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  • 1
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    Pseudoprogression after high-dose busulfan-thiotepa with autologous stem cell transplantation and radiation therapy in children with brain tumors: Impact on survival (2012)
    Oxford University Press
    Details
    Publication Date: 2012-10-25
    Description: Children with a brain tumor treated with high-dose busulfan-thiotepa with autologous stem cell transplantation (ASCT) and radiation therapy (RT) often experience radiographic changes during follow-up. The purpose of the study was to identify the incidence, time course, risk factors, and clinical outcome of this complication. From May 1988 through May 2007, 110 patients (median age, 3.6 years; range, 1 month to 15.3 years) with a brain tumor had received 1 course of high-dose busulfan-thiotepa with stem cell rescue, followed or preceded by RT as part of their treatment. All MRI follow-up examinations were systematically reviewed. Twenty-three patients (21%) developed neuroradiological abnormalities at a median time of 9.2 months (range, 5.6–17.3 months) after ASCT. All contrast-enhancing lesions appeared in patients who had received RT after ASCT and were localized inside the 50–55Gy isodoses. They disappeared in 14 of 23 patients after a median time of 8 months (range, 3–17 months), leaving microcalcifications in some cases. The presence of MRI abnormalities was an independent prognostic factor for overall survival in the multivariate analysis (hazard ratio, 0.12; 95% confidence interval [CI], 0.04–0.33), with a 5-year overall survival rate of 84% among patients with MRI abnormalities (95% CI, 62–94), compared with 27% (95% CI, 19–37) among those without lesions. MRI-detectable pseudoprogression is a common early finding in children treated with high-dose busulfan-thiotepa followed by radiation therapy and is correlated with a better outcome.
    Print ISSN: 1522-8517
    Electronic ISSN: 1523-5866
    Topics: Medicine
    Published by Oxford University Press on behalf of The Society for Neuro-Oncology (SNO).
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  • 2
    Electronic Resource
    Electronic Resource
    Pseudotumoural fibrous dysplasia of the maxilla: Radiological studies and computed tomography contribution (1980)
    Springer
    Skeletal radiology 5 (1980), S. 99-103 
    Details
    ISSN: 1432-2161
    Keywords: Fibrous dysplasia ; Maxilla ; Computed tomography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Clinical, radiological, and histological problems arise relating to fibrous dysplasia of the maxilla. Clinically, 11 of our 39 cases developed so rapidly that the lesions were suspected of being malignant. The histological diagnosis may be very difficult, since any tumoural, reactive, or healing process may simulate fibrous dysplasia. As a general rule, the diagnosis is established most easily by the radiological examination. The radiologist's responsibility is important, as mistakes may have serious consequences. We report four pseudotumoural forms of maxillary sinus fibrous dysplasia. All were characterised clinically by rapid evolution, radiologically by opacity of the sinus with apparent destruction of its wall, and histologically by difficulty in establishing the diagnosis. In two cases indeed, the initial histological interpretation was an osteogenic sarcoma. Due to its excellent densitometric resolution, computed tomography provides an invaluable contribution by displaying the fibrous wall of an intact or even thickened maxillary sinus when conventional radiology has suggested a destructive process. In difficult cases of maxillary fibrous dysplasia, computed tomography should be used as a supplementary investigation to establish the correct diagnosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00347329
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  • 3
    Electronic Resource
    Electronic Resource
    Computed tomography in the evaluation of 41 cases of Ewing's sarcoma (1982)
    Springer
    Skeletal radiology 9 (1982), S. 8-13 
    Details
    ISSN: 1432-2161
    Keywords: Ewing's sarcoma ; Computed tomography ; Chemotherapy ; Radiotherapy ; Follow-up ; Recurrence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Computed tomography (CT) has already proved extremely effective both in cerebral and abdominal pathology. Several recent publications describing first heterogeneous series [1, 2, 7, 11–17], then studies of a single type of lesion [3–6, 8] have illustrated its usefulness in the study of bone lesions. This report deals with 41 cases of Ewing's sarcoma studied by CT at the Institut Gustave Roussy from October 1977 to July 1981, and tries to show both the limitations and indications of this technique for the diagnosis, treatment, and follow-up of Ewing's sarcoma as well as in the diagnosis of any eventual recurrence.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00367374
