Background:Meningiomas are the most common primary brain tumors in adults, typically managed with surgery, stereotactic radiosurgery (SRS), or hypofractionated stereotactic radiotherapy (hFSRT). While local control rates are high, volumetric regression dynamics and radiobiological parameters remain underexplored. This study evaluates meningioma regression after SRS and hFSRT and estimates the α/β ratio to refine radiotherapy strategies. Materials and methods:A retrospective analysis included 150 patients with intracranial meningiomas treated between 2010-2021. Volumetric assessment was performed for 62 lesions (1-10 cm3) treated with SRS (1 × 14 Gy) or hFSRT (3 × 7 Gy, 5 × 5 Gy, 5 × 6 Gy). Tumor volumes were measured pre-treatment and during follow-up using 3D MRI reconstruction. Radiobiological modeling and α/β calculation employed linear-quadratic (LQ) and linear-quadratic-linear (LQ-L) models. Results:SRS achieved significantly faster regression, with tumors shrinking by 32.7% at 2 years and 67.4% at 4 years, compared with 15.3% and 31.7% for hFSRT (p = 0.003). The α/β ratio was calculated at 3.15 Gy [95% confidence interval (CI): 3.07-3.23], refining understanding of meningioma radiobiology. Local control reached 91.3%, with comparable outcomes for SRS (91.4%) and hFSRT (91.3%). Symptomatic complications included brain edema (7.9%) and radiation necrosis (2.6%). Conclusion:CyberKnife SRS and hFSRT are effective and safe for meningiomas, though SRS induces faster volumetric regression (19% vs. 9% annual reduction for hFSRT). The α/β ratio of 3.15 Gy provides novel radiobiological insight, supporting more personalized treatment strategies.

OBJECTIVES:To compare ultrasonography (US) and computed tomography (CT) in detecting clear cell renal cell carcinoma (ccRCC) according to tumor stage and mode of presentation. METHODS:We conducted a monocentric cross-sectional study of patients undergoing surgery for renal tumors between 2011 and 2020. Patients were classified by detection mode, imaging modality, histological subtype, and tumor stage. Logistic and linear regression models were used to assess associations adjusted for relevant covariates. RESULTS:Among 804 eligible patients, 576 had ccRCC, of whom 83.3% were detected incidentally. US and CT were used in 52.1% and 47.9% of cases, respectively. Overall detection rates did not differ significantly between modalities (OR 1.08; p = 0.381). However, US was more likely to detect incidental ccRCC at stages I-II (OR 1.26; 95% CI: 1.05-1.52; p = 0.012). Incidental ccRCC was more likely to be detected by US than symptomatic ccRCC (adjusted OR 2.32; p = 0.001). Mean age at diagnosis increased with tumor stage, with an adjusted age-stage gradient of 3.03 years between stage III-IV and stage I-II ccRCC (p = 0.002). CONCLUSIONS:US was associated with incidental early-stage ccRCC detection. The observed age-stage gradient provides hypothesis-generating evidence compatible with time-dependent ccRCC progression.

BACKGROUND: HPV-negative head and neck squamous cell carcinoma (HNSCC) has a poorer prognosis than HPV-positive tumours, yet real-world outcomes remain understudied. This study analyses a multicentre cohort of HPV-negative HNSCC patients, including those over 65 years of age. MATERIALS AND METHODS: This retrospective study included HPV-negative HNSCC patients treated with definitive radiotherapy (RT) or chemoradiotherapy (CRT) between 2015 and 2020. RT protocols included standard fractionation (70 Gy, 35 fractions), simultaneous integrated boost (69.96 Gy, 33 fractions), or concomitant boost (72.5 Gy, 50 fractions). RESULTS: Among 225 patients (62 over 65 years), 138 (61%) received CRT. Local progression occurred in 83 (37%), and 177 (79%) died. Median overall survival (OS) was 23.1 months, with 3-year OS and local control (LC) rates of 37% and 35%, respectively. ECOG predicted outcomes (p < 0.001 for OS, p = 0.040 for LC), while comorbidity burden and disease stage were significant only for OS (p < 0.001 and p = 0.006). CRT improved OS over RT alone (p = 0.059). Older patients more often had hypopharyngeal/laryngeal tumours (p = 0.033), received CRT less frequently (29% vs. 74%, p < 0.001), and chemotherapy did not affect outcomes. CONCLUSIONS: Real-world outcomes for inoperable HPV-negative HNSCC remain poor. Personalized approaches are needed to improve care for this challenging population.

