Surgical strategies and outcomes after induction therapy for non-small cell lung cancer (original) (raw)
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Induction treatment before surgery for non-small cell lung cancer
Lung Cancer, 2003
Surgery alone is currently still accepted ''standard of care'' for patients with operable NSCLC, this includes stages IA and IIB, as well as selected early subsets of IIIA disease. In more advanced and inoperable stage III disease, combinations of chemotherapy and radiotherapy remain the standard treatment approach for patients with good performance status. The role of surgery following induction therapy in these advanced stage III patients is at the moment not conclusively defined. More evidence from randomized trials is clearly needed to tailor treatment for the large From the IASLC Workshop Bruges, 1st Á/4th September 2002.
Present status of induction treatment in stage IIIA-N2 non-small cell lung cancer: a review
European Journal of Cardio-Thoracic Surgery, 1998
Background: Surgical exploration in mediastinoscopy proven N2 non-small cell lung cancer (NSCLC) is unrewarding. Theoretical concepts suggest a beneficial role for preoperative induction treatment. The solidity of the therapeutic results with this approach in the currently available data is examined. Methods: Literature on induction therapy followed by surgical exploration, consisting of randomized reports and phase II reports meeting some essential criteria, are reviewed. Results: Of the twenty-four analyzed phase II studies, thirteen lack adequate surgical staging. Stratification for various important prognostic factors in N2 disease is missing in many instances. Results with induction with a cisplatinum dose of less than 80 mg/m 2 seem to be inferior. The use of mitomycin-C in patients scheduled for lung resection or irradiation deserves caution. No evident difference in efficacy between induction chemotherapy or chemo-radiotherapy is suggested, but toxicity and mortality appear to be somewhat higher with chemo-radiotherapy. Pathological complete response is mainly found after an at least partial clinical response. Effect on survival in non-controlled phase II studies and small randomized reports is encouraging. Conclusions: the role of chemotherapy induction in improving the long-term survival of N2 NSCLC is promising, but needs to be confirmed by large multi-center randomized data. Adequate surgical staging and attention to important prognostic factors in N2 disease should minimize the numerous institution based differences interfering in the currently available non-controlled studies.
Adjuvant and induction chemotherapy in non-small cell lung cancer
Annals of Oncology, 1999
About 25%-30% of patients with non-small cell lung cancer can be resected with curative intent. However, systemic relapses occur in up to 70% of these patients. Thus, postoperative adjuvant chemotherapy was evaluated in several randomised trials but the results of these trials were inconclusive with a survival benefit only in some trials. Shortcomings of these trials included low number of patients, poor patient compliance and inadequate chemotherapy protocols. A recent meta-analysis suggested an absolute survival benefit of 5% at five years for postoperative cisplatin-based chemotherapy as compared to surgery alone. Thus adjuvant chemotherapy with both improved chemotherapy protocols and improved anti-emetics is currently re-evaluated in several randomised trials on large patient populations.
Journal of Thoracic Oncology, 2011
Objective: We previously reported a high mortality after induction therapy and pneumonectomy for non-small cell lung cancer. Recent reports suggest that operative mortality in these patients is declining. We analyzed our contemporary results to define operative mortality and factors determining surgical risk. Methods: Eligible patients were identified from our prospective surgical database. Complications were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events 3.0. Uni-and multivariate logistic regression models assessed the association of preoperative tests and clinical characteristics with outcome. Receiver operating characteristic curves and area under the receiver operating characteristic curve (AUC) statistics were calculated in a leave-one-out crossvalidation scheme to evaluate the predictive value of various models. Results: From January 2000 to December 2006, 549 patients underwent surgery after induction therapy. Median patient age was 64 years (range: 30-86), and 54% were women (298/549). All received chemotherapy, and 17% also had radiation. Lobectomy (388/549, 71%) and pneumonectomy (70/549, 13%) were the most common procedures. Complications occurred in 250 patients (46%), with grade 3 or higher in 23% (126/549). Inhospital mortality was 1.8% (10/549), with only one death after right pneumonectomy (1/30, 3%). Multivariate analysis showed that predicted postoperative (PPO) pulmonary function was associated with postoperative morbidity. By receiver operating characteristic curves, PPO product (AUC ϭ 0.75, p Ͻ 0.001), PPO diffusion capacity (AUC ϭ 0.70, p Ͻ 0.001), and preoperative % predicted PPO diffusion capacity (AUC ϭ 0.66, p Ͻ 0.001) predicted mortality. Conclusion: Our current experience shows that resection of nonsmall cell lung cancer after induction therapy, including pneumonectomy, is associated with low mortality. PPO pulmonary function is the strongest predictor of operative risk and should be used to select patients for surgery.
