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T Wiebe

Publications and source records attributed to T Wiebe.

At least 19 recordsLinked to original sources
PubMed2003

Scandinavian Sarcoma Group Osteosarcoma Study SSG VIII: prognostic factors for outcome and the role of replacement salvage chemotherapy for poor histological responders.

From 1990 to 1997, 113 eligible patients with classical osteosarcoma received neo-adjuvant chemotherapy consisting of high-dose methotrexate, cisplatin and doxorubicin. Good histological responders continued to receive the same therapy postoperatively, while poor responders received salvage therapy with an etoposide/ifosfamide combination. With a median follow-up of 83 months, the projected metastasis-free and overall survival rates at 5 years are 63 and 74%, respectively. Independent favourable prognostic factors for outcome were tumour volume < 190 ml, 24-h serum methotrexate > 4.5 microM and female gender. The etoposide/ifosfamide replacement combination did not improve outcome in the poor histological responders. In conclusion, this intensive multi-agent chemotherapy results in > 70% of patients with classical osteosarcoma surviving for 5 years. The data obtained from this non-randomised study do not support discontinuation and exchange of all drugs used preoperatively in histological poor responders. As observed in previous Scandinavian osteosarcoma studies, female gender appears to be a strong predictor of a favourable outcome.

Adolescent↗
PubMed2000

Cytogenetics of hepatoblastoma: further characterization of 1q rearrangements by fluorescence in situ hybridization: an international collaborative study.

BACKGROUND: Hepatoblastoma (HBT) is the most common hepatic neoplasm in children. This notwithstanding, little is known about pathogenetic factors, such as genetic abnormalities, of importance for the development and progression of this tumor type. To date, only 33 cytogenetically abnormal HBT have been published, and trisomies for chromosomes 2 and 20 have been shown to be the most frequent aberrations. Recently, unbalanced translocations involving proximal 1q have been described in several HBT, suggesting that a pathogenetically important gene maps to 1q. PROCEDURE: Six primary and one recurrent HBT were cytogenetically analyzed after short-term tissue culture. In addition, fluorescence in situ hybridization (FISH) studies, using locus-specific probes, were performed on three of these pediatric HBT as well as on one previously reported adult HBT. RESULTS: Total or partial trisomy 8, gain of chromosome 20, and structural rearrangements of chromosome 1 were detected in three HBT, and overrepresentation of chromosome 2 material was found in two HBT. The adjacent chromosome bands 1q12 and 1q21 were involved in three translocations, t(1;2), t(1;4), and t(1;11), which were all unbalanced and resulted in gain of 1q material. The previously reported adult HBT displayed 1q deletions with breakpoints at 1q12-21. FISH analyses of the 1q rearrangements revealed that all breakpoints were within the heterochromatic region. CONCLUSIONS: These findings provide further support for the importance of trisomies 2, 8, and 20 and rearrangements of 1q in the development of HBT. Furthermore, the consistent localization of breakpoints within the heterochromatic segment of chromosome 1 suggests that the important pathogenetic consequence of 1q abnormalities is the resulting genomic imbalance rather than a specific gene rearrangement.

Child, Preschool↗
PubMed2000

Five-year results in Ewing's sarcoma. The Scandinavian Sarcoma Group experience with the SSG IX protocol.

