mRECIST Criteria Research Articles

3:45 PMAbstract No. 341 - Hepatic radioembolization for treatment of metastatic sarcoma as salvage therapy after failed chemotherapy: single center midterm results

Sarcomas encompass a range of pathologies with surgical resection as the curative treatment for local disease. Unfortunately, metastatic disease is common with chemotherapy as the mainstay treatment. Selective internal radiation therapy (SIRT) has become a dominant treatment therapy for both primary and metastatic cancers. The goal of this study was to evaluate safety, efficacy and survival in patients with hepatic metastatic leiomyosarcoma and angiosarcoma (HMS) after failed chemotherapy. A retrospective review was performed of patients with HMS treated with SIRT as salvage therapy after failed chemotherapy. SIR-Spheres (Sirtex Medical, Woburn, MA) and Theraspheres (BTG, Surrey,UK) were chosen at the physicians discretion. Patient demographics, laboratory values, treatment history, procedure details, technical success, and adverse events (AEs) were recorded. Six patients (3 males, 3 females, mean age of 50.5 years at diagnosis) with HMS (leiomyosarcoma (n=4), angiosarcoma (n=2)) underwent 11 total SIRT treatments (7 SIR-spheres, 4 Theraspheres) with 100% technical success. 30-day mortality was 0% with no major AEs reported by CTCAE criteria, version 4.03. There was no significant change in total bilirubin from pre-treatment to 3 months post SIRT. 6-month survival post initial SIRT was 67% (75% in leiomyosarcoma group and 50% in angiosarcoma group). 50% of the leiomyosarcoma group was alive at 2 years post initial SIRT. 33% had partial response and 67% had stable disease by mRECIST criteria at 3-month imaging post initial SIRT. 4 of the 6 patients had 6-month imaging post initial SIRT which showed stable disease in 75% and progression of disease in 25%. Four patients underwent a second SIRT which showed partial response in 25% and stable disease in 75% by mRECIST at 3 months. A single patient underwent a third SIRT with progression of disease at 3 month imaging. SIRT for HMS as salvage therapy in patients who have failed chemotherapy is a safe treatment option with encouraging efficacy by mRECIST criteria at 3 months and a modest survival benefit. Larger trials with longer follow up are necessary to further examine outcomes.

3:18 PMAbstract No. 338 - Pre and post-procedural evaluation of imaging biomarkers after radioembolization for hepatocellular carcinoma as an indicator of progression

The purpose of this study is to evaluate possible imaging biomarkers on contrast-enhanced CT and MRI exams that predict local progression per modified Response Evaluation Criteria in solid tumors (mRECIST) criteria post radioembolization of hepatocellular carcinoma (HCC). Among patients who underwent radioembolization for HCC between May 1, 2005 and May 1, 2015 at a single institution, 34 patients had adequate pre and at least 2 post-procedural exams. Local response to treatment was classified as progressive (PD) or stable disease (SD) using mRECIST. Imaging markers, including portal venous phase enhancement (PVE), lobulated enhancement (LE), presence of arterioportal shunting (APS), and portal vein thrombosis (PVT) were assessed in each imaging examination. Wilcoxen Rank-Sum (WRS) and log-rank analyses were performed to establish statistically significant differences in local progression free survival (LPFS). The mean imaging follow-up time was 12.64 months. Local progression was seen in 25 patients (73.5%) following radioembolization. Average time to progression was 2.9 months. PVT, APS, and PVE seen on pre or post-procedural imaging were not significant predictors of LPFS. LE on immediate post-procedural imaging was a significant predictor of progression by WRS (p=0.039) and log-rank analysis (p=0.037), however LE on pre-procedural imaging was not a significant predictor. 9 patients with and 0 patients without progression showed LE on pre or post-procedural imaging, respectively. PVT, APS, and portal venous enhancement were not statistically significant predictors of local progression, whereas immediate post-procedural LE demonstrated a statistically significant decrease in LPFS in patients with hepatocellular carcinoma treated with radioembolization.

BIOSHARE multicenter neoadjuvant phase 2 study: Results of pre-operative sorafenib in patients with resectable hepatocellular carcinoma (HCC)—From GERCOR IRC.

