PubMed Health⌕ Search

Biomedical subjects

Sylvie Bonvalot

Publications and source records attributed to Sylvie Bonvalot.

12 recordsLinked to original sources

[Diagnosis and treatment of gastrointestinal stromal tumours].

Gastrointestinal stromal tumours (GISTs) are most common in the stomach (60-70%), followed by small intestine (20-25%), colon and rectum (5%), and esophagus (<5%). They are characterized by expression of the transmembrane receptor tyrosine kinase KIT, which is defined by the CD117 antigen and is the product of the kit proto-oncogene. Metastatic risk is based on tumour size and mitotic count. The treatment options have evolved rapidly with the discovery of imatinib (Gleevec) that selectively inhibits KIT. Complete resection without tumour rupture remains the mainstay of treatment in patients with localized, resectable disease. Imatinib has been shown to be the first successful systemic therapy for patients with metastatic or unresectable disease and is also currently being tested as an adjuvant therapy after the resection of high risk primary GIST. New blockers of the tyrosine-kinase activity are currently in development in cases of resistance.

Algorithms↗

Management of gastrointestinal stromal tumors in the imatinib era: selected case studies.

The introduction of imatinib, an orally administered inhibitor of the KIT receptor tyrosine kinase, is prompting revision of the management algorithms that have traditionally guided the treatment of gastrointestinal stromal tumor (GIST). Historically, patients with GISTs have had substantial rates of relapse as well as limited long-term survival even after complete surgical resection of a primary tumor. Imatinib has been shown to induce durable tumor responses in more than half of the patients with malignant metastatic or unresectable GISTs and to halt disease progression in an additional third. These encouraging results have led to the initiation of clinical trials of imatinib as an adjuvant or neoadjuvant therapy with surgery. Until relevant data are reported to provide definitive direction for the management of operable or potentially operable GISTs, treatment decisions must be made on the basis of the available evidence and clinical experience with imatinib. This paper presents selected case studies describing approaches to the combined use of surgery and systemic therapy that have been applied in the treatment of individual GIST patients. The management of GIST in these cases required a coordinated, multidisciplinary approach involving medical oncologists, diagnostic radiologists, gastroenterologists, surgeons, and pathologists.

Adult↗

Gastrointestinal stromal tumors treated with imatinib: monitoring response with contrast-enhanced sonography.

OBJECTIVE: The purpose of this study was to evaluate contrast-enhanced Doppler sonography with perfusion software as a predictor of early tumor response to imatinib (Glivec) in c-kit-positive gastrointestinal stromal tumors (GISTs). SUBJECTS AND METHODS: Thirty patients (59 tumors) with metastases or a recurrence from a GIST were prospectively included in a single-center imaging trial. Contrast-enhanced Doppler sonography was performed with an Aplio scanner the day before (day-1) starting oral treatment (400 mg) and at days 1, 7, 14, 60, 90, and 6 months, 9 months, and 1 year. The percentage of contrast uptake (Levovist or Sonovue) before treatment and at the different stages of follow-up was evaluated by two radiologists. Digitized quantification was performed using Photoshop software. To define the benchmark standard, all patients were rated as responders or nonresponders at 2 and 6 months by a board consisting of oncologists and radiologists who had all clinical and imaging data at their disposal. Changes in the percentage of contrast uptake at each sonographic examination were compared statistically. RESULTS: A total of 185 examinations were performed. Forty-four lesions in 24 patients were completely evaluated at 2 months, and 29 lesions in 15 patients were completely evaluated at 6 months. Initial contrast uptake at day 1 was predictive of the future response. A strong correlation was found between the decline in tumor contrast uptake at days 7 and 14 and tumor response (p < 10(-4)). CONCLUSION: Contrast-enhanced Doppler sonography is a noninvasive imaging technique that allows the early prediction of tumor response in c-kit-positive GIST treated with Glivec.

Antineoplastic Agents↗

[Neoadjuvant chemotherapy in sarcoma].

