IntroductionTelemedicine offers a potential solution to the challenges of long-term follow-up for the growing population of breast cancer survivors. However, its acceptance and the factors influencing it among Chinese patients are not well understood. MethodsThis cross-sectional study evaluated telemedicine acceptance and its associated factors among 812 breast cancer patients at a tertiary hospital in Eastern China (June 2026) using structured telephone interviews.ResultsOverall, 72.3% of patients showed high acceptance, yet familiarity was low: only 27.7% had prior telemedicine use and 53.4% were familiar with it. Multivariate logistic regression revealed that unmarried/divorced/widowed status (OR = 0.32), unemployment (OR = 0.30), and higher risk concerns (OR = 0.44) were independently linked to lower acceptance (all P<0.05), while higher education (junior high: OR = 2.77; bachelor+: OR = 5.97), diagnosis duration >12 months (OR = 2.67), and greater perceived benefits (OR = 12.00) were associated with higher acceptance (all P<0.05). Moderation analysis showed technological barriers reduced acceptance, but their interactions with perceived benefits (P = 0.125) and risk concerns (P = 0.090) were not significant. Telephone consultation was the most preferred modality (62.4%), especially among older, less educated, and lower-income patients, whereas video consultation was favored by younger, more educated, and higher-income patients. DiscussionWhile acceptance of telemedicine is high among Eastern Chinese breast cancer patients, familiarity and experience remain limited. These findings may inform future approaches to telemedicine implementation, including patient education, attention to technological barriers, and flexible modality options, particularly for vulnerable subgroups.
Third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) have markedly improved outcomes for patients with EGFR-mutant non-small-cell lung cancer (NSCLC). However, acquired resistance remains a critical clinical challenge.Here, we present the case of a 62-year-old male with stage IIB poorly differentiated lung adenocarcinoma harboring an EGFR L858R mutation. The patient received adjuvant aumolertinib following surgical resection. Serial sampling and dynamic next-generation sequencing (NGS) revealed a sequential bypass resistance clone evolution trajectory in this patient: initial MET amplification was followed by the detection of a BRAF V600E mutation concurrent with RET fusion, while in the terminal phase, MET amplification re-emerged alongside a progressively increasing TP53 variant allele frequency (VAF).Genotype-guided therapy adjustments yielded an 11-month progression-free survival (PFS) with aumolertinib plus savolitinib, whereas subsequent selpercatinib combined with chemotherapy provided only transient disease stabilization. Ultimately, the patient died of respiratory and circulatory failure due to progressive disease complicated by diffuse carcinomatous lymphangitis. Based on current evidence, we speculate that these bypass resistance alterations are driven by reactivation of the MAPK and PI3K/AKT signaling cascades. The progressive increase in TP53 mutant allele frequency was temporally concordant with the sequential emergence of bypass resistance mechanisms, suggesting an unfavorable prognosis. However, its utility in guiding therapeutic modifications requires further validation. This case illustrates that EGFR L858R-mutant lung adenocarcinoma can undergo stepwise clonal evolution of multiple bypass resistance mechanisms under aumolertinib selective pressure. Dynamic NGS profiling enables real-time tracking of resistant clone evolution to inform individualized treatment strategies.