252 Background: This open-label, multicenter, phase II study aimed at investigating the activity of sorafenib including radiological, pathological and biological changes in tumor from patients with resectable HCC. Methods: Preoperative administration of sorafenib 400 mg bid for 4 weeks was followed by surgery. Primary endpoints were antitumor activity and histological changes on paired tumor samples and plasma biomarkers between baseline and post sorafenib. Secondary endpoints were safety, R0 surgery and post-surgical complications. Results: Among 30 patients enrolled, 28 were evaluable for safety. Neoadjuvant sorafenib was not feasible in 3 patients (early limiting toxicities). Twenty-five patients (21 men; median age: 61.5 years) were evaluable for the primary endpoints. Baseline median tumor size was 37 mm and 21 patients (84%) had a single lesion. Median duration and dosing of sorafenib were 28 days and 793 mg/day respectively. Overall, the safety profile of preoperative sorafenib was good. According to RECIST criteria, all patients showed stable disease. Among 19 patients evaluated according to mRECIST and Choi criteria, objective responses were observed for 6 (32%) and 10 (53%) patients respectively. All evaluable patients went on liver resection and no unexpected complication occurred. R0 tumor resection was achieved in 22 patients (88%). Surgical specimen showed macrovascular and microvascular invasion in 12% and 48%, respectively. Intratumor necrosis was observed in 17 (68%) surgical specimen with necrosis ≥ 50% in 24 % of cases. Blood biomarkers analysis showed a trend toward increased angiogenesis biomarkers (VEGF-A, VEGF-C and PlGF) after sorafenib treatment. Biomarkers from pre- and post-treatment tissue will be presented during the meeting. Conclusions: Neoadjuvant sorafenib displays a favorable toxicity profile and yields significant activity in patients with resectable HCC. BIOSHARE trial also allows exploration of drug effects on tumor biology. Clinical trial information: NCT01182272.

Use of yttrium-90 radioembolization for patients with unresectable liver metastases: experience from a single center

Background: Yttrium-90 (Y-90) radioembolization is an intra-arterial, catheter-based therapy that delivers high doses of internal radiation to tumors while sparing normal surrounding tissue. Metastatic liver disease, in general, is associated with a poor prognosis from a variety of primary gastrointestinal malignancies. As a result, Y-90 radioembolization has an emerging role in locoregional control of patients with unresectable liver metastases. Methods: Patients with cancer that metastasized to the liver and treated with Y-90 radioembolization between 2005 and 2015 (n=21) were evaluated retrospectively. Patients were selected based on multidisciplinary evaluation; inclusion criteria included data that were abstracted from medical records including patient records, laboratory data, and radiographic studies. Toxicities were recorded using Common Terminology Criteria 3.0. Response was recorded according to mRECIST criteria. Results: Twenty-one patients received treatments with SIR-Spheres Y-90 radioembolization. The median treatment activity delivered was 1.3 gBq (range, 0.7–1.7 gBq). The median treatment dose delivered was 95.5 Gy (range, 50–120 Gy). The median lung shunt fraction was 2.0% (range, 0.5–5.8%). Toxicities as measured by laboratory values were overall low, with alkaline phosphatase (Alk Phos) being most commonly elevated following treatment in 52% of patients, followed by AST and ALT derangements in 29% and 33% of patients, respectively. The most common clinical toxicities among all patients were abdominal pain (43%), followed by nausea/vomiting (38%), fatigue (19%), anorexia (14%), and diarrhea (10%). A clinical benefit response was seen in 71% [defined as patients achieving complete response (CR), partial response (PR), or stable disease (SD)]. PR was seen in 33% of cases; progressive disease (PD) was noted in 29%. Post-initial treatment, patients survived for a median 9 months (range, 6.01–14.1 months) after their first radioembolization treatment, and survival from the time of diagnosis of liver metastasis was 21.8 months (range, 14.2–40.2 months). Conclusions: For patients with nonresectable metastasis of cancer to the liver, Y-90 radioembolization is a safe and well-tolerated procedure and a potentially useful option in hepatic malignancies that are not satisfactorily addressed by existing treatment modalities. This data suggest that a significant percentage of patients achieve clinical benefit including many with PR. Survival after treatment from this single-center is consistent with preexisting evidence. Prospective, randomized data is required to compare radioembolization with other therapies including chemoembolization and systemic chemotherapy.

Percutaneous Treatment of Localized Infiltrative Hepatocellular Carcinoma Developing on Cirrhosis.

Infiltrating hepatocellular carcinoma (HCC) is characterized by a difficult diagnosis, dismal prognosis, and limited therapeutic options. We describe long-term results of percutaneous treatment of infiltrative HCC, i.e., multibipolar radiofrequency ablation (mbpRFA) and percutaneous intra-arterial ethanol injection (PIAEI). All cirrhotic patients with localized (up to two segments) infiltrating HCC treated by mbpRFA or PIAEI between 2002 and 2012 were included. Survival was analyzed using the Kaplan-Meier method, log-rank test, and Cox univariate followed by multivariate analyses. Fifty-one patients were considered eligible for mbpRFA (n=20) or PIAEI (n=31). Cirrhosis etiologies were alcohol (67%), hepatitis C (33%), hepatitis B (16%), and/or NASH (16%). HCC were multinodular in 31% of cases, with a median main tumor size of 60mm (range 30-200) and macrovascular invasion in 59% of cases. The median serum level of alphafetoprotein was 125ng/ml (range 2-215,000). Treatment-related adverse events occurred in 58%, mainly postablation syndrome (31%), and one death (2%). Median overall survival was 18.3months, with 63, 35, 20, and 12% survival at 1, 2, 3, and 4years, respectively. Baseline serum bilirubin >normal [hazard ratio (HR) 2.98; 95% confidence interval (CI) 1.38-6.50; P=0.0057] and tumor burden >70mm (HR 1.02; 95% CI 1.003-1.04; P=0.0221) were associated with poorer overall survival. The radiological response using mRECIST criteria and an alphafetoprotein decrease 1month post-procedure was associated with increased overall survival (P=0.0002 and P=0.024, respectively). Despite its overall poor prognosis, localized infiltrating HCC can be safely treated using percutaneous approaches, with potential survival benefits for these difficult-to-treat patients.

