Search Results (705)

Introduction: Radiotherapy plays a critical role in the management of head and neck squamous-cell carcinoma (HNSCC); however, the influence of overall treatment time on patient outcomes remains an area of ongoing investigation. The use of radiation, either in conjunction with concurrent chemotherapy or on its own, is crucial when treating HNSCC. Despite the longstanding hypothesis that treatment gaps may adversely affect tumor response and overall survival, there is a paucity of literature on this particular area. This study aims to bridge the knowledge gap and assess the correlation of treatment gaps on recurrences in HNSCC patients. Materials and Methodology: This retrospective study is based on an analysis of data obtained from a single institution between 2017 and 2021. Patients were selected on the basis of the presence of treatment gaps. Data were extracted from medical records and analyzed to evaluate the association between overall treatment time and various patient and treatment-related factors. Various factors thought to contribute to treatment gaps, such as age, TNM Stage, radiation dose, and use of concurrent chemotherapy, were also examined. Results: A total of 212 patients with treatment gaps were evaluated. Of these, 80 individuals experienced recurrences. It was observed that compared to distant metastases, locoregional failure was more frequent (n = 2, 4.2% vs. n = 45, 95.74%). The patients underwent both adjuvant and definitive therapy and were treated with a dose range of 60–70 Gy and concurrent cisplatin chemotherapy. It was noticed that this cohort had a range of 4–43 days of treatment gaps. Notably, 19 out of 47 patients had treatment gaps ≤ 5 days, while 28 out of 47 had gaps exceeding 5 days. It was also observed that patients with treatment gaps of >5 days had poorer quality of life and overall survival. Conclusions: This study identified that the Overall Treatment Time (OTT) had a strong statistical correlation with the development of recurrences. Further, the age of the patient, presence of neutropenia and the duration of the treatment gap were also identified to significantly correlate with the chance of developing recurrences. Full article

Background: Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality. Transarterial radioembolization (TARE) has emerged as a locoregional therapy to downstage tumors and expand surgical eligibility. Methods: This retrospective study included patients with HCC who underwent TARE as a bridging treatment. The primary outcomes assessed were the efficacy of TARE in facilitating curative surgery and long-term oncological outcomes, specifically overall survival (OS) and disease-free survival (DFS). Results: This study included 25 patients. 17 patients subsequently underwent surgical resection and eight underwent living-donor liver transplantation (LDLT). At a median follow-up of 33.4 months, the median disease-free survival (DFS) was 11.2 months. Patients with recurrence had a median DFS of 3.65 months, and those without recurrence had a median DFS of 27.1 months. The median overall survival (OS) for the cohort was 33.4 months. At the last follow-up, 76% of patients were alive and disease-free. Kaplan–Meier analysis demonstrated sustained OS in the LDLT group, while resection patients gradually declined within the first two years. Conclusions: TARE is an effective bridging strategy that enables curative-intent surgery in selected patients with HCC and supports favorable long-term oncological outcomes. Careful patient selection and multidisciplinary management remain essential to optimize survival benefits. Full article

Liver function plays a pivotal role in the management of hepatocellular carcinoma (HCC). Consequently, managing HCC requires a dual focus on both tumour staging and liver function assessment to guide therapeutic decisions. Comprehensive liver function evaluation involves clinical tools such as the Child–Pugh classification and the Model for End-Stage Liver Disease (MELD) score. This is supplemented by newer metrics, including the MELD-Na score, the albumin–bilirubin (ALBI) grade and liver stiffness measurements. These assessments are integral to tailoring treatments, ranging from curative approaches such as surgical resection and liver transplantation to locoregional options (percutaneous ablation, transarterial chemoembolisation and radioembolisation), and systemic therapies. This review explores strategies for balancing the aggressiveness of cancer therapy with the need to preserve hepatic function, particularly in patients with advanced liver dysfunction. A multidisciplinary approach, incorporating expertise from hepatology, oncology, radiology and surgery, is essential for optimising outcomes. Advanced imaging techniques and biochemical markers also improve decision-making and ensure individualised care. Full article

