PubMed Health⌕ Search

Biomedical subjects

W H Meyer

Publications and source records attributed to W H Meyer.

At least 37 records · Page 2Linked to original sources

Comparison of primary osteosarcoma of flat bones with secondary osteosarcoma of any site.

BACKGROUND: The authors hypothesized that the outcomes for young patients who present with primary osteosarcoma of flat bones or secondary osteosarcoma after other primary malignancies are similar because the sites of these tumors rarely makes them amenable to complete surgical resection. METHODS: The authors reviewed their experience with 27 patients with primary osteosarcomas involving flat bones and 18 patients with secondary osteosarcomas of any site, evaluating treatment, metastatic patterns, and outcome. RESULTS: Eleven of the 27 primary osteosarcomas and 10 of the 18 secondary osteosarcomas were at least partially resectable at the time of initial diagnosis. At last follow-up, 10 of the 27 patients with primary flat bone osteosarcoma were alive, eight of whom were disease free. Three of 18 with the secondary osteosarcoma patients were alive, including one with locally recurrent disease after recent disease resections. Chemotherapy with single or combinations of agents rarely yielded responses for primary flat bone or secondary osteosarcomas. CONCLUSIONS: Outcome for both groups of patients was poor due to metastases and failure of local control. Sixteen of the 27 patients with primary osteosarcoma of flat bones died of their tumor; an additional patient died of doxorubicin-related cardiomyopathy and had microscopic disease in the primary site at autopsy. Thirteen of the 18 patients with secondary osteosarcoma died of their second metastatic cancer, 2 additional patients died of doxorubicin-related cardiomyopathy/coccidioidomycosis, and another of acute renal toxicity.

Adolescent↗

Second malignant neoplasms occuring in survivors of osteosarcoma.

BACKGROUND: Second malignant neoplasms have been noted infrequently in survivors of osteosarcoma treated before 1970. METHODS: For the above reason, the authors surveyed their patients to determine the actuarial incidence and relative risk of second malignancies among patients treated with adjuvant chemotherapy for osteosarcoma. RESULTS: Between March 1962 and March 1996, 334 patients received chemotherapy for newly diagnosed primary or metastatic osteosarcoma. Of these patients, 47 presented with metastases, 14 had multifocal osteosarcoma, and 273 had localized disease. Nine patients developed second malignant neoplasms 0.45-17.8 years (median, 6.3 years) after receiving definitive surgery and adjuvant chemotherapy for primary osteosarcoma; 2 of these patients had pulmonary metastasectomies before receiving adjuvant chemotherapy. The second neoplasms comprised two cases of malignant fibrous histiocytoma and one case each of melanoma, glioblastoma multiforme, chondrosarcoma, and carcinoma of the breast: stomach, colon, rectum. The overall 10-year cumulative incidence of second malignancies was 2% +/- 1%; by comparison, this rate was 2% +/- 1% for patients with localized osteosarcoma but was 8% +/- 5% (P = 0.15) for those who presented with metastatic disease. CONCLUSIONS: Since the advent of successful adjuvant chemotherapy, more patients are surviving primary osteosarcoma; therefore, the number of osteosarcoma patients who develop second malignancies can be expected to increase. Recognition of osteosarcoma patients who are members of families with Li-Fraumeni syndrome may lead to earlier intervention for these individuals.

Adolescent↗

Is primitive neuroectodermal tumor of the kidney a distinct entity?

BACKGROUND: Primitive neuroectodermal tumors (PNETs) constitute a family of neoplasms of presumed neuroectodermal origin, most often presenting as bone or soft tissue masses in the trunk or axial skeleton in adolescents and young adults. As a soft tissue neoplasm, PNET arising in the kidney has not been well described, with only three cases previously reported. METHODS: Four patients with PNET of the kidney were diagnosed and treated at St. Jude Children's Research Hospital. The authors reviewed the clinical, radiologic, and pathologic features and outcomes of these cases and of those previously described. RESULTS: The authors' patients were age 4-20 years. They presented with unilateral renal masses and metastatic disease in the lymph nodes (three patients), lungs (three patients), bone (two patients), liver (one patient), and bone marrow (one patient). Treatment included surgery, radiotherapy, and multiagent chemotherapy. Three of the patients died of progressive disease within 14 months of diagnosis. Features and outcomes were similar to those of the three previously reported cases. CONCLUSIONS: PNET of the kidney appears to be a distinct entity. Although rare, it must be included in the differential diagnosis of renal tumors in children and young adults. Patients usually present with advanced disease and show poor response to combined-modality therapy.

