Results of induction chemotherapy in children older than 18 months with stage-4 neuroblastoma treated with an adaptive-to-response modified N7 protocol (mN7)

Purpose. We report the response rate in children older than 18 months with stage 4 Neuroblastoma, using a modified dose-intensive, response-adaptive, induction mN7 protocol. Methods. From 2005 to 2012, 24 patients were treated with the mN7 protocol. Phase 1 included five MSKCC N7 cycles and surgery and two high-dose cyclophosphamide-topotecan (HD-CT) cycles for those who did not achieve complete remission (CR) and negative bone marrow (BM) minimal residual disease (MRD) status (CR+MRD-). Phase 2 consisted of myeloablative doses of topotecan, thiotepa and carboplatin plus hyperfractionated RT. Phase 3 included isotretinoin and 3F8 immunotherapy plus GM-CSF. BM MRD was monitored using GD2 synthase, PHOX2B and cyclin D1 mRNAs. Results. After 3 cycles, all patients showed BM complete histological clearance and 6 (25 %) were MRD-. Twenty of 21 s-look surgeries achieved macroscopic complete resection. After 5 cycles and surgery, 123I-MIBG scan was negative in 15 (62.5 %) cases, BM disease by histology was negative in 23 (96 %) and 10 (42 %) patients were MRD-. Twelve (50 %) pts were in CR, 2 in very good partial response (VGPR), 9 partial response (PR) and one had progressive disease. With 2 HD-CT extra cycles, 17 (71 %) pts achieved CR+MRD- status moving to phase 2. Overall and event-free survival at 3 years for the 17 patients who achieved CR+MRD- is 65 and 53 %, respectively, median follow-up 47 months. Seven (29 %) patients never achieved CR+MRD-. Univariate Cox regression analysis shows CR+MRD- status after mN7 induction as the only statistically significant prognostic factor to predict overall survival. Conclusions. mN7 induction regimen produced a CR+MRD- rate of 71 %. CR+MRD- status following induction was the only predictive marker of long-term survival (AU)

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Results of induction chemotherapy in children older than 18 months with stage-4 neuroblastoma treated with an adaptive-to-response modified N7 protocol (mN7).

PURPOSE: We report the response rate in children older than 18 months with stage 4 Neuroblastoma, using a modified dose-intensive, response-adaptive, induction mN7 protocol. METHODS: From 2005 to 2012, 24 patients were treated with the mN7 protocol. Phase 1 included five MSKCC N7 cycles and surgery and two high-dose cyclophosphamide-topotecan (HD-CT) cycles for those who did not achieve complete remission (CR) and negative bone marrow (BM) minimal residual disease (MRD) status (CR+MRD-). Phase 2 consisted of myeloablative doses of topotecan, thiotepa and carboplatin plus hyperfractionated RT. Phase 3 included isotretinoin and 3F8 immunotherapy plus GM-CSF. BM MRD was monitored using GD2 synthase, PHOX2B and cyclin D1 mRNAs. RESULTS: After 3 cycles, all patients showed BM complete histological clearance and 6 (25 %) were MRD-. Twenty of 21 s-look surgeries achieved macroscopic complete resection. After 5 cycles and surgery, (123)I-MIBG scan was negative in 15 (62.5 %) cases, BM disease by histology was negative in 23 (96 %) and 10 (42 %) patients were MRD-. Twelve (50 %) pts were in CR, 2 in very good partial response (VGPR), 9 partial response (PR) and one had progressive disease. With 2 HD-CT extra cycles, 17 (71 %) pts achieved CR+MRD- status moving to phase 2. Overall and event-free survival at 3 years for the 17 patients who achieved CR+MRD- is 65 and 53 %, respectively, median follow-up 47 months. Seven (29 %) patients never achieved CR+MRD-. Univariate Cox regression analysis shows CR+MRD- status after mN7 induction as the only statistically significant prognostic factor to predict overall survival. CONCLUSIONS: mN7 induction regimen produced a CR+MRD- rate of 71 %. CR+MRD- status following induction was the only predictive marker of long-term survival.

Early-onset acral basal cell carcinomas in Gorlin syndrome.

Two patients are reported in whom early-onset, distal papules with a histopathological diagnosis of basal cell carcinoma were the first manifestation of Gorlin syndrome (GS). These lesions showed no progression and remained stable through follow-up. Two different PTCH1 gene mutations were detected in the two patients, and thus a phenotype-genotype correlation of this manifestation of GS was not possible.