BackgroundMicrosatellite instability (MSI)/mismatch-repair deficiency (dMMR), Epstein–Barr virus (EBV), human epidermal growth factor receptor 2 (HER2), programmed death-ligand 1 (PD-L1), and claudin 18 isoform 2 (CLDN18.2) are clinically relevant biomarkers in gastric and gastroesophageal junction (GEJ) adenocarcinoma, but molecular and immunohistochemical (IHC) testing is costly and not universally available. Deep learning (DL) applied to routine hematoxylin and eosin (H&E) slides may enable inexpensive pre-screening. We assessed the accuracy of DL models predicting these five biomarkers directly from H&E.MethodsWe searched PubMed, Embase, Cochrane CENTRAL, and Web of Science Core Collection from inception through 8 August 2026 for studies applying DL to H&E whole-slide or tissue-microarray images to predict MSI/dMMR, EBV, HER2, PD-L1, or CLDN18.2 status in gastric/GEJ adenocarcinoma. Two reviewers independently selected studies and re-extracted performance estimates from full texts, tables, footnotes, and supplementary materials. Risk of bias was assessed with Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) and Prediction model Risk Of Bias ASsessment Tool (PROBAST) and certainty was assessed with Grading of Recommendations Assessment, Development and Evaluation (GRADE). Because the requirements for independent, variance-supported area under the receiver-operating-characteristic curve (AUROC) estimates or threshold-specific 2 × 2 data were not met, study-level estimates were displayed without statistical pooling.ResultsOf 1,094 records identified, 701 unique records were screened and 28 studies were included: 18 addressed MSI/dMMR, 14 addressed EBV, 2 addressed HER2, 2 addressed PD-L1, and 1 addressed CLDN18.2; marker categories overlapped. External-independent AUROCs were 0.767 (95% CI, 0.726–0.830) for MSI/dMMR, 0.941 (0.920–0.970) and 0.859 (0.823–0.919) for EBV, and 0.856 (0.775–0.926) for CLDN18.2; broader held-out AUROCs were 0.760 and 0.880 (MSI/dMMR) and 0.980 (EBV). One report each provided eligible 2 × 2 data for EBV, MSI/dMMR, and CLDN18.2; none did for HER2 or PD-L1. No pooling or final-model calibration was supported. All 28 reports (42 analytic scopes) were high risk under PROBAST; QUADAS-2 risk was high for 40 scopes and unclear for 2. Certainty was very low for MSI/dMMR, EBV, HER2, and PD-L1 and low for CLDN18.2.ConclusionIndividual held-out models sometimes showed promising discrimination, particularly for EBV and MSI/dMMR, but the evidence was too sparse, dependent, and heterogeneous to define a stable summary performance or a clinically deployable triage threshold. Certainty was very low for MSI/dMMR, EBV, HER2, and PD-L1 and low for CLDN18.2; clinical utility and calibrated threshold performance remain unestablished.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD420261449992.
Second primary cancers (SPCs) are an important challenge in cancer survivorship, yet their heterogeneous biological origins cannot be reduced to treatment exposure. Inherited susceptibility shared environmental and tissue-field effects, ageing, pre-existing somatic mosaicism and treatment-associated mutagenesis contribute to SPC risk. High-resolution studies show that therapy can alter somatic selection, clonal architecture and persistent immune or stromal states in normal tissues. We propose the therapy-conditioned host as a State-Transition framework integrating these observations in survivorship. In this framework, a pre-treatment host state (H0) is perturbed by therapy (P), generating evolving post-treatment states H(t), defined by interacting genomic, clonal, immune and stromal/tissue features. H(t) describes biological state at time t, whereas the sequence H0→H(t1)→H(t2)… defines the host trajectory. Equivalent exposures may generate different trajectories, while distinct treatments may converge on similar biological states. Treatment history is therefore an imperfect proxy for biological consequence. The framework does not imply that all SPCs are therapy-induced, that post-treatment conditioning is inherently carcinogenic, or that clonal expansion is equivalent to malignant progression. It proposes that the magnitude, direction and persistence of treatment-associated changes may influence the evolutionary opportunities of normal and premalignant cells. We outline testable predictions and a translational pathway requiring longitudinal validation, incremental predictive value beyond baseline susceptibility and treatment history, clinical actionability and evidence that intervention improves outcomes without disproportionate harm. The central question is not only what treatment a survivor received, but what biological state it produced, how that state evolves over time, and whether its trajectory meaningfully alters subsequent cancer risk.
IntroductionEfforts to validate claims-based algorithms for identifying patients with interstitial lung disease (ILD), an important safety concern in Japan, are limited.PurposeWe developed and validated a claims-based algorithm for identifying ILD in Japanese patients with cancer using machine-learning modeling.MethodsThis Japanese observational study used administrative claims and electronic medical record data collected in January 2013–March 2019 (Phase 1) and January 2015–March 2021 (Phase 2). Patients were classified as ILD cases based on chest computed tomography reports using natural language processing, with confirmatory reviews (ILDCT+). Machine-learning modeling strategies (logistic regression, least absolute shrinkage and selection operator [LASSO] logistic regression, and eXtreme Gradient Boosting) selected ILD identification variables from prespecified candidates. Model performances were estimated. Approximately 30% of randomly selected ILDCT+ cases were adjudicated using medical records; algorithm performance was adjusted using adjudication results. The best-performing algorithm was validated using an external claims database.ResultsAmong 13,601 eligible patients, 415 were ILDCT+ cases; 123 were selected for adjudication. The best-performing model was the LASSO reduced model (using only the top variables identified in the full model) (sensitivity: 33.5%; specificity: 99.3%; positive predictive value [PPV]: 76.7%); identified variables were confirmed ILD diagnosis codes, Krebs von den Lungen-6/serum surfactant protein-D codes, age, and sex. This model showed similar performance in an external database (sensitivity: 19.8%; specificity: 99.4%; PPV: 65.5%), when a cutoff of 0.5 was used as a threshold to classify patients per their modeled probability of having ILD.ConclusionsDespite limited sensitivity, this validated algorithm’s acceptable PPV may enable confident identification of true positive cases of ILD when suspected positive from claims data in Japanese patients with cancer, potentially making it valuable as a case-confirmation tool for retrospective studies using healthcare claims databases, particularly for those comparing relative risks between treatments.
