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Beyond survival: Testicular tissue cryopreservation for fertility preservation during childhood cancer, experiences from a single center.

INTRODUCTION: Approximately 30% of all male childhood cancer survivors receive gonadotoxic therapy increasing their risk for infertility. The only current option for potential fertility preservation in prepubertal males is through testicular tissue cryopreservation (TTC), available through clinical trials. Our aim was to evaluate our experience and identify barriers to enrollment in the TTC study. METHODS: A retrospective review was conducted to describe a single center experience with TTC, including an assessment of factors impacting the decision to enroll or not enroll in the TTC trial. RESULTS: A total of 61 patients were found to be eligible for enrollment in the TTC trial, with 23 patients (34%) choosing to enroll and undergo testicular tissue cryopreservation including 19 (83%) oncology patients. In patients who underwent TTC there were no unexpected delays in starting disease directed therapy. For families that declined enrollment, many did not see fertility preservation as a priority at the time of counseling. (n = 17, 44%). Other barriers included concerns about post-operative complications and a feeling of being overwhelmed at the time of counseling. DISCUSSION: Despite being the only preservation option for pre-pubertal boys facing risk of infertility, TTC enrollment was not pursued by a majority of eligible patients and families. Identifying potential barriers or misconceptions, particularly in regard to post operative complication risks, offer opportunities for improved counseling and education. Early introduction of the Fertility Navigation team allows for procedural coordination success and access for patients that are interested. Success is not measured in how many patients proceed with TTC, rather that all patients have the opportunity for counseling and discussion. CONCLUSION: TTC can be offered and completed safely without delays in disease-directed treatment timelines. A Fertility Navigation Program allows for equal opportunity for education and enrollment on TTC protocol which should be the goal for pediatric institutions, though is not pursued by many patients. A majority of those who declined the study did not see fertility as a priority at the time of treatment while others were concerned regarding peri-operative risks.

Humans

BMT4me En Español: Multisite Feasibility and Usability Testing of a Spanish-Language mHealth Adherence Support App for Spanish-Speaking Caregivers of Children After Hematopoietic Stem Cell Transplantation and Cancer Treatment.

BACKGROUND: Medication nonadherence during the first 100 days after pediatric hematopoietic stem cell transplantation (HSCT) and during oncology treatment increases risk for complications. BMT4me is a caregiver-facing mobile health (mHealth) application providing medication reminders, symptom tracking, and note-taking features to support medication management. Spanish-speaking caregivers are frequently excluded from digital adherence interventions due to the lack of language-accessible tools. PROCEDURE: We conducted a multisite, mixed-methods usability testing of a Spanish-language version of BMT4me ("BMT4me en Español") with Spanish-speaking caregivers of children (ages 2-17 years) post-HSCT or with an oncology diagnosis on active treatment. Caregivers completed a facilitated, three-step usability session (unobtrusive observation, interactive observation, and debriefing), followed by a semi-structured interview, and then completed the system usability scale (SUS). Quantitative outcomes were summarized descriptively; qualitative data were analyzed using content analysis with constant comparison. RESULTS: Fifteen participants enrolled at each site for a total of 30 participants. Across both sites, the recruitment rate was 91%. All participants completed all parts of the study. The SUS score (M = 80.09; SD = 17.35) was above average (>68). Two key qualitative themes emerged: (1) the perceived positive impact of BMT4me on managing a serious illness and (2) the acceptance and sociocultural relevance of BMT4me for Spanish-speaking families. Caregivers also shared suggestions to add educational content and multiuser functionalities to BMT4me. CONCLUSIONS: The acceptance and perceived positive impact of the Spanish BMT4me app indicates that socioculturally relevant, Spanish mHealth interventions have strong potential to support Spanish-speaking caregivers in pediatric oncology and HSCT settings. CLINICAL TRIALS NCT: NCT06361173.

Adolescent

Health-Related quality of life (HRQoL) and health state utility values (HSUV) in patients with head and neck Cancer: A systematic review and Meta-Analysis.

