-level demand, evidenced by a 4.8 percentage point increase in delays during the second six-month period and higher referral rates. Clinicians and health systems must account for these “spillover effects” on existing cancer diagnostic pathways when implementing population-based screening interventions to ensure timely care for all suspected cancer patients.
10.1001/jama.2026.6803
Addition of Intravesical Recombinant BCG to Perioperative Chemo-Immunotherapy in Muscle-Invasive Bladder Cancer: Primary Analysis of the Single-Arm Phase 2 Trial SAKK 06/19.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This single-arm phase II trial (SAKK 06/19) investigated neoadjuvant intravesical recombinant BCG (rBCG) combined with chemo-immunotherapy (atezolizumab, cisplatin/gemcitabine) in 47 patients with cT2-T4a N0-1 muscle-invasive bladder cancer (MIBC) prior to radical cystectomy. The primary endpoint, centrally reviewed pathological complete response (pCR), was 68% (27/40), with a pathological overall response (PaR) of 83% (33/40). These high response rates are clinically significant for MIBC, a cancer with substantial morbidity, suggesting a promising new neoadjuvant strategy. The findings warrant further investigation in prospective randomized trials to potentially improve outcomes for MIBC patients.
10.1200/JCO-26-00845
Sacituzumab tirumotecan plus pembrolizumab versus pembrolizumab in PD-L1-positive advanced non-small-cell lung cancer (OptiTROP-Lung05): interim analysis of a randomised, open-label, phase 3 trial.
LANCET · Q1 JOURNAL - RANK #1/332TOP-TIER
This phase 3 randomized trial (OptiTROP-Lung05) evaluated the efficacy of sacituzumab tirumotecan plus pembrolizumab versus pembrolizumab monotherapy as first-line treatment for 413 patients with PD-L1-positive advanced non-small-cell lung cancer. The combination therapy significantly improved median progression-free survival compared to pembrolizumab alone (not reached vs. 5.7 months; HR 0.35, p<0.0001), with consistent benefits across PD-L1 expression subgroups. While grade 3 or higher adverse events were more frequent in the combination group (55% vs. 31%), the substantial survival benefit suggests a potential new standard of care for advanced NSCLC. This study directly addresses the clinician’s interest in cancer research by providing high-level evidence for a novel therapeutic strategy in a major malignancy.
10.1016/S0140-6736(26)00968-2
Updated Results of the POSITIVE (Pregnancy Outcome and Safety of Interrupting Therapy for Women with Endocrine Responsive Breast Cancer) Trial.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This single-arm prospective trial (POSITIVE) evaluated temporary interruption of adjuvant endocrine therapy (ET) for up to 2 years to allow pregnancy in 518 women under 42 with hormone receptor-positive early breast cancer. At a median follow-up of 71 months, 5-year breast cancer-free interval events were 12.3% in POSITIVE versus 13.2% in matched SOFT/TEXT controls (difference -0.9%; CI -4.2 to 2.6%), and distant recurrence-free interval events were 6.2% vs 8.3% (difference -2.1%; CI -4.5 to 0.4%). Among 497 women, 76% had at least one pregnancy and 69% had at least one live birth, with 440 offspring. These updated results confirm that temporarily pausing ET for pregnancy does not increase short-term cancer recurrence risk, supporting shared decision-making in young patients desiring pregnancy.
10.1016/j.annonc.2026.05.699
Circulating Tumor DNA in Early Breast Cancer: A Review.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
This review summarizes current data on circulating tumor DNA (ctDNA) minimal residual disease (MRD) assays in early breast cancer, evaluating their potential as a noninvasive biomarker. Key findings indicate ctDNA dynamics during neoadjuvant therapy are associated with pathologic complete response, and post-treatment ctDNA positivity strongly correlates with future distant recurrence. While ctDNA assays show established analytical and clinical validity, their optimal clinical utility and impact on patient outcomes through guided management remain uncertain. The study emphasizes that ctDNA holds promise for refining risk stratification and earlier recurrence detection in early breast cancer, but prospective interventional trials are essential to demonstrate improved outcomes.
10.1001/jamaoncol.2026.1465
Colorectal cancer screening: An update to the American Cancer Society guideline, 2026.
CA-CANCER J CLIN · Q1 JOURNAL - RANK #1/326TOP-TIER
The American Cancer Society (ACS) updated its colorectal cancer (CRC) screening guideline, systematically reviewing new molecular-based tests and modeling studies to assess their impact on incidence and mortality. The ACS reaffirms screening at age 45. New next-generation mt-sDNA and mt-sRNA tests, showing high sensitivity for CRC and moderate for advanced precancerous lesions, are now preferred stool-based options every 3 years. Blood-based tests demonstrated lower sensitivity for advanced precancerous lesions and stage I cancers, predicting less effectiveness, and are recommended only for individuals declining preferred tests. This update provides critical guidance for clinicians on effective cancer screening strategies, emphasizing patient choice and timely colonoscopy follow-up for positive non-colonoscopy results to improve CRC detection.
10.3322/caac.70083
No Smoker Left Behind: Evaluation of a Population-Based, Opt-Out Smoking Cessation Program for Patients With Cancer Who Smoke.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This study evaluated the “No Smoker Left Behind” program, a population-based, opt-out smoking cessation initiative involving 3,706 eligible smokers within a cohort of 37,478 cancer patients at a comprehensive cancer center. Among patients receiving referrals, 16.2% achieved ≥8-day abstinence at 180 days, with significantly higher quit rates in patients with smoking-related cancers (23.7%) compared to non-smoking-related types (14.7%). The program demonstrated high reach among Black and publicly insured patients, though racial disparities in abstinence rates (14.4% for Black vs. 25.7% for White patients) persist. With a cost-per-quit of $6,067, this proactive outreach model offers a feasible, resource-efficient strategy for integrating essential tobacco cessation services into standard oncology practice to improve patient outcomes.
10.1200/JCO-25-02029
Long-Term Analysis of NRG Oncology RTOG 0539: A Phase II Trial of Observation for Low-Risk Meningioma and Radiotherapy for Intermediate- and High-Risk Meningioma.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This phase II trial evaluated a risk-adapted management strategy for WHO grade 1-3 meningioma, utilizing observation for low-risk patients and specific radiotherapy doses (54 Gy or 60 Gy) for intermediate- and high-risk cohorts. At a 12-year median follow-up, 10-year progression-free survival rates were 85.2% for low-risk, 72.2% for intermediate-risk, and 42.5% for high-risk groups, while overall survival reached 94.1%, 84.7%, and 51.1%, respectively. The study demonstrates that observation is viable for low-risk tumors, while radiotherapy provides structured control for more aggressive grades, despite grade 3+ toxicities occurring in up to 15.1% of high-risk patients. These long-term results establish definitive benchmarks for meningioma management and validate risk-stratification protocols in neuro-oncology practice.
10.1200/JCO-25-01441
Zanidatamab with and without Tislelizumab in HER2-Positive Gastroesophageal Cancer.
NEW ENGL J MED · Q1 JOURNAL - RANK #2/332TOP-TIER
This phase 3 trial compared zanidatamab plus chemotherapy, with or without tislelizumab, against trastuzumab plus chemotherapy as first-line treatment for HER2-positive advanced gastroesophageal adenocarcinoma. At 25.9 months median follow-up, zanidatamab-tislelizumab-chemotherapy and zanidatamab-chemotherapy significantly improved progression-free survival (median 12.4 months for both) versus trastuzumab-chemotherapy (8.1 months) (HR 0.63 and 0.65, P<0.001). Overall survival was also longer with zanidatamab-tislelizumab-chemotherapy (26.4 months) compared to trastuzumab-chemotherapy (19.2 months) (HR 0.72, P=0.004). These results indicate that zanidatamab-based regimens, especially with tislelizumab, offer superior efficacy for this specific cancer, potentially establishing new first-line treatment standards.
10.1056/NEJMoa2517729
Predicting neoadjuvant breast cancer therapy response using BRIDGE from tumor transcriptomics and histopathology.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This study developed BRIDGE, a computational framework, to predict pathological complete response (pCR) to neoadjuvant breast cancer therapy by analyzing pre-treatment tumor transcriptomics and histopathology. Trained on 10 and tested on 24 datasets, BRIDGE outperformed commercial signatures, achieving ROC-AUCs of 0.84 (OR=8) in ER+/HER2- tumors, 0.77 (OR=8.3) in HER2+, and 0.73 (OR=3.1) in TNBC. A histology-based version, BRIDGE-Slide, also showed superior performance, offering a potential fast, low-cost biomarker. This framework directly addresses a critical need in cancer management by enabling early, personalized treatment decisions for breast cancer patients.
10.1016/j.annonc.2026.05.700
Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, 2026.3.1.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This ASCO Living Guideline provides evidence-based recommendations for targeted therapy in Stage IV non-small cell lung cancer (NSCLC) with driver alterations. It focuses on molecular subtypes such as EGFR, ALK, ROS1, BRAF, and others, offering treatment algorithms. Clinical outcomes include improved progression-free survival and overall survival with matched targeted agents compared to chemotherapy. The guideline directly supports clinical decision-making for advanced NSCLC, aligning with the clinician’s interest in cancer-focused research.
10.1200/JCO-26-00843
Fibroblast growth factor receptor inhibition for succinate dehydrogenase-deficient gastrointestinal stromal tumors: a phase 2 trial.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This phase 2 trial investigated the pan-fibroblast growth factor receptor inhibitor rogaratinib in 24 patients with advanced succinate dehydrogenase-deficient gastrointestinal stromal tumors (SDH-deficient GIST). The study found an objective response rate of 41.7%, with a median progression-free survival of 31.0 months and a 1-year PFS of 77.4%. Rogaratinib demonstrated manageable toxicities, including hyperphosphatemia, consistent with target engagement. This research highlights a successful targeted cancer therapy for SDH-deficient GIST, predicated on an epigenetic mechanism of oncogene activation, offering a promising new treatment strategy.
10.1038/s41591-026-04376-9
Therapy for Stage IV Non-Small Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, 2026.3.1.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This ASCO living guideline provides evidence-based recommendations for the systemic treatment of patients with Stage IV non-small cell lung cancer (NSCLC) lacking actionable driver alterations. The update synthesizes data from recent clinical trials, emphasizing first-line combinations of immune checkpoint inhibitors with or without platinum-based chemotherapy to improve overall survival. For patients with high PD-L1 expression (≥50%), pembrolizumab monotherapy remains a standard, while doublet chemotherapy plus immunotherapy is recommended for others. These guidelines offer clinicians a practical framework for navigating complex treatment algorithms to optimize outcomes in advanced oncology.
