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Biomedical subjects

L J Stalpers

Publications and source records attributed to L J Stalpers.

15 recordsLinked to original sources

[Malignant intracranial germ cell tumor treated with chemotherapy and radiotherapy without histopathological confirmation].

In two men aged 19 and 24 years, a rare malignant intracranial germ cell tumour was diagnosed in the pineal gland region and in the second patient in a suprasellar position as well. Although histological confirmation is required in general to diagnose a malignancy, obtaining it can be difficult and potentially dangerous in case of intracranial neoplasms. The clinical picture of a young patient with an intracerebral tumour localised in the midline of the brain and increased levels of the tumour markers alpha-foetoprotein and/or human chorion gonadotrophin (beta-HCG) in blood and/or CSF makes any other diagnosis highly unlikely. There is no place for radical surgery in the first-line treatment of malignant intracerebral germ cell tumours because of the sensitivity to radio- and chemotherapy. Also, the sensitivity to chemotherapy makes it possible to reduce radiation volume and dose in an effort to avoid the serious complications of craniospinal irradiation. Both patients responded well to chemotherapy based on cisplatin followed by radiotherapy.

Adult↗

Additive cytotoxic effect of cisplatin and X-irradiation on human glioma cell cultures derived from biopsy-tissue.

PURPOSE: Investigation of the in vitro cytotoxic effect of X-rays, either alone or combined with cisplatin on early passage cell cultures derived from human glioblastoma multiforme biopsy tissue. MATERIALS AND METHODS: Fresh tumour specimens from four patients were processed to cell cultures. The U373 glioma cell line was used as a reference. Early passage cell cultures were X-irradiated (0-8 Gy) either alone or in combination with cisplatin (0.5-1 microgram/ml). Cell survival was determined by either clonogenic assay or the colorimetric MTT assay. Survival curves were generated and mathematically analysed using the linear quadratic model, to obtain the radiosensitivity parameters alpha, beta, and SF2, i.e., the Surviving Fraction after 2 Gy. RESULTS: Two patient-derived glioma cell cultures and the U373 cell line showed rather high SF2 values of 0.61-0.72 in the clonogenic assay, indicating relative high radiation resistance. Cisplatin alone (1 microgram/ml) reduced cell survival by 10-30% (n = 4). When combined with irradiation, a clear additive cytotoxic effect of cisplatin was demonstrated by the unaltered value of the alpha-parameter for reproductive cell death. CONCLUSION: Cisplatin exerted an additive rather than radiosensitising cytotoxic effect in uncharacterised patient derived glioma cell cultures.

Adult↗

Reirradiation of primary CNS tumors.

PURPOSE: Primary central nervous system (CNS) tumors are seldom reirradiated due to toxicity concerns and sparse clinical data regarding efficacy. METHODS AND MATERIALS: We retrospectively reviewed 34 patients with primary brain tumors retreated with fractionated external beam irradiation at the University of California, San Francisco from 1977-1993. Tumors included 15 medulloblastomas, 10 high-grade gliomas, 7 low-grade gliomas, and 2 meningiomas. RESULTS: Initial course of radiation was radical in intent for all patients. Median age at initial diagnosis was 19.8 years (range: 3.6-67). Median interval between radiation courses was 16.3 months (range: 3.8-166). Median Karnofsky Performance Status (KPS) prior to reirradiation was 80 (range: 40-100). Reirradiation volumes overlapped previous treatment in 30 patients and were nonoverlapping in 4 patients. Fractionation schemes used were hyperfractionated in 17, conventionally fractionated in 9, and hypofractionated in 8. Cumulative maximum overlap dose within the CNS ranged from 43.2-111 Gy (median: 79.7 Gy). Retreatment was completed as planned in 27 out of 34 patients and modified or aborted in 7 (four tumor progression on retreatment, three patient request). As measured from the time of retreatment median progression free and overall survival was 3.3 and 8.3 months. Clinical and radiographic indices were stabilized or improved in about half of patients evaluable at a median of 3 months postretreatment. Complications (early or late) potentially attributable to retreatment were noted in 10 of 34 (29%) of patients. Overt necrosis was noted in 3 of 34 (9%) of patients and the actuarial risk of necrosis was 22% at 1 year following retreatment. CONCLUSIONS: Reirradiation of primary central nervous system tumors was associated with only modest palliative and survival benefits in this retrospective review. Difficulties separating toxicity due to retreatment vs. tumor progression and limited patient survival following retreatment preclude definite conclusions regarding the safety of this practice.