BackgroundPerineural invasion (PNI) is a pathological feature associated with aggressive tumor behavior in several solid malignancies. In colorectal cancer (CRC), PNI has been reported to correlate with poorer prognosis, as well as increased risks of postoperative recurrence and metastasis. However, the available evidence regarding the prognostic significance of PNI in CRC remains limited and inconsistent. Unlike previous meta-analyses that included studies across broader time span. This study focuses on recent evidence and specifically investigates the sources of heterogeneity and its clinical significance. Therefore, this study aimed to evaluate the prognostic and clinicopathological value of PNI in CRC.MethodsThe PubMed, Web of Science, Embase, and Cochrane Library databases were all thoroughly searched between January 1, 2020, and October 9, 2025.Studies included in this review comprised cohort, case–control that reported on PNI status and survival outcomes in CRC. Two reviewers independently extracted the data and evaluated the studies’ quality in accordance with PRISMA recommendations. The Newcastle–Ottawa Scale was used to evaluate the studies’ quality. By computing the hazard ratio (HR) and its 95% confidence interval (CI), the prognostic significance of PNI for CRC was evaluated.ResultsA total of 9 retrospective studies were included. The pooled analysis suggested that PNI was associated with worse OS (HR = 2.23, 95%CI: 1.48-3.35, P < 0.001) and DFS (HR = 1.94, 95%CI: 1.44-2.64, P < 0.05) in patients with CRC. However, substantial heterogeneity was observed in both analyses (OS: I²=79.7%; DFS: I²=67.4%), and publication bias was suggested by Egger’s tests (OS: p=0.0097; DFS: p=0.0085).ConclusionsBased on recent studies, PNI was associated with poorer OS and DFS in CRC and may serve as a useful pathological marker for risk stratification. However, the findings should be interpreted cautiously because all included studies were retrospective and substantial heterogeneity and potential publication bias were present.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251161522.
BackgroundSpinal glioblastoma (GBM) is an exceptionally rare entity and poses significant diagnostic challenges due to a substantial risk of neurological morbidity with surgical biopsy. Tissue-based analyses are frequently limited by sampling constraints and tumor heterogeneity. Conventional diagnostic modalities, including MRI and cerebrospinal fluid (CSF) cytology, often lack specificity and sensitivity. Commercially available CSF liquid biopsy platforms offer a minimally invasive approach for detecting tumor-derived cell-free DNA (cfDNA) to enable genomic profiling.MethodsWe report a case of a 37-year-old male with spinal GBM who underwent prospective CSF cfDNA analysis using Belay Summit™ and GTC Liquid Trace™, yielding a provisional diagnosis of GBM and raising suspicion for Lynch syndrome.ResultsSubsequent tissue-based molecular profiling with Tempus™ confirmed the diagnosis of GBM, while germline testing via Ambry Genetics™ established Lynch syndrome.ConclusionBased on the findings of mismatch repair deficiency and Lynch syndrome, the decision to proceed with immunotherapy was made. CSF cfDNA is a promising ancillary tool for guiding therapy in difficult-to-biopsy cases.
