C. H. Carrasco

Retrovirus-mediated wild-type p53 gene transfer to tumors of patients with lung cancer

A retroviral vector containing the wild–type p53 gene under control of a β–actin promoter was produced to mediate transfer of wild–type p53 into human non–small cell lung cancers by direct injection. Nine patients whose conventional treatments failed were entered into the study. No clinically significant vector–related toxic effects were noted up to five months after treatment. In situ hybridization and DNA polymerase chain reaction showed vector–p53 sequences in posttreatment biopsies. Apoptosis (programmed cell death) was more frequent in posttreatment biopsies than in pretreatment biopsies. Tumor regression was noted in three patients, and tumor growth stabilized in three other patients.

Treatment of uveal melanoma metastatic to the liver. A review of the M. D. Anderson cancer center experience and prognostic factors

Background. Liver metastasis develops in approximately two‐thirds of patients with recurrent uveal melanoma. Despite therapy, the median survival of those with liver metastasis is 5 to 7 months. The recognition of a grave prognosis associated with liver metastasis has led to evaluation of new modalities of therapy, including the use of regional therapies such as intrahepatic arterial chemotherapy and either embolization or chemoembolization of hepatic metastases. In this study, the results of an institutional experience over the past 2 decades are reviewed and prognostic factors that affect survival from the time the liver metastasis is diagnosed are assessed.

Extraskeletal osteosarcoma : a clinicopathologic review of 26 cases

The clinical records and histopathologic features in 26 cases of extraskeletal osteosarcoma (ESOS) diagnosed at M. D. Anderson Cancer Center (Houston) between 1950 and 1987 were reviewed. Presentation was usually that of an enlarging soft tissue mass. The thigh (11 cases), upper extremity/shoulder girdle (three cases), and retroperitoneum (three cases) were the most common anatomic sites. Tumor size ranged from 2.5 to 30 cm. The predominant histologic pattern was osteoblastic in four cases, chondroblastic in two, fibroblastic or pleomorphic malignant fibrous histiocytoma (MFH)‐like in four, giant cell type MFH‐like in one, and small cell in one. Various mixtures of these patterns were seen in the remaining 14 tumors. The telangiectatic pattern was not seen as the predominant component in any primary tumor but was observed as a minor component. Thirteen tumors recurred locally and 16 metastasized; five patients had distant metastases at presentation. The lungs, bone, and soft tissue were the most frequent metastatic sites. Sixteen patients died of disease at 2 to 54 months, one patient died of unrelated causes at 61 months, seven patients were alive with no evidence of disease (NED) at 30 to 122 months, and two patients were alive with disease at 28 and 54 months, respectively. Tumor size (< 5 cm versus < 5 cm) was the main prognostic factor; all patients alive with NED for whom accurate tumor measurements were available (six of seven) had neoplasms measuring < 5 cm that were amenable to complete surgical excision. Histologic pattern and other clinicopathologic features did not significantly affect outcome.

Decreased cardiac toxicity of doxorubicin administered by continuous intravenous infusion in combination chemotherapy for metastatic breast carcinoma

Two hundred and seventy‐four consecutive patients with measurable metastatic breast cancer, without prior exposure to cytotoxic agents were treated with tamoxifen, 5‐fluorouracil, doxorubicin, and cyclophosphamide (FAC). The initial 133 patients received doxorubicin by bolus IV administration and for the next group of 141 patients doxorubicin was administered via a central venous catheter over a 48‐hour (79 patients) or 96‐hour (62 patients) continuous infusion schedule. Patients treated with bolus doxorubicin had this agent discontinued usually when 450 mg/m2 were reached; for patients in the infusion group treatment was continued until evidence of progressive disease or clinical or subclinial cardiac dysfunction developed. The complete remission rate was 21% the partial remission rate, 59%. There were no differences in response rate, response duration, or survival duration between groups of patients treated with doxorubicin by bolus, 48‐hour or 96‐hour infusion FAC. The incidence of moderate and severe nausea and vomiting was lower in the group of patients treated with infusion FAC as compared to bolus FAC (P < 0.001); however, the incidence of mucositis was higher in the infusion group than in the bolus group (P < 0.001). Doxorubicin administered by continuous infusion schedules was less cardiotoxic than when administered by bolus, as shown by a >75% decrease in the frequency of clinical congestive heart failure at cumulative dosages ≥ 450 mg/m2 (P = 0.004). Doxorubicin administered as a 48‐hour or 96‐hour continuous IV infusion is safer, and better tolerated than doxorubicin administered by bolus.