Adolescent↗

Gamma knife radiosurgery in children.

52 pediatric patients were treated with radiosurgery at the University of California, San Francisco. Arteriovenous malformations were treated in 27 patients. Complete obliteration was noted in 4 of 12 patients imaged more than 2 years after radiosurgery. Arteriovenous malformation rebleed was noted in 1 patient. Symptomatic T2 changes were noted in 2 patients. Among 29 neoplasms treated in 25 patients, local control was noted in 5 of 7 low-grade gliomas, 5 of 14 high-grade gliomas, 4 of 5 craniopharyngiomas and 3 of 3 sarcomas. Three patients treated for neoplasms developed necrosis after radiosurgery.

Adolescent↗

Yearly chest radiography in the early detection of lung cancer following laryngeal cancer.

In a retrospective study of 556 patients (505 men, 51 women) with laryngeal cancer the incidence and prognosis of lung malignancies was studied in patients who were examined yearly by chest radiography. In 69 patients (12.4%) a lung malignancy was diagnosed, with 28 having a histologically confirmed second primary malignancy. All of these 69 patients were men. The incidence of radiologically detected lung malignancies, both second primary and metastatic cancer, is higher and more prolonged following supraglottic carcinoma than following glottic carcinoma. In 47 patients (68%) without symptoms, the lung malignancy was detected by routine annual chest radiography. The survival rate in patients with lung cancer detected by the yearly radiography was significantly higher than in patients diagnosed after symptoms (median survival 10 and 4 months, respectively). However, taking into account the lead time between early radiologic diagnosis and the time a tumor would have been diagnosed following symptoms, the observed survival benefit of yearly radiography was much lower, or even nil.

Actuarial Analysis↗

Breast-conserving treatment or mastectomy in early breast cancer: a clinical decision analysis with special reference to the risk of local recurrence.

A clinical decision analysis was performed to judge the impact of local recurrences after breast-conserving treatment (BCT) on the (quality-adjusted) life expectancy of breast cancer patients. A life-long follow-up of two patient groups, one of which had undergone mastectomy and one BCT, was simulated by a Markov model of medical prognosis. Data used in the model originated from the literature. Since results in the source papers were not split according to stage, we performed two analyses: one with data from all source studies (T1 and T2) and one with data from source studies, concerning only T1 patients. In both analyses, the conclusion was that BCT yields better quality-adjusted life expectancy than mastectomy. Sensitivity analysis, however, identified subgroups of patients who should preferably undergo mastectomy. These subgroups are: patients preferring mastectomy to BCT, patients with a high risk of local recurrence, young patients and patients at high age, if they also have a high local recurrence risk. For these groups, patient preferences should play a major role in recommending treatment.

Adult↗

[Utility assessment in clinical decision making].

In clinical decision analysis a quantitative value is attached to a longevity or a life quality by means of utility assessment. The actual value of the utility can determine the result of the decision analysis. In this article utility theory is briefly discussed. Four kinds of utility tests (direct scaling methods, the basic reference gamble, the time trade-off test and additive conjoint measurement) are introduced on the basis of an example and their pros and cons are discussed. It is concluded that additive conjoint measurement has the best formal infrastructure, but that the test method is not always easily applicable.

Choice Behavior↗

Radiotherapy or surgery for T2N0M0 glottic carcinoma? A decision-analytic approach.

Decision analysis was used to evaluate the results of treatment of T2N0M0 glottic carcinoma as presented in the literature. Based on mean values for recurrence, salvage eligibility after recurrence and salvage success, the 5-year survival after radiotherapy and surgery proved to be almost identical, 85 and 86%. If the recurrence rates and the salvage rates were varied, a marginal advantage for surgery in small tumours (T2a) and a major advantage in more extended (T2b) tumours was seen if only survival is considered. To take the quality of speech into account, a utility analysis was performed. A utility scale was defined ranging from 0.0 as the value for death, to 1.0 for a successfully irradiated patient with preservation of normal speech. A utility of 0.99 or less for the laryngectomized patient would favour radiotherapy over surgery for all T2 tumours. In patients with T2b tumours and in extreme circumstances, e.g. if failure rates of radiotherapy are extremely high or if recurrence rates after surgery are extremely low, an exact assessment of patient utilities may be pivotal. Under normal circumstances radiotherapy is preferred for T2N0M0 glottic carcinoma if both survival and the quality of speech are taken into account.

