Shortened Radiation Therapy for Head and Neck Cancer

Overseen By Etta Pisano, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: American College of Radiology

Must not be taking: High-dose chemotherapy

Disqualifiers: Recurrence, Lupus, Scleroderma, Pregnancy, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a shorter, more intense form of radiation therapy, called hypofractionated radiation, is safe for individuals with intermediate-risk head and neck cancer after surgery. The goal is to use fewer radiation sessions over four weeks to treat cancers in the oral cavity, oropharynx, or larynx. Suitable candidates have undergone surgery to remove their cancer, have no remaining cancer, and possess certain risk factors, such as cancer cells near nerves or blood vessels. Individuals who have had head and neck cancer surgery and meet these criteria may consider participating in this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on high-dose systemic chemotherapy or multiple systemic therapy agents, you may not be eligible to participate.

What prior data suggests that hypofractionated radiation therapy is safe for head and neck cancer patients?

Research has shown that hypofractionated radiation therapy, which involves delivering radiation in larger doses over a shorter period, is generally well tolerated. Studies on this treatment for head and neck cancer found that administering these higher doses over three weeks did not cause major short-term side effects. This finding is encouraging for patients, suggesting the treatment might be safe and more convenient. However, as the treatment remains in early testing, further research is needed to fully understand its long-term safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Hypofractionated Postoperative Radiotherapy (H-PORT) for head and neck cancer because it offers a shorter treatment duration compared to traditional radiation therapies. While standard treatments often require six to seven weeks of daily sessions, H-PORT delivers the same total dose in just four weeks. This condensed schedule not only enhances patient convenience but may also reduce the overall burden of treatment, leading to potential improvements in patient quality of life without compromising effectiveness. Additionally, a shorter treatment period could mean faster recovery times and earlier return to normal activities for patients.

What evidence suggests that hypofractionated radiation therapy might be an effective treatment for head and neck cancer?

Research has shown that hypofractionated radiation therapy, which involves delivering larger doses of radiation over a shorter period, holds promise for treating head and neck cancer. In this trial, participants will receive Hypofractionated Postoperative Radiotherapy (H-PORT) of 50 Gy over 4 weeks. Studies have found that patients who underwent surgery for these cancers generally tolerate this therapy well. In some cases, it effectively controlled cancer in the treated area. Additionally, this method has demonstrated only limited short-term side effects. Overall, early evidence suggests that hypofractionated radiation could be a viable option for treating head and neck cancer post-surgery. ^{1 4 5 6 7}

Who Is on the Research Team?

Etta Pisano, MD

Principal Investigator

American College of Radiology

Are You a Good Fit for This Trial?

This trial is for individuals who've had surgery for intermediate-risk head and neck cancer, specifically squamous cell carcinoma. Eligible participants should not have distant metastases, must have completed a total resection of the cancer with no residual disease, and can't have hypopharynx primaries due to higher complication risks.

Inclusion Criteria

I have been diagnosed with squamous cell carcinoma in my head or neck.

Agreement to use medically effective birth control for sexually active participants

Study-specific informed consent provided prior to study entry

Exclusion Criteria

I've had radiation in the same area as my current cancer.

I expect to need strong chemotherapy or several treatments.

I have a history of lupus or scleroderma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Patients undergo surgery per standard of care

Radiation

Patients receive hypofractionated radiotherapy of 50 Gy over 4 weeks

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Visits at 1 month, 3 months, 6 months, and 12 months post-therapy

What Are the Treatments Tested in This Trial?

Interventions

• Hypofractionated Postoperative Radiotherapy

Trial Overview The study is testing if a standard dose of radiation therapy can be safely given over a shorter period following surgery in patients with intermediate-risk head and neck cancer. This approach is called hypofractionated postoperative radiotherapy.

How Is the Trial Designed?

Group I: Hypofractionated Postoperative Radiotherapy (H-PORT) Experimental Treatment 1 Intervention

H-PORT of 50 Gy given over 4 weeks.

Who Is Running the Clinical Trial?

American College of Radiology

Lead Sponsor

Trials

24

Recruited

8,055,000+

RTOG Foundation, Inc.

