National Patterns of Care and Outcomes After Combined Modality Therapy for Stage IIIA Non–Small-Cell Lung Cancer (original) (raw)
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Acta Oncologica, 2014
Background. Concurrent chemo-radiotherapy (CON-CRT) is recommended for selected patients with stage III non-small cell lung cancer (NSCLC), but utilization varies. We assessed the response to national guidelines introduced in 2004 and the impact on outcomes. Material and methods. Retrospective study of stage III NSCLC patients treated with radical intent non-surgical treatment during 2003-2010 in a university medical center characterized by multidisciplinary assessment, routine use of four-dimensional computed tomography for radiotherapy planning, and rapid implementation of radiotherapy advances. Results. Between 2003 and 2010, 319/435 (73%) patients with stage III NSCLC received (chemo) radiotherapy. The number receiving CON-CRT in successive two-year periods increased from 13/48 (27%)-40/80 (50%)-63/90 (70%), to 74/101 (73%). Median overall survival (OS) from start of radiotherapy was 18.6 months for CON-CRT (190/319) and 17.4 months for sequential (SEQ), typically hypofractionated, CRT (90/319) (p ϭ 0.78). Eleven months OS with radiotherapy alone (39/319) was signifi cantly shorter (p ϭ 0.006). OS did not differ between the four periods (p ϭ 0.87). CON-CRT was not over-represented in the 16% of patients dying within fi ve months of starting radiotherapy. Conclusions.
Radiotherapy and Oncology, 2009
Improved local tumor control (LC) improves survival of patients with non-small cell lung cancer (NSCLC). We estimated the capability of surgical and non-surgical options to improve LC further in this disease. Methods: Eligible studies were phase III trials reporting 2-year survival data as well as the incidence of LC and/or distant metastases. Effect estimates, as well as the statistical uncertainty of these, were combined in order to estimate the benefit in terms of LC from combining multiple modalities. Results: It was estimated that the highest rates of LC can be obtained with high-dose concurrent chemoradiation followed by surgery. In this situation, escalating the pre-operative radiation dose from 45 to 66 Gy, delivered concurrently with chemotherapy, could increase LC from 58% to 76%. Toxicity may also be higher, but could not be estimated. Without surgery, the gain in LC from concurrent chemo-radiation versus sequential, corresponds to a radiation dose increase from 65 to 72 Gy. Conclusions: We hypothesize that high-dose concurrent chemo-radiation followed by surgery could be superior to other current treatment approaches for selected patients with stage III NSCLC, provided toxicity would be low. At present, high-dose concurrent chemo-radiation followed by surgery should be considered experimental.
Clinical Lung Cancer, 2000
Combined modality treatment of patients with stage III non-small-cell lung cancer (NSCLC) has recently become widely accepted. Standard combinations are neoadjuvant chemotherapy followed by radiotherapy or concurrent chemotherapy and radiotherapy. The effect of combined modality treatment on survival is dependent on both the efficacy of chemotherapy to eradicate micrometastases and optimal local control. The European Organization for Research and Treatment of Cancer (EORTC) Lung Cancer Cooperative Group has chosen to investigate in a comparative way the side effects and the effect on survival of radiotherapy versus surgery in stage IIIA (N2) NSCLC.
The Lancet, 2009
Background Results from phase II studies in patients with stage IIIA non-small-cell lung cancer with ipsilateral mediastinal nodal metastases (N2) have shown the feasibility of resection after concurrent chemotherapy and radiotherapy with promising rates of survival. We therefore did this phase III trial to compare concurrent chemotherapy and radiotherapy followed by resection with standard concurrent chemotherapy and defi nitive radiotherapy without resection. Methods Patients with stage T1-3pN2M0 non-small-cell lung cancer were randomly assigned in a 1:1 ratio to concurrent induction chemotherapy (two cycles of cisplatin [50 mg/m² on days 1, 8, 29, and 36] and etoposide [50 mg/m² on days 1-5 and 29-33]) plus radiotherapy (45 Gy) in multiple academic and community hospitals. If no progression, patients in group 1 underwent resection and those in group 2 continued radiotherapy uninterrupted up to 61 Gy. Two additional cycles of cisplatin and etoposide were given in both groups. The primary endpoint was overall survival (OS). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00002550. Findings 202 patients (median age 59 years, range 31-77) were assigned to group 1 and 194 (61 years, 32-78) to group 2. Median OS was 23•6 months (IQR 9•0-not reached) in group 1 versus 22•2 months (9•4-52•7) in group 2 (hazard ratio [HR] 0•87 [0•70-1•10]; p=0•24). Number of patients alive at 5 years was 37 (point estimate 27%) in group 1 and 24 (point estimate 20%) in group 2 (odds ratio 0•63 [0•36-1•10]; p=0•10). With N0 status at thoracotomy, the median OS was 34•4 months (IQR 15•7-not reached; 19 [point estimate 41%] patients alive at 5 years). Progression-free survival (PFS) was better in group 1 than in group 2, median 12•8 months (5•3-42•2) vs 10•5 months (4•8-20•6), HR 0•77 [0•62-0•96]; p=0•017); the number of patients without disease progression at 5 years was 32 (point estimate 22%) versus 13 (point estimate 11%), respectively. Neutropenia and oesophagitis were the main grade 3 or 4 toxicities associated with chemotherapy plus radiotherapy in group 1 (77 [38%] and 20 [10%], respectively) and group 2 (80 [41%] and 44 [23%], respectively). In group 1, 16 (8%) deaths were treatment related versus four (2%) in group 2. In an exploratory analysis, OS was improved for patients who underwent lobectomy, but not pneumonectomy, versus chemotherapy plus radiotherapy. Interpretation Chemotherapy plus radiotherapy with or without resection (preferably lobectomy) are options for patients with stage IIIA(N2) non-small-cell lung cancer.
