Amedeo Fiorillo

Radiation late effects in children treated for orbital rhabdomyosarcoma.

BACKGROUND AND PURPOSE The experience resulting from large cooperative studies shows that correct radiation therapy at doses adequate to the tumor bulk are crucial for local control of rhabdomyosarcoma. The aim of the present study was to document the correlation between modalities and doses of radiotherapy and radiation side effects. PATIENTS AND METHODS Between 1980 and 1997, 19 patients affected by primary orbital rhabdomyosarcoma have been followed at the University Federico II of Naples. All but three patients, who received 45, 54 and 55 Gy respectively, have been treated by immediate radiation at the dose of 60 Gy, delivered in 2 Gy fractions, five times per week, by cobalt 60 megavoltage equipment. Combined chemotherapy using vincristine and vincristine plus dactinomycin on alternate weeks was also administered as part of induction therapy. RESULTS An overall survival rate of 94.7% was registered. In our patients the majority of radiation late effects were paid by orbit and ocular adnexa. Side effects to lens and ocular structures were fewer and of low grade. CONCLUSIONS Radiation therapy is still essential for local control of orbital rhabdomyosarcoma, however radiation side effects have to be carefully considered together with the therapeutic goal to be obtained.

Multidisciplinary treatment of primary orbital rhabdomyosarcoma. A single-institution experience.

Orbital rhabdomyosarcoma accounts for one‐fourth of the primary tumors in the head and neck region. Modern treatment modalities have led to a 2‐year survival rate of about 90% in these patients. However, new therapeutic trials are designed to reduce complications and salvage more than 90% of orbital cases. Between 1979 and 1990, 12 children affected by primary orbital rhabdomyosarcoma have been diagnosed and treated at the University of Naples. Ten of them have been uniformly treated by biopsy, followed by immediate radiation and combined chemotherapy. All 12 patients are alive and free of detectable disease, from a minimum of 7 months to a maximum of 123 months after diagnosis. In all children, ocular structures have been spared and the complications observed until now have been few. The above results suggest that the association of immediate radiation therapy and chemotherapy might represent an optimal tool for treatment of orbital rhabdomyosarcoma.

Shunt Related Abdominal Metastases in an Infant with Medulloblastoma: Long Term Remission by Systemic Chemotherapy and Surgery

This is the first reported case of long remission of abdominal metastases spread through a ventriculo-peritoneal shunt in an infant diagnosed, four years ago, at age 1 year and 10 months, to have cerebral medulloblastoma. Two years later, while in second complete remission of his cerebral tumor, he showed abdominal metastases, successfully treated by platinum based chemotherapy and surgery. One year later, a second abdominal relapse and hepatic metastases were treated by doxorubicin administration and surgery. Since then the child remained in continuous complete remission. This unusual favorable outcome can be explained by an extreme responsiveness of the tumor, unprotected by the blood brain barrier, to systemic chemotherapy, particularly to doxorubicin administration. The need for careful surveillance of patients with ventriculo-peritoneal shunts is emphasized. Searching for new tools, such as entrapment of doxorubicin in liposomes, able to overcome the blood–brain barrier and to expose brain tumors to effective drugs, probably represents the best choice for future treatment strategies of CNSbreak tumors.

Second-line chemotherapy with the association of liposomal daunorubicin, carboplatin and etoposide in children with recurrent malignant brain tumors.

Progressive or recurrent high-grade gliomas are characterized by a very poor prognosis, and the relevance of second-line chemotherapy is still unassessed.Although it has been reported that liposomal anthracyclines and carboplatin show some activity in these patients, their association has never been investigated.We have treated six children with recurrent high-grade glioma after surgery, radiotherapy and chemotherapy, and one child with progressive teratoid/rhabdoid tumor with the combination of liposomal daunorubicin and carboplatin plus etoposide. Five out of seven children showed a major response and the 29 month progression-free survival was 38%. The above regimen was feasible and children showed only little and transient hematological toxicity.In our opinion, these results justify further investigation of the above combination chemotherapy for recurrent or progressive malignant brain tumors in children.

Cytogenetic evaluation of isochromosome 17q in posterior fossa tumors of children and correlation with clinical outcome in medulloblastoma

