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Biomedical subjects

C M Pinsky

Publications and source records attributed to C M Pinsky.

At least 19 recordsLinked to original sources
PubMed1997

Use of carcinoembryonic antigen radioimmunodetection and computed tomography for predicting the resectability of recurrent colorectal cancer.

OBJECTIVE: The objective was to determine the role of arcitumomab (CEA-Scan; Immunomedics, Morris Plains, NJ), an anticarcinoembryonic antigen (CEA) Fab' labeled with technetium-99m, in the presurgical evaluation of patients with recurrent or metastatic colorectal carcinoma. SUMMARY BACKGROUND DATA: Surgical resection is the only method known to cure recurrent or metastatic colorectal carcinoma. The location and extent of disease must be determined before surgery. The role of antibody imaging, a new cancer detection modality, in preoperative evaluation for resection of locally recurrent or metastatic colorectal cancer has not been established, either alone or in combination with standard diagnostic modalities. METHODS: In a blinded analysis of 209 patients with known or suspected colorectal cancer, the accuracy of arcitumomab, alone and combined with computed tomography (CT), was compared to that of CT for predicting abdominopelvic tumor resectability by correlating the results with surgical and histopathologic findings. RESULTS: Arcitumomab alone or combined with CT was found to be significantly more accurate for predicting surgical outcome than CT alone. When the results of CT and arcitumomab were concordant for abdominopelvic resectability, nonresectability, or absence of disease, the prediction was accurate in 67%, 100%, and 64%, respectively. Thus, the concordance for nonresectability (100% correct) may obviate the need for other diagnostic modalities or exploratory surgery. When the two tests were discordant, arcitumomab was correct substantially more often than CT. Because the liver is the most common site of distant metastasis in colorectal cancer, a subset of patients with hepatic disease was also analyzed; findings were similar to the overall resectability results. The product's safety profile was excellent: the incidence of induction of an immune response against arcitumomab was <1% and that of potentially adverse events was 1.2%. CONCLUSIONS: The accuracy of arcitumomab for assessing resectability status is greater than that of CT, both in all patients undergoing evaluation for curative abdominopelvic resection of colorectal cancer and in the subset of patients with suspected or proven liver metastases. The additional use of arcitumomab with CT potentially doubles the number of patients who could be saved the cost, morbidity, and mortality of unnecessary abdominopelvic surgery and increases those who are potentially resectable for cure by 40%.

Adult↗
PubMed1996

Rapid imaging of infections with a monoclonal antibody fragment (LeukoScan).

The diagnostic accuracy for imaging infection with a technetium-99m-labeled antigranulocyte Fab' fragment (LeukoScan) was prospectively examined in a multicenter study. Scintigraphy was performed in 53 patients at 1 to 6 hours and at 24 hours after injection of the labeled antibody fragment. Thirty-nine sites of infection were detected and confirmed by histologic study, cytologic study, other imaging procedures, or by followup. Thirty-eight of the 53 patients also were studied with technetium-99m-Exametazim or indium-111-oxine labeled leukocytes within 1 week of the LeukoScan study. In 21 patients with 25 osteomyelitic lesions, LeukoScan recognized 13 of the lesions as being true positive ones, 10 as being true negative ones, and 2 as being false negative ones, whereas the leukocyte scan showed 9 true positive results, 5 true negative results, and 2 false negative ones. Sensitivity specificity, and diagnostic accuracy of LeukoScan were 90.0 %, 84.6 %, and 87.9 %; and with autologous leukocyte scintigraphy were 83.9%, 76.5%, and 81.3%, respectively. The sensitivity of LeukoScan was independent of the amount of the labeled antibody injected (0.1 - < 0.5 mg, 96.2%; 0.5 - < 0.9 mg, 80.0%; 0.9 - 1.0 mg, 77.8%). False positive lesions were detected in a periprosthetic calcification, a frontal hyperostosis, and 2 periprosthetic hips that had loosened. Human antimouse antibody could not be detected in any of the 13 patients tested 1 or 3 months after injection. LeukoScan is suitable for imaging infectious lesions and may have diagnostic advantages compared with autologous leukocyte scintigraphy.

