Biomedical subjects

Karin Dieckmann

Publications and source records attributed to Karin Dieckmann.

34 records · Page 2Linked to original sources

PubMed2003

Does bulky disease at diagnosis influence outcome in childhood Hodgkin's disease and require higher radiation doses? Results from the German-Austrian Pediatric Multicenter Trial DAL-HD-90.

PURPOSE: The identification of risk factors is required for risk-adapted treatment strategies in the treatment of Hodgkin's disease. To assess the influence of bulky disease at diagnosis as compared with other risk factors on event-free survival (EFS) in pediatric Hodgkin's disease such as stage, B-symptoms, number of involved lymph node regions, histology, and remission status after chemotherapy, we analyzed the outcome of 552 patients treated with a risk-adapted treatment strategy consisting of OPPA(OEPA)/COPP (vincristine, procarbazine, etoposide, prednisone, adriamycin, cyclophosphamide) and involved-field radiotherapy. METHODS AND MATERIALS: Between 1990 and 1995, 578 patients with primary Hodgkin's disease (HD) were enrolled in the German/Austrian Pediatric Hodgkin's Disease Study Group (DAL) Multicenter Study (HD-90). Patients were stratified into three treatment groups (TGs) for early, intermediate, and advanced stage. All patients received induction chemotherapy (CT) with two cycles of OEPA for boys and two cycles of OPPA for girls. Patients in TG2 and TG3 received another two or four cycles, respectively, of COPP. Chemotherapy was followed by involved-field radiotherapy. The radiation field, which was prescribed by the study center, was treated with a dose of 25 Gy/25 Gy/20 Gy (TG1/TG2/TG3), and in case of insufficient remission with a local boost of 5 Gy to 10 Gy. The following prognostic factors were analyzed with regard to their impact on EFS: bulky disease, mediastinal tumor, number of involved lymph node regions, histology, treatment group, B-symptoms, sex, age, and remission status after chemotherapy. RESULTS: Significant univariate predictive factors for the EES were: nodular sclerosis type 2 (NS2) histology (relative risk [RR] 3.43; p = 0.0002), presence of B-symptoms (RR 2.70; p = 0.0014), number of involved regions (1.55; p = 0.019), and treatment groups (RR 1.33; p = 0.017). There was a higher risk (RR 1.92; p = 0.040) for patients with bulky compared with nonbulky disease (5-year EFS 89.6%/94.6%). In the multiple regression model, only NS2 and B-symptoms remained strong predictive factors. The remission status after chemotherapy did not correlate with EFS (p = 0.66). CONCLUSION: Treatment strategies in Hodgkin's disease have an impact on different risk factors. In the risk-adapted treatment strategy of the HD-90 study, tumor burden indicated as bulky disease or as number of involved lymph nodes loses its importance, whereas NS2 histology and B-symptoms have a major impact on treatment outcome. Bulky disease at diagnosis might require higher radiation doses only in case of insufficient remission.

Adolescent↗

PubMed2003

Survival improvement in patients with glioblastoma multiforme during the last 20 years in a single tertiary-care center.

METHODOLOGY: The survival of 357 consecutive patients with newly diagnosed glioblastoma multiforme (GBM) in three treatment groups reflecting different time-periods of diagnosis (A: 1982-1984; B: 1994/1995; C: 1996-1998) was analysed to assess the impact and the potential improvement of changing treatment strategies in our tertiary-care center. PATIENTS AND METHODS: Group A (n = 100) included all consecutive patients diagnosed from 1982 to 1984 and served as the historical control. Group B (n = 93) included all consecutive patients diagnosed in 1994/1995 and group C (n = 164) those diagnosed from 1996 to 1998. Survival in the three treatment groups (A vs. B vs. C) was analysed according to treatment given after neurosurgical intervention (i.e. no specific therapy versus radiotherapy versus combined radio-/chemotherapy), and according to first-line chemotherapy, age (< 40, 40-60, > 60), sex, and tumor location (hemispheric versus bilateral or multifocal tumors, and tumors involving eloquent brain areas). Survival was analysed using Kaplan-Meier's non-parametric method. A p-value < 0.05 was considered statistically significant. RESULTS: Patients in groups A and B received radio- and/or chemotherapy to a varying extent (radiotherapy: group A: 22%, group B: 62%; chemotherapy: group A: 6%, group B: 33%). Chemotherapy was administered after termination of radiotherapy in both groups. In group C, 96% of patients received combined radio-/chemotherapy which was administered concomitantly and started within three weeks after surgery. Median survival was 5.2 months in group A, 5.1 months in group B and 14.5 months in C (p < 0.0001). Nine patients in group A (9%), 9 in group B (10%) and 40 in group C (25%) survived more than 18 months (p < 0.05). CONCLUSIONS: Survival improvement in group C might be attributable to the early start of combined radio-/chemotherapy. Therapy was administered on a complete outpatient basis, enabled by a dedicated interdisciplinary neuro-oncologic team caring for group C. Toxicity was mild and patients' acceptance excellent.

