[Randomised phase III trial of fotemustine versus fotemustine plus whole brain irradiation in cerebral metastases of melanoma]. / Essai de phase III randomisé comparant la fotémustine seule ou associée à une irradiation encéphalique dans les métastases cérébrales de mélanome.

PURPOSE: The main objective of this prospective multicenter randomised phase III study was to compare a combined regimen of fotemustine plus whole brain irradiation versus fotemustine alone in terms of cerebral response and time to cerebral progression in patients with melanoma brain metastases. PATIENTS AND METHODS: Seventy-six patients (instead of the 106 planned patients; study was stopped after the interim analysis) were randomised receiving either fotemustine (arm A, n = 39) or fotemustine and whole brain irradiation (arm B, n = 37). Fotemustine was administered intravenously at 100 mg m(-2) on day 1, 8 and 15, followed by a 5-week rest period, then every 3 weeks in non-progressive patients. In arm B, a concomitant whole brain irradiation was performed at the total dose of 37.5 Gy (2.5 Gy/d(-1), days 1-5, 3 consecutive weeks). RESULTS: Although patients who received fotemustine alone had worse prognostic factors, there was no significant difference in brain response (arm A: 7.4%, B: 10.0%) or control rates (objective response plus stable disease) after seven weeks (arm A: 30%, B: 47%) and overall survival (arm A: 86d, B: 105d). However, there was a significant difference in favour of arm B for the time to brain progression (p = 0.028, Wilcoxon test). CONCLUSION: Fotemustine plus whole brain irradiation delayed the time to brain progression of melanoma cerebral metastases compared to fotemustine alone but without a significant improvement in terms of objective control or overall survival.

Ewing's family of tumors in adults: multivariate analysis of survival and long-term results of multimodality therapy in 182 patients.

PURPOSE: To assess the outcome and the prognosis of adults with a neoplasm related to the Ewing's sarcoma family of tumors. PATIENTS AND METHODS: The outcomes of 182 consecutive patients older than 15 years with Ewing's sarcoma or related neoplasms managed from 1982 to 1992 were reviewed, without any selection according to primary tumor site or disease extension. RESULTS: Of 182 patients, 53 had evidence of metastases at presentation (29%). Tumor size was greater than 10 cm in 70 patients (41%). With a median follow-up duration of 66 months, the 5-year overall survival (OS) rate was 41%. In patients with localized disease, 5-year OS rate was 54% and 5-year progression-free survival (PFS) rate, 43%. Late relapses after 5 years accounted for 9% of relapses. Metastasis at presentation (P = .00001), pelvic primary lesion (P = .0025), and tumor size greater than 10 cm (P = .004) were independent prognostic factors for survival. Five-year OS was 67% in patients with nonpelvic tumors < or = 10 cm, 52% in those with pelvic tumors less than 10 cm or extrapelvic tumors > or = 10 cm, 16% in those with pelvic tumors greater than 10 cm, and 9% in those with metastasis (P = .00001). CONCLUSION: Based on our experience and a review of the literature, we concluded that the natural history and the prognosis of the Ewing's family of tumors in adults are not different from that found in children. A greater tumor bulk in adults may explain the less favorable prognosis previously reported by others. Outcome could be adequately monitored by a simple prognostic index.

Predictive factors for complete removal in soft tissue sarcomas: a retrospective analysis in a series of 592 cases.

BACKGROUND AND OBJECTIVES: In order to specify the indications for conservative surgery and preoperative therapeutic approaches of soft tissues sarcomas (STS), we looked for the clinico-pathological parameters associated with the failure to obtain a complete removal (CRm) of the tumor. METHODS: We retrospectively analyzed a series of 592 cases of primary non-metastatic STS. Surgery was performed in 495 cases as a primary treatment and in 88 cases after chemo- or radiotherapy. Nine patients were treated by chemotherapy-radiotherapy. In a univariate analysis, 20 parameters were tested for their association with CRm. A multivariate analysis was then used to define the independent parameters linked to the achievement of a CRm. RESULTS: In the univariate analysis, 15 parameters were found to be linked to the achievement of a CRm. Three of them proved to be independent in the multivariate analysis: T in the TNM classification, tumor location, and tumor necrosis. By the combination of these risk factors, four groups of patients were defined, with respective rates of CRm of 97% (no factor), 95% (one factor), 70% (two factors), and 48% (three factors). CONCLUSIONS: The achievement of a CRm after surgery of STS depends not only on the accessibility of the lesion, but also on tumor aggressiveness, a reflection of which is necrosis. The detection of necrosis by imaging procedures may thus help predicting the resectability of tumors and defining the indications for neoadjuvant therapies, likely to broaden the use of conservative surgery.

[Role of adjuvant chemotherapy in the treatment of soft tissue sarcoma]. / Place de la chimiothérapie adjuvante dans le traitement des sarcomes des tissus mous de l'adulte.

