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Elena Verzoni, Paolo Grassi, Isabella Testa, Roberto Iacovelli, Pamela Biondani, Enrico Garanzini , Filippo De Braud, Giuseppe ProcopioDepartment of Medical Oncology 1, Fondazione IRCCS Istituto Nazionale Tumori, Milan, ItalyAbstract: Antiangiogenesis options have evolved rapidly in the last few years, with an increasing number of agents currently approved by the US Food and Drug Administration and European Medicines Agency. Angiogenesis inhibitors have been shown to be very effective for the treatment of metastatic renal cancer cell. Axitinib is a third-generation inhibitor of vascular endothelial growth factor receptor and is currently being developed for the treatment of various malignancies. The pharmacokinetic properties of axitinib may have a selective therapeutic effect, with minimal adverse reactions and enhanced safety. In a large Phase III study of previously treated patients with metastatic renal cell carcinoma, axitinib achieved a longer progression-free survival than sorafenib with an acceptable safety profile and good quality of life. This review focuses on the pharmacology, pharmacokinetics, and clinical activity of axitinib in the current treatment of renal cell carcinoma. The role of axitinib in the adjuvant and/or neoadjuvant setting needs to be evaluated in further clinical trials.Keywords: axitinib, renal cell carcinoma, vascular endothelial growth factor receptor, angiogenesis

Stability analysis remains a fundamental step in developing a successful imaging biomarker to personalize oncological strategies. This study proposes an in silico contour generation method for simulating segmentation variations to identify stable radiomic features. Ground-truth annotation provided for the whole prostate gland on the multi-parametric MRI sequences (T2w, ADC, and SUB-DCE) were perturbed to mimic segmentation differences observed among human annotators. In total, we generated 15 synthetic contours for a given image-segmentation pair. One thousand two hundred twenty-four unfiltered/filtered radiomic features were extracted applying Pyradiomics, followed by stability assessment using ICC(1,1). Stable features identified in the internal population were then compared with an external population to discover and report robust features. Finally, we also investigated the impact of a wide range of filtering strategies on the stability of features. The percentage of unfiltered (filtered) features that remained robust subjected to segmentation variations were T2w-36% (81%), ADC-36% (94%), and SUB-43% (93%). Our findings suggest that segmentation variations can significantly impact radiomic feature stability but can be mitigated by including pre-filtering strategies as part of the feature extraction pipeline.

Objectives: To evaluate the inter-observer reliability of modified Response Evaluation Criteria In Solid Tumours (mRECIST) of patients with hepatocellular carcinoma (HCC) undergoing neo-adjuvant treatments before liver transplant (LT). The agreement of tumor number, size, transplant criteria, and the radiological-pathological concordance were also assessed., Methods: A total of 180 radiological studies before/after neo-adjuvant therapies performed on 90 patients prior to LT were reviewed from three expert centers. Kappa-statistic and intraclass correlation (ICC) were evaluated on mRECIST and on tumoral features. Complete radiological response (CR) was compared with complete pathological response (CPR)., Results: Before neo-adjuvant therapies, the agreement on tumor number, size, and transplant criteria ranged from moderate (defined as ICC of 0.41-0.60) to almost perfect (ICC of 0.81-0.99), being higher with magnetic resonance imaging (MRI) than CT (0.657-0.899 and 0.422-0.776, respectively). After neo-adjuvant therapies, the agreement decreased, as ICCs ranged between 0.518 and 0.663 with MRI and between 0.508 and 0.677 with CT. Concordant mRECIST pairs were 201 of 270 reviews (76.3%) with a kappa of 0.648 indicating substantial agreement. When the three observers completely agreed on CR, the positive predictive value for CPR was 51.6%. The negative predictive value was 94.2% with a kappa of 0.512 indicating fair agreement between radiology and pathology., Conclusions: mRECIST agreement was substantial among the three observers involved. The agreement on tumor number, size, and transplant criteria ranged from moderate to almost perfect, with the highest ICCs obtained with MRI before neo-adjuvant therapies. Finally, the predictive value of mRECIST in the diagnosis of CPR was only fair., Key Points: • The review of 180 radiological exams of patients with hepatocellular carcinoma before and after neo-adjuvant therapies showed that the concordance among three different raters on mRECIST diagnosis was substantial. • The inter-observer reliability on fulfilment of transplant criteria slightly decreased when evaluated through CT and after loco-regional therapies. • The radiological diagnosis of complete response after neo-adjuvant therapies was predictive of complete pathological response in only 51.6% of cases., (© 2021. European Society of Radiology.)

