Reduced Radiation Therapy for Oropharyngeal Cancer

Recruiting at 1 trial location

Overseen By Peter Ahn, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Georgetown University

Disqualifiers: Perineural invasion, Lymphovascular invasion, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 5 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a lower dose of radiation can effectively treat certain types of throat cancer in individuals with minimal or no smoking history who have undergone surgery for HPV/p16(+) oropharyngeal cancer. The researchers aim to determine if this approach can control the tumor as effectively as traditional higher-dose radiation. Participants will receive reduced radiation targeting only the neck area, avoiding the original tumor site. Ideal candidates are non-smokers (for at least 6 months) with a low smoking history (15 pack-years or less) who have already undergone specific surgeries for throat cancer. The trial will use Proton Beam Therapy, a type of radiation therapy, to deliver the reduced radiation dose. As an unphased trial, it offers participants the chance to contribute to innovative research that could lead to less invasive treatment options.

Do I have to stop taking my current medications for the trial?

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.

What prior data suggests that this radiation therapy protocol is safe?

Research has shown that proton beam therapy, a type of radiation treatment, is generally manageable for patients with oropharyngeal cancer. Studies have found that patients receiving this therapy experience fewer side effects than those undergoing other radiation treatments. For instance, one study discovered that proton therapy was linked to a lower risk of death from any cause and cancer-specific death, suggesting it might be a safer choice for many patients. Another study noted that, compared to traditional radiation methods, patients reported similar or even better outcomes with proton therapy, including fewer unwanted side effects. Overall, existing research suggests that proton beam therapy is a promising option with a good safety record for treating oropharyngeal cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Proton beam therapy is unique because it precisely targets cancer cells with a precision that minimizes damage to surrounding healthy tissues. Unlike traditional radiation therapies, which can affect a broader area, proton therapy uses charged particles to deliver energy directly to the tumor site. This targeted approach reduces side effects and can potentially offer a better quality of life during and after treatment. Researchers are excited about its potential to lower radiation doses while still effectively treating oropharyngeal cancer, particularly reducing the risk of tumor recurrence.

What evidence suggests that this trial's treatments could be effective for oropharyngeal cancer?

Studies have shown that proton beam therapy, which participants in this trial will receive, can improve outcomes for patients with head and neck cancer, specifically in the throat area. Research indicates that this treatment often results in fewer short-term and long-term side effects compared to intensity-modulated radiation therapy (IMRT), a more common type of radiation therapy. Proton beam therapy is associated with a better overall quality of life for patients. Its effectiveness lies in its precise targeting of cancer cells, potentially reducing harm to nearby healthy tissues. These benefits make proton beam therapy a promising option for treating throat cancer. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals with HPV-positive oropharyngeal cancer who have had Transoral Robotic Surgery and are light smokers or non-smokers. They should be intermediate-risk patients, meaning their condition isn't the most severe.

Inclusion Criteria

Neutrophil:lymphocyte ratio ≤ 5 within 8 weeks of registration

My hemoglobin level is at least 10, possibly after a transfusion.

I had surgery to remove my cancer through the mouth and also had surgery on the neck on the same side.

Exclusion Criteria

I have ECE but no biopsy showing squamous cell carcinoma in neck lymph nodes.

My cancer has spread into the lymph or blood vessels at the original site.

My cancer has spread to the muscles in my neck.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo treatment with a lower than standard radiation dose (50Gy in 25 fractions) to the neck only, excluding the original site of tumor in the oropharynx

5 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments including physical examinations and surveillance imaging

2 years

Quality of Life Assessment

Quality of Life will be measured by validated questionnaires at baseline and at various intervals after completion of radiotherapy

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Proton Beam Therapy

Trial Overview The study tests if a lower dose of radiation therapy (50Gy in 25 fractions) to a smaller area (neck only, excluding tumor's original site in the oropharynx) works as well as standard treatments for these cancer patients.

How Is the Trial Designed?

Group I: Radiation dose: 50Gy Experimental Treatment 1 Intervention

50Gy in 25 fractions to the neck at risk for tumor recurrence, excluding the primary site

Proton Beam Therapy is already approved in United States, European Union, Japan, Canada for the following indications:

Approved in United States as Proton Beam Therapy for:

• Various cancers including prostate, breast, lung, liver, and head and neck cancers

Approved in European Union as Proton Therapy for:

• Various cancers including ocular melanoma, chordomas, chondrosarcomas, and certain pediatric cancers

Approved in Japan as Proton Beam Therapy for:

• Various cancers including prostate, liver, and ocular melanoma

Approved in Canada as Proton Therapy for:

• Various cancers including ocular melanoma and certain pediatric cancers

Who Is Running the Clinical Trial?

