Complete Transurethral Resection before Radical Cystectomy May Improve Oncological Outcomes.

OBJECTIVES: The objective of this study was to assess the impact of complete transurethral resection of bladder tumors (TURBTs) before radical cystectomy on pathological and oncological outcomes of patients with muscle-invasive bladder cancer (MIBC) and high-risk non-MIBC. MATERIALS AND METHODS: The charts of all patients who underwent radical cystectomy for bladder cancer in 2 academic departments of urology between 1996 and 2016 were retrospectively reviewed. Patients were divided into 2 groups according to the completeness of the last endoscopic resection before radical cystectomy: macroscopically complete transurethral resection (complete) or macroscopically incomplete transurethral resection (incomplete). The primary end point was the recurrence-free survival (RFS). Secondary end points included cancer-specific survival (CSS) and rates of pT0 and downstaging. RESULTS: Out of 486 patients included for analysis, the TURBT immediately preceding radical cystectomy was considered macroscopically complete in 253 patients (52.1%) and incomplete in 233 patients (47.9%). In multivariate analysis, macroscopically complete TURBT was the strongest predictor of both pT0 disease (OR = 3.1; p = 0.02) and downstaging (OR = 7.1; p < 0.0001). After a median follow-up of 41 months, macroscopically complete TURBT was associated with better RFS (5-year RFS: 57 vs. 37%; p < 0.0001) and CSS (5-year CSS: 70.8 vs. 54.5%; p = 0.002). In multivariate analysis adjusting for multifocality, weight of endoscopic resection specimen, cT4 stage on preoperative imaging, interval between endoscopic resection and radical cystectomy, neoadjuvant chemotherapy, pT stage, and associated carcinoma in situ, macroscopically complete endoscopic resection remained the main predictor of better RFS (HR = 0.4; p = 0.0003) and the only preoperative factor associated with CSS (HR = 0.5; p = 0.01). CONCLUSION: A macroscopically complete TURBT immediately preceding radical cystectomy may improve pathological and oncological outcomes in patients with MIBC and high-risk MIBC.

Yttrium-90 glass microspheres radioembolization (RE) for biliary tract cancer: a large single-center experience.

PURPOSE: Radioembolization (RE) is a promising treatment option for biliary tract cancers (BTC). We report here the largest series to date using this treatment modality. METHODS: We retrospectively studied data from 64 patients treated outside prospective clinical trial at our institution. We studied baseline characteristics as potential prognostic factors. We studied dose delivered to the tumor as predictive factors of outcomes in patients not receiving concomitant chemotherapy. RESULTS: The Progression-Free Survival and Overall Survival (OS) were 7.6 months [95% Confidence Interval (CI): 4.6-10.6] and 16.4 months [95% CI: 7.8-25.0] in the whole cohort. The factors independently associated with OS in multivariable analysis were the primary localization of ICC (HR = 0.27, 95% CI: 0.11-0.68, p = 0.005) and a PS > 0 (HR = 2.21, 95% CI: 1.11-4.38, p = 0.024). During follow-up, 12 patients (19%) underwent surgery following downstaging, with a median OS of 51.9 months. In patients not treated with concomitant chemotherapy (n = 31), OS was significantly higher in patients with a dose delivered to the tumor 260Gy or higher than in patients with a dose delivered to the tumor lower than 260Gy (median 28.2 vs 11.4 months, log-rank p = 0.019). CONCLUSION: Our results confirm that RE is a promising treatment modality in BTC. A high proportion of patients could be downstaged to surgery, with promising long-term survival. Dose delivered to the tumor correlated with clinical outcomes when chemotherapy was not used concomitantly.

Dynamic contrast-enhanced MRI: Study of inter-software accuracy and reproducibility using simulated and clinical data.

