International Recommendations on Postoperative Management for Potentially Resectable Locally Recurrent Nasopharyngeal Carcinoma.

Locally recurrent nasopharyngeal carcinoma (NPC) presents substantial challenges in clinical management. Although postoperative re-irradiation (re-RT) has been acknowledged as a potential treatment option, standardized guidelines and consensus regarding the use of re-RT in this context are lacking. This article provides a comprehensive review and summary of international recommendations on postoperative management for potentially resectable locally recurrent NPC, with a special focus on postoperative re-RT. A thorough search was conducted to identify relevant studies on postoperative re-RT for locally recurrent NPC. Controversial issues, including resectability criteria, margin assessment, indications for postoperative re-RT, and the optimal dose and method of re-RT, were addressed through a Delphi consensus process. The consensus recommendations emphasize the need for a clearer and broader definition of resectability, highlighting the importance of achieving clear surgical margins, preferably through an en bloc approach with frozen section margin assessment. Furthermore, these guidelines suggest considering re-RT for patients with positive or close margins. Optimal postoperative re-RT doses typically range around 60 Gy, and hyperfractionation has shown promise in reducing toxicity. These guidelines aim to assist clinicians in making evidence-based decisions and improving patient outcomes in the management of potentially resectable locally recurrent NPC. By addressing key areas of controversy and providing recommendations on resectability, margin assessment, and re-RT parameters, these guidelines serve as a valuable resource for clinical experts involved in the treatment of locally recurrent NPC.

Circulating Tumor DNA Assay Detects Merkel Cell Carcinoma Recurrence, Disease Progression, and Minimal Residual Disease: Surveillance and Prognostic Implications.

PURPOSE: Merkel cell carcinoma (MCC) is an aggressive skin cancer with a 40% recurrence rate, lacking effective prognostic biomarkers and surveillance methods. This prospective, multicenter, observational study aimed to evaluate circulating tumor DNA (ctDNA) as a biomarker for detecting MCC recurrence. METHODS: Plasma samples, clinical data, and imaging results were collected from 319 patients. A tumor-informed ctDNA assay was used for analysis. Patients were divided into discovery (167 patients) and validation (152 patients) cohorts. Diagnostic performance, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), was assessed. RESULTS: ctDNA showed high sensitivity, 95% (discovery; 95% CI, 87 to 99) and 94% (validation; 95% CI, 85 to 98), for detecting disease at enrollment, with corresponding specificities of 90% (95% CI, 82 to 95) and 86% (95% CI, 77 to 93). A positive ctDNA during surveillance indicated increased recurrence risk, with hazard ratios (HRs) of 6.8 (discovery; 95% CI, 2.9 to 16) and 20 (validation; 95% CI, 8.3 to 50). The PPV for clinical recurrence at 1 year after a positive ctDNA test was 69% (discovery; 95% CI, 32 to 91) and 94% (validation; 95% CI, 71 to 100), respectively. The NPV at 135 days after a negative ctDNA test was 94% (discovery; 95% CI, 90 to 97) and 93% (validation; 95% CI, 89 to 97), respectively. Patients positive for ctDNA within 4 months after treatment had higher rates of recurrence, with 1-year rates of 74% versus 21% (adjusted HR, 7.4 [95% CI, 2.7 to 20]). CONCLUSION: ctDNA testing exhibited high prognostic accuracy in detecting MCC recurrence, suggesting its potential to reduce frequent surveillance imaging. ctDNA also identifies high-risk patients who need more frequent imaging and may be best suited for adjuvant therapy trials.

Standardised definitions and diagnostic criteria for extranodal extension detected on histopathological examination in head and neck cancer: Head and Neck Cancer International Group consensus recommendations.

Detection of extranodal extension on histopathology in surgically treated head and neck squamous cell carcinoma indicates poor prognosis. However, there is no consensus on the diagnostic criteria, interpretation, and reporting of histology detected extranodal extension, which has contributed to conflicting evidence in the literature, and likely clinical inconsistency. The Head and Neck Cancer International Group conducted a three-round modified Delphi process with a group of 19 international pathology experts representing 15 national clinical research groups to generate consensus recommendations for histology detected extranodal extension diagnostic criteria. The expert panel strongly agreed on terminology and diagnostic features for histology detected extranodal extension and soft tissue metastasis. Moreover, the panel reached consensus on reporting of histology detected extranodal extension and on nodal sampling. These consensus recommendations, endorsed by 19 organisations representing 34 countries, are a crucial development towards standardised diagnosis and reporting of histology detected extranodal extension, and more accurate data collection and analysis.

