Biomedical subjects

D Harms

Publications and source records attributed to D Harms.

At least 19 recordsLinked to original sources

PubMed2005

[Morphological variability of synovial sarcoma in childhood].

We report on an unusual locally recurrent plantar soft tissue sarcoma in a 7-years-old boy. Due to an unusual morphology a clear diagnosis was initially not possible. The histologically different recurrent tumor was classified as synovial sarcoma by means of immunohistochemistry, ultrastructural and molecular analysis. This case demonstrates the variable morphological appearance of synovial sarcoma and the value of modern diagnostic procedures in such circumstances.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

AFP/beta-HCG secreting CNS germ cell tumors: long-term outcome with respect to initial symptoms and primary tumor resection. Results of the cooperative trial MAKEI 89.

PURPOSE: The aim of the present study was to evaluate survival and factors influencing long-term outcome of patients with AFP/beta-HCG secreting (non-seminomatous) central nervous system germ cell tumors (secCNSGCT), who were prospectively collected in the cooperative MAKEI (German: maligne Keimzelltumoren) 89 protocol. PATIENTS AND METHODS: Between January 1989 and January 1994, 28 patients with secCNS GCT were registered and treated according to the MAKEI 89 protocol. The protocol recommended, after a clinically or histologically proven diagnosis and cisplatin-based chemotherapy, a resection of residual tumor and craniospinal irradiation (30 Gy) with a tumor boost (20 Gy). RESULTS: The estimated (Kaplan-Meier) event-free survival (EFS) of protocol patients is 0.57 +/- 0.09 (n = 28) and the relapse-free survival (RFS) is 0.67 +/- 0.10 (at five and ten years). With respect to long-term survival, the combination of marked neurological symptoms at diagnosis along with primary tumor resection seem to be the main negative prognostic risk factors (Fisher exact test p < 0.05). CNS dissemination at diagnosis can also be considered as a negative risk factor as 3 of 5 patients with primary dissemination died of the disease. CONCLUSION: Cisplatin-based three agent chemotherapy followed by resection of the residual tumor and craniospinal irradiation (CSI) with tumor boost is a successful and well-tolerated treatment for secCNSGCTs. The possibility of a clinical diagnosis based on MRI and tumor markers together with the use of modern neurosurgical techniques gives us the chance to postpone or even avoid major surgery. This gives an additional chance to reduce acute morbidity and further decrease late effects.

Adolescent↗

PubMed2005

Patients with extreme obesity: change in mental symptoms three years after gastric banding.

OBJECTIVE: Extreme obesity causes grave psychosocial and psychopathological problems in addition to somatic morbidity. One possible treatment is gastric banding, a surgical reduction of stomach volume. The aim of this study was to investigate whether gastric banding leads to lasting change in: 1) the Body Mass Index (BMI); 2) social factors such as work and partnerships, eating behavior, anxiety and depression symptoms; and 3) health related quality of life. METHOD: We surveyed a sample of 50 adipose women (BMI > 40 kg/m2). Primary outcome measures were self-reported changes on the scales of the Three-Factor Eating Questionnaire (TFEQ), the Hospital Anxiety and Depression Scale (HADS-D), and the Health Survey (SF-36). RESULTS: In comparison with the control group, we observed significant changes in BMI (p < 0.01) and the existence of a partnership (p < 0.01), on all three scales of the TFEQ (p < 0.01), on both scales of the HADS-D (anxiety: p < 0.05; depression:p < 0.01), and on all scales of the SF-36 Health Survey (p between < 0.05 and < 0.01 in every case). The most marked changes in all the qualities investigated occurred within the first 12 months of surgery. CONCLUSIONS: Three years after gastric banding, positive changes in BMI reduction, partnership, eating behavior, anxiety, depressive symptomatology, and health related quality of life could be observed. There was also a significant correlation between BMI reduction and reduction firstly on the depression scale (HADS-D) and secondly on the SF-36 scales for physical functioning (PHFU), role physical (ROPH), mental health (PSYC), and vitality (VITA).

