PURPOSE: To evaluate treatment outcomes and toxicity in patients with stage T1-3N0M0 oral cancer treated with surgery followed by high-dose-rate brachytherapy (HDR-BT). METHODS AND MATERIALS: Retrospective study of 50 patients with stage T1-T3N0 tongue and floor-of-mouth cancer who underwent tumour excision (+ elective neck dissection) followed by postoperative HDR-BT due to the presence of negative prognostic factors (close or positive resection margins, lymphovascular and/or perineural invasion, deep invasion). The plastic tube technique (dose: 18 x 3 Gy b.i.d.) was used. Survival outcomes, toxicity, and prognostic factors were evaluated. RESULTS: At a median follow-up of 81 months (range, 4-121), actuarial 5-year local control (LC), nodal control (NC) and progression-free survival (PFS) rates were 79%, 69%, and 64%. After salvage treatment (surgery + external beam radiotherapy), LC, NC, and PFS increased to 87%, 77%, and 72.3%, respectively. Five-year overall survival and cancer-specific survival (CSS) rates were 73% and 77%. Treatmentrelated toxicity included two cases of mandibular osteoradionecrosis and five cases of small soft tissue necrosis. T stage was significantly correlated with nodal control (p=0.02) and CSS (p=0.04). Tumour grade correlated with DFS (p=0.01). CONCLUSION: Postoperative HDR-BT 18 x 3 Gy b.i.d. seems to be an effective method in patients with T1-3N0M0 oral cancer with negative prognostic factors after tumour resection.

• MeSH
• Brachytherapy * methods   MeSH
• Radiotherapy Dosage * MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Survival Rate MeSH
• Mouth Neoplasms * radiotherapy   pathology   surgery   MeSH
• Prognosis MeSH
• Retrospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Neoplasm Staging * MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND AND OBJECTIVE: Apalutamide (APA) is a treatment for metastatic castration-sensitive prostate cancer (mCSPC). In the ARON-3 study we investigated real-world experiences with APA treatment for mCSPC. METHODS: We retrospectively assessed real-world clinical outcomes for patients with mCSPC treated with APA in the ARON-3 study. Overall survival (OS) was calculated from APA initiation to death from any cause. PSA90 was defined as a prostate-specific antigen decline of ≥90% from baseline, and PSA0.2 as achievement of a PSA level ≤0.2 ng/ml. Data for adverse events were retrospectively collected from electronic and paper charts and categorized according to Common Terminology Criteria for Adverse Events v5.0. KEY FINDINGS AND LIMITATIONS: We included 531 patients with mCSPC treated with APA. High-volume disease was reported for 214 patients (40%), and 56 (11%) had visceral metastases. Median OS was not reached. PSA90 was experienced by 461 patients (87%) and PSA0.2 by 368 (69%). Median OS was significantly longer for patients with PSA90 or PSA0.2 than for subjects without these responses (p < 0.001). The incidence of grade 3-4 fatigue was higher among elderly patients (≥80 yr) than among younger patients (19% vs 5%), but the incidence of other adverse events was comparable between the age groups. CONCLUSIONS AND CLINICAL IMPLICATIONS: APA is an effective and tolerable treatment for mCSPC in the real-world setting. PATIENT SUMMARY: The ARON-3 project collects data for patients with prostate cancer treated in multiple centers worldwide to assess outcomes in the real-world setting. We analyzed data for patients with metastatic hormone-sensitive prostate cancer receiving apalutamide. Our results show that apalutamide is a safe and effective drug in the real-world setting as well as in clinical trials.

• MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Metastasis MeSH
• Prostatic Neoplasms, Castration-Resistant drug therapy   pathology   mortality   MeSH
• Prostate-Specific Antigen blood   MeSH
• Antineoplastic Agents therapeutic use   MeSH
• Retrospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Thiohydantoins * therapeutic use   MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

