Loredana Amoroso - Academia.edu (original) (raw)

Papers by Loredana Amoroso

OncoImmunology, Jul 30, 2018

Journal of immunology research, 2016

The role of nonclassical HLA-class Ib molecules HLA-G and HLA-E in the progression of Neuroblasto... more The role of nonclassical HLA-class Ib molecules HLA-G and HLA-E in the progression of Neuroblastoma (NB), the most common pediatric extracranial solid tumor, has been characterized in the last years. Since BM infiltration by NB cells is an adverse prognostic factor, we have here analyzed for the first time the concentration of soluble (s)HLA-G and HLA-E in bone marrow (BM) plasma samples from NB patients at diagnosis and healthy donors. sHLA-G and sHLA-E are present in BM plasma samples, and their levels were similar between NB patients and controls, thus suggesting that these molecules are physiologically released by resident or stromal BM cell populations. This hypothesis was supported by the finding that sHLA-G and sHLA-E levels did not correlate with BM infiltration and other adverse prognostic factors (MYCN amplification and age at diagnosis). In contrast, BM plasma levels of both molecules were higher in patients with metastatic disease than in patients with localized NB, thus suggesting that concentration of these molecules might be correlated with disease progression. The prognostic role of sHLA-G and sHLA-E concentration in the BM plasma for NB patients will be evaluated in future studies, by analyzing the clinical outcome of the same NB patients at followup.

Journal of Cellular and Molecular Medicine, Feb 27, 2020

This is an open access article under the terms of the Creative Commons Attribution License, which... more This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

OncoImmunology, Oct 24, 2016

Pediatric Blood & Cancer, Nov 19, 2009

Journal of Clinical Oncology, Jun 1, 2023

Journal of Clinical Oncology, May 20, 2011

9549 Background: More effective regimens with acceptable toxicity are needed to improve prognosis... more 9549 Background: More effective regimens with acceptable toxicity are needed to improve prognosis of children with high-risk neuroblastoma. Iodine-131-metaiodobenzylguanidine (131I-MIBG) has been used for targeted radiotherapy of neural crest tumors, including neuroblastoma. By this retrospective study, we have evaluated feasibility and toxicity of 131I-MIBG combined to myeloablative chemotherapy (HD-CHT) with peripheral blood stem cell (PBSC) rescue in children with refractory neuroblastoma. METHODS Between October 1983 and October 2005 a total of 53 patients with refractory neuroblastoma received therapeutic 131I-MIBG combined with HD-CHT. Patients were divided in 2 cohorts. First cohort (FC) patients (n=34) received 131I-MIBG before HD-CHT. Second cohort (SC) patients (n=19) received 131I-MIBG after HD-CHT. Median age at diagnosis was 39 months (range, 7-198). FC patients received 131I-MIBG at the median dose of 7.26 mCi/kg (range, 3.75-16.66), at 16-45 days (median, 20) before HD-CHT. SC patients received 131I-MIBG at the median dose of 6 mCi/kg (range, 2.28-10), at 27-103 days (median, 57) after HD-CHT. Ten types of regimens were used as HD-CHT. RESULTS Both 131I-MIBG infusion and HD-CHT were well tolerated. Hematologic toxicity was comparable for the 2 cohorts. Median times to neutrophil (>0.5 x 103/µL) and platelet (> 50 x 103/µL) engraftment were 13 days (range, 8-30) and 21 days (range, 12->60), respectively. The predominant non hematopoietic toxicity was oral mucositis, of grade 4 in 23 patients (16 in the FC and 7 in the SC patients) and grade 3 in 9 (3 in the FC and 6 in the SC). Pulmonary complications occurred in 2 children. The predominant long-term toxicity was hypothyroidism which occurred in 9 FC and 6 SC patients. CONCLUSIONS Treatment with 131I-MIBG in combination to HD-CHT was feasible with acceptable toxicity. Future studies are warranted to evaluate the efficacy of this combination.

