Proton Beam Therapy vs. IMRT for Esophageal Cancer

Not currently recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Pregnancy, Breastfeeding, Uncontrolled cardiac, others

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: 13

Duration: 5.5 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of two types of radiation therapy for esophageal cancer. It compares proton-beam therapy (PBT), a newer method designed to reduce radiation exposure to healthy tissues, with the more established intensity modulated radiation therapy (IMRT). The goal is to determine which option is safer and more effective when combined with chemotherapy. Individuals diagnosed with esophageal cancer, including those whose cancer might be surgically removable, may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for the trial?

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

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study showed that proton beam therapy (PBT) holds promise for patients with esophageal cancer, linking it to fewer side effects than traditional photon radiation, particularly in reducing heart and lung issues. Another study found that PBT reduced the severity of unwanted side effects while maintaining similar rates of cancer stability over time compared to intensity modulated radiation therapy (IMRT).

Research on IMRT suggests it can protect the heart and lungs from radiation. However, consensus on its safety and effectiveness for esophageal cancer remains elusive. While IMRT offers some benefits, further research is necessary to fully understand its safety.

Both PBT and IMRT aim to target cancer while minimizing harm to nearby healthy tissue. Available studies suggest that PBT might be safer, especially for heart and lung health. However, both treatments have their pros and cons, and ongoing research, like this trial, is crucial for gaining more insight. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Proton Beam Therapy (PBT) for esophageal cancer because it offers a more precise delivery of radiation compared to traditional treatments like Intensity Modulated Radiation Therapy (IMRT). PBT targets cancer cells with pinpoint accuracy, minimizing damage to surrounding healthy tissue, which could lead to fewer side effects. This precision is due to the unique properties of protons, which can be controlled to stop at a specific depth in the body, unlike X-rays used in IMRT that release energy along their entire path. By potentially reducing collateral damage, PBT holds promise for improving patient outcomes and quality of life during and after treatment.

What evidence suggests that this trial's treatments could be effective for esophageal cancer?

This trial will compare Proton Beam Therapy (PBT) with Intensity Modulated Radiation Therapy (IMRT) for treating esophageal cancer. Studies have shown that both PBT and IMRT effectively treat esophageal cancer. Research suggests that PBT might offer benefits, such as reducing side effects while maintaining good survival rates. For instance, one study found that PBT had a 5-year overall survival rate of 41.1% and helped lower side effects. Another study showed that PBT had a two-year survival rate specific to esophageal cancer of 62.03%, compared to 51.77% for IMRT. Both treatments aim to precisely target the cancer, but PBT might better protect the healthy tissues around the tumor. Participants in this trial will receive either PBT or IMRT to evaluate these potential differences. ^{5 6 7 8 9}

Who Is on the Research Team?

Steven H. Lin, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults over 18 with esophageal cancer, who can communicate in English and have a performance status indicating they are able to carry out some activity. They must not be pregnant or breastfeeding, should agree to use contraception, and cannot have active stage 4 cancers or uncontrolled major diseases. Prior treatments like chemotherapy are allowed if there's little overlap with the new treatment area.

Inclusion Criteria

I had a procedure to remove cancer from my esophagus and it was stage II-III.

Able to communicate in the English language

I can care for myself but may not be able to do active work.

Exclusion Criteria

I do not have any major uncontrolled health issues like heart failure or recent heart attack.

I have another cancer, but treating my esophageal cancer is the priority.

I have had radiation without chemo or chemo alone.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline

Baseline assessments including blood tests, performance status, imaging, lung function tests, and questionnaires

1 week

1 visit (in-person)

Treatment

Participants receive radiation therapy (PBT or IMRT) 5 days a week for up to 28 treatments, possibly with concurrent chemotherapy

5.5 weeks

5 visits per week (in-person)

Initial Follow-up

4-6 week break with bi-weekly contact for symptom and quality of life questionnaires

4-6 weeks

2 contacts per week (virtual)

Post-Treatment Follow-up

Comprehensive assessments including medical history, physical exam, imaging, and questionnaires

4-6 weeks after treatment

1 visit (in-person)

Long-term Follow-up

Routine follow-up visits every 3-4 months for 2 years, then every 4-6 months for 3 years, including assessments and imaging

5 years

Every 3-4 months for 2 years, then every 4-6 months

What Are the Treatments Tested in This Trial?

Interventions

• Intensity Modulated Radiation Therapy (IMRT)
• Proton Beam Therapy (PBT)
• Questionnaires

Trial Overview The trial is testing the safety and effectiveness of Proton Beam Therapy (PBT) versus Intensity-Modulated Radiation Therapy (IMRT), both combined with chemotherapy. PBT is newer and may reduce radiation damage to surrounding tissue compared to IMRT; this study aims to confirm that.

How Is the Trial Designed?

Group I: Proton Beam Therapy (PBT) Experimental Treatment 2 Interventions

Radiation therapy 1 time each day, 5 days a week (Monday through Friday) for up to 28 treatments. 1.8 Gy (or at RBE ("Relative Biologic Equivalence" for PBT)) to be delivered to the periphery of the planning target volume (PTV).

Group II: Intensity Modulated Radiation Therapy (IMRT) Active Control 2 Interventions

Radiation therapy 1 time each day, 5 days a week (Monday through Friday) for up to 28 treatments. 1.8 Gy to be delivered to the periphery of the planning target volume (PTV).