Adolescent↗

Phase I trial of subcutaneous interleukin-1 alpha in children with malignant solid tumors.

Interleukin-1 alpha (IL-1 alpha) is myeloprotective in a variety of animal models of cancer chemotherapy and is similarly beneficial in adults treated with carboplatin, 5-fluorouracil, and after autologous bone marrow transplantation. There are no trials of this agent in children. Our purpose was to determine the toxicity and maximum tolerated dose (MTD) of recombinant human interleukin-1 alpha (rhuIL-1 alpha) in children with solid tumors receiving intensive cancer chemotherapy and to evaluate its myelo-protective effects. Cohorts of patients received rhuIL-1 alpha in doses of 0.1-10 micrograms/m2 for 4 days by subcutaneous injection prior to ICF chemotherapy (ifosfamide, 2 g/m2/day x 3, carboplatin targeted to an area under the curve of 8 mg/ml x min on day 1, and etoposide, 100 mg/m2 daily for 3 days). Patients were randomized to receive rhuIL-1 alpha before either the first or second course of therapy. After the MTD of rhuIL-1 alpha was determined an additional group of patients received rhuIL-1 alpha at the dose immediately following ICE chemotherapy. The dose-limiting toxicities of rhuIL-1 alpha in the 27 children tested comprised systemic symptoms of fever, chills, headache, and hypotension. The MTD was 3 micrograms/m2/day. There were no differences in chemotherapy-induced hematologic toxicity with increasing doses of rhuIL-1 alpha or in comparisons before or after ICE chemotherapy. Although rhuIL-1 alpha can be given safely to children receiving myelosuppressive chemotherapy, clinical usefulness would mandate a significant hematopoietic benefit in view of the trouble some side effects identified. We saw no evidence of a hematoprotective effect.

Adolescent↗

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↗

Topoisomerase I interactive drugs in children with cancer.

Topotecan, irinotecan, and 9-aminocamptothecin (9-AC) are analogs of the plant alkaloid 20(S)-camptothecin (CMT), the prototypical DNA topoisomerase I interactive agent. These agents interact with the topoisomerase I-DNA complex and prevent resealing topoisomerase I-mediated DNA single-strand breaks. This eventual leads to double-strand DNA breaks and apoptosis or cell death. Topotecan, irinotecan, and 9-AC have shown significant activity in mice bearing pediatric solid tumor xenografts; the greatest antitumor responses were found with protracted continuous schedules. Preclinical data also suggest that maintenance of an exposure-duration threshold (EDT) may be required to achieve optimal cytotoxicity. Pediatric Phase I trials have evaluated the toxicity and safety to camptothecin analogs in children with relapsed solid tumors and relapsed acute leukemia. The primary dose-limiting toxicity (DLT) for the CMT analogs in children has been myelosuppression, except for mucositis observed with the 120-hr continuous topotecan infusion schedule. Pharmacodynamic relationships with these analogs have been reported between systemic exposure, and myelosuppression and mucositis. Although not a primary objective of the early Phase I studies, antitumor responses have been reported. In this review, the pharmacokinetic and pharmacodynamics of the CMT analogs studied in children are summarized, and future studies of these agents are discussed.

Animals↗

P-glycoprotein expression at diagnosis may not be a primary mechanism of therapeutic failure in childhood rhabdomyosarcoma.

