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Advances in Radiation Therapy for Head and Neck Cancer
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Advances in Radiation Therapy for Head and Neck Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 3401

Special Issue Editor

Dr. Vassilis Kouloulias

E-Mail Website
Guest Editor
2nd Department of Radiology, Radiotherapy Unit, ATTIKON University Hospital, 124 62 Athens, Greece
Interests: head and neck cancer; breast cancer; prostate cancer; skin cancer; quality assurance
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Head and neck (HN) cancer represents is of the most common types of neoplasia all over the world. Beyond surgical resection, if possible, radiotherapy (RT) is generally the treatment of choice, while almost 75% of patients will benefit from irradiation. In the early stages of HN cancer, radiotherapy can replace the need for surgical resection. Cancer patients can be treated concomitantly with chemoradiotherapy for local advanced cancer or with surgical resection followed by adjuvant radiotherapy. Over the last few decades, technology has rapidly improved, with new techniques such as intensity-modulated RT (IMRT), image-guided RT (IGRT), proton therapy, and magnetic-resonance-guided RT (MR-LINAC) now included in routine clinical practice, further improving the quality of life for cancer patients. Moreover, adaptive RT and artificial intelligence (AI) have shown excellent results following the improvement of clinical practice in terms of time-consuming procedures. Nanoparticles and hyperthermia, along with immunotherapy, have also been reported as adjuvant modalities used for improving responses to RT treatment. Re-irradiation remains a crucial subject with new data available. Alternative schemes of RT, such as hyper- or hypo-fractionation, have also shown really impressive results, while radiobiology plays an important role for RT. 

Dr. Vassilis Kouloulias
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • adaptive radiotherapy 
  • hyper- and hypo-fractionated radiotherapy 
  • artificial intelligence in radiotherapy for head and neck cancer 
  • quality assurance and set-up errors associated with IMRT, VMAT, IGRT, and SGRT techniques 
  • protons and heavy ions for radiotherapy 
  • re-irradiation 
  • nanoparticles plus radiotherapy 
  • hyperthermia plus radiotherapy 
  • radiotherapy plus immunotherapy 
  • the de-escalation of radiation therapy

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Published Papers (4 papers)

