Chemosensitivity testing of human solid tumors. A review of 1582 assays with 258 clinical correlations

Abstract

To improve clinical interpretation and use of in vitro clonogenic assay results, the authors reviewed their experience to date with chemosensitivity testing of over 1500 solid tumors. All clonogenic assays were performed using a double-layer-soft-agar system with continuous exposure of cells to one concentration of standard anticancer drugs. Significant growth was defined as 230 colonies/control plate. Clinical responses were determined according to standard criteria. Data were analyzed using two different criteria of in vitro sensitivity (250% and 275% inhibition of colony formation) and independently for each histologic type of tumor. Overall, 68% of specimens plated produced significant growth in vitro. Cloning ability varied from 57% to 82% depending on tumor histology. The assay was 57% reliable for predicting in vivo sensitivity, and 92% reliable for in vivo resistance. Predictive accuracy for sensitivity varied from 30% to 86%, depending on the tumor histology. Use of 250% ICF (inhibition of colony formation) as criteria for differentiating sensitivity from resistance proved most reliable, although criteria should be individualized for each tumor type to maximize predictive accuracy.Cancer 53:1240-1245, 1984.OR OVER TWO DECADES, clinical investigators have F pursued the goal of developing an in vitro test that could accurately predict the chemosensitivity of a malignant tumor. A number of assay techniques have evolved, including the double-layer-soft-agar method reported by Hamburger and Salmon in 1977.' This technique, now commonly referred to as the "clonogenic assay," has been the most extensively studied and clinically applied chemosensitivity test. A number of retrospective reports indicate that the clonogenic assay can predict in vivo sensitivity with approximately 50% to 70% accuracy and in vivo resistance with greater than 85% accuracy.'-' Despite the early favorable reports, there is still considerable skepticism, and several recent critical appraisals of the assay have been published.'-'' Current problems in assay methods have been stressed, including low plating

Murine Models to Evaluate Novel and Conventional Therapeutic Strategies for Cancer

“…Clinically ineffective agents were also found to be negative with 97% accuracy, an observation confirmed by other reports. 8,[32][33][34][35] However, the HTSC assay 8,36 is limited because of the low plating efficiency of most solid tumors and the poor availably of tumor tissue. Thus, only breast, colorectal, kidney, lung, melanoma, and ovarian tumors have been found to provide sufficient cells for evaluation, although strategies have been suggested to improve the growth rates of primary tumor tissues.…”

Prediction of chemotherapeutic effect on postoperative recurrence by in vitro anticancer drug sensitivity testing in non-small cell lung cancer patients

“…Several in vitro anticancer drug sensitivity tests have been developed in various types of malignant tumors, and such tests have been preliminarily applied experimentally as well as clinically [3,4]. The collagen gel droplet embedded culture drug test (CD-DST) is an in vitro anticancer drug sensitivity test, that has been applied for chemotherapy to NSCLC as well as mesothelioma patients [5][6][7][8].…”

In Vitro Chemo-Sensitivity Assay Guided Chemotherapy is Associated with Prolonged Overall Survival in Cancer Patients

“…The growth rates (73-96%) were equal to or higher than what has been determined in other assays (i.e. 57-82% in (14), 87% for ovarian cancer in (15), 40-70% in (13), 66-90% in (3). They differed markedly depending on histological diagnosis.…”

“…Since the first reports of oncobiograms (11) and the human tumour clonogenic assay (12) appeared, different methods were established to determine in vitro chemosensitivity. Some of these methods are, for instance, taking measurements of radiolabeled DNA-precursors, the fluorescent cytoprint assay (FCA), the differential staining cytotoxicity assay and the ATP-cell viability assay (ATP-CVA) (13), which has shown a predictive accuracy for in vivo sensitivity of 30-86% and for in vivo resistance of 92% in an analysis of 258 in vitro/in vivo associations for various tumour entities (14). Similar results were reported by other authors (15)(16)(17)(18).…”