BackgroundFirst-line chemoimmunotherapy has become a major therapeutic strategy for advanced gastric and gastroesophageal junction cancer, yet the magnitude of survival benefit, regional consistency, and toxicity trade-offs remain important considerations. We conducted an systematic review and meta-analysis of randomized controlled trials evaluating PD-1/PD-L1 inhibitor plus chemotherapy versus chemotherapy alone or placebo plus chemotherapy.MethodsPubMed/MEDLINE, Embase, Cochrane CENTRAL, Web of Science, and ClinicalTrials.gov were searched from inception to March 1, 2026. Eligible studies enrolled adults with previously untreated unresectable, recurrent, locally advanced, or metastatic gastric or gastroesophageal junction cancer. Hazard ratios were pooled for overall survival and progression-free survival, and risk ratios were pooled for objective response rate and safety outcomes using random-effects models. Risk of bias was assessed using RoB 2, and certainty of evidence was evaluated using GRADE.ResultsSeven randomized controlled trials including 6,517 patients were analyzed. PD-1/PD-L1 inhibitor plus chemotherapy significantly improved overall survival and progression-free survival. Objective response rate was also increased (RR, 1.24; 95% CI, 1.18–1.31), with negligible observed heterogeneity (I² = 0.0%). Overall survival effects were similar in global trials (HR, 0.79; 95% CI, 0.75–0.85) and Asian-only or China-only trials (HR, 0.81; 95% CI, 0.73–0.91; P for subgroup difference = 0.70). The progression-free survival effect was greater in Asian-only or China-only trials (HR, 0.66 vs. 0.78; P for subgroup difference = 0.02), although this analysis was exploratory. Combination therapy increased grade ≥3 treatment-related adverse events (RR, 1.15; 95% CI, 1.08–1.23), serious treatment-related adverse events (RR, 1.53; 95% CI, 1.29–1.83), and treatment discontinuation (RR, 1.53; 95% CI, 1.37–1.72). The pooled estimate for treatment-related death was statistically inconclusive (RR, 1.54; 95% CI, 0.75–3.16); the wide confidence interval indicated substantial imprecision and could not exclude clinically important increases or decreases in treatment-related mortality.ConclusionsFirst-line PD-1/PD-L1 inhibitor + chemotherapy provides a consistent survival and response benefit in advanced gastroesophageal junction or gastric cancer, but with increased clinically relevant toxicity. These findings support chemoimmunotherapy as a preferred first-line strategy for appropriately selected patients, with treatment decisions guided by biomarker status, patient fitness, and toxicity risk.
BackgroundBenign metastasizing leiomyoma (BML) is a rare smooth-muscle tumor that occurs in patients with a history of uterine leiomyoma, with the lungs being the most commonly involved extrauterine site. Pulmonary BML can mimic metastatic malignancy on imaging. Decades-long intervals after uterine surgery have been reported, and 18F-FDG uptake may vary among lesions.Case presentationA 59-year-old postmenopausal, nonsmoking woman presented with multiple bilateral pulmonary nodules 30 years after hysterectomy for uterine leiomyoma. 18F-FDG PET/CT demonstrated mild FDG uptake in the dominant pulmonary lesion, with a maximum standardized uptake value (SUVmax) of 2.44. Although the uptake was not strongly suggestive of an aggressive malignancy, a low-grade neoplasm could not be excluded. Video-assisted thoracoscopic wedge resection was therefore performed. Histological examination revealed bland spindle-cell proliferation arranged in fascicles, with mitotic activity of < 1 per 10 high-power fields and a Ki-67 labeling index of approximately 2%. The spindle cells expressed desmin, vimentin, and estrogen receptor, whereas focal TTF-1 staining was restricted to entrapped bronchial epithelial cells. In conjunction with the bilateral multifocal pulmonary distribution and remote history of uterine leiomyoma, these findings supported a clinicopathological diagnosis of pulmonary BML. The patient recovered uneventfully without endocrine therapy. During postoperative telephone follow-up, she reported no new discomfort, and regular chest CT surveillance was recommended.ConclusionPulmonary BML should be considered in the differential diagnosis of multiple pulmonary nodules in women with a remote history of uterine leiomyoma. Mild FDG uptake cannot distinguish pulmonary BML from a low-grade malignancy. Integrated clinical, radiological, and pathological assessment is therefore required to establish the diagnosis and avoid unnecessary treatment.
Unresectable locally advanced pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, particularly after distant metastasis. Irreversible electroporation (IRE) is a nonthermal ablative technique used for pancreatic tumors adjacent to major vessels, but evidence on late repeat pancreatic IRE remains limited. We report a 62-year-old man who presented with obstructive jaundice. Multidisciplinary evaluation classified the tumor as unresectable locally advanced PDAC involving the superior mesenteric vein-portal vein confluence. In January 2021, he underwent pancreatic IRE with biliary bypass, followed by sequential systemic therapy. Liver metastases developed approximately 10 months later and were treated locally, after which he continued multimodal therapy. In April 2025, gastroscopy revealed deformity and luminal narrowing of the duodenal bulb, accompanied by gastric retention, for which laparoscopic gastrojejunostomy was performed. In late 2025, a marked rise in carbohydrate antigen 19-9 (CA19-9) and tumor progression prompted multidisciplinary reassessment. Nearly 5 years after the initial procedure, he underwent repeat pancreatic IRE combined with radiofrequency ablation of a hepatic metastasis. During subsequent multimodal management, CA19–9 decreased from 12,280.0 to 291.4 U/mL. As of March 2026, he remained alive with disease, with an overall survival exceeding 62 months. This case demonstrates the technical feasibility of repeat pancreatic IRE after a prolonged interval and supports its potential role as an individualized local treatment within long-term multidisciplinary management.
