Decline of posttreatment tumor marker levels after therapy of nonsmall cell lung cancer. A useful outcome predictor.

BACKGROUND: The assessment of treatment efficacy in nonsmall cell lung cancer (NSCLC) is limited by the lack of a clear association between clinical response and survival. The prognostic usefulness of treatment-induced tumor-marker declines in NSCLC has not been established. The authors investigated the prognostic significance of treatment-induced declination in tumor marker levels of carcinoembryonic antigen, CA 19-9, and CA 125 in a group of patients with NSCLC treated with a brief course of cisplatin-based chemotherapy. METHODS: Eighty-three patients with NSCLC enrolled on 2 related treatment protocols had pretreatment tumor-marker determinations. Patients were restaged 10 to 12 weeks after study entry, and clinical and marker responses were determined. RESULTS: Thirty-eight patients (46%) had elevated pretreatment tumor markers, 36 (42%) of whom were evaluable for both clinical and marker responses. Pretreatment, the latter 36 individuals had measurable or evaluable disease, and at least one elevated tumor marker (greater than twice normal); posttreatment, they had follow-up measurements of both parameters. Of the 36 patients, 8 had normalization of tumor marker levels, 13 had 50-99% marker level declination, and 15 had less than 50% or no declination. In the same group of 36 patients, there were, 1 patient with complete clinical response, 11 with partial response, 19 with stable disease, and 5 with progressive disease. Marker responses occurred with equal frequency in clinical responders and nonresponders. There was no association between clinical response and survival, but there was a strong association between marker response and survival. CONCLUSIONS: In patients with nonsmall cell lung cancer with elevated pretreatment tumor marker levels, treatment-induced marker level declination can be a surrogate indicator for survival.

A phase II evaluation of ifosfamide and mesna in unresectable diffuse malignant mesothelioma. A Southwest Oncology Group study.

BACKGROUND: Malignant mesothelioma is a highly treatment-resistant neoplasm. This study represents an attempt to define an effective form of systemic therapy. METHODS: Twenty-six patients with unresectable diffuse malignant mesothelioma were enrolled in Southwest Oncology Group (SWOG) study 8731 and treated with ifosfamide, 2 g/m2 intravenously for 4 days, and mesna 2 g/m2 intravenously for 5 days, every 3 weeks. Patients were either previously untreated with chemotherapy or had at most one prior systemic treatment. RESULTS: Two patients, or 8% (95% confidence interval, 1-25%), achieved partial response, with response durations of 4 and 6 months. One additional patient met criteria for tumor size reduction but not duration criteria. Thirteen (50%) patients had stable disease of 4 months' median duration (range, 1-13 months). The median survival of the entire group was 6.5 months. The dose-limiting toxicity was granulocytopenia (11 patients, < or = 250/microliters). CONCLUSIONS: Ifosfamide/mesna has modest activity in malignant mesothelioma. It could be tested using alternate dosage schedules and in combination with other agents in treating this highly resistant neoplasm.

Mucin-positive epithelial mesothelioma.

Mucin-positive epithelial mesothelioma is a rare, frequently unrecognized entity that should not be misinterpreted as metastatic adenocarcinoma, as each is associated with differing treatment and prognosis. Presented herein is a case of an acidic and neutral mucin-positive papillary mesothelioma of the right pleura, with cytologic, histologic, histochemical, immunohistochemical, and ultrastructural evaluation.

Normal pressure hydrocephalus in a patient with systemic lupus erythematosus.

We describe a patient who had concomitant systemic lupus erythematosus (SLE) and a normal pressure hydrocephalus. She improved only after appropriate therapy for each. Although 6 patients with arthritis and normal pressure hydrocephalus have been described, this is the first report of it occurring in a patient with SLE. It has been emphasized that normal pressure hydrocephalus can easily be overlooked in elderly patients with arthritic conditions. Since neuropsychiatric symptoms are likelier to occur in patients with SLE than in other rheumatologic conditions, the diagnosis of normal pressure hydrocephalus may be delayed or overlooked. Because normal pressure hydrocephalus is a potentially reversible cause of neurologic dysfunction, it should be considered in appropriate populations.

