Proton Beam Radiation Therapy for Non-Small Cell Lung Cancer

Overseen By Aparna H. Kesarwala, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Must not be taking: Investigational agents

Disqualifiers: Stage IV disease, Small cell lung cancer, EGFR/ALK alterations, 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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This clinical trial tests proton beam radiation therapy in patients with non-small cell lung cancer who have undergone surgical resection and have lymph nodes involving the middle of the chest. Proton therapy is a type of radiation treatment that kills cancer cells while avoiding surrounding healthy tissue. Proton beam therapy is sometimes used after cancer surgery to reduce the risk of cancer recurrence (coming back). Giving proton beam radiation therapy may work better than conventional radiation treatment after surgery in patients with non-small cell lung cancer.

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, it mentions that patients should not have had systemic therapy less than 2 weeks before starting radiotherapy, which might imply a need to pause certain treatments. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Proton Beam Radiation Therapy for Non-Small Cell Lung Cancer?

Proton Beam Therapy (PBT) for non-small cell lung cancer (NSCLC) may be promising because it can deliver lower doses to the lung and heart compared to traditional photon therapy, potentially reducing side effects. Clinical outcomes from a multi-institutional registry suggest that PBT can be effective for locally advanced NSCLC, although more high-quality studies are needed to confirm these findings. ^{1 2 3 4 5}

Is proton beam therapy safe for humans?

Proton beam therapy (PBT) is generally considered safe and has the potential to reduce side effects compared to traditional radiation therapy, but long-term safety data, especially for lung cancer, is still being gathered. ^{2 6 7 8 9}

How is proton beam radiation therapy different from other treatments for non-small cell lung cancer?

Proton beam radiation therapy is unique because it can deliver high doses of radiation directly to the tumor while minimizing damage to surrounding healthy tissues, unlike traditional radiation therapies. This precision reduces side effects and may allow for safer combination with other treatments like chemotherapy or surgery. ^{2 4 10 11 12}

Research Team

William Stokes

Principal Investigator

Emory University Hospital/Winship Cancer Institute

Eligibility Criteria

This trial is for adults over 18 with non-small cell lung cancer who've had surgery to remove the tumor and affected lymph nodes. They should be in decent health, have a life expectancy of more than 12 weeks, and not be pregnant or planning to become so during the trial. Participants must agree to use contraception and have finished any previous cancer treatments at least two weeks before starting.

Inclusion Criteria

I am willing and able to follow the study's schedule and procedures.

I had surgery to remove lung cancer completely, including part of the lung and lymph nodes.

My white blood cell count is at least 2000/uL without recent medical help.

Exclusion Criteria

My tumor has specific changes in the EGFR or ALK genes.

I have had radiation therapy to the chest area before.

I do not have any serious illnesses or social situations that would stop me from following the study's requirements.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Treatment Planning

Patients undergo radiation treatment planning

1 week

Proton Beam Radiation Therapy

Patients undergo proton beam radiation therapy and collection of blood samples

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Treatment Details

Interventions

• Proton Beam Radiation Therapy

Trial Overview The study is testing proton beam radiation therapy as a post-surgery treatment for lung cancer patients. Proton therapy targets cancer cells while sparing healthy tissue, potentially reducing recurrence risk compared to conventional radiation.

Participant Groups

Group I: Treatment (proton beam radiation therapy) Experimental Treatment 3 Interventions

Patients undergo radiation treatment planning and then undergo proton beam radiation therapy on study. Patients also undergo collection of blood samples.

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Proton radiotherapy for non-small-cell lung cancer (NSCLC) showed a 5-year overall survival rate of 29%, with significantly better outcomes for early-stage patients, particularly a 70% survival rate for Stage IA patients.

