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Biomedical subjects

H O Hustu

Publications and source records attributed to H O Hustu.

At least 37 records · Page 2Linked to original sources
PubMed1987

Metastatic Ewing's sarcoma: remission induction and survival.

Eighteen patients with previously untreated metastatic Ewing's sarcoma (ES) entered a protocol designed to evaluate the response rate to cyclophosphamide and doxorubicin induction therapy delivered before delayed surgery and delayed lower dose, limited-field radiation therapy, (RT), and maintenance chemotherapy. With chemotherapy and delayed surgery, 14 of 18 were rendered free of gross tumor. RT was delivered to the primary site of 11 of these responding patients, plus four of those not free of gross disease. Following RT, two more attained complete clinical remission. Site of primary or metastases did not influence outcome; however, the size of the primary at diagnosis did appear to do so. Ten patients remain disease-free 16 to 82 months (median, 47 months) from diagnosis.

Adolescent↗
PubMed1986

Mediastinal nonlymphoblastic lymphomas in children: a clinicopathologic study.

The records of 25 pediatric patients with mediastinal nonlymphoblastic lymphoma (NLBL) were reviewed. These patients comprise approximately 5% of all patients with non-Hodgkin's lymphoma (NHL) in the pediatric age group. There were 15 females and ten males. The median age was 13.5 years (range, 2 to 19). Most patients presented with symptoms attributable to a large mediastinal mass, and superior vena cava syndrome was a common feature. Disease was localized to the supradiaphragmatic area in 17 patients (71%) at diagnosis. Pathologic review revealed 22 of these lymphomas to be diffuse histiocytic type in the Rappaport classification, and 20 were large-cell immunoblastic type in the Working Formulation. Treatment regimens were not uniform, but included multiagent chemotherapy in 23 patients and radiation to the mediastinum in 20 patients. Twenty-three patients (92%) attained a complete remission (CR). Of these, 17 (74%) remain disease-free 13 to 65 months from diagnosis (median, 43 months). No CNS relapses have been observed. Mediastinal NLBL in the pediatric age group has distinctive clinicopathologic features that warrant special consideration in the design of treatment protocols.

Adolescent↗
PubMed1986

Therapy for childhood soft-tissue sarcomas other than rhabdomyosarcoma: a review of 62 cases treated at a single institution.

The rarity and diverse characteristics of the nonrhabdomyosarcomatous soft-tissue sarcomas (NRSTS) in children have hindered study of their clinical presentations and response to therapy. Here we describe the findings of a retrospective analysis of 62 cases of NRSTS seen in a single institution from 1962 through 1983. The most common histopathologic diagnosis was synovial sarcoma, occurring in 18 patients, followed by malignant schwannoma in 12. The median age at diagnosis was 11 years (range, 2 months to 20 years). Anatomic sites of primary tumors were the trunk (28), extremity (24), and head and neck (10). Of the 31 patients whose tumors were completely resected, 26 (84%) survive with no evidence of disease. Postoperative chemotherapy, administered to nearly one half of this group, did not produce any demonstrable gains in survival. Only one of the 26 patients with local or metastatic gross tumor after resection survives. We conclude that an aggressive surgical approach is imperative in patients with NRSTS and that the contribution of other treatment modalities needs to be defined in a collaborative group trial.

Adolescent↗
PubMed1985

Central nervous system morbidity following an initial isolated central nervous system relapse and its subsequent therapy in childhood acute lymphoblastic leukemia.

