Proton vs Photon Radiation for Retroperitoneal Sarcoma

Recruiting at 9 trial locations

Overseen By Thomas DeLaney, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Massachusetts General Hospital

Must not be taking: Chemotherapy, Antiretrovirals, others

Disqualifiers: Prior radiation, Pregnancy, Metastases, others

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

Compensation: Varies

Number of Visits: 7

80 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study is a Phase I clinical trial. Phase I clinical trials test the safety of an investigational intervention. Phase I studies also try to define the appropriate dose of the investigational therapy to use for further studies. "Investigational" means that the intervention is still being studied and that research doctors are trying to find out more about it. Retroperitoneal sarcomas are soft tissue tumors located at the far back of the abdomen. Typically, patients with retroperitoneal sarcomas either have surgery for the removal of their tumors alone, or have their tumors removed, followed by standard radiation therapy, or have pre-operative radiation followed by surgery. When conventional radiation therapy is delivered after surgery, it can damage normal tissue. In this study, you will undergo proton beam radiation therapy or IMRT before undergoing surgery for the removal of your tumor. Proton radiation and IMRT are FDA approved radiation delivery systems. Protons are tiny particles with positive charge that can be controlled to travel a certain distance and stop inside the body. In theory, this allows better control of where the radiation dose is delivered as compared to photons. Since proton radiation is more targeted, it may help to reduce unwanted side effects from radiation. In this study, a standard dose of radiation will be given to the majority of the tumor, while a simultaneously integrated boost of additional radiation will be given to certain areas of the tumor identified as higher risk. This means that a higher radiation dose will be given to the higher risk areas of the tumor. The purpose of this study is to determine the highest dose of radiation therapy with protons or IMRT that can be delivered safely in patients with retroperitoneal sarcomas and the effectiveness of proton beam radiation therapy as an intervention for patients with retroperitoneal sarcomas.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you have had chemotherapy within 4 weeks before the study or are receiving other investigational agents.

What data supports the effectiveness of the treatment Proton vs Photon Radiation for Retroperitoneal Sarcoma?

Research shows that intensity-modulated proton therapy (IMPT) can effectively target tumors while minimizing damage to surrounding healthy organs, which is particularly beneficial for retroperitoneal sarcomas located near vital organs. Additionally, studies comparing proton therapy to other radiation methods suggest that proton therapy may offer better protection for normal tissues, making it a promising option for treating these types of tumors. ^{1 2 3 4 5}

Is proton radiation therapy safe for humans?

Proton radiation therapy, including intensity-modulated proton therapy (IMPT), has been studied for various cancers like prostate and pancreatic cancer. It generally shows a reduced risk of complications compared to traditional radiation methods, as it targets tumors more precisely and limits exposure to surrounding healthy tissues. ^{1 2 3 6 7}

How is the treatment IG-IMPT, IG IMRT different from other treatments for retroperitoneal sarcoma?

The treatment IG-IMPT, IG IMRT is unique because it uses proton therapy, which can more precisely target tumors while minimizing damage to surrounding healthy organs, compared to traditional photon-based radiation. This approach may allow for higher doses to the tumor and potentially reduce the risk of local recurrence. ^{1 2 3 4 8}

Research Team

Thomas DeLaney, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for people with a life expectancy over 2 years who have measurable, histologically confirmed primary soft tissue sarcoma in the retroperitoneum. It's not for those previously treated with radiation for this condition, pregnant or breastfeeding individuals, patients on other investigational drugs, those with multifocal disease or metastases, sensitivity to radiation therapy, HIV on anti-retrovirals, uncontrolled illnesses, recent chemotherapy recipients within 4 weeks prior to the study start date.

Inclusion Criteria

My cancer is a type of sarcoma that started in the tissue behind my stomach.

Life expectancy of greater than 2 years

My cancer can be measured by tests.

Exclusion Criteria

History of sensitivity to radiation therapy

My cancer has spread to lymph nodes or other parts of my body.

