Felix Bock

Background: This study sought to evaluate 30- and 60-day mortality following palliative whole-brain radiotherapy (WBRT) in patients with metastatic non-small cell lung cancer (NSCLC), and to identify readily accessible clinical predictors to guide therapeutic decisions. Methods: This retrospective single-centre study analyzed 392 patients treated with WBRT. Pretreatment factors were assessed using multivariable Cox regression and translated into the six-point Bedside Early Mortality Score (BEMS). The score’s ability to predict mortality within 30 and 60 days of WBRT completion was evaluated using receiver operating characteristic (ROC) analysis and compared with Lung-specific Graded Prognostic Assessment (Lung GPA) and Recursive Partitioning Analysis (RPA). Results: Overall, 115 patients (29.3%) died within 30 days and 178 (45.4%) within 60 days. The score included four parameters readily available during bedside consultation: age ≥65 years, direct inpatient transfer, and abnormal mental status at initiation of WBRT each contributed one point, while impaired mobility contributed three points. Each additional point increased the risk of mortality by 55% (HR 1.55, 95% CI 1.46–1.64). Thirty- and sixty-day mortality according to score were, respectively, 2.2% and 8.5% (0–1 points), 10% and 36.7% (2–3 points), 57.8% and 85.7% (4–5 points), and 85.8% and 90.5% (6 points). Areas under the ROC curve for 30- and 60- day mortality were 0.855 and 0.881, compared with 0.685 and 0.740 for Lung GPA and 0.833 and 0.899 for RPA. Conclusions: The Bedside Early Mortality Score may complement clinical evaluation and support shared decision making in WBRT. Independent validation is required.

Radiotherapy is an established treatment for low-grade primary cutaneous B-cell lymphoma. Recommendations on its use differ internationally, which prompted our group to conduct this analysis. Twenty-two institutions participated in this international study. Patient eligibility required a diagnosis of limited (T1/T2) primary cutaneous marginal zone or follicle center lymphoma treated with radiotherapy between 1995 and 2023. Data were collected retrospectively until February 2024 within the framework of the International Lymphoma Radiation Oncology Group. Overall, 535 patients were analyzed. Predominant locations were the head (40%) and trunk (36%). Radiotherapy had a median dose of 24 Gy in fractions of 2 Gy. Complete responses were observed in 91% at a median time of 3.6 months following radiotherapy. There was no statistically significant difference between treatments ≤4 Gy and >4 Gy for complete or overall response rates (P = .077 and P = .056, respectively). However, there was an inferior duration of local control with ≤4 Gy (5-year local control 73% ± 12% vs 96% ± 2%; P< .001). Radiation dose was the main prognostic factor in the univariate and multivariable Cox analysis; however, higher doses did not translate into an overall survival benefit. Toxicities rarely exceeded grade 2 but were more frequent in the >4 Gy group. Radiotherapy remains an effective treatment option for indolent skin lymphoma with low toxicity. High response rates are observed with low doses of ≤4 Gy. In comparison to conventional doses, these treatments have a shorter duration of local control but a favorable toxicity profile.

Durvalumab consolidation after definitive chemoradiotherapy (CRT) is the standard of care for unresectable stage III non-small cell lung cancer (NSCLC) but real-world data comparing PD-L1-defined subgroups are limited. This retrospective single-centre study analyzed overall survival (OS) and progression-free survival (PFS) in 142 patients with inoperable stage III NSCLC with definitive CRT between 2015 and 2022. All tumours were assessed for PD-L1 expression, including retrospective testing, where required. Patients were assigned into three cohorts: PD-L1-positive with (PD-L1+mD; n = 57) and without (PD-L1+oD; n = 44) durvalumab maintenance and PD-L1-negative without durvalumab (PD-L1−oD; n = 41). Mean follow-up was 44.0 months. Median OS was 27.3, 15.1 and 23.4 months for PD-L1+mD, PD-L1+oD, and PD-L1−oD, respectively. Median PFS was 18.4, 10.5 and 13.4 months for PD-L1+mD, PD-L1+oD, and PD-L1−oD, respectively. OS and PFS were significantly improved with durvalumab in PD-L1-positive patients (p = 0.043 and p = 0.027). PD-L1-negative patients showed no significant OS or PFS differences versus PD-L1+oD. Immunotherapy-related pneumonitis ≥grade 1 was documented in 15.7% patients. In real-world practice, durvalumab improves OS and PFS in PD-L1-positive unresectable stage III NSCLC and its omission appears particularly unfavourable.