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  • 4
    Electronic Resource
    Electronic Resource
    Ultrasonography and computed tomography for diagnosis and follow-up of biliary duct rhabdomyosarcomas in children (1987)
    Springer
    Pediatric radiology 17 (1987), S. 127-131 
    Details
    ISSN: 1432-1998
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstracts The authors report eight cases of biliary duct rhabdomyosarcoma in children, examined by US and CT. There were five boys and three girls, aged 2 to 17 years. At presentation, US demonstrates the tumor mass within the liver or the hepatic hilum; it allows measurement of it and defines the relationship with portal vessels, biliary tract and other important structures. CT complements the US evaluation and determines operability. As US and CT cannot assess the histological origin of the tumor, a biopsy is mandatory before treatment. If complete surgical excision does not seem possible, percutaneous biopsy is preferrable to incomplete excision and its possible complications. During the follow-up period, US can be repeated to measure tumor regression under chemotherapy. After surgery, CT seems preferable because of gas interposition. Both US and CT proved to be valuable for the early detection of local recurrence. The prognosis of these tumors remains bad. However, with more aggressive and hopefully more efficient chemotherapy a precise evaluation of the tumor extension by US and CT is very important. Surgery will then be performed only on localized tumors or on residual masses after chemotherapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02388089
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  • 5
    Electronic Resource
    Electronic Resource
    Ultrasonography and computed tomography for diagnosis and follow-up of pelvic rhabdomyosarcomas in children (1987)
    Springer
    Pediatric radiology 17 (1987), S. 132-136 
    Details
    ISSN: 1432-1998
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The authors report 18 cases of pelvic rhabdomyosarcomas in children examined at presentation and followed on US and CT. There were 11 boys, 7 girls; tumor location was bladder, prostate or uterus in 12, perineum in 4, buttock in 2. US is good to define tumoral extension within the bladder CT is better to delineate the extension outside the bladder and regional spread to iliac nodes. CT is the only useful examination for perineal tumors. During chemotherapy US can be frequently repeated to appreciate tumoral regression and to give measurement of the mass. Preoperative CT should be performed when tumoral regression seems sufficient to permit complete tumoral excision without pelvic exanteration. Correlation between US and CT and surgical findings proved to be good. US and CT are also very useful in the follow-up when the child has finished treatment as it can demonstrate a local recurrence before clinical symptoms appear. However, post-surgical and post-radiation changes may be difficult to recognize. These aspects are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02388090
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  • 6
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    Subclonal ALK Mutations in Neuroblastoma at Diagnosis (2015)
    The American Association for Cancer Research (AACR)
    Details
    Publication Date: 2015-11-03
    Description: Purpose: In neuroblastoma, activating ALK receptor tyrosine kinase point mutations play a major role in oncogenesis. We explored the potential occurrence of ALK mutations at a subclonal level using targeted deep sequencing. Experimental Design: In a clinically representative series of 276 diagnostic neuroblastoma samples, exons 23 and 25 of the ALK gene, containing the F1174 and R1275 mutation hotspots, respectively, were resequenced with an extremely high depth of coverage. Results: At the F1174 hotspot (exon 23), mutations were observed in 15 of 277 samples (range of fraction of mutated allele per sample: 0.562%–40.409%). At the R1275 hotspot (exon 25), ALK mutations were detected in 12 of 276 samples (range of fraction of mutated allele: 0.811%–73.001%). Altogether, subclonal events with a mutated allele fraction below 20% were observed in 15/27 ALK -mutated samples. The presence of an ALK mutation was associated with poorer 5-year overall survival (OS: 75% vs. 57%, P = 0.0212 log-rank test), with a strong correlation between F1174 ALK mutations and MYCN amplification being observed. Conclusions: In this series, deep sequencing allows the detection of F1174 and R1275 ALK mutational events at diagnosis in 10% of cases, with subclonal events in more than half of these, which would have gone undetected by Sanger sequencing. These findings are of clinical importance given the potential role of ALK mutations in clonal evolution and relapse. These findings also demonstrate the importance of deep sequencing techniques for the identification of patients especially when considering targeted therapy. Clin Cancer Res; 21(21); 4913–21. ©2015 AACR . See related commentary by George, p. 4747
