Consolidation immunotherapy postchemoradiotherapy is standard for unresectable stage III non-small-cell lung cancer (NSCLC) per PACIFIC and GEMSTONE-301, but optimal integration with chemoradiotherapy is unclear, especially for large tumours. Induction immunotherapy before concurrent chemoradiotherapy (cCRT) may enhance tumour downstaging and immune synergy, while adaptive radiotherapy with strict lung constraints (V20 ≤20%) could reduce toxicity. This trial aims to evaluate the efficacy and safety of sintilimab with induction chemotherapy followed by adaptive radiotherapy and consolidation sintilimab in patients with unresectable stage III NSCLC.

This prospective, multicentre, single-arm phase II trial will enrol 35 patients with histologically or cytologically confirmed unresectable stage III NSCLC, without sensitising mutations, and Eastern Cooperative Oncology Group(ECOG) performance status 0-1. Patients will receive two cycles of induction sintilimab (200 mg, day 1, every 3 weeks) plus platinum-based doublet chemotherapy, followed by definitive cCRT with adaptive radiotherapy planning strictly limiting both lung V20 ≤20%. Radiotherapy dose can be delivered in three optional regimens based on tumour volume and distribution: (1) planning gross tumour volume (PGTV) 60-66 Gy/2.0-2.2 Gy/30F with planning target volume (PTV) 54 Gy/1.8 Gy/30F; (2) PGTV 54-66 Gy/2.0-2.2 Gy/30F without PTV irradiation or (3) PGTV 50 Gy/2.0 Gy/25F without PTV irradiation. During radiotherapy, patients will receive two additional cycles of sintilimab plus chemotherapy. Consolidation sintilimab will continue for up to 1 year or until disease progression/unacceptable toxicity.

This study was approved by the Institutional Ethics Committee of The Third Xiangya Hospital, Central South University (approval number: R25063; the approval letter is provided as online supplemental file 1). The study results will be disseminated through publication in peer-reviewed journals, presentations at national and international scientific conferences and communication to participants and the public via institutional channels and patient advocacy groups. Individual participant data will be available on reasonable request after study completion, subject to institutional and ethical approvals.

NCT07138755.

HER2-positive advanced breast cancer remains challenging after trastuzumab-based therapy because available regimens differ in survival, response, and toxicity. We compared therapies used in second-line and later settings.

This PRISMA-NMA-compliant review was registered with PROSPERO (CRD420251244047). PubMed, Embase, Web of Science, and CENTRAL were searched through July 24, 2026. Phase II or III randomized controlled trials after trastuzumab-based therapy were eligible. Bayesian network meta-analysis summarized PFS and OS as hazard ratios and confirmed ORR and safety outcomes as odds ratios. Random-effects models were used where heterogeneity was estimable; fixed-effect Bayesian models were used for the sparse SAE and ILD/pneumonitis networks. DoR was analyzed exploratorily using a fixed-effect Bayesian normal model after prespecified conversion of arm-level summary statistics; TTP was not quantitatively synthesized when the required summary measures were unavailable or clinically non-equivalent.

Sixteen reports representing seven independent randomized trial families and 3,339 unique randomized participants were included. Relative to T-DXd, T-DM1 had less favorable PFS (HR 3.30, 95% CrI 2.06-5.28) and OS (HR 1.52, 1.19-2.01). However, T-DXd was not represented in the second-line-only OS network or the Asia-dominant PFS/OS networks; therefore, its survival ranking reflects evidence primarily from mixed-line, non-Asia-dominant trials. T-DXd produced higher confirmed ORR than Lap-Cap (OR 7.43, 3.80-13.16), PTN-Cap (OR 3.35, 1.24-8.19), and T-DM1 (OR 6.31, 3.98-10.32). DoR showed no clear between-treatment difference in the EMILIA/NALA network, and TTP could not be quantitatively synthesized. Any-grade AE estimates did not indicate a safety advantage for T-DXd. SAE comparisons were also inconclusive: T-DM1 vs Lap-Cap OR 0.90 (0.67-1.21) and T-DXd vs T-DM1 OR 1.30 (0.87-1.93). T-DXd had higher ILD/pneumonitis odds than T-DM1 (OR 5.55, 2.79-12.16); LVD differences were unclear.

Within the connected overall networks, T-DXd showed a favorable survival profile and the highest confirmed ORR, although its survival ranking was not estimable in the second-line-only OS or Asia-dominant survival networks. Its increased ILD/pneumonitis risk relative to T-DM1 is clinically important. Indirect survival comparisons and sparse safety networks require cautious interpretation.

