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Purpose In uveal melanoma patients, liver metastases can be treated by hepatic artery infusion chemotherapy (HAIC). During this procedure, melphalan or, less frequently, fotemustine is infused into the hepatic artery or the hepatic lobe arteries in regularly repeated interventions to achieve local tumor control. The aim of this study was to investigate the radiation exposure of HAIC. Material and methods In this retrospective study, dose data from 841 procedures in 140 patients (mean age 65.3 ± 9.9 years, 74 female) who underwent HAIC between 06/2017 and 10/2021 at one of three different angiography systems were analyzed. Results In the overall population, dose area product (DAP) (median (IQR)) was 1773 cGy·cm2 (884–3688). DAP was significantly higher in the first intervention, where a complete diagnostic workup of the vasculature was performed, than in follow-up interventions: 5765 cGy·cm2 (3160–8804) versus 1502 cGy·cm2 (807–2712) (p 2 (633–2717), two positions 1985 cGy·cm2 (1118–4074), three positions 6407 cGy·cm2 (2616–11590) (p Conclusion In uveal melanoma patients with liver metastases undergoing HAIC, radiation exposure is significantly higher both at the first intervention compared to follow-up interventions, but also with increasing number of infusion positions. Level of evidence: 3

Poster-Abstract

Background/aim 18 kDa Translocator protein (TSPO) is a mitochondrial protein up-regulated in colorectal carcinoma (CRC). Our purpose was to develop a TSPO-targeted doxorubicin prodrug (Dox-TSPO) which can be loaded onto drug-eluting beads for transarterial chemoembolization. Furthermore, we evaluated its loading and release kinetics and effects on cell viability. Materials and methods N-Fmoc-DOX-14-O-hemiglutarate was coupled with a TSPO ligand, 6-TSPOmbb732, using classical N,N,N',N'-tetramethyl-O-(1H-benzotriazol-1-yl)uranium hexafluorophosphate coupling to produce Dox-TSPO. Loading and elution studies were performed using DC beads™. Cell viability studies were performed using CellTiter-Glo® Luminescent Cell Viability Assay. Results Dox-TSPO was successfully synthesized and readily loaded onto and eluted from DC beads™, albeit at a slower rate than free doxorubicin. CRC cell lines expressing TSPO were 2- to 4- fold more sensitive to Dox-TSPO compared to free doxorubicin at 72 h. Conclusion Dox-TSPO is a promising candidate for targeted and directed cancer treatment of CRC liver metastases.