10.1200/JCO-26-00842
Neoadjuvant Durvalumab ± Tremelimumab in Combination With Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin in Muscle-Invasive Bladder Carcinoma: Results of the Phase I/II NEMIO Study.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This phase I/II NEMIO study evaluated the efficacy and safety of neoadjuvant ddMVAC combined with durvalumab ± tremelimumab in 119 patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy. Key findings showed overall Bayesian posterior mean pathologic complete response (pCR) rates of 48.70% with doublet and 46.27% with triplet therapy, with PD-L1-high tumors achieving 68.25% pCR. Grade ≥3 treatment-related adverse events occurred in 40.95% overall (30.48% doublet; 49.63% triplet), while 2-year event-free and overall survival rates were encouraging. These results suggest neoadjuvant ddMVAC plus durvalumab is a promising chemoimmunotherapy strategy for localized MIBC, warranting further comparative trials, noting that adding tremelimumab increased toxicity without improving pCR.
10.1200/JCO-25-03045
Autologous T Cell Antigen Coupler Targeting HER2 (TAC01-HER2) in Advanced or Metastatic Solid Tumors.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This Phase 1 clinical trial evaluated the safety and preliminary efficacy of TAC01-HER2, an autologous T cell therapy targeting HER2, in 23 patients with advanced or metastatic HER2-positive solid tumors. The study found TAC01-HER2 to be safe and well-tolerated, with cytokine release syndrome being the most common adverse event (60.9%), and no treatment-related deaths. Early efficacy signals included partial responses in 2 of 9 gastric/GEJ cancer patients and a 61.1% disease control rate, with a 6-month overall survival rate of 57.9%. These results suggest TAC01-HER2 is a promising, manageable cellular therapy for heavily pre-treated HER2-positive gastric, GEJ, or esophageal adenocarcinomas, warranting further investigation.
10.1016/j.annonc.2026.05.696
May 18 – May 25, 2026
Treatment Effect Reanalysis of the Randomized Individual Screening Trial of Innovative Glioblastoma Therapy in Newly Diagnosed Glioblastoma With External Control Data.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This study reanalyzed three experimental arms of the INSIGhT platform trial for newly diagnosed glioblastoma by comparing internal control data with propensity score-matched external control data from real-world and clinical sources. Results showed no survival benefit for abemaciclib (HR 1.00; 95% CI, 0.75–1.34), neratinib (HR 0.93; 95% CI, 0.70–1.24), or CC-115 (HR 0.88; 95% CI, 0.41–1.88), which mirrored the original trial’s internal control findings. For clinicians treating glioblastoma, the study demonstrates that carefully matched external controls can produce reliable treatment effect estimates in early-phase testing of experimental therapies. These findings suggest that hybrid randomized designs leveraging external data may accelerate oncology drug development, provided comprehensive data on potential confounders are available to mitigate bias.
10.1200/JCO-25-01586
Overcoming Primary and Acquired Resistance to Immunotherapy in Non-Small Cell Lung Cancer: Mechanisms, Challenges, and Emerging Strategies.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This review article summarizes current understanding of acquired resistance (AR) to immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) and highlights emerging therapeutic strategies. Key mechanisms of AR include impaired antigen presentation, T-cell exhaustion, and tumor microenvironment remodeling. Novel approaches under investigation involve next-generation ICIs (e.g., TIGIT, LAG-3), epigenetic modulators, metabolic agents, and cellular immunotherapies. The study emphasizes the need for biomarker-driven patient selection and rational combinations to overcome AR, aiming for more durable and personalized immunotherapy outcomes in NSCLC practice.
10.1200/JCO-25-03026
Beyond sex determination: the Y chromosome in male cancers.
NAT REV CANCER · Q1 JOURNAL - RANK #3/326TOP-TIER
This review article synthesizes evidence on Loss of the Y chromosome (LOY) as the most prevalent somatic genomic alteration in males, linking it to susceptibility, progression, and poor outcomes across multiple cancer types, including haematological malignancies and solid tumours. Functional studies demonstrate LOY’s direct effects on immune surveillance, DNA repair, and the tumour immune microenvironment. The article discusses LOY’s potential as a biomarker for cancer risk, prognosis, and guiding precision therapy, including immunotherapy response and treatment stratification. While LOY’s precise causal role remains unresolved, its clinical implications for male cancer management are significant.
10.1038/s41568-026-00935-x
Five-Year Survival with Tebentafusp in Metastatic Uveal Melanoma.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This phase 3 trial evaluated the five-year overall survival of HLA-A*02:01-positive patients with metastatic uveal melanoma treated with tebentafusp compared to investigator’s choice of therapy. Tebentafusp significantly improved median overall survival to 21.6 months versus 16.9 months in the control group (HR 0.67), with a five-year survival rate of 16% compared to 8%. Survival benefits persisted across poor-prognosis subgroups and in patients treated beyond radiographic progression, while ctDNA reductions ≥50% by week 9 strongly correlated with improved outcomes. These findings solidify tebentafusp as the standard of care for this population, demonstrating durable long-term efficacy in a historically difficult-to-treat malignancy.
10.1016/j.annonc.2026.05.695
Datopotamab deruxtecan (Dato-DXd) in combination with durvalumab as first-line treatment for unresectable locally advanced or metastatic triple-negative breast cancer: results from arms 7 and 8 of the phase Ib/II BEGONIA study.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This phase Ib/II study evaluated the safety and efficacy of datopotamab deruxtecan (Dato-DXd) combined with durvalumab as first-line treatment for patients with unresectable locally advanced or metastatic triple-negative breast cancer. In Arm 7 (all PD-L1 levels), the confirmed objective response rate (cORR) was 79.0% with a median progression-free survival of 14.0 months, while Arm 8 (PD-L1-high) showed a cORR of 81.8%. These results demonstrate substantial and durable antitumor activity with a manageable safety profile, regardless of PD-L1 expression status. This combination therapy offers a promising first-line clinical strategy for improving outcomes in a high-need oncological population.
10.1016/j.annonc.2026.05.693
Peripheral Measurable Residual Disease Activity Assessment by MALDI-TOF Mass Spectrometry in Patients With Newly Diagnosed Multiple Myeloma in the Phase III GMMG-HD7 Trial.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This phase III GMMG-HD7 trial evaluated MALDI-TOF mass spectrometry (MS) for minimally invasive detection of monoclonal proteins in 617 patients with newly diagnosed multiple myeloma. MS demonstrated superior sensitivity over serum protein electrophoresis and provided strong prognostic value, with MS negativity at 12 months of maintenance significantly improving progression-free survival (HR 0.25; 95% CI, 0.15–0.43). The study highlights that combining serum MS with bone marrow measurable residual disease (MRD) assessments refines risk stratification and identifies patients at highest risk for relapse. These findings support integrating MS as a reproducible, practical biomarker for longitudinal cancer monitoring and potential risk-adapted treatment strategies in clinical practice.
10.1200/JCO-25-02957
Bladder Adjuvant Radiotherapy: Phase III Multicenter Randomized Controlled Trial of Adjuvant Radiotherapy or Observation for Postcystectomy Muscle-Invasive Bladder Cancer.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This multicenter, phase III randomized trial investigated adjuvant radiotherapy (RT) versus observation after radical cystectomy and chemotherapy in 153 high-risk muscle-invasive bladder cancer (MIBC) patients. After a median 47-month follow-up, adjuvant RT significantly improved 2-year locoregional recurrence-free survival (87.1% vs 76.0%, HR 0.43, p=.04). Trends for improved disease-free, bladder cancer-specific, and overall survival were also observed without additional severe toxicity. These findings suggest adjuvant pelvic IMRT can enhance locoregional control in high-risk MIBC, offering a crucial strategy to reduce recurrence in clinical practice.
10.1200/JCO-25-02093
Prostate Cancer Mortality After Relabeling Low-Grade Prostate Cancer as Precancerous.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
This decision analytical model evaluated the impact of relabeling Grade Group 1 (GG1) prostate cancer as a precancerous condition on US mortality rates. The study found that relabeling would avoid six times more annual prostate cancer deaths than it would cause (2,835 vs. 452) by increasing screening uptake. Even with conservative estimates, such as a 50% increase in progression rates or only a 3% increase in screening, a net reduction in mortality was maintained. These findings suggest that removing the cancer label from low-grade lesions could significantly reduce population-level mortality by mitigating the deterrents of overdiagnosis and overtreatment.
10.1001/jamaoncol.2026.1391
CRISPR-Cas9 CD33-deleted allogeneic hematopoietic cell transplantation with gemtuzumab ozogamicin maintenance in AML: a phase 1/2 trial.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This phase 1/2a open-label study investigated CRISPR-Cas9 CD33-deleted allogeneic HCT (trem-cel) followed by gemtuzumab ozogamicin (GO) maintenance in 30 high-risk AML/MDS patients. All patients achieved neutrophil engraftment by day 28 (median 10 days, 95% CI: 9-10). GO maintenance was safely tolerated up to 2 mg/m² in 19 patients, with no prolonged high-grade cytopenias observed. This approach demonstrates safe, rapid engraftment and enables CD33-targeted maintenance without significant hematologic toxicity, offering a promising strategy for high-risk hematologic cancer patients.
10.1038/s41591-026-04362-1
Pathogenic germline variations and cancer risks in pediatric patients referred for genetic testing.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This study investigated cancer predisposition and tumor characteristics in 75,602 pediatric patients undergoing genetic testing. Analyzing exome sequencing data, 501 pathogenic/likely pathogenic (P/LP) germline variants were identified in tumor susceptibility genes. Among patients with tumors, 32.6% harbored causative P/LP variants, notably in NF1, TSC2, RB1, and WT1. Crucially, prospective follow-up revealed a significantly higher incidence of malignant tumors (3.23 per 1,000 person-years) in P/LP carriers compared to other variants, emphasizing the need for proactive genetic counseling and surveillance for cancer risk in this population.
10.1038/s41591-026-04423-5
Longitudinal transcriptomic profiling identifies predictors of response to neoadjuvant chemoimmunotherapy in triple-negative breast cancer: results from the NeoTRIPaPDL1 trial.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This phase III trial analyzed longitudinal transcriptomic profiles from 280 patients with high-risk triple-negative breast cancer to identify predictors of response to neoadjuvant chemoimmunotherapy. Researchers found that baseline high proliferation and low metabolic signatures, alongside early on-treatment immune activation and tumor clearance, strongly predicted pathologic complete response (pCR). Specifically, the absence of tumor cells in early biopsies served as a robust surrogate for surgical pCR across both treatment arms. These findings suggest that integrating baseline tumor-intrinsic features with early treatment-induced microenvironment remodeling can guide response-adapted neoadjuvant strategies in clinical oncology.