BACKGROUND: Head and neck cancer (HNC) and its treatment can substantially impair speech, swallowing, eating, appearance, and social functioning, resulting in persistent reductions in health-related quality of life (HRQoL). Although the EuroQol 5-Dimensions questionnaire (EQ-5D) is widely used to assess generic HRQoL and derive health state utility values (HSUVs), EQ-5D-based evidence in HNC has not been comprehensively synthesized. This study aimed to summarize EQ-5D-based HRQoL and HSUVs in HNC, estimate pooled utility and EQ-VAS scores, explore subgroup differences, and identify predictors of poorer HRQoL. METHODS: A systematic review and meta-analysis was conducted according to PRISMA guidelines and registered in PROSPERO (CRD420261307907). PubMed, EMBASE, Web of Science, Cochrane Library, and Scopus were searched from inception to February 10, 2026. Studies reporting baseline EQ-5D utility values and/or EQ-VAS scores in patients with HNC were included. Random-effects meta-analyses using the DerSimonian-Laird (DL) estimator with the Hartung-Knapp-Sidik-Jonkman (HKSJ) adjustment were performed to pool mean scores. Between-study variance (τ2) and 95 % prediction intervals (PI) were calculated to capture parameter dispersion. Subgroup analyses were conducted across clinical and methodological vectors. RESULTS: Twenty studies involving 7,403 patients were included. The pooled mean EQ-5D utility score was 0.79 (95 % CI: 0.75-0.83; τ2 = 0.0011; 95 % PI: 0.72-0.86). The pooled mean EQ-VAS score was 69.36 (95 % CI: 65.71-73.01; τ2 = 38.4586; 95 % PI: 55.11-83.61). Extreme heterogeneity was observed (I2 = 96.4 % and 97.1 %, respectively). Utility values were significantly higher in studies utilizing the EQ-5D-5 L than the EQ-5D-3 L version (0.82 vs. 0.76). By tumor subsite, nasopharyngeal cancer showed the highest utility value (0.85, exploratory), whereas oral cancer demonstrated the lowest (0.73). Adjusted multivariable models revealed that advanced stage, high treatment intensity, severe pharyngolaryngeal pain, dysphagia, malnutrition, and older age were robust predictors of poorer HRQoL. CONCLUSIONS: Patients with HNC experience substantial and persistent HRQoL impairment, with meaningful variations driven by tumor subsites and instrument versions. In light of the extreme heterogeneity, these pooled findings establish a macro-level, broad reference estimate rather than a fixed target. These parameters directly inform localized survivorship care planning, health technology evaluations, and cost-utility decision-making modeling in head and neck oncology.

Humans

Compliance With Ecological Momentary Assessment Among Patients With Cancer: Systematic Review and Meta-Analysis.

BACKGROUND: Patients with cancer often experience substantial fluctuations in psychological states during disease management. Traditional research tools are limited in capturing these dynamic changes in real time, constraining clinicians' understanding of patients' true conditions. Ecological momentary assessment (EMA) enables high-frequency, real-time data collection, providing patient-reported data with greater ecological validity. However, the effectiveness of EMA studies critically depends on patient compliance, and reported compliance rates vary widely, with a lack of systematic quantitative synthesis. OBJECTIVE: This study aims to systematically review and quantitatively analyze compliance with EMA among patients with cancer, and to examine whether EMA design characteristics were associated with compliance. METHODS: Web of Science, PubMed, Embase, Cochrane Library, CINAHL, PsycINFO, CNKI, and Wanfang databases were searched for literature published up to April 30, 2026. Compliance was defined as completed prompts divided by delivered prompts. Single-group proportions were pooled using logit transformation and random-effects models with the Hartung-Knapp-Sidik-Jonkman adjustment. Prediction intervals were calculated to describe the expected distribution of compliance in future comparable settings. Subgroup analyses, univariable meta-regressions, leave-one-out sensitivity analyses, and tests for small-study effects were performed. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data, methodological reporting quality was assessed using a modified Checklist for Reporting EMA Studies, and certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: Twenty-three studies involving 13,565 participants were included. The pooled compliance rate was 78.55% (95% CI 73.48%-82.87%), with a prediction interval of 48.59%-93.41%. Subgroup analyses identified no robust differences across study characteristics. Although study length showed a statistically significant subgroup test, the result was not stable after excluding singleton categories. Meta-regression analyses similarly found no significant linear associations for study length, prompts per day, items per prompt, or assessment window. Leave-one-out analyses showed that no single study drove the pooled estimate. Regarding the risk of bias, 2 studies were judged as low, while 21 were judged as moderate risk. Quality scores ranged from 6.5 to 9.0, and the certainty of evidence for the pooled compliance rate was rated as very low according to the Grading of Recommendations Assessment, Development, and Evaluation approach. CONCLUSIONS: Overall compliance with EMA among patients with cancer was moderate to high, suggesting that repeated real-world assessment may be feasible in oncology research settings. Nevertheless, the very high heterogeneity, wide prediction interval, and very low certainty of evidence indicate that compliance is context-dependent. The pooled estimate should therefore be interpreted as an approximate benchmark rather than a universal expected rate. Future oncology EMA studies should use standardized compliance denominators, report missing prompts transparently, and prospectively evaluate patient-centered design strategies that reduce burden while preserving data quality.

