Radiotherapy + Radiopharmaceutical Therapy for Thyroid Cancer

Overseen by Harry Quon, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Disqualifiers: Pregnancy, Breastfeeding, CNS metastases, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests a combination of radioactive iodine and targeted radiation therapy for thyroid cancer that has spread and cannot be fully removed by surgery. The goal is to deliver higher doses of radiation directly to the cancer cells, making the treatment more effective. Radioactive iodine therapy has been used for several decades to treat thyroid cancer by leveraging the ability of thyroid cells to uptake iodine.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, you must have adequately recovered from any prior chemotherapy, and any toxicities from previous therapies should have improved to a certain level. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the treatment Radiotherapy + Radiopharmaceutical Therapy for Thyroid Cancer?

Research shows that combining external beam radiotherapy (EBRT) and radioactive iodine (RAI) can be beneficial for certain thyroid cancer patients, especially those with high-risk features or residual disease after surgery. EBRT has been found to improve local control and reduce relapse rates in selected patients, while RAI is commonly used post-surgery to target remaining cancer cells. ^{1 2 3 4 5}

What safety data exists for radiotherapy and radiopharmaceutical therapy in thyroid cancer treatment?

Radioactive iodine (RAI) treatment can cause short-term side effects like nausea, vomiting, loss of taste, and salivary gland swelling. Long-term risks include dry mouth, mouth pain, dental issues, lung problems, tear duct blockage, and the possibility of developing other cancers. External beam radiotherapy (EBRT) safety data is less clear, but it is used in certain thyroid cancer cases. ^{1 5 6 7 8}

How is the combination of radiotherapy and radiopharmaceutical therapy unique for treating thyroid cancer?

This treatment combines external beam radiotherapy (XRT) and radioactive iodine (RAI) to target thyroid cancer more effectively, especially in cases where the cancer is advanced or has recurred. It is unique because it uses both radiation from outside the body and a radioactive substance taken internally to attack cancer cells, potentially improving outcomes for patients with high-risk or residual disease. ^{1 2 5 9 10}

Research Team

Harry Quon, MD

Principal Investigator

Johns Hopkins, School of Medicine, Radiation Oncology

Eligibility Criteria

This trial is for adults aged 18-85 with well-differentiated thyroid cancer that's spread and can't be fully removed by surgery. They should have a life expectancy of at least 8 weeks, adequate organ function, and a Karnofsky performance status over 50%. Pregnant or breastfeeding individuals, those recently exposed to iodinated contrast, or sexually active premenopausal patients not using contraception are excluded.

Inclusion Criteria

I have recovered from my last chemotherapy with mild or no side effects.

I am able to care for myself but cannot do normal activities or work.

My thyroid cancer has spread to my neck and/or other parts of my body and cannot be fully removed by surgery.

Exclusion Criteria

I have advanced brain metastases or critical lesions in my hip or spine that make certain treatments risky.

Pregnancy or breastfeeding

I have not been exposed to iodinated contrast in the last 6 weeks.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive combined radioactive iodine (RAI, 131-I) and external beam radiotherapy (XRT) to optimize the radiation dose for treating well-differentiated thyroid cancers

2 weeks

Multiple visits for radiotherapy sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment, with primary focus on safety as defined by the incidence of maximum grade 3 or greater NCI CTCAE toxicity

4 weeks

1-2 visits (in-person)

Efficacy Evaluation

Efficacy of the treatment is evaluated at 6 months using RECIST criteria, SPECT imaging, and changes in serum thyroglobulin levels

6 months

Treatment Details

Interventions

• External Beam Radiotherapy (XRT) (Radiation)
• Radioactive Iodine (RAI) (Radiopharmaceutical Therapy)

Trial Overview The study tests combining external beam radiation (XRT) with radioactive iodine (RAI) treatment in patients with metastatic thyroid cancer. The aim is to safely deliver higher tumor radiation doses through precise dosimetric planning. Researchers will monitor safety based on severe toxicity incidence during and after treatment.