Adult↗

PubMed2004

[Proliferation and hTERT expression in neuroblastoma].

BACKGROUND: Transcription of the catalytic subunit of telomerase, human Telomerase Reverse Transcriptase (hTERT), and increased tumor cell proliferation are powerful prognostic factors in neuroblastoma. We therefore investigated their relationship in a large group of neuroblastomas. METHODS: RT-PCR analysis was used to discriminate between the various hTERT transcripts. Tumor cell proliferation was assessed immunohistochemically using two different cell-cycle specific antibodies and the results were compared by statistical analysis. RESULTS AND CONCLUSIONS: 54 out of 115 neuroblastomas showed hTERT transcripts, 25 of which also possessed full-length transcripts. Full-length hTERT transcripts were correlated with MYCN-amplification, with a Ki67-proliferation index > or = 25% and a repp86-proliferation index > or = 10% (p<0,0001), but only a Ki67-proliferation index > or = 25% was associated with general hTERT transcription (p=0,001). Our data confirm the close relationship between hTERT transcription and tumor cell proliferation and further strengthen the exceptional prognostic power of the repp86-proliferation index.

Cell Division↗

PubMed2004

[Soft tissue malignancies in childhood and adolescence. Pathology and clinical relevance based on data from the kiel pediatric tumor registry].

Soft tissue malignancies in childhood and adolescence encompass a wide variety of histologically and genetically different tumor entities. In the files of the Kiel Pediatric Tumor Registry, 4,272 soft tissue malignancies were collected since 1977. Rhabdomyosarcomas are by far the most frequent sarcomas (44.6 % of the cases), followed in decreasing order of frequency by the family of Ewing tumors (peripheral primitive neuroectodermal tumors and extraosseous Ewing's sarcomas; altogether 22.3 %), malignant peripheral nerve sheath tumors (8.1 %), synovial sarcomas (5.0 %), leiomyosarcomas (3.2 %), fibrosarcomas (2.4 %), extrarenal malignant rhabdoid tumors (2.0 %), and alveolar soft tissue sarcomas (1.1 %). A further group (11.3 %) includes rare tumors, intermediate fibrohistiocytic tumors, and unclassified sarcomas. Embryonal rhabdomyosarcomas are 2.5 times more frequent than the alveolar rhabdomyosarcomas, which are prognostically unfavorable and located predominantly in the extremities and the trunk. With regard to clinical findings, histology, molecular biology and prognosis, embryonal and alveolar rhabdomyosarcomas have to be considered as two different tumor types. The family of Ewing tumors includes extraosseous Ewing's sarcoma and peripheral primitive neuroectodermal tumors (synonym: malignant peripheral neuroectodermal tumors), the former tumors without and the latter with neural differentiation. Many cases of infantile malignant peripheral nerve sheath tumors and infantile fibrosarcomas are low-grade malignancies and prognostically more favorable than their "adult" counterparts.

Adolescent↗

PubMed2003

Ovarian sex cord-stromal tumors in children and adolescents.

PURPOSE: To develop diagnostic standards and a risk-adapted therapeutic strategy for ovarian sex cord-stromal tumors (OSCST). PATIENTS AND METHODS: Fifty-four patients were prospectively enrolled as follow-up patients onto the German Maligne Keimzelltumoren protocols. Surgical protocols and histopathology were reviewed centrally (53 patients with complete data). Surgery included ovariectomy in 18 patients, salpingo-ovariectomy in 34 patients, and hysterectomy in one patient. Patients with stage IA tumors were followed-up at regular intervals, whereas nine patients with stage IC and six patients with stage II to III tumors were treated with cisplatin-based chemotherapy. RESULTS: International Federation of Gynecology and Obstetrics stage was IA in 27 patients, IC in 21 patients, II in three patients, and III in three patients. After a median follow-up of 59 months (range, 6 to 193 months), event-free survival +/- SD was 0.86 +/- 0.05 (47 of 54 patients) and overall survival was 0.89 +/- 0.05 (49 of 54 patients). Prognosis correlated with stage (event-free survival +/- SD: IA, 1.0 [27 of 27 patients]; IC, 0.76 +/- 0.09 [16 of 21 patients]; and II/III, 0.67 +/- 0.19 [four of six patients]; P =.02). Ten of 15 patients treated with chemotherapy, including four of six stage II to III patients, are alive after a median follow-up of 33 months. CONCLUSION: On the basis of a standardized clinical and histopathologic assessment, risk-adapted therapeutic strategies for OSCST can be evaluated. Considering our experience, we would recommend that stage IA tumors be followed up at regular intervals, whereas we would recommend cisplatin-based chemotherapy in stage IC tumors with preoperative rupture or malignant ascites, especially those with high mitotic activity. Finally, cisplatin-based chemotherapy also seems to be effective in advanced-stage tumors.