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Research

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17 pages, 3391 KiB  
Article
A New Model to Investigate the Action of Radiation and Cigarette Smoke on Head and Neck Cancer Cells
by Kylie Lopes Floro, Rhys Gillman, Miriam Wankell, Brittany Dewdney, Madhavi Chilkuri, Ashley Shackelford, Leslie Kuma, Marcus Powers and Lionel Hebbard
Cancers 2025, 17(8), 1346; https://doi.org/10.3390/cancers17081346 - 17 Apr 2025
Viewed by 281
Abstract
Background/Objectives: Smokers are at an increased risk of developing mucosal head and neck squamous cell cancers (HNSCCs) and have a worse prognosis when treated. The cellular and molecular mechanisms underlying the latter has not been established. We therefore developed an in vitro [...] Read more.
Background/Objectives: Smokers are at an increased risk of developing mucosal head and neck squamous cell cancers (HNSCCs) and have a worse prognosis when treated. The cellular and molecular mechanisms underlying the latter has not been established. We therefore developed an in vitro model to investigate the effects of radiation and smoking on mucosal HNSCCs. FaDu hypopharyngeal cancer cells were subjected to daily fractionated radiation and cultured with and without cigarette-smoke-exposed media. Methods: The cells were characterised using assays for tumour sphere formation, proliferation, migration, invasion, CD44 and ALDH expression, and next generation sequencing. We also evaluated CD44 and ALDH1 expression in patient tumour samples. Results: Radiation and smoking separately reduced FaDu tumour sphere/Cancer Stem Cell (CSC) number and proliferation, and increased cell migration and invasion. Combined, they further reduced CSC number proliferation and promoted migration. CD44 and ALDH co-expression was reduced in conditions with cigarette smoke. Through next generation sequencing, radiation and smoking produced a gene signature related to cell invasion, angiogenesis, and survival. Immunohistochemistry for CD44 and ALDH1 on patient tumour specimens did not demonstrate a relationship with smoking status, supported our in vitro findings. Conclusions: The data show the utility of a new experimental model to test the combination of radiation and smoking on mucosal HNSCCs behaviour. Full article
(This article belongs to the Special Issue Advances in Radiation Therapy for Head and Neck Cancer)
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16 pages, 3935 KiB  
Article
Prediction of Persistent Tumor Status in Nasopharyngeal Carcinoma Post-Radiotherapy-Related Treatment: A Machine Learning Approach
by Hsien-Chun Tseng, Chao-Yu Shen, Pan-Fu Kao, Chun-Yi Chuang, Da-Yi Yan, Yi-Han Liao, Xuan-Ping Lu, Ting-Jung Sheu and Wei-Chih Shen
Cancers 2025, 17(1), 96; https://doi.org/10.3390/cancers17010096 - 31 Dec 2024
Viewed by 803
Abstract
Background/Objectives: The duration of the response to radiotherapy-related treatment is a critical prognostic indicator for patients with nasopharyngeal carcinoma (NPC). Persistent tumor status, including residual tumor presence and early recurrence, is associated with poorer survival outcomes. To address this, we developed a prediction [...] Read more.
Background/Objectives: The duration of the response to radiotherapy-related treatment is a critical prognostic indicator for patients with nasopharyngeal carcinoma (NPC). Persistent tumor status, including residual tumor presence and early recurrence, is associated with poorer survival outcomes. To address this, we developed a prediction model to identify patients at a high risk of persistent tumor status prior to initiating treatment. Methods: This retrospective study included 104 patients with NPC receiving radiotherapy-related treatment who had completed a 3-year follow-up period; 29 were classified into the persistent tumor status group and 75 into the disease-free group. Radiomic features were extracted from pretreatment positron emission tomography (PET) images and used to construct a prediction model by employing machine learning algorithms. The model’s diagnostic performance was assessed using the area under the receiver operating characteristic curve (AUC), whereas SHapley Additive exPlanations (SHAP) analysis was conducted to determine the contribution of individual features to the model. Results: The prediction model developed using the AdaBoost algorithm and validated through five-fold cross-validation achieved the highest AUC of 0.934. Its sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 89.66%, 86.67%, 72.22%, 95.59%, and 87.5%, respectively. SHAP analysis revealed that the feature of high dependence low metabolic uptake emphasis50 had the greatest impact on model predictions. Furthermore, patients classified as disease-free exhibited markedly higher overall survival rates compared with those with persistent tumor status. Conclusions: In conclusion, the proposed prediction model efficiently identified patients with NPC at a high risk of persistent tumor status by using radiomic features extracted from pretreatment PET images. Full article
(This article belongs to the Special Issue Advances in Radiation Therapy for Head and Neck Cancer)
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14 pages, 1267 KiB  
Article
The Role of Radiotherapy to the Primary Site in Oropharyngeal Cancer with Limited Metastases—An Analysis of a Hospital-Based Registry
by Michael Kharouta, F. Jeffrey Lorenz, Sean Mahase, Hongyun Shi, Neerav Goyal and Min Yao
Cancers 2024, 16(24), 4130; https://doi.org/10.3390/cancers16244130 - 11 Dec 2024
Viewed by 835
Abstract
Background/Objectives: Limited metastatic squamous cell carcinoma of the oropharynx (OPC) lacks clear management guidelines, especially for HPV-associated disease. The objective of this study was to investigate if primary site radiotherapy (RT) benefits overall survival in limited metastatic OPC. Methods: Utilizing the National Cancer [...] Read more.
Background/Objectives: Limited metastatic squamous cell carcinoma of the oropharynx (OPC) lacks clear management guidelines, especially for HPV-associated disease. The objective of this study was to investigate if primary site radiotherapy (RT) benefits overall survival in limited metastatic OPC. Methods: Utilizing the National Cancer Database (NCDB), patients aged 18–90 with OPC presenting as cM1 with limited metastatic disease to one distant site were identified. Propensity score matching, Cox-proportional hazards models, and Kaplan–Meier estimates were employed to assess factors associated with overall survival. Results: In this study, 1056 patients were included with metastases involving bone (19.0%), brain (0.8%), lung (52.9%), liver (10.1%), and lymph nodes (20.4%). Treatment modalities included 54.6% receiving primary site RT, 45.4% receiving no RT, and 69.9% undergoing systemic therapy. For HPV-positive patients, RT (HR 0.64, p = 0.0026) and receipt of chemotherapy (HR = 0.57, p = 0.0057) were associated with improved overall survival, while bone and lung metastases were associated with decreased survival (HR = 1.75 and 1.39, p = 0.0041 and 0.041, respectively). In HPV-negative cases, survival also correlated with RT (HR = 0.65, p = 0.0047), receipt of chemotherapy (HR = 0.45, p < 0.001), clinical T4 disease (HR = 1.99, p = 0.012), presence of bone metastases (HR = 2.52, p < 0.001), lung metastases (HR = 1.49, p = 0.035), and lymphovascular invasion (HR = 1.10, p < 0.001). Overall, patients who received RT showed increased median overall survival from 9.9 to 16.1 months (p < 0.001) compared to those who did not. When stratified by RT and HPV status, there was higher median survival for both HPV-positive (from 17.1 to 24.9 months, p < 0.001) and HPV-negative patients (from 8.4 to 12.9 months, p = 0.0016) who received RT compared to those who did not. Conclusions: Primary-site radiotherapy may positively impact overall survival in limited metastatic OPC, irrespective of HPV status. Full article
(This article belongs to the Special Issue Advances in Radiation Therapy for Head and Neck Cancer)
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Review

