Hypofractionated vs Conventional Radiotherapy for Laryngeal Cancer

(G-FORCE Trial)

Overseen By Sarah Neufeld

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: Investigational agents

Disqualifiers: Stage III/IV cancer, Arytenoid involvement, Prior chemotherapy, Synchronous primaries, others

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

Compensation: Varies

Number of Visits: 9

Duration: 5-29 fractions over 5-29 weeks

67 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot be on other investigational agents or have uncontrolled illnesses that might affect your participation.

What data supports the effectiveness of the treatment for laryngeal cancer?

Research shows that hypofractionated radiotherapy, which involves giving higher doses of radiation over fewer sessions, has a local control rate of 85-95% for early-stage laryngeal cancer. Additionally, intensity-modulated radiotherapy (IMRT) is associated with similar survival rates as traditional methods but may reduce side effects, making it a promising option for treatment. ^{1 2 3 4 5}

Is hypofractionated radiotherapy safe for treating laryngeal cancer?

Research shows that hypofractionated radiotherapy, including techniques like SBRT and IMRT, is generally safe for treating laryngeal cancer, with most side effects being mild to moderate. Some studies report higher mild toxicity compared to conventional treatment, but severe side effects are not significantly different. ^{1 2 3 4 6}

How does the treatment of hypofractionated vs conventional radiotherapy for laryngeal cancer differ from other treatments?

This treatment is unique because it uses hypofractionated radiotherapy, which involves giving higher doses of radiation in fewer sessions compared to conventional methods. This approach, including techniques like IMRT and SABR, aims to maintain effective cancer control while potentially reducing the overall treatment time and minimizing long-term side effects. ^{1 4 7 8 9}

What is the purpose of this trial?

To compare the acute tolerance of highly conformal hypofractionated versus conventional radiotherapy.

Research Team

David Sher, MD

Principal Investigator

University of Texas Southwestern Medical Center

Eligibility Criteria

This trial is for adults with early-stage laryngeal cancer who haven't had certain surgeries or treatments. They must be able to perform daily activities (ECOG 0-2) and agree to use contraception if of childbearing potential. Excluded are those with advanced disease, prior radiation in the area, heavy smokers, or uncontrolled illnesses.

Inclusion Criteria

I have a confirmed diagnosis of squamous cell cancer in my vocal cords.

My larynx cancer is in an early stage and hasn't spread according to scans.

I can take care of myself and perform daily activities.

Exclusion Criteria

Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

Subjects may not be receiving any other investigational agents.

I have more than one primary cancer in my head or neck.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive either highly conformal hypofractionated radiotherapy or conventional radiotherapy

5-29 fractions over 5-29 weeks

5-29 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

3 visits (in-person)

Treatment Details

Interventions

• IMRT
• LT-SABR

Trial Overview The study compares two types of radiotherapy: LT-SABR (a precise high-dose technique) versus IMRT (a standard method). It aims to see which one patients tolerate better during treatment for laryngeal cancer.

Participant Groups

Group I: Highly conformal hypofractionated radiotherapy Experimental Treatment 1 Intervention

LT-SABR 42.5 Gy in 5 fractions Low-risk: twice/week Moderate-risk: weekly

Group II: Conventional radiotherapy Experimental Treatment 1 Intervention

Conventional Radiotherapy 63 Gy in 28 fractions (T1) 65.25 Gy in 29 fractions (T2)

IMRT is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Intensity-Modulated Radiation Therapy for:

• Head and neck squamous cell carcinoma (HNSCC)
• Prostate cancer
• Breast cancer
• Lung cancer
• Brain tumors

Approved in European Union as Intensity-Modulated Radiation Therapy for:

• Head and neck squamous cell carcinoma (HNSCC)
• Prostate cancer
• Breast cancer
• Lung cancer
• Brain tumors

Approved in Canada as Intensity-Modulated Radiation Therapy for:

• Head and neck squamous cell carcinoma (HNSCC)
• Prostate cancer
• Breast cancer
• Lung cancer
• Brain tumors

Approved in Japan as Intensity-Modulated Radiation Therapy for:

• Head and neck squamous cell carcinoma (HNSCC)
• Prostate cancer
• Breast cancer
• Lung cancer
• Brain tumors

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Findings from Research

Hypofractionated stereotactic body radiation therapy (SBRT) for early-stage glottic laryngeal cancer is safe and feasible, with a significant reduction in treatment duration from 15 to 5 fractions while maintaining acceptable toxicity levels.

After a median follow-up of 13.4 months, the treatment showed an 82% local disease-free survival rate and a 100% overall survival rate, indicating promising efficacy comparable to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SBRT for early-stage glottic larynx cancer-Initial clinical outcomes from a phase I clinical trial. Schwartz, DL., Sosa, A., Chun, SG., et al.[2018]

In a study of 67 patients with locally advanced head and neck cancer, intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) resulted in significantly less toxicity compared to conventional 3D-conformal radiotherapy, particularly in terms of dysphagia, dermatitis, xerostomia, fibrosis, and lymphedema.

After a median follow-up of 31 months, the locoregional control rates were comparable, with 73% for IMRT-SIB and 78% for 3D-RT, indicating that IMRT-SIB is a feasible treatment option that reduces side effects without compromising effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moderately Hypofractionated Intensity-modulated Radiotherapy With a Simultaneous Integrated Boost for Locally Advanced Head and Neck Cancer - Do Modern Techniques Fulfil Their Promise? Wichmann, J., Durisin, M., Hermann, RM., et al.[2021]

A study of 116 patients with squamous cell carcinomas of the larynx and hypopharynx treated with intensity-modulated radiation therapy with simultaneous integrated boost (IMRT-SIB) showed a high overall survival rate of 87% at two years and 82% at three years, indicating its efficacy in managing advanced stage disease.

