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Biomedical subjects

N Jaffe

Publications and source records attributed to N Jaffe.

At least 91 records · Page 5Linked to original sources

Weekly high-dose methotrexate and doxorubicin for osteosarcoma: the Dana-Farber Cancer Institute/the Children's Hospital--study III.

Weekly high-dose methotrexate with leucovorin rescue and vincristine (HDMTX) and doxorubicin was administered as adjuvant postoperative therapy to 46 patients with a diagnosis of conventional high-grade nonmetastatic osteosarcoma of an extremity between July 1976 and December 1981. The primary lesions were managed by wide or radical amputation (26 patients) or by limb-sparing resection in 20 selected patients. The margins of the resections were retrospectively classified as marginal in three, wide in 16, and radical in one. The 5-year relapse-free survival (RFS) for all patients is 59% (95% confidence interval [CI], 43%, 74%) and overall survival is 78% (95% CI, 65%, 91%). The RFS for patients initially having a limb resection procedure is 55% (95% CI, 32%, 77%) compared with 62% (95% CI, 43%, 81%) for those initially having amputations (P = .52). Using multivariate analysis, the only significant prognostic variables that predicted RFS of greater than or equal to 3 years, were the presence of moderate to marked lymphocytic infiltration of the primary tumor (P less than .002), primary site outside of the proximal humerus (P less than .005), and the absence of a predominance of osteoblastic pattern in the primary tumor (P less than .03).

Actuarial Analysis↗

[Recent advances in the treatment of childhood osteosarcoma: therapeutic modalities at the M.D. Anderson Hospital and Tumor Institute].

Osteosarcoma (OS) is the most common malignant tumor of bone affecting the preteenage and teenage individual. During the past decade, major progress has been made in the treatment of OS. Multi-drug combination chemotherapy has been utilized as adjuvant therapy for destruction of micrometastases which are considered to be present in most patients at diagnosis. This approach has produced three-year survival rates of between 55 and 80%, as opposed to the figure of less than 20% among historical control patients. Recent advances with intraarterial chemotherapy have secured the local control of the tumor and offer hope that increased numbers of patients may become eligible for limb-salvage procedure.

Antineoplastic Combined Chemotherapy Protocols↗

Therapy for primary non-Hodgkin's lymphoma of bone and a comparison of results with Ewing's sarcoma. Ten years' experience at the Istituto Ortopedico Rizzoli.

The authors report on the results obtained in 30 consecutive cases of primary non-Hodgkin's lymphoma of bone (PNHLB) treated at the Istituto Ortopedico Rizzoli between 1972 and 1982. Four patients were treated with radiotherapy only and 26 were treated with radiotherapy plus adjuvant chemotherapy. At a median follow-up of 86 months (range, 30-160), among the 26 patients treated with chemotherapy also there were 3 relapses (2 had meningeal involvement and 1 had recurrence in another bone). Relapse (local recurrence plus multiple new localizations) was observed in one of the four patients treated with radiotherapy only. These results are compared with the results of 68 patients with Ewing's sarcoma who were treated during the same period with radiation therapy and adjuvant chemotherapy and reported in a previous study. In this group, the disease-free survival rate was only 32% (20/68) with a much higher incidence of local recurrence (31%). The necessity of making a clear distinction between PNHLB and Ewing's sarcoma is discussed.

Adolescent↗

Metastatic epidural osteosarcoma initially diagnosed as cisplatin neuropathy.

Unexpected early epidural spinal metastasis in a case of osteosarcoma occurred in a patient receiving treatment with cis-diamminedichloroplatinum-II (cisplatin). The initial neurologic symptomatology manifested as paresthesias in the feet which developed 2 months after initiation of treatment (cumulative dose of cisplatin 450 mg/M2) at which stage the primary tumor demonstrated a marked response. Concurrently two small pulmonary metastases appeared. Epidural metastasis in osteosarcoma is generally considered a late complication and is usually associated with disseminated disease. This communication draws attention to changes in the metastatic pattern which may occur with the administration of seemingly effective treatment and the potential for confusing the symptomatology of epidural spinal metastasis with cisplatin neuropathy.

Adolescent↗

Adriamycin-methotrexate high dose versus adriamycin-methotrexate moderate dose as adjuvant chemotherapy for osteosarcoma of the extremities: a randomized study.

