RESUMEN
Increasing treatment intensity has improved outcomes for children with neuroblastoma. We performed a pilot study in the Children's Oncology Group to assess the feasibility and toxicity of a tandem myeloablative regimen without TBI supported by autologous CD34-selected peripheral blood stem cells. Forty-one patients with high-risk neuroblastoma were enrolled; eight patients did not receive any myeloablative consolidation procedure and seven received only one. Two patients out of 41 (4.9%) experienced transplant-related mortality. CD34 selection was discontinued after subjects were enrolled due to serious viral illness. From the time of study enrollment, the overall 3-year EFS and OS were 44.8 ± 9.6% and 59.2 ± 9.2% (N=41). These results demonstrate that tandem transplantation in the cooperative group setting is feasible and support a randomized comparison of single vs tandem myeloablative consolidation with PBSC support for high-risk neuroblastoma.
Asunto(s)
Neuroblastoma/mortalidad , Neuroblastoma/terapia , Trasplante de Células Madre de Sangre Periférica , Acondicionamiento Pretrasplante/métodos , Autoinjertos , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Proyectos Piloto , Acondicionamiento Pretrasplante/efectos adversos , Virosis/etiología , Virosis/mortalidadRESUMEN
Children with neuroblastoma receiving high-dose carboplatin as part of their conditioning regimen for autologous marrow transplantation have a high incidence of speech frequency hearing loss. We evaluated hearing loss in 11 children with advanced stage neuroblastoma who underwent autologous marrow transplantation, following a conditioning regimen containing high-dose carboplatin (2g/m2, total dose). Audiometric evaluations were obtained at diagnosis, prior to and following transplant. Exposure to other known ototoxins also was assessed. All patients sustained worsening of hearing following high-dose carboplatin. Nine of the 11 children (82%) had evidence of speech frequency hearing loss post transplant for which hearing aids were recommended (grades 3-4). Three of the nine children had speech frequency loss prior to transplant which progressed following transplant. The entire group was heavily pre-treated with platinum-containing chemotherapy pre-BMT and had extensive exposure to other ototoxins, including aminoglycoside antibiotics, diuretics, and noise exposure - all of which could have exacerbated the effects of carboplatin. High-dose carboplatin is ototoxic, particularly in patients who have been primed with previous platinum therapy or other ototoxic agents. We conclude that further efforts are needed to monitor and minimize this complication. In cases where hearing loss is inevitable due to cumulative ototoxic exposures, families need to be adequately prepared for the tradeoffs of potentially curable therapy.
Asunto(s)
Antineoplásicos/efectos adversos , Trasplante de Médula Ósea , Neoplasias Encefálicas/terapia , Carboplatino/efectos adversos , Trastornos de la Audición/inducido químicamente , Neuroblastoma/terapia , Adolescente , Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/patología , Carboplatino/uso terapéutico , Niño , Preescolar , Terapia Combinada , Femenino , Humanos , Lactante , Masculino , Neuroblastoma/patología , Trasplante AutólogoRESUMEN
PURPOSE: Desmoplastic round cell tumor (DSCT) is a highly malignant abdominal tumor first described in 1991, with subsequent cases predominantly noted in pathologic case reports. The authors evaluated response to alternating, intensive chemotherapy in three patients with DSCT, and reviewed the clinical experience with this newly described tumor as reported in the literature. PATIENTS AND METHODS: Three adolescent boys with DSCT were treated intravenously with vincristine 2 mg/m2, doxorubicin 75 mg/m2, cyclophosphamide 1.8 g/m2, alternating with 5-day cycles of etoposide 100 mg/m2/day, ifosfamide 1.8 g/m2/day for a total of 11-15 courses. RESULTS: Each patient showed initial tumor regression during chemotherapy, but developed progressive disease within 8-18 months. One patient subsequently showed a transient response to doxorubicin 45 mg/m2 plus 5-fluorouracil 500-600 mg/m2. All three patients died of disease within 20 months of diagnosis. A comprehensive literature review of clinical data on 101 reported cases of DSCT is presented. The median age was 21 years (range 6-38 years) with 78 male patients and 23 female patients. Ninety-nine cases involved tumor mass in the abdominal-pelvic cavity in proximity to the mesentery. Metastatic seeding to the omentum was most common, followed by spread of disease to liver, distant lymph nodes, lung, and occasionally to scrotum or to ovary. Tumor response to chemotherapy was noted in approximately 50% of 40 patients who received combinations of doxorubicin, cisplatin, cyclophosphamide, etoposide, and/or 5-fluorouracil. Four of 13 patients who received additional radiotherapy were alive at 24-48 months. Median survival was 17 months (range: 3-72 months), with only two patients reported disease free beyond 2 years at 40 and 48 months. CONCLUSION: DSCT should be included in the differential diagnosis of small round cell tumors in children and young adults. Tumor regression has been noted during multiagent chemotherapy, but prolonged survival is rare with current therapies.
