RESUMEN
While irinotecan has been studied in various pediatric solid tumors, its potential role in Wilms tumor (WT) is less clear. We evaluated response and outcome of irinotecan-containing regimens in relapsed WT and compared our results to the available literature. Among 14 evaluable patients, one complete response (CR) and two partial responses (PRs) were observed in patients with initial intermediate-risk (CR and PR) and blastemal-type histologies (PR). Two patients were alive at last follow-up showing no evidence of disease. Our results and the reviewed literature suggest some effectiveness of irinotecan in the setting of relapsed WT.
Asunto(s)
Camptotecina/análogos & derivados , Neoplasias Renales/tratamiento farmacológico , Tumor de Wilms/tratamiento farmacológico , Adolescente , Camptotecina/administración & dosificación , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Irinotecán , Masculino , Factores de RiesgoRESUMEN
PURPOSE: TW2003, the third Italian prospective study on Wilms tumor, aimed to improve survival in patients with stage III-IV tumors, de-escalate therapy for stage I-II nonanaplastic tumors, refine the risk stratification of therapy, and develop a national infrastructure for biobanking and central pathology review. MATERIALS AND METHODS: TW2003 recruited children 18 years old or younger with primary intrarenal tumors. Local physicians chose nephrectomy with or without preoperative chemotherapy as the initial treatment based on the risk of unsafe and/or incomplete immediate surgery. The main drivers for adjuvant therapy were tumor stage and diffuse anaplasia. A new risk stratification schema was investigated, incorporating patient age, reason for stage III designation and completeness of lung nodule response in stage IV disease. RESULTS: We report on 453 patients with unilateral Wilms tumor. Preoperative chemotherapy was administered to 42% of patients. The 5-year event-free survival and overall survival rates were 89.1% (95% CI 83.6-94.9) and 97.0% (93.7-100) for stage I; 85.1% (79.6-91.1) and 94.0% (90.1-98.1) for stage II (160); 82.7% (75.3-90.8) and 90.9% (85.0-97.1) for stage III (101); and 72.1% (61.9-84.0) and 82.5% (73.1-93.1) for stage IV (69), respectively. On multivariable analysis only anaplasia was significant for event-free survival (HR 2.68, 95% CI 1.48-4.86, p=0.001; bias corrected c-index 0.580) and overall survival (HR 5.29, 95% CI 2.52-11.12, p <0.001; bias corrected c-index 0.697). CONCLUSIONS: The survival rates achieved and the proposed risk stratification schema provide a basis for future comparisons of Wilms tumor treatment burden and patient outcome.
Asunto(s)
Protocolos Clínicos , Neoplasias Renales/diagnóstico , Estadificación de Neoplasias , Medición de Riesgo/métodos , Tumor de Wilms/diagnóstico , Adolescente , Adulto , Niño , Preescolar , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Lactante , Recién Nacido , Italia/epidemiología , Neoplasias Renales/epidemiología , Neoplasias Renales/terapia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tasa de Supervivencia/tendencias , Tumor de Wilms/epidemiología , Tumor de Wilms/terapia , Adulto JovenRESUMEN
BACKGROUND: Children with Wilms' tumor (WT) aged under 24 months (infants) have a better prognosis than older patients. Our aim was to study the epidemiology of this age group, with focus on the modality of diagnosis, tumor size, and association with malformations/syndromes, seeking to understand if any of these factors might be related to prognosis. PATIENTS AND METHODS: Infants diagnosed with WT between 2003 and February 2010 were evaluated. A query form was used to collect data on the modality of WT diagnosis (symptomatic or incidental), tumor volume, maximum diameter, site, and stage. RESULTS: Data were collected for 117 of 124 WT infants registered. Twenty-four cases had an incidental diagnosis (ID) of renal mass, usually arising from an abdominal ultrasound performed for other reasons, and 93 had been diagnosed based on clinical signs/symptoms. The incidental cohort displayed unifocal disease, mean tumor diameter 5.52 cm, mean tumor volume 84.30 ml, and 14 patients showed associated malformations. Symptomatic patients had mean maximum tumor diameter of 10.18 cm, mean tumor volume of 451.18 ml, and six had associated malformations. CONCLUSIONS: Our study showed that 20% of the infants had an ID of WT; they had a relatively smaller nonmetastatic tumor and a higher rate of malformations than infants of the symptomatically diagnosed group, but we did not detect any difference in age at diagnosis between the two groups. Conversely, we found a significant difference in the 5-year event-free survival rate (P = 0.018) between infants under 1 year (96%), more frequently associated with congenital malformations, and infants 1-2 years (80%).