Background: MRI based radiomics has the potential to better define tumor biology compared to qualitative MRI assessment and support decisions in patients affected by nasopharyngeal carcinoma. Aim of this review was to systematically evaluate the methodological quality of studies using MRI- radiomics for nasopharyngeal cancer patient evaluation., Methods: A systematic search was performed in PUBMED, WEB OF SCIENCE and SCOPUS using "MRI, magnetic resonance imaging, radiomic, texture analysis, nasopharyngeal carcinoma, nasopharyngeal cancer" in all possible combinations. The methodological quality of study included ( = 24) was evaluated according to the RQS (Radiomic quality score). Subgroup, for journal type (imaging/clinical) and biomarker (prognostic/predictive), and correlation, between RQS and journal Impact Factor, analyses were performed. Mann-Whitney U test and Spearman's correlation were performed. P value < .05 were defined as statistically significant., Results: Overall, no studies reported a phantom study or a test re-test for assessing stability in image, biological correlation or open science data. Only 8% of them included external validation. Almost half of articles (45 %) performed multivariable analysis with non-radiomics features. Only 1 study was prospective (4%). The mean RQS was 7.5 ± 5.4. No significant differences were detected between articles published in clinical/imaging journal and between studies with a predictive or prognostic biomarker. No significant correlation was found between total RQS and Impact Factor of the year of publication (p always > 0.05)., Conclusions: Radiomic articles in nasopharyngeal cancer are mostly of low methodological quality. The greatest limitations are the lack of external validation, biological correlates, prospective design and open science., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: To assess a correlation between the shrinkage of the fibroid and the course of the symptoms., Material and Methods: Fourteen patients with symptomatic uterine leiomyomas (mean fibroid volume: 111.45 cm 3 ) underwent percutaneous microwave ablation. Contrast-enhanced MRI follow-up was performed before and after treatment to evaluate the volume shrinkage. Two scores obtained from the Uterine Fibroids Symptom and Quality of Life questionnaire were used to perform a clinical follow-up to evaluate the symptoms and the quality of life at baseline, and at 3, 6 and 12 months after treatment., Results: All patients were treated, no complications occurred. During a mean MR follow-up of 8.1 months we observed shrinkage of the fibroids in all patients (mean 70.3 cm 3 ). During 12 months clinical follow-up, we observed a significant improvement of symptoms and an excellent improvement of quality of life ( p  < .001)., Conclusion: Uterine fibroids percutaneous microwave ablation is a safe tool to obtain a significant improvement in quality of life for all the patients of our cohort.