Asunto(s)
Neoplasias Abdominales/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Abdominales/tratamiento farmacológico , Neoplasias Abdominales/patología , Neoplasias Abdominales/terapia , Adolescente , Adulto , Trasplante de Médula Ósea , Niño , Femenino , Humanos , Masculino , Tomografía Computarizada por Rayos XRESUMEN
To our knowledge intra-abdominal desmoplastic round cell tumor has not previously been described in the pediatric urological literature. This lesion has only recently been recognized as a clinicopathological entity with predilection for adolescent boys. We report on 2 patients who presented with urological symptoms and a large abdominal or pelvic tumor that was biopsied at exploratory laparotomy. Complete surgical excision was impossible in both patients, who subsequently underwent multiagent chemotherapy. Histological and immunohistochemical staining are distinctive in this condition. The tumor is associated with a poor prognosis, despite multidisciplinary, multimodal therapy.
Asunto(s)
Neoplasias Abdominales/patología , Trastornos Urinarios/etiología , Neoplasias Abdominales/complicaciones , Adolescente , Niño , Humanos , MasculinoRESUMEN
BACKGROUND: Fewer than 20% of children with intrinsic brain stem tumors survive longer than 2 years. Although some improvement has been noted in recent trials using higher doses of hyperfractionated radiation therapy (HRT), the feasibility of pre-irradiation chemotherapy has not been explored in these patients with poor prognosis. METHODS: Between February 1988 and March 1989, 37 patients were entered onto a Phase II Pediatric Oncology Group study for evaluating the feasibility, response, and toxicity of treating children with high-risk brain stem tumors with chemotherapy followed by HRT (66 Gy). Chemotherapy consisted of four cycles of cisplatin (100 mg/m2) plus cyclophosphamide (3 g/m2). RESULTS: Of 32 eligible patients, 65% improved clinically during the first 2-3 cycles of chemotherapy; 75% of those improving were weaned from steroids. On neuroradiology review of scans before and after chemotherapy, 3 patients had partial responses (PR, > 50% shrinkage), 23 had stable disease (SD), and 6 had progressive disease (PD). The median survival was 9 months. The three patients who attained a PR on chemotherapy were among the longest survivors at 38 plus, 44 plus, and 40 months. Toxicities included profound but brief marrow suppression, transient electrolyte-renal dysfunction, and ototoxicity. Brain stem swelling from intravenous fluids caused transient deterioration in two patients. Six patients developed an unusual syndrome of transient marrow suppression after HRT. CONCLUSIONS: This study suggests that pre-irradiation chemotherapy can be successfully added to the treatment of patients with brain stem tumors with both clinical and objective responses noted, but that other agents must be identified to overcome the apparent development of drug resistance and to improve survival.