The treatment was found to be very safe, with 92% of patients experiencing only mild acute lung toxicity (Grade 1 or less), and minimal late toxicity, indicating a favorable safety profile for proton therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical evaluation of proton radiotherapy for non-small-cell lung cancer. Shioyama, Y., Tokuuye, K., Okumura, T., et al.[2019]

Proton beam therapy for lung cancer significantly reduces the average dose of radiation to the lungs (Dmean) and the volume of lung receiving higher doses (V20, V10, V5) compared to both three-dimensional conformal photon radiotherapy (3D-CRT) and intensity-modulated photon radiotherapy (IMRT), based on an analysis of six clinical trials.

While proton therapy does not lower the average dose to the esophagus, it does reduce the dose to the heart, suggesting a safer profile for patients undergoing lung cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Dosimetric comparing between protons beam and photons beam for lung cancer radiotherapy: a meta-analysis]. Tian, G., Li, N., Li, G.[2021]

In a study of 195 patients with locally advanced non-small cell lung cancer (LA-NSCLC) treated with proton beam therapy (PBT), the treatment showed low rates of severe side effects, with only a few grade 3 adverse events reported and no grade 4 events, indicating a favorable safety profile.

The median overall survival (OS) for patients was 19.0 months, and factors such as good performance status, the use of pencil beam scanning, and higher doses of radiation were associated with improved survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Outcomes After Proton Beam Therapy for Locally Advanced Non-Small Cell Lung Cancer: Analysis of a Multi-institutional Prospective Registry. Jongen, A., Charlier, F., Baker, K., et al.[2022]

Proton therapy for non-small-cell lung cancer generally maintains effective dose delivery, with only a slight maximum decrease in target coverage (1.4%) for most patients, indicating its safety and efficacy compared to traditional photon therapy.

However, for small tumors located deep within lung tissue, there can be significant underdosing (up to 26%), highlighting the need for further research to address this issue and improve treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analytical modeling of depth-dose degradation in heterogeneous lung tissue for intensity-modulated proton therapy planning. Winter, J., Ellerbrock, M., Jäkel, O., et al.[2022]

In a study of 51 patients with advanced inoperable non-small cell lung cancer (NSCLC), treatment with intensity-modulated proton therapy (IMPT) combined with chemotherapy resulted in a median overall survival of 33.9 months and a disease-free survival of 12.6 months, indicating effective disease control.

The treatment was well tolerated, with an 18% rate of grade 3 toxicities, primarily esophagitis and dermatitis, and no severe (grade 4 or 5) toxicities reported, suggesting a favorable safety profile for this combined therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes after intensity-modulated proton therapy with concurrent chemotherapy for inoperable non-small cell lung cancer. Elhammali, A., Blanchard, P., Yoder, A., et al.[2020]

In a study of 99 patients with locally advanced nonsmall cell lung cancer treated with proton beam therapy (PBT), 21% experienced grade 2 or higher radiation pneumonitis, indicating a notable risk of this complication.

The existing photon-based QUANTEC models for predicting radiation pneumonitis were found to be applicable to PBT with only minor adjustments needed, suggesting that these models can help tailor treatment plans for patients undergoing PBT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updating Photon-Based Normal Tissue Complication Probability Models for Pneumonitis in Patients With Lung Cancer Treated With Proton Beam Therapy. Jain, V., Niezink, AGH., Frick, M., et al.[2021]

In a study of 64 patients with unresectable stage III non-small cell lung cancer (NSCLC), concurrent chemotherapy and proton beam radiotherapy (PBT) resulted in a median overall survival of 26.5 months and a 5-year overall survival rate of 29%, indicating promising efficacy for this treatment approach.

The treatment was associated with relatively low rates of severe toxic effects, with no grade 5 toxicities reported, suggesting that PBT may reduce the harmful side effects compared to traditional photon therapy, although further optimization of the technique is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton Beam Radiotherapy and Concurrent Chemotherapy for Unresectable Stage III Non-Small Cell Lung Cancer: Final Results of a Phase 2 Study. Chang, JY., Verma, V., Li, M., et al.[2022]

High-dose proton beam therapy (PBT) for Stage I non-small-cell lung cancer (NSCLC) showed promising efficacy, with 2-year local progression-free and overall survival rates of 80% and 84%, respectively, based on a study of 37 patients treated between 1999 and 2003.

