The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of..., 2018
BACKGROUND The aim of this study was to assess the prognostic value of postoperative 123I-MIBG sc... more BACKGROUND The aim of this study was to assess the prognostic value of postoperative 123I-MIBG scintigraphy, including systematic SPECT/CT and semiquantification of the uptake at the surgical site, in a prospective series of NB patients. METHODS Patients operated for neuroblastoma and who had benefited from postoperative 123I-MIBG scintigraphy were prospectively and consecutively included. Completeness of surgery was assessed on operative report. One month postoperative 123I-MIBG scintigraphy included planar acquisition and SPECT/CT. Semi-quantification of the 123I-MIBG SPECT/CT uptake at the surgical site was performed and ratios to reference (liver and mediastinum) areas were calculated. RESULTS Thirty patients were included between August 2012 and July 2015. Median follow-up was 36 months (range 10-98). Surgery was considered as complete in 23 patients and incomplete in 7 patients. Eight patients (26.7%) presented progressive disease (1 progression and 7 recurrences). Seven patie...
9515 Background: Alkylating agents are associated with a risk of male gonadal damage, even in pat... more 9515 Background: Alkylating agents are associated with a risk of male gonadal damage, even in patients treated during childhood. The purpose of this work was to compare this risk after treatment by ifosfamide vs cyclophosphamide during childhood. Methods: Evaluation was based on basal FSH measurement known for its correlation with spermatogenesis. LH and testosterone were also measured in most of the patients. 159 males were evaluated after treatment of a soft tissue sarcoma (79), osteoasarcoma (39), ewing (10), lymphoma (28), other (3). 100 patients received ifosfamide as unique alkylating agent and the other 59 received cyclophosphamide as the other unique alkylating agent between 1973 and 2000. Median age at treatment was 11.2 years (0–18 yrs). Median interval after the end of the treatment was 10.7 years (4.1–20.2 yrs), median age at evaluation was 21.4 years (17.5–36.1 yrs). Median dose of ifosfamide was 54 g/m2 (18- 114), median dose of cyclo was 8.3 g/m2 (4.6–22). Age at trea...
Ewing sarcoma (EWS), a pediatric tumor predominantly occurring in children of European ancestry, ... more Ewing sarcoma (EWS), a pediatric tumor predominantly occurring in children of European ancestry, is characterized by the EWSR1-FLI1 fusion oncogene. We performed a genome-wide association study (GWAS) of 749 EWS cases and 1,378 unaffected individuals of European ancestry. Our study replicated previously reported susceptibility loci at 1p36.22, 10q21.3, and 15q15.1 and identified new loci at 6p25.1, 8q24.23, 20p11.22, and 20p11.23 (P-values <5x10-8). Effect estimates exhibited odds ratios (ORs) in excess of 1.7, which is high for cancer GWAS, and striking in light of the rarity of EWS cases in familial cancer syndromes. In expression quantitative trait locus (eQTL) analyses, we observed altered expression patterns for plausible candidate genes at 6p25.1 with RREB1, a RAS-responsive element, and at 20p11.23 with KIZ, a centrosomal stabilization protein. The 20p11.22 locus is also near NKX2-2, a highly overexpressed gene in EWS. Interestingly, most loci reside near GGAA repeat seque...
This study aimed to compare pethidine and morphine on efficacy and toxicity in children with seve... more This study aimed to compare pethidine and morphine on efficacy and toxicity in children with severe mucositis following chemotherapies. From March 2000 to November 2003, 35 hospitalized children with chemotherapy-related mucositis were randomly assigned to receive double blindly "patient-controlled analgesia" (PCA) bolus doses of morphine or pethidine. The mucositis pain score was the mean of pain measured four times a day with a Visual Analogue Scale from day 2 to 5 of PCA. Study stops before total accrual for difficulties of recruitment. Out of the 29 patients with more than one day of PCA, the median (range) of the Mean Pain Score was 44 (13-72) and 33 (3-89) in the morphine (n = 14) and pethidine (n = 15) groups, respectively (P = 0.32). PCA was stopped for failure in 10 cases (five in each group). Constipation requiring specific treatment was higher in the morphine group (43% versus 0%). PCA with pethidine appears not inferior to morphine, with less constipation requi...
