Germline TP53 p.R72P polymorphism has been associated with lung cancer susceptibility, somatic TP53 mutation acquisition, and differential apoptotic signaling. Its influence on pathologic response to neoadjuvant immune checkpoint inhibition (ICI) has not been previously evaluated. This study investigates the impact of germline TP53 p.R72P genotype on response to neoadjuvant ICI therapy in nonsmall cell lung cancer (NSCLC). NSCLC patients treated with neoadjuvant anti-PD-1 therapy followed by resection were stratified by germline p.R72P status and the presence of concomitant somatic TP53 mutations. Histopathologic review assessed immunotherapy-associated histopathologic features of tumor regression, and the findings were correlated with PD-L1 tumor proportion scores (TPS) and next-generation sequencing data. The subgroup harboring both germline p.R72P and somatic TP53 mutations achieved a complete pathologic response (cPR) rate of 75% (3 of 4 cases), numerically higher than that observed in p.R72P-positive/TP53-wild-type tumors (25%, 2 of 8 cases), p.R72P-negative/TP53-mutant tumors (50%, 4 of 8 cases), and p.R72P-negative/TP53-wild-type controls (0%, 0 of 6 cases) (p < 0.05). In this single-center, exploratory cohort, germline TP53 p.R72P status was associated with differences in pathologic response to neoadjuvant therapy. Tumors with combined germline p.R72P polymorphism and somatic TP53 mutation might represent a genomic subgroup with a higher cPR rate.

Existential distress is common among patients with advanced cancer receiving palliative care and is associated with hopelessness, loss of meaning, spiritual distress, and desire for death. Meaning-centered psychotherapy (MCP) has shown potential in reducing existential suffering and improving psychological well-being in patients with advanced cancer. This article presents a case report describing the application of MCP in a young woman with advanced cancer experiencing depressive symptoms, trauma-related distress, hopelessness, and loss of meaning near the end of life.

We report the case of a 24-year-old Vietnamese woman with advanced cancer who was referred for psychological intervention because of severe depressive symptoms, emotional instability, passive wishes for death, and childhood relational trauma. Sixteen psychotherapy sessions were delivered within a multidisciplinary palliative care team. The intervention followed a phased approach, beginning with Trauma-Focused Cognitive Behavioral Therapy-informed stabilization and subsequently transitioning to adapted Individual MCP. Clinical outcomes were evaluated using the Depression Anxiety Stress Scale-21, Beck Depression Inventory-II, and qualitative clinical observations.

Psychological reassessment demonstrated marked reductions in depression, anxiety, and stress, accompanied by improved emotional regulation, interpersonal functioning, illness acceptance, and relational reconnection. As her condition deteriorated, psychotherapy increasingly emphasized spiritual reflection, reconciliation, and preparation for death. Before death, she reaffirmed her Christian faith, received baptism, and fulfilled her wish for a Protestant funeral ceremony.

This case illustrates the feasibility of integrating adapted MCP within multidisciplinary palliative care to address existential distress, facilitate meaning reconstruction, support spiritual integration, and promote end-of-life preparation in patients with advanced cancer.

BACKGROUND Hepatic epithelioid hemangioendothelioma (HEHE) is a rare vascular tumor of endothelial origin with variable clinical behavior, posing significant diagnostic and therapeutic challenges. Due to its nonspecific presentation and diverse imaging features, it is frequently misdiagnosed. We present a unique case of HEHE with recurrent liver involvement and distant metastases over a 14-year period, emphasizing diagnostic markers, treatment strategies, and the prognostic value of serial biomarker assessment. CASE REPORT A 48-year-old woman underwent right partial hepatectomy in 2011 after a routine health check-up incidentally revealed a liver lesion. Histological examination revealed characteristic epithelioid and dendritic tumor cells, confirmed by immunohistochemistry (CD31+, CD34+, Ki-67 5%). Postoperative surveillance detected tumor recurrence 7 years later in the left lobe, necessitating laparoscopic left partial hepatectomy. In 2020, further progression to the caudate lobe and regional lymph nodes prompted complex resection, with Ki-67 rising to 15%. Serial Ki-67 assessments across sequential specimens demonstrated a progressive increase in proliferative activity: 5% (2011), 15% (2020), and ultimately 40% in a pleural metastasis biopsy (2024), correlating closely with clinical progression. The patient received repeated surgical resections and adjuvant interferon alpha-2b, with palliative nab-paclitaxel attempted during the terminal stage but proving ineffective. The patient died in August 2025, approximately 14 years after initial diagnosis. CONCLUSIONS This case highlights the importance of the Ki-67 index as a dynamic biomarker for monitoring tumor evolution and guiding treatment decisions in recurrent HEHE. Regular long-term follow-up and a multidisciplinary approach are crucial for managing this unpredictable neoplasm, given its potential for late recurrence and metastasis.

