Despite best clinical management, patients with meningiomas frequently experience tumor recurrence. During recent decades, efforts have been made to improve the prognostic stratification of meningiomas by incorporating molecular data. A subgroup of tumors harboring a homozygous CDKN2A deletion was identified, and a higher risk of tumor progression was observed, suggesting the potential use of cyclin-dependent kinases as biomarkers. In this retrospective single-center study, the immunohistochemical staining for the cyclin-dependent kinases p16, phosphoRB1 (pRB1), CDK4 and CDK6 was analyzed in 1751 paraffin-embedded meningioma samples. For the assessment of p16, CDK4 and CDK6, a semi-quantitative score was applied, whereas an automated quantification tool was used for pRB1. The distribution and association with histopathological results, clinical data and progression-free survival (PFS)—defined by radiographic tumor recurrence—were assessed. Of all meningioma samples, 14.9

Background Biomarkers are desirable to characterize individual tumors and to personalize multimodal treatment in locally advanced rectal cancer patients. In this regard, monitoring of High Mobility Group Box 1 (HMGB1) protein in blood samples is of interest in radiotherapy as HMGB1 is a consensus marker for immunogenic cell death (ICD) during anticancer treatment.Patients and methods Plasma levels of HMGB1 were monitored weekly during long-term neoadjuvant chemoradiotherapy in 19 patients with locally advanced rectal cancer. HMGB1 levels were correlated with outcome and tumor volumes in magnetic resonance imaging (MRI) pre-therapeutically as well as in week 2 and week 5 of treatment. Furthermore, the association with circulating cell-free tumor DNA (ctDNA) was evaluated.Results Higher pre-therapeutic levels of HMGB1 correlated positively with bigger initial MRI volumes and higher allele frequencies of ctDNA in the corresponding baseline blood sample. Courses of HMGB1 during treatment were variable and mostly undulating. Predominant ascent was observed in four patients who showed poor pathologic response. Declining levels in week 2 / 3 were associated with bigger percentage decrease of MRI tumor volume at the end of week 2.Conclusions HMGB1 seems to be associated mostly with tumor burden as indicated by correlation with MRI volumes and ctDNA levels, rather than ICD induction or side effects as previously reported. Changes during treatment might predict clinical disease course.

Postoperative radiotherapy following surgical stabilization in patients with bone metastases is commonly recommended. The aim of the study was to validate existing prognostic scores and parameters for local control and survival in patients with bone metastases treated with surgical resection with or without radiotherapy. This retrospective single-institution study analyzed consecutive patients with bone metastases undergoing resection and/or stabilization mostly due to pathologic or impending fractures (with or without spinal compression). Additive radiotherapy was considered the standard of care. Various fractionated radiotherapy regimens have been applied; equivalent dose in 2 Gy fractions (EQD2) has been calculated to enable comparison between fractionations. Prognostic factors influencing local progression-free survival (LPFS) and overall survival (OS) were evaluated. The median follow-up was 9 months (range 1–121 months). A total of 142 patients were included. Most patients underwent surgery due to pathologic (n = 86, 60.6

We report long-term outcomes from the phase 3 SAKK 09/10 trial that randomly assigned men with biochemical progression after radical prostatectomy to conventional-dose (64 Gy) or dose-intensified (70 Gy) salvage radiotherapy (SRT) to the prostate bed without hormonal therapy. The primary endpoint was freedom from biochemical progression (FFBP). Secondary endpoints included clinical progression-free survival (PFS), time to hormonal treatment, overall survival (OS), and late toxicity. Between February 2011 and April 2014, 350 patients were randomly assigned (175 per arm). Median prostate-specific antigen (PSA) at randomization was 0.3 ng/ml. After median follow-up of 8.6 yr, median FFBP was 8.7 yr (95% confidence interval [CI] 7.1-not reached [NR]) after 64 Gy and 8.7 yr (95% CI 6.7-NR) after 70 Gy (log-rank p = 0.87), with a hazard ratio of 1.03 (95% CI 0.75-1.41). There was no significant difference in clinical PFS, time to hormonal treatment, or OS. While late genitourinary toxicity did not significantly differ between the arms, late grade 2 and 3 gastrointestinal toxicity was more frequent with 70 Gy (p = 0.015). After long-term follow-up dose-intensified SRT was not superior to conventional-dose SRT, but was associated with a higher rate of late grade ≥2 gastrointestinal toxicity. PATIENT SUMMARY: The optimal radiotherapy dose for patients who have higher levels of tumor markers after surgery for prostate cancer is unclear. Our long-term follow-up confirms that a higher dose only increases the chances of gastrointestinal side effects without providing any benefits to the patient. This trial is registered on ClinicalTrials.gov as NCT01272050.

