Biomedical subjects
J van Eys
Publications and source records attributed to J van Eys.
Clinical and biologic features predict a poor prognosis in acute lymphoid leukemias in infants: a Pediatric Oncology Group Study.
Analysis of remission induction rates for 1,117 children 18 months to 10 years of age (group 1) and 90 infants less than 18 months of age (group 2) with acute lymphoid leukemia (ALL) and of duration of continuous complete remission (CCR) for 454 in group 1 and 33 in group 2 revealed that infants fared significantly worse in both measures of outcome (P = .03 and P less than .0001). To examine potential reasons for the poor prognosis of affected infants, clinical and biologic features of their ALL were compared. Infants had higher WBC counts (P less than .001), a higher incidence of massive splenomegaly (P less than .001), massive hepatomegaly (P less than .001), more central nervous system (CNS) disease at diagnosis (P less than .01), and lower platelet counts (P less than .001). Also, their blasts were less often PAS+ (P = .02). The incidence of non(T, B, pre-B), T and pre-B immunophenotypes of ALL did not differ significantly between the two groups. However, in patients with non(T, B, pre-B) ALL, the majority (51%) of infants had common ALL antigen (CALLA)-negative blasts, as compared with only 7% in group 1 (P less than .001). Furthermore, infants with non(T, B, pre-B) cell ALL who were less than 12 months of age were almost always CALLA- (18 of 21). The blasts of children from both groups usually expressed Ia-like antigens. These data illustrate that infants with ALL have extensive and bulky disease more often than do older children and are more often affected with a prognostically unfavorable phenotype of acute leukemia (AL) which expresses Ia-like antigens but is more often PAS- and CALLA-. We believe that these clinical and biological differences predict and explain in part the observed poor response to treatment of infants with ALL.
Clinical and biologic features predict poor prognosis in acute lymphoid leukemias in children and adolescents: a Pediatric Oncology Group review.
Although the prognosis of children with ALL has improved markedly, approximately one-half of children continue to relapse. Clinical and biologic features of ALL have been studied at the time of diagnosis and many of these features have been shown to predict the risk of relapse, permitting tailoring of therapy based on relapse hazard. Results of studies of the Pediatric Oncology Group (POG) detailed here demonstrate that high white blood cell (WBC) count at diagnosis, very young or older age within childhood, and the presence of a mediastinal mass or central nervous system leukemia predict a poor prognosis within the context of certain therapies. However, not only age and WBC count, but immunophenotype of ALL as well, were especially predictive of prognosis in these POG studies. The information reviewed here has special importance for the planning of clinical trials for children with ALL.
Science and the three laws of robotics: a view of science, medicine, and ethics.
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Cisplatin in recurrent pediatric brain tumors. A POG Phase II study. A Pediatric Oncology Group Study.
Forty-six evaluable pediatric patients with primary recurrent brain tumors resistant to standard therapy were treated with cisplatin, 60 mg/m2/day, X2 days every 3 to 4 weeks, to study the efficacy and toxicity of this drug. Complete and partial responses, documented by computed tomography (CT) scan, were demonstrated in 4 of 10 patients with medulloblastoma and 3 of 15 patients with ependymoma. No activity was documented in astrocytic tumors. Dose limiting major toxicities were renal and auditory. It is recommended that the new analogues of cisplatin with less toxicity be studied in these tumors.
MOPP regimen as primary chemotherapy for brain tumors in infants.
Seventeen infants with central nervous system malignancies, all with tissue diagnosis, were treated with the combination chemotherapy nitrogen mustard, vincristine, procarbazine and a steroid (MOPP) as primary therapy following surgery. Diagnoses include: 7 astrocytomas (grade: 3-I, 3-II, 1-III), 6 medulloblastomas, 2 ependymoma/astrocytoma mixed, 1 ependymoma and 1 primitive neuroectodermal tumor. Fourteen were under 2 years of age, 2 between 2 and 3 years of age, and 1 between 3 and 4 years of age. Fifteen responded and 2 failed. Of the responders, 6 are in continuous complete remission (median duration 28.9+ months) and 9 are in relapse (median duration of remission 10.3 months). Of the 2 patients who failed and 9 who relapsed, 4 expired and 6 are living in partial or complete remission. We conclude that MOPP therapy is well tolerated, has effectiveness, and allows postponement of potentially debilitating radiotherapy in infants with brain tumors.
