Academic literature on the topic 'Modified CHOI criteria'

407 Background: The objective of this study is to predict progression-free survival (PFS) and overall survival (OS) in metastatic RCC on sunitinib therapy using initial post-therapy CT imaging changes as a biomarker. Methods: An IRB-approved HIPAA-compliant analysis of CT imaging and survival data from 213 randomly selected patients on sunitinib therapy from a prospective phase III trial of metastatic RCC treated with sunitinib (N=375) versus interferon-alpha (N=375) was performed. Up to 5 target lesions were identified, and response per RECIST 1.1, Choi Criteria, Modified Choi Criteria, and MASS Criteria were made in comparison with the baseline images, while blinded to clinical data. Imaging responses on the first post-therapy CT were associated with PFS and OS by log-rank test, descriptive statistics, and cox proportional hazards models. Results: All criteria had predictive capacity for PFS and OS (log-rank p < 0.0004 each). Only hazard ratios (HRs) of the best and worst response for Modified-Choi (0.60/2.60) and MASS Criteria (0.46/14.8) were both significantly different from the middle category for predicting PFS (p = 0.002/p = 0.008 and p < 0.001/p < 0.001). Only HRs of the best and worst response for RECIST (0.46/9.78) and MASS Criteria (0.56/7.18) were both significantly different from the middle category for predicting OS (p = 0.007/p < 0.001 and p = 0.001/ p <0.001). The overall accuracy for detecting a good clinic outcome (PFS > 250 days) was 51% for RECIST, 62% for Choi Criteria, 67% for Modified Choi Criteria, and 76% for MASS Criteria. The overall accuracy for detecting a poor clinical outcome (PFS<250 days) was 58% for RECIST, 57% for Choi Criteria, 58% for Modified Choi Criteria, and 58% for MASS Criteria. Conclusions: MASS Criteria had the best overall accuracy for predicting PFS and OS in metastatic RCC on sunitinib therapy.

AbstractThe rapid recent advances in oncology have made the dream of precision oncology a reality, with targeted therapy available for various tumors depending on the molecular genotype. This has led to the corresponding development of personalized radiology as well, with various tumor response criteria used to characterize disease response/progression depending on chemotherapy used. In these two review articles, we review the various tumor response criteria widely applied in both research and clinical settings. These include the classic size-based criteria such as RECIST (Response Evaluation Criteria In Solid Tumors) 1.1 and the WHO (World Health Organization) criteria, as also various other criteria such as Choi and modified Choi criteria for tumors treated by targeted therapy, EASL (European Association for the Study of the Liver) and modified RECIST (mRECIST) criteria for hepatocellular carcinomas, immune-related response criteria (irRC) and immune RECIST (iRECIST) for patients on immunotherapy. Other clinically important criteria such as PERCIST (PET Response Criteria In Solid Tumors) for positron emission tomography–computed tomography (PET-CT), and the MD Anderson criteria for evaluating bone metastases are also highlighted.

AbstractThe rapid recent advances in oncology have made the dream of precision oncology a reality, with targeted therapy available for various tumors depending on the molecular genotype. This has led to the corresponding development of personalized radiology as well, with various tumor response criteria used to characterize disease response/progression depending on chemotherapy used. In these two review articles, we review the various tumor response criteria widely applied in both research and clinical settings. These include the classic size-based criteria such as RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 and the WHO (World Health Organization) criteria, as also various other criteria such as Choi and modified Choi criteria for tumors treated by targeted therapy, EASL and modified RECIST (mRECIST) criteria for hepatocellular carcinomas, and immune-related response criteria (irRC) and immune RECIST (iRECIST) for patients on immunotherapy. Other clinically important criteria such as PERCIST (PET Response Criteria In Solid Tumors) for positron emission tomography–computed tomography (PET-CT) and the MD Anderson criteria for evaluating bone metastases are also highlighted.