Asunto(s)
Neoplasias Renales/diagnóstico , Tumor de Wilms/diagnóstico , Factores de Edad , Anomalías Congénitas , Femenino , Humanos , Lactante , Neoplasias Renales/epidemiología , Masculino , Pronóstico , Estudios Retrospectivos , Tumor de Wilms/epidemiologíaRESUMEN
BACKGROUND: The potential impact of diagnostic delays on patients' outcomes is a debated issue in pediatric oncology and discordant results have been published so far. We attempted to tackle this issue by analyzing a prospective series of 351 consecutive children and adolescents with solid malignancies using innovative statistical tools. METHODS: To address the nonlinear complexity of the association between symptom interval and overall survival (OS), a regression tree algorithm was constructed with sequential binary splitting rules and used to identify homogeneous patient groups vis-à-vis functional relationship between diagnostic delay and OS. RESULTS: Three different groups were identified: group A, with localized disease and good prognosis (5-year OS 85.4%); group B, with locally or regionally advanced, or metastatic disease and intermediate prognosis (5-year OS 72.9%), including neuroblastoma, Wilms tumor, non-rhabdomyosarcoma soft tissue sarcoma, and germ cell tumor; and group C, with locally or regionally advanced, or metastatic disease and poor prognosis (5-year OS 45%), including brain tumors, rhabdomyosarcoma, and bone sarcoma. The functional relationship between symptom interval and mortality risk differed between the three subgroups, there being no association in group A (hazard ratio [HR]: 0.96), a positive linear association in group B (HR: 1.48), and a negative linear association in group C (HR: 0.61). CONCLUSIONS: Our analysis suggests that at least a subset of patients can benefit from an earlier diagnosis in terms of survival. For others, intrinsic aggressiveness may mask the potential effect of diagnostic delays. Based on these findings, early diagnosis should remain a goal for pediatric cancer patients.
Asunto(s)
Neoplasias/diagnóstico , Neoplasias/terapia , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Neoplasias/mortalidad , Estudios Prospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Various projects dedicated specifically to adolescents and young adults (AYA) with cancer have been developed in recent years. A critical aspect of such programs is the ability to demonstrate its value, and therefore how to measure desired outcomes. METHODS: A list of metrics to consider for demonstrating the advantages of an AYA program was identified and used to assess the activity of the Youth Project operating at the Pediatric Oncology Unit of the Istituto Nazionale Tumori in Milan. RESULTS: The number of newly diagnosed AYA patients seen at the Unit has increased since the formal launch of the Youth Project, from 65 to 81.2 cases/year. Concerning the 78 AYA patients presenting with malignant neoplasms in 2015, 82% were included in clinical trials (the other 18% in prospective observational studies). Fertility preservation measures were implemented for 59% of AYA patients considered at risk, and specific psychological support was provided in 70.6% of cases; 72.5% of patients actively participated in support activities. Other parameters considered were a preliminary satisfaction questionnaire administered to patients and the program's scientific recognition and acknowledgment by the community. CONCLUSIONS: The study proposed a number of potentially reproducible, practical parameters to consider in assessing the value of a program dedicated to AYA. These metrics were examined in terms of the activities of our Youth Project, and confirmed its efficacy. To be sustainable over time, AYA projects have to be accepted as a standard of care at the community and government levels.
Asunto(s)
Neoplasias/terapia , Adolescente , Adulto , Femenino , Humanos , Masculino , Apoyo Social , Nivel de Atención , Adulto JovenRESUMEN
BACKGROUND: The awareness that adolescents can have cancer is probably insufficient, not only among teenagers and their families, but also among physicians, and adolescent patients are reportedly often referred to qualified cancer institutes after a considerable delay. PROCEDURE: A prospective series of 425 patients (28% of them adolescents) with solid tumors was analyzed to investigate the correlation between symptom interval and age, and the different contributions to symptom interval in terms of the time from symptom onset to the first contact with a doctor (patient delay), referral to the oncologist (referral delay), and final diagnosis (oncologist delay). RESULTS: The median symptom interval was 47 days for 0 to 14-year-old patients and 137 for those ≥15 years (P < 0.001). The greatest delay in the adolescent group related to the patient delay (63.3% of the total symptom interval). CONCLUSION: Adolescents are often diagnosed with longer delay as compared to children. The main contribution to symptom interval in adolescents appears to be due to the time they first go to a doctor; however, also the time taken by the physician to the patient to a specialist (oncologist or surgeon) able to define the diagnosis of cancer was longer for adolescents than for younger patients.
