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Biomedical subjects

N Jaffe

Publications and source records attributed to N Jaffe.

At least 37 records · Page 2Linked to original sources
PubMed1989

Osteosarcoma metastatic to the kidney.

Two clinically silent renal metastatic lesions from primary osteogenic sarcoma were first detected on radionuclide bone scan. A needle biopsy performed under the guidance of abdominal ultrasonography confirmed the diagnosis. Prior to nephrectomy, further definition of the metastatic lesion was attained using enhanced computed tomography. A review of the English literature revealed only six previous cases of metastatic osteosarcoma detected in the kidney prior to autopsy.

Adolescent↗
PubMed1989

Chemotherapy for malignant bone tumors.

Chemotherapy has had a major impact in malignant bone tumors. In osteosarcoma, metastasis-free survival has been achieved in approximately 50 to 75 per cent of patients. Additional improvement based on the altered pattern of pulmonary metastases has also been reported. Preoperative chemotherapy has facilitated surgical resection of the primary tumor. The effects on the primary tumor may be utilized as a predictive factor and to design postoperative adjuvant therapy. Similar results have been achieved in Ewing's sarcoma with survival rates in the vicinity of 50 to 80 per cent. The interaction of chemotherapy with radiation has augmented the ability to achieve local control of the primary tumor. The tumoricidal properties of chemotherapy in destroying micrometastases may possibly also contribute to local control. Finally, initial treatment with chemotherapy may yield a complete response and facilitate definitive surgical treatment of the primary tumor. This may eliminate the need for radiation therapy and its delayed consequences.

Bone Neoplasms↗
PubMed1988

In vitro and in vivo effect of adriamycin therapy on monocyte activation by liposome-encapsulated immunomodulators.

The purpose of these studies was to determine the effect of Adriamycin (ADR) on the ability of liposome-encapsulated immunomodulators to activate human blood monocytes to the tumoricidal state. We undertook these experiments because we envisioned using encapsulated activators in addition to chemotherapy to destroy pulmonary micrometastases in patients with osteosarcoma (OS). Prior to the initiation of such therapy, it was important to determine whether chemotherapy interferes with monocyte function. First, human peripheral blood monocytes were isolated from normal donors and preincubated with ADR (0.5-500 ng/ml) for 1 h and then washed prior to the addition of free or liposome-encapsulated activators. After 18-24 h incubation, the activating agents were washed off and [125I]IdUrd-labeled A375 melanoma cells were added. Lysis of radiolabeled tumor cells was quantified 72 h later. Monocytes were also incubated with ADR for 24 h in the presence of free or liposome-encapsulated activators and their cytotoxicity quantified. ADR had no effect on the ability of either free or liposome-encapsulated agents to activate monocyte tumoricidal function. We also studied the in vivo effect of ADR therapy on monocyte function in nine patients with OS. At the time of diagnosis and 1 month after ADR therapy (75 mg/m2) patient monocytes could be activated to the tumoricidal state by liposome-encapsulated agents at levels equal to or greater than pretherapy levels. Monocytes isolated from four patients with OS 1 day after ADR therapy and then activated by liposome-encapsulated agents also demonstrated tumoricidal activity. These studies indicated that the monocytes isolated from osteosarcoma patients treated with ADR can be activated in vitro to kill tumor cells and that additional therapy with liposome-encapsulated immunomodulators may be combined with ADR in the treatment of metastatic pulmonary OS.

Adjuvants, Immunologic↗
PubMed1988

Male reproductive function in long-term survivors of childhood cancer.

We evaluated reproductive function in 27 male long-term survivors of childhood cancer treated during the prepubertal and pubertal period. Sperm samples were obtained from 23 patients; four who refused to provide specimens indicated that they had fathered normal healthy children. Thirteen patients were 12 years old or younger at the time of diagnosis and initiation of therapy. Chemotherapy was calculated according to the cumulative amount of drug administered and correlated with the surface area. Sterility was associated with large doses of single alkylating agents or reduced doses administered with other agents in combination regimens. It was noted in boys treated in both the prepubertal and pubertal period. Sterility was also observed in patients who received testicular radiation alone or in combination with chemotherapy. However, it was not an inevitable consequence in all patients, despite treatment with similar or identical regimens. Fertility potential could not be predicted by clinical examination (testicular size) or gonadotrophin and testosterone values. The results were compared to published reports of treatment-induced sterility in adult males. Additional investigations are required to establish more accurate correlations of dosage with reproductive potential.

Adolescent↗
PubMed1988

Neuropsychological effects of childhood cancer treatment.