AbstractBackground.A number of chromosomal abnormalities have been described in the presence of central nervous system tumors; isochromosome 17q, representing a loss of heterozygosity for the short arm of the chromosome 17, is the one most frequently reported in association with medulloblastoma. The purpose of this study was to evaluate the prognostic correlation of this variable, compared with other variables (surgery extent and radiotherapy), with survival. Methods and results.We looked for the presence of i(17q) in 32 children affected by posterior fossa tumors, including 16 medulloblastomas and 2 teratoid/rhabdoid tumors. For our study we used both karyotypic analysis and the fluorescence in situ hybridization (FISH) procedure, both on fresh and on paraffin-embedded tissues. Cytogenetic analysis allowed us to detect a hitherto unreported abnormality in medulloblastoma: ins(1;10)(q31;q23q26). Moreover, 16 of the 32 patients analyzed by FISH were found to be positive for the presence of i(17q): the 2 with teratoid/rhabdoid tumors, 11 of 16 with medulloblastomas, plus 1 with ependymoblastoma and 2 with anaplastic astrocytomas. As far as the outcome of medulloblastoma patients is concerned, we found that 8 out of the 10 children whose tumor had been totally removed had a favorable outcome regardless of the presence of i(17q): 4 were i(17q) positive and 4 i(17q) negative. Conclusions.Although it was impossible to draw any definitive conclusion about detection of i(17q) in central nervous system tumors in infancy, particularly in the case of medulloblastoma, we suggest that this chromosomal abnormality is not an independent prognostic factor, but may be a marker for uncontrolled cell proliferation.

Angioimmunoblastic lymphadenopathy with dysproteinemia: report of the first case in childhood evolving toward spontaneous remission.

This is the first known report of a case of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) in childhood which evolved toward a spontaneous remission. The disease had an acute onset with generalized lymphadenopathy, hepatosplenomegaly, highgrade fever and polyclonal hypergammaglobulinemia. The lymph nodes met all of the histologic criteria required for diagnosis as established by Frizzera et al. It is emphasized that AILD should be taken into consideration in the differential diagnosis of lymphadenopathy in childhood.

Efficacy of Sequential Chemotherapy Including Methotrexate and Doxorubicin in an Infant with Partially Resected Choroid Plexus Carcinoma

This report refers to a 3-month-old male, with a residual choroid plexus carcinoma following partial resection, who was successfully treated with sequential chemotherapy without any postoperative radiation therapy. Along with carboplatin, we also used doxorubicin and methotrexate, hypothesizing that, given the patient’s age, the blood-brain barrier should not hamper drug delivery to the tumor. According to this hypothesis, the treatment achieved complete remission of the disease, which lasts 27 months after the diagnosis. This result deserves further studies to assess the possible curative role of chemotherapy in very young patients suffering from choroid plexus carcinoma.

Prolonged survival of a patient with disseminated neuroblastoma

SURVIVAL in childhood neuroblastoma is related to several factors, chiefly to the patients age and to the extent of disease at onset? Spontaneous regression in infants is well documented, 2,3 whereas reports of cure in patients older than two years are exceptional? We report here the case of a 13-year-old boy with widespread disease which underwent spontaneous regression; the occurrence of hepatitis B at the onset Of the remission is noted. CASE REPORT At age 13 years a boy was admitted to a local hospital because of severe abdominal pain; an intravenous pyelogram showed a suprarenal mass displacing the right kidney downward and containing fine calcifications. The initial evaluation revealed a high urinary vanillylmandelic acid value of 31 mg/24 hours (normal value up to 9 mg/24 hours). Skeletal survey revealed destructive lesions involving the fifth thoracic vertebra, and computerized tomography of the abdomen showed multiple retroperitoneal masses (Fig. 1, a). The bone marrow contained clumps of tumor cells. At exploratory laparotomy a diffuse, massive neoplastic invasion of the retroperitonenm was found, but only a small portion of the tumor could be excised. The histologic diagnosis was highly undifferentiated neuroblastoma. The patient was then treated with abdominal irradiation (3,000 rads to the entire abdomen with proper shielding of the liver and kidneys, and 3,400 rads to the thoracic vertebra) in association with cyclophosphamide, vincristine, and adriamycin; ADR was administered iv in a dose of 40 mg/m 2 on days 1 and 2, CX iv in a dose of 600 mg/m 2 on days 3 and 4, and VCR iv in a dose of 1.5 mg/m z on day two and then weekly for three months.

Non-Hodgkin's Lymphoma in Childhood Presenting as Thyroid Enlargement

The authors report a case of a 10-year-old girl with early involvement of the thyroid gland by non-Hodgkins lymphoma, an uncommon site of presentation of childhood lymphomas. In pediatrics, thyroid enlargement is more often caused by lymphocytic thyroiditis. The good response to therapy, in spite of the advanced stage of the disease, is noted.

Congenital Hepatic Fibrosis with Gastrointestinal Bleeding in Early Infancy

We report a case of a 19-month-old infant with congenital hepatic fibrosis. The clinical features consisted of portal hypertension with massive gastrointestinal bleeding, recurrent cholangitis, and cystic dysplasia of the kidneys, without im pairment of renal function. The dramatic course of the disease required surgical treatment. Congenital hepatic fibrosis with life-threatening gastrointestinal bleed ing is extremely rare below three years of age. The purpose of the present report is to stress the need of looking for varices in all cases of congenital hepatic fibrosis, even when occurring in early infancy.