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Jiim/DIAGNDSTIC NUCLEAR MEDICINE Scintigraphic Criteria For jIIm/DIAGNDSTIC NUCLEAR MEDICINE Scintigraphic Criteria for Hepatic Metastases from Cancer of the Colon and Breast David E. Drum and Judith M. Beard Harvard Medical Sc/zoo! and the Joint Program in Nuclear Medicine of Peter Bent Brigham Hospital, Children's Hospital Medical Center, and Sidney Farber Cancer Center, Boston, Massachusetts Scintigraphic criteria Jor hepatic metastases were studied by examination of 333 liver scintigrams performed on 275 patients with primary cancers of the colon or breast. Focal defects in radiocolloid distribution correctly signaled the presence of metastatic colon carcinoma in 88% of the patients with that disease and incorrectly pointed to only 6% of the patients with out such metastases. In contrast, the same criterion detected only 67% of hepatic metastases from breast carcinoma. This lower sensitivity could be improved to 87% by adding heterogeneity or hepatomegaly to the criteria for abnormality when patients with breast cancer are examined. Scinti graphic indicators of metastatic disease may vary according to the site of primary cancer. JNuclMed 17: 677-480, 1976 Scintigraphy of the liver plays a major role both aminations of I 67 patients with primary adenocar in detecting hepatic metastases and in evaluating cinoma of the colon or rectum and from 125 exam their response to cancer chemotherapy. Despite evi inations of I08 patients with primary carcinoma of dence that the features of biologic growth of various the breast formed the basis for the analyses. No pa primary tumors differ widely ( 1) , no effort has been tient had more than one primary tumor. All repeat made to discern whether such variations are reflected examinations were made more than I month apart. in the scintigraphic properties of their hepatic me Each liver was examined either by closed needle tastases. biopsy, surgical observation, surgical biopsy, or post Recently, hepatic scintigraphy was reported to be mortem examination within 4 weeks of scintigraphy. 77% accurate in the detection of tumor metastases Any liver proven by these methods to contain meta when the primary disease was breast carcinoma and static deposits was assumed to have contained them 85 % accurate in the detection of metastatic colon at the time of scintigraphy. Further, any liver proven cancer (2). These data raise the question of whether free of metastases at postmortem examination was the growth features of metastases from these two considered to have been free of metastases at the common primary sources are sufficiently different to time of imaging. generate intrinsically different scintigraphic images, Hepatic scintigraphy. Hepatic scintiscans were be with the implication that the criteria for abnormality gun 10—30 mm after intravenous injection of 3—5 may depend upon the nature of the primary tumor. mCi of 9omTcsulfur colloid. An Anger scintillation In order to investigate this hypothesis, we studied the camera with 19 photomultiplier tubes, a 25-cm-diam medical charts of 275 patients whose livers had been directly examined shortly after hepatic scintigraphy. Received Dec. 3, 1975; revision accepted Feb. 23, 1976. MATERIALS AND METHODS For reprints contact: David E. Drum, Dept. of Radiology, Harvard Medical School, 25 Shattuck St., Boston, MA Data base.The scintigraphic findings from 208 cx 02115. Volume I 7, Number 8 677 DRUM ANDBEARD crystal, and a I40-keV diverging collimator was em scintigraphic criteria resulted in a similar true-posi ployed in all cases. Anterior (650,000 counts), p05- tive ratio (0.89) , but the false-positive ratio was tenor (650,000 counts), and right lateral (540,000 considerably larger (0.27). Thus, either strict or counts) views were obtained for every patient. For liberal criteria detected metastatic colon carcinoma all examinations two point sources, 10 cm apart, with equal sensitivity. The liberal criteria were less were photographed at the collimator face to aid esti specific, however, and would have indicated incor mation of organ size. rectly the presence of metastases in some livers when The scintigraphic images of the liver were evalu they were in fact absent. The general accuracy of ated for the following features: scintigraphy, expressed as the ratio of correctly iden Focal defect(s): One or more clearly delimited tified normal and abnormal livers to the total num areas of absent or minimal radiocolloid ac ber examined, was 9 1% with the strict criterion and cumulation surrounded by areas of normal 79% with the liberal criteria. radiocolloid uptake. Carcinoma of the breast exhibited distinctly dif Heterogeneity: Irregular distribution of radio ferent accuracy parameters (Table 2) . The strict colloid within the liver. criterion for scintigraphic abnormality led