Evidence of a hereditary p53 syndrome in cancer-prone families.
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Adolescent↗
Biomedical subjects
C Lasset
Publications and source records attributed to C Lasset.
Clinical relevance of CD44 cell-surface expression and N-myc gene amplification in a multicentric analysis of 121 pediatric neuroblastomas.
PURPOSE: In contrast to other human tumors, a repression of the cell-surface glycoprotein CD44 on neuroblastoma is a marker of aggressiveness that usually correlates to N-myc amplification. We thus compared the prognostic value of both markers in the initial staging of 121 children treated for neuroblastoma in collaborative institutions. METHODS: Frozen samples were analyzed by a rapid and well-standardized technique of immunostaining with monoclonal antibodies (MoAbs) against epitopes in the CD44 constant region. RESULTS: In this retrospective series, CD44 was expressed on 102 specimens and strongly correlated with favorable tumor stages and histology, younger age, and normal N-myc copy numbers. In univariate analysis, CD44 expression and normal N-myc were the most powerful markers of favorable clinical outcome (P < 10(-6) and chi 2 = 65.40 and P < 10(-6) and chi 2 = 42.56, respectively), but analysis of CD44 affords significant prognostic discrimination in subgroups of patients with or without N-myc-amplified tumors. In the subgroup of stage IV neuroblastomas, CD44 was the only significant prognostic marker (P < .02, chi 2 = 5.76), whereas N-myc status was not discriminant. In multivariate analysis of five factors, ie, N-myc amplification, CD44 expression, age, tumor stage, and histology, the only independent prognostic factors of event-free survival were CD44 expression and tumor stage. CONCLUSION: The analysis of CD44 cell-surface expression must be recommended as an additional biologic marker in the initial staging of the disease.
Antibodies, Monoclonal↗
Early lymphopenia after cytotoxic chemotherapy as a risk factor for febrile neutropenia.
PURPOSE: Febrile grade four (ie, < or = 500/microL) neutropenia (FN) is a frequent life-threatening complication of cancer chemotherapy. Although its incidence correlates to the dose of chemotherapy, FN may occur after almost any cytotoxic regimen. At present, there is no predictive method to identify patients who will experience FN. PATIENTS AND METHODS: Univariate and multivariate analyses of risk factors for FN were performed on a retrospective cohort of 112 consecutive patients treated with various chemotherapy regimens. Two independent risk factors were identified by the logistic regression and used to create a risk model for FN. The validity of the model was tested in three distinct groups of patients: two prospective groups of patients treated in two institutions (Centre Léon Berard [CLB] and Institut G. Roussy [IGR]) and the group of patients with intermediate- or high-grade non-Hodgkin's lymphoma (NHL) treated with the doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) regimen between 1988 and 1992 at CLB. RESULTS: Within the retrospective group, 23 of 47 (49%) patients with lymphocyte counts < or = 700/microL at day 5 after chemotherapy experienced FN compared with seven of 65 (11%) of other patients (P = .00002). The type of chemotherapy (high dose v others) was also significantly correlated to FN (48% v 11%, P = .0003). Age, performance status, the number of previous chemotherapy cycles, or polymorphonuclear leukocyte (PMN) counts, were not significantly correlated to the incidence of FN in univariate analyses. Two independent risk factors were identified in the logistic regression: day 5 lymphocyte counts (beta = 1.97 +/- 0.53) and the type of chemotherapy regimen (beta = 1.91 +/- 0.53). The calculated probability to experience FN in patients with none, one, and both of these risk factors was 4.3%, 24.0%, and 68.8%, respectively. The validity of this model was tested in the three groups of patients used as validation samples. The observed incidences of FN in the above defined risk subgroups were 3%, 19%, and 67%, respectively, within the CLB prospective series and 6%, 19%, and 75% within the IGR prospective series. In the ACVBP group, the incidence of FN was 33% and 72%, respectively, in patients from the intermediate- and high-risk groups. In the two prospective groups and in the ACVBP series, the observed numbers of FN in the different risk groups did not differ significantly from those calculated by the model (P = .89, P = .86, and P = .72 for these three groups, respectively). CONCLUSION: Day 5 lymphocyte counts < or = 700/microL and the type of chemotherapy regimen enable oncologists to define subgroups of patients treated with chemotherapy as those with a high intermediate, and low risk of FN. These criteria could be used to select subjects in whom prophylactic measures for FN, in particular hematopoietic growth factors, should be proposed.
Adolescent↗
Non-metastatic childhood ependymomas.
PURPOSE: Intracranial ependymomas of childhood are relatively infrequent. There are significant disagreements concerning optimal postoperative treatment as well as the patterns of relapse following treatment. The purpose of this retrospective study was the analysis of the recurrence pattern and therefore the implication on the extent of the radiotherapy fields. Data from 37 patients referred within 19 years were used for this study. PATIENTS AND METHODS: From April 1975 to July 1993, 37 children aged 1-14 years were referred for postoperative treatment of an intracranial ependymoma. Twenty-eight children received postoperative radiation therapy and 26 patients received chemotherapy. The median follow-up is 6 years (range 2 months to 19 years). RESULTS: Overall survival and event free survival at 5 and 10 years were 40%. Eighteen children relapsed. Relapses occurred from 1.5 months to 3.6 years post treatment. Relapses were distant in four cases and local in 14. Age, sex, extent of primary resection, chemotherapy and type of radiation therapy did not influence the outcome. Children with poorly differentiated tumors who did not receive postoperative radiation therapy had a higher relapse rate but this difference is not statistically significant. CONCLUSIONS: Despite doses of radiation > or = 50 Gy the majority of recurrences were local. Our results, despite the small number of patients are in accordance to those previously published, suggest that prophylactic craniospinal irradiation is superfluous. Better means of achieved local control are required, such as three-dimensional conformal radiation therapy with dose-escalation study or hyperfractionation regimen.
Adolescent↗
[Systematic screening for neuroblastoma].
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Humans↗
Evaluation of CD44 prognostic value in neuroblastoma: comparison with the other prognostic factors.
CD44 gene products are potential markers of aggressiveness in different tumour models, a result which prompted us to study clinical neuroblastoma (NB) specimens. CD44 expression was determined by immunostaining of 52 tumour samples from newly diagnosed NB with a monoclonal antibody (J173) directed against an epitope common to all CD44 isoforms. CD44 immunoreactivity was detected in 37 of the tumours (71%). CD44 was expressed in all 22 NBs with favourable prognoses (stages 1, 2 or 4S), but only 50% (15/30) of advanced NB (stages 3 and 4) (P < 10(-4)), suggesting that the absence, rather than the overexpression, of CD44 is a signal of tumour aggressiveness. The cumulative progression-free survival was significantly longer in patients with CD44 positive tumours compared with patients with CD44 negative tumours (P < 10(-5)). More importantly, progression-free survival was also significantly higher in CD44 positive patients within the high-risk group (P < 0.01). In univariate analysis, we tested the prognostic value of tumour expression of CD44 in comparison with tumour stage, age, tumour histology, and presence or absence of amplification of the MYCN protooncogene. All five measures had significant prognostic value. The expression of CD44 and the absence of MYCN amplification were the most powerful predictors of a favourable outcome. In a multivariate analysis of these measures, CD44 expression and tumour stage were the only independent prognostic factors for the prediction of patient survival. NB is the first clinical model described in which tumour aggressiveness correlates with repression rather than stimulation of CD44 expression. We recommend the use of CD44 as an additional biological marker in the initial staging of NB.
Adolescent↗
Is neuroblastoma screening evaluation needed and feasible?
Despite the five million children who have been screened for neuroblastoma in Japan through detection of catecholamine metabolites, it is still uncertain whether screening for this disease is beneficial. The Japanese study has clearly indicated that screening at 6 months or earlier leads to heavy overdiagnosis. It is shown in this paper that screening at a later age may give the same reduction in mortality with possibly less overdiagnosis. However, it is estimated that, even with two screens at 12 and 18 months, the reduction in mortality would not greatly exceed 25%, under realistic hypotheses on the length of the preclinical phase of the disease. The evaluation of the efficacy of this screening strategy would need the recruitment of half a million children per year over 5-7 years and the follow-up of an equal number of controls. Such a trial would improve our knowledge of the natural history of the disease and might help to answer some questions raised recently regarding its biological heterogeneity.
Age Factors↗
[CD44 expression: a new prognostic factor in neuroblastoma].
CD44 gene products are potential markers of aggressiveness in different tumor models, a result which prompted us to study clinical neuroblastoma (NB) specimens. CD44 expression was determined by immunostaining of 52 NB with a monoclonal antibody (J173) directed against an epitope common to all CD44 isoforms. All tumors were from patients (pts) with newly diagnosed NB treated with standardized protocols. They were classified according to international criteria [11]. CD44 immunoreactivity was detected in 37 tumors (71%). CD44 was expressed in 100% of favorable NB stages (1, 2 or 4S), but only 50% of advanced NB (stages 3 and 4) (p = 0.0001), suggesting that the absence rather that the overexpression of CD44 is a signal of tumor aggressiveness. The cumulative event-free survival was significantly longer in pts with CD44-positive tumors as compared to pts with CD44-negative tumors (p < 10(-5)). More importantly, progression-free survival was also significantly higher in CD44-positive pts within the high-risk group (p < 0.01). In univariate analyses, we tested the prognostic value of tumor expression of CD44 in comparison with tumor stage, age, tumor histology and presence or absence of N-myc proto-oncogene amplification. All five measures had significant prognostic value. The expression of CD44 and the absence of N-myc amplification were the most powerful predictors of a favorable clinical outcome. In a multivariate analysis of these measures, CD44 expression and tumor stage were the only independent prognostic factors for the prediction of patient survival. NB is the first clinical model described in which tumor aggressiveness correlates with a repression rather than a stimulation of CD44 expression. We recommend the use of CD44 as an additional biological marker in the initial staging of neuroblastoma.
Adolescent↗
Impact of megatherapy in children with high-risk Ewing's tumours in complete remission: a report from the EBMT Solid Tumour Registry.
The European BMT Solid Tumour Registry (EBMT-STR) received reports from 21 European transplant centers on 63 patients (50 Ewing's sarcomas and 13 peripheral neuroectodermal tumours) in first (n = 32) or second CR (n = 31) consolidated with megatherapy and BM and/or PSC rescue between December 1982 and November 1992. There were 31 males and 32 females with a median age of 12 years (range 1-30 years) at megatherapy. The median follow-up time since megatherapy is 4 years (range 1 month to 10 years), Thirty-two patients with metastatic disease at diagnosis (22 had metastases to the bone and/or bone marrow) and consolidated in CR1 reached an actuarial event-free survival (EFS) of 21% at 5 years. Thirty one patients in CR2 achieved an actuarial EFS of 32% at 5 years. Favourable outcome was limited to relapse patients with localised disease at initial diagnosis. Distant relapse had a more favourable prognosis than local failure. Analysis of the different megatherapy strategies could not identify a significantly superior approach, nor is there convincing evidence in favour of double graft procedures. From the above results it appears that consolidation treatment by megatherapy contributes to improved EFS rates in high-risk patients compared with historical experience. Major questions for the future to be addressed prior to randomised studies include agreement on the definition of high-risk patients and the most efficient megatherapy procedure.
Adolescent↗
[Considerations on the organization of oncologic-genetic consultations (a first step towards the publication of clinical practice guidelines)].
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Decision Trees↗
[Ovarian cancer epidemiology].
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Environmental Exposure↗
Multivariate analysis of prognostic factors in adult patients with medulloblastoma. Retrospective study of 156 patients.
BACKGROUND: Medulloblastoma is a rare disease in adult patients, with an annual incidence rate of 0.05 per 100,000 per year. Results are, therefore, sparse and comprise small series over long periods. The real survival rate, the prognostic factors, the optimal postoperative radiation dose, and the role of adjuvant chemotherapy are still unknown for this disease in adults. METHODS: The authors collected 156 cases of histologically proven medulloblastoma in patients older than 18 years of age who were treated between January 1975 and December 1991 in 13 French institutions. They analyzed the prognostic factors for survival and the impact of postoperative treatment on survival. RESULTS: The 5- and 10-year event free survival rates, 61 and 48%, respectively, are similar to those observed in children. The median time to recurrence is 30 months, but late relapses after 5 years remain frequent. Multivariate analysis identified postoperative performance status, spinal axis radiation dose, fourth ventricular floor involvement, and desmoplastic histologic subtype as factors significantly correlated with event free survival. No benefit of concomitant chemotherapy was demonstrated, and complete resection resulted only in severely reduced postoperative performance status. CONCLUSIONS: The prognostic factors in adult medulloblastoma are comparable to those of medulloblastoma in children, but a new parameter, postoperative performance status, was identified in this adult series. Postoperative craniospinal irradiation remains the standard treatment for adults with medulloblastoma. A reduced dose to the supratentorial compartment should be tested in a prospective protocol.
Adult↗
Metastatic medulloblastoma: the experience of the French Cooperative M7 Group.
A retrospective analysis was performed to determine the outcome of children with metastatic medulloblastoma given a standardised treatment programme. Of 68 consecutive patients treated in the French M7 protocol for medulloblastoma, 23 presented with metastatic disease. They were uniformly treated with surgery, and the same protocol of chemotherapy and craniospinal radiotherapy. The 7-year relapse-free survival rate is 43% for metastatic patients compared to 68% for patients with localised disease. Survival did not correlate with age, sex, location of metastases, extent of initial surgery and the dose of radiation therapy on the posterior fossa. Survival did correlate with the dose to the cranial field with a threshold dose of 30 Gy. Patients with metastatic disease have a worse prognosis and require more aggressive therapies at initial presentation. The prognostic impact of the different sites of metastatic disease requires further evaluation in cooperative studies.
Adolescent↗
Comparison of auto versus allografting as consolidation of primary treatments in advanced neuroblastoma over one year of age at diagnosis: report from the European Group for Bone Marrow Transplantation.
A case control study was performed to investigate the potential advantage of allogeneic bone marrow transplantation in advanced or poorly responding neuroblastoma first remission patients using the European BMT Solid Tumor Registry. Seventeen allogeneic and 34 autologous bone marrow transplantation (BMT) cases were matched based on a number of prognostic factors including age, sex, prior treatment duration, pre-graft response status and bone and BM involvement before BMT. Only single BMT procedures are included. The median age at diagnosis was 47 months (range 18-113 months). The median follow-up time since BMT is 58 months (range 13-133 months). The only significant prognostic factor within the allogeneic BMT (p = 0.012) and autologous BMT groups (p = 0.025) was residual skeletal disease before BMT, detected by mIBG in 86% of the cases. However, the progression-free survival was not significantly different: 35% and 41% at 2 years, respectively. Only half of the allogeneic BMT patients had developed graft-versus-host disease (GVHD): 7 of 9 grade I-II and only 2 of 9 grade IV. The median donor age was very young with 74 months (range 20-240 months) and 10 of 17 were sex matched. Thus absence of GVHD risk factors in young children could be the major obstacle in achieving an anti-tumor effect with allogeneic BMT in neuroblastoma.
Bone Marrow Transplantation↗
CD44--a new prognostic marker for neuroblastoma.
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Biomarkers, Tumor↗
Prospective multicentric study of the etiology of 1051 bacteremic episodes in 782 cancer patients. CEMIC (French-Belgian Study Club of Infectious Diseases in Cancer).
A total of 1051 bacteremic episodes (782 patients) were prospectively recorded in 10 cancer centers (9 French, 1 Belgian), with: patient's age (mean 53, range 1-89 years), underlying cancer, neutropenia (< 1000 neutrophils/microliters; 233), signs and symptoms, type of i.v. line (percutaneous central: 534; peripheral: 228; central implanted: 304), treatment, blood culture system, number of positive blood culture bottles/total obtained, time to growth. Of all episodes, 23.2% occurred within 48 h of admission. The patients were receiving systemic antibiotics at sampling (on AB) in 34.6% of cases. The 1147 pathogens isolated (86 polymicrobial) were: E. coli (10.7%), Klebsiella-Enterobacter-Serratia (6.1%), other enterobacteriaceae (2.2%), Pseudomonas aeruginosa (4.8%), other nonfermenters (4.7%), coagulase-negative staphylococci (CNS, 40.8%), Staphylococcus aureus (9.9%), streptococci (5.4%), enterococci (2.2%), anaerobes (3.4%), yeasts (3.5%), and other bacteria (6.9%). The CDC (Centers for Disease Control) criteria (1988) were used to assess significance: group 1: pathogenic species (616 episodes; 59%); group 2: clinical signs and isolation of a "contaminant" species (47; 4.5%); group 3: as in group 2 with an i.v. line and empiric antibiotic treatment (181 episodes including 176 CNS; 17%); group 4: non-significant (207 episodes including 203 CNS; 20%). Groups 1-3, in which the episodes were considered to be significant (844 episodes; 80%) were compared with non-significant episodes (Fisher). Significant differences (P < or = 0.05) were seen in time to growth (median growth within 24 h vs 48 h), fever (86% vs 54%), chills (40% vs 3%), hypotension (10% vs 2%), septic shock (9% vs 1%), polymicrobial etiology (10% vs 0.5%), and initiation of empiric antibiotic treatment (71% vs 4%). Bacteremic episodes of CDC groups 1, 3 and 4 were further studied in episodes with a single isolate as a doubtful clinical significance (482 episodes) and episodes with > or = 2 bottles positive of probable clinical significance (569 episodes; 54%). In group 1 (218 doubtful, 398 probably significant episodes) significant differences were seen in chills (36% vs 52%), shock (7% vs 13%), polymicrobial (8% vs 17%), initiation of empiric antibiotic treatment (60% vs 72%); in group 3 (87 doubtful, 94 probably significant) in time to growth delay; in group 4 (177 doubtful, 30 probably significant) in proportion with implanted catheter (26% vs 52%), fever (62% vs 10%), and time to growth. This study confirms the predominant role of Gram-positive cocci in bacteremia occurring in cancer patients.
Adolescent↗
Phase II study of fotemustine as second-line treatment after failure of immunotherapy in metastatic renal cell carcinoma.
Sixteen patients who after prior systemic immunotherapy had progressing disease received fotemustine (100 mg/m2) i.v. on days 1, 8, and 15 followed by a 5-week rest period. In responding or stabilized patients, maintenance therapy consisted of 100 mg/m2 fotemustine given once every 3 weeks until progression on toxicity occurred. No objective response was observed. Four patients showed stable disease (median duration: 4 months; range: 3-19). The main toxicities were neutropenia (WHO grade 3 and 4: 27%) and thrombocytopenia (WHO grade 3 and 4: 27%). Fotemustine was administered on an outpatient basis and was generally well tolerated, but in our series of patients it had no antitumour activity in metastatic renal cell carcinoma after failure of immunotherapy.
Adult↗
Medulloblastoma in adults: survival and prognostic factors.
The authors report a series of 30 adults with medulloblastoma treated after surgery between 1975 and 1990. Half the patients presented a classical medulloblastoma and the other half presented desmoplastic medulloblastoma. Brainstem infiltration was noted in 3 patients, cerebellar peduncle infiltration in 6 cases and 4 patients had cerebrospinal fluid (CSF) involvement. Tumor resection was achieved in all patients except 1, and in 5 surgery was incomplete. All patients but 2 received postoperative cerebral radiotherapy. Six patients did not receive chemotherapy before radiotherapy, 7 patients received CCNU-Vincristine concomitantly with and after irradiation, 1 patient was given a CHOP regimen, and the remaining 16 patients received the 8 drugs in a 1-day (8/1) regimen before irradiation. The median follow-up time was 104 months. The 5- and 10-year overall survival rates were 58.5% and 41%, respectively. Two toxic deaths occurred under the 8/1 regimen, and no better survival was observed for this group of patients in comparison with those receiving other regimens. Persistence of malignant cells in the CSF, brainstem involvement, cerebellar peduncle infiltration, non-radical surgery and a postoperative performance status (PS) of more than 2 were significantly correlated with an adverse outcome for overall survival in adult patients with medulloblastoma.
Adolescent↗