Adolescent↗

PubMed2003

Prognostic value of tumor size, metastases, extension into bone, and increased tumor marker in children with malignant sacrococcygeal germ cell tumors: a prospective evaluation of 71 patients treated in the German cooperative protocols Maligne Keimzelltumoren (MAKEI) 83/86 and MAKEI 89.

PURPOSE: To evaluate the prognostic value of metastases, extension into bone, and alpha-fetoprotein (AFP) elevation in children with malignant sacrococcygeal germ cell tumors (GCTs) prospectively collected in two cooperative Maligne Keimzelltumoren (MAKEI) protocols (83/86 and 89). PATIENTS AND METHODS: Between October 1983 and October 1995, 76 of 210 registered patients with sacrococcygeal primaries presented either with pure yolk sac tumor, embryonal carcinoma (EC), or yolk sac tumor and EC mixed with immature and mature teratoma elements. Stages T1 and T2 disease were diagnosed in 15 and 61 children, respectively, 41 patients had metastases, and 35 children presented with extension into bone. At diagnosis, 22 children had an AFP elevation of less than 10,000 ng/mL. Thirty-six children showed an AFP level between 10,000 and 100,000 ng/mL, and 12 patients had values of greater than 100,000 ng/mL. Five patients died of complication during treatment and were excluded from further evaluation. Seventy-one patients could be analyzed. RESULTS: The 5-year relapse-free survival rate (RFS, Kaplan-Meier) was 0.76 +/- 0.03 (54 of 71 patients; median observation time, 54 months after diagnosis). The RFS of patients with and without metastases was different, but not significantly so (0.71 v 0.82). The outcome of patients with extension into bone (n = 31) and without this extension (n = 40) was 0.71 versus 0.80 (RFS, 5 years). Above-normal AFP level had no prognostic significance (P =.52). CONCLUSION: In children with malignant sacrococcygeal GCTs treated with an intensive, short-interval, platinum-based regimen, the stage, extent of metastases, extension into bone, and AFP level had no prognostic significance.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

The influence of preoperative chemotherapy and surgical technique in the treatment of hepatoblastoma--a report from the German Cooperative Liver Tumour Studies HB 89 and HB 94.

UNLABELLED: Despite the success of chemotherapy in the treatment of hepatoblastoma (HB), the complete surgical resection of the primary liver tumour and metastases is the most important factor for survival. METHODS: From 1989 to 1998, 141 children with HB were treated in the German Cooperative Paediatric Liver Tumour Study HB 89 and HB 94. The study determines the results of surgical strategy, which adapts the procedure at the initial operation to the tumour extension in the liver and the occurrence of metastases. RESULTS: The median follow-up of the survivors was 72 months (range 24 - 132 months). 98/141 (78 %) patients were alive and 31/141 (22 %) died. 12/141 (8.5 %) children had no surgical treatment. A complete resection of the primary tumour was achieved in 107/129 (83 %) cases. Forty-eight children were primary resected and eighty-one children were operated on after initial chemotherapy. In 36 cases, an atypical tumour resection, in 90 cases an anatomical liver resection, was performed. Three children were transplanted. There was no perioperative death. 14/48 (30 %) children with primary tumour resection had microscopical or macroscopical residual tumour in the liver. Despite the larger number of advanced HB in the primary chemotherapy group, an incomplete tumour resection was performed in only 15/78 (19 %) cases after liver resection (p < 0.044). 14/36 (38 %) cases with atypical tumour resection and only 16/90 (18 %) cases with anatomical liver resection had residual tumours in the liver (p < 0.019). These results underline the necessity for preoperative chemotherapy in all HB, which was accepted in the following study HB 99. Atypical tumour resection should be avoided because of the higher rate of incomplete tumour resections and local relapse compared to the group with anatomical tumour resection.