Asunto(s)
Diagnóstico Tardío , Neoplasias/diagnóstico , Adolescente , Factores de Edad , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Factores de TiempoRESUMEN
PURPOSE: We retrospectively report strategies used for medulloblastoma patients progressing after craniospinal irradiation where we aimed for: symptom control, a satisfactory quality of life, accrual in phase 1-2 trials, when available, and the first two conditions could no longer be satisfied by already experienced second-line strategies. METHODS: Surgery was used in cases of doubtful relapse or when only one site was affected. Radiotherapy was given whenever possible, especially to relieve symptoms. The main chemotherapy regimens were oral temozolomide/etoposide, intravenous (iv.) cisplatin/etoposide, iv. gemcitabine/oxaliplatin, an oral sonic hedgehog pathway inhibitor and oral melphalan. RESULTS: Between 1998 and 2011, we treated 18 patients relapsed after median 20 months. Nine had relapsed locally, four had dissemination, three single metastases, and two had one synchronous local and metastatic recurrence. Responses to chemotherapy were seen in 32% of cases. The median hospital stay for treatments/complications was 19 days. The 1- and 3-year progression-free survival (PFS) rates were 28 ± 10% and 0%, respectively, for OS, they were 44 ± 12% and 22 ± 10% but no patient was cured. The median PFS after a first relapse was 7 months (range 1-29); the median OS was 7 months (range 4-44). No patients died due to treatment toxicity. Late recurrence (more than 1-2 years after diagnosis) and involvement of single sites were favorable prognostic factors. CONCLUSIONS: Without succeeding in patients cure, we ensured them further treatment with short hospital stay thus affording low personal and social costs. The chances of cure may emerge from tailored therapies according to genetic stratification.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Cerebelosas/terapia , Irradiación Craneana/métodos , Meduloblastoma/terapia , Recurrencia Local de Neoplasia/terapia , Administración Intravenosa , Administración Oral , Adolescente , Adulto , Neoplasias Encefálicas/terapia , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Niño , Preescolar , Cisplatino/administración & dosificación , Ensayos Clínicos Fase I como Asunto , Ensayos Clínicos Fase II como Asunto , Dacarbazina/administración & dosificación , Dacarbazina/análogos & derivados , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Etopósido/administración & dosificación , Femenino , Humanos , Irinotecán , Masculino , Melfalán/administración & dosificación , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Selección de Paciente , Calidad de Vida , Radioterapia/métodos , Estudios Retrospectivos , Terapia Recuperativa , Temozolomida , Adulto Joven , GemcitabinaRESUMEN
Despite the excellent survival rate of Wilms tumor (WT) patients, only approximately one-half of children who suffer tumor recurrence reach second durable remission. This underlines the need for novel markers to optimize initial treatment. We investigated 77 tumors using Illumina 370CNV-QUAD genotyping BeadChip arrays and compared their genomic profiles to detect copy number (CN) abnormalities and allelic ratio anomalies associated with the following clinicopathological variables: relapse (yes vs. no), age at diagnosis (≤ 24 months vs. >24 months), and disease stage (low stage, I and II, vs. high stage, III and IV). We found that CN gains at chromosome region 1q21.1-q31.3 were significantly associated with relapse. Additional genetic events, including allelic imbalances at chromosome arms 1p, 1q, 3p, 3q, and 14q were also found to occur at higher frequency in relapsing tumors. Interestingly, allelic imbalances at 1p and 14q also showed a borderline association with higher tumor stages. No genetic events were found to be associated with age at diagnosis. This is the first genome wide analysis with single nucleotide polymorphism (SNP) arrays specifically investigating the role of genetic anomalies in predicting WT relapse on cases prospectively enrolled in the same clinical trial. Our study, besides confirming the role of 1q gains, identified a number of additional candidate genetic markers, warranting further molecular investigations.
