Reduced Radiation Therapy for Oropharyngeal Cancer

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

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to learn whether for intermediate-risk patients who have undergone Transoral Robotic Surgery for HPV/p16(+) oropharyngeal cancer and have minimal smoking history, whether these patients can be treated with a lower-than standard dose, with omission of the primary site in the oropharynx. The main questions it aims to answer are: Does radiotherapy site and dose-de-escalation lead to similar outcomes compared to historical data on tumor control in patients who are treated with standard radiation doses and treatment fields? Participants will: Undergo treatment with a lower than standard radiation dose (50Gy in 25 fractions, with either Intensity Modulated Radiation Therapy (IMRT) or proton beam therapy) and to a smaller than standard radiation field (to the neck only, excluding the original site of tumor in the oropharynx)

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 data supports the effectiveness of the treatment Proton Beam Therapy for Oropharyngeal Cancer?

Proton Beam Therapy (PBT) can target tumors more precisely, reducing damage to surrounding healthy tissues, which may lead to fewer side effects and better quality of life for patients with oropharyngeal cancer. Early clinical experiences and reviews suggest that PBT might improve outcomes by decreasing both immediate and long-term side effects compared to traditional radiation therapy. ^{1 2 3 4 5}

Is proton beam therapy safe for humans?

Proton beam therapy (PBT) is generally considered safe and may reduce side effects by limiting radiation exposure to healthy tissues. Studies have shown it can lower toxic effects in various cancers, including head and neck cancers, and may lead to fewer long-term adverse events compared to traditional radiation therapy. ^{3 6 7 8 9}

How is proton beam therapy different from other treatments for oropharyngeal cancer?

Proton beam therapy (PBT) is unique because it can precisely target cancer cells while minimizing damage to surrounding healthy tissue, potentially reducing side effects compared to traditional radiation therapy. This makes it particularly beneficial for treating sensitive areas like the head and neck. ^{3 4 6 10 11}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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 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]

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 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 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) 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]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Systematic review of methodology used in clinical studies evaluating the benefits of proton beam therapy. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

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

3. United States pubmed.ncbi.nlm.nih.gov

Proton Beam Radiation Therapy for Oropharyngeal Squamous Cell Carcinoma. [2023]

4. Thailand pubmed.ncbi.nlm.nih.gov

A Systematic Review of the Economic Burden of Proton Therapy in Head and Neck Cancer. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Proton Therapy for Locally Advanced Oropharyngeal Cancer: Initial Clinical Experience at the University of Washington. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Proton therapy for pediatric head and neck malignancies. [2017]

7. Germany 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. [2018]

8. United States 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. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

A Model-Based Approach to Predict Short-Term Toxicity Benefits With Proton Therapy for Oropharyngeal Cancer. [2019]

10. China pubmed.ncbi.nlm.nih.gov

Clinical outcomes and toxicities of proton radiotherapy for gastrointestinal neoplasms: a systematic review. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Proton beam therapy and concurrent chemotherapy for esophageal cancer. [2022]