Reduced Radiation Therapy for Oropharyngeal Cancer

Recruiting at 1 trial location

Overseen By Heather Franklin, BSN, RN, OCN

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Duke University

Disqualifiers: Prior head/neck radiotherapy, Metastatic disease, others

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

Compensation: Varies

Number of Visits: Unknown

120 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to use intra-treatment 18FDG-PET/CT during definitive radiation therapy for human papillomavirus (HPV)-related oropharyngeal cancer (OPC) as an imaging biomarker to identify and select patients with a favorable response for chemoradiation dose de-escalation. This study will prospectively evaluate the clinical outcomes for patients undergoing dose de-escalation.

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.

What data supports the effectiveness of reduced radiation therapy for oropharyngeal cancer?

Research shows that oropharyngeal cancer linked to human papillomavirus (HPV) responds well to lower doses of radiation, maintaining high cure rates while reducing side effects. This is because HPV-positive cancers are more sensitive to radiation, allowing for effective treatment with less intensity. ^{1 2 3 4 5}

Is reduced radiation therapy for oropharyngeal cancer safe?

Research shows that reducing the radiation dose for HPV-associated oropharyngeal cancer can lower side effects like severe mouth sores and swallowing difficulties, while still maintaining good survival rates. However, long-term follow-up is needed to confirm these findings. ^{1 2 5 6 7}

How is reduced radiation therapy different from standard treatments for oropharyngeal cancer?

Reduced radiation therapy for oropharyngeal cancer involves using a lower dose of radiation compared to the standard treatment. This approach is being studied because it may reduce side effects and improve quality of life for patients, especially those with HPV-positive cancer, which tends to respond better to treatment. ^{1 2 3 5 8}

Research Team

David Brizel, MD

Principal Investigator

DUHS

Eligibility Criteria

This trial is for adults over 18 with HPV-related oropharyngeal cancer, confirmed by specific tests, who haven't had chemotherapy for their current diagnosis. They should be in good physical condition with minimal weight loss recently and have early to mid-stage cancer treatable with chemo.

Inclusion Criteria

I am fully active or can carry out light work.

I have lost less than 10% of my weight in the last 3 months.

My cancer is stage I-III and I will receive chemotherapy as standard care.

Exclusion Criteria

My cancer has spread to distant parts of my body.

I have not had any cancer except for non-melanoma skin cancer in the past 5 years.

I have had radiation therapy to my head or neck.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive definitive radiation therapy with interim 18FDG-PET/CT imaging to assess response for potential dose de-escalation

7 weeks

Weekly visits for radiation therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of acute and long-term adverse events

2 years

Treatment Details

Interventions

• 18 fluorodeoxyglucose (FDG)-positron emission tomography (PET)-Computed Tomography (CT)
• De-escalated radiation dose
• Standard radiation dose

Trial Overview The study uses advanced imaging (FDG-PET/CT scans) during standard radiation therapy to see if some patients can receive lower doses of radiation safely. It aims to find out if reducing the dose after a positive response affects treatment outcomes.

Participant Groups

Group I: Interim PET-CT with dose de-escalation Experimental Treatment 2 Interventions

Participants will receive an interim PET-CT approximately 2 weeks into radiation therapy.

Group II: Interim PET-CT with standard radiation Active Control 2 Interventions

De-escalated radiation dose is already approved in United States, European Union for the following indications:

Approved in United States as De-escalated radiation therapy for:

• HPV-associated oropharyngeal cancer

Approved in European Union as De-escalated radiation therapy for:

• HPV-positive oropharyngeal squamous cell carcinoma

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Findings from Research

Oropharyngeal carcinoma linked to human papillomavirus (HPV) is on the rise, but it has better treatment outcomes compared to traditional head and neck cancers, prompting a focus on treatment de-escalation strategies.

Current strategies for reducing treatment intensity include adjusting radiation doses, using selective nodal irradiation, and evaluating patient responses to induction chemotherapy, all aimed at minimizing side effects while preserving quality of life for younger, healthier patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regional Radiation Therapy for Oropharyngeal Cancer in the HPV Era. Tam, M., Hu, K.[2019]

In a study of 759 patients with HPV-positive oropharyngeal squamous cell carcinoma, dose de-escalated radiation therapy (DDRT) did not result in inferior overall survival compared to standard dose radiation therapy (SDRT), with 3-year survival rates of 82.2% for DDRT and 79.3% for SDRT (P = 0.85).

The findings suggest that reducing radiation dose in HPV-positive OPSCC patients may be safe, as there was no significant difference in survival outcomes, indicating that ongoing randomized trials are needed to further explore this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation therapy dose de-escalation compared to standard dose radiation therapy in definitive treatment of HPV-positive oropharyngeal squamous cell carcinoma. Gabani, P., Lin, AJ., Barnes, J., et al.[2020]

De-escalated radiotherapy (RT) is currently used in only 15-20% of patients with HPV+ oropharyngeal squamous cell carcinoma (OPSCC) in the United States, indicating low adoption despite ongoing trials.