Hepatocellular Carcinoma Response to Local Regional Therapy; Correlations between Pre-Liver Transplants Imaging and Explant Pathology

Background/Aim: Modified Response Evaluation Criteria in Solid Tumors (mRECIST) were developed to assess the response to treatment in patients with HCC, based on measuring the amount of viable tumor using dynamic imaging (CT/MRI). Our aim to compare the estimated viable HCC after locoregional therapy (LRT) by CT imaging and prior to liver transplant to the histopathological assessment of viable HCC in the hepatic explant. Methods: We prospectively evaluated 44 patients with HCC who underwent both LRT and liver transplantation at London health science center. Using mRECIST criteria, the response to LRT was assessed by two blinded radiologists and the percentage of necrosis was reported separately for the reference CT (rCT) done after the last LRT and prior to liver transplantation. The report obtained from each radiologist was combined then was compared to the findings of an expert pathologist reporting on viable tumour present and tumour necrosis in the hepatic explants. Both parties were blinded to prevent bias in the results. Results: A total of forty-one transplant recipients fulfilled the inclusion criteria for the study. At time of listing 100% were within total volume criteria, 86% within UCSF, and 68% within Milan. The average time from the last reference CT scan to liver transplant was 57.7 days; the average time from last LRT to reference CT was 72.5 days. Thirty-four recipients (83%) had accurate assessment for necrosis (mRECIST) within 20% comparing rCT to explant (i.e. concordant). Ninteen, 19 (46%) of the 41 predicted 100% concordance. Only 7/41 (17%) had a poor concordance (>50%) between histology and reference CT images. positive correlation was detected with the correlation coefficient is calculated as 0.5723. Our study demonstrated CT-pathologic correlation in predicting number and size of tumors with Correlation coefficient 0.64 and 0.31, respectively. However, there was poor correlation in predicting total volume with correlation coefficient is calculated as 0.014. Conclusion: Dynamic CT is an accurate tool to evaluate the tumour response prior to liver transplantation and the likelihood of underestimating the tumour burden is low. With expert radiologists and pathologists, the correlation is acceptable and supports the ongoing use of frequent dynamic imaging to evaluate responses to LRT and determining transplant eligibility.

RECIST criteria: our experience in daily practice

Content organisation Our cases will be presented in a pictorial essay mode. Key differential diagnostic points will be highlighted in the discussion of each case. It is important to consider: Complete knowledge of clinical-oncologic status and treatments time points. Recognition of smallest measured value (NADIR) between time points for adequate selection of comparative review. Sum of target lesions (baseline and current time points) including percentage of change. Select no more than two target lesions by sector. Complete knowledge of actinic extension field which often could present different behavior than other lesional sites. Local tumour growth over vital organs regardless strict RECIST criteria in exceptional cases. Further criteria utilization in line with oncological disease being studied (mRECIST criteria for hepatocellular carcinoma or CHOI criteria for GIST). Use of SUL on baseline PET CT studies with greater accuracy in assessing response on further evaluations (PERCIST criteria).

Safety and efficacy of transarterial chemoembolization in patients with transjugular intrahepatic portosystemic shunts

BackgroundTransarterial chemoembolization (TACE) for the treatment of hepatocellular carcinoma (HCC) is an important option as the majority of patients present with advanced disease. Data regarding treatment outcomes in patients who have undergone transjugular intrahepatic portosystemic shunts (TIPS) are limited. The present study seeks to evaluate the safety and efficacy of TACE in HCC patients with a TIPS. MethodsA retrospective review identifying patients with HCC and concomitant TIPS who were treated with TACE was performed. ResultsFrom 1999 to 2014, 16 patients with HCC underwent a total of 27 TACE procedures; eight patients required multiple treatments. The median patient age at the time of the initial TACE was 60.5 years [interquartile range (IQR) : 52.5–67.5] with the majority being male (n = 12, 75%) and Childs–Pugh Class B (n = 12, 75%). At 6 weeks after TACE, 56.3% of patients achieved an objective response rate (complete and partial response) by mRECIST criteria. Clavien Grade 3 or higher complications occurred in 11.1% of TACE procedures. There were no peri-procedural deaths. The median progression-free (PFS) and overall survival (OS) were 9 and 22 months, respectively, when censored for liver transplantation (median follow-up: 11.5 months). ConclusionTACE is an effective treatment strategy for HCC in TIPS patients; albeit may be associated with higher complication rates.

Prognostic Relevance of Objective Response According to EASL Criteria and mRECIST Criteria in Hepatocellular Carcinoma Patients Treated with Loco-Regional Therapies: A Literature-Based Meta-Analysis.

