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Biomedical subjects

L E Kun

Publications and source records attributed to L E Kun.

At least 19 recordsLinked to original sources
PubMed1992

Neuraxis dissemination in pediatric brain tumors. Response to preirradiation chemotherapy.

Of 29 consecutive children treated for malignant primary tumors of the central nervous system (CNS) at this institution, postoperative examination showed radiographic or cytologic evidence of neuraxis dissemination in 10 (34%). Given the historically poor results in disseminated CNS tumors treated with surgery and radiation therapy alone, these ten patients were treated prospectively with an investigational Phase II protocol consisting of preirradiation cisplatin (90 mg/m2 on day 1) and etoposide (150 mg/m2 on days 3 and 4). The diagnoses included medulloblastoma (n = 4), malignant glioma (n = 3), cerebral primitive neuroectodermal tumor (n = 1), pineoblastoma (n = 1), and mixed glioma of the brainstem (n = 1). Postoperative neuraxis scanning with computed tomography, magnetic resonance imaging, or spinal myelography showed measurable intracranial or spinal metastases in all children. The cerebrospinal fluid (CSF) cytologic examination was positive for tumor cells in five. The best responses, based on serial imaging of neuraxis metastases, included two complete responses, four partial responses, and three stable disease states. One patient had progressive disease at the primary site despite stable disease in the spine; progressive neuraxis disease was documented in only one patient during chemotherapy. Clearance of tumor cells from the CSF was documented in three patients. The adverse effects of chemotherapy, consisting of transient myelosuppression and mild ototoxicity, were minimal. Reversible neurologic deterioration occurred in two patients; one patient became acutely quadriplegic after a prolonged convulsive seizure without radiographic evidence of tumor progression.

Adolescent↗
PubMed1992

Long-term survivors of leukemia treated in infancy: factors associated with neuropsychologic status.

PURPOSE: Because of concerns about late toxicities of treatment among infants diagnosed with acute lymphoblastic leukemia (ALL), and especially the effects of cranial radiation therapy (CRT), we compared the functional and neuropsychologic status of 26 long-term survivors of ALL who were diagnosed in the first 24 months of life versus 26 children who were treated previously for Wilms' tumor. PATIENTS AND METHODS: Of the children with ALL, CNS prophylaxis included no CRT in six, 18 Gy CRT in five, 20 Gy CRT in seven, and 24 Gy CRT in five. Three additional children experienced CNS relapse and received total CRT doses of 24, 40, and 44 Gy. All children received neuropsychologic testing; children with ALL also participated in diagnostic imaging studies. RESULTS: As a group, the children who were treated for ALL did not differ significantly from those who were treated for Wilms' tumor on objective measures of global functional status. However, children treated for ALL had a significantly lower mean intelligence quotient (IQ) (87 v 96), poorer performance on four of six measures of visual and auditory memory, lower achievement with regard to arithmetic skills, and a greater frequency of special educational intervention than those who were treated for Wilms' tumor. IQ and auditory memory performance in the ALL group was correlated inversely with time since the completion of therapy and total CRT dose. CONCLUSIONS: These results reinforce the contemporary trend of prophylactic CRT omission in very young children except for those who are at risk for CNS relapse. For infants and very young children who require CRT, evidence is presented that supports the approach for the delay of CRT until the child is older.

Adolescent↗
PubMed1991

Importance of histologic condition and treatment of pediatric cerebellar astrocytoma.