PIK3CA mutations are among the most common driver mutations in cervical cancer (CC), yet therapeutic strategies targeting PIK3CA mutations are still under investigation. This study aims to evaluate the efficacy and safety of immune checkpoint inhibitors (ICIs) combined with tyrosine kinase inhibitors (TKIs) in patients with PIK3CA-mutated recurrent or metastatic (R/M) CC.

This study was based on two prospective clinical trials (ChiCTR1900023015 and the CLAP study) and retrospective data from Fujian Cancer Hospital, comparing ICIs combined with TKIs with physician's-choice Non-ICI/TKI conventional treatments in PIK3CA-mutated R/M CC. The primary endpoint was objective response rate (ORR), and secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.

A total of 55 patients were included, with 27 in the ICIs plus TKIs treatment group and 28 in the Non-ICI/TKI conventional treatment group. The ORR in the ICIs plus TKIs group was 85.19% (95% CI, 67.52%-94.08%), significantly higher than 28.57% (95% CI, 15.25%-47.06%) in the Non-ICI/TKI conventional treatment group (P < 0.001). The PFS in the ICIs plus TKIs group was 21.03 months, significantly longer than 9.13 months in the Non-ICI/TKI conventional treatment group (HR, 0.49; 95% CI, 0.26-0.94, P = 0.033). Although the OS difference was not statistically significant (HR, 0.65; 95% CI, 0.31-1.34, P = 0.24), the ICIs plus TKIs group showed superior clinical efficacy. The incidence of hypertension (P < 0.001), rash (P = 0.004), hypothyroidism (P < 0.001), proteinuria (P = 0.010), and palmoplantar erythrodysesthesia syndrome (P = 0.023) was higher in the ICIs plus TKIs group compared to the Non-ICI/TKI conventional treatment group. The observed adverse events were generally manageable. Although grade ≥3 adverse events occurred, no grade ≥3 immune-related adverse events or treatment-related deaths were observed.

ICIs plus TKIs demonstrated significant efficacy in treating PIK3CA-mutated R/M CC. Although there were some safety concerns, the adverse reactions were manageable, no grade ≥3 immune-related adverse events or treatment-related deaths were observed.

Japan's rapidly aging population has led to an increase in elderly patients undergoing gastrectomy for gastric cancer. However, the impact of postoperative complications on survival in patients aged ≥80 years remains unclear. This study aimed to evaluate the association between postoperative complications and survival outcomes in patients aged ≥80 years with gastric cancer.

We retrospectively analyzed 61 patients aged ≥80 years who underwent gastrectomy with D2 lymph node dissection between 1999 and 2020. Postoperative complications were classified according to the Clavien-Dindo (CD) classification into a "no or minor complication group" (CD Grade ≤ II, including no postoperative complications) and a "major complication group" (CD Grade ≥ III), and the impact of postoperative complications on survival outcomes were assessed. A subgroup analysis excluding macroscopic type 4 was also performed.

Postoperative complications occurred in 24 patients (39.3%), of which 8 (13.1%) experienced major complications. Patients in the major complication group had a significantly longer postoperative hospital stay, while other baseline characteristics were similar between groups. Kaplan-Meier analysis showed a trend toward poorer OS in the major complication group (P = 0.063), and recurrence-free survival (RFS) was significantly worse in this group (P = 0.004). Multivariate analysis showed that postoperative complications of CD grade ≥ III were independently associated with poorer OS (HR 2.51; 95% CI 1.01-6.24; P = 0.049). Subgroup analysis in patients without type 4 also showed significantly worse OS in the major complication group (P = 0.036).

This study showed that postoperative complications were associated with poorer OS and RFS even in patients aged ≥80 years with gastric cancer. Future large-scale studies are needed to further clarify this association and optimize treatment strategies for this population.

Internet search engines serve as primary gateways to cancer information; yet, the commercialization of health content within organic search results remains understudied. While covert promotional content-such as native advertising and stealth marketing-has been documented in various contexts, systematic comparisons across structurally divergent search platforms are lacking.

This study examined the prevalence, distribution, and information quality characteristics of covert promotional cancer-related content across Naver and Google, South Korea's 2 dominant search engines, which have fundamentally different platform architectures.