Adult↗
PubMed1996

Clinical utility of external immunoscintigraphy with the IMMU-4 technetium-99m Fab' antibody fragment in patients undergoing surgery for carcinoma of the colon and rectum: results of a pivotal, phase III trial. The Immunomedics Study Group.

PURPOSE: To assess the performance and the potential clinical impact of a new antibody imaging agent, CEA-Scan (Immunomedics Inc, Morris Plains, NJ), in 210 presurgical patients with advanced recurrent or metastatic colorectal carcinomas. METHODS: CEA-Scan, an anti-carcinoembryonic antigen (CEA) Fab antibody fragment labeled with technetium-99m-pertechnetate (99mTc), was injected intravenously (IV), and external scintigraphy was performed 2 to 5 and 18 to 24 hours later. Imaging with conventional diagnostic modalities (CDM) was also performed, and findings were confirmed by surgery and histology. RESULTS: The sensitivity of CEA-Scan was superior to that of CDM in the extrahepatic abdomen (55% v 32%; P = .007) and pelvis (69% v 48%; P = .005), and CEA-Scan findings complemented those of CDM in the liver. Among 122 patients with known disease, the positive predictive value was significantly higher when both modalities were positive (98%) compared with each alone (68% to 70%), potentially obviating the need for histologic confirmation when both tests are positive. Imaging accuracy also was significantly improved by adding CEA-Scan to CDM. In 88 patients with occult cancer, imaging accuracy was enhanced significantly by CEA-Scan combined with CDM (61% v 33%). Potential clinical benefit from CEA-Scan was demonstrated in 89 of 210 patients. Only two patients developed human antimouse antibodies (HAMA) to CEA-Scan after a single injection, and none of 19 assessable patients after two injections. CONCLUSION: CEA-Scan affords high-quality, same-day imaging, uses an inexpensive and readily available radio-nuclide, adds clinically significant information in assessing extent and location of disease in colorectal cancer patients, and only rarely induces a HAMA response.

Antibodies, Monoclonal↗
PubMed1995

Improved staging of B-cell non-Hodgkin's lymphoma patients with 99mTc-labeled LL2 monoclonal antibody fragment.

Radioimmunodetection (RAID) with the 99mTc-labeled Fab' fragment of monoclonal antibody (MoAb) LL2 has been reported to have a high lesion detection rate for malignant lymph nodes as well as for visceral and skeletal tumor masses (20). Our purpose in this study was to evaluate the safety and staging efficacy of the 99mTc-labeled Fab' fragment of MoAb LL2 in patients with various grades and stages of B-cell non-Hodgkin's lymphoma (NHL). Thirty adult patients, 13 male and 17 female, ranging in age from 20 to 80 years, with at least one biopsy-proved malignant node (> or = 0.5 cm) and a Karnofsky performance score of > or = 60% were enrolled in this study. Patients underwent selected planar and single photon emission computed tomographic imaging at 6 and 18 h after receiving an i.v. infusion of 0.25-1 mg of LL2 Fab' fragment labeled with 25-30 mCi of 99mTc. RAID findings were compared with physical examination, chest radiography, computed tomography, magnetic resonance imaging, and bone and 67Ga scan findings. The RAID scan was positive in all but three patients. The sensitivity for known lesions was 90% and for suspected lesions, 89%, with an overall positive predictive value of 96%. Twenty-nine of the 30 patients had either low- or intermediate-grade NHL. Fifteen of 16 (94%) low-grade patients were correctly staged by RAID; three of these patients were correctly upstaged. Twelve of the 13 (92%) intermediate-grade patients were correctly staged by RAID; two of these patients were correctly upstaged. The high-grade NHL patient was staged correctly by RAID. Infused doses of 99mTc-labeled LL2 Fab' of 0.5 and 1.0 mg did not affect lesion sensitivity. The RAID sensitivity decreased as the total tumor burden increased > or = 100 g. On the basis of these initial results, the 99mTc-labeled Fab' fragment of MoAb LL2 (LymphoScan) seems to yield useful clinical information, especially for the staging of B-cell NHL patients who do not have bulky disease (i.e., tumor burdens of < or = 100 g).