PurposeThe reverse-sequence endoscopic-assisted nipple-sparing mastectomy (R-E-NSM), with or without direct-to-implant breast reconstruction (DTI-BR), has become increasingly popular in China. This study aimed to evaluate whether previous breast surgery (PBS) affects surgical complications and aesthetic outcomes after R-E-NSM.MethodsClinical data of patients who underwent R-E-NSM at the Breast Center, West China Hospital, Sichuan University, between April 30, 2020, and April 30, 2025, were prospectively collected and analyzed.ResultsA total of 1081 patients were enrolled in the study. Among them, 89 had intraoperative breast surgery (IBS), 56 had short-term previous breast surgery (SPBS), 75 had long-term previous breast surgery (LPBS), and 861 had no previous breast surgery (NPBS). SPBS and IBS were not significantly associated with increased complication risk after multivariable adjustment (all P > 0.05). LPBS was significantly associated with lower odds of any complications (OR, 0.238; 95% CI, 0.089–0.633; P = 0.040), minor complications (OR, 0.304; 95% CI, 0.122–0.752; P = 0.010), and CDC ≥ 2 complications (OR, 0.333; 95% CI, 0.125–0.885; P = 0.027). BREAST-Q scores did not differ significantly among groups. Compared with the NPBS group, the SPBS group showed a statistically significant difference in Ueda scores at 3 months (P = 0.014). Oncologic outcomes did not differ significantly among the four groups (all P > 0.05).ConclusionFor patients with SPBS, implementing R-E-NSM warrants careful clinical evaluation due to potential safety concerns. Among patients with LPBS, current evidence indicates that incorporating R-E-NSM is not an independent risk factor and may be linked to a significantly lower incidence of complications.
BackgroundBleeding is a potentially serious but underrecognized adverse event associated with BCR-ABL tyrosine kinase inhibitors (TKIs). Although hematologic and cardiovascular toxicities of these agents have been extensively investigated, the spectrum and characteristics of bleeding-related adverse events in real-world settings remain incompletely understood. This study aimed to characterize bleeding-related adverse event signals associated with five BCR-ABL TKIs using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).MethodsA pharmacovigilance study was conducted using FAERS data from 2004Q1 to 2026Q1. Reports involving imatinib, dasatinib, nilotinib, ponatinib, and bosutinib as primary suspected drugs were identified. Bleeding-related adverse events were screened using Medical Dictionary for Regulatory Activities (MedDRA) Preferred Terms (PTs). Disproportionality analysis was performed using the reporting odds ratio (ROR) method to detect potential bleeding signals. Demographic characteristics, clinical outcomes, and distributions of bleeding-related signals across System Organ Classes (SOCs) were further evaluated.ResultsAmong 20, 326, 782 deduplicated FAERS reports, 124, 797 reports involving BCR-ABL TKIs were identified, including 3, 648 bleeding cases and 121, 149 non-bleeding cases. Bleeding reports were associated with higher proportions of hospitalization (19.8% vs. 14.4%) and life-threatening outcomes (2.7% vs. 1.5%) than non-bleeding reports. A total of 64 positive bleeding-related signals were detected across the five study drugs. Gastrointestinal disorders, nervous system disorders, and eye disorders represented the most frequently involved organ systems. Gastrointestinal haemorrhage, cerebral haemorrhage, and eye haemorrhage were recurrent signals detected across multiple TKIs. Several gastrointestinal bleeding-related signals were identified for dasatinib, including enterocolitis haemorrhagic (ROR = 28.98), while multiple bleeding-related PTs involving diverse organ systems were detected for imatinib. In addition, several uncommon PTs demonstrated elevated disproportionality estimates, although these findings were based on relatively small numbers of reports.ConclusionsBleeding-related adverse events associated with BCR-ABL TKIs involve multiple organ systems and encompass a broad spectrum of clinical manifestations. Gastrointestinal, neurological, and ocular haemorrhagic events accounted for the majority of detected signals. These findings provide real-world evidence regarding the characteristics of bleeding-related adverse events associated with BCR-ABL TKIs and may contribute to pharmacovigilance monitoring, individualized safety management, and future investigations of haemorrhagic toxicity during TKI therapy.