Histologic classification and treatment of pediatric cerebellar astrocytomas is an area of controversy. At the Medical College of Wisconsin, 34 patients less than 15 years of age (median, 7.3 years of age) with cerebellar astrocytomas were seen from 1965 to 1988. Effect of histologic condition and treatment on overall survival (OS) and progression-free survival (PFS) was analyzed. Progression was defined as radiographic evidence of an enlarging mass and/or signs and symptoms indicative of advancing disease. Histologic material was reviewed and classified by the system of Winston and Gilles. Twenty-eight patients had glioma A tumors, and six patients had glioma B tumors. For patients with glioma A (n = 28), 5-year actuarial OS rate was 100%. For patients with glioma B (n = 6), 5-year actuarial OS rate was 41%. PFS rate was 66% and 0% for patients with glioma A and glioma B, respectively. The poorer PFS for patients with B histologic tumors was statistically significant (P less than 0.001). The median time to progression was 36 months and 23 months for patients with glioma A and B, respectively. Patients were retrospectively divided into total resection and observation, total resection and irradiation, subtotal resection and observation, and subtotal resection and irradiation groups, which were composed of 12, 2, 3, and 17 patients, respectively. Five-year actuarial OS rates were 100%, 50%, 50%, and 100%, respectively. PFS rates were 60%, 50%, 33% and 58%, respectively. These data support the Gilles classification as a prognostic tool because patients with B tumors had a higher incidence of disease progression and accounted for all deaths. Postoperative irradiation after subtotal resection seems to be beneficial, but additional investigation, ideally with a prospective randomized trial, will be necessary to firmly establish this.

Adolescent↗
PubMed1991

Cranial nerve palsy in childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma.

Forty-five children with acute lymphoblastic leukemia or non-Hodgkin's lymphoma had cranial nerve palsy (CNP) as a complication of their disease. Twenty-two of these children had CNP initially and 23, at relapse, with or without previous hematologic relapse. Only one of the 23 patients with CNP at relapse was a long-term survivor. In contrast, 11 of the 22 children who had CNP initially survived in remission for 3+ months to 13+ years. Two factors are associated with an improved outcome for patients with CNP at diagnosis: treatment after 1979 (P less than 0.004) and male gender (P less than 0.01). Patients who received radiation therapy fared better than those for whom radiation was not given (disease-free survival at 2 years 53% versus 29%). The authors conclude that CNP signifies an aggressive or advanced disease requiring intensive systemic chemotherapy and that the role of irradiation should be examined for this group of patients.

Child↗
PubMed1991

Concomitant cisplatin and hyperfractionated external beam irradiation for advanced malignancy of the head and neck.

The combination of cisplatin and hyperfractionated external beam irradiation (HEBI), followed by salvage surgery when indicated, was evaluated in patients with advanced stage squamous cell carcinoma of the head and neck. Thirty patients with stage III (n = 5) or IV (n = 25) disease received intravenous cisplatin 100 mg/m2 by 6-hour continuous infusion on days 1, 21, and 42 of HEBI. Radiation fractions of 110 cGy were given twice daily, separated by 4 to 6 hours, beginning within 12 hours after cisplatin delivery. Doses to the primary site ranged from 60 to 76.35 Gy (median: 72.3 Gy), with 60 to 74 Gy to nodal sites. Follow-up ranged from 4 to 28 months (median: 19 months). Clinical complete response of the primary site was seen in 27 of 29 patients (93%), and complete clinical clearance of adenopathy in 20 of 26 (76%). A second biopsy 6 to 8 weeks after completion of treatment showed residual disease in both the primary and nodal sites in three patients, and in only the primary site in one patient. Four patients with persistent adenopathy had pathologic confirmation at surgery. Four patients had recurrence after negative biopsy results 6 to 9 months after treatment biopsy. At present, with median follow-up of 19 months, eight patients (26%) have died secondary to uncontrolled primary or nodal disease. Two patients have died of nonrelated causes. Overall, 10 of 30 patients (66%) remain alive with no evidence of disease. Mucositis and weight loss were the most common side effects of treatment. Seven patients developed significant xerostomia, and four have cisplatin-related hearing loss requiring amplification. The early evidence of excellent response (89% pathologic complete response of primary sites; 78% complete response of nodal sites), coupled with acceptable treatment morbidity, warrants further study of this approach.

Adult↗
PubMed1991

Ewing's sarcoma: local tumor control and patterns of failure following limited-volume radiation therapy.