The frequency and types of major CNS toxicity and morbidity were analyzed in 107 children with acute lymphoblastic leukemia (ALL) following an isolated primary CNS relapse. Seventy-nine (73%) have had multiple subsequent marrow or CNS relapses requiring intensive and prolonged therapy to the CNS. Median survival time is two years. Of these 79 patients, two thirds have had one or more types of major CNS toxicity, including epileptiform seizures (35), moderate to severe structural abnormalities (24 of 27 evaluated), major motor disabilities (9), blindness (2), CNS infection (6), cranial nerve palsies (2), and intracranial lymphoma (2). The remaining 28 patients (26%) have had no or one additional CNS relapse and have received therapy for a median of eight years. One half of this surviving group of patients have had major CNS toxicity, including seizures (9), major motor disability (2), and intracranial calcifications (12/19). When neuropsychologic evaluations were compared between the 28 survivors and 50 of their contemporaries who had been in initial continuous complete remission, the CNS survivors had significantly lower Full Scale IQ scores (83 +/- 16 v 99 +/- 14, P = less than .001) with similarly lower measures of academic performance. The relative contributions of meningeal leukemia itself and intrathecal or radiation therapy to these effects cannot be determined. Since major CNS sequelae occurred in the majority of patients who had a primary isolated CNS relapse, and the frequency of CNS relapse is dependent on the efficacy of the method of CNS prophylaxis, the best method of avoiding major CNS sequelae is the most effective form of CNS prophylaxis.

Acute Disease↗
PubMed1985

Tooth root growth impairment after mantle radiation in long-term survivors of Hodgkin's disease.

The tooth root growth impairment that resulted from 35 to 37 Gy mantle port radiation in 47 long-term survivors of childhood Hodgkin's disease was quantified and related to specific age groups and categories of teeth. Root measurements of the mandibular permanent canines, first and second premolars, and first and second molars were made from sequential panoramic radiographs taken at the time of radiation therapy and after the closure of root apexes. The severity of root growth impairment was greatest in patients who received radiation during the early stages of odontogenesis. With later stages of odontogenesis, and as the age increased at the time of treatment, less impairment occurred. The potential difficulties of using repeated panoramic radiographs to assess tooth lengths in longitudinal studies also were discussed.

Adolescent↗
PubMed1985

Advanced stage (III-IV) Burkitt's lymphoma and B-cell acute lymphoblastic leukaemia in children: kinetic and pharmacologic rationale for treatment and recent results (1979-1983).

Since 1979, we have treated a total of 29 children with advanced-stage B-cell tumours (diffuse undifferentiated, small non-cleaved cells): 18 stage III and three stage IV, according to a clinical staging classification (Murphy, 1980), and eight with B-cell acute lymphoblastic leukaemia (B-ALL). Treatment has been based upon appreciation of rapid tumour growth kinetics and has consisted of high-dose fractionated cyclophosphamide courses, vincristine, adriamycin and infusions of cytosine arabinoside (Ara-C) with intrathecal chemotherapy. The first 12 patients (1979-1981) received, in addition, superfractionated radiotherapy (twice a day) to the involved field (22.5 Gy) and the craniospinal axis (18 Gy). Since January 1981, radiation therapy has been omitted, and subsequent patients have received the same agents as above plus high doses of methotrexate coordinated with the escalating doses of Ara-C infusions. Toxicity has consisted mainly of universal, severe but reversible haematopoietic suppression with attendant febrile episodes. Complete-remission rate for all 29 patients has been 86%, with three early failures due to progressive disease and one death from infection. Overall disease-free survival for children with stage III disease has been excellent (78%). Initial involvement of central nervous system (CNS) and/or marrow is grave: none of three patients with stage IV lymphoma and only one of eight with B-ALL is surviving off therapy without evidence of disease, suggesting a need for alternative therapies for these cases. Results are significantly better than our historical institutional experience.

Adolescent↗
PubMed1984

Isolated testicular relapse in acute lymphocytic leukemia of childhood: categories and influence on survival.

Isolated testicular relapse complicating first hematologic remission was identified in 31 of 521 boys with acute lymphocytic leukemia (ALL). Three categories of involvement were apparent and could be related to presenting clinical features, duration of initial complete remission, and length of hematologic remission. Among 12 patients with early testicular relapse, most had unfavorable prognostic features when ALL was first diagnosed. All but two of these children experienced marrow recurrence within seven months of testicular relapse. In contrast, the 12 patients who developed testicular disease late in their clinical course have responded much better to further therapy; ten remain in bone-marrow remission for a median of four years beyond testicular relapse. Similarly, five of the seven patients with subclinical testicular leukemia, found at elective biopsy, continue in marrow remission for prolonged periods. Early testicular recurrence is a sign of drug-resistant disease; late recurrence after elective cessation of therapy may represent residual, incompletely treated but still responsive leukemia.

