Adjuvant and concurrent temozolomide for 1p/19q non-co-deleted anaplastic glioma (CATNON; EORTC study 26053-22054): second interim analysis of a randomised, open-label, phase 3 study.

Background: The CATNON trial investigated the addition of concurrent, adjuvant, and both current and adjuvant temozolomide to radiotherapy in adults with newly diagnosed 1p/19q non-co-deleted anaplastic gliomas. The benefit of concurrent temozolomide chemotherapy and relevance of mutations in the IDH1 and IDH2 genes remain unclear.

Methods: This randomised, open-label, phase 3 study done in 137 institutions across Australia, Europe, and North America included patients aged 18 years or older with newly diagnosed 1p/19q non-co-deleted anaplastic gliomas and a WHO performance status of 0-2.

Ga-FAPI-PET/CT improves diagnostic staging and radiotherapy planning of adenoid cystic carcinomas - Imaging analysis and histological validation.

Background: Adenoid cystic carcinomas (ACCs) are rare epithelial tumors mostly situated in the head and neck region and characterized by infiltrative growth. The tumor stroma of ACCs includes cancer-associated fibroblasts (CAFs) expressing Fibroblast Activation Protein (FAP), a new target for positron emission tomography (PET) imaging. Here we describe the value of PET/ computed tomography (PET/CT) imaging using Ga-labelled FAP-Inhibitors (Ga-FAPI-PET/CT) and their clinical potential for staging and radiotherapy planning in 12 ACC patients (7 primary, 5 recurrent).

A practical implementation of risk management for the clinical introduction of online adaptive Magnetic Resonance-guided radiotherapy.

Background And Purpose: The clinical introduction of on-table adaptive radiotherapy with Magnetic Resonance (MR)-guided linear accelerators (Linacs) yields new challenges and potential risks. Since the adapted plan is created within a highly interdisciplinary workflow with the patient in treatment position, time pressure or erroneous communication may lead to various possibly hazardous situations. To identify risks and implement a safe workflow, a proactive risk analysis has been conducted.

3D-printed individualized tooth-borne tissue retraction devices compared to conventional dental splints for head and neck cancer radiotherapy: a randomized controlled trial.

Background: Despite modern treatment techniques, radiotherapy (RT) in patients with head and neck cancer (HNC) may be associated with high rates of acute and late treatment-related toxicity. The most effective approach to reduce sequelae after RT is to avoid as best as possible healthy tissues and organs at risk from the radiation target volume. Even small geometric changes can lead to a significant dose reduction in normal tissue and better treatment tolerability.

Individualized 3D-Printed Tissue Retraction Devices for Head and Neck Radiotherapy.

Background: Radiotherapy for head and neck cancer may cause various oral sequelae, such as radiation-induced mucositis. To protect healthy tissue from irradiation, intraoral devices can be used. Current tissue retraction devices (TRDs) have to be either individually manufactured at considerable cost and time expenditure or they are limited in their variability.

Spot-Scanning Hadron Arc (SHArc) Therapy: A Study With Light and Heavy Ions.

Purpose: To evaluate the clinical potential of spot-scanning hadron arc (SHArc) therapy with a heavy-ion gantry.

Methods And Materials: A series of in silico studies was conducted via treatment plan optimization in FRoG and the RayStation TPS to compare SHArc therapy against reference plans using conventional techniques with single, parallel-opposed, and 3-field configurations for 3 clinical particle beams (protons [p], helium [He], and carbon [C] ions). Tests were performed on water-equivalent cylindrical phantoms for simple targets and clinical-like scenarios with an organ-at-risk in proximity of the target.

Development of Immunotherapy Combination Strategies in Cancer.

Harnessing the immune system to treat cancer through inhibitors of CTLA4 and PD-L1 has revolutionized the landscape of cancer. Rational combination strategies aim to enhance the antitumor effects of immunotherapies, but require a deep understanding of the mechanistic underpinnings of the immune system and robust preclinical and clinical drug development strategies. We review the current approved immunotherapy combinations, before discussing promising combinatorial approaches in clinical trials and detailing innovative preclinical model systems being used to develop rational combinations.

Prognostic Value of microRNA-221/2 and 17-92 Families in Primary Glioblastoma Patients Treated with Postoperative Radiotherapy.

MicroRNAs (miRs) are non-coding master regulators of transcriptome that could act as tumor suppressors (TSs) or oncogenes (oncomiRs). We aimed to systematically investigate the relevance of miRs as prognostic biomarkers in primary glioblastoma multiforme (GBM) treated with postoperative radio(chemo)therapy (PORT). For hypothesis generation, tumor miR expression by Agilent 8x15K human microRNA microarrays and survival data from 482 GBM patients of The Cancer Genome Atlas (TCGA cohort) were analyzed using Cox-PH models.

Immunotherapy and Radiotherapy for Older Cancer Patients during the COVID-19 Era: Proposed Paradigm by the International Geriatric Radiotherapy Group.

Background: Older cancer patients with locally advanced or metastatic disease may benefit from chemotherapy alone or combined with radiotherapy. However, chemotherapy is often omitted either because of physician bias or because of its underlying comorbidity, thus compromising their survival. The coronavirus disease 19 (COVID-19) pandemic is compounding this issue because of the fear of immunosuppression induced by chemotherapy on the elderly which makes them more vulnerable to the virus.