PURPOSE: To evaluate the prognostic significance of tumor cell P-glycoprotein (Pgp) expression at diagnosis in children with rhabdomyosarcoma. PATIENTS AND METHODS: A panel of three anti-Pgp monoclonal antibodies (mAb) (C219, C494, and JSB-1) that recognize different Pgp epitopes was used to measure Pgp expression in rhabdomyosarcoma specimens obtained at diagnosis from 76 patients treated at St Jude Children's Research Hospital from 1969 to 1991. Two separate experiments using different immunohistochemical methods (immune alkaline phosphatase and immunoperoxidase) were performed to evaluate Pgp expression. The immunostaining was graded using a semiquantitative scale corresponding to the percentage of tumor cells with detectable staining. The influence of Pgp expression on outcome was assessed by the Kaplan-Meier method and Cox regression analysis with stepwise selection. The relationship between Pgp expression and clinical features was assessed using the Mantel-Haenszel method. RESULTS: Pgp expression at diagnosis did not predict worse overall survival or progression-free survival when tested in either experiment with C219, C494, or JSB-1 separately. No association was shown between Pgp expression and clinical features (clinical group, primary site, or histology) or response. However, in the immune alkaline phosphatase experiment, patients whose tumors had more than 10% tumor cell staining with all three mAbs had a significantly higher rate of estimated 5-year survival (78% +/- 10%) than did all other patients (38% +/- 8%; P = .025). In this instance, Pgp expression had independent prognostic value after adjusting for clinical group. CONCLUSION: We found no strong association between Pgp expression at diagnosis and clinical features or extent of disease in pediatric rhabdomyosarcoma. Depending on the criteria used to define it, high Pgp expression at diagnosis does not predict poor outcome. Although a large prospective study is needed to provide definitive conclusions, our findings suggest that Pgp-mediated multidrug resistance may not be a primary mechanism of therapeutic failure in rhabdomyosarcoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Outcome of treatment for childhood cancer in black as compared with white children. The St Jude Children's Research Hospital experience, 1962 through 1992.

OBJECTIVE: To determine whether there is a racial difference in prognosis among childhood cancers. DESIGN: An overall (30-year) survival analysis by race was followed by separate studies for "early" and "recent" treatment eras, defined by time points at which significantly improved outcome was demonstrated for specific tumor types. Stratified analyses were performed to adjust for recognized prognostic features. SETTING: Pediatric oncology research and treatment center. PATIENTS: The study included 798 black and 4507 white children with newly diagnosed malignancies treated from January 1962 through June 1992. These patients were accepted for treatment regardless of their financial status and were enrolled on disease-specific protocols. RESULTS: Across the 30-year study period, black children had a significantly poorer rate of survival than white children (P < .001, log-rank test). In the early treatment era, a significant difference was seen for all forms of cancer combined (P < .001), with 10-year Kaplan-Meier estimates (+/- SE) of 37% +/- 3% for black children and 50% +/- 1% for white children. This difference largely reflected the poorer prognosis of black children with the most common childhood cancer, acute lymphoblastic leukemia. In the recent treatment era, there were no significant differences in treatment outcome by race for specific disease categories or for all forms of cancer combined. Ten-year survival rates were 67% +/- 6% for black children and 66% +/- 3% for white children, indicating a significantly greater improvement in the former group. CONCLUSION: With equal access to effective contemporary treatment, black children with cancer fare as well as white children when treated with protocol-based therapy at a pediatric oncology research center.

Adolescent↗

A phase I study of sulofenur in refractory pediatric malignant solid tumors.

The diarylsulfonylureas have shown promise in xenograft models of childhood cancer. Sulofenur has been evaluated in phase I and II trials in adults with a variety of solid tumors, but the toxicity and maximum tolerated dose of sulofenur in children and adolescents have not been determined. In a phase I study, sulofenur was administered to 13 patients with refractory pediatric malignant solid tumors. Daily dosages of 640, 800, and 960 mg/M2 in two divided oral doses were given for 5 consecutive days each week for 3 weeks. The primary and dose-limiting toxicity was methemoglobinemia, which occurred at all dose levels and required transfusions of packed red blood cells, administration of methylene blue, or both. Anemia and, less frequently, leukopenia and thrombocytopenia were also observed. A maximum tolerated daily dosage was not defined, as methemoglobinemia was noted with each dosage level. There were no measurable tumor responses. The toxicity of this agent makes it unattractive for further investigation in pediatric patients.

Adolescent↗

Indications for hemiscrotectomy in the management of genitourinary tumors in children.

