Chemotherapy-free innovations in locally advanced head and neck cancer: a comprehensive review

The treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC) has traditionally relied on a multimodal approach, combining surgery, radiation therapy (RT), and chemotherapy. While chemotherapy plays a critical role in improving cure rates and functional outcomes, its substantial...

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Main Authors: Shatha Abu Taha, Taher Abu Hejleh, Mostafa ElHaddad, Akram Al-Ibraheem, Ahmed Abbasi, Abdulrahman Sumaida, Ahmad Bushehri, Ahmad Mostafa, Bassem Youssef, Ibrahim Alotain, Ibrahim Abu-Gheida, Mohammed Aldehaim, Majed Alghamdi, Mohamed Shelan, Mohammed Al Dohan, Maysa Al-Hussaini, Nadeem Pervez, Shoukri Temraz, Saad Alrashidi, Wael El-Sheshtawy, Zahid Al-Mandhari, Hamza Ghatasheh, Ali Hosni, Issa Mohamad
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Oncology
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Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1552337/full
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author Shatha Abu Taha
Taher Abu Hejleh
Mostafa ElHaddad
Akram Al-Ibraheem
Ahmed Abbasi
Abdulrahman Sumaida
Ahmad Bushehri
Ahmad Mostafa
Bassem Youssef
Ibrahim Alotain
Ibrahim Abu-Gheida
Mohammed Aldehaim
Mohammed Aldehaim
Majed Alghamdi
Majed Alghamdi
Mohamed Shelan
Mohammed Al Dohan
Maysa Al-Hussaini
Nadeem Pervez
Shoukri Temraz
Saad Alrashidi
Wael El-Sheshtawy
Zahid Al-Mandhari
Hamza Ghatasheh
Ali Hosni
Issa Mohamad
author_facet Shatha Abu Taha
Taher Abu Hejleh
Mostafa ElHaddad
Akram Al-Ibraheem
Ahmed Abbasi
Abdulrahman Sumaida
Ahmad Bushehri
Ahmad Mostafa
Bassem Youssef
Ibrahim Alotain
Ibrahim Abu-Gheida
Mohammed Aldehaim
Mohammed Aldehaim
Majed Alghamdi
Majed Alghamdi
Mohamed Shelan
Mohammed Al Dohan
Maysa Al-Hussaini
Nadeem Pervez
Shoukri Temraz
Saad Alrashidi
Wael El-Sheshtawy
Zahid Al-Mandhari
Hamza Ghatasheh
Ali Hosni
Issa Mohamad
author_sort Shatha Abu Taha
collection DOAJ
description The treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC) has traditionally relied on a multimodal approach, combining surgery, radiation therapy (RT), and chemotherapy. While chemotherapy plays a critical role in improving cure rates and functional outcomes, its substantial toxicity remains a major concern, particularly in older patients. These challenges are especially relevant for those who are unfit for chemotherapy or decline conventional concurrent chemoradiotherapy (CCRT), highlighting the need for alternative therapeutic options. Many patients are at high risk for severe side effects, often preventing them from completing the full chemotherapy regimen. This review explores alternative strategies to definitive CCRT of carcinomas of the larynx, hypopharynx and oropharynx, aiming to optimize treatment outcomes while minimizing toxicity. We discuss altered fractionation strategies as a promising alternative to conventional RT, offering a balance between treatment efficacy and quality of life. Additionally, we examine emerging approaches, including the combining of targeted therapies, immunotherapy, hyperthermia, photodynamic therapy and nanoparticle-based treatments with RT, which provide alternative or complementary options to traditional therapies in the management of LA-HNSCC.
