Unilateral vs Bilateral Radiotherapy for Head and Neck Cancer

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: AHS Cancer Control Alberta

Disqualifiers: Previous radiation, Pregnancy, Connective tissue disease

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

Compensation: Varies

Number of Visits: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of giving radiotherapy to only one side of the neck for people with head and neck cancer, instead of both sides. Typically, radiation targets both sides after surgery, but this can lead to many side effects. The trial aims to determine if focusing radiation on one side can reduce these side effects and improve quality of life without compromising safety. Researchers will compare two groups: one receiving radiation on both sides and the other on one side. Suitable candidates have undergone surgery for head and neck cancer, with cancer removed from one side of the neck but not the other. As an unphased trial, this study provides a unique opportunity to explore innovative treatment options that could enhance quality of life.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that administering radiation to just one side of the neck can be safe for some head and neck cancer patients. Studies have found that patients with tumors on one side can tolerate this treatment well. For example, one study found that one-sided radiation led to few complications in patients with small tonsil cancers on one side. Another study supported its safety for carefully selected patients with oropharyngeal cancer on one side.

These findings suggest that targeting radiation only on the side with the tumor might reduce side effects while remaining effective. This approach could improve patients' quality of life by limiting unnecessary radiation exposure. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores whether radiotherapy to just one side of the neck (ipsilateral radiotherapy) can be as effective as treating both sides (bilateral radiotherapy) in head and neck cancer. Unlike the standard approach, which typically involves radiating both sides to prevent cancer spread, the experimental method targets only the side with the tumor. This approach could potentially reduce side effects and improve the quality of life for patients by minimizing exposure to healthy tissues. If successful, it may lead to a more targeted and patient-friendly treatment option.

What evidence suggests that this trial's treatments could be effective for head and neck cancer?

Research has shown that radiation therapy to just one side of the neck can be effective for certain head and neck cancers. In this trial, participants will receive either radiotherapy to the ipsilateral neck lymphatics and tumor bed (one side) or to the bilateral neck lymphatics and tumor bed (both sides). Studies have found that for patients with small tonsil cancers on one side, treating only the affected side results in a low risk of cancer appearing on the untreated side. Other research indicates that this approach leads to fewer side effects, improving patients' quality of life. This method has been safely used in well-defined head and neck cancers, suggesting it could be a promising way to avoid unnecessary treatment. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

Adults over 18 with squamous cell carcinoma of the head and neck who've had surgery to remove lymph nodes, with no disease found on one side. They must understand and agree to the study's process, have had a PET/CT scan showing no disease on the opposite side, and be able to follow treatment and check-ups.

Inclusion Criteria

My cancer is confirmed as squamous cell carcinoma.

I have squamous cell carcinoma in my head or neck and am having surgery as my first treatment.

The contralateral neck is pathologically negative

Exclusion Criteria

Pregnancy

I have had radiation therapy to my head or neck.

I do not have severe conditions that make radiation unsafe for me.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Surgical procedure to remove lymph nodes on both sides of the neck

1 day

1 visit (in-person)

Radiotherapy

Radiotherapy to either one or both sides of the neck, starting a maximum of 8 weeks post-surgery

6 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Visits at 6, 12, 18, and 24 months post-radiotherapy

What Are the Treatments Tested in This Trial?

Interventions

• Radiotherapy to ipsilateral neck lymphatics and tumor bed
• Radiotherapy to the bilateral neck lymphatics and tumor bed

Trial Overview This trial is testing if it's safe for patients with head and neck cancer to receive radiotherapy only on the affected side of their neck instead of both sides after surgery. Participants are randomly placed in two groups: one gets standard radiotherapy on both sides; the other gets experimental therapy just on one side.

How Is the Trial Designed?

Group I: Experimental intervention Experimental Treatment 1 Intervention

Radiotherapy to ipsilateral neck lymphatics and tumor bed (radiotherapy to one side of the neck).

Group II: Non-experimental intervention Active Control 1 Intervention

Radiotherapy to the bilateral neck lymphatics and tumor bed (radiotherapy to both sides of the neck).

Radiotherapy to ipsilateral neck lymphatics and tumor bed is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Unilateral Neck Radiotherapy for:

• Head and neck cancer
• Squamous cell carcinoma of the tonsil
• Oropharyngeal carcinoma

Approved in United States as Unilateral Neck Radiotherapy for:

• Head and neck cancer
• Squamous cell carcinoma of the tonsil
• Oropharyngeal carcinoma

Approved in Canada as Unilateral Neck Radiotherapy for:

• Head and neck cancer
• Squamous cell carcinoma of the tonsil
• Oropharyngeal carcinoma

Who Is Running the Clinical Trial?

AHS Cancer Control Alberta

Lead Sponsor

Trials

188

Recruited

26,900+

Cross Cancer Institute

Collaborator

Trials

62

Recruited

19,200+

Published Research Related to This Trial

In a study of 228 patients with tonsillar carcinoma treated with ipsilateral radiotherapy over 21 years, the risk of cancer recurrence in the opposite neck was low, with only 3.5% experiencing failure.

The study found a 77% local control rate and a 76% cause-specific survival rate, indicating that carefully selected patients can benefit from targeted treatment while minimizing risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The benefits and pitfalls of ipsilateral radiotherapy in carcinoma of the tonsillar region. O'Sullivan, B., Warde, P., Grice, B., et al.[2019]

Ipsilateral radiotherapy for well lateralized tonsil cancer showed high effectiveness, with a five-year local progression-free survival rate of 95% and an overall survival rate of 95% among 20 patients followed for a median of 64 months.