10.1016/j.annonc.2026.05.694
Tucidinostat Plus R-CHOP vs R-CHOP in MYC/BCL2 Double-Expressor Diffuse Large B-Cell Lymphoma: A Randomized Clinical Trial.
JAMA-J AM MED ASSOC · Q1 JOURNAL - RANK #4/332TOP-TIER
This phase 3 randomized trial evaluated tucidinostat plus R-CHOP versus R-CHOP alone in 423 patients with MYC/BCL2 double-expressor lymphoma (DEL), a high-risk DLBCL subtype. Median follow-up was 41.3 months; the combination reduced the risk of progression, relapse, or death by 28% (HR 0.72; 95% CI 0.54-0.96; P=0.02), with 2-year event-free survival of 60.3% vs 50.5%. Complete response rate improved from 61.8% to 73.0% (difference 11.1%; 95% CI 2.3%-20.0%), and toxicity was manageable. This provides a new first-line option for a poor-prognosis DEL population, directly addressing the clinician’s interest in cancer-focused research.
10.1001/jama.2026.4199
Regulation of immune checkpoint molecules in cancer immune evasion and therapy.
NAT REV CANCER · Q1 JOURNAL - RANK #3/326TOP-TIER
This review investigates the multilayered regulatory mechanisms (genetic to post-translational) that govern immune checkpoint molecule abundance and function in cancer cells and the immune microenvironment. It highlights that while PDL1-PD1, CTLA4, and LAG3 inhibitors have transformed cancer therapy, most patients achieve only limited or transient benefit due to checkpoint dysregulation. The study connects these regulatory processes to immune evasion and therapeutic resistance in cancer. This knowledge is critical for developing biomarkers and mechanism-guided strategies to improve immunotherapy outcomes for cancer patients.
10.1038/s41568-026-00934-y
Survival Analysis of the WSG TP-II Trial: Neoadjuvant Trastuzumab and Pertuzumab Plus Endocrine Therapy Versus Chemotherapy in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
The WSG TP-II trial compared neoadjuvant trastuzumab and pertuzumab plus endocrine therapy versus chemotherapy in 207 patients with hormone receptor-positive/HER2-positive early breast cancer, followed for 5 years. The paclitaxel arm achieved a superior pathologic complete response rate of 56.4% compared to 23.7% in the endocrine therapy arm. At 5 years, overall survival was 100% in the ET arm versus 97.9% in the paclitaxel arm, with invasive disease-free survival rates of 97.7% versus 79.8% respectively. This study confirms excellent survival outcomes with de-escalated neoadjuvant therapy, supporting pCR-guided adjuvant strategies for this specific breast cancer subtype.
10.1200/JCO-25-01047
Ultra-hypofractionated stereotactic ablative body radiotherapy for primary renal cell carcinoma: 5-year outcomes from a pooled analysis of the FASTRACK trials.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This pooled analysis of two prospective trials (FASTRACK and FASTRACK II) evaluated stereotactic ablative body radiotherapy (SABR) for inoperable primary renal cell carcinoma. Among 103 treated patients (median age 76.9 years) with median 5-year follow-up, local control at 5 years was 98% (89-100), with only one local progression. Grade 3 adverse events occurred in 8% of patients (most commonly abdominal pain), with no grade 4 events or treatment-related deaths. These findings demonstrate durable long-term local control and low severe toxicity, supporting SABR as a non-invasive alternative for patients who are not surgical candidates.
10.1016/S1470-2045(26)00170-1
Biomarker-Based Eligibility for Lung Cancer Screening: Validation of the Protein-Based INTEGRAL-Risk Model.
JAMA-J AM MED ASSOC · Q1 JOURNAL - RANK #4/332TOP-TIER
This study developed and validated the protein-based INTEGRAL-Risk model to improve lung cancer screening eligibility in individuals with a smoking history. Using a large cohort (n=3695) across multiple regions, the model was trained and tested, demonstrating superior 1-year prediction (AUC 0.88) compared to the PLCOm2012 model (AUC 0.79; P<.001). It captured 85% of lung cancer cases versus 63% by USPSTF 2021 criteria at the same specificity. This model offers a practical advancement for identifying high-risk individuals, potentially enhancing the effectiveness of lung cancer screening programs.
10.1001/jama.2026.8044
Real-world heart and lung doses from 30 000 National Health Service radiotherapy treatment plans in England: a national audit of breast radiotherapy practice.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This national audit characterized real-world heart and lung doses in routine breast radiotherapy across 48 NHS centers in England, analyzing 26,236 anonymized plans. For breast-only treatments, median mean heart doses were 0.57 Gy (left) and 0.25 Gy (right), with over 99% below 2 Gy, while nodal plans had higher median MHDs (3.3 Gy left, 2.3 Gy right), with 98.3% meeting the 6 Gy constraint. Most plans met optimal lung dose constraints, though volumetric-modulated arc therapy delivered superior target coverage but higher MHDs. This study provides crucial real-world data on breast cancer radiotherapy safety, identifying opportunities for quality improvement in practice.
10.1016/S1470-2045(26)00185-3
Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcoma: The Phase 2 DOREMY Nonrandomized Clinical Trial.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
This phase 2 nonrandomized trial (DOREMY) evaluated the efficacy of a reduced preoperative radiotherapy dose of 36 Gy followed by surgical resection in 90 patients with localized myxoid liposarcoma. At a median follow-up of 66.4 months, the study reported a 5-year local recurrence-free survival rate of 97.4% and an overall survival rate of 88.5%. Wound complications occurred in 21% of patients, while late grade 3 toxic effects were minimal at only 3%. These findings demonstrate that dose reduction maintains excellent local control with a favorable toxicity profile, supporting its adoption as a standard treatment option for this specific cancer subtype.
10.1001/jamaoncol.2026.1577
Long-term outcomes of stereotactic ablative body radiotherapy for primary kidney cancer (TROG 15.03 FASTRACK II): a multicentre, non-randomised, phase 2 study.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This multicentre phase 2 trial (TROG 15.03 FASTRACK II) evaluated the long-term efficacy and safety of stereotactic ablative body radiotherapy (SABR) in 70 patients with primary renal cell carcinoma. Results demonstrated an impressive 100% local control rate at 36, 60, and 84 months, with a median follow-up of 62 months. Grade 3 treatment-related adverse events were limited to 10% of the cohort, and no grade 4 events or treatment-related deaths occurred. These findings establish SABR as a potent, non-invasive treatment option for non-surgical kidney cancer patients, offering durable local control and a manageable safety profile.
10.1016/S1470-2045(26)00091-4
Twenty-year results of the randomized European Organization for Research and Treatment of Cancer trial 22922/10925 evaluating internal mammary chain and medial supraclavicular lymph node irradiation in stage I-III breast cancer.
CA-CANCER J CLIN · Q1 JOURNAL - RANK #1/326TOP-TIER
This randomized trial evaluated the 20-year impact of internal mammary and medial supraclavicular lymph node irradiation (IM-MS-RT) in 4,004 patients with stage I-III breast cancer. While IM-MS-RT significantly reduced breast cancer mortality (18.6% vs. 22.4%; HR 0.82, p=.006), it did not improve overall survival (61.0% vs. 61.8%; HR 1.00, p=.967) due to a concurrent increase in non-cancer deaths. The treatment was associated with higher rates of lung and cardiac fibrosis, as well as cardiac disease (15.2% vs. 11.7%), particularly emerging after 15 years of follow-up. These findings suggest that the oncological benefits of regional nodal irradiation may be offset by long-term treatment-related toxicities, highlighting the necessity for very long-term monitoring in breast cancer survivors.
10.3322/caac.70082
Preclinical characterization and phase 1 results of TQB2102, a first-in-class HER2 biparatopic antibody-drug conjugate, in patients with advanced solid tumors.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This phase 1, first-in-human trial evaluated the safety, efficacy, and pharmacokinetics of TQB2102, a novel HER2 biparatopic ADC, in 195 patients with advanced solid tumors, primarily metastatic breast, colorectal, and gastric/GEJ cancers. The study found a manageable safety profile with no DLTs and MTD not reached, establishing 6.0 and 7.5 mg/kg as RP2D. Preliminary antitumor activity was observed, with objective response rates of 52.4% in MBC, 38.7% in CRC, and 40.0% in G/GEJ adenocarcinoma, including 47.2% in HER2-low MBC. These findings suggest TQB2102 is a promising therapeutic agent for advanced HER2-expressing solid tumors, warranting further investigation in a phase 3 trial for HER2-low MBC.
10.1016/j.annonc.2026.05.003
May 11 – May 18, 2026
Transforming perioperative treatment of gastro-oesophageal adenocarcinoma: triumphs, setbacks and future horizons.
NAT REV CLIN ONCOL · Q1 JOURNAL - RANK #2/326TOP-TIER
This review consolidates developments in gastro-oesophageal adenocarcinoma (GEA) management, aiming to provide clinicians with a comprehensive guide to state-of-the-art perioperative strategies by synthesizing insights from recent clinical trials. It highlights substantial transformations in GEA treatment, driven by evolving epidemiology and the integration of new therapeutic strategies, including chemotherapy, radiotherapy, immune checkpoint inhibitors, and targeted therapies. The review directly addresses cancer by focusing on GEA, offering crucial updates on its perioperative treatment, encompassing established and investigational approaches like organ preservation and ctDNA-based stratification. This provides clinicians with a structured understanding of current GEA management, emphasizing clinical implications and future directions, thereby enhancing evidence-based practice in oncology.
10.1038/s41571-026-01156-9
Overall Survival Among Patients With Hepatocellular Carcinoma Treated With External Beam Radiation Therapy: Individual Patient Data Outcomes From a Multinational Cohort.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This multinational cohort study analyzed individual patient data from 4,913 patients with hepatocellular carcinoma (HCC) treated with external beam radiation therapy (EBRT) to assess overall survival (OS). Median OS was 6.8 years for BCLC-0 and 4.6 years for BCLC-A stage; in treatment-naïve patients, median OS was not reached for BCLC-0 and was 5.4 years for BCLC-A. The study directly addresses your interest in cancer-focused research, providing robust evidence that EBRT yields OS outcomes comparable to resection and thermal ablation for early-stage HCC. Clinically, these data support incorporating EBRT into BCLC decision-making algorithms for very early- and early-stage HCC patients.