Participant Groups

Group I: High-risk thyroid cancer patients Experimental Treatment 1 Intervention

All study patients will have histologically confirmed recurrence of thyroid cancer that is incompletely responsive to initial surgery.

External Beam Radiotherapy (XRT) is already approved in Canada, Japan, China, Switzerland for the following indications:

Approved in Canada as External Beam Radiotherapy for:

• Thyroid cancer
• Breast cancer
• Lung cancer
• Prostate cancer
• Brain tumors

Approved in Japan as External Beam Radiotherapy for:

• Thyroid cancer
• Breast cancer
• Lung cancer
• Prostate cancer
• Brain tumors

Approved in China as External Beam Radiotherapy for:

• Thyroid cancer
• Breast cancer
• Lung cancer
• Prostate cancer
• Brain tumors

Approved in Switzerland as External Beam Radiotherapy for:

• Thyroid cancer
• Breast cancer
• Lung cancer
• Prostate cancer
• Brain tumors

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Dr. William G. Nelson

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Director since 1992

MD, PhD

Dr. Elizabeth Jaffee

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Chief Medical Officer since 2023

MD

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

Radioactive iodine (RAI) is an important adjuvant therapy for differentiated thyroid cancer, providing significant benefits when used in properly selected patients.

External beam radiation therapy (EBRT) enhances locoregional control and offers palliative effects for high-risk patients, although recommendations for both therapies are primarily based on retrospective studies due to the lack of prospective randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A risk-adapted approach to the use of radioactive iodine and external beam radiation in the treatment of well-differentiated thyroid cancer. Tuttle, RM., Rondeau, G., Lee, NY.[2017]

Patients with well-differentiated thyroid carcinoma who received external beam radiotherapy (XRT) reported significant declines in quality of life, particularly in chewing, swallowing, and appetite, as well as increased pain compared to those treated with total thyroidectomy (TT) or TT with radioactive iodine (RAI).

The study found that while both RAI and XRT negatively impacted quality of life compared to TT alone, XRT led to additional morbidity, highlighting the need for careful consideration of treatment options in managing advanced thyroid cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of life impact of external beam radiotherapy for advanced thyroid carcinoma. Gal, TJ., Streeter, M., Burris, J., et al.[2019]

A retrospective review of 1300 patients with papillary thyroid carcinoma (PTC) suggests that postoperative radioactive iodine (RAI) treatment is recommended for patients with pT2-pT4 and pN0-pN1b classifications, while external beam radiotherapy (EBRT) is advised for those with more aggressive features such as gross residual disease or positive margins.

The study highlights the potential benefits of EBRT in select high-risk patients with PTC, indicating that while there is variability in treatment recommendations across different centers, EBRT can add value to the management of PTC in specific cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of external beam radiotherapy in the treatment of papillary thyroid cancer. Lee, N., Tuttle, M.[2022]

External-beam radiation therapy (EBRT) can effectively improve local control in differentiated thyroid cancer, especially in patients with gross residual disease after surgery, as indicated by retrospective studies.

EBRT is particularly beneficial for patients over 45 years old with a high risk of relapse, as it can enhance the local relapse-free rate and is safe with acceptable acute toxicity and rare serious long-term complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

External-beam radiation therapy in the treatment of differentiated thyroid cancer. Brierley, JD., Tsang, RW.[2019]

In a study of 36 patients with differentiated thyroid cancer, external-beam radiotherapy (EBRT) doses greater than 50 Gy significantly improved control rates of metastatic or recurrent lesions, achieving a 100% control rate for this dosage group.

Adding radioactive iodine therapy (RAIT) after EBRT resulted in a much higher two-year control rate of 89% compared to 45% for those who did not receive RAIT, indicating that this combination therapy can enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment intensity and control rates in combining external-beam radiotherapy and radioactive iodine therapy for metastatic or recurrent differentiated thyroid cancer. Makita, K., Hamamoto, Y., Tsuruoka, S., et al.[2020]

Radioactive iodine (RAI) therapy, used since 1946 to treat thyroid cancer, effectively ablates residual thyroid tissue and treats metastases, but it carries both acute and long-term risks.

