This study summary is an excerpt from the book 2 Minute Medicine’s The Classics in Medicine: Summaries of the Landmark Trials
1. Stereotactic body radiotherapy (SBRT) achieved a 3 year local tumor control rate of 92% with limited toxicity, making SBRT a valuable treatment option in inoperable (and potentially even operable) patients
Original Date of Publication: July 2009
Study Rundown: Lung cancer is the most common cancer worldwide, and non-small cell lung cancer (NSCLC) accounts for the majority of cases. Surgical resection remains the mainstay of treatment for patients with stage I NSCLC approved for surgery. Historically, medically inoperable patients with NSCLC were managed with radiation therapy (RT) and showed poor five-year survival rates, presumably from insufficient doses. Phase II trials, however, have shown that SBRT – a method using precise targeted radiation to minimize radiation to adjacent tissue – produces tumor control rates even higher than surgical intervention. SBRT can thus administer biologic doses up to twice as high as RT without harmful affects to normal tissue. Though studies have shown good rates of local tumor control and toxicity for SBRT, the vast majority have been retrospective. Given the paucity of prospective trials and the lack of long-term follow-up data, application of SBRT remains limited. This multicenter prospective phase II study assessed the 36 month survival of NSCLC and evaluated tumor control, survival, and toxicity based on SBRT. The results indicate a tumor control rate similar to surgery in operative cases, a favorable 3 year cancer specific-survival rate, and minimal toxicity. The later Radiation Therapy Oncology Group (RTOG) 0236 trial from Timmerman et al. reported an even high rate of primary tumor control with minimal toxicity. It is noted that the optimal dose and schedule for SBRT is still undefined for treating NSCLC.
In-Depth [prospective cohort]: This prospective phase II study recruited 60 patients with medically inoperable stage I NSCLC, mainly due to COPD (60%) or cardiovascular disease (25%) across 7 centers in Nordic countries. Patients with prior malignancy or a primary tumor next to the trachea, main bronchus, or esophagus were excluded to ensure safety. After patients were referred to RT units, two were excluded based on insufficient radiation dose and one was lost to follow-up. The remaining 57 patients with NSCLC (70% T1N0M0 and 30% T2N0M0) were treated with SBRT using 6 MV from a linear accelerator, after defining the gross tumor volume (GTV, the size of the macroscopic tumor), clinical target volume (CTV, the volume of microscopic and gross malignant tissue), and planning target volume (PTV, the CTV plus a margin of safety around the tumor). CT was performed before each treatment to verify target reproducibility. Patients were then assessed with toxicity grading and chest CT or x-ray at 6 weeks, every 3 months for the first 18 months, and at 24 and 36 months following treatment. Lung function was measured at 3, 9, and 18 months using the Karnofsky performance score. After the study’s conclusion at 36 months, the Kaplan-Meier estimated progression-free survival rate was 52%. The lung cancer-specific survival rates at 1, 2, and 3 years were 93%, 88%, and 88%, respectively. The Kaplan-Meier estimated local tumor control at 3 years was 92%. Four patients (7%), all with T2N0M0 tumors, showed local tumor progression. No patient was lethally affected by SBRT and 14 patients (25%) had no pulmonary adverse effects.
Baumann P, Nyman J, Hoyer M, Wennberg B, Gagliardi G, Lax I, et al. Outcome in a Prospective Phase II Trial of Medically Inoperable Stage I Non–Small-Cell Lung Cancer Patients Treated With Stereotactic Body Radiotherapy. JCO. 2009 Jul 10;27(20):3290–6.
Timmerman R, Paulus R, Galvin J, Michalski J, Straube W, Bradley J, et al. Stereotactic Body Radiation Therapy for Inoperable Early Stage Lung Cancer. JAMA. 2010 Mar 17;303(11):1070–6.
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