Criteria for the diagnosis of extranodal extension detected on radiological imaging in head and neck cancer: Head and Neck Cancer International Group consensus recommendations.

Extranodal extension of tumour on histopathology is known to be a negative prognostic factor in head and neck cancer. Compelling evidence suggests that extranodal extension detected on radiological imaging is also a negative prognostic factor. Furthermore, if imaging detected extranodal extension could be identified reliably before the start of treatment, it could be used to guide treatment selection, as patients might be better managed with non-surgical approaches to avoid the toxicity and cost of trimodality therapy (surgery, chemotherapy, and radiotherapy together). There are many aspects of imaging detected extranodal extension that remain unresolved or are without consensus, such as the criteria to best diagnose them and the associated terminology. The Head and Neck Cancer International Group conducted a five-round modified Delphi process with a group of 18 international radiology experts, representing 14 national clinical research groups. We generated consensus recommendations on the terminology and diagnostic criteria for imaging detected extranodal extension to harmonise clinical practice and research. These recommendations have been endorsed by 19 national and international organisations, representing 34 countries. We propose a new classification system to aid diagnosis, which was supported by most of the participating experts over existing systems, and which will require validation in the future. Additionally, we have created an online educational resource for grading imaging detected extranodal extensions.

Assessment of endpoint definitions in curative-intent trials for mucosal head and neck squamous cell carcinomas: Head and Neck Cancer International Group consensus recommendations.

Robust time-to-event endpoint definitions are crucial for the assessment of treatment effect and the clinical value of trial interventions. Here, the Head and Neck Cancer International Group investigated endpoint use in phase 3 trials and trials considered potentially practice-changing published between 2008 and 2021 in the curative-intent setting for patients with mucosal head and neck squamous cell carcinoma. Of the 92 trials reviewed, we show that all core components of endpoint reporting were heterogeneous, including definitions of common terms, such as overall survival and progression-free survival. Our report highlights the urgent need for harmonisation of fundamental components of clinical trial endpoints and the engagement of all stakeholders to ensure the transparent reporting of endpoint details.

Assessment of endpoint definitions in recurrent and metastatic mucosal head and neck squamous cell carcinoma trials: Head and Neck Cancer International Group consensus recommendations.

Transparent and precise endpoint definitions are a crucial aspect of clinical trial conduct and reporting, and are used to communicate the benefit of an intervention. Previous studies have identified inconsistencies in endpoint definitions across oncological clinical trials. Here, the Head and Neck Cancer International Group assessed endpoint definitions from phase 3 trials or trials considered practice-changing for patients with recurrent or metastatic mucosal head and neck squamous cell carcinoma, published between 2008 and 2021. We identify considerable and global heterogeneity in endpoint definitions, which undermines the interpretation of results and development of future studies. We show how fundamental components of even incontrovertible endpoints such as overall survival vary widely, highlighting an urgent need for increased rigour in reporting and harmonisation of endpoints.

Association of a 40-Gene Expression Profile With Risk of Metastatic Disease Progression of Cutaneous Squamous Cell Carcinoma and Specification of Benefit of Adjuvant Radiation Therapy.

PURPOSE: Adjuvant radiation therapy (ART) for cutaneous squamous cell carcinoma is recommended based on a number of wide-ranging clinicopathologic features, which encompass a broad array of patients. The 40-gene expression profile (GEP) test classifies cutaneous squamous cell carcinoma tumors into low (class 1), higher (class 2A), or highest (class 2B) risk of nodal and/or distant metastasis. This study's hypotheses are as follows: (1) local recurrence is associated with metastatic disease progression and (2) 40-GEP, by identifying high risk for metastasis, could predict a metastasis-specific benefit from ART. METHODS AND MATERIALS: Samples were obtained from 920 patients (ART-untreated: 496 class 1, 335 class 2A, and 33 class 2B; ART-treated: 11 class 1, 35 class 2A, and 10 class 2B) who were matched on clinical risk factors and stratified by ART status to create 49 matched patient strata. To control for the variety of characteristics and treatment selection bias, randomly sampled pairs of matched ART and non-ART patients comprising 10,000 resampled cohorts were each analyzed for 5-year metastasis-free survival and predicted time to metastatic event. RESULTS: Of 96 patients experiencing local recurrence, 56.3% experienced metastasis; of those experiencing both, 88.9% experienced local recurrence before (75.9%) or concurrently (13.0%) with metastasis. After matching for clinicopathologic risk, median 5-year disease progression rates for resampled cohorts demonstrated approximately 50% improvement for class 2B ART-treated compared with ART-untreated cohorts. ART-treated class 2B cohorts had a 5-fold delay in predicted time to metastatic event and deceleration of disease progression compared with ART-untreated cohorts (Kolmogorov-Smirnov test, P < .01); this was not observed for patients with class 1 or 2A cSCC (P > .05 for each). No risk factor or staging system combined with ART status identified groups that would benefit from ART as well as 40-GEP. CONCLUSIONS: Forty-GEP identifies patients at the highest risk of nodal/distant metastasis who may derive the greatest benefit from ART, as well as patients who may have clinical indications for ART but are at low risk of metastasis. Compared with current guidelines, 40-GEP could provide greater specificity concerning the benefit of ART in individual patients.