To analyze tumor response, survival and safety in patients with non-resectable hepatocellular carcinoma (HCC) treated with transarterial hepatic chemoembolization using degradable starch microspheres (DSM-TACE) combined with doxorubicin who had no local interventional or systemic therapy alternative according to an interdisciplinary conference. In this retrospective study, 28 patients (23 male, 5 female, median age 67 years) with unresectable HCC, serum bilirubin levels 3 mg/dl and contraindications to Sorafenib, RFA, SIRT or cTACE were included. DSM-TACE was performed using Embocept DSM-TACE could be technically successfully performed in all 28 patients. At control imaging after three treatments, the overall rates of complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) were 14.3 %, 25 %, 39.3 % and 21.4 %, respectively, according to mRECIST. With regard to BCLC stages, the results were as follows (CR, PR, PD): BCLC A (n = 8): 7.1 %, 7.1 %, 10.7 %, 1.2 %; BCLC B (n = 12): 0 %, 10.7 %, 17.9 %, 14.3 %; BCLC C (n = 5): 0 %, 3.6 %, 10.7 %, 3.6 %; BCLC D (n = 3): 3.6 %, 3.6 %, 0 %, 3.6 %. According to this, DSM-TACE showed an overall good median survival of 682 days, although the patients' survival was strictly dependent on BCLC stage. DSM-TACE is a safe and promising treatment alternative for patients with unresectable HCC who are ineligible for other loco-regional therapies. · DSM-TACE is a safe treatment alternative for patients ineligible for other local or systemic treatments.. · DSM-TACE did not influence the MELD-score in our study population.. · Patients treated with DSM-TACE showed an overall good median survival of 682 days, strictly dependent on BCLC stage..· Haubold J, Reinboldt MP, Wetter A et al. DSM-TACE of HCC: Evaluation of Tumor Response in Patients Ineligible for Other Systemic or Loco-Regional Therapies. Fortschr Röntgenstr 2020; 192: 862 - 869. Die Studie wurde durchgeführt, um das Tumoransprechen, das Überleben und die Sicherheit der Behandlung durch transarterielle Chemoembolisation mit abbaubaren Stärke-Mikropartikeln in Kombination mit Doxorubicin (DSM-TACE) bei Patienten mit inoperablem hepatozellulärem Karzinom (HCC) zu analysieren. Die Patienten hatten dabei gemäß einer interdisziplinären Konferenz keine lokale oder systemische Therapiealternative. In diese retrospektive Studie wurden 28 Patienten (23 männlich, 5 weiblich, mittleres Alter 67 Jahre) mit inoperablem HCC, Serum-Bilirubinspiegel 3 mg/dl und Kontraindikationen gegen andere lokale oder systemische Therapien eingeschlossen. DSM-TACE wurde 3-mal alle 4–6 Wochen mit Embocept DSM-TACE konnte bei allen 28 Patienten technisch erfolgreich durchgeführt werden. Bei der Kontrollbildgebung nach 3 Therapien lagen die Gesamtraten für das vollständige Ansprechen (CR), das partielle Ansprechen (PR), die stabile Erkrankung (SD) und die progressive Erkrankung (PD) laut mRECIST bei 14,3 %, 25 %, 39,3 % bzw. 21,4 %. In Bezug auf die BCLC-Stufen ergaben sich folgende Ergebnisse (CR, PR, PD): BCLC A (n = 8): 7,1 %, 7,1 %, 10,7 %, 1,2 %; BCLC B (n = 12): 0 %, 10,7 %, 17,9 %, 14,3 %; BCLC C (n = 5): 0 %, 3,6 %, 10,7 %, 3,6 %; BCLC D (n = 3): 3,6 %, 3,6 %, 0 %, 3,6 %. Dementsprechend zeigte die DSM-TACE ein insgesamt gutes medianes Überleben von 682 Tagen, wobei das Überleben der Patienten streng vom BCLC-Stadium abhängig war. DSM-TACE ist eine sichere und vielversprechende Behandlungsalternative für Patienten mit einem inoperablen HCC, die für andere lokale und systemische Therapien nicht geeignet sind. · DSM-TACE ist eine sichere Behandlungsalternative für Patienten mit einem HCC, die für andere lokale und systemische Therapien nicht geeignet sind.. · DSM-TACE hatte in unserer Studienpopulation keinen Einfluss auf den MELD-Score.. · Die mit DSM-TACE behandelten Patienten zeigten ein insgesamt gutes medianes Überleben von 682 Tagen, das strikt vom BCLC-Stadium abhängig war..

OBJECTIVE During cochlear implantation, electrophysiological tests are performed to document safe technical functioning of implant and electrodes. In rare cases, the apical part of the electrode folds over during insertion. The data from transimpedance matrix (TIM) measurements enable the generation of a heat map or TIM profile measuring the spatial distribution of voltage. The aim of this study was to determine the accuracy of heat-map TIM profiles and compare them with spread of excitation (SOE) measurements and intraoperative imaging for prediction of electrode malposition. STUDY DESIGN Non-randomized study. SETTING Tertiary referral center. PATIENTS AND INTERVENTIONS One hundred patients who underwent cochlear implantation with completed TIM measurements, SOE data and perioperative imaging met the inclusion criteria and were enrolled. MAIN OUTCOME MEASURE The electrophysiological data on the electrode array positioning was compared with temporal bone imaging. RESULTS In seven cases, TIM measurements showed irregular results. In two cases, irregular TIM profiles were registered, but SOE data and 3D x-ray of the temporal bone didn't display deviated electrode positioning. A 3D x-ray of the skull displayed electrode tip fold-over in four cases and electrode buckling in one case. Sensitivity of TIM measurements and SOE data was 100%, specificity of TIM measurements was 97.89%, and specificity of SOE data was 98.93%. CONCLUSION Out of 100 patients using TIM measurements for detection of electrode malpositioning, no false negative cases were detected. TIM measurements successfully detect electrode malposition in an intraoperative setting. Different heat map patterns may be observed depending on location and type of malposition.