BackgroundThe European Association for the Study of the Liver (EASL) criteria and the modified Response Evaluation Criteria in Solid Tumors (mRECIST) are currently adopted to evaluate radiological response in patients affected by HCC and treated with loco-regional procedures. Several studies explored the validity of these measurements in predicting survival but definitive data are still lacking.AimTo conduct a systematic review of studies exploring mRECIST and EASL criteria usefulness in predictive radiological response in HCC undergoing loco-regional therapies and their validity in predicting survival.MethodsA comprehensive search of the literature was performed in electronic databases EMBASE, MEDLINE, COCHRANE LIBRARY, ASCO conferences and EASL conferences up to June 10, 2014. Our overall search strategy included terms for HCC, mRECIST, and EASL. Loco-regional procedures included transarterial embolization (TAE), transarterial chemoembolization (TACE) and cryoablation. Inter-method agreement between EASL and mRECIST was assessed using the k coefficient. For each criteria, overall survival was described in responders vs. non-responders patients, considering all target lesions response.ResultsAmong 18 initially found publications, 7 reports including 1357 patients were considered eligible. All studies were published as full-text articles. Proportion of responders according to mRECIST and EASL criteria was 62.4% and 61.3%, respectively. In the pooled population, 1286 agreements were observed between the two methods (kappa statistics 0.928, 95% confidence interval 0.912–0.944). HR for overall survival (responders versus non responders) according to mRECIST and EASL was 0.39 (95% confidence interval 0.26–0.61, p<0.0001) and 0.38 (95% confidence interval 0.24–0.61, p<0.0001), respectively.ConclusionIn this literature-based meta-analysis, mRECIST and EASL criteria showed very good concordance in HCC patients undergoing loco-regional treatments. Objective response according to both criteria confirms a strong prognostic value in terms of overall survival. This prognostic value appears to be very similar between the two criteria.

Visceral fat area predicts survival in patients with advanced hepatocellular carcinoma treated with tyrosine kinase inhibitors

BackgroundAnthropometric measurements have been linked to resistance to anti-angiogenic treatment and survival. MethodsPatients with advanced hepatocellular carcinoma treated with sorafenib or brivanib in 2008–2011 were included in this retrospective study. Anthropometric measurements were assessed using computed tomography and were correlated with drug toxicity, radiological response, and overall survival. Results52 patients were included, Barcelona Clinic Liver Classification B (38%) and C (62%), with a mean value of α-fetoprotein of 29,554±85,654ng/mL, with a median overall survival of 10.5 months. Sarcopenia was associated with a greater rate of hand–foot syndrome (P=0.049). Modified Response Evaluation Criteria In Solid Tumours (mRECIST) and Choi criteria were significantly associated with survival, but RECIST criteria were not. An absence of hand–foot syndrome and high-visceral fat area were associated with progressive disease as assessed by RECIST and mRECIST criteria. In multivariate analyses, high visceral fat area (HR=3.6; P=0.002), low lean body mass (HR=2.4; P=0.015), and presence of hand–foot syndrome (HR=1.8; P=0.004) were significantly associated with overall survival. In time-dependent multivariate analyses; only high visceral fat area was associated with survival. ConclusionVisceral fat area is associated with survival and seems to be a predictive marker for primary resistance to tyrosine kinase inhibitors in patients with advanced hepatocellular carcinoma.

Phase I/II safety and antitumor activity of nivolumab in patients with advanced hepatocellular carcinoma (HCC): CA209-040.

LBA101 Background: Overexpression of PD-L1 in HCC has a poor prognosis. Safety and preliminary antitumor efficacy of nivolumab, a fully human IgG4 monoclonal antibody PD-1 inhibitor, was evaluated in a multiple ascending-dose, phase I/II study in patients (pts) with HCC. Methods: Pts with histologically confirmed advanced HCC with Child-Pugh (CP) score ≤ B7 and progressive disease (PD) on, intolerant of, or refusing sorafenib were enrolled. Dose escalation occurred in parallel cohorts based on etiology: no active hepatitis virus infection or virus-infected HCC pts. Pts received nivolumab 0.1 – 10 mg/kg intravenously for up to two years. The primary endpoint was safety. Secondary endpoints included antitumor activity using mRECIST criteria, pharmacokinetics, and immunogenicity. Results: The study has enrolled 41 pts with a CP score of 5 (n = 35) or 6 (n = 6), ECOG score of 0 (n = 26) or 1 (n = 15), 73% with extrahepatic metastasis and/or portal vein invasion, and 77% with prior sorafenib use. Eighteen pts remain on study, and 23 discontinued treatment due to PD (n = 17), complete response (CR; n = 2), drug-related adverse events (AEs; n = 2) and non-drug–related AEs (n = 2). Drug-related AEs of any grade occurred in 29 pts (71%; 17% grade 3/4), with ≥ 10% of pts experiencing aspartate aminotransferase (AST) increase and rash (each 17%), alanine aminotransferase(ALT) and lipase increase (each 15%), and amylase increase (12%). Grade 3 and 4 AEs ≥ 5% were AST increase (12%), ALT increase (10%) and lipase increase (5%). A dose-limiting toxicity occurred in an uninfected pt at 10 mg/kg; no maximum tolerated dose was defined in any cohort. Response was evaluable in 39 pts: 2 CR (5%) and 7 partial responses (PR; 18%). Response duration was 14–17+ months for CR, &lt; 1–8+ months for PR, and 1.5–17+ months for stable disease (SD). Overall survival (OS) rate at 6 months is 72%. Conclusions: Nivolumab has a manageable AE profile and produced durable responses across all dose levels and HCC cohorts, with a favorable 6-month OS rate. Updated safety, antitumor activity, and biomarker data will be presented. Clinical trial information: NCT01658878. [Table: see text]

