Radiation therapy results in preferential tumor antigen-specific lymphodepletion in head and neck cancer.

Human Papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) remains a challenging malignancy, with radiotherapy, alone or combined with immune checkpoint inhibitors, often failing to achieve durable disease control. Here, by conducting longitudinal multi-omic analyses of pre- and post-radiation biopsies from patients receiving a pre-operative hypofractionated radiation regimen, we uncover that radiation rapidly depletes a subpopulation of tumor-infiltrating lymphocytes (TIL), characterized by a proliferative, cytotoxic, and tissue-resident gene signature (T). We provide multi-dimensional evidence for tumor antigen-specificity of T clonotypes and show that post-radiation tumors are instead repopulated by regulatory and non-specific clones.

Personalizing Approaches to Management of HPV+ Oropharyngeal Cancer.

HPV+ oropharyngeal cancer represents a unique disease entity in the realm of head and neck cancer with distinct incidence and prevalence, pathogenesis, and treatment outcome. Management of this disease needs to be personalized in consideration of a combination of factors of both patient and disease characteristics. Overall outcomes in this patient population are excellent.

Quantification and Dosimetric Impact of Normal Organ Motion During Adaptive Radiation Therapy Planning Using a 1.5 Tesla Magnetic Resonance-Equipped Linear Accelerator (MR-Linac).

Purpose: Patients receiving adaptive magnetic resonance guided radiation therapy (MRgRT) undergo contour modification prior to treatment delivery, which takes 15 to over 60 minutes. We hypothesized that during the time required to create an adaptive MRgRT plan, organ movement will result in dosimetric changes to regional organs at risk (OARs). This study quantifies the dosimetric impact of OAR motion during the time required to perform adaptive MRgRT.

Hypofractionated Radiation Therapy in the Definitive Management of Head and Neck Cancer.

The use of hypofractionated radiation therapy has increased among many cancers, although its use in head and neck cancers remains limited due to concerns regarding acute and late toxicities. Recent retrospective and prospective studies demonstrate the preliminary safety and efficacy of hypofractionation in the definitive, postoperative, and preoperative settings for head and neck treatment. This article seeks to comprehensively review the rationale and data for novel fractionation schemes in this disease site.

Quantitative magnetic resonance imaging responses in head and neck cancer patients treated with magnetic resonance-guided hypofractionated radiation therapy.

Background And Purpose: Quantitative MRI (qMRI) has been explored for detecting tumor changes during radiation therapy (RT) in head and neck squamous cell cancer (HNSCC). Clinical trials show prolonged survival with PD-1 targeted immune checkpoint inhibition. Hypofractionated radiation regimens are being studied to counteract radioresistant clonogen formation.

Locked Dimerized CXCL12 Exerts Radiosensitizing Effects in Head and Neck Cancer.

Background: Head and neck squamous cell carcinoma (HNSCC) presents significant treatment challenges, particularly in cases unrelated to human papillomavirus (HPV). The chemokine receptor CXCR4, interacting with its ligand CXCL12, plays a crucial role in tumor proliferation, metastasis, and treatment resistance. This study explores the therapeutic potential of engineered monomeric and dimerized CXCL12 variants (CXCL12 and CXCL12, respectively) in HNSCC and evaluates potential additive effects when combined with radiation therapy.

Radiotherapy with cetuximab or durvalumab for locoregionally advanced head and neck cancer in patients with a contraindication to cisplatin (NRG-HN004): an open-label, multicentre, parallel-group, randomised, phase 2/3 trial.

Background: Management of patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC) when cisplatin is contraindicated is controversial. We aimed to assess whether radiotherapy with concurrent and adjuvant durvalumab would improve outcomes compared with radiotherapy with cetuximab.

Methods: NRG-HN004 was designed as an open-label, multicentre, parallel-group, randomised, phase 2/3 trial with safety lead-in conducted at 89 academic and community medical centres in North America.

Radiation Therapy for HPV-Positive Oropharyngeal Squamous Cell Carcinoma: An ASTRO Clinical Practice Guideline.

Purpose: Human Papilloma Virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is a distinct disease from other head and neck tumors. This guideline provides evidence-based recommendations on the critical decisions in its curative treatment, including both definitive and postoperative radiation therapy (RT) management.

Methods: ASTRO convened a task force to address 5 key questions on the use of RT for management of HPV-associated OPSCC.

Type I interferon signaling promotes radioresistance in head and neck cancer.

Despite the promise of concurrent radiotherapy (RT) and immunotherapy in head and neck cancer (HNC), multiple randomized trials of this combination have had disappointing results. To evaluate potential immunologic mechanisms of RT resistance, we compared pre-treatment HNCs that developed RT resistance to a matched cohort that achieved curative status. Gene set enrichment analysis demonstrated that a pre-treatment pro-immunogenic tumor microenvironment (TME), including type II interferon [interferon gamma (IFNγ)] and tumor necrosis factor alpha (TNFα) signaling, predicted cure while type I interferon [interferon alpha (IFNα)] enrichment was associated with an immunosuppressive TME found in tumors that went on to recur.