210 Background: The novel oncolytic virus JX-595 has demonstrated anti-cancer mechanisms of action, as defined in preclinical models, which includes cytolysis, intra-tumoral vascular disruption, and immune-mediated tumor targeting. Methods: To determine whether mechanism(s) of action (MOA) of the novel anti-cancer oncolytic virus JX-594 could be demonstrated by MRI imaging in patients with advanced hepatocellular carcinoma (HCC), dynamic contrast-enhanced MRI of the liver was performed at baseline, day 5, and week 8 following intra-tumoral injection. Images were evaluated by a central reviewer blinded to treatment and dose using both modified RECIST and Choi response criteria. 17/30 subjects underwent day 5 (D5) post-treatment imaging; 28/30 had week 8 (W8) imaging. Results: Choi responses correlated more reliably than RECIST with JX-594 MOA. Evidence of intra-tumoral vascular shutdown, manifest by areas of reduced or non-enhancement (Choi response), was observed in 6 of 17 subjects on D5 5 MRI scans. Day 5 Choi responses were a predictor of week 8 Choi responses in all but 1 subject. Of the 11/17 D5 Choi non-responders, 3 were Choi responders at 8 weeks. Increase in size at D5 of small lesions present at baseline (“unmasking”) is compatible with oncolytic flare due to intra-tumoral edema contributed to by cell lysis and immune infiltration. RECIST criteria tumor measurements did not identify MOA of JX-594, and resulted in the appearance of pseudoprogression at D5 in some subjects. Conclusions: Hyperacute MRI post-therapy can be used to detect activity of the JX-594, a novel oncolytic anti-cancer therapy. Day 5 Choi responses were a predictor of subsequent response at week 8. Clinical trial information: NCT00554372.

e16062 Background: Targeted therapy is now the standard of care in advanced Renal Carcinoma (RCC). Response assessment by RECIST criteria is insensitive as treated tumours often have only a modest change in size despite the induction of significant necrosis and does not correlate with time to progression (TTP). The Choi criteria (10% size reduction or 15% contrast enhancement reduction) are routinely used in the assessment of GIST tumours treated with targeted agents. We report the use of combined size and density assessment in RCC metastases treated with either sunitinib or cediranib. Methods: CT scans from 32 patients with metastatic RCC treated with either sunitinib (18) or cediranib (14) were assessed. Scans from 10 patients were not evaluable as non-contrast enhanced scans were performed due to impaired renal function. Scans from a further 2 patients were excluded as they ceased treatment due to toxicity rather than progression. Scans from 20 evaluable patients at baseline and 12 weeks on treatment were assessed using RECIST, Choi, and modified criteria in which both a 10% decrease in size and 15% decrease in enhancement in the arterial phase were required to define a response (PR). A total of 60 lesions were assessed. Response assessment was performed using each of the three methods and correlated with time to disease progression (itself RECIST defined). Statistical analysis was performed using the Mann-Whitney U test. Results: There was no difference in TTP between RECIST defined PR (346.8 days) and SD (328.5 days) (P=0.965). TTP in Choi defined PR (358.4 days) and SD (189.6 days) groups showed improved but non-significant separation of TTP duration (P=0.266). TTP in PR (421.5 days) and SD (200.3 days) groups defined by a combined assessment of reduction in size and enhancement showed greatly improved separation (P=0.064). Conclusions: A combined reduction in both size and arterial phase enhancement of RCC metastases treated with TKIs correlates with time to progression. RECIST and standard Choi criteria appear inferior. No significant financial relationships to disclose.