Adolescent↗

PubMed2003

Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue of the head and neck area: high rate of disease recurrence following local therapy.

BACKGROUND: Mucosa-associated lymphoid tissue (MALT) lymphoma is a distinct entity with specific clinical and pathologic features that may affect diverse organs. MALT-lymphomas remain localized within their original environment for a long period of time. As recent data have demonstrated a relatively high rate of multiorgan involvement at diagnosis, the authors have retrospectively evaluated 36 patients presenting with MALT-lymphoma in the head and neck area. The authors focused on patients' disease localization, initial treatment, clinical course, and follow-up. METHODS: Thirty-six patients with a histologically verified diagnosis of an extranodal marginal zone B-cell MALT-lymphoma arising in the head and neck area were included in this retrospective analysis. RESULTS: Treatment consisted of surgical resection as the sole treatment in 4 patients (11%), surgical resection with consecutive radiotherapy in 13 patients (36%), radiotherapy alone in 11 patients (31%), chemotherapy in 2 patients (6%), surgical resection plus radiotherapy and chemotherapy in 4 patients (11%), and combined radiation and chemotherapy in 1 patient (3%). Complete and partial disease remissions after initial treatment were achieved in 22 (61%) and 13 patients (36%), respectively, whereas one patient refused any therapy. Four patients (11%) were lost to follow-up and 15 patients (43%) have had disease recurrence after a median time of 11 months (range, 3-80 months). CONCLUSIONS: These data suggest that MALT-lymphomas of the head and neck area are preferentially treated using local modalities such as radiation and/or resection. This practice, however, is associated with an unexpectedly high rate of dissemination or disease recurrence. Obtaining an initial complete response is crucial in these patients. According to previous data, the possibility of understaging in such patients cannot be ruled out. Clinical trials with application of systemic treatment are warranted for these patients.

Adult↗

PubMed2003

Impact of a micromultileaf collimator on stereotactic radiotherapy of uveal melanoma.

PURPOSE: To evaluate the impact of a micro multileaf collimator (mMLC) on Linac-based stereotactic radiotherapy (SRT) of uveal melanoma by comparing circular arc with static conformal, dynamic arc, and intensity-modulated SRT. MATERIALS AND METHODS: Forty uveal melanoma patients were selected from approximately 100 patients treated with SRT since 1996. For each patient, four treatment plans (BrainSCAN XL, V5.0) were made: conventional arc, static conformal, dynamic arc plan, and intensity-modulated radiotherapy (IMRT). The goal of treatment planning was to fully encompass the planning target volume (PTV) by the 80% isodose while minimizing doses to the optic nerve and lens. The following parameters were evaluated: target conformity; target homogeneity; ratio of the target volume and 50% isodose volume; normal tissue receiving doses >/=80%, >/=50%, and >/=20%; central nervous system volume irradiated to >/=20%; optical nerve volume irradiated >/=50%, D(max) of the lens; lens volume receiving >/=20%; and monitor units. RESULTS: PTVs ranged from 0.68 to 4.90 cm(3) (mean 1.97 +/- 0.97 cm(3)). The average reduction of the prescription isodose volume was 1-1.5 cm(3) for conformal (range 2.6-0.3 cm(3)), dynamic arc (range 2.5-0.3 cm(3)), and IMRT plans (range 3.9-0.1 cm(3)), compared with conventional arc therapy. Central nervous system volumes irradiated to doses >/=20% were smallest for conventional or dynamic arc treatments. Average target dose homogeneity values were 1.74 +/- 0.50 for arc, 1.27 +/- 0.02 for static mMLC, 1.26 +/- 0.01 for dynamic arc, and 1.15 +/- 0.03 for IMRT plans. IMRT helped to reduce doses to the lens but did not provide an advantage for optical nerve sparing. When applying IMRT, the monitor units increased by approximately one-third compared with static mMLC-based SRT. CONCLUSIONS: Conformal mMLC and dynamic arc SRT are the treatment options of choice for Linac-based SRT of uveal melanoma. They present dosimetric advantages, while being highly efficient in treatment planning and delivery.

