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Improving Radiotherapy Response in the Treatment of Head and Neck Cancer.

ABSTRACT: The application of radiotherapy to the treatment of cancer has existed for over 100 years. Although its use has cured many, much work remains to be done to minimize side effects, and in-field tumor recurrences. Resistance of the tumor to a radiation-mediated death remains a complex issue that results in local recurrence and significantly decreases patient survival. Here, we review mechanisms of radioresistance and selective treatment combinations that improve the efficacy of the radiation that is delivered. Further investigation into the underlying mechanisms of radiation resistance is warranted to develop not just novel treatments, but treatments with improved safety profiles relative to current radiosensitizers. This review is written in memory and honor of Dr. Peter Stambrook, an avid scientist and thought leader in the field of DNA damage and carcinogenesis, and a mentor and advocate for countless students and faculty.

SUBMITTER: Wicker CA

PROVIDER: S-EPMC10228519 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Improving Radiotherapy Response in the Treatment of Head and Neck Cancer.

Wicker Christina A CA Petery Taylor T Dubey Poornima P Wise-Draper Trisha M TM Takiar Vinita V

Critical reviews in oncogenesis 20220101 2

The application of radiotherapy to the treatment of cancer has existed for over 100 years. Although its use has cured many, much work remains to be done to minimize side effects, and in-field tumor recurrences. Resistance of the tumor to a radiation-mediated death remains a complex issue that results in local recurrence and significantly decreases patient survival. Here, we review mechanisms of radioresistance and selective treatment combinations that improve the efficacy of the radiation that i ...[more]

PMID: 36734873

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Improving compliance with swallowing exercise to decrease radiotherapy-related dysphagia in patients with head and neck cancer.

Project description:ObjectiveDysphagia, one of the most common complications in head and neck cancer (HNC) treated with radiotherapy, can severely affect patients' quality of life. Currently, because no "gold standard" treatment exists, swallowing exercise remains the main rehabilitation strategy for dysphagia. However, patients' compliance with long-term swallowing exercise is only 40%, thus, greatly compromising outcomes. This article aims to analyze thefactors influencing swallowing exercise compliance in patients with HNC and explains strategies developed to date for improved rehabilitation outcomes.MethodsResearch studies published between 2005 and 2022 were retrieved from seven databases: PubMed, Cochrane Library, Embase, CINAHL, CNKI, Wan Fang Database, and VIP Database, and 21 articles were shortlisted and systematically reviewed.ResultsThe swallowing exercise compliance in patients with HNC undergoing radiotherapy was affected by multiple factors, including socio-demographic factors, illness-associated factors, treatment-associated factors, and psychosocial factors. Regarding the interventions, current strategies mainly address psychosocial issues via developing various education programs.ConclusionsDifferent factors influencing swallowing exercise compliance are important and should be observed. Measures including developing multidisciplinary teams, applying innovative equipment, refining the intervention procedure, and applying systematic theory frameworks should be performed to achieve better outcomes of compliance interventions.

| S-EPMC9792737 | biostudies-literature

Comparison of intensity-modulated radiotherapy, adaptive radiotherapy, proton radiotherapy, and adaptive proton radiotherapy for treatment of locally advanced head and neck cancer.

Project description:Background and purposeVarious radiotherapy planning methods for locally advanced squamous cell carcinoma of the head and neck (SCCHN) have been proposed to decrease normal tissue toxicity. We compare IMRT, adaptive IMRT, proton therapy (IMPT), and adaptive IMPT for SCCHN.Materials and methodsInitial and re-simulation CT images from 10 consecutive patients with SCCHN were used to quantify dosimetric differences between photon and proton therapy. Contouring was performed on both CTs, and plans (n=40 plans) and dose-volume histograms were generated.ResultsThe mean GTV volume decreased 53.4% with re-simulation. All plans provided comparable PTV coverage. Compared with IMRT, adaptive IMRT significantly reduced the maximum dose to the mandible (p=0.020) and mean doses to the contralateral parotid gland (p=0.049) and larynx (p=0.049). Compared with IMRT and adaptive IMRT, IMPT significantly lowered the maximum doses to the spinal cord (p<0.002 for both) and brainstem (p<0.002 for both) and mean doses to the larynx (p<0.002 for both) and ipsilateral (p=0.004 IMRT, p=0.050 adaptive) and contralateral (p<0.002 IMRT, p=0.010 adaptive) parotid glands. Adaptive IMPT significantly reduced doses to all critical structures compared with IMRT and adaptive IMRT and several critical structures compared with non-adaptive IMPT.ConclusionsAlthough adaptive IMRT reduced dose to several normal structures compared with standard IMRT, non-adaptive proton therapy had a more favorable dosimetric profile than IMRT or adaptive IMRT and may obviate the need for adaptive planning. Protons allowed significant sparing of the spinal cord, parotid glands, larynx, and brainstem and should be considered for SCCHN to decrease normal tissue toxicity while still providing optimal tumor coverage.

