Search Results (1,641)

Background/Objectives: Percutaneous microwave (MW) ablation is a nephron sparing treatment for localized renal cell carcinoma (RCC). We compared perioperative, renal functional, and oncologic outcomes for clinical stage 1 RCC treated with MW ablation, PN, or RN. Methods: Adults with clinical T1 kidney masses treated with MW ablation, PN, or RN from 2001–2025 were identified. Outcomes included: 90-day overall and major complication rate, 30-day readmission rate, length of hospital stay (LOS), change in renal function, local recurrence-free survival (LRFS), metastasis-free survival (MFS), and cancer-specific survival (CSS). Univariable and multivariable analyses evaluated outcomes adjusted for confounders. Results: A total of 2201 patients with renal masses ≤ 7 cm and no evidence of locally advanced or metastatic disease were treated with MW ablation (708), PN (729), or RN (764). MW ablation patients were older and more comorbid compared to both PN/RN, whereas RN patients had larger, higher-grade tumors. Ninety-day overall complications were lowest after MW ablation (8.9% vs. 20.3% PN, p < 0.001 and 8.9% vs. 19.9% RN, p < 0.001). LOS was shortest after MW ablation (median 1 day vs. 3 days PN/RN, p < 0.001 for each). Six-month eGFR decline was similar after MW ablation and PN (−5.2% and −4.7%, p = 0.84) but greater after RN (−32.9%, p < 0.001). Local recurrences were more common with MW ablation, with five-year LRFS 96.4% versus 99.7% for PN (p < 0.001). Five-year MFS (99.5% vs. 99.7%, p = 0.24) and CSS (99.3% vs. 99.7%, p = 0.71) did not differ between MW ablation and PN. Conclusions: Percutaneous MW ablation has comparable metastasis free and cancer specific survival with lower perioperative morbidity and comparable renal preservation to PN, despite worse baseline comorbidity and renal function. These findings support MW ablation as an effective nephron-sparing option for appropriately selected patients with clinical T1 RCC when performed at an experienced center. Full article

Background/Objectives: Male breast cancer (MBC) is rare, accounting for less than 1% of all breast cancers. Given its low incidence, male breast cancer (MBC) remains understudied; this 33-year Serbian cohort was assessed for clinicopathological features, therapeutic approaches, genetic alterations, and survival. Methods: We retrospectively analyzed MBC patients diagnosed between 1991 and 2024 at the Institute for Oncology and Radiology of Serbia. Data included demographics, tumor characteristics, and stage, treatment, hormone receptor and HER2 status, Ki-67 index, genetic testing, and survival. Results: A total of 191 patients were identified (median age 66). Family history was negative in 91% and positive in 5.8%. T2 tumors were most frequent (36%), and 96% presented without metastasis. Mastectomy with axillary or sentinel lymph node dissection was performed in 78.5%. Neoadjuvant chemotherapy and radiotherapy were administered in 5.8% and 8.4%. Estrogen receptor positivity was 72%, progesterone receptor 88%, HER2 overexpression 11.0%, and triple-negative tumors 2.6% (40% with axillary involvement). High Ki-67 (≥15%) was recorded in 28.8%. Adjuvant chemotherapy, radiotherapy, and hormone therapy were given in 36%, 58%, and 68%. Among 37 genetically tested patients, seven had pathogenic variants (BRCA1, BRCA2, CHEK2, PALB2). Disease recurrence occurred in 30%. Median follow-up was 53 months. Median disease-free survival (DFS) was 82 months (1-, 2-, 5-, 10-year DFS: 87%, 73%, 57%, 39%). Median overall survival (OS) 131 months (1-, 2-, 5-, 10-year OS: 95%, 93%, 73%, 53%). Conclusions: This long-term cohort highlights the predominance of hormone-receptor positivity, the infrequency of germline mutations, and moderate survival rates, informing patient management and guiding future studies. Full article

