External irradiation versus external irradiation plus endobronchial brachytherapy in inoperable non-small cell lung cancer: a prospective randomized study
Introduction
Radiotherapy is an effective treatment modality in the palliation of most respiratory symptoms among patients with inoperable non-small cell lung cancer (NSCLC) [18], [20], [21], [26]. In two randomized studies conducted by the Medical Research Council (MRC) investigating different palliative schedules in inoperable NSCLC, the rates of symptom relief varied from 48 to 65% for cough, from 72 to 86% for haemoptysis and from 59 to 80% for chest pain [20], [21].
In a large number of studies, the results of endobronchial brachytherapy (EBB) with or without external irradiation (XRT) as palliative treatment for centrally localized lung cancer have been reported [5], [6], [11], [13], [22], [24], [30]. In earlier studies, EBB was particularly used as palliative treatment in case of endobronchial recurrences after XRT. In this category of patients, EBB offered adequate symptomatic relief in a substantial proportion of patients [3], [9], [12], [23], [24], [25], [27], [32]. Later, EBB was also combined with XRT as primary treatment [2], [6], [8], [30]. Speiser and co-workers [27] reported on a prospective study among 342 patients with endobronchial tumours treated by the combination of XRT (30 to 60 Gy) and concomitant EBB during week 1, 3 and 5. The results achieved with this approach were quite remarkable, with response rates of 99% for haemoptysis, 85% for cough and 86% for dyspnea. In a retrospective study, Chang and co-workers [6] reported comparable results with the combination of XRT (20 to 70 Gy) and concomitant EBB (3×7 Gy HDR) during week 2, 4 and 6. They observed response rates of 79% for cough, 95% for haemoptysis and 87% for dyspnea.
Many patients with centrally localized lung cancer present with post-obstructive pneumonia or atelectasis. With XRT alone, the proportion of patients in whom a partial or complete re-expansion of collapsed lung has been achieved varies from 21 to 61% [7], [19], [29]. With the combination of EBB and XRT, much higher rates of re-expansion have been observed, varying from 67 to 99% [2], [6], [30].
These results suggest that with the combination of XRT and EBB, post-obstructive features such as pneumonitis and atelectasis are likely to be treated more adequately compared to XRT alone. This could also account for the higher response rates for those respiratory symptoms associated with post-obstructive features, in particular, for dyspnea.
However, the definitions used for response of symptoms, re-expansion of collapsed lung, and the methods used to assess these responses, differed widely between the aforementioned studies. Moreover, the inclusion criteria of these studies differed widely and no randomized studies have been published investigating the additional value on palliation of respiratory symptoms of EBB plus XRT versus XRT alone. Therefore, the additional value of EBB concomitantly with XRT is not yet well defined.
This prospective randomized phase III study was conducted to test two specific hypotheses. Firstly, we expected that among patients with centrally localized NSCLC, the addition of concomitant EBB during XRT would result in higher rates of re-expansion of post-obstructive infiltration/atelectasis and/or higher rates of prevention of these post-obstructive features. Secondly, we expected that these higher rates of re-expansion would result in higher levels of palliation of respiratory symptoms, in particular for dyspnea and cough, as well as in greater levels of improvement in quality of life (QoL). Furthermore, the higher dose that can be administered with EBB to the endobronchial-obstructing tumour may lead to higher a degree of desobstruction and an additional beneficial effect on respiratory symptoms, even in the absence of an atelectasis.
Section snippets
Eligibility criteria
To be eligible for the study, patients had to have biopsy proven NSCLC, stage I, II, IIIa or IIIb disease according to the UICC 1992 [1], endobronchial tumour in the proximal main bronchus or lobar bronchus, a World Health Organization performance status 0–3 and no prior or planned chemotherapy, prior surgery, prior radiotherapy, other malignancies, pleuritis carcinomatosa, distant metastases or superior vena cava syndrome. Prior treatment with Neodymium-YAG laser was not allowed and,
Patient population
Between June 1994 and December 1998, 98 patients were randomized into the study. Unfortunately, the study was ended prematurely due to insufficient patient accrual. Of the 98 patients randomized, three were excluded because they did not fulfil the eligibility criteria of the study. The reasons for exclusion were the presence of distant metastases, cervical carcinoma in the history of one patient and no histologic confirmation of the diagnosis NSCLC. The analysis was based on the remaining 95
Discussion
In the present study, the additional value of early concomitant EBB during XRT was investigated with a prospective randomized design. The two treatment groups were well balanced concerning pre-treatment characteristics. The first hypothesis to be tested was whether the addition of EBB to XRT offered better rates of re-expansion of collapsed lung. Both methods used to evaluate this, i.e. radiological re-expansion and improvement of the inspiratory vital capacity showed that the level of
Acknowledgements
The assistance of Annet de Mol, who was responsible for the distribution and collection of the QoL questionnaires was greatly appreciated. Furthermore, we would like to thank the Dutch Cancer Society for supporting this study
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