Radiotherapy Versus Chemotherapy plus Radiotherapy in Surgically Treated IIIA N2 Non–Small-Cell Lung Cancer (original) (raw)
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Annals of Oncology, 2004
Background: The aim of this study was to analyse the outcome of surgically staged IIIA-N2 non-small-cell lung cancer (NSCLC) treated with induction chemotherapy followed by surgical exploration. Methods: Univariate and multivariate analyses were carried out on a prospective cohort of 131 mediastinoscopy-proven IIIA-N2 NSCLC patients. Three preoperative cycles of vindesine -ifosfamide -cisplatin (VIP) were given. Patients with at least stable disease (SD) were considered for surgery, or radical radiotherapy in selected cases. Results: The response rate after VIP was 54% (95% confidence interval 45% to 63%) and was important for the final outcome. The median and 5-year survival for the total group were 24 months and 21% (38 months and 30% in responders), respectively. Involvement of subcarinal nodes at diagnosis was the most important prognostic factor (P = 0.022). Seventy-five patients were considered for surgery. Downstaging occurred in 34 of 70 resection specimens, with a pathological complete response in six. Median and 5-year survival in the surgical cohort were 45 months and 35%, respectively. Surgery was rewarding both in patients with a response and in those with SD, although the complete resection rate was significantly lower in the latter. On multivariate analysis, favourable prognostic factors were low pathological T-stage (P = 0.001) and downstaging of mediastinal nodes in the resection specimen (P = 0.008). Conclusions: VIP induction chemotherapy followed by surgical exploration was rewarding in mediastinoscopy-proven stage IIIA-N2 NSCLC, both in cases of response and SD, despite a lower complete resection rate in the latter. Patients with subcarinal nodes at diagnosis (5-year survival 8.5%) or without nodal downstaging at post-induction surgery (13.7%) might preferably be treated with a non-surgical approach.
Annals of Thoracic Surgery, 2004
Background. Pulmonary resection after chemotherapy and concurrent full-dose radiotherapy (>59 Gy) has previously been associated with unacceptably high morbidity and mortality. Subsequently neoadjuvant therapy protocols have used reduced and potentially suboptimal radiotherapy doses of 45 Gy. We report a series of 40 patients with locally advanced non-small-cell lung cancer who successfully underwent pulmonary resection after receiving greater than 59 Gy radiation and concurrent chemotherapy. Operative results and midterm survival follow-up are presented.
The Journal of Thoracic and Cardiovascular Surgery, 1993
Surgical resection of stage IlIA and stage IIIB non-smaIl-cell lung cancer after concurrent induction chemoradiotherapy A Southwest Oncology Group trial Recent studies suggest that preoperative induction chemotherapy ± radiotherapy can improve the historicaUy poor resectability and survival of patients with stage InA non-smaU-ceU lung cancer, but sometimes with significant associated morbidity and mortality. Such treatment has not been studied in stage IllB non-small-cell lung cancer, usuaUy considered unresectable. This multiinstitutional phase II trial tested the feasibility of concurrent preoperative chemoradiotherapy for stages lIlA and IIIB non-smaU-ceU lung cancer. Methods: Eligible patients had pathologicaUy documented TI-4 N2-3 disease (without pleural effusions). Induction therapy was cisplatin, 50 mg/m 2 , days 1, 8, 29, and 36 plus VP-16, 50 mg/m 2 , days 1 to 5, and 29 to 33 plus concurrent radiotherapy (4500 cGy, 180 cGy fractions). Resection was attempted 3 to 5 weeks after induction if the response was stable, partial, or complete. Complete nodal mapping at thoracotomy was required. Results: One hundred forty-six patients were entered. This interim analysis is based on the first 75 eligible patients for whom complete surgical data are available. There were 49 men and 26 women, median age 58 years (range 32 to 75 years). Sixty-eight of 75 (91 %) patients were eligible for operation, and 63 of 75 patients (84%) underwent thoracotomy. Fifty five of 75 patients (73%), including 12 of 16 with a stable response, had a complete resection. Four of 63 patients died postoperatively (6%). Approximately one third required a "complex" resection, for example, lobectomy plus chest waD or spine resection, but mean operating time was 3.2 hours and mean blood loss was less than 1000 ml for both stages lIlA and IIIB. Complete pathology data are currently available from 53 patients: 11 (21 %) had no residual tumor; 20 (30%) had rare microscopic foci of residual cancer. The 2-year survival is 40 % for both stages lIlA and IIIB. Conclusions: This combined modality therapy has been weU tolerated and has been associated with high response and resectability rates in both stage lIlA and stage IIIB non-smaU-celllung cancer. Current survival is significantly better than survivorship among historical control patients and provides a firm basis for subsequent phase III clinical trials.
Is surgery indicated in patients with stage IIIa lung cancer and mediastinal nodal involvement?
Interactive cardiovascular and thoracic surgery, 2011
The role of surgery in the treatment of patients with stage IIIa non-small cell lung cancer (NSCLC) and mediastinal node involvement is examined in this best evidence topic according to a structured protocol. A total of 579 papers were identified using the outlined search, 12 of which were deemed to represent the best available evidence. From the data summarized, we conclude that surgery, as part of a multimodality therapeutic approach, offers a survival benefit for patients with resectable N2 NSCLC. Overall five-year survival rates following primary resection ranged from 17% to 20% (four studies). Improved five-year survival was demonstrated with multimodality therapy (19-45%; 13 studies). Subgroup analysis demonstrates a five-year survival of 30.5% with postoperative chemo-radiotherapy, 22.2% with chemotherapy alone, and 27% with radiotherapy alone. In our review, we address three major issues regarding the management of stage IIIa NSCLC, the first of which is primary vs. postindu...