Acetyl phosphate (AcP) is a microbial metabolite acting as a link between cell metabolism and signaling, providing the survival of bacteria in the host. AcP was also identified as an intermediate of pyruvate oxidation in mammalian mitochondria and was found in the human blood in some severe pathologies. The possible contribution of circulating AcP to the maintenance of the physiological or pathological states of the body has not been studied. Since AcP can function as a donor of phosphate groups, we have examined in vitro the influence of AcP on calcium signaling in mitochondria and cells by measuring the membrane potential and the calcium retention capacity of mitochondria by selective electrodes and by assaying the cell calcium signaling by Fura-2AM fluorescent radiometry. AcP was shown to induce a concentration-dependent increase in the mitochondrial resistance to calcium ion loading both in the control and in the presence of ADP. This effect was especially pronounced when mitochondria were incubated in a phosphate-free medium; under these conditions, AcP strongly raised the membrane potential and increased the rate of calcium uptake and the calcium retention capacity several times. Moreover, AcP induced similar changes in human cells when calcium signaling was activated by ATP, to a greater extent in neuroblastoma cells than in astrocytes. In the presence of AcP, a tendency for an increase in the amplitude and a decrease in the continuance of the ATP-induced calcium response was observed. These changes are probably associated with the activation of calcium buffering by mitochondria due to the delivery of phosphate during the hydrolysis of AcP. The results show that AcP is involved in the regulation of the Ca²⁺ balance in cells by activating the accumulation of calcium ions by mitochondria, especially under phosphate deficiency. A shift in calcium signaling mediated by AcP supplementation may be caused by hyperphosphatemia, which is now considered as one of basic contributors to cellular dysfunction and progression of various diseases, including sepsis. Full article

Background: Desmoid tumors (DTs) are rare, locally aggressive fibroblastic neoplasms with highly heterogeneous clinical behavior. The present work constitutes the second part of a two-part project, following our previously published multidisciplinary review of the diagnostic and therapeutic landscape of DTs. It provides a comprehensive analysis of our institutional experience as a national reference center for sarcoma. We aim to describe real-world diagnostic pathways, management strategies, and clinical outcomes in a high-volume cohort. Methods: We conducted a retrospective cohort study that included patients diagnosed with DT at our center between 2014 and 2024. Demographic, clinical, molecular, treatment, and outcome data were collected. Management strategies were analyzed according to tumor location, symptoms, progression patterns, and multidisciplinary decision-making. Outcomes included response rates, event-free survival (EFS), need for active treatment, response to systemic therapy, and recurrence after local treatments. Results: A total of 109 patients were included (median age 36.8 years; 56.9% women). Somatic CTNNB1 mutations were identified in 23 of 29 tested patients, predominantly T41A, while germline alterations were found in 18 patients, mainly in APC. Initial management was conservative in 40.4% of patients and active in 59.6%, primarily through surgery. After a median follow-up of 41.5 months, 44.9% of patients experienced disease progression. Among patients managed with active surveillance, spontaneous regression occurred in 22.2%, and 58% remained treatment-free. Surgical relapse occurred in 35.8% of patients undergoing upfront resection, with major postoperative complications limited to externally operated cases. Cryoablation achieved radiological responses in most evaluable patients, while systemic therapies showed clinical activity but relevant toxicity, particularly with tyrosine kinase inhibitors. The median EFS for the whole cohort was 57 months. Conservative initial management and R1/2 surgical margins were independently associated with worse EFS. Conclusions: Our results support a personalized, multidisciplinary management strategy for DTs, prioritizing conservative approaches when appropriate and reserving active treatments for progressive or symptomatic disease. Outcomes achieved in a specialized referral center are comparable to those reported in large international retrospective series, underscoring the value of expert multidisciplinary care in optimizing DT management. Full article

