Reduced-Dose Radiation Therapy for Head and Neck Cancer

Overseen By Danielle N. Margalit, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Dana-Farber Cancer Institute

Disqualifiers: Prior head and neck cancer, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

111 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study is studying lowering the standard dose of radiation and chemotherapy after surgery, to minimize the side effects and improve the quality of life.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment De_Intensified Postoperative Radiation Therapy for head and neck cancer?

Research suggests that reducing treatment intensity in selected patients with head and neck cancer may improve overall survival without increasing side effects. Additionally, combining chemotherapy with radiation therapy has shown improved survival in patients with advanced head and neck cancer. ^{1 2 3 4 5}

Is reduced-dose radiation therapy for head and neck cancer safe?

Research on deintensified radiation therapy for head and neck cancer, such as the AVOID trial, has focused on safety and effectiveness, indicating it is generally safe for humans. However, specific side effects and tolerance can vary, and it's important to discuss individual risks with a healthcare provider. ^{5 6 7 8 9}

How is De-Intensified Postoperative Radiation Therapy different from other treatments for head and neck cancer?

De-Intensified Postoperative Radiation Therapy is unique because it reduces the radiation dose to minimize side effects on the swallowing apparatus and salivary glands, which can improve quality of life for patients compared to standard high-dose radiation treatments. ^{5 10 11 12 13}

Research Team

Danielle N. Margalit, MD, MPH

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for adults who've had surgery for HPV-related squamous cell carcinoma of the throat, with a history of light or no smoking (≤20 pack-years), good performance status, and no prior head and neck cancer or radiation. They must have normal organ function and no serious illnesses that could affect study participation.

Inclusion Criteria

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

My cancer is a type of throat cancer that's p16 positive.

absolute neutrophil count ≥1,000/mcL

Exclusion Criteria

I am not pregnant or breastfeeding if I want to join this study.

I do not have any serious illnesses that would stop me from following the study's requirements.

I have had radiation therapy on my head or neck before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive reduced-dose radiation or observation based on risk level

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Quality of Life Assessment

Assessment of physical, social/family, emotional, and functional wellbeing

2 years

Treatment Details

Interventions

• De_Intensified Postoperative Radiation Therapy

Trial Overview The study tests whether a lower dose of postoperative radiation therapy can reduce side effects while still being effective against HPV-associated oropharyngeal squamous cell carcinoma. It aims to improve quality of life after treatment.

Participant Groups

Group I: Low Risk Experimental Treatment 1 Intervention

Observation without adjuvant therapy * Pathologic T0-2, N0-1 * Minimum of 15 lymph nodes retrieved on neck dissection per dissected side of the neck * Single positive lymph node up to 3cm * No extranodal extension * Clear margins * Undetectable postoperative circulating tumor HPV DNA

Group II: Intermediate Risk Experimental Treatment 1 Intervention

Reduced-dose radiation (46Gy) * Pathologic T0-2N0-2 and any one of the following features: * 2 or more positive lymph nodes * single node \>3cm * \<15 lymph nodes retrieved on neck dissection for each side of the neck * Positive lymph nodes in level IB, IV, or V -≤1mm extranodal extension * Positive lymph node(s) contralateral to the primary tumor * Close margins * Detectable postoperative circulating tumor HPV DNA

Group III: High Risk Experimental Treatment 1 Intervention

Postoperative radiation (60Gy) without chemotherapy * Pathologic T0-4N0-2 and any one of the following features: -\>1mm extranodal extension * Microscopic positive margins

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Findings from Research

The SCHARC protocol, which combines hyperfractionated radiation therapy with chemotherapy, showed a 3-year overall survival rate of 57% in 64 patients with advanced head and neck cancer, indicating its effectiveness in long-term disease control.

While the treatment resulted in significant acute toxicities, such as mucositis and skin toxicity, no patients died from complications, and maintaining a hemoglobin level above 10.5 g/dl was associated with better survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Split course hyperfractionated accelerated radio-chemotherapy (SCHARC) for patients with advanced head and neck cancer: influence of protocol deviations and hemoglobin on overall survival, a retrospective analysis. Stadler, P., Putnik, K., Kreimeyer, T., et al.[2019]

The biphasic accelerated radiotherapy regimen for postoperative treatment of advanced head and neck cancers was feasible, with 93% of the 29 enrolled patients completing the treatment without interruptions.