314 Background: Second-line options in treatment of HCC are limited. Axitinib is a multi-targeted tyrosine kinase inhibitor (TKI) of VEGFRs 1, 2, and 3, PDGFR and c-KIT that warrants exploration in HCC. Methods: This is an open-label, single-arm, two-stage phase II trial of axitinib in advanced HCC. Eligible patients (pts) are Child-Pugh A/B7, with measurable progressive disease after TKIs/antiangiogenic drugs. Axitinib starts at 5 mg bid orally, titrated to 10 mg bid as tolerated. Treatment continues to progression (PD) or intolerable toxicity. Primary endpoint is response defined by reduction in size by RECIST 1.1 on CT scan at 16 wks, secondary endpoints to compare response by RECIST 1.1 to Choi criteria and modified RECIST, explore dynamic imaging models, feasibility, safety, PFS and overall survival. Results: We present results of 15 (of 29) pts enrolled from 01/11 - 09/12. Median age; 62y (range 18-78) with ECOG PS 0 (5 pts), 1 (10 pts) with prior therapy of Temsirolimus/Bevacizumab (2 pts), sorafenib (13 pts). A planned safety/futility interim analysis was passed. Most common axitinib-related AEs were hypertension (HTN) (60%), hand-foot skin reaction (HFSR) (60%), diarrhea (60%), fatigue (50%). Most common axitinib-related grade 3 (G3) AEs were HTN (20%) and diarrhea (20%). There were no G3 HFSR. There was 1 G4 hyperbilirubinaemia. 60% of pts had dose interruptions due to AEs; most common reasons included fatigue (20%), HTN (10%), and HFSR (10%). 20% required dose reductions, 14% of pts tolerated dose escalation above 5 mg bid. As of 09/12, 8 pts remain on study, 7 pts discontinued (4pts: PD, 3pts: AEs). Med duration of treatment; 4.0 mo (range 6 d - 15.5 mo). Out of 9 evaluable for response, there was 1 confirmed PR per RECIST 1.1; 3 other pts had tumor reduction; 10%, 22%, 23%, 2 PR by Choi criteria and none by modified RECIST. Early on-treatment perfusion changes were noted on functional imaging. Of the 9 pts with evaluable AFP response, 3 (33%) had >50% decrease from baseline. 11 pts are still alive, 4 pts are deceased secondary to PD. Conclusions: Axitinib is tolerated and has shown preliminary efficacy in this VEGF pretreated HCC pt population.This is early analysis and updated data will be presented. Clinical trial information: NCT01334112.

In this work central bursting in drawing and extrusion of metals is investigated. The analysis is based on a modified stress distribution within the die zone due to Shield (Shield, R. T., 1955, J. Mech. Phys. Solids, 3, pp. 246–258) together with Gurson–Tvergaard’s yield function (Tvergaard, V., 1981, Int. J. Fract., 17, pp. 389–407) and its associated flow rule for voided solids. The effects of hardening and evolution of void shape on void growth are considered. Various fracture criteria are employed to predict the process conditions at which central bursting occurs. The first criterion is due to Avitzur (Avitzur, B., 1968, ASME J. Eng. Ind., 90, pp. 79–91 and Avitzur, B., and Choi, J. C., 1986, ASME J. Eng. Ind., 108, pp. 317–321), the second and simplest criterion is based on vanishing mean stress while a suggested third criterion depends on the current value of the void volume fraction. Two other criteria which are basically due to Thomason’s internal necking condition (Thomason, P. F., 1990, Ductile Fracture of Metals, Pergamon, Oxford) as well as McClintock’s shear band formation criterion are applied (McClintock, F. A., Kaplan, S. M., and Berg, C. S., 1966, Int. J. Fract. Mech., 2, p. 614, and McClintock, F. A., 1968, in Ductility, ASM, Metals, Park, OH). The critical process conditions are predicted and compared with the available experimental data. Comparison showed that predictions based on the vanishing mean stress and the current void volume fraction criteria are closer to experiments than those based on Thomason’s internal necking and McClintock criteria.