PURPOSE: To test the reproducibility and accuracy of pharmacokinetic parameter measurements on five analysis software packages (SPs) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), using simulated and clinical data. MATERIALS AND METHODS: This retrospective study was Institutional Review Board-approved. Simulated tissues consisted of pixel clusters of calculated dynamic signal changes for combinations of Tofts model pharmacokinetic parameters (volume transfer constant [K(trans) ], extravascular extracellular volume fraction [ve ]), longitudinal relaxation time (T1 ). The clinical group comprised 27 patients treated for rectal cancer, with 36 3T DCE-MR scans performed between November 2012 and February 2014, including dual-flip-angle T1 mapping and a dynamic postcontrast T1 -weighted, 3D spoiled gradient-echo sequence. The clinical and simulated images were postprocessed with five SPs to measure K(trans) , ve , and the initial area under the gadolinium curve (iAUGC). Modified Bland-Altman analysis was conducted, intraclass correlation coefficients (ICCs) and within-subject coefficients of variation were calculated. RESULTS: Thirty-one examinations from 23 patients were of sufficient technical quality and postprocessed. Measurement errors were observed on the simulated data for all the pharmacokinetic parameters and SPs, with a bias ranging from -0.19 min(-1) to 0.09 min(-1) for K(trans) , -0.15 to 0.01 for ve , and -0.65 to 1.66 mmol.L(-1) .min for iAUGC. The ICC between SPs revealed moderate agreement for the simulated data (K(trans) : 0.50; ve : 0.67; iAUGC: 0.77) and very poor agreement for the clinical data (K(trans) : 0.10; ve : 0.16; iAUGC: 0.21). CONCLUSION: Significant errors were found in the calculated DCE-MRI pharmacokinetic parameters for the perfusion analysis SPs, resulting in poor inter-software reproducibility. J. Magn. Reson. Imaging 2016;43:1288-1300.

Percutaneous Ablation Versus Surgical Resection for Local Recurrence Following Partial Nephrectomy for Renal Cell Cancer: A Propensity Score Analysis (REPART Study-UroCCR 71).

BACKGROUND: Data comparing percutaneous ablation (PCA) and surgical resection (SR) for an isolated local recurrence (LR) following partial nephrectomy (PN) for renal cell carcinoma (RCC) are lacking. OBJECTIVE: To examine the outcomes between PCA and SR for an isolated LR following PN for RCC. DESIGN, SETTING, AND PARTICIPANTS: Patients who underwent PN for RCC and developed an LR between 2013 and 2019 were included. An LR was defined as the appearance of a mass in contact with the resection bed or the development of a tumor in the same region of the homolateral kidney as the original site. INTERVENTION: PCA or SR. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: To achieve balance in baseline characteristics, we used inverse probability of treatment weighting (IPTW) based on propensity to receive treatment. Oncological outcomes, complications, and renal function were evaluated between groups using logistic, linear, and Cox proportional hazard regression models. RESULTS AND LIMITATIONS: A total of 81 patients with an isolated LR were included (PCA: 42; SR: 39). The median follow-up was 23 mo. After adjustment, excellent balance was achieved for the majority of propensity score variables. In IPTW analysis, PCA was associated with a lower risk of postoperative complications (odds ratio=0.22; p=0.006) and a smaller change in eGFR (beta=-16.18; p=0.001). There were no significant differences in the risk of disease recurrence (hazard ratio [HR]=0.72; p=0.61), new LR (HR=1.51; p=0.59), and distant metastasis (HR=0.19; p=0.09). Limitations include the sample size and unmeasured confounding factors. CONCLUSIONS: Our results suggest that PCA provides comparable oncological outcomes to repeat surgery with fewer complications and better renal function preservation for the management of an LR after PN. PATIENT SUMMARY: This report shows that percutaneous ablation can be used for treating a local recurrence of renal cell carcinoma after partial nephrectomy, without significantly compromising cancer control.

Selective Internal Radiation Combined with Chemotherapy Maintains the Quality of Life in Intrahepatic Cholangiocarcinomas.