Myxoid liposarcoma (MLPS) is a rare subtype of soft tissue sarcoma. This entity has a specific clinical behavior, characterized with a distinct pattern of hematogenous spread, as well as with a unique radiosensitivity and chemosensitivity. Oncologic results, metastatic patterns and treatment response after multimodal therapy were evaluated in a unicentric patient cohort. Patients with myxoid liposarcoma were retrospectively analyzed in a single institution analysis (n = 31). Oncologic outcomes were evaluated in 28 patients with localized MLPS treated with multimodal therapy in curative intent. Metastatic pattern was analyzed in additional 3 patients with initially metastatic disease. In patients treated with concomitant MR-guided hyperthermia in the preoperative setting (n = 7), tumor size response was evaluated longitudinally during radio(-chemo)therapy in thermometry MRIs and before surgery (based on preoperative imaging). The median follow-up was 4.1 ± 1.0 years. The most common anatomic localization was the lower extremity (78.6

Penile squamous cell carcinoma (PeCa) is a rare malignancy with poor outcomes in pN+ cases. Prognosis is particularly poor in patients with extranodal extension (ENE) or pelvic lymph node (PLN) involvement. Despite advancements in surgical techniques, the role of adjuvant therapy (AT)-including radiotherapy (ART), chemotherapy (ACT), and chemoradiotherapy (ACRT)-following radical lymphadenectomy (LAD) remains undefined, and optimal strategies are yet to be established. This review evaluates the impact of AT on survival and recurrence in pN+ PeCa, assesses associated toxicities, and explores personalized treatment approaches. A systematic search of PubMed, Web of Science, Cochrane Library, and Scopus identified studies published between January 2000 and December 2024. Eligible studies focused on AT after LAD, including radiotherapy, chemotherapy, targeted therapies, or combination regimens. ART improves locoregional control in patients with ≥ 2 positive inguinal lymph nodes, particularly in HPV+ tumors. ACT with TIP or TPF regimens enhances disease-free and overall survival in high-risk pN+ patients, including those with PLN involvement. ACRT provides modest benefits in ENE cases but is associated with significant toxicity. Emerging biomarkers, such as HPV status and p53 mutations, show potential for predicting treatment response, while novel agents and immunotherapies represent promising investigational areas. AT improves outcomes in pN+ PeCa but requires individualized strategies based on risk factors and molecular profiles. Prospective, collaborative studies are essential to refine AT protocols, reduce toxicities, and integrate immunotherapies, targeted agents, and biomarkers into treatment algorithms. Multidisciplinary management and centralized care are critical for optimizing outcomes in this malignancy.