Adolescent↗
PubMed1984

Failure of late intensification therapy to improve a poor result in childhood lymphoblastic leukemia.

This clinical study, begun in 1975, tested the efficacy of early and delayed intensification treatments in children with acute lymphoblastic leukemia. Regardless of presenting features, all patients received 4 weeks of conventional induction therapy with daily prednisone and weekly vincristine and daunorubicin. One-third were randomized to receive, in addition, two doses of asparaginase during induction therapy, while another one-third received four doses of both asparaginase and cytarabine after remission induction. Preventive central nervous system therapy uniformly included 2400 rads cranial irradiation and five doses of intrathecal methotrexate. Remissions were maintained with daily p.o. mercaptopurine and weekly i.v. methotrexate. Of the 277 assessable patients, 254 (92%) entered complete remission, and 102 (37%) remain clinically free of leukemia for 4.6 to 8.0 years (median, 6.3 years). The three treatment groups showed no significant differences in either remission induction rate or outcome, even when the analysis was based on risk assignment. A "late intensification" phase of therapy, added to the maintenance protocol for 65 patients who had been in continuous complete remission for 14 to 30 months, failed to extend remission durations, as judged from statistical comparison with matched controls (p = 0.84). When tested as a time-dependent covariate in the Cox proportional-hazards model, delayed intensification again showed no important effect on duration of complete remission. We conclude that limited early or aggressive late intensification of therapy, as described here, does not improve outcome in childhood acute lymphoblastic leukemia.

Adolescent↗
PubMed1983

Hydrocele formation in patients with Hodgkin's disease.

Hydroceles developed in 12 (7.7%) of 155 consecutive male patients who had Hodgkin's disease treated between 1962 and 1981. Except for one patient who had a hydrocele at diagnosis, all developed this complication during remission, 8 months to 7.5 years after inverted-Y or abdominopelvic 60Co irradiation (3000-3800 rad). Hydroceles were bilateral in five patients and on the right side in seven. No tumor was found in the hydrocele sacs of the ten patients who underwent hydrocelectomy. Lymphatic obstruction was evidenced by lymphatic dilation in the hernia sac in six patients. The authors believe postirradiation fibrosis of the lymphatic pathway was the main cause of hydrocele formation.

Adolescent↗
PubMed1983

Surgicopathologic staging of neuroblastoma: prognostic significance of regional lymph node metastases.

Of 254 children with neuroblastoma treated at St. Jude Children's Research Hospital, 102 (40%) had clinically localized tumors. Using a surgicopathologic staging system, 66 of these 102 children had localized tumor and 36 had tumor dissemination to regional lymph nodes. Survival of these two groups has been markedly different; 57 of 66 (87%) with localized tumor survive, compared with 11 of 35 (33%) with node dissemination, five of whom are less than two years from diagnosis. Our data indicate that the prognosis for children with neuroblastoma metastatic only to regional lymph nodes is no different from that of patients of similar age with widely disseminated tumor.

Age Factors↗
PubMed1983

The response of Ewing's sarcoma to sequential cyclophosphamide and adriamycin induction therapy.

