Lung cancer radiotherapy
Dose to heart substructures is associated with non-cancer death after SBRT in stage I–II NSCLC patients

https://doi.org/10.1016/j.radonc.2017.04.017Get rights and content

Abstract

Background and purpose

To investigate potential associations between dose to heart (sub)structures and non-cancer death, in early stage non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiation therapy (SBRT).

Methods

803 patients with early stage NSCLC received SBRT with predominant schedules of 3 × 18 Gy (59%) or 4 × 12 Gy (19%). All patients were registered to an average anatomy, their planned dose deformed accordingly, and dosimetric parameters for heart substructures were obtained. Multivariate Cox regression and a sensitivity analysis were used to identify doses to heart substructures or heart region with a significant association with non-cancer death respectively.

Results

Median follow-up was 34.8 months. Two year Kaplan–Meier overall survival rate was 67%. Of the deceased patients, 26.8% died of cancer. Multivariate analysis showed that the maximum dose on the left atrium (median 6.5 Gy EQD2, range = 0.009–197, HR = 1.005, p-value = 0.035), and the dose to 90% of the superior vena cava (median 0.59 Gy EQD2, range = 0.003–70, HR = 1.025, p-value = 0.008) were significantly associated with non-cancer death. Sensitivity analysis identified the upper region of the heart (atria + vessels) to be significantly associated with non-cancer death.

Conclusions

Doses to mainly the upper region of the heart were significantly associated with non-cancer death. Consequently, dose sparing in particular of the upper region of the heart could potentially improve outcome, and should be further studied.

Section snippets

Patient characteristics

From 2005 to 2013, 1337 patients with mostly peripheral, inoperable stage T1a–T2bN0 NSCLC were treated with SBRT in five different international institutes (The Netherlands Cancer Institute, Amsterdam, The Netherlands; William Beaumont Hospital, Royal Oak, Michigan; University of Wuerzburg, Wuerzburg, Germany; Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada; and Thomas Jefferson University Hospital, Philadelphia, PA). Eight-hundred and three patients were included (

Results

Patient characteristics: Four-hundred and thirty-one were male, 372 female, with a median age of 74.8 years (41–92 years). The median tumor diameter was 2.24 cm (0.7–7 cm), 3% of patients had a tumor >5 cm. Sixteen percent of patients had a central tumor (within 2 cm of the proximal bronchus, RTOG 0236 definition). Tumors were mostly located in the upper lobes (63.6%).

The median follow-up was 34.8 months (range 0.1–121.5) calculated using the Kaplan–Meier method [12]. The 2 year Kaplan–Meier overall

Discussion

In this analysis of 803 early stage NSCLC patients treated with SBRT, doses to most heart substructures were significantly associated with non-cancer death, where doses to the left atrium and superior vena cava showed the strongest significant association after a multivariate analysis. Strong correlations between doses to the various heart substructures make it difficult to obtain dose constraints, and this work was not designed to obtain these. However, this work does show that the doses to

Conflict of interest

This work was sponsored in part by a research grants from Elekta Oncology Systems Ltd.

Co-author Nicolette O'Connell is an employee of Elekta Oncology Systems Ltd.

Acknowledgements

This work was sponsored in part by a research grant from the Dutch Cancer Society (NKI 2009-4568).

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