Humans

Instruments for measuring body image in breast cancer patients: a systematic review of measurement properties.

PURPOSE: To evaluate the psychometric properties of PROMs for measuring body image in breast cancer patients. METHODS: In December 2024, a psychometric systematic review was performed in the nine databases. The COSMIN checklist was employed to evaluate the methodological quality and psychometric properties of the included body image measures. The level of evidence was assessed using the GRADE framework, and final recommendations were formulated for the scale. RESULTS: Thirty-eight articles evaluating fifteen PROMs were included in this review. Structural validity, internal consistency, and hypothesis testing had been most frequently evaluated. Measurement error had not been assessed for all PROMs. Twelve instruments show potential application value but require further research. The BAS-BC, PSPP, and ASI-R are not recommended for use, as these instruments do not meet the strict COSMIN thresholds for full recommendation. CONCLUSION: The BIS can be recommended as a temporary screening tool for assessing body image outcome in clinical practice. The BIRS can be tentatively advised for measuring specific postoperative body image changes. However, further comprehensive studies are required to validate the psychometric properties of existing PROMs.

Female

MET-Aberrant non-small cell lung cancer: from kinase dependence to cell-surface targetability-mechanistic basis and biomarker framework for bispecific antibodies and antibody-drug conjugates.

MET-aberrant non-small cell lung cancer (NSCLC) is not a uniform therapeutic entity. Its biology, diagnostic pathways, and treatment sensitivity differ across MET exon 14 skipping alteration (METex14), MET amplification, and MET overexpression. This heterogeneity cannot be fully explained by conventional event-based classification and is reflected in the distinct clinical activity of MET tyrosine kinase inhibitors (MET-TKIs), bispecific antibodies (BsAbs), and antibody-drug conjugates (ADCs). With the emergence of antibody-based therapies, MET has evolved from a signaling driver to a cell-surface target for receptor modulation and payload delivery. We therefore propose a clinically anchored two-dimensional framework for interpreting therapeutic relevance in MET-aberrant NSCLC: kinase dependence and cell-surface targetability. Neither dimension should be regarded as a directly measurable binary variable. Kinase dependence is inferred from genomic and treatment-contextual proxies, most strongly METex14 and, more conditionally, high-level focal MET amplification. Cell-surface targetability is approximated by drug-specific IHC assessment of assay-defined c-MET protein expression; however, receptor internalization, intracellular trafficking, and payload delivery capacity remain incompletely measurable in routine clinical practice. Within this framework, MET-TKIs have the most evidence-supported established role in tumors with evidence of MET-driven kinase dependence. EGFR × MET BsAbs have demonstrated clinical activity in broad post-osimertinib EGFR-mutant NSCLC, while EGFR/MET co-dependence or MET-mediated bypass activation provides a mechanistic rationale for their use; MET-defined preferential benefit remains to be prospectively established. MET-directed antibody-drug conjugates (MET-ADCs) are supported in drug- and assay-defined populations with high c-MET protein overexpression, although the predictive relevance of delivery-related factors remains hypothesis-generating. Accordingly, MET testing should shift from single-event detection to platform-oriented stratification: next-generation sequencing (NGS) for driver alterations and resistance profiles, fluorescence in situ hybridization (FISH) for high-level focal amplification, and immunohistochemistry (IHC) for surface expression relevant to antibody-based therapies. This framework is intended to organize current biological and clinical evidence rather than to replace drug-specific companion diagnostics, regulatory indications, or prospectively validated treatment-selection algorithms. Precision treatment of MET-aberrant NSCLC is thus moving from event-based drug selection toward mechanism-based therapeutic matching. Future priorities include standardizing biomarkers, defining optimal target populations, and aligning biological subtypes, diagnostic strategies, and therapeutic platforms.

