Radiotherapy for Throat Cancer

(SAVER Trial)

Recruiting at 5 trial locations

Overseen By Matthew Witek, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Maryland, Baltimore

Disqualifiers: Oral cancer, Metastasis, Prior chemotherapy, others

Stay on Your Current Meds You can continue your current medications while participating

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

52 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new radiation therapy method for patients with a specific type of throat cancer. It aims to reduce side effects by focusing radiation only on high-risk areas, potentially lowering issues like dry mouth and swallowing difficulties.

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 Intensity modulated radiotherapy (IMRT)/volumetric modulated arc therapy (VMAT), Pencil beam proton therapy (PBPT) for throat cancer?

Research shows that VMAT can improve patient comfort by reducing treatment time compared to traditional methods, and PBPT can effectively target cancer while sparing nearby healthy organs, potentially reducing side effects. These treatments have shown promise in managing head and neck cancers, which include throat cancer. ^{1 2 3 4 5}

Is radiotherapy for throat cancer safe for humans?

Research shows that proton therapy, a type of radiotherapy, can reduce the dose to healthy tissues compared to traditional methods, potentially leading to fewer side effects. Studies on head and neck cancers indicate that proton therapy may result in lower rates of acute side effects like nausea and mouth dryness compared to other radiation therapies. ^{6 7 8 9 10}

How does the treatment of IMRT/VMAT and PBPT for throat cancer differ from other treatments?

This treatment is unique because it combines advanced radiotherapy techniques like IMRT/VMAT, which offer precise targeting and shorter treatment times, with PBPT, which can reduce radiation exposure to nearby healthy tissues. This combination aims to improve patient comfort and minimize side effects compared to traditional radiation therapies. ^{1 2 3 4 11}

Research Team

Matthew E. Witek

Principal Investigator

University of Maryland/Maryland Proton Treatment Center

Eligibility Criteria

This trial is for adults with p16 positive oropharyngeal squamous cell carcinoma needing radiotherapy. They must have a good performance status, no prior invasive malignancies within 3 years (except skin cancer), and agree to use contraception if applicable. Pregnant/nursing individuals, those with certain head/neck surgeries, previous chemotherapy/radiotherapy for the study cancer, or evidence of contralateral nodal disease are excluded.

Inclusion Criteria

Does the patient require elective contralateral radiotherapy in the definitive or adjuvant setting (i.e. base of tongue primary or tonsil with base of tongue invasion, soft palate invasion, or medialized as defined by > 1/3 of the distance from the tonsil to the midline of the soft palate?

Was the patient's Zubrod Performance Status 0-1 within 30 days prior to registration?

Does the patient have clinical stage T1-4, N0, N1 or N3, and M0 disease (AJCC 8th edition) as defined by physical examination and appropriate imaging (PET/CT preferred, CT neck with IV contrast with CT chest without contrast as recommended alternative to PET/CT)?

Exclusion Criteria

Does the patient have a carcinoma of the neck of unknown primary origin?

Does the patient have prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years?

Did the patient have prior surgery of the head and neck excluding superficial removal of cutaneous skin malignancies?

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiotherapy Treatment

Participants receive reduced contralateral elective nodal volume treatment via IMRT/VMAT or PBPT

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on nodal failure, PEG-tube rate, xerostomia, and dysphagia

2 years

Treatment Details

Interventions

• Intensity modulated radiotherapy (IMRT)/volumetric modulated arc therapy (VMAT)
• Pencil beam proton therapy (PBPT)

Trial Overview The trial tests whether reducing radiation treatment volumes on one side of the neck can prevent cancer recurrence in patients undergoing definitive or adjuvant radiotherapy. It compares Intensity Modulated Radiotherapy (IMRT)/Volumetric Modulated Arc Therapy (VMAT) against Pencil Beam Proton Therapy (PBPT).

Participant Groups

Group I: Reduced C/L elective nodal volume Experimental Treatment 1 Intervention

All patients will receive the reduced C/L elective nodal volume as described. Treatment will be delivered via IMRT/VMAT or PBPT.

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Findings from Research

Volumetric Modulated Arc Therapy (VMAT) significantly reduces radiation exposure to critical organs, such as the parotid glands and oral cavity, compared to Intensity-Modulated Radiation Therapy (IMRT), with average doses decreasing from 27.2 Gy to 25.0 Gy and from 39.4 Gy to 36.7 Gy, respectively.