Adjuvant chemotherapy comprising Adriamycin (ADM) and Methotrexate (MTX) with Citrovorum Factor (CF) was administered on a randomization basis to 2 groups of patients with osteosarcoma after surgical ablation of the primary tumor. One group received high dose MTX (regimen I) and the other moderate dose MTX (regimen II). In both groups a short period of heparin treatment was also administered to prevent neoplastic emboli during surgery. All patients were free of metastasis at the beginning of therapy. The efficacy of therapy was determined by recording the percentage of continuously disease-free patients. This was compared to the disease-free survival in 132 patients previously treated with other ADM or ADM-MTX regimens and to a group of 39 patients treated during this period with amputation only. The latter did not receive adjuvant chemotherapy for a variety of reasons and are equated to a concurrent control group. Over the ensuing 27-66 months, 31 of 56 patients (55%) treated with regimen I and 25 of 50 (50%) treated with regimen II were disease-free. The overall disease-free survival in both regimens was 53%. This is similar to the 132 patients treated with previous adjuvant chemotherapy protocols (45-50%). However, the percentage of continuously disease-free patients treated with adjuvant chemotherapy was significantly better than the 39 patients (12%) treated contemporaneously with surgery only (P less than 0.0005). Survival in the latter is similar to that of historical control patients. These results do not suggest any change in the natural history of osteosarcoma and reveal benefits which may accrue with adjuvant chemotherapy. These results also demonstrate that in adjuvant treatment of osteosarcoma performed with ADM and MTX the high and the moderate doses of MTX are equally efficacious.

Adult↗

Transient neurologic disturbances induced by high-dose methotrexate treatment.

Temporary neurologic abnormalities were detected in 9 of 60 patients undergoing treatment with high-dose methotrexate and citrovorum factor rescue (MTX-CF) for osteosarcoma. The incidence of abnormalities and abnormalities themselves were more severe than previously reported. This was attributed to an increased dose and more frequent administration of MTX-CF. In view of the transient nature of the abnormalities, a biochemical cause is implicated, and the mechanisms by which it may occur are discussed.

Bone Neoplasms↗

Staging, therapy and prognosis of primary non-Hodgkin's lymphoma of bone and a comparison of results with localized Ewing's sarcoma: ten years experience at the Istituto Ortopedico Rizzoli.

Thirty consecutive cases of localized primary non-Hodgkin's lymphoma of bone (PNHLB) were treated in a 10-year period at the Istituto Ortopedico Rizzoli with localized radiation (4 cases) and localized radiation and adjuvant chemotherapy (26 cases). The doses of radiation varied from 3000-4500 rad. A variety of staging procedures evolving with new diagnostic techniques over the 10 years were performed. Adjuvant chemotherapy comprised two different regimens of vincristine, adriamycin and cyclophosphamide. Twenty-four of the 26 patients (92%) have been free of disease with a median follow-up of 75.5 months (18-144 months). Two patients developed meningeal involvement and one patient, treated with radiation therapy only, developed a local recurrence. The results are compared to the management of 68 Ewing's sarcoma patients treated during the same period. Here, higher doses of localized radiation therapy (approximately 5000 rad) and similar adjuvant chemotherapy were administered. The survival was 32% (22/68) with a higher incidence of local recurrence (21%). These data indicate that PNHLB should be considered a separate entity from Ewing's sarcoma and can be treated successfully with lower doses of radiation to the primary tumor and adjuvant chemotherapy. The observations are also compared to a variety of other biological characteristics of Ewing's sarcoma. Since only two patients developed meningeal relapse, our experience does not permit a firm recommendation for routine prophylactic treatment of the central nervous system in PNHLB.

Adolescent↗

Control of primary osteosarcoma with chemotherapy.

High-dose methotrexate with citrovorum factor "rescue" (MTX-CF) produced an apparent complete response of the primary tumor in three patients with osteosarcoma. The response was sustained with MTX-CF, intra-arterial cis-diamminedichloroplatinum II (CDP) and Adriamycin (doxorubicin) for 18 months. Treatment was then electively discontinued. Local recurrence occurred in two patients, 6 and 4 months later, respectively. MTX-CF was reinstated and a complete response was again achieved in one patient. This has been maintained for 15+ months with MTX-CF and intra-arterial CDP administered for 13 of the 15+ months. Reinduction with MTX-CF failed in the second relapsed patient but an apparent remission was again achieved with radiation and intra-arterial CDP. This has been maintained with intravenous CDP, cyclophosphamide and phenylalanine mustard for 14+ months. A complete response in the primary tumor was still present in the nonrelapsed patient, 42 months from diagnosis. All patients have remained free of pulmonary metastases, 40+ to 42+ months from diagnosis.

Adolescent↗

Successful treatment of pulmonary and abdominal metastatic osteosarcoma.

A patient with telangiectatic osteosarcoma of the proximal fibula while receiving adjuvant chemotherapy, developed pulmonary and, later, mesenteric metastases. The pulmonary metastases were resected and the mesenteric metastasis was eradicated with surgery and intra-arterial cis-diamminedichloroplatinum II. This represents an additional example of an alteration in the clinical pattern of metastases induced by chemotherapy and the ability to achieve cure with a multidisciplinary approach.