Changes in Daily Apparent Diffusion Coefficient on Fully Quantitative Magnetic Resonance Imaging Correlate With Established Genomic Pathways of Radiation Sensitivity and Reveal Novel Biologic Associations.

Purpose: Changes in quantitative magnetic resonance imaging (qMRI) are frequently observed during chemotherapy or radiation therapy (RT). It is hypothesized that qMRI features are reflective of underlying tissue responses. It's unknown what underlying genomic characteristics underly qMRI changes.

Intensity-Modulated Reirradiation Therapy With Nivolumab in Recurrent or Second Primary Head and Neck Squamous Cell Carcinoma: A Nonrandomized Controlled Trial.

Importance: Intensity-modulated radiation therapy (IMRT) reirradiation of nonmetastatic recurrent or second primary head and neck squamous cell carcinoma (HNSCC) results in poor progression-free survival (PFS) and overall survival (OS).

Objective: To investigate the tolerability, PFS, OS, and patient-reported outcomes with nivolumab (approved standard of care for patients with HNSCC) during and after IMRT reirradiation.

Design, Setting, And Participants: In this multicenter nonrandomized phase 2 single-arm trial, the treatment outcomes of patients with recurrent or second primary HNSCC who satisfied recursive partitioning analysis class 1 and 2 definitions were evaluated.

Obtaining organ-specific radiobiological parameters from clinical data for radiation therapy planning of head and neck cancers.

Different radiation therapy (RT) strategies, e.g. conventional fractionation RT (CFRT), hypofractionation RT (HFRT), stereotactic body RT (SBRT), adaptive RT, and re-irradiation are often used to treat head and neck (HN) cancers.

Photoactivated HPPH-Liposomal therapy for the treatment of HPV-Negative head and neck cancer.

Objectives: Human Papillomavirus (HPV)-negative head and neck cancer (HNC) is an aggressive malignancy with a poor prognosis. To improve outcomes, we developed a novel liposomal targeting system embedded with 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH), a chlorin-based photosensitizer. Upon exposure to 660 nm light, HPPH phototriggering generates reactive oxygen species.

A phase 2 trial of a topical antiseptic bundle in head and neck cancer surgery: Effects on surgical site infection and the oral microbiome.

Background: Head and neck cancer (HNC) surgery remains an important component of management but is associated with a high rate of surgical site infection (SSI). We aimed to assess the safety and efficacy of a topical mucosal antiseptic bundle in preventing SSI and evaluate microbial predictors of infection through a genomic sequencing approach.

Methods: This study was an open-label, single-arm, single-center, phase 2 trial of a topical mucosal antiseptic bundle in patients with HNC undergoing aerodigestive tract resection and reconstruction.

A volume-independent conformity index for stereotactic radiosurgery.

Purpose: To develop a volume-independent conformity metric called the Gaussian Weighted Conformity Index (GWCI) to evaluate stereotactic radiosurgery/radiotherapy (SRS/SRT) plans for small brain tumors.

Methods: A signed bi-directional local distance (BLD) between the prescription isodose line and the target contour is determined for each point along the tumor contour (positive distance represents under-coverage). A similarity score function (SF) is derived from Gaussian function, penalizing under- and over-coverage at each point by assigning standard deviations of the Gaussian function.

Chronic stress promotes an immunologic inflammatory state and head and neck cancer growth in a humanized murine model.

Background: Despite the importance of immune response and environmental stress on head and neck cancer (HNC) outcomes, no current pre-clinical stress model includes a humanized immune system.

Methods: We investigated the effects of chronic stress induced by social isolation on tumor growth and human immune response in subcutaneous HNC tumors grown in NSG-SGM3 mice engrafted with a human immune system.

Results: Tumor growth (p < 0.

General and custom deep learning autosegmentation models for organs in head and neck, abdomen, and male pelvis.

Purpose: To reduce workload and inconsistencies in organ segmentation for radiation treatment planning, we developed and evaluated general and custom autosegmentation models on computed tomography (CT) for three major tumor sites using a well-established deep convolutional neural network (DCNN).

Methods: Five CT-based autosegmentation models for 42 organs at risk (OARs) in head and neck (HN), abdomen (ABD), and male pelvis (MP) were developed using a full three-dimensional (3D) DCNN architecture. Two types of deep learning (DL) models were separately trained using either general diversified multi-institutional datasets or custom well-controlled single-institution datasets.

Magnetic resonance linear accelerator technology and adaptive radiation therapy: An overview for clinicians.

Radiation therapy (RT) continues to play an important role in the treatment of cancer. Adaptive RT (ART) is a novel method through which RT treatments are evolving. With the ART approach, computed tomography or magnetic resonance (MR) images are obtained as part of the treatment delivery process.