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Jul 20 – Jul 27, 2026
A phase I dose-escalation/expansion study of fractionated-dose and multiple cycle anti-PSMA-targeted alpha emitter 225Ac-J591 in patients with prostate cancer.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
This phase I, open-label dose-escalation/expansion trial prospectively evaluated two 225Ac-J591 prostate-specific membrane antigen–targeted radiotherapeutic regimens in men with metastatic castration-resistant prostate cancer. Forty-two patients received a single fractionated cycle (45–65 kBq/kg on days 1 and 15) and 18 received up to four 6-weekly cycles at the same activity; prior 177Lu-PSMA therapy was allowed in predefined cohorts. Dose-limiting toxicities occurred in 3/42 patients on the fractionated schedule, establishing a recommended phase-II dose of 60 kBq/kg × 2, whereas 7/18 patients on the multiple-cycle regimen experienced DLTs, leading to discontinuation of that approach. Hematologic adverse events were frequent (thrombocytopenia 93% overall, grade ≥3 in 32%) and xerostomia occurred in 62%; PSA declines ≥50% were achieved by 60% of fractionated-dose recipients versus 28% of multiple-cycle recipients. The authors conclude that fractionated 225Ac-J591 is tolerable and shows promising antitumor activity warranting further study.
10.1158/1078-0432.CCR-26-0689
Del immune V and microbiome restructuring in colorectal cancer surgery: a randomized double blind placebo controlled trial.
FRONT CELL INFECT MI · Q1 JOURNAL - RANK #32/163
The study aimed to evaluate the immunomodulatory and microbiome restructuring effects of Del-Immune V in colorectal cancer patients undergoing elective surgery. In this randomized, double-blind, placebo-controlled Phase I clinical trial including 39 patients (22 Del-Immune V, 17 placebo), participants received 100 mg capsules twice daily from 7-15 days presurgery until 15 days postsurgery. Results showed significant reductions in IL-6 (p=0.012), improvement in patient quality-of-life scores, and microbiome restructuring, including enrichment of short-chain fatty acid-producing genera and a reduction in cancer-associated taxa (dysbiosis index, p=0.024). The trial concluded that Del-Immune V is a safe adjunct therapy with immunomodulatory and microbiome-modulating properties, potentially enhancing recovery and long-term outcomes in colorectal cancer patients.
10.3389/fcimb.2026.1853373
Personalising radiotherapy dose in anal cancer (PLATO) Platform: 6-month patient reported outcomes across ACT3, ACT4 and ACT5 trials.
RADIOTHER ONCOL · Q1 JOURNAL - RANK #22/212
This study reports 6-month patient-reported outcomes from the PLATO platform of three prospective clinical trials in anal squamous cell carcinoma: ACT3 (adjuvant chemoradiotherapy vs observation after local excision), ACT4 (reduced- vs standard-dose chemoradiotherapy), and ACT5 (three dose-escalated chemoradiotherapy regimens). PROs (EORTC QLQ-C30 and QLQ-ANL27) were collected at multiple time points with >10-point mean score differences deemed clinically relevant; 709 patients were enrolled (706 mITT) across 36 UK sites, PRO consent was 98.9% and 6-month completion 86.0%. ACT5 patients had worse baseline function/symptoms; all treated groups showed large declines at end of treatment with most returning to baseline by 6 months, though ACT5 had persistent bowel deficits and ACT4 standard-dose and ACT5 reported poorer sexual function at 6 months. The authors conclude risk-adapted radiotherapy dosing is feasible with excellent PRO compliance, and longer follow-up will define late effects.
10.1016/j.radonc.2026.111706
IL-6 receptor inhibition promotes expansion of cytolytic CD4+ T cells after cellular immunotherapy.
BLOOD · Q1 JOURNAL - RANK #2/98TOP-TIER
This study aimed to investigate the immunological effects of IL-6 receptor (IL-6R) inhibition during allogeneic hematopoietic stem cell transplantation (HSCT), using single-cell RNA sequencing of patient samples from a prospective clinical trial comparing tocilizumab (TCZ) and placebo. Results showed IL-6R inhibition promoted Type-I IFN transcriptional programs and enhanced differentiation of cytolytic CD4+ T cells, including the Eomes+ subset, linked to favorable immunotherapy outcomes. Experimental systems confirmed IL-6 signaling attenuation improved anti-tumor effects by expanding cytolytic CD4+ T cells and reducing Th1/Th17 differentiation. These findings suggest IL-6R inhibition during HSCT may modulate immune responses to enhance cytolytic CD4+ T cells with implications for cancer immunotherapy optimization.
10.1182/blood.2025032420
Enfortumab Vedotin and Pembrolizumab in Cisplatin-Eligible Bladder Cancer.
NEW ENGL J MED · Q1 JOURNAL - RANK #2/332TOP-TIER
This phase 3, open-label, randomized trial compared perioperative enfortumab vedotin plus pembrolizumab (EV+P) with neoadjuvant cisplatin-gemcitabine in cisplatin-eligible adults with muscle-invasive bladder cancer undergoing cystectomy. Participants received 4 neoadjuvant cycles of EV+P followed by cystectomy and adjuvant EV+P, or 4 neoadjuvant cycles of cisplatin-gemcitabine followed by cystectomy; primary endpoint was event-free survival (EFS), with overall survival (OS) and pathological complete response (pCR) as key secondary endpoints. Among 405 vs 403 participants and median follow-up 33.6 months, 2-year EFS was 79.4% vs 66.2% (HR 0.53, 95% CI 0.41–0.70; P<0.001), OS 86.9% vs 81.3% (HR 0.65, 95% CI 0.48–0.89; P=0.006), and pCR 55.8% vs 32.5% (P<0.001). Grade ≥3 adverse events were 75.7% with EV+P vs 67.2% with cisplatin-gemcitabine; EV+P improved EFS, OS, and pCR with higher toxicity.
10.1056/NEJMoa2601486
Vactosertib plus pembrolizumab in patients with non-microsatellite instability-high metastatic colorectal or gastric cancer: a multicenter, phase Ib/IIa study.
NAT COMMUN · Q1 JOURNAL - RANK #10/135TOP-TIER
This multicenter, open-label, single-arm phase Ib/IIa clinical trial assessed vactosertib plus pembrolizumab in 120 patients with non-MSI-high metastatic colorectal (n=108) or gastric cancer (n=12). The primary objective was to evaluate safety and tolerability, with secondary endpoints including various efficacy outcomes; the regimen demonstrated manageable safety, with treatment-related adverse events in 70.8% of patients (pruritus and rash most common). Among colorectal cancer patients, an objective response rate of 12.6% (higher in those without liver metastases: 22.5% vs. 6.3%) and a median overall survival of 13.2 months were reported; no objective responses were observed in gastric cancer patients. The study concluded vactosertib plus pembrolizumab has clinical activity in non-MSI-high mCRC, especially in patients without liver metastases.
10.1038/s41467-026-75595-4
Eribulin versus taxane as first-line chemotherapy combined with dual HER2 blockade in patients with HER2-positive locally advanced or metastatic breast cancer: final survival outcomes of the JBCRG-M06/EMERALD study.
ESMO OPEN · Q1 JOURNAL - RANK #36/326
The phase III JBCRG-M06/EMERALD study compared eribulin and taxane combined with dual HER2 blockade as first-line chemotherapy for HER2-positive locally advanced or metastatic breast cancer (LABC/MBC). A total of patients were randomized 1:1 and primary outcomes included progression-free survival (PFS) and overall survival (OS). Median OS was 78.5 months for eribulin and not reached for taxane (HR 1.25, 95% CI 0.92-1.71, P=0.19), with 60-month OS rates of 59.7% and 65.2% respectively. The study concluded that both regimens provided over 6-year median survival with no significant differences, while ctDNA PIK3CAm+ mutations were prognostic of shorter survival and ctDNA HER2 amp+ was linked to longer survival.
10.1016/j.esmoop.2026.108325
Domvanalimab plus zimberelimab in unresectable and immunotherapy refractory biliary tract cancers: a phase 2 trial.
NAT COMMUN · Q1 JOURNAL - RANK #10/135TOP-TIER
This phase 2, prospective clinical trial (NCT05724563) investigated the Fc-silent anti-TIGIT antibody domvanalimab combined with the anti-PD-1 antibody zimberelimab in 29 patients with unresectable biliary tract cancers that had progressed after prior PD-1/L1 therapy. Participants received the combination therapy and were assessed for confirmed objective response rate (primary end-point) alongside disease control rate, 6-month progression-free survival, duration of response, overall survival, and safety. The confirmed objective response rate was 10.3 % (95 % CI 2.2–27.4 %), disease control rate 44.8 %, 6-month PFS rate 17.2 % (95 % CI 6.0–35.8 %), and median duration of response 13.6 months; treatment-related adverse events occurred in 36.4 %, mainly low-grade pruritus and rash. Although the prespecified ORR target was not met, the durable responses, favorable safety, and translational biomarker insights support further evaluation of anti-TIGIT-based combinations in refractory biliary tract cancer.
10.1038/s41467-026-75554-z
Associations Between Cardiac Radiation Dose-Volume Metrics and Health-Related Quality of Life for Patients With Breast Cancer on the RadComp Trial.
INT J RADIAT ONCOL · Q1 JOURNAL - RANK #14/212
This study analyzes data from the RadComp pragmatic randomized clinical trial comparing proton versus photon radiotherapy in breast cancer patients. The primary objective was to evaluate associations between cardiac radiation dose-volume metrics and health-related quality of life (HRQOL) outcomes. Key findings include significantly lower mean heart dose with protons (0.89 Gy vs 2.99 Gy, p<0.001) but no significant associations between any dose-volume histogram parameters and cardiac-related HRQOL measures over 6 months post-treatment. The authors conclude that proton therapy confers lower cardiac doses but that no early HRQOL differences were detected, with grade ≥3 toxicity remaining uncommon (≤5.5%).
10.1016/j.ijrobp.2026.06.3055
CD20 expression dynamics in adult B-cell acute lymphoblastic leukemia and impact on anti-CD20 treatment.
J HEMATOL ONCOL · Q1 JOURNAL - RANK #1/98TOP-TIER
This prospective GMALL 08/2013 trial evaluated the clinical impact of baseline CD20 expression levels on B-cell acute lymphoblastic leukemia (B-ALL) and explored rituximab’s effect on treatment outcomes. Patients received a cyclophosphamide/dexamethasone prephase, induction, and consolidation therapy with four rituximab doses in BCR::ABL1-negative cases, and CD20 expression was measured repeatedly in marrow and blood samples. Higher CD20 expression correlated with improved early MRD responses and higher molecular complete remission rates (30.5% vs 10.6% after Induction I; 72.6% vs 50.0% after Consolidation I). The authors conclude that reassessing CD20 expression post-prephase identifies additional patients for rituximab therapy, potentially improving outcomes.
10.1186/s13045-026-01832-4
Phase 1/2 study of IMC-C103C, a T cell receptor bispecific (MAGE-A4×CD3) ImmTAC targeting MAGE-A4-expressing malignancies.