Clinical and pathologic features of primary gastric rhabdomyosarcoma.

The authors report a case of a collision tumor composed of a primary gastric rhabdomyosarcoma intermingled with an adjacent infiltrating gastric adenocarcinoma. Only eight cases of gastric rhabdomyosarcoma have been reported previously and little information is recorded about the behavior of this tumor. Gastric rhabdomyosarcoma has several distinctive clinical features. It is a highly aggressive tumor (median survival, 2.5 months) occurring in both children and adults and frequently presents as metastatic disease to lung or cervical lymph node. The initial diagnosis is often difficult to establish, especially on biopsy material. In several instances, the correct diagnosis was established only at autopsy. The authors' patient was correctly diagnosed during life and received considerable benefit from cyclophosphamide, doxorubicin, and vincristine (CAV) therapy and survived for 26 months after diagnosis. Two of the previously reported eight cases of primary gastric rhabdomyosarcoma and this case have adjacent admixed glandular gastric adenocarcinomas. Since three of the nine known cases of primary gastric rhabdomyosarcoma have an adjacent admixed gastric adenocarcinoma, there appears to be a greater than chance association between these two tumors.

ViVACCy--a drug schedule based on G2 blockade and prolonged infusion of multiple tubulin-binding agents. A pilot study.

A drug schedule has been devised based on a strategy of G2 blockade followed by prolonged infusion of tubulin-binding agents. The regimen consists of doxorubicin 32 mg/m2 i.v. and cyclophosphamide 320 mg/m2 i.v. on day 1 followed by vinblastine (0.3 to 1.2 mg/m2/day), cisplatin (3 to 12 mg/m2/day), and vincristine (0.04 to 0.16 mg/m2/day) by continuous intravenous infusion on days 5 to 12. Courses are repeated every 28 days. Eighteen patients with advanced solid tumors received 37 courses of chemotherapy in a pilot study to determine safe drug concentrations for the three-drug infusion for 7 days. Dose limiting toxicity was myelosuppression. Patients who received prior mitomycin-C experienced more profound thrombocytopenia than those who did not. Nonhematologic toxicities included mild nausea, vomiting, and transient elevations of serum alkaline phosphatase and serum creatinine. One patient with squamous cell carcinoma of the esophagus who erroneously received vincristine 0.8 mg/m2 instead of 0.08 mg/m2 for 4 1/2 days developed transient myalgia, ileus, and a transient peripheral neuropathy; the patient achieved a sustained complete remission for 15 months and died of unrelated causes. Minor responses and stable disease were seen in two patients with renal cell carcinoma (1 and 2.5 months), three patients with colorectal carcinoma (1.5, 2, and 4 months), and one patient with squamous cell carcinoma of the tongue (2 months). The ViVACCy drug regimen can be given without undue toxicity and may be active in solid tumors.

Hematologic complications of gastric bypass for morbid obesity.

Of 530 patients who have had a gastric bypass operation for morbid obesity at Allegheny General Hospital, 41 had decreases in serum iron, vitamin B12, and/or folate levels. These abnormalities were detected eight months to eight years (median, two years) after the operation. The hemoglobin level ranged from 7.4 to 14.1 gm/dl at the time of detection, and mean corpuscular volume (MCV) ranged from 58 to 119 cu microns. The most common problem was combined iron and vitamin B12 deficiencies. Physicians should be aware that folate, vitamin B12, and iron deficiencies occur after gastric bypass, though the time to development is variable. Hemoglobin level and MCV are not predictive of these deficiencies.

A phase II evaluation of cisplatin in unresectable diffuse malignant mesothelioma: a Southwest Oncology Group Study.