Humans↗

PubMed2003

Acute side effects during 3-D-planned conformal radiotherapy of prostate cancer. Differences between patient's self-reported questionnaire and the corresponding doctor's report.

BACKGROUND: Radiotherapy-induced side effects are often scored retrospectively according to the EORTC/RTOG scores for organs at risk by reviewing the medical records. Some studies could prove an over- or underestimation of side effects as assessed by the medical professionals. The aim of this study was to prospectively evaluate differences in side effects as described by the doctors and the patients. PATIENTS AND METHODS: 47 patients with prostate cancer were questioned about their side effects by a radiotherapist and asked to fill in a questionnaire at the start, in the middle and at the end of radiotherapy. The data of this questionnaire and the doctor's report were scored according to the German version of the EORTC/RTOG scores for gastrointestinal (GI) and genitourinary (GU) side effects and subsequently compared. We distinguished between "moderate" disagreement (better/worse by one grade, assessed by the doctor) and "pronounced" disagreement (better/worse by two grades, assessed by the doctor). RESULTS: The number of GI and GU side effects increased during radiotherapy both according to data obtained from the doctor and the patient questionnaire. Comparing doctors' reports with patients' questionnaires, for GI side effects an agreement was found in 22/47 patients, "moderately better" scores by the doctor's report were found in 13/47 patients, and "moderately worse" scores in 9/47 patients on average. "Pronouncedly better and worse" scores were found in 2/47 patients. For GU side effects an agreement was seen in 22/47 patients, "moderately better" scores in 17/47 patients and "moderately worse" scores in 3/47 patients. Regarding GU side effects, only pronouncedly better scores, as assessed by the doctor, were found in a mean of 4/47 patients. If the EORTC/RTOG score is used in its original English version, a difference is found, particularly in the assessment of GU side effects, resulting in an higher amount of agreement concerning GU side effects and a minor amount of "pronounced disagreement". CONCLUSION: In order to evaluate radiation-induced side effects, a patient's self-reported questionnaire should be included in the analysis of morbidity, above all for grade 0, 1, and 2 side effects. The validity of data seems to be questionable, particularly in the assessment of grade 0, 1 and 2 side effects, if only data from the doctors' reports are taken into account. The German version of the EORTC/RTOG score--not including the pretreatment status--leads to different results, particularly in the assessment of grade 0, 1, and 2 urinary side effects, which asks for a revision.

Acute Disease↗

PubMed2003

Current and future strategies in radiotherapy of childhood low-grade glioma of the brain. Part II: Treatment-related late toxicity.

