This phase 1 study aimed to determine the maximum tolerated dose (MTD) and evaluate the safety and preliminary efficacy of rucaparib (RUB), a poly(adenosine diphosphate ribose) polymerase (PARP) inhibitor, combined with liposomal irinotecan (nal-IRI) and 5-fluorouracil (5-FU) in metastatic gastrointestinal (GI) cancers. RUB targets DNA repair pathways, showing efficacy in tumors with homologous recombination deficiency, such as BRCA mutations. Preclinical data suggest synergy with irinotecan, but overlapping toxicities pose challenges.

Concurrent chemoradiotherapy (CCRT) has remained the standard treatment for unresectable locally advanced esophageal squamous cell carcinoma (ESCC), yet survival remains poor. This single-arm, phase II trial aims to evaluate the efficacy and safety of two cycles of induction chemotherapy with camrelizumab followed by CCRT in previously untreated patients with unresectable locally advanced ESCC. The primary endpoint, the 1-year overall survival (OS) rate in the per-protocol population (N = 46), was 87.0% (95% confidence interval [CI]: 77.7%-97.3%), exceeding the pre-specified target. Secondary endpoints included OS in the intention-to-treat (ITT) population, progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), duration of response, safety, and health-related quality of life. In the ITT population (N = 49), the 1-year OS rate was 85.7% (95% CI: 76.5%-96.1%). The 1-year PFS rates in the per-protocol and ITT populations were 71.7% (95% CI: 59.8%-86.0%) and 71.4% (95% CI: 59.8%-85.3%), respectively. The median OS, PFS, and duration of response were not reached. Following CCRT, the ORR was 93.5%, with a DCR of 95.7%. Lymphopenia was the most frequent Grade ≥3 adverse event (100%). One patient died from treatment-related myelosuppression. Health-related quality of life generally improved after induction therapy, with significant improvements in global health status, emotional functioning, and some symptom relief, despite a slight decline in physical functioning. Here, we show that induction chemoimmunotherapy followed by CCRT exhibits promising efficacy and manageable safety in patients with unresectable locally advanced ESCC, thus warranting further randomized controlled trials. Trial number: ChiCTR2000034304.

Despite advancements in several malignancies, the treatment atlas of natural killer (NK) cell therapy for pancreatic cancer remains inadequate, and the dynamic immune landscape underlying the various responses is still incompletely understood. This phase 1b/2 trial evaluated the safety and efficacy of allogeneic NK cell therapy combined with gemcitabine and S-1 as a first-line treatment for advanced pancreatic cancer (APC) and explored the dynamic responsive immune landscape (ChiCTR1900021764). The administration of 1 × 109 to 8 × 109 NK cells to 24 patients was well tolerated, with no graft-versus-host disease or dose-limiting toxicity. Among the 19 evaluable patients, the objective response rate was 31.6%, and the disease control rate was 73.7%. The median progression-free survival was 6.6 months, and the overall survival was 10.8 months. Further longitudinal single-cell RNA sequencing (scRNA-seq) of 19 paired-blood samples revealed an increased proportion of certain NK cell subsets (c4-ZEB2, c5-IL7, c6-IL15, c10-NCR3, and c11-TNFSF8) and T-cell subsets (CD8+ Teff and CD4+ Tem) in responders, characterized by increased expression of proinflammatory and effector molecules. Bulk T-cell receptor (TCR) Vβ repertoire sequencing of responders indicated potential T-cell clonal expansion, manifested as a greater abundance of large and hyperexpanded clonotypes. Our first-in-human trial demonstrated its safety and potentially preliminary efficacy, warranting further clinical evaluation. Multiomic profiling identified specific circulating NK and T-cell subsets potentially associated with clinical outcomes, providing novel insights into the dynamic transcriptional underpinnings of the immune landscape in response to NK cell-based therapy.

This study aimed to investigate the efficacy and safety of fruquintinib plus sintilimab in mismatch repair-proficient (pMMR)/microstatellite stable (MSS) refractory metastatic colorectal cancer (mCRC).