Twenty-four consecutive patients with Ewing's sarcoma were treated in a protocol designed to deliver induction chemotherapy with postinduction surgical-pathologic evaluation of the primary tumor site. This was followed by delayed radiotherapy, the dose and port of which was dependent on the response to induction chemotherapy. All patients received 5 courses of sequential cyclophosphamide and adriamycin during the 3-mo induction period. Nineteen of 23 evaluable patients had no gross residual tumor following this therapy. Of the remaining 4, 2 had complete surgical excision of residual gross disease. Of the 22 patients who were free of gross tumor following induction chemotherapy and surgery, 5 received no radiotherapy, 16 received moderate-dose limited port radiotherapy (3000-3500 R), and 1 received high-dose limited port radiotherapy (5000 R). All 14 patients with localized disease attained remission and are surviving 9-41+ mo (median 21+) with 2 local recurrences occurring after 10 and 33 mo of remission. Of the 10 patients presenting with metastatic disease, 8 attained complete remission with 4 of the 8 remaining disease-free 12-34+ mo from diagnosis. This study indicates that Ewing's sarcoma is very sensitive to moderate-dose 2 drug chemotherapy of low toxicity and that it is possible to delay radiotherapy and any extensive surgical procedure until remission is induced.

Adolescent↗
PubMed1983

End results of treating children with localized non-Hodgkin's lymphomas with a combined modality approach of lessened intensity.

From 1978 to 1982, 28 children with localized non-Hodgkin's lymphomas, stages I and II, were treated with a combined modality protocol, reduced in intensity in comparison to our previous institutional protocol (1975-1978, reported in Cancer 45: 630-637, 1980), and modest by comparison to many current intensive regimens in widespread use. Induction consisted of vincristine (6 weekly doses, 1.5 mg/m2), cyclophosphamide (3 doses, on days 0, 21, and 42, 600 mg/m2 IV), and oral prednisone (40 mg/m2, daily for 1 mo) combined with low-dose, involved-field, supervoltage radiotherapy (2000 rads). Prophylactic treatment of the central nervous system was not given to all children, but only to those with primary tumors in the head and neck region, and consisted of intermittent intrathecal methotrexate only (12 mg/dose, three times in induction, and subsequently every 6 wk). Maintenance therapy, consisting of oral daily 6-mercaptopurine (75 mg/m2) and oral weekly methotrexate (30 mg/m2), was continued for a total duration of 15 mo from diagnosis. Overall, there were 15 children with stage I and 13 with stage II disease, and the majority of the cases (17 of 28) were localized to the head and neck. In addition, 7 children, all stage II, had completely resected gastrointestinal tumors; the other 4 cases presented in inguinal nodes. Histologically, 27 of the 28 tumors were high-grade diffuse (13 undifferentiated, i.e., small noncleaved cell type; 11 histiocytic, i.e., 5 large noncleaved cell type, and 6 immunoblastic type; and 3 lymphoblastic type); 1 case was mixed cell type, nodular and diffuse. All children were judged to be in complete remission at the end of induction, and 24 of 28 (85.7%) remain free of disease 4+ mo to nearly 4 yr from diagnosis (median 24+ mo); 19 have completed all planned therapy and are in unmaintained remission. The 4 cases failing therapy all were characterized by diffuse undifferentiated (small noncleaved cell) histology and exhibited regrowth of local tumor, resulting in a failure rate for this group (4 of 13, 30%) significantly different than for all remaining cases of other histologies (0 of 15), p less than 0.02 by log rank analysis. Patient tolerance to therapy was excellent, with negligible acute toxicity, and ambulatory outpatient management was the norm. Long-term follow-up will be necessary to judge whether adverse late consequences of treatment have been reduced by this approach. We conclude that a reduction in the intensity of therapy for children with stage I and II non-Hodgkin's lymphomas is feasible, apparently without significantly jeopardizing their excellent chance for cure.

Adolescent↗
PubMed1983

Second central nervous system prophylaxis in children with acute lymphoblastic leukemia who relapse after elective cessation of therapy.

A treatment plan to achieve better disease control in patients with acute lymphoblastic leukemia (ALL) who relapse after elective cessation of therapy was assessed. The principal modifications were (1) a second preventive treatment of the central nervous system (CNS) at relapse and every six weeks throughout therapy, using intrathecal methotrexate with cytosine arabinoside, and (2) a four-week course of systemic chemotherapy given immediately before therapy was stopped a second time. Twenty-four patients were studied. There have been no meningeal relapses, in contrast to seven among 16 similar patients who were retreated without CNS prophylaxis. Although the median length of second hematologic remission was not significantly different from the outcome in the comparison group, a much higher proportion of patients (eight of 24 versus zero of 17) remain in prolonged reinduced complete remission (48-79 months). Children whose first relapse occurred later than six months after cessation of therapy had significantly longer subsequent remissions. These end results establish the value of intrathecal CNS prophylaxis in relapsed ALL and suggest that a late intensive phase of therapy will extend remissions in a substantial proportion of patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1982

Metastatic epidural tumors in children.