J IMMUNOTHER CANCER · Q1 JOURNAL - RANK #12/183TOP-TIER
Phase 1/2 IMC-C103C-101 (NCT03973333) evaluated the safety, PK/PD, biomarkers, and preliminary antitumor activity of the MAGE-A4×CD3 ImmTAC IMC‑C103C in HLA‑A*02:01 adults with previously treated advanced solid tumors via weekly IV step‑up dosing and mTPI‑2–guided dose escalation. Sixty‑eight patients (56 in 10 dose‑escalation cohorts, 12 in an ovarian carcinoma expansion; 64% OC) received 0.5–240 µg; DLT rates at the two highest dose levels were 1/6 and 2/10, with no treatment‑related discontinuations or deaths. A 15‑45‑140 µg regimen was selected for expansion, with mainly grade 1/2 cytokine‑mediated adverse events including CRS; 71% of tumors were MAGE‑A4+, median H‑score 16. Clinical and PD activity began at 15 µg and was more consistent at ≥90 µg, where MAGE‑A4+ OC showed deeper tumor and ctDNA reductions and a trend toward longer overall survival; IMC‑C103C was well tolerated up to 140 µg.
10.1136/jitc-2025-014638
Safety and efficacy of fecal microbiota transplantation in solid cancers resistant to immune checkpoint inhibitors: results of the MITRIC trial.
J IMMUNOTHER CANCER · Q1 JOURNAL - RANK #12/183TOP-TIER
This single-arm phase IIa basket trial (MITRIC; NCT05286294) tested the safety, feasibility, and efficacy of fecal microbiota transplantation (FMT) from immune checkpoint inhibitor (ICI) responders to patients with advanced cancers refractory to ICIs. Patients received up to five FMT administrations in combination with ICIs, with FMT-related adverse events and objective response as co-primary endpoints. Among 12 participants with various solid tumors, no objective responses were observed, five achieved stable disease, and median progression-free survival and overall survival were 1.5 and 10.1 months, respectively. Although FMT plus ICIs proved safe and feasible, clinical activity was limited, highlighting the need for further studies.
10.1136/jitc-2026-015122
The WinPro trial: window-of-opportunity study of endocrine therapy with micronised progesterone in ER-positive breast cancer.
NPJ BREAST CANCER · Q1 JOURNAL - RANK #42/326
The WinPro trial is a randomized, multi-centre, prospective, phase 2 window-of-opportunity study of micronised progesterone (MP) in post-menopausal women with ER+, PR+, HER2- breast cancer. The methodology involved random assignment to letrozole, letrozole plus MP, or tamoxifen plus MP for 14 days preoperatively with Ki67 suppression as the primary endpoint. Among 189 evaluable patients, Ki67 suppression was similar in the letrozole (88.2%) versus letrozole+MP (89.2%) groups (p=0.39), but was lower in the tamoxifen+MP arm (61.5%), with fewer hot flushes in the letrozole+MP group (13.3%). The study concludes that while MP combined with letrozole did not significantly enhance Ki67 suppression compared to letrozole alone, the combination was associated with reduced vasomotor side effects and warrants further investigation.
10.1038/s41523-026-01008-w
A prospective national precision medicine trial evaluating the feasibility of blood-based molecular profiling in patients with Cancer of Unknown Primary (CUP-COMP).
BRIT J CANCER · Q1 JOURNAL - RANK #47/326
The prospective CUP-COMP study (NCT04750109) examined the feasibility of integrating blood- and tissue-based molecular profiling with a National Molecular Tumour Board for patients with histologically confirmed Cancer of Unknown Primary from seven UK sites. Among 117 patients, 115 received successful molecular profiling, with higher rates for blood-based (93%) than tissue-based (61%), identifying potentially actionable alterations in 63% (73/115), and 26% (31/117) were treated using a precision medicine approach. Retrospective analysis revealed a median overall survival of 9.5 months and noted that 33% of patients had a tumour fraction below 1%. The study concludes that liquid biopsies are highly feasible for CUP and can rapidly guide targeted therapy decisions, though tissue-based profiling is still preferred.
10.1038/s41416-026-03519-6
Higher rates of immune-related adverse events in circulating tumor DNA (ctDNA)-negative patients following adjuvant checkpoint inhibitor therapy.
ESMO OPEN · Q1 JOURNAL - RANK #36/326
This study prospectively compared muscle-invasive urothelial carcinoma patients (n=781) treated with adjuvant atezolizumab (n=384) or observation (n=397), analyzing associations between circulating tumor DNA (ctDNA) status and immune-related adverse events (irAEs) using Cox models, sensitivity analyses, and landmark analysis. The primary objective was to explore the relationship between ctDNA status and time to first irAE. Key findings included higher all-grade irAE rates in baseline ctDNA-negative AA patients versus positive (54.7% vs. 32.5%; HR 1.91, 95% CI: 1.25–2.90), and lower irAE rates with increasing ctDNA (HR 0.92 per log-MTM/ml, 95% CI: 0.87–0.97); discontinuation for adverse events was also higher in ctDNA-negative patients. The study concluded that ctDNA-negative patients receiving AA experienced more toxicity without survival benefit, suggesting ctDNA could inform treatment decisions.
10.1016/j.esmoop.2026.107701
Patient-reported Outcomes After Prostate Stereotactic Body Radiotherapy at 5 yr: Results from the PACE-B Trial.
EUR UROL · Q1 JOURNAL - RANK #3/133TOP-TIER
This phase 3 international randomized PACE-B trial compared stereotactic body radiotherapy (SBRT) versus conventionally fractionated radiotherapy (CRT) in men with localized prostate cancer, reporting patient-reported outcomes (PROMs) from baseline to 5 years. At 5 years, urinary incontinence outcomes were similar: leak-free 64% (164/258) SBRT vs 69% (172/249) CRT, pad-free 91% (233/257) SBRT vs 90% (225/250) CRT, and moderate/big leakage 6% (15/250) SBRT vs 4% (9/244) CRT. Sexual function declined in both groups: intercourse-adequate erections fell from 35% (133/374) to 17% (43/250) for SBRT and from 40% (157/391) to 20% (47/240) for CRT; moderate/big sexual problems rose to 31% (74/242) SBRT and 32% (77/238) CRT. Bowel effects were low and comparable (moderate/big bowel problems 5% at 5 years in both arms; stool incontinence 2% SBRT vs 3% CRT).
10.1016/j.eururo.2026.05.034
The Role of Locoregional Treatment in Non-Progressive De Novo Metastatic Breast Cancer under Systemic Treatment: A Randomized Controlled Trial (LTMBC).
ANN SURG ONCOL · Q1 JOURNAL - RANK #39/312
This randomized controlled trial examined the role of locoregional treatment (LRT) compared to systemic treatment (ST) in patients with non-progressive de novo metastatic breast cancer (DnMBC) under systemic therapy. A total of 250 patients were randomized to an LRT group (n = 158) and an ST-only group (n = 92), with follow-ups every three months over five years. The study found no significant differences in overall survival (OS) between the LRT (median OS: 53 months) and ST (median OS: 55 months) groups (adjusted HR: 0.08; 95% CI: 0.9-1.3; p = 0.35). However, patients with HER2+ status (HR: 1.86; p = 0.005) and lung metastases (HR: 1.5; p = 0.03) exhibited an increased risk of death, concluding that LRT did not improve long-term OS outcomes in DnMBC cases under systemic therapies.
10.1245/s10434-026-20187-1
Jul 13 – Jul 20, 2026
ctDNA-Based MRD Detection in Stage III NSCLC Treated With Chemoradiotherapy and Durvalumab.
J THORAC ONCOL · Q1 JOURNAL - RANK #3/108TOP-TIER
In this prospective multicenter study (NCT04392505), the primary objective was to evaluate a personalized tumor-agnostic ctDNA-based MRD assay for identifying patients with unresectable stage III NSCLC at high relapse risk after standard-of-care chemoradiotherapy plus durvalumab. The trial measured ctDNA detection at screening, after CRT, and during and after durvalumab in 659 plasma samples from 84 patients. Detectable ctDNA prior to the seventh durvalumab cycle (HR: 2.45, 95% CI: 1.18-5.11, p=0.013) and 3 months post-treatment (HR: 5.37, 95% CI: 1.93-14.93, p<0.001) predicted shorter progression-free survival. Researchers concluded that serial ctDNA-based MRD assessment may help guide targeted or intensified treatments to reduce the risk of early relapse.
10.1016/j.jtho.2026.103992
OPTIM: a randomized phase II trial of nivolumab followed by nivolumab-ipilimumab or docetaxel at progression in recurrent/metastatic squamous cell carcinoma of the head and neck (OPTIM; AIO-KHT-0117).
BRIT J CANCER · Q1 JOURNAL - RANK #47/326
This randomized phase II trial investigated staggered immune checkpoint inhibition versus docetaxel in nivolumab-refractory recurrent/metastatic squamous cell carcinoma of the head and neck. Adults received nivolumab and were randomized at progression to nivolumab-ipilimumab (NIVO-IPI) or docetaxel (DOCE). Among 31 patients, ORR was 0% (NIVO-IPI) versus 17.6% (DOCE), with median PFS of 1.97 vs 3.66 months (P=0.036) and median OS of 3.97 vs 11.9 months (P=0.356). NIVO-IPI did not improve efficacy over docetaxel, showing numerically inferior survival, while docetaxel had greater grade ≥3 toxicity (68.8% vs 38.5%).
10.1038/s41416-026-03558-z
Non-Armored GCC-targeting CAR-T cell therapy demonstrates significant efficacy in patients with advanced colorectal cancer.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
This single-arm, open-label, phase 1 trial aimed to assess the safety, expansion, and preliminary anti-tumor efficacy of non-armored, nanobody-derived GCC-targeted CAR-T cells in twenty-four patients with heavily pretreated metastatic colorectal cancer. Participants received CAR-T cells at four dose levels (0.5×10^5, 1×10^6, 2×10^6, or 3×10^6 cells/kg), and the study measured toxicities, antitumor activity, and pharmacokinetics. The overall response rate and disease control rate were 33% and 63%, respectively, with a median progression-free survival of 57 days and median overall survival of 190 days. Despite encouraging antitumor activity and proof-of-concept for GCC as a valid target, response durability remained limited, requiring further optimization of dose, patient selection, and toxicity management.
10.1158/1078-0432.CCR-26-0854
Tumor infiltrating lymphocytes as a predictor of adjuvant avelumab efficacy in patients with high-risk triple negative breast cancer.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
This study is a prospective, randomized phase III clinical trial (A-BRAVE) evaluating avelumab adjuvant immunotherapy versus observation in 466 patients with high-risk early triple-negative breast cancer. The primary objective was to investigate the prognostic and predictive value of tumor-infiltrating lymphocytes (TILs) for treatment outcomes. Higher baseline TILs (>=30%) significantly predicted avelumab benefit, with 3-year distant disease-free survival rates of 92.0% vs. 58.7% (HR 0.20) in high-TIL patients versus 70.4% vs. 70.1% (HR 0.92) in low-TIL patients (interaction p=0.019). The authors conclude TILs may guide adjuvant immunotherapy strategies pending validation.
10.1158/1078-0432.CCR-26-0975
A Phase 1 Trial of Dose-Escalated Hypofractionated Adaptive Radiation Therapy With Atezolizumab for Advanced Head and Neck Cancers.