BACKGROUND AND OBJECTIVE: While active surveillance (AS) is an alternative to surgical interventions in patients with small renal masses (SRMs), evidence regarding its oncological efficacy is still debated. We aimed to evaluate oncological outcomes for patients with SRMs who underwent AS in comparison to surgical interventions. METHODS: In April 2024, PubMed, Scopus, and Web of Science were queried for comparative studies evaluating AS in patients with SRMs (PROSPERO: CRD42024530299). The primary outcomes were overall (OS) and cancer-specific survival (CSS). A random-effects model was used for quantitative analysis. KEY FINDINGS AND LIMITATIONS: We identified eight eligible studies (three prospective, four retrospective, and one study based on Surveillance, Epidemiology and End Results [SEER] data) involving 4947 patients. Pooling of data with the SEER data set revealed significantly higher OS rates for patients receiving surgical interventions (hazard ratio [HR] 0.73; p = 0.007), especially partial nephrectomy (PN; HR 0.62; p < 0.001). However, in a sensitivity analysis excluding the SEER data set there was no significant difference in OS between AS and surgical interventions overall (HR 0.84; p = 0.3), but the PN subgroup had longer OS than the AS group (HR 0.6; p = 0.002). Only the study based on the SEER data set showed a significant difference in CSS. The main limitations include selection bias in retrospective studies, and classification of interventions in the SEER database study. CONCLUSIONS AND CLINICAL IMPLICATIONS: Patients treated with AS had similar OS to those who underwent surgery or ablation, although caution is needed in interpreting the data owing to the potential for selection bias and variability in AS protocols. Our review reinforces the need for personalized shared decision-making to identify patients with SRMs who are most likely to benefit from AS. PATIENT SUMMARY: For well-selected patients with a small kidney mass suspicious for cancer, active surveillance seems to be a safe alternative to surgery, with similar overall survival. However, the evidence is still limited and more studies are needed to help in identifying the best candidates for active surveillance.

• MeSH
• Ablation Techniques methods   MeSH
• Humans MeSH
• Kidney Neoplasms * surgery   mortality   pathology   MeSH
• Nephrectomy * methods   MeSH
• Watchful Waiting * MeSH
• Tumor Burden MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Comparative Study MeSH
• Systematic Review MeSH

BACKGROUNDS: SWI/SNF complexes represent a family of multi-subunit chromatin remodelers that are affected by alterations in >20% of human tumors. While mutations of SWI/SNF genes are relatively uncommon in prostate cancer (PCa), the literature suggests that deregulation of various subunits plays a role in prostate tumorigenesis. To assess SWI/SNF functions in a clinical context, we studied the mutually exclusive, paralogue accessory subunits SMARCD1, SMARCD2, and SMARCD3 that are included in every known complex and are sought to confer specificity. METHODS: Performing immunohistochemistry (IHC), the protein levels of the SMARCD family members were measured using a tissue microarray (TMA) comprising malignant samples and matching healthy tissue of non-metastatic PCa patients (n = 168). Moreover, IHC was performed in castration-resistant tumors (n = 9) and lymph node metastases (n = 22). To assess their potential role as molecular biomarkers, SMARCD1 and SMARCD3 protein levels were correlated with clinical parameters such as T stage, Gleason score, biochemical recurrence, and progression-free survival. RESULTS: SMARCD1 protein levels in non-metastatic primary tumors, lymph node metastases, and castration-resistant samples were significantly higher than in benign tissues. Likewise, SMARCD3 protein expression was elevated in tumor tissue and especially lymph node metastases compared to benign samples. While SMARCD1 levels in primary tumors did not exhibit significant associations with any of the tested clinical parameters, SMARCD3 exhibited an inverse correlation with pre-operative PSA levels. Moreover, low SMARCD3 expression was associated with progression to metastasis. CONCLUSIONS: In congruence with previous literature, our results implicate that both SMARCD1 and SMARCD3 may exhibit relevant functions in the context of prostate tumorigenesis. Moreover, our approach suggests a potential role of SMARCD3 as a novel prognostic marker in clinically non-metastatic PCa.

