Proton vs Photon Radiotherapy for Head and Neck Cancer

Not currently recruiting at 11 trial locations

Overseen By Christopher Barker, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Prior head/neck irradiation, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines two types of radiation treatments for head and neck cancer: photon intensity modulated radiation therapy (IMRT) and proton beam radiotherapy (PBRT). The researchers aim to determine if PBRT, which may cause less harm to healthy tissues, is better, the same, or worse than IMRT regarding side effects. Suitable candidates for this trial include those diagnosed with specific types of head and neck cancer, such as salivary gland cancer, skin cancer, or melanoma, and who require radiation on only one side of the neck. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both photon intensity modulated radiation therapy (IMRT) and proton beam radiotherapy (PBRT) are safe for treating head and neck cancer. Studies have found that both therapies effectively control tumors and have fewer long-term side effects than expected.

Research involving thousands of patients indicates that IMRT is generally well-tolerated. This treatment reduces radiation exposure to healthy tissues, lowering the risk of severe side effects.

PBRT, on the other hand, shows promise because it can target tumors more precisely, minimizing damage to nearby healthy tissues. This precise targeting results in fewer complications compared to traditional radiation therapies.

Both treatments have good safety records and are considered viable options for head and neck cancer. Ongoing studies aim to determine if one might be more effective or have fewer side effects than the other. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer innovative approaches to targeting head and neck cancer. Proton beam radiotherapy (PBRT) is unique due to its ability to deliver radiation more precisely to the tumor, minimizing damage to surrounding healthy tissues. This precision can potentially lead to fewer side effects compared to the traditional photon intensity modulated radiation therapy (IMRT), which is the current standard of care. Both treatments aim to deliver a similar radiation dose, but PBRT's advanced targeting capabilities could make it a game-changer in improving patient outcomes and quality of life.

What evidence suggests that this trial's treatments could be effective for head and neck cancer?

This trial will compare Proton Beam Radiotherapy (PBRT) and Photon Intensity Modulated Radiation Therapy (IMRT) for treating head and neck cancer. Research has shown that both PBRT and IMRT are effective for this purpose. Studies suggest that PBRT usually causes fewer side effects and improves quality of life compared to IMRT, while still controlling cancer effectively. In one study involving 60,485 patients, proton therapy was associated with better survival rates and fewer instances of cancer recurrence. Both treatments effectively prevent cancer from returning, with IMRT slightly better at 96.8% compared to 94.3% for PBRT. Overall, PBRT is a promising option with potentially fewer complications for healthy tissues. Participants in this trial will receive either PBRT or IMRT to further evaluate these outcomes. ^{1 2 3 6 7}

Who Is on the Research Team?

Nancy Lee, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with certain types of head and neck cancer, including salivary gland, skin cancer, melanoma, or HNSCC requiring one-sided radiation. Participants must be in good physical condition (Karnofsky score ≥70) and women able to have children must not be pregnant.

Inclusion Criteria

I have been diagnosed with salivary gland cancer, skin cancer, melanoma, or head and neck cancer needing radiation on one side.

I am a woman under 51 and have a negative pregnancy test.

I am able to care for myself but may not be able to do active work.

Exclusion Criteria

My doctor has recommended radiation therapy for my mucosal surfaces.

My condition cannot be treated with surgery.

My doctor has recommended radiation therapy for both sides of my neck.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive either IMRT or PBRT to a standard dose of 60-66Gy

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Photon intensity modulated radiation therapy (IMRT)
• Proton beam radiotherapy (PBRT)

Trial Overview The study compares two types of radiation therapy: Photon IMRT and Proton PBRT. It aims to determine if PBRT results in fewer side effects by reducing exposure to healthy tissues compared to the more traditional IMRT method.

How Is the Trial Designed?

