Randomized Controlled Trial of Resection Versus Radiotherapy After Induction Chemotherapy in Stage IIIA-N2 Non-Small-Cell Lung Cancer

Meerbeeck, Jan P. van; Kramer, G.; Schil, Paul Van; Legrand, Catherine; Smit, Egbert F.; Schramel, Franz M.N.H.; Tjan‐Heijnen, Vivianne C. G.; Biesma, Bonne; Debruyne, Channa; Zandwijk, Nico van; Splinter, Ted A.W.; Giaccone, Giuseppe

doi:10.1093/jnci/djk093

Cited by 633 publications

(320 citation statements)

References 29 publications

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“…[4][5][6][7][8] More recently, van Meerbeeck et al conducted a phase 3 trial that investigated the role of surgery versus radiotherapy after induction chemotherapy in 579 patients with pathologically documented stage IIIA, N2, NSCLC. 16 Patients received 3 cycles of platinum-based chemotherapy, and nonprogressors were then randomized for surgery (n ¼ 164) or thoracic radiotherapy (n ¼ 165). The median and 5-year OS values for patients assigned to the resection group versus the radiotherapy group were 16.4 versus 17.5 months and 15.7% versus 14%, respectively (HR ¼ 1.06 [95% CI ¼ 0.84-1.35]).…”

Section: Discussionmentioning

confidence: 99%

A phase 3 study of induction treatment with concurrent chemoradiotherapy versus chemotherapy before surgery in patients with pathologically confirmed N2 stage IIIA nonsmall cell lung cancer (WJTOG9903)

Katakami

Tada

Mitsudomi

et al. 2012

Cancer

114

107

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BACKGROUND: This study sought to ascertain whether induction-concurrent radiotherapy added to chemotherapy could improve the survival of patients undergoing surgery for stage IIIA N2 nonsmall cell lung cancer (NSCLC). METHODS: Patients with pathologically proven N2 disease were randomized to receive either induction chemotherapy (docetaxel 60 mg/m 2 and carboplatin AUC [area under the receiver operating characteristic curve] ¼ 5 for 2 cycles) plus concurrent radiation therapy (40 Gy) followed by surgery (CRS arm) or induction chemotherapy followed by surgery (CS arm). They subsequently underwent pulmonary resection when possible. RESULTS: Sixty patients were randomly assigned between December 2000 and August 2005. The study was prematurely terminated in January 2006 because of slow accrual. The most common toxicity was grade 3 or 4 leukopenia in 92.9% of patients in the CRS arm and 46.4% in the CS arm. Induction therapy was generally well tolerated, and there were no treatment-related deaths in either arm. Downstaging in the CS arm and CRS arm was 21% and 40%, respectively. The progression-free survival (PFS) and overall survival (OS) in the CS arm were 9.7 months and 29.9 months (PFS, hazard ratio [HR] ¼ 0.68, P ¼ .187), and those in the CRS arm were 12.4 months and 39.6 months (OS, HR ¼ 0.77, P ¼ .397), respectively. The PFS with and without downstaging was 55.0 and 9.4 months, respectively (HR ¼ 3.39, P ¼ .001). The OS with and without downstaging was 63.3 and 29.5 months, respectively (HR ¼ 2.62, P ¼ .021). CONCLUSIONS: The addition of radiotherapy to induction chemotherapy conferred better local control without significant adverse events. Tumor downstaging is important for prolonging the OS in patients with stage IIIA (N2) NSCLC. Cancer 2012;118:6126-35.

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Section: Discussionmentioning

confidence: 99%

A phase 3 study of induction treatment with concurrent chemoradiotherapy versus chemotherapy before surgery in patients with pathologically confirmed N2 stage IIIA nonsmall cell lung cancer (WJTOG9903)

Katakami

Tada

Mitsudomi

et al. 2012

Cancer

114

107

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“…For many years thoracic surgeons and oncologists have been debating the role of surgery in this group of patients. A randomised controlled trial of lung resection versus radiotherapy after induction chemotherapy in patients with stage IIIA disease, published in 2007, showed no survival benefit in the surgical arm [90]. Thoracic surgeons have argued that, in this trial, the mediastinal nodal status was not reassessed routinely by mediastinoscopy and that the N2 group is an heterogeneous group of patients with some having a better prognosis than others.…”

Section: N2 Diseasementioning

confidence: 97%

“…The role of surgery in patients with N2 disease remains controversial [87,89,90]. For many years thoracic surgeons and oncologists have been debating the role of surgery in this group of patients.…”

Section: N2 Diseasementioning

confidence: 99%

“…Thoracic surgeons have argued that, in this trial, the mediastinal nodal status was not reassessed routinely by mediastinoscopy and that the N2 group is an heterogeneous group of patients with some having a better prognosis than others. It is recognised that patients who present with bulky N2 disease at clinical staging have a different prognosis from those with microscopic N2 disease diagnosed at thoracotomy or final pathology [90]. Although patients with multiple and bulky N2 disease are certainly not ideal surgical candidates, those with single station N2 disease, especially station 5 or 6 and left upper lobe cancer and station 4R and right upper lobe cancer, represent a subgroup of patients likely to benefit from surgical resection as part of multimodality therapy [91].…”

