Elsevier

Clinical Oncology

Volume 27, Issue 6, June 2015, Pages 353-361
Clinical Oncology

Original Article
Comparison of Single-fraction and Multi-fraction Stereotactic Radiotherapy for Patients with 18F-fluorodeoxyglucose Positron Emission Tomography-staged Pulmonary Oligometastases

https://doi.org/10.1016/j.clon.2015.01.004Get rights and content

Highlights

  • Sixty-five patients were staged with FDG-PET/CT and treated for 1-3 pulmonary oligometastases (n = 85) with SABR.

  • Overall survival at 1 and 2 years were 93% and 71%, respectively. The freedom from local failure at 1 and 2 years was 93%.

  • There were no significant differences between overall survival (P = 0.14), time to distant progression (P = 0.06) or toxicity rates (P = 0.75) between single- and multi-fraction cohorts.

  • We suggest updated R50% SABR conformity indices to use in future lung trials.

Abstract

Aim

To compare outcomes of single-fraction and multi-fraction stereotactic ablative body radiotherapy (SABR) for pulmonary metastases.

Materials and methods

A retrospective review from two academic institutions of patients with one to three pulmonary metastases staged with 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scans. For single-fraction SABR, 26 Gy was prescribed for peripheral targets and 18 Gy for central targets. In the multi-fraction cohort, 48 Gy/4 or 50 Gy/5 was prescribed for peripheral targets and 50 Gy/5 was prescribed for central targets. Three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) plans were delivered using heterogeneity corrections. Conformity indices at an intermediate dose (R50%) and at a high dose (R100%) were used to assess a relationship with the planning target volume (PTV). Overall survival, local and distant progression and toxicity rates were analysed from the date of treatment completion.

Results

Between February 2010 and June 2013, 65 patients with 85 pulmonary metastases were reviewed. The median follow-up was 2.1 years. Metastases most commonly originated from colorectal cancer (31%), followed by non-small cell lung cancer (25%). 3D-CRT was used in 52 targets, IMRT in 21 and VMAT in 12. 3D-CRT showed a lower median R50% (P = 0.01), but a higher median R100% than IMRT/VMAT (P = 0.04). The R50% index was inversely correlated to the PTV with all techniques (P = 0.01). Overall survival at 1 and 2 years in all patients was 93% (95% confidence interval 87–100%) and 71% (95% confidence interval 58–86%), respectively. The 2 year freedom from local and distant progression was 93% (95% confidence interval 86–100%) and 38% (95% confidence interval 27–55%), respectively. There were no significant differences between overall survival (P = 0 .14), time to distant progression (P = 0.06) or toxicity rates (P = 0.75) between single- and multi-fraction cohorts.

Conclusion

We report comparable local control, overall survival and toxicity rates between single-fraction and multi-fraction SABR treatments in patients with FDG-PET-staged pulmonary oligometastases. We propose a guideline for R50% conformity incorporating 3D-CRT/IMRT/VMAT techniques with heterogeneity corrected planning algorithms.

Introduction

The management of patients with distant metastases from solid tumours is usually conducted with palliative intent. On analysis of the Surveillance, Epidemiology, and End Results (SEER) database, the 5 year survival of patients with metastatic disease of common malignancies such as colorectal, breast and lung cancer was 7, 19 and 2%, respectively [1]. In Australia, the burden of disease for these malignancies in 2005 showed 4165 deaths from colorectal cancer, 2726 deaths from breast cancer and 7427 deaths from lung cancer [2], with most patients dying from metastatic rather than localised disease. Treatment predominantly involves palliative chemotherapy to address widespread disease without expectation of long-term survival. By contrast, Hellman and Weichselbaum [3] hypothesised the existence of an intermediate state between widespread metastatic disease and locally confined disease and coined the term ‘oligometastasis’. In this setting, targeted local therapies have procured significant long-term survival. Systematic reviews of the resection of hepatic metastases showed a 5 year survival of 25–30% [4], [5]. Similarly, a multinational registry of 5206 patients undergoing surgical resection of lung metastases showed a 5 year survival rate of 36%, with the median survival being 35 months [6].

Stereotactic ablative body radiotherapy (SABR) is a modern radiotherapy technique that is being increasingly utilised in the setting of patients with limited pulmonary ‘oligometastases’. In this context, SABR can result in effective local control and, in selected patients, long-term survival in patients with oligometastatic disease [7]. In comparison with surgery, it is non-invasive and associated with relatively low toxicity. SABR is a rapidly evolving technique that has been implemented widely throughout Europe, North America and Japan. A recent survey of 1600 American radiation oncologists showed that 63.9% of physicians used SABR, of whom nearly half adopted it in 2008 or later [8]. The lung was the most popular site of SABR use (89%), with the three- and four-fraction SABR schemes accounting for 68% of prescribed treatments. By contrast, a single-fraction approach is more commonly used by some institutions in Europe [9], [10], [11], [12], [13]. Stereotactic lung radiotherapy is an emerging technique in Australia and, similarly, several dose-fractionation schedules have been developed. There is little direct comparative evidence to suggest the superiority of one technique over the other.

The purpose of study was to critically assess the clinical outcomes of single- and multi-fraction SABR practices from two Australian academic institutions that use screening 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) as part of patient selection. The primary objective was to assess local control. Secondary objectives were to assess survival outcomes, time to distant failure and dosimetric factors associated with treatment techniques. Furthermore, we compared the high-dose conformity index (R100%) and the intermediate-dose conformity index (R50%) between treatment techniques to assess differences in SABR plan quality, as described by the Radiation Therapy Oncology Group (RTOG) [14].

Section snippets

Materials and Methods

This was an independent ethics board approved retrospective study of consecutive patients treated with SABR for pulmonary oligometastatic disease at the Peter MacCallum Cancer Centre (PMCC) and the Northern Sydney Cancer Centre (NSCC) between January 2010 and July 2013, using both institutional databases and medical chart review. Institutional policy at both centres was to screen all patients with FDG-PET/CT to exclude occult extrathoracic metastatic disease before treatment. Eligible patients

Results

Within the study period there were 65 patients included who were treated with SABR for a total of 85 pulmonary metastases. The median follow-up was 2.1 years. Metastases most commonly originated from colorectal cancer (31%), followed by non-small cell lung cancer (25%). The most common histology was adenocarcinoma (43%). In total, 23 patients (40%) had undergone prior pulmonary metastasectomy before referral for SABR. Systemic chemotherapy for metastatic disease was used in 13/65 patients

Discussion

When considering aggressive local therapies for metastatic disease, adequate patient selection is essential, irrespective of whether extirpative or ablative approaches are planned. The use of FDG-PET to exclude occult widespread metastatic disease is one strategy to improve the selection of those patients who would probably benefit from local therapies. In this cohort of patients undergoing pretreatment FDG-PET, the 2 year overall survival was 64%. These results are comparable with the 70%

Conclusions

We report comparable local control, overall survival and toxicity rates between single-fraction and multi-fraction SABR treatments in patients with pulmonary oligometastases. The use of FDG-PET staging to exclude occult extrapulmonary metastatic disease may allow for the selection of patients more likely to obtain favourable survival outcomes after SABR. Using heterogeneity-corrected planning algorithms we propose a suggested guideline for acceptable R50% conformity indices.

Acknowledgement

Shankar Siva received National Health and Medical Research Council scholarship funding for this research, APP1038399.

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