Adolescent↗

PubMed2001

Metabolic activity and clinical features of primary ganglioneuromas.

BACKGROUND: Ganglioneuroma (GN) is considered by most to be a benign tumor of neural crest origin. It may evolve from differentiating neuroblastoma or may be diagnosed as primary ganglioneuroma. The rarity of this tumor and the lack of understanding of its biology often lead to inaccurate diagnosis and treatment. METHODS: The authors analyzed clinical features and biologic behavior of primary ganglioneuroma in 49 patients who were registered with but were not part of the national neuroblastoma trials. Data included age and symptoms at diagnosis, gender, tumor localization and size, (123)I-metaiodobenzylguanidine (mIBG) scintigraphy, secretion of catecholamines, histology, treatment, and outcome, whenever available. RESULTS: Patients with primary ganglioneuroma were significantly older than patients with neuroblastoma. Median age at diagnosis was 79 months compared with 16 months (P < 0.0001). Ganglioneuroma were equally distributed between males and females (1.13:1). A preference of thoracic (41.5%) and abdominal, nonadrenal tumors (37.5%) was observed compared with adrenal GN (21%). At diagnosis, thoracic tumors appeared larger than nonthoracic ones. Local lymph node metastases occurred in two patients. One ganglioneuroma had metastasized to soft tissues. (123)I-mIBG scintigraphy detected mIBG uptake at tumor site in 57% of the GN tumors. Levels of catecholamines in plasma and/or urine were increased in 39%. Slight immaturity of ganglion cells was observed in 93% of all ganglioneuroma tumors. None of the 22 tumors analyzed exhibited MYCN gene alterations. Although 12 patients had macroscopic residuals, no tumor progression or recurrence was observed in a median follow-up of 25 months. CONCLUSIONS: Ganglioneuroma may present with metabolic activity such as increased secretion of catecholamines and/or mIBG uptake. There are no specific diagnostic signs or symptoms discriminating ganglioneuroma and neuroblastoma tumors. Therefore, ganglioneuroma requires tissue investigation for diagnosis. Prognosis after surgical resection without further therapy seems to be excellent.

3-Iodobenzylguanidine↗

PubMed2001

Multimodal treatment of malignant sacrococcygeal germ cell tumors: a prospective analysis of 66 patients of the German cooperative protocols MAKEI 83/86 and 89.