Group I: Proton beam radiotherapy (PBRT) Experimental Treatment 1 Intervention

PBRT to standard dose of 60-66Gy

Group II: Photon intensity modulated radiation therapy (IMRT) Experimental Treatment 1 Intervention

IMRT to standard dose of 60-66Gy

Photon intensity modulated radiation therapy (IMRT) is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Intensity Modulated Radiation Therapy for:

• Head and neck cancer
• Brain tumors
• Breast cancer
• Esophageal cancer
• Gynecological cancers
• Liver cancer
• Lung cancer
• Pancreatic cancer
• Prostate cancer

Approved in United States as Intensity Modulated Radiation Therapy for:

• Head and neck cancer
• Brain tumors
• Breast cancer
• Esophageal cancer
• Gynecological cancers
• Liver cancer
• Lung cancer
• Pancreatic cancer
• Prostate cancer

Approved in Canada as Intensity Modulated Radiation Therapy for:

• Head and neck cancer
• Brain tumors
• Breast cancer
• Esophageal cancer
• Gynecological cancers
• Liver cancer
• Lung cancer
• Pancreatic cancer
• Prostate cancer

Approved in Japan as Intensity Modulated Radiation Therapy for:

• Head and neck cancer
• Brain tumors
• Breast cancer
• Esophageal cancer
• Gynecological cancers
• Liver cancer
• Lung cancer
• Pancreatic cancer
• Prostate cancer

Approved in China as Intensity Modulated Radiation Therapy for:

• Head and neck cancer
• Brain tumors
• Breast cancer
• Esophageal cancer
• Gynecological cancers
• Liver cancer
• Lung cancer
• Pancreatic cancer
• Prostate cancer

Approved in Switzerland as Intensity Modulated Radiation Therapy for:

• Head and neck cancer
• Brain tumors
• Breast cancer
• Esophageal cancer
• Gynecological cancers
• Liver cancer
• Lung cancer
• Pancreatic cancer
• Prostate cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Mayo Clinic

Collaborator

Trials

3,427

Recruited

3,221,000+

Mount Sinai Hospital, New York

Collaborator

Trials

37

Recruited

892,000+

Published Research Related to This Trial

Proton radiation therapy, particularly intensity-modulated proton therapy (IMPT), offers better dose localization compared to conventional photon radiation therapy, potentially reducing damage to surrounding healthy tissues in patients with head and neck and skull base tumors.

Initial clinical experiences suggest that IMPT may lead to fewer acute and long-term toxicities, and ongoing multi-institutional trials aim to further establish its effectiveness in treating these complex tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton radiation therapy for head and neck cancer. Chan, AW., Liebsch, NJ.[2018]

Proton beam radiation therapy (PBRT) significantly reduces radiation exposure to healthy tissues in the mandible compared to intensity-modulated radiation therapy (IMRT), with much lower doses to critical areas like the oropharynx and parotid glands.

The study, which evaluated dosimetric distributions in patients with head and neck cancer receiving ≥60 Gy of PBRT, suggests that PBRT may lead to less radiation-related toxicity, making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of mean radiation dose and dosimetric distribution to tooth-bearing regions of the mandible associated with proton beam radiation therapy and intensity-modulated radiation therapy for ipsilateral head and neck tumor. Owosho, AA., Yom, SK., Han, Z., et al.[2018]

In a study of 68 patients with head and neck squamous cell carcinoma treated with particle beam radiotherapy (PBRT), the 3-year overall survival rate was 79.0%, indicating promising therapeutic outcomes.

While PBRT showed manageable toxicity, with only a few cases of severe mucositis and late mucosal necrosis, the results suggest that PBRT could be a beneficial treatment option for HNSCC, warranting further prospective studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary clinical outcomes of head and neck squamous cell carcinoma treated with particle beam radiation therapy. Huang, Q., Hu, J., Hu, W., et al.[2023]

Intensity-modulated proton therapy is safer for patients with head and neck cancer as it reduces damage to normal tissues compared to traditional intensity-modulated photon therapy, leading to less treatment-related toxicity and better quality of life.