Adult↗
PubMed1992

Polyinosinic-polycytidylic acid complexed with poly-L-lysine and carboxymethylcellulose in combination with interleukin 2 in patients with cancer: clinical and immunological effects.

We have performed a phase IB study of polyinosinic-polycytidylic acid complexed with poly-L-lysine and carboxymethylcellulose (poly-ICLC) in combination with interleukin 2 (IL-2) in 25 patients with a variety of cancers. Patients received weekly or biweekly poly-ICLC by i.m. injection, at doses ranging from 0.01 to 1.0 mg/m2, for 1 month. This was followed by 2 months of outpatient therapy with biweekly i.m. poly-ICLC in combination with IL-2 (3 x 10(6) units/m2) given i.v. by 24-h continuous infusion twice weekly, using a portable infusion pump. No objective tumor responses were observed. Toxicity was moderate at all poly-ICLC doses tested and increased only slightly following the addition of IL-2. No increases in peripheral blood natural killer (NK) activity were observed after treatment with poly-ICLC alone. However, high dose poly-ICLC (greater than or equal to 0.3 mg/m2) in combination with IL-2 resulted in NK activity greater than that seen using the same dose of IL-2 in combination with lower poly-ICLC doses. Increases in the number and percentage of CD56+ cells were evident only after initiation of IL-2 therapy and were unaffected by the poly-ICLC dose. In the majority of patients, these increases were preferentially associated with the subset of CD56+ cells coexpressing CD8, while the CD56+/CD16+ population was elevated to a lesser extent. Moderate increases in serum neopterin levels and 2',5'-oligoadenylate synthetase activity in peripheral blood mononuclear cells were noted at 72 h following initial treatment with 1.0 mg/m2 poly-ICLC. No induction of alpha or gamma interferon was detected. This study shows that the addition of poly-ICLC to a well tolerated IL-2 regimen can significantly enhance NK activity. Poly-ICLC can be used to enhance IL-2-induced NK lytic activity without increases in the dose and, therefore, the toxicity of IL-2 treatment.

Antigens, CD↗
PubMed1992

Lymphoma imaging with a new technetium-99m labelled antibody, LL2.

The lesion detection capability of a new technetium-99m labelled B-cell lymphoma monoclonal antibody (MoAb) imaging agent, LL2, was evaluated in 8 patients with non-Hodgkin's lymphoma and 1 patient with chronic lymphocytic leukaemia. The MoAb kit consists of a 1-vial, 1-mg Fab' form of LL2 ready for instant labelling with technetium. The patients were injected with approximately 925 MBq (25 mCi) of 99mTc-LL2 Fab' (1 mg), and planar and single photon emission tomography (SPET) studies were performed at 3-4 h post injection and at 24 h. There was no evidence of thyroid or stomach activity up to 24 h. Uniform splenic uptake was seen in all patients. Two non-lymphoma patients were also administered with the same agent and demonstrated a similar splenic distribution; therefore, splenic targeting was not scored as tumour-specific. A total of 29 from 48 tumour sites were detected by scintigraphy, including tumours of various grades and histological types. Excluding 1 patient who had a large tumour burden of over 500 g, 29 of 33 lesions were detected. One patient was free of disease at the time of the study and had a negative scan. Another patient showed excellent targeting of gallium-negative sites in the liver and bone. The bone involvement was not known prior to the antibody study and was subsequently confirmed by a bone scan. Additional sites of MoAb localization could not be followed in this group, since most patients went on to radioimmunotherapy immediately following the 99mTc-LL2 study.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1989

Imaging of colorectal carcinoma with radiolabeled antibodies.