BACKGROUND: For more than 60 years, radiation therapy has been an integral part in the management of childhood low-grade glioma. As this tumor carries an excellent long-term prognosis, the risk of late effects is of particular clinical importance and impinges upon radiotherapeutic treatment strategies. MATERIAL AND METHODS: Studies on the use of radiation therapy in children with low-grade glioma were systematically reviewed for data on radiotherapy-induced side effects on brain parenchyma, endocrine dysfunction, growth retardation, neurocognitive dysfunction, vasculopathy, and secondary neoplasms. RESULTS: Data on late effects are scarce and heterogeneous. Past reports included only retrospective series from the 1930s to present days, a time during which treatment policies and radiation techniques widely varied and considerably changed in recent years. Often, considerable uncertainty existed regarding pretreatment health status and radiotherapy-related factors (e.g., total dose, dose per fraction, treatment fields). In spite of these shortcomings and often conflicting observations, it appears that especially younger children and children with neurofibromatosis (NF) are at risk of endocrinopathies in terms of growth retardation and developmental abnormalities, as well as neurocognitive dysfunction expressed as problems in the psychosocial environment such as in education and occupation. However, both observations may be attributed to the higher proportion of NF in the very young who frequently develop large tumors spreading along the entire supratentorial midline. The risk of radiation-induced disturbances in visual function is low (no case reported). Young children with NF appear to have an increased risk of vasculopathies. 33 cases of moyamoya disease were found (preferably in the very young), 18 of whom were NF-positive. Other cerebrovascular accidents (24 cases, of whom 14 were NF-positive) and secondary neoplasms (15 cases, of whom only five occurred in field--four were high-grade astrocytomas) are a rare condition. The latter cannot be distinguished from late relapses with malignant transformation. Modern treatment techniques appear to reduce the risk of radiation-induced late effects. CONCLUSIONS: More studies and clear definitions of clinical endpoints such as neurocognitive and endocrinological outcome are needed in order to clarify the impact of radiation therapy on the risk of late sequelae. Presently, the strategy to postpone radiotherapy in the younger children, especially with NF, is justified to reduce the risk of late effects. These information and the contribution of tumor, surgery and chemotherapy will help to define the role of radiation therapy in the future management of childhood low-grade glioma and whether the use of highly sophisticated and expensive treatment techniques is justifiable. The recently initiated prospective study of the APRO (Pediatric Radiooncology Working Party) on documentation of dose prescription to organs at risk and the network of the GPOH to explore late effects as well as the forthcoming prospective SIOP/GPOH (International Society of Pediatric Oncology/German Society of Pediatric Oncology and Hematology) LGG 2003 trial are addressing these issues.

Adolescent↗

PubMed2003

Current and future strategies in radiotherapy of childhood low-grade glioma of the brain. Part I: Treatment modalities of radiation therapy.

BACKGROUND: Treatment of childhood low-grade gliomas is a challenging issue owing to their low incidence and the lack of consensus about "optimal" treatment approach. MATERIAL AND METHODS: Reports in the literature spanning 60 years of radiation therapy, including orthovoltage, megavoltage and recently modern high-precision treatments, were reviewed with respect to visual function, survival, prognostic factors, dose prescriptions, target volumes, and treatment techniques. Based on these experiences, future strategies in the management of childhood low-grade glioma are presented. RESULTS: Evaluation of published reports is difficult because of inconsistencies in data presentation, relatively short follow-up in some series and failure to present findings and results in a comparable way. Even with the shortcomings of the reports available in the literature, primarily concerning indications, age at treatment, dose response, timing and use of "optimal" treatment fields, radiation therapy continues to play an important role in the management of these tumors achieving long-term survival rates up to 80% or more. Particularly in gliomas of the visual pathway, high local tumor control and improved or stable visual function is achieved in approximately 90% of cases. Data on dose-response relationships recommend dose prescriptions between 45 and 54 Gy with standard fractionation. There is consensus now to employ radiation therapy in older children in case of progressive disease only, regardless of tumor location and histologic subtype. In younger children, the role of radiotherapy is unclear. Recent advances in treatment techniques, such as 3-D treatment planning and various "high-precision" treatments achieved promising initial outcome, however with limited patient numbers and short follow-ups. CONCLUSIONS: Radiation therapy is an effective treatment modality in children with low-grade glioma regarding tumor control and improvement and/or preservation of neurologic function or vision, respectively. More prospective studies are needed to address the impact of modern radiation therapy technologies (including intensity-modulated radiotherapy) on outcome especially in the very young and to define the role of radiation therapy as a part of a comprehensive treatment approach. The forthcoming prospective trial SIOP/GPOH LGG RT 2003 is addressing this issue.

Adolescent↗

PubMed2003

LINAC based stereotactic radiotherapy of uveal melanoma: 4 years clinical experience.