693 Background: Platinum-based chemotherapy followed by avelumab 1L maintenance treatment for patients with nonprogressive disease is a standard of care in la/mUC. In the Czech Republic, following EU approval, there is a requirement to provide real-world data for “highly innovative medicinal products” and obtaining reimbursement requires registry creation for data collection. Interim results from a retrospective analysis of a national reimbursement registry for avelumab 1L maintenance treatment in the Czech Republic were reported previously; here, we report longer-term results. Methods: Registry data were collected by the Health Insurance Bureau for patients with la/mUC receiving avelumab 1L maintenance treatment between Oct 2021 and Jan 2024. The primary endpoint was overall survival (OS) from start of avelumab 1L maintenance (index date); secondary endpoints included progression-free survival (PFS) and safety. Descriptive statistics were used to analyze the data. OS, PFS, and probability of ongoing response were estimated using the Kaplan-Meier method. Results: Overall, 107 patients with la/mUC were treated with avelumab 1L maintenance (77 male/30 female). 1L platinum-based chemotherapy was cisplatin based in 55 patients (51.4%) and carboplatin based in 46 patients (43.0%); 6 patients (5.6%) switched regimens. At the start of avelumab, median age was 72 years (range, 45-92), and 41 patients (38.3%) had visceral metastases. Median follow-up was 8.2 months (range, 0-26.2). Median duration of avelumab treatment was 9.7 months (range, 1.0-29.2). The table shows effectiveness data for avelumab 1L maintenance. Overall, 16 adverse events were reported in 18 patients (16.8%), including 1 patient with a grade 3 infusion reaction and 2 patients with grade 2 diarrhea. At data cutoff (Jan 31, 2024), 88 patients were alive, and 23 had started subsequent treatment. Conclusions: These updated data are generally consistent with results from the JAVELIN Bladder 100 phase 3 trial and other real-world studies, supporting the effectiveness and favorable safety profile of avelumab as 1L maintenance treatment in patients with la/mUC that has not progressed with 1L platinum-based chemotherapy. N=107 Median OS, months Not reached OS rate, % (95% CI) 6 months12 months18 months 93.4 (88.4-98.7)79.3 (69.8-90.2)68.0 (54.6-84.6) Median PFS, months (95% CI) 11.0 (8.6-not estimable) PFS rate, % (95% CI) 6 months12 months18 months 67.8 (58.7-78.2)48.9 (38.8-61.6)39.1 (27.5-55.4) Objective response rate, n (%) Complete response Partial response 29 (27.1)12 (11.2)17 (15.9) Median duration of response, months Not reached Probability of ongoing response, % (95% CI) 6 months12 months18 months 91.1 (80.0-100)80.4 (64.7-99.8)80.4 (64.7-99.8) Median time to response, months 3.4 (1.8-18.2)

Oral squamous cell carcinoma (OSCC), a subset of head and neck cancers, primarily originates in the epithelial tissues of the oral cavity. Despite advancements in treatment, the mortality rate for OSCC remains around 50%, underscoring the urgent need for improved prognostic markers. This review explores the role of the BRCA1 and BRCA2 genes—traditionally associated with breast and ovarian cancers—in the context of OSCC. We discuss the molecular pathways involving BRCA genes, their potential as diagnostics and prognostic biomarkers, and their implications for personalized treatment strategies, including addressing chemotherapy resistance. Furthermore, this review emphasizes the significance of genome stability in cancer progression and examines both current and emerging methodologies for detecting BRCA mutations in OSCC patients. Despite limited prevalence of BRCA mutations in OSCC compared to other cancers, their role in DNA repair and therapeutic response underscores their potential as clinical biomarkers. However, standardized, multicenter studies are still needed to validate their utility in OSCC management. A better understanding of the role of BRCA genes in OSCC could pave the way for more effective therapeutic approaches and improved patient outcomes.