To evaluate the safety and efficacy of transarterial chemoembolization with degradable starch microspheres (DSM-TACE) for the treatment of hepatocellular carcinoma (HCC) with a high tumor burden ineligible for or failing other palliative therapies, 121 patients from three European centers were included. Kaplan–Meier analysis was used for median overall survival (OS) and time to progression (TTP, mRECIST criteria) in months with a 95% confidence interval (95% CI). Uni- (UVA) and multivariate (MVA) analyses were performed using the Cox Proportional Hazard Model. The median OS of the study cohort was 15.5 (13.3–18.7) months. The UVA identified HCC lesions ≤10 cm, unilobar involvement, lower Child–Pugh class and Barcelona Clinic Liver Cancer (BCLC) stage, absence of vascular invasion, and extrahepatic metastases as factors for prolonged survival. MVA confirmed lesions of ≤10 cm and unilobar disease as independent OS factors. Median TTP was 9.5 (7.6–10.3) months. The best response was achieved after a median of 3 (range: 1–6) treatments with CR/PR/SD/PD in 13.5%/44.5%/25.2%/16.8%, respectively. DSM-TACE was well tolerated with no major clinical adverse events and only limited major laboratory events. Preserved liver function was observed after repetitive DSM-TACE treatments. Repetitive DSM-TACE is a safe, well-tolerated and effective treatment option for HCC patients with high tumor burden ineligible or failing other palliative therapies.

Objective: Evaluation of the efficacy and safety of atezolizumab/bevacizumab in a real-world HCC cohort, including patients with impaired liver function and prior systemic therapy. Methods: Retrospective analysis of 147 HCC patients treated with atezolizumab/bevacizumab at six sites in Germany and Austria. Results: The overall response rate and disease control rate were 20.4% and 51.7%, respectively. Seventy-three patients (49.7%) met at least one major exclusion criterion of the IMbrave150 trial (IMbrave-OUT), whereas 74 patients (50.3%) were eligible (IMbrave-IN). Median overall survival (mOS) as well as median progression-free survival (mPFS) was significantly longer in IMbrave-IN versus IMbrave-OUT patients [mOS: 15.0 months (95% confidence interval (CI): 10.7–19.3] versus 6.0 months (95% CI: 3.2–8.9; p Conclusion: In this real-world cohort, efficacy was comparable to the results of the IMbrave150 study and not affected by prior systemic treatment. ALBI grade and ECOG score were independently associated with survival. IMbrave-OUT patients were more likely to experience hepatic decompensation.

Background To investigate the impact of insurance status on outcomes in patients with hepatocellular carcinoma (HCC). Methods Patients diagnosed with HCC in the cancer registry from 2005 to 2016 were retrospectively stratified by insurance group. Overall survival was assessed via Kaplan‐Meier curves and Cox proportional hazard models including potential confounders in multivariable analyses. Results Seven hundred and sixty‐nine patients met inclusion criteria (median age 63 years, 78.8% male, 65.9% Caucasian). 44.5% had private insurance (n = 342), 29.1% had Medicare (n = 224), and 26.4% had Medicaid (n = 203). At diagnosis, Medicaid patients had higher rates of Child‐Pugh B (32.0%) and C disease (23.6%) vs Medicare (28.6% and 9.8%) and private insurance (26.9% and 6.7%, P, Medicaid is associated with advanced liver cirrhosis at time of hepatocellular carcinoma diagnosis. Primary insurance is not an independent predictor of survival.

