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Biomedical subjects

L F Sinks

Publications and source records attributed to L F Sinks.

At least 19 recordsLinked to original sources
PubMed1986

Intermediate dose methotrexate in childhood acute lymphoblastic leukemia resulting in decreased incidence of testicular relapse.

Six hundred thirty-four children with acute lymphoblastic leukemia (ALL) were randomized to receive sanctuary therapy consisting of either cranial irradiation (CRT) plus intrathecal (IT) methotrexate (MTX) or three courses of intermediate-dose methotrexate (IDM) plus intrathecal methotrexate. Two hundred sixty-six male patients achieved a complete response and were evaluable for the effects of prophylactic therapy on the duration of remission. There was one isolated testicular relapse (0.8%) in the IDM group compared with 14 (10%) in the CRT group. The incidence of testicular relapse was significantly lower in the patients treated with IDM (P less than 0.001). High plasma levels of MTX achieved during the 24-hour infusions may result in increased penetration of MTX into the interstitium of the testes, thus allowing for the eradication of sequestered leukemic cells and preventing the emergence of drug resistance resulting from exposure to sublethal concentration of MTX.

Actuarial Analysis↗
PubMed1986

Adjuvant adriamycin and cisplatin in newly diagnosed, nonmetastatic osteosarcoma of the extremity.

Twenty-two patients with newly diagnosed nonmetastatic osteosarcoma of the extremity were treated with an adjuvant chemotherapeutic regimen consisting of Adriamycin (Adria Laboratories, Columbus, Ohio) and cisplatin. Fourteen of the 22 patients remain continuously disease free for 65+ to 113+ months, with a median time on study of 70+ months. The 72-month disease-free survival estimate is 64%. Pulmonary metastases occurred in six patients, an isolated stump recurrence was seen in one patient, and one patient had a local recurrence following a limb-salvage procedure. For those patients in whom pulmonary metastases developed, the onset was late in three of six, and the number of metastases was three or fewer in all patients. Two patients with pulmonary metastases and one with a stump recurrence have apparently been salvaged, thus resulting in a 77% 72-month survival. Toxicity observed in patients treated with this regimen was in keeping with previous reports. This chemotherapeutic regimen is effective in the adjuvant therapy of nonmetastatic osteosarcoma of the extremity. It should be incorporated into other adjuvant protocols in an effort to continue to improve the outcome in patients with osteosarcoma.

Adolescent↗
PubMed1985

The influence and reliability of neurologic assessment and Karnofsky performance score on prognosis.

The neurologic examination is important in the early diagnosis of brain tumors in children. Only in brain stem gliomas may the neurologic examination be better than computed tomographic scans in determining the progression. However, in general, the traditional neurologic examination has little or no value for prognosis. Reversible, associated features of brain tumors such as seizures or increased intracranial pressure may alter the patient's ability to function neurologically, but may not influence the prognosis regarding the tumor status. The Karnofsky functional status, to a large extent, reflects an adult's ability to work and has prognostic value but is largely inapplicable to children. Thus, a quality-of-life scale for children is needed.

Adult↗
PubMed1985

Toward the development of a play performance scale for children (PPSC).

Performance scales (i.e., Karnofsky), as they measure quality of life, have been used effectively as an integral part of repeated assessment of adult cancer patients for the last several years. An equally concise measure of performance has not been developed for children. The task of developing a scale to assess performance in infants, toddlers, school-age children, and adolescents is formidable, as the activity measured should be of equal merit at each age level. Although all childhood cancer patients could benefit from a simple-to-administer, rapid assessment, children with brain tumors have the greatest need for a repeated measure of performance. The goal, then, is to develop a simplified set of criteria that can be used for assessment of children with brain tumors during hospitalization, at the time of clinic visits, and/or at the time of diagnostic procedures when the patient is in a reasonable state of health. The assessment should be able to performed by nonprofessional persons.

Adolescent↗
PubMed1983

Comparison of intermediate-dose methotrexate with cranial irradiation for the post-induction treatment of acute lymphocytic leukemia in children.

We compared two regimens with respect to their ability to prolong disease-free survival in 506 children and adolescents with acute lymphocytic leukemia. All responders to induction therapy were randomized to treatment with 2400 rad of cranial irradiation plus intrathecal methotrexate or to treatment with intermediate-dose methotrexate plus intrathecal methotrexate, as prophylaxis for involvement of the central nervous system and other "sanctuary" areas. Patients were then treated with a standard maintenance regimen. Complete responders were stratified into either standard-risk or increased-risk groups on the basis of age and white-cell count at presentation. Among patients with standard risk, hematologic relapses occurred in 9 of 117 given methotrexate and 24 of 120 given irradiation (P less than 0.01). The rate of central-nervous-system relapse was higher in the methotrexate group (23 of 117) than in the irradiation group (8 of 120) (P = 0.01). Among patients with increased risk, radiation offered greater protection to the central nervous system than methotrexate (P = 0.03); there was no difference in the rate of hematologic relapse. In both risk strata the frequency of testicular relapse was significantly lower in the methotrexate group (1 patient) than the radiation group (10 patients) (P = 0.01). Methotrexate offered better protection against systemic relapse in standard-risk patients and better protection against testicular relapse overall, but it offered less protection against relapses in the central nervous system than cranial irradiation.