This document describe s the proposed clinical practices guidelines for neoadjuvant chemotherapy in soft tissue sarcomas proposed by the French Sarcoma Group.Neo-adjuvant chemotherapy remains an experimental therapeutic procedure in soft tissue sarcomas. Neo-adjuvant chemotherapy may be proposed in three different types of situations: 1) a locally advanced tumor, non accessible to R0 or 1 removal of the lesion. Its objective is there to allow for R0 or R1 surgical removal of the tumor. 2) A locally advanced tumor, accessible to R0 or 1 removal of the lesion, but with a mutilating surgery (amputation). Its objective is there to allow for R0 or R1 conservative surgical removal of the tumor. In both situation, the strategy should be discussed beforehand in a multidisciplinary specialized consultation for sarcoma. 3) In the case where complete (R0 or R1) surgical removal of the tumor can be performed, neooadjuvant chemotherapy has no demonstrated role. The only randomized phase III clinical trial testing neo-adjuvant chemotherapy in this setting, i.e. the STBSG 62871 STBSG trial, failed to demonstrate any benefit in terms of overall or progression free survival. The selection of the type of chemotherapy regimen given in the neoadjuvant setting should be discussed in a multidisciplinary setting, considering the age and the general status of the patient; young patients, without associated concomittent illnesses should be proposed for a combined chemotherapy regimen, combining doxorubicin (> or = 50 mg/m2) and ifosfamide (> 5 g/m2) on the basis of randomized trials demonstrating an improvement of response rate versus single agent therapy with doxorubine. In elderly and/or frail patients, conversely, single agent doxorubicin may be the preferred option.

Antineoplastic Agents↗

[Retroperitoneal sarcomas imaging].

Retroperitoneal sarcomas are rare neoplasms. The aim of this article is to expose imaging protocols and useful radiological signs, to show the core biopsy technique for diagnosis, to precise imaging key points before treatment and for survey.

Biopsy, Needle↗

[Place and technical aspects of external beam radiation therapy in the treatment of adult soft tissue sarcomas].

In soft tissue sarcoma, surgical resection remains the cornerstone of therapy for localized disease. Quality of margins is very important to evaluate. In case of marginal or incomplete resection, a new enlarged surgical resection should always be discussed before administration of any adjuvant treatments. Many retrospective studies and 2 randomized studies (one of adjuvant brachytherapy and one of external beam radiotherapy) have shown that adjuvant radiotherapy after complete surgery reduces significantly the risk of local recurrence in extremity soft tissue sarcomas. Combination of surgery and pre- or postoperative radiotherapy has therefore become the standard treatment with a local recurrence rate <or=25% and very few amputations. A recent randomized study has compared pre-op to postoperative radiotherapy. The results in terms of local control are similar in both arms (93 and 92% at 5 years) but the risk of early complications is higher in the preoperative arm and the risk of late sequela is higher in the postoperative arm. Surgical resection without radiotherapy may be considered after discussion at best within a multidisciplinary meeting, if surgical margins are considered satisfactory, in superficial, small tumours and low-grade. In retroperitoneal sarcomas, adjuvant radiotherapy is not a standard. It may decrease the risk of local recurrence but at the price of an increased gastro-intestinal toxicity. A randomized trial is warranted. Because of its rarity, and the risk of recurrence both local and metastatic, treatment should preferentially be discussed with a multimodality specialized approach.

Adult↗

Role of computed tomography in the follow-up of hepatic and peritoneal metastases of GIST under imatinib mesylate treatment: a prospective study of 54 patients.

PURPOSE: To prospectively analyze the evolution of hepatic and peritoneal unresectable metastases from gastrointestinal stromal tumors (GIST) under imatinib mesylate, a new targeted treatment, which induces changes in lesion structure. MATERIALS AND METHODS: 54 patients with metastases from GIST underwent an abdominal and pelvic computed tomography examination without and with contrast enhancement, before and during treatment with imatinib mesylate. The number and size of lesions and contrast enhancement were noted before treatment and every 2 weeks for the first 2 months, then every 2 months for the first year of treatment and every 3 months thereafter. RESULTS: 27 patients presented with both hepatic and peritoneal metastases, 14 had only peritoneal and 13, only hepatic disease. On baseline imaging, all metastases were hypodense heterogeneous lesions with progressive, concentric enhancement. After treatment (mean duration of follow-up: 23 months) metastases decreased in size number and enhancement in 35/54 patients, remained stable in 2 patients and increased in 14 patients. In 13/39 patients with hepatic metastases a cyst-like appearance was noted. Reactivation after a partial response appeared first as a focal, peripheral, solid nodule in the wall of a cystic lesion, or an increase in lesion density, before size regrew. CONCLUSION: Besides the classic size criterion, a decrease in density and in contrast enhancement with stable "near cystic" lesions signifies a good response. A more aggressive approach (surgery or radiofrequency ablation) may be indicated for initially focal recurrences with a stable size.

Adult↗

[Recommendations for the management of GIST patients].