A 2-phase cross-sectional content analysis was conducted. Phase 1 used natural language processing to identify 34 cancer-related keywords from 1400 preliminary posts. Phase 2 systematically collected 5848 posts in October 2023, yielding 919 unique posts (598 from Naver and 321 from Google) that covered 7 major cancer types, collectively accounting for over 70% of Korean cancer incidence. Two trained coders analyzed promotional status, intensity, institutional sources, and information quality indicators (citation practices, information depth, and source attribution), with intercoder reliability exceeding κ=0.80. Chi-square tests were used to examine associations between platform and content characteristics across cancer type.

Covert promotional content appeared in 48.6% (447/919) of analyzed posts, with a significantly higher prevalence on Google (174/321, 54.2%) than on Naver (273/598, 45.7%; χ²₁=5.78; P=.02). Platform differences were pronounced. Naver promotional posts predominantly originated from blogs (262/273, 96.0%) and exhibited full promotional intensity (126/242, 52.1%), while Google posts primarily came from hospital websites (141/174, 81.0%) with simple institutional identification (52/90, 57.8%). Institutional source distribution varied significantly by platform (χ²₅=209.642; P<.001). Traditional medicine institutions dominated Naver (119/120, 99.2%), whereas university-affiliated hospitals predominated on Google (96/113, 85.0%). Information quality also differed substantially. Indirect citation was more common on Google (142/174, 81.6%) than on Naver (160/273, 58.6%; χ²₁=25.653; P<.001), while comparative informational depth was higher on Google (97/174, 55.7%) versus Naver (53/273, 19.4%; χ²₂=64.683; P<.001).

Covert promotional cancer content is pervasive in Korean search results, with platform architecture systematically shaping promotional patterns, institutional sources, and information quality rather than reflecting deliberate marketing strategies. These findings underscore the need for platform-sensitive regulation and enhanced digital health literacy to protect vulnerable cancer information seekers from commercial exploitation embedded within ostensibly neutral search environments.

Older patients undergoing esophagectomy remain at high risk for perioperative morbidity. This study evaluated the feasibility, safety and adherence of a multimodal prehabilitation program integrated with geriatric co-management in patients aged ≥ 65 years scheduled for transthoracic esophagectomy and explored perioperative outcomes.

In this single-center prospective feasibility study, patients aged ≥ 65 years scheduled for transthoracic esophagectomy completed a 4-week home-based program of endurance, respiratory, resistance and balance training combined with comprehensive geriatric assessment and medication optimization. Feasibility outcomes were retention, adherence and data completeness. Perioperative outcomes were compared with a 2:1 matched historical control cohort using cluster-robust linear regression for continuous outcomes and Firth penalized logistic regression for binary outcomes.

Twenty-six patients were enrolled; 22 completed the intervention and were matched to 42 control records. At the first check-in 61.5% reported complete and 84.6% complete or mostly complete adherence; documentation was missing for 69.2% at the second. Despite matching, controls had more favorable performance status (p = 0.023) and comorbidity burden (p = 0.014). Postoperative complications, anastomotic leakage, hospital mortality and length of stay did not differ significantly. Intensive care unit (ICU) readmission was lower after prehabilitation (4.5% vs. 26.2%; odds ratio 0.19, 95% confidence interval 0.02-0.90; p = 0.035), but not after adjustment for surgical approach (adjusted odds ratio 0.30; p = 0.172).

Multimodal prehabilitation with geriatric co-management was feasible and safe in this population. Overall postoperative morbidity was unchanged. The lower ICU readmission rate did not withstand adjustment and is hypothesis-generating requiring an adequately powered randomized trial. Future programs need more robust adherence monitoring.

ClinicalTrials.gov NCT05167682, registered 9 December 2021, retrospectively registered.

Individuals with BRCA1/2 germline variants face complex, preference-sensitive medical decisions under psychological distress. Structural constraints in genetic counseling create support gaps during waiting periods, prompting patients to rely on fragmented or misleading online information. Conversational AI may offer low-threshold, continuous informational support, yet methods for its responsible integration into clinical care remain unclear.

This study identifies and systematizes stakeholder-informed sociotechnical design requirements and governance conditions for a clinically bounded conversational AI system intended to support comprehension, appraisal, and appropriate use of complex hereditary cancer information in BRCA1/2-related care.

We conducted an exploratory, qualitative, predevelopment requirements study using 2 structured participatory workshops with interdisciplinary stakeholders (N=18). Guided exercises included stakeholder analysis, the value proposition canvas, and the sustainability awareness framework. Structured workshop outputs, field notes, and artifacts were analyzed using inductive thematic analysis.