I am HIV positive and on combination anti-retroviral therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Radiation Therapy

Participants receive proton beam radiation therapy or IMRT with a simultaneously integrated boost to high-risk areas of the tumor

6 weeks

5 visits per week (in-person)

Pre-Surgery Assessment

Participants are assessed for side effects of radiation and undergo imaging and blood tests before surgery

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after surgery, with follow-up visits scheduled within one month and four months post-surgery, then twice yearly for five years, and annually thereafter

Long-term

Multiple visits (in-person)

Treatment Details

Interventions

• IG-IMPT
• IG IMRT

Trial Overview The study tests two FDA-approved radiation therapies: proton beam therapy (IG-IMPT) and IMRT before surgery to remove retroperitoneal sarcomas. The goal is to find the safest high dose of these radiations that can be given by targeting most of the tumor and giving an extra boost to higher risk areas.

Participant Groups

Group I: Treatment Arm IMRT Experimental Treatment 1 Intervention

IG IMRT with SIB to the high risk margin

Group II: Treatment Arm IMPT Experimental Treatment 1 Intervention

IG-IMPT with SIB to the high risk margin

IG-IMPT is already approved in United States, European Union, Japan for the following indications:

Approved in United States as Proton Therapy for:

• Various cancers including but not limited to prostate cancer, brain tumors, spinal tumors, and soft tissue sarcomas like retroperitoneal sarcomas

Approved in European Union as Proton Therapy for:

• Various cancers including but not limited to ocular tumors, brain tumors, and soft tissue sarcomas

Approved in Japan as Proton Therapy for:

• Various cancers including but not limited to prostate cancer, brain tumors, and ocular tumors

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Mayo Clinic

Collaborator

Trials

3,427

Recruited

3,221,000+

Rush University Medical Center

Collaborator

Trials

448

Recruited

247,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Roswell Park Cancer Institute

Collaborator

Trials

427

Recruited

40,500+

Dana-Farber Cancer Institute

Collaborator

Trials

1,128

Recruited

382,000+

University of Utah

Collaborator

Trials

1,169

Recruited

1,623,000+

Washington University School of Medicine

Collaborator

Trials

2,027

Recruited

2,353,000+

Duke University

Collaborator

Trials

2,495

Recruited

5,912,000+

Findings from Research

In a phase 1 trial involving 11 patients with retroperitoneal sarcoma, intensity modulated proton therapy (IMPT) successfully escalated the radiation dose to 63 GyRBE without causing acute dose limiting toxicities, indicating a promising safety profile for higher doses.

After 18 months of follow-up, there were no local recurrences of the tumor, suggesting that the IMPT approach may effectively reduce the risk of local recurrence in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 trial of preoperative image guided intensity modulated proton radiation therapy with simultaneously integrated boost to the high risk margin for retroperitoneal sarcomas. DeLaney, TF., Chen, YL., Baldini, EH., et al.[2020]

In a study involving eight patients with retroperitoneal or intra-abdominal sarcomas, both intensity-modulated proton therapy (3DCPT) and intensity-modulated photon therapy (IMRT) provided better conformity and homogeneity in radiation delivery compared to 3D conformal photon therapy (3DCRT).

Proton therapy (3DCPT) showed a significant reduction in radiation exposure to surrounding healthy tissues, particularly the bowel and kidneys, suggesting it may lead to lower gastrointestinal and genitourinary toxicity compared to IMRT and 3DCRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of three-dimensional (3D) conformal proton radiotherapy (RT), 3D conformal photon RT, and intensity-modulated RT for retroperitoneal and intra-abdominal sarcomas. Swanson, EL., Indelicato, DJ., Louis, D., et al.[2022]

Intensity modulated proton therapy (IMPT) significantly reduces the integral dose to organs at risk (OAR) compared to intensity modulated photon therapy (IMPT), with reductions in mean doses to the heart, lungs, kidneys, stomach, and liver by factors ranging from 1.3 to 25.

Both IMPT and IM photon therapy provide optimal tumor coverage, but IMPT allows for dose escalation to the tumor without exceeding normal tissue dose limits, enhancing treatment efficacy while maintaining safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A treatment planning comparison of intensity modulated photon and proton therapy for paraspinal sarcomas. Weber, DC., Trofimov, AV., Delaney, TF., et al.[2022]

Intensity modulated radiation therapy (IMRT) significantly improved tumor coverage for retroperitoneal sarcomas, increasing the percentage of the tumor receiving the prescribed dose from 95.3% with 3D-conformal treatment to 98.6% with IMRT.

