SPACE – A randomized study of SBRT vs conventional fractionated radiotherapy in medically inoperable stage I NSCLC

doi:10.1016/j.radonc.2016.08.015

Radiotherapy and Oncology

Volume 121, Issue 1, October 2016, Pages 1-8

https://doi.org/10.1016/j.radonc.2016.08.015 Get rights and content

Abstract

Background

Stereotactic body radiotherapy (SBRT) has been introduced for small lung tumors due to excellent local control and few side effects, even though there are no comparative studies. SPACE (Stereotactic Precision And Conventional radiotherapy Evaluation) is the first randomized phase II trial comparing SBRT and conventional fractionated radiotherapy (3DCRT).

Methods

Patients with stage I medically inoperable NSCLC were randomized to receive SBRT to 66 Gy in 3 fractions (one week) or 3DCRT to 70 Gy (7 weeks). Patients were followed to assess efficacy, toxicity and HRQL.

Findings

Between 2007 and 2011, 102 patients were randomized. Mean age 74 (57–86), 60% women, the vast majority (92%) had COPD or cardiovascular comorbidity. The SBRT arm included more patients with T2-tumors (p = 0.02) and male gender (p = 0.35). The median follow-up was 37 months with a 1-, 2- and 3-year PFS of: SBRT: 76%, 53%, 42% and 3DCRT: 87%, 54% 42%, HR = 0.85 (95% CI 0.52–1.36) with no difference between the groups and no difference in OS (HR = 0.75, 95% CI 0.43–1.30). At the end of the study 70% of SBRT patients had not progressed compared to 59% (3DCRT, p = 0.26). Toxicity was low with no grade 5 events. Pneumonitis of any grade was observed in 19% (SBRT) and 34% (3DCRT, p = 0.26), and esophagitis in 8% and 30% respectively (p = 0.006).

HRQL was evaluated with the EORTC QLQ 30 and LC14 module and patients treated with 3DCRT experienced worse dyspnea (p = 0.01), chest pain (p = 0.02) and cough (>10 points difference).

Interpretation

There was no difference in PFS and OS between SBRT and conventionally treated patients despite an imbalance of prognostic factors. We observed a tendency of an improved disease control rate in the SBRT group and they experienced better HRQL and less toxicity. SBRT is convenient for patients and should be considered standard treatment for patients with inoperable stage I NSCLC.

Section snippets

Methods

The inclusion criteria were patients in WHO performance status zero to two with stage I (T_1–2N0M0, AJCC 6th edition) non-small cell lung cancer who were medically inoperable or refused surgery. The tumors should be morphologically verified. If that was impossible due to peripheral lesion and poor lung function (intolerance for pneumothorax), there had to be an increasing tumor size in repeated CT-scans and a positive PET-scan. The main exclusion criteria were central tumor growth adjacent to

Results

Between January 2007 and July 2011, 102 patients were randomized in nine Scandinavian centers to receive either SBRT to 66 Gy in three fractions during one week (n = 49, arm A) or conventionally fractionated 3DCRT to 70 Gy in 35 fractions during seven weeks (n = 53, arm B). The mean age was 74 years (range 57–86) and the population was 60% women. Significant comorbidity, COPD and/or cardiovascular disease, was seen in 92% of the patients. With regard to lung function, the mean FEV1 was 1.4L (range

Discussion

SBRT has become the recommended standard of care for medically inoperable patients with stage I NSCLC, for example in the ESMO guidelines [21], even though there is no randomized evidence for superiority over conventional therapy. However, favorable results in terms of local control (74–100%), low rate of grade three to five toxicities, and a stable quality of life post-treatment, have been reported for peripheral tumors in an extensive body of literature [3], [4], [5], [6], [7], [8], [9], [10]

Contributors

JN, RL and IL were involved in the study design. JN, AH, JÅL, OTB, PB, and SF ran the trial. BB was responsible for the quality of life analyses and EH for the statistics. All of the authors were responsible for data interpretation and analysis. JN and AH wrote the initial manuscript, with review and revisions made available to all of the authors.

Conflicts of interest

None of the authors have any relevant conflicts of interest to disclose.

Acknowledgements

This study was supported by grants from the Nordic Cancer Union, NCU, and King Gustav V Jubilee Clinic Cancer Foundation in Gothenburg. We would like to thank the co-investigators: Stefan Bergström Gävle Hospital, Britta Lödén Karlstad Central Hospital, Morten Høyer Århus University Hospital, Ninni Drugge Sahlgrenska University Hospital and Kristina Nilsson Uppsala University Hospital.

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Phase III randomised trialSPACE – A randomized study of SBRT vs conventional fractionated radiotherapy in medically inoperable stage I NSCLC

Abstract

Background

Methods

Findings

Interpretation

Section snippets

Methods

Results

Discussion

Contributors

Conflicts of interest

Acknowledgements

Lung Cancer

Int J Radiat Oncol Biol Phys

Lung Cancer

Int J Radiat Oncol Biol Phys

Radiother Oncol

J Thorac Oncol

Int J Radiat Oncol Biol Phys

Cancer Treat Rev

Lung Cancer

Int J Radiat Oncol Biol Phys

J Thorac Oncol

J Thorac Oncol

Radiother Oncol

Radiother Oncol

Ann Oncol

Int J Radiat Oncol Biol Phys

Phase III randomised trial
SPACE – A randomized study of SBRT vs conventional fractionated radiotherapy in medically inoperable stage I NSCLC