PURPOSE: To evaluate a multimodal approach including surgery and cisplatinum chemotherapy for treatment of children with malignant sacrococcygeal germ cell tumors (GCT) and to compare adjuvant and neoadjuvant strategies in advanced tumors. PATIENTS AND METHODS: Between 1983 and 1995, 71 patients with malignant sacrococcygeal GCT were prospectively enrolled onto the German protocols for nontesticular GCT Maligne Keimzelltumoren 83/86 and 89. Five patients who received no chemotherapy (n = 2) or nonplatinum chemotherapy (n = 2) or who did not undergo tumor resection (n = 1) were excluded from this analysis. Among the 66 patients analyzed were 14 boys and 52 girls. The median age was 17.4 months (range, 7 months to 119 months). Median follow-up was 79 months (range, 4 months to 145 months). RESULTS: Fifty-two patients presented with locally advanced stage T2 tumors, and 30 patients had distant metastases at diagnosis. Patients received a median of eight cycles (range, four to nine cycles) of cisplatinum-based chemotherapy. Thirty-five patients underwent tumor resection at diagnosis and received adjuvant cisplatinum-based chemotherapy (group A). Thirty-one patients received up-front chemotherapy followed by delayed tumor resection (group B). Group B included more metastatic tumors than group A (group B, 19 of 31 patients; group A, 11 of 35 patients, P =.01). Preoperative chemotherapy facilitated complete tumor resections (group B, 20 of 31 patients; group A, five of 35 patients, P <.001) and avoided second-look surgery. Metastases at diagnosis and completeness of the first attempt of tumor resection were significant prognostic predictors; however, metastases were not predictive for patients treated with up-front chemotherapy. At 5 years follow-up, event-free survival was 0.76 +/- 0.05 (50 of 66 patients), and overall survival was 0.81 +/- 0.05 (54 of 66 patients). Four patients died as a result of therapy-related complications, and eight patients died of their tumors. Patients with locally advanced and metastatic tumors (T2b M1) fared better with neoadjuvant treatment [overall survival: 0.83 +/- 0.09 (16 of 19 patients) versus 0.45 +/- 0.15 (five of 11 patients), P =.01]. CONCLUSION: Even locally advanced and metastatic sacrococcygeal GCT can be successfully treated with up-front cisplatinum-based chemotherapy followed by delayed but complete tumor resection.

Actuarial Analysis↗

PubMed2001

Localized Ewing tumor of bone: final results of the cooperative Ewing's Sarcoma Study CESS 86.

PURPOSE: Cooperative Ewing's Sarcoma Study (CESS) 86 aimed at improving event-free survival (EFS) in patients with high-risk localized Ewing tumor of bone. PATIENTS AND METHODS: We analyzed 301 patients recruited from January 1986 to July 1991 (60% male; median age 15 years). Tumors of volume >100 mL and/or at central-axis sites qualified patients for "high risk" (HR, n = 241), and small extremity lesions for "standard risk" (SR, n = 52). Standard-risk patients received 12 courses of vincristine, cyclophosphamide, and doxorubicin alternating with actinomycin D (VACA); HR patients received ifosfamide instead of cyclophosphamide (VAIA). Tumor sites were pelvis (27%), other central axis (28%), femur (19%), or other extremity (26%). The initial tumor volume was <100 mL in 33% of cases and > or =100 mL in 67%. Local therapy was surgery (23%), surgery plus radiotherapy (49%), or radiotherapy alone (28%). Event-free survival rates were estimated by Kaplan-Meier analyses, comparisons were done by log-rank test, and risk factors were analyzed by Cox models. RESULTS: On May 1, 1999 (median time under study, 133 months), the 10-year EFS was 0.52. Event-free survival did not differ between SR-VACA (0.52) and HR-VAIA (0.51, P =.92). Tumor volume of >200 mL (EFS, 0.36 v 0.63 for smaller tumors; P =.0001) and poor histologic response (EFS, 0.38 v 0.64 for good responders; P =.0007) had negative impacts on EFS. In multivariate analyses, small tumor volumes of <200 mL, good histologic response, and VAIA chemotherapy augured for fair outcome. Six of 301 patients (2%) died under treatment, and four patients (1.3%) developed second malignancies. CONCLUSION: Fifty-two percent of CESS 86 patients survived after risk-adapted therapy. High-risk patients seem to have benefited from intensified treatment that incorporated ifosfamide.

Adolescent↗

PubMed2001

Evidence of chromaffin oxygen sensing in neuroblastoma.

With the aid of IGF2 and VEGF in situ hybridization; tyrosine hydroxylase, chromogranin A, and Ki67 immunohistochemistry; and TUNEL staining applied to a large series of clinical neuroblastomas and to an animal model, we show here that stroma-poor neuroblastomas show evidence of chromaffin differentiation similar to that of type 1 small intensely fluorescent (SIF) cells and that this occurs in a vascular-dependent fashion, indicating a role for local tumor hypoxia in the differentiation process.

Animals↗

PubMed2001

[Congenital pulmonary fibrosarcoma. Differential diagnosis of infantile pulmonary spindle cell tumors].

