Reduced Radiation Therapy for Oropharyngeal Cancer

Overseen By J. Nicholas Lukens, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Abramson Cancer Center at Penn Medicine

Disqualifiers: Prior radiation, T4 disease, others

Stay on Your Current Meds You can continue your current medications while participating

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether using lower doses of radiation on a smaller area of the head and neck effectively reduces the recurrence of oropharyngeal cancer, a type of throat cancer. Researchers aim to determine if this method works as well as standard treatment but with fewer side effects. The trial involves patients with p16-positive oropharyngeal squamous cell carcinoma. Those diagnosed with this cancer type who have not previously received radiation to the head and neck may be suitable candidates. As an unphased trial, it offers patients the chance to contribute to innovative research that could lead to more personalized and less invasive treatment options.

Do I need to stop 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 is safe for treating oropharyngeal cancer?

Research has shown that using a lower dose of radiation for certain HPV-positive throat cancers may be safer and still effective. One study found that reducing the radiation dose improved patients' quality of life. Another study found that in some patients, lowering the radiation dose did not increase the risk of cancer recurrence. This suggests that the treatment is well-tolerated. Evidence indicates that reducing the radiation dose can still safely target the cancer while potentially reducing side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this reduced radiation therapy for oropharyngeal cancer because it aims to minimize the radiation exposure to patients without compromising the effectiveness of the treatment. Unlike traditional radiation therapies that deliver higher doses, this approach reduces the dose to the high-risk neck area from 60 Gy to 50 Gy and further decreases the exposure to the low-risk neck to 45 Gy. This could potentially lead to fewer side effects and better quality of life for patients, while still effectively targeting cancer cells in critical areas.

What evidence suggests that reduced radiation therapy is effective for oropharyngeal cancer?

Research has shown that lower doses of radiation for HPV-related throat cancer can be effective. In past studies, survival rates after two years exceeded 96%. Additionally, using less radiation significantly reduces side effects and enhances patients' quality of life. In this trial, all participants will receive reduced radiation therapy, with the volume treated and radiation dose to the regional lymphatics decreased based on the primary site's characteristics and involved lymph nodes. Clinical trials have found that certain HPV-positive throat cancer cases can be treated with less radiation without compromising safety. This method not only aims to control the cancer but also makes the treatment more manageable. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with a specific throat cancer (p16+ oropharyngeal squamous cell carcinoma) that hasn't spread too far. They should be in good physical shape and have no more than four affected lymph nodes. People with very advanced disease, distant spread of cancer, previous head/neck radiation, or more than four positive lymph nodes can't join.

Inclusion Criteria

My cancer is at an early or middle stage according to its size and extent.

My throat cancer is confirmed to be p16 positive.

My cancer has spread to fewer than 5 lymph nodes.

Exclusion Criteria

My cancer has spread to distant parts of my body.

My cancer has spread to nearby tissues.

>= 5 lymph nodes

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Participants undergo Transoral Robotic Surgery (TORS) and neck dissection

4-6 weeks

Radiation

Participants receive de-intensified adjuvant radiation therapy to the primary site and regional lymphatics

6-8 weeks

Follow-up

Participants are monitored for safety, effectiveness, and quality of life outcomes after treatment

2.5 years

What Are the Treatments Tested in This Trial?

Interventions

• Radiation Therapy

Trial Overview The study tests if using lower doses of radiation to a smaller area in the head and neck region is effective for treating throat cancer without it coming back within two years. It's a Phase II trial where all participants receive this modified radiation therapy.

How Is the Trial Designed?

Group I: Arm 1 Experimental Treatment 1 Intervention

All patients will have the volume treated and radiation dose delivered to the regional lymphatics decreased according to the characteristics of the primary site and involved lymph nodes. The high risk neck will receive 50 Gy instead of 60 Gy, and the treated volume of the contralateral low risk neck will be reduced and receive only 45 Gy.

Radiation Therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in United States as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Canada as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Japan as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in China as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Switzerland as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Who Is Running the Clinical Trial?

Abramson Cancer Center at Penn Medicine

Lead Sponsor

Trials

425

Recruited

464,000+

Abramson Cancer Center of the University of Pennsylvania

Lead Sponsor

Trials

360

Recruited

108,000+

Published Research Related to This Trial

Intensity-modulated radiation therapy (IMRT) significantly reduced the incidence of late xerostomia (dry mouth) in patients with oropharyngeal cancer compared to conventional radiation therapy (CRT), indicating a safety advantage for IMRT.

The study, which followed 430 patients over a median of 3.9 years, found that IMRT did not negatively affect tumor control or disease-free survival rates, demonstrating its efficacy in treating oropharyngeal carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiation therapy reduces late salivary toxicity without compromising tumor control in patients with oropharyngeal carcinoma: a comparison with conventional techniques. Chao, KS., Majhail, N., Huang, CJ., et al.[2022]

In a study of 20 patients undergoing intensity-modulated radiotherapy (IMRT) for head and neck cancer, acute side effects were common, with 19 patients experiencing xerostomia (dry mouth) and 18 reporting mucositis (inflammation of the mucous membranes).

Long-term effects included persistent xerostomia in 11 out of 14 patients and an increase in trismus (restricted jaw movement) in 4 patients, indicating that while some acute symptoms improved, certain complications remained significant after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral complications of head and neck radiotherapy: prevalence and management. Germano, F., Melone, P., Testi, D., et al.[2017]

Intensity-modulated radiotherapy (IMRT) shows excellent local-regional control rates of 92% for patients with squamous cell carcinoma of the oropharynx, based on a study of 107 patients with a median follow-up of 29 months.