Image-guided locoregional therapies (LRTs) have long been a vital part of treatment regimens for hepatocellular carcinoma (HCC). Ablation, chemoembolization, and radioembolization are examples of commonly used treatment techniques for HCC. This review describes the various methods utilized to treat HCC in the field of interventional oncology and also focuses on new and novel treatment concepts being developed in the field including the use of novel immunotherapy agents and combination therapy of LRTs with immunotherapy.

Checkpoint inhibitors have demonstrated clinical impact in colorectal cancer with deficient mismatch repair and high microsatellite instability. However, the majority of patients have disease with stable microsatellites that responds poorly to immunotherapies. Combinations of checkpoint inhibitors are under investigation as a way of increasing immunogenicity and promoting a robust anti-tumor immune response. The purpose of this study is to quantify the immune responses induced by mono and dual checkpoint inhibition in a mismatch repair proficient model of colorectal cancer (CRC). Tumor growth rates were monitored over time and compared between groups. We utilized fluorescence-activated cell sorting to analyze CD8+ and CD4+ T cells after treatment with either single PD-1 inhibition or dual PD-1 and CTLA-4 inhibition. Additionally, we sought to quantify the expression of co-inhibitory surface molecules PD-1, LAG3, and TIM3. Dual checkpoint inhibition was associated with a significantly slower growth rate as compared to either mono PD-1 inhibition or control (p + T cells demonstrated significantly less expression of PD-1 (1700 vs. 2545 and 2462; p p p

Purpose Numerous endeavors have been undertaken to preserve hearing in cochlear implant (CI) patients. Particularly, optimization of electrode array design aims at preservation of residual hearing (RH). This study examines whether a slim perimodiolar (PM) electrode array could bear the capability to preserve hearing. Methods A total of 47 patients underwent cochlear implantation receiving the PM electrode. (i) Patients with pure tone audiogram (PTA) thresholds better than 85 dB and/or hearing loss for Freiburg speech test numbers less than 60 dB and more than 50% maximum monosyllabic understanding were assigned to the RH group (n = 17), while all others belonged to the noRH group (n = 30). (ii) Another group implanted with a slim straight, lateral wall (LW) electrode was recruited for comparison. Results We compared 17 RH–30 noRH patients all receiving the PM electrode. RH in PM recipients decreased faster than in LW recipients. No significant differences were observed between both (RH v/s noRH) groups in NRT thresholds, Freiburg speech test and A§E® phonemes. Analogous satisfaction levels were indicated through the questionnaires in terms of sound quality, hearing in silence, noise and directional hearing in both groups. Conclusions The results suggest that hearing preservation is influenced not only by electrode shape but various factors. This study opens an avenue for further investigations to elucidate and enumerate the causes for progressive hearing loss.

Imaging of CD8 receptors on T-cells by positron emission tomography (PET) has been considered a promising strategy for monitoring the treatment response to immunotherapy. In this study, a trial of imaging CD8 with our newly developed sequential multiple-agent receptor targeting (SMART) technology was conducted. Mice bearing a subcutaneous colorectal CT26 tumor received three times different immunotherapy treatments (PD1 or CTLA4 or combined). On either day 7 or day 14 after the first time treatment, the PET imaging study was performed with sequentially administered TCO-modified anti-CD8 antibody and 64Cu-labeled MeTz-NOTA-RGD. However, no positive response was detected, probably due to (1) inappropriate selection of biomarkers for the SMART strategy, (2) limited TCO modification on the anti-CD8 antibody, and (3) inadequate response of the CT26 tumor to the selected immunotherapies. Therefore, the potential of applying SMART in imaging CD8 was not demonstrated in this study, and further optimization will be necessary before it can be applied in imaging CD8.