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spelling doaj-art-0fc6aff1c2ea4437ad81e9884a7c5fef2025-08-20T03:14:53ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-04-011510.3389/fonc.2025.15523371552337Chemotherapy-free innovations in locally advanced head and neck cancer: a comprehensive reviewShatha Abu Taha0Taher Abu Hejleh1Mostafa ElHaddad2Akram Al-Ibraheem3Ahmed Abbasi4Abdulrahman Sumaida5Ahmad Bushehri6Ahmad Mostafa7Bassem Youssef8Ibrahim Alotain9Ibrahim Abu-Gheida10Mohammed Aldehaim11Mohammed Aldehaim12Majed Alghamdi13Majed Alghamdi14Mohamed Shelan15Mohammed Al Dohan16Maysa Al-Hussaini17Nadeem Pervez18Shoukri Temraz19Saad Alrashidi20Wael El-Sheshtawy21Zahid Al-Mandhari22Hamza Ghatasheh23Ali Hosni24Issa Mohamad25Department of Radiation Oncology, King Hussein Cancer Center, Amman, JordanDepartment of Medical Oncology, King Hussein Cancer Center, Amman, JordanClinical Oncology Department, Kasr Al-Ainy Center of Clinical Oncology and Nuclear Medicine, Kasr Al-Ainy School of Medicine, Cairo University, Cairo, EgyptDepartment of Nuclear Medicine, King Hussein Cancer Center, Amman, JordanDepartment of Radiation Oncology, Aga Khan University Hospital, Karachi, PakistanOncology: Radiation Oncology, Tawam Hospital, Al Ain, United Arab EmiratesDepartment of Radiation Oncology, Kuwait Cancer Control Center, Kuwait, KuwaitClinical oncology department, Minia Oncology, Center, Minia, EgyptDepartment of Radiation Oncology, American University of Beirut Medical Centre, Beirut, Lebanon0Department of Radiation Oncology, King Fahad Specialist, Dammam, Saudi Arabia1Department of Radiation Oncology, Burjeel Medical City, Abu Dhabi, United Arab Emirates2Department of Radiation Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia3College of Medicine, Alfaisal University, Riyadh, Saudi Arabia4Radiation Oncology, Princess Noorah Oncology Center, King Abdulaziz Medical City, Ministry of National Guard Health Affairs-Western Region, Jeddah, Saudi Arabia5Collage of Medicine, King Saud Bin Abdulaziz University for Health Science, Jeddah, Saudi Arabia6Department of Radiation Oncology, Inselspital Bern, University of Bern, Bern, Switzerland7Department of Radiation Oncology, King Fahad Medical City, Riyadh, Saudi Arabia8Department of Cell Therapy and Applied Genomics, King Hussein Cancer Center, Amman, Jordan9Department of Radiation Oncology, United Arab Emirates (UAE) University, Al Ain, United Arab Emirates0Clinical Oncology Department, Mansoura University hospital, Mansour, Egypt1Department of Radiation Oncology, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia2Department of Clinical Oncology, Al-Azhar University, Cairo, Egypt3Department of Radiation Oncology, Sultan Qaboos Comprehensive Cancer Care and Research Centre, Muscat, OmanDepartment of Radiation Oncology, King Hussein Cancer Center, Amman, Jordan4Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, CanadaDepartment of Radiation Oncology, King Hussein Cancer Center, Amman, JordanThe treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC) has traditionally relied on a multimodal approach, combining surgery, radiation therapy (RT), and chemotherapy. While chemotherapy plays a critical role in improving cure rates and functional outcomes, its substantial toxicity remains a major concern, particularly in older patients. These challenges are especially relevant for those who are unfit for chemotherapy or decline conventional concurrent chemoradiotherapy (CCRT), highlighting the need for alternative therapeutic options. Many patients are at high risk for severe side effects, often preventing them from completing the full chemotherapy regimen. This review explores alternative strategies to definitive CCRT of carcinomas of the larynx, hypopharynx and oropharynx, aiming to optimize treatment outcomes while minimizing toxicity. We discuss altered fractionation strategies as a promising alternative to conventional RT, offering a balance between treatment efficacy and quality of life. Additionally, we examine emerging approaches, including the combining of targeted therapies, immunotherapy, hyperthermia, photodynamic therapy and nanoparticle-based treatments with RT, which provide alternative or complementary options to traditional therapies in the management of LA-HNSCC.https://www.frontiersin.org/articles/10.3389/fonc.2025.1552337/fullhead and neck cancerconcurrent chemoradiationaltered fractionationimmunotherapytargeted therapyhyperthermia
spellingShingle Shatha Abu Taha
Taher Abu Hejleh
Mostafa ElHaddad
Akram Al-Ibraheem
Ahmed Abbasi
Abdulrahman Sumaida
Ahmad Bushehri
Ahmad Mostafa
Bassem Youssef
Ibrahim Alotain
Ibrahim Abu-Gheida
Mohammed Aldehaim
Mohammed Aldehaim
Majed Alghamdi
Majed Alghamdi
Mohamed Shelan
Mohammed Al Dohan
Maysa Al-Hussaini
Nadeem Pervez
Shoukri Temraz
Saad Alrashidi
Wael El-Sheshtawy
Zahid Al-Mandhari
Hamza Ghatasheh
Ali Hosni
Issa Mohamad
Chemotherapy-free innovations in locally advanced head and neck cancer: a comprehensive review
Frontiers in Oncology
head and neck cancer
concurrent chemoradiation
altered fractionation
immunotherapy
targeted therapy
hyperthermia
title Chemotherapy-free innovations in locally advanced head and neck cancer: a comprehensive review
title_full Chemotherapy-free innovations in locally advanced head and neck cancer: a comprehensive review
title_fullStr Chemotherapy-free innovations in locally advanced head and neck cancer: a comprehensive review
title_full_unstemmed Chemotherapy-free innovations in locally advanced head and neck cancer: a comprehensive review
title_short Chemotherapy-free innovations in locally advanced head and neck cancer: a comprehensive review
title_sort chemotherapy free innovations in locally advanced head and neck cancer a comprehensive review
topic head and neck cancer
concurrent chemoradiation
altered fractionation
immunotherapy
targeted therapy
hyperthermia
url https://www.frontiersin.org/articles/10.3389/fonc.2025.1552337/full
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