European Journal of Cancer, Aug 1, 2020

Background: The phase I component of a phase I/II study defined the recommended phase II dose and... more Background: The phase I component of a phase I/II study defined the recommended phase II dose and established the tolerability of nab-paclitaxel monotherapy in paediatric patients with recurrent or refractory solid tumours. The activity and safety of nabpaclitaxel monotherapy was further investigated in this phase II study. Patients and methods: Paediatric patients with recurrent or refractory Ewing sarcoma, neuroblastoma or rhabdomyosarcoma received 240 mg/m 2 of nab-paclitaxel on days 1, 8 and 15 of each 28-day cycle. The primary end-point was the overall response rate (ORR; complete response [CR] þ partial response [PR]). Secondary end-points included duration of response, disease control rate (DCR; CR þ PR þ stable disease [SD]), progression-free survival, 1-year overall survival, safety and pharmacokinetics. Results: Forty-two patients were enrolled, 14 each with Ewing sarcoma, neuroblastoma and rhabdomyosarcoma. The ORRs were 0%, 0% and 7.1% (1 confirmed PR), respectively. The DCRs were 30.8% (4 SD), 7.1% (1 SD) and 7.1% (1 confirmed PR and 0 SD) in the Ewing sarcoma, neuroblastoma and rhabdomyosarcoma groups, respectively. The median progression-free survival was 13.0, 7.4 and 5.1 weeks, respectively, and the 1-year overall survival rates were 48%, 25% and 15%, respectively. The most common grade III/4IVadverse events were haematologic (neutropenia [50%] and anaemia [48%]), and grade III/IV peripheral neuropathy occurred in 2 patients (14%) in the rhabdomyosarcoma group. Pharmacokinetics analyses revealed that paclitaxel tissue distribution was both rapid and extensive. Conclusions: In this phase II study, limited activity was observed; however, the safety of nabpaclitaxel in paediatric patients was confirmed. Trial registration: NCT01962103 and EudraCT 2013-000144-26.

Annals of Oncology, May 1, 2013

Background: Cure rate for subjects with refractory or relapsing metastatic neuroblastoma is <5%. ... more Background: Cure rate for subjects with refractory or relapsing metastatic neuroblastoma is <5%. In the search for a novel therapy, continuous daily oral administration of imatinib mesylate was evaluated. Patients and methods: Twenty-four subjects were enrolled in a two-stage study. Imatinib was administered for the first 4 weeks (cycle) at 170 mg/sqm b.i.d. If no major toxicity occurred, the dose was escalated to 300 mg/sqm b.i.d. for a maximum of 12 cycles. Clinical response and toxicity were evaluated according to international criteria. Pharmacokinetics (PK) profiles and tyrosine hydroxylase (TH) mRNA expression were also determined in a subset of subjects. Results: Five (21%) complete responses, with one subject still alive at 68 months, and 2 (8%) partial responses lasting up to 29 months were obtained. No grade 4 toxicity was observed. At steady-state, PK exposure (69.7 µg h/ml) was similar to that of adults receiving 1000 mg/die. Responses appear to correlate with the absence or presence of metastasis in the bone marrow (BM) alone, with low TH expression levels at study entry and low imatinib exposure. Conclusions: Imatinib mesylate was well-tolerated and effective in the subset of subjects with low BM infiltration as only site of metastasis.

Pediatric Blood & Cancer, Aug 24, 2016

Few randomized trials have been conducted in children with relapsed/refractory neuroblastoma and ... more Few randomized trials have been conducted in children with relapsed/refractory neuroblastoma and data about outcomes including progression-free survival (PFS) in these patients are scarce. A meta-analysis of three phase II studies of children with relapsed/refractory neuroblastoma conducted in Europe (temozolomide, topotecan-vincristine-doxorubicin and topotecan-temozolomide) was performed. Individual patient data with extended follow-up were collected from the trial databases after publication to describe trial outcomes (response rate, clinical benefit ratio, duration of treatment, PFS, and overall survival [OS]). Characteristics of subjects with relapsed/refractory neuroblastoma were compared. Data from 71 children and adolescents with relapsed/refractory neuroblastoma were collected. Response definitions were not homogeneous in the three trials. Patients were on study for a median of 3.5 months (interquartile range [IQR] 1.9-6.2). Of those, 35.2% achieved a complete or partial response, 26.3% experienced a response after more than two cycles, and 23.9% received more than six cycles. Median PFS from study entry for all, refractory, and relapsed patients was 6.4 ± 1.0, 12.5 ± 6.8, and 5.7 ± 1.0 months, respectively (P = 0.006). Median OS from study entry for all, refractory, and relapsed patients was 16.1 ± 4.3, 27.9 ± 20.2, and 11.0 ± 1.6 months, respectively (P = 0.03). Baseline data for response rate, clinical benefit ratio, duration of treatment, PFS, and OS were provided. Two subpopulations (relapsed/refractory) were clearly distinct and should be included in the interpretation of all trials. These results should help informing the design of forthcoming studies in relapsed/refractory neuroblastoma.