Antibody‒drug conjugates (ADCs) represent a major advance in precision oncology, yet their effectiveness depends critically on adequate target antigen expression. Tumour heterogeneity and dynamic antigen expression during treatment pose major challenges for conventional tissue biopsies used in patient selection. Liquid biopsy components such as circulating tumour cells (CTCs) enable real-time, minimally invasive monitoring of tumour burden, molecular characteristics and target antigen status. This review evaluates the potential of CTC analysis to overcome the key challenges in ADC therapy, including real-time target profiling, enhanced patient stratification and longitudinal monitoring of treatment response. While acknowledging that direct clinical evidence for CTC-guided ADC selection remains limited and prospective validation is still needed, we integrate clinical evidence from CTC-guided trials across different cancer types and propose pragmatic decision-making frameworks to incorporate CTC testing into ADC treatment strategies. We also examine how artificial intelligence (AI) has improved CTC detection accuracy and discuss exploratory AI models for multi-omics integration and hypothetical AI-guided ADC recommendation systems, clearly distinguishing these by their current level of clinical evidence. Liquid biopsy-guided ADC selection has the potential to enable more personalised cancer treatment as CTC technologies advance and standardisation improves.

Acrokeratosis paraneoplastica (Bazex syndrome) is an obligate paraneoplastic dermatosis characterized by symmetrical acral psoriasiform lesions and nail dystrophy.

We conducted a PRISMA-compliant systematic review of 99 publications (89 case reports, 10 case series) describing 106 patients to re-examine the syndrome's epidemiology, oncologic associations, clinical features, treatment response, and prognosis.

The mean age at onset was 63.5 years (median: 62.5 years; interquartile range (IQR): 57-70 years); men comprised 72.6% (n = 77; 95% CI, 63.5-80.2%), yielding a male-to-female ratio of 2.7:1. Squamous cell carcinoma accounted for 51.9% (55/106; 95% CI, 42.5-61.2%) of associated malignancies, followed by adenocarcinomas (18.9%; 95% CI, 12.6-27.4%) and hematologic neoplasms (8.5%; 95% CI, 4.5-15.4%). Cutaneous lesions preceded the cancer diagnosis in 80.6% (83/103) of patients with reported chronology, with a median lead-time of 5 months (IQR 2-10 months). Nail involvement was documented in 73.6% (78/106). Following oncologic therapy, complete cutaneous clearance occurred in 36.8% (95% CI, 28.2-46.3%) and partial improvement in 30.2% (95% CI, 22.3-39.5%) of cases. In univariable analyses, distant metastasis (p = 0.021) and an aerodigestive primary site (p = 0.026) were nominally associated with reported mortality, although neither remained significant after multiple-comparison correction.

Bazex syndrome should be suspected in patients presenting with treatment-resistant acral psoriasiform lesions and nail dystrophy, prompting rigorous malignancy screening.