Improving the therapeutic ratio of craniospinal irradiation in medulloblastoma.
Radiation therapy delivered to the entire cerebrospinal axis is indicated for a number of pediatric brain tumors, especially medulloblastoma. Improved radiotherapy techniques have changed the near fatal prognosis for children with medulloblastoma to a 50%, 5-year survival. Nevertheless, the treatment results in substantial acute toxicity, and many survivors have serious sequelae. Further improvement in survival with optimal surgery and radiotherapy is not expected unless chemotherapy is added. Refinements in radiotherapy technique, however, can improve the therapeutic ratio of the treatment by lowering its side effects. In the last year children who required craniospinal irradiation at M. D. Anderson Hospital were treated with 6 MV photons to the brain and primary tumor and with 15-17 MeV electrons to the spinal canal. The elective dose to the whole brain was 30 Gy in 17 fractions and 30 Gy in 20 fractions to the spine. The primary tumor received an additional 20-25 Gy. An electron-beam dose distribution was drawn on a computerized tomography (CT) reconstructed sagittal plane. The electron energy was selected so that the 90% isodose line was at least 3 mm anterior to the cord after correction for bone heterogeneity. The treatment was well tolerated in the first five patients. It is projected that the current technique will cause fewer late effects and improve the tolerance to chemotherapy.
Immunologic evaluation in the nutritional assessment of children with cancer.
Eighty-one newly diagnosed untreated pediatric cancer patients (48 hematopoeitic malignancies, 17 solid tumors, 16 benign diseases) were evaluated with immunologic and nutritional parameters. The mean absolute lymphocyte count was adequate in the three groups. Reduced T-lymphocytes were seen in the solid tumors. Mitogenic response of hematopoietic and solid tumor patients' lymphocytes was low. Correlation of immunologic, dietary, and nutritional factors showed that for patients with solid tumors there was a positive significant correlation between weight/height percent and lymphocyte reactivity to phytohemagglutinin, concanavalin A, and pokeweed mitogen (p less than .05). Iron intake showed a significant positive correlation with in vitro mitogen reactivity for the solid tumor group (p less than .05) and benign diseases (p less than 0.01). Immune derangements found among patients with hematopoietic malignancies can be due to replacement of normal bone marrow with malignant cells. In solid tumor patients mitogen reactivity appears to be a reflection of nutritional state, and dietary iron is a possible factor.
Nutrition and cancer: physiological interrelationships.
There are many tumors that have paraneoplastic syndromes. Furthermore, location of certain tumors can result in very specific effects on the host, especially tumors in the hypothalamus, the intestinal tract, or the liver. Finally, tumors of the immune system can have significant distant consequences. However, from direct experimental evidence, from model systems, and from the utilization of nutritional manipulation in the treatment of cancer, the data suggest very strongly that there is no unique cancer malnutrition. Early diagnosed cancer does not show malnutrition as a presenting symptom. Furthermore, all metabolic disturbances can be explained on the basis of the metabolic differences of tumor cells and normal cells and are very frequently proportional to the bulk of the tumor. The cachexia that is associated with malignancies is more likely cachexia in cancer patients than it is a specific cancer cachexia, unless the tumor burden is very large. This point was clearly made in a short review of the causes of cachexia in nearly 1500 cancer patients in Russia (145). Brennan also feels that most cases of malnutrition are uncomplicated starvation, and cancer cachexia has many features seen in major injury or sepsis (16). This distinction has great implications in the management of cancer patients.
Medulloblastoma in infants and children: computed tomographic follow-up after treatment.