Journal of Clinical Oncology, Jun 1, 2023

Cancer Research, Jun 15, 2022

Background: Neuroblastoma (NB) represents the most frequent form of extracranial solid tumor of i... more Background: Neuroblastoma (NB) represents the most frequent form of extracranial solid tumor of infants, responsible for 15% of childhood cancer deaths. Nucleolin (NCL) prognostic value in NB was here investigated. Methods: NCL protein expression was evaluated in NB patients at diagnosis and after induction chemotherapy. NCL mRNA prognostic value was first assessed in a cohort of 20 stage M NB patients and confirmed in the MultiPlatform786 including 786 NB patients of all stages. Overall and event-free survival curves were plotted by Kaplan-Meier method and compared by log-rank test. Findings: NCL protein resulted significantly overexpressed in NB tumors compared to the non tumoral counterpart, and higher in stage M compared to stage L patients. In the stage M cohort and in MultiPlatform786 dataset, patients with high NCL mRNA expression revealed a significant lower survival probability than those with low NCL expression. In MultiPlatform786 dataset, NCL mRNA expression was significantly higher in patients with age &gt;18 months, in stage M and in MYCN amplified tumors than in patients with age ˂18 months and in stage L or MS and with MYCN non amplified tumors, respectively. Multivariate analysis suggested NCL has a significant prognostic value even in the model adjusted for established prognostic markers. NCL significantly stratified patients with age &lt;18 and age &gt;18, stage M, &gt;18 months and stage M tumor, stages L or MS, and with MYCN not amplified. A significant correlation between NCL and MYCN, MYC, and TERT was found in two independent datasets. Gene set enrichment analysis revealed a significant positive enrichment of MYC target genes and genes involved in telomerase maintenance. NCL protein resulted down-modulated after chemotherapy, in association with morphological features of neuroblastic differentiation. Interpretation: NCL is a novel and independent prognostic marker for NB. Funding: IMH-EuroNanoMed II-2015 (ER-2015-2360441-Eranet) and AIRC IG n. 24397 to PF. Citation Format: Davide Cangelosi, Chiara Brignole, Veronica Bensa, Roberto Tamma, Fabiana Malaguti, Barbara Carlini, Enzo Calarco, Patrizia Perri, Domenico Ribatti, Nuno A. Fonseca, Joao N. Moreira, Alessandra Eva, Loredana Amoroso, Massimo Conte, Alberto Garaventa, Angela R. Sementa, Maria V. Corrias, Mirco Ponzoni, Fabio Pastorino. Nucleolin has prognostic value in neuroblastoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1276.

Archives De Pediatrie, Jun 1, 2008

M. Bey et al Archives de Pédiatrie 2008 ; 15 : p923-p1019 indispensables chez les sujets apparemm... more M. Bey et al Archives de Pédiatrie 2008 ; 15 : p923-p1019 indispensables chez les sujets apparemment sains. La radiothérapie et plus récemment l'hydroxyurée représentent les traitements de choix.

Archives De Pediatrie, Jun 1, 2008

M. Bey et al Archives de Pédiatrie 2008 ; 15 : p923-p1019 indispensables chez les sujets apparemm... more M. Bey et al Archives de Pédiatrie 2008 ; 15 : p923-p1019 indispensables chez les sujets apparemment sains. La radiothérapie et plus récemment l'hydroxyurée représentent les traitements de choix.

