HYPO-RT-PC was the first phase 3 trial showing the long-term efficacy and safety of extremely hypofractionated radiotherapy schedules (ultra-hypofractionation or stereotactic body radiotherapy) compared with standard radiotherapy in localised prostate cancer. We aimed to verify their safety in the context of a clinical trial, by comparing events of potentially radiotherapy-related morbidity according to routinely collected health data between the arms and with men unexposed to prostate radiotherapy.

Preoperative immunotherapy targeting PD-1/-L1 with chemotherapy induces histopathological responses and improves survival in patients with resectable non-small cell lung cancer (NSCLC). NEOpredict-Lung (NCT04205552) established the feasibility of dual blockade of PD-1 and LAG-3 immune checkpoints prior to curatively intended resection. Here we report extended follow-up, postoperative treatments and patterns of response and recurrence.

Bevacizumab and temsirolimus target angiogenic and mTOR pathways in cancer progression.

Few treatment options are available for patients with epidermal growth factor receptor (EGFR) mutation-positive metastatic non-squamous non-small cell lung cancer (NSCLC) who failed treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKIs). We aimed to assess the efficacy and safety of atezolizumab plus bevacizumab in these patients.

Following curative treatment for non-small cell lung cancer (NSCLC), surveillance to detect recurrence is recommended. While computed tomography (CT) is the current standard for follow-up imaging, the optimal surveillance strategy remains debated. This study compares the diagnostic accuracy of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT; hereafter referred to as PET/CT) and CT for NSCLC surveillance.

A local anaesthetic ultrasound-guided transperineal (LATP) prostate biopsy has advantages over transrectal ultrasound (TRUS)-guided biopsy, with improved magnetic resonance imaging (MRI)-guided prostate cancer detection and lower rates of infection-related complications. However, uncertainty remains regarding the cost effectiveness of an LATP biopsy compared with a TRUS biopsy.

E7386 is an orally active inhibitor reported to block the CBP/β-catenin interaction. We present data from the dose-escalation and expansion part 1 of Study 103 (phase I) of E7386 in patients with advanced, unresectable, or recurrent (A/U/R) solid tumors.

Low-grade serous carcinoma (LGSOC) of the ovary, fallopian tube, or peritoneum is a hormonally driven, relatively chemoresistant malignancy with limited treatment options in the recurrent setting. Given frequent estrogen receptor (ER) expression and dysregulation of the cyclin-dependent kinases 4 and 6 (CDK4/6)-p16-Rb pathway, features shared with hormone receptor-positive breast cancer, dual endocrine, and CDK4/6 inhibition is a biologically rational strategy. This phase II trial evaluated ribociclib plus letrozole in recurrent LGSOC.

Outcomes for children with relapsed and refractory high-risk neuroblastoma (RR-HR-NBL) remain dismal. Here, we investigate addition of the anti-GD2 monoclonal antibody, dinutuximab beta (dB), to temozolomide (T)-based chemotherapy.

Neoadjuvant chemotherapy is standard for high-risk hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer. This study evaluates whether 12 months of letrozole plus abemaciclib could be an alternative.

We conducted a phase II multicenter clinical trial to test the hypothesis that 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)-based chemoradiation (CRT) dose deescalation would provide noninferior locoregional control compared with historical controls among patients with early-stage p16+ oropharyngeal cancer. We also hypothesized that human papillomavirus (HPV) circulating tumor DNA (ctDNA) changes during treatment predict locoregional recurrence (LRR).

Laparoscopic hemihepatectomy (LH) has favorable short-term outcomes compared with open hemihepatectomy (OH), including shorter hospital stay. An in-depth healthcare utilization and cost-effectiveness analysis of the international multicenter ORANGE II PLUS randomized controlled trial comparing LH and OH was performed.

Metformin and liraglutide have been gradually used in the treatment of polycystic ovary syndrome (PCOS) due to their metabolic benefits, but also with some adverse reactions. Evidence suggests that gut microbiota imbalance plays an important role in the pathogenesis of PCOS. This study comprised a clinical trial to evaluate the efficacy of metformin, liraglutide, and their combination in PCOS women, and a parallel animal experiment to explore the potential involvement of gut microbiota.