| S-EPMC3174314 | biostudies-literature

Radiotherapy changes the salivary proteome in head and neck cancer patients: evaluation before, during and after treatment

Project description:Objectives: Salivary glands are affected during radiotherapy in the head and neck region, leading to a reduction in salivary flow and changes its composition. Besides negatively affecting the oral soft tissues, this can also lead to dental impairment. Thus, we evaluated the effect of radiotherapy in the proteomic profile of the saliva in patients with head-and-neck-cancer (HNC). Materials and methods: HNC patients had their saliva collected before (BRT), during (2-5 weeks; DRT) and after (3-4 months; ART) radiotherapy. Saliva was also collected from healthy volunteers (control; C). Samples were processed for proteomic analysis. Results: In total 1.055 proteins were identified, among which 46 were common to all groups, while 86, 86, 286 and 395 were exclusively found in C, BRT, DRT and ART, respectively. Remarkably, alpha-enolase was increased 35-fold DRT compared with BRT, while proline-rich proteins were decreased. ART there was a 16-fold increase in scaffold attachment factor-B1 and a 3-fold decrease in alpha-enolase and several cystatins. When compared with C, salivary proteins of BRT patients showed increases cystatin-C, lysozyme C, histatin-1 and proline-rich proteins. Conclusion/Clinical revelance: Both HNC and radiotherapy remarkably change the salivary protein composition. Altogether, our results, for the first time, suggest investigating alpha-enolase levels in saliva DRT in future studies as a possible biomarker and strategy to predict the efficiency of the treatment. Moreover, our data provide important insights for designing dental products that are more effective for these patients and contribute to a better understanding of the progressive changes in salivary proteins induced by radiotherapy.

2021-10-12 | PXD028594 | Pride

FMISO-Based Adaptive Radiotherapy in Head and Neck Cancer.

Project description:Concurrent chemoradiotherapy represents one of the most used strategies in the curative treatment of patients with head and neck (HNC) cancer. Locoregional failure is the predominant recurrence pattern. Tumor hypoxia belongs to the main cause of treatment failure. Positron emission tomography (PET) using hypoxia radiotracers has been studied extensively and has proven its feasibility and reproducibility to detect tumor hypoxia. A number of studies confirmed that the uptake of FMISO in the recurrent region is significantly higher than that in the non-recurrent region. The escalation of dose to hypoxic tumors may improve outcomes. The technical feasibility of optimizing radiotherapeutic plans has been well documented. To define the hypoxic tumour volume, there are two main approaches: dose painting by contour (DPBC) or by number (DPBN) based on PET images. Despite amazing technological advances, precision in target coverage, and surrounding tissue sparring, radiation oncology is still not considered a targeted treatment if the "one dose fits all" approach is used. Using FMISO and other hypoxia tracers may be an important step for individualizing radiation treatment and together with future radiomic principles and a possible genome-based adjusting dose, will move radiation oncology into the precise and personalized era.

| S-EPMC9410424 | biostudies-literature

Combining Radiotherapy and Immunotherapy in Head and Neck Cancer.

Project description:Head and neck squamous cell carcinoma (HNSCC) is a leading cause of morbidity and mortality globally. Despite significant advances in well-established treatment techniques, prognosis for advanced-stage HNSCC remains poor. Recent, accumulating evidence supports a role for immunotherapy in HNSCC treatment. Radiation therapy (RT), a standard treatment option for HNSCC, has immunomodulatory and immunostimulatory effects that may enhance the efficacy of immunotherapy. In several cancer types, combining RT and immunotherapy has been shown to improve tumor response rates, increase survival, and reduce toxicity compared to traditional chemotherapy and radiation therapy. This review provides a timely overview of the current knowledge on the use of RT and immunotherapy for treating HNSCC. It highlights the potential advantages of combining these therapies, such as improved tumor response rates, increased survival, and reduced toxicity. The review also discusses the challenges that need to be addressed when redefining the standard of care in HNSCC, and proposes further research to optimize treatment combinations, minimize radiation-induced toxicity, and identify suitable patient populations for treatment.

| S-EPMC10452591 | biostudies-literature

Neck muscle training improving the setup of reproducibility in patient with head and neck cancer receiving radiotherapy - a prospective randomized controlled study.