Management of resectable esophageal cancer has evolved into a multidisciplinary paradigm centered on multimodality therapy. Historically, induction chemoradiotherapy followed by surgery, as established by the CROSS trial, became the standard of care for locally advanced disease due to improvements in R0 resection rates and overall survival. More recently, the ESOPEC trial reexamined this paradigm in esophageal adenocarcinoma, demonstrating superior survival and improved systemic disease control with perioperative chemotherapy using the FLOT regimen compared with chemoradiotherapy. In parallel, the MATTERHORN trial further advanced perioperative treatment by showing improved event-free survival with the addition of the immune checkpoint inhibitor durvalumab to FLOT chemotherapy. Alongside these systemic therapy advances, surgical management has transitioned toward minimally invasive and robotic-assisted esophagectomy, offering equivalent oncologic outcomes with reduced perioperative morbidity. This review summarizes the evolving evidence from pivotal clinical trials, highlights ongoing studies integrating immunotherapy, and discusses emerging strategies such as adoptive cell transfer which currently is under investigation for metastatic recurrence, but in the future may provide additional treatment options for resectable esophageal cancer. Full article

Recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) carries a poor prognosis; however, immune checkpoint inhibitors have emerged as critical therapeutic options. Although the KEYNOTE-048 trial established the efficacy of pembrolizumab, the population was restricted to major sites (e.g., oral cavity, oropharynx, hypopharynx, and larynx), excluding subsites such as the paranasal sinuses and nasopharynx. To evaluate outcomes in these populations, we conducted a multicenter retrospective study of 167 patients with R/M SCCHN treated with pembrolizumab between December 2019 and February 2022. The cohort comprised 127 patients with tumors in included sites and 27 in excluded subsites. Primary endpoints included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), and immune-related adverse events (irAEs). In the excluded subsite group, median OS was 15.2 months (1-year rate: 70.6%), and median PFS was 4.9 months (1-year rate: 21.2%). The ORR was 22.2% and the DCR was 59.3%. The incidence of irAEs was 25.9%, with Grade ≥ 3 events in 3.7%. Survival outcomes did not differ significantly from those in included sites. These findings suggest the potential efficacy and safety of pembrolizumab in subsites excluded from KEYNOTE-048, warranting validation in prospective trials. Full article

Robot-assisted radical prostatectomy (RARP) is the definitive surgical treatment for localized prostate cancer (PCa). Some patients with post-RARP biological recurrence (BCR) eventually develop distant metastases and subsequent PCa-related mortality. The objective of this study was to clarify the predictive factors for the risk of metastatic disease after BCR in patients with PCa who underwent RARP. This multicenter retrospective cohort study was conducted in nine Japanese institutions and enrolled 491 men with BCR, detected between 2011 and 2024. During the median 59-month follow-up period, 44 patients (9.0%) had radiological confirmation of distant metastasis. Patients with developed metastases after BCR exhibited higher biopsy Gleason grade and pathological T stage, increased lymphovascular invasion (LVI) in the surgical specimen, and a shorter interval from RARP to BCR. In univariate analysis, LVI and a time to BCR after RARP of ≤14.9 months were significant predictors of distant metastasis. In the multivariate analysis, LVI constituted a significant independent predictor of distant metastasis (p = 0.011). The 3-year metastasis-free survival (MFS) rates were 85.5% and 94.1% in patients with and without LVI, respectively. The MFS was significantly prolonged in patients with negative LVI compared to those with positive LVI (p = 0.007). In Japanese males with BCR after RARP, LVI was identified as an independent predictor of metastatic progression. Full article

