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Outcomes of Stereotactic Ablative Radiotherapy

October 1, 2012
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By Samir P. Kanani, MD, Associate Clinical Professor of Neurosurgery and Radiation Oncology, George Washington University, Radiation Oncology, Inova Fairfax Hospital, Falls Church, VA. Dr. Kanani reports no financial relationships relevant to this field of study.

Synopsis: Potentially operable patients with Stage I non-small cell lung cancer who were treated with stereotactic ablative radiotherapy (SABR) between 1993-2010 were retrospectively identified in a prospectively collected database. Despite the median age of 76 years and the median comorbidity score of 2 in these 177 potentially operable patients, the 3-year survival was 85%. Post-SABR 30-day mortality was 0%, while predicted 30-day mortality for a lobectomy, derived using the Thoracoscore predictive model, would have been 2.6%. Local control at 3 years was 93%. Regional and distant failure rates at 3 years were each 9.7%. Toxicity was mild, with grade ≥ 3 radiation pneumonitis and rib fractures in 2% and 3%, respectively. The outcomes in this SABR population compare well with previously reported surgical series.

Source: Lagerwaard FJ, et al. Outcomes of stereotactic ablative radiotherapy in patients with potentially operable Stage I non-small cell lung cancer. Int J Radiation Oncol Biol Phys 2012; 83:348-353.

While an anatomical surgical resection is considered the gold standard for patients with early-stage lung cancer, between one-third and two-thirds will not undergo a resection because of comorbid medical conditions and patient preference. Traditionally, these patients were treated with conventional fractionated radiotherapy alone to doses between 6000 and 7000 cGy. Many of these patients passed away within 3 years of their other medical problems; however, many suffered from symptomatic local recurrences. The use of conventionally fractionated radiotherapy for this medically inoperable group of patients has largely been replaced by stereotactic ablative radiotherapy (SABR). Local control rates of approximately 90% for Stage I non-small cell lung cancer are routinely reported in single and multicenter trials.1 These encouraging results in inoperable patients have led to at least two ongoing prospective, randomized trials evaluating SABR in operable patients as well as two single-arm Phase 2 trials that have yet to be reported. This series is a retrospective study of patients who were potentially resectable and who declined surgery at the VU medical center in the Netherlands.

The study cohort consisted of 706 patients who underwent SABR between 2003 and 2010 at the VU medical center for Stage IA-IB NSCLC who were entered into a prospective database. The database was retrospectively analyzed to determine a cohort of 177 patients who were potentially resectable with good pulmonary function (FEV1 > 50% predicted and DLCO > 50% predicted), WHO performance status 1 or 2, and lack of serious comorbidities precluding surgery such as recent myocardial infarction or renal failure. SABR was delivered as an outpatient in three (non-central and non-peripheral), five (peripheral adjacent to chest wall), or eight (central) fractions to a total dose of 60 Gy prescribed to the 80% isodose line depending on tumor size and location.

The majority of patients were Stage IA (60%). Two-thirds of patients did not have a biopsy, but nearly every patient had a positive PET scan. The patients who were treated without a biopsy had > 90% probability of malignancy based on a previously validated Dutch model. With a median follow-up of 31.5 months, the median overall survival (OS) for all patients was 61.5 months, with OS rates at 1 and 3 years of 94.7% and 84.7%, respectively. The actuarial local control rates at 1 and 3 years were 98% and 93%, respectively. In total, a relapse at any location (local, regional, or distant) was observed in 25 patients (14.1%) and was locoregional in nine patients. Three of those nine patients underwent lobectomy as salvage treatment, and another two patients received high-dose radiotherapy. Four patients received no salvage treatment. Freedom from any progression at 3 years was 81% both for patients with and without pathological verification.

No early side effects were reported by 42% of patients, and Grade 1 to 2 early side effects reported were fatigue (25%), cough (14%), local chest wall pain (11%), and dyspnea (10%), with some patients reporting more than one side effect. Severe late toxicity was uncommon, with Grade 3 radiation pneumonitis seen in four patients (2%). Rib fractures developed in five patients (3%). A total of 34 patients have died, and the cause of death could be determined in 29 patients. Of those patients, 14 patients died from disseminated lung cancer, six patients from cardiovascular events, four patients from other primary malignancies diagnosed after SABR, two patients from unrelated pulmonary hemorrhage, and two patients from renal failure. The 30-day mortality rate observed in the SABR cohort of 177 patients was 0%. In contrast, in these patients, the calculated 30-day mortality after lobectomy would have been 2.6% according to the Thoracoscore.2 The Thoracoscore is a validated prognostic model derived from an analysis of 10,122 patients undergoing thoracic surgery that estimates early mortality based on a number of clinical factors.

Commentary

The authors conclude that SABR results in local control and survival comparable to surgery and justify the current ongoing randomized trials comparing surgery to SABR. The results from this trial are on par with other reports from the literature demonstrating 3-year survival rates of 70-86%.3,4 The observed 3-year survival rate of 84.7% following SABR is comparable to that reported after surgery.5

One criticism of the series is that two-thirds of the patients were treated without a biopsy. The authors highlight surgical series where operations are done in Western European countries without a biopsy that demonstrate a low 4% rate of finding benign lesions. In addition, the current series found no difference in local control or survival in patients who were treated with or without pathologic confirmation.

The authors should be lauded for this retrospective review and their conclusions. Clearly, the authors are not recommending SABR in potentially operable patients, but they are adding to the growing body of literature regarding the use of SABR. It is likely that surgery will "cure" more patients than non-invasive radiotherapy when compared in randomized trials, but at what price? It is clear from the Thoracoscore model that some patients will suffer mortality and serious morbidity from surgery. Borderline resected patients should ideally be jointly evaluated by thoracic surgery and radiation oncology and the alternatives of surgery and SABR should be candidly discussed with patients. This will be even more salient as lung cancer screening becomes more widely accepted and early-stage lung cancers grow in prevalence. The results of ongoing Phase 2 and Phase 3 studies evaluating SABR and surgery are eagerly anticipated.

References

1. Timmerman R, et al. Stereotactic body radiation therapy for inoperable early stage lung cancer. JAMA 2010;303:1070-1076.

2. Falcoz PE, et al. The thoracic surgery scoring system (Thoracoscore): Risk model for in-hospital death in 15,18 patients requiring thoracic surgery. J Thorac Cardiovasc Surg 2007;133:325-332.

3. Uematsu M, et al. Computed tomography-guidedframeless stereotactic radiotherapy for stage I non-small cell lung cancer: A 5-year experience. Int J Radiat Oncol Biol Phys 2001;51:666-670.

4. Onishi H, et al. Stereotactic body radiotherapy (SBRT) for operable stage I non-small-cell lung cancer: Can SBRT be comparable to surgery? Int J Radiat Oncol Biol Phys 2010 (Epub).

5. Schuchert MJ, et al. Anatomic segmentectomy for stage I non-small-cell lung cancer: Comparison of video-assisted thoracic surgery versus open approach. J Thorac Cardiovasc Surg 2009;138:1318-1325.