Radiotherapy for Head and Neck Cancers

Overseen By Sarah Neufeld

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: Investigational agents

Disqualifiers: Distant metastasis, Prior invasive malignancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 7 weeks

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two methods of using radiotherapy to treat certain head and neck cancers. It aims to determine which method better reduces cancer recurrence in the neck area. The trial seeks participants with squamous cell carcinoma in the oropharynx, larynx, or hypopharynx who have noticeable disease in these areas. Participants must be able to undergo imaging tests like CT and PET scans. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important research.

Do I need to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss your specific medications with the trial team to get a clear answer.

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

Research has shown that both elective neck irradiation (ENI) and involved nodal radiotherapy (INRT) for head and neck cancers have been studied for safety. Studies have found that ENI is generally safe, with long-term results demonstrating its benefits. In one study, patients who received a lower dose of ENI experienced similar safety and effectiveness as those who received higher doses, indicating that ENI is well-tolerated without significant extra risks.

For INRT, research also indicates promising safety results. One study suggested that not using ENI may not increase cancer risks and can improve quality of life. Patients treated with INRT had low rates of cancer recurrence in critical areas, supporting its safe use.

Both treatments have been tested in clinical settings, showing a good safety record. These findings suggest they are generally well-tolerated by patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for head and neck cancers because they introduce innovative ways to target lymph nodes. The standard approach, elective neck irradiation (ENI), involves treating multiple lymph node areas, which can sometimes affect healthy tissue. The new technique, involved and suspicious lymph node delineation and targeting, uses AI-Radiomics to precisely identify and treat only the suspicious lymph nodes, potentially reducing unnecessary exposure. This targeted approach might offer a more personalized treatment, minimizing side effects and improving outcomes.

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

In this trial, participants will receive either Elective Neck Irradiation (ENI) or Involved Node Radiotherapy (INRT) as separate treatment arms. Studies have shown that ENI can reduce long-term side effects and improve the quality of life for patients with head and neck cancer by using a lower dose of radiation, resulting in fewer harmful effects. Conversely, INRT targets cancerous and suspicious lymph nodes, potentially extending patients' lives. Research suggests that this targeted approach can improve overall survival for patients with cancers that have spread to the lymph nodes. Both treatments offer benefits: ENI aims to reduce side effects, while INRT focuses on increasing survival rates. ^{1 3 6 7 8}

Who Is on the Research Team?

David Sher, MD

Principal Investigator

University of Texas Southwestern Medical Center

Are You a Good Fit for This Trial?

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent.

I have had a neck CT, neck MRI, and PET-CT.

My cancer is between stages I and IVB, but it's not in the early stages of glottic cancer.

Exclusion Criteria

My cancer has spread, and I can't have a CT scan with contrast.

Subjects may not be receiving any other investigational agents.

History of allergic reactions attributed to compounds of similar chemical or biologic composition to the chemotherapy agents in this study (if necessary).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either elective nodal irradiation (ENI) or involved nodal radiotherapy (INRT) with doses up to 63 Gy in 35 fractions

7 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of dermatitis and dysphagia

2 years

What Are the Treatments Tested in This Trial?

Interventions

• ENI
• INRT

How Is the Trial Designed?

Group I: Involved and suspicious lymph node delineation and targeting Experimental Treatment 2 Interventions

After the involved and suspicious nodes are contoured, the physician will contour remaining nodes that are present on more than one CT slice and submit them to the AI-Radiomics module for assessment.The nodal gross tumor volume (GTVn, GTVns and GTVnps for involved, suspicious nodes or potentially suspicious) will be contoured on the planning CT, using radiographic and clinical information to define its extent. The total dose for GTVns is 63 Gy in 35 fractions, and the total dose for GTVnps is 56 Gy in 35 fractions. For lymph nodes identified as potentially suspicious by the AI- Radiomics module that are outside of the expected primary draining zone, physicians may not treat the lymph node if the module assesses its estimation uncertainty as greater than 50%.

Group II: Standard radiotherapy with elective neck irradiation (ENI) Active Control 2 Interventions

The elective neck dose is 56 Gy in 35 fractions Lymph nodes measuring 17 mm or greater in any dimension, or showing FDG above adjacent blood pool, may receive 63 Gy in 35 fractions per physician discretion.The elective neck field is determined by the primary site. The Oropharynx: Node-positive side: Levels IB-V and RP nodes Node-negative side: Levels II-IV, RP at discretion of physician For ipsilateral tonsil decision-making, see 4.1.1.6.3 The Larynx: Node-positive side: Levels IB-V Node-negative side: Levels II-IV Subglottic extension: Level VI Hypopharynx: Node-positive side: Levels IB-V and RP nodes Node-negative side: Levels II-V and RP nodes Pyriform sinus involvement: Level VI

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 67 patients with head and neck squamous cell carcinoma, eliminating elective neck irradiation (ENI) resulted in a 0% risk of solitary elective nodal recurrence after 2 years, indicating that targeted treatment of involved lymph nodes is effective.

The approach also showed favorable quality-of-life outcomes, with minimal impact on swallowing function and a low rate of gastrostomy tube dependence, suggesting that this method may reduce unnecessary radiation exposure to healthy tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Quality-of-Life Following Involved Nodal Radiotherapy for Head and Neck Squamous Cell Carcinoma: The INRT-AIR Phase II Clinical Trial. Sher, DJ., Moon, DH., Vo, D., et al.[2023]

Intensity-Modulated Radiotherapy (IMRT) provides more uniform coverage of the target area (PTV) in head-and-neck cancer treatment compared to traditional 3D Conformal Radiotherapy (3DCRT), significantly improving the precision of radiation delivery.