While most patients experienced mucositis, the acute toxicity was considered acceptable, with no severe Grade 5 reactions, indicating that this treatment approach could be safely implemented in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative radiotherapy for head and neck squamous cell carcinomas: feasibility of a biphasic accelerated treatment schedule. Sanguineti, G., Corvo', R., Vitale, V., et al.[2019]

Current treatments for locally advanced head and neck cancer are highly intense and can lead to significant acute toxicities, which may contribute to patient mortality despite improvements in locoregional control.

There is potential to improve overall survival by reducing treatment intensity for selected patients, especially given advancements in radiotherapy and understanding of survivorship factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimising the therapeutic ratio in head and neck cancer. Corry, J., Peters, LJ., Rischin, D.[2022]

Intensity-modulated radiation therapy (IMRT) for head and neck cancer improves tumor coverage while reducing damage to surrounding healthy tissues, making it a safer treatment option.

The use of altered fractionation techniques like SMART or SIB shows promise in enhancing treatment effectiveness, particularly for early-stage cancers (I and II) without chemotherapy, and for advanced stages (III and IV) when combined with chemotherapy, although further clinical studies are needed to establish definitive protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[IMRT and head and neck tumors: does differential fractionation have a role?]. Giraud, P., Servagi-Vernat, S.[2018]

Recent randomized trials have shown that adding high-dose cisplatin chemotherapy to postoperative radiotherapy significantly improves treatment efficacy for patients with locally or regionally advanced head and neck cancers, particularly those with poor prognostic features.

Patients with positive surgical margins or nodal extracapsular spread benefit the most from this combined treatment approach, establishing it as the new standard for managing resected poor-risk disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant therapy in patients with resected poor-risk head and neck cancer. Bernier, J., Vermorken, JB., Koch, WM.[2013]

In a phase 2 clinical trial involving 60 patients with HPV-associated oropharyngeal squamous cell carcinoma, a novel deintensified radiation therapy approach resulted in a remarkable 2-year local control rate of 98.3%, indicating high efficacy in preventing cancer recurrence after surgery.

The treatment was found to be safe, with only 3.3% of patients experiencing late soft tissue necrosis that resolved quickly, and no patients required feeding tubes during or after treatment, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 2 Trial of Alternative Volumes of Oropharyngeal Irradiation for De-intensification (AVOID): Omission of the Resected Primary Tumor Bed After Transoral Robotic Surgery for Human Papilloma Virus-Related Squamous Cell Carcinoma of the Oropharynx. Swisher-McClure, S., Lukens, JN., Aggarwal, C., et al.[2020]

In a study of 30 patients with locally advanced head and neck cancer, a treatment regimen of accelerated radiation therapy combined with chemotherapy resulted in a high incidence of acute mucositis, increasing from 33.3% in the first week to 93.3% by the end of the fifth week, but showed a decrease to 70% in the sixth week.

The treatment approach demonstrated a significant reduction in complications during the final weeks of therapy, suggesting that the combination of accelerated radiation and chemotherapy with celecoxib may improve tolerance and manage side effects effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concomitant boost chemoradiotherapy in locally advanced head and neck cancer: treatment tolerance and acute side effects. Majdaeen, M., Kazemian, A., Babaei, M., et al.[2015]

In a phase II trial involving 32 patients with advanced head and neck cancer, the aggressive combination of cisplatinum and paclitaxel with hyperfractionated-accelerated radiotherapy resulted in a 5-year overall survival rate of 48% and a disease-free survival rate of 43%.

While the treatment showed promising response rates, with 69% achieving a complete response, it was associated with significant acute toxicities, including high rates of grade 3 mucositis (71%) and erythema (28%), indicating the need for extensive supportive care during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of a simultaneous radiochemotherapy with cisplatinum and paclitaxel in combination with hyperfractionated-accelerated radiotherapy in locally advanced head and neck tumors. Kuhnt, T., Becker, A., Bloching, M., et al.[2022]

In a phase II study involving 94 patients with locally advanced unresectable head and neck carcinoma, the combination of weekly cisplatin and accelerated radiation therapy showed promising efficacy, with a median overall survival of 27 months and a 4-year survival rate of 41%.

The treatment was generally well-tolerated, with manageable toxicity; however, 85% of patients experienced grade III mucositis, and 50% had pharyngeal-oesophageal toxicity, indicating that while the regimen is effective, it does come with significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of concomitant boost radiation plus concurrent weekly cisplatin for locally advanced unresectable head and neck carcinomas. Medina, JA., Rueda, A., de Pasos, AS., et al.[2013]

In the DIREKHT trial involving 30 patients with head and neck cancer, de-intensified radiotherapy resulted in significantly smaller planning target volumes (PTVs), reducing from an average of 1166 mL in standard treatment plans to 662 mL in study plans.