INT J RADIAT ONCOL · Q1 JOURNAL - RANK #14/212
This single-center, prospective phase 1 clinical trial evaluated the safety and maximum-tolerated dose (MTD) of dose-escalated hypofractionated adaptive radiation therapy (50, 55, or 60 Gy in 15 fractions) combined with atezolizumab in patients with advanced head and neck squamous cell carcinomas. Eighteen patients received either concurrent or adjuvant atezolizumab, with study amendments after toxicity observed in the initial cohort. After the amendment, no dose-limiting toxicities were reported, establishing 60 Gy with adjuvant atezolizumab as the MTD, and among 7 patients at the highest dose, 1-year progression-free survival was 71.4%. The study concluded that radiation dose escalation to 60 Gy is safe with adjuvant atezolizumab, whereas concurrent delivery resulted in excess herpes virus toxicity.
10.1016/j.ijrobp.2026.06.3053
Teclistamab-based induction treatment in transplant-eligible, newly diagnosed multiple myeloma: a phase 2 trial.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This ongoing phase 2 GMMG-HD10/DSMM-XX (MajesTEC-5) trial prospectively evaluated teclistamab-based induction in transplant-eligible, newly diagnosed multiple myeloma, assigning 49 patients to Tec-DR (teclistamab/daratumumab/lenalidomide) or Tec-DVR (plus bortezomib) and following through induction, autologous transplant, and premaintenance. Primary endpoints were safety (AEs/SAEs), with secondary efficacy endpoints (ORR, MRD negativity, MRD-negative CR). Grade 3–4 TEAEs occurred in 91.8% (lymphopenia 59.2%, neutropenia 59.2%, leukopenia 18.4%); SAEs in 55.1%; infections in 81.6% (grade 3–4: 36.7%); CRS in 67.3% (all grade 1–2, resolved); no grade 5 TEAEs or treatment-related ICANS. Efficacy was notable with ORR 100% (49/49), MRD-negative CR 91.8% (45/49) by premaintenance, and 100% MRD negativity in evaluable samples at postinduction cycles and premaintenance, supporting the feasibility and high activity of Tec-D(V)R induction.
10.1038/s41591-026-04471-x
Artificial intelligence-assisted detection and optical differentiation of colorectal lesions in Lynch syndrome surveillance (CADLY2): a multicentre, open-label, randomised controlled superiority trial.
LANCET GASTROENTEROL · Q1 JOURNAL - RANK #2/147TOP-TIER
This multicentre, open-label, randomised controlled superiority trial evaluated the efficacy of computer-aided detection (CADe) and computer-aided optical diagnosis (CADx) for colorectal lesion detection in Lynch syndrome surveillance. 757 adults with genetically confirmed Lynch syndrome were randomized to high-definition white-light colonoscopy (HD-WL) or HD-WL plus AI-assisted CADe, with the primary outcome being adenoma detection rate, and CADx diagnostic accuracy as a secondary endpoint. The adenoma detection rate was 30.9% in the HD-WL group versus 33.8% in the AI-assisted group (odds ratio 1.14 [95% CI 0.83–1.57], p=0.41), and CADx achieved a sensitivity of 85.9% and specificity of 91.4% for differentiating neoplastic from non-neoplastic lesions. The study concluded that CADe did not significantly improve adenoma detection rate compared with conventional colonoscopy in this high-risk population.
10.1016/S2468-1253(26)00163-9
PD-1 blockade unleashes local hepatitis B virus-related B cell response inhibiting hepatocellular carcinoma.
CANCER CELL · Q1 JOURNAL - RANK #5/326TOP-TIER
This study investigated the mechanisms of anti-PD-1 therapy in a phase 2 clinical trial (NCT04615143) involving patients with resectable recurrent hepatocellular carcinoma (HCC). Using single-cell multi-omics, clonal antibody repertoire analysis, and spatially paired scRNA-seq/BCR-seq, the study identified a distinct B cell–driven immune subtype marked by somatic hypermutation and antibody responses targeting hepatitis B virus antigens within tumor tertiary lymphoid structures. Mechanistically, these antibodies activate a complement-mediated antitumor response, augmenting anti-PD-1 efficacy. The findings reveal enhanced antiviral B cell immunity as a mechanism of action in anti-PD-1-treated HCC patients, with preclinical validation in mouse models demonstrating improved therapeutic outcomes.
10.1016/j.ccell.2026.06.010
Three-Year Follow-Up of the Randomized Trial Comparing Open Versus Laparoscopic Surgery for Primary Tumor Resection in Patients With Non-Curable Stage IV Colon Cancer (JCOG1107).
DIS COLON RECTUM · Q1 JOURNAL - RANK #33/312
This multicenter, open-label, randomized phase III trial evaluated non-inferiority of laparoscopic versus open primary tumor resection in symptomatic non-curable stage IV colon cancer. A total of 195 patients were randomized (95 open, 100 laparoscopic), followed by chemotherapy. Median follow-up was 24.4 months. Three-year progression-free survival was 5.3% (open) vs. 3.0% (laparoscopic) (HR 1.028, p=0.02 for non-inferiority), and three-year overall survival was 31.5% vs. 28.5% (HR 1.048). Laparoscopic surgery was concluded to be non-inferior and an acceptable option.
10.1097/DCR.0000000000004373
Effectiveness of silver diamine fluoride in preventing radiation-induced caries: A pilot study.
J AM DENT ASSOC · Q1 JOURNAL - RANK #24/162
This randomized, single-blind, placebo-controlled clinical trial evaluated the effectiveness of professionally applied 38% silver diamine fluoride (SDF) in preventing radiation-induced dental caries in 56 head and neck cancer patients undergoing radiotherapy. Participants were assigned to receive SDF or placebo before and after radiotherapy, with caries increment, salivary flow, gingival index, and oral health-related quality of life assessed at 1, 3, and 6 months. At 3 and 6 months, median caries increments were significantly lower in the SDF group (3 months: 1.0 vs 2.0, P=.027; 6 months: 2.0 vs 3.0, P=.030), and 47.1% of SDF participants developed no new lesions compared to 5.9% on placebo (P=.017). The study concluded that topical SDF reduces caries progression in this population, serving as a practical preventive intervention.
10.1016/j.adaj.2026.05.008
Durvalumab With Radiation Therapy in Patients With Inoperable Locally Advanced Non-Small Cell Lung Cancer Ineligible for Concurrent Chemoradiotherapy (DART).
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This multicenter, single-arm, prospective phase II trial evaluated thoracic radiation plus concurrent and up to 12 months of consolidative durvalumab (1,500 mg every 4 weeks) in cCRT-ineligible patients with inoperable, locally advanced NSCLC. The primary endpoint targeted a 2-year PFS of 36% versus historical 20% with sequential CRT; 58 patients (median age 82) received conventionally fractionated RT and durvalumab, and associations with ECOG and PD-L1 were explored. The study met its primary endpoint with 2-year PFS 39% (one-sided CI 29–100) and reported 2-year OS 54%; grade 3/4 treatment-related AEs occurred in 21%, grade 5 in 7% (radiation pneumonitis n=2, cardiac arrest n=2), with durvalumab discontinued due to AEs in 31%. Better performance status and PD-L1 positivity correlated with improved PFS/CSS, supporting durvalumab with RT as a promising option for cCRT-ineligible LA-NSCLC.
10.1200/JCO-25-02517
Recurrence Score® gene group components and outcomes in the RxPONDER trial (SWOG S1007).
JNCI-J NATL CANCER I · Q1 JOURNAL - RANK #44/326
The RxPONDER trial assessed the impact of Recurrence Score® gene components on outcomes in 3,102 patients with HR+/HER2- breast cancer (RS ≤ 25, 1-3 positive nodes), randomized to endocrine therapy ± chemotherapy. Subgroup analyses revealed significant ethnic variations in proliferation (e.g., NHB vs. NHW, p=0.003) and other gene pathways (e.g., Asian women had higher HER2 scores, p=0.006), with no statistically significant IDFS differences in NHB women (HR 1.41, 95% CI 0.98-2.03) but improved IDFS in Asian women (HR 0.63, 95% CI 0.43-0.91). Multivariable Cox modeling underscored disparities in pathway contributions to prognosis. The study advocates for greater focus on pathway-specific biology beyond composite RS to address outcome disparities and enhance precision in risk stratification.
10.1093/jnci/djag221
Extracellular vesicles as prognostic biomarkers: results of a neoadjuvant chemoimmunotherapy clinical trial in stage IIIA (N2) non-small-cell lung cancer (SAKK 16/14).
FRONT IMMUNOL · Q1 JOURNAL - RANK #32/183
This study analyzes longitudinal extracellular vesicle (EV) dynamics as prognostic biomarkers in a prospective single-arm phase II clinical trial (SAKK 16/14) of neoadjuvant chemoimmunotherapy (cisplatin, docetaxel, durvalumab) followed by surgery and adjuvant durvalumab in patients with resectable stage IIIA (N2) non-small-cell lung cancer. Serum samples were collected at five time points; EV markers (PD-L1, PanEV, PanCK, EpCAM, CD45) were assessed via flow cytometry after galectin-based isolation, with nanoparticle tracking analysis and electron microscopy confirming successful isolation. Results showed a trend of decreasing EV-MFI after initial therapy; elevated post-therapeutic PanEV/PanCK double-positive EV levels were significantly associated with reduced event-free survival (p=0.001) and overall survival (p=0.003). The study concludes that EV-based liquid biopsies offer complementary prognostic information in heterogeneous cancer stages, supporting personalized treatment strategies.
10.3389/fimmu.2026.1807542
Surgical Outcomes of Perioperative Toripalimab in Stage III Resectable Non-Small Cell Lung Cancer: Post Hoc Analysis of the Neotorch Randomized Clinical Trial.
JAMA SURG · Q1 JOURNAL - RANK #1/312TOP-TIER
This multicenter, double-blind, placebo-controlled phase 3 randomized trial (Neotorch, NCT04158440) enrolled 404 patients with resectable stage III NSCLC, randomizing them 1:1 to three neoadjuvant and one adjuvant cycle of toripalimab (240 mg) plus platinum-based chemotherapy versus placebo plus chemotherapy, followed by 13 maintenance cycles of either toripalimab or placebo. Among 314 operated patients (166 vs 148), the toripalimab group had fewer surgery cancellations (17.8% vs 26.7%; P = .03), higher tumor downstaging (80.7% vs 50.7%; P < .001) and lymph-node downstaging (67.5% vs 48.6%; P = .001), with similar perioperative complication rates. After a median 18.3-month follow-up, toripalimab improved event-free survival, particularly in patients achieving tumor or nodal downstaging (median EFS not estimable vs 17.5–22.0 months; P values .004–.009). The authors conclude that perioperative toripalimab plus chemotherapy offers comparable surgical safety and confers superior downstaging and EFS benefits in resectable stage III NSCLC.
10.1001/jamasurg.2026.2711
Toxicity during induction of pulsed versus continuous prednisolone in children with acute lymphoblastic leukaemia: a multi-centre, open label, randomised, phase 3 trial from India (2016-2022).