The first Scandinavian protocol for Ewing's sarcoma, SSG IV, resulted in a local control rate of 74% and 5-year metastasis-free survival (MFS) of 43%. The second protocol, SSG IX, was started in order to improve upon these results. It featured four chemotherapy cycles, each consisting of two courses of VAI (vincristine, doxorubicin, ifosfamide) alternating with one course of PAI (cisplatin, doxorubicin, ifosfamide) at 3-weekly intervals. Total treatment time was 35 weeks. Local therapy was given at week 9. Inoperable or non-radically operated patients received hyperfractionated accelerated radiotherapy 1.5 Gy twice daily between chemotherapy courses to a total dose of 42-60 Gy, depending on surgical radicality and tumour localisation. 88 patients were included (58 male, 30 female, mean age 20 years; range 5-65 years). The tumour (73 M0 and 15 M1) was located centrally in 31 patients (35%), in the extremities in 34 (39%) and other sites in 23 (26%) of cases. The median size of tumour was 10 cm (range 2-23), soft tissue was invaded in 87%. Surgery was the local therapy for 60 (68%) patients: amputation in 8 and local excision in 52. The surgical margins were wide in 35 patients, marginal in 14 and intralesional in 3. Radiotherapy was given to 17 non-radically operated patients postoperatively and to 28 patients with inoperable tumours primarily. Histological responses were evaluated in 52 patients. 9 local recurrences were observed (10%). Distant metastases developed in 24 M0 patients (33%). The estimated 5-year MFS was 58% and overall survival (OS) 70% for M0 and 27% and 28% for M1 patients, respectively. Survival was favourable in patients with non-metastatic extremity tumours (90%) and tumours operated with wide margins (90%). Patients with a total necrosis after chemotherapy had a better OS than those with a partial or poor response (P=0.003). The toxicity (World Health Organisation) was acceptable (gastrointestinal G1-2; haematological G3-4). The SSG IX protocol gave better local control and survival rates than the SSG IV. Whether this is due to a higher therapeutic efficacy of the present protocol cannot be ascertained in this comparison with a historical control.

Adolescent↗
PubMed2000

Interferon-alpha and ribavirin treatment of hepatitis C in children with malignancy in remission.

Twenty-eight cases of hepatitis C virus (HCV) infection were identified in children in a pediatric oncology ward during 2 nosocomial outbreaks. HCV infection spontaneously cleared in 6 patients (21%). Eleven patients with persistent HCV viremia who had malignant diseases in remission after treatment were given a 48-week course of combined therapy with interferon-alpha (5x106 U 3 times weekly) and oral ribavirin (15 mg/kg/d). Seven (64%) of the 11 patients had sustained virological responses 6 and 12 months after cessation of therapy. Side effects were common but generally were mild or moderate.

Adolescent↗
PubMed2000

Granulocytic sarcomas in body cavities in childhood acute myeloid leukemias with 11q23/MLL rearrangements.

Three childhood acute monoblastic leukemias (AML M5) with granulocytic sarcomas (GSs) are described. All displayed 11q23/MLL abnormalities, t(9;11)(p22;q23) in two cases and t(11;17)(q23;q21) in one case, constituting around 20% of all 11q23-positive AML cytogenetically investigated in our department. Two of the patients had GS in multiple locations, and all three had abdominal GS. In two of them, t(9;11)-positive GS was diagnosed prior to the diagnosis of AML. Fourteen (1.9%) of 752 published AML cases with 11q23 aberrations have had GS, either as a presenting feature or during disease progression. The incidence of GS has varied significantly (P < 0.05) between children (3.8%) and adults (0.8%). The most common AML subtype has been AML M5 ( approximately 75%) and the most frequent GS sites have been the skin, abdomen, orbit, and thorax. Considering the possibility of underreporting of GS in published cases and the relatively high frequency in our own series, we believe that 11q23/MLL rearrangements may predispose to GS development. Although extramedullary infiltrates in the skin are known to be frequent in cases of AML M5, which is often associated with 11q23 aberrations, the present findings indicate that GS in the abdomen, orbit, and thorax may also be common, especially in pediatric AML. Thus, the possibility of 11q23/MLL-positive GS should be suspected when tumors of uncertain derivation occur in these sites. Finally, the identification of 11q23/MLL abnormalities in GSs in two patients without overt AML underscores the importance of using cytogenetic and molecular genetic investigations as a diagnostic approach in the evaluation of tumorous lesions of unknown origin. Genes Chromosomes Cancer 27:136-142, 2000.

Abdomen↗
PubMed1999

Epidemiologic and molecular investigation of outbreaks of hepatitis C virus infection on a pediatric oncology service.

BACKGROUND: Despite screening of blood donors, hepatitis C virus (HCV) infection can occur in patients who receive multiple transfusions. OBJECTIVE: To clarify mechanisms of nosocomial transmission of HCV. DESIGN: Epidemiologic and molecular analyses of hepatitis C outbreaks. SETTING: Pediatric oncology ward. PATIENTS: Children with cancer. MEASUREMENTS: Epidemiologic analysis, HCV RNA detection, genotyping, and hypervariable region 1 (HVR1) sequencing. RESULTS: Ten cases of infection with acute HCV genotype 3a occurred between 1990 and 1993. Sequencing of HVR1 revealed three related strains. Despite an overhaul of hygiene procedures, a patient infected with genotype 1b generated nine subsequent infected patients in 1994. Several patients had high virus titers and strongly delayed anti-HCV antibody responses. All had permanent intravenous catheters. Multidose vials used for flushing or treatment had probably been contaminated during periods of overlapping treatment. CONCLUSIONS: Contamination of multidose vials was the most likely mode of HCV transmission; therefore, use of such vials should be restricted. Rigorous adherence to hygiene routines remains essential to preventing transmission of bloodborne infections.