The study also achieved significant dose reductions of over 10 Gy to critical areas such as the swallowing apparatus and contralateral salivary glands, indicating a potential for reduced side effects while maintaining treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose Reduction to the Swallowing Apparatus and the Salivary Glands by De-Intensification of Postoperative Radiotherapy in Patients with Head and Neck Cancer: First (Treatment Planning) Results of the Prospective Multicenter DIREKHT Trial. Haderlein, M., Speer, S., Ott, O., et al.[2020]

The HART-CN treatment, which combines intensified radiotherapy with chemotherapy, was feasible for patients with locally advanced HPV/p16-negative head and neck cancer, showing a 3-year overall survival rate of 74%.

While 67% of patients experienced severe acute toxicity such as dysphagia and mucositis, the long-term side effects were considered acceptable, with only a small percentage of patients suffering from severe late complications after 3 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DAHANCA 28: A phase I/II feasibility study of hyperfractionated, accelerated radiotherapy with concomitant cisplatin and nimorazole (HART-CN) for patients with locally advanced, HPV/p16-negative squamous cell carcinoma of the oropharynx, hypopharynx, larynx and oral cavity. Saksø, M., Jensen, K., Andersen, M., et al.[2021]

In a study of 70 patients with head and neck cancer, those receiving at least 60 Gy of radiation to the primary tumor and upper neck had an 80% chance of being disease-free after 2 years, compared to 53% for those receiving less than 60 Gy.

Patients who received more than 50 Gy to the lower neck had an 85% chance of being disease-free at 2 years, highlighting the importance of adequate radiation dosing in improving postoperative outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant postoperative external beam radiotherapy in head and neck cancer. Ampil, F., Datta, R., Shockley, W.[2019]

The standard treatment for locally advanced head-and-neck cancers now includes high-dose chemoradiation, specifically using concurrent radiotherapy and bolus cisplatin, based on evidence from two phase III studies involving multiple centers.

Future advancements in treatment should focus on improving irradiation techniques and combining radiotherapy with more effective cytotoxic drugs or targeted therapies to enhance patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adjuvant treatment of head and neck cancers: advances and challenges]. Bernier, J.[2011]

References

1. England pubmed.ncbi.nlm.nih.gov

Split course hyperfractionated accelerated radio-chemotherapy (SCHARC) for patients with advanced head and neck cancer: influence of protocol deviations and hemoglobin on overall survival, a retrospective analysis. [2019]

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

Postoperative radiotherapy for head and neck squamous cell carcinomas: feasibility of a biphasic accelerated treatment schedule. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Optimising the therapeutic ratio in head and neck cancer. [2022]

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

[IMRT and head and neck tumors: does differential fractionation have a role?]. [2018]

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

Adjuvant therapy in patients with resected poor-risk head and neck cancer. [2013]

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

A Phase 2 Trial of Alternative Volumes of Oropharyngeal Irradiation for De-intensification (AVOID): Omission of the Resected Primary Tumor Bed After Transoral Robotic Surgery for Human Papilloma Virus-Related Squamous Cell Carcinoma of the Oropharynx. [2020]

7. India pubmed.ncbi.nlm.nih.gov

Concomitant boost chemoradiotherapy in locally advanced head and neck cancer: treatment tolerance and acute side effects. [2015]

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

Phase II trial of a simultaneous radiochemotherapy with cisplatinum and paclitaxel in combination with hyperfractionated-accelerated radiotherapy in locally advanced head and neck tumors. [2022]

9. Ireland pubmed.ncbi.nlm.nih.gov

A phase II study of concomitant boost radiation plus concurrent weekly cisplatin for locally advanced unresectable head and neck carcinomas. [2013]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Dose Reduction to the Swallowing Apparatus and the Salivary Glands by De-Intensification of Postoperative Radiotherapy in Patients with Head and Neck Cancer: First (Treatment Planning) Results of the Prospective Multicenter DIREKHT Trial. [2020]

11. Ireland pubmed.ncbi.nlm.nih.gov

DAHANCA 28: A phase I/II feasibility study of hyperfractionated, accelerated radiotherapy with concomitant cisplatin and nimorazole (HART-CN) for patients with locally advanced, HPV/p16-negative squamous cell carcinoma of the oropharynx, hypopharynx, larynx and oral cavity. [2021]

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

Adjuvant postoperative external beam radiotherapy in head and neck cancer. [2019]

13. France pubmed.ncbi.nlm.nih.gov

[Adjuvant treatment of head and neck cancers: advances and challenges]. [2011]