Primary pulmonary mesenchymal tumors are rare causes of intrathoracic lesions in newborns. We describe a case of pulmonary spindle-cell tumor with features of infantile fibrosarcoma and discuss the differential diagnosis of spindle-cell lesions in this location. In view of further case reports of the literature, this neoplasia can best be categorized in a spectrum of fibroblastic/myofibroblastic differentiated spindle-cell tumors, with excellent prognosis. Especially in congenital lesions a favorable clinical course is to be expected after complete surgical resection. Additional radio- and/or chemotherapy is not recommended.

Diagnosis, Differential↗

PubMed2001

[Histopathological aspects of Langerhans cell histiocytosis. With emphasis on the pulmonary form].

Langerhans cell histiocytosis (LCH) occurs principally but not exclusively in younger age groups. It can present as a single lesion or as multiple lesions and can affect one or several organ systems. Diagnosis of LCH requires the identification of CD1a and S-100 positive histiocytes. The range of synonyms used for LCH reflects both the variable clinical presentation and the variations in the histological "development stage" of the individual lesions from one case to another. The term LCH has now been accepted for all manifestations of the disease. The extent of the disease in a given case is specified by determining the number and location of foci and by ascertaining whether one or several organ systems are affected, and whether organ dysfunction exists. Among cases of LCH in adults, pulmonary LCH has a special status, as this usually results from cigarette smoking and is generally limited to the lungs. The lungs may also be affected in "conventional" LCH, and organ dysfunction may also exist in this form of the disease. In general, the morphology of LCH is sufficiently characteristic that the differential diagnosis versus other types of histiocytosis should not be difficult, provided an adequate specimen is available for examination.

Adult↗

PubMed2001

Regulation of telomerase activity by alternate splicing of human telomerase reverse transcriptase mRNA in a subset of neuroblastomas.

It has been proposed that the regulation of telomerase takes place at the transcriptional level, the expression of the catalytic subunit human telomerase reverse transcriptase (hTERT) being crucial for telomerase activity (TA). Recently, differential splicing of hTERT mRNA has been demonstrated in various tissues during embryonal development, and it has been suggested that only full-length transcripts translate into functionally active telomerase. With this in view, we analyzed the different hTERT transcripts by reverse transcriptase-polymerase chain reaction in neuroblastic tumors and compared the results with the TA, the tumor growth fraction, and the MYCN status. In a series of 38 neuroblastic tumors, high TA and full-length hTERT transcripts were found in nine samples, whereas nine samples showed absence of both enzymatic activity and hTERT transcripts. Interestingly, in another eight samples, low or absent TA coincided with a lack of full-length hTERT transcripts. Eleven samples contained hTERT transcripts with low or undetectable TA and one sample had low TA but no hTERT transcripts. TA correlated with MYCN amplification and was weakly associated with the proliferative activity. Moreover, a significant correlation with tumor progression was observed. Our findings point at a posttranscriptional regulation of TA in a subset of neuroblastic tumors. Because high TA was detected only in tumors with full-length hTERT transcripts, reverse transcriptase-polymerase chain reaction analysis of archival neuroblastic tumor samples might help to appraise the malignant potential in individual cases.

Alternative Splicing↗

PubMed2001

Disseminated choriocarcinoma in infancy is curable by chemotherapy and delayed tumour resection.

Infantile choriocarcinoma has a poor prognosis with only 2 surviving children reported in the literature. 2 additional successfully treated children are presented. 2 infants (age 3 and 4 months at diagnosis) suffering from rapidly progressive choriocarcinoma with widespread haematogenous metastases involving the liver were treated according to the cooperative germ cell tumour treatment protocol (MAKEI 96) of the German Society of Pediatric Oncology and Hematology (GPOH). PEI-chemotherapy (cisplatin, etoposide, ifosfamide; no ifosfamide before the age of 4 months) was combined with delayed tumour resection. Treatment resulted in sustained remission in both children (event-free survival 42 and 40 months). Interphase fluorescent in situ hybridisation (FISH) analysis of the paraffin-embedded tumour sample from case one revealed four to eight copies of chromosomes X, 1 and 17 and two Y chromosomes. Hybridisation with sub-telomere and centromere specific probes for chromosome 1 displayed an imbalance between the short and long arms of chromosome 1. In the tumour cells from case 2, only a polysomy of chromosome X could be proven, other aberrations were not analysed in this case for technical reasons.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

Clinical impact of histologic subtypes in localized non-anaplastic nephroblastoma treated according to the trial and study SIOP-9/GPOH.