The 2022 revision of the Japanese Classification of Esophageal Cancer reclassified certain lymph node metastases previously considered locoregional as distant lymph node metastasis. Consequently, some patients previously diagnosed with stage IVA or III disease and treated with definitive chemoradiotherapy (dCRT) are now categorized as stage IVB disease with distant lymph node metastasis (IVB-Lym). We retrospectively evaluated the outcomes of dCRT in patients initially diagnosed with stage IVA or III disease and subsequently reclassified under the revised system. Among patients with esophageal cancer who underwent dCRT between January 2017 and December 2020 at our institution, 65 were reclassified as stage IVA (n = 19) or stage IVB-Lym (n = 46). Best overall response, overall survival (OS), progression-free survival (PFS) and chemotherapy-related adverse events (AEs) were evaluated. Complete or partial response was achieved in 84.2% of patients with stage IVA and 84.4% of those with stage IVB-Lym. The median OS and PFS were 26 and 8 months, respectively, in the stage IVA group and 35 and 9 months, respectively, in the stage IVB-Lym group. No significant differences were observed in OS (P = 0.69) or PFS (P = 0.67) between the two groups. The incidence and severity of AEs were generally comparable. No significant differences in efficacy or toxicity were observed between patients with reclassified stage IVB-Lym and those with stage IVA disease. These findings suggest that dCRT may be considered a treatment option for carefully selected patients with stage IVB-Lym following comprehensive clinical evaluation.

Recent evidence suggests the JAK2V617F mutation may confer an elevated risk of ischemic stroke, likely mediated by systemic inflammation, abnormal cell activation, and endothelial dysfunction. The JAK2V617F mutation is an acquired driver mutation reported in up to 11.3% of patients with ischemic stroke in a recent Danish case-control study. It is the main driver mutation in Philadelphia-negative myeloproliferative neoplasms and even in the absence of overt myeloproliferative neoplasm, an increasingly recognized risk factor for cardiovascular disease. In this review, we summarize current knowledge on the biological role of the JAK2V617F mutation in thrombosis, its contribution to cerebrovascular risk, and the emerging relevance of JAK2V617F in stroke neurology. Current knowledge underscores the value of JAK2V617F testing in stroke patients for early detection of myeloproliferative neoplasms or pre-myeloproliferative neoplasm states and personalized secondary stroke prevention. Further studies are needed to refine risk stratification, evaluate targeted interventions, and determine the clinical utility of integrating JAK2V617F mutation profiling into stroke care.

This study evaluated the clinical outcomes and safety of risk-adapted stereotactic body radiotherapy (SBRT) using non-standard fractionation schedules for lung tumors adjacent to organs at risk (OARs). We retrospectively analyzed 81 consecutive patients (92 lesions, 2008-25) who received SBRT, including repeat irradiation outside prior fields, with non-standard regimens (56 Gy/7 fractions [fr], 50 Gy/10 fr, 60 Gy/10 fr, 48 Gy/6 fr and 35 Gy/5 fr). Endpoints included overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), locoregional progression-free survival, local control (LC) and Grade ≥ 3 adverse events. At a median follow-up of 22.2 months (IQR, 12.1-42.9), the median OS was 26.4 months (95% CI: 17.2-43.0), with 1- and 3-year OS rates of 78.6% and 44.1%, respectively. The median PFS was 14.5 months (95% CI: 9.4-21.1), and the median CSS was 43.7 months (95% CI, 22.7-64.4). Median LC was not reached. No significant survival disparities were identified between primary and metastatic cohorts. Grade ≥ 3 toxicities occurred in 10 patients (12.3%), including two Grade 5 events. The 3-year cumulative incidence of Grade ≥ 3 toxicity in ultracentral tumors was 12.6%, with no significant differences among groups. In conclusion, risk-adapted SBRT with increased fractionation demonstrated encouraging LC while maintaining an acceptable toxicity profile for central and ultracentral lung tumors. However, the risk of severe toxicity remains, requiring careful patient selection and optimized OAR dose constraints.

Gastric cancer remains the fourth leading cause of cancer-related mortality worldwide, with delayed diagnosis contributing to poor prognosis. Current biomarkers lack sensitivity for early detection. Interleukin-8 (IL-8), a pro-inflammatory chemokine implicated in H. pylori-associated gastric carcinogenesis, has not been rigorously evaluated in longitudinal studies for its ability to predict malignant progression in patients with precancerous lesions.

