Choroid plexus tumors: a review of 28-year experience.

The aims of the study were to review the patients with choroid plexus tumor (CPT) treated in Slovenia between 1972-1999, to calculate the incidence of CPTs, and to evaluate treatment results in respect to tumor histology and mode of therapy. Cancer Registry of Slovenia database was used for patients identification. Histological specimens and medical records were reviewed. Twelve patients (7 females, 5 males), 0.8-43 years old (median 6.1 years; <15 years: 10/12,83%) with CPT, representing 0.36% of all intracranial tumors registered during the period under study, were identified. Considering children less than 15 years old only, the corresponding percentage was 3.69. There were eight papillomas (CPPs) and four carcinomas (CPCs) with no difference in age distribution between the groups. Of seven patients with gross tumor resection in CPP group, one patient died of postoperative meningitis and one had local recurrence 1.6 years after surgery; the latter is disease-free 17.9 years after re-operation. One patient with macroscopic residue after surgery is alive and asymptomatic after 16.5 years. In the CPC-group, only the patient who received adjuvant BEP chemotherapy and craniospinal irradiation following incomplete surgery is alive with no signs of disease after 6.5 years. Ten-year disease-specific survival for all CPTs and for CPP subgroup was 73% and 100%, respectively. In Slovenia, CPTs represent 0.36% of intracranial tumors. In children, the incidence is 3.69%. CPPs are twice as frequent as CPCs. In CPPs, the treatment of choice is surgery alone. After incomplete surgery, wait-and-see policy seems to be justified. For CPCs, adjuvant multiagent chemotherapy and craniospinal radiotherapy following surgery should be considered.

Late cardiac damage of anthracycline therapy for acute lymphoblastic leukemia in childhood.

Long-term leukemia survivors (46) underwent cardiac evaluation, including physical examination, ECG, exercise testing, and echocardiography. They were 2-17 years old at diagnosis and 5-23 years old after treatment. Thirty-four survivors received anthracyclines (AC) (mean 203 mg/m2), 12 of them had also alkylating agents (AA) and 12 had no AC. Exercise tolerance was bellow predicted values in 21 (48%) survivors and 21 survivors had ECG abnormalities, which were more frequent in those treated with AC. Concomitant AC with AA was correlated with prolonged isovolumic relaxation time (IVRT) and influenced significantly the volume of left atrium (p = .02). Sixteen (52%) survivors had IVRT > or = 90 ms. There were no significant differences in other parameters of diastolic or systolic function. Despite the lack of clinical symptoms in the survivors treated with lower doses of AC, subtile abnormalities in myocardial function were found, mainly manifest as abnormal diastolic function. Prolonged IVRT may be a sensitive indicator for early detection of AC cardiotoxicity.

Secondary intracranial meningiomas after high-dose cranial irradiation: report of five cases and review of the literature.

PURPOSE: To review cases of secondary intracranial meningiomas following high-dose cranial irradiation (>/= 10 Gy) identified in Slovenia between 1968 and 1998, to determine their histological profile and to review the literature on this topic. METHODS AND MATERIALS: Personal files of patients treated for secondary intracranial meningioma during a 31-year period were reviewed. In cases which met the criteria for radiation-induced tumors, steroid hormone receptor and Ki-67 status were analyzed. For the literature review, computerized database systems and reference lists from respective publications were used. RESULTS: Five patients (2 females, 3 males), 3-11 years old at the time of cranial irradiation, developed secondary meningioma after a latency period of 9.5-31.5 years. Three patients had multiple tumors and 2 developed recurrent disease. Of 9 histologically examined tumors, 5 were graded as benign and 4 as atypical meningiomas, with Ki-67 proliferative index 3.2 +/- 3.6 and 10 +/- 6, respectively. The ratio between positive and negative meningiomas regarding immunostaining for progesterone and estrogen receptors was eight-to-one and six-to-three, respectively. Cumulative actuarial risk of secondary meningioma in a cohort of 445 children 16 years or younger treated with high-dose cranial irradiation between 1968 and 1990 in Slovenia at 10, 20, and 25 years was 0.53%, 1.2%, and 8.18%, respectively. Out of 126 cases of radiation-induced meningiomas reported, 57% were females and 43% were males, with mean age at presentation 33 +/- 17.3 years. The majority (68%) of patients was irradiated during childhood. The latency period was significantly shorter in those who aged 5 years or less at the time of cranial irradiation (p = 0.04), and in those with atypical/anaplastic tumor (p = 0.01). Correlation between radiation dose and latency period could not be found. CONCLUSION: Secondary meningiomas following high-dose cranial irradiation are characterized by younger age at presentation, by higher male-to-female ratio and by biologically more aggressive variants compared to primary spontaneous meningiomas. Latency period correlated with the age at the time of cranial irradiation and with tumor grade but not with irradiation dose. Ki-67 immunoreactivity correlated with histological grade. The progesterone and estrogen receptor immunoreactivity was high. The risk for development of secondary meningioma after high-dose cranial irradiation was increasing with the time of follow-up.