BackgroundLiver metastases are rare in children with Wilms tumor (WT), and their impact on the ou... more BackgroundLiver metastases are rare in children with Wilms tumor (WT), and their impact on the outcome is unclear.Patients and methodsThe French cohort of patients with WT presenting liver metastases at diagnosis and enrolled in the International Society of Pediatric Oncology (SIOP) 2001 study was reviewed.ResultsFrom 2002 to 2012, 906 French patients were enrolled in the SIOP2001 trial. Among them, 131 (14%) presented with stage IV WT and 18 (1.9%) had liver metastases at diagnosis. Isolated liver metastases were displayed in four of them. After preoperative chemotherapy, persistent liver disease was reported in 14/18 patients, and 13 of them underwent metastasectomy after nephrectomy. In resected liver lesions, the same histology of the primary tumor was reported for three patients, blastemal cells without anaplasia were identified in one patient with DA‐WT, and post‐chemotherapy necrosis/fibrosis was identified for the other 10 patients. For the four patients who had liver and lu...
Recent studies on human NK cells have identified a number of surface antigens that can be utilize... more Recent studies on human NK cells have identified a number of surface antigens that can be utilized to define this population of cells and to identify functionally distinct subsets within this heterogeneous population. In addition, it has been possible to associate specific functional activities with several antigens expressed on NK cells as well as other hematopoietic cells. This information, which is summarized in Table III can be utilized to develop a framework for the classification of cytolytic effector cells. Of primary importance, this classification identifies subsets of cytolytic cells with distinct functional repertoires and distinct cytolytic mechanisms. The majority of NK cells in unstimulated peripheral blood and the majority of NK clones express NKH1 and CD2 antigens but do not express CD3 antigen. These cells morphologically appear as large granular lymphocytes and have broad cytolytic activity against a variety of allogeneic targets without primary sensitization. Consistent with the finding that these cells are CD3 negative, they have not been found to have rearrangement of genes encoding for TCR, or functional mRNA transcripts of either TCR alpha, TCR beta, or TCR gamma genes. In addition, these cells do not express heterodimeric surface proteins similar to those that have now been demonstrated to be MHC-restricted T cell receptors for antigen. Taken together, these findings provide strong evidence that NKH1+CD3- NK clones do not interact with target cells through a T cell receptor-like structure. Nevertheless, these NK cells do share several properties with conventional CTL. These functional T cell characteristics include (1) expression of CD2-T11/E rosette receptor antigen, and (2) utilization of LFA-1 surface antigen to enhance effector cell adhesion to target cells. As previously demonstrated for T cells, NK cells can be activated through the CD2 molecule and this has recently been shown to result in the enhancement of cytolytic function by these effectors. Since CD2 can also function as a cell surface ligand for LFA-3, an antigen expressed on NK targets, the CD2 molecule may be considered as a potential NK receptor structure. The fact that a very small subset of NK cells (approximately equal to 10%) as well as some NK clones (JT11) does not express CD2 argues against a potential role for CD2 as the NK cell receptor. Certainly, further studies will be necessary to clarify the role of CD2 on NK cells and to identify the mechanisms whereby NKH1+CD3- NK cells interact with targets in a non-MHC-restricted fashion.(ABSTRACT TRUNCATED AT 400 WORDS)
ABSTRACT The three-drug combination of melphalan (M), etoposide (E), and carboplatin (C) followed... more ABSTRACT The three-drug combination of melphalan (M), etoposide (E), and carboplatin (C) followed by autologous stem-cell (ASC) rescue has been evaluated prospectively by the French Society of Pediatric Oncology (SFOP) in pediatric high-risk recurrent (HRR) Wilms&#39; tumor (WT) patients with chemotherapy-responsive disease. From October 1988 to October 1994, 29 patients with HRR WT were treated in nine SFOP centers. Two additional patients with stage IV anaplastic WT were consolidated in first complete response (CR) with the same regimen and have been studied separately. The regimen consisted of M 180 mg/m2 for 1 day, E 200 mg/m2/d for 5 days, and C at a daily targeted area under the concentration-time curve (AUC) of 4 mg x min/mL for 5 days. ASCs were reinfused 48 hours after M. Twelve of 28 assessable patients with HRR WT are still in continuous CR at a median of 48.5 months (range, 36 to 96) after consolidation. Disease-free survival (DFS) and overall survival (OS) estimated by the Kaplan-Meier method at 3 years were 50%+/-17% and 60%+/-18%, respectively. Sixteen patients relapsed at a median of 8.5 months (range, 3 to 53) after consolidation. Toxicity data are available in 31 grafted patients. Grade III and IV toxicities included hematologic side effects (n=31), hemorrhage (n=8), mucositis (n=24), diarrhea (n=12), renal disorders (n=8), and pneumonitis (n=3). The adverse prognostic factors (APF) used to select patients for this dose-intensive chemotherapy define children with very-poor-risk recurrent WT. Despite high treatment-related toxicity, about half of these patients remain disease-free at 3 years. Patient outcome is statistically better when high-dose chemotherapy (HDCT) is performed as early as the second CR or partial response (PR). Novel therapeutic approaches with innovative preparative regimens are warranted for the remaining high-risk patients.
