D. Grunenwald

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.

Patterns of relapse of N2 nonsmall-cell lung carcinoma patients treated with preoperative chemotherapy

Although it induces a relevant reduction in the risk of both visceral metastases and locoregional recurrences, the combination of chemotherapy and surgery only marginally improves the survival of patients with Stage IIIA(N2) (International Union Against Cancer staging and classification system) nonsmall‐cell lung carcinoma (NSCLC). The purpose of the current study was to analyze the patterns of relapse in these patients.

Concurrent cisplatin-vindesine and hyperfractionated thoracic radiotherapy in locally advanced nonsmall cell lung cancer

PURPOSE Local failure is a major problem in locally advanced nonsmall cell lung cancer. The main objective of this Phase II trial was to test the feasibility of a combined concurrent radiotherapy and chemotherapy approach in an attempt to improve local control. METHODS AND MATERIALS From December 1989 to December 1992, 34 patients were included. The treatment schedule consisted of hyperfractionated radiotherapy (60 Gy in 48 fractions and 6 weeks with two daily sessions of 1.25 Gy), cisplatin (6 mg/m2 every day of radiotherapy), and vindesine (2.5 mg/m2 once weekly). After a 3-week rest period, two full cycles of cisplatin (120 mg/m2 on weeks 10 and 14) and vindesine (2.5 mg/m2 on weeks 11, 12, and 13) were given. Treatment evaluation with thoracic computed scan, bronchoscopy, and bronchial biopsies was performed 3 months after completion of radiation therapy. Failure rates were estimated using a competing risk approach. RESULTS The complete response rate was 50%. Local failure rates at 1 and 3 years were 53 and 56%, respectively. Distant metastases rates at 1 and 3 years were 26.5 and 29%. Overall survival rates at 1, 2, and 3 years were respectively 53, 33, and 12%. Severe esophagitis was observed in three patients (9%). Lethal toxicity was observed in two patients. CONCLUSION This Phase II trial confirms the feasibility of this type of approach with specific dose reduction and suggests that it may improve local control compared to conventional approaches.

Neoadjuvant chemotherapy of locally advanced non-small cell lung cancer

Neoadjuvant chemotherapy was tested in non-small cell lung cancer in an attempt to increase the resectability of the tumor and to treat the microscopic metastatic disease known to be responsible for the majority of failures in surgically treated patients. This review deals with published trials. Most of them are feasibility studies in Stage III NSCLC. Obviously, the heterogeneity of eligibility criteria from one study to another prevents general conclusions on the usefulness of neoadjuvant chemotherapy. However, it is possible to conclude that neoadjuvant chemotherapy has an antitumor activity; the majority of the studies report a 60% objective response rate including a significant number of complete responses and a 50% complete resection rate. Neoadjuvant chemotherapy does not increase morbidity after surgery except when it is combined with preoperative radiation therapy. At the time of writing, one Phase III randomized study comparing neoadjuvant chemotherapy followed by surgery with surgery alone has been published. This study concludes that the combined modality treatment improves the survival of patients with locally advanced non-small cell lung cancer. Taken as a whole, the literature deserves further studies to determine the place of neoadjuvant chemotherapy in lung cancer.

Nuclear expression of CXCR4 is an independent prognostic factor for overall and progression-free survival in malignant pleural mesothelioma

7196 Background: CXCR4 is a chemokine receptor which takes part in diverse events like the migration of lymphocytes to sites of inflammation, internalization of the HIV particle by lymphocytes, and homing of metastasizing tumor cells. Recent studies suggest that nuclear -rather than membranous or cytoplasmic- expression of CXCR4 may signify a different function. In this study, we aimed to evaluate the prognostic significance of nuclear CXCR4 expression in patients with malignant pleural mesothelioma (MPM). METHODS The records of 66 MPM patients were reviewed and CXCR4 expression of their tumors were assessed by immunohistochemistry. Prognostic significance of this marker was evaluated using Log rank test and a Cox proportional hazards model. RESULTS The mean age of patients was 61±10 years (min: 41, max: 85). Fifty-one patients were males (77%), and 15 were females (23%). The median percentage of cells expressing nuclear CXCR4 was 5.1% (min-max: 0-95), and this was used as the cut-off to define CXCR4-positive and negative tumors. Patients whose tumor expressed nuclear CXCR4 had a median overall survival (OS) of 20.9 months (95% confidence interval [CI]: 11.8-30.0) while those with negative tumors had an OS of 11.9 mths (95% CI: 11.3-12.5; p=0.03). Similarly, median progression-free survival (PFS) was 13.6 mths (95% CI: 9.2-18.0) and 7.4 mths (95% CI: 4.6-10.3) for CXCR4-positive and negative cases, respectively (p=0.02). A multivariate model including other possible prognostic factors like age, sex, stage and histological subtype showed that nuclear CXCR4 expression is an independent prognostic factor, both for OS and PFS (p=0.01 and p=0.005, respectively). CONCLUSIONS Nuclear expression of CXCR4 is associated with better OS and PFS in patients with MPM. The mechanisms underlying the favorable impact of the aberrant localization of this molecule merits further investigation. No significant financial relationships to disclose.

Combined treatment modalities in non-small cell lung cancer: a French experience

Non-small cell lung carcinoma (NSCLC), which accounts for 80% of lung cancers, is the first cause of mortality from cancer in males in western countries [l]. Its curative treatment is surgery. In most cases, however, the disease is inoperable at the time of presentation because of either locally advanced tumor (stage III) or distant metastasis (stage IV). Sixty to 70% of patients with locally advanced NSCLC will die from intrathoracic disease, with or without distant metastases [2,3] and the median survival of such patients is less than 6 months without treatment 141. A complete radiologic response can be obtained in 7 to 30% of cases after radical radiotherapy [5] but, even in the case of apparent local control, long-term survival remains disappointing because of the high rate of distant metastases [6]. Better local control and a decrease in distant metastases are required to improve survival. There is, however, a need for an optimal definition of locoregional staging which would facilitate the design of a therapeutic strategy which might include surgery, radiotherapy (RT) and/or chemotherapy (CT). The purpose of this paper is to summarize the experience of French groups conducting randomized trials on the combined management of NSCLC.