Asunto(s)
Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/radioterapia , Tronco Encefálico , Glioma/radioterapia , Adolescente , Adulto , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/mortalidad , Quimioterapia Adyuvante , Niño , Preescolar , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Terapia Combinada , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Esquema de Medicación , Estudios de Factibilidad , Femenino , Glioma/diagnóstico por imagen , Glioma/tratamiento farmacológico , Glioma/mortalidad , Humanos , Imagen por Resonancia Magnética , Masculino , Manitol/administración & dosificación , Pronóstico , Dosificación Radioterapéutica , Tomografía Computarizada por Rayos XRESUMEN
Three patients with a new, pathologically distinct solid tumor of childhood have been treated recently. The disease is characterized by male predominance, adolescent onset, an extensive abdominal primary tumor, and aggressive metastases to regional lymph nodes, liver, and lung. Two patients presented with vague abdominal pain and the third with testicular pain. All three noted fatigue and malaise of less than two months' duration with minimal associated weight loss. Computed tomography (CT) scans of the abdomen and chest were obtained for initial preoperative staging, and then all three underwent surgical exploration. Widespread disease was found in each case. In no instance was complete tumor extirpation possible because of extensive peritoneal spread and lymphatic and hepatic metastases. Histologically, all three tumors consisted of round blue cells with a dense desmoplastic reaction and focal rhabdoid features. Immunohistochemical markers for epithelial, neural, and muscle elements were positive. Aggressive multidrug chemotherapeutic regimens were used in each case, and all three patients are alive and well but with known residual disease. We conclude that in cases of the desmoplastic round cell tumor of childhood, CT scans underestimate the extent of disease, and exploratory laparotomy is necessary for diagnosis and appropriate staging. Surgery is usually palliative because of extensive spread. Awareness of this newly recognized aggressive solid tumor of childhood is essential to define its natural history and guide the development of effective multidisciplinary therapeutic regimens.
Asunto(s)
Carcinoma de Células Pequeñas/cirugía , Neoplasias del Colon/cirugía , Neoplasias Pélvicas/cirugía , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/análisis , Carcinoma de Células Pequeñas/tratamiento farmacológico , Carcinoma de Células Pequeñas/patología , Quimioterapia Adyuvante , Niño , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Terapia Combinada , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Metástasis Linfática , Masculino , Neoplasias Pélvicas/tratamiento farmacológico , Neoplasias Pélvicas/patologíaRESUMEN
Two infants, ages 14 and 4 months, with extensive optic pathway tumors were treated with intensive chemotherapy called MADDOC: nitrogen mustard, doxorubicin, cis-platinum, dacarbazine, vincristine, and cyclophosphamide. The first child had hydrocephalus with an enhancing mass at the hypothalamus which followed the optic radiation to include the lateral geniculate body and medial temporal lobe. A v-p shunt was placed, and biopsy revealed a Grade II astrocytoma. One month later, the child developed malignant ascites. Intensive induction chemotherapy was then begun with cis-platinum 100 mg/m2 and cyclophosphamide 3 g/m2 for two initial cycles. The ascites resolved within one week, and chemotherapy was continued for 10 courses of the 6-drug MADDOC regimen. CT scans showed a gradual shrinkage of the tumor mass by approximately 70%. The enhancing areas continued to decrease in size through 20 months after completing MADDOC. The child has not received radiation and is well 4 years 7 months post diagnosis. The second infant had massive enlargement of the right optic nerve with an enhancing chiasmatic mass extending into the suprasellar space, hypothalamus, and brain stem. This infant was not biopsied; she also received induction MADDOC chemotherapy for 12 cycles. CT scans showed a definite decrease in the chiasmatic mass by the fifth cycle, with continued reduction by approximately 40% after 10 months. Twenty-three months from diagnosis there was asymptomatic evidence of tumor growth. The child is being treated with carboplatinum and remains ophthalmologically and radiographically stable 43 months from diagnosis.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Astrocitoma/tratamiento farmacológico , Neoplasias de los Nervios Craneales/tratamiento farmacológico , Quiasma Óptico , Enfermedades del Nervio Óptico/tratamiento farmacológico , Ascitis/tratamiento farmacológico , Ascitis/etiología , Astrocitoma/complicaciones , Astrocitoma/patología , Astrocitoma/secundario , Derivaciones del Líquido Cefalorraquídeo/efectos adversos , Cisplatino/administración & dosificación , Neoplasias de los Nervios Craneales/complicaciones , Neoplasias de los Nervios Craneales/patología , Ciclofosfamida/administración & dosificación , Dacarbazina/administración & dosificación , Doxorrubicina/administración & dosificación , Enanismo Hipofisario/inducido químicamente , Femenino , Humanos , Hidrocefalia/etiología , Hidrocefalia/cirugía , Lactante , Masculino , Mecloretamina/administración & dosificación , Invasividad Neoplásica , Enfermedades del Nervio Óptico/complicaciones , Enfermedades del Nervio Óptico/patología , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/etiología , Neoplasias Peritoneales/secundario , Vincristina/administración & dosificación , Trastornos de la Visión/etiologíaRESUMEN
Before the advent of multiagent chemotherapy, the prognosis for patients with Stage IV neuroblastoma of all ages was dismal. More recently, marked improvement in infants with Stage IV neuroblastoma has been reported. Twenty-four infants with Stage IV neuroblastoma have been treated at the Dana-Farber Cancer Institute/The Children's Hospital, and the Joint Center For Radiation Therapy, Boston, Massachusetts, between 1970 and 1988. Twenty-three of these patients were treated with multiagent chemotherapy and one with a single drug. In the initial report, ten of 11 patients were alive without evidence of disease after intensive therapy. In this report the authors update their initial series of patients and include 13 additional patients who subsequently presented to our institutions with Stage IV neuroblastoma younger than 1 year of age. The 5-year actuarial event-free survival for the 24 patients is 75%. No patient without bone metastases died from neuroblastoma, and 12 of 16 patients with bone metastases remained disease free. These results confirm that infants with Stage IV neuroblastoma have a very good prognosis when treated with intensive multiagent chemotherapy.