Background & Aims: In the context of liver transplantation (LT) for hepatocellular carcinoma (HCC), prediction models are used to ensure that the risk of post-LT recurrence is acceptably low. However, the weighting that 'response to neoadjuvant therapies' should have in such models remains unclear. Herein, we aimed to incorporate radiological response into the Metroticket 2.0 model for post-LT prediction of "HCC-related death", to improve its clinical utility., Methods: Data from 859 transplanted patients (2000-2015) who received neoadjuvant therapies were included. The last radiological assessment before LT was reviewed according to the modified RECIST criteria. Competing-risk analysis was applied. The added value of including radiological response into the Metroticket 2.0 was explored through category-based net reclassification improvement (NRI) analysis., Results: At last radiological assessment prior to LT, complete response (CR) was diagnosed in 41.3%, partial response/stable disease (PR/SD) in 24.9% and progressive disease (PD) in 33.8% of patients. The 5-year rates of "HCC-related death" were 3.1%, 9.6% and 13.4% in those with CR, PR/SD, or PD, respectively (p <0.001). Log 10 AFP (p <0.001) and the sum of number and diameter of the tumour/s (p <0.05) were determinants of "HCC-related death" for PR/SD and PD patients. To maintain the post-LT 5-year incidence of "HCC-related death" <30%, the Metroticket 2.0 criteria were restricted in some cases of PR/SD and in all cases with PD, correctly reclassifying 9.4% of patients with "HCC-related death", at the expense of 3.5% of patients who did not have the event. The overall/net NRI was 5.8., Conclusion: Incorporating the modified RECIST criteria into the Metroticket 2.0 framework can improve its predictive ability. The additional information provided can be used to better judge the suitability of candidates for LT following neoadjuvant therapies., Lay Summary: In the context of liver transplantation for patients with hepatocellular carcinoma, prediction models are used to ensure that the risk of recurrence after transplantation is acceptably low. The Metroticket 2.0 model has been proposed as an accurate predictor of "tumour-related death" after liver transplantation. In the present study, we show that its accuracy can be improved by incorporating information relating to the radiological responses of patients to neoadjuvant therapies., Competing Interests: Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Aim: To compare clinical success and patient satisfaction of percutaneous cervical nucleoplasty (PCN) and percutaneous cervical discectomy (PCD) in contained cervical disc herniation treatment., Materials and Methods: We retrospectively identified 50 consecutive patients in our institution: 24 underwent the PCD treatment and 26 patients were treated by the PCN procedure. All patients complained of radicular pain with or without neck pain; diagnosis of contained cervical disc herniation was obtained by MRI; all patients had received conservative therapy which did not result in symptom improvement. Exclusion from our series consisted of patients who had undergone previous surgery at the indicated level, or those with myelopathy, or those in whom more than a sole herniation was treated in the same session. Overall procedure time, fluoroscopy time, radiation dose and complications were recorded. The MacNab scale score was used to assess clinical success in terms of pain relief at 2- and 6-month follow-up. After 4-6 months, a cervical MRI was obtained in 24 patients., Results: Neither major nor minor complications were reported. Regarding patient satisfaction, overall median modified MacNab score was excellent both at 2 and 6 months after treatment. No significant statistical difference was found in mean modified MacNab score at 2 and 6 months among patients grouped by treatment choice (p = 0.319 and 0.847, respectively); radiation dose was inferior in PCN group than in PCD, with no significant statistical difference., Conclusion: PCD and PCN were found to be safe and effective in terms of pain relief in contained cervical herniation treatment.

Renal cell carcinoma (RCC) local recurrence after radical nephrectomy is uncommon. When feasible, surgical removal remains the primary treatment strategy; nevertheless, local RCC relapse management is controversial, and less invasive procedures may represent an attractive option to achieve oncologic control. The aim of our study was to assess the feasibility, safety, and clinical outcomes of image-guided percutaneous microwave ablation (MWA) for RCC local recurrence in patients initially treated with nephrectomy with curative intent. 10 consecutive patients underwent CT-guided percutaneous MWA of a total of 10 retroperitoneal nodules. Inclusion criteria were: histologically verified retroperitoneal metastases, previous radical nephrectomy, lesion no larger than 3 cm, no other metastatic site elsewhere. All the procedures were performed under moderate sedation choosing the most favorable patient decubitus. If deemed necessary, pneumodissection was induced before ablation. After the antenna placement inside the target lesion, thermal ablation was achieved by maintenance of a power of 100 W for a total time between 2 and 4 min. All patients were observed overnight and discharged the following day if clinically stable. Technical success was obtained in 100% of patients. One patient was re-treated to complete oncologic response with repeat MWA. No major complications were observed. No patients demonstrated local recurrence at a mean follow-up of 26 months. MWA is a safe and effective treatment strategy for loco-regional relapse of RCC following radical nephrectomy. This technique may represent a valuable approach for patients who are not eligible for surgery.

