Target volume delineation of the neck for radiotherapy in nasopharyngeal carcinoma: CSTRO, CACA, CSCO, HNCIG, ESTRO, and ASTRO guidelines and contouring atlas.

The Chinese Society for Therapeutic Radiology Oncology, the Chinese Anti-Cancer Association, the Chinese Society of Clinical Oncology, the Head and Neck Cancer International Group, the European Society for Radiotherapy and Oncology, and the American Society for Radiation Oncology collaboratively developed evidence-based guidelines and a comprehensive contouring atlas for neck target volume delineation in nasopharyngeal carcinoma. These guidelines address five key challenges in modern radiotherapy practice: margin design of clinical target volume; nodal target volume delineation after induction chemotherapy; delineation of equivocal nodes evident on imaging; low-risk clinical target volume delineation based on regional stepwise extension patterns; and modifications for anatomical boundaries of lymphatic areas. Developed through a rigorous systematic review and expert appraisal process by a panel of 50 international, multidisciplinary members from 17 countries and regions, these guidelines incorporate the latest advances in nasopharyngeal carcinoma diagnosis and treatment.

Primary target volume delineation for radiotherapy in nasopharyngeal carcinoma: CSTRO, CACA, CSCO, HNCIG, ESTRO, and ASTRO guidelines and contouring atlas.

The Chinese Society for Therapeutic Radiology Oncology, the Chinese Anti-Cancer Association, the Chinese Society of Clinical Oncology, Head and Neck Cancer International Group, the European Society for Radiotherapy and Oncology, and the American Society for Radiation Oncology jointly developed evidence-based guidelines and a contouring atlas for primary target volume delineation for radiotherapy in nasopharyngeal carcinoma. The guidelines systematically address three crucial challenges: margin design of clinical target volumes; target volume delineation after induction chemotherapy; and low-risk clinical target volume delineation based on local stepwise extension patterns. Based on a comprehensive systematic review and critical appraisal by an international multidisciplinary panel of 50 nasopharyngeal carcinoma specialists from 17 countries and regions, these guidelines are in keeping with advances in nasopharyngeal carcinoma diagnosis and treatment, embodying contemporary treatment concepts, and elaborating on the differences in practice.

Xevinapant or Placebo Plus Platinum-Based Chemoradiotherapy in Unresected Locally Advanced Squamous Cell Carcinoma of the Head and Neck (TrilynX): A Randomized, Phase III Study.

Purpose: TrilynX was a randomized, double-blind, phase III study evaluating the addition of xevinapant (an inhibitor of apoptosis proteins inhibitor) or placebo to chemoradiotherapy (CRT) in patients with unresected locally advanced squamous cell carcinoma of the head and neck (LA SCCHN).

Methods: Patients with unresected LA SCCHN (oropharynx [p16-negative only], hypopharynx, or larynx) were randomly assigned 1:1 to six cycles of oral xevinapant 200 mg/day or matched placebo (once daily on Days 1-14 of a 21-day cycle) plus CRT for the first three cycles (cisplatin [100 mg/m once on Day 2 of every cycle] plus intensity-modulated radiotherapy [70 Gy; 35 fractions of 2 Gy/day, 5 days/week]). The primary end point was event-free survival (EFS) assessed by the blinded independent review committee.

Alternative Radiotherapy Delivery Approaches to Modulate Radiation Response.

Spatially fractionated (SFRT) and FLASH radiotherapy (RT) are alternative means of dose delivery that are expected to widen the therapeutic window of clinical RT. The biological mechanisms for the observed effects of normal tissue-sparing with maintained tumor control probability are unknown. First, we introduce the preclinical research technologies for SFRT and FLASH-RT with photon beams, which include carbon nanotubes and modifications of standard small animal irradiators.

Modulating T-cell Responses to Enhance the Effects of Radiotherapy.

Radiotherapy has been a key component of cancer treatment for over a hundred years, with the understanding that its action was driven only by direct and indirect toxic effects on the tumor cells. With the advent of immunotherapy in recent decades, interest in radiotherapy has expanded beyond just its ability to kill malignant cells directly, to include the potential for augmenting the antitumor immune response in combination with immunotherapy. However, radiotherapy has also been clearly demonstrated to exert immunosuppressive effects, reported in both preclinical and clinical settings, and this means that it has a double-edged immune effect.

Association of quality of life with mortality in patients with adenoid cystic carcinoma using an internationally-validated QoL questionnaire (EQ-5D-5L).

Background/objectives: An evaluation of quality of life (QoL) is increasingly required for approval and reimbursement of new drug therapies. To support the evaluation of the impact of new drug therapies on QoL in single-arm studies in adenoid cystic carcinoma (ACC), we sought to determine the QoL baseline in a cohort of patients with ACC during routine follow up visits and to assess for associations with clinical or prognostic factors.