The promising therapeutic outcomes of neoadjuvant chemoimmunotherapy (NCIT) in locally advanced esophageal squamous cell carcinoma (ESCC) have been confirmed by multiple phase II clinical trials and are widely used in clinical practice. However, there are some cases, such as clinical T3N+ stage, that achieve poor tumor regression after receiving NCIT, reflecting the insufficient efficacy of NCIT for advanced T-type tumors. It may be necessary to add concurrent radiotherapy to further improve the local control effect of tumor, but it also means higher adverse events and immune suppression when irradiating tumor-draining lymph nodes. Nevertheless, node-sparing radiotherapy can enhance the effect of NCIT with fewer adverse effects, which has been applied to other solid tumors. The aim of this study was to evaluate the safety and efficacy of NCIT combined with node-sparing radiotherapy for clinical T3N+ locally advanced ESCC (CINSREC trial).

Plan-of-the-day (PoD) adaptive radiation therapy (ART) is based on a library of treatment plans, with 3D daily imaging guiding the plan selection. In a phase II multi-institutional trial of cone-beam CT (CBCT)-guided PoD-ART for locally advanced cervical carcinoma (LACC), this study aimed at evaluating the PoD selection, its geometric and dosimetric impact and characterizing a sub-population of patients associated with dosimetric improvement from ART.

Background Radiology staging reports (ie, oncologic reports) are written for referring physicians using complex medical terminology. Large language models (LLMs) show promise for simplifying medical text for patient use, but controlled studies evaluating the impact of LLM simplification on patients' comprehension of radiology reports are lacking. Purpose To evaluate whether LLM-based simplification of oncologic CT reports improves patients' cognitive workload, text comprehension, perception, and reading time. Materials and Methods This prospective, controlled, open-label, quasi-randomized trial enrolled 200 adults with cancer who underwent routine CT restaging. Between April and May 2025, participants were alternately assigned to receive either standard CT reports (100 participants) or LLM-simplified versions created using Llama 3.3 70B (Meta) with mandatory radiologist review (100 participants). The primary outcomes were participant-reported scores on nine seven-point Likert scale items, and composite scores, in the domains of cognitive workload, text comprehension, and report perception, as well as reading time. Secondary outcomes included readability metrics and independent radiologist assessments of report errors, usefulness, and quality. Statistical analyses included logistic regression adjusted for participant characteristics. Results Among the 200 participants (mean age, 64 years ± 14 [SD]; 112 male participants), simplified reports reduced the median reading time from 7 minutes to 2 minutes (P < .001). Participants who received simplified reports reported lower cognitive workload (adjusted odds ratio [OR], 0.18 [95% CI: 0.13, 0.25]), better comprehension (adjusted OR, 13.28 [95% CI: 9.31, 18.93]), and better perception of report usefulness (adjusted OR, 5.46 [95% CI: 3.55, 8.38]) than did those who received standard reports (all P < .001). Simplification improved report readability (mean Flesch-Kincaid Grade Level, 8.89 ± 0.93 vs 13.69 ± 1.13; P < .001). Radiologist review revealed factual errors in 6% (moderate, 2%; severe, 4%), content omissions in 7% (minor, 2%; moderate, 1%; severe, 4%), and inappropriate additions in 3% (minor, 1%; moderate, 2%) of simplified reports. Conclusion LLM simplification of oncologic CT reports improved patient comprehension and reduced reading burden. However, clinically relevant errors were identified. © RSNA, 2025 Supplemental material is available for this article.

Current treatment options for nonmetastatic laryngeal squamous cell carcinoma include radiotherapy, chemoradiotherapy, and surgery, which can result in significant morbidity. This study reports the 20-year outcomes of a single-modality chemotherapy as a larynx preservation strategy in patients with stage II-IVa laryngeal squamous cell carcinoma (LSCC).