Surgery as part of combined modality treatment in stage IIIB non-small cell lung cancer
The Annals of Thoracic Surgery, 2002
Background The role of surgery after neo-adjuvant chemotherapy in patients with stage IIIB non-small cell lung cancer (NSCLC) remains unclear. Methods A prospective multicenter trial of neo-adjuvant chemotherapy followed by surgery or radiotherapy or both was conducted with 41 patients with stage IIIB NSCLC. End points were toxicity, response, downstaging, complete resectability, and survival. The diagnostic value of repeat mediastinoscopy after neoadjuvant chemotherapy (three courses of gemcitabine/cisplatin) was also studied. Results Response rate after neo-adjuvant chemotherapy was 66% (27/41). Fifteen patients underwent repeat mediastinoscopy, which proved to be inadequate in 6 patients. Two repeat mediastinoscopies were false negative. Resection was performed in 18 patients, of which 10 proved to be radical. Hospital mortality was 2.4% (n=1). Major complications occurred in 6 patients (fistula, empyema, haemorrhage). Histopathologically proven downstaging was seen in 16 patients (39%). Twenty-three patients underwent radiotherapy of whom 14 were diagnosed with stable/progressive disease and 9 patients with partial/complete response. Median survival for all patients was 15.1 months, for non-responders 8.4 months and for responders 16.8 months (p=0.11). Patients with partial/complete response had a mean survival of 21.5 months after resection and 13.0 months after radiotherapy (p=0.0003). Conclusion Radical surgery can be performed in 37% (10/27) of the responders resulting in a prolonged survival. Surgery as part of combined modality treatment is feasible in stage IIIB NSCLC. Results of a repeat mediastinoscopy are disappointing and proved to be a not so effective restaging tool because of the high number of incomplete procedures and because it yields false negative results. Combined modality treatment in stage IIIB NSCLC 85
Objective: Multi-modality approaches are increasingly employed to improve prognosis in surgically treated stage III non-small cell lung cancer (NSCLC). Risk and benefit of the preoperative therapeutic chemotherapy or combined radiochemotherapy on surgical morbidity and mortality are still a matter of debate. Methods: In 1995, a national phase III trial was started to compare (arm A) preoperative chemotherapy followed by twice-daily chemoradiation and consecutive surgery, with (arm B) preoperative chemotherapy alone followed by surgery and consecutive radiotherapy. An interim analysis with 277 patients was performed to assess surgical risk and complication rates. Results: Of the 385 patients, 273 (71%) underwent thoracotomy, 130 (73%) in arm A and 143 (69%) in arm B. Of the 273 patients undergoing thoracotomy, 168 had stage IIIB disease. Complete resection (R0) was achieved in 212 patients (78%), 104 in arm A (80%) and 108 in arm B (76%) (PZ n.s.). There was no difference in the proportion of complex resections between treatment arms (41% in arm A; 48% in arm B). Whilst bronchial stump insufficiency (3.8 vs 2.1%) and bleeding requiring re-thoracotomy (1.5 vs 0.7%) prevailed slightly in arm A, the occurrence of pneumonia divided similar on both treatment arms (4.6 vs 4.9%). Surgical mortality reached 6.1% in arm A (8/130) and 5.6% in arm B (6/143) (PZn.s.). Conclusions: In both treatment arms, a similar percentage of patients could be forwarded to surgery, even in stage IIIB disease. Bimodality induction seems to be superior with regard to resection rates (R0) (n.s.), but was associated with a higher complication rate, especially bronchial stump insufficiency. q
Journal of Thoracic Oncology, 2007
Introduction: Current primary treatment options for esophageal cancer are surgery only or concomitant chemoradiotherapy (CRT) and the long-term survival of patients with locally-advanced disease is rare. Pre-operative concomitant CRT seems to be beneficial, mostly in patients who achieve a complete pathologic response (pCR) after CRT. Objectives: In this study the efficiency and toxicity of pre-operative CRT in patients with locally-advanced esophageal cancer was analyzed as well as the influence of CRT on the survival. Material and Methods: Thirty patients with stages II and III esophageal cancer were randomly assigned to surgery alone and another 30 patients were assigned to surgery after 80 mg/m 2 cisplatin on day 1, 800 mg/m 2 fluorouracil on days 1-4, with concurrent radiotherapy of 45 Gy given in 22 fractions over 4.5 weeks. The primary end-point was progression-free survival and the secondary end-points were overall survival, tumor response, toxic effects, patterns of failure and quality of life. Results: Progression-free survival and overall survival did not differ between both groups (PFT P=0.16, Median survival P=0.34). The chemo-radiotherapy and surgery group had more complete resections with clear margins than did the surgery alone group (24 of 30 [80%] versus 14 of 30 [47%], P = 0.001), and had fewer positive lymph nodes (11 of 30 [37%] versus 20 of 30 [67%], P = 0.012). Conclusion: Neo-adjuvant chemo-radiation (NCRT) followed by surgery is associated with a small nonstatistically significant improvement in the overall survival. Whether this benefit is sufficient to warrant the considerable expense and risk associated with NCRT should be the subject of further larger randomized trials.
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.