BACKGROUND: In the Yttrium-90 Microspheres in Cholangiocarcinoma (MISPHEC) single-arm phase 2 trial, concomitant chemotherapy and selective internal radiotherapy (SIRT) showed antitumor activity as a first-line treatment of unresectable intrahepatic cholangiocarcinomas (ICCs). In this sub-analysis, we aimed to evaluate one of the secondary endpoints, the health-related quality of life (QoL), evaluated with an EORTC QLQ-C30 instrument at the baseline and during treatment. METHODS: The MISPHEC trial included treatment-naïve patients with an unresectable ICC between November 2013 and June 2016. Patients received concomitant first-line chemotherapy with cisplatin and gemcitabine for 8 cycles; SIRT was administered during cycle 1 (for patients with unilobar disease) or cycles 1 and 3 (for patients with bilobar disease) using glass Yttrium-90 microspheres. We evaluated the QoL-measured by the QLQ-C30 questionnaire-at the baseline, every 8 weeks during chemotherapy and follow-up, between 12 and 15 weeks after embolization and every 12 weeks after a liver resection if applicable. RESULTS: A total of 41 patients were included, of which 34 completed questionnaires at the baseline. No clinically significant changes in the global health score or the sub-scales of the QLQ-C30 were observed during follow-up. The physical, social and role function mean score worsened during treatment and fatigue, nausea and pain scores increased although the differences were not clinically significant. In patients undergoing subsequent surgery, the QoL was not impaired. CONCLUSIONS: A combination of SIRT and chemotherapy with gemcitabine and cisplatin as the first-line treatment of unresectable ICCs was found to maintain the QoL.

Performance of B-mode ratio and 2D shear wave elastography for the detection and quantification of hepatic steatosis and fibrosis after liver transplantation.

OBJECTIVES: To evaluate the diagnostic performance of B-mode ratio and shear wave elastography (SWE) for the assessment of steatosis and liver fibrosis after liver transplantation. MATERIALS AND METHODS: Patients hospitalized for a systematic check-up after liver transplantation underwent the same day hepatic ultrasound with B-mode ratio and SWE, followed by liver biopsy and biological examinations. Steatosis was measured using hepatorenal sonographic index of B-mode ratio and liver stiffness using SWE. Liver biopsy, used as gold standard, graded steatosis S0(<5%), S1(5-<33%), S2(33-<66%), or S3(≥66%) and liver fibrosis according to the Metavir score. The results were tested against two external validation cohorts. RESULTS: Fifty-eight patients were included. Mean B-ratio value was significantly higher in patients with steatosis (0.95 ± 0.13 versus 1.39 ± 0.41, P < 0.001). A B-mode ratio cutoff values at least 0.985 was found optimal for steatosis' detection [area under the receiver operating characteristic curve (AUROC) 0.902 ± 0.05, sensitivity 95%, specificity 79%]. A B-mode ratio value below 0.9 ruled out steatosis and above 1.12 ruled in steatosis. Mean SWE value for patients without significant fibrosis (≤F1) was 15.90 ± 9.2 versus 19.27 ± 7.7 kPa for patients with fibrosis (P = 0.185). A 2D-SWE value below 7.85 kPa ruled out significant fibrosis and above 26.35 kPa ruled it in. CONCLUSION: The B-mode ratio is an efficient and accurate tool for the noninvasive diagnostic of steatosis in postliver transplantation patients. Yet, because liver stiffness is higher in postliver transplantation patients, 2D-SWE is not reliable in the diagnosis of significant fibrosis after liver transplantation.

Radioembolization Plus Chemotherapy for First-line Treatment of Locally Advanced Intrahepatic Cholangiocarcinoma: A Phase 2 Clinical Trial.

