Proton Therapy for Small Cell Lung Cancer

Overseen By Kristin Higgins, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Emory University

Disqualifiers: Prior radiation, Pregnancy

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the use of intensity-modulated proton therapy (IMPT), a type of targeted radiation treatment, for small cell lung cancer (SCLC). The researchers aim to determine if IMPT is safe and effective for SCLC patients, with a focus on potential side effects, particularly those affecting the heart. Suitable participants should have a diagnosis of small cell lung cancer and a recommendation from their doctor for this specific radiation therapy. As an unphased trial, this study offers patients the chance to contribute to pioneering research in targeted radiation therapy for SCLC.

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 prior data suggests that intensity-modulated proton therapy is safe for small cell lung cancer?

Research has shown that intensity-modulated proton therapy (IMPT) is generally well-tolerated by patients with lung and chest cancers. In one study, 34 patients received IMPT, and all completed their treatment without major problems. Another study compared proton therapy to traditional X-ray radiation and found that IMPT might cause fewer side effects due to its precise targeting of tumors. This precision helps protect the healthy tissues surrounding the cancer.

Although researchers are still studying IMPT specifically for small cell lung cancer, these findings provide some reassurance about its safety. The treatment's ability to focus on the tumor could lower the risk of harming other parts of the body, potentially reducing side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike traditional radiation therapies for small cell lung cancer, Intensity-Modulated Proton Therapy (IMPT) uses proton beams that can be more precisely targeted to the tumor. This precision helps minimize damage to surrounding healthy tissues, especially the heart, potentially reducing treatment-related side effects. Researchers are excited about IMPT because it offers a promising approach to improve safety and effectiveness, particularly by adapting the treatment plan throughout the course of therapy to better suit the patient's needs.

What evidence suggests that intensity-modulated proton therapy is effective for small cell lung cancer?

Research has shown that Intensity-Modulated Proton Therapy (IMPT), which participants in this trial will receive, could be a promising treatment for lung cancer. Studies have found that IMPT protects vital organs like the heart and lungs more effectively than other radiation methods. This precision allows it to target cancer more accurately, causing less harm to healthy tissue. IMPT has effectively controlled tumors and resulted in fewer side effects in past cases. While more data is needed specifically for small cell lung cancer, the technique's accuracy and reduced side effects offer hope for better outcomes. ^{2 6 7 8 9}

Who Is on the Research Team?

Kristin Higgins, MD

Principal Investigator

Emory University-Winship Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults over 18 with small cell lung cancer (SCLC), either limited or extensive stage, who are recommended to undergo thoracic radiotherapy using intensity-modulated proton therapy (IMPT) delivering specific doses. Pregnant individuals or those who have had prior radiation that overlaps with the target area cannot participate.

Inclusion Criteria

I am recommended to undergo a specific type of chest radiation therapy.

My lung cancer is confirmed to be small cell type.

Exclusion Criteria

I've had radiation therapy that overlaps with the area planned for my current treatment.

Pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive intensity-modulated proton therapy (IMPT) for small cell lung cancer with adaptive planning throughout the radiation course

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of cardiac events and other toxicities

Up to 1 year

Long-term follow-up

Participants are monitored for long-term outcomes such as local control, distant metastases, and patterns of failure

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Intensity-Modulated Proton Therapy (IMPT)

Trial Overview The study is examining the safety and effectiveness of a type of targeted radiation called intensity-modulated proton therapy (IMPT) in treating patients with small cell lung cancer. The IMPT will be administered in specified doses and number of sessions.

How Is the Trial Designed?

Group I: Prospective Study of Intensity-Modulated Proton Therapy (IMPT) Experimental Treatment 1 Intervention

This is the first prospective study to investigate the safety and efficacy of IMPT for the treatment of SCLC. We will utilize adaptive planning throughout the radiation course. In addition, we will study the dosimetric parameters of IMPT and their correlation with treatment-related toxicities, particularly cardiac events.

Intensity-Modulated Proton Therapy (IMPT) is already approved in United States, European Union for the following indications:

Approved in United States as Intensity-Modulated Proton Therapy (IMPT) for:

• Head and neck cancers
• Prostate cancer
• Small cell lung cancer
• Pediatric tumors
• Brain tumors
• Cancers of the nasal and sinus cavities
• Oral cavity cancers
• Salivary gland cancers
• Tongue and tonsil cancers
• Larynx cancers
• Eye cancers
• Base of skull and spine cancers

Approved in European Union as Intensity-Modulated Proton Therapy (IMPT) for:

• Head and neck cancers
• Prostate cancer
• Small cell lung cancer
• Pediatric tumors
• Brain tumors

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

Published Research Related to This Trial

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 25 patients with limited-stage small cell lung cancer, the combination of proton and carbon-ion radiotherapy with concurrent chemotherapy resulted in promising 2-year overall and locoregional progression-free survival rates of 81.7% and 66.7%, respectively.

The treatment was generally well tolerated, with most patients experiencing only mild to moderate acute toxicities, although 20% had grade 3 toxicities, primarily related to hematological changes, indicating a need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary Safety and Efficacy of Proton Plus Carbon-Ion Radiotherapy With Concurrent Chemotherapy in Limited-Stage Small Cell Lung Cancer. Ma, NY., Chen, J., Ming, X., et al.[2022]

Pencil beam scanned intensity modulated proton therapy (IMPT) in breath-hold was found to be feasible and dosimetrically robust for treating 15 patients with locally advanced non-small cell lung cancer (NSCLC), with 99.8% of the clinical target volume receiving the prescribed dose.

