Proton Radiation for Esophageal Cancer

Overseen By Proton Referral Office First call: Referral Office intake personnel

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Loma Linda University

Disqualifiers: Cervical esophageal carcinoma, T1N0, T4, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

38 Participants Needed

Trial Summary

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 Proton Radiation for Esophageal Cancer?

Research shows that proton therapy for esophageal cancer can lead to excellent survival rates and lower side effects compared to traditional photon radiation. Studies have found that it reduces damage to healthy tissues and has fewer postoperative complications, making it a promising treatment option. ^{1 2 3 4 5}

Is proton radiation therapy safe for treating esophageal cancer?

Proton radiation therapy for esophageal cancer has shown lower rates of serious side effects compared to traditional photon radiation therapy. Studies have reported some mild to moderate side effects, like esophageal ulcers and rare cases of heart or lung issues, but these were generally manageable and less severe than with other treatments. ^{2 4 6 7 8}

How is proton radiation treatment different for esophageal cancer?

Proton radiation treatment for esophageal cancer is unique because it allows energy to be deposited at a specific depth, reducing damage to healthy tissue and potentially leading to fewer side effects compared to traditional photon radiation therapy. This makes it safer for treating tumors near critical organs and may result in better outcomes and lower toxicities. ^{1 2 3 4 9}

What is the purpose of this trial?

The goal of this phase II study is to investigate the feasibility, toxicity and efficacy of a regimen incorporating a proven systemic regimen, carboplatin /paclitaxel, with conformal proton modality, followed by definitive surgery. In most combined-modality trials to date, chemotherapy regimens have included cisplatin, usually in conjunction with 5-fluorouracil. In designing the regimen, the investigators attempt to improve on the standard cisplatin/5-fluorouracil regimen in several ways. First, full-dose paclitaxel is added to the regimen. This agent has activity against advanced esophageal cancer and is also a potent radiosensitizer. Second, the substitution of carboplatin for cisplatin has resulted in reduced toxicity of various combination regimens similar to that used by CROSS trial and allows for easier administration in the outpatient setting.4 Third, for localized esophageal cancer, dose distribution patterns achievable with proton beam could potentially offer important clinical advantages relative to those achievable with x-rays (photons).19 Based on this, the investigators believe that this study should be conducted with the radiation modality that offers the best dosimetry achievable at our institution.

Research Team

Gary Yang, MD

Principal Investigator

[e-mail]

Eligibility Criteria

This trial is for adults with confirmed primary squamous cell or adenocarcinoma of the esophagus, involving mid to lower regions or junction. They must have adequate organ function, no prior treatments for esophageal cancer, and be fit for surgery post-therapy. Pregnant women and those unable to use contraception are excluded.

Inclusion Criteria

I have had an endoscopy with a tissue sample taken.

Endoscopic ultrasound

My liver is working well.

Exclusion Criteria

My cancer is either very small and not spread to lymph nodes or very large.

I cannot undergo surgery to remove my esophagus due to health reasons.

Severe, active co-morbidity impacting survival

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Participants receive a regimen of carboplatin and paclitaxel, which includes proton radiation therapy

6-8 weeks

Surgery

Definitive surgery is performed following chemotherapy and radiation

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• Proton Radiation

Trial Overview The study tests a treatment combining carboplatin/paclitaxel chemotherapy with proton radiation therapy followed by surgery. It aims to improve outcomes over traditional chemo regimens by reducing toxicity and using proton beam technology for better dose distribution in localized esophageal cancer.

Participant Groups

Group I: Proton radiation Experimental Treatment 1 Intervention

Proton radiation

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

Approved in United States as Proton Therapy for:

• Brain tumors
• Breast cancer
• Esophageal cancer
• Eye cancer
• Gynecological cancers
• Head and neck cancer
• Liver cancer
• Lung cancer
• Lymphoma
• Pancreatic cancer
• Prostate cancer
• Rectal cancer
• Sarcomas
• Spinal cord tumors

Approved in European Union as Proton Therapy for:

• Similar indications as in the United States, with specific approvals varying by country

Approved in Canada as Proton Therapy for:

• Similar indications as in the United States, with specific approvals varying by province

Approved in Japan as Proton Therapy for:

• Similar indications as in the United States, with specific approvals varying by region

Who Is Running the Clinical Trial?

Loma Linda University

Lead Sponsor

Trials

322

Recruited

267,000+

Findings from Research

Proton beam therapy shows promise as an effective treatment for locally confined esophageal cancer, with a 5-year overall survival rate of 34% among 46 patients studied, and a notably higher survival rate of 55% for those with early-stage T1 disease.