Asunto(s)
Genoma Humano , Tumor de Wilms/genética , Adolescente , Desequilibrio Alélico , Niño , Preescolar , Aberraciones Cromosómicas , Variaciones en el Número de Copia de ADN , Femenino , Marcadores Genéticos/genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Lactante , Estimación de Kaplan-Meier , Masculino , Polimorfismo de Nucleótido Simple , Estudios Prospectivos , RecurrenciaRESUMEN
To reduce the sequelae of craniospinal irradiation (CSI) in children under 10 (≥3) years old and to improve the prognosis for high-risk medulloblastoma in adolescents, we adjusted postoperative chemotherapy and CSI doses to patients' stage and age. From 1986 to 1995, 73 patients entered the study. Children under 10 and adolescents with metastases, residual disease (RD) or stage >T3 received postoperative IV vincristine and high-dose (HD) ± intrathecal (IT) methotrexate, while standard-risk adolescents were given IV vincristine and IT methotrexate. Chemotherapy was followed by CSI (19.8 Gy for children <10; 36 Gy for adolescents), with a 54-Gy posterior fossa boost. Maintenance chemotherapy with lomustine and vincristine was administered for a year afterwards. A total of 39 children were under 10 of whom 20 had metastases. Response to chemotherapy was recorded in 70%, but 5-year EFS and OS were only 48 and 56%, respectively. Results were significantly worse for metastatic cases, patients under 10, those with RD, and those staged without MRI (unavailable early in the study). Efforts to preserve survivors' quality of life did not pay off, and most patients over 30 still depended on their parents' income and had severe cognitive/endocrine disabilities. In conclusion, despite a very high response rate with this preradiation HD methotrexate schedule, the outcome for high-risk medulloblastoma patients did not improve (especially when lower CSI doses were used) and patients still developed severe morbidities.
Asunto(s)
Neoplasias Cerebelosas/tratamiento farmacológico , Neoplasias Cerebelosas/radioterapia , Quimioterapia de Mantención/métodos , Meduloblastoma/tratamiento farmacológico , Meduloblastoma/radioterapia , Adolescente , Factores de Edad , Antineoplásicos/uso terapéutico , Niño , Preescolar , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/etiología , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Metotrexato/uso terapéutico , Mielografía , Enfermedades del Sistema Nervioso/diagnóstico , Enfermedades del Sistema Nervioso/etiología , Pruebas Neuropsicológicas , Dosificación Radioterapéutica , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Vincristina/uso terapéutico , Adulto JovenRESUMEN
Hypothyroidism remains a common late effect after irradiation of the neck/mediastinum for Hodgkins lymphoma (HL). We evaluated the protective effect of TSH suppression during neck/mediastinum irradiation. From 1998 to 2001, 14 consecutive euthyroid children were given, before and until the end of their radiotherapy on neck/mediastinum, L-thyroxine at TSH-suppressive doses. The 14 patients had adequate TSH suppression during irradiation in 8, inadequate in 6. The 8-year hypothyroidism-free-survival after irradiation was 75 ± 15% for the former group, 0% for the latter (P = 0.009). TSH suppression could have a protective effect on thyroid function as shown in a small group of patients with HL.
