Comparison of neoadjuvant cisplatin-based chemotherapy versus radiochemotherapy followed by resection for stage III (N2) NSCLC

Abstract

Objective: Comparison of prospectively treated patients with neoadjuvant cisplatin-based chemotherapy vs radiochemotherapy followed by resection for mediastinoscopically proven stage III N2 non-small cell lung cancer with respect to postoperative morbidity, pathological nodal downstaging, overall and disease-free survival, and site of recurrence. Methods: Eighty-two patients were enrolled between January 1994 to June 2003, 36 had cisplatin and doxetacel-based chemotherapy (group I) and 46 cisplatin-based radiochemotherapy up to 44 Gy (group II), either as sequential (25 patients) or concomitant (21 patients) treatment. All patients had evaluation of absence of distant metastases by bone scintigraphy, thoracoabdominal CT scan or PET scan, and brain MRI, and all underwent pre-induction mediastinoscopy, resection and mediastinal lymph node dissection by the same surgeon. Results: Group I and II comprised T1/2 tumors in 47 and 28%, T3 tumors in 45 and 41%, and T4 tumors in 8 and 31% of the patients, respectively (PZ0.03). There was a similar distribution of the extent of resection (lobectomy, sleeve lobectomy, left and right pneumonectomy) in both groups (PZ0.9). Group I and II revealed a postoperative 90-d mortality of 3 and 4% (PZ0.6), a R0-resection rate of 92 and 94% (PZ0.9), and a pathological mediastinal downstaging in 61 and 78% of the patients (P!0.01), respectively. 5y-overall survival and disease-free survival of all patients were 40 and 36%, respectively, without significant difference between T1-3 and T4 tumors. There was no significant difference in overall survival rate in either induction regimens, however, radiochemotherapy was associated with a longer disease-free survival than chemotherapy (PZ0.04). There was no significant difference between concurrent vs sequential radiochemotherapy with respect to postoperative morbidity, resectability, pathological nodal downstaging, survival and disease-free survival. Conclusions: Neoadjuvant cisplatin-based radiochemotherapy was associated with a similar postoperative mortality, an increased pathological nodal downstaging and a better disease-free survival as compared to cisplatin doxetacel-based chemotherapy in patients with stage III (N2) NSCLC although a higher number of T4 tumors were admitted to radiochemotherapy. Q

ERS/ESTS clinical guidelines on fitness for radical therapy in lung cancer patients (surgery and chemo-radiotherapy)

“…Induction chemo-radiotherapy may indeed be a prelude to significant morbidity and mortality [258][259][260], although recent evidence from institutional studies shows increased safety in adding radiotherapy to chemotherapy induction regimens [261][262][263][264]. A prospective randomised trial powered on postoperative morbidity and mortality is needed to compare chemotherapy versus chemo-radiotherapy followed by surgery to clarify this issue.…”

Risks of Neoadjuvant Chemotherapy and Radiation Therapy

“…Fowler [15] 8/13 (62%) 3/13 (23%) Deutsch [31] 3/16 (19%) 3/16 (19%) Macchiarini [52] 6/23 (28%) 2/23 (8.6%) Albain [8] 59/101 (58%) 8/101 (7.9%) Rice [53] 11/36 (31%) 4/36 (11%) Grunenwald [32] 7/29 (24%) 2/29 (7%) DeCamp [54] 30/105 (31%) 7/105 (6.6%) Stamatis [55] 180/392 (46%) 18/392 (4.6%) Semik [33] 50/130 (38%) 8/130 (6.2%) Intergroup 0139 [56] d 10/202 (5%) Pezzetta [28] d 2/46 (4%) Fujita [34] 54/124 (43.5%) 9/124 (7.3%) [13] d (7%) Roth [12] d (0%) Sugarbaker [24] 20/63 (31%) 2/63 (3.2%) Doddoli [25] 35/69 (51%) 6/69 (9%) Martin [17] 179 study, univariate analysis demonstrated that higher age (O70 years) and lower performance status (Karnofsky index !80%) adversely affected the incidence of mortality [47]. Recent reports by Brouchet and colleagues [48] and Cerfolio and colleagues [49] confirm the higher risk for developing major morbidity in elderly patients if they underwent neoadjuvant treatment before resection.…”

Multimodality Treatment With Surgery for Locally Advanced Non–Small-Cell Lung Cancer With N2 Disease: A Review Article

“…There are many retrospective studies reporting the treatment outcomes of preoperative chemoradiotherapy followed by subsequent resection in patients with stage III disease, [33][34][35][36][37][38][39][40][41][42][43] and several prospective studies have been conducted to evaluate preoperative treatment, including concurrent chemoradiotherapy, followed by surgery in those with stage III NSCLC. [21][22][23][24][44][45][46][47][48][49][50] However, the results are inconsistent, and conclusive evidence has yet to be obtained.…”