A phase II/III randomized trial is currently comparing the effectiveness of proton therapy versus photon therapy for advanced-stage oropharyngeal tumors, with a focus on progression-free survival as the main measure of success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing Intensity-Modulated Proton Therapy With Intensity-Modulated Photon Therapy for Oropharyngeal Cancer: The Journey From Clinical Trial Concept to Activation. Frank, SJ., Blanchard, P., Lee, JJ., et al.[2020]

Intensity modulated proton therapy (IMPT) shows significant dosimetric advantages over traditional intensity modulated radiation therapy (IMRT) for head and neck cancers, particularly in sparing nearby organs like the larynx and salivary glands.

Clinical evidence suggests that IMPT can reduce treatment-related toxicities, such as the need for feeding tubes, indicating its potential benefits in improving patient quality of life during and after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity modulated proton therapy (IMPT) - The future of IMRT for head and neck cancer. Moreno, AC., Frank, SJ., Garden, AS., et al.[2020]

Intensity-modulated proton therapy (IMPT) for oropharyngeal carcinoma shows a potential reduction in severe weight loss and feeding tube dependency compared to intensity-modulated radiotherapy (IMRT), based on a study of 150 matched patients with a median follow-up of 32 months.

Despite these benefits, there were no significant differences in overall survival or progression-free survival between IMPT and IMRT, indicating that IMPT does not compromise treatment effectiveness while potentially improving quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated proton beam therapy (IMPT) versus intensity-modulated photon therapy (IMRT) for patients with oropharynx cancer - A case matched analysis. Blanchard, P., Garden, AS., Gunn, GB., et al.[2022]

Proton beam radiation therapy (PBRT) significantly spares normal tissues compared to intensity-modulated radiation therapy (IMRT), as shown by lower radiation doses to critical structures like the brainstem and spinal cord in a study of 41 patients with head and neck cancers.

Patients receiving PBRT experienced significantly lower rates of acute treatment-related toxicities, including dysgeusia, mucositis, and nausea, indicating that PBRT may be a safer option for treating ipsilateral head and neck cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton beam radiation therapy results in significantly reduced toxicity compared with intensity-modulated radiation therapy for head and neck tumors that require ipsilateral radiation. Romesser, PB., Cahlon, O., Scher, E., et al.[2022]

Citations

1. astro.org astro.org/news-and-publications/news-and-media-center/news-releases/2025/imrt-matches-proton-therapy-in-patient-reported-outcomes-for

Intensity-modulated radiation therapy (IMRT) matches ... At a median follow-up of 28.3 months, two-year freedom from cancer returning at or near the original tumor site was 94.3% for protons and 96.8% ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.6006

Phase III randomized trial of intensity-modulated proton ... Conclusions: IMPT is non-inferior to IMRT and has emerged as a standard of care CRT approach for OPC that reduces malnutrition and gastrostomy- ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5474304/

Intensity modulated proton beam therapy (IMPT) versus ... IMPT used for oropharyngeal carcinoma patients has the ability to reduce the dose to organs at risk compared to intensity-modulated radiotherapy (IMRT) while ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0167814023898656

Comparing the oncologic outcomes of proton therapy and ... This study of 60,485 patients with HNSCC found that proton therapy was associated with better overall and cancer-specific survival and lower locoregional ...

5. mskcc.org mskcc.org/clinical-updates/proton-beam-reduces-acute-toxicities-compared-to-imrt-for-head-and-neck-cancer-patients-who-receive-unilateral-radiation

Proton Beam Reduces Acute Toxicities Compared to IMRT ... Proton beam radiotherapy resulted in similar oncologic outcomes with less toxicity and improved quality of life than photon beam ...

6. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/hed.27877

Efficacy and safety of proton therapy versus intensity‐ ... A total of 3087 head and neck cancer patients treated with proton therapy (PT) and intensity-modulated radiation therapy (IMRT) were included in ...

7. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2798320

Toxicity Profiles and Survival Outcomes Among Patients ... This cohort study compares the toxic effects and oncologic outcomes associated with intensity-modulated radiation therapy (IMRT) vs ...