Is radioembolization (90Y) better than doxorubicin drug eluting beads (DEBDOX) for hepatocellular carcinoma with portal vein thrombosis? A retrospective analysis

IntroductionThis study compares radioembolization (90Y) versus doxorubicin drug eluting beads (DEBDOX) in the treatment of unresectable hepatocellular carcinoma with portal vein thrombosis. MethodsUsing our prospectively maintained, multi-center, non-controlled intra-arterial therapy registry, we identified 28 consecutive patients with hepatocellular carcinoma (HCC) and portal vein thrombosis (PVT) treated with DEBDOX and 20 with 90Y. Follow-up protocol consisted of a 3-phase CT scan of the liver within 3 months post-treatment. Tumor response rates were measured according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. ResultsThere were 65 and 29 treatments in the DEBDOX and 90Y groups respectively. Median age of DEBDOX was 59.8 (35–81) and 90Y was 66.5 (49–82) years. A defined number of lesions were seen in 78% DEBDOX and 50% 90Y patients. Patients were similar in the remaining 8 baseline characteristics including performance status, Child Pugh and extent of PVT. There were fewer overall side effects in the DEBDOX group compared to the 90Y group (11% vs 39%; P = 0.03). There was better disease control (mRECIST) in the DEBDOX group compared to the 90Y group (67% vs 20%; P = 0.0014). Median survival times were 10 months in DEBDOX and 3 months in the 90Y group respectively from first treatment (log-rank, P = 0.037). ConclusionDEBDOX is safe for patients with HCC and PVT and may have lower toxicity than 90Y. It may also provide better disease control and survival benefit. Further studies are warranted to validate our observations and to determine if current clinical practice should be altered.

Would the combination of everolimus with endocrine-therapy help in FGFR2 positive serous endometrial cancer?

Chemotherapy is a critical approach in the treatment of advanced or recurrent endometrial cancer. The use of chemotherapy is now the standard treatment for women with early-stage disease. However, there are no agents approved by the US Food and Drug Administration for the metastatic setting of endometrial cancer, which has a very low chance to be treated with success. Due to the great expectation on novel targeting agents in advanced endometrial cancer, new drugs against specific molecular pathways with particular focus on PI3KCA/AKT/mTOR axis are emerging as promising treatments for endometrial cancer with aggressive phenotype [1]. The very issue is the lack of progress in cancer treatment due to the heterogeneity and the genetic complexity of many tumours leading to an urgent knowledge of the molecular profile of an individual's tumour to guide appropriate treatment selection. We have read with enthusiasm the article by Slomovitz et al published in Journal of Clinical Oncology on January 26, 2015 where it was reported the increased clinical benefit rate with the combination of letrozole and everolimus in women with recurrent endometrial cancer along with a manageable toxicity [2]. Moreover, patients with endometriod histotype carrying the CTNNB1 mutations underwent to a good response to treatment. On the counterpart the serous histology did not respond with the same rate to mTOR inhibition; moreover they have not identified based on the molecular analysis they performed a possible responsive-subtype of the serous cancer. The Cancer Genome Atlas has led to the molecular reclassification of endometrial cancer. These genomic advances are determinant for the proper selection of the adequate therapy in the future of the patient care. In the genomic era, clinicians and molecular oncologists should invest their efforts in finding “druggable” targets for the available drugs on the market. In our clinical experience, letrozole alone is already able to modulate the mTOR axis in breast cancer [3] suggesting its use also in other endocrine-related cancer such as estrogen receptors positive endometrial cancer. In our experience, the molecular analysis of the primary tumor or of the metastasis from endometrial cancer showed low percentage rate of mutations of PIK3CA and KRAS according on what reported by Slomovitz et al [2]. As previously reported that from the minimal genetic variations in the PI3K or FGFR pathways or CCND1, derives the most benefit from EVE based-therapy (HR = 0.27 vs 0.40 for the full NGS population) [4], in three serous endometrial cancers not responsive to conventional therapies, we applied for further molecular analysis, a part KRAS, PIK3CA and proliferation related genes, with particular regards to the staining of the estrogen receptor and FGFR2 FISH-based evaluation (Figure 1 A e B). The combination of 1gr medroxyprogesterone acetate daily and 10 mg everolimus daily induced stable radiological response of the liver metastases and partial radiological response in lung metastases during the time course of treatment in 2 patients with FGFR2 amplification (Figure 1 C and D). No response was detected in 1 patient without amplification of FGFR signal. Amplification or mutation of fibroblast growth factor receptor (FGFR) has been reported in endometrial cancers with a frequency of 10% and FGFR2 may represent a novel molecular target for the treatment of endometrial cancer [5]. Activation of FGFR induces PI3K and AKT activities through recruitment and tyrosine phosphorylation of the docking protein Gab1 that results in the activation of PI3K [6]. In our FGFR2+ve patients, we obtained, accordingly to the mRECIST Criteria, stable disease longer than 12 months in line with the positive data from the recent progression free survival analysis from the BOLERO-2 trial [7]. These results suggest that longer stable disease maybe achieved in the absence of a direct alteration in the PI3K/AKT/mTOR pathway, even when multiple molecular aberrations are present. However, FGFR2 may modulate the PIK3CA/AKT/mTOR axis perhaps explaining in part the response. Slomovitz et reported that only few patients with serous endometrial cancer responded to the combination of letrozole/everolimus and maybe they were FGFR 1 or 2 amplified. Figure 1 Biological and radiological features: A) Estrogen Receptor, B) FGFR2 Amplification; C) Target lesion at basal CT scan, D) Target lesion after 12 months of treatment Thus, the combination of everolimus and aromatase inhibitors has the change to show some activity in the particular subtype of EC as the FGFR2+ve serous carcinoma. Tumors with ER expression are dependent upon downstream growth factor signaling and may respond better with the addition of molecular inhibitors based on the proper target selection. Indeed, our reports encourage the perspective investigation of combination of everolimus along with hormone-therapy in pre-treated FGFR2+ recurrent endometrial cancer patients. Specific molecular analysis with focus on FGFR signalling in serous endometrial cancer is mandatory.