LANCET REG HLTH-SE A · Q1 JOURNAL - RANK #10/185
This open-label, multicentre, randomised phase 3 trial in India compared continuous versus pulsed prednisolone during induction therapy for children ≤10 years with newly diagnosed standard- or intermediate-risk B-cell precursor acute lymphoblastic leukaemia. 1,246 eligible patients were randomised 1:1 to continuous 60 mg/m²/day for 4 weeks with taper (R1A) or pulsed dosing on days 1–14 and 22–28 (R1B); primary endpoint was grade 3-5 toxicity, with CR, MRD, 3-year event-free survival (EFS) and overall survival (OS) as secondary endpoints. Induction deaths were significantly lower with pulsed dosing (1.3% vs 3.5%; absolute risk difference 2.3%, p=0.0149; HR 3.06), while grade 3-5 toxicities were comparable (45.4% vs 46.4%); CR rates (98.0-98.8%), MRD ≥0.01% (26-28%), 3-year EFS (72.2-72.7%) and OS (85-87%) did not differ. Authors conclude that pulsed prednisolone reduces treatment-related mortality without impairing remission or survival, and that anthracycline use independently elevates mortality and toxicity risks.
10.1016/j.lansea.2026.100788
Continuous or Fixed-Duration Maintenance Therapy in Multiple Myeloma.
NEW ENGL J MED · Q1 JOURNAL - RANK #2/332TOP-TIER
This phase 3 clinical trial aimed to compare the efficacy of indefinite-duration versus fixed-duration lenalidomide maintenance therapy in newly diagnosed multiple myeloma patients with standard risk, who were not undergoing up-front autologous stem-cell transplantation. A total of 516 patients were randomly assigned to either the indefinite-duration (260 patients) or fixed-duration (256 patients, 2 years of treatment) groups after induction therapy. At a median follow-up of 86 months, overall survival between the groups did not significantly differ (7-year survival: 68.6% vs. 69.0%, P=0.93), while progression-free survival at 7 years was slightly higher in the indefinite-duration group (36.1% vs. 29.7%). Indefinite-duration therapy was associated with a higher incidence of grade ≥3 nonhematologic adverse events (48.2% vs. 31.5%) and marginally higher rates of secondary primary cancers (11.2% vs. 8.3%).
10.1056/NEJMoa2600157
Perioperative tislelizumab plus chemotherapy for locally advanced gastric cancer: A randomized, prospective phase 2 trial.
CANCER CELL · Q1 JOURNAL - RANK #5/326TOP-TIER
This prospective, randomized, multicenter phase 2 trial aimed to assess the efficacy of perioperative tislelizumab plus chemotherapy for locally advanced gastric or gastroesophageal junction cancer, stratified by tumor-specific MHC class II (tsMHC-II) expression. A total of 136 operable cT3-4aN+M0 patients were randomly assigned to receive either tislelizumab plus chemotherapy or chemotherapy alone. Among tsMHC-II-positive patients, the addition of tislelizumab significantly increased the major pathological response rate (61.8% vs. 26.5%, p=0.003) and pathological complete response rate (32.4% vs. 5.9%, p=0.006). These findings highlight the potential of tsMHC-II as a predictive biomarker for perioperative immunotherapy and underscore the need for further validation.
10.1016/j.ccell.2026.06.015
Dose-escalated versus Standard Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer: 9-year Results of a Randomized Phase 2 Trial.
INT J RADIAT ONCOL · Q1 JOURNAL - RANK #14/212
This prospective, randomized phase II trial (NCT02195141) in 106 patients with stage II/III rectal adenocarcinoma compared standard (50 Gy/25 fractions) and dose-escalated SIB-CRT (50 Gy to the pelvis with SIB to 56–60 Gy) before planned radical surgery. The primary endpoint was pathological complete response (pCR), with secondary outcomes including DFS, OS, MFS, LC, CSS, and toxicity. At a median follow-up of 116.6 months, the SIB-CRT group demonstrated higher 9-year DFS (70.8% vs 47.4%, HR 0.46, P=0.013), OS (74.3% vs 48.9%, HR 0.43, P=0.008), and LC (87.1% vs 70.1%, HR 0.40, P=0.038), with comparable pCR rates (15.2% vs 18.4%). These findings highlight the significant survival advantage afforded by dose escalation, especially in patients who did not receive perioperative chemotherapy.
10.1016/j.ijrobp.2026.07.004
Adjuvant Chemotherapy ± Chemoradiotherapy for Adenocarcinoma of the Pancreatic Head: Results of the Radiotherapy Random Assignment of NRG Oncology/RTOG 0848.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This multicenter, randomized phase III clinical trial evaluated whether adding fluoropyrimidine-sensitized radiotherapy (CXRT) to adjuvant chemotherapy after curative resection for pancreatic head adenocarcinoma improves overall survival (OS). In step 2, 354 patients were randomized to chemotherapy alone (n=174) or chemotherapy plus CXRT (n=180) after initial chemotherapy. Median OS was 2.6 years for chemotherapy and 2.3 years for chemotherapy + CXRT, with 5-year OS rates of 23.1% and 27.9%, respectively; the primary OS endpoint was not met (HR, 0.96; 90% CI, 0.79–1.18). CXRT increased grade 3 toxicity (38% vs 19%, p<.001), but improved OS and DFS in node-negative patients (p=.0063 and p=.014, respectively).
10.1200/JCO-25-02520
Larotrectinib in TRK fusion differentiated thyroid carcinoma: updated trial data.
ENDOCR-RELAT CANCER · Q1 JOURNAL - RANK #43/191
This pooled analysis from three phase 1-2 larotrectinib clinical trials prospectively evaluated 24 patients with TRK fusion differentiated thyroid carcinoma (DTC) using an independent review committee. The primary endpoint was overall response rate (ORR) per RECIST v1.1, with secondary endpoints including duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. ORR was 79% (95% CI 58-93), with 13% complete responses, median DoR 35 months (95% CI 22-NE), median PFS 44 months (95% CI 35-NE), and 6-year OS rate 71% (95% CI 50-91); treatment-related adverse events were mainly Grade 1/2 with no discontinuations. The authors conclude larotrectinib continues to demonstrate durable disease control, extended survival, and a favorable long-term safety profile in advanced TRK fusion DTC.
10.1530/ERC-25-0531
GPC3-specific dnTGFβRII-armoured CAR T cells for hepatocellular carcinoma.
NATURE · Q1 JOURNAL - RANK #2/135TOP-TIER
This first-in-human, dose-escalation clinical trial (NCT05155189) evaluated GPC3-directed CAR T cells incorporating a dominant-negative TGFβ receptor II (C-CAR031) in adults with advanced, treatment-refractory hepatocellular carcinoma. Thirty-six participants received a single infusion at four escalating doses (0.75×106–4.0×106 cells /kg) and were followed prospectively for safety, tumour response, and survival. Cytokine-release syndrome occurred in 34/36 patients (grade 3 in 2), with nine grade ≥3 non-haematological adverse events; tumour regression was seen in 32 patients, giving an objective response rate of 44.4 %, median best tumour reduction of 41.6 %, median response duration of 4.4 months, progression-free survival of 4.2 months, and overall survival of 14.2 months. The study concludes that C-CAR031 is tolerable and shows encouraging antitumour activity, though resistance mechanisms may involve GPC3 loss and elevated TGFβ.
10.1038/s41586-026-10786-z
AdvanTIG-302: Phase 3 Study of Ociperlimab (Anti-TIGIT) + Tislelizumab (Anti-PD-1) Versus Pembrolizumab in Untreated, Locally Advanced, Unresectable, or Metastatic Non-Small Cell Lung Cancer With PD-L1 ≥50.
J THORAC ONCOL · Q1 JOURNAL - RANK #3/108TOP-TIER
This phase 3 randomized trial evaluated ociperlimab plus tislelizumab versus pembrolizumab and tislelizumab in 662 previously untreated patients with locally advanced or metastatic NSCLC with PD-L1 ≥50%. Patients were randomized 5:5:2 to one of the three arms, and the primary endpoint was overall survival (OS), with secondary endpoints including progression-free survival (PFS) and overall response rate (ORR). The interim analysis found median OS for arms A (ociperlimab+tislelizumab), B (pembrolizumab), and C (tislelizumab) to be 31.9, 29.4, and 27.7 months, respectively, with a stratified hazard ratio for A vs B of 0.97 (95% CI: 0.76–1.23), while PFS and ORR results did not indicate clear superiority. The combination therapy did not improve OS compared to pembrolizumab, and all arms showed acceptable safety profiles.
10.1016/j.jtho.2026.104089
Preclinical characterization and phase 1 clinical testing of targeting mitochondrial peroxiredoxin 3 in cancer.
NAT COMMUN · Q1 JOURNAL - RANK #10/135TOP-TIER
In a phase 1 clinical trial (NCT05278975), researchers evaluated weekly intrapleural administration of a novel thiostrepton-based drug (RSO-021) to target peroxiredoxin 3 in relapsed pleural mesothelioma. They aimed to assess safety, tolerability, and dose, while exploring secondary endpoints (pharmacokinetics, objective response rate, disease control rate, and progression-free survival). The therapy was well tolerated at 90 mg and achieved 67% disease control at 12 weeks. The authors conclude that inhibiting mitochondrial PRX3 may be an effective pro-oxidant strategy to enhance anti-tumor activity.
10.1038/s41467-026-75153-y
Surgical window of opportunity clinical trial of abemaciclib and letrozole for endometrioid adenocarcinoma of the endometrium.
GYNECOL ONCOL · Q1 JOURNAL - RANK #11/140
Investigators conducted a single-arm prospective multicenter surgical window of opportunity clinical trial to assess abemaciclib and letrozole for endometrioid adenocarcinoma of the endometrium. Patients planned for hysterectomy received abemaciclib 150 mg twice daily plus letrozole 2.5 mg once daily for 14 days. Mean Ki-67 was reduced from 34% to 19% (SD 23%, p < 0.001) in 25 evaluable patients, with no serious adverse events. These results suggest that short-term neoadjuvant abemaciclib and letrozole can reduce tumor proliferation in endometrioid endometrial cancer.
10.1016/j.ygyno.2026.07.001
Quality of life results of addition of androgen deprivation therapy and pelvic lymph node treatment to prostate bed salvage radiotherapy: NRG Oncology/RTOG 0534 SPPORT.
INT J RADIAT ONCOL · Q1 JOURNAL - RANK #14/212
This randomized, prospective NRG Oncology/RTOG 0534 SPPORT trial assessed quality of life (QOL) among men with detectable PSA after prostatectomy, comparing PBRT alone (Arm 1), 4–6 months of short-term ADT plus PBRT (Arm 2), and pelvic lymph node RT plus ADT plus PBRT (Arm 3). QOL was measured at baseline, 6 weeks after RT start, and 1 and 5 years post-RT using EPIC, HSCL-25, EQ-5D, and QALYs, with pairwise tests and mixed-effects modeling controlling for multiplicity. EPIC bowel/urinary scores dropped at 6 weeks and improved by years 1 and 5 but not to baseline; sexual and hormonal domains were worse with ADT at 6 weeks and 1 year, with no arm differences at 5 years; HSCL-25 differences at 6 weeks were not clinically significant. Freedom-from-progression QALY means favored intensification (5.5 vs 6.2 vs 6.6 years for Arms 1, 2, 3; Arms 3 and 2 significantly over Arm 1), while overall survival QALYs did not differ.
