International Expert-Based Consensus Definition, Classification Criteria, and Minimum Data Elements for Osteoradionecrosis of the Jaw: An Inter-Disciplinary Modified Delphi Study.

Purpose: Osteoradionecrosis of the jaw (ORNJ) is a severe iatrogenic disease characterized by bone death after radiation therapy (RT) to the head and neck. With over 9 published definitions and at least 16 classification systems, the true incidence and severity of ORNJ are obscured by lack of a standard for disease definition and severity assessment, leading to inaccurate estimation of incidence, reporting ambiguity, and likely under-diagnosis worldwide. This study aimed to achieve consensus on an explicit definition and phenotype of ORNJ and related precursor states through data standardization to facilitate effective diagnosis, monitoring, and multidisciplinary management of ORNJ.

CD8 Tumor-Infiltrating Lymphocytes in Head and Neck Cancer: A Review.

CD8 tumor-infiltrating lymphocytes (TILs) are increasingly used in oncology as a prognostic and predictive tool to guide patient management. This review summarizes current literature on CD8 TILs in head and neck squamous cell carcinoma (SCC). Published meta-analyses and clinical trials evaluating CD8 TILs were analyzed.

Safety and efficacy of pembrolizumab, radiation therapy, and surgery versus radiation therapy and surgery for stage III soft tissue sarcoma of the extremity (SU2C-SARC032): an open-label, randomised clinical trial.

Background: Approximately half of patients with localised, high-risk soft tissue sarcoma of the extremity develop metastases. We aimed to assess whether the addition of pembrolizumab to preoperative radiotherapy and surgery would improve disease-free survival.

Methods: We completed an open-label, randomised clinical trial in patients with grade 2 or 3, stage III undifferentiated pleomorphic sarcoma or dedifferentiated or pleomorphic liposarcoma of the extremity and limb girdle.

Computational staining of CD3/CD20 positive lymphocytes in human tissues with experimental confirmation in a genetically engineered mouse model.

Introduction: Immune dysregulation plays a major role in cancer progression. The quantification of lymphocytic spatial inflammation may enable spatial system biology, improve understanding of therapeutic resistance, and contribute to prognostic imaging biomarkers.

Methods: In this paper, we propose a knowledge-guided deep learning framework to measure the lymphocytic spatial architecture on human H&E tissue, where the fidelity of training labels is maximized through single-cell resolution image registration of H&E to IHC.

Clinical commissioning and introduction of an in-house artificial intelligence (AI) platform for automated head and neck intensity modulated radiation therapy (IMRT) treatment planning.

Background And Purpose: To describe the clinical commissioning of an in-house artificial intelligence (AI) treatment planning platform for head-and-neck (HN) Intensity Modulated Radiation Therapy (IMRT).

Materials And Methods: The AI planning platform has three components: (1) a graphical user interface (GUI) is built within the framework of a commercial treatment planning system (TPS). The GUI allows AI models to run remotely on a designated workstation configured with GPU acceleration.

Enhancing radiotherapy response via intratumoral injection of a TLR9 agonist in autochthonous murine sarcomas.

Radiation therapy (RT) is frequently used to treat cancers, including soft-tissue sarcomas. Prior studies established that the toll-like receptor 9 (TLR9) agonist cytosine-phosphate-guanine oligodeoxynucleotide (CpG) enhances the response to RT in transplanted tumors, but the mechanisms of this enhancement remain unclear. Here, we used CRISPR/Cas9 and the chemical carcinogen 3-methylcholanthrene (MCA) to generate autochthonous soft-tissue sarcomas with high tumor mutation burden.

NETosis Impact on Tumor Biology, Radiation, and Systemic Therapy Resistance.

Neutrophil extracellular trap (NET)osis via lytic neutrophil death or neutrophil activation is associated with standard cancer therapies, notably including radiotherapy; is immunosuppressive; and may enhance metastasis and treatment resistance. This emerging area of research should be prioritized in drug development and standard of care treatment paradigms including radiation therapy, chemotherapy, and immunotherapy. See related article by Teijeira et al.

Prevention and Management of Osteoradionecrosis in Patients With Head and Neck Cancer Treated With Radiation Therapy: ISOO-MASCC-ASCO Guideline.

Purpose: To provide evidence-based recommendations for prevention and management of osteoradionecrosis (ORN) of the jaw secondary to head and neck radiation therapy in patients with cancer.

Methods: The International Society of Oral Oncology-Multinational Association for Supportive Care in Cancer (ISOO-MASCC) and ASCO convened a multidisciplinary Expert Panel to evaluate the evidence and formulate recommendations. PubMed, EMBASE, and Cochrane Library databases were searched for randomized controlled trials and observational studies, published between January 1, 2009, and December 1, 2023.

Health Care Cost Reductions with Machine Learning-Directed Evaluations during Radiation Therapy - An Economic Analysis of a Randomized Controlled Study.

Background: Machine learning (ML) may cost-effectively direct health care by identifying patients most likely to benefit from preventative interventions to avoid negative and expensive outcomes. System for High-Intensity Evaluation During Radiation Therapy (SHIELD-RT; NCT04277650) was a single-institution, randomized controlled study in which electronic health record-based ML accurately identified patients at high risk for acute care (emergency visit or hospitalization) during radiotherapy (RT) and targeted them for supplemental clinical evaluations. This ML-directed intervention resulted in decreased acute care utilization.