European Journal of Cancer

Cancers

Neuroblastoma (NB) is the most common extracranial solid tumor in childhood. Patients with relaps... more Neuroblastoma (NB) is the most common extracranial solid tumor in childhood. Patients with relapsed/refractory disease have a poor prognosis, and additional therapeutic options are needed. Mutations and amplifications in the ALK (Anaplastic Lymphoma Kinase) gene constitute a key target for treatment. Our goal, within the Italian project of PeRsonalizEdMEdicine (PREME), was to evaluate the genomic status of patients with relapsed/refractory NB and to implement targeted therapies in those with targetable mutations. From November 2018 to November 2021, we performed Whole Exome Sequencing or Targeted Gene Panel Sequencing in relapsed/refractory NB patients in order to identify druggable variants. Activating mutations of ALK were identified in 8(28.57%) of 28 relapsed/refractory NB patients. The mutation p.F1174L was found in six patients, whereas p.R1275Q was found in one and the unknown mutation p.S104R in another. Three patients died before treatment could be started, while five patie...

Journal of Clinical Oncology, 2013

10016 Background: This study evaluated the activity and toxicity of a topotecan-vincristine-doxor... more 10016 Background: This study evaluated the activity and toxicity of a topotecan-vincristine-doxorubicin (TVD) combination administered to patients with stage 4 neuroblastoma failing to achieve adequate metastatic remission after induction therapy (rapid COJEC) according to the HR-NBL-1 SIOPEN protocol. Methods: Patients above 1 year of age with stage 4 neuroblastoma, who failed to achieve adequate metastatic remission with rapid COJEC were eligible. Topotecan was administered at 1.5 mg/m²/day for 5 days, followed by a 48-hour infusion of vincristine, 2 mg/m² and doxorubicin, 45 mg/m². Tumour response was assessed after 2 TVD courses, according to the INSS criteria. Patients achieving CR or VGPR (metastatic CR) or PR (≤ 3 skeletal MIBG spots and cytomorphological CR on 2 bone marrow aspirates) underwent myeloablative therapy (MAT) followed by PBSC rescue. Patients who failed to achieve PR after 2-4 TVD courses, or developed PD were withdrawn from the study and were treated at physici...

OncoImmunology, Jul 30, 2018

Journal of immunology research, 2016

The role of nonclassical HLA-class Ib molecules HLA-G and HLA-E in the progression of Neuroblasto... more The role of nonclassical HLA-class Ib molecules HLA-G and HLA-E in the progression of Neuroblastoma (NB), the most common pediatric extracranial solid tumor, has been characterized in the last years. Since BM infiltration by NB cells is an adverse prognostic factor, we have here analyzed for the first time the concentration of soluble (s)HLA-G and HLA-E in bone marrow (BM) plasma samples from NB patients at diagnosis and healthy donors. sHLA-G and sHLA-E are present in BM plasma samples, and their levels were similar between NB patients and controls, thus suggesting that these molecules are physiologically released by resident or stromal BM cell populations. This hypothesis was supported by the finding that sHLA-G and sHLA-E levels did not correlate with BM infiltration and other adverse prognostic factors (MYCN amplification and age at diagnosis). In contrast, BM plasma levels of both molecules were higher in patients with metastatic disease than in patients with localized NB, thus suggesting that concentration of these molecules might be correlated with disease progression. The prognostic role of sHLA-G and sHLA-E concentration in the BM plasma for NB patients will be evaluated in future studies, by analyzing the clinical outcome of the same NB patients at followup.

Journal of Cellular and Molecular Medicine, Feb 27, 2020

This is an open access article under the terms of the Creative Commons Attribution License, which... more This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

