Edward Martin

Radioimmunoguided surgery using monoclonal antibody

The potential proficiency of radioimmunoguided surgery in the intraoperative detection of tumors was assessed using labeled monoclonal antibody B72.3 in 66 patients with tissue-proved tumor. Monoclonal antibody B72.3 was injected 5 to 42 days preoperatively, and the hand-held gamma-detecting probe was used intraoperatively to detect the presence of tumor. Intraoperative probe counts of less than 20 every 2 seconds, or tumor-to-adjacent normal tissue ratios less than 2:1 were considered negative (system failure). Positive probe counts were detected in 5 of 6 patients with primary colon cancer (83 percent), in 31 of 39 patients with recurrent colon cancer (79 percent), in 4 of 5 patients with gastric cancer (80 percent), in 3 of 8 patients with breast cancer (37.5 percent), and in 4 of 8 patients with ovarian cancer (50 percent) undergoing second-look procedures. Additional patients in each group were scored as borderline positive. Overall, radioimmunoguided surgery using B72.3 identified tumors in 47 patients (71.2 percent), bordered on positive in 6 patients (9.1 percent), and failed to identify tumor in 13 patients (19.7 percent). Improved selection of patients for antigen-positive tumors, the use of higher affinity second-generation antibodies, alternate routes of antibody administration, alternate radionuclides, and more sophisticatedly bioengineered antibodies and antibody combinations should all lead to improvements in radioimmunoguided surgery.

Second-look Surgery for Colorectal Cancer

Eighty-six colorectal cancer patients who entered the Radioimmunoguided Surgery (RIGS) protocol study were evaluated for 2-, 3-, 4-, and 5-year survival following second-look surgical procedures. Strict preoperative evaluation criteria eliminated patients with extra-abdominal tumor involvement. A saturated potassium iodide preparation was given before the intravenous administration of the B72.3 monoclonal antibody (1 mg) radiolabeled with 2 mCi of iodine-125 by the IODOGEN method. Precordial monitoring of the biologic clearance by the handheld, gamma-detecting probe (Neoprobe 1000 instrument) was conducted at weekly intervals until the average count was less than 20 counts in 2 seconds. Once the drug cleared from the blood, surgery was performed. The mean time interval between injection and operation was 24 days, with a range of 21 to 28 days and a median of 23 days. At surgery the abdomen was explored through the traditional methods of palpation and inspection, and the surgeon committed to a planned procedure. The abdomen was then re-explored with the handheld, gamma-detecting probe and the surgeon stated another intraoperative assessment. After using both traditional and RIGS detection methods, the surgeon stated whether his or her surgical plans changed because of the additional intraoperative information provided by the RIGS system. Fifty-three patients (62%) were deemed resectable by the traditional methods of palpation and inspection, but only 40 (47%) were specified as resectable by RIGS exploration. Two-, three-, four-, and five-year survival data could be gathered for each of the three groups: RIGS resectable (n = 40), traditional nonresectable (n = 33), and RIGS nonresectable (n = 13). At 2 years 95% of the resectable, 36% of the traditional nonresectable, and 53% of RIGS nonresectable patients survived. At 3 years 83%, 7%, and 30% of these patients survived, respectively. For the resectable patients, 74% survived at 4 years and 60% at 5 years, with no survivors from either nonresectable group. Use of the RIGS system increased accurate selection of resectable patients undergoing second-look surgery for recurrent colorectal cancer.

Radioimmunoguided surgery for colorectal cancer

This article provides a basic understanding of the RIGS (radioimmunoguided surgery) technique and reviews the evolution of the technology from its inception as an experimental technique in animal models to the current clinical trials in patients. A review of published data from the laboratory and from preclinical and clinical trials is updated by a statement of the current status of RIGS. A look at the future of RIGS as an experimental and clinical tool highlights current areas of investigation based on this technology.AbstractBackground: Operations for patients with colorectal cancer are based on traditions established by historical experience. Radioimmunoguided surgery (RIGS) provides new information that challenges these traditions.nMethods: Thirty-two patients with primary colorectal cancer underwent RIGS after being injected with anti-TAG-72 murine monoclonal antibody CC49 labeled with iodine-125. Sixteen of the patients had all gross tumor and RIGS-positive tissue removed (RIGS-negative group), and 16 had only traditional extirpation of the tumor because RIGS-positive tissue was too diffuse (RIGS-positive group).nResults: In the 16 patients having all RIGS-positive tissue removed, five had traditional regional en bloc resections and 11 had additional extraregional tissues resected. Identification of extraregional disease added two liver resections and 25 lymphadenectomies: 10 of the gastrohepatic ligament, five celiac axis, six retroperitoneal, and four iliac. With a median follow-up of 37 months, survival in the RIGS-negative group is 100%. In 14 of 16 patients (87.5%) there is no evidence of disease. In the RIGS-positive group, follow-up shows 14 of 16 patients are dead and two are alive with disease (p<0.0001).nConclusion: These results suggest that RIGS identifies patterns of disease dissemination different from those identified by traditional staging techniques. Removal of additional RIGS-positive tissues in nontraditional areas may improve survival.

Staging of colorectal cancer: Biology vs. morphology

PURPOSE: An accurate determination of the extent or staging of a disease is critical, because it provides the basis for making therapeutic decisions. Staging is a collaborative effort by the surgeon and the pathologist. Radioimmunoguided surgery has been evaluated for its ability to help surgeons determine the extent of disease during surgery, when management decisions have the most impact on patient care. This study was done to compare radioimmunoguided surgery “biostaging” with traditional pathologic staging (TNM) as predictors of survival in patients undergoing curative resections for colorectal cancer. METHODS: Ninety-seven patients with colorectal cancer were prospectively enrolled in radioimmunoguided surgery protocols. Evaluation of follow-up survival data was performed. All patients underwent exploratory laparotomy and radioimmunoguided surgery with resection of their primary colorectal tumor. Survival data were analyzed with the Kaplan-Meier method with log-rank comparisons. RESULTS: Of 97 patients enrolled in the study, 59 were evaluable and completely resectable by radioimmunoguided surgery. Mean follow-up was 62 months, with a range of 34 to 89 months. By traditional staging 13 patients were pStage I, 18 patients were pStage II, and 28 patients were pStage III. By radioimmunoguided surgery biostaging, 24 patients were radioimmunoguided surgery-negative whereas 35 patients were radioimmunoguided surgery-positive. Survival rates by pathologic stage approached a significant difference, but did not, as of the conclusion of the study period, reach it (P=0.12). Survival rates based on radioimmunoguided surgery status demonstrated a highly significant difference (P=0.0002). CONCLUSIONS: Radioimmunoguided surgery biostaging provides new information intraoperatively on cancer staging that has not been available before. This may lead to new strategies for therapy that can be individualized and optimized for each patient with cancer.