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

Trial Summary

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 radiotherapy for head and neck cancers generally safe for humans?

Radiotherapy for head and neck cancers has been studied for safety, and while it can cause side effects, approaches like SPECT/CT-guided treatment may reduce these effects and improve quality of life. ^{1 2 3 4 5}

How does the treatment ENI, INRT differ from other treatments for head and neck cancers?

The treatment ENI, INRT for head and neck cancers is unique because it uses intensity-modulated radiation therapy (IMRT), which allows for precise targeting of the tumor with high doses of radiation while minimizing exposure to surrounding healthy tissues. This approach can potentially improve tumor control and reduce side effects compared to traditional radiation therapies. ^{6 7 8 9 10}

What is the purpose of this trial?

To determine the risk of solitary elective volume recurrence following involved nodal radiotherapy (INRT) versus elective nodal irradiation (ENI)

Research Team

David Sher, MD

Principal Investigator

University of Texas Southwestern Medical Center

Eligibility Criteria

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

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

Treatment Details

Interventions

• ENI
• INRT

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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 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]

References

1. United States 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. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Electronic patient-reported outcomes and toxicities during radiotherapy for head-and-neck cancer. [2023]

3. United States 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. [2022]

4. Ireland 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. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Patient-reported quality-of-life outcomes in relation to provider-assessed adverse events during head and neck radiotherapy. [2020]

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

Target coverage for head and neck cancers treated with IMRT: review of clinical experiences. [2018]

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

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

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

Intensity-modulated radiation therapy. [2022]

9. Ireland 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. [2005]

10. France pubmed.ncbi.nlm.nih.gov

[Intensity-modulated radiation therapy for head and neck cancers with bilateral irradiation of the neck : preliminary results]. [2018]