Numerous factors contributed to coronavirus 2019 (COVID-19) disease recovery and death rates. In many countries, socioeconomics, morbidities, the experience of symptoms and access to healthcare services are major contributors to recovery and death rates. A retrospective cohort study was conducted to determine the morbidity, mortality, survival probability, and risk factors associated with COVID-19 among children in the Free State province, South Africa. A total of 846 patients’ records were used in the study. Using SPSS version 28 software, survival probability was determined using Kaplan–Meier estimation curves and Cox regression was used to determine the effect of sociodemographics and clinical manifestation information on time of death. The COVID-19 mortality rate was 13.12% in our study. There were more female patients (60%) than male patients (40%). In total, 71 patients had two or more morbidities, while 414 patients were asymptomatic. Patients between 5 and 18 years old were at twice the risk of dying of COVID-19, and male children were at a higher risk as well. Having more than one symptom was also a risk for dying in this study. Severe COVID-19 is attributed to numerous factors, and these are closely associated with surrounding environments and public health systems. The findings are important for the clinical management of similar diseases and circumstances in the future. Full article

Background and Objectives: This study aimed to identify clinicopathological factors associated with axillary pathological complete response (ApCR) in patients with HER2-positive breast cancer presenting with clinically node-positive disease (cN+) confirmed by biopsy who received neoadjuvant therapy (NAT), and to assess the prognostic significance of ApCR on survival outcomes. Materials and Methods: A total of 221 patients with clinically node-positive (cN+) HER2-positive invasive breast cancer, with nodal involvement confirmed by fine-needle aspiration or core needle biopsy, who received neoadjuvant therapy (NAT) and subsequently underwent surgery at three centers between January 2015 and January 2025 were retrospectively reviewed. The association between clinicopathological factors and axillary pathological complete response (ApCR) was analyzed using logistic regression. Survival analyses were performed using the Kaplan–Meier method. Results: The median follow-up duration was 34.3 months. Axillary pathological complete response (ApCR) was achieved in 67.9% of patients. The ApCR rate was higher in stage II disease compared with stage III (76.9% vs. 62.9%). Patients with HER2 3+ tumors demonstrated a higher ApCR rate (70.8%) than those with HER2 2+/FISH+ tumors (46.2%). In multivariable logistic regression, HER2 3+ status (OR = 2.745; 95% CI: 1.138–6.619; p = 0.025) and lower clinical stage (OR = 2.251; 95% CI: 1.182–4.287; p = 0.014) were independently associated with a higher likelihood of achieving ApCR. In survival analyses, the 3-year event-free survival rate was 92% (95% CI: 86–98%) in the ApCR group, compared with 75% (95% CI: 63–87%) in the non-ApCR group. Kaplan–Meier analysis demonstrated that ApCR was a significant prognostic factor for EFS (p = 0.001). Median overall survival (OS) was not reached in either group due to the limited number of death events. Conclusions: ApCR was frequent in node-positive HER2-positive breast cancer after neoadjuvant therapy. HER2 3+ status and lower clinical stage independently predicted ApCR, which in turn was associated with improved event-free survival. These findings underscore the prognostic relevance of ApCR in this setting. Full article

Background: Head and neck (H&N) cutaneous melanomas have poorer outcomes than melanomas at other sites, yet sentinel lymph node biopsy (SLNB)—a key prognostic tool in clinically node-negative disease—is less frequently performed, particularly outside tertiary centers. We evaluated the feasibility and prognostic relevance of SLNB in a medium-volume regional institution. Methods: We retrospectively reviewed patients with primary H&N cutaneous melanoma who underwent SLNB at the Department of Oral and Maxillofacial Surgery, University of Szeged, between 2010 and 2022. Clinicopathological features, nodal outcomes, recurrence patterns, recurrence-free survival (RFS), and overall survival (OS) were analyzed using Kaplan–Meier methods and univariate Cox regression. Results: Thirty-eight patients underwent SLNB, with a 100% sentinel lymph node identification rate and no major complications. Positive sentinel lymph nodes were identified in 8 patients (21.1%). Two false-negative events occurred, resulting in a false-omission rate of 6.7% and a negative predictive value of 93.3%. SLN-negative patients demonstrated longer RFS and OS, although differences were not statistically significant. Among patients with intermediate-risk melanoma (pT1b–pT3a), 18.5% had a positive SLN. Conclusions: SLNB is a safe and clinically meaningful staging procedure for H&N melanoma in a medium-volume regional center. Sentinel node status provides important prognostic information and supports appropriate patient selection for contemporary adjuvant therapy. Full article