Islet Cell Tumors Metastatic to the Liver: Effective Palliation by Sequential Hepatic Artery Embolization

The value of sequential percutaneous hepatic artery embolization with polyvinyl alcohol particles was examined in 22 patients with islet cell carcinoma metastatic to the liver. Nine patients had gastrinoma, 2 had glucagonoma, and 11 had no discernible hormonal secretions or syndromes. Ninety-seven embolizations were done with a median number of 4 (range, 1 to 12) per patient. The interval between embolizations ranged from 1 to 8 months. Twelve of twenty evaluable patients had a partial remission, frequently associated with subjective improvement and decrease in hormone levels. The projected median survival of all 22 patients from the initiation of embolization is 33.7 months (range, 1 to 72). Nausea, vomiting, fever, and abdominal pain occurred with each embolization and subsided usually by day 10 (range, 3 to 35). Sequential hepatic artery occlusion is an effective method for prolonged palliation in this selected group of patients.

Intraperitoneal adoptive immunotherapy of ovarian carcinoma with tumor-infiltrating lymphocytes and low-dose recombinant interleukin-2: A pilot trial

A pilot study was conducted in patients who had advanced epithelial ovarian carcinoma, and who were refractory to platinum-based chemotherapy, to determine the feasibility and clinical effects of a schedule of intraperitoneal (IP) tumor-infiltrating lymphocytes (TIL) expanded in recombinant interleukin-2 (rIL-2), and low-dose rIL-2 IP. TIL were expanded from solid metastases or malignant effusions in serum-free AIM V medium supplemented with low concentrations (600 IU/ml) or rIL-2 using a four-step method of expansion that included a hollow fiber bioreactor (artificial capillary culture system). Patients received IP TIL suspended in dextrose 5% in sodium chloride 0.2% containing 0.1% human albumin and 6 x 10(5) IU rIL-2 on day 1, followed by 6 x 10(5) IU rIL-2/m2 body surface area, administered daily by bolus IP injection, on days 2-4, 8-11, and 15-18. In the absence of disease progression, two additional 4-day cycles of IP rIL-2 were administered. Patients (n = 3) whose TIL failed to grow in vitro received IP IL-2 alone. Eight patients received rIL-2 expanded TIL (10(10)-10(11) range) plus rIL-2 followed by several cycles of rIL-2 alone. One of these patients was treated twice with TIL plus rIL-2. Expanded TIL were primarily CD3+CD4+TCR alpha beta+ (eight TIL-derived T-cell lines). One TIL-derived T-cell line was comprised mostly of CD3+CD8+TCR alpha beta+ cells. Eleven patients (eight treated with TIL plus rIL-2 and three patients treated with rIL-2 alone) received a total of 38 cycles of rIL-2 without TIL. Grade 3 clinical toxicity (peritonitis) occurred in 1 of 9 cycles of TIL plus rIL-2 and 1 of 38 cycles of rIL-2 alone. Each cycle was 4 days long. Grade 3 anemia occurred in 1 of 9 TIL plus rIL-2 cycles and 3 of 38 cycles of rIL-2 alone. There were no measurable responses; however, four of eight patients treated with IP TIL plus rIL-2 had some indication of clinical activity: ascites regression (two patients), tumor and CA-125 reduction (one patient), and surgically confirmed stable tumor and CA-125 values (one patient). The schedule of IP TIL plus low-dose rIL-2 shows manageable toxicity and is worthy of further evaluation in patients with epithelial ovarian cancer who have less tumor burden.