Colorectal cancer has been the tumor type most frequently studied with radiolabeled antibodies. Among the various antibodies, a majority of patients with colorectal cancer have received xenogeneic polyclonal or monoclonal antibodies against carcino-embryonic antigen. This review summarizes the current status of colorectal cancer imaging with radiolabeled antibodies, ie, radioimmunodetection (RAID), and examines the published studies involving carcinoembryonic antigen (CEA) antibodies and 17-1A, 19-9, and B72.3, and other monoclonal antibodies. In order to better address the issue of the current and future clinical usefulness of this emerging technology, particular attention is given to the protocols, methods, and results of the published studies. Despite differences in study parameters, antibodies and forms, labels, administration routes and doses, and scanning instruments and methods, it has been found that (1) almost no adverse reactions have been evident; (2) antibody fragments are preferred over whole immunoglobulin G reagents because they achieve higher tumor-to-background ratios earlier, thus reducing or precluding the need for dual-isotope subtraction methods or long delays before imaging; (3) use of antibody fragments, including the monovalent Fab' form, permits imaging with short-lived radionuclides of excellent photon properties, such as 123I and 99mTc; (4) circulating antigens against which the imaging antibody is directed can complex with the injected antibody, but such complexes have not prevented successful RAID; (5) patients with high serum titers of the appropriate antigen target usually have higher rates of positive RAID; (6) patients who are seronegative for the tumor antigen being studied can have positive RAID findings, which can represent the detection of occult lesions; (7) single photon emission computed tomography appears to provide better image resolution than planar scanning; (8) regardless of the sensitivity reported in any particular study, almost all investigators have observed the disclosure of occult neoplasms by RAID; and (9) RAID, a more functional test of usually high specificity, can complement other radiological methods, such as computed tomography scans, which are limited to structural information.

Antibodies, Monoclonal↗
PubMed1987

Toxicity of intravesical BCG and its management in patients with superficial bladder tumors.

Toxicity of bacillus Calmette-Guerin (BCG) Pasteur strain, given in a dose of 120 mg once a week for 6 weeks, was retrospectively evaluated in a study of 107 patients with recurrent superficial bladder cancer. Only six patients had no symptoms of toxicity. Severe cystitis (ten patients) was most likely to occur in those with decreased bladder compliance before treatment. Systemic symptoms resembling those of influenza (flu) were severe in six patients. Potentially serious complications occurred in six patients. Overall, toxic reactions were mild and self limited, and toxicity often could be easily managed by a reduction in the BCG dose (17 patients), temporary interruption of treatment (five patients), or cessation (four patients). Late occurrence of bladder granulomas (32 patients) and cystoscopic appearance of significant cystitis (55 patients) did not correlate with posttreatment voiding symptoms, and these changes were temporary and confined to the first 6 months after treatment. There were no cases of late bladder contracture, and none of the patients free of voiding symptoms before treatment had such symptoms afterward. Extravesical granulomas were observed in 37 patients and were the cause of obstruction of the urinary tract in nine. Pretreatment skin reactivity did not correlate with toxicity, and concurrent percutaneous administration of BCG had no effect on toxicity. BCG has a cumulative effect, so increased toxicity is to be expected during long-term administration. BCG toxicity is primarily a response of the cell-mediated immune system, and transient local or systemic infection appears to be important. This fact suggests that immunosuppression is a relative contraindication to BCG use.

Adult↗
PubMed1987

A prospective randomized trial of maintenance versus nonmaintenance intravesical bacillus Calmette-Guérin therapy of superficial bladder cancer.

