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The results of a 10-year prospective observational study in patients with stage I renal cell carcinoma (RCC) show that percutaneous cryoablation (PCA) yielded a disease-specific survival of 94%. The study included 134 patients (61 men and 73 women) with single, sporadic, biopsy-proven RCC. Researchers calculated the 10-year overall survival, recurrence-free survival, and disease-specific survival following PCA, and then compared the results with matched partial nephrectomy (PN) and radical nephrectomy (RN) cohorts from the National Cancer Database (NCDB). At 5 and 10 years, overall survival after PCA was 86% and 72%, respectively, while recurrence-free survival was 85% and 69% and disease-specific-survival was 94% at both periods, similar to surgery. The 5- and 10-year overall survival for PN was estimated at 78% and 49%, respectively, while the rates for RN were 67% and 43%, respectively. The rate of complications associated with PCA was low, at 8%, while the 10-year risk of transitioning to hemodialysis was 2.3%. The risk of metachronous RCC was 6%. Analysis of the Charlson/Deyo Combined Comorbidity score revealed decreasing overall survival with increasing comorbidity index. In addition, the researchers note, patients in the PCA cohort outperformed both the RN and PN matched subgroups for all Charlson/Deyo Combined Comorbidity score categories.
Radiology (08/01/20) Vol. 296, No. 2, P. 452 J Morkos; KAP Rodriguez; A Zhou; et al.
French researchers conducted a cost-benefit analysis of transarterial radioembolization (TARE) with yttrium-90 microspheres compared with continuous oral sorafenib for locally advanced and inoperable hepatocellular carcinoma. The study used patient-level data from the SARAH (Sorafenib Versus Radioembolization in Advanced Hepatocellular Carcinoma) trial, which found no significant survival benefits for patients treated with TARE vs. sorafenib. Noting the improved toxicity profile of TARE recipients in the trial could lead to a quality-of-life benefit in economic evaluations, the researchers assessed resource use, progression-free and overall survival, and quality of life for the within-trial period for patients who received at least one dose of sorafenib or one treatment with TARE based on their randomization. Compared with sorafenib, TARE resulted in an average loss of 0.036 life-years and an increase of 0.0006 quality-adjusted life-years (QALYs). Additionally, the average cost for the TARE arm was €17,179 more than the sorafenib arm, and the incremental cost-effectiveness ratio was €3,153,086/QALY. In the probabilistic sensitivity analysis, there was a 50% risk that the TARE strategy was dominated. All sensitivity analyses demonstrated that TARE was either dominated by sorafenib or had an incremental cost-effectiveness ratio of more than €450,000/QALY. Based on their findings, the researchers concluded that treating hepatocellular carcinoma with TARE was not cost-effective at generally accepted willingness-to-pay levels.
Clinical Therapeutics (05/21) K Zarca; M Mimouni; H Pereira; et al.
For patients with locally advanced hepatocellular carcinoma (HCC), personalized dosimetry significantly improved the objective response rate compared with standard dosimetry, according to a new study. Researchers for the DOSISPHERE-01 Study Group evaluated the efficacy of the two approaches of selective internal radiation therapy with yttrium-90-loaded glass microspheres in patients with HCC at four health care facilities in France. Eligible patients were aged 18 years or older, had unresectable locally advanced HCC, at least one measurable lesion 7 cm or more in size, a hepatic reserve of at least 30% after selective internal radiation therapy, no extrahepatic spread, and no contraindications to selective internal radiation therapy. Sixty patients were randomized to receive either standard dosimetry (120?±?20 Gy) targeted to the perfused lobe or personalized dosimetry (=205 Gy targeted to the index lesion). The modified intention-to-treat group included 56 patients (28 in each group). Of those patients, 71% (20/28) in the personalized dosimetry group and 36% (10/28) in the standard dosimetry group had an objective response in the index lesion, based on European Association for the Study of the Liver criteria, three months after treatment. In the safety analysis population, there was at least one serious adverse event in 20% (7/35) patients in the personalized dosimetry group and 33% (7/21) in the standard dosimetry group. The most common grade 3 or higher adverse events were ascites, occurring in one patient in the personalized dosimetry group vs. two in the standard dosimetry group; hepatic failure, with two cases vs. none; lymphopenia, 12 vs. nine; increased aspartate aminotransferase concentrations, three vs. two; increased alanine aminotransferase concentrations, three vs. none; anemia, two vs. one; gastrointestinal hemorrhage, none vs. two; and icterus, with none vs. two. There was one treatment-related death in each treatment group.
The Lancet Gastroenterology & Hepatology (01/01/21) Vol. 6, No. 1, P. 17 E Garin; L Tselikas; B Guiu; et al.