BACKGROUND/PURPOSE:High doses to healthy cardiac substructures (CS) in stereotactic arrhythmia radioablation (STAR) raise concerns regarding potential treatment-induced cardio-toxicity. However, CS contours are not routinely created, hindering the understanding of the CS dose-effect relationships. To address this issue, the alignment of CS contouring was initiated within the STOPSTORM consortium. In this study, we developed and evaluated auto-contouring models trained to delineate CS and major vessels in ventricular tachycardia (VT) patients. METHODS:Eight centres provided standard treatment planning computed tomography (CT) and/or contrast-enhanced CT datasets of 55 VT patients, each including 16 CS. Auto-contouring models were trained to contour either large structures or small structures. Dice Similarity Coefficient (DSC), 95 % Hausdorff distance (HD95) and volume ratio (VR) were used to evaluate model performance versus inter-observer variation (IOV) on seven VT patient test cases. Significant differences were tested using the Mann-Whitney U test. RESULTS:The performance on the four chambers and the major vessels (median DSC: 0.88; HD95: 5.8-19.4 mm; VR: 1.09) was similar to the IOV (median DSC: 0.89; HD95: 4.8-14.0 mm; VR: 1.20). For the valves, model performance (median DSC: 0.37; HD95: 11.6 mm; VR: 1.63) was similar to the IOV (median DSC: 0.41; HD95: 12.4 mm; VR: 3.42), but slightly worse for the coronary arteries (median DSC: 0.33 vs 0.42; HD95: 24.4 mm vs 16.9 mm; VR: 1.93 vs 3.30). The IOV for these small structures remains large despite using contouring guidelines. CONCLUSION:CS auto-contouring models trained on VT patient data perform similarly to IOV. This allows for time-efficient evaluation of CS as possible organs-at-risk.

IntroductionIn the era of personalized medicine and treatment optimization, use of immune biomarkers holds promise for estimating the prognosis of patients with head and neck squamous cell carcinoma (HNSCC) undergoing definitive treatment.MethodsTo evaluate the prognostic potential of immune biomarkers, we conducted a prospective monocentric cohort study with loco-regionally advanced HNSCC patients indicated for definitive radiotherapy/radiochemotherapy at the Department of Oncology, Ostrava University Hospital, Czech Republic, between June 2020 and August 2023. We focused on the expression of programmed death ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs) relative to overall survival (OS) and specific survival rates. Associations between biomarkers and survival rates were assessed by crude and adjusted hazard ratios (cHR, aHR, respectively) obtained from Cox proportional hazards regression.ResultsAmong a total of 55 patients within a median follow-up of 19.7 months, there were 21 (38.2%) all-cause deaths and 15 (27.3%) cancer-related deaths. An overall survival (OS) rate of 61.8% and a disease-specific survival (DSS) rate of 72.7% were recorded. A significant association between survival rates and a ≥10% difference in PD-L1 expression on immune versus tumor cells (high PD-L1IC expression) was documented regardless of the type of analysis (univariate or multivariate). In addition, a stronger association was confirmed for OS and the composite biomarker high PD-L1IC expression along with either median-higher CD8+ TIL count or increased TIL density ≥30%, as indicated by an aHR of 0.08 (95% CI, 0.01 to 0.52) and 0.07 (95% CI, 0.01 to 0.46), respectively. Similar results were demonstrated for other specific survival rates.DiscussionThe early outcomes of the present study suggest the utility of a strong prognostic factor involving a composite biomarker high PD-L1IC expression along with increased TIL density in HNSCC patients undergoing definitive radiotherapy and radiochemotherapy.Trial registrationThe study is registered with Clinicaltrials.gov. – NCT05941676

ImportanceThe failure or success of radical treatment in patients with head and neck squamous cell carcinoma (HNSCC) is associated with many known and unknown factors; hence, there is a search for further prognostic markers to help optimize therapeutic strategy and improve treatment outcomes.ObjectiveTo assess the association of programmed cell death ligand 1 (PD-L1) expression on immune or tumor cells, including its composite expression on both cell types, with overall survival (OS) or specific survival.Data SourcesMEDLINE, Embase, PQSciTech, and HCAPlus databases were systematically searched for cohort studies focused on the prognostic role of PD-L1 expression in patients with HNSCC in curative stages of the disease. Search results generated publications from January 1, 2010, to January 6, 2023.Study SelectionOf 3825 publications identified, a total of 17 cohort studies in the English language met inclusion criteria of this systematic review and meta-analysis. Eligible studies reported adjusted hazard ratios (aHRs) with 95% CIs for the association of PD-L1 expression levels with OS and arbitrary specific survival.Data Extraction and SynthesisData from studies were extracted independently by 2 researchers strictly adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines and recommendations. The risk of bias was assessed using the Quality in Prognosis Studies tool and Newcastle-Ottawa Scale. Pooled effect estimates were obtained using a random-effect or fixed-effect model based on homogeneity of studies.Main Outcomes and MeasuresThe primary outcome was to investigate whether there was an association between PD-L1 expression on immune or tumor cells and OS.ResultsIn 17 cohort studies of the association of PD-L1 expression with survival in 3190 patients with HNSCC, high PD-L1 expression on immune cells was associated with a favorable OS (pooled aHR, 0.39; 95% CI, 0.25-0.59). There was no association between composite PD-L1 expression on immune and tumor cells and OS (pooled aHR, 0.79; 95% CI, 0.55-1.14) or between PD-L1 expressed only on tumor cells and OS (pooled aHR, 1.22; 95% CI, 0.87-1.70). A high level of PD-L1 expression on immune cells was associated with favorable specific survival (pooled aHR, 0.52; 95% CI, 0.38-0.72). There were no interactions between tumor location or type of primary treatment (ie, surgery vs radiotherapy or radiochemotherapy) and the association between PD-L1 expression and OS.Conclusions and RelevanceThis study’s findings suggest that PD-L1 expression on immune cells may serve as a new prognostic biomarker in patients with HNSCC. However, future studies may be warranted to verify this potential role given the limited number of studies on this topic conducted and published to date.