Cisplatin was given intravenously to 35 evaluable patients with unresectable malignant mesothelioma on Southwest Oncology Group (SWOG) Study 8418. Five patients (14.3%) achieved partial response with median response duration of six months (range 2-12 months); eleven patients (31.4%) had stable disease of median duration of 5.5. months (range 2-21 months). Median survival for all patients was 7.5 months, 9 months for responders. Toxicity was as expected except that 12 patients (34.2%) discontinued cisplatin because of side effects. Cisplatin has moderate activity in mesothelioma and further studies with platinum analogues should be pursued.

Radiation-induced leiomyosarcoma of the great vessels presenting as superior vena cava syndrome.

A patient with a pleomorphic intravascular leiomyosarcoma of the great vessels of the neck and mediastinum presented clinically with a superior vena cava syndrome. A latent period of 29 years elapsed between receiving orthovoltage radiation to the neck and right side of chest to treat recurrent ganglioneuroblastoma, and the appearance of a leiomyosarcoma and subsequent recurrences. The patient underwent partial resection of the tumor, received adjunct chemotherapy, and was shown to be free of disease by clinical tests and by magnetic resonance imaging (MRI) 17 months after completion of chemotherapy. The criteria for the diagnosis of radiation-induced sarcomas are reviewed in relation to the present case. The critical role of magnetic resonance imaging in both the diagnosis and continued follow-up of the patient is described. This would appear to be the first reported case of radiation-induced intravascular leiomyosarcoma of the great vessels of the neck and mediastinum presenting as a superior vena cava syndrome.

Pseudo-Gaucher cells in the bone marrow of a patient with Hodgkin's disease.

The authors studied an 18-year-old woman with stage IIIB nodular sclerosis Hodgkin's disease whose bone marrow contained abnormal storage cells that resembled Gaucher cells by light microscopic examination ("pseudo-Gaucher" cells). Electron microscopic examination revealed that these cells differed from true Gaucher cells and resembled storage cells previously described in chronic myelogenous leukemia. The patient's peripheral blood leukocyte beta-glucosidase and serum acid phosphatase levels were elevated, ruling out the diagnosis of inherited Gaucher's disease. After treatment with six monthly cycles of systemic chemotherapy (nitrogen mustard, vincristine, procarbazine, bleomycin, doxorubicin, and prednisone), all signs of Hodgkin's disease and pseudo-Gaucher cells disappeared. Repeat leukocyte beta-glucosidase and serum acid phosphatase levels were unchanged. The present case is unique with its documentation of classical enzyme patterns for beta-glucosidase and acid phosphatase and electron microscopic features. The authors postulate that pseudo-Gaucher cells result from excessive cell breakdown with an overload of available beta-glucosidase.

Pancreatic giant cell carcinoma of the osteoclastic type: response to 5-fluorouracil and radiation.

A case of pancreatic giant cell carcinoma of the osteoclastic type is presented. The findings of endoscopic retrograde cholangiography, angiography, computerized tomography, and magnetic resonance imaging scans are described for the first time for this rare neoplasm, showing a large, nonresectable pancreatic tumor. The patient's clinical course is followed during treatment with 5-fluorouracil and radiation therapy, documenting response by computerized tomography scan. The cases reported in the literature are reviewed and surgical and medical treatments are discussed. A combination of 5-fluorouracil and radiation therapy is the first medical treatment with a documented response.

Treatment of six cases of mesothelioma with doxorubicin and cisplatin.

Six patients with unresectable malignant mesothelioma were treated with chemotherapy consisting of doxorubicin and cisplatin every 3 weeks. One patient with paratesticular mesothelioma metastatic to lungs entered complete remission for 8 months; his disease has relapsed but he is alive 32 months after initiation of chemotherapy. One patient with peritoneal mesothelioma achieved partial response for 12 months. Two patients with pleural mesothelioma achieved a partial response of 5- and 6-month durations, respectively. Two patients with pleural mesothelioma failed to respond to this regimen. Thus, four of six patients responded to doxorubicin-cisplatin chemotherapy. These preliminary results merit further study and confirmation; future investigations of cisplatin alone are necessary to better define the role of this agent in mesothelioma.

Combination chemotherapy for advanced sarcomas of bone and mesothelioma utilizing rubidazone and DTIC: a Southwest Oncology Group Study.

