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

15 Participants Needed

Trial Summary

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 data supports the effectiveness of the treatment Hypofractionated Postoperative Radiotherapy for head and neck cancer?

Research suggests that postoperative radiotherapy (RT) can reduce the risk of cancer returning in patients with head and neck squamous cell carcinoma, especially those at high risk. Hypofractionated RT, which involves fewer but higher doses of radiation, is being explored for its potential to shorten treatment time while maintaining effectiveness. ^{1 2 3 4 5}

Is hypofractionated radiation therapy generally safe for humans?

Research shows that hypofractionated radiation therapy, which involves giving higher doses of radiation over a shorter period, is generally safe for humans. Studies in head and neck, prostate, and breast cancer have shown limited toxicity, although some increased risk of late side effects like fibrosis (thickening and scarring of tissue) has been noted in breast cancer patients. ^{1 6 7 8 9}

How is the shortened radiation therapy treatment for head and neck cancer different from other treatments?

This treatment is unique because it uses a shorter, more intense schedule of radiation therapy, known as hypofractionation, which reduces the overall treatment time compared to traditional methods. This approach can lower costs and lessen the treatment burden on patients while maintaining similar outcomes. ^{1 2 3 10 11}

What is the purpose of this trial?

This phase I trial is looking to determine if hypofractionated radiation therapy can be given safely after surgery for intermediate-risk head and neck cancer.

Research Team

Etta Pisano, MD

Principal Investigator

American College of Radiology

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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 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]

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 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 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]

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]

References

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

HYPORT: Phase 1 Study of 3-Week Hypofractionated Postoperative Radiation Therapy for Head and Neck Squamous Cell Carcinoma. [2023]

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

Postoperative radiotherapy for squamous cell carcinoma of the head and neck. [2019]

3. Greece 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. [2018]

4. France pubmed.ncbi.nlm.nih.gov

[Hypofractionated stereotactic radiotherapy of bone metastases]. [2018]

5. England pubmed.ncbi.nlm.nih.gov

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

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

Hypofractionated Radiation Therapy to the Prostate Bed With Intensity-Modulated Radiation Therapy (IMRT): A Phase 2 Trial. [2021]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Hypofractionated radiotherapy after conservative surgery may increase low-intermediate grade late fibrosis in breast cancer patients. [2022]

8. Greece pubmed.ncbi.nlm.nih.gov

Limited Toxicity of Hypofractionated Intensity Modulated Radiation Therapy for Head and Neck Cancer. [2022]

9. Poland pubmed.ncbi.nlm.nih.gov

Hypofractionated radiotherapy in breast cancer: a 10-year single institution experience. [2022]

10. England 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. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Feasibility of concomitant cisplatin with hypofractionated radiotherapy for locally advanced head and neck squamous cell carcinoma. [2019]