10.1200/JCO-25-02399
MRI-guided adaptive radiotherapy for high grade glioma (UNITED): a single-centre, single-arm, non-inferiority, phase 2 trial.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This phase 2 trial evaluated the safety of a small-margin (5 mm), MRI-guided adaptive radiotherapy approach using a 1.5 T MR-Linac for 98 patients with glioblastoma. The primary outcome demonstrated a marginal failure risk of only 4% (95% CI 0–8), successfully meeting non-inferiority criteria compared to historical controls using larger margins. By utilizing weekly gadolinium-enhanced online adaptation, clinicians can significantly reduce the volume of irradiated healthy brain tissue without increasing the risk of local recurrence. These results support the feasibility of margin de-escalation in high-grade glioma treatment, potentially reducing treatment-related toxicity while maintaining oncological control.
10.1016/S1470-2045(26)00088-4
Addition of autologous stem-cell transplantation to an ibrutinib-containing first-line treatment in patients aged 18-65 years with mantle cell lymphoma (TRIANGLE): 4·5-year follow-up of a three-arm, randomised, open-label, phase 3 superiority trial of the European MCL Network.
LANCET · Q1 JOURNAL - RANK #1/332TOP-TIER
This phase 3 trial investigated if adding autologous stem-cell transplantation (ASCT) to an ibrutinib-containing regimen improves outcomes in 870 younger mantle cell lymphoma patients. After 54.9 months, ibrutinib-containing groups (with or without ASCT) significantly improved 4-year failure-free survival (81-82% vs 70%) and overall survival (88-90% vs 81%) compared to ASCT alone. However, adding ASCT to ibrutinib offered no supplementary benefit but increased grade 3-5 adverse events (e.g., haematological disorders 54% vs 28%). Therefore, ibrutinib with immunochemotherapy and 2-year ibrutinib maintenance should be considered a new standard of care, potentially sparing patients from ASCT-related toxicity.
10.1016/S0140-6736(26)00362-4
Multicenter Cohort Study of Original or Substitute Systemic Therapy With or Without Brain Radiotherapy for Extensive-Stage Small Cell Lung Cancer With Brain-Only Progression After First-Line Treatment.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This multicenter cohort study evaluated treatment strategies for extensive-stage small cell lung cancer (ES-SCLC) patients with brain-only progression after first-line therapy. Among 203 patients, continuing original systemic therapy plus brain radiotherapy (OTP + BRT) yielded significantly superior median overall survival (14.7 months) compared to substitution therapy alone (10.2 months; HR 1.68, p=0.028) or substitution plus BRT (9.8 months; HR 1.67, p=0.023). Second-line progression-free survival also favored OTP + BRT (8.0 vs 4.0 months; p=0.024), with greatest benefit in patients with prior immunotherapy and initial PFS ≥7.5 months. Clinically, this supports a site-of-progression-directed strategy maintaining an effective systemic backbone, directly relevant to managing brain metastases in SCLC without abandoning active first-line therapy.
10.1200/JCO-25-02536
Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 10-year efficacy and late normal tissue effects from a multicentre, open-label, non-inferiority, phase 3, randomised controlled trial and 5-year efficacy results from a randomised axillary substudy.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
The FAST-Forward phase 3 randomized controlled trial investigated the 10-year efficacy and late normal tissue effects of 1-week hypofractionated adjuvant radiotherapy (26 Gy or 27 Gy in five fractions) versus standard 3-week (40 Gy in 15 fractions) for early-stage breast cancer, including a 5-year axillary substudy. With a median 10.1-year follow-up for 4087 participants, 10-year ipsilateral breast recurrence was 3.6% (40 Gy), 2.9% (27 Gy), and 2.1% (26 Gy). Clinician-reported moderate or marked breast/chest wall effects were 13.1% (40 Gy), 19.3% (27 Gy), and 14.4% (26 Gy). The 26 Gy schedule demonstrated non-inferior efficacy and similar normal tissue effects, supporting its use as a standard of care for breast or chest wall radiotherapy.
10.1016/S1470-2045(26)00076-8
Temporal Trends in Lung Cancer Cases Diagnosed at Early Stage.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
This descriptive surveillance study analyzed US Cancer Statistics data from 2003 to 2022, involving over 4.3 million cases, to evaluate temporal trends in early-stage lung cancer diagnoses following the 2013 USPSTF screening recommendations. Results show early-stage diagnoses rose from 17.6% in 2003 to 30.1% in 2022, with a notable sharp increase starting in 2015 (21.4%) through 2016 (24.6%). The findings highlight a significant shift toward earlier detection, which correlates with improved treatment efficacy and expanded therapeutic options for patients. Despite these gains, low screening uptake—reported at under 20% in 2024—suggests a critical need for clinicians to prioritize screening awareness and patient education to further improve cancer control outcomes.
10.1001/jamaoncol.2026.1199
Age-Dependent Interplay of Modifiable Risk Factors and Genetic Risk in Pancreatic Cancer.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
This prospective cohort study investigated the age-dependent interplay of modifiable and genetic risk factors for pancreatic cancer (PC) in 290,645 UK Biobank participants over 11.7 years. It found that while polygenic risk (PRS) consistently increased PC risk across all ages, modifiable risk (MRS) showed stronger associations in younger adults (<60 years, HR 1.69; 95% CI, 1.43-2.01). The absolute difference in 10-year cumulative incidence between high and low MRS was most pronounced among high PRS individuals, particularly in younger age groups (6.1-fold greater). These findings highlight the critical importance of initiating early-life prevention strategies, especially targeting modifiable risk factors in younger adults with high genetic predisposition to PC.
10.1001/jamaoncol.2026.1192
Efficacy and Safety of Camrelizumab Plus Apatinib in Patients With Refractory Chordoma: A Phase II Clinical Trial.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This phase II trial evaluated camrelizumab plus apatinib in 33 patients with refractory chordoma. The objective response rate was 24.2% per RECIST 1.1 and 48.5% per Choi criteria, with a median progression-free survival of 28.4 months. For a clinician focused on cancer, chordoma is a rare sarcoma, and the combination demonstrates meaningful antitumor activity in a treatment-refractory setting. The manageable toxicity profile and potential biomarker (CDKN2A alterations) offer actionable insights for clinical practice in advanced chordoma.
10.1200/JCO-25-02719
Concurrent Versus Sequential Radiation Dose Escalation to the Surgical Cavity for Conservative Treatment of High-Risk Early Breast Cancer: NRG/RTOG 1005 Phase III Trial.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This phase III trial (NRG/RTOG 1005) randomized 2,255 high-risk early breast cancer patients to compare concurrent radiation boost (40 Gy in 15 fractions) against sequential boost (50/42.7 Gy plus 12/14 Gy) following lumpectomy. At 7.3 years median follow-up, 5-year ipsilateral breast recurrence (IBR) was 1.9% for concurrent versus 2.1% for sequential arms, meeting noninferiority criteria (HR 1.31, 90% CI 0.84-2.04). The study demonstrates that concurrent boost delivery maintains oncologic control and cosmetic outcomes while significantly reducing overall treatment duration for cancer patients. Clinicians can adopt concurrent boost protocols as a standard, more efficient alternative to sequential dosing without compromising safety or survival in high-risk breast cancer populations.
10.1200/JCO-25-02465
Long-term effects of colonoscopy screening on colorectal cancer incidence and mortality: a multicountry, population-based randomised controlled trial.
LANCET · Q1 JOURNAL - RANK #1/332TOP-TIER
This multicountry, population-based randomized controlled trial assessed the 13-year effects of colonoscopy screening on colorectal cancer (CRC) incidence and mortality in 84,583 individuals. Colonoscopy significantly reduced CRC incidence (1.46% vs. 1.80% in no-screening; RR 0.81 [0.71-0.90]), especially for distal CRC. However, it did not significantly reduce CRC mortality (0.41% vs. 0.47%; RR 0.88 [0.68-1.08]) over this period. This study provides critical evidence for cancer prevention, indicating colonoscopy’s role in reducing CRC incidence but highlighting the need for further investigation into its long-term mortality impact.
10.1016/S0140-6736(26)00508-8
May 04 – May 11, 2026
Ficerafusp Alfa (BCA101) With Pembrolizumab for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Two-Year Results of an Expansion Cohort of a Phase I/Ib Trial.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This phase I/Ib trial investigated ficerafusp alfa plus pembrolizumab as first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) overexpressing PD-L1, assessing safety, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Among 42 patients, 45% experienced grade ≥3 treatment-related adverse events. Confirmed ORRs were 54% (21% complete response) for HPV-negative (n=28) and 27% for HPV-positive (n=11) tumors. For HPV-negative patients, median PFS was 9.9 months and median OS was 21.3 months, demonstrating promising antitumor activity directly relevant to cancer treatment. This combination shows favorable safety and efficacy, particularly in HPV-negative R/M HNSCC, suggesting a potential new first-line therapeutic strategy for this challenging cancer population.
10.1200/JCO-25-02027
A chemotherapy-free, pathological response-adapted strategy using trastuzumab-pertuzumab and T-DM1 in HER2-positive early breast cancer: the PHERGain-2 study.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This phase II study evaluated a chemotherapy-free, pathological complete response (pCR)-guided strategy using neoadjuvant trastuzumab-pertuzumab followed by response-adapted adjuvant therapy in 396 patients with HER2-positive early breast cancer. Results showed a high pCR rate of 59.6%, with a 1-year health-related quality of life decline observed in 42.8% of the total population. The strategy demonstrated manageable toxicity, with only 5.6% of patients experiencing grade 3 or higher treatment-related adverse events. These findings suggest that a chemotherapy-free approach can achieve pCR rates comparable to standard regimens while preserving quality of life, offering a potential de-escalation path for selected node-negative patients.
10.1016/j.annonc.2026.01.013
Survival outcomes in POD1UM-303/InterAACT-2: a phase 3 study of retifanlimab plus carboplatin-paclitaxel in first-line advanced squamous anal cancer.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This phase 3, randomized, double-blind trial (POD1UM-303/InterAACT-2) evaluated the efficacy of adding retifanlimab to carboplatin-paclitaxel as first-line treatment for 308 patients with advanced or metastatic squamous cell carcinoma of the anal canal. Results demonstrated a significant improvement in median overall survival (32.8 vs. 22.2 months; HR 0.75) and progression-free survival (HR 0.62) compared to chemotherapy alone. The combination therapy achieved a higher overall response rate of 56.5% versus 44.8% and maintained a consistent benefit across all analyzed subgroups without new safety concerns. These findings establish retifanlimab plus chemotherapy as a new reference standard of care for patients with inoperable, locally recurrent, or metastatic anal cancer.
10.1016/j.annonc.2026.04.016
Multicenter, Randomized, Phase II Trial of Olaparib Plus Radium-223 Versus Radium-223 in Men With Castration-Resistant Prostate Cancer With Bone Metastases (COMRADE).