• MeSH
• Chromosomal Proteins, Non-Histone * genetics   metabolism   MeSH
• Immunohistochemistry MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Recurrence, Local pathology   metabolism   genetics   MeSH
• Lymphatic Metastasis MeSH
• Biomarkers, Tumor * genetics   metabolism   MeSH
• Prostatic Neoplasms, Castration-Resistant pathology   genetics   metabolism   MeSH
• Prostatic Neoplasms * pathology   metabolism   genetics   MeSH
• Prognosis MeSH
• Aged MeSH
• Neoplasm Grading MeSH
• Transcription Factors genetics   metabolism   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with patients having unresectable or metastatic disease at diagnosis, with poor prognosis and very short survival. Given that genetic variation within autophagy-related genes influences autophagic flux and susceptibility to solid cancers, we decided to investigate whether 55,583 single nucleotide polymorphisms (SNPs) within 234 autophagy-related genes could influence the risk of developing PDAC in three large independent cohorts of European ancestry including 12,754 PDAC cases and 324,926 controls. The meta-analysis of these populations identified, for the first time, the association of the BIDrs9604789 variant with an increased risk of developing the disease (ORMeta = 1.31, p = 9.67 × 10-6). We also confirmed the association of TP63rs1515496 and TP63rs35389543 variants with PDAC risk (OR = 0.89, p = 6.27 × 10-8 and OR = 1.16, p = 2.74 × 10-5). Although it is known that BID induces autophagy and TP63 promotes cell growth, cell motility and invasion, we also found that carriers of the TP63rs1515496G allele had increased numbers of FOXP3+ Helios+ T regulatory cells and CD45RA+ T regulatory cells (p = 7.67 × 10-4 and p = 1.56 × 10-3), but also decreased levels of CD4+ T regulatory cells (p = 7.86 × 10-4). These results were in agreement with research suggesting that the TP63rs1515496 variant alters binding sites for FOXA1 and CTCF, which are transcription factors involved in modulating specific subsets of regulatory T cells. In conclusion, this study identifies BID as new susceptibility locus for PDAC and confirms previous studies suggesting that the TP63 gene is involved in the development of PDAC. This study also suggests new pathogenic mechanisms of the TP63 locus in PDAC.

• MeSH
• Autophagy * genetics   MeSH
• White People genetics   MeSH
• Carcinoma, Pancreatic Ductal * genetics   pathology   MeSH
• Forkhead Transcription Factors MeSH
• Genetic Predisposition to Disease * MeSH
• Hepatocyte Nuclear Factor 3-alpha genetics   metabolism   MeSH
• Polymorphism, Single Nucleotide * MeSH
• Cohort Studies MeSH
• Humans MeSH
• Biomarkers, Tumor * genetics   MeSH
• Tumor Suppressor Proteins * genetics   MeSH
• Pancreatic Neoplasms * genetics   pathology   MeSH
• Case-Control Studies MeSH
• Transcription Factors genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH

PURPOSE OF REVIEW: This review explores the design and endpoints of perioperative platforms in clinical trials for muscle-invasive bladder cancer (MIBC). RECENT FINDINGS: The choice of clinical trial design in perioperative platforms for MIBC must align with specific research objectives to ensure robust and meaningful outcomes. Novel designs in perioperative platforms for MIBC integrate bladder-sparing approaches. Primary endpoints such as pathological complete response and disease-free survival are highlighted for their role in expediting trial results in perioperative setting. Incorporating patient-reported outcomes is important to inform healthcare decision makers about the outcomes most meaningful to patients. Given the growing body of evidence, potential biomarkers, predictive and prognostic tools should be considered and implemented when designing trials in perioperative platforms for MIBC. SUMMARY: Effective perioperative platforms for MIBC trials are critical in enhancing patient outcomes. The careful selection and standardization of study designs and endpoints in the perioperative platform are essential for the successful implementation of new therapies and the advancement of personalized treatment approaches in MIBC.

• MeSH
• Cystectomy methods   adverse effects   MeSH
• Neoplasm Invasiveness * MeSH
• Clinical Trials as Topic MeSH
• Humans MeSH
• Urinary Bladder Neoplasms * surgery   pathology   therapy   mortality   MeSH
• Perioperative Care methods   standards   MeSH
• Endpoint Determination MeSH
• Treatment Outcome MeSH
• Research Design MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

