Surgery vs Stereotactic Radiotherapy for Lung Cancer

(VALOR Trial)

Recruiting at 15 trial locations

Overseen By Matt Leiner, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Disqualifiers: Metastasis, Prior lung cancer, others

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

Compensation: Varies

Number of Visits: 7

Duration: Varies based on treatment type

670 Participants Needed

Trial Summary

What is the purpose of this trial?

Patients with stage I non-small cell lung cancer have been historically treated with surgery whenever they are fit for an operation. However, an alternative treatment known as stereotactic radiotherapy now appears to offer an equally effective alternative. Doctors believe both are good treatments and are therefore conducting this study to determine if one may be possibly better than the other.

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 this treatment for lung cancer?

Research shows that stereotactic ablative radiotherapy (SABR) is a standard treatment for early-stage non-small cell lung cancer (NSCLC) and offers similar local control and safety compared to surgery, especially for patients who cannot undergo surgery. SABR has been shown to improve tumor control and overall survival in patients with primary and secondary lung tumors. ^{1 2 3 4 5}

Is stereotactic radiotherapy safe for treating lung cancer?

Stereotactic radiotherapy, also known as SABR or SBRT, is generally safe for treating lung cancer, but it can cause some side effects, including potential damage to nearby structures. While serious toxic effects are rare, some patients may experience changes that require long-term management. ^{2 6 7 8 9}

How does the treatment of surgery vs stereotactic radiotherapy for lung cancer differ from other treatments?

Stereotactic radiotherapy (SBRT/SABR) is a non-invasive treatment that delivers high doses of radiation with precision over a few sessions, making it a suitable option for patients who cannot undergo surgery. It offers similar outcomes to surgery for early-stage non-small cell lung cancer (NSCLC), especially for those who are medically inoperable, providing an alternative to the traditional surgical removal of lung tissue. ^{2 3 10 11 12}

Research Team

Drew Moghanaki, MD MPH

Principal Investigator

VA Greater Los Angeles Healthcare System, West Los Angeles, CA

David H Harpole, MD

Principal Investigator

Durham VA Medical Center, Durham, NC

Eligibility Criteria

This trial is for adults over 18 with stage I Non-Small Cell Lung Cancer (NSCLC) that's less than or equal to 5cm, confirmed by biopsy or imaging. They must be fit for surgery or stereotactic radiotherapy, have a Karnofsky performance status of at least 70, and no history of certain cancers or thoracic treatments. Pregnant women and those with metastatic disease are excluded.

Inclusion Criteria

I am considered fit for lung surgery that is not a wedge resection.

I am 18 years old or older.

I have or am suspected to have early-stage lung cancer.

Exclusion Criteria

I have had cancer before, but it wasn't follicular lymphoma, chronic lymphocytic leukemia, or hormone-sensitive prostate cancer.

I am a woman under 61 or haven't had a hysterectomy and my pregnancy test is positive.

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either stereotactic radiotherapy or undergo surgery based on randomization

Varies based on treatment type

Multiple visits for treatment sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Regular visits every 6 months

Long-term follow-up

Participants are monitored for overall survival and lung cancer mortality

Up to 10 years

Treatment Details

Interventions

• Anatomic Pulmonary Resection
• Stereotactic Radiotherapy

Trial Overview The study compares two treatments for early-stage lung cancer: traditional lung surgery (anatomic pulmonary resection) versus a newer approach called stereotactic radiotherapy. It aims to find out which treatment might be better by randomly assigning participants to one of the two options.

Participant Groups

Group I: Stereotactic radiotherapy Experimental Treatment 1 Intervention

Stereotactic radiotherapy is an FDA approved treatment for lung cancer. However, for purposes of this study, it is being delivered to an operable population that is typically treated with surgical resection. Participants randomized to stereotactic radiotherapy will be treated according to the location of the tumor. Peripheral tumors will receive either 18 Gy x 3, 14 Gy x 4, or 11.5 Gy x 5 fractions, while central tumors will be treated with 10 Gy x 5. There will not be any elective coverage of local microscopic spread or regional lymph nodes.

Group II: Surgery Active Control 1 Intervention

Participants randomized to surgery will undergo a standard lobectomy or limited anatomic pulmonary resection (segmentectomy) under general anesthesia. Non-anatomic (wedge) resections are not permitted. Pathological specimens must contain a separately divided pulmonary artery and bronchus, as well as sampled lymph nodes from mediastinal lymph node stations. Participants found to have incidental nodal involvement after surgery will be referred for adjuvant chemotherapy, with our without postoperative radiotherapy.

Anatomic Pulmonary Resection is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Anatomic Pulmonary Resection for:

• Non-small cell lung cancer
• Stage I lung cancer

Approved in United States as Anatomic Pulmonary Resection for:

• Non-small cell lung cancer
• Stage I lung cancer

Approved in Canada as Anatomic Pulmonary Resection for:

• Non-small cell lung cancer
• Stage I lung cancer

Approved in Japan as Anatomic Pulmonary Resection for:

• Non-small cell lung cancer
• Stage I lung cancer

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Findings from Research

Stereotactic ablative radiotherapy (SABR) is the standard treatment for medically inoperable early-stage non-small cell lung cancer (ES-NSCLC) and has shown benefits over lower-dose radiotherapy regimens.