Purpose Accurate therapeutic management of the neck is a challenge in patients with supraglottic laryngeal cancer. Nodal metastasis is common at all disease stages, and treatment planning relies on clinical staging of the neck, for both surgical and non-surgical treatment. Here, we compared clinical and surgical staging results in supraglottic carcinoma patients treated with primary surgery to assess the accuracy of pre-therapeutic clinical staging and guide future treatment decisions. Methods Retrospective analysis of clinical, pathological, and oncologic outcome data of 70 patients treated with primary surgery and bilateral neck dissection for supraglottic laryngeal cancer. Patients where clinical and pathological neck staging results differed, were identified and analyzed in detail. Results On pathologic assessment, patients with early stage (pT1/2) primaries showed cervical lymph node metastases in 55% (n = 17/31) of cases, compared to 67% (n = 26/39) of patients with pT3/4 tumors. In 24% (n = 17/70) of all patients, cN status differed from pN status, resulting in an upstaging in 16% of cases (n = 11/70) and a downstaging in 9% (n = 6/70) of cases. 14% of patients with cN0 status had occult metastases (n = 5/30). As assessed by a retrospective tumor board, in case of a non-surgical treatment approach, the inaccurate clinical staging of the neck would have led to an over- or undertreatment of the neck in 20% (n = 14/70) of all patients. Conclusion Our data re-emphasize the high cervical metastasis rates of supraglottic laryngeal cancer across all stages. Inaccurate clinical staging of the neck is common and should be taken into consideration when planning treatment.

Background Inflammation and the immune system significantly impact the development, progression, and treatment response of hepatocellular carcinoma (HCC). This retrospective study investigated the neutrophil‐to‐lymphocyte ratio (NLR) as a prognostic biomarker in Western patients with HCC in the setting of chronic viral hepatitis. Methods Patients diagnosed with HCC from 2005 to 2016 were selected from a tertiary care institution. NLR was calculated within 30 days prior to treatment and dichotomized at the median. Kaplan–Meier overall survival (OS) curves and Cox hazard proportional models were utilized. Tumor and liver reserve parameters were included in multivariable analyses (MVA). Results A total of 581 patients met inclusion criteria (median age 61.0 yr; 78.3% male; 66.3% Caucasian) with median OS = 34.9 mo. 371 patients (63.9%) had viral hepatitis, of which 350 had hepatitis C (94.3%). The low‐NLR group (, Lower baseline NLR was associated with increased overall survival in HCC. Chronic viral hepatitis serves as an effect modifier of NLR, attenuating its prognostic relevance in this hepatitis C‐predominant population.