Methods: An internationally-validated QoL questionnaire (EQ-5D-5L) was completed by patients with ACC referred to an experimental medicine centre.

Tumor control and immune activation through palliative irradiation and ATR inhibition, PATRIOT Part C: a phase Ib trial.

Ataxia telangiectasia and Rad3-related kinase (ATR) is a rational radiosensitization target. In this study, we explore the combination of the ATR inhibitor, ceralasertib, and palliative radiotherapy, with primary endpoint the identification of maximum tolerated dose, and secondary endpoints the determination of adverse event causality, pharmacokinetics (PK) and anti-tumor activity. Twenty-seven patients were dosed in escalating dose cohorts from 20 to 80 mg twice daily (BD) with concomitant radiation, 20 Gy in 10 fractions or 30 Gy in 15 fractions.

Patient experience of head and neck treatment on a 1.5 T MR-Linac: is the ATS-lite adaptive solution tolerable?

Introduction: Head and neck cancer (HNC) treatment on the Unity MR-Linac (MRL) (Elekta AB, Stockholm, Sweden) has been developed using the novel adapt-to-shape Lite (ATS-lite) method to create clinically acceptable adaptive treatments clinician-free. Here we investigate patient experience and acceptability of this technique.

Methods: Ten HNC patients treated to 65 Gy in 30 fractions with MRI-guided adaptive radiotherapy (MRIgART) within the PERMIT trial (NCT03727698), were included.

Normal tissue outlining guidelines development for soft tissue sarcoma of the extremities.

Introduction: Radiotherapy (RT) plans for soft tissue sarcoma of the extremities (STSE) are optimised to achieve maximum target coverage whilst avoiding high doses to weight-bearing bones and intermediate doses to the normal tissue (NT) limb corridor. Within this study, novel lower extremity NT outlining guidelines and atlas were developed based on the hypothesis that using these for RT planning may reduce RT toxicity. Usability and applicability of the guidance were also investigated.

The PARP inhibitor talazoparib synergizes with reovirus to induce cancer killing and tumour control in vivo in mouse models.

Reovirus type 3 Dearing (RT3D) is an oncolytic, double-stranded RNA virus. To identify potential RT3D drug-viral sensitizer, here we use a high-throughput screen of therapeutic agents and find a PARP-1 inhibitor, talazoparib, as a top hit. RT3D interacts with retinoic acid-induced gene-1 (RIG-I) and activates PARP-1, with consequent PARylation of components of the extrinsic apoptosis pathway.

RP1 Combined With Nivolumab in Advanced Anti-PD-1-Failed Melanoma (IGNYTE).

Purpose: Effective treatment options for melanoma after immune checkpoint blockade failure are limited. RP1 (vusolimogene oderparepvec) is a herpes simplex virus type 1-based oncolytic immunotherapy, here evaluated in combination with nivolumab in anti-PD-1-failed melanoma.

Methods: Patients had advanced melanoma that had confirmed progression on anti-PD-1 (≥8 weeks, last prior treatment).

Neoadjuvant and Adjuvant Pembrolizumab in Locally Advanced Head and Neck Cancer.

Background: The benefit of the addition of perioperative pembrolizumab to standard care with surgery and adjuvant therapy for patients with locally advanced head and neck squamous-cell carcinoma (HNSCC) is unclear.

Methods: In this phase 3, open-label trial, we randomly assigned participants with locally advanced HNSCC in a 1:1 ratio to receive 2 cycles of neoadjuvant pembrolizumab and 15 cycles of adjuvant pembrolizumab (both at a dose of 200 mg every 3 weeks) in addition to standard care (pembrolizumab group) or standard care alone (control group). Standard care was surgery and adjuvant radiotherapy with or without concomitant cisplatin.

Expanding access to cancer immunotherapy: A systematic review of low-dose PD-(L)1 inhibitor strategies.

Background: Anti-PD-(L)1 inhibitors have transformed cancer treatment. However, their high costs severely restrict their accessibility, especially in low- and middle-income countries (LMIC). Low-dose regimens, inferior to weigh-based or flat dosings, may help address this barrier.

LiGeR-HN phase III trials of petosemtamab + pembrolizumab and petosemtamab monotherapy in recurrent or metastatic HNSCC.

Patients with recurrent/metastatic (r/m) head and neck squamous cell carcinoma (HNSCC) have limited treatment options and a dismal prognosis, especially when their cancer is resistant to standard treatments like anti-programmed cell death protein 1 and platinum-based therapies. Petosemtamab - a human, common light chain, bispecific antibody with enhanced antibody-dependent cellular cytotoxicity targeting epidermal growth factor receptor (EGFR) and leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) - demonstrated antitumor activity in r/m HNSCC. In many tumor types, including HNSCC, EGFR is an oncogenic driver, while LGR5 is upregulated.