While SABR is generally safe and cost-effective, it can lead to increased toxicity in patients with tumors near the tracheobronchial tree or those with interstitial lung disease, highlighting the need for careful patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiation therapy in lung cancer: an emerging standard. Mutsaers, A., Chen, H., Louie, AV.[2019]

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]

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]

In a phase 2 trial involving 40 patients with early-stage non-small cell lung cancer (NSCLC), neoadjuvant stereotactic ablative radiotherapy (SABR) resulted in a pathologic complete response (pCR) rate of 60%, indicating a significant tumor response but lower than expected.

The combined approach of neoadjuvant SABR followed by surgery showed no perioperative mortality and manageable toxicity, with a 2-year overall survival rate of 77%, suggesting it is a safe option for patients fit for surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measuring the Integration of Stereotactic Ablative Radiotherapy Plus Surgery for Early-Stage Non-Small Cell Lung Cancer: A Phase 2 Clinical Trial. Palma, DA., Nguyen, TK., Louie, AV., et al.[2022]

Stereotactic ablative body radiotherapy (SABR) is a significant advancement in radiotherapy that has been shown to improve tumor control and overall survival in patients with lung tumors.

The review highlights the current evidence supporting the efficacy of SABR for both primary and secondary lung tumors, along with ongoing trials that may further validate its benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative body radiotherapy (SABR) for primary and secondary lung tumours. Goldsmith, C., Gaya, A.[2022]

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 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]

Stereotactic body radiotherapy (SBRT) for lung tumors near the pulmonary hilum showed promising safety and efficacy, with 1-year and 2-year overall survival rates of 90.0% and 62.2%, respectively, based on a study of 21 patients.

While SBRT was generally well-tolerated, severe late toxicity occurred in three patients, highlighting the importance of careful planning to avoid multiple treatments to the same bronchus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy for lung tumors at the pulmonary hilum. Oshiro, Y., Aruga, T., Tsuboi, K., et al.[2021]

In a study of 40 patients with central and ultracentral non-small cell lung cancer (NSCLC) treated with stereotactic ablative radiotherapy (SABR), those with ultracentral tumors experienced worse overall survival (OS) and progression-free survival (PFS) compared to those with central tumors, indicating a need for careful consideration in treatment planning.

The incidence of severe treatment-related toxicities (grade ≥3) was higher in the ultracentral group, with 12.5% of patients experiencing significant complications, including severe bronchial obstruction and esophageal perforation, highlighting the potential risks associated with SABR in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes in patients with central and ultracentral non-small cell lung cancer treated with stereotactic body radiotherapy: single-institution experience. Song, X., Zhao, L., Jiang, N., et al.[2023]

In a study of 340 patients with early-stage non-small-cell lung cancer (NSCLC), both surgery and stereotactic ablative radiotherapy (SABR) showed similar overall survival rates, indicating that SABR is a viable alternative for patients who cannot undergo surgery.

However, SABR was associated with significantly higher rates of locoregional recurrences compared to surgery, particularly due to more nodal failures, highlighting the need for better staging and treatment strategies for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patterns of Recurrence and Survival after Surgery or Stereotactic Radiotherapy for Early Stage NSCLC. van den Berg, LL., Klinkenberg, TJ., Groen, HJM., et al.[2022]

Surgery and stereotactic ablative radiotherapy (SABR) show comparable outcomes in treating early-stage non-small cell lung cancer (ES-NSCLC), indicating that both options are viable.

A multidisciplinary team approach that emphasizes shared decision-making is recommended for patients, allowing for personalized treatment choices based on individual circumstances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy and surgery: two gold standards for early-stage non-small cell lung cancer? Chen, H., Louie, AV.[2020]

In a study comparing 462 surgical patients and 76 patients treated with stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer, surgical patients had better overall health and local tumor control, with a 5-year survival rate of 55% compared to 32% for SBRT.

However, when adjusting for patient characteristics through propensity score matching, both treatment methods showed similar rates of local recurrence and disease-specific survival, indicating that SBRT can be a viable alternative for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy versus surgical resection for stage I non-small cell lung cancer. Crabtree, TD., Denlinger, CE., Meyers, BF., et al.[2022]

References

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

Stereotactic ablative radiation therapy in lung cancer: an emerging standard. [2019]

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

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

3. 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]

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

Measuring the Integration of Stereotactic Ablative Radiotherapy Plus Surgery for Early-Stage Non-Small Cell Lung Cancer: A Phase 2 Clinical Trial. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Stereotactic ablative body radiotherapy (SABR) for primary and secondary lung tumours. [2022]

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

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

7. Ireland pubmed.ncbi.nlm.nih.gov

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

8. Germany pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy for lung tumors at the pulmonary hilum. [2021]

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

Long-term outcomes in patients with central and ultracentral non-small cell lung cancer treated with stereotactic body radiotherapy: single-institution experience. [2023]

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

Patterns of Recurrence and Survival after Surgery or Stereotactic Radiotherapy for Early Stage NSCLC. [2022]

11. China pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy and surgery: two gold standards for early-stage non-small cell lung cancer? [2020]

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

Stereotactic body radiation therapy versus surgical resection for stage I non-small cell lung cancer. [2022]