Selective internal radiation therapy (SIRT) and sorafenib are used for patients with liver metastases from uveal melanoma. We conducted a phase I study to determine the optimal timing of administration of sorafenib in combination with radioembolisation.

Approximately 50% of breast cancer patients receiving neoadjuvant therapy do not achieve pathological complete response (pCR). Identifying personalized optimal therapeutic strategy is an unmet major challenge. Here, based on 4371 eligible patients from 31 datasets, we develop GDnet, an interpretable deep learning model integrating drug representations and tumor transcriptome profiles to predict the responses to neoadjuvant therapies and aid in selecting optimal treatment strategy. We demonstrate that GDnet significantly outperforms transcriptome-only model in predicting treatment response. Then we conduct two series of in-silico simulated clinical trials based on I-SPY2 trial and test datasets respectively and show that GDnet can significantly increase the pCR rate in all trials. Moreover, the odds ratios for pCR increase from 1.6 to 2.5 linearly as optimization intensifies. Overall, GDnet can function as a digital drug-testing surrogate to optimize treatment decision-making. This approach may have broader applications across various treatment settings and cancer types.

Patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy remain at significant risk of pelvic recurrence. We aim to report acute toxicity from a multicentric phase II randomized trial evaluating adjuvant radiotherapy (ART).

Despite treatment advances in newly diagnosed advanced-stage ovarian cancer (aOC), improved outcomes are needed.

Richter transformation is one of the most challenging B-cell lymphomas to treat, particularly in patients with high-risk chronic lymphocytic leukaemia features or who have had previous therapy for chronic lymphocytic leukaemia. Median survival remains 6-12 months across various therapeutic approaches. We evaluated the safety and preliminary activity of epcoritamab monotherapy, a subcutaneous CD3×CD20 bispecific antibody, in patients with Richter transformation.

Standard-of-care therapies for metastatic non-small-cell lung cancer (mNSCLC) have mixed outcomes that remain unsatisfactory. Durvalumab (anti-PD-L1) plus oleclumab (anti-CD73) might provide a synergistic antitumor effect by antagonizing separate immune pathways. We report safety, efficacy, pharmacokinetics, and immunogenicity findings of durvalumab + chemotherapy ± oleclumab as first-line treatment of mNSCLC from Arms B1 and B3 in the phase 1B MAGELLAN (NCT03819465) study.

BACKGROUNDWP1066 is an orally bioavailable, small-molecule inhibitor of activated phosphorylated STAT3 (p-STAT3) that has demonstrated preclinical efficacy in pediatric brain tumor models.METHODSIn a first-in-child, single-center, single-arm 3+3 design phase I clinical trial, 10 patients were treated with WP1066 twice daily, Monday-Wednesday-Friday, for 14 days of each 28-day cycle to determine the maximum tolerated dose/maximum feasible dose of WP1066. Compassionate-use treatment with WP1066 in 3 pediatric patients with H3.3G34R/V-mutant high-grade glioma (HGG) is also described.RESULTSThere was no significant toxicity, and the maximum feasible dose (MFD) was determined to be 8 mg/kg. Treatment-related adverse events were grade 1-2 (diarrhea and nausea most common); there were no dose-limiting toxicities. Median progression-free and overall survival was 1.8 months and 4.9 months, respectively. One partial response was observed in a patient with pontine glioma. Among the H3.3G34R/V-mutant HGG patients not on study, WP1066 was administered after upfront radiation to one patient for 17 months. At all dose levels tested, WP1066 suppressed p-STAT3 expression by peripheral blood mononuclear cells (PBMCs). Single-cell RNA sequencing analysis of PBMCs demonstrated increased CD4+ and CD8+ T cells, proinflammatory TNFA signaling, differentiation activity in myeloid cells, and downregulation of Tregs after WP1066 treatment, consistent with systemically inhibited STAT3 activity.CONCLUSIONWP1066 is safe, has minimal toxicity, and induces antitumor immune responses in pediatric brain tumor patients. Phase II investigation of WP1066 at the MFD in this patient population is warranted.TRIAL REGISTRATIONClinicalTrials.gov NCT04334863.FUNDINGCURE Childhood Cancer and Peach Bowl Inc.