Background/Objectives: Hepatocellular carcinoma (HCC) immunotherapy provides limited clinical benefits, partly due to the lack of reliable efficacy biomarkers. Radiomics, which non-invasively analyzes tumor heterogeneity, shows promising potential for predicting treatment outcomes. Methods: The present study systematically evaluated the predictive performance and methodological quality of radiomics models for assessing immunotherapy efficacy in patients with HCC. A literature search was conducted in PubMed, Web of Science, Embase, and the Cochrane Library for studies published up to 21 June 2025, which developed CT- or MRI-based radiomics models to predict immunotherapy efficacy in HCC. Study quality was assessed using the radiomics quality score (RQS) and the METhodological RadiomICs Score (METRICS). Results: A total of 11 studies were included and categorized by immunotherapy regimen: ICIs alone (1/11), ICIs combined with targeted therapy (6/11), and ICIs combined with targeted therapy plus locoregional therapy (4/11). The models primarily predicted treatment response (7/11), overall survival (OS) (4/11), or progression-free survival (PFS) (4/11). In the ICI monotherapy cohort, AUC values for predicting treatment response ranged from 0.705 to 0.772. In the ICI plus targeted therapy cohorts, AUC or concordance index (C-index) values for predicting the above efficacy endpoints were 0.792–0.956, 0.63–0.77, and 0.54–0.837, respectively. In the combination therapy cohorts incorporating locoregional treatment, predictive models showed AUC or C-index values of 0.721–0.92, 0.817–0.838, and 0.59. Quality assessment revealed a median RQS of 15 (range: 11–19) and a median METRICS of 72.5% (range: 56.0–79.5%) across all studies. Conclusions: CT/MRI-based radiomics uses routine imaging to non-invasively quantify whole-tumor phenotype and heterogeneity, enabling repeatable, longitudinal assessment in hepatocellular carcinoma. Evidence suggests that it can help to identify patients likely to benefit from immunotherapy before treatment. However, clinical implementation requires standardized imaging and analysis protocols, external validation, and transparent reporting. Full article

Background/Objectives: Breast cancer is the most common cancer among women worldwide. Surgical treatments include breast-conserving therapy (BCT) and mastectomy, often followed by reconstruction, but the impact of reconstruction on locoregional recurrence (LRR) remains unclear. This study evaluated LRR, survival, and risk factors following primary breast reconstruction performed simultaneously with mastectomy compared with mastectomy without reconstruction. Methods: This population-based, retrospective cohort included 2475 women with breast cancer treated between 2004 and 2018 at the Tumor Center and Caritas St. Josef Hospital in Regensburg, Germany. Patients were grouped into not primarily reconstructed, primary autologous reconstruction, primary allogeneic reconstruction, and primary combined reconstruction. Overall survival (OS), recurrence-free survival (RFS), and cumulative recurrence rates (CRR) were assessed using Kaplan–Meier methods and Cox proportional hazards models adjusted for age, nodal status, tumor biology, and adjuvant therapies. Results: Of 14,046 eligible cases, 2475 met inclusion criteria: no primary reconstruction (87%), autologous reconstruction (3.1%), allogeneic reconstruction (9.0%), and combined reconstruction (0.4%). Patients undergoing reconstruction were younger and more likely to receive chemotherapy. The 5-year OS was 71.8% without primary reconstruction, 82.1% after autologous reconstruction, and 90.0% after allogeneic reconstruction. Allogeneic reconstruction was associated with improved OS (HR 0.570, p = 0.015) and RFS (HR 0.669, p = 0.039), whereas autologous reconstruction was associated with higher hazards of LRR and distant metastases compared to no primary reconstruction. Conclusions: The 5-year cumulative LRR was 5.2%, 13.5%, and 4.8%, respectively. Immediate allogeneic reconstruction after mastectomy was therefore associated with favorable survival and recurrence outcomes, while autologous reconstruction was linked to higher LRR and distant metastasis rates in this cohort. The retrospective design, small autologous subgroup, and absence of detailed lifestyle and metabolic data are important limitations of these findings. These associations likely reflect differences in tumor stage, biology, and unmeasured risk factors, and should be interpreted as hypothesis generating. Prospective multicenter studies with detailed risk profiling are needed to clarify the oncologic safety of different reconstructive strategies. Full article