PURPOSE: To study local tumor control and radiogenic side effects after fractionated LINAC based stereotactic radiotherapy for selected uveal melanoma. PATIENTS AND METHODS: Between June 1997 and March 2001, 90 patients suffering from uveal melanoma were treated at a LINAC with 6 MV. The head was immobilized with a modified stereotactic frame system (BrainLAB). For stabilization of the eye position a light source was integrated into the mask system in front of the healthy or the diseased eye. A mini-video camera was used for on-line eye movement control. Tumors included in the study were either located unfavorably with respect to macula and optical disc (<3 mm distance) or presented with a thickness >7 mm. Median tumor volume was 305+/-234 mm3 (range 70-1430 mm3), and mean tumor height was 5.4+/-2.3 mm (range 2.7-15.9 mm). Total doses of 70 (single dose 14 Gy @ 80% isodose) or 60 Gy (single dose 12 Gy @ 80% isodose) were applied in five fractions within 10 days. The first fractionation results in total dose (TD) (2 Gy) of 175 Gy for tumor and 238 Gy for normal tissue, corresponding values for the second fractionation schedule are 135 and 180 Gy, respectively. RESULTS: After a median follow-up of 20 months (range 1-48 months) local control was achieved in 98% (n=88). The mean relative tumor reductions were 24, 27, and 37% after 12, 24 and 36 months. Three patients (3.3%) developed metastases. Secondary enucleation was performed in seven patients (7.7%). Long term side effects were retinopathy (25.5%), cataract (18.9%), optic neuropathy (20%), and secondary neovascular glaucoma (8.8%). CONCLUSION: Fractionated LINAC based stereotactic photon beam therapy in conjunction with a dedicated eye movement control system is a highly effective method to treat unfavorably located uveal melanoma. Total doses of 60 Gy (single dose 12 Gy) are considered to be sufficient to achieve good local tumor control.

Adult↗

PubMed2003

Psychometric- and quality-of-life assessment in long-term glioblastoma survivors.

BACKGROUND: Multimodal treatment of patients with glioblastoma multiforme (GBM) allows an increasing number of patients to survive beyond one year. On account of various neurological and psychophysiological impairments, however, these patients may not benefit in terms of quality of life (QOL). We evaluated the subjective QOL, clinical psychophysiological and cognitive functions in patients with GBM surviving 18 months after diagnosis. PATIENTS AND METHODS: Thirteen patients underwent psychophysiological and psychometric measurements for central-nervous activation, habituation of skin-conductance reaction, crystallized intelligence, verbal and psychovisual memory. QOL was assessed by the symptom check-list for somatization (SCS-Score). RESULTS: We found various impairments such as central-nervous deactivation (n = 9) or high activation (n = 3), psychovegetative overexcitement (n = 3) or attenuation (n = 1), reduced verbal (n = 5) and/or psychovisual (n = 5) memory and loss in attention (n = 7) or concentration (n = 5). Severe physical symptoms (grade 5) were fatigue, convulsion, headache, nausea and micturition difficulties. Eleven patients expressed high satisfaction with life in general, whereas only 4 were satisfied with their general state of health. All patients were independent and 8 patients returned to work. CONCLUSION: Despite various psychophysiological and cognitive impairments, subjective QOL appears mostly unaffected in this patient setting.

Adolescent↗

PubMed2003

Feasibility of long-term intraventricular therapy with mafosfamide (n = 26) and etoposide (n = 11): experience in 26 children with disseminated malignant brain tumors.

Treatment options for leptomeningeal disseminated brain tumors are limited by the lack of effective drugs for intrathecal therapy of non-hematologic malignancies. We report on our experience with an intraventricular therapy consisting of mafosfamide, a preactivated cyclophosphamide derivative, and etoposide. Between May 1994 and 2002, 26 patients aged 2-19 years with various intensely pretreated disseminated brain tumors received intraventricular mafosfamide via an indwelling subcutaneous reservoir. Twenty-three of them received a dose of 20 mg. Mafosfamide was administered once or twice weekly until remission was achieved and every 2-6 weeks thereafter as maintenance therapy for a total of 736 administrations (2-63/patient). Since March 1998, two patients were switched to receive intraventricular etoposide and nine received etoposide alternating with mafosfamide. Etoposide was given at a dose of 0.5 mg x 5 d every 3-6 weeks for a total of 122 courses (1-29/patient). Immediate toxicities such as transient headaches, nausea, and vomiting occurred with mafosfamide but were manageable with premedication. Etoposide did not cause any discomfort. No long-term toxicities attributable to intrathecal therapy as evidenced by magnetic resonance imaging or neurologic evaluation were observed. Since all patients received some sort of concurrent anti-cancer therapy, the efficacy of intrathecal therapy cannot be assessed independently. However, seven of 13 patients evaluable for response by cerebrospinal fluid (CSF) cytology developed CSF dissemination under systemic chemotherapy and cleared their CSF only after administration of intrathecal mafosfamide. In conclusion, intraventricularly administered mafosfamide at a dose of 20 mg and etoposide at a dose of 0.5 mg x 5 d for patients over 2 years of age are feasible and safe and may produce responses.