Despite the high local control, distant metastases were a significant concern, with 7 patients experiencing them as the first site of failure, highlighting the need for ongoing monitoring and potential additional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiotherapy in the treatment of oropharyngeal cancer: clinical outcomes and patterns of failure. Daly, ME., Le, QT., Maxim, PG., et al.[2022]

Modern radiation therapy, particularly intensity-modulated radiation therapy (IMRT), significantly reduces xerostomia (dry mouth) and improves the quality of life for patients with oropharyngeal cancer.

Intensity-modulated proton therapy may offer even greater benefits by minimizing radiation-related toxicities, which is crucial for patients with HPV-positive oropharyngeal carcinoma who are likely to have long-term survival after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in radiation oncology for the management of oropharyngeal tumors. Gunn, GB., Frank, SJ.[2018]

Intensity Modulated Radiation Therapy (IMRT) combined with Image Guided Radiation Therapy (IGRT) enhances treatment for head and neck cancer by improving tumor coverage while minimizing damage to normal tissues, leading to similar tumor control rates with less toxicity compared to conventional methods.

In the context of systemic therapy, platinum-based radiochemotherapy remains the standard treatment, and early evidence suggests that adding Cetuximab to cisplatin-based therapy does not provide additional benefits in primary treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current strategies in radiotherapy of head and neck cancer. Pütz, M., Wenz, F.[2021]

Intensity modulated radiation treatment (IMRT) for oropharyngeal squamous cell carcinoma showed excellent locoregional control, with a 3-year locoregional progression-free survival rate of 98.8% among 66 patients treated between 2000 and 2004.

Despite the high locoregional control, there was a concerning rate of distant metastasis, with a 3-year distant metastasis-free survival rate of only 80.4%, indicating a need for further research into systemic treatments for patients at risk of distant disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changing failure patterns in oropharyngeal squamous cell carcinoma treated with intensity modulated radiotherapy and implications for future research. Yao, M., Nguyen, T., Buatti, JM., et al.[2006]

Intensity-modulated radiation therapy (IMRT) can significantly reduce the amount of mucosal tissue exposed to high radiation doses in patients with early oropharyngeal cancer, especially when a dose objective is set for the mucosa.

In a study involving 5 patients, IMRT with a mucosal dose objective resulted in up to a 30% reduction in mucosal exposure to high doses compared to standard three-field technique (3FT) radiotherapy, indicating that IMRT may offer a safer treatment option with less risk of damaging healthy tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there a "mucosa-sparing" benefit of IMRT for head-and-neck cancer? Sanguineti, G., Endres, EJ., Gunn, BG., et al.[2006]

Intensity-modulated radiotherapy (IMRT) for oropharyngeal squamous cell carcinoma showed promising 5-year local control rates, with 87% overall and varying by cancer stage, indicating its efficacy in managing advanced disease.

The treatment resulted in a 5-year cause-specific survival rate of 85% and an overall survival rate of 76%, with a relatively low incidence of severe late complications (8%), suggesting that IMRT is a safe and effective option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiotherapy for oropharyngeal squamous cell carcinoma. Mendenhall, WM., Amdur, RJ., Morris, CG., et al.[2022]

In a study of 148 oropharynx cancer patients treated with either IMRT alone or a combination of IMRT and IMPT, the combination therapy showed significantly lower rates of severe acute toxicities, such as mucositis and pain, indicating a safer treatment option.

Despite similar overall survival and progression-free survival rates between the two groups, the IMRT/IMPT combination resulted in fewer patients experiencing grade ≥ 3 mucositis and pain, suggesting improved patient comfort during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Clinical Outcomes of Intensity Modulated Radiation Therapy/Intensity Modulated Proton Therapy Combination in Comparison with Intensity Modulated Radiation Therapy Alone in Oropharynx Cancer Patients. Yoon, HG., Ahn, YC., Oh, D., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36660712/

Reduced-dose radiation in human papillomavirus ... The 2- and 3-year overall survival rates in the reduced-dose group (95.66% and 91.51%, respectively) were superior to those in the standard-dose group (88.36% ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.20.03128

Reduced-Dose Radiation Therapy for HPV-Associated ... Two-year overall survival rates were 96.7% for IMRT + C and 97.3% for IMRT. Acute adverse events (AEs) were defined as those occurring within ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0360301624025343

Outcomes of Reduced Elective Nodal Radiation Dose for ... Reducing elective nodal irradiation dose can decrease treatment toxicity and improve quality of life for head and neck cancer patients.

4. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2788326

Elective Radiotherapy Dose and Field in HPV-Associated ... Several clinical trials have shown that in patients with select HPV-positive OPC, radiation dose to gross disease can be safely reduced, ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9843369/

Reduced-dose radiation in human papillomavirus ... Reducing the radiation dose in patients with HPV-related OPC substantially alleviates the treatment toxicities and optimizes the quality of life of patients.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12316137/

Clinical Benefit and Safety of Reduced Elective Dose in ... The primary outcome was normalcy of diet score at 1 year. The secondary outcome was recurrence in electively irradiated nodes at 2 years in the ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8078254/

Reduced-Dose Radiation Therapy for HPV-Associated ... Reducing radiation treatment dose could improve the quality of life (QOL) of patients with good-risk human papillomavirus–associated oropharyngeal squamous ...

8. jci.org jci.org/articles/view/198351

Genomic adjusted radiation dose stratifies radiotherapy ... Genomic adjusted radiation dose stratifies radiotherapy dosing based on tumor-specific sensitivity in HPV+ oropharyngeal cancer.

9. 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 ...