Norman Jaffe

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.

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 intraarterial 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. Cancer 59:701‐709, 1987.

Effective clearance of methotrexate using high-flux hemodialysis membranes

We report the first series demonstrating effective clearance of methotrexate using acute intermittent hemodialysis with a high-flux dialyzer. The study was performed on six patients, two females and four males aged 13 to 72 years. All were patients at M.D. Anderson Cancer Center. Patients were dialyzed for 4 to 6 hours daily using a Fresenius F-80 membrane (Fresenius Inc, Walnut Creek, CA). Following the initiation of dialysis, there was a reduction in arterial and venous serum concentration of methotrexate with time. Mean plasma clearance of methotrexate during dialysis in these six patients was 92.1 +/- 10.3 mL/min. One patient who was nearly functionally anephric was studied in detail. In this patient, following a high dose of methotrexate (7.2 g/m2), approximately 63% of this dose was cleared with 6 hours of hemodialysis. With subsequent dialysis performed daily for 6 hours, the drug was cleared completely in 5.6 +/- 0.3 days (n = 7 separate methotrexate treatments). A reduction in plasma methotrexate concentration from 1,733 +/- 40 micromol/L 1 hour postinfusion to less than 0.3 micromol/L in 5 to 6 days was observed for these seven separate treatments. We conclude that significant clearance of methotrexate can be achieved with high-flux dialyzers, making methotrexate therapy a viable treatment option in patients with responsive malignancies despite the presence of renal failure.

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.

Radiation induced osteochondroma in long-term survivors of childhood cancer☆

The records of 200 long term survivors of childhood cancer where reviewed. Radiation induced osteochondromata were detected in 12 patients (6%). Radiation had been administered in doses ranging from 1250 R (approximately 1500 rad) to 5500 rad between the ages of 8 months and 11 1/2 years. Radiation-induced osteochrondromata were detected 3 to 13 1/2 years later, with a median of 5 years. The osteochrondomata were single in 7 patients and multiple (2-4) in 5. Two occurred at sites of previous thoracotomy. Factors related to radiation induced osteochondromata are discussed.

Sociooccupational and physical outcomes more than 20 years after the diagnosis of osteosarcoma in children and adolescents: Limb salvage versus amputation

To the best of the authors knowledge, there has been relatively little research published to date regarding very long‐term survivors of childhood and adolescent osteosarcoma. In the current study, the authors compared the very long‐term survival outcomes of patients with osteosarcoma who were treated with either limb salvage procedures or amputation.

Recurring Congenital Lesion of the Cheek

A 3-cm purple area was present on the left cheek of a newborn white female, and a biopsy showed atypical cells in fibroadipose tissue. The lesion increased in size and the infant was referred to the M. D. Anderson Hospital. By 6 weeks, the lesion formed an irregular 6-cm paranasal mass, compressing the nostril and depressing the corner of the mouth. It was soft and mobile with a nodular, erythematous, excoriated surface. Three small satellite masses were also present. Another biopsy was obtained, establishing the presence of a malignant neoplasm. Vincristine, adriamycin, and cyclophosphamide produced a rapid decrease in size of the lesion, and by 6 months it was considerably smaller and firmer. Total surgical excision was then performed. The well-circumscribed 3-cm nodule had a glistening, tan-gray cut surface. The wound was closed with a skin graft, andBy 11 months, the lesion had recurred as a firm, round mobile nodule in the premaxillary area, lateral to the previous surgical site. The reexcision speci...

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.

Paratesticular rhabdomyosarcoma in childhood.

The clinical and morphologic features of 18 patients with paratesticular rhabdomyosarcoma are reviewed. Although medical attention was sought frequently within 2 months the lesion was mistaken initially for other more common scrotal conditions in more than a third of the patients, delaying a correct diagnosis for 3 weeks to 4 months. Half of the patients had retroperitoneal lymph node metastases. However, with multimodal therapy 61 per cent remain free of disease at a median of 6 years from diagnosis.

Cancer of the Adrenal Gland in Children: Experience at the M.D. Anderson Hospital and Tumor Institute

Adrenal cortical carcinoma is a rare neoplasm in infancy. Most cases present with Cushing’s syndrome, hirsuitism, precocious puberty, or rarely inappropriate ADH secretion. Associated congenital anomalies and concurrent central nervous system and hepatic tumors have also been documented. Occasionally, the tumor may be non-functioning. Three cases have been seen at the M.D. Anderson Hospital and Tumor Institute with a variety of presentations and outcome.