Between August 1981 and July 1984, 93 patients with polychronotopic superficial papillary carcinoma (Ta and/or T1), flat carcinoma in situ (Tis), or concomitant superficial papillary and in situ bladder carcinoma were entered into a prospective randomized trial of maintenance v nonmaintenance intravesical bacillus Calmette-Guérin (BCG) therapy. Forty-six patients who received BCG weekly for 6 weeks were compared with 47 patients receiving the six-weekly doses of BCG plus monthly BCG for 2 years. Both groups were evaluated every 3 months by cytology, cystoscopy, and biopsy. A significant reduction in the number of recurrent tumors per patient-month was demonstrated for both groups (P less than .0001); however, the difference in reduction of tumors between the two groups was not significant. Additionally, patients receiving maintenance and nonmaintenance therapy had similar tumor recurrence and progression rates. These results indicate that monthly maintenance BCG does not prevent, delay, or reduce tumor recurrence or progression observed with the 6-week regimen. Maintenance BCG was associated with increased local toxicity, primarily dysuria, frequency, and urgency. Dosage reduction was required in 22 of 47 patients (46.8%). When the data were subjected to multivariate analysis, the presence or absence of tumor following induction BCG and PPD skin test results were found to be significant variables. Controlling for either the presence or absence of tumor following induction BCG, tumor recurrence and progression rates were not significantly different for the two treatment groups. However, the absence of tumor after induction BCG was associated with a longer disease-free duration (P = .00001) and time to progression (P = .095). Patients with a reactive tuberculin skin test before and after induction BCG had significantly less tumor recurrences than patients with different PPD skin tests results (P = .02). Tumor progression was not related to tuberculin skin testing.

BCG Vaccine↗
PubMed1986

Long-term effect of intravesical bacillus Calmette-Guerin on flat carcinoma in situ of the bladder.

Intravesical bacillus Calmette-Guerin is effective therapy for multifocal carcinoma in situ of the bladder. The duration of this favorable response and its effect on disease progression are the subject of this report. Between March 1978 and July 1981, 47 patients with diffuse, often symptomatic, carcinoma in situ were treated with intravesical bacillus Calmette-Guerin and followed every 3 to 4 months with cystoendoscopy, biopsy and urine cytology for 3 to 6 years. All patients had had prior or concurrent superficial papillary tumors controlled initially by transurethral resection and fulguration 2 to 3 weeks before bacillus Calmette-Guerin treatment. Of the 47 patients 23 were entered into a randomized study, and received intravesical and percutaneous bacillus Calmette-Guerin. Another 24 patients with carcinoma in situ were treated with intravesical bacillus Calmette-Guerin alone. Bacillus Calmette-Guerin (Pasteur strain) was given intravesically (120 mg. in 50 ml. saline) weekly for 6 weeks. Of the 47 patients 32 (68 per cent) are free of disease (negative urine cytology, cystoendoscopy and biopsy): 15 (65 per cent) after combined bacillus Calmette-Guerin for a median duration of 51 months (range 37 to 75 months) and 17 (71 per cent) after intravesical bacillus Calmette-Guerin alone for a median of 45 months (range 36 to 53 months). Of the 23 patients in the randomized study 4 (17 per cent) have required cystectomy for local progression of disease compared to 17 of 26 controls (65 per cent) who were randomized to transurethral resection and fulguration alone. Cystectomy was performed 3 to 27 months after bacillus Calmette-Guerin treatment and in 3 patients tumor was localized to the prostate gland (no tumor found within the bladder). These data indicate that intravesical bacillus Calmette-Guerin is capable of producing long-term remissions of carcinoma in situ in high risk patients and may prevent or delay progression of disease necessitating cystectomy.

Biological Products↗
PubMed1986

Local administration of immunomodulators.

This summary of results with local BRM administration has been brief because the number of clinical situations in which this approach is applicable is quite limited. On the other hand, when applied in an appropriate patient population, clinical responses are frequent. In addition, detailed study of the effector cells and cytokines that appear in responding patients may yield information concerning the mechanism of action when BRM therapy is effective. Finally, comparison of the results from clinical trials with the results in experimental animals may help to further elucidate the mechanism by which BRMs exert antitumor effects.

