Clinical Investigation
Dose–Response Relationship for Image-Guided Stereotactic Body Radiotherapy of Pulmonary Tumors: Relevance of 4D Dose Calculation

https://doi.org/10.1016/j.ijrobp.2008.06.1939Get rights and content

Purpose

To evaluate outcome after image-guided stereotactic body radiotherapy (SBRT) for early-stage non–small-cell lung cancer (NSCLC) and pulmonary metastases.

Methods and Materials

A total of 124 patients with 159 pulmonary lesions (metastases n = 118; NSCLC, n = 41; Stage IA, n = 13; Stage IB, n = 19; T3N0, n = 9) were treated with SBRT. Patients were treated with hypofractionated schemata (one to eight fractions of 6–26 Gy); biologic effective doses (BED) to the clinical target volume (CTV) were calculated based on four-dimensional (4D) dose calculation. The position of the pulmonary target was verified using volume imaging before all treatments.

Results

With mean/median follow-up of 18/14 months, actuarial local control was 83% at 36 months with no difference between NSCLC and metastases. The dose to the CTV based on 4D dose calculation was closely correlated with local control: local control rates were 89% and 62% at 36 months for >100 Gy and <100 Gy BED (p = 0.0001), respectively. Actuarial freedom from regional and systemic progression was 34% at 36 months for primary NSCLC group; crude rate of regional failure was 15%. Three-year overall survival was 37% for primary NSCLC and 16% for metastases; no dose–response relationship for survival was observed. Exacerbation of comorbidities was the most frequent cause of death for primary NSCLC.

Conclusions

Doses of >100 Gy BED to the CTV based on 4D dose calculation resulted in excellent local control rates. This cutoff dose is not specific to the treatment technique and protocol of our study and may serve as a general recommendation.

Introduction

Stereotactic body radiotherapy (SBRT) is considered as the treatment of choice for patients with early stage non–small-cell lung cancer (NSCLC), who are inoperable because of medical comorbidities or who refuse surgical resection. However, there is still controversy about the SBRT treatment dose, which is sufficient to achieve local control. Multiple institutions published similar local control rates between 80% and >90% for a large range of treatment doses 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11. Differences in patient and tumor characteristics, length of follow-up, and definition of local failure may partially explain this inconsistent dose–response relationship.

Additional facts make a true comparison of data from the literature difficult. Uncertainties in treatment planning and delivery may result in large discrepancies between the prescribed/reported dose and the dose, which was actually delivered to the pulmonary tumor. A well-known uncertainty is breathing-induced tumor motion: gated treatment delivery, irradiation in breath hold, real-time tumor tracking, or addition of safety margins in free breathing are methods for compensation of this uncertainty (12). Because of large differences in density between the tumor and the surrounding lung tissue, the dose calculation algorithm is considered highly relevant in treatment planning (13). Internal variability of the tumor position independent from the bony anatomy and the stereotactic system was shown to result in reduced doses to the target unless these setup errors are corrected by image guidance (14).

This study describes a single institution experience of 124 patients treated with SBRT for early-stage NSCLC and pulmonary metastases. Dose response was calculated with consideration of the uncertainties breathing motion, dose calculation, and patient setup: the effects of tumor motion were estimated by four-dimensional (4D) dose calculation, heterogeneity correction with collapsed cone dose calculation algorithm was standard protocol, and setup errors at the time of treatment were minimized by routine computed tomography (CT)-based image guidance.

Section snippets

Methods and Materials

This retrospective single institution analysis is based on 124 consecutive patients treated for 159 pulmonary target volumes between 1997 and 2007. Patient and treatment characteristics are summarized in Table 1.

Local control

After mean/median follow-up of 18 months/14 months, actuarial local control rate was 83% at 36 months for the whole patient group. Local control was not different between early stage NSCLC and pulmonary metastases: 3-year actuarial local control rate was 84% and 82% for early-stage NSCLC and pulmonary metastases, respectively.

Table 2 shows all fractionation schedules with BED doses to the PTV based on 3D dose calculation and BED doses to the CTV based on 4D dose calculation. Treatment dose

Discussion

This retrospective single-institution study reports outcome of SBRT for early-stage NSCLC and pulmonary metastases. We correlated clinical outcome not only with prescribed doses based on 3D treatment planning, but also with the estimated doses that were actually delivered to the mobile pulmonary targets.

The collapsed cone algorithm was shown to be accurate for dose calculation in the thoracic region; differences between calculated and measured doses are acceptable 13, 20. Monte Carlo dose

Conclusions

Doses of >100 Gy BED to the CTV based on 4D dose calculation resulted in excellent local control rates for image-guided SBRT of primary early-stage NSCLC and pulmonary metastases. This cutoff dose is not specific to the treatment technique and protocol of our study, but may serve as a general recommendation.

References (35)

Cited by (174)

View all citing articles on Scopus

Conflict of interest: none.

View full text