Definition and validation of a radiomics signature for loco-regional tumour control in patients with locally advanced head and neck squamous cell carcinoma

Purpose: To develop and validate a CT-based radiomics signature for the prognosis of loco-regional tumour control (LRC) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated by primary radiochemotherapy (RCTx) based on retrospective data from 6 partner sites of the German Cancer Consortium - Radiation Oncology Group (DKTK-ROG). Material and methods: Pre-treatment CT images of 318 patients with locally advanced HNSCC were col-lected. Four-hundred forty-six features were extracted from each primary tumour volume and then fil-tered through stability analysis and clustering. First, a baseline signature was developed from demographic and tumour-associated clinical parameters. This signature was then supplemented by CT imaging features. A final signature was derived using repeated 3-fold cross-validation on the discovery cohort. Performance in external validation was assessed by the concordance index (C-Index). Furthermore, calibration and patient stratification in groups with low and high risk for loco-regional recurrence were analysed. Results: For the clinical baseline signature, only the primary tumour volume was selected. The final sig-nature combined the tumour volume with two independent radiomics features. It achieved moderatel

DNA-Methylome based Tumor Hypoxia Classifier Identifies HPV-negative Head & Neck Cancer Patients at Risk for Locoregional Recurrence After Primary Radiochemotherapy

BACKGROUND Tumor hypoxia is a paradigmatic negative prognosticator of treatment resistance in Head and Neck Squamous Cell Carcinoma (HNSCC). The lack of robust and reliable hypoxia classifiers limits the adaptation of stratified therapies. We hypothesized that the tumor DNA methylation landscape might indicate epigenetic reprogramming induced by chronic intratumoral hypoxia. METHODS A DNA methylome-based tumor hypoxia classifier (Hypoxia-M) was trained in the TCGA-HNSCC cohort based on matched assignments using gene expression-based signatures of hypoxia (Hypoxia-GES). Hypoxia-M was validated in a multicenter DKTK-ROG trial consisting of Human Papilloma Virus (HPV)-negative HNSCC patients treated with primary radiochemotherapy (RCHT). RESULTS While hypoxia-GSEs failed to stratify patients in the DKTK-ROG, Hypoxia-M was independently prognostic for local recurrence (LR, HR=4.3, p=0.001) and overall survival (OS, HR=2.34, p=0.03) but not distant metastasis (DM) after RCHT in the both cohorts. Hypoxia-M status was inversely associated with CD8 T-cells infiltration in both cohorts. Hypoxia-M was further prognostic in the TCGA-PanCancer cohort (HR=1.83, p=0.04), underscoring the breadth of this classifier for predicting tumor hypoxia status. CONCLUSIONS Our findings highlight an unexplored avenue for DNA Methylation-based classifiers as biomarkers of tumoral hypoxia for identifying high-risk features in patients with HNSCC tumors. TRIAL REGISTRATION Retrospective observational study from the German Cancer Consortium (DKTK-ROG), not interventional

Randomisierte Phase-IIB-Studie zur Protonentherapie vs. intensitätsmodulierte Photonentherapie für lokal fortgeschrittene Ösophaguskarzinome

Purpose!#!This study aims to evaluate the best possible practice using hybrid volumetric modulated arc therapy (H-VMAT) for hypofractionated radiation therapy of breast cancer. Different combinations of H‑VMAT-a combination of three-dimensional radiotherapy (3D-CRT) and VMAT-were analyzed regarding planning target volume (PTV), dose coverage, and exposure to organs at risk (OAR).!##!Methods!#!Planning computed tomography scans were acquired in deep-inspiration breath-hold. A total of 520 treatment plans were calculated and evaluated for 40 patients, comprising six different H‑VMAT plans and a 3D-CRT plan as reference. H‑VMAT plans consisted of two treatment plans including 3D-CRT and VMAT. During H‑VMAT planning, the use of hard wedge filters (HWF) and beam energies were varied. The reference plans were planned with mixed beam energies and the inclusion/omission of HWF.!##!Results!#!Compared to the reference treatment plans, all H‑VMAT plans showed consistently better PTV dose coverage, conformity, and homogeneity. Additionally, OAR protection was significantly improved with several H‑VMAT combinations (p < 0.05). The comparison of different H‑VMAT combinations showed that inclusion of HWF in the base plan had a negative impact on PTV dose coverage, conformity, and OAR exposure. It also increased the planned monitor units and beam-on time. Advantages of using lower beam energies (6-MV photons) in both the base plan and in the VMAT supplementary dose were observed.!##!Conclusion!#!The H‑VMAT technique is an effective possibility for generating homogenous and conformal dose distributions. With the right choice of H‑VMAT combination, superior OAR protection is achieved compared to 3D-CRT