Carcinoma↗

The role of yearly chest radiography in the early detection of lung cancer following oral cancer.

In a study of 213 patients with oral cancer, we investigated the incidence and prognosis of lung malignancies in patients offered a yearly chest radiography in the follow-up. Three conclusions can be drawn. (1) Metastatic or primary lung cancer was diagnosed in 22 (10.3%) patients. The 2-year actuarial incidence rate of lung cancer following cancer of the oral cavity is 13%. No new lung cancers were detected after 2 years follow-up. This suggests that after this period, yearly chest radiography may be superfluous for the early detection of lung cancer. (2) The survival rate of patients with a lung malignancy following cancer of the oral cavity is poor (1-year = 25%). The survival rate of patients detected by the yearly chest radiography without symptoms is higher than for patients detected after symptoms (p = 0.006). It is not clear to what extent this different survival rate is biased by lead-time and selection of patients with a favourable prognosis. A randomized study would be required to assess whether patients with oral cancer do benefit from the yearly chest radiography compared with no regular chest radiography. (3) Of 22 patients with lung cancer, 13 (59%) were detected by chest radiography without symptoms. In the first year following oral cancer, 11 patients were diagnosed with lung cancer. Only 4 of these 11 patients (36%) were detected by chest radiography in an asymptomatic stage. The detection of patients with lung cancer in an asymptomatic stage may be increased by more frequent chest radiography examinations in the 1st year following oral cancer.

Adult↗

Drug-induced skin reactions in patients with acute non-lymphocytic leukaemia.

The incidence of drug-induced skin rashes and related factors were analysed in a retrospective study of 151 patients with acute non-lymphocytic leukaemia (ANLL). 91 (60%) developed a drug-related toxicodermia to one or more drugs during remission, induction and maintenance therapy. The incidence of rashes was mainly confined to the blastic stage of leukaemia and occurred significantly less often during remission. Patients with acute myeloid leukaemia, FAB classification M1, M2 and M3 (M1-3) developed skin reactions more often than those of types M4 and M5 (M4-5). Women suffered more frequently from drug-induced skin lesions than men. The incidence of drug-associated rashes was significantly higher in patients with ANLL than in the general population for: Allopurinol (16%), co-trimoxazole (14%), miconazole (28%), and ketoconazole (18%). The incidence for the penicillins (12%) and cephalosporins (3%) conformed to the upper limit as reported for the general population. Additional toxic effects of combined therapy could not explain the differences observed and a dearrangement of the immunesystem during the blastic stage of leukaemia is suggested.

Acute Disease↗

The effects of irradiation on cell migration from glioblastoma multiforme biopsy spheroids.

BACKGROUND: Glioblastoma multiforme (GBM) is a primary brain tumour with a very poor prognosis despite aggressive multi-modality treatment. This pre-clinical experimental study focuses on the effect of irradiation on three-dimensional glioma biopsy spheroids in vitro using an outgrowth assay to evaluate cell survival and migrational capacity of the glioma cells. MATERIALS AND METHODS: Tumour tissue of 16 patients with high-grade glioma and two GBM cell lines were used for spheroid preparation. Outgrowth and cell density were the parameters chosen to evaluate cell cytotoxicity and migrational capacity after irradiation (20 Gy and 4 x 5 Gy). RESULTS: Radiation inhibited outgrowth of cell line spheroids, but not of the biopsy spheroids. All biopsy and cell line spheroids showed a significantly lower cell number (95 vs. 24 cells/0.25 mm2) in the outgrowth area after irradiation. CONCLUSION: Irradiation has a cytotoxic effect in GBM biopsy spheroids but it hardly affects cell migration. No correlation was found between patient survival and cell migration nor with cytotoxicity.

Adult↗