Quantification of the environmental impact of radiotherapy and associated secondary human health effects: a multi-institutional retrospective analysis and simulation.

BACKGROUND: The health-care industry is a substantial contributor to global greenhouse gas emissions, yet the specific environmental impact of radiotherapy, a cornerstone of cancer treatment, remains under-explored. We aimed to quantify the emissions associated with the delivery of radiotherapy in the USA and propose a framework for reducing the environmental impact of oncology care. METHODS: In this multi-institutional retrospective analysis and simulation study, we conducted a lifecycle assessment of external beam radiotherapy (EBRT) for ten anatomical disease sites, adhering to the International Organization for Standardization's standards ISO 14040 and ISO 14044. We analysed retrospective data from Jan 1, 2017, to Oct 1, 2023, encompassing patient and staff travel, medical supplies, and equipment and building energy use associated with the use of EBRT at four academic institutions in the USA. The primary objective was to measure the environmental impacts across ten categories: greenhouse gases (expressed as kg of carbon dioxide equivalents [CO2e]), ozone depletion, smog formation, acidification, eutrophication, carcinogenic and non-carcinogenic potential, respiratory effects, fossil fuel depletion, and ecotoxicity. Human health effects secondary to these environmental impacts were also estimated as disability-adjusted life years. We also assessed the potential benefits of hypofractionated regimens for breast and genitourinary (ie, prostate and bladder) cancers on US greenhouse gas emissions using an analytic model based on the 2014 US National Cancer Database for fractionation patterns and patient commute distances. FINDINGS: We estimated that the mean greenhouse gas emissions associated with a standard 25-fraction EBRT course were 4310 kg CO2e (SD 2910), which corresponded to 0·0035 disability-adjusted life years per treatment course. Transit and building energy usage accounted for 25·73% (1110 kg CO2e) and 73·95% of (3190 kg CO2e) of total greenhouse gas emissions, respectively, whereas supplies contributed only 0·32% (14 kg CO2e). Across the other environmental impact categories, most of the environmental impact also stemmed from patient transit and energy use within facilities, with little environmental impact contributed by supplies used. Hypofractionated treatment simulations suggested a substantial reduction in greenhouse gas emissions-by up to 42% for breast and 77% for genitourinary cancer-and environmental impacts more broadly. INTERPRETATION: This comprehensive lifecycle assessment of EBRT delineates the environmental and secondary health impacts of radiotherapy, and underscores the urgent need for sustainable practices in oncology. The findings serve as a reference for future decarbonisation efforts in cancer care and show the potential environmental benefits of modifying treatment protocols (when clinical equipoise exists). They also highlight strategic opportunities to mitigate the ecological footprint in an era of escalating climate change and increasing cancer prevalence. FUNDING: Mount Zion Health Fund.

A Hard Truth to Swallow: Critically Evaluating the MD Anderson Dysphagia Inventory (MDADI) as an Endpoint in Human Papillomavirus-associated Oropharyngeal Cancer Trials.