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
    Published by The American Association for Cancer Research (AACR)
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  • 7
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    Validation of Postinduction Curie Scores in High-Risk Neuroblastoma: A Childrens Oncology Group and SIOPEN Group Report on SIOPEN/HR-NBL1 (2018)
    The Society of Nuclear Medicine (SNM)
    Details
    Publication Date: 2018-03-06
    Description: A semiquantitative 123 I-metaiodobenzylguanidine ( 123 I-MIBG) scoring method (the Curie score, or CS) was previously examined in the Children’s Oncology Group (COG) high-risk neuroblastoma trial, COG A3973, with a postinduction CS of more than 2 being associated with poor event-free survival (EFS). The validation of the CS in an independent dataset, International Society of Paediatric Oncology European Neuroblastoma/High-Risk Neuroblastoma 1 (SIOPEN/HR-NBL1), is now reported. Methods: A retrospective analysis of 123 I-MIBG scans obtained from patients who had been prospectively enrolled in SIOPEN/HR-NBL1 was performed. All patients exhibited 123 I-MIBG–avid, International Neuroblastoma Staging System stage 4 neuroblastoma. 123 I-MIBG scans were evaluated at 2 time points, diagnosis ( n = 345) and postinduction ( n = 330), before consolidation myeloablative therapy. Scans of 10 anatomic regions were evaluated, with each region being scored 0–3 on the basis of disease extent and a cumulative CS generated. Cut points for outcome analysis were identified by Youden methodology. CSs from patients enrolled in COG A3973 were used for comparison. Results: The optimal cut point for CS at diagnosis was 12 in SIOPEN/HR-NBL1, with a significant outcome difference by CS noted (5-y EFS, 43.0% ± 5.7% [CS ≤ 12] vs. 21.4% ± 3.6% [CS 〉 12], P 〈 0.0001). The optimal CS cut point after induction was 2 in SIOPEN/HR-NBL1, with a postinduction CS of more than 2 being associated with an inferior outcome (5-y EFS, 39.2% ± 4.7% [CS ≤ 2] vs. 16.4% ± 4.2% [CS 〉 2], P 〈 0.0001). The postinduction CS maintained independent statistical significance in Cox models when adjusted for the covariates of age and MYCN gene copy number. Conclusion: The prognostic significance of postinduction CSs has now been validated in an independent cohort of patients (SIOPEN/HR-NBL1), with a postinduction CS of more than 2 being associated with an inferior outcome in 2 independent large, cooperative group trials.
    Print ISSN: 0022-3123
    Topics: Medicine
    Published by The Society of Nuclear Medicine (SNM)
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  • 8
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    Molecular Screening for Cancer Treatment Optimization (MOSCATO-01) in Pediatric Patients: A Single-Institutional Prospective Molecular Stratification Trial (2017)
    The American Association for Cancer Research (AACR)
    Details
    Publication Date: 2017-10-14
    Description: Purpose: This single-institutional feasibility study prospectively characterized genomic alterations in recurrent or refractory solid tumors of pediatric patients to select a targeted therapy. Experimental Design: Following treatment failure, patients with signed consent and ages above 6 months, underwent tumor biopsy or surgical resection of primary or metastatic tumor site. These newly acquired samples were analyzed by comparative genomic hybridization array, next-generation sequencing for 75 target genes, whole-exome and RNA sequencing. Biological significance of the alterations and suggestion of most relevant targeted therapies available were discussed in a multidisciplinary tumor board. Results: From December 2012 to January 2016, 75 patients were included, 73 patients underwent 79 interventions, 56 of which were research biopsies with a low complication rate. All patients were pretreated, 37.0% had a brain tumor, and 63.0% had an extra-cranial solid tumor. Median tumor cell content was 70% (range, 0%–100%). Successful molecular analysis in 69 patients detected in 60.9% of patients an actionable alteration in various oncogenic pathways (42.4% with copy-number change, 33.3% with mutation, 2.1% with fusion), and change in diagnosis in three patients. Fourteen patients received 17 targeted therapies; two had received a matched treatment before inclusion. Conclusions: Research biopsies are feasible in advanced pediatric malignancies that exhibit a considerable amount of potentially actionable alterations. Genetic events affecting different cancer hallmarks and limited access to targeted agents within pediatric clinical trials remain the main obstacles that are addressed in our two subsequent precision medicine studies MAPPYACTS and AcSé-ESMART. Clin Cancer Res; 23(20); 6101–12. ©2017 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