Concomitant chemoradiotherapy for incompletely resected supratentorial low-grade astrocytoma in children: preliminary report.

BACKGROUND: In incompletely resected low-grade supratentorial astrocytoma, long-term survival is poor; the effect of any additional treatment to surgery still remains poorly defined. The aim of this study was to evaluate the response, the survival, and the benefit of concomitant chemoradiotherapy in eight children who had incompletely resected supratentorial low-grade astrocytoma. PROCEDURE: There were six boys and two girls, aged 4-15 years. Four tumors were in the cerebral hemispheres, one in the hemisphere and thalamus, two in the third ventricle and/or thalamus, and one in the basal ganglia. Partial resection of the tumor was performed in four patients, biopsy in four; the extent of surgery was additionally evaluated with computed tomographic (CT) and/or magnetic resonance imaging (MRI) studies. A tumor dose of 50-56 Gy was delivered postoperatively in 1.8-2.1 Gy daily fractions five times per week. Chemotherapy was intercalated concomitantly in the radiotherapy protocol: cisplatin 20 mg/m2/2 weeks intravenously (IV) and vincristine 1.5 mg/m2/week IV (up to a maximum dose of 2 mg) were planned, starting on day 1 of irradiation. There were one to three cisplatin applications and one to seven vincristine applications. RESULTS: Seven patients are alive 5.5-11.5 years (median, 8 years) after therapy. Six of seven are without evidence of tumor on CT and/or MRI. A residual mass is still visible in one patient, 11.5 years after therapy. He was treated at the age of 4; he is handicapped due to mental retardation and severe neurological impairment. One patient died 5 years after chemoradiotherapy, due to secondary glioblastoma multiforme, without recurrence at the site of the first tumor. Chemotherapy was discontinued in two patients because of severe nausea and vomiting; there was no hematologic or neurologic toxicity. CONCLUSION: In view of the encouraging results, all patients with incompletely resected supratentorial low-grade astrocytomas will be treated as above.

Combined radiation and chemotherapy for advanced undifferentiated nasopharyngeal carcinoma in children.

Five children, 11-16 years of age at diagnosis, with advanced (stage IV) undifferentiated nasopharyngeal carcinoma, are reviewed. All had radiotherapy and chemotherapy, four at first treatment, are disease free in 3 months, 6, 10, and 13 years from diagnosis. One patient who had radiotherapy only as primary treatment and chemotherapy for metastases, died 15 months from diagnosis. One patient who received 60 Gy and chemotherapy according to the BACON protocol had severe early toxicity and severe late sequelae of treatment. Three patients who received chemotherapy according to a modified UICC-2 protocol for nasopharyngeal carcinoma and 50 to 54 Gy to the primary site had only mild early toxicity and mild late effects of treatment. With lower radiation doses, adjusted to the effect of preradiation chemotherapy, complete tumor control was achieved and acute and long-term morbidity reduced.

Half-body irradiation in the treatment of multiple myeloma: a report of nine cases.

