Surgery vs Stereotactic Ablative Radiotherapy for Lung Cancer

(STABLE-MATES Trial)

Recruiting in Palo Alto (17 mi)

+24 other locations

Overseen by Robert Timmerman, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: University of Texas Southwestern Medical Center

Disqualifiers: Distant metastases, Prior radiation, Pregnancy, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

To Determine if SAbR improves survival over SR in High Risk Operable Stage I NSCLC

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 Surgery vs Stereotactic Ablative Radiotherapy for Lung Cancer?

Research shows that stereotactic ablative radiotherapy (SABR) is a standard treatment for early-stage non-small cell lung cancer (NSCLC) in patients who cannot undergo surgery, with outcomes comparable to surgery in terms of local control and side effects. However, direct comparisons in operable patients are still needed to fully assess survival benefits. ^{1 2 3 4 5}

Is Stereotactic Ablative Radiotherapy (SABR) generally safe for treating lung cancer?

Stereotactic Ablative Radiotherapy (SABR) is generally considered safe for treating early-stage non-small cell lung cancer, with low chances of severe side effects, although some patients may experience mild radiological changes. However, it can cause toxic effects, including potential damage to central structures, and there is a risk of pneumonitis (lung inflammation) especially in patients with previous lung surgery. ^{1 2 6 7 8}

How does the treatment of surgery compare to stereotactic ablative radiotherapy for lung cancer?

Stereotactic ablative radiotherapy (SABR) is a non-invasive treatment that uses precise, high doses of radiation over a few sessions, making it a good option for patients who cannot undergo surgery due to age or other health issues. Unlike surgery, which involves physically removing lung tissue, SABR targets the cancer with radiation, offering similar local control and survival outcomes for early-stage non-small cell lung cancer. ^{1 2 9 10 11}

Research Team

Robert Timmerman, MD

Principal Investigator

UTSW Medical Center

Eligibility Criteria

This trial is for adults over 18 with high-risk operable Stage I non-small cell lung cancer (NSCLC) that can be removed by surgery. Candidates must have a tumor ≤ 4 cm, located peripherally in the lung, and no distant metastases. They should not have had previous thoracic radiation therapy or treatment for this lung cancer and must not be pregnant.

Inclusion Criteria

I can take care of myself and am up and about more than half of my waking hours.

Ability to understand and the willingness to sign a written informed consent

My lung cancer has not spread to certain lymph nodes, confirmed by a biopsy.

Exclusion Criteria

My cancer has spread to distant parts of my body.

pregnant and lactating women

I have had radiation therapy not aimed at my lungs and no lung surgery on the affected side.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-randomization

Patients are pre-randomized to either SR or SAbR and informed consent is obtained

1-2 weeks

Treatment

Participants receive either Sublobar Resection (SR) or Stereotactic Ablative Radiotherapy (SAbR)

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Long-term follow-up

Participants are monitored for progression-free survival and overall survival

5 years

Treatment Details

Interventions

• Lung Surgery (Surgery)
• SAbR (Radiation Therapy)

Trial Overview The study aims to compare survival outcomes between two treatments: sublobar resection (SR), which is a type of lung surgery, and stereotactic ablative radiotherapy (SAbR). It's designed to see if SAbR offers better survival rates than SR in patients with early-stage NSCLC who are at high risk from traditional surgery.

Participant Groups

Group I: Arm 2 radiation therapy Experimental Treatment 1 Intervention

Stereotactic Ablative Radiotherapy (SAbR)

Group II: Arm 1 lung surgery Active Control 1 Intervention

Sublobar Resection (SR)

Lung Surgery is already approved in Canada, Japan, China, Switzerland for the following indications:

Approved in Canada as Lung Surgery for:

• Lung cancer
• Infections
• Trauma
• Lung transplants
• Tuberculosis
• Lung abscess
• Emphysema
• Benign tumors
• Fungal infections

Approved in Japan as Lung Surgery for:

• Lung cancer
• Infections
• Trauma
• Lung transplants
• Tuberculosis
• Lung abscess
• Emphysema
• Benign tumors
• Fungal infections

Approved in China as Lung Surgery for:

• Lung cancer
• Infections
• Trauma
• Lung transplants
• Tuberculosis
• Lung abscess
• Emphysema
• Benign tumors
• Fungal infections

Approved in Switzerland as Lung Surgery for:

• Lung cancer
• Infections
• Trauma
• Lung transplants
• Tuberculosis
• Lung abscess
• Emphysema
• Benign tumors
• Fungal infections

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Daniel K. Podolsky

University of Texas Southwestern Medical Center

Chief Executive Officer since 2008

MD from Harvard Medical School

Robert L. Bass

University of Texas Southwestern Medical Center

Chief Medical Officer since 2019

MD from University of Texas Southwestern Medical School

Findings from Research

A meta-analysis of 15 studies involving 7,810 patients with T1-3N0M0 non-small cell lung cancer (NSCLC) found that patients treated with SBRT/SABR had significantly worse 5-year survival rates compared to those who underwent surgery, indicating that surgery may be a more effective treatment option.

The study also revealed that SBRT/SABR resulted in lower recurrence-free survival rates, suggesting that surgical interventions like lobectomy or sublobectomy are preferable for better long-term outcomes in NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy or stereotactic ablative radiotherapy versus surgery for patients with T1-3N0M0 non-small cell lung cancer: a systematic review and meta-analysis. Li, M., Yang, X., Chen, Y., et al.[2022]

Stereotactic ablative radiotherapy (SABR) is an effective treatment for early-stage non-small cell lung cancers (NSCLCs) that are medically inoperable, providing local control and toxicity levels comparable to surgical resection.

SABR is gaining interest as a noninvasive treatment option for patients with borderline resectable lung cancers, although further randomized studies are needed to evaluate its survival benefits in operable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy (SABR) for non-small cell lung cancer. Iyengar, P., Westover, K., Timmerman, RD.[2013]

In a study of 382 patients with clinical stage I non-small cell lung cancer, the 3-year overall survival rate was significantly higher for those who underwent sublobar resection (86.6%) compared to those who received stereotactic body radiotherapy (57%).

However, after adjusting for various factors like age and pulmonary function, the type of treatment (SLR vs. SBRT) did not significantly impact survival outcomes, suggesting that SBRT may be a viable treatment option for selected high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sublobar Resection versus Stereotactic Body Radiation Therapy for Clinical Stage I Non-Small Cell Lung Cancer: A Study Using Data from the Korean Nationwide Lung Cancer Registry. Yun, J., Cho, JH., Hong, TH., et al.[2023]

In a multicenter phase 3 trial involving 101 patients with inoperable stage 1 non-small-cell lung cancer, stereotactic ablative body radiotherapy (SABR) demonstrated significantly better local control compared to standard radiotherapy, with a 68% reduction in the risk of local treatment failure (hazard ratio 0.32).

SABR was associated with a similar safety profile to standard radiotherapy, showing no increase in major toxicity, making it a preferred treatment option for patients with this type of lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy versus standard radiotherapy in stage 1 non-small-cell lung cancer (TROG 09.02 CHISEL): a phase 3, open-label, randomised controlled trial. Ball, D., Mai, GT., Vinod, S., et al.[2022]

A meta-analysis of eight studies found that while stereotactic ablative radiotherapy (SABR) and lobectomy showed similar one-year overall survival (OS) and cause-specific survival (CSS), lobectomy significantly improved three-year and five-year OS and CSS for patients with early-stage non-small cell lung cancer (NSCLC).

Lobectomy also demonstrated better recurrence-free survival (RFS) at three years compared to SABR, indicating that surgical intervention may offer more favorable long-term outcomes for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy versus lobectomy for stage I non-small cell lung cancer: A systematic review. Wang, S., Wang, X., Zhou, Q., et al.[2018]

In a study of 102 patients treated with stereotactic ablative radiation therapy (SABR) for early-stage non-small-cell lung cancer, a significant correlation was found between higher Biological Equivalent Doses (BED) over 300 Gy and the development of radiological changes such as organizing pneumonia and lung affectation over a 2-year follow-up.

Radiological changes were more pronounced in patients receiving BEDs greater than 300 Gy to healthy lung volumes of at least 30 cc, suggesting that these findings could inform future radiotherapy dose constraints to minimize pulmonary toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological equivalent dose is associated with radiological toxicity after lung stereotactic ablative radiation therapy. Cases, C., Benegas, M., Sánchez, M., et al.[2023]

The iSABR trial demonstrated that individualized stereotactic ablative radiotherapy (SABR) for lung tumors resulted in high local control rates, with freedom from local recurrence at 1 year ranging from 94% to 97% across different patient groups.