OncoImmunology, Oct 24, 2016

Pediatric Blood & Cancer, Nov 19, 2009

Journal of Clinical Oncology, Jun 1, 2023

Journal of Clinical Oncology, May 20, 2011

9549 Background: More effective regimens with acceptable toxicity are needed to improve prognosis... more 9549 Background: More effective regimens with acceptable toxicity are needed to improve prognosis of children with high-risk neuroblastoma. Iodine-131-metaiodobenzylguanidine (131I-MIBG) has been used for targeted radiotherapy of neural crest tumors, including neuroblastoma. By this retrospective study, we have evaluated feasibility and toxicity of 131I-MIBG combined to myeloablative chemotherapy (HD-CHT) with peripheral blood stem cell (PBSC) rescue in children with refractory neuroblastoma. METHODS Between October 1983 and October 2005 a total of 53 patients with refractory neuroblastoma received therapeutic 131I-MIBG combined with HD-CHT. Patients were divided in 2 cohorts. First cohort (FC) patients (n=34) received 131I-MIBG before HD-CHT. Second cohort (SC) patients (n=19) received 131I-MIBG after HD-CHT. Median age at diagnosis was 39 months (range, 7-198). FC patients received 131I-MIBG at the median dose of 7.26 mCi/kg (range, 3.75-16.66), at 16-45 days (median, 20) before HD-CHT. SC patients received 131I-MIBG at the median dose of 6 mCi/kg (range, 2.28-10), at 27-103 days (median, 57) after HD-CHT. Ten types of regimens were used as HD-CHT. RESULTS Both 131I-MIBG infusion and HD-CHT were well tolerated. Hematologic toxicity was comparable for the 2 cohorts. Median times to neutrophil (>0.5 x 103/µL) and platelet (> 50 x 103/µL) engraftment were 13 days (range, 8-30) and 21 days (range, 12->60), respectively. The predominant non hematopoietic toxicity was oral mucositis, of grade 4 in 23 patients (16 in the FC and 7 in the SC patients) and grade 3 in 9 (3 in the FC and 6 in the SC). Pulmonary complications occurred in 2 children. The predominant long-term toxicity was hypothyroidism which occurred in 9 FC and 6 SC patients. CONCLUSIONS Treatment with 131I-MIBG in combination to HD-CHT was feasible with acceptable toxicity. Future studies are warranted to evaluate the efficacy of this combination.

European Journal of Cancer, Aug 1, 2020

Background: The phase I component of a phase I/II study defined the recommended phase II dose and... more Background: The phase I component of a phase I/II study defined the recommended phase II dose and established the tolerability of nab-paclitaxel monotherapy in paediatric patients with recurrent or refractory solid tumours. The activity and safety of nabpaclitaxel monotherapy was further investigated in this phase II study. Patients and methods: Paediatric patients with recurrent or refractory Ewing sarcoma, neuroblastoma or rhabdomyosarcoma received 240 mg/m 2 of nab-paclitaxel on days 1, 8 and 15 of each 28-day cycle. The primary end-point was the overall response rate (ORR; complete response [CR] þ partial response [PR]). Secondary end-points included duration of response, disease control rate (DCR; CR þ PR þ stable disease [SD]), progression-free survival, 1-year overall survival, safety and pharmacokinetics. Results: Forty-two patients were enrolled, 14 each with Ewing sarcoma, neuroblastoma and rhabdomyosarcoma. The ORRs were 0%, 0% and 7.1% (1 confirmed PR), respectively. The DCRs were 30.8% (4 SD), 7.1% (1 SD) and 7.1% (1 confirmed PR and 0 SD) in the Ewing sarcoma, neuroblastoma and rhabdomyosarcoma groups, respectively. The median progression-free survival was 13.0, 7.4 and 5.1 weeks, respectively, and the 1-year overall survival rates were 48%, 25% and 15%, respectively. The most common grade III/4IVadverse events were haematologic (neutropenia [50%] and anaemia [48%]), and grade III/IV peripheral neuropathy occurred in 2 patients (14%) in the rhabdomyosarcoma group. Pharmacokinetics analyses revealed that paclitaxel tissue distribution was both rapid and extensive. Conclusions: In this phase II study, limited activity was observed; however, the safety of nabpaclitaxel in paediatric patients was confirmed. Trial registration: NCT01962103 and EudraCT 2013-000144-26.