We report the results of treatment of 9 patients with advanced multiple myeloma (MM) using half-body irradiation. Six nonresponders to chemotherapy received it as consolidation therapy after the plateau phase of MM had been observed, and 4 patients received it as salvage therapy of refractory or relapsing MM. One of the patients received it twice, first as consolidation and later during the course of her disease also as salvage therapy. Objective response was obtained in 1 of 6 patients who received half-body irradiation as consolidation therapy and in 3 of 4 patients who received it as salvage therapy. Responders to half-body irradiation generally achieved a longer relapse-free interval. Treatment with half-body irradiation was especially effective in combination with human leukocyte interferon as salvage therapy in 2 of the patients with refractory MM, leading to a relapse-free interval of more than 27 months in one of them. Symptomatic relief was observed in 5 of 6 patients. All had transient post-irradiation pancytopenia, with pneumonitis, nausea and vomiting observed in those who had the upper half of the body irradiated first. It is thus our opinion that halfbody irradiation should not be used as consolidation therapy in nonresponders to chemotherapy, because it causes undue toxicity to heavily pretreated patients. Its role in the treatment of refractory or relapsing MM in combination with human leukocyte interferon should be fully evaluated.

Pediatric oncology in Slovenia.

Slovenia, a new country and formerly a part of Yugoslavia, has had its Childrens Hospital in Ljubljana since 1865. This became a part of the University Hospital in 1945, and in the early 1960s the Department of Pediatric Hematology-Oncology was established. The Oncological Institute of Slovenia was established in 1938 and has developed into a modern facility for comprehensive cancer care, research, and teaching. In close cooperation, established in the 1960s, a team from these two institutions takes care of the approximately 60 children per year who develop cancer in Slovenia. Consisting of pediatricians, radiation oncologists, pathologists, cytologists, surgeons, and other ad hoc specialists, the team meets at least twice weekly to plan treatment, follow the patients, discuss the results, and teach. All patients are subject to regular follow-up indefinitely. A separate team has been formed to study the late effects of cancer treatment on survivors, who by now are mostly adults.

Two unusual recurrences of intracranial germinoma.

Two recurrent cases of intracranial suprasellar germinoma, with relapses at 55 and 16 months, respectively, after the end of primary therapy strongly effective against pure germinoma, are presented. Human chorionic gonadotropin beta subunit was elevated in the cerebrospinal fluid and in the serum in both patients at the time of recurrence but not before. This and resulting treatment failures suggest that there were also other, more resistant elements within the primary tumor, which have not been identified in biopsy specimens. The problem of adequate diagnosis and its impact on patients' survival are discussed.

Hepatoblastoma in fine needle aspirates.

OBJECTIVE: To analyze cytomorphologic characteristics of hepatoblastoma (HB) and evaluate the feasibility of recognizing its histologic subtypes in smears. STUDY DESIGN: Fine needle aspirates from 14 primary and 1 metastatic HB were reexamined. The diagnosis of HB was confirmed by tissue examination (10 cases) and by clinical and laboratory findings alone (5 cases). RESULTS: In 12 samples, neoplastic cells resembled immature hepatocytes but were smaller and had a higher nuclear/cytoplasmic ratio. In nine of these smears the cells were rather uniform, while the other three presented with moderate pleomorphism. The cells were arranged in three-dimensional clusters, loose sheets, cords, rosettelike structures and occasional pseudopapillae and were dispersed. CONCLUSION: With knowledge of the cellular features and architectural patterns of HB, a reliable diagnosis could be obtained in 12/15 cases without the use of special techniques. In the remaining three aspirates the tumor cell population partly or entirely differed from normal hepatocytes, requiring ancillary techniques for proper diagnosis. On reexamination of the 10 cases with tissue diagnoses, 4/6 mixed HBs could be correctly subtyped, whereas the distinction between embryonal and fetal cells in four cases of epithelial HB seemed questionable.

Radiotherapy in the SIOP (International Society of Pediatric Oncology) nephroblastoma studies: a review.

