Aggravation of dyspnea in stage I non-small cell lung cancer patients following stereotactic body radiotherapy: Is there a dose-volume dependency?

Aarhus University Hospital, Aarhus, Central Jutland, Denmark
Acta Oncologica (Impact Factor: 3). 02/2006; 45(7):818-22. DOI: 10.1080/02841860600915314
Source: PubMed


In SBRT for NSCLC, highly potent radiation doses are delivered to patients with frequent pre-irradiatory compromise of pulmonary function. For the risk of pulmonary toxicity to be minimized during SBRT planning, data on its dose-volume dependency is needed. In the present study, we analyse the association of dose-volume histogram parameters with changes in dyspnea. The study concerns 28 medically inoperable stage I NSCLC patients that received SBRT at our department between 2000 and 2003. A central dose of 45 Gy/3 fractions was delivered in 5-8 days. WHO toxicity scoring of dyspnea was prospectively performed at baseline and during a 6-month follow-up post-SBRT. DVH parameters for pulmonary tissue were retrieved from the 3-D dose distributions. Aggravated dyspnea was registered in 11 patients (40%). We found no association between DVH parameters and changes in dyspnea. Nor did we find any consistent temporal variations of dyspnea after SBRT. We identified COPD as the factor showing the closest association with aggravation of dyspnea. The observed aggravation of dyspnea following SBRT reflects habitual exacerbations of COPD rather than treatment-related toxicity. Concern about pulmonary toxicity should not be prohibitive for future studies targeting limitations to dose and volume.

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Available from: Morten Høyer, Aug 06, 2014
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    • "Pulmonary function decline may be asymptomatic or transient in some patients.[45,49] In a study from Aarhus University, late dyspnea was not correlated to any dose-volume parameters, and no consistent temporal variations of dyspnea after SBRT were observed.[50] Worsening dyspnea was more attributable to pre-existing chronic obstructive pulmonary disease as opposed to late radiation effects. "
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    ABSTRACT: Stereotactic body radiation (SBRT) is an emerging tool in radiation oncology in which the targeting accuracy is improved via the detection and processing of a three-dimensional coordinate system that is aligned to the target. With improved targeting accuracy, SBRT allows for the minimization of normal tissue volume exposed to high radiation dose as well as the escalation of fractional dose delivery. The goal of SBRT is to minimize toxicity while maximizing tumor control. This review will discuss the basic principles of SBRT, the radiobiology of hypofractionated radiation and the outcome from published clinical trials of SBRT, with a focus on late toxicity after SBRT. While clinical data has shown SBRT to be safe in most circumstances, more data is needed to refine the ideal dose-volume metrics.
    Full-text · Article · Nov 2008 · Radiation Oncology
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    • "We could, however, not correlate the occurrence of pneumonitis or fibrosis with irradiated lung volumes or with doses. These findings are in conformity with other studies of SBRT where no relation between V20 and pneumontis has been proven [20] [30]. However, this is in contrast to the situation after conventionally fractionated radiotherapy where V20 > 25% is associated with an increased risk of radiation pneumonitis [31]. "
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    ABSTRACT: In a retrospective study using stereotactic body radiotherapy (SBRT) in medically inoperable patients with stage I NSCLC we previously reported a local control rate of 88% utilizing a median dose of 15Gyx3. This report records the toxicity encountered in a prospective phase II trial, and its relation to coexisting chronic obstructive pulmonary disease (COPD) and cardio vascular disease (CVD). Sixty patients were entered in the study between August 2003 and September 2005. Fifty-seven patients (T1 65%, T2 35%) with a median age of 75 years (59-87 years) were evaluable. The baseline mean FEV1% was 64% and median Karnofsky index was 80. A total dose of 45Gy was delivered in three fractions at the 67% isodose of the PTV. Clinical, pulmonary and radiological evaluations were made at 6 weeks, 3, 6, 9, 12, 18, and 36 months post-SBRT. Toxicity was graded according to CTC v2.0 and performance status was graded according to the Karnofsky scale. At a median follow-up of 23 months, 2 patients had relapsed locally. No grade 4 or 5 toxicity was reported. Grade 3 toxicity was seen in 12 patients (21%). There was no significant decline of FEV1% during follow-up. Low grade pneumonitis developed to the same extent in the CVD 3/17 (18%) and COPD 7/40 (18%) groups. The incidence of fibrosis was 9/17 (53%) and pleural effusions was 8/17 (47%) in the CVD group compared with 13/40 (33%) and 5/40 (13%) in the COPD group. SBRT for stage I NSCLC patients who are medically inoperable because of COPD and CVD results in a favourable local control rate with a low incidence of grade 3 and no grade 4 or 5 toxicity.
    Full-text · Article · Oct 2008 · Radiotherapy and Oncology
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    • "In a similar study by Paludan et al. [32] reporting dose-volume related parameters in a similar number of patients (N = 28), no relationship between DVH parameters and changes in dyspnea was found. They found that deterioration of lung function was more likely related to the patient co-morbidity (COPD) than to dose-volume related parameters. "
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    ABSTRACT: To determine the usefulness of dose volume histogram (DVH) factors for predicting the occurrence of radiation pneumonitis (RP) after application of stereotactic radiation therapy (SRT) for lung tumors, DVH factors were measured before irradiation. From May 2004 to April 2006, 25 patients were treated with SRT at the University of Tokyo Hospital. Eighteen patients had primary lung cancer and seven had metastatic lung cancer. SRT was given in 6-7 fields with an isocenter dose of 48 Gy in four fractions over 5-8 days by linear accelerator. Seven of the 25 patients suffered from RP of symptomatic grade 2-5 according to the NCI-CTC version 3.0. The overall incidence rate of RP grade2 or more was 29% at 18 months after completing SRT and three patients died from RP. RP occurred at significantly increased frequencies in patients with higher conformity index (CI) (p = 0.0394). Mean lung dose (MLD) showed a significant correlation with V5-V20 (irradiated lung volume) (p < 0.001) but showed no correlation with CI. RP did not statistically correlate with MLD. MLD had the strongest correlation with V5. Even in SRT, when large volumes of lung parenchyma are irradiated to such high doses as the minimum dose within planning target volume, the incidence of lung toxicity can become high.
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