ObjectiveOral squamous cell carcinoma (OSCC) originates from the mucosal lining of the oral cavity. Almost half of newly diagnosed cases are classified as advanced stage IV disease, which makes resection difficult. In this study, we investigated the pathological features and mutation profiles of tumor margins in OSCC.MethodsWe performed hierarchical clustering of principal components to identify distinct patterns of tumor growth and their association with patient prognosis. We also used next-generation sequencing to analyze somatic mutations in tumor and marginal tissue samples.ResultsOur analyses uncovered that the grade of worst pattern of invasion (WPOI) is strongly associated with depth of invasion and patient survival in multivariable analysis. Mutations were primarily detected in the DNA isolated from tumors, but several mutations were also identified in marginal tissue. In total, we uncovered 29 mutated genes, mainly tumor suppressor genes involved in DNA repair including BRCA genes; however none of these mutations significantly correlated with a higher chance of relapse in our medium-size cohort. Some resection margins that appeared histologically normal harbored tumorigenic mutations in TP53 and CDKN2A genes.ConclusionEven histologically normal margins may contain molecular alterations that are not detectable by conventional histopathological methods, but NCCN classification system still outperforms other methods in the prediction of the probability of disease relapse.

Introduction: The incidence of advanced oral cavity and oropharyngeal cancers is generally high. Treatment outcomes for patients, especially those unfit for comprehensive cancer treatment, are unsatisfactory. Therefore, the search for factors to predict response to treatment and increase overall survival is underway. Objective: This study aimed to analyze the presence of 32 HPV genotypes in tumor samples of 34 patients and the effect of HPV status and RAD51 on overall survival. Method: Tumor samples of 34 patients with locally advanced oropharyngeal or oral cavity cancer treated with accelerated radiotherapy in monotherapy were analyzed using reverse hybridization and immunohistochemistry for the presence of HPV and RAD51. Its effect on overall survival was examined. Results: Only two types of HPV were identified—HPV 16 (dominant) and HPV 66 (two samples). The HPV positivity was associated with a borderline insignificant improvement in 2-year (p = 0.083), 5-year (p = 0.159), and overall survival (p = 0.083). Similarly, the RAD51 overexpression was associated with borderline insignificant improvement in 2-year (p = 0.083) and 5-year (p = 0.159) survival. Conclusion: We found no statistically significant differences but detected trends toward improvement in the survival of HPV-positive and RAD51 overexpressing patients unfit for surgical treatment or chemotherapy treated with hyperfractionated radiotherapy. The trends, however, indicate that in a larger group of patients, the effects of these two parameters would likely be statistically significant.

Concurrent chemoradiotherapy represents one of the most used strategies in the curative treatment of patients with head and neck (HNC) cancer. Locoregional failure is the predominant recurrence pattern. Tumor hypoxia belongs to the main cause of treatment failure. Positron emission tomography (PET) using hypoxia radiotracers has been studied extensively and has proven its feasibility and reproducibility to detect tumor hypoxia. A number of studies confirmed that the uptake of FMISO in the recurrent region is significantly higher than that in the non-recurrent region. The escalation of dose to hypoxic tumors may improve outcomes. The technical feasibility of optimizing radiotherapeutic plans has been well documented. To define the hypoxic tumour volume, there are two main approaches: dose painting by contour (DPBC) or by number (DPBN) based on PET images. Despite amazing technological advances, precision in target coverage, and surrounding tissue sparring, radiation oncology is still not considered a targeted treatment if the "one dose fits all" approach is used. Using FMISO and other hypoxia tracers may be an important step for individualizing radiation treatment and together with future radiomic principles and a possible genome-based adjusting dose, will move radiation oncology into the precise and personalized era.