Major hepatectomy (MH) has traditionally been associated with higher R0 rates in colorectal liver metastases (CRLM), but at the cost of increased morbidity. Parenchymal-sparing hepatectomy (PSH) has emerged as an alternative approach aimed at reducing perioperative complications while preserving functional liver parenchyma without compromising oncological outcomes. We retrospectively analyzed 248 consecutive patients undergoing liver resection for CRLM between 2016 and 2025, classified as PSH (n = 215, 86.7%) or MH (n = 33, 13.3%). MH was performed more frequently in patients with greater tumor burden, including larger lesions, more numerous metastases, and bilobar disease (all p < 0.001). PSH was associated with shorter hospital stay, fewer postoperative complications, and lower 30-day readmission rate. In multivariable Cox analyses, surgical strategy was not associated with recurrence-free survival or overall survival, which were primarily driven by tumor burden. Among patients who developed liver recurrence, repeat hepatectomy was more often feasible after PSH than MH (p = 0.026), emphasizing the long-term value of preserving functional parenchyma. Overall, PSH was associated with lower postoperative morbidity, enabling earlier recovery, while facilitating future liver resections when needed in this chronically evolving disease. Full article

Background/Objectives: This study evaluated the efficacy and safety of salvage interstitial brachytherapy (S-ISBT) for isolated local recurrence (ILR) of cervical and endometrial carcinoma, stratifying patients by pelvic irradiation history (PIH). Methods: Patients with ILR treated with S-ISBT were retrospectively reviewed and categorized by initial treatment: Group A (surgery alone); Group B (surgery + postoperative radiotherapy (RT)); and Group C (definitive RT). Overall survival (OS), progression-free survival (PFS), local control (LC) rates, and the cumulative incidence functions (CIFs) for Grade ≥ 3 late adverse events (AEs) were estimated. Multivariate analysis identified prognostic factors. Results: The study included 70 patients (A: 28, B: 17, C: 25) with a median follow-up of 33.4 months. The 3-year OS, PFS, LC, and CIFs for Grade ≥ 3 late AEs for Groups A, B, and C were 80.8%, 66.7%, and 30.4% (p < 0.001); 56.4%, 41.5%, and 11.6% (p < 0.001); 89.1%, 61.4%, and 43.0% (p = 0.002); and 26.4%, 13.3%, and 32.0% (p = 0.40), respectively. Multivariate analysis suggested the type of PIH, disease-free interval, and tumor volume as independent prognostic factors. While no significant differences were observed between Groups A and B (OS: HR = 0.47, p = 0.19; PFS: HR = 0.60, p = 0.28), Group C exhibited a significantly higher risk than Group B (OS: HR = 3.08, p = 0.018; PFS: HR = 3.41, p = 0.004). Conclusions: S-ISBT could be considered for patients with prior postoperative RT, whose outcomes are significantly better than those with prior definitive RT. Full article

Background/Objectives: Non-small-cell lung cancer (NSCLC) is a common disease with a high mortality rate and is often treated with immunotherapies; however, prognostic markers are required to identify patients who are most likely to benefit from these treatments. Therefore, we designed this study to assess the prognostic significance of the C-PLAN index, which includes performance status (PS) and C-reactive protein (CRP). Methods: A total of 560 patients were included in this multicenter study. Patients had been diagnosed with NSCLC and had received nivolumab therapy. The C-PLAN index, defined in 2022, is a score derived from the combination of PS, CRP, lactate dehydrogenase (LDH), albumin, and neutrophil–lymphocyte ratio (NLR). Patients were classified into good-, moderate-, and poor-prognosis groups according to the C-PLAN score. Results: The median metastatic overall survival was 25 months in the group with a C-PLAN score < 2 and 6 months in the group with a C-PLAN score ≥ 2 (p < 0.001). The median metastatic progression-free survival was 11 months in the group with a C-PLAN score < 2 and 3 months in the group with a C-PLAN score ≥ 2. Conclusion: This is the first comprehensive study demonstrating that the C-PLAN index can be used for prognostic purposes in immunotherapy. This score, which can be easily, economically, and practically calculated in outpatient clinics, can predict patient prognosis and determine who should receive longer durations of immunotherapy. Full article