For decades radiation has generally been accepted as a valuable supplement to surgery in the treatment of Wilms' tumor; unfortunately, it may produce undesirable late effects. It turned out, however, that when treatment is adjusted to known variables, the risk for late sequelae can be diminished in some groups of children. SIOP clinical trials have been based on children with unilateral tumors of standard histology and free of metastasis at diagnosis. The first two clinical trials, SIOP-1 (started in 1971) and SIOP-2 (started in 1974), established the beneficial effect (such as less ruptures, lower stage) of preoperative radiation and actinomycin D (AMD) in SIOP-2, with all children having radiation therapy either preoperatively, postoperatively, or both. In the SIOP-5 trial (started in 1977), preoperative radiation therapy and AMD were compared with preoperative chemotherapy resulting in only 50% of children having radiation. The result permitted disuse of preoperative radiation in the SIOP-6 trial (started in 1980), where only one-third of the patients received postoperative radiation therapy. At present, in the SIOP-9 trial (started in 1987), fewer than 20% of children are having radiotherapy. The survival rates meanwhile have been increasing steadily from 64% in SIOP-1 to 84% in SIOP-6 for stages I, II, and III combined.

Addition of IFN-alpha to treatment of malignant brain tumors.

Despite many attempts to improve the survival after surgery of patients with malignant astrocytoma the prognosis is poor. We have used natural IFN-alpha in 16 patients with malignant astrocytoma treated between 1987 and 1990; 6 for recurrent tumors. Radiation therapy was given in 2 Gy fractions daily to a total dose of 50 Gy in the tumor area, 5 fractions per week and IFN twice per week, cisplatinum 60 mg/m2 i.v. every second week and vincristine 2 mg every week in 12-h i.v. infusions. Eight patients were reoperated when clinical deterioration suggested recurrent tumor; histological examination showed no residual tumor in 7 of them. Of these 8 patients 3 are alive and well, 2 of them after more than 5 years. The study suggests that malignant astrocytoma can be successfully eradicated with surgery, irradiation, IFN-alpha and chemotherapy. The treatment had, however, unacceptably high neurotoxicity. Earlier removal of the tumor necrosis, before clinical deterioration, could possibly diminish the high complication rate and consequently improve survival.

Late sequelae in children treated for brain tumors and leukemia.

Forty-two survivors treated at an age of 2-16 years for brain tumors or leukemia were, 4-21 years after treatment, subjected to an extensive follow-up investigation, including physical examination and interview; 35 of them also had endocrinological and 33 psychological evaluation. Hormonal deficiencies were found in about two-thirds of patients and were most common in those treated for brain tumors. The great majority had verbal intelligence quotient (VIQ) within normal range. Also, the performance intelligence quotients (PIQ) were normal in most patients. However, the results suggested that the primary intellectual capacity in children treated for cancer was not being fully utilized, their PIQ being on the average higher than their VIQ; this tendency was especially pronounced in the leukemia patients.

Concurrent vinblastine and radiation therapy in bladder cancer.

BACKGROUND: Since mid-1987, 29 patients with invasive transitional cell carcinoma of the urinary bladder (T1-3 N0-X M0) were treated with concurrent radiation therapy (RT) (target dose [TD], 62-66 Gy) 1.8-2.0 Gy/day for 5 days a week with a break in the middle of treatment of 2-3 weeks and vinblastine weekly 2 mg/5-12 h intravenous infusion. METHODS: Patients were divided into two groups: those had only the initial therapy (Group 1) and those who had both courses of RT combined with vinblastine (Group 2). Patients eligible for cystectomy were selected for full-dose RT, according to the results of treatment with a TD of 36 Gy. RESULTS: Tolerable toxicity rates were noted. No patient was excluded from the study. The authors report a clinical complete remission rate of 71% at early evaluation of treatment and a 3-year local progression-free survival of 66% (for Group 2 patients). These results are comparable to those obtained with more aggressive chemoradiation therapy regimens. The authors also noted improved local disease control in patients who received combination therapy in comparison with the 17 patients treated with RT alone. CONCLUSIONS: The authors suggest that concurrent RT and vinblastine therapy is an attractive alternative to other chemoradiation therapy regimens, and is especially superior to RT therapy alone in caring for old patients or patients in poor general condition.

Intrapleural application of natural IFN alpha in breast cancer patients with pleural carcinomatosis. Monitoring of immunotherapy by assaying serum interferon levels.