Sixty children with localized osseous Ewing's sarcoma were treated between 1978 and 1988 with induction chemotherapy (cyclophosphamide, adriamycin), irradiation and/or surgery, and 10 months of maintenance chemotherapy (cyclophosphamide, adriamycin, dactinomycin, vincristine). Following induction chemotherapy, 43 patients received primary radiation therapy to limited radiation volumes defined by post-chemotherapy residual soft tissue tumor extension and initial osseous tumor extent. Irradiation was defined as low dose at 30-36 Gy (median 35 Gy) for 31 cases with objective response to induction chemotherapy and high dose at 50-60 Gy (median 50.4 Gy) for 12 patients with poor response to induction chemotherapy or with tumors greater than or equal to 8 cm. Overall event-free survival at 5 years is 59% and local tumor control is 68%. Initial failures have been local (12), simultaneous local and distant failures (7), and distant (6). In the surgical resection group, 14 patients had complete resection without radiation therapy, and 3 patients had microscopic residual plus 35-41 Gy; 100% local control has been maintained. In 43 patients with primary radiation therapy group, local tumor control is 58% (p = .004). Despite limited radiation volume, 18/19 local failures occurred centrally within the bone, well within the radiation volume. Imaging response to induction chemotherapy predicted local tumor control in the radiation therapy group: 62% with complete response/partial response versus 17% with no response/progressive disease (p less than 0.01). Local tumor control related strongly to primary tumor size in the radiation therapy group; among 31 cases receiving 35 Gy, local tumor control is 90% for lesions less than 8 cm versus 52% for tumors greater than or equal to 8 cm (p = .054). The central pattern of local failure in this experience suggests the effectiveness of limited radiation volume. The overall local tumor control rate following the tested dose level of 35 Gy appears to be inadequate, although results in selected cases with tumors less than 8 cm in greatest tumor dimension indicate potential efficacy in a yet limited experience.

Adolescent↗
PubMed1991

Ewing's sarcoma. Radiotherapy versus surgery for local control.

Significant strides in the treatment of Ewing's sarcoma, the second most common bone tumor of childhood, have resulted in cure for approximately 50% of patients. Successful therapy requires systemic chemotherapy for the eradication of microscopic or overt metastatic disease and surgery or irradiation therapy for control of the primary lesion. The article debates the controversy over the extent to which surgical resection should play a role in the local management of this disease.

Bone Neoplasms↗
PubMed1991

Radiotherapy improves the outlook for patients older than 1 year with Pediatric Oncology Group stage C neuroblastoma.

Children older than 1 year of age who have neuroblastoma with complete or partial removal of the primary tumor and positive intracavitary lymph nodes (Pediatric Oncology Group [POG] stage C) are a small but higher-risk subset of patients. To further evaluate the importance of identifying patients with POG stage C neuroblastoma and to assess the efficacy and toxicity of adding concurrent radiation therapy (RT) to chemotherapy (CT) in these children, a randomized study was conducted. Eligible patients received cyclophosphamide 150 mg/m2 orally days 1 to 7 and Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) 35 mg/m2 intravenously (IV) on day 8 (CYC/ADR) every 3 weeks for five courses with or without RT to primary tumor and regional lymph nodes (24 to 30 Gy/16 to 20 fractions). Second-look surgery was advised to evaluate response and to remove residual disease. Continuation therapy alternated CYC/ADR every 3 weeks with cisplatin 90 mg/m2 day 1 followed by teniposide 100 mg/m2 day 3 (CDP/VM) for two courses each. Secondary CT with CDP/VM alone was available for patients not achieving complete response (CR) following induction treatment and second-look surgery. Of 29 eligible patients randomized to CT alone, 13 achieved CR, and nine are disease-free (NED) 1 to 52 months (median, 35 months) off therapy. Twenty-two of 33 eligible cases treated with CT/RT attained CR, and 19 are NED 1 to 77 months (median, 23 months) off therapy. Local and metastatic relapses occurred in both arms. Differences in CR, event-free survival, and survival rates were significant, P = .013, .009, and .008, respectively. Surgical compliance was excellent and complications uncommon. Therapy was tolerable in both groups but hematopoietic toxicity was more common in the CT/RT arm. We conclude that POG stage C neuroblastoma in children older than 1 year of age is a higher-risk group that should be identified, that CT/RT provides superior initial and long-term disease control compared with CT alone in this patient subset, and that the occurrence of metastatic failures in both treatment groups suggests a need for more aggressive chemotherapy.