Aim: Data from 69 well-differentiated gastroenteropancreatic neuroendocrine tumors treated with peptide receptor radionucleotide therapy + somatostatin analogs (SSAs) after SSA treatment failure were evaluated. Methods: We identified two groups: S1 - patients who kept the same SSA treatment beyond progression; S2 - patients who switched the SSA with another SSA after progression. Results: Median progression-free survival was 53 and 127 months in S1 and S2, respectively (p = 0.001; hazard ratio: 0.31; 95% CI: 0.15-0.63). Median overall survival was 69 versus 150 months in S1 and S2, respectively (p = 0.004; hazard ratio: 0.32; 95% CI: 0.14-0.71). Conclusion: In patients with advanced well-differentiated gastroenteropancreatic neuroendocrine tumors treated with peptide receptor radionucleotide therapy plus SSA after SSA failure, the 'switch' strategy of SSA after progression improve progression-free survival and overall survival.

Background: Chemotherapy for collecting duct carcinoma (CDC) has demonstrated only limited efficacy in the advanced setting. The present study evaluated the activity of targeted therapies in metastatic CDC., Patients and Methods: We evaluated a cohort of 384 consecutive patients with metastatic renal cell carcinoma (mRCC). The characteristics of patients with CDC were compared against those of the remaining cohort. All patients with CDC were treated with targeted therapies., Results: Thirteen patients with advanced CDC were referred to our Center (incidence: 3.4% of all mRCC). Median age was 57 and 62 years in the CDC and non-CDC groups, respectively. The overall disease control in the CDC population was 23%, and median overall survival was 4 (95% confidence interval(CI)=2.4-5.6) months. Three patients obtained a satisfying response (disease control lasting 6-33 months)., Conclusion: CDC has a poor prognosis compared to non-CDC renal cell carcinoma. Treatment for CDC represents a future challenge and targeted therapies may play a role in selected cases.

The introduction of targeted agents did not totally resolve the approach to the treatment of metastatic renal cell carcinoma (mRCC) because complete response is rarely achieved. Recent findings seem to indicate that metastasectomy may improve survival. The RESORT study was designed to evaluate the additional clinical benefit of metastasectomy followed by sorafenib in a population of mRCC patients. With the aim of evaluating time to recurrence, 132 patients with mRCC who underwent radical resection of metastases at the time of recurrence after nephrectomy will be randomized to receive either sorafenib or best supportive care. Targeted treatment will be administered for up to 52 weeks or discontinued in the case of disease recurrence or unacceptable toxicity. Patients will be followed for a period of 36 months.

Aim: Only few efforts have been taken to investigate the potential existence of disease-specific differences in the safety profile of everolimus. We analyze here the correlation between different patient and tumor characteristics on the safety profile of this molecule. Information on treatment response is also provided., Methods: Consecutive patients with metastatic renal cell carcinoma (mRCC), pancreatic neuroendocrine tumors (pNET) or biliary tract cancer were included in this retrospective study. All patients received everolimus 10 mg/day or 5 mg/day. Clinical assessments were performed every 3 weeks., Results: In total, 98 patients were enrolled: 51 with mRCC, 25 with pNET and 22 with biliary tract cancer. The incidence of toxicities (any grade) was 76% with mRCC, 64% with pNET and 95% with biliary tract cancer. Patients with biliary tract cancer also presented a higher frequency of severe toxicities: 64 versus 18% with mRCC and 32% with pNET. Multivariate analysis disclosed that biliary tract cancer (odds ratio [OR]: 23.8; 95% CI: 6.0-117.8; p < 0.0001) is a predictive factor for the development of toxicities during everolimus treatment. No correlations between liver metastasis and toxicities were identified. Disease control rate (DCR) was 45% in mRCC patients, 96% in pNET and 50% for biliary tract cancer patients. pNET tumors were associated with a higher DCR than the mRCC and biliary tract cancer (OR vs mRCC: 66.7; 95% CI: 6.2-276.5; p = 0.004; OR vs biliary tract cancer: 2.6; 95% CI: 0.5-14.2; p = 0.025)., Conclusion: This study suggests that the safety profile of everolimus is acceptable in patients with either mRCC or pNET. In addition, the onset of toxicities is associated with an improved DCR. In patients with biliary tract cancer, everolimus is safe but associated with a higher incidence of adverse events.