Asunto(s)
Neuroblastoma/mortalidad , Neuroblastoma/patología , Neoplasias de las Glándulas Suprarrenales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/secundario , Terapia Combinada , Femenino , Estudios de Seguimiento , Amplificación de Genes/fisiología , Genes myc/fisiología , Humanos , Lactante , Neoplasias Hepáticas/secundario , Masculino , Neoplasias del Mediastino , Estadificación de Neoplasias , Neoplasias Primarias Múltiples/mortalidad , Neoplasias Primarias Múltiples/patología , Neoplasias Primarias Múltiples/terapia , Neuroblastoma/genética , Neuroblastoma/secundario , Neuroblastoma/terapia , Tasa de SupervivenciaRESUMEN
From March 1984 through March 1989 we performed 235 audiometric tests on 39 children with malignant brain tumors who were treated with cisplatin 100 mg/m2 every 3 weeks for three courses and vincristine weekly for 9 weeks followed by cranial irradiation. Twenty-eight of the 39 children had sufficient serial testing for evaluation of ototoxicity secondary to cisplatin. Following the third cisplatin treatment (300 mg/m2 cumulative dose), 20% of the assessable children had hearing loss limited to the high frequencies of 6,000 to 8,000 Hz, 16% had hearing loss beginning at 3,000 to 4,000 Hz, and three children (11%) had loss within the speech frequencies beginning at 1,000 to 2,000 Hz. Eighteen of 19 children (95%) who were evaluated comparatively at a median of 15 months following radiation showed no significant change from preradiation testing. There was no correlation between hearing loss and patient age. We conclude that cisplatin ototoxicity was acceptable and that radiation therapy does not increase the ototoxicity of cisplatin when the drug is given before, instead of following, cranial irradiation.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/radioterapia , Cisplatino/efectos adversos , Pérdida Auditiva/inducido químicamente , Adolescente , Adulto , Factores de Edad , Audiometría , Niño , Preescolar , Cisplatino/administración & dosificación , Estudios de Seguimiento , Humanos , Lactante , Dosificación Radioterapéutica , Vincristina/administración & dosificaciónRESUMEN
From March, 1984, through June, 1987, 21 newly diagnosed children with high-risk medulloblastoma (Chang Stage T3 to T4) were treated on a 9-week postoperative, pre-irradiation chemotherapy regimen consisting of vincristine and cisplatin. The children over 2 years old then received radiation therapy. Six infants (aged 6 to 18 months) were maintained on chemotherapy consisting of MOP (nitrogen mustard, vincristine, and procarbazine) until the age of 2 years, at which time they were referred for irradiation. Of 13 children with measurable disease following surgery, five showed a definite response on computerized tomography scans to vincristine and cisplatin (one complete response and four partial responses) and five others showed clear marginal responses. Four of the six infants were disease-free at 19, 32, 35, and 57 months from diagnosis. One infant developed progressive disease at the completion of the vincristine and cisplatin course, and a second infant had progression during MOP administration. Three of the 21 children developed hearing loss within the speech frequencies during cisplatin treatments, but there were no other major toxicities. Fifteen children remained disease-free with a median follow-up period of 35 months (range 19 to 57 months). Chemotherapy given between surgery and radiotherapy may allow for the direct evaluation of a specific drug regimen and permit the postponement of radiation therapy in infants. Pre-irradiation vincristine and cisplatin was well tolerated and effective in shrinking the tumor in most children with medulloblastoma. Such chemotherapy regimens have the potential for extending long-term survival in high-risk children.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Cerebelosas/tratamiento farmacológico , Meduloblastoma/tratamiento farmacológico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Cerebelosas/radioterapia , Niño , Preescolar , Cisplatino/administración & dosificación , Terapia Combinada , Estudios de Seguimiento , Trastornos de la Audición/inducido químicamente , Humanos , Lactante , Mecloretamina/uso terapéutico , Meduloblastoma/radioterapia , Recurrencia Local de Neoplasia , Procarbazina/uso terapéutico , Vincristina/administración & dosificación , Vincristina/uso terapéuticoRESUMEN