To investigate whether serial serum IL-8 measurements predict progression to gastric cancer among Egyptian patients with H. pylori-associated atrophic gastritis and intestinal metaplasia over 24 months of follow-up.

a prospective, longitudinal biomarker, multicenter cohort study enrolled 200 participants across 5 Egyptian centers: 50 with atrophic gastritis, 50 with intestinal metaplasia, 25 with H. pylori-positive gastric cancer, 25 with H. pylori-negative gastric cancer, and 50 healthy controls. All underwent baseline clinical assessment, laboratory evaluation (including CEA, CA19-9), H. pylori testing (stool antigen and urea breath test per Maastricht VI), and endoscopy with histopathology (Updated Sydney System). Patients with precancerous lesions were followed for 24 months with serial IL-8 measurements at 0, 6, 12, 18, and 24 months, and repeat endoscopy at study completion. Group-based trajectory modeling was performed blinded to outcome status. Multivariable logistic regression with penalization was used due to low event count. Time-dependent ROC analysis used a cumulative/dynamic approach.

Of 100 patients with precancerous lesions, 94 completed follow-up, and 9 progressed to gastric cancer (7 from intestinal metaplasia, 2 from atrophic gastritis). Baseline IL-8 levels demonstrated a progressive increase across groups (controls: 9.7 ± 3.2 pg/mL; atrophic gastritis: 42.1 ± 11.8; intestinal metaplasia: 64.8 ± 14.3; gastric cancer: 107.4 ± 24.6; p < 0.001). IL-8 elevation in gastric cancer was independent of H. pylori status across all stages (p > 0.50 for all stage-stratified comparisons, though these subgroup analyses are limited by small sample sizes and may be considered exploratory). Baseline IL-8 > 52.3 pg/mL was associated with progression risk, AUC 0.84, sensitivity 88.9%, specificity 78.0%, and negative predictive value 98.5%, significantly outperforming CEA (AUC 0.62) and CA19-9 (AUC 0.58). Time-dependent AUC increased to 0.91 at 12 months and 0.94 at 18 months. Trajectory modeling, performed blinded to outcome, identified three patterns: Stable-Low (n = 42), Moderate-Rising (n = 49), and High-Accelerating (n = 9). The acceleration point in the High-Accelerating group preceded clinical cancer diagnosis by a median of 6 months (range 3-12), however, this exploratory finding requires external validation. In multivariable analysis using Firth penalized regression, baseline IL-8 (aOR per 10 pg/mL: 2.31, 95% CI: 1.48-3.61, p < 0.001) and intestinal metaplasia (aOR: 4.22, 95% CI: 1.31-13.61, p = 0.016) were independently associated with progression.

In this prospective longitudinal biomarker study, serial serum IL-8 trajectories were significantly associated with progression from H. pylori-associated precancerous lesions to gastric cancer. Rising IL-8 levels preceded clinical diagnosis by approximately 6-12 months, suggesting potential utility for risk stratification. A Baseline IL-8 > 52.3 pg/mL was independently associated with progression (adjusted HR: 6.94, p < 0.001), but this exploratory trajectory is hypothesis-generating and requires external validation before causal interpretation. However, these findings are exploratory and hypothesis-generating.

The therapeutic efficacy of immune checkpoint blockade is frequently compromised by the profound spatial heterogeneity of solid tumors, where distinct ecological niches are associated with different patterns of immune engagement. Spatial omics has substantially refined our understanding of tumor immune topographies. These range from immune-excluded hypoxic and necrotic cores to immune-infiltrated margins enriched with tertiary lymphoid structures (TLS). However, the mechanistic contribution of regulated cell death (RCD) to these spatial domains remains largely unexplored. In this review, we propose the concept of spatially organized RCD-immune coupling as a hypothesis-generating framework. We argue that RCD modalities are not uniformly distributed across tumors, but are influenced by regional microenvironmental constraints, including metabolic zonation, hypoxia, and mechanical stress. Synthesizing emerging evidence, we discuss how apoptosis, necroptosis, pyroptosis, ferroptosis, and PANoptosis may be enriched within distinct tumor niches. We further examine how region-specific release of damage-associated molecular patterns (DAMPs), cytokines, and lipid mediators may be associated with local immune activation, exhaustion, or exclusion. Importantly, we distinguish spatial association from functional causality and emphasize the need for phenotypic validation and perturbation-based studies. This framework positions RCD as a spatially organized component of tumor immune ecology and a basis for future biomarker and therapeutic studies.