Spinal cord compression is a rare but serious complication of malignant diseases in children. Epidural cord compression was noted in 81 patients within the past 17 years at this center. The complication developed at different times during the course of the primary disease. For 29 of our patients, cord dysfunction was one of the initial signs of cancer--Ewing sarcoma, neuroblastoma, Hodgkin disease, and malignant lymphoma. By contrast, for most of the patients with osteosarcoma and rhabdomyosarcoma, it appeared later in their clinical course. The treatment outcome of patients who were paraplegia with complete loss of sensory function for greater than or equal to 48 hours was poor. Only four of 22 in this group became ambulatory. Ten patients with osteosarcoma did not undergo laminectomies because they all had multiple metastases and terminal disease. Paraplegia developed in all ten. There was no difference in ambulatory rates among other patients, with or without laminectomies.

Child↗
PubMed1981

Sequential cyclophosphamide and doxorubicin for induction of complete remission in children with disseminated neuroblastoma.

When 70 children with disseminated neuroblastoma were treated for 4 months with a course of cyclophosphamide and doxorubicin (Adriamycin) 35 (52%) of 68 assessable patients achieved complete remissions, 13 had partial responses, and 20 had either less than a 50% regression of tumor or evidence of tumor progression. Of the 35 children with complete responses, three received local irradiation, but for the remainder, chemotherapy alone provided rapid control of tumor growth. Drug-induced toxicity caused the hospitalization of four of 17 infants and five of 52 older children, but was related to only two of the eight deaths that occurred during treatment. Infants less than 1 year of age were more likely to achieve a complete remission than were older children. That 52% of these patients achieved complete remissions represents a marked improvement over the 22% response rate for patients seen between 1962 and 1974. Of 35 patients with complete responses, 15 have survived, contrasted with only four of 33 patients achieving less than a complete response. Median survival for patients achieving a partial response was 14.4 months, compared to 8.4 months for patients not achieving a response. A kinetically based sequence of chemotherapy seems to produce a high rate of complete remissions in children with disseminated neuroblastoma. To consolidate this gain into curative treatment will require a continuation therapy to prevent the emergence of drug-resistant disease.

Adolescent↗
PubMed1981

Malignant germ cell tumors in 57 children and adolescents.

Fifty-seven patients with malignant germ cell tumors (GCTs) treated at our center between 1962 and 1979 were evaluated to determine 1) the prognostic value of disease stage, tumor histology, primary site, and patient age; 2) results of therapy; and 3) patterns of metastasis. The 35 girls and 22 boys were from 1 week to 18 years old (median 5 yr). Primary sites were ovarian (20), testicular (10), sacrococcygeal (12), retroperitoneal (7), mediastinal (5), and other (3). Cox regression analysis indicated that stage was the most important prognostic variable. Extragonadal tumors were usually advanced at diagnosis, but tumor site did not have prognostic value independent of disease stage. Neither patient age nor tumor histology significantly influenced outcome. Drugs active against malignant GCTs included vincristine, cyclophosphamide, and dactinomycin in combination and vinblastine, bleomycin, and cis-platinum. Radiation alone cured nondisseminated germinomas. The most common sites of metastasis were lungs, liver, central nervous system, and bone; other sites were infrequently involved. We conclude that stage was the most important prognostic variable, extragonadal tumors were usually advanced at diagnosis, and similarities in the histogenesis, metastatic pattern, and response to therapy, regardless of primary site, justify the consideration of childhood malignant GCTs as one group.

Adolescent↗