Sarcomas of the Larynx: One Institution's Experience and Treatment Protocol Analyses.

Soft tissue sarcomas in the head and neck are rare malignancies. They occur in this area in less than 1% of all malignant tumors. Some authors have described the development of sarcoma from the mesenchymal tissue in the larynx.

Retrospective analysis of outcome and toxicity after postoperative radiotherapy in patients with squamous cell carcinoma of the lip.

Background: Carcinomas of the lips are a relatively common malignancy of the head and neck region, accounting for roughly one quarter of all oral cavity cancers. Compared to other oral cancer sites, this location has a favorable prognosis, with 5-year survival rates between 85% and 95%. This study summarizes our institutional experience in utilizing postoperative radiation for patients with squamous cell carcinoma of the upper and/or lower lip following incomplete surgical resection or positive lymph node involvement with extracapsular extension.

Clinical results of fibroblast activation protein (FAP) specific PET for non-malignant indications: systematic review.

Purpose: Small molecules targeting fibroblast activation protein (FAP) have emerged as a new group of tracers for positron emission tomography (PET) in 2018. While most of the existing literature has been focussed on the application of FAP-specific PET in various kinds of cancers, some researchers have, both intentionally or unintentionally, used FAP-specific PET in patients with non-cancerous diseases. The purpose of this systematic review is therefore to summarize the available evidence of FAP-specific PET for non-malignant indications.

MR-Guided Radiotherapy: The Perfect Partner for Immunotherapy?

During the last years, preclinical and clinical studies have emerged supporting the rationale to integrate radiotherapy and immunotherapy. Radiotherapy may enhance the effects of immunotherapy by improving tumor antigen release, antigen presentation, and T-cell infiltration. Recently, magnetic resonance guided radiotherapy (MRgRT) has become clinically available.

Neoadjuvant irradiation of retroperitoneal soft tissue sarcoma with ions (Retro-Ion): study protocol for a randomized phase II pilot trial.

Background: Following surgery for soft tissue sarcoma of the retroperitoneum, the predominant pattern of failure is local recurrence, which remains the main cause of death. Radiotherapy is utilized to reduce recurrence rates but the efficacy of this strategy has not been definitely established. As treatment tolerability is more favorable with preoperative radiotherapy, normofractionated neoadjuvant treatment is the current approach.

The role of combined ion-beam radiotherapy (CIBRT) with protons and carbon ions in a multimodal treatment strategy of inoperable osteosarcoma.

Background: To investigate the role of combined ion-beam radiotherapy (CIBRT) with protons and carbon ions in a multimodal treatment strategy of inoperable osteosarcoma; final analysis of a one-armed, single center phase I/II trial.

Methods: Between August 2011 until September 2018, 20 patients with primary (N = 18), metastatic (N = 3), or recurrent (N = 2) inoperable pelvic (70%) or craniofacial (30%) osteosarcoma were treated with protons up to 54 Gy (RBE) and a carbon ion boost of 18 Gy (RBE) and followed until May 2019. A Fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) was performed before CIBRT in search for a prognostic factor.

Simultaneous integrated boost concepts in definitive radiation therapy for esophageal cancer: outcomes and toxicity.

Background: Radiation therapy and chemoradiation therapy play a major role in the definitive management of esophageal cancer. Survival in esophageal cancer patients is still relatively poor, mostly due to high rates of local recurrence and distant metastases. It is hypothesized that dose escalation in radiotherapy could improve outcomes.

How can scanned proton beam treatment planning for low-grade glioma cope with increased distal RBE and locally increased radiosensitivity for late MR-detected brain lesions?

A novel risk model has recently been proposed for the occurrence of late contrast-enhancing brain lesions (CEBLs) after proton irradiation of low-grade glioma (LGG) patients. It predicts a strong dependence on dose-weighted linear-energy transfer (LET effect) and an increased radiosensitivity of the ventricular proximity, a 4-mm fringe surrounding the ventricular system (VP effect). On this basis, we investigated (A) how these two risk factors and patient-specific anatomical and treatment plan (TP) features contribute to normal tissue complication probability (NTCP) and (B) if conventional LET -reduction techniques like multiple-field TP are able to reduce NTCP.

Sarcoma classification by DNA methylation profiling.

Sarcomas are malignant soft tissue and bone tumours affecting adults, adolescents and children. They represent a morphologically heterogeneous class of tumours and some entities lack defining histopathological features. Therefore, the diagnosis of sarcomas is burdened with a high inter-observer variability and misclassification rate.

Deciphering Time-Dependent DNA Damage Complexity, Repair, and Oxygen Tension: A Mechanistic Model for FLASH-Dose-Rate Radiation Therapy.

Purpose: Irradiation with ultrahigh dose rates (FLASH) has reemerged as a promising radiation therapy approach to effectively lower potential damage burden on normal tissue without sacrificing tumor control. However, the large number of recent FLASH studies have been conducted under vastly different experimental conditions and circumstances (ie, investigated biological endpoint, radiation quality, and environmental oxygen level), with unverified biological mechanisms of action and unexplored interplay effect of the main dependencies. To facilitate radiobiological investigation of FLASH phenomena and assessment of clinical applicability, we present an extension of the mechanistic radiobiological model "UNified and VERSatile bio response Engine" (UNIVERSE).