OBJECTIVE: To investigate the influence of statins on the survival outcomes of patients with non-muscle-invasive bladder cancer (NMIBC) treated with adjuvant intravesical bacille Calmette-Guérin (BCG) immunotherapy. PATIENTS AND METHODS: A retrospective cohort of consecutive patients with NMIBC who received intravesical BCG therapy from 2001 to 2020 and statins prescription were identified. Overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and progression-free survival (PFS) were analysed between the Statins Group vs No-Statins Group using Kaplan-Meier method and multivariable Cox regression. RESULTS: A total of 2602 patients with NMIBC who received intravesical BCG were identified. The median follow-up was 11.0 years. On Kaplan-Meier analysis, the Statins Group had significant better OS (P < 0.001), CSS (P < 0.001), and PFS (P < 0.001). Subgroup analysis indicated statins treatment started before BCG treatment had better CSS (P = 0.02) and PFS (P < 0.01). Upon multivariable Cox regression analysis, the 'statins before BCG' group was an independent protective factor for OS (hazard ratio [HR] 0.607, 95% confidence interval [CI] 0.514-0.716), and CSS (HR 0.571, 95% CI 0.376-0.868), but not RFS (HR 0.885, 95% CI 0.736-1.065), and PFS (HR 0.689, 95% CI 0.469-1.013). CONCLUSIONS: Statins treatment appears to offer protective effects on OS and CSS for patients with NMIBC receiving adjuvant intravesical BCG.

• MeSH
• Adjuvants, Immunologic therapeutic use   MeSH
• Administration, Intravesical MeSH
• BCG Vaccine * therapeutic use   MeSH
• Neoplasm Invasiveness MeSH
• Middle Aged MeSH
• Humans MeSH
• Non-Muscle Invasive Bladder Neoplasms MeSH
• Urinary Bladder Neoplasms * drug therapy   pathology   mortality   MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors * therapeutic use   MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

PURPOSE: Docetaxel resistance is a significant obstacle in the treatment of prostate cancer (PCa), resulting in unfavorable patient prognoses. Intratumoral heterogeneity, often associated with epithelial-to-mesenchymal transition (EMT), has previously emerged as a phenomenon that facilitates adaptation to various stimuli, thus promoting cancer cell diversity and eventually resistance to chemotherapy, including docetaxel. Hence, understanding intratumoral heterogeneity is essential for better patient prognosis and the development of personalized treatment strategies. METHODS: To address this, we employed a high-throughput single-cell flow cytometry approach to identify a specific surface fingerprint associated with docetaxel-resistance in PCa cells and complemented it with proteomic analysis of extracellular vesicles. We further validated selected antigens using docetaxel-resistant patient-derived xenografts in vivo and probed primary PCa specimens to interrogate of their surface fingerprint. RESULTS: Our approaches revealed a 6-molecule surface fingerprint linked to docetaxel resistance in primary PCa specimens. We observed consistent overexpression of CD95 (FAS/APO-1), and SSEA-4 surface antigens in both in vitro and in vivo docetaxel-resistant models, which was also observed in a cell subpopulation of primary PCa tumors exhibiting EMT features. Furthermore, CD95, along with the essential enzymes involved in SSEA-4 synthesis, ST3GAL1, and ST3GAL2, displayed a significant increase in patients with PCa undergoing docetaxel-based therapy, correlating with poor survival outcomes. CONCLUSION: In summary, we demonstrate that the identified 6-molecule surface fingerprint associated with docetaxel resistance pre-exists in a subpopulation of primary PCa tumors before docetaxel treatment. Thus, this fingerprint warrants further validation as a promising predictive tool for docetaxel resistance in PCa patients prior to therapy initiation.

• MeSH
• Drug Resistance, Neoplasm * MeSH
• Docetaxel * pharmacology   therapeutic use   MeSH
• Epithelial-Mesenchymal Transition drug effects   MeSH
• Humans MeSH
• Mice MeSH
• Cell Line, Tumor MeSH
• Prostatic Neoplasms * pathology   drug therapy   metabolism   MeSH
• Antineoplastic Agents pharmacology   therapeutic use   MeSH
• Xenograft Model Antitumor Assays MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Zobrazovací metoda pozitronové tomografie s výpočetní tomografií (positron emission tomography / computed tomography, PET/CT) s využitím prostatického specifického membránového antigenu (prostate-specific membrane antigen, PSMA), PSMA PET/CT, představuje zásadní pokrok v diagnostice a léčbě karcinomu prostaty. V oblasti diagnostiky nabízí výrazně vyšší senzitivitu a specificitu oproti konvenčním metodám, zejména při primárním stagingu, perzistenci prostatického specifického antigenu (PSA) po radikální prostatektomii a biochemickém relapsu po radikální léčbě. Stále častěji se uplatňuje i v rámci teranostiky, tedy propojení diagnostiky a cílené radionuklidové terapie u pacientů s metastazujícím kastračně rezistentním karcinomem prostaty. Klinické studie fáze III (např. VISION, TheraP, PSMAfore) prokázaly významný přínos PSMA značeného luteciem-177 (177Lu-PSMA-617) z hlediska přežití i kvality života ve srovnání s jinými léčebnými možnostmi. Využití PSMA PET/CT tak výrazně přispívá k personalizovanému přístupu k pacientům a mění zavedené algoritmy diagnostiky a léčby karcinomu prostaty.