The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of..., 2018
BACKGROUND The aim of this study was to assess the prognostic value of postoperative 123I-MIBG sc... more BACKGROUND The aim of this study was to assess the prognostic value of postoperative 123I-MIBG scintigraphy, including systematic SPECT/CT and semiquantification of the uptake at the surgical site, in a prospective series of NB patients. METHODS Patients operated for neuroblastoma and who had benefited from postoperative 123I-MIBG scintigraphy were prospectively and consecutively included. Completeness of surgery was assessed on operative report. One month postoperative 123I-MIBG scintigraphy included planar acquisition and SPECT/CT. Semi-quantification of the 123I-MIBG SPECT/CT uptake at the surgical site was performed and ratios to reference (liver and mediastinum) areas were calculated. RESULTS Thirty patients were included between August 2012 and July 2015. Median follow-up was 36 months (range 10-98). Surgery was considered as complete in 23 patients and incomplete in 7 patients. Eight patients (26.7%) presented progressive disease (1 progression and 7 recurrences). Seven patie...
9515 Background: Alkylating agents are associated with a risk of male gonadal damage, even in pat... more 9515 Background: Alkylating agents are associated with a risk of male gonadal damage, even in patients treated during childhood. The purpose of this work was to compare this risk after treatment by ifosfamide vs cyclophosphamide during childhood. Methods: Evaluation was based on basal FSH measurement known for its correlation with spermatogenesis. LH and testosterone were also measured in most of the patients. 159 males were evaluated after treatment of a soft tissue sarcoma (79), osteoasarcoma (39), ewing (10), lymphoma (28), other (3). 100 patients received ifosfamide as unique alkylating agent and the other 59 received cyclophosphamide as the other unique alkylating agent between 1973 and 2000. Median age at treatment was 11.2 years (0–18 yrs). Median interval after the end of the treatment was 10.7 years (4.1–20.2 yrs), median age at evaluation was 21.4 years (17.5–36.1 yrs). Median dose of ifosfamide was 54 g/m2 (18- 114), median dose of cyclo was 8.3 g/m2 (4.6–22). Age at trea...
Ewing sarcoma (EWS), a pediatric tumor predominantly occurring in children of European ancestry, ... more Ewing sarcoma (EWS), a pediatric tumor predominantly occurring in children of European ancestry, is characterized by the EWSR1-FLI1 fusion oncogene. We performed a genome-wide association study (GWAS) of 749 EWS cases and 1,378 unaffected individuals of European ancestry. Our study replicated previously reported susceptibility loci at 1p36.22, 10q21.3, and 15q15.1 and identified new loci at 6p25.1, 8q24.23, 20p11.22, and 20p11.23 (P-values <5x10-8). Effect estimates exhibited odds ratios (ORs) in excess of 1.7, which is high for cancer GWAS, and striking in light of the rarity of EWS cases in familial cancer syndromes. In expression quantitative trait locus (eQTL) analyses, we observed altered expression patterns for plausible candidate genes at 6p25.1 with RREB1, a RAS-responsive element, and at 20p11.23 with KIZ, a centrosomal stabilization protein. The 20p11.22 locus is also near NKX2-2, a highly overexpressed gene in EWS. Interestingly, most loci reside near GGAA repeat seque...
This study aimed to compare pethidine and morphine on efficacy and toxicity in children with seve... more This study aimed to compare pethidine and morphine on efficacy and toxicity in children with severe mucositis following chemotherapies. From March 2000 to November 2003, 35 hospitalized children with chemotherapy-related mucositis were randomly assigned to receive double blindly "patient-controlled analgesia" (PCA) bolus doses of morphine or pethidine. The mucositis pain score was the mean of pain measured four times a day with a Visual Analogue Scale from day 2 to 5 of PCA. Study stops before total accrual for difficulties of recruitment. Out of the 29 patients with more than one day of PCA, the median (range) of the Mean Pain Score was 44 (13-72) and 33 (3-89) in the morphine (n = 14) and pethidine (n = 15) groups, respectively (P = 0.32). PCA was stopped for failure in 10 cases (five in each group). Constipation requiring specific treatment was higher in the morphine group (43% versus 0%). PCA with pethidine appears not inferior to morphine, with less constipation requi...
BackgroundLiver metastases are rare in children with Wilms tumor (WT), and their impact on the ou... more BackgroundLiver metastases are rare in children with Wilms tumor (WT), and their impact on the outcome is unclear.Patients and methodsThe French cohort of patients with WT presenting liver metastases at diagnosis and enrolled in the International Society of Pediatric Oncology (SIOP) 2001 study was reviewed.ResultsFrom 2002 to 2012, 906 French patients were enrolled in the SIOP2001 trial. Among them, 131 (14%) presented with stage IV WT and 18 (1.9%) had liver metastases at diagnosis. Isolated liver metastases were displayed in four of them. After preoperative chemotherapy, persistent liver disease was reported in 14/18 patients, and 13 of them underwent metastasectomy after nephrectomy. In resected liver lesions, the same histology of the primary tumor was reported for three patients, blastemal cells without anaplasia were identified in one patient with DA‐WT, and post‐chemotherapy necrosis/fibrosis was identified for the other 10 patients. For the four patients who had liver and lu...