Researchers report the progressive accumulation of exhausted, unconventionally activated CD8+PD1+ T cells in livers affected by non-alcoholic steatohepatitis (NASH). Preclinical models of NASH-induced hepatocellular carcinoma (HCC) demonstrated that therapeutic immunotherapy targeted at programmed death-1 (PD1) increased activated CD8+PD1+ T cells with tumors but did not result in tumor regression. Anti-PD1 treatment given prophylactically led to an increased incidence of NASH–HCC and larger numbers and sizes of tumor nodules. However, depletion of CD8+ T cells or TNF neutralization prevented the increase in HCC from anti-PD1 treatment, indicating that CD8+ T cells may help induce NASH–HCC. Similar phenotypic and functional profiles were observed in hepatic CD8+PD1+ T cells from humans with nonalcoholic fatty liver disease or NASH. According to a meta-analysis of three randomized Phase III clinical trials testing inhibitors of programmed death-ligand 1 (PDL1) or PD1 in more than 1,600 individuals with advanced HCC, immune therapy did not increase survival in patients with non-viral HCC. Additionally, patients in two other cohorts with NASH-induced HCC who received anti-PD1 or anti-PDL1 treatment had lower overall survival compared with patients with other aetiologies. "Collectively, these data show that non-viral HCC, and particularly NASH–HCC, might be less responsive to immunotherapy, probably owing to NASH-related aberrant T cell activation causing tissue damage that leads to impaired immune surveillance," the researchers conclude.
Nature (04/15/21) Vol. 592, No. 7854, P. 450 D Pfister; NG Núñez; R Pinyol; et al.
Cases of hepatocellular carcinoma (HCC) due to nonalcoholic fatty liver disease (NAFLD) are on the rise, in tandem obesity worldwide, and are behind an overall increase in HCC incidence and related deaths. New research from Pfister and al. in Nature indicates that etiologic factors should be considered when treating HCC. The various causes of liver disease in patients with HCC affect both tumor biology and the constituency of the tumor's immune microenvironment. The study from Pfister et al. characterized the immune microenvironment and response to immune-checkpoint inhibition in nonalcoholic steatohepatitis (NASH)-induced HCC. In mouse models, inducing NASH resulted in a greater frequency of hepatic CD8+PD1+ T cells expressing markers linked to both effector function and exhaustion. Meanwhile, liver samples from humans with NASH had a similar CD8+PD1+ T-cell population with a shared gene-expression pattern. Tests of immune-checkpoint inhibition in the mouse models of NASH found that anti-programmed death 1 (PD-1) treatment did not cause tumor regression in animals with established tumors. Furthermore, for mice without tumors, anti–PD-1 therapy led to an increase in hepatic fibrosis and an increased incidence of HCC. The researchers also conducted a meta-analysis of survival outcomes according to the cause of HCC in patients enrolled in randomized trials of immune-checkpoint inhibitors as monotherapy or in combination with bevacizumab. The report, write the authors of this article, "is seminal in defining a potential linkage between NASH and response to immune-checkpoint inhibition in patients with hepatocellular carcinoma. This linkage underscores the necessity of stratification according to cause of liver disease in randomized trials and mandates a greater stringency in annotation for viral status, NASH, and NAFLD in clinical research regarding hepatocellular carcinoma."
New England Journal of Medicine (07/15/21) Vol. 385, No. 3, P. 280 RK Kelley; TF Greten
The Cardiovascular and Interventional Radiological Society of Europe (CIRSE) released a Standards of Practice document with best practices for conducting meetings on morbidity and mortality (M&M). The document aims "to raise awareness and increase implementation of M&M meetings across the global IR community," the authors write. The nine recommendations for M&M meetings focus on case identification, meeting frequency and duration, attendees, the meeting chair, case presentation format, discussion and grading of complications, recommendations and dissemination, feedback, and administrative support and record keeping. "We have outlined a recommended approach to the M&M conference in this document, based on evidence from other specialties with more experience in the M&M process," the CIRSE team concludes. "This encompasses an inclusive and blame-free environment and revolves around a continuous cycle of reporting adverse events, structured and goal-directed scrutiny of events, and implementation of SMART actions in a timely manner."
CardioVascular and Interventional Radiology (05/14/21) J-Y Chun; A Bharadwaz; JK Tun; et al.
CROSSWORD PUZZLE
Crossword Puzzle
Introducing a fun, new feature in the newsletter — an IR-related crossword puzzle. This month's puzzle, written by Christos Georgiades MD, PhD, FSIR, FCIRSE, is titled "Let It Flow." Click here for a printable version of the crossword puzzle. If you're stuck, the solution can be found below as well.

Solution
The Society of Interventional Oncology presents an opportunity to share key findings from interesting patient cases within the interventional oncology community. Access to these cases and engaging in the discussion surrounding their content is a benefit of SIO membership. New cases will be released in the SIO Insider.

August Case Spotlight - Multidisciplinary Treatment of Intrahepatic, Mass Forming Cholangiocarcinoma
This newsletter is supported by an educational grant from Varian, A Siemens Healthineers Company
Publications Committee
Christos Georgiades, MD, PhD, FSIR, FCIRSE
SIO Publications Chair

Kenneth J. Kolbeck, MD, PhD, FSIR
SIO Publications Vice Chair

Edward Kim, MD, FSIR
SIO Board Liaison
Yilun Koethe, MD, RPVI
Christine E. Boone, MD, PhD
Ji Buethe, MD
Andrew Kolarich, MD
Juan C. Camacho, MD
Anish Ghodadra, MD
Alex J. Solomon, MD
This newsletter is brought to you by the Society of Interventional Oncology (SIO) and supported by an educational grant from Varian, A Siemens Healthineers Company. SIO's mission is to advance interventional oncology by developing evidence supporting IO therapies, educating IO practitioners, and improving patient access to IO therapies.

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