BACKGROUND: Histologic subtypes of standard histology Wilms' tumor (WT) and the effect of preoperative therapy on their clinical and histologic features, deserve to be analysed in respect to outcome to find an adequate baseline for therapy. PATIENTS AND METHODS: The German Society of Paediatric Oncology & Haematology enrolled patients from January 1989 to March 1994 for therapy according the International Society of Paediatric Oncology trial & study 9. Standardised preoperative therapy with dactinomycin and vincristine for 4-8 weeks was generally applied in patients between 0.5 and 16 years with localized renal tumors and imaging typical for WT. In 99.5% of cases representative material was sent for review to the Kiel Paediatric Tumour Registry. For prospective subtyping of 329 WT (258 after preoperative therapy, 71 with immediate surgery) modified Beckwith & Palmer criteria were used. Reduction in volume measured by imaging prior to chemotherapy and surgery was used to assess response (poor response: reduction < 40%; good response: reduction > or = 40%). RESULTS: There were 39% of patients treated with immediate surgery and 12.4% of patients with preoperative therapy in the age group up to 12 months. The difference in age (P = 0.022) was linked with different amounts of epithelial WT (15.5% vs. 3.1%), median age: 0.58 and 0.93 years. Due to the effect of chemotherapy the amount of other WT changed: stromal 0% to 14%, mixed 45.1% to 29.4%, blastemal 39.4% to 9.3%). After preoperative therapy 37.6% of WT were predominantly regressive, 6.6% completely necrotic. Poor response was frequent in differentiated WT (86% of stromal, 75% of epithelial WT) but none relapsed. In the other WT with viable tumor left after preoperative therapy > 70% had good response, poor response was a risk factor (P = 0.0057). CONCLUSIONS: Subtyping according modified Beckwith & Palmer can be used in WT after preoperative therapy to stratify postoperative therapy in future. A milder therapy could be tested in differentiated WT at low stages and an intensified in the others with viable tumor left and poor response, i.e., mainly blastemal WT.

Adolescent↗

PubMed2001

Second malignancies after ewing tumor treatment in 690 patients from a cooperative German/Austrian/Dutch study.

BACKGROUND: Ewing tumor treatment involves high cumulative doses of alkylating agents and topoisomerase inhibitors, drugs capable of inducing second cancers. We analyzed the second cancer risk in a large cohort of consistently treated patients. PATIENTS AND METHODS: Six hundred ninety Ewing tumor patients were treated between 1992 and 1999 with local therapy and vincristine. doxorubicin, ifosfamide and/or cyclophosphamide, and antinomycin D, with or without etoposide as a randomized question. Second cancer incidences were estimated by competing risk analyses; standardized incidence ratios (SIR) in comparison to registry data were compiled. RESULTS: After a median observation time of 56 months (32 months for survivors), 6 of 690 patients had developed second cancers: MDS/AML, two, ALL/NHL, two, squamous cell carcinoma, one, liposarcoma, one. SIR were increased 20-30 fold in comparison to the general population. The cumulative second cancer risk five years after diagnosis of the Ewing tumor was 0.0093 for the total group, zero for patients without etoposide, and 0.0118 with etoposide. Additional phase II high-dose therapy increased the risk to 0.0398 after five years. CONCLUSIONS: The second cancder risk observed was in the range to be expected in cancer survivors. High-dose therapy, and less markedly, etoposide, may contribute to the overall second cancer risk.

Adolescent↗