For resistant local recurrence, e.g. in breast cancer, or metastatic spread, local infiltration of IFN may be an interesting new approach. The aim of this study was to find out if intrapleurally administered interferon, in breast cancer patients with pleural carcinomatosis, can cause measurable serum concentrations and how soon after administration. Serum IFN concentrations were compared with those in the pleural fluid, and correlated with the presence of malignant cells in the pleural fluid. To uncover possible rhythmicity of serum interferon levels and its relationship to the timing of therapy, natural leukocyte interferon was administered intrapleurally at 10 a.m. Data on pharmacokinetics were obtained from blood samples drawn at -2, 0, 2, 8, 14, 22 and 46 h during the course of treatment. In contrast to our previous observations in healthy volunteers, levels of serum IFN before therapy had no circadian rhythmicity. Daily pharmacokinetic profile of individual patients on interferon therapy has shown that serum IFN peaks 8 h after intrapleurally administered IFN alpha. The peak depended on frequency and number of applied doses. During treatment with IFN alpha, malignant cells degenerated and finally disappeared from pleural fluid. At the same time reactive cells appeared. This effect is rather uniformly observed, but varies in degree. The number of patients is too small, however, to permit conclusions in regard to correlation of this clinical effect and the levels of serum IFN alpha.

Human leukocyte interferon alpha (HLI-alpha) for treatment of pleural effusion caused by non small cell lung cancer. A pilot study.

Fourteen patients with ipsilateral pleural effusion from non small cell cancer of the lung, 10 of them with generalized metastasis, were treated with local application of HLI-alpha in addition to other symptomatic treatment. Cytology of pleural fluid at the beginning of treatment yielded cancer cells in all but one. HLI-alpha, 2 x 10(6) International Units (I.U.) diluted in 20 ml of distilled water was injected intrapleurally each time. The mean survival of the HLI-alpha treated patients, measured from the first treatment of the pleural effusion, was 10.8 months. The performance status improved in 9 patients following HLI-alpha treatment. The pleural effusion eventually ceased accumulating in all patients. To judge from cytology of tapped pleural fluid, the cancer cells disappeared during treatment with HLI-alpha in 11 patients.

Intracranial germinoma: report of seven cases.

Seven children with histologically verified intracranial germinomas, treated between 1983-1987, are reviewed. The four boys were 12, 14, 15, and 16 years old; two girls were 9, and one girl was 10 years old. Four tumors were suprasellar, and three were in the pineal region. Parinaud's sign was the first symptom in the pineal tumors and diabetes insipidus in the suprasellar ones. The latter four patients also had pituitary deficiencies. The tumors were totally removed in three patients, partially in three, and one patient had biopsy only. Two patients had disseminated tumor. All patients received radiation: four to the tumor bed, one to the whole brain, and two to the whole central nervous axis (CNA). The doses to the tumor were 30 Gy in three, 40 Gy in two (one whole brain), and 45 Gy in two. The dose to the CNA was 24 Gy. Five patients had chemotherapy as well: cyclophosphamid (cytoxan) 80 mg/kg in two doses, three times in 3-week intervals. All patients are alive and well. Total disappearance of tumor followed chemotherapy before radiation in three patients. Lower doses of radiation (30 Gy, 40 Gy) and irradiation of the tumor bed only were sufficient for tumor control in localized germinoma.

Controlled trial of the prophylactic administration of antibiotics in sclerotherapy of esophageal varices.

The aim of this controlled trial was to determine the usefulness of chemoprophylaxis in sclerotherapy of ruptured esophageal varices. Sixty patients bleeding from esophageal varices, without signs of infection at admission, were included in a randomized open trial of one-year duration. Thirty patients received, along with the usual standard therapy (infusions, transfusions) 4x1 g ampicillin intravenously over 3 days, and 30 patients received the standard therapy only. Bleeding varices of the esophagus were sclerosed transendoscopically intravenously using 1% polidocanol solution. Body temperature, general condition, white blood count, differential blood count and sedimentation rate were followed-up over three days. There were no statistically significant differences between the groups in the mean values of the mentioned parameters. There was no correlation between the dose of sclerosant used and body temperature or leukocyte count. Chemoprophylaxis proved to have no effect in this indication.