Surgery with or without preoperative paclitaxel and carboplatin in early-stage non-small-cell lung cancer: Southwest Oncology Group Trial S9900, an intergroup, randomized, phase III trial.

PURPOSE Patients with early-stage non-small-cell lung cancer (NSCLC) have a poor prognosis even after complete resection. Earlier studies of preoperative (induction) chemotherapy in resectable NSCLC demonstrated feasibility and encouraging survival data. This randomized phase III trial compared overall survival (OS) for preoperative paclitaxel and carboplatin followed by surgery with surgery alone in patients with early-stage NSCLC. PATIENTS AND METHODS Patients with clinical stage IB-IIIA NSCLC (excluding superior sulcus tumors and N2 disease) were eligible. Patients were randomly assigned to surgery alone or to three cycles of paclitaxel (225 mg/m(2)) and carboplatin (area under curve, 6) followed by surgical resection. The primary end point was OS; secondary end points were progression-free survival (PFS), chemotherapy response, and toxicity. RESULTS The trial closed early with 354 patients after reports of a survival benefit for postoperative chemotherapy in other studies. The median OS was 41 months in the surgery-only arm and 62 months in the preoperative chemotherapy arm (hazard ratio, 0.79; 95% CI, 0.60 to 1.06; P = .11.) The median PFS was 20 months for surgery alone and 33 months for preoperative chemotherapy (hazard ratio, 0.80; 95% CI, 0.61 to 1.04; P = .10.) Major response to chemotherapy was seen in 41% of patients; no unexpected toxicity was observed. CONCLUSION This trial closed prematurely after compelling evidence supporting postoperative chemotherapy emerged. Although OS and PFS were higher with preoperative chemotherapy, the differences did not reach statistical significance. At present, stronger evidence exists for postoperative chemotherapy in early-stage NSCLC.

Induction chemotherapy with mitomycin, vindesine, and cisplatin for stage IIIA (T1-3, N2) unresectable non-small-cell lung cancer: final results of the Toronto phase II trial.

PURPOSE: This is a phase II study to assess the role of induction chemotherapy in the management of stage IIIA non-small-cell lung cancer (NSCLC). We are now reporting the long-term follow-up of the Toronto phase II trial. METHODS: Sixty five patients with mediastinoscopy proven stage IIIA NSCLC received two cycles of preoperative MVP or VLB/P followed by thoracotomy followed by two further courses of chemotherapy. RESULTS: The overall response rate was 67.7% with three complete and 41 partial responders. Forty seven patients went on to thoracotomy with 35 complete resections. Pathologically 4.6% of patients had no tumour remaining. There were three postop deaths as well as five chemotherapy related deaths. Of the 35 patients completely resected 19 have recurred including eight in brain. The median survival for the entire 65 patients is 18.6 months with a 1 year survival of 66%, 5 year survival of 29% and a 10 year survival of 22%. CONCLUSIONS: The long-term survival of induction chemotherapy is maintained. The high incidence of brain recurrences warrants assessment of the role of prophylactic cranial radiation. The role of surgery for stage IIIA NSCLC following induction chemotherapy awaits further study.

Circulation of the spinal cord: an important consideration for thoracic surgeons.

The spinal cord has significant thoracic arterial watershed areas rendering it vulnerable to intraoperative ischemic damage, clearly mandating a need for postoperative neurologic monitoring. Mechanisms of hypoperfusion include aortic cross-clamping, rib retraction, intercostal artery interruption, and costovertebral junction bleeding. We report cases of primary lung cancer resection, resection of pulmonary metastasis adherent to the thoracic aorta, resection of cartilaginous tumor with chest wall invasion, and esophagomyotomy for achalasia-all complicated by postoperative paraplegia. We review spinal cord circulation, describe mechanisms and patterns of neurologic dysfunction of susceptible watershed areas, and outline roles of preoperative spinal angiography and intraoperative evoked potentials.

Surgical treatment of small cell lung cancer.

Chemoradiotherapy remains a gold standard in the treatment of limited-disease small cell lung cancer. Currently, three indications for the surgical treatment of very limited disease (stage I, II, or highly selected IIIa) small cell lung cancer can be identified: (1) primary surgery in peripheral clinical N0 lesions followed by adjuvant chemotherapy or chemoradiotherapy; (2) primary chemotherapy or chemoradiotherapy followed by surgery +/- radiotherapy in patients with a good response to initial treatment; and (3) salvage operations in patients who recur or persist at the primary site but still have resectable disease. The value of these approaches has been assessed in retrospective analyses and prospective nonrandomized trials. A large prospective randomized trial failed to prove any added value for surgery in the multidisciplinary treatment of limited-disease small cell lung cancer, but very few very-limited-disease patients were included.

Results of lung metastasectomy from breast cancer: prognostic criteria on the basis of 467 cases of the International Registry of Lung Metastases.