Project description:Background and purposeThe aim of this study is to evaluate the effectiveness of a cervical muscle training intervention in decreasing setup errors in patients head and neck cancer (HNC) undergoing radiotherapy (RT).Materials and methodsHNC patients opting for RT at our center. The patients were randomly allocated to either the muscle training group or the control group in a 1:1 ratio. The magnitude of the setup error was measured at the levels of the clivus, C4 and C7 vertebrae respectively. The Van Herk formula was used to determine appropriate planning target volume (PTV) margins. (Trial Registration: ChiCTR2000041009, registration date: 12/16/2020) RESULTS: A total of 221 patients were analyzed, with 109 assigned to the muscle training group and 112 enrolled in the control group. Compared with the control group, the setup errors in the X and Z direction of the clivus and the Z direction of C4 and C7 in the muscle training group were significantly lower (p = 0.031, < 0.001, < 0.001, < 0.001 respectively). The required PTV margins in the Z direction increased from 2.13 mm in the clivus to 3.63 mm in C7 in the muscle training group and from 2.89 mm in the clivus to 4.37 mm in C7 in the control group. Multivariate linear regression analysis demonstrated that the impact of neck muscle training, weight fluctuation, and cervical curvature on the setup error in the Z direction at C7 differed significantly (p = 0.000, 0.001, and 0.008, respectively).ConclusionNeck muscle training can reduce setup errors and PTV margins in the anterior-posterior direction in patients undergoing RT for HNC.

| S-EPMC11905638 | biostudies-literature

The influence of PI3K inhibition on the radiotherapy response of head and neck cancer cells.

Project description:Radiotherapy has a central role in the treatment of head and neck squamous cell carcinoma (HNSCC). Activation of the PI3K/AKT/mTOR pathway can decrease the efficiency of radiotherapy via the promotion of cell survival and DNA repair. Here, the influence of PI3K pathway inhibition on radiotherapy response was investigated. Two PI3K inhibitors were investigated and both BKM120 and GDC0980 effectively inhibited cellular and clonogenic growth in 6 HNSCC cells, both HPV-positive as well as HPV-negative. Despite targeted inhibition of the pathway and slight increase in DNA damage, PI3K inhibition did not show significant radiosensitization. Currently only one clinical trial is assessing the effectiveness of combining BKM120 with RT in HNSCC (NCT02113878) of which the results are eagerly awaited.

| S-EPMC7529775 | biostudies-literature

Quality assurance of dysphagia-optimised intensity modulated radiotherapy treatment planning for head and neck cancer.

Project description:This study aimed to assess the impact of the margin applied to the clinical target volume, to create the planning target volume, on plan quality of a novel dysphagia-optimised intensity modulated radiotherapy technique developed within a head and neck cancer multicentre randomised controlled trial. Protocol compliant plans were used for a single benchmark planning case. Larger margins were associated with higher doses to adjacent organs at risk, particularly the inferior pharyngeal constrictor muscle, but coincided with some improved low dose target coverage. A 3 mm margin is recommended for this technique if local practices allow.

| S-EPMC8560997 | biostudies-literature

The future of personalised radiotherapy for head and neck cancer.

Project description:Radiotherapy has long been the mainstay of treatment for patients with head and neck cancer and has traditionally involved a stage-dependent strategy whereby all patients with the same TNM stage receive the same therapy. We believe there is a substantial opportunity to improve radiotherapy delivery beyond just technological and anatomical precision. In this Series paper, we explore several new ideas that could improve understanding of the phenotypic and genotypic differences that exist between patients and their tumours. We discuss how exploiting these differences and taking advantage of precision medicine tools-such as genomics, radiomics, and mathematical modelling-could open new doors to personalised radiotherapy adaptation and treatment. We propose a new treatment shift that moves away from an era of empirical dosing and fractionation to an era focused on the development of evidence to guide personalisation and biological adaptation of radiotherapy. We believe these approaches offer the potential to improve outcomes and reduce toxicity.

| S-EPMC7771279 | biostudies-literature

Hypofractionated Radiotherapy for Palliation in Locally Advanced Head and Neck Cancer.

Project description:In India, a considerable proportion of patients with head and neck cancer present with locoregionally advanced disease. Symptom palliation becomes a major objective in these cases when they could not be considered for a curative approach.The aim of this study is to assess the role of palliative radiotherapy for symptom control in patients with locally advanced head and neck cancer.This was a retrospective study.Between July 2015 and June 2016, 98 patients with stage IV head and neck cancer were treated with palliative radiotherapy 25 Gray (Gy)/4 fractions (fr)/1 fraction (6.25 Gy)/week. Presenting symptoms were noted. The primary end point was relief of symptoms in the 4th week after radiotherapy. Percentage symptom relief was quantified by the patient using a rupee scale. Treatment response was noted using the WHO criteria. Acute toxicity was graded as per the Radiation Therapy Oncology Group (RTOG) criteria.The most common presenting symptom was pain. At 4 weeks after radiotherapy completion, all patients had >50% pain relief. Dysphagia was improved in 82% of patients. Respiratory distress was improved in all the symptomatic patients. Tumor complete response (CR) was seen in 2 patients, partial response in 89, stable disease in 3, and progressive disease in 4. RTOG Grade 2 and 3 acute skin and mucosal toxicities were seen in 29% and 27% cases, respectively. No patient had Grade 4 adverse effect.Hypofractionated radiation could provide effective symptom palliation in advanced head and neck cancers. The weekly schedule was well tolerated and found convenient by the patients.

| S-EPMC5545959 | biostudies-other

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