Asunto(s)
Enfermedad de Hodgkin/radioterapia , Hipotiroidismo/prevención & control , Tirotropina/antagonistas & inhibidores , Tiroxina/administración & dosificación , Adolescente , Niño , Supervivencia sin Enfermedad , Femenino , Enfermedad de Hodgkin/sangre , Enfermedad de Hodgkin/mortalidad , Humanos , Hipotiroidismo/sangre , Hipotiroidismo/etiología , Hipotiroidismo/mortalidad , Masculino , Radioterapia/efectos adversos , Radioterapia/métodos , Estudios Retrospectivos , Tasa de Supervivencia , Tirotropina/sangreRESUMEN
After successfully using cisplatin (30 mg/m(2)/day) and etoposide (150 mg/m(2)/day) in ten three-day courses for progressive low-grade gliomas, a subsequent protocol reduced the daily doses of cisplatin (to 25 mg) and etoposide (to 100 mg), with the objective of achieving the same response and three-year PFS rates with lower neurotoxicity and myelotoxicity. We treated 37 patients (median age 6 years); 23 had optochiasmatic tumours and nine were metastatic cases. Diagnoses were clinical in 13 cases and histological in 24, and comprised: pilocytic astrocytoma (17), ganglioglioma (3), pilomyxoid astrocytoma (2), and fibrillary astrocytoma (2). Treatment was prompted by radiological evidence of progression and/or clinical deterioration a median 18 months after the first diagnosis. After initial MRI staging, neurological and clinical examinations were performed before each chemotherapy cycle, with MRI after the first three courses and every three months thereafter. After a median 48 months, a volume reduction was appreciable in 24 cases (65%) and response was maximum 12 months after starting treatment. The three-year EFS and OS rates were 65 and 97%, respectively. Clinical, neurological, or functional improvements were seen in 26/37 cases. No children had a WBC nadir below 2,000/mm(3). Audiological toxicity caused damage in 4/34 cases. The previous protocol had achieved volume reductions in 70% of cases, causing audiological damage (data updated) in 11/31 (P = 0.023), with three-year PFS and OS rates of 70 and 100%, respectively. Lower doses of cisplatin/etoposide are still effective in progressive low-grade glioma, with less acute and persistent morbidity.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Cisplatino/uso terapéutico , Etopósido/uso terapéutico , Glioma/tratamiento farmacológico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/mortalidad , Niño , Preescolar , Supervivencia sin Enfermedad , Esquema de Medicación , Electroencefalografía , Potenciales Evocados Visuales/efectos de los fármacos , Femenino , Glioma/diagnóstico , Glioma/mortalidad , Humanos , Lactante , Recién Nacido , Estudios Longitudinales , Imagen por Resonancia Magnética/métodos , MasculinoRESUMEN
The combination of hyponatremia and renovascular hypertension is known as hyponatremic-hypertensive syndrome (HHS) and so rarely described in children but associated with various kinds of occlusions of the renal artery. We describe two children who presented HHS with severe hypokalemia, polyuria, and polydipsia associated with Wilms tumor, which required treatment with an angiotensin-converting enzyme inhibitor before nephrectomy. All HHS signs and symptoms resolved only following surgical resection of the tumor, allowing chemotherapy to be given.
Asunto(s)
Hipertensión Renovascular/complicaciones , Hiponatremia/complicaciones , Neoplasias Renales/complicaciones , Poliuria/complicaciones , Sed , Tumor de Wilms/complicaciones , Preescolar , Femenino , Humanos , Lactante , Masculino , SíndromeRESUMEN
AIMS AND BACKGROUND: Neuroblastoma is the most common solid extracranial tumor in children. The median age of onset is 2 years, with more than 95% of patients younger than 10 years at diagnosis. As neuroblastoma is rare in adolescents and exceedingly rare in adults, few series are reported in the literature. In the present study, we analyzed the outcomes and clinical characteristics of a mono-institutional series. METHODS: We describe 27 consecutive patients over 12 years of age (range, 12-69) with previously untreated neuroblastoma treated at our Institution between 1982 and 2001. RESULTS: Overall survival at 5 and 10 years was 40% and 20%, respectively, and progression-free survival at 5 and 10 years was 18%. In the present series, there was a long interval between the onset of signs/symptoms and diagnosis, and between recurrence/progression and death. None had MYCN amplification. CONCLUSIONS: The passive course of the disease in most of our patients did not reflect a more favorable outcome compared with younger patients, thus suggesting a possible genetically different subset of neuroblastoma in older patients.