Georgetown University

Lead Sponsor

Trials

355

Recruited

142,000+

MedStar Georgetown University Hospital

Collaborator

Trials

6

Recruited

22,900+

Published Research Related to This Trial

Proton beam therapy combined with intra-arterial chemotherapy (PBT-IACT) demonstrated promising results in treating stage III-IVB squamous cell carcinoma of the tongue, with a 3-year overall survival rate of 87% and a local control rate of 86.6% based on a study of 33 patients over a median follow-up of 43 months.

While the treatment had some significant acute toxicities, such as mucositis and neutropenia, the overall toxicity profile was considered acceptable, suggesting that PBT-IACT could be a viable option for patients with advanced tongue cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment results of alternating chemoradiotherapy followed by proton beam therapy boost combined with intra-arterial infusion chemotherapy for stage III-IVB tongue cancer. Takayama, K., Nakamura, T., Takada, A., et al.[2018]

Proton beam therapy (PBT) combined with concurrent chemotherapy (CChT) shows promising results in treating esophageal cancer, with a pathologic complete response rate of 28% in surgical patients and a near complete response rate of 50%.

While the treatment is associated with some acute toxicities, such as esophagitis and fatigue, the overall clinical outcomes are encouraging, suggesting that PBT/CChT may be a viable option for managing thoracic malignancies, warranting further comparison with traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton beam therapy and concurrent chemotherapy for esophageal cancer. Lin, SH., Komaki, R., Liao, Z., et al.[2022]

In a study of 64 patients with unresectable stage III non-small cell lung cancer (NSCLC), concurrent chemotherapy and proton beam radiotherapy (PBT) resulted in a median overall survival of 26.5 months and a 5-year overall survival rate of 29%, indicating promising efficacy for this treatment approach.

The treatment was associated with relatively low rates of severe toxic effects, with no grade 5 toxicities reported, suggesting that PBT may reduce the harmful side effects compared to traditional photon therapy, although further optimization of the technique is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton Beam Radiotherapy and Concurrent Chemotherapy for Unresectable Stage III Non-Small Cell Lung Cancer: Final Results of a Phase 2 Study. Chang, JY., Verma, V., Li, M., et al.[2022]

In a study of 69 pediatric patients treated with proton beam therapy (PBT) for head and neck malignancies, acute toxicities were low, with only 4% experiencing severe oral mucositis, indicating that PBT is a safe treatment option for this population.

The 1-year local recurrence-free survival rate was 92% and overall survival rate was 93%, suggesting that PBT is effective in managing pediatric head and neck cancers, comparable to historical outcomes with other treatment modalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton therapy for pediatric head and neck malignancies. Vogel, J., Both, S., Kirk, M., et al.[2017]

Proton beam radiotherapy (PBT) shows potential for reduced treatment-related toxicities in gastrointestinal cancers, particularly in esophageal and pancreatic cancers, while maintaining comparable local control and overall survival rates compared to traditional photon radiotherapy.

Current data suggest that PBT may lead to fewer postoperative complications and hospital stays, indicating a safer treatment option, although the overall quality and quantity of studies are limited, necessitating further randomized trials for conclusive evidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes and toxicities of proton radiotherapy for gastrointestinal neoplasms: a systematic review. Verma, V., Lin, SH., Simone, CB., et al.[2022]

Proton beam therapy (PBT) is a cost-effective treatment option for head and neck cancer (HNC), especially in patients with HPV-associated tumors, with an incremental cost-effectiveness ratio (ICER) as low as $288,000 per quality-adjusted life year (QALY) from the payer's perspective.

PBT may lead to fewer long-term side effects in younger patients, potentially reducing the need for extensive supportive care, making it a favorable choice compared to traditional intensity-modulated radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review of the Economic Burden of Proton Therapy in Head and Neck Cancer. Bharathi R, P., Ms, A., Kamath, A.[2023]

Proton beam therapy (PBT) has the potential to reduce toxicities and improve quality of life for cancer patients, but there is limited high-quality evidence from randomized controlled trials (RCTs) to support these claims, with only 8% of prospective studies being randomized.

Out of 219 studies reviewed, many lacked thorough reporting on research design and patient outcomes, highlighting the need for better collaboration and standardized methodologies in future PBT research to generate more reliable evidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review of methodology used in clinical studies evaluating the benefits of proton beam therapy. Ofuya, M., McParland, L., Murray, L., et al.[2023]

In a study of 46 patients with oropharyngeal squamous cell cancer treated with intensity-modulated proton therapy (IMPT), there were no local regional or marginal recurrences, indicating high effectiveness in controlling the disease.

