P. Baldeyrou

Surgery for lung metastases from colorectal cancer: analysis of prognostic factors.

PURPOSE To identify prognostic factors of improved survival after resection of isolated pulmonary metastases (PM) from colorectal cancer. PATIENTS AND METHODS A retrospective analysis of the records of all patients with PM from colorectal cancer who underwent thoracic surgery with curative intent before December 1992 at a single surgical center was performed. Univariate (log-rank) and multivariate (Coxs model) analyses of survival were used to identify significant prognostic factors. RESULTS Eighty-six patients with PM from colon (n = 49) or rectal (n = 37) cancer underwent 102 thoracic operations, which included 21 bilateral and 10 incomplete resections. The 5- and 10-year probabilities of survival (Kaplan-Meier) after the first thoracic operation were 24% (95% confidence interval [CI], 15% to 35%) and 20% (95% CI, 13% to 31%), respectively. Sex, age, site of the primary tumor (colon or rectum), disease-free interval (DFI), and previous resection of hepatic metastases were found not to be statistically significant prognostic factors. Complete resection, a limited number ( < two) of PM, and a normal prethoracotomy serum carcinoembryonic antigen (CEA) level were predictors of a longer survival duration by univariate analysis, but only complete resection (P = .024) and preoperative CEA level (P = .001) were identified as independent prognostic factors by multivariate analysis. The estimated 5-year survival rate of patients with a normal prethoracotomy CEA level was 60%, as compared with 4% in cases with elevated ( > 5 ng/mL) CEA level. CONCLUSION Besides resectability, the prethoracotomy serum CEA level appears the most reliable predictor of survival in patients with isolated PM from colorectal cancer.

Surgical treatment of hepatic and pulmonary metastases from colorectal cancers

BACKGROUND Selected patients with double hepatic and pulmonary metastases from colorectal cancer may benefit from operation. METHODS From 1970 to 1995, 239 patients underwent operation for resection of pulmonary metastases from colorectal cancer at two French surgical centers. Among these patients, 43 (18%) had previously undergone complete resection of hepatic metastases and constitute the subject of this retrospective study. RESULTS The median interval time between hepatic and pulmonary resections was 18 months. Two pneumonectomies, 5 lobectomies, 3 segmentectomies, 6 wedge resections, and 27 metastasectomies were performed. No postoperative mortality was observed. Two patients had major postoperative complications. Seven patients (16%) underwent subsequent pulmonary resection for recurrences. Twenty-one patients were still alive, 14 free of disease. The median survival from pulmonary resection was 19 months and the 5-year probability of survival was 11%. Prethoracotomy carcinoembryonic antigen blood levels and the number of pulmonary resection were found to be significant prognostic factors; the interval time between hepatic and pulmonary resection (> 36 months) was borderline significant (p = 0.06). CONCLUSIONS Selected patients with combined hepatic and pulmonary metastases from colorectal cancer should be considered for surgical resection. Patients with normal prethoracotomy carcinoembryonic antigen levels and late metachronous pulmonary metastasis, appear to be the best surgical candidates.

Alternating radiotherapy and chemotherapy schedules in small cell lung cancer, limited disease

Sixty-three evaluable patients with limited small cell lung carcinoma were entered into two pilot studies alternating 6 cycles of combination chemotherapy (Doxorubicin 40 mg/m2 d 1; VP16213 75 mg/m2 d 1, 2, 3; Cyclophosphamide 300 mg/m2 d 3, 4, 5, 6; and Methotrexate 400 mg/m2 d 2--plus folinic acid rescue--or Cis-Platinum 100 mg/m2 d 2) with 3 courses of mediastinal radiotherapy as induction treatment. The first course of radiotherapy started 10 days after the second cycle of chemotherapy; there was a 7 day rest between chemotherapy and radiotherapy courses. This 6 month induction treatment was followed by a maintenance chemotherapy. The total mediastinal radiation dose was increased from 4500 rad in the first study to 5500 rad in the second. Both protocols obtained a complete response (CR) rate of greater than 85% (with fiberoptic bronchoscopy and histological verification). Local control at 2 years was 61% in the first study and 82% in the second. Relapse-free survival at 2 years was 32 and 37%, respectively. Toxicity was acceptable. We conclude that our results justify further clinical research in alternating radiotherapy and chemotherapy schedules.

Total vertebrectomy for en bloc resection of lung cancer invading the spine

We describe a technique of total vertebrectomy for en bloc resection of a non-small cell lung cancer with vertebral invasion through a combination of thoracic and enlarged posterior approaches, and present our entire experience of total and partial vertebrectomy for tumors invading vertebral bodies or the costovertebral angle.