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This multicenter, randomized phase II trial (COMRADE) evaluated the efficacy and safety of combining olaparib with radium-223 versus radium-223 alone in 120 men with metastatic castration-resistant prostate cancer and bone metastases. The combination significantly improved median radiographic progression-free survival to 8.9 months compared to 4.7 months for monotherapy (HR 0.50), with even greater benefits observed in docetaxel-naive patients (13.7 vs 5.7 months). While the combination reduced the 1-year incidence of symptomatic skeletal-related events (12.7% vs 22.9%), it also increased grade ≥3 hematologic toxicities, such as lymphopenia and anemia, to 56% from 33%. These results demonstrate that adding a PARP inhibitor to radiopharmaceutical therapy provides a significant progression-free survival advantage, supporting further investigation of DNA damage-targeted strategies despite the increased toxicity profile.
10.1200/JCO-25-02835
Tumor-Infiltrating Clonal Hematopoiesis and Pan-Cancer Prognosis in Patients With Solid Tumors.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
This retrospective cohort study analyzed whole-genome sequencing data from 10,571 patients with solid tumors to evaluate the prevalence and prognostic impact of tumor-infiltrating clonal hematopoiesis (TI-CH). TI-CH was identified in 18.38% of patients, occurring most frequently in endometrial cancer (32%) and correlating with older age and prior cytotoxic chemotherapy. Results demonstrated that TI-CH is significantly associated with worse pan-cancer overall survival (HR 1.13), with particularly high risk observed in breast cancer patients (HR 1.95) and those with GATA2 variants (HR 3.00). These findings suggest that TI-CH serves as a valuable prognostic biomarker across various solid tumors, potentially refining risk stratification and personalized treatment strategies in oncology.
10.1001/jamaoncol.2026.1036
Rates of Systemic Treatment for Metastatic Non-Small Cell Lung Cancer Among Older Adults.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
This population-based study analyzed SEER-Medicare data from 254,611 older adults diagnosed with metastatic non-small cell lung cancer (mNSCLC) between 2006 and 2021 to evaluate systemic treatment rates and associated factors. Results revealed that only 46.8% of patients received systemic therapy, with oncology referral (HR 2.5) and biomarker testing (+17.8% cumulative incidence) significantly increasing treatment likelihood. For clinicians, the study highlights that age over 80 and lack of specific histology (NSCLC-NOS) are major barriers, resulting in 15.4% and 12.8% lower treatment rates, respectively. Despite therapeutic advances, treatment rates have stagnated, suggesting a critical need to improve subspecialty access and biomarker utilization to address significant undertreatment in the geriatric oncology population.
10.1001/jamaoncol.2026.1080
Pancreatic cancer.
NAT REV DIS PRIMERS · Q1 JOURNAL - RANK #3/332TOP-TIER
This abstract reviews pancreatic ductal adenocarcinoma, a deadly malignancy, focusing on advances in diagnosis, treatment, and future directions. It highlights improved outcomes with multiagent chemotherapy and surgical innovations, which have enhanced complete resection rates and converted unresectable disease. Emerging strategies include precision medicine, personalized RNA vaccines, KRAS-directed agents, and AI-assisted early detection. The review is highly relevant to cancer research, emphasizing multidisciplinary, biology-guided approaches to transform pancreatic cancer into a more manageable condition.
10.1038/s41572-026-00699-6
The transformative role of SBRT in the management of spinal metastases.
NAT REV CLIN ONCOL · Q1 JOURNAL - RANK #2/326TOP-TIER
This review evaluates the evolution and clinical impact of stereotactic body radiotherapy (SBRT) compared to conventional external beam radiotherapy for managing spinal metastases. Level 1 evidence demonstrates that SBRT achieves superior complete pain response rates and more durable local tumor control by delivering high-precision radiation doses in five or fewer fractions. The transition to SBRT represents a fundamental shift from short-term palliation to long-term disease management, supported by multidisciplinary collaboration and refined patient selection. Clinicians can utilize these findings to improve patient outcomes through better local control and integration with less-invasive surgical procedures for metastatic spinal disease.
10.1038/s41571-026-01152-z
Malignant Adult Ovarian Germ Cell Tumors: An International Multicenter Study to Identify Relevant Prognostic Risk Factors for Stage IC and Beyond.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This international multicenter study analyzed 254 patients with stage IC-IV malignant ovarian germ cell tumors (MOGCTs) to identify prognostic risk factors influencing survival. Multivariable analysis revealed that age ≥35 years (HR 2.8), stage III/IV disease (HR 1.4), and nondysgerminoma histology (HR 7.3) significantly worsened cancer-specific survival (CSS). The study demonstrated a 10-year CSS of 83.2% and highlighted that high-dose chemotherapy improves survival outcomes specifically during the first relapse rather than subsequent ones. These findings provide clinicians with critical evidence for risk-stratifying patients and optimizing treatment intensity for advanced-stage MOGCTs, particularly regarding the timing of aggressive salvage therapies.
10.1200/JCO-25-00840
Neoadjuvant Single-Cycle Pembrolizumab for Stage I-III MMR-Deficient Colon Cancer: The RESET-C Trial.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
The RESET-C trial investigated neoadjuvant single-cycle pembrolizumab for localized dMMR colon cancer, administering one cycle followed by endoscopy and surgery. Among 84 patients, 44% achieved pathologic complete response (pCR) and 57% major pathologic response (MPR), with 98% overall and 96% disease-free survival at 18.4 months. Grade 3 adverse events occurred in 11% of patients. Endoscopic images showed 77% sensitivity and 93% specificity for predicting pCR, suggesting utility for nonoperative management pathways in this cancer type.
10.1200/JCO-25-02274
Metastatic Trajectories in Non-Small Cell Lung Cancer Guide Local and Systemic Therapies.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This review introduces the concept of metastatic trajectories to characterize the spatiotemporal dynamics and intrapatient heterogeneity of metastatic non-small cell lung cancer (NSCLC). The framework shifts focus from static disease states to individual lesion behavior, analyzing genomic diversification and tumor-microenvironmental adaptation to explain divergent treatment responses. By utilizing biomarkers such as circulating tumor DNA and radiomic signatures, clinicians can track and predict trajectory evolution to refine the selection of local and systemic therapies. Integrating these trajectory-based assessments into clinical practice enables biology-informed treatment adaptation and provides a foundation for precision management in advanced cancer care.
10.1200/JCO-25-01958
Perioperative Toripalimab Plus Chemotherapy Versus Chemotherapy Alone in Locally Advanced Gastric or Gastroesophageal Junction Cancer: 3-Year Follow-Up of NEOSUMMIT-01 Trial.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
The NEOSUMMIT-01 trial’s 3-year follow-up evaluated perioperative toripalimab plus chemotherapy versus chemotherapy alone in 108 patients with locally advanced gastric or gastroesophageal junction cancer. At 43.2 months median follow-up, the combination significantly improved 3-year event-free survival (74.7% vs 56.2%; HR 0.51, p=.044) and 3-year overall survival (81.3% vs 72.2%; HR 0.45, p=.036). These findings offer a promising new treatment option, directly relevant to cancer management. The study suggests perioperative toripalimab plus chemotherapy could improve survival outcomes for this specific cancer population.
10.1200/JCO-25-02842
Effects of ovarian ablation or suppression on breast cancer recurrence and survival: patient-level meta-analysis of 15 000 women in 23 randomised trials.
LANCET · Q1 JOURNAL - RANK #1/332TOP-TIER
This patient-level meta-analysis of 23 randomized trials involving 15,075 premenopausal women evaluated the impact of ovarian function suppression (OFS) on recurrence and mortality in estrogen receptor-positive early breast cancer. OFS significantly reduced recurrence rates (RR 0.82, p<0.00001), with the most pronounced benefits observed in women under 45 years receiving OFS plus tamoxifen (RR 0.73 for recurrence; RR 0.74 for breast cancer mortality). The findings demonstrate that OFS provides additional protection against recurrence and death even when chemotherapy or tamoxifen is administered, particularly for younger patients. Clinicians should consider OFS as a standard component of adjuvant therapy for premenopausal women with ER-positive disease to improve 15-year survival outcomes.
10.1016/S0140-6736(26)00313-2
Substantial increases in cervical cancer inequalities worldwide without enhanced human papillomavirus vaccination and screening efforts: a global modelling study.
LANCET · Q1 JOURNAL - RANK #1/332TOP-TIER
This global mathematical modelling study used the HPV-ADVISE model to project cervical cancer incidence and inequalities in 67 low-income and 42 high-income countries under various HPV vaccination and screening scenarios. Findings indicate that under current strategies, LMIC incidence would decrease by only 23%, while HICs achieve elimination by 2048, leading to a substantial increase in inequalities (RR=3 in 2022 to 12 in 2105). Reaching 90% girls’ vaccination in LMICs would reduce inequalities (RR=2 in 2105) and achieve elimination outside sub-Saharan Africa. Enhanced prevention strategies, including WHO targets and universal vaccination, are crucial for cervical cancer elimination in LMICs and attenuating global disparities.
10.1016/S0140-6736(26)00410-1
Apr 27 – May 04, 2026
Targeting Regulatory T Cells for Cancer Immunotherapy: Promises and Pitfalls.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This targeted literature review examines the biological role of regulatory T cells (Tregs) in the tumor microenvironment and evaluates emerging therapeutic strategies for their modulation or depletion in cancer immunotherapy. The review identifies three primary clinical strategies—depletion via anti-CD25/CCR4/CCR8 antibodies, functional blockade of CTLA-4/TIGIT, and metabolic disruption—noting that while preclinical results are promising, clinical trials show variable efficacy and toxicity. For clinicians, the study highlights how high Treg infiltration facilitates tumor immune escape and discusses the potential of selective intratumoral Treg impairment to improve patient outcomes. Future practice may rely on identifying specific T-cell subsets, such as FOXP3+Helios+CCR8+ cells, to predict therapeutic responses and balance antitumor activity with peripheral immune tolerance.
10.1016/j.annonc.2026.04.015
Phase I Study of Telisotuzumab Adizutecan (Temab-A, ABBV-400), a Novel c-Met Antibody-Drug Conjugate, in Patients With Late-Line Colorectal Cancer and Advanced Solid Tumors.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This phase I study evaluated the safety and efficacy of Temab-A, a novel c-Met antibody-drug conjugate, in patients with advanced solid tumors and late-line metastatic colorectal cancer (mCRC). Among 122 patients with mCRC, the overall response rate was 15.6% and the disease control rate reached 74.6%, with a median progression-free survival of 4.6 months. The treatment demonstrated a manageable safety profile at the 2.4 mg/kg dose, primarily involving gastrointestinal and hematologic toxicities, while showing promising antitumor activity in heavily pretreated populations. These results support the further development of Temab-A as a potential therapeutic option for c-Met-expressing solid tumors, particularly in refractory colorectal cancer settings.