Locoregional Therapy in Patients with Hepatocellular Carcinoma: A Real Life Experience

Introduction: Hepatocellular carcinoma (HCC) has dismal prognosis but recently, survival has improved with treatment.Aims: To analyze our experience of treatment of HCC patients at our tertiary care center especially those who received locoregional therapies.Materials and Methods: We studied the records of 92 HCC patients attending our hospital from March 2013 to March 2015. Out of 92 patients, 62 received treatment and 26 patients were lost to follow up, 2 patients expired and treatment is planned for 2 patients.Results: Out of 62 treated patients with HCC, 35 received locoregional therapies, 1 patient underwent liver transplant and 1 patient underwent segmental hepatectomy. 25 patients were treated with Sorafenib due to advanced disease stage or unwillingness of patient for other treatment modalities. 35 patients (31 males, 4 females; mean age 58 years) were subjected to 43 sessions of locoregional therapies (21 – TACE, 4 – RFA, 2 – TARE and 8 – combination of these therapies). Barcelona Clinic staging in these 35 patients was: 0 – 1 patient, A – 9 patients, B – 3 patients, and C – 22 patients. No significant postprocedure complications were encountered. 82.86% (29) patients had complete response, 2.86% (1) patients had partial response and 5.71% (2) patients had stable disease at 1month of follow-up imaging as per mRECIST criteria. 3 patients were lost to follow up. At 1 year of follow-up imaging in 14 patients, only 3 had progression of disease. Overall only 22.86% (8) patients had progression of disease on follow up at the end of 2 years. Among patients who followed-up, mean survival was 15.19 months (range 1–108 months) in patients who underwent locoregional therapies where as mean survival in patients who received sorafenib was only 3 months.Conclusion: Locoregional therapies are safe and improve survival of patients with HCC. Introduction: Hepatocellular carcinoma (HCC) has dismal prognosis but recently, survival has improved with treatment. Aims: To analyze our experience of treatment of HCC patients at our tertiary care center especially those who received locoregional therapies. Materials and Methods: We studied the records of 92 HCC patients attending our hospital from March 2013 to March 2015. Out of 92 patients, 62 received treatment and 26 patients were lost to follow up, 2 patients expired and treatment is planned for 2 patients. Results: Out of 62 treated patients with HCC, 35 received locoregional therapies, 1 patient underwent liver transplant and 1 patient underwent segmental hepatectomy. 25 patients were treated with Sorafenib due to advanced disease stage or unwillingness of patient for other treatment modalities. 35 patients (31 males, 4 females; mean age 58 years) were subjected to 43 sessions of locoregional therapies (21 – TACE, 4 – RFA, 2 – TARE and 8 – combination of these therapies). Barcelona Clinic staging in these 35 patients was: 0 – 1 patient, A – 9 patients, B – 3 patients, and C – 22 patients. No significant postprocedure complications were encountered. 82.86% (29) patients had complete response, 2.86% (1) patients had partial response and 5.71% (2) patients had stable disease at 1month of follow-up imaging as per mRECIST criteria. 3 patients were lost to follow up. At 1 year of follow-up imaging in 14 patients, only 3 had progression of disease. Overall only 22.86% (8) patients had progression of disease on follow up at the end of 2 years. Among patients who followed-up, mean survival was 15.19 months (range 1–108 months) in patients who underwent locoregional therapies where as mean survival in patients who received sorafenib was only 3 months. Conclusion: Locoregional therapies are safe and improve survival of patients with HCC.