In HPV+ patients, de-escalated RT did not significantly affect overall survival compared to full-dose RT, with 3- and 5-year survival rates being similar, while HPV- patients showed significantly worse survival rates with de-escalated treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practice patterns and outcomes following radiation dose de-escalation for oropharyngeal cancer. White, R., Abel, S., Hasan, S., et al.[2020]

HPV-positive oropharyngeal squamous cell carcinoma has a better prognosis and is more sensitive to radiation than HPV-negative cancers, suggesting that lower radiation doses could be effective for treatment.

Recent studies indicate that de-escalated radiation therapy can maintain high cure rates and improve quality of life for selected patients, although challenges remain due to small sample sizes and variability in treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

De-escalated radiation for human papillomavirus virus-related oropharyngeal cancer: evolving paradigms and future strategies. Chen, AM.[2023]

Oropharyngeal cancers caused by HPV are more sensitive to chemotherapy and radiation, leading to better outcomes compared to HPV-negative cancers, which raises questions about the intensity of current treatment protocols.

Ongoing de-escalation trials suggest that less intensive treatment regimens could maintain efficacy while reducing toxicity for HPV-positive patients, but clinicians are advised to wait for clinical trial results before changing treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment de-intensification strategies for HPV-driven oropharyngeal cancer: A short review]. Lahmamssi, C., Guy, JB., Benchekroun, N., et al.[2020]

In a phase II trial involving 80 patients with HPV-associated oropharyngeal cancer, reducing the dose of adjuvant radiotherapy from 60-66 Gy to 30-36 Gy maintained a high locoregional tumor control rate of 96.2% over 2 years.

The study demonstrated low toxicity rates (0% grade 3 or worse toxicity post-treatment) and even slight improvements in swallowing function, indicating that this aggressive dose de-escalation approach can preserve quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Evaluation of Aggressive Dose De-Escalation for Adjuvant Chemoradiotherapy in Human Papillomavirus-Associated Oropharynx Squamous Cell Carcinoma. Ma, DJ., Price, KA., Moore, EJ., et al.[2021]

A systematic review of 10 prospective studies on therapy de-escalation for HPV-associated oropharyngeal cancer (OPC) suggests that reduced-dose chemoradiotherapy, especially when combined with induction chemotherapy, can achieve high 2-year progression-free survival (PFS) rates of 89% and overall survival (OS) rates of 96%.

While de-escalation strategies show promising efficacy, they also present some acute toxicities, with grade 3+ dysphagia and mucositis occurring in 9-39% of patients, indicating a need for careful patient selection and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

De-intensification of therapy in human papillomavirus associated oropharyngeal cancer: A systematic review of prospective trials. Patel, RR., Ludmir, EB., Augustyn, A., et al.[2021]

This review aims to compare overall survival rates between standard and reduced-dose radiotherapy in patients with HPV-positive oropharyngeal squamous cell carcinoma (OPSCC), potentially allowing for less toxic treatment options.

The study will include adult patients who have received curative treatment for HPV+ OPSCC, and it will systematically analyze existing literature to determine if lower radiation doses can maintain similar survival outcomes while reducing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of reduced- versus standard-dose radiotherapy on survival and radiation-associated toxicity in patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma: a systematic review protocol. Lee, TJ., Krishnan, G., Ooi, EH., et al.[2022]

References

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

Regional Radiation Therapy for Oropharyngeal Cancer in the HPV Era. [2019]

2. Ireland pubmed.ncbi.nlm.nih.gov

Radiation therapy dose de-escalation compared to standard dose radiation therapy in definitive treatment of HPV-positive oropharyngeal squamous cell carcinoma. [2020]

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

Practice patterns and outcomes following radiation dose de-escalation for oropharyngeal cancer. [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

De-escalated radiation for human papillomavirus virus-related oropharyngeal cancer: evolving paradigms and future strategies. [2023]

5. France pubmed.ncbi.nlm.nih.gov

[Treatment de-intensification strategies for HPV-driven oropharyngeal cancer: A short review]. [2020]

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

Phase II Evaluation of Aggressive Dose De-Escalation for Adjuvant Chemoradiotherapy in Human Papillomavirus-Associated Oropharynx Squamous Cell Carcinoma. [2021]

7. England pubmed.ncbi.nlm.nih.gov

De-intensification of therapy in human papillomavirus associated oropharyngeal cancer: A systematic review of prospective trials. [2021]

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

Effectiveness of reduced- versus standard-dose radiotherapy on survival and radiation-associated toxicity in patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma: a systematic review protocol. [2022]