Adjuvants, Immunologic↗
PubMed1985

The serologic response of patients with stage II melanoma to allogeneic melanoma cell vaccines.

Seventeen patients with Stage II malignant melanoma were treated with vaccines prepared from three allogeneic melanoma cell lines in an attempt to induce a humoral immune response against melanoma cell surface antigens. The patients were free of detectable melanoma at the time of vaccination. Vaccines were prepared from three melanoma cell lines that expressed highly restricted melanocyte differentiation antigens. One of these cell lines also expressed an antigen found only on this particular line. The antigens were initially identified by antibodies in autologous serum; they were thus known to be recognized by the human immune system. In addition, two of the cell lines expressed HLA-A, -B, -C, and -DR antigens; no HLA antigens were detectable on the third line. The vaccines were administered sequentially by subcutaneous injection, mixed with bacillus Calmette-Guerin (BCG) or Corynebacterium parvum. The patients' sera were tested for antibodies against cell surface antigens of the vaccine cells in protein A assays and immune adherence assays, and the specificity of observed reactions was defined by absorption tests. Antibodies against alloantigens of the vaccine cells developed in 16 patients and in 15 patients, against antigens related to fetal calf serum in the culture medium. The magnitude of the antibody response to alloantigens varied considerably, with no difference between patients who received BCG or C. parvum with their vaccines. Antibodies against the restricted melanocyte differentiation antigens or the unique melanoma antigen expressed by the vaccine cells were not detected.

Adult↗
PubMed1985

Malignant melanoma appearing in a post-mastectomy lymphedematous arm: a novel association of double primary tumors.

The association of a malignant melanoma appearing as an additional primary tumor in the swollen arm adjacent to a mastectomy for breast cancer is reported. A review of the literature revealed only one similar patient previously reported. In both patients, the melanoma and its metastasis were restricted to the lymphedematous arm, appeared 10 years post-mastectomy, and responded to therapy. The similarity to Stewart-Treves syndrome is emphasized. It is suggested that nevi developing in the lymphedematous arm post-mastectomy should be carefully monitored and excised early whenever indicated.

Arm↗
PubMed1985

Experience with intravesical bacillus Calmette-Guèrin therapy of superficial bladder tumors.

Between March, 1978, and July, 1981, 86 patients with polychronotopic superficial papillary bladder tumors and concurrent carcinoma in situ were randomized to receive either transurethral resection alone (43) or TUR plus BCG (43). The results indicate that BCG is not only active in preventing recurrences of new tumors but also effective for the diffuse, flat carcinoma in situ.

Adult↗
PubMed1985

Monitoring intravesical bacillus Calmette-Guerin treatment of bladder carcinoma with flow cytometry.

Flow cytometry of bladder irrigation specimens was studied in 22 patients with low stage bladder carcinoma who were treated by transurethral resection of visible tumor followed in 3 to 5 weeks by a course of intravesical bacillus Calmette-Guerin. The most informative examinations were just before the first bacillus Calmette-Guerin treatment, 6 weeks after completing a 6-week course of treatment (3 months) and at 9 months. Of the patients 10 had recurrent tumors after therapy; recurrence was anticipated correctly by flow cytometry at the 12-week followup examination in 6 of the 10 patients and suspected in another. Of 12 patients who remained clinically free of disease for a minimum of 15 months after bacillus Calmette-Guerin therapy flow cytometry identified correctly 7 at 12 weeks, while 1 had a partial response and the remaining 4 reverted to a negative status at 9 months. Of interest, only 4 of the 22 patients were free of disease by flow cytometry at the start of bacillus Calmette-Guerin treatment despite attempted ablation of the tumor by transurethral resection, suggesting that intravesical administration of bacillus Calmette-Guerin destroys existing carcinoma in situ in some cases.

BCG Vaccine↗