Adolescent↗
PubMed1991

Radiation therapy. Trends in treatment.

Newer techniques of radiation therapy seek to improve the therapeutic ratio in childhood brain tumors by adding potentially more effective treatment in ways that will limit radiation toxicities. In tumors marked primarily by local disease progression, the use of interstitial brain implantation "up front" or radiosurgery deserves systematic exploration. Whether local "boost therapy" with either of the latter techniques will add substantially to disease control and preserve neurologic function remains to be established both in malignant CNS tumors and in low grade gliomas. Radioactive colloids offer a potentially effective means of managing cystic tumors in children. Primary use in selected presentations (e.g., cystic astrocytomas or craniopharyngiomas in young children) is being tested in addition to trials addressing recurrent or progressive cystic lesions. The concurrent use of irradiation and radiosensitizing agents, especially cisplatin or the fluorocarbon emulsions is under investigation in pediatric tumors. Assessment of comparative efficacy and potentially heightened toxicities is important. There is considerable enthusiasm among all those caring for children with brain tumors to study modifications of radiation delivery that may result in improved treatment. Rapid accrual to an increasing number of prospective institutional or cooperative group trials should allow more informed decisions regarding the selection of newer radiation therapy modalities in the future.

Brachytherapy↗
PubMed1990

Myeloid neoplasia in children treated for solid tumours.

Therapy-related myeloid neoplasia developed 14 to 189 months after diagnosis of the primary malignancy in 12 out of 3365 children treated for malignant solid tumours; 6 of the 12 were in their first complete remission. The 10-year cumulative incidence of myeloid neoplasia was 1.3% (95% Cl 0.5-3.6) for the 447 patients with Hodgkin's disease, 1.3% (0.4-4.3) for the 420 with non-Hodgkin lymphoma, and 1.2% (0.3-5.2) for the 440 with neuroblastoma. This complication appeared in 1 of 180 children with brain tumours and in none of the 1878 with other malignancies. Risk of therapy-related myeloid neoplasia in patients with Hodgkin's disease was associated with recurrence of the primary malignancy, a combination of radiotherapy and chemotherapy with alkylating agents, and age greater than or equal to 12 years at diagnosis of Hodgkin's disease. Of the 8 patients who underwent chromosomal analysis of neoplastic myeloid cells, 2 showed complete loss of chromosome 7 and 4 showed t(9;11) or t(8;21) with or without del(16)(q22). The 2 patients who had received an epipodophyllotoxin had an 11q23 abnormality. The risk of therapy-related myeloid neoplasia is low in children with malignant solid tumours.

Adolescent↗
PubMed1990

Wilms' tumor: reduced-dose radiotherapy in advanced-stage Wilms' tumor with favorable histology.

Fifty-two children with favorable histology Wilms' tumor who had residual abdominal disease (Surgical Stages III and IV) were treated from 1979 to 1988 on a protocol designed to assess the effectiveness of reduced radiation doses. All patients received three-agent chemotherapy, beginning within 1 week after surgery. To permit assessment of disease response to initial chemotherapy, radiation therapy was delayed for a median of 28 days after surgery (range, 14-71 days). Total doses of abdominal radiation were limited to 12 Gy, given as 150 cGy daily fractions; 18 patients with Stage IV disease received 12 Gy bilateral pulmonary irradiation. Two year disease-free survival was 85% and 71% for Stage III and IV, respectively (p = .24). Abdominal relapses occurred in 3 cases (5.7%). The interval between surgery and initiation of irradiation was not related to disease-free survival. Of several patient and disease-related factors analyzed, only patient age was related to outcome. Disease-free survival was 100% at 3 years for children under the age of 3 versus 78% for children greater than age 3 (p = .05). Reduced-dose abdominal radiotherapy in conjunction with multi-agent chemotherapy and surgery provided excellent disease control with minimal toxicity in advanced-stage, favorable histology Wilms' tumor.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Changes in MR signal intensity and contrast enhancement of therapeutically irradiated soft tissue.