La cirugía de los nódulos pulmonares en oncología pediátrica / The role of surgery for lung nodules in pediatric oncology

: Objetivo.Evaluar el papel de la cirugía de los nódulos pulmonares en oncología pediátrica. Material y métodos. Se han revisado los nódulos pulmonares de los pacientes con diagnóstico de tumor maligno tratados en nuestro centro (< 18 años) desde 1993. Se han analizado datos de la clínica, de la imagen, actitud quirúrgica, anatomía patológica y evolución de aquellos que en algún momento presentaron nódulos pulmonares en la TC. Resultados. Se presentaron 94 episodios de nódulos pulmonares en 57 niños de los 857 pacientes oncológicos controlados (6,6%), bien en el curso de su enfermedad o en el seguimiento. El tumor primario fue: osteosarcoma n=17, sarcoma de Ewing n=14, rabdomiosarcoma n=5, Tumor de células germinales n=4, otros sarcomas n=4, Tumor de Wilms n=3, neuroblastoma n=3, linfoma n=2 y otros tumores n=5. Al diagnóstico 29 niños tenían nódulos; en 20 aparecieron durante el tratamiento; en 29 coincidieron con recaída en otras localizaciones, en pacientes ya fuera de tratamiento y en 16 fue un hallazgo durante el seguimiento. Se hicieron 55 procedimientos quirúrgicos con biopsia, mediante toracotomía, toracoscopia o citología del derrame pleural. En 46 se confirmó metástasis, mientras que en 9 no se halló tumor: 5, tejido pulmonar normal o fibrosis cicatricial y 4, lesiones benignas (reacción celular inflamatoria, linfangioma pleural, infección por micobacteria y pseudotumor inflamatorio). En 39 casos no se hizo biopsia, porque (..) (AU)

Aim. To evaluate the role of lung nodule surgery in pediatric cancer patients. Materials and methods.The records of all cancer patients ( < 18 y) treated at our pediatric institution since 1993 were reviewed. Clinical data, imaging features, surgical attitude, pathology and outcome were analyzed for those patients developing lung nodules on CT scan at any time. Results. Fifty-seven out of 857 (6.6%) cancer patients had lung nodules at one or more times during their disease course, totalling seventyfive episodes. The primary pathological diagnoses include: Osteosarcoma n=17, Ewing’s sarcoma n=14, Rhabdomyosarcoma n=5, Germ cell tumor n=4, other sarcomas n=4, Wilms’ tumor n=3, Neuroblastoma n=3, Lymphoma n=2. Twenty-nine cases had lung nodules at diagnosis; in 20 they were found during therapy; in 29 concomitant with other sites of relapse off therapy; and in 16 patients as an isolated event during follow-up. Fifty-five biopsy procedures were performed through thoracotomy, thoracoscopy or pleural effusion cytology. Metastasic disease was confirmed in 46, whereas in 9 no malignancy was found. Among (..) (AU)

[The role of surgery for lung nodules in pediatric oncology]. / La cirugía de los nódulos pulmonares en oncología pediátrica.

AIM: To evaluate the role of lung nodule surgery in pediatric cancer patients. MATERIALS AND METHODS: The records of all cancer patients (< 18 y) treated at our pediatric institution since 1993 were reviewed. Clinical data, imaging features, surgical attitude, pathology and outcome were analyzed for those patients developing lung nodules on CT scan at any time. RESULTS: Fifty-seven out of 857 (6.6%) cancer patients had lung nodules at one or more times during their disease course, totalling seventy-five episodes. The primary pathological diagnoses include: Osteosarcoma n = 17, Ewing's sarcoma n = 14, Rhabdomyosarcoma n = 5, Germ cell tumor n = 4, other sarcomas n = 4, Wilms' tumor n = 3, Neuroblastoma n = 3, Lymphoma n = 2. Twenty-nine cases had lung nodules at diagnosis; in 20 they were found during therapy; in 29 concomitant with other sites of relapse off therapy; and in 16 patients as an isolated event during follow-up. Fifty-five biopsy procedures were performed through thoracotomy, thoracoscopy or pleural effusion cytology. Metastasic disease was confirmed in 46, whereas in 9 no malignancy was found. Among the nine, five showed either normal lung tissue or scarring after tumor necrosis, and four had other benign diagnoses including: reactive inflammatory cells, pleural lymphangioma, mycobacteria infection and inflammatory pseudotumor. In 39 instances biopsy was not done either because the diagnosis could be made through specific tests, or because the nodules disappeared in a follow-up CT scan within 2 weeks, or because of disease progressing in spite of treatment. In 4 patients surgical removal of lung metastases has afforded cure. CONCLUSIONS: Lung nodule surgery plays a fundamental role in the management of patients with pediatric malignancies: it allows accurate staging, avoiding overtreatment in more than 15% of the cases, and gives a higher chance of cure in some patients.

Clinical relevance of molecular markers in neuroblastoma: results from a single institution.

Neuroblastomas, the most common extracranial solid tumors in children, present an extremely heterogeneous behaviour that can be explained in part by their genetic abnormalities. Thirty-four patients treated at the Pediatric Oncology Unit, Hospital Vall d'Hebron from 1993 to 1997 were prospectively studied to determine the relative prognostic impact of a number of clinical and molecular factors. The factors studied were: ploidy, MYCN and 1p status, and TRK-A expression, in addition to age, stage and histology. Their impact on prognosis was analyzed. In univariate analysis, advanced stage, unfavorable histology, diploidy, MYCN amplification, and 1p deletion were identified as adverse prognostic factors; TRK-A expression was associated with favorable prognosis. After multivariate analysis, only MYCN amplification proved to be an independent adverse prognostic factor (p=0.03), whereas TRK-A expression identified a subset of good-prognosis patients (p=0.003).