Adolescent↗
PubMed1983

Ependymoma, glioblastoma, and acute leukemia in a child.

A 5-year-old boy developed an ependymoma; 3 years later, after chemotherapy and radiotherapy, he developed glioblastoma multiforme and acute myeloblastic leukemia. His maternal grandmother had died at a young age of colon cancer. Since ependymoma is not known to predispose to other cancers, the unusual sequence of malignant disease may have been due to combined therapy in a susceptible host.

Brain Neoplasms↗
PubMed1983

Liposomal methotrexate in the treatment of murine L1210 leukemia.

To assess the therapeutic effectiveness of methotrexate (MTX) when administered in a liposome carrier, mice bearing intracranial L1210 leukemia were tested with liposomal MTX, free MTX, or saline. Single i.p. injections of liposomal MTX at doses of 5 mg/kg and 2.5 mg/kg prolonged survival of mice bearing intracranial L1210 leukemia. The same doses of the free drug did not prolong survival of the tumor-bearing mice. This system may have clinical application not only for MTX, but also other polar anticancer agents in the treatment for central nervous system malignancy.

Animals↗
PubMed1980

Comparison of three methods of central-nervous-system prophylaxis in childhood acute lymphoblastic leukaemia.

A retrospective comparison was made of three methods of central-nervous-system prophylaxis in childhood acute lymphoblastic leukaemia; (1) intrathecal methotrexate only; (2) intermediate-dose methotrexate infusion and intrathecal methotrexate and, (3) 2400 rads cranial irradiation and intrathecal methotrexate. The incidence of primary meningeal relapse was statistically significantly lower in both standard-risk patients (age grear than 24 months and less than or equal to 120 months white-cell count less than 20,000) and increased-risk patients (age less than or equal to 24 months or greater than 120 months and/or white-cell count greater than 20,000) whose central-nervous-system prophylaxis included cranial irradiation. The disease-free and overall survival of irradiated increased-risk patients was significantly better than that of unirradiated increased-risk patients. The disease-free survival of standard-risk patients who received intermediate-dose methotrexate was statistically superior to that of the remaining standard-risk patients. There were no significant differences in overall survival between the three groups of standard-risk patients.

Adolescent↗
PubMed1979

Combination chemotherapy in recurrent medulloblastoma.

Five children with recurrent medulloblastomas were treated with Vincristine, BCNU, Methotrexate and Dexamethasone. All five patients responded to therapy. Two of the patients are alive and well 30 and 48 months later; one died of disease 19 months after first recurrence; one developed a further recurrence at 18 months but responded to additional chemotherapy and is alive; and the fifth patient developed a second recurrence after 28 months but has responded to repeat chemotherapy and radiotherapy and is now asymptomatic. These results support the concept that medulloblastomas are sensitive to chemotherapy and suggest that chemotherapy should be considered in cases of recurrent medulloblastomas. In addition, the importance of trials now in progress which employ both adjuvant chemotherapy and radiotherapy in newly diagnosed medulloblastomas is apparent.

Adolescent↗
PubMed1979

Intermediate dose methotrexate (IDM) in childhood acute lymphocytic leukemia (ALL).

We employed three courses of intermediate dose Methotrexate (IDM) added onto a standard induction and maintenance program with the concept of both central nervous system (CNS) prophylaxis and simultaneous systemic intensification. Cranial radiation (RT) was not employed as CNS prophylaxis. Fifty of 52 patients (to age 18) achieved complete remission. Time on study now ranges from 22-68 months with a median time of 33 months. We separated the children into standard risk and increased risk. We defined increased risk as a WBC over 30 000/mm3 at presentation and an age of less than two years or greater than 10 years at presentation. There have been 15 relapses on these 50 patients; 11 occurred in increased risk patients (of 22 increased risk patients) and four occurred in standard risk patients (of 28 standard risk patients). There were seven CNS relapses, six systemic relapses, one simultaneous systemic and CNS relapse and one testicular relapse. Toxicity to the IDM was small with the worst problem being mucositis. No leukoencephalopathy occurred. The control of hematological relapse is excellent and the avoidance of potential long-term complications notes is even of greater importance.

Adolescent↗
PubMed1979

Correlation between volumetric CT imaging and autopsy measurements of glioblastoma size.