The MD Anderson Dysphagia Inventory (MDADI), a measure of swallowing-related quality of life, has become the preferred patient-reported outcome measure (PROM) in contemporary clinical trials evaluating the experience of human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPVOPSCC) survivors. With many potentially practice-changing studies using the MDADI composite score as either a primary or coprimary endpoint, or as a key secondary endpoint, it is important to understand its psychometric properties as judged by contemporary PROM standards, with a particular focus on its application to contemporary HPVOPSCC populations. In this critical review, we evaluate contemporary HPVOPSCC studies reporting MDADI outcomes, followed by a detailed evaluation of the psychometric properties of the MDADI. Although the focus of this review was the MDADI, the issues discussed are not unique to the MDADI and have broader applicability to the evaluation and assessment of other PROMs currently in use. First, it may be possible to improve administration of the instrument, as related to missing items, scoring, and the number of items required. Second, although in many instances, the MDADI has been intended as a direct or surrogate measure of swallowing physiology, the MDADI composite score captures a broader health-related quality of life construct affected by both swallowing and eating, the latter of which may be affected by a range of nonswallowing treatment-related toxicities. Finally, a clinically meaningful change of 10 in the MDADI composite score, widely accepted and applied to the clinical trial setting, represents an undoubtably clinically relevant difference in unselected head and neck cancer survivors. However, the smallest difference that might be clinically important to a highly functional HPVOPSCC cohort remains uncertain. Understanding the purpose and properties of the MDADI instrument and furthering the sophistication with which we apply it in this population would improve its interpretation in clinical trials.

68Ga-FAP-2286 PET of Solid Tumors: Biodistribution, Dosimetry, and Comparison with 18F-FDG.

Fibroblast activation protein (FAP), expressed in the tumor microenvironment of a variety of cancers, has become a target of novel PET tracers. The purpose of this report is to evaluate the imaging characteristics of 68Ga-FAP-2286, present the first-to our knowledge-dosimetry analysis to date, and compare the agent with 18F-FDG and FAPI compounds. Methods: Patients were administered 219 ± 43 MBq of 68Ga-FAP-2286 and scanned after 60 min. Uptake was measured in up to 5 lesions per patient and within the kidneys, spleen, liver, and mediastinum (blood pool). Absorbed doses were evaluated using MIM Encore and OLINDA/EXM version 1.1 using the International Commission on Radiological Protection publication 103 tissue weighting factor. Results: Forty-six patients were imaged with 68Ga-FAP-2286 PET. The highest average uptake was seen in sarcoma, cholangiocarcinoma, and colon cancer. The lowest uptake was found in lung cancer and testicular cancer. The average SUVmax was significantly higher on 68Ga-FAP-2286 PET than on 18F-FDG PET in cholangiocarcinoma (18.2 ± 6.4 vs. 9.1 ± 5.0, P = 0.007), breast cancer (11.1 ± 6.8 vs. 4.1 ± 2.2, P < 0.001), colon cancer (13.8 ± 2.2 vs. 7.6 ± 1.7, P = 0.001), hepatocellular carcinoma (9.3 ± 3.5 vs. 4.7 ± 1.3, P = 0.01), head and neck cancer (11.3 ± 3.5 vs. 7.6 ± 5.5, P = 0.04), and pancreatic adenocarcinoma (7.4 ± 1.8 vs. 3.7 ± 1.0, P = 0.01). The total-body effective dose was estimated at 1.16E-02 mSv/MBq, with the greatest absorbed organ dose in the urinary bladder wall (9.98E-02 mGy/MBq). Conclusion: 68Ga-FAP-2286 biodistribution, dosimetry, and tumor uptake were similar to those of previously reported FAPI compounds. Additionally,68Ga-FAP-2286 PET had consistently higher uptake than 18F-FDG PET. These results are especially promising in the setting of small-volume disease and differentiating tumor from inflammatory uptake.

Assessing the knowledge and awareness of US oncologists regarding the specialty of oral medicine.

OBJECTIVES: This cross-sectional study aimed to assess the awareness among United States (US) oncologists about oral medicine (OM) as a specialty of dentistry, and their collaboration with OM providers. METHODS: An online survey was conducted, inviting 1350 US oncologists, with data collected on demographics, practice background, comfort level with diagnosing and treating oral conditions, referral practices for oral conditions, and more. RESULTS: Of the invited 1350 oncologists, 192 responded (14% response rate). Among respondents, 46% were familiar with the OM specialty. Of these, 73% had previously sought consultation from OM specialists. The primary reasons for referral included dental clearance before initiating chemotherapy (38.5%), dental clearance before initiating radiotherapy (37%), and managing oral ulcers and oral potentially malignant disorders equally (32.2%). Regarding referrals to providers outside of OM, oncologists primarily referred patients with oral lesions to otolaryngologists (64.6%), followed by oral and maxillofacial surgeons (55.2%) and general dentists (45.3%). CONCLUSION: Our study showed that over half of US oncologists were unfamiliar with the OM specialty. However, the referral rate to OM providers was high among oncologists who had prior OM knowledge. It is advisable to enhance the collaboration between OM and oncology specialists to ensure optimal care for patients with cancer.