The potential neuropsychological effects of treatment were investigated in 124 childhood cancer patients. Children were classified into groups on the basis of treatment modality and treatment status. All patients received systemic chemotherapy. Other treatment modalities included intrathecal chemotherapy and intrathecal chemotherapy plus central nervous system radiation therapy. Treatment status was determined by whether children were newly diagnosed patients in active treatment or long-term survivors of cancer. This classification resulted in five groups; group 1 (n = 29)--children with newly diagnosed disease who were receiving intrathecal chemotherapy; group 2 (n = 21)--children with newly diagnosed disease who were receiving systemic chemotherapy without central nervous system treatment; group 3 (n = 24)--long-term survivors who had received intrathecal chemotherapy; group 4 (n = 25)--long-term survivors who had received intrathecal chemotherapy plus cranial radiotherapy; and group 5 (n = 25)--long-term survivors who had received systemic chemotherapy only (no specific central nervous system treatment). Groups were compared by using multivariate analysis of variance on sets of neuropsychological test variables that represent major cognitive domains. Results of comparisons indicated significant group differences for most dependent-variable sets. Follow-up pairwise comparisons showed that the group of long-term survivors who had received intrathecal chemotherapy plus cranial radiotherapy consistently obtained lower test scores than the other four groups. These findings are consistent with results of previous studies, thus indicating that intrathecal chemotherapy plus cranial radiotherapy is associated with significant effects on neuropsychological performance. Comparisons among newly diagnosed and long-term groups of patients who did not receive cranial radiotherapy yielded null results on measures of higher-order cognitive functions. However, significant group differences were observed on measures of fine-motor and visual-motor skills; newly diagnosed groups obtained lower scores than the nonirradiated long-term survivor groups. Findings were attributed to chemotherapy-induced peripheral neuropathy that differentially affected the newly diagnosed groups.

Adolescent↗
PubMed1987

Renal toxicity with cumulative doses of cis-diamminedichloroplatinum-II in pediatric patients with osteosarcoma. Effect on creatinine clearance and methotrexate excretion.

Sequential corrected creatinine clearance (CCC) evaluations were obtained in 30 patients treated with intra-arterial and/or intravenous cis-diamminedichloroplatinum-II (CDP). The dose was 150 mg/M2 administered with mannitol diuresis at 2 to 3 weekly intervals. Four hundred fifty-three courses were administered (range, 6-18) over 18 months. Patients also were treated with 283 courses of high-dose methotrexate (MTX) and citrovorum factor "rescue" which were interposed between treatments. Deleterious effects of cumulative courses of CDP manifested as progressive reductions in CCC and delayed excretion of serum MTX. Severe MTX toxicity was aborted by augmenting the fluid intake and prolonging citrovorum factor rescue when elevated levels of serum MTX were detected. The first indication of renal induced CDP toxicity occurred with a cumulative dose of 450 mg/M2. At the termination of treatment (cumulative CDP dose over 1050 mg/M2) renal impairment still was present.

Child↗
PubMed1987

Pathologic fracture in osteosarcoma. Impact of chemotherapy on primary tumor and survival.

Twenty patients with osteosarcoma and pathologic fractures were treated with a chemotherapeutic regimen consisting of cis-diamminedichloroplatinum-II (CDP), Adriamycin (ADR) (doxorubicin) and high-dose methotrexate with citrovorum factor "rescue" (MTX-CF). Before the introduction of the regimen, the primary tumor in two patients was treated by immediate amputation and in 13 with preoperative intra-arterial CDP. Among these 13 patients, responses (healing) were observed in 11 (one required the addition of radiation therapy). In three patients, the responses were so dramatic that, at their request, surgery was deferred and treatment exclusively with chemotherapy was instituted. Based on this experience, treatment exclusively with chemotherapy was also administered to an additional five patients who were admitted without pathologic fractures. In the course of such treatment, pathologic fractures also developed; notwithstanding, chemotherapy was maintained and healing also occurred. One of the 20 patients had pulmonary metastases at diagnosis; these were resected after treatment and pathologic examination revealed no evidence of viable tumor. The remaining 19 patients were free of pulmonary metastases but these later developed in seven patients. These data were compared to a historical control series in which 16 of 21 patients with pathologic fractures developed pulmonary metastases. Three of the chemotherapy treated patients died of nonosteosarcoma related causes (leukemia, generalized varicella, and a metabolic complication). Overall, survival was improved in the chemotherapy treated patients as compared to the historical control series: 10 of 20 versus 6 of 21, respectively. Pathologic fractures in osteosarcoma may heal under treatment with chemotherapy, which also has a favorable impact on the eradication of pulmonary metastases and survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Biological consequences of cancer and its treatment and their relationship to current treatment planning.

Advances in the treatment of childhood cancer have produced dramatic changes in survival. Unfortunately, many of the advances associated with this improvement have been accompanied by delayed sequelae induced by treatments such as surgery, radiotherapy, and chemotherapy. This article reviews published reports of treatment sequelae and examines their impact on the design of current forms of treatment. Recognition of the delayed effects of these treatment modalities has resulted in alterations in established therapies. This alteration is an ongoing process and demonstrates the concern of physicians with improving quality of life for long-term survivors of childhood cancer.

Adolescent↗
PubMed1987

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↗
PubMed1987

[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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1986

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↗