A three-dimensional reconstruction and display technique (THREAD SYSTEM) for serial computed tomography (CT) was employed in monitoring tumor volumes in two children under chemotherapy for glioblastoma multiforme of the cerebral hemispheres. Progressive diminution of tumor bulk was documented in the first patient and an increase in volume in the second. The first patient expired of the complications of his therapy and the second of transtentorial herniation. Independent measurements of the tumors as determined by a CT scan near the times of death and tumor dimensions measured at autopsy revealed good correlations between the radiographic and the anatomical data. The final CT measurement of tumor volume of 20 cm3 compared with an autopsy calculation of 13.3 cm3 in the first case. In the second case, CT volume was 417 cm3 and the actual volume of the primary tumor mass at autopsy was 437 cm3. The results suggest that the THREAD system is a practical method for monitoring the results of radiotherapy and chemotherapy in certain types of cerebral neoplasms.

Adolescent↗
PubMed1978

Non-Hodgkin's lymphoma in children.

Until recently the prognosis of childhood non-Hodgkin's lymphoma has been poor. A program of combination chemotherapy and involved area radiotherapy was instituted in the Department of Pediatrics at Roswell Park Memorial Institute in 1971. Thirty-one biopsy proven untreated children entered this study. There were 4 Stage I, 9 Stage II, 6 Stage III, and 12 Stage IV. Initial site of presentation was neck and mediastinum in 16, abdomen in 12, and other sites in three. Nineteen were lymphocytic, seven histiocytic, three undifferentiated, and one was mixed. None had well differentiated or nodular histology. Chemotherapy consisted of vincristine and steroid induction along with intrathecal methotrexate followed by a maintenance phase consisting of daily oral 6-mercaptopurine, weekly oral methotrexate and monthly pulses of vincristine, cyclophosphamide and steroid. Because of initially poor results in Stage IV disease, the protocol was altered midway and high dose methotrexate on three occasions following induction was added. Twelve of 13 Stage I and II patients remain disease free. Four of 6 Stage III patients and 4 of 12 Stage IV patients remain disease free. Only 1/7 of the Stage IV patients prior to high dose methotrexate is disease free, whereas, 3/5 patients with high dose methotrexate are disease free. In total, 19/30 (63%) are disease free for a period ranging from 15+ to 63+ months with 19 patients being disease free for over one year and 12 for over two years.

Adolescent↗
PubMed1978

Chemotherapy in recurrent noncystic low-grade astrocytomas of the cerebrum in children.

Six children with grade II astrocytomas were treated with combination chemotherapy consisting of 1,3 bis(2-chloroethyl) 1-nitrosourea (BCNU). Vincristine (VCR), intrathecal Methotrexate (i.t. MTX), and Dexamethasone. Of the children, 3 showed a partial remission, and 1 other showed clinical improvement. Our data suggest that chemotherapy is effective in low-grade astrocytomas, and there is now a need for larger trials in low-grade astrocytomas to document the role of chemotherapy accurately in these tumors. It is suggested that trials of chemotherapy as adjuvant to surgery and radiotherapy should be initiated.

Antineoplastic Agents↗
PubMed1978

Profound radiosensitivity in "leukemic" T-cell lines and T-cell-type acute lymphoblastic leukemia demonstrated by sodium [51Cr]chromate labeling.

Radiation sensitivity was determined by measuring spontaneous release from 51Cr-labeled cells in various lymphoid cell populations. Among six leukemia T-cell lines originating from acute lymphoblastic leukemia, four such lines were found to be highly radiosensitive. In contrast, two of the leukemic T-cell lines and four normal control B-cell lines were not radiosensitive. Thymocytes from six patients and leukemia T-cell blasts from three patients with T-cell leukemia were likewise found to be highly radiosensitive, whereas leukemic blasts from six patients with null-cell (non-T, non-B-cell) acute lymphoblastic leukemia were not radiosensitive. Normal peripheral blood lymphocytes and mitogen-induced normal lymphoblasts were found not to be radiosensitive. The results indicate that measurement of the radiation sensitivity of acute leukemic blasts may have a therapeutic significance in coping with the heterogeneous nature of individual leukemia cases.

Animals↗
PubMed1978

cis-Dichlorodiammineplatinum (II) in advanced osteogenic sarcoma.

Eight patients with advanced metastatic osteogenic sarcoma were treated with cis-dichlorodiammineplatinum(II) (DDP). Prior to DDP, seven patients had amputations and all had received adjuvant adriamycin (ADR) therapy. In addition, prior to DDP, six patients had received high-dose methotrexate. There was one complete response (pulmonary metastases) and four partial responses (three metastases in the lungs and one in the bone). One additional patient, with local recurrence of osteogenic sarcoma of the mandible following initial resection and adjuvant ADR, was retreated with surgery and DDP and is disease-free for greater than 3 years. The cumulative dose ranged from 300 to 660 mg/m2. Toxicity included irreversible kidney damage in two patients, transient severe hematologic suppression in two patients, and nausea and vomiting in all patients. DDP is a new effective agent in the treatment of osteogenic sarcoma.

Adolescent↗