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20 pages, 1062 KiB  
Review
The Emerging Role of Nanoparticles Combined with Either Radiotherapy or Hyperthermia in Head and Neck Cancer: A Current Review
by Elena Vlastou, Andromachi Kougioumtzopoulou, Kalliopi Platoni, Ioannis Georgakopoulos, Nefeli Lagopati, Vasileios Kouloulias and Anna Zygogianni
Cancers 2025, 17(5), 899; https://doi.org/10.3390/cancers17050899 - 6 Mar 2025
Viewed by 780
Abstract
Head and neck cancer (HNC) includes various malignancies and represents the seventh most common cancer worldwide. The early diagnosis of HNC results in a 70–90% five-year survival rate, which declines with locally advanced stages of disease. Current care employs a multimodal strategy encompassing [...] Read more.
Head and neck cancer (HNC) includes various malignancies and represents the seventh most common cancer worldwide. The early diagnosis of HNC results in a 70–90% five-year survival rate, which declines with locally advanced stages of disease. Current care employs a multimodal strategy encompassing surgery, radiation therapy (RT), chemotherapy, and immunotherapy, while treatment options vary according to the stage, tumor features, and patient characteristics. About 75% of patients with HNC will benefit from RT, either as a primary treatment or as adjuvant therapy following surgical resection. Technological improvements in RT, such as intensity-modulated RT (IMRT) and image-guided RT (IGRT), have enhanced tumor targeting and minimized adjacent healthy tissue irradiation while also expanding RT to the recurrent or metastatic setting. Innovative therapeutic strategies for HNC integrate RT with immunotherapy, gene therapy, molecular targeted therapy, photodynamic therapy, photothermal therapy, and nanoparticles (NPs), with the objective of optimizing tumor control while reducing damage to normal tissues. NPs are emerging as possible radiosensitizers in HNC treatment, enhancing the efficacy of RT, chemotherapy, and immunotherapy. In vivo and in vitro studies on the irradiation of tumors containing gold (Au), gadolinium (Gd), and hafnium oxide (HfO2) NPs show promising results in enhancing tumor destruction and survival rates, indicating their potential for clinical application. Hyperthermia, investigated as an adjunct treatment, potentially improves outcomes when combined with RT or chemotherapy, with advancements in nanotechnology renewing interest in this approach in HNC. At present, NBTXR3 is the sole NP that is being investigated in clinical trials for the enhancement of HNC RT. Full article
(This article belongs to the Special Issue Advances in Radiation Therapy for Head and Neck Cancer)
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