BACKGROUND AND PURPOSE:Primary central nervous system lymphoma (PCNSL) is a rare but aggressive disease. The application of radiotherapy (RT) as part of treatment usually involved whole-brain radiotherapy (WBRT). Focal radiotherapy (fRT) might be locally active, but comparative outcome data is lacking. MATERIALS AND METHODS:Data from a multicenter registry of the German Society of Radiation Oncology's Neuro-Radio-Oncology Working Group (DEGRO AG-NRO) was analyzed. Patients treated for PCNSL between 2007 and 2023 who received RT at any stage of their disease were included. Kaplan-Meier and Cox proportional hazards regression analyses were conducted to compare survival between focal (fRT) and whole-brain radiotherapy (WBRT). RESULTS:Survival data of 151 patients from eight centers were available. The median age at diagnosis was 66.5 years, and the median Eastern Cooperative Oncology Group Performance Status Scale (ECOG PS) was 2. Eighteen percent of patients (n = 27) received primary RT, 33 % (n = 49) consolidation RT, and 49 % (n = 73) RT for recurrent disease. Median overall survival (OS) from diagnosis was 24.1 months (95 % CI: 14.7-33.4), and median survival after RT was 7.2 months (95 % CI: 4.5-10.0). In patients treated with fRT (n = 28) median OS was 67.6 months (95 % CI: 35.7-99.6) compared to 20.1 months after WBRT (n = 123, 95 % CI: 10.5-29.8) (HR = 0.5, p = 0.016). Median survival after RT was also longer with fRT (44.0 months, 95 % CI: 5.9-82.1) than with WBRT (5.8 months, 95 % CI: 3.2-8.4) (HR = 0.5, p = 0.017). In recurrent disease median PFS after use of fRT was 3.8 months, compared to 3.0 months after WBRT (p = 0.164). After fRT, in 16/28 (39 %) patients tumor progression was observed (2/16 in-field, 3/16 out-field, 3/16 mixed, 8/16 unknown). In multivariate Cox-regression analysis, histology other than diffuse large B-cell lymphoma (HR = 0.345, p < 0.01) and fRT (HR = 0.518, p < 0.05) remained independently associated with improved OS. CONCLUSION:fRT may be a beneficial treatment option for patients with PCNSL and needs to be studied further in prospective clinical trials.

Für die Therapie des metastasierten hormonsensitiven und des kastrationsresistenten Prostatakarzinoms finden neben der medikamentösen Tumortherapie auch multimodale, interdisziplinäre Therapiekonzepte immer mehr Berücksichtigung. Für die Therapieentscheidung sind zahlreiche Faktoren relevant. Dieser Artikel beleuchtet die uroonkologische Therapiefindung für das metastasierte Prostatakarzinom (PC) aus medikamentöser und strahlentherapeutischer Sichtweise.

In der Primärtherapie des Prostatakarzinoms stehen verschiedene Stadienadaptierte radioonkologische Therapiekonzepte zur Verfügung, teilweise kombiniert mit einer antiandrogenen Therapie (ADT). Fortschritte in der bildgesteuerten (IGRT) und der intensitätsmodulierten Strahlentherapie (IMRT) und der Brachytherapie ermöglichen die Applikation hoher Strahlendosen und damit eine hohe Tumorkontrolle bei gleichzeitig günstigem Nebenwirkungsprofil.

Background. Little is known about the growth dynamics of untreated glioblastoma and its possible influence on postoperative survival. Our aim was to analyze a possible association of preoperative growth dynamics with postoperative survival. Methods. We performed a retrospective analysis of all adult patients surgically treated for newly diagnosed glioblastoma at our center between 2010 and 2020. By volumetric analysis of data of patients with availability of >= 3 preoperative sequential MRI, a growth pattern was aimed to be identified. Main inclusion criterion for further analysis was the availability of two preoperative MRI scans with a slice thickness of 1 mm, at least 7 days apart. Individual growth rates were calculated. Association with overall survival (OS) was examined by multivariable. Results. Out of 749 patients screened, 13 had >= 3 preoperative MRI, 70 had 2 MRI and met the inclusion criteria. A curve estimation regression model showed the best fit for exponential tumor growth. Median tumor volume doubling time (VDT) was 31 days, median specific growth rate (SGR) was 2.2% growth per day. SGR showed negative correlation with tumor size (rho = -0.59, P < .001). Growth rates were dichotomized according to the median SGR.OS was significantly longer in the group with slow growth (log-rank: P = .010). Slower preoperative growth was independently associated with longer overall survival in a multivariable Cox regression model for patients after tumor resection. Conclusions. Especially small lesions suggestive of glioblastoma showed exponential tumor growth with variable growth rates and a median VDT of 31 days. SGR was significantly associated with OS in patients with tumor resection in our sample.