Annals of Oncology, May 1, 2013

Background: Cure rate for subjects with refractory or relapsing metastatic neuroblastoma is <5%. ... more Background: Cure rate for subjects with refractory or relapsing metastatic neuroblastoma is <5%. In the search for a novel therapy, continuous daily oral administration of imatinib mesylate was evaluated. Patients and methods: Twenty-four subjects were enrolled in a two-stage study. Imatinib was administered for the first 4 weeks (cycle) at 170 mg/sqm b.i.d. If no major toxicity occurred, the dose was escalated to 300 mg/sqm b.i.d. for a maximum of 12 cycles. Clinical response and toxicity were evaluated according to international criteria. Pharmacokinetics (PK) profiles and tyrosine hydroxylase (TH) mRNA expression were also determined in a subset of subjects. Results: Five (21%) complete responses, with one subject still alive at 68 months, and 2 (8%) partial responses lasting up to 29 months were obtained. No grade 4 toxicity was observed. At steady-state, PK exposure (69.7 µg h/ml) was similar to that of adults receiving 1000 mg/die. Responses appear to correlate with the absence or presence of metastasis in the bone marrow (BM) alone, with low TH expression levels at study entry and low imatinib exposure. Conclusions: Imatinib mesylate was well-tolerated and effective in the subset of subjects with low BM infiltration as only site of metastasis.

Pediatric Blood & Cancer, Aug 24, 2016

Few randomized trials have been conducted in children with relapsed/refractory neuroblastoma and ... more Few randomized trials have been conducted in children with relapsed/refractory neuroblastoma and data about outcomes including progression-free survival (PFS) in these patients are scarce. A meta-analysis of three phase II studies of children with relapsed/refractory neuroblastoma conducted in Europe (temozolomide, topotecan-vincristine-doxorubicin and topotecan-temozolomide) was performed. Individual patient data with extended follow-up were collected from the trial databases after publication to describe trial outcomes (response rate, clinical benefit ratio, duration of treatment, PFS, and overall survival [OS]). Characteristics of subjects with relapsed/refractory neuroblastoma were compared. Data from 71 children and adolescents with relapsed/refractory neuroblastoma were collected. Response definitions were not homogeneous in the three trials. Patients were on study for a median of 3.5 months (interquartile range [IQR] 1.9-6.2). Of those, 35.2% achieved a complete or partial response, 26.3% experienced a response after more than two cycles, and 23.9% received more than six cycles. Median PFS from study entry for all, refractory, and relapsed patients was 6.4 ± 1.0, 12.5 ± 6.8, and 5.7 ± 1.0 months, respectively (P = 0.006). Median OS from study entry for all, refractory, and relapsed patients was 16.1 ± 4.3, 27.9 ± 20.2, and 11.0 ± 1.6 months, respectively (P = 0.03). Baseline data for response rate, clinical benefit ratio, duration of treatment, PFS, and OS were provided. Two subpopulations (relapsed/refractory) were clearly distinct and should be included in the interpretation of all trials. These results should help informing the design of forthcoming studies in relapsed/refractory neuroblastoma.

Journal of Clinical Oncology, Jun 1, 2023

Cancer Research, Jun 15, 2022

Background: Neuroblastoma (NB) represents the most frequent form of extracranial solid tumor of i... more Background: Neuroblastoma (NB) represents the most frequent form of extracranial solid tumor of infants, responsible for 15% of childhood cancer deaths. Nucleolin (NCL) prognostic value in NB was here investigated. Methods: NCL protein expression was evaluated in NB patients at diagnosis and after induction chemotherapy. NCL mRNA prognostic value was first assessed in a cohort of 20 stage M NB patients and confirmed in the MultiPlatform786 including 786 NB patients of all stages. Overall and event-free survival curves were plotted by Kaplan-Meier method and compared by log-rank test. Findings: NCL protein resulted significantly overexpressed in NB tumors compared to the non tumoral counterpart, and higher in stage M compared to stage L patients. In the stage M cohort and in MultiPlatform786 dataset, patients with high NCL mRNA expression revealed a significant lower survival probability than those with low NCL expression. In MultiPlatform786 dataset, NCL mRNA expression was significantly higher in patients with age &gt;18 months, in stage M and in MYCN amplified tumors than in patients with age ˂18 months and in stage L or MS and with MYCN non amplified tumors, respectively. Multivariate analysis suggested NCL has a significant prognostic value even in the model adjusted for established prognostic markers. NCL significantly stratified patients with age &lt;18 and age &gt;18, stage M, &gt;18 months and stage M tumor, stages L or MS, and with MYCN not amplified. A significant correlation between NCL and MYCN, MYC, and TERT was found in two independent datasets. Gene set enrichment analysis revealed a significant positive enrichment of MYC target genes and genes involved in telomerase maintenance. NCL protein resulted down-modulated after chemotherapy, in association with morphological features of neuroblastic differentiation. Interpretation: NCL is a novel and independent prognostic marker for NB. Funding: IMH-EuroNanoMed II-2015 (ER-2015-2360441-Eranet) and AIRC IG n. 24397 to PF. Citation Format: Davide Cangelosi, Chiara Brignole, Veronica Bensa, Roberto Tamma, Fabiana Malaguti, Barbara Carlini, Enzo Calarco, Patrizia Perri, Domenico Ribatti, Nuno A. Fonseca, Joao N. Moreira, Alessandra Eva, Loredana Amoroso, Massimo Conte, Alberto Garaventa, Angela R. Sementa, Maria V. Corrias, Mirco Ponzoni, Fabio Pastorino. Nucleolin has prognostic value in neuroblastoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1276.