Adolescent↗

PubMed2003

Feasibility and toxicity of CCNU therapy in elderly patients with glioblastoma multiforme.

In our institution, 103 glioblastoma multiforme (GBM) patients aged from 55 to 83 years were treated since November 1994 as follows. All patients underwent surgical intervention (gross total resection, n = 35; subtotal resection, n = 38; stereotactic biopsy, n = 30). Subsequently all patients were offered radiotherapy and chemotherapy with CCNU. Results were as follows: 101 patients started radiotherapy, 93 patients completed it (96% of the patients aged < 65 years and 85% of the patients > or =65 years). All patients received at least 1 cycle of chemotherapy (median 3 cycles). Chemotherapy-associated toxicity was generally mild, more pronounced in females and did not increase with age. Median time to progression was 10.5+/-3.2 months for the patients < 65 years and 5.1+/-1 months for patients > or =65 years. median overall survival was 17.5+/-3.8 months in patients < 65 years and 8.6+/-1 months in patients > or =65 years (p < 0.0001). In multivariate analysis, age and female sex remained independent prognostic factors. Our data indicate that a treatment concept including concomitant radio- and chemotherapy is feasible even in elderly patients with GBM.

Aged↗

PubMed2003

Survival and prognostic factors of patients with unresectable glioblastoma multiforme.

The aim of this study was to assess survival and prognostic factors of 98 consecutive patients with unresectable glioblastoma multiforme (GBM) after stereotactic biopsy. Patients were diagnosed between 1993 and 1998, and the treatment modality subsequent to stereotactic biopsy was determined by the year of diagnosis. Before 1995, patients did not receive further specific therapy after stereotactic biopsy (n=36). In 1996, patients were administered radiotherapy starting within 6 weeks after stereotactic biopsy (n=24). From 1997 to 1998, patients received combined radio-/chemotherapy (RCT; CCNU orally) starting within 2 weeks after stereotactic biopsy (n=38). Patients' age ranged from 21 to 84 (median 64) years and their median Karnofsky performance score 2 weeks after stereotactic biopsy was 80 (range 60-100). Survival and prognostic factors were analyzed with respect to administered treatment modalities (without specific therapy versus radiotherapy versus combined RCT), with respect to age (>or or=or<80), tumor location (frontal, parieto-temporal, central, occipital) and tumor size (>or 5 cm) by the Kaplan-Meier method, by log-rank test and multivariate Cox regression analysis. Post-biopsy treatment modality was the strongest predictor for survival. Median (range) survival was 9 (3-47) weeks in those without specific therapy, 13 (5-54) weeks in patients receiving radiotherapy and 31 (11-101) weeks in patients receiving combined RCT (p<or=0.001). Age<or=50 years (p<or=0.05) in addition to tumor size in multivariate Cox analysis were found to be of significant influence onto survival, too. Combined RCT could be performed on a complete outpatient basis. Toxicity consisted of mild asymptomatic thrombocytopenia. We conclude that the administration of combined RCT within a minimum interval after stereotactic biopsy yielded a significant increase in survival. Patients' acceptance was excellent. These results encourage us to treat even patients with unresectable GBM with combined RCT.

Adult↗

PubMed2003

Second-line chemotherapy with dacarbazine and fotemustine in nitrosourea-pretreated patients with recurrent glioblastoma multiforme.