Prognostic value of different discretization parameters in fluorodeoxyglucose positron emission tomography radiomics of oropharyngeal squamous cell carcinoma.

Purpose: We aim to interrogate the role of positron emission tomography (PET) image discretization parameters on the prognostic value of radiomic features in patients with oropharyngeal cancer.

Approach: A prospective clinical trial (NCT01908504) enrolled patients with oropharyngeal squamous cell carcinoma (; mixed HPV status) undergoing definitive radiotherapy and evaluated intra-treatment fluorodeoxyglucose PET as a potential imaging biomarker of early metabolic response. The primary tumor volume was manually segmented by a radiation oncologist on PET/CT images acquired two weeks into treatment (20 Gy).

Enhancing radiotherapy response via intratumoral injection of the TLR9 agonist CpG to stimulate CD8 T cells in an autochthonous mouse model of sarcoma.

Radiation therapy is frequently used to treat cancers including soft tissue sarcomas. Prior studies established that the toll-like receptor 9 (TLR9) agonist cytosine-phosphate-guanine oligodeoxynucleotide (CpG) enhances the response to radiation therapy (RT) in transplanted tumors, but the mechanism(s) remain unclear. Here, we used CRISPR/Cas9 and the chemical carcinogen 3-methylcholanthrene (MCA) to generate autochthonous soft tissue sarcomas with high tumor mutation burden.

Radiomics on spatial-temporal manifolds via Fokker-Planck dynamics.

Background: Delta radiomics is a high-throughput computational technique used to describe quantitative changes in serial, time-series imaging by considering the relative change in radiomic features of images extracted at two distinct time points. Recent work has demonstrated a lack of prognostic signal of radiomic features extracted using this technique. We hypothesize that this lack of signal is due to the fundamental assumptions made when extracting features via delta radiomics, and that other methods should be investigated.

Preclinical Evaluation of the ATR Inhibitor BAY 1895344 as a Radiosensitizer for Head and Neck Squamous Cell Carcinoma.

Purpose: Despite aggressive multimodal treatment that typically includes definitive or adjuvant radiation therapy (RT), locoregional recurrence rates approach 50% for patients with locally advanced human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC). Thus, more effective therapeutics are needed to improve patient outcomes. We evaluated the radiosensitizing effects of ataxia telangiectasia and RAD3-related (ATR) inhibitor (ATRi) BAY 1895344 in preclinical models of HNSCC.

Clinical outcomes of oropharyngeal squamous cell carcinoma stratified by human papillomavirus subtype: A systematic review and meta-analysis.

Purpose: We aim to determine if there is a survival difference between patients with oropharyngeal squamous cell carcinoma (OPSCC) associated with human papillomavirus (HPV) 16 versus HPV-non16 subtypes.

Patient And Methods: Databases were queried for full length, peer-reviewed, English language, articles published between 01/01/1980 and 06/08/2022. Studies reporting clinical outcomes of OPSCC associated with HPV16 and HPV-non16 subtypes with at least 10 patients were included.

Temporary Knockdown of p53 During Focal Limb Irradiation Increases the Development of Sarcomas.

Unlabelled: Approximately half of patients with cancer receive radiotherapy and, as cancer survivorship increases, the low rate of radiation-associated sarcomas is rising. Pharmacologic inhibition of p53 has been proposed as an approach to ameliorate acute injury of normal tissues from genotoxic therapies, but how this might impact the risk of therapy-induced cancer and normal tissue injuries remains unclear. We utilized mice that express a doxycycline (dox)-inducible p53 short hairpin RNA to reduce Trp53 expression temporarily during irradiation.

Long-term risk of carotid stenosis and cerebrovascular disease after radiation therapy for head and neck cancer.

Background: Recipients of radiation therapy (RT) for head and neck cancer (HNC) are at significantly increased risk for carotid artery stenosis (CAS) and cerebrovascular disease (CVD). We sought to determine (1) cumulative incidences of CAS and CVD among HNC survivors after RT and (2) whether CAS is associated with a RT dose response effect.

Methods: This single-institution retrospective cohort study examined patients with nonmetastatic HNC who completed (chemo)RT from January 2000 through October 2020 and subsequently received carotid imaging surveillance ≤2 years following RT completion and, in the absence of CAS, every 3 years thereafter.

Low contralateral neck recurrence risk with ipsilateral neck radiotherapy in N2b tonsillar squamous cell carcinoma.

Objectives: To characterize factors including nodal burden, pre-treatment imaging, and other patient factors which may influence the role of ipsilateral neck radiotherapy (IRT) in tonsillar squamous cell carcinoma (SCC) with multiple involved ipsilateral nodes.

Methods: Patients with cT1-2N0-2bM0 (AJCC 7th edition) tonsillar SCC treated with definitive radiation therapy (RT) at Duke University Medical Center from 1/1/1990-10/1/2019 were identified. Patient, tumor, and treatment characteristics were compared between those that received bilateral neck RT (BRT) versus IRT.