European Journal of Cardio-Thoracic Surgery, 2001
Objective: To verify if in our experience with`induction therapy' in non-small cell lung cancer (NSCLC) the clinical re-staging is really predictive of pathological staging. Materials and methods: From January 1990 to February 2000, 136 patients with locally advanced NSCLC underwent a protocol of induction therapy according to three different treatment plans: Carboplatin 1 radiotherapy ± study A; Cisplatin 1 5-Fluorouracil 1 radiotherapy ± study B; Gemcitabine 1 radiotherapy ± study C. Results: Clinical re-staging showed in the patients enrolled in study A a clinical Complete Response rate (cCR) of 2.3%; a clinical Partial Response rate (cPR) of 50%; a clinical Stable Disease (cSD) rate of 44.3%; a clinical Disease Progression (cDP) rate of 3.4%. In study B, cCR was 0%; cPR: 71.4%; cSD 10.7%; cDP: 17.9%. In study C, cCR was 0%; cPR: 23.5%; cSD: 11.8%; cDP: 64.7%. After clinical re-staging, 76 patients (47 group A; 23 group B; 6 group C) were judged to be resectable and underwent a surgical operation. Pathological staging showed no tumour in eight patients (10.5%; 8/76) (three in study A, four in study B, one in study C) and microscopic neoplastic remnants in seven (9.2%; 7/76). Thirty-nine patients were pN0. Overall downstaging rate in the operated patients was 51%. No precise correlation was found among clinical re-staging and pathological staging. We had two cCRs and eight pCRs, and all of these pCRs had been re-staged as cPR except in one case (cSD). In seven cases, where only microscopic remnants have been found, six had been clinically restaged as cPR and one as cSD. Conclusions: Our experience con®rmed how often the clinical re-staging data are unreal. Accordingly surgery should be indicated in any case where an induction therapy has been administered, if it is reasonably possible. q
Cancer, 2012
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. V C 2012 American Cancer Society.
Extended operations after induction therapy for stage IIIb (T4) non-small cell lung cancer
The Annals of Thoracic Surgery, 1994
Twenty-three patients with stage IIIb (T4) non-small cell lung cancer received induction chemotherapy (median, 2 cycles) with (n = 12) or without (n = 11) radiation (median, 45 Gy) before operation. Nine tumors involved the carina (n = 8) or lateral tracheal wall (n = l), 11 were located centrally and invaded the proximal pulmonary artery (n = 61, veins (n = 31, or both (n = 21, three were apical tumors involving T4 structures, and six were associated with histologically diseased mediastinal nodes. Five complete and 18 partial responses were observed after induction treatment. Resection of all residual tumor at the primary site and involved vestiges was possible in 21 patients (91%); in two apical tumors, tumor was left behind. Nine right tracheal sleeve and 11 intrapericardial pneumonectomies and three resections of apical tumors were performed; 1 1 patients (48%) had radical mediastinal lymph node dissection. Complete tage 11% non-small cell lung cancer (NSCLC) includes
JNCI Journal of the National Cancer Institute, 2007
Induction chemotherapy before surgical resection increases survival compared with surgical resection alone in patients with stage IIIA-N2 non-small-cell lung cancer (NSCLC). We hypothesized that, following a response to induction chemotherapy, surgical resection would be superior to thoracic radiotherapy as locoregional therapy. Selected patients with histologic or cytologic proven stage IIIA-N2 NSCLC were given three cycles of platinum-based induction chemotherapy. Responding patients were subsequently randomly assigned to surgical resection or radiotherapy. Survival curves were estimated using Kaplan-Meier analyses from time of randomization. Induction chemotherapy resulted in a response rate of 61% (95% confidence interval [CI] = 57% to 65%) among the 579 eligible patients. A total of 167 patients were allocated to resection and 165 to radiotherapy. Of the 154 (92%) patients who underwent surgery, 14% had an exploratory thoracotomy, 50% a radical resection, 42% a pathologic downstaging, and 5% a pathologic complete response; 4% died after surgery. Postoperative radiotherapy was administered to 62 (40%) of patients in the surgery arm. Among the 154 (93%) irradiated patients, overall compliance to the radiotherapy prescription was 55%, and grade 3/4 acute and late esophageal and pulmonary toxic effects occurred in 4% and 7%; one patient died of radiation pneumonitis. Median and 5-year overall survival for patients randomly assigned to resection versus radiotherapy were 16.4 versus 17.5 months and 15.7% versus 14%, respectively (hazard ratio = 1.06, 95% CI = 0.84 to 1.35). Rates of progression-free survival were also similar in both groups. In selected patients with pathologically proven stage IIIA-N2 NSCLC and a response to induction chemotherapy, surgical resection did not improve overall or progression-free survival compared with radiotherapy. In view of its low morbidity and mortality, radiotherapy should be considered the preferred locoregional treatment for these patients.