Twenty-three patients with disseminated bony sarcoma and 23 patients with malignant mesothelioma were evaluable in a Southwest Oncology Group (SWOG) clinical trial utilizing rubidazone and DTIC. One partial remission (PR) was observed in a previously untreated patient with metastatic Ewing's sarcoma. One patient with giant cell tumor of bone had an improvement, short of PR. Thirteen patients with osteogenic sarcoma and 23 with malignant mesothelioma had no response to this combination of drugs. The major toxic effects of therapy included nausea, vomiting, and myelosuppression, especially leukopenia; no cardiac toxicity was noted. We conclude that the combination of rubidazone and DTIC is inactive in bony sarcoma and mesothelioma.

Diagnosis of non-Hodgkin's lymphoma intracerebral mass lesions. Usefulness of Tc-99m pertechnetate and Ga-67 citrate brain scans.

This paper summarizes the clinical and diagnostic features of five reports of patients with intracerebral, non-Hodgkin's lymphoma. In three patients the brain lesion was the only evidence of lymphoma, while two patients also had concomitant systemic involvement. Four patients had diffuse histiocytic lymphoma and one had a mixed type of malignant lymphoma. In all patients, Tc-99m and Ga-67 brain scans disclosed discrete areas of increased radionuclide uptake consistent with a mass. In each case, brain blood perfusion studies were normal and brain computerized tomographic (CT) scans and cerebral angiograms produced variable nondiagnostic patterns. Craniotomies in four patients provided histologic confirmation of the non-Hodgkin's lymphoma in the areas of abnormality. The remaining patient had systemic histiocytic lymphoma with concomitant brain lesions that responded to irradiation. The combined use of the above noninvasive modalities in correlation with clinical findings may result in more accurate prebiopsy diagnoses of intracerebral lymphoma.

Serum colony-stimulating and colony-inhibitory activity in response to neutropenia.

Since sera from most species contain both colony-stimulating and column-inhibitory factors, the net CSA results from a balance between these opposing substances. Studies were performed to determine whether the increased CSA noted during neutropenia or endotoxemia is due to an increase in CSF or to a decline in serum inhibitors. Rats were treated with cyclophosphamide, total body irradiation, or endotoxin and bled during the peak CSA response. By separation studies using Sephadex G150, it was shown that serum levels of high-molecular-weight inhibitors were unchanged from control values. Minimal CSA was detected in normal serum fractions; increased activity was found in fractions from neutropenic animals. During a postcyclophosphamide rebound neutrophilia, serum CSA was undetectable; inhibitor levels were similar to those measured in untreated controls. These observations show that the increased serum CSA seen with neutropenia is due to a true increase in CSF and not to a decline in circulating inhibitors.

Hairy cell leukaemia: seven cases with probable B-lymphocytic origin.

Mononuclear cells from seven patients with hairy cells leukaemia were examined for features suggestive of either a lymphocytic or monocytic origin. Immunofluorescent staining of both methanol fixed and incubated cells, using monospecific antisera, revealed a predominant cell-associated immunoglobulin in each case. Three were positive for mu and kappa chains, two for gamma and kappa chains, one for delta and kappa chain determinants and one reacted only with antigamma chain serum. Formation of EAC rosettes, a feature of both B lymphocytes and monocytes, was variable. T cells, as judged by E rosettes, were not elevated in any patient. Phytohaemagglutinin reactivity was normal in six and depressed in one case. With the exception of minimal activity in assays for glass adherence and latex particle phagocytosis, none of the cells showed features typical of monocytes. Hairy cells were negative by peroxidase stain and lacked the electron microscopic characteristics of monocytes. They did not react in either rosette or phagocytic assays with anti-A or anti-D coated erythrocytes nor did they elaborate granulocyte colony stimulating factor, a monocyte-derived in vitro granulopoietin. Although unequivocal classification of these abnormal cells is not possible, the data storngly suggests that this represents a variant of a B lymphocytic neoplasm.