In the last 30 years at St Jude Children's Research Hospital, 10 boys have undergone hemiscrotectomy for primary testicular tumors or paratesticular rhabdomyosarcoma. Indications for this procedure were scrotal contamination and positive or uncertain surgical margins. Residual tumor was found in only one specimen. There were four complications in the study group. Two patients had complications directly attributable to the hemiscrotectomy, and in one patient this caused a delay in treatment. Preoperative imaging was performed in three patients. This has not been helpful in evaluating residual masses and is not indicated. Based on the authors' experience and a review of the literature, there are a number of indications for hemiscrotectomy in the management of genitourinary tumors in children. Controversies regarding some of these indications should be discussed with the families of these patients during preoperative counseling.

Adolescent↗

Molecular dynamics in stiff ionene below glass transition.

Temperature dependences of proton and fluorine second moments and spin-lattice relaxation time T1 below glass transition were measured in glassy "I-Do,Pip-Me-BF4" ionene. The existence of motions of methyl groups and segments linking the cationic centers, namely piperidinium rings and trimethylene groups, for the polymeric part of ionene were established. Isotropic rotation of the counter-ion was evidenced and its limited diffusion suggested. To interpret the proton and fluorine relaxation data, a Davidson-Cole distribution of correlation times was assumed.

Anions↗

Phase II study of 5-fluorouracil/leucovorin for pediatric patients with malignant solid tumors.

BACKGROUND: 5-Fluorouracil (5-FU) activity for various carcinomas of adults has been enhanced through the synergistic effect of leucovorin. Few pediatric studies of 5-FU in pediatric patients have been previously reported. METHODS: Fifty-eight patients were treated with a 4-hour infusion of leucovorin, 400 mg/m2, administered daily for 5 days every 3-4 weeks. 5-Fluorouracil was administered by bolus injection 1 hour into each leucovorin infusion. Eleven adolescent patients with colorectal carcinoma, Stage 3 or 4, were treated with therapeutic intent, and other patients with a variety of drug-resistant pediatric solid neoplasms received similar treatment. RESULTS: Patients with measurable disease of colorectal carcinoma responded favorably to 5-FU/leucovorin. Stable disease activity was seen with other tumor types. Specifically, there were no objective responses in 12 patients with Ewing's Sarcoma or 11 with osteosarcoma. There were 4 deaths in this study from causes related to toxicity. Nonfatal grade 3/4 toxicities included mucositis, rash, myelosuppression, nausea, vomiting, diarrhea, and infection. CONCLUSION: The authors do not plan further evaluation of 5-FU/leucovorin in additional pediatric patients with colon cancer or other heavily pretreated malignant solid tumors and are presently treating their patients with colon carcinoma with 5-FU/leucovorin/interferon-alpha 2a.

Adolescent↗

Phase I study of escalating targeted doses of carboplatin combined with ifosfamide and etoposide in treatment of newly diagnosed pediatric solid tumors.

BACKGROUND: The combination of carboplatin, ifosfamide, and etoposide has shown promising activity in a variety of relapsed childhood solid tumors but has not been studied in newly diagnosed patients. PURPOSE: The tolerance for and activity of escalating targeted doses of carboplatin combined with ifosfamide and etoposide (ICE) were assessed in children with advanced germ cell tumors or other rare solid tumors for which no standard therapy exists. METHODS: Fifteen children with newly diagnosed solid tumors received ICE chemotherapy. Individualized carboplatin doses were calculated to achieve a target area under the concentration x time curve (AUC) and adjusted for the glomerular filtration rate (estimated by 99mTc-labeled diethylene-triamine pentaacetic acid clearance). Cohorts of at least three patients received carboplatin at an initial target AUC of 6 mg.min/mL, with escalations of 2 mg.min/mL in subsequent cohorts. Carboplatin was given on day 1, followed by ifosfamide at 2 g/m2 per day and etoposide at 100 mg/m2 per day on days 2 through 4. All patients received at least two courses of therapy in the absence of progressive disease, and as many as eight courses could be given. RESULTS: The 15 patients received a total of 46 assessable courses of ICE. Myelosuppression was the dominant toxicity; 30 courses (67%) resulted in hospitalization for febrile neutropenia. Neutropenia was dose limiting at the carboplatin target AUC of 12 mg.min/mL. One complete and eight partial responses were seen in the 14 assessable patients; two additional patients had at least partial responses documented at surgery or autopsy. Six patients are without evidence of disease at a median of 548 days after diagnosis. CONCLUSION: ICE chemotherapy, with the carboplatin dose based on a target AUC of 10 mg.min/mL, is tolerable and has significant activity in a variety of rare malignancies, including extragonadal germ cell tumors. IMPLICATIONS: The combination of carboplatin, etoposide, and ifosfamide holds promise in the treatment of rare pediatric malignancies.