Beginning in 1984, we started a prospective study to evaluate the role of postoperative, pre-radiation chemotherapy in the treatment of infants and poor prognosis children with medulloblastoma. The study was designed to evaluate the role of pre-radiation chemotherapy in two specific patient populations: (a) children under the age of 2 years in which there was an attempt to delay definitive radiation and thus reduce the risk of toxicity to the developing nervous system; and (b) children over age 2 years with Stage T3 and T4 disease who were known to have a relatively poor prognosis with surgery and radiation. The five patients under age 2 years received cisplatinum (100 mg/m2) every 3 weeks and weekly vincristine (1.5 mg/m2) for a total of 9 weeks. Nitrogen mustard (6 mg/m2), procarbazine (100 mg/m2), and vincristine (1.5 mg/m2) (MOP) were given in 28 day cycles as long as there was no disease progression or until the child's second birthday, at which time the children were referred for radiation therapy. The 13 patients over 2 years of age received the 9 week course of cisplatinum and vincristine and then began radiation. Responses measured by computed tomography were obtained in 10 of 12 children with measurable disease at the start of chemotherapy. With a median follow-up of 22 months, 15 of 18 children were alive and free of disease. Except for mild ototoxicity in one child, the acute side effects have been well tolerated. In conclusion, it appears that some infants can have their radiation delayed until the age of 2 years. Although the follow-up time was short, all but three patients were free of disease, time exceeding the median time to failure with radiation alone. Pre-radiation chemotherapy might improve local control and survival in children with advanced stage medulloblastoma.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Cerebelosas/tratamiento farmacológico , Meduloblastoma/tratamiento farmacológico , Adolescente , Neoplasias Cerebelosas/radioterapia , Neoplasias Cerebelosas/cirugía , Niño , Preescolar , Cisplatino/administración & dosificación , Terapia Combinada , Femenino , Humanos , Lactante , Masculino , Mecloretamina/administración & dosificación , Meduloblastoma/radioterapia , Meduloblastoma/cirugía , Procarbazina/administración & dosificación , Vincristina/administración & dosificaciónRESUMEN
Among children over 1 year of age with Evans Stage IV neuroblastoma, there appears to be a small group with a relatively favorable prognosis. These patients have extensive lymph node metastases (cervical/axillary/thoracic/abdominal/pelvic), but no extranodal metastases. Three of six such patients (50%) are long-term disease-free survivors, compared with none of 40 patients with extranodal metastatic disease (p less than 0.0002). Patients with only lymph node metastases (Stage "IV-N") may have a biologically more favorable tumor that is curable with conventional, intensive multimodality therapy.
Asunto(s)
Neuroblastoma/patología , Neoplasias Abdominales/patología , Adolescente , Neoplasias de las Glándulas Suprarrenales/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Preescolar , Femenino , Humanos , Lactante , Metástasis Linfática , Masculino , Estadificación de Neoplasias , Neuroblastoma/tratamiento farmacológico , Neoplasias de la Parótida/patología , Neoplasias Pélvicas/patología , PronósticoRESUMEN
From 1970 to 1982 11 infants with Evans stage IV neuroblastoma who were 11 months of age or less at diagnosis were treated. All but one were treated with intensive multiagent chemotherapy; eight had attempted surgical resection; only one received radiotherapy to the primary tumor. Ten of the 11 infants remain free of disease from 2 1/2 to 13 years (median, four years). Multiagent chemotherapy has clearly improved the outcome for infants with stage IV neuroblastoma.