Background: This study sought to evaluate overall survival (OS) following palliative radiotherapy in glioblastoma and to identify clinically applicable predictors supporting patient-centred treatment decisions, with exploration of early mortality. Methods: This retrospective single-centre study analysed 169 glioblastoma patients treated with palliative radiotherapy between 2010 and 2025. Baseline clinical and treatment variables were assessed. OS calculated from the last day of radiotherapy was estimated using Kaplan–Meier analysis; predictors were analysed using Cox regression. Early mortality (≤30 and ≤60 days) was evaluated using logistic regression. Results: Median age at diagnosis was 75 years, median Karnofsky Performance Status (KPS) was 60%, with 63% of patients < 70%. Impaired mental status, sensorimotor deficits, and steroid use were observed in 47%, 68%, and 86% of patients, respectively. Median OS was 3.5 months. Impaired mental status (HR 2.25), sensorimotor deficits (HR 1.77), steroid use (HR 1.39), multilobar involvement (HR 1.44), and age (HR 1.03) were independently associated with OS, whereas KPS was not. The rate of early mortality at 30 and 60 days was 18% and 31%. Early mortality analysis indicated impaired mental status and steroid use as indicators of very limited survival. Conclusions: Impaired mental status and steroid use identify patients with limited survival, whereas KPS lacks independent prognostic value in this setting.

To enhance the treatment of tumors that are resistant to radio- and chemotherapy while minimizing the side effects of radiochemotherapy, researchers are continuously seeking new active compounds for use in combination with radiotherapy. Therefore, the aim of our study was to examine the cytotoxic and radiosensitizing effects of an extract from St. John’s Wort (Hypericum perforatum), referred to as HP01, on human epithelial tumor cells in vitro. The growth of MCF-7 (breast carcinoma) and HT-29 (colon carcinoma) cells was examined under the influence of HP01. In combination with radiation, the effects of HP01 on cytotoxicity and long-term survival were assessed using a colony formation assay. The number of DNA double-strand breaks was analyzed using the γH2AX assay, while cell cycle distribution was examined via flow cytometry. A growth-inhibiting and cytotoxic effect was observed for both tumor cell lines starting at a concentration of 10 µg/mL HP01. Treatment with HP01 resulted in an inhibition of clonogenic survival of tumor cells after ionizing radiation (6 Gy). The number of DNA double-strand breaks (DSBs) in tumor cells increased with HP01 treatment, but the repair of radiation-induced DNA DSBs was not affected. Cell cycle analysis revealed that HP01, in addition to radiation, enhanced G2/M arrest in MCF-7 and HT-29 cells. Overall, HP01 not only showed a growth-inhibiting effect but also demonstrated a radiosensitizing effect on human tumor cells for the first time. We conclude that the HP01-induced G2/M accumulation of cells may be the main rationale for the drug-induced radiosensitivity. It is therefore a promising candidate for combined therapy in tumor diseases and warrants further investigation.

Background: Liquid biopsy is a minimally invasive procedure investigating tumor mutations. Methods: In our retrospective study, we investigated whether molecular therapy monitoring of patients receiving neoadjuvant radio(chemo)therapy on a daily routine is possible in 17 patients with locally advanced rectal cancer. Six patients received short-course radiotherapy (5 × 5 Gy) with subsequent surgery, six patients were treated according RAPIDO protocol with short-course radiotherapy followed by chemotherapy (FOLFOX4) and subsequent surgery and five patients received conventional neoadjuvant radiochemotherapy with 5-FU followed by surgery. Response was assessed by Dworak. Liquid biopsies were taken before and immediately after neoadjuvant radiotherapy to isolate and ultradeeply sequence cell free DNA with a panel of 127 genes. Somatic mutations were determined bioinformatically by comparison with normal DNA from leukocytes to distinguish them from germline variants or aging mutations. Results: In 12 patients (71%) at least one somatic mutation was detected. In 8/12 patients a decrease and in 4/12 an increase or mixed response in ctDNA was seen. Statistical correlation between ctDNA analysis and clinical response could not be seen. Conclusion: ctDNA is responding to neoadjuvant therapy and liquid biopsy is easily integrated into a daily routine. As part of translational research this protocol leaves room for further investigations.

To date, oxaliplatin and irinotecan are used in combination with 5-flourouracil (5-FU) for metastatic colorectal cancer. In this study it was tested whether oxaliplatin and irinotecan and their combinations with 5-FU have an enhanced effect when treated simultaneously with ionizing radiation. In addition, it should be compared whether one combination therapy is more effective than the other. Colorectal cancer cells (HT-29) were treated with irinotecan or oxaliplatin, both alone and in combination with 5-FU, and subsequently irradiated. The cell growth, metabolic activity and proliferation of cells were investigated, and the clonogenic survival was determined. Furthermore, the assessment of radiation-induced DNA damage and the influence of the drugs and their combinations on DNA damage repair was investigated. Treatment with irinotecan or oxaliplatin in combination with 5-FU inhibited proliferation and metabolic activity as well as clonogenic survival and the DNA damage repair capacity of the tumor cells. The comparison of oxaliplatin and irinotecan with simultaneous irradiation showed the same effect of both drugs. When oxaliplatin or irinotecan was combined with 5-FU, tumor cell survival was significantly lower than with monotherapy; however, there was no superiority of either combination regimen. Our results have shown that the combination of 5-FU and irinotecan is as effective as the combination of 5-FU with oxaliplatin. Therefore, our data support the use of FOLFIRI as a radiosensitizer.