Antineoplastic Combined Chemotherapy Protocols↗

Failure of granulocyte-macrophage colony-stimulating factor to reduce febrile neutropenia in children with recurrent solid tumors treated with ifosfamide, carboplatin, and etoposide chemotherapy.

Ifosfamide, carboplatin, and etoposide (ICE) chemotherapy has promising activity against various solid tumors but produces significant myelotoxicity that might be ameliorated by hematopoietic growth factors. Twelve patients with relapsed solid tumors were treated with ICE chemotherapy. Carboplatin was given on day 1 at a targeted area under the concentration-time curve (AUC) of 8 mg/mL x min (adjusted for each patient's glomerular filtration rate), followed by ifosfamide 2 g/m2 and etoposide 100 mg/m2 on days 2 through 4. Granulocyte-macrophage colony-stimulating factor (GM-CSF), 1,000 micrograms/m2/day, was started 24 hours after each course and given for 17 days or until the absolute neutrophil count (ANC) reached 10 x 10(9)/L. Myelotoxicity and responses in these patients were compared to those of eight patients who received the same therapy without GM-CSF. Patients received a median of three courses (range, 1-8). All 20 patients developed grade 4 neutropenia and grade 3 or 4 thrombocytopenia. The median duration of neutropenia was significantly shorter in patients who received GM-CSF (16.75 vs. 10 days, P = 0.005). However, the two groups did not differ in the proportion of courses associated with hospitalization for febrile neutropenia, the duration of hospitalization, or the median duration of thrombocytopenia. There were two complete, four partial, and three objective responses in the 12 patients treated with ICE plus GM-CSF, and two partial and three objective responses in the 8 patients treated with ICE only. GM-CSF did not reduce the occurrence of febrile neutropenia or the duration of thrombocytopenia associated with ICE chemotherapy. Studies of other hematopoietic growth factors in conjunction with this promising combination are merited.

Adolescent↗

A new cytogenetic finding in an epithelioid sarcoma, t(8;22)(q22;q11).

We report a new translocation t(8;22)(q22;q11) in a single case of epithelioid sarcoma. The band involved in chromosome 22 is the same found in 70-80% of the case of Ewing's sarcoma/peripheral neuroepithelioma (PNET) with cytogenetic characterization. The histologic characteristics of this tumor were typical for epithelioid sarcoma. Immunohistochemical stains were also entirely consistent with this diagnosis, including non-reactivity with P30/32MIC2, a specific marker for Ewing's sarcoma/primitive neuroepithelioma.

Child↗

MR imaging findings in recurrent primary osseous Ewing sarcoma.

The objective of this study was to determine the value of magnetic resonance (MR) imaging in diagnosing local recurrence of Ewing sarcoma. We retrospectively reviewed radiographs, Tc99m-methylene diphosphonate (MDP) skeletal scintigraphy, computed tomography scans, and MR studies of 11 patients who had local recurrences of osseous Ewing sarcoma following initial responses to chemotherapy and local radiation. The MR images were compared to those of a control group of nine patients who had no evidence of relapse. T1- and T2-weighted MR images identified 9 of the 11 recurrences. Computed tomography was diagnostic in 4 of 6 cases evaluated, Tc99m-MDP bone scintigraphy in 4 of 11 cases, and plain radiographs in 2 of 10. MR findings at relapse included changes in signal intensity, increased extent of abnormal marrow signal on T1- and T2-weighted images, and identification of a new soft tissue mass. These findings suggest that MR imaging is valuable in the routine follow-up of primary osseous Ewing sarcoma.

Adolescent↗