Asunto(s)
Neoplasias Abdominales/diagnóstico , Neoplasias Abdominales/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neuroblastoma/diagnóstico , Neuroblastoma/terapia , Neoplasias Abdominales/tratamiento farmacológico , Neoplasias Abdominales/radioterapia , Adolescente , Adulto , Anciano , Quimioterapia Adyuvante , Fraccionamiento de la Dosis de Radiación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neuroblastoma/tratamiento farmacológico , Neuroblastoma/radioterapia , Radioterapia Adyuvante , Estudios Retrospectivos , Neoplasias Torácicas/diagnóstico , Neoplasias Torácicas/terapia , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: Brain necrosis or other subacute iatrogenic reactions has been recognized as a potential complication of radiotherapy (RT), although the possible synergistic effects of high-dose chemotherapy and RT might have been underestimated. METHODS AND MATERIALS: We reviewed the clinical and radiologic data of 49 consecutive children with malignant brain tumors treated with high-dose thiotepa and autologous hematopoietic stem cell rescue, preceded or followed by RT. The patients were assessed for neurocognitive tests to identify any correlation with magnetic resonance imaging (MRI) anomalies. RESULTS: Of the 49 children, 18 (6 of 25 with high-grade gliomas and 12 of 24 with primitive neuroectodermal tumors) had abnormal brain MRI findings occurring a median of 8 months (range, 2-39 months) after RT and beginning to regress a median of 13 months (range, 2-26 months) after onset. The most common lesion pattern involved multiple pseudonodular, millimeter-size, T1-weighted unevenly enhancing, and T2-weighted hyperintense foci. Four patients with primitive neuroectodermal tumors also had subdural fluid leaks, with meningeal enhancement over the effusion. One-half of the patients had symptoms relating to the new radiographic findings. The MRI lesion-free survival rate was 74%+/-6% at 1 year and 57%+/-8% at 2 years. The number of marrow ablative courses correlated significantly to the incidence of radiographic anomalies. No significant difference was found in intelligent quotient scores between children with and without radiographic changes. CONCLUSION: Multiple enhancing cerebral lesions were frequently seen on MRI scans soon after high-dose chemotherapy and RT. Such findings pose a major diagnostic challenge in terms of their differential diagnosis vis-à-vis recurrent tumor. Their correlation with neurocognitive results deserves further investigation.
Asunto(s)
Antineoplásicos Alquilantes/efectos adversos , Neoplasias Encefálicas , Encéfalo , Glioma , Tumores Neuroectodérmicos Primitivos , Tiotepa/efectos adversos , Adolescente , Adulto , Antineoplásicos Alquilantes/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Encéfalo/efectos de los fármacos , Encéfalo/patología , Encéfalo/efectos de la radiación , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/radioterapia , Niño , Preescolar , Cognición/efectos de los fármacos , Cognición/efectos de la radiación , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Supervivencia sin Enfermedad , Femenino , Glioma/tratamiento farmacológico , Glioma/radioterapia , Humanos , Lactante , Inteligencia/efectos de los fármacos , Inteligencia/efectos de la radiación , Imagen por Resonancia Magnética , Masculino , Meduloblastoma/tratamiento farmacológico , Meduloblastoma/radioterapia , Tumores Neuroectodérmicos Primitivos/tratamiento farmacológico , Tumores Neuroectodérmicos Primitivos/radioterapia , Tiotepa/administración & dosificaciónRESUMEN
Wilms tumour (WT), the most frequent malignant childhood renal tumour, shows a high degree of genetic and epigenetic heterogeneity. Loss of imprinting on chromosome 11p15 is found in a large fraction of cases and mutations in a few genes, including WT1, CTNNB1, WTX, TP53 and, more recently, SIX1, SIX2 and micro RNA processing genes (miRNAPGs), have been observed. However, these alterations are not sufficient to describe the entire spectrum of genetic defects underlying WT development. We inspected data obtained from a previously performed genome-wide single nucleotide polymorphism (SNP) array analysis on 96 WT samples. By selecting focal regions commonly involved in chromosomal anomalies, we identified genes with a possible role in WT development, based on the prior knowledge of their biological relevance, including MYCN, DIS3L2, MIR562, HACE1, GLI3, CDKN2A and CDKN2B, PALB2, and CHEK2. The MYCN hotspot mutation c.131C>T was detected in seven cases (7.3%). Full sequencing of the remaining genes disclosed 16 rare missense variants and a splicing mutation. Most of these were present at the germline level. Promoter analysis of HACE1, CDKN2A and CDKN2B disclosed partial methylation affecting HACE1 in a consistent fraction of cases (85%). Interestingly, of the four missense variants identified in CHEK2, three were predicted to be deleterious by in silico analyses, while an additional variant was observed to alter mRNA splicing, generating a functionally defective protein. Our study adds additional information on putative WT genes, and adds evidences involving CHEK2 in WT susceptibility.