While most patients (12 out of 15) required only three or fewer breath-holds per treatment field, three patients needed plan adjustments due to significant dose degradation, which was linked to changes in water-equivalent path lengths, highlighting the importance of monitoring these changes for treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of Pencil Beam Scanned Intensity Modulated Proton Therapy in Breath-hold for Locally Advanced Non-Small Cell Lung Cancer. Gorgisyan, J., Munck Af Rosenschold, P., Perrin, R., et al.[2018]

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 involving 10 patients with stage III non-small cell lung cancer, robustly optimized intensity modulated proton therapy (IMPT) plans maintained target coverage above clinical thresholds despite accounting for uncertainties in setup, range, and breathing motion.

IMPT demonstrated superior target homogeneity and significantly reduced doses to the lungs and heart (by about 40% and 60%, respectively) compared to traditional volumetric modulated arc therapy plans, indicating its efficacy and safety in minimizing exposure to surrounding organs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Limited Impact of Setup and Range Uncertainties, Breathing Motion, and Interplay Effects in Robustly Optimized Intensity Modulated Proton Therapy for Stage III Non-small Cell Lung Cancer. Inoue, T., Widder, J., van Dijk, LV., et al.[2017]

Intensity modulated proton therapy (IMPT) enhances the precision of proton beam delivery, allowing for better targeting of tumors while minimizing damage to surrounding healthy tissue compared to traditional X-ray therapies.

IMPT utilizes the unique Bragg peak of protons to achieve localized dose modulation, which can potentially improve treatment outcomes, but it also presents technical and clinical challenges that need to be addressed for effective implementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity modulated proton therapy. Kooy, HM., Grassberger, C.[2018]

Intensity modulated proton therapy (IMPT) was successfully used in 34 patients with lung and mediastinal cancers, showing significant improvements in sparing normal tissues compared to both intensity modulated radiation therapy (IMRT) and passive scattering proton therapy (PSPT).

IMPT achieved lower doses to critical organs like the lungs and heart while maintaining higher doses to the tumor, demonstrating effective motion management and robust treatment planning through advanced 4D CT simulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical implementation of intensity modulated proton therapy for thoracic malignancies. Chang, JY., Li, H., Zhu, XR., et al.[2022]

In a study involving ten lung cancer patients, intensity modulated proton therapy (IMPT) with unrestricted homogeneity (IMPTfull) showed higher effective uniform dose (EUD) and better target coverage (V95) compared to plans with restricted homogeneity (IMPT20%), indicating that IMPTfull may provide more effective treatment despite less uniformity.

The differences in treatment efficacy between IMPTfull and IMPT20% are primarily significant for patients experiencing large motion amplitudes (>20 mm), suggesting that motion management techniques may be necessary for optimal outcomes in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Four-dimensional Monte Carlo simulations demonstrating how the extent of intensity-modulation impacts motion effects in proton therapy lung treatments. Dowdell, S., Grassberger, C., Paganetti, H.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5651132/

Empowering Intensity Modulated Proton Therapy through ... Improvements in Robustness and Optimality with 4-Dimensional Robust Optimization of Intensity-Modulated Proton Therapy Plans for Lung Cancer Patients.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2452109417301021

Clinical outcomes of intensity modulated proton therapy ... IMPT is an effective treatment for EC, with high tumor response, good local control, and acceptable acute toxicity. Previous article in issue; Next ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6236833/

Small‐spot intensity‐modulated proton therapy and volumetric ... Small‐spot IMPT improves cord, heart, and lung sparing compared to VMAT and achieves clinically acceptable plan robustness at least for the patients included ...

4. nature.com nature.com/articles/s41598-020-60246-5

Exploring the advantages of intensity-modulated proton ... The objective of this study was to experimentally validate the enhanced biological effects using a novel beam delivery strategy with elevated LET.

5. thegreenjournal.com thegreenjournal.com/article/S0167-8140(24)00635-2/abstract

Robustness evaluation of pencil beam scanning proton ... Compared to conventional radiotherapy using X-rays, proton therapy, in principle, allows better conformity of the dose distribution to target volumes, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4628542/

Intensity modulated proton therapy - PMC - PubMed Central Intensity modulated proton therapy (IMPT) implies the electromagnetic spatial control of well-circumscribed “pencil beams” of protons of variable energy and ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4252731/

Clinical Implementation of Intensity Modulated Proton Therapy ... Thirty-four consecutive patients with lung/mediastinal cancers received IMPT to a median 66 Gy(RBE). All patients were able to undergo definitive radiation ...

8. mdpi.com mdpi.com/2072-6694/13/14/3497

Clinical Outcomes of Pencil Beam Scanning Proton ... This study compared the efficacy and safety of pencil beam scanning proton therapy (PBSPT) versus intensity-modulated (photon) radiotherapy (IMRT) in patients ...

9. jto.org jto.org/article/S1556-0864(20)30839-X/fulltext

Toxicity and Survival After Intensity-Modulated Proton ... Here, we compare toxicity profiles and clinical outcomes after IMPT versus PSPT for LA-NSCLC. Methods. This is a nonrandomized, comparative ...