The treatment resulted in a low incidence of chronic xerostomia (dry mouth), with only one patient experiencing grade 2 xerostomia, indicating that this approach can minimize side effects by sparing the contralateral salivary glands.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term results of ipsilateral radiotherapy for tonsil cancer. Koo, TR., Wu, HG.[2021]

In a study of 136 patients with tonsillar cancer treated with ipsilateral radiotherapy, factors such as N2b disease, extra-capsular spread (ECS), and a smoking history of over 10 pack-years were linked to a higher risk of contralateral nodal recurrence.

The study found a high overall survival rate of 89% and recommended considering prophylactic irradiation of the contralateral neck for patients with identified risk factors to prevent recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple cervical lymph node involvement and extra-capsular extension predict for contralateral nodal recurrence after ipsilateral radiotherapy for squamous cell carcinoma of the tonsil. Lynch, J., Lal, P., Schick, U., et al.[2022]

In a study of 76 patients with cancer of unknown primary (CUP) in the head and neck, both ipsilateral and bilateral adjuvant radiotherapy showed similar 5-year overall survival rates (67.9%) and recurrence-free survival rates (71.5%).

Ipsilateral radiotherapy was associated with significantly fewer radiation-induced acute side effects compared to bilateral radiotherapy, suggesting it may be the preferred treatment option for CUP patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bilateral vs ipsilateral adjuvant radiotherapy in patients with cancer of unknown primary of the head and neck: An analysis of the clinical outcome and radiation-induced side effects. Le, NS., Janik, S., Simmel, H., et al.[2020]

In a study of 20 patients with well lateralized squamous cell carcinomas of the oral cavity and oropharynx treated with ipsilateral radiotherapy, the five-year overall survival rate was 82.5% and loco-regional control was 100%, indicating effective tumor control.

Ipsilateral irradiation significantly spared salivary gland function, with 87.5% of patients experiencing minimal xerostomia (dry mouth), and none suffering from severe xerostomia, suggesting a safer treatment option for preserving quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipsilateral irradiation for well lateralized carcinomas of the oral cavity and oropharynx: results on tumor control and xerostomia. Cerezo, L., Martín, M., López, M., et al.[2021]

In a study of 20 patients with node-positive squamous cell carcinoma of the tonsil, treatment with ipsilateral neck radiotherapy showed no cases of in-field or contralateral nodal recurrences at a median follow-up of 19 months, indicating effective local control of the disease.

The treatment resulted in a 2-year disease-free survival rate of 79.5% and low late toxicity, with only 5% of patients experiencing grade 2 xerostomia, suggesting that this approach may reduce long-term side effects compared to traditional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Freedom from local and regional failure of contralateral neck with ipsilateral neck radiotherapy for node-positive tonsil cancer: results of a prospective management approach. Rusthoven, KE., Raben, D., Schneider, C., et al.[2009]

In a study of 66 patients with AJCC-7 T1-2N2b tonsillar cancer treated with unilateral radiation, the contralateral nodal failure rate was very low at only 3.0%, indicating that this treatment strategy is effective for managing multiple ipsilateral nodes.

The overall locoregional control rate was high at 93.9% over 2 and 5 years, with a 5-year overall survival rate of 92.4%, suggesting that unilateral radiation is a safe and effective de-escalation strategy for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Locoregional Control With Unilateral Radiation for AJCC-7 T1-2N2b Tonsillar Cancer. Frankart, AJ., Abana, CO., Geier, N., et al.[2023]

Ipsilateral radiotherapy (IPSI) for patients with cervical metastases from unknown primary cancers showed excellent local control with no ipsilateral neck failures and did not negatively impact overall survival or cause-specific survival, with 2-year and 5-year overall survival rates of 87% and 77%, respectively.

There was no significant difference in overall survival between patients receiving IPSI radiation and those receiving comprehensive (COMP) radiation therapy, indicating that IPSI may be a safe and effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapeutic management of cervical lymph node metastases from an unknown primary site. Perkins, SM., Spencer, CR., Chernock, RD., et al.[2012]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11467478/

Unilateral radiotherapy for tonsillar cancer with multiple ... The results of our study suggest that unilateral RT can be safely performed in well-lateralized tonsillar cancer patients with multiple ipsilateral neck lymph ...

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2801100

Association of Unilateral Radiotherapy With Contralateral ... In this systematic review and meta-analysis, ipsilateral neck RT was associated with a low rate of CNF in patients with small, lateralized tonsil cancers.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0167814025048042

141 - randomized trial of unilateral versus bilateral neck ... We aimed to evaluate the efficacy of bilateral versus ipsilateral-only neck irradiation in such patients. Materials and Methods: This prospective, randomized ...

4. thegreenjournal.com thegreenjournal.com/article/S0167-8140(23)89846-2/fulltext

Management of unknown primary head and neck cancer ... Improved dosimetric and clinical outcomes with intensity-modulated radiotherapy for head and neck cancer of unknown primary origin. Int J ...

5. karger.com karger.com/orl/article/86/3-4/140/913141/Unilateral-Neck-Treatment-with-either-Surgery-and

Unilateral Neck Treatment with either Surgery and/or ... Here, we present our institutional experience with treatment through ipsilateral surgical or radiotherapeutic neck management. Methods: We ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03622164

Unilateral Neck Radiotherapy in Head and Neck Cancer | ... There is growing evidence from some other studies that support the safety of omitting radiotherapy after surgery in the side of the neck with no disease. With ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0167814025045530

Unilateral vs bilateral neck irradiation: The importance of ... Unilateral neck radiotherapy is controversial for lateralized oropharyngeal cancer. · This matched analysis supports its safety in well-selected patients.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8582444/

A Rational Approach to Unilateral Neck RT for Head and ... This review explores the advantages of restricting radiation to the primary tumor/tumor bed and ipsilateral elective neck as it pertains to the ...