Patients with early-stage node-negative oral cancer undergo a sentinel lymph node biopsy (SLNB) or elective neck dissection under general anesthesia. A noninvasive imaging alternative would be of great interest. Superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI) can visualize draining lymph nodes and potentially metastases. We investigated the optimal combination of SPIO injection and T2*-weighted MRI settings to identify the sentinel lymph nodes (SLNs), the lymphatic drainage pattern, and possibly to detect metastatic SLNs.

Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) were included for evaluation of patient characteristics, dosimetric analysis, and plan evaluation of both intensity-modulated radiotherapy (RT) using simultaneous integrated boost (SIB-IMRT) and sequential IMRT (IMRTSEQ) and to compare the response and acute toxicity of both arms. This prospective single-blind randomized clinical comparative study was carried out on 60 patients, clinically and histologically confirmed to have locally advanced HNSCC at the Clinical Oncology Department, Tanta University Hospitals. All patients were randomly divided into two equal groups: Group A was treated with SEQ-IMRT with combined total doses in phases I, II, and III of 70 Gy/35 fractions, 2 Gy/fraction along the entire course, 5 days a week, in 7 weeks by 54 Gy in 27 fractions, and group B was treated with SIB-IMRT dose of 66 Gy to PTV-HR (2.2 Gy/fraction), 60 Gy to PTV-IR (2 Gy/fraction), and 54 Gy to PTV-LR (1.8 Gy/fraction), all were given at the same time in 30 fractions, 5 days a week, over 6 weeks. All patients received 3 cycles of induction chemotherapy with docetaxel (or Taxotere), platinum, and 5-fluorouracil, followed by concurrent chemo-RT with cisplatin or carboplatin. Organ at risk )OAR( was higher for group B (100%) vs. (33.3%) for group A (p = 0.035). The 1-year & 2-year OS for the whole group were (98.3% & 61.5%) respectively, while for group A and group B, 1-year OS was 96.7% for group A vs. 100.0% for group B, and the 2-year OS was 53.2% for group A vs. 71.2% for group B. the 2-year PFS was 58.3% for the whole group and 49.4% vs. 69.2% for groups A and B, respectively. The SIB-IMRT arm, with shorter total treatment duration, resulted in comparable treatment outcomes and acute toxicity rates. This reduction in treatment time not only reduces costs but also decreases the workload of busy radiation. The SIB-IMRT is well-tolerated with better treatment compliance for head and neck cancer patients.

Single-fraction preoperative ablative stereotactic partial breast irradiation (sPBI) can be safely delivered in early-stage hormone receptor-positive (HR+) breast cancer with delayed time to surgery and high pathologic complete response rates.

This study aimed to provide evidence regarding the treatment of patients with unresectable pancreatic cancer. We conducted a prospective single-arm phase II trial using the FOLFIRINOX regimen. After completing 4-8 cycles, patients underwent surgical resection when feasible. The primary endpoint was R0 resection rate. Fifteen patients were enrolled in this study. A median of six courses of FOLFIRINOX chemotherapy was administered, and a partial response or R0 resection was achieved in 26.7% and 33% of the patients, respectively. Severe adverse events due to chemotherapy and major surgical complications were observed in 33.3% and 6.7% of patients, respectively. The median overall survival of patients who underwent R0 resection or with R1 or unresectable disease was 47.8 months (95% confidence interval (CI), 22.5-73.1) or 14.5 months (95% CI, 11.8-17.2), respectively (P = 0.031). Well-selected patients with unresectable locally advanced pancreatic cancer treated with FOLFIRINOX achieved relatively high R0 resection rates and prolonged survival. Therefore, induction with FOLFIRINOX is feasible and well tolerated for locally advanced, initially unresectable pancreatic cancer and may be effective in facilitating R0 resection and prolonging survival.