Increased MR signal intensity was observed on T2-weighted, STIR, and Gadolinium-DTPA-enhanced T1-weighted images of subcutaneous and muscular soft tissue in 9 of 10 children treated with combination chemotherapy and radiation therapy (RT) for malignancy in the pelvis or an extremity. Total radiation doses ranged from 59.5 to 65 Gy. Eight of the patients with these changes received hyperfractionated RT (seven for Ewing sarcoma and one for perineal rhabdomyosarcoma); one was treated for pelvic hemangiopericytoma with once-daily fractions. Evidence of soft tissue damage became apparent as early as the sixth week of RT and was seen for up to 69 wk post-RT. There was no clear MR evidence of RT-induced soft tissue damage in one patient, who underwent hyperfractionated RT for pelvic rhabdomyosarcoma. Other MR findings in this group included evidence of bladder wall thickening in three of the seven patients given pelvic RT and increased T1-weighted signal of irradiated marrow in nine patients. All patients had clinical evidence of skin, soft tissue, or epithelial radiation effects. Increased MR signal intensity secondary to RT-induced damage can be differentiated from widespread tumor by geometric borders that conform to the margins of the radiation field.

Adipose Tissue↗
PubMed1989

Pediatric nasopharyngeal carcinoma: long term follow-up of 29 patients.

Twenty-nine untreated children diagnosed with nasopharyngeal carcinoma were consecutively admitted to St. Jude Children's Research Hospital from 1962 to 1986. The age of the patients ranged from 6 to 19 years (median of 13) at diagnosis. Histologically, all had lymphoepithelioma. Patients were retrospectively staged in the American Joint Committee System. Disease extent was T1 (n = 5), T2 (n = 7), T3 (n = 9), T4 (n = 8); N0 (n = 1), N2 (n = 7), N3 (n = 21). Two patients had distant metastasis (M1) on admission, both ultimately succumbed to their disease. Twenty-seven patients were seen initially without metastatic disease: one received pre-irradiation vincristine, 17 were treated with concomitant radiotherapy and cyclophosphamide. From 1981 to the present, four patients received pre-irradiation and one received post-irradiation cisplatin-bleomycin, vinblastine (CDDP-BLEO-VLB) regimens. Four patients received radiotherapy alone. All patients completed chemotherapy and radiation therapy. Twenty-five patients had complete tumor clearance and four had a partial response. Overall, 14 patients are alive continuously without relapse with a median follow-up of 11 years (range 4 to 20). All patients who relapsed did so within 2 years postirradiation. Four patients failed locally--all had advanced (T3-T4) local disease at presentation and three of the failures were at the margin of treatment portals. Thirteen patients failed with distant metastasis. The major prognostic factor in these patients was the local extent of disease. Among the 27 M0 patients, all ten patients with T1-2 tumors are disease-free, whereas four of nine patients with T3 and two of eight patients with T4 tumors are alive and well. In the 16 patients who are long term survivors, eight have mild neck atrophy, two have shortening of the clavicles; except for one patient who required a neck brace for shoulder drop, all had normal function. Among the seven pre-pubertal patients who are long term survivors, three have decreased growth, including one with documented decreased growth hormone. Two patients developed irregular menstrual periods. One patient developed hypothyroidism, and another had a thyroid adenoma. One patient developed bleomycin pneumonitis and one patient who received pre- and post-irradiation chemotherapy died of laryngeal edema and fibrosis, in remission. Radiotherapy is the major modality in the therapy of childhood nasopharyngeal carcinoma. The long term toxicity of radiotherapy plus or minus chemotherapy is acceptable. In early stage tumors (T1-2, N1-2), radiotherapy alone (55-60 Gy) appears to be sufficient for disease control.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