Phase II, Single-Arm Trial of Induction and Concurrent Vismodegib With Curative-Intent Radiation Therapy for Locally Advanced, Unresectable Basal Cell Carcinoma.

PURPOSE: Locally advanced, unresectable basal cell carcinoma (LA BCC) can be treated with radiation therapy (RT), but locoregional control (LRC) rates are unsatisfactory. Vismodegib is a hedgehog pathway inhibitor (HPI) active in BCC that may radiosensitize BCC. We evaluated the combination of vismodegib and RT for patients with LA BCC. METHODS: In this multicenter, single-arm, phase II study, patients with unresectable LA BCC received 12 weeks of induction vismodegib, followed by 7 weeks of concurrent vismodegib and RT. The primary end point was LRC rate at 1 year after the end of treatment. Secondary end points included objective response, progression-free survival (PFS), overall survival (OS), safety, and patient-reported quality of life (PRQOL). RESULTS: Twenty-four patients received vismodegib; five were unable to complete 12 weeks of induction therapy. LRC was achieved in 91% (95% CI, 68 to 98) of patients at 1 year. The response rate was 63% (95% CI, 38 to 84) after induction vismodegib and 83% (95% CI, 59 to 96) after concurrent vismodegib and RT. With a median follow-up of 5.7 years, 1-year PFS and OS rates were 100% and 96%, and at 5 years PFS and OS rates were 78% and 83%, respectively. Distant metastasis or BCC-related death has not been observed. The most frequent treatment-related adverse events (AEs) were dysgeusia, fatigue, and myalgias occurring in 83%, 75%, and 75% of patients. No grade 4 to 5 treatment-related AEs occurred. PRQOL demonstrated clinically meaningful improvements in all subscales, with emotions and functioning improvements persisting for a year after the end of treatment. CONCLUSION: In patients with unresectable LA BCC, the combination of vismodegib and RT yielded high rates of LRC and PFS and durable improvements in PRQOL.

Essential data variables for a minimum dataset for head and neck cancer trials and clinical research: HNCIG consensus recommendations and database.

The Head and Neck Cancer International Group (HNCIG) has undertaken an international modified Delphi process to reach consensus on the essential data variables to be included in a minimum database for HNC research. Endorsed by 19 research organisations representing 34 countries, these recommendations provide the framework to facilitate and harmonise data collection and sharing for HNC research. These variables have also been incorporated into a ready to use downloadable HNCIG minimum database, available from the HNCIG website.

International guidelines for intratumoral and intranodal injection of NBTXR3 nanoparticles in head and neck cancers.

BACKGROUND: An international multidisciplinary panel of experts aimed to provide consensus guidelines describing the optimal intratumoral and intranodal injection of NBTXR3 hafnium oxide nanoparticles in head and neck squamous cell carcinoma (HNSCC) of the oral cavity, oropharynx, and cervical lymph nodes and to review data concerning safety, feasibility, and procedural aspects of administration. METHODS: The Delphi method was used to determine consensus. A 4-member steering committee and a 10-member monitoring committee wrote and revised the guidelines, divided into eight sections. An independent 3-member reading committee reviewed the recommendations. RESULTS: After two rounds of voting, strong consensus was obtained on all recommendations. Intratumoral and intranodal injection was deemed feasible. NBTXR3 volume calculation, choice of patients, preparation and injection procedure, potential side effects, post injection, and post treatment follow-up were described in detail. CONCLUSIONS: Best practices for the injection of NBTXR3 were defined, thus enabling international standardization of intratumoral nanoparticle injection.

Higher area deprivation index is associated with poorer local control and overall survival in non-metastatic nasopharyngeal carcinoma.

BACKGROUND: Neighborhood socioeconomic deprivation impacts outcomes in various cancers. We examined this association in nasopharyngeal carcinoma (NPC) patients using the area deprivation index (ADI). METHODS: We conducted a single-institution retrospective cohort study on NPC patients treated with definitive radiotherapy from 1980 to 2023. ADI was used as the primary exposure measure. Higher ADI indicates higher levels of socioeconomic deprivation. RESULTS: Of 561 patients, those with higher ADI (6-10 vs. 1-5) presented more commonly with AJCC stage III/IV compared to I/II (87% vs. 76%, p = 0.03). Increasing ADI decile score correlated with poorer overall survival (HR 1.14, 95% CI 1.01-1.28, p = 0.04). Local control was worse in patients from the most deprived quartile in the cohort ADI 5-10 (HR 2.11, 95% CI 1.01-4.41, p = 0.05). CONCLUSIONS: NPC patients from more disadvantaged neighborhoods undergoing radiotherapy had worse local control and survival outcomes. Interventions to address structural determinants of health and neighborhood disparities may improve these outcomes.