Recent studies on human NK cells have identified a number of surface antigens that can be utilize... more Recent studies on human NK cells have identified a number of surface antigens that can be utilized to define this population of cells and to identify functionally distinct subsets within this heterogeneous population. In addition, it has been possible to associate specific functional activities with several antigens expressed on NK cells as well as other hematopoietic cells. This information, which is summarized in Table III can be utilized to develop a framework for the classification of cytolytic effector cells. Of primary importance, this classification identifies subsets of cytolytic cells with distinct functional repertoires and distinct cytolytic mechanisms. The majority of NK cells in unstimulated peripheral blood and the majority of NK clones express NKH1 and CD2 antigens but do not express CD3 antigen. These cells morphologically appear as large granular lymphocytes and have broad cytolytic activity against a variety of allogeneic targets without primary sensitization. Consistent with the finding that these cells are CD3 negative, they have not been found to have rearrangement of genes encoding for TCR, or functional mRNA transcripts of either TCR alpha, TCR beta, or TCR gamma genes. In addition, these cells do not express heterodimeric surface proteins similar to those that have now been demonstrated to be MHC-restricted T cell receptors for antigen. Taken together, these findings provide strong evidence that NKH1+CD3- NK clones do not interact with target cells through a T cell receptor-like structure. Nevertheless, these NK cells do share several properties with conventional CTL. These functional T cell characteristics include (1) expression of CD2-T11/E rosette receptor antigen, and (2) utilization of LFA-1 surface antigen to enhance effector cell adhesion to target cells. As previously demonstrated for T cells, NK cells can be activated through the CD2 molecule and this has recently been shown to result in the enhancement of cytolytic function by these effectors. Since CD2 can also function as a cell surface ligand for LFA-3, an antigen expressed on NK targets, the CD2 molecule may be considered as a potential NK receptor structure. The fact that a very small subset of NK cells (approximately equal to 10%) as well as some NK clones (JT11) does not express CD2 argues against a potential role for CD2 as the NK cell receptor. Certainly, further studies will be necessary to clarify the role of CD2 on NK cells and to identify the mechanisms whereby NKH1+CD3- NK cells interact with targets in a non-MHC-restricted fashion.(ABSTRACT TRUNCATED AT 400 WORDS)
ABSTRACT The three-drug combination of melphalan (M), etoposide (E), and carboplatin (C) followed... more ABSTRACT The three-drug combination of melphalan (M), etoposide (E), and carboplatin (C) followed by autologous stem-cell (ASC) rescue has been evaluated prospectively by the French Society of Pediatric Oncology (SFOP) in pediatric high-risk recurrent (HRR) Wilms&#39; tumor (WT) patients with chemotherapy-responsive disease. From October 1988 to October 1994, 29 patients with HRR WT were treated in nine SFOP centers. Two additional patients with stage IV anaplastic WT were consolidated in first complete response (CR) with the same regimen and have been studied separately. The regimen consisted of M 180 mg/m2 for 1 day, E 200 mg/m2/d for 5 days, and C at a daily targeted area under the concentration-time curve (AUC) of 4 mg x min/mL for 5 days. ASCs were reinfused 48 hours after M. Twelve of 28 assessable patients with HRR WT are still in continuous CR at a median of 48.5 months (range, 36 to 96) after consolidation. Disease-free survival (DFS) and overall survival (OS) estimated by the Kaplan-Meier method at 3 years were 50%+/-17% and 60%+/-18%, respectively. Sixteen patients relapsed at a median of 8.5 months (range, 3 to 53) after consolidation. Toxicity data are available in 31 grafted patients. Grade III and IV toxicities included hematologic side effects (n=31), hemorrhage (n=8), mucositis (n=24), diarrhea (n=12), renal disorders (n=8), and pneumonitis (n=3). The adverse prognostic factors (APF) used to select patients for this dose-intensive chemotherapy define children with very-poor-risk recurrent WT. Despite high treatment-related toxicity, about half of these patients remain disease-free at 3 years. Patient outcome is statistically better when high-dose chemotherapy (HDCT) is performed as early as the second CR or partial response (PR). Novel therapeutic approaches with innovative preparative regimens are warranted for the remaining high-risk patients.
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Papers by Jean Michon