IMPORTANCE: Patients with unresectable intrahepatic cholangiocarcinoma (ICC) have a poor prognosis. Selective internal radiotherapy (SIRT) is a promising treatment option for hepatic tumors, but no prospective studies of combination SIRT with chemotherapy have been published to our knowledge. OBJECTIVE: To determine the response rate after SIRT combined with chemotherapy in patients with unresectable ICC. DESIGN, SETTING, AND PARTICIPANTS: This phase 2 clinical trial, the Yttrium-90 Microspheres in Cholangiocarcinoma (MISPHEC) trial, included patients with unresectable ICC who have never received chemotherapy or intra-arterial therapy and were treated at 7 centers which had experience with SIRT between November 12, 2013, and June 21, 2016. Statistical analysis was performed from March 31, 2017, to June 17, 2019. INTERVENTIONS: Concomitant first-line chemotherapy with cisplatin, 25 mg/m2, and gemcitabine, 1000 mg/m2 (gemcitabine reduced to 300 mg/m2 for the cycles just before and after SIRT), on days 1 and 8 of a 21-day cycle for 8 cycles. Selective internal radiotherapy was administered during cycle 1 (1 hemiliver disease) or cycles 1 and 3 (disease involving both hemilivers) using glass Y90 microspheres. MAIN OUTCOMES AND MEASURES: Response rate at 3 months according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Secondary end points were toxic effects, progression-free survival, overall survival, disease control rate, and response rate according to Choi criteria. RESULTS: Of 41 patients included in the study, 26 (63%) were male, with a mean (SD) age of 64.0 (10.7) years. Response rate according to RECIST was 39% (90% CI, 26%-53%) at 3 months according to local review and was confirmed at 41% as best response by central review; disease control rate was 98%. According to Choi criteria, the response rate was 93%. After a median follow-up of 36 months (95% CI, 26-52 months), median progression-free survival was 14 months (95% CI, 8-17 months), with progression-free survival rates of 55% at 12 months and 30% at 24 months. Median overall survival was 22 months (95% CI, 14-52 months), with overall survival rates of 75% at 12 months and 45% at 24 months. Of 41 patients, 29 (71%) had grades 3 to 4 toxic effects; 9 patients (22%) could be downstaged to surgical intervention, with 8 (20%) achieving R0 (microscopic-free margins) surgical resection. After a median of 46 months (95% CI, 31 months to not reached) after surgery, median relapse-free survival was not reached among patients who underwent resection. CONCLUSIONS AND RELEVANCE: Combination chemotherapy and SIRT had antitumor activity as first-line treatment of unresectable ICC, and a significant proportion of patients were downstaged to surgical intervention. A phase 3 trial is ongoing.

Comparison of 18F-Choline PET/CT and MRI functional parameters in prostate cancer.

AIM: 18F-Choline (FCH) uptake parameters are strong indicators of aggressive disease in prostate cancer. Functional parameters derived by magnetic resonance imaging (MRI) are also correlated to aggressive disease. The aim of this work was to evaluate the relationship between metabolic parameters derived by FCH PET/CT and functional parameters derived by MRI. MATERIALS AND METHODS: Fourteen patients with proven prostate cancer who underwent FCH PET/CT and multiparametric MRI were enrolled. FCH PET/CT consisted in a dual phase: early pelvic list-mode acquisition and late whole-body acquisition. FCH PET/CT and multiparametric MRI examinations were registered and tumoral volume-of-interest were drawn on the largest lesion visualized on the apparent diffusion coefficient (ADC) map and projected onto the different multiparametric MR images and FCH PET/CT images. Concerning the FCH uptake, kinetic parameters were extracted with the best model selected using the Akaike information criterion between the one- and two-tissue compartment models with an imaging-derived plasma input function. Other FCH uptake parameters (early SUVmean and late SUVmean) were extracted. Concerning functional parameters derived by MRI scan, cell density (ADC from diffusion weighting imaging) and vessel permeability (Ktrans and Ve using the Tofts pharmakinetic model from dynamic contrast-enhanced imaging) parameters were extracted. Spearman's correlation coefficients were calculated to compare parameters. RESULTS: The one-tissue compartment model for kinetic analysis of PET images was selected. Concerning correlation analysis between PET parameters, K1 was highly correlated with early SUVmean (r = 0.83, p < 0.001) and moderately correlated with late SUVmean (r = 0.66, p = 0.010) and early SUVmean was highly correlated with late SUVmean (r = 0.90, p < 0.001). No significant correlation was found between functional MRI parameters. Concerning correlation analysis between PET and functional MRI parameters, K1 (from FCH PET/CT imaging) was moderately correlated with Ktrans (from perfusion MR imaging) (r = 0.55, p = 0.041). CONCLUSIONS: No significant correlation was found between FCH PET/CT and multiparametric MRI metrics except FCH influx which is moderately linked to the vessel permeability in prostate cancer.

Comparison of Choi criteria and Response Evaluation Criteria in Solid Tumors (RECIST) for intrahepatic cholangiocarcinoma treated with glass-microspheres Yttrium-90 selective internal radiation therapy (SIRT).

