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X Sastre

Publications and source records attributed to X Sastre.

At least 19 recordsLinked to original sources
PubMed2006

[Cavitary choroidal melanoma in a child].

Uveal melanoma is very rare in children, and in both adults and children it can in rare cases develop intralesional cavities resembling an intraocular cyst. The presence of a solid mass at the base and a thick wall surrounding the cavity can assist in differentiating cavitary melanoma from a benign cyst. We report the case of a 5-year-old girl who presented with a large intraocular pigmented mass in the left eye, showing multiple hollow cavities on ocular ultrasonography, CT scan, and MRI. The patient was treated by enucleation and the pathology confirmed the diagnosis of choroidal melanoma. FISH revealed no aberration in chromosome 3.

Child, Preschool↗
PubMed2006

[Prognostic factors for malignant uveal melanoma. Retrospective study on 2,241 patients and recent contribution of monosomy-3 research].

INTRODUCTION: We conducted a retrospective study on the clinical factors influencing the local and general prognosis of patients treated for uveal melanoma with a preliminary analysis of the prognostic value of monosomy 3. PATIENTS: and method: The patients sent to Curie Institute for uveal melanoma have a complete initial clinical evaluation, conservative management by radiotherapy or enucleation, and local and general long-term follow-up. Over the last 5 years, the status of chromosome 3 has been assessed by FISH in the tumors of enucleated patients. Findings concerning the initial workup, treatment, and follow-up are recorded prospectively. We conducted a retrospective study with multivariate analysis of the clinical factors influencing local recurrence, ocular conservation metastasis, and survival and studied the effect of monosomy 3. RESULTS: A total of 2241 patients were registered with a median follow-up of 72 months. Of these patients, 92.8% had conservative management with iodine 125 brachytherapy or proton beam therapy and 7.2% of the patients had enucleation (n=160). Tumors from 120 patients were studied for the status of chromosome 3 by FISH. The overall survival rate was 76.3% and the metastatic rate was 19.5%. The clinical factors influencing survival were the size and location of the tumor, age of the patient, gender, and initial treatment. The factors influencing the metastatic risk were the same plus retinal detachment and local recurrence. Monosomy 3 was a significant risk factor for metastatic disease. DISCUSSION: This study found the usual risk factors with the difference that location on the equator seems to be of worse prognosis than ciliary body involvement for survival and metastasis. In addition, the initial retinal detachment appears to be a risk factor for local recurrence and metastasis. At present, the evaluation of chromosome 3 is available for enucleated tumors but it could probably be done on needle biopsy performed during conservative management as well. CONCLUSION: This study confirms previous results on the prognostic factors of uveal melanoma and on the value of monosomy 3. The increasingly precise identification of a group of high-risk patients should allow us to propose adjuvant therapy and to adapt follow-up.

Disease-Free Survival↗
PubMed2003

[Bilateral uveal melanomas. Five case reports].

PURPOSE: Uveal malignant melanoma is the most common primary intraocular tumor in adults. The occurrence of bilateral uveal melanoma is an extremely rare event, but the observed frequency is nevertheless higher than what can be attributed to chance. Possible responsible factors may include a genetic predisposition. PATIENTS AND METHODS: This retrospective study investigated the charts of patients examined from July 1988 to July 2001. For each patient, the clinical characteristics of the tumor (diameter, thickness, location), treatments, and results were noted, as were the eye involved, the presence of ocular melanocytosis, cutaneous melanoma, and second primary cancers. The information was then subjected to statistical analysis. RESULTS: Of 2 461 patients with unilateral primary uveal melanoma, five were identified as having bilateral uveal melanoma (0.2%). The expected number of cases would be less than one, hypothesizing an incidence of second melanoma identical to the incidence of a primary melanoma in the general population. The interval between the diagnosis of first and second primary uveal melanomas ranged from 0 to 6 years (median, 2 years). There was no clinical evidence of ocular melanocytosis in any of the five patients. The uveal melanoma was choroidal in three patients and affected the ciliary body or iris and choroid in two patients. DISCUSSION: The discrepancy between the estimated incidence (thought by Shammas to be one case every 18 years) and the observed incidence of bilateral primary uveal melanoma could be the result of many possible factors. An increased incidence of unilateral uveal melanoma could be a cause but in fact the incidence of uveal melanoma seems stable. Uveal melanoma may have been misdiagnosed in earlier years. The presence of a genetic predisposition to uveal melanoma is a possible explanation (suspected because of bilateral cases, familial cases and association with other primary malignancies). Ocular melanocytosis, which is described as more common in patients with bilateral uveal melanoma, was not seen in our series. CONCLUSION: Bilateral primary uveal melanoma occurs more frequently than expected. Unidentified germline mutations may be involved in pathogenesis. These cases serve as a reminder of the of the importance of careful examination of the second eye.

Aged↗
PubMed2001

Predictive value of grade for metastasis development in the main histologic types of adult soft tissue sarcomas: a study of 1240 patients from the French Federation of Cancer Centers Sarcoma Group.

BACKGROUND: Histologic grade is said to be the most important prognostic factor in adult soft tissue sarcomas (STS), but most grading systems have been tested in the overall sarcoma group and the predictive value of histologic grade needs to be assessed specifically for each of the histologic categories. METHODS: From 1980 to 1994, 1240 nonmetastatic patients were entered in the French STS database. The following parameters were studied: patient's age and gender, previous history, tumor location, size and depth, neurovascular or bone involvement (NBI), histologic type and subtype, and grade (the French Federation of Cancer Centers [FNCLCC] system). Median follow-up for the survivors was 88 months; only 5% of patients were lost to follow-up. The authors performed univariate and multivariate analyses for metastasis-free survival for the overall sarcoma group and for every main histologic type. RESULTS: In order of importance, parameters were respectively retained as independent predictors of metastasis as follows: grade, tumor size, NBI and tumor depth for the overall group, grade and NBI for malignant fibrous histiocytomas (n = 349), tumor size, histologic subtype and grade for liposarcomas (n = 188), NBI, grade and tumor size for leiomyosarcomas (n = 148), grade and NBI for synovial sarcomas (n = 125), grade for unclassified sarcomas (n = 140), and sarcomas of other types (n = 158). No parameter was significant for malignant schwannomas (n = 72) or for rhabdomyosarcomas (n = 60). CONCLUSION: In this study, histologic grade appeared as an independent predictor of metastasis development in the main histologic types of adult STS, with the exception of malignant schwannomas and rhabdomyosarcomas.

Adolescent↗
PubMed2001

Consistent DNA losses on the short arm of chromosome 1 in a series of malignant gastrointestinal stromal tumors.

Fourteen malignant gastrointestinal stromal tumors (GISTs), characterized by immunohistochemistry, were analyzed by comparative genomic hybridization (CGH). The most striking feature was the detection of consistent DNA losses on the short arm of chromosome 1 in these 14 malignant tumors. Additional recurrent imbalances were also found: significant gains, which could be indicative of tumor progression, were frequent on the long arm of chromosome 1, as were losses of DNA copy number detected in chromosomes 13, 14, 15 and 22.

Adult↗
PubMed2001

[Role of adjuvant therapy in uterine sarcoma: experience of the Curie Institute].

PURPOSE: Uterine sarcoma is a rare disease and survival is poor. From 1975 to 1995, 73 uterine sarcomas were treated at the Curie Institute, and we analysed prognostics factors of survival. PATIENTS AND METHODS: Seventy-one patients underwent primary surgery, in most cases a radical non conservative surgery and a lymphadenectomy. Every patient had an irradiation (external beam irradiation and/or brachytherapy), and 24 patients received adjuvant chemotherapy. We observed that youngest patients had more leiomyosarcomas and low histologic grade tumours. Median survival was 42 months, and 5-years survival and local control were 36 and 68% respectively. Pelvic recurrences were most often before 2 years. This series demonstrates the impact of adjuvant irradiation on local control. This impact was stronger if the tumour had a high histologic grade (p < 0.01). However, irradiation, as well as chemotherapy, had no impact on the survival. CONCLUSION: The study confirmed that irradiation enable a better local control. However modalities of radiation therapy (brachytherapy and/or external beam radiotherapy, dose, volume), are still controversed.

Adult↗
PubMed2001

Leiomyosarcomas and most malignant fibrous histiocytomas share very similar comparative genomic hybridization imbalances: an analysis of a series of 27 leiomyosarcomas.

Twenty-seven tumor samples with a diagnosis of leiomyosarcomas (LMS) were characterized by comparative genomic hybridization. The results were compared with immunohistochemical analysis of the smooth muscle profile of the tumors and expression of the RB1 gene protein. The comparative genomic hybridization profiles suggested that 7 of the 27 tumors might have been misclassified. High levels of DNA amplification were detected in 20 different small regions and recurrently involved bands 1p34, q21, 12q13-15, 17p, and 22q. Most recurrent simple gains were noted at sites such as 1p3, 1q21, 15q12-15, 16p, 17p and 17q, 19, 20q, 22q, and Xp. Significant losses of chromosome 13 were detected in 19 of the 27 tumors with a putative common region of loss in bands 13q14-21. Losses of chromosomes 1q, 2p and 2q, 4q, 9p, 10p and 10q, 11p and 11q23, and 16q were also highly recurrent. A comparative analysis between the most frequent genomic imbalances observed in this study of LMS and the genomic imbalances observed in a large proportion of malignant fibrous histiocytomas (MFH) from a previous study demonstrated that both types of tumors had similar recurrent imbalances. Although MFH were once thought to be a separate member of the soft tissue sarcoma family, our observations support the hypothesis that MFH are a morphologic modulation in the tumoral progression of other sarcomas, particularly LMS.

Adult↗
PubMed2000

The RB1 gene is the target of chromosome 13 deletions in malignant fibrous histiocytoma.

Forty-four malignant fibrous histiocytomas (MFHs) were studied by comparative genomic hybridization. Among the observed imbalances, losses of the 13q14-q21 region were observed in almost all tumors (78%), suggesting that a gene localized in this region could act as a tumor suppressor gene and that its inactivation could be relevant for MFH oncogenesis and/or progression. We determined by CA repeat analyses a consensus region of deletion focusing on the RB1 region. The RB1 gene was then analyzed by protein truncation test, direct sequencing, fluorescence in situ hybridization, Southern blotting, and immunohistochemistry. RB1 mutations and/or homozygous deletions were found in 7 of the 34 tumors analyzed (20%). Among the 35 tumors with comparative genomic hybridization imbalances analyzed by immunohistochemistry, 30 (86%) did not exhibit significant nuclear labeling. The high correlation between chromosome 13 losses and absence of RB1 protein expression and the mutations detected strongly suggest that RB1 gene inactivation is a pivotal event in MFH oncogenesis. Moreover, the observation of a high incidence of MFH in patients previously treated for hereditary retinoblastoma fits well this hypothesis.

Allelic Imbalance↗
PubMed1999

Uterine sarcomas: the Curie Institut experience. Prognosis factors and adjuvant treatments.

PURPOSE: With a retrospective study at a single institution, we propose to analyze the prognosis factors and adjuvant treatment for uterine sarcomas. MATERIALS AND METHODS: From 1975 to 1995, 73 uterine sarcomas were treated at the Institut Curie, corresponding to 61 T1, 5 T2, and 8 T4 tumors. Thirteen patients had metastatic disease at the time of diagnosis. The mean age was 58 years. In 71% of patients, the presenting sign was bleeding. This series consisted of 44% leiomyosarcomas (LMS), 19% endometrial stromal sarcomas (ESS), and 31% carcinosarcomas or mixed mesodermal sarcomas (MMS). For the grading classification, we used the classification of the Sarcoma Group of the French Federation of Cancer Centres for soft tissue sarcomas. Of the patients, 66% presented a high-grade tumor. RESULTS: The median overall survival was 42 months, with a 5-year survival of 45%. Histological grade, FIGO stage, histology types, and menopausal status were the four independent factors in multivariate analysis. Eighteen patients relapsed locally (25.7%), with 77% central pelvic sites. Patients with radiotherapy and ESS had better local control in multivariate analysis. Thirty-four patients developed metastases (48.6%), mainly pulmonary (58.8%). Eight patients presented with peritoneal disease. High grades and LMS had the worst survival without metastasis in multivariate analysis. CONCLUSION: This study validated our classification for sarcoma grading and confirmed the finding of worst prognosis for LMS and the importance of radiotherapy in local control.

Adult↗
PubMed1999

Loss of chromosome 13 is the most frequent genomic imbalance in malignant fibrous histiocytomas. A comparative genomic hybridization analysis of a series of 30 cases.

Regional chromosome localizations of DNA copy number imbalances were studied by comparative genomic hybridization in 30 malignant fibrous histiocytomas: 13 primary tumors (2 myxoid, 9 storiform pleomorphic, and 2 with more undifferentiated phenotype) and 17 local recurrences (2 myxoid, 11 storiform pleomorphic, and 4 with more undifferentiated phenotype). Abnormal comparative genomic hybridization (CGH) profiles were observed in 25 tumors (83%). The most frequent gains (ratio > 1.2) corresponded, by order of frequency, to entire Xp, and bands 1q21, 19q13.1, 19p13, 5p13-p14, 1p31, 17p, 18p, 20q, 1p35, 17q23, and 22q12. High levels of gains (ratio > 1.5) were recurrently detected for Xp (10 cases), and in bands 1q21-q22 (8 cases), 3q27 (4 cases), 5p13-p14 (3 cases), 13q32-q34 (3 cases), 15q22-q26 (3 cases), and 17p11-p12 (3 cases). Losses of 13q12-q14 or 13q21 were observed in a large proportion of tumors (17 cases), suggesting that a gene localized in this region could act as a tumor suppressor gene. Losses of 11q23, 2q32, 11p13, 10p, 1q4, 9p2, 16q12, 4q3, 10q25, 3p23, 2p24, and 12p were also recurrently observed. Taken together, these results provide an overview of chromosome imbalances present in MFH, which could be of use for diagnostic purposes. They point to various chromosome regions which may harbor genes important for malignant fibrous histiocytomas (MFH) oncogenesis and progression.

Chromosome Aberrations↗
PubMed1997

[Current aspects in histopathological assessment of breast cancer].

Histopathological evaluation of breast cancers implies currently not only the assessment of the classical diagnostic and prognostic criteria, but also that of biological parameters. The importance in medical practice of some of these parameters (oestrogen receptors, proliferation index) is widely accepted, whereas the significance of others (p53, c-erb B-2, tumoral angiogenesis) is still controversial. Immunohistochemistry is both a reliable and simple method for the evaluation of these parameters in so far the indications of this analysis are accurate and the technical procedures well defined.

Biomarkers, Tumor↗
PubMed1997

Unusual clonal chromosomal evolution in a breast carcinoma and its lymph node metastasis in a patient with Down syndrome.

A cytogenetic study was performed on a primary breast carcinoma and its axillary lymph node metastasis from a 53-year-old patient with trisomy 21, a carrier of a constitutional der(21;21). A translocation t(X;21) and the loss of the other X chromosome were shared by all karyotypes from tumor cells. The primary tumor was hyperdiploid with several gains of whole chromosomes. In contrast, most cells from the metastasis shared several rearrangements and losses leading to a hypodiploid karyotype. No normal chromosome 17 was present; instead, an i(17)(q10) and a fragment, detected by chromosome painting and presumably corresponding to a rearranged 17p, were found. Immunostaining for p53 was strongly positive in the metastasis but not in the primary tumor, suggesting a mutation of the TP53 gene in the metastasis. Finally, a small cell population of the metastasis was hyperdiploid like the clone in the primary tumor, suggesting that the node was colonized twice, at an early stage and a later stage of the clonal evolution of the tumor.

Axilla↗
PubMed1996

Prognostic factors in adult patients with locally controlled soft tissue sarcoma. A study of 546 patients from the French Federation of Cancer Centers Sarcoma Group.