IMRT also reduced the mean dose to surrounding organs at risk, such as the small bowel, from 36 Gy to 27 Gy, while maintaining effective treatment, suggesting it is a safer and more effective option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity modulated radiation therapy for retroperitoneal sarcoma: a case for dose escalation and organ at risk toxicity reduction. Koshy, M., Landry, JC., Lawson, JD., et al.[2021]

Proton therapy (PT), especially intensity modulated proton therapy (IMPT), shows superior treatment planning for prostate cancer by providing better homogeneity in the planning target volume (PTV) and sparing surrounding healthy tissues, such as the rectum, compared to traditional intensity-modulated radiation therapy (IMRT).

Proton therapy significantly reduces the dose to normal tissues outside the PTV, exposing them to less than 50% of the dose delivered by IMRT, making it a promising option for prostate cancer treatment in Australian facilities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of proton therapy and IMRT treatment plans for prostate radiotherapy. Dowdell, SJ., Metcalfe, PE., Morales, JE., et al.[2019]

Intensity-modulated proton therapy (IMPT) was found to irradiate only half the tissue volume with a lower dose compared to intensity-modulated x-ray therapy (IMXT), which could reduce the risk of secondary cancers and complications.

Both treatment plans were effective in covering target volumes for patients with advanced prostate carcinoma, indicating that IMPT can be a safer alternative without compromising treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LOW DOSE BATH FROM IMPT VS. IMXT FOR THE PELVIC AREA WHEN TREATING ADVANCED PROSTATE CANCER. Navrátil, M., Vondráček, V., Andrlík, M., et al.[2020]

Pencil-beam scanning intensity modulated proton therapy (IMPT) for localized pancreatic cancer showed significant reductions in radiation exposure to surrounding organs at risk, such as the small bowel and liver, compared to volumetric modulated arc therapy (VMAT).

No patients experienced severe (grade ≥3) treatment-related adverse events, and there was no significant change in health-related quality of life scores during treatment, indicating that IMPT is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial experience with intensity modulated proton therapy for intact, clinically localized pancreas cancer: Clinical implementation, dosimetric analysis, acute treatment-related adverse events, and patient-reported outcomes. Jethwa, KR., Tryggestad, EJ., Whitaker, TJ., et al.[2022]

A dosimetric comparison of pre-operative ultra-hypofractionated intensity-modulated proton therapy (IMPT) and photon therapy (IMRT) in 10 patients with retroperitoneal sarcoma showed that IMPT significantly reduced radiation exposure to surrounding organs at risk, such as the liver and gastrointestinal tract.

IMPT maintained effective coverage of the target area while minimizing the overall radiation dose compared to IMRT, suggesting it could be a safer option for patients undergoing pre-operative treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative In Silico Analysis of Ultra-Hypofractionated Intensity-Modulated Photon Radiotherapy (IMRT) Versus Intensity-Modulated Proton Therapy (IMPT) in the Pre-Operative Treatment of Retroperitoneal Sarcoma. Gogineni, E., Chen, H., Istl, AC., et al.[2023]

References

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

Phase 1 trial of preoperative image guided intensity modulated proton radiation therapy with simultaneously integrated boost to the high risk margin for retroperitoneal sarcomas. [2020]

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

Comparison of three-dimensional (3D) conformal proton radiotherapy (RT), 3D conformal photon RT, and intensity-modulated RT for retroperitoneal and intra-abdominal sarcomas. [2022]

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

A treatment planning comparison of intensity modulated photon and proton therapy for paraspinal sarcomas. [2022]

4. Egypt pubmed.ncbi.nlm.nih.gov

Intensity modulated radiation therapy for retroperitoneal sarcoma: a case for dose escalation and organ at risk toxicity reduction. [2021]

5. Netherlands pubmed.ncbi.nlm.nih.gov

A comparison of proton therapy and IMRT treatment plans for prostate radiotherapy. [2019]

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

LOW DOSE BATH FROM IMPT VS. IMXT FOR THE PELVIC AREA WHEN TREATING ADVANCED PROSTATE CANCER. [2020]

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

Initial experience with intensity modulated proton therapy for intact, clinically localized pancreas cancer: Clinical implementation, dosimetric analysis, acute treatment-related adverse events, and patient-reported outcomes. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Comparative In Silico Analysis of Ultra-Hypofractionated Intensity-Modulated Photon Radiotherapy (IMRT) Versus Intensity-Modulated Proton Therapy (IMPT) in the Pre-Operative Treatment of Retroperitoneal Sarcoma. [2023]