Common acute side effects include nausea, loss of taste, and salivary gland swelling, while long-term complications can involve chronic mouth pain, dental issues, and an increased risk of second cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications of radioactive iodine treatment of thyroid carcinoma. Lee, SL.[2019]

In a study of 49 patients with locally advanced iodine refractory-differentiated thyroid cancer, postoperative external beam radiotherapy (EBRT) significantly improved locoregional control (LRC) and overall survival (OS), especially in patients with microscopic residual disease (R1) compared to macroscopic residual disease (R2).

The 5-year LRC rate was 84.3% for R1 and 44.9% for R2, while the 5-year OS rate was 72.1% for R1 and 33.1% for R2, indicating that EBRT is effective and has manageable side effects, primarily limited to mild acute toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative external beam radiotherapy for locoregional control in iodine refractory differentiated thyroid cancer. Groen, AH., van Dijk, D., Sluiter, W., et al.[2022]

In a study of 41 patients treated with external beam radiotherapy (EBRT) for differentiated thyroid cancer, the most common reasons for treatment included macroscopic residual disease (56%) and microscopic residual disease (25%).

The study suggests a potential dose-response relationship, as patients receiving higher doses of EBRT (>54 Gy) had lower local recurrence rates (18% recurrence) compared to those receiving lower doses (<50 Gy with 63% recurrence), indicating that higher doses may improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

External beam radiotherapy in the management of differentiated thyroid cancer. Ford, D., Giridharan, S., McConkey, C., et al.[2019]

In a study of 729 patients with differentiated thyroid cancer, radioactive iodine (RAI) treatment significantly improved the local-regional relapse-free rate (LRFR), but did not show a benefit for low-risk patients under 45 years old.

External beam radiotherapy (RT) provided a significant survival advantage for high-risk patients over 60 years old, improving both cause-specific survival (CSS) and LRFR compared to those who did not receive RT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic factors and the effect of treatment with radioactive iodine and external beam radiation on patients with differentiated thyroid cancer seen at a single institution over 40 years. Brierley, J., Tsang, R., Panzarella, T., et al.[2022]

External beam radiotherapy (EBRT) is established as an effective adjuvant treatment for anaplastic thyroid cancer, especially when combined with taxanes, enhancing treatment outcomes.

Recent evidence supports the use of EBRT in high-risk differentiated thyroid cancer, aligning with recommendations from major thyroid associations, while advancements in radiation delivery techniques promise improved efficacy and reduced toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on external beam radiation therapy in thyroid cancer. Brierley, JD.[2011]

References

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

A risk-adapted approach to the use of radioactive iodine and external beam radiation in the treatment of well-differentiated thyroid cancer. [2017]

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

Quality of life impact of external beam radiotherapy for advanced thyroid carcinoma. [2019]

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

The role of external beam radiotherapy in the treatment of papillary thyroid cancer. [2022]

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

External-beam radiation therapy in the treatment of differentiated thyroid cancer. [2019]

5. Japan pubmed.ncbi.nlm.nih.gov

Treatment intensity and control rates in combining external-beam radiotherapy and radioactive iodine therapy for metastatic or recurrent differentiated thyroid cancer. [2020]

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

Complications of radioactive iodine treatment of thyroid carcinoma. [2019]

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

Postoperative external beam radiotherapy for locoregional control in iodine refractory differentiated thyroid cancer. [2022]

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

External beam radiotherapy in the management of differentiated thyroid cancer. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Prognostic factors and the effect of treatment with radioactive iodine and external beam radiation on patients with differentiated thyroid cancer seen at a single institution over 40 years. [2022]

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

Update on external beam radiation therapy in thyroid cancer. [2011]