Fast track — ArticlesNeoadjuvant chemotherapy and radiotherapy followed by surgery in selected patients with stage IIIB non-small-cell lung cancer: a multicentre phase II trial
Introduction
Management of locally advanced non-small cell lung cancer (NSCLC) remains a challenge.1, 2 Both local relapses and distant metastases are frequent, with 5-year survival of 3–17% for inoperable disease.3, 4, 5, 6, 7 Staging has historically subdivided stage III disease into clinical stage IIIA, thought to be potentially amenable to surgery, and stage IIIB, treated by definitive radiotherapy or radiochemotherapy. Clinical trials have repeatedly shown better outcomes with combined chemotherapy and radiotherapy, albeit with substantially increased acute toxicity.8, 9
In stage IIIA resectable disease, neoadjuvant chemotherapy seems to improve outcome.10, 11, 12, 13, 14, 15 Recent third-generation induction chemotherapy regimens have shown response rates of up to 60%.16, 17 The most important prognostic factors associated with prolonged survival were pathological mediastinal18, 19, 20 and tumour downstaging,13, 21 and complete resection.16, 18 Several trials assessing induction chemoradiotherapy followed by surgery have also included patients with stage IIIB disease. Retrospective subgroup analyses of these trials, particularly Southwest Oncology Group (SWOG) 8805,18 suggest that patients with operable stage IIIB NSCLC have outcomes similar to those with stage IIIA disease.
Progress in anaesthesia coupled with improved surgical techniques by specialised thoracic surgery units has enabled surgical limits to be expanded. Among patients with locally advanced stage IIIB NSCLC, there is a subgroup whose tumours are technically amenable to complete resection, such as localised N3 or T4 disease with involvement of the carina, the pulmonary artery, vertebral bodies, or the vena cava. Recent surgical series suggested encouraging survival rates in patients with stage IIIB disease after induction chemoradiotherapy.22, 23, 24, 25
Based on previous experience in patients with stage IIIA and N2 disease,16, 19 and in patients with operable stage IIIB disease,26 we aimed to improve outcomes in patients with operable stage IIIB disease by use of an integrated trimodality approach of neoadjuvant chemotherapy, using a modern platinum-based chemotherapy combined with docetaxel, immediately followed by accelerated concomitant boost radiotherapy (44 Gy in 22 fractions over 3 weeks) and surgical resection. To improve tolerability, a rapid sequential rather than concurrent chemoradiotherapy scheme was chosen. Our aim was to show that such an approach is feasible and safe, and to assess the outcome of selected patients presenting with locally advanced stage IIIB disease.
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Patients
This open-label, multicentre, prospective phase II trial by the Swiss Group for Clinical Cancer Research (SAKK) was done in seven participating medical centres. Patients with potentially operable stage IIIB3 (T1–4, N3, M0 or T4, N0–3, M0) NSCLC were eligible for inclusion. N3 disease was considered technically operable when resection could be attempted with standard thoracotomy without additional sternotomy. Presence of malignant pleural or pericardial effusion or supraclavicular lymph-node
Results
Between September, 2001, and May, 2006, 46 patients with potentially resectable stage IIIB NSCLC were enrolled. Two patients were retrospectively considered ineligible due to the presence of metastatic disease at baseline, but all results are reported on an intention-to-treat basis including these patients. The baseline patient characteristics are shown in table 1. Most patients had good performance status. Squamous-cell carcinoma was the predominant histology (43%). Stage distribution at
Discussion
The data presented here suggest that treatment with chemotherapy and radiotherapy followed by surgery is feasible in selected patients with stage IIIB NSCLC, and might provide long-term survival and cure.
About a third of patients with newly diagnosed NSCLC present with locally advanced disease, 10–15% as stage IIIB disease.3 The optimum management of these patients remains controversial: American Society of Clinical Oncology and other treatment guidelines recommend definitive chemotherapy and
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2022, ESMO OpenCitation Excerpt :In addition, prognostic factors associated with improved outcomes were explored. The detailed study designs, inclusion and exclusion criteria, and methods of the SAKK 16/96, 16/00, 16/01, and 16/08 studies have been previously published.4-7 In brief, these studies were designed for operable stage III NSCLC, both stage IIIA N2 and IIIB.
Comparison of early tumour-associated versus late deaths in patients with central or >7 cm T4 N0/1 M0 non-small-cell lung-cancer undergoing trimodal treatment: Only few risks left to improve
2020, European Journal of CancerCitation Excerpt :grade 5 (pulmonary embolism and acute cor pulmonale 2 d after intervention) (Table 6). OS rates in the present study demonstrate a more favourable outcome for cT4 N0 M0 NSCLCs after induction radiochemotherapy and resection compared with previous trials [22,23]. Stupp et al. found a 5-year OS rate of 40% in a group of 46 patients with cT1-4 N2-3 M0 and T4 N0-1 M0 NSCLC [22].