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

150 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a single-arm Phase II study of adjuvant radiation for locally advanced p16+ oropharyngeal squamous cell carcinoma. The main purpose of this research is to determine the likelihood of cancer growing back in the throat or in the neck two years after completion of radiation if lower doses of radiation are used to a smaller area of the head and neck region than is currently used in standard of care.

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 data supports the effectiveness of the treatment for oropharyngeal cancer?

Research shows that intensity-modulated radiotherapy (IMRT) is effective for treating oropharyngeal cancer, offering benefits like reduced dry mouth and improved quality of life. Combining IMRT with proton therapy may further reduce side effects, making it a promising option for patients. ^{1 2 3 4 5}

Is reduced radiation therapy for oropharyngeal cancer safe for humans?

Modern radiation therapies like intensity-modulated radiation therapy (IMRT) and image-guided radiation therapy (IGRT) are generally safe and can reduce side effects compared to older methods. They help protect normal tissues while effectively treating tumors, leading to fewer complications such as dry mouth and better quality of life. ^{4 6 7 8 9}

How is reduced radiation therapy unique for treating oropharyngeal cancer?

Reduced radiation therapy, particularly using intensity-modulated radiation therapy (IMRT), is unique because it can target the cancer more precisely, sparing more of the healthy tissue around the tumor. This approach reduces side effects like salivary gland damage while maintaining effective tumor control. ^{2 3 8 10 11}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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 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]

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]

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]

References

1. Switzerland 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. [2021]

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

Changing failure patterns in oropharyngeal squamous cell carcinoma treated with intensity modulated radiotherapy and implications for future research. [2006]

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

Intensity-modulated radiotherapy for oropharyngeal squamous cell carcinoma. [2022]

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

Advances in radiation oncology for the management of oropharyngeal tumors. [2018]

5. Greece pubmed.ncbi.nlm.nih.gov

Simultaneously Integrated Boost Affects Survival in Locally Advanced p16-Negative Oropharyngeal Squamous Cell Carcinoma. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Current strategies in radiotherapy of head and neck cancer. [2021]

7. Italy pubmed.ncbi.nlm.nih.gov

Oral complications of head and neck radiotherapy: prevalence and management. [2017]

8. Ireland 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. [2022]

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

Intensity-modulated radiotherapy in the treatment of oropharyngeal cancer: clinical outcomes and patterns of failure. [2022]

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

Is there a "mucosa-sparing" benefit of IMRT for head-and-neck cancer? [2006]

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

Dosimetric Results for Adjuvant Proton Radiation Therapy of HPV-Associated Oropharynx Cancer. [2022]