Antibody-drug conjugate

A novel peptide encoded by circTLL1 drives osimertinib resistance in lung cancer by modulating the NT5C2/Ras/PI3K axis.

BACKGROUND: Acquired resistance to osimertinib, a third-generation EGFR tyrosine kinase inhibitor, remains a major clinical challenge in the treatment of non-small cell lung cancer (NSCLC). Although circular RNAs (circRNAs) have been increasingly implicated in drug resistance, most studies have focused on their canonical role as microRNA sponges, while their capacity to encode functional micropeptides remains largely unexplored. This study aimed to identify novel circRNAs involved in osimertinib resistance and to characterize their regulatory functions at the protein level. METHODS: Osimertinib-resistant (OR) NSCLC cell lines were established and validated. High-throughput RNA sequencing was performed to compare the circRNA expression profiles between parental and OR cells. The function of the candidate circRNA was assessed through a series of in vitro and in vivo experiments, including cell viability assays, apoptosis analysis, and xenograft mouse models. Mechanistic investigations involved mass spectrometry, co-immunoprecipitation and western blotting to explore its protein-coding potential and downstream signaling pathways. RESULTS: We identified a novel circRNA, termed circTLL1, that was stably and significantly upregulated in OR-NSCLC cells. Functionally, overexpression of circTLL1 promoted osimertinib resistance, whereas its knockdown restored drug sensitivity both in vitro and in vivo. Mechanistically, we discovered that circTLL1 harbors an open reading frame (ORF) that is translated into a novel 90-amino-acid protein, which we designated circTLL1-90aa. Further investigation revealed that circTLL1-90aa directly interacts with and promotes the degradation of 5'-nucleotidase, cytosolic II (NT5C2), thereby uncoupling nucleotide metabolism from its normal regulatory constraints. The consequent downregulation of NT5C2 leads to elevated GTP levels and leading to the sustained activation of the downstream Ras/PI3K/AKT signaling pathway. CONCLUSION: Our findings unveil a previously unrecognized circRNA/micropeptide/metabolism cascade underlying osimertinib resistance. The identification of the circTLL1-90aa/NT5C2/Ras/PI3K axis not only expands the functional repertoire of the non-coding genome but also provides new insights into the complexity of drug resistance. Given its selective upregulation in resistant cells, circTLL1-90aa holds promise both as a predictive biomarker for treatment stratification and as an actionable therapeutic target, offering a novel strategy to overcome osimertinib resistance in NSCLC patients.

Pyrimidines

Prophylactic folinic acid prevents pemetrexed myelosuppression: A randomized trial toward safer treatment with chemotherapy in non-small cell lung cancer.

Background Pemetrexed is a cornerstone in advanced non-small cell lung cancer treatment. Although generally well tolerated, severe myelosuppression occurs in 26% of patients. Preventing chemotherapy-associated toxicity has become increasingly important with the introduction of osimertinib combined with pemetrexed-based chemotherapy. Due to substantial toxicity, this regimen is often not administered to frail patients. Folinic acid prophylaxis can mitigate pemetrexed-induced toxicity, however its preventive use has not been routinely studied. We aimed to investigate the efficacy of folinic acid prophylaxis to reduce myelosuppression. Methods Fifty patients treated with pemetrexed were randomized (1:1) to receive pemetrexed with or without oral folinic acid prophylaxis on days 2-4 after each chemotherapy cycle. The primary endpoint was absolute neutrophil count (ANC) after the first chemotherapy cycle. Secondary endpoints included ANC after the second cycle, grade neutropenia, treatment efficacy, renal function and incidence of dose modifications. Results Twenty-four patients received folinic acid and twenty-six served as controls. Higher ANC were observed in the folinic acid group after the first cycle (median 3.79; IQR 2.22-4.93 vs. 1.85; IQR 1.43-3.78; p.

Humans

Randomized phase-II trial of surufatinib plus FOLFOX/FOLFIRI versus FOLFOXIRI as second-line therapy for metastatic colorectal cancer.