The imaging modality prostate specific membrane antigen positron emission tomography / computed tomography (PSMA PET/CT) represents a major advancement in the diagnosis and treatment of prostate cancer. In diagnostics, it offers significantly higher sensitivity and specificity compared to conventional methods, particularly in primary staging, persistent prostate specific antigen (PSA) following radical prostatectomy, and biochemical recurrence after radical treatment. It is increasingly utilized in theranostics, which combines diagnostic imaging with targeted radionuclide therapy in patients with metastatic castration-resistant prostate cancer. Phase III clinical trials (e.g. VISION, TheraP, PSMAfore) have demonstrated a significant benefit of 177Lu-PSMA-617 in terms of survival and quality of life compared to other treatment options. The use of PSMA PET/CT thus contributes substantially to personalized patient care and is reshaping established diagnostic and therapeutic algorithms in prostate cancer management.

Zachování funkčního hrtanu a dosažení dlouhodobé remise je základním postulátem léčby pacientů s maligními nádory hrtanu, a to i pokročilých stadií. Rozvíjeny jsou proto nechirurgické protokoly léčby a hrtan zachovávající chirurgické postupy. Totální laryngektomie je historicky základní výkon laryngeální chirurgie, jehož význam s rozvojem výše uvedených postupů klesá. Přesto jsou stále skupiny nemocných, kteří mohou profitovat z jejího provedení. Rozhodující jsou lokální i celkové charakteristiky tumoru a pacienta. Velikost tumoru, destrukce a nefunkčnost struktur hrtanu, infiltrace štítné chrupavky včetně zevního perichondria případně extralaryngeální propagace jsou faktory, kdy je předpokládaný efekt nechirurgické léčby nedostatečný nebo by vedl k zachování nefunkčního hrtanu. K výkonu také indikujeme pacienty, u nichž pro kontraindikace nemůžeme využít orgán šetřicí protokoly nebo je vysoké riziko komplikací této léčby. Totální laryngektomie má stále své místo v rámci záchranné chirurgie a u specifických malignit, u nichž není efektivní nechirurgická léčba (nejčastěji sarkomy). V této práci je představen náš pohled na indikaci totální laryngektomie v současnosti, který vychází z doporučených postupů a zkušeností s multidisciplinárním klinickým rozhodováním.

Preserving a functional larynx and achieving long-term control is the basic postulate of treating patients with malignant tumors of the larynx, even in advanced stages. Therefore, non-surgical treatment protocols and larynx-preserving surgical procedures are preferred. Total laryngectomy is historically the basic procedure of laryngeal surgery still with the best survival outcomes in advanced laryngeal cancer, but with significantly lower quality of life following surgery. Nevertheless, there are still groups of patients who can benefit from this implementation. Local and overall characteristics are important for the recommendation of treatment. Tumor size, destruction and dysfunction of laryngeal structures, infiltration of the thyroid cartilage including the external perichondrium, or extralaryngeal extent are local factors when the expected effect of non-surgical treatment is insufficient or would only lead to the preservation of a non-functional larynx. We also recommend patients in whom organ-saving protocols are not suitable due to contraindications or there is a high risk of complications. Total laryngectomy still has its place as part of salvage surgery in failure of non-surgical treatment and for specific malignancies for which a non-surgical approach is not effective (most often sarcomas). We present our current view on the indications of total laryngectomy, which is based on international recommendations and our experience with multidisciplinary clinical decision-making.

• MeSH
• Laryngectomy * history   methods   statistics & numerical data   MeSH
• Larynx, Artificial MeSH
• Larynx surgery   pathology   MeSH
• Organ Sparing Treatments methods   MeSH
• Humans MeSH
• Laryngeal Neoplasms surgery   diagnosis   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH