Biomedical subjects

H O Hustu

Publications and source records attributed to H O Hustu.

At least 19 recordsLinked to original sources

PubMed1996

Outcome in 43 children presenting with metastatic Ewing sarcoma: the St. Jude Children's Research Hospital experience, 1962 to 1992.

The purpose of this work was to review the St. Jude Children's Research Hospital experience of patients presenting with metastatic Ewing sarcoma over a 30-year period. Forty-three of 212 cases of Ewing sarcoma presented with metastases at diagnosis. These patients were analyzed to determine whether primary tumor site or size, metastatic site(s), or advances in therapy have had a positive impact on survival. The overall survival for our 43 patients was 35% (95% confidence intervals, 20% to 50%). Comparing patients treated prior to 1979 with those treated after 1979, the overall survival was significantly different (P = 0.0002). Comparing overall survival between pelvic and non-pelvic primaries (P = 0.24), among metastatic sites (P = 0.83), and between tumors measuring > 8 cm in diameter to tumors measuring < 8 cm in diameter (P = 0.12), no significant differences were observed. Approximately one-third of patients presenting with metastatic Ewing sarcoma may achieve long-term survival. Children with metastatic Ewing sarcoma may benefit from clinical trials which intensify the doses of doxorubicin, and the highly effective combination of ifosfamide/etoposide.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1996

Treatment outcome and dose-response relationship in infants younger than 1 year treated for retinoblastoma with primary irradiation.

Thirty-three infants ( < 1 year at diagnosis) were treated for retinoblastoma with primary irradiation at St. Jude Children's Research Hospital (SJCRH) between 1963 and June 1992. Staging of the 44 treated eyes was as follows: Reese-Ellsworth (R-E) Groups I (n = 20), Group II (n = 9), Group III (n = 6), Group IV (n = 2), Group V (n = 7). Irradiation was delivered using either a single anterior field (31 eyes) or lens-sparing techniques (13 eyes). Total doses ranged from 21-45 Gy (median = 36 Gy) in fractions of 150-180 cGy (n = 34) or > 180 cGy (n = 10). One child died of metastatic disease at 42 months. Three patients have developed second malignant neoplasms; two have succumbed at 88 and 125 months post-RB diagnosis; the remaining patients are alive at 6-259 months postdiagnosis (median follow-up = 127 months). Local control with irradiation alone and supplemented cryotherapy given within 2 months (n = 2) was maintained in 29 eyes, with no statistical difference seen for total doses < or = 36 Gy (21/8 eyes) vs. > 36 Gy (8/16). Of 15 eyes that required salvage therapy, tumor control has been maintained in 13. Enucleation was required for four patients, two with recurrent retinoblastoma and one with a phthisical eye. Cataract formation was documented in 23 eyes (87.5%) treated with lens-sparing techniques developed cataract. At last follow-up, 23 of 30 patients tested (77%) had visual acuity of 20/100 or better. This experience confirms early observations in that doses > or = 36 Gy do not appear to improve local control with irradiation alone in infants ( < 365 days) with retinoblastoma.

Cryotherapy↗

PubMed1995

Survival outcome following isolated central nervous system relapse treated with additional chemotherapy and craniospinal irradiation in childhood acute lymphoblastic leukemia.

PURPOSE: An analysis of survival outcome following isolated central nervous system (CNS) relapse treated with craniospinal irradiation (CSI) and additional chemotherapy in children with acute lymphoblastic leukemia (ALL) was conducted. METHODS AND MATERIALS: Eighteen of 344 pediatric patients with ALL who attained initial complete remission on the St. Jude Children's Research Hospital "Study XI" prospective protocol (1984-1988) developed a CNS relapse as first adverse event. Median interval to isolated CNS relapse was 7.5 months (range = 2-40 months) after achieving initial complete remission. At diagnosis, 14 of the 18 children were categorized as "high risk" for subsequent leukemic relapse. Preventive cranial irradiation [PCI (18 Gy)] was delivered as planned to one of the 14 "high-risk" children. The other 13 "high-risk" patients experienced a CNS relapse during the first year of continuation therapy prior to week 52 of planned PCI. All four "low-risk" patients experienced a CNS relapse beyond the first year of continuation therapy; none were scheduled to receive PCI. Following isolated CNS relapse, all 18 patients were treated on a prospective contingency of "Study XI" trial consisting of intensified reinduction chemotherapy, weekly intrathecal methotrexate/hydrocortisone/Ara-C x 4-6 injections, craniospinal irradiation (cranium to 24.0 Gy and spine to 15.0 Gy at 1.5 Gy/fraction) and maintenance systemic therapy for a minimum of 1 year. RESULTS: Ten of 18 patients remain in continuous complete secondary remission at 17 to 50 months post-CNS relapse. Second sites of relapse in the remaining eight children were as follows: CNS in four, bone marrow in three, and bilateral testicular in one patient. Each of these eight patients died of progressive leukemia. At a median followup of 40 months post-initial CNS relapse, the 3-year secondary Kaplan-Meier survival and event-free survival are 72% and 56%, respectively. Minimal long-term neurotoxicity was associated with the treatment regimen. The most important prognostic factors predicting continuous secondary remission included white blood cell count at diagnosis (p = 0.05), and duration of initial remission (p = 0.04). CONCLUSION: This trial demonstrates that more than one-half of patients may be successfully salvaged with intensified chemotherapy and craniospinal irradiation without significant morbidity following an isolated CNS relapse, despite previous multiagent chemotherapy though virtually no prior PCI in childhood ALL.

Adolescent↗

PubMed1995

Use of irradiation for therapy of retinoblastoma in children more than 1 year old: the St. Jude Children's Research Hospital experience and review of literature.

Fifteen children (> 1 year old at diagnosis) were treated for retinoblastoma (RB) with primary irradiation at St. Jude Children's Research Hospital between January 1963 and January 1992. Staging of the 19 treated eyes was as follows: Reese-Ellsworth (R-E) Groups I and II, n = 7; Group III, n = 3; Group IV, n = 1; Group V, n = 7; information on one globe is incomplete. Total dosage ranged from 25 to 45 Gy (median = 40 Gy) in fractions of 170-225 cGy delivered 5 x/week (n = 13) or 225-265 cGy delivered 4 x/week (n = 4 eyes) or x 5/week (n = 2 eyes). Treatment techniques included anterior field (n = 11) or lens-sparing technique (n = 8). One patient has died of progressive central nervous system (CNS) disease at 13 months; one patient succumbed to second malignant neoplasm within the irradiated field at 194 months; the remaining 13 patients remain alive from 27 to 301 months (median = 178 months). Local control with irradiation alone has been maintained in 12 eyes. Four eyes with local recurrence were salvaged using cryotherapy or reirradiation. Enucleation was required for three eyes for progressive disease at 4, 7, and 7 months postirradiation. Cataract formation was documented in nine eyes treated with anterior fields and in one patient treated with lens-sparing technique. At last follow-up, 7 patients had visual acuity of 20/100 or better. Radiation dose of 40 Gy appears to be adequate for local control of early stage RB (R-E Groups I-III and VB whose tumors are R-E Groups I-III) in patients > 1 year old. The results of this limited series which has lengthy follow-up is compared with the results of previously published data in an effort to define the benefits and disadvantages of the different treatment techniques which have been reported in the treatment of RB in children > 1 year old.

Cataract↗

PubMed1995

Chest wall resection for Ewing's sarcoma of the rib: an unnecessary procedure. 1988. Updated in 1995.

Approximately 10% of all cases of Ewing's sarcoma arise from a rib. Conventional management has included chest wall resection (3 or more ribs) and radiation therapy. These forms of therapy have led to complications such as scoliosis and local deformity. The addition of radiation therapy can result in damage to the lung and adjacent viscera and also potentiate pulmonary restrictive disease. Between 1971 and 1978, 9 patients were treated with surgery, radiation therapy, and combination chemotherapy (three- or four-drug regimen). Only 2 patients (22%) survive. Since 1979, 14 patients were entered into a new protocol consisting of sequential induction chemotherapy, followed by delayed surgical resection whenever feasible. Three patients had complete resection of their primary lesion at onset. Initially, 7 patients had either biopsy (N = 4) or incomplete chest wall resection N = 3). All 4 patients with biopsy only at diagnosis had excellent responses to induction chemotherapy, allowing delayed resection of the involved rib without chest wall resection. Overall, 12 of 14 patients (86%) treated since 1979 survive, with only 2 receiving radiation therapy for residual disease in the primary rib site.

Bone Neoplasms↗

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↗

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↗

PubMed1989

Primary lymphoma of bone in children.

Primary lymphoma of bone (PLB) occurs infrequently in children. Between January 1962 and November 1988, 395 children with non-Hodgkin's lymphoma (NHL) were treated at St. Jude Children's Research Hospital. Eleven of these patients (2.8%) presented with a bone primary, usually in the femur (eight of 11 patients). The median age of these seven boys and four girls at presentation was 13 years (range, 5.5 to 19 years). Seven patients had one or more additional bones involved. All patients had high-grade lymphomas based on the National Institutes of Health (NIH) Working Formulation. The histologic subtypes included six large-cell lymphomas, three lymphoblastic lymphomas, one small-noncleaved, non-Burkitt's lymphoma, and one unclassifiable lymphoma. Treatment consisted of multiagent chemotherapy combined with local radiation therapy in seven of 11 patients. Six of 10 children who received chemotherapy as a component of their initial therapy, including all who presented with localized tumor, are alive with no evidence of disease 2+ to 85+ months (median, 42.5 months) after cessation of treatment; one patient has just completed chemotherapy. Each of the four patients who died showed leukemic conversion 5 to 11 months after diagnosis, and three died of progressive disease. One patient died of sepsis during chemotherapy-induced neutropenia with no evidence of disease at necropsy. We conclude that optimal therapy for PLB, as with all other forms of NHL, should focus on the histologic subtype and stage of disease.

Adolescent↗

PubMed1988

High-dose methotrexate improves clinical outcome in children with acute lymphoblastic leukemia: St. Jude Total Therapy Study X.

High-dose methotrexate (HDMTX, 1,000 mg/m2) and cranial irradiation/sequential chemotherapy (RTSC) were compared for ability to extend complete remission durations in children with acute lymphoblastic leukemia (ALL). Three hundred thirty patients were enrolled in the study, according to our criteria for standard-risk ALL: a leukocyte count less than 100 X 10(9)/L, no mediastinal mass, no leukemic involvement of the central nervous system (CNS), and blast cells lacking sheep erythrocyte receptors and surface immunoglobulin. Prednisone-vincristine-asparaginase induced complete remissions in 95% of the patients, who were then randomized to receive either HDMTX (n = 154) or RTSC (n = 155). HDMTX was administered with intrathecal MTX for the first 3 weeks following remission induction, and then every 6 weeks with daily mercaptopurine (MP) and weekly oral MTX for a total of 18 months. The RTSC regimen consisted of 1,800 cGy cranial irradiation and intrathecal MTX for 3 weeks, followed by MP/MTX, cyclophosphamide/doxorubicin, and teniposide/cytarabine administered sequentially over 18 months. The final 12 months of treatment for both groups was MP and oral MTX; all patients received intrathecal MTX every 12 weeks. With a median follow-up of 5 years, complete remission durations have been significantly longer among children treated with HDMTX, compared with RTSC (P = .049) or historical institutional control regimens (P = .002). Approximately 67% of the patients receiving HDMTX and 56% of those receiving RTSC are expected to be in continuous complete remission at 4 years. Overall, isolated CNS relapse rates were similar (P = .17) in the two treatment groups, although by newer risk criteria cranial irradiation could be expected to provide better protection in patients with an unfavorable prognosis. These findings indicate that addition of intermittent HDMTX infusions to conventional chemotherapy is an effective method for extending complete remissions in children with ALL.

Child↗

PubMed1988

Chest wall resection for Ewing's sarcoma of the rib: an unnecessary procedure.

Adolescent↗

PubMed1988

Reduced therapy for Wilms' tumor: analysis of treatment results from a single institution.

From 1968 to 1986, 192 patients from 0 to 17 years of age were enrolled in three consecutive protocol-controlled studies of Wilms' tumor at St Jude Children's Research Hospital. Tumors were completely excised at the time of diagnosis whenever possible, and patients were subsequently treated with chemotherapy and radiotherapy according to the initial extent of disease. All patients received dactinomycin and vincristine, with doxorubicin added to the regimens in studies 2 and 3. Chemotherapy was extended to 18 months in study 2 (n = 53), but was limited to 12 months for most patients in study 3 (n = 107). In the third study, radiation was eliminated altogether for patients with stage I or II tumors and was reduced to 12 Gy for those with more advanced disease. Intensification of chemotherapy in study 2 improved the 5-year relapse-free survival rate over that in study 1 (82% v 52%), but the accompanying increase in toxicity was considered unacceptable. Comparison of 2-year relapse-free survival rates in studies 2 and 3 indicated that the reduction of therapy in the latter trial did not jeopardize disease control: 88% v 86% for patients with stage II or III disease, favorable histology; 75% v 57% for the same stages, unfavorable histology; and 57% v 61% for stage IV patients. At least 80% of all patients enrolled in study 3 will be long-term survivors. We conclude that rescheduling of effective antitumor drugs and eliminating or reducing radiotherapy are feasible alternatives in the treatment of Wilms' tumor with favorable histologic features.

Adolescent↗

PubMed1988

Significance of pulmonary computed tomography at diagnosis in Wilms' tumor.

Pulmonary lesions were found by computed tomography (CT) despite normal chest roentgenograms (CXR) at diagnosis in 11 of 124 patients with Wilms' tumor. All patients were entered on a treatment protocol at St Jude Children's Research Hospital from 1978 to 1986. The 11 patients all had favorable histology Wilms' tumor. Staging and therapy were based on interpretation of the CXR and abdominal findings. Excluding CT findings, one patient had stage I disease, two stage II, seven stage III, and one stage IV on the basis of multiple liver metastases. Four patients have relapsed: one with stage II and three with stage III. All relapses have been pulmonary. Overall, 4/11 (36%) relapsed. This relapse rate is considerably greater than the 20% overall relapse rate of patients treated according to this protocol though not statistically significant. These relapses suggest that such patients may be at increased risk for pulmonary recurrence. The results also indicate that small lesions initially noted only on CT scans of the chest in children with Wilms' tumor frequently represent metastatic tumor. Further studies of larger numbers of patients will be necessary to confirm these findings.

Antineoplastic Agents↗

PubMed1987

Challenges in the treatment of childhood fibromatosis.

Between 1968 and 1985, we treated 20 children for fibromatosis (also called desmoid tumor and aggressive fibromatosis). The primary sites included head and neck (seven patients), extremity (seven patients), and trunk (six patients). Lesions ranged from 3 to 18 cm in diameter. The tumors were smaller than 5 cm in 13 patients, and in seven patients they were larger than 5 cm. A total resection was not feasible in any of the patients with lesions larger than 5 cm. Ten of the 11 patients treated with wide local resection, in whom the margins were clearly negative or close, remained free of disease for six to 16 years. Nine patients required additional treatment with radiotherapy (nine patients) and chemotherapy (five patients). Two died of local disease progression. In the remaining seven children, the disease was controlled. We describe our strategies for managing this disease in a pediatric population.

Adolescent↗

PubMed1987

The impact of delayed surgery on radiotherapy dose and local control of rhabdomyosarcoma.

To determine if delayed surgery permits the modification of radiotherapy dose while maintaining local control in children with localized, unresectable rhabdomyosarcoma, a prospective study was launched in 1981 to test this objective. Treatment consisted of 16 weeks of preoperative chemotherapy, with or without delayed surgery, and radiotherapy using 35 to 40 Gy (3500 to 4000 rad) for microscopic and 50 to 55 Gy (5000 to 5500 rad) for gross residual tumor, plus 14 months of chemotherapy. Among 22 patients treated, surgery was feasible in 11 of 14 patients with residual tumor after chemotherapy and was performed in eight (avoiding radical surgery in three), leaving microscopic (seven patients) or gross residual (one patient) tumor. Progressive disease or amputation precluded radiotherapy in two patients. After radiotherapy local control was sustained in 12 of 14 patients with microscopic lesions vs none of six patients with gross tumor. Delayed surgery may permit the use of lower-dose radiotherapy and should be considered in the treatment plan for this subset of patients.

Adolescent↗

PubMed1987

Long-term survival in patients with Ewing's sarcoma relapsing after completing therapy.

While the proportion of patients with Ewing's sarcoma attaining and maintaining long-term remission has markedly improved, a proportion of patients suffer relapse of the tumor. In our experience relapses may occur late in the course of the disease, approximately 20% of those at risk beyond 5 years having recurrence of tumor. Review of our data indicates that for patients relapsing after therapy has been discontinued, the probability of attaining second remission is high (0.84) and that a significant proportion of these patients attaining second complete remission will survive their disease (0.60).

Child↗

PubMed1987

Mandibular third molar development after mantle radiation in long-term survivors of childhood Hodgkin's disease.

Sequential panoramic radiographs were assessed for mandibular third molar development in 47 long-term survivors of childhood Hodgkin's disease after treatment with 37 Gy mantle field radiation. To make a comparison, panoramic radiographs of 149 healthy, nonirradiated children were reviewed for the presence of mandibular third molars. In children between the ages of 7 and 12 years, bilateral agenesis of mandibular third molars was more frequent in patients who had been treated with mantle radiation than in nonirradiated patients. Unilateral agenesis, crown hypoplasia, and root growth impairment of mandibular third molars were also found. Similar, apparent, radiation-induced developmental anomalies were noted in maxillary third molars of the irradiated patients.

Abnormalities, Radiation-Induced↗

PubMed1987

Ocular relapse in the anterior chamber in childhood acute lymphoblastic leukemia.

We reviewed 11 cases of ocular relapse in the anterior chamber in children with acute lymphoblastic leukemia (ALL), representing 0.5% of all primary relapses seen at this center. Nine patients had hypopyon, and two had iris involvement only. Concomitant testicular relapse was present in two children and hematologic relapse in one. Ocular relapse occurred at 12 to 74 months (median, 36 months) from the data of initial diagnosis. Children who relapsed after therapy was discontinued did so within 1 year of completing therapy. Topical steroids and systemic chemotherapy were administered to all patients with ocular relapse; four also received radiation to the involved eye (600 to 1,050 cGy). Four children, each with a prolonged initial complete remission, remain free of disease for 15+, 32+, 34+, and 145+ months following anterior chamber relapse; three had received radiation therapy. Five patients died of recurrent leukemia, and two of infection while in remission. Aggressive retreatment appears warranted in cases of anterior chamber relapse of ALL, as some of these children may attain prolonged new remissions.

Adolescent↗

PubMed1987

Teniposide plus cytarabine improves outcome in childhood acute lymphoblastic leukemia presenting with a leukocyte count greater than or equal to 100 x 10(9)/L.

Childhood acute lymphoblastic leukemia with an initial leukocyte count greater than or equal to 100 X 10(9)/L responds poorly to conventional chemotherapy. To extend event-free survival (EFS) in this disease, we devised a protocol that specifies intensive 2-week courses of teniposide (VM-26, 165 mg/m2) plus cytarabine (ara-C, 300 mg/m2), before and immediately after standard 4-week remission induction therapy with prednisone, vincristine, and L-asparaginase. The VM-26 and ara-C combination was also administered intermittently for the first year of continuation treatment with oral 6-mercaptopurine and methotrexate. CNS prophylaxis consisted of periodic intrathecal (IT) injections of methotrexate and delayed cranial irradiation. At a median follow-up of 4 years, the estimated EFS rate for 57 consecutive patients with leukocyte counts of 100 to 1,000 X 10(9)/L was 44%, compared with 10% for matched controls (P less than .001). Remission induction rates in the two groups were similar (82% v 72%, P = .16). Twenty-five patients in the VM-26/ara-C group have survived without adverse events for 2.7 to 6.8 years, whereas only nine of the controls achieved more than a year of EFS. The most common complications during early treatment were acute hyperkalemia from rapid tumor cell lysis and infections due to prolonged marrow aplasia. Continuation chemotherapy was well tolerated. We conclude that VM-26 plus ara-C, added to each phase of an otherwise basic regimen of chemotherapy, will substantially improve prognosis in this high-risk form of childhood leukemia.

Antineoplastic Combined Chemotherapy Protocols↗