Treatment of Stage III Non-small Cell Lung Cancer
Chest, 2013
Stage III non-small cell lung cancer (NSCLC) describes a heterogeneous population with disease presentation ranging from apparently resectable tumors with occult microscopic nodal metastases to unresectable, bulky nodal disease. This review updates the published clinical trials since the last American College of Chest Physicians guidelines to make treatment recommendations for this controversial subset of patients. Methods: Systematic searches were conducted through MEDLINE, Embase, and the Cochrane Database for Systematic Review up to December 2011, focusing primarily on randomized trials, selected meta-analyses, practice guidelines, and reviews. Results: For individuals with stage IIIA or IIIB disease, good performance scores, and minimal weight loss, treatment with combined chemoradiotherapy results in better survival than radiotherapy alone. Consolidation chemotherapy or targeted therapy following defi nitive chemoradiation for stage IIIA is not supported. Neoadjuvant therapy followed by surgery is neither clearly better nor clearly worse than defi nitive chemoradiation. Most of the arguments made regarding patient selection for neoadjuvant therapy and surgical resection provide evidence for better prognosis but not for a benefi cial impact of this treatment strategy; however, weak comparative data suggest a possible role if only lobectomy is needed in a center with a low perioperative mortality rate. The evidence supports routine platinum-based adjuvant chemotherapy following complete resection of stage IIIA lung cancer encountered unexpectedly at surgery. Postoperative radiotherapy improves local control without improving survival. Conclusions: Multimodality therapy is preferable in most subsets of patients with stage III lung cancer. Variability in the patients included in randomized trials limits the ability to combine results across studies and thus limits the strength of recommendations in many scenarios. Future trials are needed to investigate the roles of individualized chemotherapy, surgery in particular cohorts or settings, prophylactic cranial radiation, and adaptive radiation. CHEST 2013; 143(5)(Suppl):e314S-e340S Abbreviations: ACCP 5 American College of Chest Physicians; EORTC 5 European Organisation for Research and Treatment of Cancer; HR 5 hazard ratio; IASLC 5 International Association for the Study of Lung Cancer; IMRT 5 intensity-modulated radiotherapy; MLND 5 mediastinal lymph node dissection; NSCLC 5 non-small cell lung cancer; PCI 5 prophylactic cranial irradiation; PORT 5 postoperative radiotherapy; RCT 5 randomized controlled trial; SWOG 5 Southwestern Oncology Group
Journal of Thoracic Oncology, 2017
Introduction: The role of postoperative radiotherapy (PORT) in the treatment of pathologic stage IIIA (N2) NSCLC remains controversial. We investigated practice patterns and outcomes for these patients in a prospectively maintained nationwide oncology outcomes database. Methods: Patients with known histologic features of pathologic stage IIIA (N2) NSCLC who underwent an operation with negative margins and received adjuvant multiagent chemotherapy from 2004 to 2013 were identified from the National Cancer Data Base and stratified by the use of PORT. Multivariable logistic regression modeling was used to examine factors associated with receiving PORT, and multivariable proportional hazards regression was used to examine the association of treatment and mortality, adjusting for demographic, socioeconomic and clinicopathologic factors. Landmark analysis and covariate balancing propensity score (CBPS) weighting were also explored to account for immortal time bias and nonrandomization. Results: A total of 2691 patients were identified, with a median follow-up of 32.32 months. In multivariable analysis, improved overall survival was associated with multiple factors, including younger age, female sex, lower Charlson-Deyo comorbidity index, histologic type (with squamous cell being better than adenocarcinoma), smaller tumor size, lower pathologic T stage, surgical procedure (with pneumonectomy or lobectomy being better than sublobar resection), and receipt of PORT (all p < 0.05). Before landmark analysis, the hazard ratio (HR) showed an overall survival benefit for patients receiving PORT (adjusted HR ¼ 0.83, 95% CI [confidence interval]: 0.72-0.95; p ¼ 0.008). This benefit remained significant after CBPS weighting (HR ¼ 0.81, 95% CI: 0.70-0.94, p ¼ 0.005), almost significant after landmark analysis (adjusted HR ¼ 0.84, 95% CI: 0.69-1.007, p ¼ 0.059), and significant after landmark analysis with CBPS weighting (HR ¼ 0.77, 95% CI: 0.63-0.94, p ¼ 0.009). Median survival past landmark time was 27.43 months in the PORT group and 25.86 months in the non-PORT group. Factors significantly associated with receiving PORT were facility location, facility type, Charlson-Deyo comorbidity index, and grade (all p < 0.05). Conclusions: Improved survival is associated with receipt of PORT for patients with pathologic stage IIIA (N2) NSCLC treated with complete resection and multiagent chemotherapy.