Metastatic uveal melanoma (MUM) remains largely refractory to immune-checkpoint inhibition, so recent research has turned to bispecific T-cell engagers (BTCEs), adoptive-cell therapies (ACTs), and oncolytic viruses (OVs). To summarize the available clinical evidence, we performed a structured literature search across PubMed, Scopus, and Europe PMC for primary studies published between 1 January 2010 and 31 May 2025 that enrolled at least three adults with MUM, treated with one of these modalities, and that reported efficacy or grade-3+ safety outcomes; two reviewers independently performed screening, data extraction, and risk-of-bias assessment, and because of notable heterogeneity, we synthesized the findings narratively. Twenty-two studies met the criteria—thirteen phase I–III trials, eight observational cohorts, and one case series—covering fifteen BTCE cohorts, four ACT cohorts, and three OV cohorts. Tebentafusp, the dominant BTCE evaluated in roughly 1150 HLA-A*02:01-positive patients, extended median overall survival from 16.0 to 21.7 months (hazard ratio 0.51, with three-year follow-up HR 0.68) in its pivotal phase-III trial despite objective response rates of only 5–12%, with early skin rash and week-12 circulating-tumor-DNA clearance emerging as consistent markers of benefit. Tumor-infiltrating lymphocyte therapy, administered to about thirty patients, produced objective responses in 11–35% and occasional durable complete remissions, although median progression-free survival remained 2–6 months and severe cytopenias were universal. Three early-phase OV studies, totaling twenty-nine patients, yielded no radiographic responses but showed tumor-specific T-cell expansion and transient disease stabilization. Safety profiles reflected the mechanism of action: tebentafusp most often caused rash, pyrexia, and usually manageable cytokine-release syndrome with grade-3+ events in 40–70% yet discontinuation in roughly 2%; TIL therapy toxicity was driven by lymphodepleting chemotherapy and high-dose interleukin-2 with one treatment-related death; and OVs were generally well tolerated with no more than 20% grade-3 events. Full article

BTK (Bruton’s tyrosine kinase) has become a key therapeutic target across several hematologic diseases, beginning with its original use in CLL/SLL. As a central mediator of B-cell receptor signaling and microenvironment interactions, BTK supports survival, proliferation, and trafficking in multiple mature B-cell malignancies (mantle cell lymphoma, marginal zone lymphoma, Waldenström macroglobulinemia, and other indolent/aggressive lymphomas) and in selected immune-mediated conditions such as chronic graft-versus-host disease. Covalent BTK inhibitors (ibrutinib, acalabrutinib, and zanubrutinib) irreversibly bind the C481 residue and have produced high response rates and durable disease control, often replacing chemoimmunotherapy in the relapsed setting and, for some entities, even in the first line. Differences in kinase selectivity lead to different safety profiles: second-generation covalent agents generally maintain efficacy while reducing significant off-target toxicities, especially atrial fibrillation and hypertension. Resistance to covalent BTK inhibitors most commonly develops through BTK C481 substitutions and activating PLCG2 mutations, with other kinase-domain variants increasingly recognized. Non-covalent BTK inhibitors (e.g., pirtobrutinib) bind BTK independently of C481, can overcome classic C481-mediated resistance, and extend BTK pathway targeting into later lines of therapy. Overall, BTK inhibition has evolved into a versatile platform enabling long-term, often chemo-free management strategies. Full article