RESUMEN
PURPOSE: Cardiac late effects are responsible for a significant burden of mortality and morbidity among pediatric Hodgkin's lymphoma (HL) survivors (HLS). The aim of our study was to assess clinical and subclinical cardiac sequelae in a cohort of childhood HLS treated in the 1980s with doxorubicin, bleomycin, vinblastine, and dacarbazine (the ABVD regimen) and limited-field radiotherapy (RT). METHODS: We retrospectively examined a series of HLS treated from 1979 to 1989. We searched for subtle cardiac abnormalities in a subgroup of asymptomatic individuals, who underwent rest and exercise echocardiography at least 20 years after completing their therapies. Their cardiac assessment included physical examination, electrocardiogram (ECG), and resting and postexercise echocardiograms. RESULTS: On thorough cardiac assessment a mean of 21 years after their diagnosis, none of the 53 unselected asymptomatic HLS showed physical signs or significant ECG abnormalities during or after the stress echo test. Twenty-two (41%) of the 53 patients revealed valvular abnormalities, with mitral regurgitation in 28%, aortic regurgitation in 9%, and both in 4%. No significant myocardial dysfunction as a result of previous combined doxorubicin treatment and chest RT was identified. Only 2 individuals had mild pericardial alterations. CONCLUSIONS: The present study shows that long-term cardiac effects are common in HLS treated with the ABVD regimen and RT. The most frequent complications observed in this sample were essentially coronary artery disease and valvular abnormalities. None of the survivors in this sample showed overt congestive heart failure, a finding in contrast with larger studies.
Asunto(s)
Quimioradioterapia/efectos adversos , Cardiopatías/epidemiología , Cardiopatías/etiología , Enfermedad de Hodgkin/terapia , Sobrevivientes/estadística & datos numéricos , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bleomicina/efectos adversos , Niño , Preescolar , Dacarbazina/efectos adversos , Doxorrubicina/efectos adversos , Femenino , Corazón/efectos de los fármacos , Corazón/efectos de la radiación , Humanos , Masculino , Estudios Retrospectivos , Vinblastina/efectos adversosRESUMEN
PURPOSE: Nonrhabdomyosarcoma soft tissue sarcomas are a heterogeneous group of tumors for which optimal treatment remains controversial. We report on a large group of 182 patients younger than 18 years old treated at a single institution over a 25-year period. PATIENTS AND METHODS: In this relatively homogeneous subgroup of adult-type histotypes, surgery was the mainstay of treatment; radiotherapy was administered to 73 patients, and chemotherapy was administered to 114 patients (70 received chemotherapy as adjuvant therapy). RESULTS: Overall survival at 5 years was 89% in patients who underwent complete resection at diagnosis, 79% in patients who had marginal resection, 52% in initially unresected patients, and 17% in patients with metastases at onset. Outcome was unsatisfactory in patients with large and high-grade tumors, even after gross resection; adjuvant chemotherapy seemed to improve the results in this group. Initially unresected patients who responded well to chemotherapy and subsequently underwent complete resection had an event-free survival rate of approximately 70%. The rate of response to chemotherapy was 58%. CONCLUSION: The identification of prognostic variables should enable risk-adapted therapies to be planned. Patients with initially unresectable disease and patients with resected large and high-grade tumors are at high risk of metastases and treatment failure. Although the limits of this retrospective analysis are self-evident, our data would suggest that intensive chemotherapy (with an ifosfamide-doxorubicin regimen) might have a more significant role in these patients than what is generally assumed.
Asunto(s)
Sarcoma/patología , Sarcoma/terapia , Neoplasias de los Tejidos Blandos/patología , Neoplasias de los Tejidos Blandos/terapia , Adolescente , Distribución de Chi-Cuadrado , Niño , Preescolar , Terapia Combinada , Femenino , Humanos , Italia/epidemiología , Masculino , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Sarcoma/epidemiología , Neoplasias de los Tejidos Blandos/epidemiología , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
AIMS AND BACKGROUND: We describe the case of a woman cured of osteosarcoma who took part in a mono-institutional study using different questionnaires to assess pediatric cancer survivors' quality of life and behavioral features 12 years after completing her cancer treatment. RESULTS: The high levels of psychological distress and psychopathologic symptoms revealed by this patient prompted us to offer her specific and prolonged support at our institution, since she refused to seek the help of other psychiatric services. The woman revealed a dysfunctional social and family setting and a borderline personality disorder. She was hospitalized after attempting suicide. No psychological distress had previously come to light during her long follow-up for cancer. CONCLUSIONS: Cancer survivors are at risk of psychological and behavioral problems, so they should be followed up over time. Questionnaires and standard scales are important, but not enough: the physician-patient relationship is crucial to bring out a patient's psychological issues and needs. This means that dedicated resources should be made available, whenever possible.
Asunto(s)
Trastornos Mentales/etiología , Trastornos Mentales/psicología , Osteosarcoma/complicaciones , Sobrevivientes/psicología , Adulto , Femenino , Humanos , Trastornos Mentales/diagnóstico , Trastornos Mentales/terapia , Calidad de Vida , Encuestas y CuestionariosRESUMEN
AIMS: To assess the efficacy and toxicity of low-dose oral etoposide (VP) 16 in relapsing/refractory Ewing sarcoma. METHODS: The records of all patients treated at our department between 1989 and 2012 for relapsing/refractory Ewing sarcoma who received oral VP-16 were analyzed. The dose was 40 mg/m2 daily for 21 consecutive days in every 28. Response was assessed after 2/3 cycles according to Response Evaluation Criteria in Solid Tumors 1.0. RESULTS: A total of 46 of 58 patients completed at least 2 cycles; 12 suspended the treatment earlier due to rapid disease progression. The patients' median age at diagnosis was 14 years and 25/58 had metastatic disease. All patients received intensive polychemotherapy including VP-16 IV as first- (n = 53) or second-line (n = 5) treatment; 21/58 had myeloablative regimens with peripheral blood stem cell rescue, and 1 underwent allogeneic stem cell transplantation. Oral VP-16 was prescribed as 2nd-, 3rd-, and 4th-line treatment for 19, 27, and 12 patients, respectively. The cycles administered totaled 241 (median 3, mean 4 per patient; range 1-14). A total of 46 of 58 patients were evaluable: 11 responded (9 partial remission, 1 very good partial remission, 1 complete remission) and 10 were stable, the response lasting a mean of 8 months. Hematologic toxicity G3/G4 (in 164/241 evaluable cycles) occurred in 15%, 16%, and 11% of cycles for leukocytes, hemoglobin, and platelets, respectively. There were 5 cases of pneumonia. Two patients developed secondary leukemia after receiving 12 and 14 cycles. CONCLUSIONS: Low-dose oral VP-16 may be suitable in a palliative setting with an acceptable toxicity. The risk of secondary leukemia is in line with reports in the literature.
Asunto(s)
Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Etopósido/administración & dosificación , Etopósido/efectos adversos , Enfermedades Hematológicas/inducido químicamente , Recurrencia Local de Neoplasia/tratamiento farmacológico , Sarcoma de Ewing/tratamiento farmacológico , Administración Oral , Adolescente , Niño , Esquema de Medicación , Femenino , Humanos , Masculino , Recurrencia , Estudios Retrospectivos , Inhibidores de Topoisomerasa II/administración & dosificación , Inhibidores de Topoisomerasa II/efectos adversos , Resultado del TratamientoRESUMEN
UNLABELLED: Beckwith-Wiedemann syndrome (BWS) is the most common (epi)genetic overgrowth-cancer predisposition disorder. Given the absence of consensual recommendations or international guidelines, the Scientific Committee of the Italian BWS Association (www.aibws.org) proposed these recommendations for the diagnosis, molecular testing, clinical management, follow-up and tumor surveillance of patients with BWS. The recommendations are intended to allow a timely and appropriate diagnosis of the disorder, to assist patients and their families, to provide clinicians and caregivers optimal strategies for an adequate and satisfactory care, aiming also at standardizing clinical practice as a national uniform approach. They also highlight the direction of future research studies in this setting. With recent advances in understanding the disease (epi)genetic mechanisms and in describing large cohorts of BWS patients, the natural history of the disease will be dissected. In the era of personalized medicine, the emergence of specific (epi)genotype-phenotype correlations in BWS will likely lead to differentiated follow-up approaches for the molecular subgroups, to the development of novel tools to evaluate the likelihood of cancer development and to the refinement and optimization of current tumor screening strategies. CONCLUSIONS: In this article, we provide the first comprehensive recommendations on the complex management of patients with Beckwith-Wiedemann syndrome.