This report details the reactivation of immune checkpoint inhibitor (ICI)-related autoimmune hepatitis triggered by stereotactic body radiation therapy (SBRT) in a 55-year-old male with hilar cholangiocellular carcinoma. Initially diagnosed in December 2021, the patient underwent successful resection and subsequent adjuvant therapy. Despite stable disease following chemotherapy augmented with durvalumab, he developed grade 3 acute hepatitis after seven cycles of durvalumab. Following a brief prednisolone regimen and normalization of liver tests, SBRT targeting para-aortic lymph nodes was initiated. Remarkably, severe hepatitis reoccurred 7 days after starting SBRT, 88 days following the last durvalumab infusion, necessitating resumed and escalated prednisolone treatment. Another course of SBRT for a newly diagnosed metastatic liver lesion was administered in September 2023, with ongoing prednisolone adjustment. By February 2024, liver tests normalized, but subsequent radiological assessments indicated tumor progression, leading to the reintroduction of chemotherapy. This case underscores the potential of SBRT for activating severe immune-mediated hepatotoxicity in patients treated with ICIs, highlighting the need for careful monitoring and management of such patients. Further, this report highlights the possible survival benefit of the strategic application of SBRT in addition to systematic treatment in recurrent and metastatic cholangiocellular carcinoma.

Liver metastases, a hallmark of systemic disease, carry a poor prognosis despite advancements in systemic therapies. Stereotactic body radiation therapy (SBRT) has emerged as a promising local treatment, offering durable tumor control with minimal toxicity. However, the optimal dosimetric strategies to maximize outcomes remain an area of active investigation. This retrospective study evaluated 76 patients with 101 liver metastases treated with SBRT between November 2012 and June 2024. Dosimetric parameters were analyzed, including prescribed dose (PD) and dose metrics for planning target volume (PTV) and gross tumor volume (GTV), with doses converted to equivalent doses in 2 Gy fractions (EQD2, α/β = 10). Tumor control probability (TCP) models and survival outcomes were assessed, with a focus on the prognostic impact of dosimetric and clinical factors. Median overall survival (OS) was 33 months, with 1-year and 3-year OS rates of 74.1

Mandibular osteoradionecrosis (ORN) is a serious complication of radiotherapy (RT) for head and neck cancer (HNC), with an incidence of 3–15

Background:Hypoxia-inducible factor-1α (HIF-1α) is a crucial transcription factor activated under hypoxic conditions, known to regulate genes associated with tumor survival, progression, and response to therapy. This study aimed to evaluate the prognostic significance of HIF-1α expression in patients with anal squamous cell carcinoma (ASCC) undergoing chemoradiation therapy. Methods:We conducted a retrospective analysis of 28 ASCC patients treated with intensity-modulated radiotherapy (IMRT) at our center from 2009 to 2022. HIF-1α expression was assessed via immunohistochemistry on formalin-fixed paraffin-embedded tissue specimens. Quantitative analysis of HIF-1α expression was performed, and its relationship with clinical outcomes, including disease-free survival (DFS), locoregional relapse-free survival (LRRFS), and overall survival (OS), was examined using Cox regression models. Furthermore, ASCC tissue specimens from 17 patients were analyzed for potential PIK3CA mutations using Sanger sequencing. Results:High HIF-1α expression was significantly associated with poorer DFS (p = 0.005), LRRFS (p = 0.012), and OS (p = 0.009). HIF1α expression was marginally significantly higher in males compared to females (p = 0.056) while there was no significant difference found based on tumor stage or p16 status. However, a positive correlation was identified between BMI and HIF-1α levels (Pearson correlation r = 0.5, p = 0.0084), suggesting a link between metabolic status and tumor hypoxia. Only one patient exhibited a PIK3CA mutation, preventing a reliable assessment of its correlation with HIF-1α expression. Conclusion:Our findings underscore the importance of HIF-1α as a potential biomarker for predicting survival outcomes in ASCC patients treated with chemoradiation. The association between higher BMI and increased HIF-1α expression may provide insights into the interplay between metabolic health and tumor biology in ASCC. Further studies with larger cohorts are needed to validate these findings and explore targeted therapies focusing on HIF-1α modulation.