BACKGROUND: Second-line treatment for metastatic colorectal cancer (mCRC) typically involves oxaliplatin- or irinotecan-based doublet chemotherapy with or without anti-angiogenic antibodies. Triplet regimens such as FOLFOXIRI have demonstrated synergy and improved efficacy as first-line therapy. Surufatinib, an oral multi-kinase inhibitor targeting VEGFR1-3, FGFR1, and CSF-1R, may enhance chemotherapy efficacy. We evaluated surufatinib combined with doublet (FOLFOX/FOLFIRI) versus triplet (FOLFOXIRI) chemotherapy as second-line treatment for mCRC. PATIENTS AND METHODS: This multicentre, open-label, randomized phase-II trial used Simon's minimax two-stage design. Eligible patients had mCRC progressing on or within 6 months after first-line doublet chemotherapy. Patients were randomized 1:1 to surufatinib 250 mg once daily plus either mFOLFOX6/FOLFIRI (doublet cohort, selected based on prior regimen) or FOLFOXIRI (triplet cohort). The primary endpoint was objective response rate (ORR). RESULTS: From September 2021 to November 2023, 57 patients were randomized (28 per cohort after one withdrawal). In the doublet cohort, ORR was 35.7% (95% CI: 18.6-55.9), median progression-free survival (PFS) was 5.4 months (95% CI: 3.8-7.0), and median overall survival (OS) was 19.0 months (95% CI: 9.2-28.8). In the triplet cohort, ORR was 39.3% (95% CI: 21.5-59.4), median PFS was 5.8 months (95% CI: 3.3-8.2), and median OS was 10.9 months (95% CI: 6.0-15.8). Grade ≥3 treatment-emergent adverse events occurred more frequently in the triplet (71.4%) versus doublet (57.1%) cohort, with higher rates of treatment delays (89.3% versus 72.0%) and discontinuations (25.0% versus 14.3%). CONCLUSIONS: Surufatinib plus doublet chemotherapy showed encouraging antitumor activity and acceptable tolerability in second-line mCRC, warranting further evaluation in a larger randomized trial. In contrast, surufatinib plus triplet chemotherapy was associated with increased toxicity, more frequent treatment delays or discontinuations, and shorter overall survival; this combination is not recommended for further investigation in this setting.ClinicalTrials.gov: NCT04734249Date of registration: January 31, 2021.

Humans

Hierarchical modeling of tumor subtypes in cell lines using large-scale genomic datasets.

Cancer cell lines (CLs) are widely used to study tumor biology and drug response, yet their translational relevance is often limited by inaccurate subtype annotations. Existing CL-tumor matching approaches are frequently constrained by flat classification schemes, weak subtype definitions, and the exclusion of normal tissue references, leading to potential confounding of tumor-specific and tissue-of-origin signals. To address these limitations, a hierarchical classification (HC) framework is presented in which CLs are aligned with patient tumors across biological resolutions, from organ to molecular subtype. Gene expression profiles from 802 CLs, 5,612 tumors from The Cancer Genome Atlas (TCGA) , and 8,939 non-cancerous tissues were integrated to separate oncogenic signals from tissue-specific signals. Node-specific features were selected using maximum relevance minimum redundancy, and balanced accuracies of 89% in cross-validation and 75%, and 80% on external datasets were achieved. Through the framework, 43 CLs were reassigned, and clinically relevant underrepresented subtypes were identified.

cancer cell lines

Insights into the regulation of the HOTAIR proximal promoter.

HOTAIR (HOX transcript antisense RNA) is a HOXC-cluster long intervening non-coding RNA (lincRNA) whose cancer relevance is tightly coupled to how its transcription is wired into hormone, hypoxia, inflammatory, and developmental signaling. HOTAIR is known to associate with cancer cell proliferation, motility, tumor invasion, and metastasis. The present mini-review focuses on the regulatory architecture and mechanistic complexity of HOTAIR transcriptional regulation, with emphasis on three organizing principles. First, we consider the impact of promoter choice between a canonical proximal promoter (P1), which supports the 2.2-2.4 kb transcript, and an alternative upstream promoter/TSS (P2), which contributes to context-dependent transcription initiation. Second, we examine the long-distance enhancer-promoter communication between HOTAIR distal enhancer and P1/P2. Third, we summarize the recent epigenetic and epi-transcriptomic mechanisms involved in HOTAIR transcript initiation and elongation. A combination of these events determines isoform-specific transcription to govern cell-type-, context-, and cancer specific modulation of HOTAIR expression that promotes tumor formation and cancer progression. Finally, the review proposes how large-scale RNA datasets, long-read sequencing, and isoform-specific studies can refine our understanding of this versatile lincRNA's regulation.