Peritoneal metastases represent one of the most dreadful manifestations of gastric cancer and continue to drive poor outcomes despite significant advances in systemic therapy. Accurate staging—beginning with laparoscopy—remains essential for avoiding non-beneficial surgery and ensuring appropriate allocation to systemic or locoregional treatment pathways. Although modern systemic agents, including immunotherapy and targeted therapies, have transformed the broader management of metastatic disease, their impact in the peritoneal compartment remains limited, reflecting its unique biological and pharmacokinetic constraints. Locoregional approaches such as CRS–HIPEC, PIPAC, and NIPS have expanded the therapeutic armamentarium and have shown encouraging signals in selected populations. Recent randomized studies, including ESTOK01 and PERISCOPE II, emphasize the importance of careful patient selection, technical standardization, and optimal sequencing, while ongoing trials—such as PREVENT, GASTRICHIP, and CONVERGENCE—seek to refine the integration of systemic and intraperitoneal strategies. Yet the field continues to advance without the benefit of validated predictive biomarkers capable of guiding therapeutic decisions. This limitation constrains clinical progress and underscores the need for a stronger translational framework. Future improvement in the management of gastric cancer with peritoneal metastases will depend on the identification of robust biological predictors of response, enabling more rational patient selection and the development of truly personalized multimodal approaches. Full article

Background: Vascular malformations (VMs) are congenital anomalies of the vascular system—capillary, venous, lymphatic, arteriovenous, or combined—frequently associated with notable morbidity and reduced quality of life. Electrochemotherapy (ECT), a locoregional treatment that combines chemotherapeutic agents (most commonly bleomycin) with electroporation, has emerged as a promising alternative in managing therapy-resistant or anatomically challenging lesions. Methods: A systematic review of the literature was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Embase, and the Cochrane Library were searched from inception to January 2025 for studies reporting on the efficacy and/or safety of ECT for vascular malformations. Data extraction encompassed study design, patient demographics, VM type, ECT protocols, outcomes, follow-up duration, and adverse events. Studies that lacked relevant outcome data or focused solely on other therapeutic approaches were excluded. Results: Twelve primary studies met the inclusion criteria and were analyzed. These covered diverse VMs, including venous, slow-flow, high-flow malformations, aggressive hemangiomas, and composite lesions in adult and pediatric populations. ECT protocols usually combined bleomycin (or occasionally other agents such as pingyangmycin or polidocanol foam) with various electroporation parameters. Across studies, ECT resulted in meaningful lesion-size reduction (50–97% in most cohorts), symptom relief (e.g., reduced pain and bleeding), and favorable cosmetic outcomes. While side effects (local edema, hyperpigmentation, procedure-related discomfort) were occasionally reported, they were typically mild and transient. Conclusions: ECT represents a valuable minimally invasive option in the therapeutic armamentarium for vascular malformations. Despite consistent demonstrations of efficacy and acceptable toxicity profiles, future high-quality, multicenter studies are warranted to confirm outcomes, refine treatment guidelines, and potentially expand its use as a standard of care. Full article

Background/Objectives: Management of hepatocellular carcinoma (HCC) with macrovascular invasion (MVI) varies between systemic immunotherapy and locoregional approaches. We compared atezolizumab plus bevacizumab (Atezo–Bev) with locoregional therapy in treatment-naïve patients. Methods: We conducted a retrospective cohort study of patients with image- or biopsy-proven HCC and MVI, Child–Pugh A/B, and ECOG 0–1 who received first-line Atezo–Bev or locoregional therapy (transarterial chemoembolization [TACE] with or without external-beam radiotherapy [RT]). Inverse probability of treatment weighting (IPTW) minimized baseline imbalances. Primary outcomes were overall survival (OS) and progression-free survival (PFS). Modified RECIST assessed radiologic response, and major adverse events were classified using Society of Interventional Radiology criteria. Results: We analyzed 475 patients (Atezo–Bev, n = 191; locoregional therapy, n = 284). Baseline characteristics were similar, and IPTW achieved covariate balance. Median OS was 9.3 months with Atezo–Bev and 10.8 months with locoregional therapy; after IPTW, OS remained comparable (hazard ratio [HR] 0.95; 95% CI 0.76–1.19; p = 0.635). Median PFS was 6.0 versus 4.1 months, favoring Atezo–Bev; this persisted after IPTW (HR 0.64; 95% CI 0.52–0.79; p < 0.001). Objective response rates were similar (45% vs. 48%; p = 0.49). Major adverse events occurred in 11% of patients in both groups. Subgroup analyses showed no OS differences and a consistent PFS advantage with Atezo–Bev. Conclusions: In HCC with MVI, first-line Atezo–Bev achieved longer PFS than locoregional therapy, with comparable OS and safety, supporting Atezo–Bev as a valid and effective first-line option for disease control while locoregional modalities remain relevant within multidisciplinary care. Full article

Background and Aims: Gastric cancer (GC) remains a leading cause of cancer-related mortality, frequently diagnosed at advanced stages. High-risk features—tumor size ≥ 40 mm, cT3/cT4, nodal involvement, diffuse histology, and Borrmann type III/IV—are associated with peritoneal metastasis (PM). Staging laparoscopy with peritoneal washing (PW) is superior to conventional preoperative imaging modalities, including contrast-enhanced CT, MRI, PET/CT and endoscopic ultrasound, in detecting occult peritoneal disease. In this era of personalized medicine and expanding loco-regional strategies such as cytoreductive surgery (CRS)/Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) and Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC), accurate staging is crucial. This study assessed the impact of SL and PW in high-risk GC. Methods: We retrospectively analyzed 113 consecutive high-risk GC patients who underwent SL and PW between 2014 and 2024 at our institution. The primary endpoint was detection of PM or positive cytology (CY+). Secondary endpoints were treatment modification, eligibility for loco-regional therapy, and safety. Results: SL/PW identified PM or CY+ in 26 patients (23%), including 16 with CY+ only. None had radiologic signs of peritoneal disease. SL findings altered treatment in all cases: 21 patients (81%) with Peritoneal Cancer Index (PCI) < 6 underwent induction chemotherapy followed by CRS + HIPEC; 5 patients (PCI > 6) were spared non-therapeutic laparotomy and treated with bidirectional systemic chemotherapy and PIPAC. In 10 patients, systemic therapy was shifted from FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) to FOLFOX (fluorouracil, leucovorin, and oxaliplatin) ± nivolumab. No perioperative complications occurred; all patients were discharged within 24 h without delay in systemic treatment. Conclusions: SL with PW is safe and significantly improves staging accuracy in high-risk GC, enabling personalized therapeutic planning. Routine integration of SL should be considered essential in treatment algorithms to guide systemic and loco-regional strategies. Full article