Archives De Pediatrie, Jun 1, 2008

M. Bey et al Archives de Pédiatrie 2008 ; 15 : p923-p1019 indispensables chez les sujets apparemm... more M. Bey et al Archives de Pédiatrie 2008 ; 15 : p923-p1019 indispensables chez les sujets apparemment sains. La radiothérapie et plus récemment l'hydroxyurée représentent les traitements de choix.

Archives De Pediatrie, Jun 1, 2008

M. Bey et al Archives de Pédiatrie 2008 ; 15 : p923-p1019 indispensables chez les sujets apparemm... more M. Bey et al Archives de Pédiatrie 2008 ; 15 : p923-p1019 indispensables chez les sujets apparemment sains. La radiothérapie et plus récemment l'hydroxyurée représentent les traitements de choix.

European Journal of Cancer

Cancers

Neuroblastoma (NB) is the most common extracranial solid tumor in childhood. Patients with relaps... more Neuroblastoma (NB) is the most common extracranial solid tumor in childhood. Patients with relapsed/refractory disease have a poor prognosis, and additional therapeutic options are needed. Mutations and amplifications in the ALK (Anaplastic Lymphoma Kinase) gene constitute a key target for treatment. Our goal, within the Italian project of PeRsonalizEdMEdicine (PREME), was to evaluate the genomic status of patients with relapsed/refractory NB and to implement targeted therapies in those with targetable mutations. From November 2018 to November 2021, we performed Whole Exome Sequencing or Targeted Gene Panel Sequencing in relapsed/refractory NB patients in order to identify druggable variants. Activating mutations of ALK were identified in 8(28.57%) of 28 relapsed/refractory NB patients. The mutation p.F1174L was found in six patients, whereas p.R1275Q was found in one and the unknown mutation p.S104R in another. Three patients died before treatment could be started, while five patie...

Journal of Clinical Oncology, 2013

10016 Background: This study evaluated the activity and toxicity of a topotecan-vincristine-doxor... more 10016 Background: This study evaluated the activity and toxicity of a topotecan-vincristine-doxorubicin (TVD) combination administered to patients with stage 4 neuroblastoma failing to achieve adequate metastatic remission after induction therapy (rapid COJEC) according to the HR-NBL-1 SIOPEN protocol. Methods: Patients above 1 year of age with stage 4 neuroblastoma, who failed to achieve adequate metastatic remission with rapid COJEC were eligible. Topotecan was administered at 1.5 mg/m²/day for 5 days, followed by a 48-hour infusion of vincristine, 2 mg/m² and doxorubicin, 45 mg/m². Tumour response was assessed after 2 TVD courses, according to the INSS criteria. Patients achieving CR or VGPR (metastatic CR) or PR (≤ 3 skeletal MIBG spots and cytomorphological CR on 2 bone marrow aspirates) underwent myeloablative therapy (MAT) followed by PBSC rescue. Patients who failed to achieve PR after 2-4 TVD courses, or developed PD were withdrawn from the study and were treated at physici...