OBJECTIVE: Metastatic breast cancer is still defined as an incurable disease. Although the prognosis after resection of isolated metastases to the lung is much better than after chemotherapy most oncologists and gynecologists disapprove of lung metastasectomy. METHODS: In order to summarize the experience of pulmonary metastatic surgery and to achieve more relevant data by an increased number of cases, we evaluate the data of the International Registry of Lung Metastases of 467 patients having lung metastases from breast cancer with regard to long-term survival and prognostic factors. RESULTS: In 84% a complete metastatic resection was possible. The survival rates are 38% after 5 years, 22% after 10 years, and 20% after 15 years. Prognostic factors are a disease-free interval of > or = 36 months with 5-year survival of 45%, a 10-year survival of 26% and a 15-year survival of 21% (P=0.0001), solitary lung metastasis is associated with a survival rate of 44% after 5 years and of 23% after 10 and 15 years, but this is not statistically significant compared to multiple metastases. When establishing prognostic groups as suggested by Pastorino and the International Registry of Lung Metastases based on the risk factors disease-free interval, number of metastases and complete resection the group with the best prognosis showed 5-year survival of 50%, 10- and 15-year survival of 26% with a median survival of 59 months. CONCLUSION: Considering the low morbidity and mortality rate, we think that lung metastasectomy today is the best treatment option in selected cases of lung metastases from breast cancer.

Long-term results of combined-modality therapy in resectable non-small-cell lung cancer.

PURPOSE: Assessment of long-term results of combined-modality therapy for resectable non-small-cell lung cancer is hampered by insufficient follow-up and small patient numbers. To evaluate this, we reviewed our collective experience. PATIENTS AND METHODS: This study was a retrospective chart review recording demographics, tumor stage, treatment, and outcome of consecutive patients undergoing surgery. Survival was analyzed by Kaplan-Meier, and prognostic factors were analyzed by log-rank and Cox regression. RESULTS: From January 1993 to December 1999, 470 patients were treated, with follow-up in 446: 27 stage I, 55 stage II, 316 stage III, 43 stage IV (solitary M1), and five uncertain. Chemotherapy was mitomycin/vinblastine/cisplatin (174 patients [39.0%]), carboplatin/paclitaxel (148 [33.2%]), and other combination (124 [27.8%]); 75 patients (16.8%) received induction radiation. Resection was complete in 77.4%, incomplete in 8.3%, attempted but with gross residual disease afterward in 1.8%, and not performed in 12.6%. Pathologic complete response occurred in 20 patients (4.5%). With median follow-up of 31.0 months for patients still alive, median and 3-year survival for pathologic stages 0, I, II, III, and IV were more than 90 months, 73%; 42 months, 52%; 23 months, 35%; 16 months, 28%; and 16 months, 23% (P <.001). In a multivariate analysis, age, complete resection, pathologic stage, and pneumonectomy, but not induction regimen, significantly influenced survival. CONCLUSION: Although pathologic complete response outside the protocol setting is low, survival of this large patient cohort is comparable to that of patients in published combined-modality trials. Survival is significantly influenced by patient age, complete resection, pathologic stage, and pneumonectomy. These results can help guide standard clinical practice and emphasize the need for novel induction regimens.

INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy.

PURPOSE: To compare the local/regional control, survival, and toxicity of combined-modality therapy using high-dose (64.8 Gy) versus standard-dose (50.4 Gy) radiation therapy for the treatment of patients with esophageal cancer. PATIENTS AND METHODS: A total of 236 patients with clinical stage T1 to T4, N0/1, M0 squamous cell carcinoma or adenocarcinoma selected for a nonsurgical approach, after stratification by weight loss, primary tumor size, and histology, were randomized to receive combined-modality therapy consisting of four monthly cycles of fluorouracil (5-FU) (1,000 mg/m(2)/24 hours for 4 days) and cisplatin (75 mg/m(2) bolus day 1) with concurrent 64.8 Gy versus the same chemotherapy schedule but with concurrent 50.4 Gy. The trial was stopped after an interim analysis. The median follow-up was 16.4 months for all patients and 29.5 months for patients still alive. RESULTS: For the 218 eligible patients, there was no significant difference in median survival (13.0 v 18.1 months), 2-year survival (31% v 40%), or local/regional failure and local/regional persistence of disease (56% v 52%) between the high-dose and standard-dose arms. Although 11 treatment-related deaths occurred in the high-dose arm compared with two in the standard-dose arm, seven of the 11 deaths occurred in patients who had received 50.4 Gy or less. CONCLUSION: The higher radiation dose did not increase survival or local/regional control. Although there was a higher treatment-related mortality rate in the patients assigned to the high-dose radiation arm, it did not seem to be related to the higher radiation dose. The standard radiation dose for patients treated with concurrent 5-FU and cisplatin chemotherapy is 50.4 Gy.

An initial experience with FDG-PET in the imaging of residual disease after induction therapy for lung cancer.

BACKGROUND: The 2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) imaging is an advance over computed tomography alone in the staging of untreated nonsmall cell lung cancer (NSCLC). Aside from one 9-patient study, there are no data comparing FDG-PET imaging with surgical staging of NSCLC after induction therapy. METHODS: We reviewed our institutional experience with FDG-PET imaging followed by surgical staging of nonsmall cell lung cancer after induction therapy. A nuclear physician blinded to surgical findings reviewed the FDG-PET scans and assigned a clinical TNM stage. A thoracic surgeon assigned a pathologic TNM stage. Then the clinical TNM stage and the pathologic TNM stage were compared. RESULTS: Fifty-six patients (30 males and 26 females; median, age 60) with nonsmall cell lung cancer underwent chemotherapy (40 patients), chemoradiation (11 patients), or radiation alone (5 patients) followed by PET and operations. PET had a positive predictive value of 98% for detecting residual viable disease in the primary tumor. PET over-staged nodal status in 33% of patients, under staged nodal status in 15%, and was correct in 52%. PET correctly classified all patients with M1 disease. CONCLUSIONS: Positron emission tomography after induction therapy accurately detects residual viable primary tumor, but not the involvement of mediastinal lymph nodes.