Inter-observer variability of response evaluation criteria for hepatocellular carcinoma treated with chemoembolization

BackgroundData comparing EASL and mRECIST criteria for response evaluation in treatment of hepatocellular carcinoma are rare. We evaluated inter-observer variability by these two response evaluation criteria in treatment-naïve patients undergoing chemoembolization. MethodsFor 133 patients undergoing chemoembolization, two radiologists independently measured sum of bi-dimensional and uni-dimensional diameters at baseline using both EASL criteria and mRECIST, and their changes on first follow-up for up to 5 target lesions. ResultsConcordance correlation coefficients for sum of bi-dimensional and uni-dimensional diameters at baseline between two observers were 0.992 and 0.988, respectively. However, those for their changes on follow-up were 0.865 and 0.877, respectively. Similarly, mean differences in sum of bi-dimensional and uni-dimensional diameters at baseline between two observers were small; −0.455 and 0.079cm, respectively. However, mean differences in changes (%) in sum of bi-dimensional and uni-dimensional diameters on first follow-up between observers increased by −9.715% and −9.320%, respectively. Regarding tumour numbers, kappa-value between observers was 0.942. For treatment response (complete or partial response, stable disease and progression), kappa-value was 0.941 by both criteria. When only up to two target lesions were assessed, kappa-value was 1.000 by both criteria. ConclusionsInter-observer agreements using both response evaluation criteria were excellent, especially when up to two targets were assessed.

Transarterial Chemoocclusion (Taco) With Degradable-Starch-Microsphere In Unresecable Hepatocellular Carcinoma: A Prospective Pilot-Study

Background: According to BCLC algorithm, Transarterial Chemoembolization is recommended for unresecable hepatocellular carcinoma (HCC) in patients with preserved liver function. The intraarterial chemotherapy with transient artery occlusion could be a valid treatment alternative in patients with high-risk of liver failure. Aim of the present study was to evaluate efficacy and safety of TACO using Degradable-Starch-Microspheres (DSM) in patients with unresecable HCC. Methods We prospectively enrolled 24 cirrhotic patients (21/3M/F, mean age 66.3±10.5 years) with unresecable HCC, to be treated with three consecutives DSM-TACO at 5-week intervals. Chemotherapy drug was Doxorubicin Chloridrate (50mg/m2) mixed with 275mg DSM (Embocept®S, PharmaCept). Liver function before and after treatmentswas evaluatedwith Child Pugh and MELD scores. Treatment responsewas assessed by CT-scan 4weeks after procedures according to mRECIST criteria. Results: Overall, Complete Response (CR) was observed in 5/24 (20.8%), 9/24 (37.5%) and14/24 (58.3%)pts after thefirst, the second and the third procedure, respectively. No patient showed Stable Disease or Disease Progression at the end of the study. Patients withmonolobar disease (14/24: 58.3%) showed significant CR after the 1st procedure compared with bilobar HCC localization (5/14 vs 0/10; p=0.017). At the end, CR did not differ between mono or bilobar disease (9/14: 64.2% vs 5/10: 50%; p=ns). Drop-outs occurred in 8 patients (33.3%): 4 after the 1st treatment (3 worsened liver function, 1 liver transplanted), 4 after the 2nd treatment (2worsened liver function, 1 liver transplanted, 1 non compliance). Postembolization syndromewas observed in 9 (37.5%), in 4 (16.6%) requiring extended hospitalization. One patient had cholecystitis resolved with medical care. Conclusions: DSM-TACO offers a valid TACE alternative in patients with unresecable HCC. Careful patients selection is required to avoid liver failure in patients with border-line liver compensation. Further investigation to define DSM-TACO effects on survival is warranted.

An investigation of the safety of continued treatment with sorafenib in patients with unresectable hepatocellular carcinoma after the first disease progression: Multicenter, open-label, phase II safety study.

462 Background: Randomized studies showed that sorafenib significantly improved outcome in patients with unresectable hepatocellular carcinoma (HCC). However, there is no clear evidence to support the safety and benefit of continued treatment of sorafenib beyond disease progression (PD) in patients with HCC treated with sorafenib. We prospectively evaluated the safety and efficacy of sorafenib beyond PD in patients with HCC whose disease has progressed after first-line treatment with sorafenib. Methods: Unresectable HCC patients with evaluable lesion were treated with sorafenib until 1st PD, followed by soafenib until 2nd PD. The primary endpoint of the study was the safety after 1st PD until 2nd PD. Secondary endpoints of the study were response rate (RR), disease control rate (DCR), time to first PD (TTP1), time to second PD during continued treatment (TTP2), overall survival (OS), and safety throughout the treatment period. Adverse event was evaluated as per The National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Tumor response was evaluated as per Modified Response Evaluation in Solid Tumors (mRECIST) criteria. The Kaplan–Meier method was used to determine TTP and OS. Results: Of 30 patients enrolled from 6 sites in Japan, 29 patients received sorafenib treatment, and one patient refused chemotherapy. Twenty patients continued sorafenib beyond PD. Grade 3/4 adverse events occurred less frequently during TTP2 than during TTP1. No critical events related to sorafenib were reported during TTP2. In the first-line therapy, 29 patients treated with sorafenib showed RR of 10.3%, DCR of 60.7% and median TTP1 of 102 days. Twenty patients who received continued sorafenib beyond PD and showed RR of 0%, DCR of 45%, and median TTP2 of 77 days. Median survival time was 306 days. Conclusions: Sorafenib beyond PD had acceptable tolerability and considerable efficacy. In the present conditions without second line treatment, sorafenib beyond PD might be one of the treatment options. Clinical trial information: UMIN000005818.