BACKGROUND: The management of gastrointestinal stromal tumors (GIST) has evolved very rapidly in the last years. A national consensus meeting was therefore organized in order to identify the optimal management procedures for patients with GIST in localized and advanced stages. METHODS: A panel of different specialties, including pathology, molecular biology, imaging, surgery, gastroenterology, medical oncology reviewed the current literature, in particular the recent Lugano conference, to identify consensus points and topics for future research in four different working groups: pathology and molecular biology, early management of small tumors and imaging, surgery, and medical treatment. Consensus points were categorized according to the Standard Options Recommendations (SOR) of the French Federation of Cancer Centers. RESULTS: The standard histological examination with immunohistochemical analysis using CD117, CD34, PS100, desmin and smooth muscle actin is considered standard. Molecular biology for the identification of KIT and PDGFRA mutation is advisable for GIST with negative CD117 staining, and otherwise is considered a research procedure. Complete tumor resection with negative tumor margins is the standard surgical treatment. Adjuvant imatinib after optimal tumor resection as well as neo-adjuvant imatinib remain experimental approaches to be performed within prospective clinical studies. Imatinib should be started at the date of diagnosis of metastatic relapse and given until development of intolerance or progressive disease. Resection of metastases is also considered as an experimental procedure which can not be recommended routinely. The criteria for tumor response to imatinib should include not only tumor size reduction or disease stabilization, but also reduction of tumor density (Hounsfield units) on computed tomography, metabolic activity (i.e. reduction of FDG uptake on positron emission tomography), and reduction of vascularisation of the tumors using contrast enhanced ultrasound evaluation. An increase in tumor size may be associated with pathologic response to imatinib therapy, and available survival data indicate that the survival of these patients is similar to that of patients with conventional tumor response. CONCLUSIONS: Consensus points in clinical management of GIST in this national conference adopted the majority of consensus points published in the Lugano conference. This multidisciplinary work will be published in the reference oncology, gastroenterology, and pathology journals in French languages.

Antineoplastic Agents↗

MR imaging in the evaluation of isolated limb perfusion: a prospective study of 18 cases.

PURPOSE: To prospectively evaluate the use of MRI with dynamic sequences during isolated limb perfusion (ILP) for soft tissue sarcomas, an aggressive local treatment using very high-dose chemotherapy and tumor necrosis factor aimed at avoiding limb amputation. DESIGN AND PATIENTS: Twenty-six patients were referred for ILP over one and a half years; eight were excluded as the lesions were either too proximal or suspicious inflammatory changes without tumor were found on the initial MRI, or the vascular status was poor. The indications for ILP were: vessel nerve involvement (13), multiple lesions (8), tumor size (4) or the presence of pulmonary metastases (2). MRI was performed 1 and 2 months after ILP, immediately prior to surgery and histological analysis. The MR examinations included T1-weighted SE and fast SE T2-weighted fat-saturated sequences, as well as dynamic sequences (T1-weighted SE repeated six times every 40 s), displaying the maximum intensity slope in each pixel. RESULTS: The tumor had disappeared in three patients. One patient still had histologically proven isolated widespread tumor cells without a mass. The tumor size had increased in two patients. In six patients, the size of the tumor had not changed but it had become completely necrotic, with a thin wall. In three patients, after an initially good result MRI demonstrated that the tumor wall had become thickened from 1 to 2 months after ILP. Dynamic MRI was mainly useful during the initial examination, demonstrating two patients with inflammatory changes without tumor. Three amputations and a second ILP were proposed based on poor results. Conservative limb-sparing surgery was successful in the other cases. CONCLUSION: MRI proved valuable in demonstrating the variable responses to ILP.

Adult↗

[Management of recurrent soft tissue sarcoma of the retroperitoneum].

Local recurrence is the determinant of tumor-related mortality in retroperitoneal sarcomas because death often occurs as a result of local progression mostly without synchronous metastasis. Complete resection of the lesion and surgical margins status are the only therapeutic factors significantly associated with local control. Further outcome improvements need multimodal therapy since prognosis of these recurrences is poor with lower rates of complete resection and higher grade of malignancy than primary. Complete resection of the recurrence often requires removal of adjacent organs to achieve negative margins. External beam radiotherapy (EBRT), eventually associated with a boost of intra-operative electron beam radiotherapy (IORT) could improve the outcome in these patients. Preoperative timing could limit its toxicity. Chemotherapy protocols may enhance local and systemic outcome and can reduce the volume of high grade tumors and therefore allow a higher rate of complete resection. Isolated pelvic perfusion with local high doses chemotherapy is under investigation. Surgical excision of lung metastases should remain the treatment of choice, if preoperative evaluation indicates that complete clearance of the metastases is possible. Intra-operative chemotherapy after cyto-reductive surgery for the treatment of sarcomatosis is disappointing and complete surgery remains the cornerstone of the treatment with best results for low grade sarcomatosis. Adequate management at the time of primary presentation is likely to afford the best chance for long-term survival.

Chemotherapy, Adjuvant↗