10.1016/j.ijrobp.2026.06.3085
Allogeneic CD70-Targeted Chimeric Antigen Receptor T-Cell Therapy for Advanced Renal Cell Carcinoma: Results From the Phase I TRAVERSE Trial.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
The phase Ia/b TRAVERSE trial prospectively assessed safety, tolerability and preliminary efficacy of ALLO-316, an allogeneic CD70-targeted CAR T-cell therapy, in adults with advanced clear-cell renal cell carcinoma resistant to immune checkpoint and VEGFR-targeted therapies. Using a modified 3 + 3 design, 51 patients received fludarabine/cyclophosphamide lymphodepletion with or without the anti-CD52 antibody ALLO-647, followed by escalating doses of ALLO-316; phase Ib confirmed the recommended regimen of FC plus 80 × 10⁶ CAR T cells. After a median 28.8-month follow-up, two dose-limiting toxicities (grade 3 autoimmune hepatitis; grade 5 cardiogenic shock) occurred, grade ≥3 cytokine release syndrome in 2%, neurotoxicity in 0%, and hemophagocytic lymphohistiocytosis-like syndrome in 6%, with hematologic toxicities (neutropenia 62%) predominating. Objective response rate was 17.4% overall, 25.0% in phase Ib, and 31.3% among tumors with CD70 ≥50%. Investigators conclude ALLO-316 shows manageable safety and promising antitumor activity, supporting further development of off-the-shelf CAR T-cell therapy for solid tumors.
10.1200/JCO-26-00388
A Randomized, Nivolumab-controlled, Phase 2 and Biomarker Study of Lomvastomig and Tobemstomig in Advanced or Metastatic Squamous Cell Carcinoma of the Esophagus.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
This phase 2 randomized, active-controlled, blinded, multicenter trial evaluated the bispecific antibodies lomvastomig and tobemstomig versus nivolumab in 190 CPI-naïve patients with advanced or metastatic squamous cell carcinoma of the esophagus. Patients were randomized 1:1:1 to lomvastomig (2100 mg Q2W, n=27, discontinued early), tobemstomig (2100 mg Q2W, n=82), or nivolumab (240 mg Q2W, n=81), with overall survival as the primary endpoint. Median OS was 4.8 months (80%CI, 2.8-5.8) for lomvastomig, 6.7 months (80%CI, 5.4-8.7) for tobemstomig, and 8.1 months (80%CI, 6.7-9.0) for nivolumab; neither bispecific antibody improved survival versus nivolumab overall. In exploratory analyses, tobemstomig showed prolonged survival in PD-L1-high (CPS≥10) and PD-L1-high/LAG3-high subgroups, suggesting PD-L1-guided treatment selection may be warranted for tobemstomig in ESCC.
10.1158/1078-0432.CCR-26-0851
Salivary Methotrexate as a Predictor of Oral Mucositis in Hematological Cancer Patients: A Phase II Randomized, Double-Blind Clinical Trial.
ORAL DIS · Q1 JOURNAL - RANK #37/162
This phase II randomized, double-blind, placebo-controlled trial aimed to evaluate prophylactic photobiomodulation therapy (PBMT) in preventing oral mucositis (OM) among adults with hematological malignancies receiving high-dose methotrexate (HD-MTX). Patients were allocated to either PBMT or sham laser therapy, administered daily until MTX clearance or five sessions total, with OM assessed over nine days. Results showed significantly reduced ulcerative OM (≥ grade 2) in the PBMT group (11.5% vs. 51.9%), a 77.7% relative risk reduction and an 8.97-fold lower odds of severe OM compared to placebo. PBMT significantly decreased the incidence and severity of OM, and salivary MTX was independently associated with increased OM severity, showing promise as a non-invasive biomarker for OM risk.
10.1111/odi.70381
Avutometinib, Abemaciclib, and Fulvestrant in Patients with HR+/HER2- Metastatic Breast Cancer Previously Treated with CDK4/6 Inhibitor: A Single-Arm Phase I Trial.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
This phase I single-arm trial evaluated the safety and efficacy of avutometinib, abemaciclib, and fulvestrant in 16 patients with HR+/HER2- metastatic breast cancer previously treated with CDK4/6 inhibitors. The primary endpoint was maximum tolerated dose (MTD), with secondary endpoints including safety, pharmacokinetics, overall response rate (ORR), clinical benefit rate (CBR), and progression-free survival (PFS). The MTD and recommended phase 2 dose were abemaciclib 100 mg BID, avutometinib 3.2 mg BIW, and fulvestrant 500 mg IM q28d, with an ORR of 13% (2/15), 24-week CBR of 40% (6/15), and median PFS of 3.6 months (95% CI: 2.1-not reached). The regimen was well-tolerated with no grade 4-5 TRAEs and showed preliminary clinical activity, prompting an ongoing phase II trial.
10.1158/1078-0432.CCR-26-0721
Divergent Tumor Immune Microenvironment and Response to Neoadjuvant Chemoimmunotherapy in Resectable Non-Small Cell Lung Cancer: A Single-Arm Phase II Trial.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
This single-arm phase II trial (NCT05383716) evaluated neoadjuvant pembrolizumab plus platinum-based chemotherapy in 80 patients with resectable NSCLC, followed by surgery and adjuvant immunotherapy, with a primary endpoint of major pathological response (MPR). Among 55 patients who underwent surgery, MPR rate was 37.5% and pathological complete response rate was 26.3%, with grade 3-4 adverse events in 26.3% of patients. Spatial transcriptomics revealed MPR tumors were enriched for T- and B-cell activation pathways, while non-MPR tumors showed immune suppression signatures, with two immune phenotypes (myeloid-enriched and lymphoid-enriched) identified. The study concluded that neoadjuvant chemoimmunotherapy is effective and safe, with distinct immune phenotypes potentially guiding adjuvant therapy stratification.
10.1158/1078-0432.CCR-25-4222
Osimertinib Plus Gefitinib in Patients with EGFR-Mutated Advanced Non-Small Cell Lung Cancer and EGFR (C797X) Mutation Following First-Line Osimertinib: ORCHARD.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
This phase II, open-label study evaluated the efficacy and safety of osimertinib plus gefitinib in patients with EGFR-mutated advanced non-small cell lung cancer (NSCLC) harboring the EGFR C797X mutation after progression on first-line osimertinib (NCT03944772). The study included 31 patients, achieving an objective response rate (ORR) of 26% (80% CI: 16-39) and a median progression-free survival (PFS) of 5.1 months (95% CI: 3.9-6.8), while median overall survival was 19.0 months (95% CI: 14.6-25.0). Safety was consistent with known drug profiles, with 35% experiencing grade ≥3 adverse events. Although the regimen demonstrated modest benefits, its risk-benefit profile suggests further evaluation is unwarranted for this population.
10.1158/1078-0432.CCR-26-0704
Long-term outcomes and exploratory analysis from a randomized phase 3 trial of radiation dose escalation in definitive chemoradiotherapy for locally advanced esophageal squamous cell carcinoma.
DRUG RESIST UPDATE · Q1 JOURNAL - RANK #2/352TOP-TIER
The goal was to examine the impact of radiation dose escalation in definitive chemoradiotherapy for unresectable ESCC. In a prospective randomized phase 3 trial, 319 patients with stage IIA-IVA ESCC received 60 Gy (n=160) or 50 Gy (n=159) of conventionally fractionated radiotherapy with concurrent chemotherapy. After a median follow-up of 99.5 months, locoregional progression-free survival at 5 and 8 years was 41.8% and 32.7% for the 60 Gy group versus 43.3% and 36.3% for the 50 Gy group (HR 1.06, 95% CI 0.80–1.39, p=0.70), without survival benefit but increased toxicity. Spatial multi-omics analyses showed immune-activated tumor microenvironments in long survivors, suggesting 50 Gy as a standard dose for these patients while identifying predictive biomarkers of resistance.
10.1016/j.drup.2026.101446
Switching to camizestrant at ESR1 mutation emergence before disease progression during first-line treatment of hormone receptor-positive advanced breast cancer (SERENA-6): extended analysis of a double-blind, placebo-controlled, randomised, phase 3 trial.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This study evaluated SERENA-6, a double-blind, placebo-controlled, randomized phase 3 trial, investigating the impact of switching to camizestrant with continued CDK4/6 inhibitor versus continuing aromatase inhibitor plus CDK4/6 inhibitor upon ESR1 mutation emergence in hormone receptor-positive advanced breast cancer. With a sample size of 315 patients and a median follow-up of 23.5 months, the switch to camizestrant improved median progression-free survival (16.8 vs. 9.2 months; HR 0.45, p<0.0001) and second progression-free survival (25.7 vs. 19.1 months; HR 0.63, p=0.0037). Grade 3-4 adverse events, including neutropenia and decreased neutrophil count, were observed, with three treatment-related deaths reported. The findings support the proposed strategy of switching at ESR1 mutation emergence to delay progression, thus optimizing first-line therapeutic outcomes in advanced breast cancer.
10.1016/S1470-2045(26)00287-1
Efficacy and safety of dabrafenib plus trametinib in adults with differentiated thyroid cancer: a randomised, double-blind, placebo-controlled, phase 3 trial.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This phase 3, double-blind, placebo-controlled trial evaluated dabrafenib plus trametinib in 153 patients with radioactive iodine-refractory BRAF-positive differentiated thyroid cancer. Patients were randomized 2:1 to receive the combination or placebo, with progression-free survival as the primary endpoint. Dabrafenib plus trametinib significantly improved median progression-free survival (12.8 vs. 3.7 months; HR 0.38, p<0.0001) and overall response rate (57% vs. 4%; p<0.0001), though interim overall survival was not significant. The authors conclude the combination is effective as second-line therapy with no new safety signals.
10.1016/S1470-2045(26)00133-6
Holistic oncologic management improves quality of life in driver gene negative advanced NSCLC a latent growth curve modeling study.
SCI REP-UK · Q1 JOURNAL - RANK #25/135
Holistic Oncologic Management (HOM) was compared to standard care for advanced driver-gene-negative NSCLC in a randomized controlled trial from October 2019 to July 2023. The study enrolled 158 participants (81 in the control group and 77 in the treatment group) who received HOM focusing on quality of life (QoL), depression, pain, and nutrition over 24 consecutive weeks. Six-point QoL trajectories based on latent growth curve modeling showed significant improvements in QoL, pain control, nutritional status, and mood, with younger patients benefiting more. The authors conclude that HOM meaningfully enhances outcomes in advanced NSCLC.
10.1038/s41598-026-62103-3
Jul 06 – Jul 13, 2026
Selective Conventional Transarterial Chemoembolization Using a Glass Membrane Emulsification Device in Hepatocellular Carcinoma: Multicenter Clinical Trial in Japan.
LIVER CANCER · Q1 JOURNAL - RANK #11/147
This multicenter phase II trial (jRCTs052200095) evaluated selective conventional transarterial chemoembolization (cTACE) using a porous glass membrane emulsification device in 50 patients with unresectable hepatocellular carcinoma (≤5 cm; Child-Pugh A or B). The emulsion of epirubicin and ethiodized oil was injected into tumor-feeding arteries, followed by gelatin sponge embolization, with the primary endpoint being complete response (CR) rate at 3 months. Among 45 patients in the efficacy analysis, the CR rate at both 1 and 3 months was 97.8% (95% CI: 88.2-99.9%), with serious adverse events including elevated AST (50.0%) and ALT (29.2%). The study concluded that this cTACE technique achieved high short-term CR rates with acceptable safety, supporting further investigation.
