Rethinking Oral Cancer Treatment: How Modern Radiotherapy Is Transforming Patient Care

Radiotherapy has long been a cornerstone of oral cancer treatment. But in the past decade, rapid advancements in imaging, precision delivery, and particle-based therapies have reshaped what doctors can achieve. A new review by Liu et al. (2025) highlights how these technologies are improving survival, reducing side effects, and opening the door to personalized cancer care.

Understanding the Challenge: Why Radiotherapy Matters

Oral cancer affects close to 400,000 people globally each year, with particularly high rates in Southeast Asia. Standard treatments like surgery and chemotherapy remain essential but can affect speech, swallowing, and facial function.

Radiotherapy offers a powerful alternative—or complement—because it:

• Targets tumors precisely, sparing more healthy tissue

  
  

• Preserves oral function and appearance better than extensive surgery

  
  

• Has fewer systemic side effects than chemotherapy

  
  

With new technologies entering the clinic, radiotherapy is now far more than just “high-energy beams”—it is becoming a personalized, high-precision therapy.

From 2D to Precision: How Radiotherapy Evolved

1. Conventional Radiotherapy: A Starting Point

Traditional radiotherapy relied on 2D X-ray films and fixed beam angles. This meant doctors could estimate, but not perfectly match, the tumor shape—sometimes leading to under- or over-exposure of tissues.

Despite limitations, this era laid the groundwork for more sophisticated systems.

2. IMRT: Sculpting Radiation with Millimeter Accuracy

Intensity-Modulated Radiotherapy (IMRT) uses computers and multi-leaf collimators to “shape” the radiation dose. It can curve around the tongue, jaw, or salivary glands—areas where surgical removal can have major functional impact.

Clinical benefits include:

• Higher tumor control

• Lower risk of xerostomia (dry mouth)

• Higher 5-year survival rates (60–75%)

IMRT became the new standard for many oral and head-and-neck cancers.

3. IGRT: Imaging While Treating

Image-Guided Radiotherapy (IGRT) adds real-time imaging before or during each session. This corrects small daily changes in patient position or tumor size.

Studies show IGRT can:

• Improve local tumor control

• Reduce treatment errors

• Shorten treatment duration

IMRT + IGRT is now a powerful pairing in modern oncology.

The New Frontier: Proton and Heavy Ion Therapy

Proton Therapy

Protons release most of their energy exactly at the tumor site (the “Bragg peak”), minimizing healthy tissue damage.

Key advantages:

• Lower rates of severe mucositis and oral pain

• Better preservation of taste, saliva, and swallowing

• Promising results in re-irradiation and complex cases

Researchers are also exploring how proton therapy alters tumor biology—such as changing protein expression and stress-response pathways.

Carbon Ion Therapy (CIRT)

Carbon ions deliver even higher biological effectiveness than protons. They create dense DNA damage that cancer cells struggle to repair.

CIRT offers:

• 2–3× stronger tumor-killing ability

• Promising results in aggressive or resistant oral cancers

• Potential synergy with immunotherapy

Early studies show that CIRT may suppress tumor invasion and metastasis through pathways like FAK-Paxillin.

Adaptive Radiotherapy: Adjusting Treatment in Real Time

Patients undergoing radiotherapy often experience tumor shrinkage, swelling, or weight changes over several weeks. Adaptive Radiotherapy (ART) recalculates the radiation plan during treatment to maintain accuracy.

Benefits include:

• Better protection of organs like the salivary glands

• Improved tumor targeting

• More personalized dose delivery

ART is becoming especially valuable for cancers in anatomically complex sites like the oral cavity.

Beyond Beams: CyberKnife, Gamma Knife, and TomoTherapy

The review also highlights advances in stereotactic radiosurgery—systems that deliver extremely precise, high-dose treatments:

• CyberKnife: Robotic arm delivers radiation that “tracks” tumor motion

• Gamma Knife: Historically used in the brain; limited but emerging use in head & neck

• TomoTherapy: Combines CT imaging with spiral radiation delivery

These tools are promising for patients with recurrent, inoperable, or difficult-to-reach tumors.

The Rise of Personalized Radiotherapy

Genomics and Biomarkers

Molecular profiling can guide treatment choices. Examples:

• EGFR overexpression predicts benefit from combining radiotherapy with EGFR inhibitors

• PRMT5 and APE1 influence DNA repair and radioresistance

• PDPN and JARID1B are emerging biomarkers linked to metastasis and treatment sensitivity

Such markers allow clinicians to tailor therapy intensity and choose combinations that maximize effectiveness.

Radiotherapy + Immunotherapy

Radiotherapy can stimulate the immune system by:

• Releasing tumor antigens

• Altering the tumor microenvironment

• Increasing T-cell and NK-cell activity

Combining radiation with PD-L1 inhibitors and other immunotherapies may boost responses in advanced or recurrent oral cancers.

Looking Ahead: The Future of Radiotherapy

The review concludes with several promising directions:

• FLASH radiotherapy (ultra-high dose rates with minimal toxicity)

• AI-guided planning for faster, more accurate treatment design

• More accessible particle therapy, especially in developing regions

• Integration of multi-omics biomarkers for ultra-personalized care

Taken together, these innovations point toward a future where radiotherapy is not only more effective but also more humane—preserving speech, appearance, and quality of life while combating one of the most challenging head-and-neck cancers.

Original Article

Liu X., Zhang Z., Deng X., Lang Z., & Wang J. (2025). Advances in radiotherapy for mouth neoplasms: emerging technologies and future perspectives. Discover Oncology, 16, 1392.

DOI: https://doi.org/10.1007/s12672-025-03249-w