IntroductionBreast cancer (BC) is the most commonly diagnosed malignancy among women globally and in India. The human epidermal growth factor receptor 2 (HER2)-positive subtype is associated with aggressive disease and poorer prognosis; however, neoadjuvant therapy combining dual HER2 blockade with chemotherapy has been shown to improve pathological complete response (pCR) rates. This study evaluated the real-world effectiveness of dual HER2 blockade in the Indian setting.MethodsThis ambispective, descriptive real-world study was conducted at KIMSHEALTH, Trivandrum, Kerala (1 October 2019–30 April 2025), comprising retrospective (1 October 2019–30 April 2024) and prospective (1 May 2024–30 April 2025) phases. Patients with HER2-positive early BC receiving intravenous (IV) or subcutaneous (SC) pertuzumab and trastuzumab were included. The primary endpoint was pCR. Secondary endpoints included comparison of pCR between the IV and SC groups; assessment of chemotherapy regimen, disease stage, and hormonal status on outcomes; and evaluation of treatment-related toxicities.ResultsA total of 74 patients (35: retrospective; 39: prospective) (mean age: 56.8 ± 9.1 years) were included in the study; 52 (70.3%) received SC, and 22 (29.7%) received IV dual HER2 blockade. The overall pCR rate was 51.4% (SC: 44.2%; IV: 68.2%; p=0.06). Tumor stage (p=0.044) and composite clinical stage (tumor, node, and metastasis) (p=0.019) were significantly associated with pCR in the overall population, whereas estrogen receptor (ER) status was not associated with pCR (p=0.064). Multivariate analysis identified the composite clinical stage as an independent predictor of pCR (odds ratio: 0.242; p=0.012). Anemia was the most common toxicity, followed by hepatic toxicity, with comparable safety between the SC and IV groups.DiscussionNeoadjuvant dual HER2 blockade in HER2-positive BC is effective and well tolerated in the Indian real-world setting, with tumor stage and composite clinical stage significantly influencing response, while ER status showed no significant association with pCR. SC and IV dual HER2 blockade demonstrated comparable efficacy and safety outcomes. These findings, which are consistent with historical data, further reinforce the therapeutic advancement from trastuzumab-based therapy to dual HER2 blockade, highlighting its improved effectiveness and clinical importance in the neoadjuvant treatment of HER2-positive BC.
Oncolytic viral therapy has broad antitumor and immuno-oncology effects that may be useful in managing malignancies, particularly in relapsed or refractory diseases following conventional therapeutic regimens. We report a case involving a patient enrolled in an ongoing phase Ib clinical trial of Olvi-Vec, a modified oncolytic vaccinia virus, in patients with platinum-relapsed/refractory advanced small cell lung cancer (SCLC). In this 58-year-old woman who had progressed after frontline treatment with platinum and etoposide, a deep and durable partial objective response (84.6% reduction in target lesion size) and progression-free survival (16.7 months) were observed following a single course of Olvi-Vec followed by re-challenge with platinum-based therapy. These findings exceed expected clinical outcomes based on historical data. Olvi-Vec therapy was well tolerated. The clinical effect observed in this patient may be related to Olvi-Vec-mediated changes in the tumor microenvironment, potentially leading to platinum re-sensitization. The results of this case report indicate that the role of Olvi-Vec as an oncolytic immunotherapy for cancer treatment warrants additional study.
BackgroundInvasive lobular carcinoma (ILC) with signet-ring-cell (SRC) differentiation of the breast is a relatively rare disease and is reported to frequently metastasize to the gastrointestinal and urinary systems.Case presentationA 66-year-old woman presented for routine breast cancer screening without any subjective symptoms. A mass detected in the upper-outer region of her right breast. Core needle biopsy led to the diagnosis of ILC with SRC of the breast. Positron emission tomography-computed tomography, urine cytology, and upper and lower gastrointestinal endoscopy revealed no abnormal findings, and the disease was diagnosed as cT1cN0M0, Stage I. Immunohistochemical examination showed estrogen receptor (ER)-positive (10%, weak), progesterone receptor (PgR)-negative (0%), human-epidermal growth factor receptor 2 (HER2) score 0, and Ki-67 index of 9.8%, suggesting a luminal B-like subtype. The patient received 4 cycles of epirubicine and cyclophosphamide followed by 4 cycles of docetaxel (DTX) as neoadjuvant chemotherapy (NAC). Because prolonged neutropenia occurred during DTX treatment, temporary treatment interruptions were required; however, all cycles were completed with a relative dose intensity of 80%. As stable disease after completion of NAC, right breast-conserving surgery with sentinel lymph node biopsy was performed. Pathological assessment after neoadjuvant chemotherapy revealed ypT1c (1.8 cm) sN0 (0/1), therapeuthic effect Grade 2b, ER- (0%), PgR- (0%), HER2 0, Ki-67 20% of residual tumor remaining in the breast. Therefore, BRACAnalysis® testing was performed as a companion diagnostic test and was negative. The patient subsequently have received postoperative radiotherapy, and 8 cycles of capecitabine therapy.ConclusionsIn our cohort of ILC patients treated at our institution, we also observed cases with gastrointestinal metastases; therefore, attention should be paid to symptoms and findings suggestive of metastasis to these sites as well.