The aim of this study was to assess the efficacy and toxicity of a combination of dacarbazine (D) and fotemustine (F) administered to a homogenous group of patients with recurrent or progressive glioblastoma multiforme (GBM). Thirty-one patients with computed tomography or magnetic resonance imaging scan evidence of recurrent or progressive GBM after first-line chemotherapy with nitrosoureas as well as radiation therapy were given a combination of D (200 mg/m2) and F (100 mg/m2). At 30 min after termination of D administration, F was given over 60 min. Treatment was performed in an outpatient setting every 21 days. A total of 140 cycles (range 1-12 cycles; median 4 cycles) was administered. One partial response (3%) lasting for 11 weeks was observed. Sixteen (52%) patients reached stable disease lasting between 7 and 94 weeks. Median survival from start of the D/F combination was 45 (range 10-150) weeks. Median time to progression was 17 (3-101) weeks for all patients. Major toxicity was myelosuppression resulting in exclusion from study in seven (23%) patients [due to thrombocytopenia common toxicity criteria (CTC) grade 2 persisting longer than 3 weeks in three patients, due to thrombocytopenia CTC grade >/=3 in three and due to leukopenia CTC grade 3 in one patient]. No other toxicity than alopecia occurred. We conclude that the D/F combination is a well-tolerated second-line regimen and can be administered in a complete outpatient setting. D/F shows efficacy even in nitrosourea-pretreated patients and justifies further investigation.

Adult↗

PubMed2002

Treatment results of childhood acute lymphoblastic leukemia in Austria--a report of 20 years' experience.

Between 1981 and 1999, 890 Austrian children with acute lymphoblastic leukemia (ALL) were treated in 5 consecutive trials using protocols from the Berlin-Frankfurt-Münster (BFM) Group. In the trials BFM-A (Austria) 81 and ALL A 84, treatment stratification was performed using a risk factor, which was calculated from the initial peripheral blast cell count, and size of liver and spleen. In the following studies (BFM-A 86, 90 and 95) early response to a 7-day systemic mono-therapy with prednisone (as measured by the peripheral blast cell count) was used as an overriding stratification factor; in order to reduce the need for cranial radiotherapy, all patients received high-dose methotrexate (5 g/m2) for preventive central nervous system treatment. Event-free survival (EFS) rates increased from study BFM-A 81 (n = 141, probability (p) of EFS: 59% +/- 4%) and study ALL A 84 (n = 127, pEFS: 67% +/- 4%) to 77% +/- 4% in trial BFM-A 86 (n = 142), 79% +/- 3% in trial BFM-A 90 (n = 256), and 84% +/- 3% in trial BFM-A 95 (n = 224). However, the prognosis for high-risk patients has not significantly improved within the last 20 years (pEFS: 50%). Furthermore, conventional risk factors such as leukocyte count and age at time of diagnosis, could not be used to indicate patients in the low and intermediate risk group who might eventually relapse. Thus, in trial BFM-A 2000, detection of minimal residual disease by polymerase chain reaction-based methods after 5 and 12 weeks of therapy was introduced for treatment stratification. Minimal residual disease was prospectively shown to predict relapses more precisely and, as a matter of fact, may allow a more exact definition of which patients are at risk and which patients belong to the subgroup with a good prognosis despite reduced treatment.

Adolescent↗

PubMed2002

Role of radiotherapy in the treatment of supratentorial primitive neuroectodermal tumors in childhood: results of the prospective German brain tumor trials HIT 88/89 and 91.