Effects of Wildfire Events on California Radiation Oncology Clinics and Patients.

Purpose: The effect of climate-driven events, such as wildfires, on health care delivery and cancer care is a growing concern. Patients with cancer undergoing radiation therapy are particularly vulnerable to treatment interruptions, which have a direct effect on survival. We report the results of a study characterizing the effect of wildfires on radiation oncology clinics and their patients. Methods and Materials: A survey of California radiation oncologists was used to evaluate emergency preparedness and the effect of wildfires on the delivery of radiation therapy services between 2017 and 2022. Descriptive statistics and Pearson's χ2 tests were performed to investigate potential relationships between provider characteristics, practice settings, and perceptions of the effect of wildfire events. California Department of Forestry and Fire Protection data were employed to map the geographic distribution of wildfires to clinic locations. Results: Response rate was 12.3% (51/415 radiation oncologists), representing 25% of clinics (43/176) in 41% (24/58) of California counties. Sixty-one percent (31/51) of respondents reported being affected by a wildfire, 2 of which are rural clinics (100%, 2/2) and 29 are (59%, 29/49) metropolitan practices. Of these, 18% (9/51) reported a clinic closure, and 29% (15/51) reported staffing shortages. Respondents reported effects on patients, including having to evacuate (55%, 28/51), cancel/reschedule treatments (53%, 27/51), and experiencing physical, mental, or financial hardship due to wildfires (45%, 23/51). Respondents described effects on clinical operations, including being forced to transfer patients (24%, 12/51), transportation interruptions (37%, 19/51), regional/community evacuations (35%, 18/51), and physical/mental health effects (27%, 14/51) on clinic personnel. Less than half of the respondents (47%, 24/51) reported their workplace had a wildfire emergency preparedness plan. Additionally, geographic analysis revealed that 100% (176/176) of clinics were located within 25 miles of a wildfire. Conclusions: This study highlights the effects of wildfires on radiation oncology clinics and patients and underscores the need for emergency preparedness planning to minimize the consequences of such disasters.

Xevinapant plus radiotherapy in resected, high-risk, cisplatin-ineligible LA SCCHN: the phase III XRay Vision study design.

There is a significant unmet need and lack of treatment options for patients with resected, high-risk, cisplatin-ineligible locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). Xevinapant, a first-in-class, potent, oral, small-molecule IAP inhibitor, is thought to restore cancer cell sensitivity to chemotherapy and radiotherapy in clinical and preclinical studies. We describe the design of XRay Vision (NCT05386550), an international, randomized, double-blind, phase III study. Approximately 700 patients with resected, high-risk, cisplatin-ineligible LA SCCHN will be randomized 1:1 to receive 6 cycles of xevinapant or placebo, in combination with radiotherapy for the first 3 cycles. The primary end point is disease-free survival, and secondary end points include overall survival, health-related quality of life, and safety.

Squamous cell carcinoma is the most common form of head and neck cancer (SCCHN) and includes cancers of the lips, mouth, throat, tongue and voice box. It is called 'locally advanced' when the cancer has spread to nearby areas but not to other parts of the body. Few treatment options are available for people with locally advanced SCCHN who have had surgery and are unable to receive a type of chemotherapy called cisplatin. Xevinapant is being developed as a possible new type of cancer treatment. It is a liquid that is taken by mouth or given through a feeding tube. Adding xevinapant to the standard treatment ­ called radiotherapy ­ aims to make radiotherapy more effective against the cancer. Researchers have started a large, international, phase III study called XRay Vision to see if adding xevinapant to radiotherapy can help stop the cancer from coming back after surgery and help people live longer. Clinical Trial Registration: NCT05386550 (ClinicalTrials.gov).

Combinatorial Approaches for Chemotherapies and Targeted Therapies With Radiation: United Efforts to Innovate in Patient Care.

Combinatorial therapies consisting of radiation therapy (RT) with systemic therapies, particularly chemotherapy and targeted therapies, have moved the needle to augment disease control across nearly all disease sites for locally advanced disease. Evaluating these important combinations to incorporate more potent therapies with RT will aid our understanding of toxicity and efficacy for patients. This article discusses multiple disease sites and includes a compilation of contributions from expert Red Journal editors from each disease site. Leveraging improved systemic control with novel agents, we must continue efforts to study novel treatment combinations with RT.