Radiotherapy and COVID-19—everything under control or just the start of a long story?

Purpose!#!To examine the equivalent uniform dose (EUD) formalism using the universal survival curve (USC) applicable to high-dose stereotactic body radiotherapy (SBRT).!##!Materials and methods!#!For nine non-small-cell carcinoma cell (NSCLC) lines, the linear-quadratic (LQ) and USC models were used to calculate the EUD of a set of hypothetical two-compartment tumor dose-volume histogram (DVH) models. The dose was varied by ±5%, ±10%, and ±20% about the prescription dose (60 Gy/3 fractions) to the first compartment, with fraction volume varying from 1% and 5% to 30%. Clinical DVHs of 21 SBRT treatments of NSCLC prescribed to the 70-83% isodose lines were also considered. The EUD of non-standard SBRT dose fractionation (EUD!##!Results!#!For non-standard SBRT fractionation, the deviation of the USC- from the LQ-EUD!##!Conclusion!#!A uniform formalism of EUD should be defined among the SBRT community in order to apply it as a single metric for dose reporting and dose-response modeling in high-dose-gradient SBRT because its value depends on the underlying cell survival model and the model parameters. Further investigations of the optimal formalism to derive the EUD through clinical correlations are warranted

Erhaltene sexuelle Funktion nach hochdosierter bildgestützter Protonentherapie des Prostatakarzinoms

Objectives!#!Mesenchymal stromal cells (MSC) in bone marrow have been shown to be radioresistant, which is related to pronounced DNA repair mechanisms. Intraoperative radiotherapy (IORT) during breast-conserving surgery for early breast cancer is an innovative technique applying low energy x‑ray to the tumor bed immediately after removal of the tumor. IORT is considered to reduce the risk of local tumor recurrence by directly targeting cells of the tumor bed and altering the local microenvironment. Aim of this study was to investigate whether IORT affects the outgrowth potential of breast adipose tissue-derived MSC (bASC) as part of the tumor bed.!##!Materials and methods!#!After surgical tumor resection, biopsies of the tumor bed were taken before (pre IORT) and after IORT (post IORT) and processed applying well-established protocols for ASC isolation and characterization.!##!Results!#!In all, 95% of pre IORT tumor bed samples yielded persistently outgrowing bASC with typical ASC characteristics: fibroblastoid morphology, proliferation, adipogenic and osteogenic differentiation and ASC surface marker expression. However, none of the post IORT samples yielded persistent outgrowth of bASC.!##!Conclusions!#!After breast-conserving surgery, approximately 90% of local recurrences emerge in close proximity to the initial tumor bed, potentially reflecting a significant contribution of the tumor bed to relapse. Our data show that IORT, besides the proven effect on breast cancer cells, efficiently modifies the tumor environment by having an impact on tumor bed bASC. This effect on tumor bed stromal cells might contribute to reduce the risk of tumor relapse and metastases

Targeting PARP for Chemoradiosensitization:Opportunities, Challenges, and the Road Ahead

No abstract available

Therapeutic options to overcome tumor hypoxia in radiation oncology

Purpose Expert review summarizing the overcome tumor cell hypoxia by treatment modification in radiation oncology.Methods An extensive literature search regarding various means of treatment modification was performed and key papers on those modifications were included in this review article.Results Based on the identified key papers the means to overcome hypoxia in radiation oncology were summarized in this review article, e.g., increasing levels of oxygen, combining radiotherapy with agents counteracting hypoxia, or modifying radiation treatment itself.Conclusions This review summarizes the results of preclinical and clinical studies counteracting hypoxia and highlights the measures that have found their way into clinical practice.</p