OBJECTIVE: To compare Choi criteria with Response Evaluation Criteria in Solid Tumors (RECIST) for the prediction of overall survival (OS) in patients treated with glass-microspheres, Yttrium-90 selective internal radiation therapy (SIRT) for intrahepatic cholangiocarcinoma (ICC). METHODS: Between 2010 and 2014, 45 adult patients with locally advanced ICC treated with SIRT were retrospectively analyzed. Computed tomography scans performed before and after treatment were analyzed using both RECIST 1.1 and Choi criteria. Response was correlated with survival. RESULTS: Patients who achieved an objective response according to Choi had a longer OS than non-responders (median OS 19.9 months [95% CI, 1.1-38.7 months] vs. 7.5 months if stable disease [uncountable CI] and 3 months if progressive disease [95% CI, 0-6.2 months], log-rank test: p=0.003) whereas there was no significant survival difference according to the RECIST response (p=0.339). Among the 39 RECIST non-responding patients, those identified as responders by Choi (n=31) had significantly better OS than Choi non-responders (median OS 19.9 months (95% CI, 5.1-34.7 months) and 5.4 months (95% CI, 0-11.6 months), p=0.005). CONCLUSIONS: Choi criteria appear more appropriate than RECIST to identify responders with long survival among patients who received SIRT for ICC.

An unusual case of adrenocortical carcinoma with liver metastasis that occurred at 23 years after surgery.

Adrenocortical carcinoma (ACC) is an uncommon and aggressive cancer occurring more frequently in women; local or distant recurrences occur in 80% of cases, typically within 1 year after curative resection. Liver is the preferred metastatic site. Herein, we report the case of a unique liver metastasis from ACC occurring 23 years after the curative prior tumor surgery. A 45-year-old woman was operated in 1991 for adrenocortical stage II without microvascular involvement or capsular infiltration. At that time, no adjuvant treatment was indicated. The initial surgery consisted on a left adrenalectomy with contemporaneous left nephrectomy and regional lymphadenectomy. Five years after surgery, the patient was considered cured. However, 23 years later, the patient presented an atypical right subcostal pain. A 4 cm liver ACC metastasis involving the segment 4 and initially diagnosed as a hemangioma was discovered. A curative resection of the segment 4 was performed. Final pathological examination confirmed the diagnosis of ACC metastasis with a complete R0 resection; no lymph node metastases were observed. This case is the latest metachronous ACC metastasis ever reported in literature. To date, the patient is alive with no signs of recurrence after a post-surgical follow-up of 13 months.

Glass Microspheres 90Y Selective Internal Radiation Therapy and Chemotherapy as First-Line Treatment of Intrahepatic Cholangiocarcinoma.

PURPOSE OF THE REPORT: Intrahepatic cholangiocarcinoma's incidence is increasing. We studied the efficacy of Y selective internal radiation therapy (SIRT) as first-line treatment, with chemotherapy, and compared with the results of chemotherapy alone. PATIENTS AND METHODS: We retrospectively studied data from patients treated at our institution with glass microspheres SIRT for intrahepatic cholangiocarcinoma as part of first-line treatment in combination with chemotherapy. We compared results with those of similar patients treated in the ABC-02 study (a study in advanced biliary tract cancer that defined the current standard chemotherapy), assessed as not progressing after the first evaluation. We assessed progression-free survival (PFS) and overall survival (OS). RESULTS: Twenty-four patients were treated with SIRT. Chemotherapy was given concomitantly in 10 (42%), as induction before SIRT in 13 (54%) or after SIRT in 1 (4%). Grade 3 adverse events were reported in 1 (4%). Median PFS after SIRT was 10.3 months. Longer PFS was observed when chemotherapy was given concomitantly than when chemotherapy was given before SIRT, with respective median of 20.0 versus 8.8 months (P = 0.001). Median OS after SIRT was not reached. Eleven patients went to surgery (46%). Thirty-three patients in ABC-02 had locally advanced nonextrahepatic cholangiocarcinoma, not progressing after first evaluation. From the start of any treatment, the median PFS was 16.0 months in our cohort versus 11.3 months in ABC-02 (P = 0.25), whereas the median OS was significantly higher in our cohort, not reached versus 17.9 months, respectively (P = 0.026). CONCLUSIONS: Selective internal radiation therapy combined with concomitant chemotherapy seems a promising strategy as first-line treatment for unresectable intrahepatic cholangiocarcinoma.