VMAT also offers a substantial reduction in treatment delivery time, averaging 5:54 minutes compared to 13:15 minutes for IMRT, enhancing patient comfort and potentially minimizing movement during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-institutional comparison of volumetric modulated arc therapy vs. intensity-modulated radiation therapy for head-and-neck cancer: a planning study. Holt, A., Van Gestel, D., Arends, MP., et al.[2022]

In a study of 385 head and neck cancer patients treated with advanced radiotherapy techniques (IMRT/VMAT) over a median follow-up of 6.4 years, locoregional control rates were high, with 2- and 5-year rates of 78.2% and 74.2%, respectively, indicating effective treatment delivery.

The study found very few recurrences outside the high-dose treatment areas, suggesting that target volume definition and treatment delivery were accurate, which is crucial for improving patient outcomes in future research on dose escalation or proton therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrence Patterns After IMRT/VMAT in Head and Neck Cancer. Bollen, H., van der Veen, J., Laenen, A., et al.[2022]

Intensity modulated proton therapy (IMPT) shows significant dosimetric advantages over traditional intensity modulated radiation therapy (IMRT) for head and neck cancers, particularly in sparing nearby organs like the larynx and salivary glands.

Clinical evidence suggests that IMPT can reduce treatment-related toxicities, such as the need for feeding tubes, indicating its potential benefits in improving patient quality of life during and after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity modulated proton therapy (IMPT) - The future of IMRT for head and neck cancer. Moreno, AC., Frank, SJ., Garden, AS., et al.[2020]

Intensity modulated proton beam therapy (IMPT) significantly reduces the average radiation dose to tooth-bearing regions in head and neck cancer patients compared to photon-based volumetric modulated arc therapy (VMAT), indicating a safer option for preserving dental health during treatment.

In a study of 121 patients, factors such as oral cavity tumors and advanced T3-T4 tumors were identified as risk factors for receiving a cumulative radiation dose of ≥40 Gy to tooth-bearing areas, which is critical for determining the need for prophylactic dental extractions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Planned dose of intensity modulated proton beam therapy versus volumetric modulated arch therapy to tooth-bearing regions. Alberga, JM., Meijer, J., Raghoebar, GM., et al.[2023]

In a study of 205 patients with advanced-stage oropharynx cancer, proton beam therapy (PBT) was found to significantly reduce the probability of treatment-related complications, such as severe dysphagia and xerostomia, compared to intensity-modulated radiation therapy (IMRT).

The normal tissue complication probability (NTCP) models indicated that PBT resulted in lower predicted toxicity rates at 6 months post-treatment, highlighting its potential as a safer option for patients undergoing radiation therapy for oropharyngeal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Model-Based Approach to Predict Short-Term Toxicity Benefits With Proton Therapy for Oropharyngeal Cancer. Rwigema, JM., Langendijk, JA., Paul van der Laan, H., et al.[2019]

Intensity-modulated proton therapy (IMPT) for oropharyngeal carcinoma shows a potential reduction in severe weight loss and feeding tube dependency compared to intensity-modulated radiotherapy (IMRT), based on a study of 150 matched patients with a median follow-up of 32 months.

Despite these benefits, there were no significant differences in overall survival or progression-free survival between IMPT and IMRT, indicating that IMPT does not compromise treatment effectiveness while potentially improving quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated proton beam therapy (IMPT) versus intensity-modulated photon therapy (IMRT) for patients with oropharynx cancer - A case matched analysis. Blanchard, P., Garden, AS., Gunn, GB., et al.[2022]

References

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

Multi-institutional comparison of volumetric modulated arc therapy vs. intensity-modulated radiation therapy for head-and-neck cancer: a planning study. [2022]

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

Proton Beam Therapy for Locally Advanced Head and Neck Tumors: An Analysis of Dosimetric and Clinical Outcomes. [2022]

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

Ways to unravel the clinical potential of carbon ions for head and neck cancer reirradiation: dosimetric comparison and local failure pattern analysis as part of the prospective randomized CARE trial. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Recurrence Patterns After IMRT/VMAT in Head and Neck Cancer. [2022]

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

Intensity modulated proton therapy (IMPT) - The future of IMRT for head and neck cancer. [2020]

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

Planned dose of intensity modulated proton beam therapy versus volumetric modulated arch therapy to tooth-bearing regions. [2023]

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

Minimal acute toxicity from proton beam therapy for major salivary gland cancer. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Is there room for combined modality treatments? Dosimetric comparison of boost strategies for advanced head and neck and prostate cancer. [2021]

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

Spot-scanning beam proton therapy vs intensity-modulated radiation therapy for ipsilateral head and neck malignancies: a treatment planning comparison. [2022]

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

A Model-Based Approach to Predict Short-Term Toxicity Benefits With Proton Therapy for Oropharyngeal Cancer. [2019]

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

Intensity-modulated proton beam therapy (IMPT) versus intensity-modulated photon therapy (IMRT) for patients with oropharynx cancer - A case matched analysis. [2022]