Background:Hepatocellular carcinoma (HCC) poses a significant challenge for patients ineligible for surgical resection or liver transplantation. Local therapies like Stereotactic Body Radiotherapy (SBRT) are crucial for those with liver-limited disease. Insulin-like growth factor-1 (IGF-1) is a potential biomarker for liver function. This study evaluates IGF-1's prognostic value in predicting survival outcomes in HCC patients undergoing SBRT. Methods:We analyzed 42 HCC patients treated with SBRT between May 2021 and January 2024, with IGF-1 levels measured within four weeks before SBRT. Patient demographics, tumor metrics, and clinical outcomes were examined. The prognostic significance of IGF-1 was assessed using Cox proportional hazards and ROC curve analysis to determine optimal IGF-1 cutoffs for survival prediction. A nomogram predicting 1-year and 2-year survival was constructed using a multivariate Cox model. Results:IGF-1 levels were significantly lower in patients with cirrhosis or sarcopenia. Median overall survival (OS) was 24 months, with a significant survival difference favoring patients with IGF-1 levels above 62.4 ng/ml (Hazard Ratio [HR]: 5.9, P = 0.0025). A multivariable Cox model including Child-Turcotte-Pugh (CTP) score, IGF-1, and tumor volume effectively predicted survival. IGF-1 and tumor volume significantly impacted OS (HR: 6.9 and 1.004, p = 0.014 and 0.0022, respectively). Integrating IGF-1 with CTP score improved predictive accuracy (c-index 0.66 to 0.75, p = 0.052).The nomogram, integrating IGF-1 with the CTP and tumour volume, exhibited robust predictive accuracy with an area under the curve (AUC) of 0.84 for 2-year survival. Conclusion:IGF-1 is a reliable biomarker for liver function and survival prediction in HCC patients undergoing SBRT. Higher IGF-1 levels indicate better prognosis. The developed nomogram, incorporating IGF-1, enhances clinical decision-making for SBRT management. Further validation in larger cohorts is needed.

2021 Background: Re-irradiation is an important treatment option for recurrent glioblastoma (rGBM). Here, we aimed to compare the oncological outcome of a re-irradiation target volume delineation based on O-(2-[18F]fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) with the one of a treatment based on contrast enhanced T1-weighted magnetic resonance imaging (T1Gd-MRI). Methods: GLIAA was a prospective, multicenter, randomized trial (NOA 10/ARO 2013-1, DKTK-a.). Patients with rGBM recurrence of 1-6 cm following initial radiotherapy were recruited at 14 centers in Germany and randomized 1:1 between a FET-PET- (arm A) and a T1Gd-MRI-based target volume delineation (arm B). The treatment consisted in a high-precision stereotactic re-irradiation with 39 Gy in 13 fractions. The primary endpoint was progression-free survival (PFS) from randomization. Secondary endpoints included overall survival (OS), local tumor control, and toxicity. Results: From November 26, 2013, to September 2, 2021, 271 patients were assessed for eligibility and 200 were randomized. 98 patients in the FET-PET arm and 97 patients in the T1Gd-MRI arm were treated per protocol. Median PFS was 4.0 months (95% confidence interval [CI] 3.7-5.2) in the FET-PET arm and 4.9 months (95% CI 3.7-6.0) in the GdT1-MRI arm (one-sided stratified log-rank test p=0.98; adjusted HR for the experimental versus the control arm 1.14 [95% CI 0.85-1.52], p=0.39). Median OS was 9.4 months (95% CI 7.8-11.1) in arm A and 9.0 months (95% CI 7.6-10.5) in arm B (HR 1.01 [95% CI 0.75-1.37], p=0.92). Local control rate at 12 months was 22% in the FET-PET arm (95% CI 14%-31%) and 20% in the GdT1-MRI arm (95% CI 12%-29%). Radiation necrosis as adverse event was documented in 25.5% of cases in arm A and in 21.6% in arm B. Of the 239 patients who received the FET tracer, 3 reported 5 severe adverse events in the timespan of 7 days after PET. No event was related to the application of the tracer. Conclusions: In this trial, FET-PET-based re-irradiation of rGBM was not superior to the GdT1-MRI-based treatment. Consequently, both options remain valid in this setting. Stereotactic re-irradiation with 39 Gy in 3 Gy fractions was shown to be safe and the FET-PET investigation was well tolerated in all cases. Due to the inclusion of FET-PET-positive patients only, our results do not impact the known diagnostic role of FET-PET in differentiating rGBM progression from post-therapeutic changes. Clinical trial information: NCT01252459 .