10.1200/JCO-25-01525
CDK4/6 inhibitors plus endocrine therapy versus endocrine monotherapy in hormone receptor-positive, HER2-negative advanced breast cancer: a reconstructed individual patient data meta-analysis of phase 3 randomised controlled trials.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This reconstructed individual patient data meta-analysis evaluated CDK4/6 inhibitors plus endocrine therapy versus endocrine monotherapy for hormone receptor-positive, HER2-negative advanced breast cancer, pooling data from 11 phase 3 trials (6035 patients). CDK4/6 inhibitors significantly improved progression-free survival in both endocrine-sensitive (HR 0.57, p<0.0001) and endocrine-resistant cancers (HR 0.51, p<0.0001). Overall survival was also improved in endocrine-sensitive (HR 0.83, p=0.0005) and endocrine-resistant (HR 0.77, p=0.0003) subgroups. While all agents improved PFS, only abemaciclib (HR 0.79, p=0.0031) and ribociclib (HR 0.73, p<0.0001) showed significant overall survival benefits. This study provides robust evidence supporting the use of CDK4/6 inhibitors in advanced breast cancer, guiding treatment decisions.
10.1016/S1470-2045(26)00053-7
Clinical trial endpoints for metastases-directed therapy in oligometastatic cancer: a review and Delphi consensus on behalf of the EORTC-ESTRO OligoCare consortium.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This systematic review and Delphi consensus involving 30 experts and five patient representatives aimed to standardize primary endpoints for clinical trials evaluating metastases-directed therapies (MDT) in oligometastatic cancer. Analysis of 121 comparative trials revealed that while overall survival (OS) and progression-free survival (PFS) are most common, consensus was reached on incorporating polymetastatic PFS and systemic therapy-free survival. These novel endpoints allow for repeat MDT without defining it as treatment failure, better reflecting the clinical management of oligometastatic disease compared to traditional metrics. Adopting these standardized, patient-centered endpoints will improve the comparability of future oncological trials and better inform clinical policy decisions regarding MDT integration.
10.1016/S1470-2045(26)00075-6
On-treatment serum prostate-specific antigen and overall survival in prostate cancer (STAMPEDE platform protocol): a post-hoc analysis of data from five phase 3 trials.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This post-hoc analysis of 7129 prostate cancer patients from five STAMPEDE phase 3 trials investigated the association between on-treatment serum PSA and overall survival. It found that PSA concentrations of 0.2 ng/mL or less at 6, 12, or 24 weeks were associated with equivalent favorable survival rates, with PSA at 24 weeks showing the strongest association. Survival rates for PSA subcategories differed significantly by metastatic volume or nodal status; for instance, 96-month overall survival for metastatic low-volume disease with PSA ≤0.2 ng/mL at 24 weeks was 64.1% versus 44.6% for high-volume. These findings suggest that on-treatment PSA, combined with radiological features, can inform prognosis and potentially guide treatment selection in prostate cancer.
10.1016/S1470-2045(26)00066-5
International multisociety Delphi consensus for liver tumour thermal ablation: margin assessment.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This international multisociety Delphi consensus aimed to standardize ablation margin assessment in liver tumour thermal ablation, utilizing a modified Delphi process with 72 experts. Formal consensus was reached for 150 (75%) of 199 statements, with strong agreement observed (only 6% disagreement). Experts agreed margins should be quantitatively assessed in 3D with CT/MRI, preferably intraprocedurally, and categorized as A0, A1, or A2. This provides best-practice recommendations for liver cancer treatment, standardizing practices to improve uniform outcomes for patients.
10.1016/S1470-2045(26)00143-9
Lung cancer brain metastases management at the dawn of personalized medicine: are we ready to break the barriers?
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This review article summarizes the evolving management of lung cancer brain metastases (BM), a complication affecting nearly half of patients and significantly impairing survival. It highlights how advances in immune checkpoint inhibitors, next-generation CNS-penetrant targeted therapies, and stereotactic radiotherapy have reshaped the therapeutic landscape, improving intracranial control and patient outcomes. The integration of personalized systemic and local approaches offers new opportunities for optimizing central nervous system disease control. This emphasizes the need for individualized treatment strategies, addressing challenges in sequencing, patient selection, and risk-adapted approaches for future clinical trial design.
10.1016/j.annonc.2026.04.014
Adult T-Cell Leukemia/Lymphoma and Targeted Maternal Screening.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
This population-based study analyzed US cancer registries (2005-2022) to estimate Adult T-cell leukemia/lymphoma (ATLL) incidence. It identified 3228 ATLL cases, finding non-Hispanic Caribbean-born US residents had an incidence rate of 14.1 per million, significantly higher than US/Canada-born populations (0.4 per million; IRR, 32.0), with rates peaking at 33.7 per million. Five-year survival was poor (23.8%), lowest among Caribbean-born individuals, highlighting a critical health disparity for this aggressive cancer. These findings identify early-life HTLV-1 infection as an actionable target for cancer prevention through maternal screening, with implications for reducing future ATLL burden.
10.1001/jamaoncol.2026.0859
Tiragolumab Plus Atezolizumab and Chemotherapy for Advanced Nonsquamous Non-Small Cell Lung Cancer: The Phase 3 SKYSCRAPER-06 Randomized Clinical Trial.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
The phase 3 SKYSCRAPER-06 trial evaluated tiragolumab plus atezolizumab plus chemotherapy versus placebo plus pembrolizumab plus chemotherapy as first-line treatment for advanced nonsquamous NSCLC in 542 previously untreated patients. The study found no significant improvement, with median progression-free survival of 8.3 months vs 9.9 months (HR 1.27; P=0.99) and overall survival of 18.9 months vs 23.1 months (HR 1.33; P=0.98). These negative results indicate the experimental regimen is not superior to the control arm. Clinically, this means the tiragolumab combination is not a recommended first-line option for this patient population.
10.1001/jamaoncol.2026.0818
Local Salvage Therapy Alone for Local Recurrence of Prostate Cancer After Radiotherapy: A Systematic Review and Meta-Analysis.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
This systematic review and meta-analysis evaluated outcomes of local salvage therapies alone for radiorecurrent prostate cancer, involving 31 studies and 4525 patients. Key findings showed pooled 2-year and 5-year ADT-free survival rates of 76.8% and 55.2%, respectively, and 2-year and 5-year metastasis-free survival rates of 90.4% and 75.2%. Severe adverse event rates ranged from 2% to 14% across different methods. These results suggest local therapies alone offer reasonable efficacy in selected patients with recurrent prostate cancer, providing an option to avoid systemic therapy while maintaining ADT-free survival and manageable toxicities.
10.1001/jamaoncol.2026.1023
Lymph node surgery and CDK4/6 inhibitors in early breast cancer: a pooled analysis from five randomised trials.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This pooled analysis of five randomized trials involving 19,541 patients evaluated whether omitting axillary surgery in early breast cancer impacts eligibility for adjuvant CDK4/6 inhibitors. Results showed that performing sentinel lymph node biopsy or completion axillary dissection solely for drug eligibility requires high numbers needed to diagnose and treat, such as 345 and 807 surgeries respectively to prevent one death at five years. The study highlights that while surgery provides staging data, the associated morbidity and costs outweigh the marginal overall survival benefits gained from subsequent CDK4/6 inhibition. Clinicians should consider these findings when balancing surgical de-escalation against the potential benefits of intensified systemic therapy in early-stage breast cancer management.
10.1016/S1470-2045(26)00064-1
Safety and antitumour activity of ipatasertib combined with endocrine therapy and a CDK4/6 inhibitor in HR+/HER2- metastatic breast cancer (TAKTIC): a single-centre, open-label, phase 1b trial.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This phase 1b, single-centre trial (TAKTIC) evaluated the safety and preliminary antitumour activity of ipatasertib combined with endocrine therapy (fulvestrant or AI) with or without palbociclib in 77 heavily pretreated women with HR+/HER2- metastatic breast cancer. The recommended phase 2 dose for the triple combination was established, yielding a median progression-free survival of 5.5 months (95% CI 3.8-7.4). Common grade 3-4 adverse events included neutropenia (39%), leukopenia (19%), and diarrhoea (18%). These findings demonstrate preliminary clinical activity and an expected safety profile, directly addressing the need for new strategies in advanced breast cancer and warranting further evaluation in CDK4/6 inhibitor-refractory disease.
10.1016/S1470-2045(26)00059-8
Bayesian sequential learning for prognostication in extremity soft tissue sarcoma (BayeSarc): a retrospective, multicentre cohort study.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This retrospective, multicentre cohort study developed BayeSarc, a Bayesian sequential learning model, to provide continuously updated and more accurate prognostication for overall survival and distant metastasis in 4916 patients with resected extremity soft tissue sarcomas. BayeSarc demonstrated superior discrimination compared to the existing Sarculator tool, with C-indices of 0.801 versus 0.773 for overall survival and 0.738 versus 0.718 for distant metastasis, alongside improved calibration and reduced uncertainty. This continuously updatable, accurate, and precise prognostic tool is highly relevant for cancer management. Its integration into the Sarculator app offers immediate clinical utility, enhancing patient counselling, guiding treatment decisions, and refining trial design for this specific cancer.
10.1016/S1470-2045(26)00067-7
International multisociety Delphi consensus for liver tumour thermal ablation: procedural and practice standards.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This international Delphi consensus aimed to standardize procedural and practice guidelines for thermal ablation of primary and metastatic liver tumours. Seventy-two experts achieved consensus on 94 (70%) of 135 statements across five domains, including credentialing and indications. Key findings emphasize prioritizing the percutaneous approach, ensuring margin adequacy, and recommending experienced operators (>100 cases) for complex ablations. This study directly informs clinicians treating liver cancer, providing crucial guidance to improve consistency, safety, and oncological outcomes in cancer care.
10.1016/S1470-2045(26)00114-2
Emerging trends in the global burden of colorectal cancer.
NAT REV CLIN ONCOL · Q1 JOURNAL - RANK #2/326TOP-TIER
This review examines the global epidemiology of colorectal cancer (CRC), currently the third most common cancer and second leading cause of cancer-related mortality worldwide. The study highlights a significant rise in early-onset CRC among individuals under 50, driven by a birth cohort effect starting in the 1960s rather than genetic susceptibility alone. Researchers identify shifting dietary patterns, gut microbiota changes, and environmental contaminants associated with urbanization as key emerging risk factors. These findings emphasize the need for expanded genomic research in non-Western populations to improve global early detection and interception strategies for younger cohorts.