10.1159/000552424
Randomized, multicenter phase 3 study evaluating radiotherapy versus concurrent chemoradiotherapy in nasopharyngeal carcinoma patients achieving CR/PR after induction chemotherapy.
BMC MED · Q1 JOURNAL - RANK #19/332
This multicenter, randomized, open-label, phase 3 noninferiority trial at 7 Chinese hospitals compared radiotherapy (RT) versus concurrent chemoradiotherapy (CCRT) in 220 nasopharyngeal carcinoma patients who achieved complete or partial response after induction chemotherapy. Patients were allocated 1:1 to IC+RT (n=109) or IC+CCRT (n=111), with progression-free survival as the primary endpoint. Five-year PFS was 87.0% vs. 80.7% (P=0.21), with no significant differences in secondary survival endpoints; the IC+RT group had significantly lower grade 3-4 hematologic and gastrointestinal toxicities. The trial was terminated early due to slow accrual, and the authors conclude that IC+RT has a favorable safety profile but definitive noninferiority cannot be claimed.
10.1186/s12916-026-05064-8
Intermittent olaparib with neoadjuvant platinum-based chemotherapy in BRCA-mutated un-resectable ovarian cancer: the NUVOLA trial.
INT J GYNECOL CANCER · Q1 JOURNAL - RANK #8/140
The NUVOLA trial evaluated the feasibility and efficacy of adding olaparib to neoadjuvant chemotherapy in 36 patients with newly diagnosed BRCA-mutated advanced epithelial ovarian cancer. This open-label, single-arm phase II study administered weekly carboplatin and paclitaxel with intermittent olaparib, targeting a primary endpoint of complete pathological response (achieved in 8.6% of patients) and secondary endpoints including an 89% overall response rate and median progression-free survival of 39.7 months. Treatment-related adverse events occurred in 86% of patients, with 58% requiring dose reductions and 11% discontinuing treatment. The study concluded that concurrent olaparib with neoadjuvant chemotherapy did not significantly improve complete pathological response, suggesting its benefit may lie primarily in post-chemotherapy maintenance.
10.1016/j.ijgc.2026.104816
Lactobacillus reuteri lozenges and chemotherapy-induced oral mucositis in breast cancer outpatients: an exploratory randomized controlled trial.
SCI REP-UK · Q1 JOURNAL - RANK #25/135
This exploratory, single-center, open-label, randomized controlled trial examined the effect of Lactobacillus reuteri lozenges on chemotherapy-induced oral mucositis in breast cancer outpatients receiving anthracycline- or taxane-based chemotherapy. Sixty-seven patients were randomized to receive L. reuteri lozenges twice daily for 12 weeks or no intervention, with 61 analyzed. The primary outcome of Grade ≥2 oral mucositis showed no significant difference in cycles 1-2, but lower incidence in the L. reuteri group in cycles 3 (22.6% vs. 50.0%) and 4 (19.4% vs. 43.3%); a mixed-effects model found no significant time-by-intervention effect. The authors conclude that L. reuteri lozenges may be associated with reduced oral mucositis in later cycles, with no intervention-related adverse events.
10.1038/s41598-026-61752-8
Single, early intravesical instillation of pirarubicin in the prevention of bladder recurrence after radical nephroureterectomy for upper tract urothelial carcinoma (JCOG1403): a multicentre, open-label, randomised, phase 3 trial.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This phase 3 trial evaluated the efficacy and safety of a single, postoperative intravesical instillation of pirarubicin versus observation in preventing bladder recurrence after radical nephroureterectomy for upper tract urothelial carcinoma. Conducted at 44 Japanese institutes, 348 patients were randomized post-surgery, with stratification by clinical factors. The pirarubicin group had a 3-year relapse-free survival of 60.0% compared to 47.0% in the observation group, achieving statistical significance (HR 0.67; p=0.0066), with minimal grade 3-4 adverse events reported. The study concludes that pirarubicin instillation is an effective and tolerable option to reduce bladder recurrence risk in this patient population.
10.1016/S1470-2045(26)00130-0
Acute toxicity and quality of life with stereotactic body radiotherapy versus conventional fractionated intensity-modulated radiotherapy to the prostate and pelvis in high-risk prostate cancer (SRAM): A randomized phase II trial.
INT J RADIAT ONCOL · Q1 JOURNAL - RANK #14/212
This randomized phase II trial evaluated the impact of once-weekly stereotactic body radiotherapy (SBRT) versus conventional fractionated intensity-modulated radiotherapy (IMRT) to the prostate and pelvis in 121 patients with high-risk prostate cancer. Investigators administered SBRT (40 Gy/5 weekly fractions for prostate, 36.25 Gy for seminal vesicles, 25 Gy for pelvis) or IMRT (76 Gy/38 daily fractions for prostate/pelvis) plus androgen deprivation therapy for 18–24 months. They observed lower acute grade ≥2 GI toxicity with SBRT (8.3%) compared with IMRT (39.0%, p<0.0001), while grade ≥2 GU toxicity was 23.3% versus 36.1% (p=0.126). SBRT significantly reduced acute GI toxicity, resulted in comparable GU safety with no grade ≥3 events, and improved early patient-reported outcomes, justifying additional study in phase III trials.
10.1016/j.ijrobp.2026.06.3080
Quality of life and cost-effectiveness of preoperative accelerated versus postoperative conventional radiotherapy for oral cavity cancer: Results from the randomised ARTSCAN 2 trial.
RADIOTHER ONCOL · Q1 JOURNAL - RANK #22/212
This randomized controlled trial compared preoperative accelerated fractionation radiotherapy with postoperative conventional radiotherapy for oral cavity cancer in 240 patients. The methodology involved HRQoL assessment using validated questionnaires at five timepoints over five years, alongside direct and indirect cost analyses for cost-utility evaluation (based on QALYs) in 204 patients. Results showed preoperative AF RT resulted in significantly worse HRQoL scores on certain head-and-neck domains up to two years post-treatment, and was less effective and more expensive than postoperative CF RT. The authors conclude postoperative CF RT remains the preferred standard due to superior HRQoL and cost-effectiveness.
10.1016/j.radonc.2026.111688
Brief Report: First-line Chemoimmunotherapy and Chemotherapy Outcomes in Patients with RET Fusion-Positive Lung Cancer in LIBRETTO-431.
J THORAC ONCOL · Q1 JOURNAL - RANK #3/108TOP-TIER
This study aimed to evaluate the outcomes of chemoimmunotherapy and chemotherapy alone in patients with RET fusion-positive lung cancer within the phase 3 LIBRETTO-431 clinical trial. A total of 83 patients received chemoimmunotherapy, and 19 received chemotherapy alone. Progression-free survival (PFS) and overall survival (OS) were not significantly different between the two groups, with median PFS by BICR of 11.2 months for chemoimmunotherapy patients, and OS not reached in either group. The results suggest that chemotherapy alone is a reasonable first-line strategy for oncogene-driven RET fusion-positive lung cancer, with selective RET inhibitors being the preferred treatment option as supported by the broader findings from the trial.
10.1016/j.jtho.2026.104086
MRD-negativity by PBMCs and ctDNA confirms deep and durable responses following epcoritamab monotherapy in R/R FL.
BLOOD ADV · Q1 JOURNAL - RANK #13/98
This abstract evaluates minimal residual disease (MRD) negativity as a marker of deep and durable responses following epcoritamab monotherapy in relapsed/refractory follicular lymphoma (R/R FL) using data from the EPCORE NHL-1 prospective clinical trial (NCT03625037). MRD status was assessed using the clonoSEQ assay on peripheral blood mononuclear cells (PBMCs) and circulating tumor DNA (ctDNA) at prespecified time points. Key findings include rapid conversion to MRD-negativity by cycle 3 day 1 (C3D1), which correlated with prolonged progression-free survival (PFS; median not reached) regardless of radiographic response. The authors conclude that MRD-negativity complements conventional response assessment and may inform future clinical trial design.
10.1182/bloodadvances.2025017565
Anti-LAG-3 with or without anti-PD-1 in recurrent glioblastoma: a phase 1 trial.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This phase 1, open-label, multicenter trial evaluated the safety and preliminary activity of the anti-LAG-3 antibody relatlimab alone or combined with the anti-PD-1 antibody nivolumab in 46 patients with recurrent glioblastoma. Neoadjuvant administration stimulated intratumoral CD8 T cell infiltration, and 12-month overall survival rates reached 34.8% for relatlimab alone and 52.2% for combination therapy. Treatment-related grade 3-4 adverse events occurred in six patients on combination therapy, and no such events occurred with monotherapy. Overall, these results demonstrated an acceptable safety profile and suggest potential clinical benefit requiring further investigation.
10.1038/s41591-026-04475-7
Long-term follow-up of a phase 1/2 trial of anti-GDF-15 antibody visugromab plus anti-PD-1 antibody nivolumab in anti-PD-1/-L1 relapsed/refractory solid tumors.
J HEMATOL ONCOL · Q1 JOURNAL - RANK #1/98TOP-TIER
This multicenter phase 1/2a clinical trial evaluated visugromab, an anti-GDF-15 antibody, plus nivolumab in 77 patients with anti-PD-1/PD-L1-relapsed/refractory locally advanced/metastatic non-squamous NSCLC, urothelial carcinoma, or hepatocellular carcinoma. Patients received both drugs every two weeks until progression or unacceptable toxicity, and responses were assessed via RECIST v1.1. Objective response rates were 18.2% (NSCLC), 18.5% (UC), and 14.3% (HCC), with median duration of response ranging from 19.4 to 32.2 months and 53.8% of responses ongoing; 61.5% achieved confirmed complete or metabolic response. The study concludes that GDF-15 blockade with visugromab enhances response rates and durability versus prior anti-PD-1/PD-L1 therapy, suggesting its value for further randomized investigation.
10.1186/s13045-026-01818-2
Phase 3 Study of Niraparib-Plus-Pembrolizumab as Maintenance Therapy for Advanced/Metastatic Non-Small Cell Lung Cancer (ZEAL-1L).
J THORAC ONCOL · Q1 JOURNAL - RANK #3/108TOP-TIER
This randomized, double-blind, phase 3 trial evaluated niraparib-plus-pembrolizumab versus placebo-plus-pembrolizumab as maintenance therapy in 666 adults with advanced/metastatic NSCLC lacking targetable driver alterations (ClinicalTrials.gov: NCT04475939). Patients responded to initial chemotherapy plus pembrolizumab and were then randomized (1:1) to either treatment, with the primary endpoint of progression-free survival (PFS) by blinded independent central review (BICR). Median PFS for the complete/partial response group was identical in both arms at 5.55 months (HR 1.00, 95% CI 0.79-1.27; 1-sided p=0.502), and no improvements in efficacy were observed; common grade ≥3 hematologic adverse events included anemia, thrombocytopenia, and neutropenia. The study concluded that niraparib addition did not improve efficacy or lead to new safety signals in this population.
10.1016/j.jtho.2026.104087
Neoadjuvant Chemotherapy with Trastuzumab with or without Concurrent Radiotherapy in HER2-Positive Locally Advanced Inoperable Breast Cancer- A Phase 2 Randomized Controlled Trial (NEOTRAC STUDY).
