External beam radiation therapy for bronchial stump recurrence of non-small-cell lung cancer after complete resection

Abstract

Background and purpose: External beam radiation therapy (EBRT) is occasionally used in the treatment of bronchial stump recurrences after complete surgical resection in patients with non-small-cell lung cancer (NSCLC), but no prospective study exists, so far. The objective of this review is to determine effectiveness of high-dose EBRT in this disease.

Methods: A systematic review was undertaken using electronic databases, reference lists and hand searching of journals to identify potentially eligible studies. Selection criteria included studies that provided outcome after high-dose EBRT in this disease. Six retrospective studies were reviewed, including a total of 54 patients.

Results and conclusion: High-dose EBRT appears to be an effective treatment modality for recurrent NSCLC confined to the bronchial stump after curative resection with a median survival time of approximately 30 months and 5-year survival of approximately 30%. Although small patient numbers and unclear indications for radical versus palliative EBRT may obscure the overall conclusions, among patients with intrathoracic recurrence those with bronchial stump recurrence only do better than those with non-stump recurrence. It seems there is a dose–response effect in this patient population and a predominantly local pattern of failure, both observations having an implication for future studies. The optimal dose/fractionation pattern or treatment fields must be further investigated in the future. Identification of an unfavourable subset of patients may help optimize treatment in the future by omitting high-dose, curative RT in those patients who may be best treated with palliative RT. Prospective studies on EBRT in both bronchial stump and other post-surgical recurrences are urgently needed.

Introduction

The treatment of choice for early stage non-small-cell lung cancer (NSCLC) is surgery, and this may also apply for a subset of patients with stage IIIA [26], [27]. There is an increasing possibility of using induction (neoadjuvant) chemotherapy and surgery in selected cases of locally advanced NSCLC [30], [32], [33]. It is, therefore, anticipated that more patients will be undergoing surgery alone or combined with chemotherapy in the future.

Although loco-regional recurrence is a well-documented event in these cases, occurrence of systemic failure in completely resected patients renders them incurable [31]. As the first site of failure, loco-regional recurrence can range from as low as 3–9% to as high as 32 or even 38% [8], [10], [11], [16], [22], [23], [35], [36], [37]. After curative resection, therefore, 5-year survival can be as high as 54–83% for stage I squamous cell carcinoma (SCC) but as low as 10–21% for stage IIIA adenocarcinoma [9], [24], [25].

Since the majority of post-surgical failures are distant ones, there have been few reports on the treatment of patients with isolated intrathoracic recurrence. Such patients have been treated with a more aggressive surgical approach [2], [5], [23], [28] or endobronchial irradiation [7]. Photodynamic therapy was shown to be ineffective in this patient population, especially those with bronchial stump recurrence. In a series by Lam et al. [19], as many as 75% patients with bronchial stump recurrence re-recurred after photodynamic therapy, despite achieving an initial response. However, there are also reports [1], [3], [6], [14], [15], [17], [18], [20], [21], [34], [38] indicating the effectiveness of radiation therapy (RT) when given as a sole treatment. As a rule, these reports covered long periods of time during which great variance in the diagnostic and radiotherapeutic approaches occurred. All of these series were concentrating on a number of different recurrent tumour locations, such as bronchial stump, lymph node, and chest wall/pleura, with a number of possible combinations between various locations included in these reports. These reports, therefore, inevitably suffered from a mixture of potentially different entities frequently treated with wide range of doses used and different fractionation patterns. Radiation therapy was also sometimes combined with chemotherapy or brachytherapy. All of these factors contributed to a confusing picture of the use of external beam (EB) RT in this disease, in spite of the fact that some reports clearly indicated effectiveness of EBRT with results showing at least similar effectiveness to those obtained with surgery. This was an observation of our previous report [14], too, and this review was undertaken to summarize the evidence about the role of EBRT alone in this disease, focusing on patients with bronchial stump recurrences after presumed complete resection of NSCLC.