Background: Drugs targeting angiogenic pathway remain the mainstay of treatment for metastatic renal cell carcinoma (mRCC). Tyrosine Kinase Inhibitors (TKI) as Sunitinib, Pazopanib as single agents and humanised monoclonal antibody bevacizumab (Bev) in combination with Interferon- α2a (IFN) have established as the first-line therapy for mRCC. Despite improvements in treatment, there are multiple questions which remain unanswered. In the combination of Bev and IFN, the respective role of each drug and whether any additional anti-angiogenic activity is gained by adding IFN to Bev remains unknown. As the clinical benefit obtained with these cytostatic agents does not always correlate with the conventional response assessment techniques as RECIST, it is necessary to reconsider the methods by which we assess benefit from these therapies. In this thesis, I report three studies aiming to answer these questions. Methods: With the clinical trial reported here, I explore whether Bev induced changes in vascular parameters measured by Dynamic Contrast Enhanced MRI (DCE-MRI) is significantly enhanced by the addition of IFN. In a phase II, randomised, open labelled, multicentre trial, treatment naïve mRCC patients were randomised to receive Bev on its own or in combination with a low dose (3MU) or standard dose (9MU) IFN. DCE-MRI was used to assess the changes in vascularity with the primary endpoint being, changes in transfer coefficient (Ktrans) after six weeks of treatment. I also report two retrospective imaging-based studies, using contrast-enhanced CT scans, performed to improve the methodology of response assessment for these antiangiogenic therapeutics. Here I explore the use of a) combining changes in size and arterial phase contrast enhancement measured using CT scan and b) changes in CT texture as methods of therapeutic response assessment in mRCC patients treated with TKI. Results: With the phase 2 clinical trial, we faced significant difficulty in recruitment as a result of restrictions in access to treatment in NHS, other competing studies and restrictions proposed by the DCE-MRI inclusion criteria. With slow recruitment, an unplanned analysis was performed after 21 patients were recruited. Analysis of primary endpoint showed no trend in the difference between arms with no correlation found between change in Ktrans and addition of IFN to bevacizumab. Effect size analysis performed due to the small numbers recruited failed to show any significance in the observed difference in Ktrans. Change in Ktrans and Kep may identify a group of patients likely to have PFS > 6 months, but this observation needs to evaluation in a larger sample size. Measuring size and change in arterial phase enhancement retrospectively using CT, a new criterion "modified" Choi, which prerequisite a combination of a decrease in arterial phase density by 15% and a decrease in size by 10% for response was proposed. Response assessment was measured with RECIST, Choi and modified Choi individually in 20 evaluable patients retrospectively and clinical benefit compared with Kaplan-Meier statistics and Log-Rank test. Response assessment as defined by the modified Choi criteria successfully identified patients who received clinical benefit from the treatment. Time to progression (TTP) was 448 days for the partial response and 89 days for stable disease as per the new criteria which were statistically significant with a p-value of 0.002. The second retrospective analysis explored the textural changes in enhanced CT scan. Performed in collaboration with researchers from Brighton University who developed the software algorithm used to assess changes in entropy and uniformity, 87 metastases from 39 patients with mRCC were analysed at baseline and after two cycles of TKI treatment. Textural parameters and response assessment criteria were correlated with TTP. After two cycles of TKI, the decrease in tumour entropy was 3%-45%, and increase in uniformity was 5%-21%. At a threshold change of -2% with uniformity, on a coarse scale of 2.5, the textural change was able to separate responders from non-responders. With Kaplan-Meier analysis comparing all four criteria, the percentage change in uniformity was statistically more significant than for RECIST, Choi, and Modified Choi criteria. Cox regression analysis showed that texture uniformity was an independent predictor of time to progression. Discussion: With the studies reported here, I was able to demonstrate the importance of improving the methodology in assessment of therapeutic response to targeted anti-angiogenic therapy in metastatic renal cell carcinoma. Even though the clinical trial, terminated early due to slow recruitment, did not reach its primary endpoint, changes in other vascular parameters as Kep combined with changes Ktrans showed tendency towards identifying a group of patients who derived clinical benefit of >6months with these therapies. This is particularly exciting as given the vascular stabilisation effect proposed for bevacizumab, the effusion parameter Kep may be a better tool in assessing response rather than Ktrans and warrants further assessment in a larger cohort. Modified choi criterion and textural analysis are two important methodological improvements in response assessment of cytostatic anti-angiogenic therapy. In the analyses reported here, both techniques have shown superiority over RECIST in response assessment and differentiating mRCC patients who is likely to gain clinical benefit by TKI therapy. Validation of these criteria on a larger patient cohort is important. As these criterions are assessed on standard enhanced CT scans, incorporating these criteria, especially modified choi criterion, as part of standard CT assessment could be performed and will provide a real world validation. Retrospective assessment using larger cohort of patients from previous phase 3 trials or inclusion of these parameters prospectively in phase 3 trials would also help us in evaluating these modalities further.