Humans

A system-level metastable model of cancer evolution: integrating replication stress, cell cycle deregulation and chromosomal instability.

INTRODUCTION: Cancer cell proliferation occurs within the context of persistent genomic instability. In this review, we propose the RS-CCD-CIN axis as a systems-level framework in which replication stress (RS), cell cycle deregulation (CCD) and chromosomal instability (CIN) form an interdependent triad that shapes tumour evolution. This axis represents a constrained metastable state in which genomic instability is tolerated and buffered. The objective of this review is to synthesize the current understanding of how the RS-CCD-CIN axis contributes to tumour heterogeneity, adaptability and therapy response. DISCUSSION: Evidence indicates that RS, CCD and CIN operate as a dynamic, interconnected network rather than as independent processes. Replication stress induces DNA damage and mutagenesis, while partial checkpoint disruption permits cells with unresolved lesions to proliferate. Chromosomal instability generates both structural and numerical alterations, contributing to intratumoural heterogeneity. Together, these processes facilitate adaptation to environmental and therapeutic pressures. Extrachromosomal DNA, micronuclei formation and cytosolic DNA signalling, including the cGAS-STING pathway, connect genomic instability to adaptive responses and immune modulation. Single-cell and spatial profiling reveal temporal and spatial variability in RS, CCD and CIN states, highlighting the limitations of static biomarkers. Therapeutically, targeting individual components often yields limited durability, whereas approaches that simultaneously perturb multiple aspects of the RS-CCD-CIN axis may improve clinical outcomes. CONCLUSIONS: This review highlights the RS-CCD-CIN axis as a fragile and metastable architecture that supports cancer evolution, while also being susceptible to collapse. A deeper understanding of this interconnected framework may inform the development of therapeutic strategies and enhance the management of resistance.

Humans

Adjuvant oxaliplatin with S-1 (SOX) versus S-1 for stage II-III gastric cancer (CAPITAL): A randomized, open-label, phase 3 trial.

BACKGROUND: Adjuvant chemotherapy following D2 gastrectomy constitutes the standard-of-care for resectable gastric or gastroesophageal junction (GEJ) carcinoma. The CAPITAL trial is a multicenter, randomized, phase 3 study, aiming to assess the efficacy and safety of adjuvant oxaliplatin plus S-1 (SOX) versus S-1 alone. METHODS: Patients with histologically confirmed pathological stage II-III gastric or GEJ adenocarcinoma after gastrectomy with D2 lymphadenectomy were randomly assigned (1:1) to receive either the SOX regimen (n = 362) or the S-1 regimen (n = 362). The primary endpoint was overall survival. This study is registered with ClinicalTrials.gov (NCT01795027). FINDINGS: The median follow-up was 74.0 months (interquartile range [IQR], 35.5-89.3). The 5-year overall survival rates were 70.9% (95% confidence interval [CI], 66.0-76.1) in the SOX group and 62.9% (95% CI, 57.8-68.5) in the S-1 group (hazard ratio [HR], 0.74; 95% CI, 0.58-0.95; p = 0.018). The 3- and 5-year disease-free survival rates were 71.2% (95% CI, 66.5-76.3) and 66.2% (95% CI, 61.2-71.6) in the SOX group, as compared with 65.1% (95% CI, 60.2-70.5) and 55.6% (95% CI, 50.4-61.3) in the S-1 group (HR, 0.76; 95% CI, 0.61-0.96). Treatment-related adverse events of grade 3-4 occurred in 87 (25%) of 349 patients in the SOX group and 45 (13%) of 347 patients in the S-1 group. The most common grade 3-4 adverse event was neutropenia, occurring in 44 (13%) of 349 patients in the SOX group and 23 (7%) of 347 patients in the S-1 group. CONCLUSIONS: The addition of adjuvant oxaliplatin to S-1 chemotherapy significantly improved overall survival and disease-free survival in patients with gastric cancer. FUNDING: This research was supported by the National Natural Science Foundation of China (82573092 and 82573387).