Background/Objectives. Prostate cancer (PCa) is the second leading cause of cancer-related mortality among men in the United States. Treatment with second-generation androgen receptor (AR) inhibitors, such as enzalutamide, can trigger lineage plasticity, promoting the transdifferentiation of PCa cells into an AR-independent, poorly differentiated neuroendocrine phenotype (NEPC). The receptor tyrosine kinase EPHA3 is a critical driver for NEPC. It is overexpressed in PCa, particularly in androgen-independent and neuroendocrine subtypes. EPHA3 activates c-Myc signaling to enhance EZH2 expression, promoting histone H3K27 trimethylation. The neural transcription factor BRN2 functions upstream of both EZH2 and ASCL1. The latter regulates the Notch pathway ligand DLL3, thereby orchestrating neuroendocrine differentiation. Elevated expression of classical neuroendocrine markers CHGA and SYP is characteristic of the NEPC phenotype. This study reports the novel usage of the olive phenolic S-(-)-hydroxyoleocanthal (HOC, oleacein) to effectively control NEPC by targeting the EPHA3–BRN2–EZH2–ASCL1–DLL3–SYP–CHGA oncogenic network. Methods. Cell viability assays were conducted to assess in vitro effects. To model NEPC progression and recurrence, NCI-H660-Luc cells were xenografted into male athymic nude mice. RNA-sequencing was performed to compare the differentially expressed genes between placebo control and treated tumors. Results. HOC significantly attenuated the proliferation of NEPC NCI-H660 cells in vitro. Daily oral administration of HOC at 10 mg/kg body weight markedly suppressed the progression of NEPC NCI-H660-Luc tumors. Continued HOC treatments after surgical excision of the primary tumors substantially reduced locoregional recurrence. HOC significantly downregulated the expression of EPHA3, BRN2, EZH2, ASCL1, DLL3, SYP, and CHGA in treated primary and recurrence tumors versus placebo control. Conclusions. These findings establish HOC as a multifaceted therapeutic entity capable of disrupting key NEPC oncogenic networks, highlighting its potential as a novel lead intervention for aggressive NEPC. Full article

Background/Objectives: Oropharyngeal squamous cell carcinoma (OPSCC) management has shifted following recognition of HPV-driven disease. Neoadjuvant chemotherapy (NAC) has historically failed to improve overall survival (OS) in mixed head and neck cohorts, although contemporary HPV-stratified series suggest NAC may enable treatment de-escalation. We aimed to narratively synthesize OPSCC-specific evidence on NAC focusing on primary and nodal response, pathologic complete response (pCR), survival, and functional outcomes. Methods: We conducted a narrative review of PubMed, selecting primary studies in which OPSCC outcomes were reported separately (surgery- or chemoradiotherapy [CRT]-based strategies; HPV status when available). We extracted study design, treatment regimens, response outcomes, survival, and toxicity data. Results: Pre-HPV studies showed variable responses and no consistent OS advantage over locoregional therapy. In the HPV era, non-comparative cohorts of NAC followed by transoral surgery reported substantial downstaging and high pCR rates at both the primary site and regional nodes, with 3–5-year OS frequently ≥80%. NAC+CRT paradigms demonstrated high clinical CR rates and OS exceeding 80–90%, and lower feeding-tube dependence and reduced swallowing morbidity in de-escalated regimens. Comparative retrospective series suggest NAC + surgery may be associated with lower rates of distant metastases and feeding-tube use compared with CRT or upfront surgery, although interpretation is limited by selection bias, regimen heterogeneity, and small sample sizes. Conclusions: While randomized trials have not established an OS advantage for NAC over standard CRT in head and neck cancer overall, HPV-positive OPSCC shows emerging evidence that systemic intensification with NAC may enable surgical and/or radiation de-escalation with promising oncologic and functional outcomes. Full article