INT J RADIAT ONCOL · Q1 JOURNAL - RANK #14/212
This phase 2 randomized controlled trial (NEOTRAC) evaluated neoadjuvant concurrent chemoradiotherapy (NACCRT) with trastuzumab versus standard neoadjuvant chemotherapy (NACT) in 118 patients with HER2-positive, inoperable locally advanced breast cancer (stage III). Patients were randomized 1:1 to Arm A (NACT+trastuzumab) or Arm B (NACCRT+trastuzumab), both receiving anthracycline/taxane-based chemotherapy with trastuzumab; Arm B received concurrent radiotherapy (46 Gy) during paclitaxel. The primary endpoint pCR was 46.6% (Arm A) vs. 50.9% (Arm B) (P=0.64), with no significant differences in 3-year event-free survival (79.8% vs. 76.8%) or overall survival (88.7% vs. 87.4%). The study concluded NACCRT with trastuzumab is feasible, safe, and significantly shortens treatment duration without compromising survival, warranting further evaluation.
10.1016/j.ijrobp.2026.06.3086
Concurrent Chemoradiotherapy Plus Immunotherapy Versus Concurrent Chemoradiotherapy in Locally Advanced Cervical Cancer: A Randomized, Single-Center, Phase II Trial of Early Tumor Regression and Pro-Inflammatory Tumor Microenvironment Remodeling.
MEDCOMM · Q1 JOURNAL - RANK #14/195TOP-TIER
This randomized, single-center, Phase II trial investigated the addition of immunotherapy to concurrent chemoradiotherapy (CICRT) in 18 patients with high-risk Stage III-IVA locally advanced cervical cancer (LACC) to assess early tumor regression and immune modulation. CICRT showed a numerical advantage in reducing tumor volume compared to CCRT alone (mean residual tumor volume: 3.0% vs. 7.4%, p = 0.080, 95% CI: -9.3%-0.6%, Cohen’s d = 0.180), though these findings were not statistically significant. Single-cell RNA sequencing of paired biopsies (n = 12) demonstrated pro-inflammatory remodeling of the tumor microenvironment, including upregulation of MHC-II genes and reduced regulatory T cells. The results suggest the potential of CICRT for overcoming TME suppression in LACC, although further research is warranted to confirm efficacy and statistical significance.
10.1002/mco2.70856
Adjuvant penpulimab in very-high risk clear cell renal cell carcinoma: a prospective, non-randomized, controlled phase II trial with integrated plasma multi-omics analyses.
J IMMUNOTHER CANCER · Q1 JOURNAL - RANK #12/183TOP-TIER
This multicenter, prospective, non-randomized controlled phase II trial investigated whether adjuvant penpulimab improves outcomes in 174 patients with very-high-risk clear cell renal cell carcinoma after nephrectomy. After 1:1 propensity score matching, 87 patients received penpulimab and 87 underwent routine surveillance; disease-free survival (DFS) was the primary endpoint, with overall survival (OS), safety, and plasma proteomic/metabolomic biomarkers as secondary or exploratory endpoints. Penpulimab prolonged DFS versus surveillance (hazard ratio 0.37, 95% CI 0.16–0.89, p = 0.026), with 1-year and 2-year DFS rates of 94.3% and 88.7% compared with 80.5% and 75.4%, respectively; OS data were still immature. Most adverse events were grade 1–2, and multi-omics analyses highlighted immune-response pathways and circulating biomarkers associated with reduced progression, supporting penpulimab as a promising adjuvant therapy that warrants further validation.
10.1136/jitc-2026-015686
Durvalumab Plus Chemotherapy for Advanced Biliary Tract Cancer: A Post Hoc Analysis of the TOPAZ-1 Randomized Clinical Trial.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
This post hoc analysis of the global, double-blind, placebo-controlled, phase 3 TOPAZ-1 randomized clinical trial assessed 4-year overall survival (OS) and safety of durvalumab plus gemcitabine/cisplatin (GemCis) vs placebo+GemCis in advanced biliary tract adenocarcinoma. 685 adults were randomized at 105 sites in 17 countries; treatment was GemCis on days 1 and 8 every 3 weeks for up to 8 cycles, then durvalumab or placebo every 4 weeks; outcomes were assessed ≈48 months after the last randomization (data cutoff Feb 28, 2025). Median OS was 13.0 months (95% CI, 11.6-14.1) with durvalumab+GemCis vs 11.4 months (95% CI, 10.1-12.5) with placebo+GemCis (HR, 0.75; 95% CI, 0.64-0.88); 48-month OS rates were 11.8% vs 4.3%. Serious treatment-related adverse events occurred in 15.4% vs 17.3%, and discontinuations in 6.2% vs 5.3%, supporting clinically manageable safety and durable survival benefit.
10.1001/jamaoncol.2026.2204
Consolidative Thoracic Radiotherapy With Atezolizumab Maintenance in Extensive-Stage Small Cell Lung Cancer: The Phase 2 TREASURE Randomized Clinical Trial (AIO-TRK-0320).
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
This multicenter, open-label, phase 2 randomized trial (NCT04462276) evaluated whether adding consolidative thoracic radiotherapy (30 Gy/10 fractions) to atezolizumab maintenance after carboplatin–etoposide–atezolizumab induction improves outcomes in extensive-stage small-cell lung cancer. Sixty-eight patients with at least stable disease after induction chemoimmunotherapy were randomized 1:1 to atezolizumab plus radiotherapy (arm A) or atezolizumab alone (arm B) and followed until September 2024, with a survival update in April 2026. Median overall survival was 6.7 months (95 % CI 5.1-9.0) in arm A versus 13.4 months (95 % CI 10.7-17.5) in arm B (HR 1.55, P = 0.34); median progression-free survival was 2.4 versus 2.6 months (HR 0.92, P = 0.85). Radiotherapy markedly increased severe adverse events (61.3 % vs 18.2 %, P < 0.001) and fatalities (19.4 % vs 3.0 %, P = 0.04); investigators concluded that unselected use of consolidative thoracic radiotherapy with maintenance atezolizumab confers excess toxicity without survival benefit.
10.1001/jamaoncol.2026.2330
Aspirin for cancer prevention in individuals with Lynch syndrome: first results from the CaPP3 multicentre, randomised, double-blind, non-inferiority trial.
LANCET GASTROENTEROL · Q1 JOURNAL - RANK #2/147TOP-TIER
The CaPP3 trial assessed the efficacy of lower aspirin doses (100 mg or 300 mg daily) compared to 600 mg daily for cancer prevention in 1879 Lynch syndrome carriers across five countries, using a multicentre, double-blind, non-inferiority design. Primary outcomes measured new Lynch syndrome cancers, with non-inferiority defined as HR and IRR upper 95% CI <1.5. Results showed 100 mg was non-inferior to 600 mg in intention-to-treat analysis (HR 0.97 [0.67-1.42], IRR 0.94 [0.65-1.38]), but 300 mg failed non-inferiority (HR 1.28 [0.91-1.80], IRR 1.12 [0.79-1.61]). Adverse events increased with dose (25.0% at 100 mg vs. 31.2% at 600 mg; p=0.03), with fewer bleeding events at lower doses (0% at 100 mg vs. 1.5% at 600 mg; p=0.004). The study concluded that 100 mg aspirin may offer comparable cancer prevention with reduced side effects, though formal non-inferiority was not established for both doses.
10.1016/S2468-1253(26)00114-7
Quality of Life After Postprostatectomy Radiotherapy: A TROG 08.03 RAVES Randomized Controlled Trial Substudy.
EUR UROL ONCOL · Q1 JOURNAL - RANK #7/133
This planned secondary analysis of the TROG 08.03 RAVES randomized trial evaluated whether timing of postprostatectomy radiotherapy (adjuvant vs salvage triggered by PSA >0.2 ng/ml) affects patient-reported quality of life. QOL was assessed longitudinally using EORTC QLQ-C30 and QLQ-PR25, with minimal clinically important change defined as >0.5 SD decline from baseline over 1–5 years. Compared with salvage patients who did not receive RT, adjuvant RT was associated with more bowel symptom MCIC events and higher severe urinary incontinence at 5 years (16% vs 2%, p=0.01); however, among those who received RT, adjuvant vs salvage showed no significant differences in urinary, bowel, or sexual function 1–5 years after RT. Regression indicated sRT timing had no significant impact, suggesting postprostatectomy RT modestly worsens bowel symptoms and long-term incontinence, but timing has limited QOL implications.
10.1016/j.euo.2026.06.014
Addition of angiogenesis inhibitors to CDK4/6 inhibitors and fulvestrant in hormone receptor-positive, HER2-negative advanced breast cancer.
CHINESE MED J-PEKING · Q1 JOURNAL - RANK #23/332
This prospective phase Ib/II trial evaluated the feasibility and efficacy of combining the angiogenesis-targeting tyrosine kinase inhibitor famitinib with dalpiciclib and fulvestrant in HR+/HER2- advanced breast cancer. A standard 3+3 dose-escalation design identified 10 mg famitinib plus 100 mg dalpiciclib daily, along with fulvestrant, as the recommended phase II dose. Among 28 phase II participants, the confirmed objective response rate was 51.9% (95% CI: 32.0%-71.3%) and the median progression-free survival reached 15.7 (95% CI: 7.3-25.4) months. Although the combination showed promising response rates, overlapping hematologic toxicities led to early termination of enrollment.
10.1097/CM9.0000000000004191
Incidence and Predictors of Fat Necrosis After Single-Fraction Stereotactic Partial Breast Irradiation for Early-Stage Breast Cancer: Results From a Phase II Clinical Trial.
INT J RADIAT ONCOL · Q1 JOURNAL - RANK #14/212
This study evaluated predictive factors for fat necrosis (FN) after stereotactic partial breast irradiation (S-PBI) in early-stage breast cancer through a prospective phase II clinical trial involving 148 patients treated with a 17.5 Gy single dose using GammaPod™ technology. FN was clinically and radiologically assessed with a median follow-up of 29.9 months. FN occurred in 12.1% of patients, with symptomatic FN in 4.1%, and the cumulative incidence increased over time. The study concluded S-PBI was well-tolerated, and advanced age (≥60) and higher dosimetric volumes (V19.3 ≥5 cc) were significant risk predictors for FN, with further statistical analyses affirming these findings.
10.1016/j.ijrobp.2026.06.3089
Fecal microbiome and metabolome dynamics during immunotherapy-based total neoadjuvant therapy in rectal cancer: associations with treatment response and toxicity.
FRONT IMMUNOL · Q1 JOURNAL - RANK #32/183
Investigators performed a longitudinal fecal multi-omics study in 102 samples from microsatellite-stable locally advanced rectal cancer patients receiving immunotherapy-based total neoadjuvant therapy as part of the prospective TORCH trial (NCT04518280). They integrated metagenomic sequencing and untargeted metabolomics to identify gut microbiome and metabolic changes that correlated with therapeutic response and toxicity. They found that iTNT induced significant shifts in microbial diversity and metabolic pathways, with an enrichment of Firmicutes and gamma-aminobutyric acid (GABA) associated with therapy non-response. The authors conclude that GABA may reduce antitumor efficacy of radiotherapy plus immunotherapy, offering a novel immune modulation target and potential biomarkers for treatment stratification.
