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REVIEW article

Front. Oncol.

Sec. Head and Neck Cancer

Volume 15 - 2025 | doi: 10.3389/fonc.2025.1552337

Chemotherapy-Free Innovations in Locally Advanced Head and Neck Cancer: A Comprehensive Review

Provisionally accepted
Shatha Abutaha Shatha Abutaha 1Taher Abu Hejleh Taher Abu Hejleh 2Mostafa ElHaddad Mostafa ElHaddad 3Akram Al-Ibraheem Akram Al-Ibraheem 4Ahmed Abbasi Ahmed Abbasi 5Abdulrahman Sumaida Abdulrahman Sumaida 6Ahmad Bushehri Ahmad Bushehri 7Ahmad Mostafa Ahmad Mostafa 8Bassem Youssef Bassem Youssef 9Ibrahim Alotain Ibrahim Alotain 10Ibrahim Abu-Gheida Ibrahim Abu-Gheida 11,12Mohammed Aldehaim Mohammed Aldehaim 13,14Majed Alghamdi Majed Alghamdi 15,16Mohamed Shelan Mohamed Shelan 17Mohammed Al Dohan Mohammed Al Dohan 18Maysa Al-Hussaini Maysa Al-Hussaini 19Nadeem Pervez Nadeem Pervez 20Shoukri Temraz Shoukri Temraz 21Saad Alrashidi Saad Alrashidi 18Wael El-Sheshtawy Wael El-Sheshtawy 22Zahid Al-Mandhari Zahid Al-Mandhari 23Hamza Ghatasheh Hamza Ghatasheh 1Ali Hosni Ali Hosni 24Issa Mohamad Issa Mohamad 1*
  • 1 Department of Radiation Oncology, King Hussein Cancer Center, Amman, Jordan
  • 2 2. Department of Medical Oncology, King Hussein Cancer Center, Amman, Jordan
  • 3 3. Clinical Oncology Department, Kasr Al-Ainy Center of Clinical Oncology and Nuclear Medicine, Kasr Al-Ainy School of Medicine, Cairo University, Cairo, Egypt
  • 4 4. Department of Nuclear Medicine, King Hussein Cancer Center, Amman, Jordan
  • 5 5. Department of Radiation Oncology, Aga Khan University Hospital, Stadium Road, Karachi, Pakistan
  • 6 Department of Radiation Oncology, Tawam Hospital, Al Ain, United Arab Emirates
  • 7 7. Department of Radiation Oncology, Kuwait Cancer Control Center, Kuwait, Kuwait
  • 8 8. Clinical oncology department, Minia Oncology, Center, Minia, Egypt
  • 9 Department of Radiation Oncology, American University of Beirut Medical Center, Beirut, Lebanon
  • 10 10. Department of Radiation Oncology, King Fahad Specialist, Dammam, Saudi Arabia
  • 11 11. Department of Radiation Oncology, Burjeel Medical City, Abu Dhabi, United Arab Emirates
  • 12 12. Emirates Oncology Society, Dubai, United Arab Emirates
  • 13 Department of Radiation Oncology, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
  • 14 14. College of Medicine, Alfaisal University,, Riyadh,, Saudi Arabia
  • 15 15. Radiation Oncology, Princess Noorah Oncology Center, King Abdulaziz Medical City, Ministry of National Guard Health Affairs-Western Region,, Jeddah,, Saudi Arabia
  • 16 16. Collage of Medicine, King Saud Bin Abdulaziz University for Health Science,, Jeddah,, Saudi Arabia
  • 17 17. Department of Radiation Oncology, Inselspital Bern, University of Bern,, Bern,, Switzerland
  • 18 18. Department of Radiation Oncology, King Fahad Medical City,, Riyadh,, Saudi Arabia
  • 19 19. Department of Cell Therapy and Applied Genomics, King Hussein Cancer Center,, Amman, Jordan
  • 20 20. Department of Radiation Oncology, Sheikh Shakhbout Medical City Abu Dhabi, United Arab Emirates, Abu Dhabi,, United Arab Emirates
  • 21 21. Clinical Oncology Department, Mansoura University hospital,, Mansour,, Egypt
  • 22 23. Department of Clinical Oncology, Al-Azhar University,, Cairo,, Egypt
  • 23 24. Department of Radiation Oncology, Sultan Qaboos Comprehensive Cancer Care and Research Centre,, Muscat,, Oman
  • 24 25. Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, University of Toronto,, Toronto, Ontario,, Canada

The final, formatted version of the article will be published soon.

    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.

    Keywords: head and neck cancer, Concurrent chemoradiation, altered fractionation, Immunotherapy, targeted therapy, hyperthermia, nanoparticle

    Received: 27 Dec 2024; Accepted: 02 Apr 2025.

    Copyright: © 2025 Abutaha, Abu Hejleh, ElHaddad, Al-Ibraheem, Abbasi, Sumaida, Bushehri, Mostafa, Youssef, Alotain, Abu-Gheida, Aldehaim, Alghamdi, Shelan, Al Dohan, Al-Hussaini, Pervez, Temraz, Alrashidi, El-Sheshtawy, Al-Mandhari, Ghatasheh, Hosni and Mohamad. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Issa Mohamad, Department of Radiation Oncology, King Hussein Cancer Center, Amman, Jordan

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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