To assess serum lactate dehydrogenase (LDH) as a pretreatment prognostic factor in patients with uveal melanoma liver metastases treated with transarterial hepatic chemoperfusion (THC). 56 patients (48 % male, median age: 63.5 years) underwent a median of 4 THC sessions. Kaplan-Meier for median overall survival (OS) and time to hepatic progression (TTP; 95 %CI) in months and Cox proportional hazards model for uni- (UVA)multivariate analyses (MVA) for hazard ratio (HR) evaluation were calculated. The median OS was 9.4 months. The pretreatment LDH value before 1st THC was the strongest OS predictor with 19.8 months for normal (≦ 280 units per liter (U/L)), 9.7 for intermediate ( 280- 1000 U/L), and 3.84 months for high (≧ 1000 U/L) LDH. LDH significantly predicted a median TTP with 8 months, 4 months, and 1 month for normal, intermediate, and high LDH, respectively. UVA revealed intermediate (16.5) and high (77.3) LDH, bilirubin the upper limit of normal (ULN) (2.89), alkaline phosphatase 1.5 ULN (6.8), leukocytes ULN (4.2), gamma-glutamyl transferase (GGT) ULN (7), extrahepatic metastases (1.8) and liver lesions ≥ 5 cm (3.6) as significant predictors for worse OS. MVA confirmed intermediate (5) and high (27.1) LDH, bilirubin (5.7), GGT (2.9), and tumor size ≥ 5 cm (3.7) as significant independent predictors for worse OS. Patients with decreasing vs. increasing LDH 10 % between 1st and 2nd THC (median: 38 days) survived longer (14.6 vs. 4.3 months) and progressed later (7 months vs. 1 month). Elevated pretreatment serum LDH is an essential and robust OS and TTP predictor, potentially allowing for the identification of patients benefiting most from transarterial hepatic chemoperfusion.· Pretherapeutic LDH is the most reliable prognosticator for OS and TTP. · Therapy-related LDH decrease 10 % between 1st and 2nd THC had prolonged OS and TTP. · Lower Values of LDH, bilirubin, gamma-glutamyl transferase, and tumor size are independent pretherapeutic predictors for longer OS. · Extrahepatic metastases do not have an independent influence on overall survival.· Ludwig J, Haubold J, Heusner T et al. Lactate Dehydrogenase Prior to Transarterial Hepatic Chemoperfusion Predicts Survival and Time to Progression in Patients with Uveal Melanoma Liver Metastases. Fortschr Röntgenstr 2021; 193: 683 - 691.ZIEL: Beurteilung der Serum-Laktatdehydrogenase (LDH) als prätherapeutischer prognostischer Faktor bei Patienten mit Lebermetastasen eines Aderhautmelanoms, die mit der transarteriellen hepatischen Chemoperfusion (THC) behandelt wurden. 56 Patienten (48 % männlich, medianes Alter: 63,5 Jahre) erhielten im Median 4 Behandlungen. Die Kaplan-Meier-Analyse für das mediane Gesamtüberleben und die Zeit bis zur hepatischen Tumorprogression (TTP; 95 %-KI) in Monaten sowie das Cox-Proportional-Hazard-Modell für die univariate (UVA) und multivariate Analyse (MVA) zur Bewertung des Risikoquotienten (HR) wurden berechnet. Das mediane Überleben betrug 9,4 Monate. Der LDH-Wert vor der ersten Behandlung war der stärkste Prädiktor für das Überleben mit 19,8 Monaten für normale (≦ 280 Einheiten/Liter (U/L)), 9,7 Monaten für mittlere ( 280– 1000 U/L) und 3,84 Monaten für hohe (≧ 1000 U/L) LDH-Werte. Die LDH war der signifikanteste Vorhersagewert für die TTP mit 8, 4 und 1 Monaten für normale, mittlere bzw. hohe LDH-Werte. Die UVA identifizierte mittlere (16,5) und hohe (77,3) LDH-Werte, Bilirubin Obergrenze des Normalbereichs (ULN) (2,89), alkalische Phosphatase 1,5 ULN (6,8), Leukozyten ULN (4,2), Gamma-Glutamyltransferase (GGT) ULN (7), extrahepatische Metastasen (1,8) und Leberläsionen ≥ 5 cm (3,6) als signifikante Prädiktoren für ein kürzeres Überleben. Die MVA bestätigte mittlere (5,0) und hohe (27,1) LDH-Werte, Bilirubin (5,7), GGT (2,9) und eine Tumorgröße von ≥ 5 cm (3,7) als unabhängige signifikante Prädiktoren für das Überleben. Patienten mit einer LDH-Abnahme vs. einer Zunahme 10 % zwischen der ersten und zweiten Behandlung (median: 38 Tage) überlebten länger (14,6 vs. 4,3 Monate) und zeigten eine spätere Progression (7 vs. 1 Monate). Ein erhöhter prätherapeutischer LDH-Wert ist ein wesentlicher und robuster OS- und TTP-Prädiktor, der es potenziell ermöglicht die Patienten zu identifizieren, welche am meisten von der transarteriellen hepatischen Chemoperfusion profitieren.· Prätherapeutisches LDH ist der stärkste prognostische Faktor für das Überleben und die Tumorprogression. · Eine therapiebedingte LDH-Abnahme 10 % zwischen der ersten und zweiten Behandlung ist mit einem längeren OS und TTP assoziiert. · Niedrigere LDH, Bilirubin und Gamma-Glutamyl-Transferase Werte sowie kleinere Tumore sind unabhängige prätherapeutische Prädiktoren für ein längeres Gesamtüberleben. · Extrahepatische Metastasen haben keinen unabhängigen Einfluss auf das Gesamtüberleben.