The therapy resulted in a 5-year disease-specific survival rate of 67%, indicating that proton therapy can effectively target cancer while potentially minimizing damage to surrounding healthy tissue, although further research is needed to optimize treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical results of proton beam therapy for cancer of the esophagus. Sugahara, S., Tokuuye, K., Okumura, T., et al.[2018]

Proton beam radiation therapy (PT) offers significant advantages over traditional photon radiation therapy for esophageal cancer, including reduced toxicity to healthy tissues and improved safety for tumors located near critical organs, as supported by recent multicenter studies.

A randomized phase II study confirmed that PT resulted in significantly lower toxicities compared to IMRT, and ongoing phase III trials are investigating whether PT could become the standard treatment for locally advanced and resectable esophageal cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The role of proton therapy in esophageal cancer]. Créhange, G., Goudjil, F., Krhili, SL., et al.[2022]

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]

In a study of 44 patients with clinical T1 esophageal squamous cell carcinoma (ESCC) treated with concurrent chemo-proton therapy (CCPT), 98% achieved a complete response, indicating high efficacy of this treatment approach.

The 3-year overall survival rate was 95.2%, and even among the 11% who experienced local recurrence, all were successfully treated and remained recurrence-free after a median follow-up of 23 months, highlighting the safety and effectiveness of salvage endoscopic therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic results of proton beam therapy with concurrent chemotherapy for cT1 esophageal cancer and salvage endoscopic therapy for local recurrence. Sato, D., Motegi, A., Kadota, T., et al.[2021]

Proton-beam therapy for locoregionally advanced esophageal cancer showed a high response rate, with 92% of patients (40 out of 51) achieving either a complete or partial response within 4 months of treatment.

The treatment was well-tolerated, with no interruptions due to radiation-induced side effects, and the overall 5-year survival rate was 21.1%, indicating that proton-beam therapy is a promising option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical results of proton-beam therapy for locoregionally advanced esophageal cancer. Mizumoto, M., Sugahara, S., Nakayama, H., et al.[2021]

In a study of 202 patients with esophageal cancer treated with proton beam therapy, the 3-year overall survival rate was 66.7% and the 5-year survival rate was 56.3%, indicating promising efficacy for this treatment.

Proton beam therapy demonstrated lower rates of severe toxicities, with only 1% of patients experiencing grade three pericardial effusion and 0.5% experiencing grade three pneumonia, suggesting it may be a safer alternative to traditional photon radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Results of Proton Beam Therapy for Esophageal Cancer: Multicenter Retrospective Study in Japan. Ono, T., Wada, H., Ishikawa, H., et al.[2020]

Proton beam therapy (PBT) may reduce radiation exposure to healthy tissues compared to traditional photon-based radiotherapy for early-stage esophageal cancer, potentially lowering the risk of cardiac and pulmonary complications.

Despite promising dosimetric studies suggesting advantages of PBT, there is still limited clinical data on its effectiveness in large populations and its impact on patients' quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton Beam Therapy for Esophageal Cancer. Solidum, JGN., Rojo, RD., Wo, JY., et al.[2022]

In a study of 15 patients with esophageal carcinoma treated with proton beam irradiation (with or without x-ray), all primary tumor lesions disappeared, indicating high efficacy of this treatment approach.

Despite some patients developing esophageal ulcers post-treatment, these healed with conservative management, and the treatment showed promising long-term survival, with four patients living over five years and no local recurrences in superficial carcinoma cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton beam therapy for patients with esophageal carcinoma. Koyama, S., Tsujii, H., Yokota, H., et al.[2018]

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]

References

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

Clinical results of proton beam therapy for cancer of the esophagus. [2018]

2. France pubmed.ncbi.nlm.nih.gov

[The role of proton therapy in esophageal cancer]. [2022]

3. Switzerland 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. [2022]

4. Japan pubmed.ncbi.nlm.nih.gov

Therapeutic results of proton beam therapy with concurrent chemotherapy for cT1 esophageal cancer and salvage endoscopic therapy for local recurrence. [2021]

5. Germany pubmed.ncbi.nlm.nih.gov

Clinical results of proton-beam therapy for locoregionally advanced esophageal cancer. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Results of Proton Beam Therapy for Esophageal Cancer: Multicenter Retrospective Study in Japan. [2020]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Proton Beam Therapy for Esophageal Cancer. [2022]

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

Proton beam therapy for patients with esophageal carcinoma. [2018]

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

Proton beam therapy and concurrent chemotherapy for esophageal cancer. [2022]