ObjectiveAtypical teratoid/rhabdoid tumor (ATRT) is the most common brain tumor in children less than one-year-old. Previous studies have identified three epigenetic subgroups of ATRT: ATRT-SHH, ATRT-TYR, and ATRT-MYC. Interestingly, it was found that ATRT-TYR/MYC (mesenchymal) subgroups are sensitive to receptor-tyrosine kinase inhibitors (RTKIs), particularly those that inhibit the platelet-derived growth factor receptor B (PDGFRB), highlighting the importance of PDGF signaling in ATRTs. In addition, the ATRT-TYR/MYC subgroups show upregulation of the macrophage migration inhibitory factor (MIF), with dysregulation of the MIF signaling pathway, which was found to have immunosuppressive effects in other cancers. While PDGF and MIF pathways have been found to promote tumorigenesis of other cancers including glioma, their roles in ATRTs remain unknown. We hypothesized that PDGF and MIF signaling pathways contribute to maintaining malignant phenotypes in ATRT-TYR/MYC subgroups.MethodsTo test this hypothesis, our project aimed to characterize PDGF signaling and investigate PDGF-MIF crosstalk in ATRT-TYR/MYC subgroups, using CRISPR/Cas9 stable knockouts (KOs) of various PDGF receptor and ligands.ResultsWe have shown that the PDGF pathway primarily promotes maintenance of malignant phenotypes in ATRT-TYR/MYC via modulation of the cell cycle. Furthermore, our studies reveal a plausible PDGFRB, MIF, and CD44 oncogenic signaling axis, that could modulate invasion and cellular phenotypic plasticity in ATRT-TYR/MYC, via regulation of neural stemness and epithelial-mesenchymal transition (EMT) marker expression.ConclusionsOur collective study findings point to an important role for PDGFRB-MIF-CD44 signaling in the maintenance of malignant cellular phenotypes in ATRT-TYR/MYC cell lines.
BackgroundSocial isolation and loneliness are associated with mortality, but their impact on cause-specific mortality in cancer survivors remains unclear.MethodsThis cohort study enrolled UK Biobank participants with cancer at baseline, followed up from March 2006 to September 2024. Social isolation and loneliness were assessed by self-reported questionnaires. Outcomes included all-cause, cancer-specific, and cardiovascular disease (CVD)-related mortality. Associations were evaluated using Cox proportional hazards models.ResultsA total of 32,524 participants were included in this study (60.2% women; mean age, 60.3 years). During a median 15.7-year follow-up, 5,945 deaths occurred. Social isolation was significantly associated with increased all-cause (HR, 1.22; 95%CI, 1.12–1.32), cancer-specific (HR, 1.16; 95%CI, 1.04–1.28), and CVD-related (HR, 1.32; 95%CI, 1.07–1.63) mortality. Loneliness was not associated with all-cause mortality (HR, 0.98; 95%CI, 0.93–1.04), but independently associated with increased CVD-related mortality (HR, 1.26; 95%CI, 1.08–1.47). Exploratory analyses identified distinct prognostic impacts of specific isolation measures: living alone was linked to higher all-cause and non-cancer mortality across most cancer types, while weekly social activities and monthly family/friends visits were protective.ConclusionsSocial isolation was associated with increased risks of all-cause, cancer-specific, and CVD-related mortality. Loneliness was associated with elevated CVD-related mortality.