e16119 Background: Assessment of the clinical outcomes and prognostic value of genomic mutations in colorectal liver metastases treated with Y90 radioembolization. Methods: Multi-institution retrospective study of patients who underwent Y-90 radioembolization treatment after tumor genotyping was completed for CRLM. Patients treated between 2008 and 2019 were included from 7 institutions within the United States and Europe. Patient demographics, tumor characteristics, pre- and post- treatment regimens, serum laboratory evaluation and overall survival were analyzed between patients with differing histopathologic and genomic status. Tumor genotyping was obtained for KRAS, BRAF, PIK3CA, AKT, MEK, NRAS and MMR genes. Kaplan-Meier survival estimation and multivariate Cox regression were analyzed. Results: 434 patients treated with Y90 radioembolization fulfilled the inclusion criteria. Of the total cohort, 399 patients were available who had sufficient documented tumor profiling data. Average age at diagnosis was found to be 58.8 years for all patients (60.1% male, 39.9% female). Decreased survival post Y-90 treatment was shown in those patients with increased number of documented tumor mutations (n = 0,1 or ≥2 mutations: median OS 9.63 mos vs. 6.2 mos vs. 5.3 mos; p < 0.0001). Additionally, the median survival in patients with mutated BRAF was 5.0 months, as compared to 9.4 months in those patients with wild-type BRAF (p = 0.0009). Primary colon cancer sidedness was also shown to demonstrate significant difference in survival post-Y90 treatment with left sided primaries showing improved median overall survival (left = 7.5 mos vs. right = 6.3 mos; p = 0.04.) Patient demographics including gender, age and race were not shown to be significant in overall survival post-Y90 treatment (p-values > 0.05). Number of tumor mutations (p < 0.0001, HR = 1.69 CI: 1.39-2.05), BRAF status (p = 0.02, HR = 2.6 CI:1.20-4.9), primary sidedness (p = 0.01, HR = 0.65 CI:0.47-0.90), pre-treatment neutrophil-lymphocyte ratio (p = 0.04, HR = 1.42 CI: 1.02-1.98) and KRAS mutation status (p < 0.0001, HR = 1.81 CI: 1.45-2.26) all persisted as significant predictors of survival on multivariate analysis. Conclusions: Number of tumor mutations, BRAF mutation status, primary tumor sidedness, neutrophil-lymphocyte ratio and KRAS mutation status are all shown to be significant prognostic factors in patients with colorectal liver metastases receiving Y90 radioembolization.

Interventional oncology (IO) and oncoimmunology (OI) are fields that have significantly evolved during the last two decades and are providing new opportunities to conquer cancer with a safe and effective treatment profile. Novel IO treatments have the potential to complement OI and sensitize “cold” tumors to immunostimulatory therapies with the ultimate aim of improving patient outcomes. In this manuscript, we provide an overview of the current knowledge of the immune system in cancer, the potential for IO to modulate the immune system, and how IO and OI may synergize.

