Clinical usefulness of an algorithm for the early diagnosis of spinal metastatic disease.

We have previously reported an algorithm that invokes several imaging modalities in the early detection of metastatic and benign disease of the spine in patients with cancer (J Clin Oncol 4:576, 1986). The development of new lesions (shown by Tc99m bone scans) in cancer patients with normal neurological examinations is further evaluated with plain radiographs, spinal computed tomography (CT), and CT myelography (CT-M). Of 60 patients in the original study, 28% were diagnosed as having only benign disease and the remainder had spinal metastases. Thecal sac impingement was seen in 47% of patients with metastatic disease and disruption of the posterior vertebral cortex was noted in all patients with epidural compression. We now report the 2-year follow-up of 55 of these patients. Without treatment, the 17 patients diagnosed with benign disease have shown no evidence of local failure in the spine and median survival is greater than 27 months. Thirty-eight patients diagnosed with spinal metastases had a median survival time of 16.9 months. Radiation therapy directed by CT-M findings provided pain relief in 78% of patients with back pain and metastatic disease. No patient, including 19 with thecal sac impingement, developed clinical myelopathy. These results demonstrate the usefulness of an imaging algorithm for the early identification and distinction of spinal metastatic disease and benign disease in patients with cancer.

Spinal computed tomography and computed tomographic metrizamide myelography in the early diagnosis of metastatic disease.

New lesions were shown by Tc99m bone scans to have developed in sixty patients with known metastatic cancer or high-risk primary cancer and normal neurologic examinations; they were further evaluated with plain radiographs, spinal computed tomography (CT), and CT myelography (CT-M) according to an algorithm. Three groups were identified based on plain radiographs: group 1 (normal radiograph), group 2 (compression fracture as indicated by radiograph), group 3 (evidence of metastasis as indicated by radiograph). In group 1 (n = 18), spinal CT revealed that 33% of the patients had benign disease and 67%, metastases; epidural compression was seen in 25% of the patients with metastasis as indicated by CT-M. In group 2 (n = 26), CT-M disclosed that 38% had a benign compression fracture and 62% had metastases and that 63% of the patients with metastases had an epidural compression. In group 3 (n = 16), spinal CT revealed that 15 patients had metastases (one patient had benign disease). Epidural cord compression was seen in 47% of the patients with metastatic disease. In all groups, the presence of cortical bone discontinuity around the neural canal (seen in 31 patients) was highly associated with epidural compression (seen in 20 patients). Our approach allowed the early and accurate diagnosis of spinal metastasis and epidural tumor as well as the diagnosis of benign disease and was useful in planning optimal local therapy.

High-dose cisplatin in hypertonic saline: reduced toxicity of a modified dose schedule and correlation with plasma pharmacokinetics. A Northern California Oncology Group Pilot Study in non-small-cell lung cancer.

Although increased efficacy has been described with a five-day schedule of high-dose cisplatin (CDDP) in hypertonic saline, severe myelosuppression and cumulative neurotoxicity have limited the usefulness of this therapy. In order to evaluate a possible dose-response relationship in non-small-cell lung cancer (NSCLC), 17 patients with metastatic disease were treated with a modified dose schedule delivering the same total dose (200 mg/m2) in a divided day 1 and 8 schedule. During a pilot study, a total of 47 cycles of therapy were administered, with a median of three cycles per patient and a median total cumulative dose of 600 mg/m2. Nine of 17 patients received at least 600 mg/m2. While nephrotoxicity was similar to previous reports of the five-day schedule, the incidence and severity of myelosuppression and peripheral neuropathy were markedly reduced. Using this modified schedule, severe myelosuppression did not occur. Clinically severe peripheral neuropathy developed in only one patient (6%). The overall response rate was 47% (eight of 17 patients). Plasma platinum pharmacokinetics during five cycles of the modified day 1 and 8 schedule were compared with pharmacokinetics of the five-day schedule. Accumulation of plasma ultrafiltrate platinum occurred in the five-day schedule, but not in the day 1 and 8 schedule. This difference in pharmacokinetics is one possible explanation for the reduced toxicity of this modified schedule. Although the degree of activity seen in this pilot study is encouraging, the efficacy of high-dose CDDP in NSCLC remains to be defined. In view of reduced myelosuppression and neurotoxicity, further trials with this modified schedule are indicated.

Heparin-like anticoagulant associated with plasma cell myeloma.