Using Step-and-Shoot (SS) techniques with 10 or more intensity levels yields similar effectiveness to the Sliding Window (SW) method in sparing surrounding healthy tissues (OARs), while reducing the mean dose to critical areas like the parotids by an average of 13.5 Gy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing 3DCRT and inversely optimized IMRT planning for head and neck cancer: equivalence between step-and-shoot and sliding window techniques. Longobardi, B., De Martin, E., Fiorino, C., et al.[2005]

In a study of 110 head and neck squamous cell carcinoma patients, a dose of 50 Gy for elective nodal irradiation (ENI50) was found to be as effective as 60 Gy (ENI60) in controlling locoregional disease, with similar 3-year control rates (78.7% vs 77%).

Using the lower dose of 50 Gy significantly reduced the risk of salivary and thyroid toxicity, with fewer patients developing hypothyroidism and better recovery of salivary function compared to those receiving 60 Gy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elective nodal dose of 60 Gy or 50 Gy in head and neck cancers: A matched pair analysis of outcomes and toxicity. Murthy, V., Gurram, L., Kannan, S., et al.[2022]

In a study of 50 patients with head and neck squamous cell carcinoma, SPECT/CT-guided elective nodal irradiation (ENI) resulted in a very low rate of contralateral regional failure (2%) after a median follow-up of 33 months, indicating its effectiveness.

Patients receiving SPECT/CT-guided ENI experienced significantly fewer side effects, such as severe swallowing difficulties (54% vs. 82% in the standard treatment group) and late dry mouth (9% vs. 54%), along with improved health-related quality of life, compared to those who underwent standard bilateral ENI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SPECT/CT-guided elective nodal irradiation for head and neck cancer is oncologically safe and less toxic: A potentially practice-changing approach. de Veij Mestdagh, PD., Walraven, I., Vogel, WV., et al.[2022]

Intensity-modulated radiation therapy (IMRT) is effective for treating head and neck cancers, as it delivers precise radiation doses to tumors while minimizing exposure to surrounding healthy tissues.

The ability of IMRT to escalate doses safely is particularly beneficial in head and neck cancer treatment, and ongoing studies are examining its long-term clinical outcomes and potential toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiation therapy. Lee, NY., Terezakis, SA.[2022]

In a study of 10 patients with head and neck squamous cell carcinoma treated with intensity-modulated radiotherapy (IMRT), no patients experienced death or loco-regional relapse, indicating promising efficacy of the treatment.

The study found that limiting the radiation dose to the contralateral parotid gland was more achievable with a maximum IMRT dose of 50 Gy, resulting in lower acute toxicity and a 50% rate of grade 0-1 late xerostomia at 3 months, suggesting potential for better long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Intensity-modulated radiation therapy for head and neck cancers with bilateral irradiation of the neck : preliminary results]. Lapeyre, M., Marchesi, V., Mege, A., et al.[2018]

In a study of 65 patients undergoing head-and-neck radiotherapy, significant declines in quality of life (QOL) were observed, particularly in fatigue, social activity, and overall QOL, with 70.8% of patients reporting these issues during treatment.

The study highlighted that concurrent chemoradiotherapy (CCRT) led to more severe adverse events, including grade 3 complications in 35.4% of patients, significant weight loss averaging 5.5 kg, and a high need for supportive care interventions like intravenous hydration and feeding tube placement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electronic patient-reported outcomes and toxicities during radiotherapy for head-and-neck cancer. Niska, JR., Halyard, MY., Tan, AD., et al.[2023]

Intensity-modulated radiation therapy (IMRT) is becoming increasingly popular for treating head and neck cancers, showing promising preliminary results in improving tumor coverage and disease control.

IMRT aims to reduce radiation toxicity while effectively targeting tumors, prompting oncologists to reconsider traditional treatment practices and explore new therapeutic approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Target coverage for head and neck cancers treated with IMRT: review of clinical experiences. Garden, AS., Morrison, WH., Rosenthal, DI., et al.[2018]

Intensity-modulated radiation therapy (IMRT) allows for higher doses of radiation to be delivered precisely to cancerous areas while minimizing exposure to surrounding healthy tissues, which can improve safety and reduce side effects.

IMRT is particularly beneficial for treating head and neck cancers due to the close proximity of tumors to critical structures, although there are concerns about the potential long-term risks of radiation exposure to non-target tissues, especially in younger patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiation therapy in the treatment of head and neck cancer. Eisbruch, A.[2018]

In a study of 65 patients undergoing head-and-neck radiotherapy, those with higher-grade adverse events reported significantly worse quality-of-life outcomes, particularly in areas like fatigue and overall well-being, especially at the beginning of treatment.

As treatment progressed, the negative impact of adverse events on quality of life appeared to decrease, suggesting that patients may adapt over time, and highlighting the importance of considering both patient-reported outcomes and provider-assessed adverse events for a comprehensive understanding of treatment effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported quality-of-life outcomes in relation to provider-assessed adverse events during head and neck radiotherapy. Niska, JR., Thorpe, CS., Halyard, MY., et al.[2020]

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In this review, we outline principles for de-escalating head and neck ENI dose and volume and highlight the emerging paradigm of ENI omission.

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The primary objective of this study is to treat the first HNSCC patients with individual elective lymph node irradiation by means of a Magnetic Resonance-linac ...