Humans

Splenic hilum nodal involvement in resected left-sided pancreatic cancer: meta-analysis.

BACKGROUND: Splenectomy is standard of care during left pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) to obtain adequate lymphadenectomy. However, evidence supporting this approach is lacking. Splenic preservation would reduce short-term morbidity and is essential for emerging oncological adjunctive therapies, including immunotherapy and personalized cancer vaccines. This study reviewed the incidence of splenic hilum nodal involvement (SHNI) in left-sided PDAC. METHODS: A systematic review of the PubMed, Embase, and Cochrane databases was performed, identifying studies published from inception to July 2026. Outcomes of interest were the rate of SHNI (station 10), overall survival, and the rate of splenic artery nodal involvement (SANI; station 11). Meta-analyses were conducted using random-effects models. Subgroup analyses for SHNI were performed per tumour localization (pancreatic neck, body, tail). RESULTS: Among 2776 screened studies, 22 with 2260 patients undergoing left pancreatectomy for PDAC were included. The pooled prevalence of SHNI was 3.7% (95% confidence interval (c.i.) 2.2% to 6.2%); 1.1% for pancreatic body PDAC (95% c.i. 0.3% to 4.3%) and 9.7% for pancreatic tail PDAC (95% c.i. 3.5% to 24.0%). SHNI was not significantly associated with survival (pooled hazard ratio 2.05; 95% c.i. 0.89% to 4.72; P = 0.072). The pooled prevalence of SANI was 39.1% (95% c.i. 25.1% to 55.1%). CONCLUSION: In patients undergoing left pancreatectomy for PDAC, the presence of SHNI is rare, particularly in pancreatic body cancer (1.1%). These findings suggest that the relevance of routine splenectomy remains unclear, especially for pancreatic body PDAC. However, because the quality of current evidence is low, further investigation in prospective studies is required.

Humans

Cost-effectiveness analysis of a virtually administered pain coping skills training intervention in women with breast cancer in underserved areas.

OBJECTIVES: Women with cancer who live in medically underserved areas could benefit from behavioral pain interventions, but access is limited. A randomized trial reported that a 4-session virtual program incorporating pain coping skills training (mPCST) was effective in improving pain outcomes compared to an attention-control condition. We performed a cost-effectiveness analysis of mPCST vs. control. METHODS: Data on medical resource use, therapist time, and participants' attendance at intervention sessions and time associated with travel and using a mobile app were collected. The 5-level EuroQol 5-Dimension (EQ-5D-5L), a preference-weighted measure of health-related quality of life (HRQOL), was administered at baseline, after the intervention period, and 3 and 6 months later. Medicare payments were used to value medical resource use and therapist time to deliver mPCST. Patient time was valued using the average US wage. RESULTS: Medical resource utilization was similar for both groups, but hospitalizations trended higher in the mPCST group. EQ-5D-5L preference weights were higher by an average of 0.066 (p = 0.04) with mPCST across the follow-up period, representing an incremental gain of 0.04 quality-adjusted life years (QALYs) (95% CI: 0.00-0.08). When including the base-case cost of mPCST of \$500 vs. \$0 for the control group, the incremental cost-effectiveness ratio (ICER) was \$12,725 per QALY (95% CI: 5,566-69,343). Including the value of patient time added \$303 to mPCST costs resulting in an ICER of \$20,438 per QALY (95% CI: 9,051-111,403). SIGNIFICANCE OF RESULTS: mPCST is a cost-effective program that improves HRQOL for women with cancer living in medically underserved areas.