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Proton beam therapy (PBT) significantly reduced radiation exposure to the lungs and heart compared to photon-based radiotherapy in a study of 31 patients with locally advanced esophageal squamous cell carcinoma (ESCC).

Despite the dosimetric advantages of PBT, there were no significant differences in short-term postoperative outcomes or overall and disease-free survival rates between the PBT and photon groups after a median follow-up of 17 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Comparative Analysis of Photon versus Proton Beam Therapy in Neoadjuvant Concurrent Chemoradiotherapy for Intrathoracic Squamous Cell Carcinoma of the Esophagus at a Single Institute. Choi, JH., Lee, JM., Kim, MS., et al.[2022]

Intensity modulated proton beam therapy (IMPT) shows a clinically significant dosimetric advantage over intensity modulated photon therapy (IMRT) for esophageal cancer, particularly in sparing the heart and lungs, but both treatments resulted in similar acute toxicities and short-term clinical outcomes.

In a study of 64 patients, IMPT demonstrated comparable local control, progression-free survival, and overall survival rates to IMRT, indicating that IMPT is a safe and effective option for treating esophageal cancer, although longer follow-up is needed to fully assess its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Toxicities and Short-Term Patient Outcomes After Intensity-Modulated Proton Beam Radiation Therapy or Intensity-Modulated Photon Radiation Therapy for Esophageal Carcinoma: A Mayo Clinic Experience. Bhangoo, RS., DeWees, TA., Yu, NY., et al.[2022]

Proton beam therapy (PBT) combined with concurrent chemotherapy (CChT) shows promising results in treating esophageal cancer, with a pathologic complete response rate of 28% in surgical patients and a near complete response rate of 50%.

While the treatment is associated with some acute toxicities, such as esophagitis and fatigue, the overall clinical outcomes are encouraging, suggesting that PBT/CChT may be a viable option for managing thoracic malignancies, warranting further comparison with traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton beam therapy and concurrent chemotherapy for esophageal cancer. Lin, SH., Komaki, R., Liao, Z., et al.[2022]

In a study of 343 esophageal cancer patients treated with definitive chemoradiotherapy, proton beam therapy (PBT) showed significantly better overall survival and progression-free survival compared to intensity-modulated radiation therapy (IMRT).

PBT was particularly beneficial for patients with stage III disease, demonstrating a 5-year overall survival rate of 34.6% compared to 25.0% for IMRT, while no significant differences were found for patients with earlier stages of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Outcomes After Definitive Chemoradiotherapy Using Proton Beam Therapy Versus Intensity Modulated Radiation Therapy for Esophageal Cancer: A Retrospective, Single-Institutional Analysis. Xi, M., Xu, C., Liao, Z., et al.[2018]

In a randomized trial involving 145 patients with locally advanced esophageal cancer, proton beam therapy (PBT) significantly reduced the total toxicity burden (TTB) compared to intensity-modulated radiation therapy (IMRT), with TTB being 2.3 times higher for IMRT.

Despite the reduced toxicity with PBT, the progression-free survival (PFS) and overall survival rates were similar between the two treatment modalities, indicating that PBT offers a safer option without compromising treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Phase IIB Trial of Proton Beam Therapy Versus Intensity-Modulated Radiation Therapy for Locally Advanced Esophageal Cancer. Lin, SH., Hobbs, BP., Verma, V., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7142393/

Comparison between Intensity-Modulated Radiotherapy ... In conclusion, we found that overall survival significantly improved with IMRT-treated, compared with that of 3D-CRT-treated esophageal cancer patients, but we ...

2. jto.org jto.org/article/S1556-0864(23)02430-9/fulltext

Comparative Effectiveness of Intensity-Modulated Proton ... Specifically, at the two-year mark, ESCC-specific survival rates for patients undergoing IMPT and IMRT stood at 62.03% and 51.77%, respectively.

3. sciencedirect.com sciencedirect.com/science/article/pii/S2331518024000751

Esophageal Cancer Outcomes After Definitive ... Long-term survival and toxicity were excellent after IMPT for locally advanced esophageal cancer treated definitively with concurrent chemoradiation therapy.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.19.02503

Randomized Phase IIB Trial of Proton Beam Therapy ... Conclusion. For locally advanced esophageal cancer, PBT reduced the risk and severity of AEs compared with IMRT while maintaining similar PFS.

5. redjournal.org redjournal.org/article/S0360-3016(15)01698-3/fulltext

Long-term Efficacy Analysis Of Intensity Modulated ... For all patients, the 1-, 3- and 5-year local control rates and overall survival rates were 72.9%, 61.2%, 58.4% and 66.5%, 39.1%, 24.0%, respectively. Subgroup ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0936655524004539

Comparative Outcomes and Toxicity in Patients With ... Freilich et al. Comparative outcomes for three-dimensional conformal versus intensity-modulated radiation therapy for esophageal cancer. Dis Esophagus. (2015).

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7557123/

Acute Toxicities and Short-Term Patient Outcomes After ... Intensity modulated proton beam radiation therapy (IMPT) has a clinically significant dosimetric advantage over intensity modulated photon radiation therapy ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5605282/

Long-term survival and toxicity outcomes of intensity ... In patients with esophageal cancer (EC), intensity modulated radiation therapy (IMRT) improves dose sparing to the heart and lung, with some evidence showing ...

9. redjournal.org redjournal.org/article/S0360-3016(16)31328-1/fulltext

Outcomes and Toxicity in Patients Treated With Intensity ... There is not yet a consensus on the efficacy and safety of IMRT for the treatment of patients with esophageal carcinomas.