    Published by The American Association for Cancer Research (AACR)
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  • 9
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    Genomic Copy Number Profiling Using Circulating Free Tumor DNA Highlights Heterogeneity in Neuroblastoma (2016)
    The American Association for Cancer Research (AACR)
    Details
    Publication Date: 2016-11-16
    Description: Purpose: The tumor genomic copy number profile is of prognostic significance in neuroblastoma patients. We have studied the genomic copy number profile of cell-free DNA (cfDNA) and compared this with primary tumor arrayCGH (aCGH) at diagnosis. Experimental Design: In 70 patients, cfDNA genomic copy number profiling was performed using the OncoScan platform. The profiles were classified according to the overall pattern, including numerical chromosome alterations (NCA), segmental chromosome alterations (SCA), and MYCN amplification (MNA). Results: Interpretable and dynamic cfDNA profiles were obtained in 66 of 70 and 52 of 70 cases, respectively. An overall identical genomic profile between tumor aCGH and cfDNA was observed in 47 cases (3 NCAs, 22 SCAs, 22 MNAs). In one case, cfDNA showed an additional SCA not detected by tumor aCGH. In 4 of 8 cases with a silent tumor aCGH profile, cfDNA analysis revealed a dynamic profile (3 SCAs, 1 NCA). In 14 cases, cfDNA analysis did not reveal any copy number changes. A total of 378 breakpoints common to the primary tumor and cfDNA of any given patient were identified, 27 breakpoints were seen by tumor aCGH, and 54 breakpoints were seen in cfDNA only, including two cases with interstitial IGFR1 gains and two alterations targeting TERT . Conclusions: These results demonstrate the feasibility of cfDNA copy number profiling in neuroblastoma patients, with a concordance of the overall genomic profile in aCGH and cfDNA dynamic cases of 97% and a sensitivity of 77%, respectively. Furthermore, neuroblastoma heterogeneity is highlighted, suggesting that cfDNA might reflect genetic alterations of more aggressive cell clones. Clin Cancer Res; 22(22); 5564–73. ©2016 AACR . See related commentary by Janku and Kurzrock, p. 5400
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
    Published by The American Association for Cancer Research (AACR)
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  • 10
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    Whole-Exome Sequencing of Cell-Free DNA Reveals Temporo-spatial Heterogeneity and Identifies Treatment-Resistant Clones in Neuroblastoma (2018)
    The American Association for Cancer Research (AACR)
    Details
    Publication Date: 2018-02-16
    Description: Purpose: Neuroblastoma displays important clinical and genetic heterogeneity, with emergence of new mutations at tumor progression. Experimental Design: To study clonal evolution during treatment and follow-up, an innovative method based on circulating cell-free DNA (cfDNA) analysis by whole-exome sequencing (WES) paired with target sequencing was realized in sequential liquid biopsy samples of 19 neuroblastoma patients. Results: WES of the primary tumor and cfDNA at diagnosis showed overlap of single-nucleotide variants (SNV) and copy number alterations, with 41% and 93% of all detected alterations common to the primary neuroblastoma and cfDNA. CfDNA WES at a second time point indicated a mean of 22 new SNVs for patients with progressive disease. Relapse-specific alterations included genes of the MAPK pathway and targeted the protein kinase A signaling pathway. Deep coverage target sequencing of intermediate time points during treatment and follow-up identified distinct subclones. For 17 seemingly relapse-specific SNVs detected by cfDNA WES at relapse but not tumor or cfDNA WES at diagnosis, deep coverage target sequencing detected these alterations in minor subclones, with relapse-emerging SNVs targeting genes of neuritogenesis and cell cycle. Furthermore a persisting, resistant clone with concomitant disappearance of other clones was identified by a mutation in the ubiquitin protein ligase HERC2 . Conclusions: Modelization of mutated allele fractions in cfDNA indicated distinct patterns of clonal evolution, with either a minor, treatment-resistant clone expanding to a major clone at relapse, or minor clones collaborating toward tumor progression. Identification of treatment-resistant clones will enable development of more efficient treatment strategies. Clin Cancer Res; 24(4); 939–49. ©2017 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
    Published by The American Association for Cancer Research (AACR)
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