PURPOSE: To evaluate the outcome of children with supratentorial primitive neuroectodermal tumors after surgery, irradiation, and chemotherapy and to identify factors predictive for survival. PATIENTS AND METHODS: Sixty-three children in the prospective trials HIT 88/89 and HIT 91 were eligible. Complete resection was performed in 21 patients. Patients were randomized for preirradiation chemotherapy, consisting of two cycles of ifosfamide, etoposide, methotrexate, cisplatin, and cytarabine (n = 40), or chemotherapy after irradiation, consisting of eight cycles with cisplatin, vincristine, and lomustine (n = 23). Irradiation volume was recommended to encompass the neuraxis with 35.2-Gy total dose followed by a boost (20.0 Gy) to the primary tumor site (n = 54). Seven patients were irradiated to the tumor region only with a total dose of 54.0 Gy. RESULTS: Overall survival at 3 years was 48.4%. Progression occurred in 38 children, with local recurrences in 27 patients. The only significant prognostic factor was dose and volume of radiotherapy (progression-free survival after 3 years was 49.3% with correct treatment compared with 6.7% for 15 children with major violations of radiotherapy). Ten early progressions occurred during adjuvant therapy (eight before and two during radiotherapy), nine of them treated with preirradiation chemotherapy. There was a positive trend in outcome for nonmetastatic and pineal tumors. CONCLUSION: Significant predictive factors were dose and volume of radiotherapy. Volume of irradiation should encompass the whole CNS with additional boost to the tumor region. Local doses of at least 54 Gy and a craniospinal dose of 35 Gy are necessary. Preirradiation chemotherapy seems to increase risk of early progression.

Adolescent↗

PubMed2002

Up-front centralized data review and individualized treatment proposals in a multicenter pediatric Hodgkin's disease trial with 71 participating hospitals: the experience of the German-Austrian pediatric multicenter trial DAL-HD-90.

BACKGROUND AND PURPOSE: A systematic procedure for up-front centralized data review and the set-up of individualized treatment proposals was integrated prospectively into the German-Austrian multicenter trial DAL-HD-90 for pediatric Hodgkin's disease (HD) in order to introduce local radiotherapy according to the individual patient's spread of disease within a combined-modality treatment. This paper investigates the feasibility of such a procedure and its impact on the final definition of the extent and stage of disease as well as on the choice of treatment. PATIENTS AND METHODS: Between October 1990 and July 1995, 578 children and adolescents <18 years (259 girls, 319 boys, median age 12.9 years) with HD were enrolled into the HD-90 trial. After clinical and pathological staging (66.4/33.6%), patients were allocated to treatment groups (TG) 1 'early stage', TG2 'intermediate stage', or TG3 'advanced stage'. All groups underwent two cycles of OPPA (vincristine, prednisone, procarbazine, doxorubicin) (girls) or OEPA (E, etoposide) (boys) for induction chemotherapy. TG2 and TG3 continued on as two or four cycles, respectively, of COPP (C, cyclophosphamide). Low-dose local radiotherapy was given to the initially involved sites, with radiation doses of 25 Gy in TG1/TG2, and 20 Gy in TG3. All documentation forms, radiographs, and chest and abdominal computed tomography (CT) scans were centrally reviewed, addressing in particular the individual patient's extent and stage of disease. This review and the set-up of individualized treatment proposals were in the hands of the study coordinator, one additional pediatrician and two radiation oncologists and radiologists at the study center. During a time slot of at least 8 weeks (two cycles of standard chemotherapy in all three TGs) the individualized treatment proposals were to be sent to the participating hospital. RESULTS: Complete sets of documentation from 564/578 patients (97.6%) were submitted sufficiently early to the study center. A total of 285 out of 574 chest radiographs, 468 out of 553 chest CT scans and 421 out of 548 abdominal CT scans were available from 71 hospitals. A total of 564 individualized treatment proposals were worked out by the review group and sent to the hospitals before radiotherapy began. Re-analysis of images and documentation forms, including laboratory and clinical data, resulted in a revision of stage in 115/571 patients (20.1%) and of TG in 76/571 patients (13.3%). A total of 67/76 patients were shifted into a higher TG, 60 patients on account of additionally detected extralymphatic involvement, five patients because of additionally detected lymph node involvement and two patients due to clinical data which had to be classified as B-symptoms. A total of 9/76 patients were shifted into a lower TG; in three patients extranodal disease and in six patents local lymph node involvement could not be confirmed. CONCLUSIONS: The up-front centralized review of patient data and consecutive set-up and delivery of individualized treatment proposals for almost every patient are feasible within a large multicenter trial. Sufficient time and manpower at the study center are needed for the review process and the set-up of individualized treatment proposals. Such a procedure has a significant impact on the homogeneity of stage definition, allocation to TG, and individualized treatment proposals.

Adolescent↗