Base Sequence↗
PubMed1999

Cytogenetic aberrations in Ewing sarcoma: are secondary changes associated with clinical outcome?

BACKGROUND: Ewing sarcoma is associated with a nonrandom pattern of primary and secondary chromosomal aberrations. Whereas the finding of rearrangements of chromosome 22, usually in the form of a balanced translocation t(11;22)(q24;q12), is important diagnostically, nothing is known about the potential prognostic impact of the secondary chromosomal aberrations. PROCEDURE: During a 1 3-year-period, short-term cultured tumor samples from 21 children and young adults with Ewing sarcoma were cytogenetically analyzed successfully. RESULTS: Clonal chromosome aberrations were detected in 18 patients, 17 of whom had the characteristic t(11;22)(q24;q12) or variants thereof. The most frequent secondary change was +8, followed by +12, +2, +5, +9, +15, and gain of material from the long and short arms of chromosome 1. The only recurrent secondary change that was restricted to tumors from the ten patients that were dead at latest follow-up was gain of 1q material. Furthermore, all three patients with tumors with chromosome numbers over 50 had died, and the only patient with a tumor karyotype lacking chromosome 22 rearrangement was alive without evidence of disease. CONCLUSIONS: These data and previously published results indicate that the karyotypic pattern not only may be of diagnostic significance but also may be important prognostically.

Adolescent↗
PubMed1999

Bilateral Wilms' tumor.

During a 16-year period, 49 children were treated for Wilms' tumor (WT); 7 were bilateral, 5 synchronous and 2 metachronous. The age at primary diagnosis was 6 months to 5 years (mean 2.4 years). All but 1 child received preoperative chemotherapy with tumor reduction. Unilateral nephrectomy was performed in 2 metachronous cases. In 3 synchronous WTs, the tumor was enucleated in 5 kidneys and a heminephrectomy was performed in 1 kidney with a double pelvis. Two children were not operated upon. At relapse in the contralateral kidney the tumor was enucleated. Three patients died of WT, 1 is alive with disease, and 3 are without evidence of disease. Renal salvage procedures were technically feasible without complications and are advocated to preserve renal function.

Antineoplastic Agents↗
PubMed1999

Chemotherapy in Ewing's sarcoma. The Scandinavian Sarcoma Group experience.

During the past 15 years the Scandinavian Sarcoma Group has treated 140 patients with Ewing's sarcoma. Two protocols have been used. SSG IV included 52 patients between 1984 and 1990 and SSG IX, 88 patients since 1990. After 5 years of treatment, local recurrences occurred in 19% of the patients (M0 + M1) in the SSG IV group and 10% in the SSG IX group. Distant metastases developed in 57% of the M0-patients in the SSG IV group and in 33% in the SSG IX group. Tumor-related survival (overall) of M0-patients was 49% in SSG IV and 70% in SSG IX, and the metastasis-free survival rate 45% and 58%, respectively. Patients having a localized extremity tumor had a survival rate of 90% (SSG IX). In both treatment groups, good responders to chemotherapy had a better survival rate than poor ones (SSG IV, p < 0.02, GI-II vs. G II-IV and SSG IX, p < 0.003, GI-III vs. G IV). In conclusions local control and survival rates were better with SSG IX than SSG IV.

Adolescent↗
PubMed1998

Ewing's sarcoma treatment in Scandinavia 1984-1990--ten-year results of the Scandinavian Sarcoma Group Protocol SSGIV.