Background:The PRIDE trial (NOA-28; ARO-2024-01; AG-NRO-06; NCT05871021) is designed to determine whether a dose escalation with 75.0 Gy in 30 fractions can enhance the median overall survival (OS) in patients with methylguanine methyltransferase (MGMT) promotor unmethylated glioblastoma compared to historical median OS rates, while being isotoxic to historical cohorts through the addition of concurrent bevacizumab (BEV). To ensure protocol-compliant irradiation planning with all study centers, a dummy run was planned and the plan quality was evaluated. Methods:A suitable patient case was selected and the computed tomography (CT), magnetic resonance imaging (MRI) and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) contours were made available. Participants at the various intended study sites performed radiation planning according to the PRIDE clinical trial protocol. The treatment plans and dose grids were uploaded as Digital Imaging and Communications in Medicine (DICOM) files to a cloud-based platform. Plan quality and protocol adherence were analyzed using a standardized checklist, scorecards and indices such as Dice Score (DSC) and Hausdorff Distance (HD). Results:Median DSC was 0.89, 0.90, 0.88 for PTV60, PTV60ex (planning target volume receiving 60.0 Gy for the standard and the experimental plan, respectively) and PTV75 (PTV receiving 75.0 Gy in the experimental plan), respectively. Median HD values were 17.0 mm, 13.9 mm and 12.1 mm, respectively. These differences were also evident in the volumes: The PTV60 had a volume range of 219.1-391.3 cc (median: 261.9 cc) for the standard plans, while the PTV75 volumes for the experimental plans ranged from 71.5-142.7 cc (median: 92.3 cc). The structures with the largest deviations in Dice score were the pituitary gland (median 0.37, range 0.00-0.69) and the right lacrimal gland (median 0.59, range 0.42-0.78). Conclusions:The deviations revealed the necessity of systematic trainings with appropriate feedback before the start of clinical trials in radiation oncology and the constant monitoring of protocol compliance throw-out the study. Trial registration:NCT05871021.

Background and purpose: The PRIDE trial (NOA-28; ARO-2022-12; NCT05871021) is scheduled to start recruitment in October 2023. Its primary objective is to enhance median overall survival (OS), compared to historical median OS rates, in patients with methylguanine methlyltransferase (MGMT) promotor unmethylated glioblastoma by incorporating isotoxic dose escalation to 75 Gy in 30 fractions. To achieve isotoxicity and counteract the elevated risk of radiation necrosis (RN) associated with dose-escalated regimens, the addition of protective concurrent bevacizumab (BEV) serves as an innovative approach. The current study aims to assess the dosimetric feasibility of the proposed concept. Materials and methods: A total of ten patients diagnosed with glioblastoma were included in this dosimetric analysis. Delineation of target volumes for the reference plans adhered to the ESTRO-EANO 2023 guideline. The experimental plans included an additional volume for the integrated boost. Additionally, the 60 Gy-volume was reduced by using a margin of 1.0 cm instead of 1.5 cm. To assess the risk of symptomatic RN, the Normal Tissue Complication Probability (NTCP) was calculated and compared between the reference and experimental plans. Results: Median NTCP of the reference plan (NTCPref) and of the experimental plan (NTCPex) were 0.24 (range 0.11–0.29) and 0.42 (range 0.18–0.54), respectively. NTCPex was a median of 1.77 (range 1.60–1.99) times as high as the NTXPref. In a logarithmic comparison, the risk of RN is enhanced by a factor of median 2.00 (range 1.66–2.35). The defined constraints for the organs at risk were feasible. Conclusion: When considering the potential protective effect of BEV, which we hypothesized might reduce the risk of RN by approximately two-fold, achieving isotoxicity with the proposed dose-escalated experimental plan for the PRIDE trial seems feasible.