Stakeholder workshops revealed that responsible design was shaped less by consensus around standalone responsible AI principles than by three recurrent cross-stakeholder tensions: (1) accessibility and continuity of support versus clinical role boundaries, (2) simplification and emotional reassurance versus medical precision and epistemic transparency, and (3) technical scalability versus governance, data protection, and institutional accountability. These tensions translated into design requirements for constrained system authority, mandatory human oversight, context-sensitive communication, and integration into clinical and regulatory governance structures.

Conversational AI in this context should be explicitly constrained and embedded within clinical governance structures to be perceived as responsible. Responsible implementation requires transparent design, human oversight, integration into existing care pathways, and early alignment with German/European Union (EU) regulatory requirements concerning data protection, medical device classification, genetic data, and AI transparency.

Adipokines are currently the subject of numerous intensive studies due to their multidirectional effects in the formation and development of many cancers, including ovarian cancer. Therefore, the purpose of the present study was to analyse the concentration of new adipokines, including asprosin, follistatin-like protein 1, isthmin-1, meteorin and neuregulin-4 in serum and peritoneal fluid of patients with serous ovarian cancer and to determine whether there is a relationship between the concentration of the studied parameters and the degree of histological differentiation of the cancer.

The study group consisted of 32 patients diagnosed with serous carcinoma of the ovary (Cystadenocarcinoma papillare serosum IIIc). The reference group consisted of 16 patients diagnosed with benign neoplasm (Cystadenoma serosum). Concentration of asprosin, follistatin-like protein 1, isthmin-1, meteorin and neuregulin-4 were determined using ELISA immunoenzymatic assay.

Significant fluctuations in the concentrations of the measured markers were observed in the serum and peritoneal fluid of patients with ovarian cancer and the existence of an association of the concentrations of some of them with the degree of histological differentiation of the tumour.

The occurring systemic and local changes in the immune system involving the tested adipokines indicate the potential involvement of these markers in ovarian cancer pathogenesis, serving as key immune mechanisms that drive tumor progression and modulate the associated inflammatory response. Determination of the concentration of the adipokines studied, in combination with other markers, could prove valuable for developing future diagnostic and treatment approaches in ovarian cancer care, though additional studies are required.

Nowadays, an increasing number of emerging therapeutic modalities are flourishing due to the high recurrence and intractability of cancer. Among them, NO gas therapy (NO GT) relies on NO donors that release NO radicals upon external or internal stimulation. Photodynamic therapy (PDT) is realized by the specific photosensitizers and light source. However, the clinical translation of NO is limited by its gaseous nature and the need for precise control over dosage and spatiotemporal distribution. Meanwhile, the efficacy of PDT is often compromised by tumor hypoxia. Consequently, the synergistic integration of PDT and NO GT has emerged as a cutting-edge paradigm in cancer treatment. Among the various NO donors, 4-nitro-3-trifuoromethylaniline (NTA) and its derivatives, as a prominent class of NO photodonors, have garnered sustained attention, which displayed various advantages such as high and controllable NO release ability and outstanding structural modification. In this review, we highlight the design of such bimodal therapeutic systems based on two methods of the combination of NTA and photosensitizers, namely, nanoassembly and molecular hybridization. By elucidating the design principles and synergistic antitumor effects of these two strategies, we summarize future development directions and remaining bottlenecks to provide rational guidelines for subsequent molecular design and biomedical research.

This study investigates the transcriptional impact of Q901, a highly selective cyclin-dependent kinase 7 (CDK7) inhibitor in clinical development. Q901 primarily disrupted MYC and E2F-dependent transcription programs, down-regulating cell cycle control and DNA damage repair pathways. CDK7 binding at the promoter-proximal regions was markedly stabilized by Q901, leading to reduced occupancy of MYC, E2F, and RNA polymerase II (RNAPII). These findings offered a novel therapeutic strategy to enhance cancer susceptibility to topoisomerase I (TOP1) DNA-protein cross-links (TOP1-DPCs) induced by TOP1 inhibitors. Resistance to TOP1 inhibitors arises through activation of DNA repair pathways when elongating RNAPII encounters TOP1-DPCs. By suppressing RNAPII transition from initiation to elongation and DNA repair pathways, Q901 stabilizes TOP1-DPCs and sensitizes tumors to TOP1 inhibitors. Preclinical studies demonstrated enhanced tumor suppression when combining Q901 with TOP1 inhibitor-based antibody-drug conjugates (TOP1i-ADCs), highlighting its potential as a therapeutic option for cancers resistant to TOP1i-ADC therapy.