Phase I and II Clinical Studies of the STING Agonist Ulevostinag with and without Pembrolizumab in Participants with Advanced or Metastatic Solid Tumors or Lymphomas.

Purpose: We report results from two clinical trials of the cyclic dinucleotide stimulator of IFN genes (STING) agonist ulevostinag.

Patients And Methods: In a phase I study (NCT03010176) with an accelerated titration design/modified toxicity probability interval method, participants with advanced/metastatic solid tumors or lymphomas received intratumoral ulevostinag (±intravenous pembrolizumab). In an expansion phase, participants with head and neck squamous cell carcinoma (HNSCC) or triple-negative breast cancer received the combination.

International Consensus Guideline on Delineation of the Clinical Target Volumes at Different Dose Levels for Nasopharyngeal Carcinoma (2024 Version).

Purpose: Radiation therapy planning for nasopharyngeal carcinoma is one of the most challenging tasks for radiation oncologists due to the notoriously narrow therapeutic margin. The first International Guideline (IG-2018 Version) has served as a practical guide for contouring clinical target volumes (CTVs). With increasing data on locoregional extension patterns and outcomes from studies on optimizing CTV and doses, an updated International Guideline is pressingly needed to provide a reference for enhancing precision.

Palbociclib and dsRNA sensor co-operate to enhance anti-cancer effects through ER stress and modulation of immune evasion.

Cytoplasmic pattern recognition receptors (PRR) for double-stranded RNA, such as RIG-I/MDA5, are key mediators of anti-viral responses. Here we screen for synergistic drug-virotherapy combinations and find that the reovirus type III Dearing strain (Rt3D)-palbociclib combination augments oncolytic virus-induced stress responses and increases interferon production and signaling. Data from RIG-I agonist and ER stress-inducing agents further confirms the crosstalk between RNA-sensing and ER stress in inducing cancer cell death and interferon production.

KDM6A, ARID1A and SETD2 loss-of-function mutations as prognostic biomarkers and their association with sites of metastatic progression in locally-advanced, recurrent or metastatic adenoid cystic carcinoma.

Objectives: Recurrent/metastatic (R/M) adenoid cystic carcinoma (ACC) is typically slow growing however, some patients have more rapid progression. We sought to classify mutations in chromatin regulating genes in ACC to determine the impact of chromatin regulatory disfunction on clinical outcomes.

Materials And Methods: Matched clinical-genomic data from 271 pts with non-resectable or R/M ACC were included in this study.

International consensus on laryngeal preservation strategies in laryngeal and hypopharyngeal cancer.

This Policy Review summarises an expert Delphi consensus process on larynx-preservation treatments in patients affected by intermediate-to-advanced laryngeal or hypopharyngeal squamous cell carcinoma. The experts, who represented all perspectives involved in multidisciplinary management of these patients and included patient representatives, approved 137 consensus statements that cover several relevant areas in the field of larynx-preserving treatments. Statements are grouped in the following topics: granular indications for T2-T3 cancer, indications for T4a cancer, indications for salvage organ-preservation surgery after chemoradiation failure, laryngeal function at baseline, which comorbidities are contraindications and to what extent, organ preservation in older patients: selection criteria, post-treatment surveillance, prognostic and predictive factors, listening to the patient's preferences: tools and implementation, prehabilitation and rehabilitation protocols, and cost-effectiveness of different laryngeal preservation approaches.

INTERLINK-1: A Phase III, Randomized, Placebo-Controlled Study of Monalizumab plus Cetuximab in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma.

Purpose: Treatment options for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) after failure of immune checkpoint inhibitor treatment and platinum-based chemotherapy are limited. Preliminary data suggested that monalizumab plus cetuximab had clinical activity in R/M HNSCC.

Patients And Methods: INTERLINK-1 (NCT04590963) was a double-blind, phase III study.

Clinical trials for patients with salivary gland cancers: A systematic review of worldwide registers and an evaluation of current challenges.

Background: Clinical trials (CT) are crucial for generating scientific evidence and improving clinical outcomes, but they can be challenging in the context of rare cancers. Salivary gland cancers (SGC) are rare and heterogeneous tumors, without standard-of-care approved systemic therapies. We analyzed completed and ongoing CTs to assess the current state of clinical research activity in the field.

Pembrolizumab with or without chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma: 5-year follow-up from the randomized phase III KEYNOTE-048 study.

Background: Pembrolizumab monotherapy and pembrolizumab-chemotherapy demonstrated superior overall survival (OS) versus cetuximab-chemotherapy (EXTREME) in the primary analysis of the phase III KEYNOTE-048 study of recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) in the first-line setting. We report updated data with 5 years of follow-up.

Methods: Adults with previously untreated R/M HNSCC incurable by local therapy were randomly assigned 1:1:1 to pembrolizumab, pembrolizumab plus chemotherapy, or EXTREME.