Fine needle aspiration diagnosis of intraabdominal and retroperitoneal lymphomas by a morphologic and immunocytochemical approach

We reviewed 238 fine needle aspiration biopsies (FNA) of intraabdominal or retroperitoneal (IA/RP) masses in 192 patients with known or suspected lymphoma. A limited battery of immunocytochemical stains, including kappa (k) and lambda (l) light chains and Leu‐4, was performed in 104 aspirates. On hundred twenty‐eight of the FNA were diagnostic of or consistent with lymphoma, and three were diagnostic of carcinoma. Twenty‐eight were considered negative for malignancy and 79 were suspicious for lymphoma or were nondiagnostic. For 135 of the FNA, a histologic biopsy specimen was available for comparison purposes. Overall, only one false‐positive result was seen in a specimen lacking immunocytochemical data. The sensitivity of FNA lymphoma diagnosis was 66%. False‐negative results due to sampling error were not uncommon, giving a predictive value of a negative result as 42%. The classification of the lymphomas by FNA was identical to that of the surgical biopsy in 86% of specimens and concurrently discrepant in 6%. We conclude that the routine performance of immunocytochemical studies on FNA of IA/RP masses is a feasible and valuable technique. Whereas suboptimal sensitivity and sampling error may make a negative diagnosis unreliable, lymphoma marker studies (combined with morphology) allow for an accurate and confident diagnosis and subclassification of lymphoma in the majority of cases.

Effect of cumulative courses of intraarterial cis-diamminedichloroplatin-II on the primary tumor in osteosarcoma.

Preoperative chemotherapy with intraarterial cis‐diamminedichloroplatin‐II (CDP) and mannitol diuresis was administered to the primary tumor in 42 patients with osteosarcoma. The dose was 150 mg/m2 and more than 90% of the infusions were administered during a 2‐week period. On occasion this period was extended to 3 weeks because of temporary renal insufficiency or logistical circumstances. Definitive surgical specimens were prepared by means of an arteriogram‐directed plane of dissection with mapping and random sections. Histologically, tumor destruction was evaluated in terms of necrosis, inflammatory response, and fibrovascular regeneration. Quantification of the percent of tumor necrosis was as follows: less than 40% (consistent with spontaneous necrosis and/or no chemotherapy effect); 40% to 60% (possible chemotherapy effect); 60% to 90% (chemotherapy effect—partial response); and 90% to 100% (complete response). Therapeutic efficacy also was correlated with the number of CDP courses (one to three, four to five, and six to seven) and tumor subtype. Significant therapeutic effect (>60% destruction) was observed with four or more CDP courses (one of nine tumors [one to three courses] versus 26 of 33 tumors [four to seven courses] [P = 0.01]). More than 60% of the tumor destruction was observed in the following subtypes: osteoblastic (22 of 28), fibroblastic (three of six), and telangiectatic (two of five). These data demonstrate that four or more courses of intraarterial CDP are required to achieve optimum effects and that osteoblastic osteosarcoma is highly responsive.

Percutaneous skeletal biopsy.

Percutaneous bone biopsy has become an accepted means for tissue diagnosis in indeterminate metastatic disease, whereas needle biopsy for the evaluation of primary skeletals neoplasms is controversial. Needle biopsies are also of value in the diagnosis of inflammatory lesions and eosinophilic granuloma. The diagnostic accuracy of this procedure ranges from 50 to 94% in malignant disease, but is less favorable in benign disease. The low complication rate of about 0.2% makes the percutaneous approach an attractive alternative to surgical biopsy.

Percutaneous nephrostomy catheter use in gynecologic malignancy: M. D. Anderson Hospital experience

The clinical courses of 30 patients with 41 nephrostomy catheters were followed. Duration of drainage ranged from 2 days to 15 months with a mean of 3.7 months. The most common complications were hemorrhage (28%), infection (70%), and blockage of catheter (65%). No deaths occurred as a result of these complications. Renal function recovered in 14 of 20 patients (70%) who presented with elevated creatinine values. Twenty-six of 28 patients with malignant obstruction were able to receive further therapy. The only long-term survivors presented with primary advanced cervical cancer.