10.3389/fimmu.2026.1871586
Randomized phase-II trial of surufatinib plus FOLFOX/FOLFIRI versus FOLFOXIRI as second-line therapy for metastatic colorectal cancer.
ANN MED · Q1 JOURNAL - RANK #39/332
This multicentre, open-label, randomized phase-II trial evaluated surufatinib plus FOLFOX/FOLFIRI versus FOLFOXIRI as second-line therapies for metastatic colorectal cancer, enrolling 57 patients from September 2021 to November 2023. Patients were randomized 1:1, and the primary endpoint was objective response rate (ORR); the doublet cohort (surufatinib plus mFOLFOX6/FOLFIRI) had ORR of 35.7% and median progression-free survival (PFS) of 5.4 months, while the triplet cohort (surufatinib plus FOLFOXIRI) had ORR of 39.3% and median PFS of 5.8 months. The triplet cohort experienced more grade ≥3 treatment-emergent adverse events (71.4% vs. 57.1%) and shorter median overall survival (10.9 vs. 19.0 months). The study concludes surufatinib plus doublet chemotherapy shows promising activity and manageable toxicity, while the triplet regimen is not recommended due to excess toxicity and reduced survival.
10.1080/07853890.2026.2698360
Plasma proteomics predicts pathological complete response and reveals LIF as a potential mediator of resistance to neoadjuvant immunochemotherapy in resectable NSCLC.
J IMMUNOTHER CANCER · Q1 JOURNAL - RANK #12/183TOP-TIER
The study aimed to identify plasma protein biomarkers predictive of pathological complete response (pCR) to neoadjuvant immunochemotherapy (nICT) in resectable non-small cell lung cancer (NSCLC) and explore resistance mechanisms. Pretreatment plasma samples from 86 patients were analyzed using Olink assays, with predictive models developed via logistic regression, random forest, and XGBoost, validated internally (AUC=0.845) and externally (AUC=0.801). Elevated baseline LIF levels were associated with inferior survival (OS HR=13.003, PFS HR=3.75) and reduced CD8+ T-cell infiltration, while murine models showed LIF blockade enhanced therapy efficacy. The study concludes that plasma proteomics can predict nICT response and highlights LIF as a therapeutic target, warranting prospective validation.
10.1136/jitc-2026-015312
Dynamic immune profiling predicts response to radiation plus anti-PD-1 therapy in oligometastatic renal cell carcinoma.
NAT COMMUN · Q1 JOURNAL - RANK #10/135TOP-TIER
The RAPPORT trial was a prospective phase I/II study of stereotactic ablative body radiotherapy (SABR) combined with pembrolizumab in 30 patients with oligometastatic clear cell renal cell carcinoma. The primary endpoint was safety, and secondary endpoints were overall survival, time to local progression, distant progression-free survival, objective/disease control rates, duration of response, and pain outcomes. Pre-treatment analyses indicated that responders exhibited elevated intra-tumoural cytotoxic T cell infiltration, while non-responders demonstrated immunosuppressive and angiogenic signatures; post-treatment, responders showed bursts of activated CD8 T cells and sustained tumour-enriched T cell receptor clones. The trial suggests that trafficking and maintenance of pre-existing tumour-specific T cells predict improved responses to SABR plus anti-PD-1 therapy.
10.1038/s41467-026-74255-x
Olaparib in HR-deficient, metastatic triple-negative breast and platinum-sensitive relapsed ovarian cancers without germline mutations in BRCA1/2: phase 2 EMBRACE trial.
BRIT J CANCER · Q1 JOURNAL - RANK #47/326
This single-arm phase 2 trial evaluated olaparib 300 mg orally twice daily in 22 patients with platinum-sensitive relapsed high-grade serous ovarian cancer (HGSOC) and metastatic triple-negative breast cancer (mTNBC) harboring non-germline BRCA homologous recombination deficiency (HRD). Tumor methylation (BRCA1/RAD51C) and non-BRCA HR gene mutations were analyzed with high-resolution melting PCR and targeted sequencing, with promoter methylation detected in 8/15 HGSOC and 5/7 TNBC. The 6-month objective tumor response rate (OTRR) was 40% in HGSOC (6/15) and 0% in mTNBC (0/7), while 6-month/12-month progression-free survival (PFS) rates were 53%/25% for HGSOC and 17%/0% for mTNBC. Olaparib demonstrated encouraging activity in HGSOC beyond germline BRCA1/2 mutations, but showed limited efficacy in pre-treated mTNBC.
10.1038/s41416-026-03535-6
Venetoclax in combination with cytarabine with or without idarubicin or azacitidine in children, adolescents, and young adults with relapsed or refractory acute myeloid leukaemia (VENAML): a multicentre, phase 1 expansion study.
LANCET HAEMATOL · Q1 JOURNAL - RANK #3/98TOP-TIER
This multicenter, phase 1 study evaluated the efficacy and safety of venetoclax combined with cytarabine ± idarubicin or azacitidine in pediatric patients (ages 2–24) with relapsed/refractory acute myeloid leukemia. The expansion cohort phase results included 44 patients treated at the recommended phase 2 dose (RP2D). After one treatment cycle, 57% (95% CI 41-72) of patients achieved a complete response with or without hematologic recovery, with measurable residual disease negativity in 19 cases; however, grade 3/4 adverse events such as febrile neutropenia (52%) and severe infections (25%) were notable. Venetoclax in combination with cytarabine demonstrated activity and acceptable safety, supporting further investigation in pediatric phase 3 trials (e.g., NCT05183035).
10.1016/S2352-3026(26)00136-5
A phase Ib/II, open-label, multicenter, randomized umbrella study evaluating the combination of atezolizumab with sacituzumab govitecan in patients with locally advanced or metastatic urothelial carcinoma and previously treated with a platinum-based treatment regimen (MORPHEUS-Urothelial Carcinoma).
ESMO OPEN · Q1 JOURNAL - RANK #36/326
MORPHEUS-UC is a global, phase Ib/II, open-label, randomized umbrella trial in checkpoint inhibitor–naïve patients with platinum-treated locally advanced or metastatic urothelial carcinoma, comparing atezolizumab plus sacituzumab govitecan versus atezolizumab alone; primary endpoints were investigator-assessed ORR and safety, with secondary PFS, DOR, DCR, and OS. Fifteen patients received the combination and 30 received atezolizumab monotherapy. Confirmed ORR was 6.7% with the combination versus 27.6% with atezolizumab, and there was no improvement in ORR, PFS, or OS with the addition of sacituzumab govitecan. Treatment-related adverse events included anemia, neutropenia, pruritus, nausea, and alopecia with the combination, and pruritus, decreased appetite, rash, and fatigue with atezolizumab; no grade 5 TRAEs occurred, leading to the conclusion of limited rationale for further development of the combination in this setting.
10.1016/j.esmoop.2026.108303
Phase II study of trastuzumab-pkrb plus gedatolisib in patients with HER2-positive metastatic breast cancer who progressed after two or more HER2-directed therapies.
ESMO OPEN · Q1 JOURNAL - RANK #36/326
This multicenter, single-arm, phase II trial prospectively assessed trastuzumab-pkrb (8 mg/kg loading, then 6 mg/kg Q3W) plus the PI3K/mTOR inhibitor gedatolisib (180 mg IV on days 1, 8, 15 of each 21-day cycle) in 44 patients with HER2-positive metastatic breast cancer harboring PI3K-pathway alterations who had progressed after ≥2 prior HER2-directed therapies. The primary objective was objective response rate (ORR); secondary endpoints included disease control, progression-free survival (PFS), overall survival (OS), safety, and circulating tumor-DNA dynamics. ORR reached 43.2 % (95 % CI 28.3–59.0) with two complete and 17 partial responses; disease control rate was 86.4 %, median PFS 6.01 months (95 % CI 5.03–7.69), and median OS 24.74 months after 32.05 months follow-up. Toxicities were mainly oral mucositis (90.9 %, 15.9 % grade ≥3) and hyperglycemia (25.0 %, 2.3 % grade 3), leading investigators to conclude the dual HER2/PI3K strategy shows clinically meaningful activity and manageable safety in heavily pretreated patients.
10.1016/j.esmoop.2026.107706
The clinical relevance of regional lymph node microarchitecture in oesophageal cancer patients - Results from the UK MRC OE02 trial.
EUR J CANCER · Q1 JOURNAL - RANK #45/326
This study aimed to determine whether neoadjuvant chemotherapy and/or the presence of tumor alters lymph node (LN) microarchitecture and to assess associations with survival in patients from the prospective UK MRC OE02 trial. Microarchitectural features (lymphocytes, germinal centers, histiocytes) were measured in 433 LNs from 333 patients randomly assigned to neoadjuvant chemotherapy plus surgery (n=165) or surgery alone (n=168). Among patients with tumor-free nodes, germinal center density was lower in those receiving combination therapy (1% vs 2%; p=0.0004), and in the surgery-alone arm low histiocyte content correlated with improved OS (HR:0.67, 95%CI:0.46-0.97; p=0.03). These findings suggest LN microarchitecture could be an informative biomarker for immune modulation and prognosis in resectable oesophageal cancer.
10.1016/j.ejca.2026.116910
Quality of life and patient-reported outcomes after non-surgical management of early-stage endometrial cancer and endometrial hyperplasia with atypia: a long-term follow-up of the feMMe phase II randomized clinical trial.
INT J GYNECOL CANCER · Q1 JOURNAL - RANK #8/140
This prospective, open-label, randomized phase II trial evaluated long-term quality of life, self-efficacy, social support, and patient-reported experiences following fertility-sparing, non-surgical management of early-stage endometrial adenocarcinoma and endometrial hyperplasia with atypia. Participants were randomized to one of three arms: levonorgestrel intra-uterine device alone, levonorgestrel intra-uterine device plus weight loss, or levonorgestrel intra-uterine device plus metformin, and followed for a median of 63 months. Among 44 patients, overall quality of life was high (mean FACT-General total score = 80.5 ± 16.4), with higher self-efficacy for physical activity among those achieving complete response at trial completion (p = .002). The authors concluded that long-term patient-reported outcomes were favorable, supporting non-surgical, fertility-preserving approaches and highlighting the importance of survivorship-focused outcomes in shared treatment decision-making.
10.1016/j.ijgc.2026.104806
Pharmacologic activity, safety, and preliminary efficacy of GEN3009, a CD37-targeting DuoHexaBody, in relapsed or refractory B-cell non-Hodgkin’s lymphoma.
J IMMUNOTHER CANCER · Q1 JOURNAL - RANK #12/183TOP-TIER
To evaluate safety and efficacy of GEN3009 (DuoHexaBody-CD37), a phase 1 dose-escalation trial enrolled 46 adults with R/R B-cell non-Hodgkin’s lymphoma. This open-label, multicenter, first-in-human study used a modified Bayesian optimal interval design to identify the recommended phase 2 dose (RP2D). In participants treated up to 1600 mg, no dose-limiting toxicities were observed, with neutropenia (89.1%), infusion-related reactions (84.8%), and thrombocytopenia (39.1%) as the most common adverse events. Preliminary data showed an acceptable safety profile, a 1200 mg RP2D, and modest clinical activity correlated with changes in complement levels (p=0.008).
10.1136/jitc-2025-014311