Clinical Investigation
Adding Ipsilateral V20 and V30 to Conventional Dosimetric Constraints Predicts Radiation Pneumonitis in Stage IIIA–B NSCLC Treated With Combined-Modality Therapy

https://doi.org/10.1016/j.ijrobp.2009.01.036Get rights and content

Purpose

To determine lung dosimetric constraints that correlate with radiation pneumonitis in non–small-cell lung cancer patients treated with three-dimensional radiation therapy and concurrent chemotherapy.

Methods and Materials

Between June 2002 and December 2006, 97 patients with locally advanced non–small-cell lung cancer were treated with concomitant radiochemotherapy. All patients underwent complete three-dimensional treatment planning (including dose-volume histograms), and patients were treated only if the percentage of total lung volume exceeding 20 Gy (V20) and 30 Gy (V30), and mean lung dose (MLD) had not exceeded the constraints of 31%, 18%, and 20 Gy, respectively. The total and ipsilateral lung dose–volume histogram parameters, planning target volume, and total dose delivered were analyzed and correlated with pneumonitis incidence.

Results

If dose constraints to the total lung were respected, the most statistically significant factors predicting pneumonitis were the percentage of ipsilateral lung volume exceeding 20 Gy (V20ipsi), percentage of ipsilateral lung volume exceeding 30 Gy (V30ipsi), and planning target volume. These parameters divided the patients into low- and high-risk groups: if V20ipsi was 52% or lower, the risk of pneumonitis was 9%, and if V20ipsi was greater than 52%, the risk of pneumonitis was 46%; if V30ipsi was 39% or lower, the risk of pneumonitis was 8%, and if V30ipsi was greater than 39%, the risk of pneumonitis was 38%. Actuarial curves of the development of pneumonitis of Grade 2 or higher stratified by V20ipsi and V30ipsi were created.

Conclusions

The correlation between pneumonitis and dosimetric constraints has been validated. Adding V20ipsi and V30ipsi to the classical total lung constraints could reduce pulmonary toxicity in concurrent chemoradiation treatment. V20ipsi and V30ipsi are important if the V20 to the total lung, V30 to the total lung, and mean lung dose have not exceeded the constraints of 31%, 18%, and 20 Gy, respectively.

Introduction

In the overall treatment strategy for non–small-cell lung cancer (NSCLC) patients, the pulmonary toxicity is an important limiting factor. Several authors have previously explored the role of dosimetric predictive factors, such as the percentage of total lung volume exceeding a defined dose (Vdose) and mean lung dose (MLD), to plan for an optimized strategy to reduce radiation pneumonitis (RP) and/or escalate radiation dose. Among these, Graham et al.(1) and Hernando et al.(2) have correlated the value of percentage of lung volume exceeding 20 Gy (V20), percentage of lung volume exceeding 30 Gy (V30), and MLD stratifying the risk of RP developing.

Their data have been widely used by the community and have improved the way in which curative radiation doses are delivered. This applies, as well, in patients receiving concurrent chemoradiation (3).

Nevertheless, the role of concurrent chemotherapy to radiation in treating locally advanced NSCLC has been gaining substantial value in the recent years, and this has encouraged some authors to review their data and report the RP rate in patients receiving a multimodality treatment (4).

Paradoxically, the Vdose and MLD referring to both lungs as a single functional unit do not take into account the possible chances of an imbalance among the doses to the lung with the primary tumor and the contralateral lung; substantially, the final value of each dosimetric parameter is just a mean value for the total lung parenchyma. So, an extreme case could be characterized by no dose to the contralateral lung by concentrating the radiation beams on one lung.

The focus of this trial is to assess the relevance of ipsilateral dosimetric parameters on RP. We report the results of our experience in patients treated with concurrent chemoradiotherapy for NSCLC obtained by analyzing the value of adding ipsilateral V20 (V20ipsi), ipsilateral V30 (V30ipsi), and ipsilateral MLD (MLDipsi) to total lung volume constraints.

Section snippets

Methods and Materials

Between June 2002 and December 2006, after Institutional Review Board approval, 97 consecutive patients with locally advanced NSCLC underwent concomitant radiochemotherapy indicated and applied with radical or neoadjuvant (inductive) intent.

The patients' characteristics, tumor stage, and radiation dose delivered are shown in Table 1. Minimum follow-up was 6 months.

In all patients a history was obtained and physical examination and staging studies were performed. These included chest, upper

Results

After a median follow-up period of 29 months (range, 6–45 months), 14 of the 97 patients had RP of Grade 2 or higher, yielding a mean rate of 14.4% (Table 2). In the group of surgically resected patients, the incidence was 8.7% (4 of 46), whereas in the nonresected patients, it was 19.6% (10 of 51) (p = 0.15).

For the entire cohort, the lung injury arose after a median period of 79 days from the beginning of radiotherapy; in the surgical and nonsurgical groups, the median time was 123 and 55

Discussion

A review of published studies shows that the ideal dose–volume histogram metric for the prediction of the risk of RP has not yet been identified (14). However, it has been established with certainty that adding chemotherapy to radiation therapy will cause a rise in toxicity rate (4).

In the study of Graham et al.(1) half of the patients were treated with radiotherapy and half with radiochemotherapy. The incidence of pneumonitis was up to 20% at 24 months but just 7% if the V20 value was 31% or

References (22)

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    Citation Excerpt :

    In radiotherapy, the dose-volume relationship for the normal lung is one of the most important factors, and this has been evaluated using a dose-volume histogram (DVH) in previous studies of CCRT. The importance of the lung volume irradiated at ≥ 20 Gy (V20) has been established for radiation pneumonitis [7,10], and parameters such as V10, V30, and mean lung dose (MLD) have also been suggested as significant risk factors for radiation pneumonitis [7,10–19]. In the PACIFIC study, the incidence of pneumonitis was infrequent [2]; however, it is unclear if previous dose-volume parameters can be used for radiotherapy with durvalumab.

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Note—An online CME test for this article can be taken at http://asro.astro.org under Continuing Education.

Conflict of interest: none.

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