Hepatocellular carcinoma (HCC) poses a unique challenge due to its predilection for developing on compromised livers, often limiting surgical options. Stereotactic body radiotherapy (SBRT) has emerged as a promising local treatment modality for HCC. This study aims to assess the effectiveness of SBRT in HCC patients not suitable for surgery, focusing on local control, optimal radiation dosing, and prognostic factors. In this retrospective analysis, 52 HCC patients treated with SBRT were examined. The study assessed local control, progression-free survival (PFS), and overall survival (OS) while conducting dosimetric analyses. The relationship between mean liver dose and Child–Pugh score (CPS) progression was also explored. SBRT demonstrated 93.4

Background Radiotherapy is one of the main treatment options for patients with esophageal cancer; however, it has been linked with an increased risk of cardiac toxicities. In the current study, we evaluated the effect of planning the radiation in deep-inspiration breath hold (DIBH) on the dose sparing of cardiac substructures and lung. Materials and methods In this study, we analyzed 30 radiation therapy plans from 15 patients diagnosed with esophageal cancer planned for neoadjuvant radiotherapy. Radiation plans were generated for 41.4 Gy and delivered in 1.8 Gy per fraction for free-breathing (FB) and DIBH techniques. We then conducted a comparative dosimetric analysis, evaluating target volume coverage, the impact on cardiac substructures, and lung doses across the two planning techniques for each patient. Results There was no significant disparity in target volume dose coverage between DIBH and FB plans. However, the D mean , D2%, and V30% of the heart experienced substantial reductions in DIBH relative to FB, with values of 6.21 versus 7.02 Gy ( p = 0.011), 35.28 versus 35.84 Gy ( p = 0.047), and 5% versus 5.8% ( p = 0.048), respectively. The D mean of the left ventricle was notably lower in DIBH compared to FB (4.27 vs. 5.12 Gy, p = 0.0018), accompanied by significant improvements in V10. Additionally, the D mean and D2% of the left coronary artery, as well as the D2% of the right coronary artery, were significantly lower in DIBH. The dosimetric impact of DIBH on cardiac substructures proved more advantageous for middle esophageal (ME) than distal esophageal (DE) tumors. Conclusion Radiotherapy in DIBH could provide a method to reduce the radiation dose to the left ventricle and coronaries, which could reduce the cardiac toxicity of the modality.

Treatment of Epstein-Barr virus(EBV)-positive nasopharyngeal carcinoma (NPC) with cisplatin/5-fluorouracil (5-FU) induction chemotherapy, followed by radiochemotherapy and subsequent interferon‑β, has yielded high survival rates in children, adolescents, and young adults. A previous study has shown that reduction of radiation dose from 59.4 to 54.0 Gy appears to be safe in patients with complete response (CR) to induction chemotherapy. As immune checkpoint-inhibitors have shown activity in NPC, we hypothesize that the addition of nivolumab to standard induction chemotherapy would increase the rate of complete tumor responses, thus allowing for a reduced radiation dose in a greater proportion of patients. This is a prospective multicenter phase 2 clinical trial including pediatric and adult patients with their first diagnosis of EBV-positive NPC, scheduled to receive nivolumab in addition to standard induction chemotherapy. In cases of non-response to induction therapy (stable or progressive disease), and in patients with initial distant metastasis, treatment with nivolumab will be continued during radiochemotherapy. Primary endpoint is tumor response on magnetic resonance imaging (MRI) and positron emission tomography (PET) after three cycles of induction chemotherapy. Secondary endpoints are event-free (EFS) and overall survival (OS), safety, and correlation of tumor response with programmed cell death ligand 1 (PD-L1) expression. As cure rates in localized EBV-positive NPC today are high with standard multimodal treatment, the focus increasingly shifts toward prevention of late effects, the burden of which is exceptionally high, mainly due to intense radiotherapy. Furthermore, survival in patients with metastatic disease and resistant to conventional chemotherapy remains poor. Primary objective of this study is to investigate whether the addition of nivolumab to standard induction chemotherapy in children and adults with EBV-positive NPC is able to increase the rate of complete responses, thus enabling a reduction in radiation dose in more patients, but also offer patients with high risk of treatment failure the chance to benefit from the addition of nivolumab. EudraCT (European Union Drug Regulating Authorities Clinical Trials Database) No. 2021-006477-32.