Background/Objectives. Prostate cancer (PCa) is among the leading causes of death from cancer in men. Frequent use of androgen receptor inhibitors induces PCa transdifferentiation, leading to poorly differentiated neuroendocrine PCa (NEPC). ROR2 is critical for NEPC pathogenesis by activating ASCL1, promoting lineage plasticity. Protein lysine methylation mediated by N-lysine methyltransferases SMYD2 and its downstream effector EZH2 upregulates the NEPC marker ASCL1 and enhances c-MET signaling, promoting PCa aggression. Epidemiological studies suggest a lower incidence of certain malignancies in Mediterranean populations due to their intake of an olive-phenolics-rich diet. Methods. Cell viability, gene knockdown, and immunoblotting were used for in vitro analyses. A nude mouse NEPC xenograft model evaluated the anti-tumor efficacy of purified and crude oleocanthal. Xenograft tumors were subjected to RNA-seq, qPCR, and Western blot analyses, with clinical validation performed using tissue microarrays. Results. A tissue microarray analysis showed that SMYD2 expression was significantly elevated in PCa tissues with higher IHS versus normal prostate tissue cores. The olive phenolic S–(–)–oleocanthal (OC) suppressed the de novo NEPC NCI-H660 cells proliferation. Male athymic nude mice xenografted with the NCI-H660-Luc cells were used to assess OC effects on de novo NEPC progression and recurrence. Male NSG mice transplanted with LuCaP 93 PDX tumor tissues generated a heterogeneous in vivo model used to assess OC effects against t-NEPC progression. Daily oral 10 mg/kg OC administration significantly suppressed the NCI-H660-Luc tumor progression and locoregional recurrence after primary tumor surgical excision. OC treatments effectively suppressed the progression of LuCaP 93 PDX tumors. OC-treated tumors revealed downregulation of ROR2, ASCL1, SMYD2, and EZH2, as well as activated c-MET levels versus the placebo control. RNA sequencing of the collected treated NEPC tumors showed that OC disrupted NEPC splicing, translation, growth factor signaling, and neuronal differentiation. Conclusions. This study’s findings validate OC as a novel lead entity for NEPC management by targeting the ROR2-ASCL1-SMYD2-EZH2-c-MET axis. Full article

Background: As demonstrated by the PACIFIC trial, biomarker-driven patient selection is crucial. While treatment based on programmed death ligand-1 (PD-L1) and mutational status have become routine, tests for biomarkers available from pretherapeutic blood samples are currently a topic of scientific interest. Methods: This analysis was conducted on patients from the ALLSTAR RWD study, which is a nationwide, prospective registry for inoperable non-small cell lung cancer (NSCLC) stage III. Patients were amenable if they had a full routine pre-treatment blood sample, from which the following biomarkers were extracted: neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), derived monocyte-to-lymphocyte ratio (dMLR) and lactate dehydrogenase (LDH) levels. The intention was to find a cutoff for each of these biomarkers to predict locoregional control (LRC), progression-free survival (PFS) and overall survival (OS). Results: MLR and dMLR demonstrated their predictive potential with cutoff values of 0.665 and 0.945, respectively. Stratifying the whole cohort by means of these cutoffs demonstrated significantly better locoregional control for patients below the threshold, both in the whole cohort (N = 175; 55.7% vs. 75.5%; p-value = 0.018) and in the Durvalumab subgroup (N = 106; 57.5% vs. 77.3%; p-value = 0.030). Similar findings were observed for PFS in the whole cohort (N = 175; 20.5% vs. 56.1%; p-value p < 0.001) and in the Durvalumab subgroup (N = 106; 31.2% vs. 64.6%, p-value < 0.001). dMLR could also significantly predict PFS (N = 173; 17.4% vs. 56.3%; p-value < 0.001), which was corroborated in the Durvalumab subgroup (N = 108; 23.1% vs. 64.1%; p-value = 0.003). Conclusions: This explorative analysis demonstrates the predictive potential of MLR and dMLR for LRC and PFS. These blood biomarkers can be readily integrated into clinical routines since they are easily available. Full article