PURPOSE: To define the prognostic factors in adult patients with locally controlled soft tissue sarcoma (STS) and to determine which patients should be considered for adjuvant treatment. PATIENTS AND METHODS: Five hundred forty-six patients with a nonmetastatic and locally controlled STS, collected in a cooperative data base by the French Federation of Cancer Centers (FNCLCC) Sarcoma Group from 1980 and 1989, were studied. Histologic slides of all patients were collegially reviewed. Initial treatment consisted of complete tumor resection with amputation in only 4% of the patients. Adjuvant radiotherapy was administered to 57.9% and adjuvant chemotherapy to 31%. Relationships between tumor characteristics were analyzed, and univariate and multivariate analyses were performed using Cox models for the hazards rate of tumor mortality, development of distant metastasis, and strictly local recurrence. RESULTS: Unfavorable characteristics with an independent prognostic value for tumor mortality were: grade 3 (P = 3 x 10(-10)), male sex (P = 1.5 x 10(-5)), no adjuvant chemotherapy (P = 5.4 x 10(-5)), tumor size > or = 5 cm (P = 3.8 x 10(-3)), and deep location (P = 4.6 x 10(-3)). Unfavorable characteristics for the development of distant metastasis were: grade 3 (P = 4 x 10(-12)), no adjuvant chemotherapy (P = 6.4 x 10(-4)), tumor size > or = 10 cm (P = 9.8 x 10(-4)), and deep location (P = 1.3 x 10(-3)). For the development of local recurrence, the unfavorable characteristics were: no adjuvant radiotherapy (P = 3.6 x 10(-6)), poor surgery (local excision) (P = 2 x 10(-4)), grade 3 (P = 7.6 x 10(-4)), and deep location (P = 10(-2)). Grade, depth, and tumor size were used to define groups of patients according to the metastatic risk. Adjuvant chemotherapy was beneficial in terms of overall survival and metastasis-free survival in grade 3 tumor patients only. Despite worse characteristics concerning tumor depth, tumor-node-metastasis (TNM) and American Joint Committee (AJC)/International Union Against Cancer (UICC) classifications and grade in patients with adjuvant radiotherapy, the latter experienced significantly fewer local recurrences than patients with no radiotherapy. CONCLUSION: Grade, tumor depth, and tumor size could be used to select patients with a high metastatic risk, for which adjuvant chemotherapy could be beneficial.

Adolescent↗
PubMed1996

Ifosfamide seven-day infusion for recurrent and cisplatin refractory ovarian cancer.

BACKGROUND: The prognosis of advanced ovarian cancer is very poor, with about 15% of patients surviving at five years. Since most of these patients will relapse and/or progress while on therapy, effective salvage treatments are needed. A phase II trial was designed to evaluate the feasibility, toxicity, and response of a seven-day ambulatory continuous infusion of ifosfamide in patients with recurrent or chemoresistant advanced ovarian cancer. PATIENTS AND METHODS: Nineteen patients with progressive ovarian cancer following a cisplatin-based induction chemotherapy were treated with continuous infusion ifosfamide with mesna at 1 g/m2/d and 400 mg/m2/d, respectively, for seven days every 28 days. RESULTS: The overall response rate was 37%. Responses were observed both in patients who relapsed after induction chemotherapy (4/6) and in those who were resistant to cisplatin (3/13). Toxicity was mild and tolerable in these heavily pretreated patients. CONCLUSION: Ifosfamide, when administered as a protracted continuous infusion is an active drug in ovarian cancer and can be safely administered in an out-patient setting. Toxicity is minor even in heavily pretreated patients. Responses are observed in cisplatin refractory ovarian cancer.

Adult↗
PubMed1995

Differences in the antigens recognized by cytolytic T cells on two successive metastases of a melanoma patient are consistent with immune selection.

We have studied the patterns of antigens recognized by autologous cytolytic T lymphocytes (CTL) on two melanoma cell lines derived from metastases that were removed from patient LB33 at several years distance. Cell line LB33-MEL.A was obtained after surgery in 1988. A large number of CTL clones directed against LB33-MEL.A was obtained with blood lymphocytes collected from the patient in 1990. In vitro selection of melanoma cells that were resistant to these CTL clones indicated that at least five different antigens were recognized on LB33-MEL.A by autologous CTL. Four of these antigens were found to be presented by HLA-A28, B13, B44 and Cw6, respectively. The patient remained disease-free until 1993 when a metastasis was detected and was used to obtain cell line LB33-MEL.B. This cell line proved resistant to lysis by all the CTL clones directed against the LB33-MEL.A cells and showed no expression of HLA class I molecules except for HLA-A24. Using LB33-MEL.B cells to stimulate blood lymphocytes collected from the patient in 1994 we derived CTL clones that lysed these cells. All these CTL clones recognized a new antigen presented by HLA-A24. These results suggest that in patient LB33 the melanoma cells may have lost the expression of several HLA molecules under the selective pressure of an anti-tumor CTL response.

Adult↗