Background:This retrospective analysis evaluated the long-term outcome of spinal stereotactic body radiotherapy (SBRT) treatment for hemangioblastomas.Materials and methods:Between 2010 and 2018, 5 patients with 18 Von-Hippel Lindau-related pial-based spinal hemangioblastomas were treated with fractionated SBRT. After precisely registering images of all relevant datasets, we delineated the gross tumor volume, spinal cord (including intramedullary cysts and/or syrinxes), and past radiotherapy regions. A sequential optimization algorithm was used for dose determinations, and patients received 25-26 Gy in five fractions or 24 Gy in three fractions. On-line image guidance, based on spinal bone structures, and two orthogonal radiographs were provided. The actuarial nidus control, surgery-free survival, cyst/syrinx changes, and progression-free survival were calculated with the Kaplan-Meier method. Toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0.Results:The median follow-up was 5 years after SBRT. Patients displayed one nidus progression, one need of neurosurgery, and two cyst/syrinx progressions directly connected to symptom worsening. No SBRT-related complications or acute adverse radiation-related events occurred. However, one asymptomatic radiological sign of myelopathy occurred two years after SBRT. All tumors regressed; the one-year equivalent tumor volume reduction was 0.2 mL and the median volume significantly decreased by 28% (p = 0.012). Tumor volume reductions were not correlated with the mean (p = 0.19) or maximum (p = 0.16) dose.Conclusions:SBRT for pial-based spinal hemangioblastomas was an effective, safe, viable alternative to neurosurgery in asymptomatic patients. Escalating doses above the conventional dose-volume limits of spinal cord tolerance showed no additional benefit.

Background To report prostate deformation during treatment, based on an analysis of fiducial marker positional differences in a large sample. Material and methods This study included 144 patients treated with prostate stereotactic body radiation therapy after implantation in each of 4 gold fiducial markers (FMs), which were located and numbered consistently. The center of mass of the FMs was recorded for every pair of X-ray images taken during treatment. The distance between each pair of fiducials in the live X-ray images is calculated and compared with the respective distances as determined in the CT volume. The RBE is the difference between these distances. Mean RBE and intrafraction and interfraction RBE were evaluated. The intrafraction and intefraction RBE variability were defined as the standard deviation, respectively, of all RBE during 1 treatment fraction and of the mean daily RBE over the whole treatment course. Results We analyzed 720 treatment fractions comprising 24,453 orthogonal X-ray image acquisitions. We observed a trend to higher RBE related to FM4 (apex) during treatment. The fiducial marker in the prostate apex could not be used in 16% of observations, in which RBE was > 2.5 mm. The mean RBEavg was 0.93 ± 0.39 mm (range 0.32–1.79 mm) over the 5 fractions. The RBEavg was significantly lower for the first and second fraction compared with the others ( P < .001). The interfraction variability of RBEavg was 0.26 ± 0.16 mm (range 0.04–0.74 mm). The mean intrafraction variability of all FMs was 0.45 ± 0.25 mm. The highest Pearson correlation coefficient was observed between FM2 and FM3 (middle left and right prostate) (R = 0.78; P < .001). Every combination with FM4 yielded lower coefficients (range 0.66–0.71; P < .001), indicating different deformation of the prostate apex. Conclusions Ideally, prostate deformation is generally small, but it is very sensitive to rectal and bladder filling. We observed RBE up to 11.3 mm. The overall correlation between FMs was affected by shifts of individual fiducials, indicating that the prostate is not a “rigid” organ. Systematic change of RBE average between subsequent fractions indicates a systematic change in prostate shape.

BACKGROUND:Chronic wounds and their problematic healing is a widely discussed topic in all branches of medicine. In recent years, vacuum therapy appears to be a very successful non-invasive method supporting the healing of these wounds. The aim of this paper is to demonstrate the possibility of utilizing a vacuum system in the orofacial area where other conservative and surgical procedures have failed.CASES:The case reports demonstrate the use of vacuum therapy in non-healing postoperative wounds in cancer patients.CONCLUSION:Vacuum therapy has limited use in the orofacial area, but based on our experience, we can conclude that it has a very positive effect on the healing of chronic wounds. Thanks to this treatment, it was possible to reduce the frequency of dressings and significantly shorten the length of hospital stay. Despite these advantages, however, it is necessary to adhere to the conditions for the application of vacuum treatment.

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