High-dose-rate brachytherapy as sole modality for early-stage endobronchial carcinoma

PURPOSE To evaluate exclusive high-dose-rate brachytherapy for localized early-stage non-small-cell bronchial carcinoma; to develop new insights in treatment-catheter positioning and tumor-volume assessment by computed tomography (CT) scan. METHODS AND MATERIALS Between 1992 and 1996, 34 patients with non-small-cell bronchial carcinoma were treated by brachytherapy alone. All patients were medically inoperable and had contraindications for external beam irradiation. The treatment protocol was six sessions of 5 Gy over 6 weeks. The treatment catheter was placed under fiberoscopy and was positioned with the help of spacer catheters or with a surrounding plastic tube; CT scan was performed in 50% of the cases to measure the spacing between the applicator and the bronchial wall. Dose prescription was individually based on clinical and radiologic evaluation of tumor volume. RESULTS Local disease failure occurred in 5 patients (15%). With a median follow-up of 2 years, the local control rate was 85% and the survival rate 78%. No acute toxicity was found, except one pneumothorax. CONCLUSION Brachytherapy alone can give an optimal therapeutic ratio in small endobronchial carcinomas without radiation-induced morbidity. Such results are achieved after careful tumor volume evaluation and individualized treatment catheter positioning.

Docetaxel and interstitial pulmonary injury

Mr. A., 73 years old, with no relevant medical history, presented in July 1992 with an abnormal chest X-ray. Physical examination revealed no particular abnormality. The CT scan showed a bulky mass (80 x 70 mm) located in the posterior segment of lower left lobe of the lung (Figure 1), mediastinal lymph node involvement and a contralateral metastatic lesion. There were no radiological sign of interstitial infiltrate. Biopsies obtained by fiberoptic bronchoscopy were consistent with the diagnosis of lung adenocarcinoma. No other metastatic lesions were found. First-line chemotherapy with docetaxel was started in July 1992. The treatment schedule consisted of intra-

Cancer Resection on the Residual Lung After Pneumonectomy for Bronchogenic Carcinoma

BACKGROUND After pneumonectomy for bronchogenic carcinoma, the residual lung may be the site of a new lung cancer or metastatic spread. METHODS From 1989 to 1995, 13 patients with carcinoma on the residual lung after pneumonectomy for lung cancer were operated on. Three segmentectomies and 7 simple wedge resections were performed, 2 patients had multiple wedge resections, and 1 patient had an exploratory thoracotomy. Nine patients had a primary metachronous bronchogenic carcinoma, 3 had metastases from bronchogenic carcinoma, and no definite conclusion was reached in 1 case. RESULTS No postoperative mortality was observed. Four patients had postoperative complications. The mean postoperative hospital stay was 14 days. Seven patients are alive, including 5 patients without evidence of disease. Six patients died of their disease, all with pulmonary recurrences. The overall median survival was 19 months, with a probability of survival at 3 years (Kaplan-Meier) of 46% (95% confidence interval, 22% to 73%). CONCLUSIONS Limited pulmonary resection for lung cancer after pneumonectomy for bronchogenic carcinoma is feasible with very low morbidity. In highly selected patients, surgical resection might prolong survival.

Alternating radiotherapy and chemotherapy in 173 consecutive patients with limited small cell lung carcinoma

One-hundred seventy-three patients with limited small cell lung cancer were included in three consecutive protocols alternating radiotherapy and chemotherapy. The alternating schedule consisted of six courses of chemotherapy (doxorubicin, VP16213, cyclophosphamide, and methotrexate in the first protocol; methotrexate being replaced by cisplatinum in the other two protocols) and three series of thoracic radiotherapy delivering a total dose of 45, 55, and 65 Gy in each consecutive protocol. Radiotherapy was started after the second course of chemotherapy. A 1-week gap was respected between each course of chemotherapy and each series of radiotherapy. Seventy percent of patients were in complete remission at the end of the induction treatment. The actuarial 5-year local control was 60% and the 5-year overall survival was 18%. Sixty percent of patients developed distant metastases. The death rate unrelated to cancer was 10%. These results show that alternating radiotherapy and chemotherapy schedules are reproducible, and provide a consistent long-term local control and a long-term survival rate exceeding 15% in limited disease.

Phase I–II study of vinorelbine (Navelbine®) plus cisplatin in advanced non-small cell lung cancer

32 patients with advanced non-small cell lung cancer previously untreated by chemotherapy were included in a phase I-II study in order to determine the feasibility of the combination of vinorelbine and cisplatin, each administered at its optimal dose, i.e. 30 mg/m2 weekly and 120 mg/m2 every 4-6 weeks, respectively. There were 27 males and 5 females with a mean age of 55 years and a median performance status of 80%. 13 had locally advanced disease and 19 had distant metastases at the time of inclusion. Our study demonstrated the feasibility of this protocol. Dose intensities could be maximised by adapting vinorelbine doses rather than by postponing treatment in the event of neutropenia. Both response rate (33%) and overall survival of the population (median 11 months) justify further studies.

Limited small cell lung cancer treated by combined radiotherapy and chemotherapy: evaluation of a grading system of lung fibrosis*

A grading system of radiological fibrosis was defined and applied by four observers for the reading of 218 posterior-anterior chest X-rays of 78 patients. These patients with limited small cell lung cancer were treated from May 1980 to July 1983 in two consecutive alternating radiotherapy-chemotherapy schedules. Chest X-rays performed at each 6-month interval were read by each observer. A second reading was performed the day after. The analysis of results showed that in spite of some systematic variations in intra- and inter-observations, the proposed grading system had a good reproducibility. The radiological lung fibrosis score progressed between 6 and 12 months but was stable after one year of follow-up. There was no difference in the score of lung fibrosis between the two protocols which delivered a total dose of 45 and 55 Gy to the mediastinum. There was no significant correlation between the radiological changes and clinical symptoms.