This study aimed to evaluate the efficacy and safety of argon-helium cryoablation combined with Programmed Death-1 (PD-1) inhibitors versus PD-1 inhibitors plus chemotherapy in treating non-small cell lung cancer (NSCLC). Patient/material and methods: In this single-center, open-label, randomized controlled trial, 60 NSCLC patients treated between December 2020 and December 2023 were enrolled. Patients were randomly assigned (1:1) to either a study group (argon-helium cryoablation + PD-1 inhibitor, n = 30) or a control group (PD-1 inhibitor + chemotherapy, n = 30). Allocation was concealed using sequentially numbered, opaque, sealed envelopes (SNOSE). Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included short-term efficacy - objective response rate (ORR), disease control rate (DCR) - immune function changes (CD4+, CD8+, CD4+/CD8+), and adverse reactions, assessed after four cycles and during a 1-year follow-up.

Small molecule inhibition of BCL-XL with navitoclax resulted in on-target dose-limiting thrombocytopenia. DT2216 was more effective than navitoclax and reduced platelet toxicity in preclinical models by selectively degrading BCL-XL via the VHL E3 ligase, which is minimally expressed in platelets.

Patients with BRAF V600E-mutated/microsatellite stable (MSS) metastatic colorectal cancer (mCRC) are associated with a poor prognosis. Backline treatment has minimal efficacy. Multi-target inhibitors of the RAS-RAF-MEK signaling pathway combined with PD-1 monoclonal antibody may be a promising strategy for BRAF V600E-mutated mCRC.

This study aimed to evaluate the safety and feasibility of two neoadjuvant chemotherapy (NAC) regimens, gemcitabine plus nab-paclitaxel (GA) and gemcitabine plus S-1 (GS), for elderly patients (aged 75 years and older) with resectable and borderline resectable pancreatic ductal adenocarcinoma (R/BR-PDAC). A post hoc analysis was conducted using data from a randomized controlled trial on NAC for R/BR-PDAC (CSGO-HBP-015). Patients were divided into two groups: those aged 75 years and older (7/46 in GS and 16/48 in GA) and those under 75 years. Short-term outcomes, including resection rates, adverse events (AEs), postoperative complications, and the administration of adjuvant chemotherapy, were compared between age groups for both regimens. The incidence of AEs in patients aged 75 years and older tended to be higher than those of younger patients in both chemotherapy arms, but the differences were not statistically significant. However, the resection rates, postoperative complication rates, and the administration of adjuvant chemotherapy were not affected by age. Both regimens showed comparable safety profiles in elderly and younger cohorts. The GA and GS regimens can be safely administered as NAC for R/BR-PDAC in elderly patients without adversely affecting postoperative outcomes. These findings suggest that both regimens are feasible NAC options even for patients 75 years and older, supporting the need for further randomized controlled trials to validate these outcomes in the elderly population.Trial registration. UMIN Clinical Trials Registry UMIN000021484. This trial began in April 2016, and first registration (First Posted date) is 01/04/2016.

Brain metastases reduce overall survival rates of patients with non-small cell lung cancer (NSCLC); patients with epidermal growth factor receptor 2 (ERBB2 [formerly HER2])-mutant NSCLC are more likely to have baseline brain metastases. Trastuzumab deruxtecan (T-DXd) is an approved ERBB2-directed treatment for previously treated unresectable or metastatic ERBB2-mutant NSCLC.

This study aimed to observe and compare the efficacy and safety of different anticoagulants combined with immunotherapy and chemotherapy for advanced nonsmall cell lung cancer (NSCLC).

Radiotherapy induces multiple forms of tumor cell death, including immunogenic cell death (ICD) like GSDME-mediated pyroptosis and MLKL-mediated necroptosis; and ICD has been increasingly accepted as a crucial element leading to enhanced anti-tumor adaptive immunity. We aim to clarify whether a vaccine-like effect is intrinsic for radiation-induced tumor cell death, and to explore potential applications.

Esophageal squamous cell carcinoma (ESCC) imposes a heavy disease burden in China, accounting for over 50% of global cases and approximately 301,000 annual deaths. Current prognostic markers inadequately predict recurrence in early-stage patients. This study investigates microRNA-107 (miR-107) as a novel prognostic biomarker for ESCC.