Preoperative chemotherapy with and without additional radiochemotherapy: benefit and risk for surgery of stage III non-small cell lung cancer?

Abstract

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

Postoperative complications after induction chemoradiotherapy in patients with non-small-cell lung cancer

“…Previous studies have reported that the rate of postoperative morbidity ranged from 40 to 60%, and mortality ranged from 4 to 20% [8,10,[12][13][14][15]. The morbidity of 43.5% and mortality of 7.3% in our series are very similar to the findings in those reports.…”

“…To date, the results of many large trials indicate that pathological downstaging, particularly mediastinal nodes, is the most important predictor for long-term survival [4][5][6][7]. Radiotherapy in combination with chemotherapy before surgery seems to be beneficial in this context, because a better response rate is estimated as compared with chemotherapy alone, and this advantage has been shown in some studies [8,9].…”

How to evaluate the risk/benefit of trimodality therapy in locally advanced non-small-cell lung cancer

“…The results of neither trial, the one showing a positive (Fleck et al, 1993) and the other showing a negative (Sauvaget et al, 2000) effect, have been published as full articles. More recently, another larger trial from Germany compared preoperative chemoradiotherapy with preoperative chemotherapy and postoperative radiotherapy, and reported no significant differences in the results (Semik et al, 2004). However, the actual issue should be viewed as an evaluation of the timing or sequence of the therapy, rather than as an investigation of the usefulness of the trimodality approach itself.…”

9 years tumor free survival after resection, intraoperative radiotherapy (IORT) and whole brain radiotherapy of a solitary brain metastasis of non-small cell lung cancer

“…The tumor was clinically staged as T2N2M0 (stage IIIA). The patient was then recruited for the Muenster lung cancer trial [7]. She received three cycles of neoadjuvant CE chemotherapy followed by combined hyperfractionated radiochemotherapy with 45 Gy, carboplatin and vindesine.…”