Neoadjuvant Therapy for Resectable Non–Small Cell Lung Cancer with Mediastinal Lymph Node Involvement
Section snippets
Mediastinal staging
The prognosis and optimal treatment of patients diagnosed with NSCLC depends on accurate staging [2], [5], [6], [7]. Nodal involvement can be determined by either noninvasive or invasive measures. Although on computerized tomography (CT) imaging a lymph node larger than 1 cm in diameter is considered abnormal, studies have shown that size is not a reliable predictor of tumor involvement [8], [9]. Toloza and colleagues [10] reported in a meta-analysis of 3438 patients imaged with CT a
Induction chemotherapy
Numerous nonrandomized phase II trials using induction chemotherapy can be found in the literature. In a summary by Meko and Rusch [14], chemotherapy followed by surgery in highly selected patients with and without postoperative radiation therapy suggested there may be an improvement in resectability and possibly improved survival over single-modality therapy. Martini and colleagues [15] published their experience with the administration of two to three cycles of cisplatin, vindesine or
Induction chemotherapy with third-generation agents
Phase II trials evaluating the efficacy of third-generation chemotherapy agents have been performed with varying results. Results of studies evaluating induction chemotherapy with third-generation agents are summarized in Table 2.
The Swiss Group for Clinical Cancer Research (SAKK) enrolled 90 patients in a nonrandomized trial to receive three cycles of cisplatin and docetaxel followed by surgery. Postoperative radiation was given to 33 patients with positive surgical margins, with involvement
Induction chemoradiotherapy
Given that concurrent chemoradiation is superior to sequential therapy in the definitive management of unresectable locally advanced NSCLC [29], [30], a combined-modality approach has been investigated in the neoadjuvant setting for potentially resectable locally advanced NSCLC. Results of trials evaluating induction chemoradiotherapy are summarized in Table 3.
The phase II Southwest Oncology Group (SWOG) 8805 study was one of the first trials looking at induction chemoradiotherapy. This study
Role of surgery
The appropriate selection of patients for surgery following neoadjuvant therapy continues to be a challenge for all specialists who deal with locally advanced NSCLC. Concern about increased morbidity and mortality of resection following induction therapy emphasizes the importance of selecting patients who may benefit from surgical intervention [32], [33]. Accurate restaging is essential to identify disease refractory to induction therapy in order to reduce the operative risk of surgery in
Induction therapy with molecularly targeted agents
A number of molecularly targeted agents have now been shown to prolong life for patients with NSCLC in the setting of advanced disease. These include monoclonal antibodies as well as a small molecule tyrosine kinase inhibitor. A large number of new targeted agents are in various stages of testing and clinical development. Bevacizumab, a monoclonal antibody targeted against vascular endothelial growth factor (VEGF), has been shown to prolong survival in combination with chemotherapy for patients
Summary
The optimal treatment for stage IIIA (N2) NSCLC remains controversial. Numerous studies with induction chemotherapy or chemoradiotherapy show that both approaches in the neoadjuvant setting are feasible. Outcomes following induction therapy have been associated with mediastinal nodal response, with residual mediastinal involvement a negative predictor of survival. Appropriate selection of patients to undergo resection following induction therapy is critical. Lobectomy may be safely performed
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Predictive factors for node metastasis in patients with clinical stage i non-small cell lung cancer
2013, Annals of Thoracic SurgeryCitation Excerpt :When lymph node metastasis is confirmed, open surgery is recommended over VATS because VATS not only increases the chance of breaking capsules but also makes it difficult to completely dissect the nodes when extranodal invasion is present. Recently, some studies have reported that complete node dissection via VATS is also possible even in patients with lymph node metastasis [18–20]. However, complete node dissection in such cases is more likely to be possible only by highly experienced surgeons.
Induction Therapy for Lung Cancer: Sailing Across the Pillars of Hercules
2012, Thoracic Surgery ClinicsCitation Excerpt :As already noted, recent evidence provided from authoritative surgical centers seems to dispute these findings.39 Neoadjuvant chemotherapy has become a recommended treatment for potentially resectable stage IIIA-N2 NSCLC.46,47 In the early 1990s, two small randomized phase 3 trials had demonstrated an advantage in survival of induction chemotherapy with second-generation platinum combinations followed by surgery versus surgery alone.2,3
Utility of PET/CT for mediastinal staging of non-small cell lung cancer in stage III (N2)
2011, Revista Espanola de Medicina NuclearCitation Excerpt :Based on the literature consulted, after the neoadjuvant treatment, three possibilities exist: a favorable response (about 55–65%); staging of the disease (30–40%) and rarely, its progression. ( <5%).16–18 In the mediastinal lymph node staging, the CT+C has been shown to be unreliable in 20% of the cases with lymph nodes on the short axis inferior to one centimeter.19
Should progression-free survival be the primary measure of efficacy for advanced NSCLC therapy?
2010, Annals of OncologyCitation Excerpt :This alteration identifies a new molecular subset of patients with distinct clinical and therapeutic characteristics and the potential for high sensitivity to the ALK tyrosine kinase inhibitor PF-02341066 [5]. Alternative treatment strategies for NSCLC include maintenance therapy, neoadjuvant therapy, vaccination, and combinations of biological and chemotherapies [94–97]. In current clinical trials of NSCLC, an increasing number of studies are using PFS as a primary end point.
Mediastinal staging for lung cancer: the influence of biopsy volume
2010, European Journal of Cardio-thoracic Surgery