to a true Hepatomegaly: Any liver image with a vertical positive ratio of only 0.67 and a false-positive ratio @ height greater than 17 cm and a horizontal of 0.09. In contrast, the liberal criteria generated a width greater than 18 cm (3). true-positive ratio of 0.87 and a false-positive ratio In order to judge which scintigraphic features most of 0.29. Thus, for breast carcinoma the liberal cri accurately reflected the presence or absence of he teria were more sensitive to the presence of hepatic patic metastases, two kinds of criteria were em metastases than were focal defects alone. This en ployed: hanced detection was accomplished at the expense Strict: The scintigram was considered positive for metastases only when one or more focal defects could be seen (2—8). Liberal: The scintigram was considered positive TABLE 1. PARAMETERSFOR EVALUATION for metastases when focal defects, heteroge OF THE LIVER SCINTIGRAM OF PATIENTS neity, hepatomegaly, or any combination of WITH COLON CARCINOMA* these was apparent. Critera formetostasesFocal Data analyses. The scintigraphic data were ana defects,heterogeneity, lyzed for accuracy, sensitivity, and specificity accord orFocal ing to the following definitions: onlyhepatomegalyAnalysisdefects (strictcrterion)(liberal crteria) True-positive ratio: The fraction of livers that generated abnormal scintigraphic images and True.positive ratio 0.88 0.88 False.positiveratio 0.06 0.27 were proven to have metastatic disease (a False.negative ratio 0.12 0.11 measure of sensitivity). True.negative ratio 0.94 0.73 False-positive ratio: The fraction of livers with *Atotalof208liverswere imaged: of these, 88 were out metastatic disease that generated abnor found to have metastases. mal scintigraphic images. True-negative ratio: The fraction of livers with out metastatic disease that generated normal scintigraphic images (a measure of speci ficity). TABLE 2. PARAMETERSFOR EVALUATION OF THE LIVER SCINTIGRAM OF PATIENTS False-negative ratio: The fraction of livers that WITH BREASTCARCINOMA* generated normal scintigraphic images in spite of proven metastatic disease. Criteria formetastasesFocal Each ratio was calculated twice : once with the strict defects,heterogenety, criterion for scintigraphic evidence of metastases and or- onlyhepotomegalyAnalysis Focal defects once with the liberal criteria. (strictcriterion)(liberal criteria) True-positive ratio 0.67 0.87 RESULTS False.positive ratio 0.09 0.29 False.negative ratio 0.33 0.13 Among the 208 scintigrams of patients with pri True.negative ratio 0.91 0.71 mary carcinoma of the colon or rectum, the strict S A total of 1 25 livers were imaged: of these, 60 were criterion yielded a true-positive ratio of 0.88 and a found to have metastases. false-positive ratio of 0.06 (Table I ). The liberal 678 JOURNAL OF NUCLEAR MEDICINE DIAGNOSTIC NUCLEAR MEDICINE of a considerable increase in false-positive interpre liver disease (9). In particular, when the primary tations. Consequently, the general accuracy was simi tumor was carcinoma of the colon, the overall accu lar for scintigrams interpreted by either strict or racy of the liver scan was 90% . This figure is unsur liberal criteria (Table 2) : 80% and 79%, respec passed by any other noninvasive technique. Meta tively. static breast carcinoma appeared to cause focal Livers without metastases generated similar scm.. defects in this series less frequently than colon car tigraphic features regardless of the nature of the cinoma. Hence, its detection accuracy was lower primary tumor. Judged by the strict criterion, the (i.e., 80%). false-positive ratio was 0.06 for patients with colon When the strict criterion of focal defects was em primaries and 0.09 for patients with breast primaries. ployed as an indication of metastases, the false According to the liberal criteria, the corresponding positive ratios were identical for patients with colon ratios were 0.27 for colon carcinoma and 0.29 for or breast primaries. Livers not involved with meta breast carcinoma. Among the patients with colon static deposits were so defined by the liver scan primaries whose scintigrams were judged by the strict independently of the nature of the primary cancer criterion, three of seven false-positive interpretations and of the regimen used in managing these patients. arose from fatty infiltration, two from portal inflam Application of more liberal scintigraphic criteria matory infiltrates, one from macroscopic cirrhosis, for detecting metastatic colon carcinoma diminished and one from severe systemic and abdominal sepsis. overall accuracy by increasing the false-positive ra Three of these images exhibited significant extra tio. Thus, heterogeneity or hepatomegaly are seldom hepatic radiocolloid localization. Two of the seven unique manifestations of
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