Adolescent↗

Recurrence of Wilms tumor after apparent cure.

The recurrence of Wilms tumor after a 5-year disease-free interval is rare. We present two patients who had recurrent disease after a disease-free interval of greater than 7 years. Three additional patients, registered with the National Wilms Tumor Study who had a recurrence after 5 years, are also described. Of these three patients, two had nephroblastomatosis. Because more patients are achieving long-term survival, careful surveillance after apparent "cure" is recommended, particularly if nephroblastomatosis is identified in the original nephrectomy specimen.

Child, Preschool↗

Comparison of intra-arterial cis-diamminedichloroplatinum II with high-dose methotrexate and citrovorum factor rescue in the treatment of primary osteosarcoma.

A randomized two-arm study was undertaken to determine relative tumoricidal effects of intra-arterial cis-diamminedichloroplatinum II (I/A-CDP) and high-dose methotrexate with citrovorum factor rescue (MTX-CF) in the treatment of the primary tumor in patients with osteosarcoma. Responses were evaluated by clinical, radiographic, angiographic, and pathologic parameters. Fifteen patients were randomized to receive MTX-CF and 15 to I/A-CDP. In the MTX-CF arm there were four responses (three complete responses, one partial response) whereas in the I/A CDP arm there were nine responses (seven complete responses, two partial responses). Two patients who failed MTX-CF and requested alternative treatment with I/A-CDP also responded. The total I/A-CDP response was 11/17.

Adolescent↗

Computed tomography of osteosarcoma after intraarterial chemotherapy.

The response to intraarterial cis-diamminedichloroplatinum II (CDP) chemotherapy was evaluated by computed tomography (CT) in 33 patients with pathologically proved osteosarcoma of the long or flat bones. Twenty-one of the 33 patients had a CT scan before chemotherapy was started. In the other 12 patients, a CT scan was obtained after at least two courses of treatment, and additional studies were performed during the course of therapy. In those patients responding to treatment, the posttherapy scan revealed a remarkable decrease or complete disappearance of the associated soft-tissue mass and clear reestablishment of the fat planes between the muscle bundles that had been obscured. There was sharp definition of the peripheral margins of the calcified healing neoplasm, and the calcification in the healing tumor could be differentiated easily from that of the original bone neoplasm. The findings of CT were compared with those of conventional studies and pathologic results. CT was more accurate than conventional studies in detecting healing process and diagnosis of remission.

Adolescent↗

Neuropsychological sequelae of childhood cancer in long-term survivors.

In order to assess the effects of various cancer treatments on neuropsychological functioning, 74 long-term survivors of childhood cancer were examined. A comprehensive battery of tests was administered to two CNS treatment groups (irradiated and nonirradiated leukemia and lymphoma patients) and a control group (solid tumor and Hodgkin disease patients receiving no CNS treatment). The CNS-irradiated group obtained lower scores than the other two groups, with significant differences in visual-motor and fine motor skills, spatial memory, and arithmetic achievement resulting in significant differences in IQ scores (VIQ, PIQ, FSIQ). The results are discussed in relation to: (1) the effects of CNS irradiation on cognitive development; (2) the specificity of these effects; and (3) the relationship of age at diagnosis to treatment effects. It is concluded that although there is a general lowering of scores after CNS irradiation, the effect is most pronounced for nonlanguage skills. Age at diagnosis was less important than the type of treatment, with CNS irradiation reducing performance regardless of when cancer was diagnosed. There were indications that children with any type of cancer diagnosed before age 5 years are more likely to have some cognitive difficulties.

Age Factors↗

Drug precipitation within i.v. tubing: a potential hazard of chemotherapy administration.

Because relatively undiluted concentrations of drugs are maintained for prolonged periods in the Y-side arm of rapidly flowing iv infusions, we visually determined compatibilities of ten commonly used cancer chemotherapy drugs and four adjunctive drugs including droperidol, metoclopramide, furosemide, and heparin. Droperidol was found to be incompatible with furosemide, methotrexate, leucovorin, heparin, and 5-FU. Furosemide was incompatible with metoclopramide, doxorubicin, vincristine, and vinblastine in addition to droperidol. Doxorubicin was incompatible with heparin. If these drugs were administered sequentially into the Y-side arm of an iv infusion, precipitation would be expected with drug inactivation and possible drug embolization to the pulmonary circulation. Flushing the Y-side arm with a compatible solution after drug administration will prevent this problem.

Antineoplastic Agents↗