The treatment demonstrated a favorable safety profile, with no acute grade 4 or 5 toxicities reported, and the most common side effects were manageable grade 3 dermatitis and mucositis, suggesting that IMPT may reduce severe side effects compared to conventional radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton Therapy for Locally Advanced Oropharyngeal Cancer: Initial Clinical Experience at the University of Washington. Aljabab, S., Liu, A., Wong, T., et al.[2022]

Proton beam therapy (PBT) may lead to lower acute and late toxicity compared to intensity-modulated radiation therapy (IMRT) for treating oropharyngeal squamous cell carcinoma, although the reduction in toxicity can vary based on specific technical factors.

The effectiveness of PBT in controlling the disease appears to be comparable to that of IMRT, making it a promising treatment option, though its widespread use will depend on patient access to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton Beam Radiation Therapy for Oropharyngeal Squamous Cell Carcinoma. Mendenhall, WM., Beitler, JJ., Saba, NF., et al.[2023]

In a study of 205 patients with advanced-stage oropharynx cancer, proton beam therapy (PBT) was found to significantly reduce the probability of treatment-related complications, such as severe dysphagia and xerostomia, compared to intensity-modulated radiation therapy (IMRT).

The normal tissue complication probability (NTCP) models indicated that PBT resulted in lower predicted toxicity rates at 6 months post-treatment, highlighting its potential as a safer option for patients undergoing radiation therapy for oropharyngeal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Model-Based Approach to Predict Short-Term Toxicity Benefits With Proton Therapy for Oropharyngeal Cancer. Rwigema, JM., Langendijk, JA., Paul van der Laan, H., et al.[2019]

Proton therapy (PT) for oropharyngeal carcinoma appears to improve quality of life (QOL) and patient-reported outcomes (PROs) compared to traditional photon-based therapy, particularly in areas like xerostomia (dry mouth) and appetite, based on a review of seven studies.

While PT shows benefits in reducing certain side effects, some issues like sexual symptoms did not improve as much, and overall, QOL and PROs did not fully return to baseline levels after treatment, indicating the need for further research on long-term effects and cost-effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of Life and Patient-Reported Outcomes Following Proton Therapy for Oropharyngeal Carcinoma: A Systematic Review. Yahya, N., Manan, HA.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10137022/

Quality of Life and Patient-Reported Outcomes Following ... Compared to patients treated with photon radiotherapy, patients treated with proton beam therapy have better outcomes across most time points.

2. floridaproton.org floridaproton.org/blog-spot/oropharyngeal-cancer

Oropharyngeal Cancer Treatment with Proton Therapy The results showed that proton beam therapy (IMPT) improved outcomes for patients treated for head and neck oropharyngeal cancer. Fewer ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S233151802300241X

Proton Beam Radiation Therapy for Oropharyngeal ... Proton beam therapy likely results in reduced acute and late toxicity as compared with intensity-modulated radiation therapy (IMRT).

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

Toxicity Profiles and Survival Outcomes Among Patients ... In this cohort study of 292 patients with nonmetastatic OPC, IMPT was associated with fewer acute toxic effects compared with IMRT and with few chronic toxic ...

5. mdpi.com mdpi.com/2072-6694/16/11/2085

Current Status and Future Directions of Proton Therapy for ... The aim of the present paper is to compare protons and photons outcomes in the context of oropharyngeal and nasopharyngeal cancer and provide an updated ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9652753/

Toxicity Profiles and Survival Outcomes Among Patients ... Patients with oropharyngeal carcinoma (OPC) treated with radiotherapy often experience substantial toxic effects, even with modern techniques ...

7. 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 ... Survival rates were similarly high for both groups. At a median follow-up of 28.3 months, two-year freedom from cancer returning at or near the ...

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

Comparing the oncologic outcomes of proton therapy and ... Patients who received proton therapy had significantly lower risks of all-cause mortality (adjusted hazard ratio, aHR = 0.43), cancer-specific death (aHR = 0.44) ...

9. guidelines.carelonmedicalbenefitsmanagement.com guidelines.carelonmedicalbenefitsmanagement.com/proton-beam-therapy-2025-03-23/

Proton Beam Therapy 2025-03-23 - Carelon Clinical Guidelines Proton therapy was associated with an improved overall survival of 31 months vs 14 months with photons. The proton-treated patients had a significantly lower ...