While PBT was generally safe with no serious acute toxicities, late pulmonary toxicities were observed in 6 patients, indicating a need for further investigation, especially for those with Stage IB disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose proton beam therapy for Stage I non-small-cell lung cancer. Nihei, K., Ogino, T., Ishikura, S., et al.[2018]

Proton beam therapy (PBT) offers a promising approach to lung cancer treatment by potentially reducing radiation toxicity due to its unique Bragg peak, which allows for more targeted delivery of radiation.

Current data suggests that PBT is effective for early-stage and locally-advanced non-small cell lung cancer (NSCLC), although there are technical challenges such as managing anatomical changes and patient movement during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton Beam Therapy for Non-Small Cell Lung Cancer: Current Clinical Evidence and Future Directions. Berman, AT., James, SS., Rengan, R.[2022]

Proton-beam therapy is an effective treatment option for non-small-cell lung cancer (NSCLC), especially for patients who cannot undergo surgery due to advanced disease or other medical conditions.

This type of radiotherapy allows for precise targeting of tumors, delivering high doses to the cancer while sparing surrounding healthy tissues, making it a promising alternative for lung cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of proton-beam therapy in the treatment of non-small-cell lung cancer. Oshiro, Y., Sakurai, H.[2013]

Proton stereotactic body radiation therapy (SBRT) was found to be effective and well tolerated in 15 patients with medically inoperable stage I non-small-cell lung cancer (NSCLC), achieving a 2-year overall survival rate of 64% and a local control rate of 100%.

The treatment was associated with minimal toxicity, with only one case of grade 3 pneumonitis and a few instances of grade 2 side effects, indicating that proton SBRT may be a safe option for patients with significant pulmonary comorbidities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton SBRT for medically inoperable stage I NSCLC. Westover, KD., Seco, J., Adams, JA., et al.[2021]

Proton therapy is a promising treatment option for lung cancer, particularly for patients with non-small cell lung cancer (NSCLC), as it can deliver higher radiation doses to tumors while minimizing exposure to surrounding healthy tissues, potentially reducing treatment-related toxicities.

This therapy not only allows for safer reirradiation but also facilitates the combination of radiation therapy with chemotherapy and surgery, enhancing treatment options for patients with early-stage and locally advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of proton therapy in the treatment of lung cancers. Simone, CB., Rengan, R.[2022]

References

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

Clinical evaluation of proton radiotherapy for non-small-cell lung cancer. [2019]

2. China pubmed.ncbi.nlm.nih.gov

[Dosimetric comparing between protons beam and photons beam for lung cancer radiotherapy: a meta-analysis]. [2021]

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

Clinical Outcomes After Proton Beam Therapy for Locally Advanced Non-Small Cell Lung Cancer: Analysis of a Multi-institutional Prospective Registry. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Analytical modeling of depth-dose degradation in heterogeneous lung tissue for intensity-modulated proton therapy planning. [2022]

5. Ireland pubmed.ncbi.nlm.nih.gov

Clinical outcomes after intensity-modulated proton therapy with concurrent chemotherapy for inoperable non-small cell lung cancer. [2020]

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

Updating Photon-Based Normal Tissue Complication Probability Models for Pneumonitis in Patients With Lung Cancer Treated With Proton Beam Therapy. [2021]

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

Proton Beam Radiotherapy and Concurrent Chemotherapy for Unresectable Stage III Non-Small Cell Lung Cancer: Final Results of a Phase 2 Study. [2022]

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

High-dose proton beam therapy for Stage I non-small-cell lung cancer. [2018]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Proton Beam Therapy for Non-Small Cell Lung Cancer: Current Clinical Evidence and Future Directions. [2022]

10. England pubmed.ncbi.nlm.nih.gov

The use of proton-beam therapy in the treatment of non-small-cell lung cancer. [2013]

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

Proton SBRT for medically inoperable stage I NSCLC. [2021]

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

The use of proton therapy in the treatment of lung cancers. [2022]