Collaborator

Trials

7

Recruited

1,500+

RTOG Foundation

Collaborator

Trials

1

Recruited

20+

Published Research Related to This Trial

In a phase 1 study involving 12 patients with resected head and neck squamous cell carcinoma, moderately hypofractionated radiation therapy (RT) was found to be well tolerated, with no dose-limiting toxicities reported.

The study determined that a dose of 44.4 Gy in 12 fractions was the maximum tolerated, but 46.5 Gy in 15 fractions was recommended for further testing due to better tolerability and equivalent effectiveness, indicating a promising approach to reduce treatment time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HYPORT: Phase 1 Study of 3-Week Hypofractionated Postoperative Radiation Therapy for Head and Neck Squamous Cell Carcinoma. Moon, DH., Avkshtol, V., Vo, D., et al.[2023]

In a study of 100 patients with T1N0M0 squamous cell carcinoma of the larynx treated with hypofractionated radiotherapy, locoregional control rates were high at 92% at 2 years and 88% at 5 years, demonstrating the efficacy of this treatment approach.

The treatment resulted in excellent cause-specific survival rates of 99% at 2 years and 97% at 5 years, while also preserving voice function, making it a viable option compared to longer fractionation schedules.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome of T1N0M0 squamous cell carcinoma of the larynx treated with short-course radiotherapy to a total dose of 50 Gy in 16 fractions: the Birmingham experience. Cheah, NL., Lupton, S., Marshall, A., et al.[2022]

In a phase 2 trial involving 64 patients who underwent radical prostatectomy, postoperative hypofractionated radiation therapy (RT) to the prostate bed was found to be safe, with only 11.5% experiencing acute genitourinary (GU) grade ≥2 toxicity and 13.1% experiencing acute gastrointestinal (GI) grade ≥2 toxicity.

After a median follow-up of 16 months, the treatment showed promising outcomes with a 2-year biochemical failure-free survival rate of 95.1%, indicating its potential efficacy in preventing cancer recurrence, although further large-scale studies are needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated Radiation Therapy to the Prostate Bed With Intensity-Modulated Radiation Therapy (IMRT): A Phase 2 Trial. Leite, ETT., Ramos, CCA., Ribeiro, VAB., et al.[2021]

In a study of 56 patients with head and neck cancers treated with hypofractionated intensity modulated radiation therapy (H-IMRT), the two-year locoregional control rate was 87%, and the median overall survival was 46 months, indicating promising efficacy.

The treatment was well tolerated, with no severe grade 4 or 5 toxicities reported, and only 79% of patients experienced acute grade 2 or 3 toxicity, suggesting that H-IMRT is a safe option for patients with head and neck cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Limited Toxicity of Hypofractionated Intensity Modulated Radiation Therapy for Head and Neck Cancer. Mayo, ZS., Ilori, EO., Matia, B., et al.[2022]

In a study of 25 head and neck cancer patients treated with hypofractionated stereotactic radiotherapy (hSRT) using CyberKnife, there was a high response rate of 96%, with 18 patients achieving complete responses and 6 partial responses after a median follow-up of 28 months.

The study found that smaller planning target volumes (PTV ≤ 20 cm³) were associated with significantly better progression-free survival (92%) and overall survival (100%) compared to larger volumes, indicating that both the size of the treatment area and initial response to treatment are important predictors of patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated stereotactic radiotherapy using CyberKnife as a boost treatment for head and neck cancer, a multi-institutional survey: impact of planning target volume. Yamazaki, H., Ogita, M., Himei, K., et al.[2018]

The trial demonstrated that moderate hypofractionated radiotherapy (HYP-RT) combined with cisplatin (CDDP) is feasible for treating locally advanced head and neck cancer (LAHNC), with all 20 enrolled patients completing the treatment regimen.

Acute toxicity rates were manageable, with 95% of patients receiving at least 3 cycles of chemotherapy and only two instances of grade 4 toxicity, indicating that HYP-RT's safety profile is comparable to standard chemoradiation approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of concomitant cisplatin with hypofractionated radiotherapy for locally advanced head and neck squamous cell carcinoma. Jacinto, AA., Batalha Filho, ES., Viana, LS., et al.[2019]

Postoperative radiotherapy (RT) significantly reduces the risk of local-regional recurrence in patients with squamous cell carcinoma of the head and neck, particularly those with unfavorable pathologic features.