Important improvements in local control with increasing function-sparing treatment have been achieved in adult soft tissue sarcomas (STS). However, the global prognosis of these diseases remains poor and 40% of patients with STS currently die of metastases within 5 years. In fact, the impact of chemotherapy remains debated, particularly in the adjuvant setting. Thirteen randomized clinical trials with no-treatment control arms have been published to assess adjuvant chemotherapy. A benefit has been demonstrated in 2 studies for overall survival, and in 5 studies when considering disease-free survival (DFS). Globally, despite large differences between studies (patient selection and treatment modalities), overall survival, DFS and local control of the chemotherapy arm were always better than those of the observed arm. These effects were also confirmed in 3 meta-analyses on published data. However, according to the preliminary results of a meta-analysis on individual patient data, overall survival does not appear to be significantly affected. Therefore, adjuvant chemotherapy for STS remains investigational. Randomized studies have to be pursued on the basis of previously performed trials in order to assess which patient group really benefits from adjuvant chemotherapy.

Comparative study of the National Cancer Institute and French Federation of Cancer Centers Sarcoma Group grading systems in a population of 410 adult patients with soft tissue sarcoma.

PURPOSE: Several histologic grading systems have been validated in soft tissue sarcomas (STS), but no system is currently accepted worldwide. The National Cancer Institute (NCI) and French Federation of Cancer Centers Sarcoma Group (FNCLCC) systems were examined comparatively in the same population of patients with STS to determine which system is the best prognosticator with regard to metastasis development and tumor mortality. PATIENTS AND METHODS: Four hundred ten adult patients with nonmetastatic STS were examined. Histologic grade was established according to the NCI and FNCLCC systems in each case. The prognostic value of both systems was examined using univariate and multivariate (Cox's model) analyses, and special attention was devoted to tumors with discordant grades. RESULTS: In univariate analysis, both the NCI and FNCLCC systems were of prognostic value to predict metastasis development and tumor mortality. In multivariate analysis, high-grade tumors, irrespective of the system used, size > or = 10 cm, and deep location were found to be independent prognostic factors for the advent of metastases. Tumor grade had a higher predictive value than size or depth, and higher prognostic weight was assigned to the FNCLCC grading system in Cox models. Grade discrepancies were observed in 34.6% of the cases. An increased number of grade 3 STS, a reduced number of grade 2 STS, and a better correlation with overall and metastasis-free survival within subpopulations with discordant grades were observed in favor of the FNCLCC system. CONCLUSION: The FNCLCC system showed slightly increased ability to predict distant metastasis development and tumor mortality. The use of this system to evaluate STS aggressiveness might be favored.

Histopathologic grading in spindle cell soft tissue sarcomas.

Tumor grade is currently the most important factor in the staging of patients with soft tissue sarcomas. In previous studies, a histopathologic grading system was described and its reproducibility was tested. The current study reports the value of this grading system in spindle cell sarcomas, which represent about one half of all adult soft tissue sarcomas, the precise identification of which is often difficult. One hundred twenty-five such tumors were studied retrospectively. Malignant fibrous histiocytoma was the most frequent histologic type, followed by leiomyosarcoma, neurosarcoma, and fibrosarcoma. Tumor grade was correlated with the advent of metastases and survival, and was the main prognostic factor according to multifactorial analysis introducing clinical prognostic factors.

Improved control of cisplatin-induced emesis with a combination of high doses of methylprednisolone and metoclopramide: a single-blind randomized trial.

Forty-seven patients undergoing their first course of chemotherapy containing cisplatin in combination with other drugs were randomized to compare the antiemetic efficacy of high dose metoclopramide vs. high dose methylprednisolone added to metoclopramide. The number of patients who experienced no emetic episodes was significantly higher with the combination regimen (P less than 0.01). In addition, both the mean number of emetic episodes (P = 0.01) and the duration of nauseas (P = 0.025) were decreased with the combination regimen. Both antiemetic regimens were well tolerated. Sex affected the response, with women having more nausea and vomiting than did men (P less than 0.05).

[Histological changes after chemotherapy of soft tissue sarcomas in the adult]. / Modifications histologiques après chimiothérapie des sarcomes des tissus mous de l'adulte.

The variations of histologic patterns inside the primary tumor have been studied in 15 patients with locally advanced soft tissue sarcomas who were given induction (neo adjuvant) chemotherapy. Increase of tumor necrosis and decrease of tumor cellularity were the predominant aspects identified. The mitosis count tend to be lower, while the nuclear atypies and the number of giant malignant cells tend to increase. In 2 cases, a better tumor differentiation, attributable to the induction chemotherapy was noted. In 10/15 cases, it was concluded to a tumoricidal effect of the chemotherapy. According to tumor grade, 6 among 10 patients with grade III tumor presented a histological response (greater than 50 p. cent of tumor destruction) while none among 5 lesions of grade I or II exhibited a response of such a level. So, the histological study allows an evaluation of the response to chemotherapy which usefully completes the clinical appreciation, and that may be useful for the selection of postoperative adjuvant treatment, as it is in osteosarcomas.