18F-Deoxyglucose Uptake in Stage I Non–Small-Cell Lung Cancer: Time to Move to Randomized Trials
Authors: Dirk De Ruysscher
Journal: Journal of Thoracic Oncology (2013)

Stereotactic body radiotherapy (SBRT) or stereotactic ablative radiotherapy is increasingly used to treat early-stage non–small-cell lung cancer. In large series, at 5 years, control rates for the primary tumor were reported to be approximately 90%, regional control about 85%, whereas distant recurrences were observed in 20% of patients.1Senthi S Lagerwaard FJ Haasbeek CJ Slotman BJ Senan S Patterns of disease recurrence after stereotactic ablative radiotherapy for early stage non-small-cell lung cancer: a retrospective analysis.Lancet Oncol. 2012; 13: 802-809Abstract Full Text Full Text PDF PubMed Scopus (349) Google Scholar These results have been confirmed in many, including multicenter, reports.2Guckenberger M Allgäuer M Appold S et al.Safety and efficacy of stereotactic body radiotherapy for stage i non-small-cell lung cancer in routine clinical practice: a patterns-of-care and outcome analysis.J Thorac Oncol. 2013; 8: 1050-1058Crossref PubMed Scopus (159) Google Scholar Toxicity is mostly mild with less than 10% grade 3 adverse events. The patterns of failure after SBRT have been reported to be similar to those after lobectomy or pneumonectomy.3Robinson CG DeWees TA El Naqa IM et al.Patterns of failure after stereotactic body radiation therapy or lobar resection for clinical stage I non-small-cell lung cancer.J Thorac Oncol. 2013; 8: 192-201Crossref PubMed Scopus (92) Google Scholar Although randomized trials have not been reported, on comparison of prospective series, SBRT showed similar cancer control than sublobar resection but with a favorable toxicity.4Crabtree T Puri V Timmerman R et al.Treatment of stage I lung cancer in high-risk and inoperable patients: comparison of prospective clinical trials using stereotactic body radiotherapy (RTOG 0236), sublobar resection (ACOSOG Z4032), and radiofrequency ablation (ACOSOG Z4033).J Thorac Cardiovasc Surg. 2013; 145: 692-699Abstract Full Text Full Text PDF PubMed Scopus (125) Google Scholar Long-term results with radiofrequency ablation are lacking.4Crabtree T Puri V Timmerman R et al.Treatment of stage I lung cancer in high-risk and inoperable patients: comparison of prospective clinical trials using stereotactic body radiotherapy (RTOG 0236), sublobar resection (ACOSOG Z4032), and radiofrequency ablation (ACOSOG Z4033).J Thorac Cardiovasc Surg. 2013; 145: 692-699Abstract Full Text Full Text PDF PubMed Scopus (125) Google Scholar Whereas in early series the vast majority of patients had significant comorbidities, more recently borderline or undoubtedly operable patients also have been successfully treated with SBRT.5Shirvani SM Chang JY Roth JA Can stereotactic ablative radiotherapy in early stage lung cancers produce comparable success as surgery?.Thorac Surg Clin. 2013; 23: 369-381Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar It is clear that improving these outcomes will be challenging and will require the identification of patients at high risk for recurrence to select them for clinical trials. Ideally, prognostic factors that identify individuals at risk for either local, regional, or distant relapses would be needed. Increasing local tumor control simply by escalation of the radiotherapy dose is unlikely to affect the outcome.6van Baardwijk A Tomé WA van Elmpt W et al.Is high-dose stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC) overkill? A systematic review.Radiother Oncol. 2012; 105: 145-149Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar Indeed, the radiation doses that are delivered to typical small coin lesions such as three fractions of 18 Gy already exceed the levels required to kill all cancer cells. Data from a meta-analysis suggest that these high doses may even be an overkill for many patients with tumors up to 3 cm in diameter.6van Baardwijk A Tomé WA van Elmpt W et al.Is high-dose stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC) overkill? A systematic review.Radiother Oncol. 2012; 105: 145-149Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar If SBRT is delivered with appropriate techniques,7De Ruysscher D Faivre-Finn C Nestle U et al.European Organisation for Research and Treatment of Cancer recommendations for planning and delivery of high-dose, high-precision radiotherapy for lung cancer.J Clin Oncol. 2010; 28: 5301-5310Crossref PubMed Scopus (219) Google Scholar including motion management, it is more likely that individualizing the margins of microscopic extensions (the clinical target volume [CTV]) around the visible tumor (the gross tumour volume) may result in even lower local recurrences than observed in recent series. Computed tomography or 18F-deoxyglucose (FDG)-positron emission tomography (PET) image features can predict the CTV.8van Loon J Siedschlag C Stroom J et al.Microscopic disease extension in three dimensions for non-small-cell lung cancer: development of a prediction model using pathology-validated positron emission tomography and computed tomography features.Int J Radiat Oncol Biol Phys. 2012; 82: 448-456Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar,9Salguero FJ Belderbos JS Rossi MM Blaauwgeers JL Stroom J Sonke JJ Microscopic disease extensions as a risk factor for loco-regional recurrence of NSCLC after SBRT.Radiother Oncol. 2013; 109 (doi:pii: S0167-8140(13)00428-3. 10.1016/j.radonc.2013.08.028. [Epub ahead of print]): 26-31Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar These studies show that a significant proportion of tumors may have been irradiated with too small volumes and that incorporating these novel image features in the CTV definition may decrease failures resulting from geographical miss.9Salguero FJ Belderbos JS Rossi MM Blaauwgeers JL Stroom J Sonke JJ Microscopic disease extensions as a risk factor for loco-regional recurrence of NSCLC after SBRT.Radiother Oncol. 2013; 109 (doi:pii: S0167-8140(13)00428-3. 10.1016/j.radonc.2013.08.028. [Epub ahead of print]): 26-31Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar The results reported by Takeda and colleagues10Takeda A Sanuki N Fujii H et al.Maximum standardized uptake value on FDG-PET is a strong predictor of overall and disease-free survival for non-small-cell lung cancer patients after stereotactic body radiotherapy.J Thor Oncol. 2014; 9: 65-73Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar in this issue give insight on how FDG-PET-computed tomography data may be the basis for outcome improvement. In this retrospective series in 152 patients with early non–small-cell lung cancer treated with SBRT, the maximal standardized uptake value was a predictor for outcome. This included local control, regional recurrence, and distant metastases. Obviously, the maximal standardized uptake value thresholds that were identified in this retrospective series are not for standard clinical use and it may even be questioned whether this parameter will turn out to be the most optimal. Moreover, some patients definitely had noninvasive adenocarcinoma in situ, a disease that is associated with a better outcome and low FDG avidity. Nevertheless, this study adds to the existing literature11Satoh Y Onishi H Nambu A Araki T Volume-based parameters measured by using FDG PET/CT in patients with stage I NSCLC treated with stereotactic body radiation therapy: prognostic value.Radiology. 2013 Sep 12; ([Epub ahead of print])Google Scholar that on the basis of FDG-PET patients who need a more intensive treatment than current SBRT may be selected. As already mentioned, this may include other CTV margins, adjuvant irradiation on hilar and mediastinal lymph node regions, and adjuvant chemotherapy in fit patients. The time has come to move to randomized trials addressing these questions. This will ultimately result in a more tailored approach with even better outcome with SBRT.