Humans

Non-parametric differential methylation analysis characterizes histotype-specific promoter regions in epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is a heterogenous disease with frequent late-stage diagnosis and high mortality rates, for which no reliable screening tests exist. In recent years, epigenetic biomarkers in the form of DNA methylation in CpG-rich regions have gained increased attention in the scientific community due to their robust nature and accessibility, allowing for diagnosis without the need for invasive surgery. In this study, we investigated the aberrant methylation of promoter regions in early stage EOC through non-parametric methods, with the purpose of characterizing candidate epigenetic biomarkers. The approach was used on a cohort of early stage EOC samples, and results were compared to existing programs for differential methylation. Significant regions were then used to construct a CpG panel for stratifying EOC histotypes through predictive classification in external data. Identified promoter regions were highly reproducible across cohorts, and the constructed CpG model stratified histotypes in external cohorts through predictive classification. Comparisons against other DMP and DMR callers showed a degree of homogeneity between results but also revealed promoter regions that were overlooked despite clear signs of aberrant methylation. Finally, EOC histotypes were found to differ in their methylation distribution types, and results indicate that methods sensitive to non-normally distributed data may be poorly suited to compare groups with different distribution types. The non-parametric approach identified aberrantly methylated promoter regions that were highly reproducible across cohorts. Results from predictive classification indicate that these regions may be useful for the purpose of EOC histotype stratification.

Humans

Meaning in Life in Palliative Cancer Care: Psychosocial and Existential Outcomes-A Systematic Review.

BackgroundExistential distress, marked by hopelessness, loss of meaning, and spiritual suffering, is prevalent among patients with advanced illness, and is associated with psychological burden and a wish to hasten death (WTHD).PurposeThis systematic review aimed to synthesize current evidence on meaning in life (MIL) in adult palliative care (PC) populations, focusing on its associations with quality of life (QOL), mental health, existential and spiritual well-being (SWB), and WTHD.MethodsMEDLINE, Web of Science, Scopus, and the Cochrane Library were searched for eligible studies (English, 2016-2024) involving adult cancer patients receiving PC. MIL was examined as a central intervention component or outcome. Risk of bias was assessed: findings were synthesized narratively. The review was registered in PROSPERO.ResultsEight studies (n = 1733 participants) were included: four cross-sectional, two randomized controlled trials, one longitudinal observational study, and one qualitative study. Several studies had small samples and substantial attrition. Risk of bias was high (n = 7), and moderate in one cross-sectional study. MIL was inversely associated with depression, anxiety, demoralization, and WTHD; and positively associated with QOL and SWB. MIL may also mediate psychological outcomes (eg, purpose, coherence, and personal values). However, heterogeneity in MIL conceptualization and measurement, combined with low methodological quality, limited comparability and certainty of findings.ConclusionMIL may be relevant to psychosocial/existential outcomes in PC. Conclusions are constrained by a small and methodologically weak evidence base. Further high-quality, longitudinal research is needed before MIL-centered interventions can be recommended for routine clinical practice.

Humans

Treatment of Hot Flashes in Men With Prostate Cancer Undergoing Androgen Deprivation Therapy.

BACKGROUND: Hot flashes are common and often debilitating side effects of castration therapy; a cornerstone in the treatment of metastatic prostate cancer (PCa) as well as in localized or locally advanced PCa when combined with radiotherapy. The evidence for relieving vasomotor symptoms is limited. This systematic review presents both pharmacological and non-pharmacological interventions for treating hot flashes in men with PCa undergoing castration therapy, primarily androgen deprivation therapy (ADT). METHODS: a systematic literature search was conducted in PubMed using ("hot flash*" OR "hot flush*" OR "vasomotor*") AND ("prostate") as keywords. Studies with intervention for hot flashes due to castration therapy, estimation of treatment response (e.g., reduction in frequency or impact on quality of life) and patients with PCa (any stage) were eligible. RESULTS: Of 469 papers, 35 were included in the review. The included studies evaluated cyproterone acetate, estrogen or estrogen derivatives, progesterone derivatives, selective serotonin reuptake inhibitors (SSRIs), gabapentin, oxybutynin, and clonidine, as well as non-pharmacological interventions such as acupuncture, cognitive behavioral therapy (CBT), and dietary supplements (e.g., Dong Quai/Angelica Sinensis, Serelys Homme, soy protein, and Salvia officinalis). Across all blinded pharmacological interventions, the relative reduction in hot flash frequency ranged from -21% to -84%, and the placebo effect was between -19% and -30%. CONCLUSION: Hormonal agents such as cyproterone acetate and estrogen appear to be the most effective treatments, although they are associated with side effects. Non-pharmacological options like acupuncture and CBT may offer some benefit, while dietary supplements seem to be ineffective. Future studies are needed also to evaluate newer treatments, such as fezolinetant, in this patient population.

Humans