A 54-year-old man with plasma cell myeloma had sustained bleeding develop after prophylactic hip hemiarthroplasty. Routine coagulation studies revealed significant prolongation of the prothrombin time, activated partial thromboplastin time, and thrombin time. Further evaluation showed failure of the activated partial thromboplastin time to correct in a 1:1 mixture with pooled normal plasma, correction of the prolonged thrombin time by addition of protamine, and a normal reptilase time. A purified preparation of the immunoglobulin component of patient plasma produced the same pattern of coagulation abnormalities, suggesting the paraprotein possessed heparin-like anticoagulant activity. This appears to be a rare mechanism of bleeding diathesis in plasma cell myeloma.

Treatment of refractory chronic lymphocytic leukemia with prednimustine: a phase II study using strict response criteria.

Twenty-one patients with refractory chronic lymphocytic leukemia (CLL) were entered into this Northern California Oncology Group (NCOG) study of prednimustine, an ester of chlorambucil and prednisolone. All patients had active disease and were refractory to standard alkylating agent chemotherapy. Treatment consisted of prednimustine 100 mg/m2/day orally for 3 consecutive days every 2 weeks. By strict response criteria used in this study there was one complete remission (CR), no partial remissions (PR), and three cases of clinical improvement (CI) in 18 evaluable patients, for a total response rate of 22%. The median duration of response is 20+ months, with two patients continuing to respond. Toxicity of this intermittent prednimustine regimen consisted primarily of mild to moderate thrombocytopenia and neutropenia. No episodes of treatment-associated infection or hemorrhage occurred, and nonhematologic toxicity was minor. Using strict response criteria, this study fails to confirm previous reports of high response rates for prednimustine in patients with CLL refractory to standard therapy. The significance of the response category of clinical improvement in CLL is demonstrated by the substantial improvement in objective parameters and the long duration of response. This study also emphasizes the need for standardization of response criteria for this disease.

A phase II study of prednimustine in acute non-lymphocytic leukemia, smouldering leukemia, and refractory anemia with excess blasts.

Prednimustine, an ester of chlorambucil and prednisolone, was evaluated for efficacy and toxicity in a selected group of leukemia patients with a poor prognosis. Disease subsets consisted of patients with acute non-lymphocytic leukemia (ANLL) over age 60; ANLL refractory to standard therapy; smouldering leukemia; and refractory anemia with excess blasts (RAEB). In agreement with previous studies, toxicity from Prednimustine was relatively mild, consisting primarily of infrequent myelosuppression, gastrointestinal side-effects, and mild hyperglycemia. This study did not, however, confirm previously reported remission rates in ANLL: in 41 evaluable patients only two complete remissions were achieved. Both occurred in the subset of patients with smouldering leukemia. We conclude that Prednimustine has limited activity in this patient population.

Prolymphocytic leukemia. Serial responses to therapy.

Prolymphocytic leukemia is a rare lymphoproliferative disorder characterized by marked lymphocytosis, massive splenomegaly, minimal lymphadenopathy, and poor prognosis. Previous reports have noted very short survival, and poor response to single agent alkylator chemotherapy. A small number of reports have shown response to combination chemotherapy regimens including Adriamycin (doxorubicin). A case of prolymphocytic leukemia with serial responses to combination chemotherapy and splenectomy resulting in significant prolongation of survival is reported.

Hepatic dysfunction and jaundice following high-dose cytosine arabinoside.

Two patients with poor-prognosis leukemia were treated with high-dose cytosine arabinoside (Ara-C), 3 g/m2, for induction. Both patients developed serious jaundice in the second posttreatment week. Clinically, the jaundice was characterized by conjugated hyperbilirubinemia, normal amino transferase levels, significant elevation of alkaline phosphatase, and no evidence of obstruction. Microscopic examination of the liver showed only passive congestion with blood, and no bile lakes or plugs. This was believed to be most consistent with drug-induced intrahepatic cholestasis, possibly as a result of injury to the hepatocyte transport system.

Spinal computed tomography scanning in the evaluation of metastatic disease.

Twenty patients with known metastatic cancer or high-risk primary cancer developed new lesions on Tc 99m bone scans and had normal plain radiographs. Spinal computed tomography (CT) was performed on all new bone-scan-positive lesions in minimal examination time. Fifteen patients had extensive metastatic vertebral disease and received local radiotherapy. One patient with new metastatic vertebral disease on CT was treated only with chemotherapy and developed acute spinal cord compression. Four patients had discogenic disease or degenerative disease but no evidence of metastases. Radionuclide bone scans are more sensitive but less specific than plain radiographs in detecting early bone metastases. Early and accurate diagnosis of metastasis is particularly important in the axial spine to prevent epidural compression and fracture. Spinal CT is valuable for identifying the presence and extent of vertebral metastases, as well as the presence of benign disease in cancer patients.