Background and Objectives: Nasopharyngeal carcinoma (NPC) displays marked geographic and histopathological heterogeneity, and prognostic determinants in non-endemic regions remain incompletely defined. This study aimed to evaluate the impact of clinicopathological characteristics and treatment modalities on survival outcomes among patients with stage II–IVA NPC treated with curative intent at a single tertiary cancer center. Materials and Methods: A retrospective analysis was conducted on 81 consecutive patients with histologically confirmed NPC treated between 2000 and 2022. Demographic, clinical, and treatment parameters were extracted from institutional records. Survival outcomes—including disease-free survival (DFS), locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), cancer-specific survival (CSS), and overall survival (OS)—were estimated using the Kaplan–Meier method and compared using the log-rank test. Prognostic variables identified in univariate analysis were further assessed by multivariable Cox proportional hazards regression (Cox’s model). Results: The cohort included 59 men (72.8%) and 22 women (27.2%), with a median age of 50.8 years (range, 19–78). Most patients presented with locally advanced disease (T3–T4, 53.1%; N2, 60.5%; stage III–IVA, 87.7%). Non-keratinizing undifferentiated carcinoma (World Health Organization [WHO] type III) was the predominant histology (71.6%), followed by the non-keratinizing differentiated subtype (17.3%). Median DFS and OS were 94.6 and 139.4 months, respectively. According to the univariate analysis, histological subtypes and a family history of cancer were significantly associated with DFS, whereas comorbid systemic disease showed an unexpected association with longer DMFS. The multivariable Cox model identified the histological subtype as an independent predictor of disease recurrence (HR = 2.23, 95% CI: 1.00–4.94; p = 0.049). For OS, both histological subtype (HR = 2.40, 95% CI: 1.10–5.25; p = 0.029) and age at diagnosis (HR = 1.05, 95% CI: 1.02–1.09; p = 0.005) were independent adverse prognostic factors. Conclusions: In this long-term, single-center study from a non-endemic region, histological subtype emerged as the most powerful determinant of prognosis, significantly influencing both DFS and OS. Patients with non-keratinizing undifferentiated (WHO type III) carcinoma demonstrated superior outcomes compared with those with differentiated histology. Additionally, increasing age at diagnosis was independently associated with poorer OS. In contrast, inflammatory and nutritional biomarkers, the Pan-Immune–Inflammation Value (PIV) and the Prognostic Nutritional Index (PNI), showed no prognostic significance. These findings underscore the continued prognostic relevance of histopathologic classification and age and highlight the need for large-scale, standardized studies integrating Epstein–Barr virus (EBV) status and host-related factors in non-endemic NPC populations. Full article

Introduction: The incidence of NSCLC increases with age, with a median of approximately 70 years at diagnosis. Historically, treatment strategies for locally advanced cancers have been developed predominantly in younger populations, often excluding elderly patients who may present with multiple comorbidities, severely impaired lung function, or decreased performance status, leading to a lack of age-relevant clinical data. Therefore, we performed a subanalysis of real-world data from the ALLSTAR study to investigate the impact of durvalumab and the radiation regimen (sequential versus concurrent) on clinical outcome in elderly patients with unresectable stage III NSCLC. Methods: We included a total of 171 patients in this subanalysis. All patients were diagnosed with unresectable stage III NSCLC. Patients were divided into two age groups, ≥70 (41%) and <70 years (59%). All of them received curative chemoradiotherapy with (66%) or without (34%) durvalumab. Results: Patients were followed up for a median time of 25.1 months (range: 3.3–52.1). In the elderly group, patients who did not receive durvalumab consolidation had a median PFS of 17 months (95%-CI: 12.4—not reached) and a higher risk of progression (HR = 2.2; 95%-CI: 1–4.6) than those treated with durvalumab, which had a median PFS of 37 months (95%-CI: 24.5—not reached). This difference was statistically significant (log rank p = 0.026). Moreover, the Cox model yielded a hazard ratio suggesting a higher risk of locoregional (HR = 3.8; 95%-CI: 1.28–11.48; log rank p-value =0.01) as well as local recurrence (HR = 5.5: 95%-CI: 1.67–18.1: p-value =0.002) in patients who received sequential chemoradiotherapy compared to those with concomitant chemoradiotherapy in the same age group. In an exploratory analysis based on a Mann–Whitney U test, we did not find significant difference in toxicity between the two age groups. Conclusions: Durvalumab was associated with prolonged progression-free survival, while concomitant radiotherapy showed a trend towards improvement in locoregional and local control in patients aged ≥70. There was no significant difference in treatment toxicity found in the exploratory Mann–Whitney U analysis between the two age groups. Full article