Individualized Tumor Response (ITR) Profiling for Drug Selection in Tailored Therapy: Meta-Analysis of 1929 Cases of Leukemia and Lymphoma.
Authors: Bosanquet Andrew G. , Kaspers Gertjan J. , Larsson Rolf , Nagourney Robert A. , Nygren Peter , Pieters Rob , Staib Peter , Tidefelt Ulf , Zwaan C. Michel , Weisenthal Larry M. 
Published: October 2019

Abstract
Background. There has been a long history of Individualized Tumor Response (ITR) testing to aid drug selection in tailored therapy for leukemia and lymphoma. Almost all the published evidence suggests that the results produced provide useful prognostic information and added value that is independent of other patient variables. Trials have shown ITR test results correlate with subsequent patient response and survival. However, results have not been so readily accessible due, in part, to multiple descriptive terms.
Terminology. As a result, groups undertaking ITR with leukemias, lymphomas and solid tumors have agreed to use the term ’Individualized Tumor Response’ to describe the ’effect of anticancer treatments on whole living tumor cells freshly removed from cancer patients’. This term does not include tests with subcellular fractions, animals or cell lines.
Methods. All methods measure cell death: fresh tumor is removed from the patient, treated with an anticancer regimen in vitro for 2–7 days and tumor survival assessed. ITR testing for chemotherapy and radiotherapy has recently been extended to cover newer agents (Weisenthal, 2007).
Results. Multiple publications have shown assays correlate well with each other, allowing this meta-analysis. We found 1929 published ITR test results compared with patient response and analysed them to determine relative risk (Rel Risk) of clinical response after treatment with ITR-test-sensitive (ITR+) vs. ITR-test-resistant (ITR-) regimens:
Comparison of ExVTR test results with clinical response rate (RR) and relative risk (Rel Risk) Diagnosis # Clinical RR RR ITR+ RR ITR− Rel Risk IVT+ Rel Risk IVT− *, 2P=0.025; **, 2P=0.002; *** 2P<0.0001; #, number of patients ALL 304 81.3 90.6 49.3 0.90** 1.65*** ANLL 621 72.0 87.9 35.8 0.82*** 2.01*** CLL 720 69.0 82.5 18.8 0.83*** 3.66*** NHL 85 54.1 72.9 11.5 0.74* 4.69*** Other 199 61.3 78.2 8.3 0.78*** 7.36*** Total 1929 70.4 84.6 28.3 0.83*** 2.48***
Overall, the response rate for patients given ITR+ drugs (84.6%) is significantly greater than for patients treated with ITR- drugs (28.3%). The relative risk of not responding was significantly reduced by treatment with an IVT+ regimen (0.83; 95% Confidence Interval 0.80–0.86) but increases to 2.48 (2.15–2.87) when treated with an IVT- regimen. Published comparisons of ITR with patient survival have all shown better survival for patients treated with ITR+ drugs compared with patients treated with ITR- drugs. A randomised controlled clinical trial of the efficacy of ITR in CLL is ongoing.
Conclusions. Compared with newer methods being developed to provide tailored therapy (such as genomic analyses), ITR testing provides a functional profile of how whole tumor cells respond to toxic insult. This is far closer to what happens in the patient than the measurement of the effect on genes or proteins. Further investment in ITR testing - technologies that produce clinically significant results for tailored therapy - is warranted.