The trial showed a low incidence of severe toxic effects (only 5%), indicating that personalized dosing strategies can minimize risks while maintaining effective treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Individualized Stereotactic Ablative Radiotherapy for Lung Tumors: The iSABR Phase 2 Nonrandomized Controlled Trial. Gensheimer, MF., Gee, H., Shirato, H., et al.[2023]

In a study of 84 patients with early-stage lung cancer treated with stereotactic body radiation therapy (SBRT), the incidence of radiation pneumonitis (RP) was low and similar between patients with and without previous lung surgery, indicating that SBRT is safe for those who have undergone anatomic lung resection.

While there was a trend towards increased pulmonary toxicity in patients with prior lung surgery, the overall rates of toxicity were low, and SBRT demonstrated comparable local control and survival outcomes for both groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of Pneumonitis After Stereotactic Body Radiation Therapy in Patients With Previous Anatomic Lung Resection. Hayes, JT., David, EA., Qi, L., et al.[2018]

Stereotactic body radiation therapy (SBRT) is emerging as a significant alternative to surgery for treating early-stage non-small cell lung cancer, demonstrating its potential effectiveness.

The study presents two cases where SBRT was used, and subsequent imaging and biopsies were conducted to monitor for recurrence, highlighting the importance of follow-up in assessing treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Illustrative cases of false positive biopsies after stereotactic body radiation therapy for lung cancer based on abnormal FDG-PET-CT imaging. Singhvi, M., Lee, P.[2023]

In a study comparing video-assisted thoracoscopic surgery (VATS) lobectomy and stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC), VATS lobectomy showed significantly better long-term outcomes, including overall survival (68.5% vs. 37.3% at 5 years) and recurrence-free survival (60.4% vs. 19.5% at 5 years).

The study involved 413 patients undergoing VATS lobectomy and 104 patients receiving SBRT, with a follow-up period of up to 120 months, indicating that VATS lobectomy may be a more effective treatment option for operable patients with early-stage NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Video-assisted thoracoscopic lobectomy versus stereotactic radiotherapy for stage I lung cancer. Hamaji, M., Chen, F., Matsuo, Y., et al.[2022]

In a study of 2373 patients with stage I non-small cell lung cancer, those who underwent lobectomy had better survival rates compared to those treated with stereotactic ablative radiotherapy (SABR) at both 1 and 2 years post-treatment.

Patients receiving SABR experienced significant delays in treatment (median of 73 days) compared to those undergoing surgery (median of 17 days), which may contribute to the poorer long-term outcomes associated with SABR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-treatment survival difference between lobectomy and stereotactic ablative radiotherapy in stage I non-small cell lung cancer in England. Khakwani, A., Harden, S., Beckett, P., et al.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy or stereotactic ablative radiotherapy versus surgery for patients with T1-3N0M0 non-small cell lung cancer: a systematic review and meta-analysis. [2022]

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

Stereotactic ablative radiotherapy (SABR) for non-small cell lung cancer. [2013]

3. Korea (South) pubmed.ncbi.nlm.nih.gov

Sublobar Resection versus Stereotactic Body Radiation Therapy for Clinical Stage I Non-Small Cell Lung Cancer: A Study Using Data from the Korean Nationwide Lung Cancer Registry. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy versus standard radiotherapy in stage 1 non-small-cell lung cancer (TROG 09.02 CHISEL): a phase 3, open-label, randomised controlled trial. [2022]

5. Singapore pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy versus lobectomy for stage I non-small cell lung cancer: A systematic review. [2018]

6. Ireland pubmed.ncbi.nlm.nih.gov

Biological equivalent dose is associated with radiological toxicity after lung stereotactic ablative radiation therapy. [2023]

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

Individualized Stereotactic Ablative Radiotherapy for Lung Tumors: The iSABR Phase 2 Nonrandomized Controlled Trial. [2023]

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

Risk of Pneumonitis After Stereotactic Body Radiation Therapy in Patients With Previous Anatomic Lung Resection. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Illustrative cases of false positive biopsies after stereotactic body radiation therapy for lung cancer based on abnormal FDG-PET-CT imaging. [2023]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Video-assisted thoracoscopic lobectomy versus stereotactic radiotherapy for stage I lung cancer. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Post-treatment survival difference between lobectomy and stereotactic ablative radiotherapy in stage I non-small cell lung cancer in England. [2022]