10.1038/s41571-026-01149-8
The clinical landscape of HIF2α inhibitors in oncology.
NAT REV CLIN ONCOL · Q1 JOURNAL - RANK #2/326TOP-TIER
This review examines the clinical development and therapeutic landscape of HIF2α inhibitors, specifically focusing on the first-in-class antagonist belzutifan and emerging small-molecule or RNA-based modulators. Belzutifan has achieved regulatory approval for treating von Hippel-Lindau disease-associated tumors, sporadic clear-cell renal cell carcinoma, and pheochromocytoma, demonstrating significant efficacy by targeting the PAS-B domain. The research highlights the validation of HIF2α as a druggable target in oncology, addressing management of on-target toxicities like anemia and the potential for combination therapies to overcome resistance. Future clinical practice may expand HIF2α inhibition to various hypoxia-adapted malignancies, provided that predictive biomarkers are identified to optimize patient selection and treatment outcomes.
10.1038/s41571-026-01145-y
Circulating Tumor DNA Assessment of Disease Response in Large B-Cell Lymphoma: Lisocabtagene Maraleucel Versus Autologous Stem Cell Transplantation Standard Therapy.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
The TRANSFORM study (NCT03575351) compared lisocabtagene maraleucel (liso-cel) versus standard of care (ASCT) in 136 patients with second-line large B-cell lymphoma (LBCL), utilizing ultrasensitive circulating tumor DNA (ctDNA) to assess disease response. ctDNA clearance predicted longer event-free survival (EFS) in both arms, with significantly more liso-cel-treated patients achieving measurable residual disease (MRD) negativity. Liso-cel demonstrated superior outcomes, including longer EFS and progression-free survival (PFS), compared to ASCT, and ctDNA re-emergence predicted relapse. This research establishes ctDNA-MRD as a valuable prognostic biomarker beyond PET for treatment response and relapse prediction in LBCL, supporting its role in clinical practice.
10.1200/JCO-25-03051
Enhancer and metabolic rewiring by KMT2C-COMPASS or KMT2D-COMPASS family loss in cancer creates druggable vulnerabilities.
NAT REV CANCER · Q1 JOURNAL - RANK #3/326TOP-TIER
This review article explores the functional roles of KMT2C-COMPASS and KMT2D-COMPASS epigenetic regulatory complexes and the impact of their mutations on cancer progression. It highlights that KMT2C, KMT2D, and KDM6A are among the most frequently mutated genes across human cancers, especially epithelial cancers. These mutations create tumour-specific and potentially druggable vulnerabilities, offering new avenues for therapeutic intervention. The review outlines strategies to exploit these vulnerabilities in cancer cells, including targeting epigenetic activity, metabolic rewiring, and immune responses, providing a framework for novel cancer treatments.
10.1038/s41568-026-00919-x
Apr 20 – Apr 27, 2026
The sleeping threat: targeting cancer dormancy to transform metastasis therapy.
NAT REV CANCER · Q1 JOURNAL - RANK #3/326TOP-TIER
This review synthesizes recent advances in understanding metastatic cancer cell dormancy, a critical determinant of cancer relapse. It explores microenvironmental drivers, epigenetic programs, and immune evasion mechanisms in both solid and hematologic malignancies. Key insights reveal how niche signals and molecular programs maintain disseminated cancer cell quiescence, and how these cells evade immune surveillance. Despite mechanistic understanding, clinical translation remains limited, underscoring challenges and opportunities to leverage dormancy biology for preventing metastatic recurrence and improving patient outcomes.
10.1038/s41568-026-00928-w
Expert Opinion on the Diagnosis and Treatment of Hematologic Malignancies During Pregnancy.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This expert opinion paper reviews the diagnostic and therapeutic management of various hematologic malignancies diagnosed during pregnancy, addressing the increasing global incidence in this population. The authors evaluate the safety and efficacy of diagnostic modalities and treatment options, including chemotherapy, radiation therapy, and immunotherapy, for conditions such as acute leukemia and lymphomas. It provides clinical guidance on balancing maternal oncological care with fetal safety, emphasizing that more women are now receiving adequate treatment without compromising pregnancy outcomes. The findings suggest that multidisciplinary approaches allow for expanded treatment possibilities, though specific numerical survival data were not provided in this qualitative expert consensus.
10.1200/JCO-25-02351
Canine Olfaction Combined With Bayesian Modeling for Multicancer Detection From Breath Samples: A Phase II Study in India.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This Phase II study evaluated a multicancer breath detection system using trained dogs and Bayesian modeling in a case-control study across six hospitals in India, enrolling 3,275 participants including 283 biopsy-confirmed cancer cases. The system achieved 90.8% sensitivity and 91.3% specificity for multicancer detection, with an AUC of 0.962. Notably, sensitivity for early-stage disease (stage I-II) was 90.6% and consistent across cancer types. These findings establish high analytical accuracy for a low-cost, high-sensitivity cancer triage test, highly relevant for population screening, supporting prospective evaluation in true screening populations.
10.1200/JCO-25-02310
Colorectal cancer detection using non-contrast CT and deep learning: a multicenter and international cohort study.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This multicenter, international cohort study developed COCA, a deep learning method utilizing non-contrast CT for colorectal cancer (CRC) screening, aiming for a non-invasive, cost-effective, and scalable solution. In validation across 2,053 patients, COCA achieved an AUC of 0.967-0.996 for CRC detection, improving sensitivity by 20.4% and specificity by 5.4% over radiologists. Real-world validations across 27,433 patients further demonstrated robust performance, maintaining high sensitivity (86.6-88.2%) and specificity (99.5-99.8%) for CRC detection. These findings indicate COCA’s strong potential as a practical tool for large-scale opportunistic CRC screening, directly aligning with the clinician’s interest in cancer research and early diagnosis.
10.1016/j.annonc.2026.04.009
Re-Evaluating Antibody-Drug Conjugate Linker Stability: Assessment, Interpretation, and Clinical Translation.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This review examines the role of linker stability in antibody-drug conjugate (ADC) design, challenging the assumption that increased stability necessarily improves clinical outcomes in cancer therapy. Analysis reveals that several successful ADCs utilize relatively unstable linkers, while more stable designs have frequently failed to improve efficacy or have resulted in unexpected toxicities. The study highlights the limitations of preclinical models in predicting human payload exposure and emphasizes the complex relationship between systemic half-life and off-target toxicity. These findings suggest that future ADC development must move beyond simple stability metrics toward more rational, clinically-informed strategies to optimize the therapeutic index for oncology patients.
10.1016/j.annonc.2026.04.008
Context-dependent synthetic lethality - an emerging precision therapeutic approach.
NAT REV CANCER · Q1 JOURNAL - RANK #3/326TOP-TIER
This review examines context-dependent synthetic lethality as a precision oncology strategy to exploit cancer-intrinsic vulnerabilities beyond direct oncogene inhibition. The authors identify key mechanistic themes such as DNA repair defects and metabolic imbalances, highlighting clinical successes with PARP, HIF-2, and SMO inhibitors. It emphasizes that the therapeutic index, often derived from functional genomics, is a critical determinant for target prioritization and achieving selectivity in cancer treatment. These insights provide a framework for developing more selective and durable cancer therapies by matching specific molecular mechanisms with optimal therapeutic modalities.
10.1038/s41568-026-00929-9
Including tumor-infiltrating lymphocytes into the PREDICT prognostic model for triple-negative breast cancer survival.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This study aimed to integrate stromal tumor-infiltrating lymphocytes (sTILs) into the PREDICT prognostic model for early-stage triple-negative breast cancer (TNBC) to refine chemotherapy decisions. Utilizing a Cox regression model on 3698 TNBC patients, the updated PREDICT_sTILs model demonstrated strong internal-external validity with pooled O/E ratios of 0.98 at 5 years and 0.99 at 10 years, and AUCs of 0.74. Compared to PREDICT, it identified 19-60 additional net true low-risk and 3-10 additional net true high-risk patients per 1000 chemotherapy-naïve patients. This enhancement improves chemotherapy guidance for early-stage TNBC, particularly in identifying low-risk individuals who may safely forgo treatment, directly impacting cancer management.
10.1016/j.annonc.2026.04.011
IO102-IO103 immune-modulatory cancer vaccine and pembrolizumab in melanoma.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This Phase 3 trial evaluated the efficacy of the IO102-IO103 immune-modulatory vaccine combined with pembrolizumab versus pembrolizumab monotherapy in 407 patients with untreated advanced melanoma. The combination arm achieved a median progression-free survival (PFS) of 19.4 months compared to 11.0 months for monotherapy (HR 0.77; P=0.0558), though it narrowly missed the predefined statistical significance threshold. Notable benefits were observed in PD-L1-negative patients (16.6 vs. 3.0 months PFS) and anti-PD-1 naïve patients, with no significant increase in grade ≥3 adverse events (14.5% vs. 15.6%). While the primary endpoint was not statistically met, the favorable safety profile and clinically meaningful PFS improvements in specific subgroups suggest potential for this vaccine-checkpoint inhibitor combination in first-line melanoma management.
10.1016/j.annonc.2026.04.010
Duvelisib Induces Deep Responses in PTCL: Final Results of the Phase 2 PRIMO Trial of Duvelisib in Relapsed/Refractory Peripheral T-Cell Lymphoma.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This phase 2 PRIMO trial evaluated the efficacy and safety of duvelisib, an oral dual PI3K-δ/γ inhibitor, in 123 patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). Results demonstrated an objective response rate of 48.0% and a complete response rate of 33.3%, with a median overall survival of 12.4 months across the total cohort. Notably, the angioimmunoblastic T-cell lymphoma subgroup showed superior outcomes, including a 62.2% response rate and 18.1-month median overall survival, despite a 74.0% incidence of grade ≥3 adverse events. These findings establish duvelisib as a clinically significant treatment option for aggressive PTCL, particularly for T-follicular helper cell subtypes, warranting further development in oncology practice.
10.1200/JCO-25-03120
Postoperative Hepatic Arterial Infusion With Oxaliplatin After Surgery of Four or More Colorectal Liver Metastases: A Randomized Phase II Trial.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This randomized phase II trial evaluated the efficacy of adjuvant hepatic arterial infusion (HAI) of oxaliplatin versus intravenous (IV) chemotherapy in 99 patients following surgery for four or more colorectal liver metastases. Results demonstrated a significant improvement in median hepatic recurrence-free survival (25 vs. 12 months; HR 0.63; p=0.047) and median recurrence-free survival (14 vs. 9 months; HR 0.63; p=0.03) favoring the HAI group. Although Grade 3-4 adverse events were higher in the HAI arm (58% vs. 32%), the five-year overall survival reached 62% compared to 47% in the IV arm. These findings suggest that adjuvant HAI oxaliplatin effectively reduces regional recurrence in high-risk cancer patients, supporting its consideration in specialized surgical oncology settings pending phase III validation.