Thirty-six proven cases of medulloblastoma were reviewed by serial CT follow-up examinations from 4 months to 10 years, 2 months after the initial diagnosis, with a mean follow-up time of 3 years, 9 months. The children ranged in age from 10 months to 16 years, 7 months at the time of follow-up. The tumor recurred at the primary site in 20 cases (56%). Leptomeningeal metastasis was demonstrated on CT in 14 cases (39%); seven of these patients also presented with solid subarachnoid metastases. Thirteen patients (36%) showed evidence of severe brain atrophy, which was confined to the posterior fossa in seven of the 13. Calcification resulting from mineralizing microangiopathy developed in five cases (14%), including three patients who had extensive dystrophic calcification in the corticomedullary junction and the deep-seated nuclei of the cerebrum and cerebellum. Only one case of leukoencephalopathy was observed. The patterns of tumor recurrence in the posterior fossa that is severely deformed by surgery and other treatment modalities and leptomeningeal spread of tumor are discussed.
Medical and oncological management of pediatric brain tumors.
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Caring toward cure.
Care determines cure and, therefore, the mode of care dictates the outcome. The medical needs do not determine care, but rather define the reality within which the child has to live. Where that care is given to the child should be a haven, just as home ought to be a secure place to be oneself. The child participates in the therapeutic community as much as the child participates in the family. Therefore, the treatment environment of the child should be designed to foster caring toward cure. The care that is given will determine the truly cured child. The children must be allowed to be themselves so that they can be cared for and thereby their cure assured. To accomplish that, medical care must be incorporated into a normalizing, structured, therapeutic community wherein the child can exercise autonomy and the care givers, compassion.
Code of ethics for the University of Texas System Cancer Center M.D. Anderson Hospital and Tumor Institute.
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The physician's responsibility toward hopelessly ill patients.
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Nutrition in the treatment of cancer in children.
Most malnutrition in children is iatrogenic, which, like all iatrogenic complications, ought to be averted. Data showing the consequences of malnutrition on the outcome of the child with cancer is examined, with a recommendation made for taking the nutritional state of such a patient into account. Efficacy of nutritional intervention is discussed, as are the role of micronutrients. On these bases, the suggestion to treat malnutrition in the child with cancer is strongly urged.
FDA regulations as applied to research in cancer centers. Review of problems and possible solutions.
The Food and Drug Administration is charged to insure that the general public is not exposed to drugs that are either harmful or ineffective; yet, the regulations issued by the Food and Drug Administration are perceived to be in conflict with therapeutic human research. This article briefly reviews some considerations relevant to the problem. The regulations create both tensions and conflicts, but in themselves are reasonable exercises of the authority under which the FDA acts. However, regulations cannot be made either so general or so detailed that they will apply to all eventualities. A major problem is the degeneration of accountability and evaluation, from a compliance with the spirit of the recommendation to a compliance with documentation. When the review of compliance of documentation is done by inexperienced individuals, adversary relationships develop and the scientific and ethical problems are not addressed. A regulation that is meeting determined and widespread opposition is not enforceable unless it is subjected to continuous official scrutiny and to continuous coercion. The regulating agency must acquaint the regulated with the regulations, but must also convince the regulated of the necessity of the regulations. The research center serves to accentuate the differences and the problems that exist between the FDA and the research community, but is not unique in and of itself.
Confidentiality of medical records in pediatric cancer care. Myths, perceptions, and reality.
Confidentiality is a complex requirement and impossible to enforce within the scientific-medical setting. Legal constraints include a patchwork of federal, state, and local laws and regulations. The setting of the teaching hospital brings its own multifaceted breaches in confidentiality. Insurance and third party payment claims necessitate opening of the patient's records. But research medicine in particular broadly disseminates large amounts of detailed information about patients, creating a situation in which it is not possible to avoid revealing the patient's identity. A distinction must be made between the breach of confidentiality in connection with dissemination of the label of the diagnosis, and breach of confidentiality in relation to details of care and clinical investigation. The problem in relation to confidentiality of diagnosis is intimately entwined with the patient's self-concept. The problem in connection with details of care and clinical investigation is the consequence of the antipathy between the physician-scientist-investigator and the physician-healer-priest. These two roles are not truly compatible and, therefore, the problem of confidentiality could be greatly alleviated if the records for those two separate roles (clinical investigator and personal physician) were kept separately.
The truly cured child and the Tower of Babel.
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