Use of Initial Modified RECIST Tumor Response Evaluation Criteria for Predicting Survival in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization with Drug-Eluting Beads

Introduction: Transarterial chemoembolization (TACE) reduces tumor growth and increases survival in patients with hepatocellular carcinoma (HCC). Drug-eluting beads (DEB) deliver slow-release chemotherapy and reduce systemic toxicity during TACE. This study correlated initial tumor response according to modified RECIST (mRECIST) criteria and 1-year survival in patients with HCC treated with TACE-DEB, and identified predictors of tumor response. Methods: Fifty-two patients with HCC received TACE-DEB loaded with doxorubicin 75 mg during a 6-month period. Tumor response was evaluated 1 month after the procedure according to mRECIST criteria. Results: Most patients were cirrhotic and etiology of liver disease was hepatitis C in 26/52 (50%). Similar numbers of patients had Barcelona Clinic Liver Cancer (BCLC) A and BCLC B disease. Most patients had one nodule (66%). Complete response (CR) was achieved in 12/52 (23%), partial response in 19/52 (37%), stable disease in 4/52 (8%) and progressive disease in 17/52 (32%). Largest HCC ≤58 mm and BCLC stage A were associated with CR. The 1-year survival was 74%, with survival rates of 95% and 56% in the BCLC A and B groups, respectively. Variables reflecting tumor extension were associated with better survival. CR according to mRECIST criteria was a predictor of better 1-year survival (100% vs. 64%, P studies are needed to evaluate other predictors of survival and to determine if tumor response predicts long-term survival.

Efficacy of RECIST and mRECIST criteria as prognostic factors in patients undergoing repeated iodized oil chemoembolization of intermediate stage hepatocellular carcinoma.

Given that transarterial chemoembolization (TACE) is usually a repeated procedure for treatment of hepatocellular carcinoma (HCC), repeated radiologic response assessments rather than a single time point assessment may have different clinical implications through the repeated course of TACE. To evaluate the efficacy of RECIST and mRECIST criteria as a survival predictor across early time points after repeated TACE of HCC. Ninety-eight patients with intermediate stage HCC received repeated iodized oil TACE. Treatment response was assessed according to RECIST and mRECIST criteria at 1, 3, and 6 months after initial TACE. Cox proportional model was used for survival analysis and the predicting power of each time point response was evaluated with C-statistics and time-dependent area under the receiver operating characteristic curve (AUC). Inter-method agreement was assessed with the κ coefficient. mRECIST was not applicable in 15 patients because of patchy uptake of iodized oil after TACE. On multivariate analysis, responders at 6 months by RECIST, responders at 3 months, and 6 months by mRECIST showed better survival than non-responders (P < 0.05). Predicting power of response criteria improved over time and mRECIST at 6 months showed the best performance. The degree of agreements was poor or fair between RECIST and mRECIST. mRECIST predicted long-term survival as early as 3 months after TACE of intermediate stage HCC. The predicting power of the uni-dimensional response criteria tended to be stronger over time.

Survival and tolerability of liver radioembolization: a comparison of elderly and younger patients with metastatic colorectal cancer

AimTo evaluate the outcomes among elderly (≥70 years) and younger patients (<70 years) with liver-dominant metastatic colorectal cancer (mCRC) who received radioembolization (RE) as salvage therapy. MethodsA retrospective review of 107 consecutive patients with unresectable mCRC treated with RE after failing first- and second-line chemotherapy. ResultsFrom 2002 to 2012, 44 elderly and 63 younger (<70 years) patients received RE. Patients had similar previous extensive chemotherapy and liver-directed interventions. Using modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria, either a stable or a partial radiographical response was seen in 65.8% of the younger compared with 76.5% of the elderly patients. RE was equally well tolerated in both groups and common procedure-related adverse events were predominantly grade 1–2 and of short duration. No significant difference was found with regard to overall median survival between younger [8.4 months; 95% confidence interval (CI) = 6.2–10.6] or elderly patients (8.2 months; 95% CI = 5.9–10.5, P = 0.667). The presence of extrahepatic disease at the time of RE was associated with a significantly worse median survival in both groups. ConclusionRadioembolization appears to be as well tolerated and effective for the elderly as it is for younger patients with mCRC. Age alone should not be a discriminating factor for the use of radioembolization in the management of mCRC patients.