10.1200/JCO-25-01737
Durvalumab in Combination With Neoadjuvant Chemotherapy in Early Triple-Negative Breast Cancer: Long-Term Analysis From the GeparNuevo Trial.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This phase II trial evaluated the long-term efficacy of adding durvalumab to neoadjuvant chemotherapy in 174 patients with early triple-negative breast cancer. At 86.4 months median follow-up, durvalumab significantly improved invasive disease-free survival (HR 0.56), distant disease-free survival (HR 0.41), and overall survival (HR 0.33) compared to placebo. Exploratory analyses revealed a pronounced benefit for patients with nodal involvement and highlighted the prognostic value of stromal tumor-infiltrating lymphocytes in residual disease. These findings suggest that neoadjuvant durvalumab provides sustained survival benefits without the need for adjuvant checkpoint inhibition, potentially refining standard treatment protocols for early-stage breast cancer.
10.1200/JCO-25-02311
First-in-Human, Phase I Study of Sigvotatug Vedotin, an Integrin Beta-6-Directed Antibody-Drug Conjugate: Results From Dose Expansion in Advanced Non-Small Cell Lung Cancer.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This phase I dose-expansion study evaluated the safety and efficacy of sigvotatug vedotin (SV), a novel integrin beta-6-directed antibody-drug conjugate, in 117 patients with advanced non-small cell lung cancer (NSCLC). Results showed a manageable safety profile, with grade ≥3 adverse events occurring in 35% of patients receiving the optimized 1.8 mg/kg AiBW bi-weekly regimen. The overall objective response rate was 19%, which increased to 29% with a 12.8-month median duration of response in nonsquamous, taxane-naïve patients. These findings support the clinical development of SV as a targeted therapy for advanced lung cancer, particularly using adjusted ideal body weight dosing to minimize pharmacokinetic variability.
10.1200/JCO-25-02016
Cibisatamab and FAP-4-1BBL in microsatellite-stable colorectal cancer: a phase 1b trial.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This phase 1b dose-escalation study evaluated the safety and efficacy of cibisatamab, a CEA-directed T cell-engager, combined with FAP-4-1BBL co-stimulation in 52 patients with microsatellite-stable metastatic colorectal cancer. Results demonstrated a manageable safety profile with a 13.5% confirmed partial response rate and dose-limiting toxicities occurring in only 3.8% of participants. The study directly addresses the clinician’s interest in cancer by exploring novel immunotherapy combinations for treatment-refractory colorectal malignancies. These findings support the feasibility of tumor-localized co-stimulation to enhance T cell engagement, providing a potential therapeutic pathway for immunologically “cold” tumors.
10.1038/s41591-026-04380-z
In vivo generation of anti-BCMA CAR-T cells in relapsed or refractory multiple myeloma: a phase 1 study.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This phase 1 trial evaluated the safety and efficacy of ESO-T01, an immune-shielded lentiviral vector designed to generate anti-BCMA CAR-T cells directly in vivo for patients with relapsed or refractory multiple myeloma. Among five heavily pretreated patients, four achieved objective responses, including three stringent complete remissions and 100% (4/4) minimal residual disease negativity by day 60. While all patients experienced grade 3 or higher adverse events, including cytokine release syndrome in 80% of participants, no dose-limiting toxicities were observed despite the absence of lymphodepleting chemotherapy. These results demonstrate the preliminary feasibility of bypassing complex ex vivo manufacturing, potentially streamlining access to advanced cellular immunotherapy for hematologic malignancies.
10.1038/s41591-026-04244-6
Advancing AI for multi-omics and clinical data integration in basic and translational cancer research.
NAT REV CANCER · Q1 JOURNAL - RANK #3/326TOP-TIER
This review examines how artificial intelligence (AI) integrates multi-omics and clinical data to advance cancer research. AI enables comprehensive analysis of high-dimensional datasets, driving progress in early diagnosis, patient stratification, and prediction of therapeutic response. The approach directly supports precision oncology by elucidating drug resistance mechanisms and aiming for patient-specific digital twins. Critical implementation requires explainable AI to build clinical trust and address challenges in data accessibility and model generalizability.
10.1038/s41568-026-00922-2
Epigenetic fingerprints link early-onset colon and rectal cancer to pesticide exposure.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This study utilized weighted methylation risk scores as proxies for environmental exposures to investigate the rising incidence of early-onset colorectal cancer (EOCRC) compared to late-onset cases. Researchers identified the herbicide picloram as a significant risk factor (adjusted P = 1.5 × 10⁻² in meta-analysis), a finding validated across nine cohorts and 94 US counties (P = 4.52 × 10⁻⁴). The results provide a molecular link between specific pesticide exposure and the development of colorectal malignancies in patients under age 50, addressing a critical gap in oncological epidemiology. These findings suggest that environmental ‘epigenetic fingerprints’ can identify high-risk populations, supporting the need for targeted screening and policy-level interventions to mitigate pesticide-related cancer risks.
10.1038/s41591-026-04342-5
Clinical and molecular biomarkers for prediction of endocrine response after short preoperative endocrine therapy in the WSG ADAPT-HR+/HER2- and ADAPTcycle trials (N=7914).
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This study analyzed 7,914 patients from the WSG ADAPT-HR+/HER2- and ADAPTcycle phase III trials to identify predictors of endocrine therapy (ET) response, defined as Ki67 ≤10% after 2-4 weeks of preoperative treatment. Results showed significantly higher ET-response rates with aromatase inhibitors (76.7-81.4%) compared to tamoxifen (34.7-40.1%), with ovarian function suppression further improving outcomes in premenopausal women to levels comparable with postmenopausal patients. For clinicians treating breast cancer, the study demonstrates that ET-responders with high recurrence scores (RS >25) achieved a 5-year disease-free survival of 87.0% compared to 80.7% in non-responders. These findings suggest that combining short-term ET-response with genomic testing can effectively identify luminal early breast cancer patients who may safely avoid chemotherapy.
10.1016/j.annonc.2026.04.007
Targeting MEK in cancer and beyond: mechanistic insights and therapeutic opportunities.
LANCET · Q1 JOURNAL - RANK #1/332TOP-TIER
This review examines the therapeutic landscape of MEK inhibitors, focusing on their established role in BRAF-driven cancers and the challenges of toxicity and resistance in RAS-mutant tumors. While effective in BRAF-mutant melanoma, clinical utility is often limited by severe dermatological and gastrointestinal adverse effects, necessitating the development of predictive biomarkers like MAPK pathway activity. Emerging strategies emphasize dual-targeting drug design and combination regimens with immune checkpoint inhibitors or PI3K-mTOR inhibitors to improve durability and expand the therapeutic window. Refined patient selection through biomarker-guided approaches remains essential for optimizing MEK inhibition in oncology while exploring potential applications in non-oncological inflammatory and fibrotic disorders.
10.1016/S0140-6736(26)00199-6
Apr 13 – Apr 20, 2026
DART (NCI/SWOG S1609): Comprehensive Final Results from Dual Checkpoint Inhibition with CTLA-4 and PD-1 Blockade in Rare Cancers.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
The NCI/SWOG S1609 (DART) trial was a prospective, open-label, multicenter phase 2 study evaluating dual CTLA-4 and PD-1 inhibition (ipilimumab plus nivolumab) across 53 refractory rare cancer cohorts. Among 727 eligible patients, 24 of 53 cohorts (45%) demonstrated clinical activity, with a median objective response rate of 12% and a 3-year overall survival of 23%. This study is highly relevant to clinicians interested in cancer, particularly those managing patients with refractory rare cancers, by demonstrating meaningful responses to immunotherapy in a population with limited options. The findings suggest that ipilimumab plus nivolumab can provide clinical benefit in various rare cancer types, offering a potential therapeutic strategy, though further characterization of responsive subsets is needed.
10.1016/j.annonc.2026.04.004
Atezolizumab for Alveolar Soft Part Sarcoma: A Clinical Trial Update.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This phase II trial update reports on three additional years of observation for 53 patients with alveolar soft part sarcoma (ASPS) treated with atezolizumab monotherapy. The median duration of response increased to 37.0 months, with an objective response rate (ORR) of 35.8% and median progression-free survival (mPFS) of 20.8 months. Patients with ASPSCR1::TFE3 type 1 fusion showed higher ORR (43.9%) and mPFS (28.3 months) compared to type 2 (0% ORR, 7.5 months mPFS). These long-term results provide crucial evidence for the efficacy of atezolizumab in treating a specific cancer, ASPS, and suggest that prolonged treatment is beneficial, with drug holidays potentially feasible for some patients.
10.1200/JCO-25-02811
Selpercatinib and the Crossover Conundrum: Potential Impact of Postprogression Therapies on Overall Survival.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This abstract addresses the critical challenge of interpreting overall survival (OS) in randomized cancer trials, particularly due to high crossover rates and varied postprogression therapies, using Study LIBRETTO-431 as a case study. LIBRETTO-431 was an ex-US multiregional, open-label, randomized trial comparing selpercatinib to chemoimmunotherapy in treatment-naïve advanced RET fusion-positive non-small cell lung cancer. While selpercatinib showed a large improvement in progression-free survival, the immature OS analysis yielded a hazard ratio of 1.26, favoring the chemoimmunotherapy arm. This highlights the need for prespecified plans for OS data collection and analytical methods in cancer trials to accurately account for postprogression therapies and ensure reliable interpretation for clinical practice.
10.1200/JCO-25-02375
Microbiota and immune-related adverse events in cancer immunotherapy.
NAT REV CANCER · Q1 JOURNAL - RANK #3/326TOP-TIER
This review examines the role of tissue microbiomes, specifically in the gastrointestinal tract, lung, and skin, as potential mediators of immune-related adverse events (irAEs) in patients receiving cancer immunotherapy with immune checkpoint inhibitors (ICIs). The authors specifically analyze clinical and preclinical data regarding ICI-induced colitis, highlighting the complex interplay between microbial drivers and immune responses that lead to off-target toxicities. While specific numerical outcomes are not detailed in this review abstract, the synthesis of evidence points toward the microbiome as a critical factor in determining the risk and severity of treatment-limiting side effects. These findings suggest that modulating the microbiome could offer a therapeutic pathway to mitigate irAEs without compromising the anti-tumor efficacy of ICI regimens in clinical practice.
10.1038/s41568-026-00921-3