A report on the long-term follow up of the first cooperative Scandinavian Sarcoma Group study in Ewing's sarcoma of bone is presented. Fifty-two previously untreated patients entered the study between 1984 and 1990. Half of the tumors were located in the extremities and one quarter in the pelvis. The combined modality treatment consisted of 5 cycles of chemotherapy--including vincristine, methotrexate, doxorubicin, cyclophosphamide, bleomycin and dactinomycin. The first two cycles were followed by local resection or amputation in 35 patients and by radiotherapy alone in 17 patients. When surgery was not performed, was incomplete or yielded poor margins radiotherapy was given at a dose of 40-60 Gy. Local tumor relapses developed in 10 patients and in all but one patient were accompanied by metastatic disease. Five patients had metastasis at diagnosis and distant metastases developed after primary treatment in 27 patients after a median of 14 months. The median follow-up time for the 20 surviving patients is 10 years. At 5 years the tumor-related survival was 46% and the metastasis-free survival 43%. Late tumor relapses occurred in 4 patients, which reduced the 10-year tumor related survival to 41% and the metastasis-free survival to 38%. Histopathological tumour response correlated with survival with 5-year metastasis-free survival rates of 73% for the good responders and 35% for the poor responders.

Adolescent↗
PubMed1998

Wilms' tumour in infancy.

During a 15-y period, 48 children were treated for Wilms' tumour (WT). Seven of them were < 1 y of age at diagnosis. One child presented with non-traumatic haematuria, but in all the other children WT was revealed as a palpable abdominal mass at routine examination or investigation due to another disease. The four children under 6 months of age at diagnosis were primarily operated upon; the others received preoperative chemotherapy. Two children had chromosomal aberrations in the WT tumour specimen. The follow-up revealed that postoperatively six children are healthy with no evidence of relapse from WT, but one child had a contralateral relapse successfully enucleated. The clinical behaviour and management of WT in infants differ compared with that in older children. The diagnosis may be uncertain and it can be difficult to distinguish between malignant and non-malignant lesions. It is essential to realize the possibility of WT, even in children < 1 y of age.

Chromosome Aberrations↗
PubMed1997

Chromosomal aberrations in Wilms' tumour.

In 26 consecutive patients operated for Wilms' tumour samples from the tumour were genetically analyzed. Clonal acquired chromosome aberrations were found in 13 patients and a constitutional trisomy 18 as the sole change in 1. The chromosome number was altered in 13 patients. Numerical changes occurred in 16 patients and breakpoint of chromosome 1 in 6 patients. There was no structural alteration of chromosome 11. The observed cytogenetic heterogeneity illustrates the complexity of genetic changes involved in the genesis and progression of Wilms' tumour. To further elucidate the phenotypic impact of chromosomal aberrations the correlation to histology and the clinical course will be important.

Child↗
PubMed1997

Prognostic factors in bone sarcomas.

Based on a literature review and the SSG experience, the most important prognostic factors in high-grade osteosarcoma appear to be the presence of detectable metastases at diagnosis, tumour volume, old age, sex, histologic response, and possibly tumoral P-glycoprotein expression. However, for an adolescent patient with non-metastatic extremity disease, there is no consensus regarding prognostic factors at initial presentation, and currently there is thus no established method for dividing them into high- and low risk groups for the purpose of treatment differentiation. It should also be remembered that available prognostic factors have been identified only in a retrospective manner, following aggressive treatment of all patients. Thus patients in "favourable" prognostic groups may simply be patients who have had a good effect from aggressive treatment, and how they would have done with reduced treatment remains to be shown. Obviously the best method for prognostication would be the direct demonstration of micrometastatic disease in the lungs or in peripheral blood. In the relatively near future, this may become possible with immunoscintigrapy or immunohistochemistry utilizing monoclonal antibodies [29-31]. In Ewing's sarcoma, the most powerful factors indicating poor prognosis are metastases at diagnosis, poor histologic response, large tumour size and possibly pelvic localisation. There appears to be a somewhat better international consensus regarding prognostic factors in Ewing's sarcoma than in osteosarcoma. Although several studies have implemented intensified treatment for poor prognostic groups [8, 32], the role (if any) of high-dose treatment with stem cell rescue remains to be proven. The same factors are prognostic both for the development of metastases and local recurrence, but in addition, surgical treatment as opposed to radiotherapy appears to reduce local failure rate [12, 17, 33, 34]. As in osteosarcoma, the near future offers promise regarding the detection and quantification of micrometastatses and minimal residual disease, by means of PCR techniques recognizing specific genetic changes in the Ewing family of tumors [35].

Adolescent↗