Section: N2 Diseasementioning

confidence: 99%

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Surgery for nonsmall cell lung cancer

Lang-Lazdunski

2013

European Respiratory Review

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Surgery remains the best curative option in patients with early stage lung cancer (stage I and II). Developments in minimally invasive techniques now allow surgeons to perform lung resections on elderly patients, patients with poor pulmonary function or significant cardiopulmonary comorbidities. New techniques, such as stereotactic radiotherapy and ablative procedures, are being evaluated in early-stage lung cancer and may represent an alternative to surgery in patients unfit for lung resection. Perioperative mortality rates have dropped significantly at most institutions in the past two decades and complications are managed more efficiently. Progress in imaging and staging techniques have helped cut futile thoracotomy rates and offer patients the most adequate treatment options. Large randomised trials have helped clarify the role of neoadjuvant, induction and adjuvant chemotherapy, as well as radiotherapy. Surgery remains an essential step in the multimodality therapy of selected patients with advanced-stage lung cancer (stage III and IV). Interventional and endoscopic techniques have reduced the role of surgery in the diagnosis and staging of nonsmall cell lung cancer, but surgery remains an important tool in the palliation of advanced-stage lung cancer. Large national/international surgical databases have been developed and predictive risk-models for surgical mortality/morbidity published by learned surgical societies. Nonetheless, lung cancer overall survival rates remain deceptively low and it is hoped that early detection/screening, better understanding of tumour biology and development of biomarkers, and development of efficient targeted therapies will help improve the prognosis of lung cancer patients in the next decade. @ERSpublications Despite progress in surgical techniques, radiotherapy techniques and targeted therapy, lung cancer prognosis remains poor

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“…therapy following induction chemotherapy (18). However, the different selection criteria determining the optimal approach may be difficult to evaluate, due to the significant heterogeneity among N2 patients.…”

Section: Patient No (%) --------------------------------------------mentioning

confidence: 99%

Surgery following neoadjuvant chemotherapy for non-small-cell lung cancer patients with unexpected persistent pathological N2 disease

Duan

Jiang

et al. 2015

Molecular and Clinical Oncology

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Abstract.Patients with mediastinal lymph node (LN) downstaging following neoadjuvant chemotherapy exhibit improved outcomes compared with patients with persistent N2 disease. The aim of this study was to compare clinicopathological characteristics and survival between patients with unexpected and expected persistent N2 disease following surgery for non-small-cell lung cancer (NSCLC). This retrospective analysis included 348 patients with NSCLC who underwent surgery following chemotherapy at the Shanghai Pulmonary Hospital, Tongji University School of Medicine, between 1995 and 2012. According to the results of the imaging examinations and postoperative pathology, the patients were divided into three groups, namely groups I (nodal downstaging, pN0-1), II (expected persistent N2 disease) and III (unexpected persistent N2 disease). The rates of overall survival (OS) and disease-free survival (DFS) were estimated by the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify the independent risk factors for OS and DFS. The mortality rate was 1.1% during the postoperative period. Perioperative complications occurred in 45 patients (12.9%). The 5-year OS rate was 32.2, 6.3 and 25.9% in groups I, II and III, respectively (group I vs. III, P=0.023; and group III vs. II, P<0.001). The 5-year DFS rate was 30.1, 5.1 and 22.4% in groups I, II and III, respectively (group I vs. III, P=0.012; and group III vs. II, P<0.001). Grouping, predicted forced expiratory volume in 1 sec, N downstaging and skip N2 metastasis were identified as independent predictive factors associated with OS, whereas the independent risk factors associated with DFS were grouping and N downstaging. Patients with unexpected persistent N2 disease exhibited better survival compared with those with expected persistent N2 disease. Surgery following chemotherapy remains the optimal approach for a proportion of patients with persistent N2 disease.

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Randomized Controlled Trial of Resection Versus Radiotherapy After Induction Chemotherapy in Stage IIIA-N2 Non-Small-Cell Lung Cancer

Cited by 633 publications

References 29 publications

A phase 3 study of induction treatment with concurrent chemoradiotherapy versus chemotherapy before surgery in patients with pathologically confirmed N2 stage IIIA nonsmall cell lung cancer (WJTOG9903)

A phase 3 study of induction treatment with concurrent chemoradiotherapy versus chemotherapy before surgery in patients with pathologically confirmed N2 stage IIIA nonsmall cell lung cancer (WJTOG9903)

Surgery for nonsmall cell lung cancer

Surgery following neoadjuvant chemotherapy for non-small-cell lung cancer patients with unexpected persistent pathological N2 disease

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