High-risk patients may benefit from more aggressive RT schedules and adjuvant cisplatin-based chemotherapy, which can improve survival rates and the probability of cure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative radiotherapy for squamous cell carcinoma of the head and neck. Mendenhall, WM., Hinerman, RW., Amdur, RJ., et al.[2019]

Hypofractionated stereotactic radiotherapy effectively delivers high doses to bone metastases while minimizing damage to surrounding healthy tissue, which can help with pain relief and improve local control of the cancer.

Studies indicate that this treatment approach has limited toxicity, even during re-irradiation, and may enhance long-term control of metastatic disease in patients with oligometastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hypofractionated stereotactic radiotherapy of bone metastases]. Pichon, B., Thillays, F., Bourgier, C., et al.[2018]

Hypofractionated radiotherapy is effective for early-stage head and neck cancers, allowing for shorter treatment times without increasing side effects, while advanced tumors require hyperfractionation for effective control.

The study highlights that the presence of cancer stem cells (CSCs) and the tumor's oxygen levels significantly influence the choice of radiotherapy schedule, indicating that more aggressive treatments may be necessary for tumors with low oxygenation and high CSC levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of hypofractionated radiotherapy in the management of head and neck cancer - a modelling approach. Marcu, LG., Marcu, D.[2020]

In a study of 393 breast cancer patients treated with moderately hypofractionated radiotherapy (HYPO-RT) over a median follow-up of 5.7 years, the overall survival rates were high at 96.0% at 5 years and 79.3% at 10 years, indicating the efficacy of this treatment.

HYPO-RT demonstrated excellent local control with only 4.3% local recurrences and low toxicity rates, with severe acute dermatitis occurring in just 0.9% of patients, highlighting its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated radiotherapy in breast cancer: a 10-year single institution experience. Najas, GF., Stuart, SR., Marta, GN., et al.[2022]

In a study of 447 patients with early-stage breast cancer, postoperative hypofractionated radiotherapy (MARA-1) showed a very low incidence of Grade 3 late skin toxicity (0.0%) compared to standard fractionated radiotherapy (1.5%), indicating it may be safer in terms of severe skin side effects.

However, patients receiving hypofractionated RT experienced a higher incidence of Grade 1 and 2 late subcutaneous toxicity, suggesting that while it may reduce severe skin reactions, it could lead to more mild side effects, highlighting the need for careful patient monitoring and potential adjustments in treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated radiotherapy after conservative surgery may increase low-intermediate grade late fibrosis in breast cancer patients. Digesù, C., Deodato, F., Macchia, G., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37380084/

Phase 1 Study of 3-Week Hypofractionated Postoperative ... Conclusions: Moderately hypofractionated RT delivered over 3 weeks is well tolerated in the short term in this phase 1 cohort of patients with ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1053429625000025

Hypofractionated Radiation Therapy in the Definitive ... Hypofractionated radiation in the definitive setting for HNSCCs has shown early safety and promise even using 2D techniques.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12228546/

Phase 1 Study of 3-Week Hypofractionated Postoperative ... Moderately hypofractionated RT delivered over 3 weeks is well tolerated in the short term in this phase 1 cohort of patients with head and neck ...

4. redjournal.org redjournal.org/article/S0360-3016(22)01243-3/abstract

HYPORT: A Phase I Study of Hypofractionated Post ... Moderately hypofractionated RT delivered over 3 weeks is well-tolerated in patients with HNSCC following surgical resection.

5. ar.iiarjournals.org ar.iiarjournals.org/content/42/4/1845

Limited Toxicity of Hypofractionated Intensity Modulated ... The primary outcomes were acute and late toxicity. Results: Two-year locoregional control was 87% and median overall survival was 46 months. There were no acute ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301623006004

Phase 1 Study of 3-Week Hypofractionated Postoperative ... Conclusions. Moderately hypofractionated RT delivered over 3 weeks is well tolerated in the short term in this phase 1 cohort of patients with head and neck ...

7. redjournal.org redjournal.org/article/S0360-3016(23)00600-4/abstract

HYPORT: Phase 1 Study of 3-Week Hypofractionated ... Conclusions. Moderately hypofractionated RT delivered over 3 weeks is well tolerated in the short term in this phase 1 cohort of patients with head and neck ...