IMRT-SIB was associated with a lower risk of recurrence and reduced acute toxicity, such as mucositis, compared to traditional radiation therapies, making it a safer option for patients undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome and toxicity of intensity-modulated radiotherapy with simultaneous integrated boost in patients with pharyngo-laryngeal cancer. Fondevilla Soler, A., López-Guerra, JL., García Fernández, A., et al.[2020]

Hypofractionated radiotherapy for early-stage squamous cell carcinoma of the glottic larynx shows promising local control rates between 85% and 95%, indicating its efficacy as a treatment option.

While acute laryngeal toxicity is higher with moderate hypofractionation compared to conventional treatment, severe toxicity rates remain similar, suggesting a manageable safety profile for this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Radiotherapy for patients with early-stage glottic squamous cell carcinoma of the larynx: Interest of hypofractionation?] Tonneau, M., Matta, R., Lals, S., et al.[2021]

In a study of 4,319 patients with early stage squamous cell carcinoma of the glottic larynx, intensity-modulated radiotherapy (IMRT) showed similar overall survival rates compared to traditional 3D conformal radiotherapy (3DCRT), indicating that IMRT can be a safe alternative without compromising patient outcomes.

Patients receiving slight hypofractionation (a different radiation dose schedule) had improved survival compared to those on conventional fractionation, suggesting that adjusting treatment schedules may enhance efficacy in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patterns of Care and Outcomes of Intensity-Modulated Radiotherapy and 3D Conformal Radiotherapy for Early Stage Glottic Cancer: A National Cancer Database Analysis. Korpics, MC., Turchan, WT., Rooney, MK., et al.[2020]

In a study involving 60 patients with advanced squamous cell cancer of the larynx/hypopharynx, dose-escalated intensity-modulated radiotherapy (IMRT) at a higher dose (DL2) resulted in improved 5-year local control rates (75%) and overall survival (67.6%) compared to a lower dose (DL1) which had 68% local control and 61.9% overall survival.

The treatment demonstrated a low incidence of severe toxicities, with only a few cases of benign pharyngeal strictures reported, indicating that the higher dose of IMRT can be safely administered while achieving better treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final long-term results of a phase I/II study of dose-escalated intensity-modulated radiotherapy for locally advanced laryngo-hypopharyngeal cancers. Gujral, DM., Miah, AB., Bodla, S., et al.[2022]

This phase 1 study of hypofractionated radiation therapy for early-stage glottic larynx squamous cell carcinoma showed promising results with a 5-fraction stereotactic ablative radiation therapy (SABR) regimen, demonstrating good tolerability and excellent long-term voice quality outcomes.

Despite some patients experiencing dose-limiting toxicities, such as laryngeal edema and dysphagia, the overall efficacy was encouraging, with only 5 local recurrences among 29 patients over a median follow-up of 39.2 months, suggesting that this treatment approach is worth further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 Fractional Dose-Escalation Study of Equipotent Stereotactic Radiation Therapy Regimens for Early-Stage Glottic Larynx Cancer. Sher, DJ., Timmerman, RD., Nedzi, L., et al.[2020]

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 study of 40 patients with glottic cancer, hypofractionated radiotherapy (3D-HFRT) was found to be as effective as conventional radiotherapy (3D-CRT) in terms of local control of the tumor, with a 100% control rate for hypofractionated treatment compared to 96% for conventional treatment after 3 years.

Both treatment methods resulted in similar levels of voice quality recovery and minimal toxicity, suggesting that hypofractionated radiotherapy is a well-tolerated alternative for early glottic cancer without compromising oncological outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of conventional or hypofractionated radiotherapy on voice quality and oncological outcome in patients with early glottic cancer. Di Nicola, L., Gravina, GL., Marampon, F., et al.[2019]

References

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

SBRT for early-stage glottic larynx cancer-Initial clinical outcomes from a phase I clinical trial. [2018]

2. Greece pubmed.ncbi.nlm.nih.gov

Moderately Hypofractionated Intensity-modulated Radiotherapy With a Simultaneous Integrated Boost for Locally Advanced Head and Neck Cancer - Do Modern Techniques Fulfil Their Promise? [2021]

3. Italy pubmed.ncbi.nlm.nih.gov

Outcome and toxicity of intensity-modulated radiotherapy with simultaneous integrated boost in patients with pharyngo-laryngeal cancer. [2020]

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

[Radiotherapy for patients with early-stage glottic squamous cell carcinoma of the larynx: Interest of hypofractionation?] [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Patterns of Care and Outcomes of Intensity-Modulated Radiotherapy and 3D Conformal Radiotherapy for Early Stage Glottic Cancer: A National Cancer Database Analysis. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Final long-term results of a phase I/II study of dose-escalated intensity-modulated radiotherapy for locally advanced laryngo-hypopharyngeal cancers. [2022]

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

Phase 1 Fractional Dose-Escalation Study of Equipotent Stereotactic Radiation Therapy Regimens for Early-Stage Glottic Larynx Cancer. [2020]

8. 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]

9. Greece pubmed.ncbi.nlm.nih.gov

The impact of conventional or hypofractionated radiotherapy on voice quality and oncological outcome in patients with early glottic cancer. [2019]