IntroductionSexual health challenges after breast cancer commonly include physical symptoms of genitourinary syndrome of menopause (GSM) (e.g., vaginal pain) and psychological problems (e.g., negative body image) necessitating interventions that address both issues.ObjectiveTo assess the feasibility of a multicomponent intervention of hypnotic relaxation and vaginal moisturizer to improve GSM, sexual desire, and body image in female breast cancer survivors.MethodsThis two-arm pilot randomized controlled trial tested an 8-week self-administered multicomponent intervention, hypnotic relaxation intervention (HRI) with vaginal moisturizer, compared to a vaginal moisturizer-only group (VMO). All participants used vaginal moisturizer daily in weeks 1 and 2. In weeks 3–8, vaginal moisturizer use decreased to every other day. In addition to vaginal moisturizer, HRI participants added hypnotic relaxation 3 times per week in weeks 3–8. Eligible women reported vaginal or vulvar dryness and/or pain with sexual activity, negative body image changes, and/or decreased sexual desire.Main outcomes and measuresThe primary outcomes were accrual, retention, and adherence rates. Preliminary intervention effects on sexual function were assessed using the Sexual Function Inventory (FSFI) and PROMIS Sexual Function and Satisfaction V2 (SexFS V2) as well as on body image using the Breast Cancer Impact of Treatment Scale (BITS) at baseline and 8 weeks.ResultsThirty participants were randomized to HRI (n = 14) or VMO (n = 16); all completed the study. Adherence was excellent for both HRI (92%) and VMO (90%). Sexual desire, body image, and GSM-related outcomes (lubrication and pain) improved for both groups. Small to moderate effects were found in the change scores favoring the HRI group compared to the VMO group for SexFS V2 interest (d = 0.37) and body image (d = 0.42). In the full sample, large effects were found for an increase in lubrication, d = 1.50 (0.97, 2.02), and a reduction in pain, d = 0.81 (0.39, 1.22), on the FSFI.Conclusions and relevanceThis randomized controlled pilot trial supported the feasibility of hypnotic relaxation and vaginal moisturizer for female breast cancer survivors with sexual problems. Hypnotic relaxation coupled with vaginal moisturizer appears to be a promising intervention, particularly for improving body image, and a larger, well-powered study is needed to confirm these findings.Trial registrationClinicalTrials.gov, Identifier NCT05692960.
BackgroundGlioblastoma exhibits significant spatial heterogeneity, with perfusion variability that may reflect angiogenesis, hypoxia, and biological aggressiveness. Arterial spin labeling (ASL) offers non-contrast perfusion imaging, and radiomics quantifies tumor texture beyond basic ROI metrics. However, radiomic texture features can be confounded by tumor volume -- rarely tested directly. Diffusion tensor imaging along the perivascular space (DTI-ALPS) may capture perivascular/neurofluid dynamics, but its added prognostic value in glioblastoma is uncertain.MethodsWe retrospectively included 322 patients with IDH-wildtype WHO grade 4 glioblastoma. ASL radiomic features (shape features excluded) were tested against tumor volume, clinical covariates, and DTI-ALPS in volume-adjusted Cox proportional hazards models. A machine-learning classification analysis of 12-month mortality (N=259; ALPS-valid subset N=100) compared clinical, volume-aware, and ASL-augmented models across six classifiers, with proportional-hazards assumptions formally tested.ResultsHigher ASL heterogeneity was associated with mortality within 365 days of imaging, after adjustment for tumor volume and clinical variables (HR 1.39, 95% CI 1.07 -1.81, p=0.015), with proportional hazards confirmed within this window. This association persisted when the candidate feature pool was widened from the pre-specified 26-feature family to all 1,209 non-shape ASL features screened within training folds (HR 1.33, 95% CI 1.05 -1.69). The association was unchanged under flexible modeling of tumor volume (HR 1.40 -1.49 across spline, polynomial, and quantile-indicator specifications), showed no heterogeneity across volume strata (I²=0%), and persisted after orthogonalizing the score with respect to volume (HR 1.25 -1.27, all p<0.03). The association was time-varying -- strongest in the first 180 days (HR 1.37) and attenuating beyond one year. In contrast, the unadjusted association with overall survival did not remain significant after accounting for tumor volume, and machine-learning classification showed no incremental value from ASL radiomics beyond a volume-aware clinical baseline. DTI-ALPS did not improve classifier performance or show independent survival association.ConclusionsASL perfusion heterogeneity was associated with early, but not overall, mortality in this cohort, with a modest component not explained by tumor volume -- a signal specific to the first year after imaging. Findings for overall survival and machine-learning classification were substantially attributable to tumor volume rather than radiomic texture, underscoring the importance of volume-adjusted testing in radiomics research. Tumor-aware DTI-ALPS provided no additional prognostic value. These findings are hypothesis-generating and require prospective, multi-center validation.