Purpose To compare adverse events and survival outcomes, including cancer-specific survival and overall survival (OS), in patients with T1aN0M0 renal cell carcinoma (RCC) who are undergoing partial nephrectomy (PN), radical nephrectomy (RN), thermal ablation (TA), or active surveillance (AS). Materials and Methods Through use of the Surveillance, Epidemiology, and End Results-Medicare-linked database from 2002 to 2011 with at least 1 year of consecutive follow-up, a HIPAA-compliant retrospective propensity score-matched study of patients with T1aN0M0 RCC who underwent PN, RN, TA, or AS was performed. Medicare beneficiaries (n = 10 218) with T1aN0M0 RCC as first primary cancer diagnosis were included. Survival and adverse health outcomes were compared across treatment groups. Results Overall, cancer-specific survival significantly differed in the PN versus RN (P.001), AS versus TA (P = .03), and AS versus PN (P = .002) groups. There were no significant differences when TA was compared with PN or RN, with 9-year cancer-specific survival rates of 96.4% versus 96.3% (PN vs TA, P = .07) and 96.1% versus 96.0% (RN vs TA, P = .14), respectively. With the exception of cancer-specific survival in AS versus RN groups (P = .29), cancer-specific survival and OS for all AS comparisons were significantly lower. In addition, compared with the patients undergoing TA, those in the PN and RN groups had increased rates of renal, cardiovascular, and thromboembolic adverse events up to 1 year after the procedure (P.05 for all comparisons). Conclusion For T1aN0M0 RCC, TA confers cancer-specific survival and OS similar to those seen with surgical management, with significantly fewer adverse outcomes at 1 year after the procedure and similar rates of secondary cancer events compared with surgery.

The use of immunomodulation to treat malignancies has seen a recent explosion in interest. The therapeutic appeal of these treatments is far reaching, and many new applications continue to evolve. In particular, immune modulating drugs have the potential to enhance the systemic anticancer immune effects induced by locoregional thermal ablation. The immune responses induced by ablation monotherapy are well documented, but independently they tend to be incapable of evoking a robust antitumor response. By adding immunomodulators to traditional ablative techniques, several researchers have sought to amplify the induced immune response and trigger systemic antitumor activity. This paper summarizes the work done in animal models to investigate the immune effects induced by the combination of ablative therapy and immunomodulation. Combination therapy with radiofrequency ablation, cryoablation, and microwave ablation are all reviewed, and special attention has been paid to the addition of checkpoint blockades. CA extern

Purpose To systematically review the safety and efficacy of transarterial drug-eluting beads, irinotecan (DEBIRI) for the treatment of pretreated patients with unresectable colorectal liver metastases (CRLM). Methods A systematic search of the current literature was conducted to extract publications reporting on the use of DEBIRI for CRLM. Data on the safety and efficacy was extracted and tabulated. Weighted average values (WAV) were calculated for each variable to provide a single value representing the pooled safety and efficacy data. Results 13 studies (15 treatment arms) were evaluated, comprising a total of 850 patients. There were 6 prospective phase I/II trials, 5 retrospective trials and 2 randomized control trials. All papers involved patients previously treated with systemic chemotherapy. The weighted average all-grade toxicity rate was 35.2% (range; 6–100%). The high-grade WAV toxicity rate was 10.1% (range; 0–32%). Weighted average response rates were 56.2% and 51.1% according to RECIST (Response Evaluation Criteria in Solid Tumors) and modified RECIST/EASL (European Association for the Study of the Liver) response criteria respectively. The weighted average progression-free survival and overall survival were 8.1 months and 16.8 months, respectively. Conclusion Transarterial DEBIRI is safe and effective in the treatment of unresectable CRLM to the liver. Further studies are warranted to better define its role in the treatment algorithm of this patient subset.

// Meaghan S. Dendy 1,2 , Johannes M. Ludwig 2 and Hyun S. Kim 2,3 1 Drexel University College of Medicine, Philadelphia, PA, USA 2 Department of Radiology and Biomedical Imaging, Division of Interventional Radiology, Yale School of Medicine, New Haven, CT, USA 3 Yale Cancer Center, Yale University, New Haven, CT, USA Correspondence to: Hyun S. Kim, email: // Keywords : colorectal cancer, liver cancer, radioembolization, Y 90 , biomarkers Received : December 28, 2016 Accepted : February 27, 2017 Published : March 08, 2017 Abstract This critical review aims to explore predictive and prognostic biomarkers of Yttrium-90 (Y 90 ) radioembolization therapy of colorectal liver metastases. A brief overview of established predictive and prognostic molecular and genetic biomarkers in colorectal cancer therapies will be discussed. A review of the literature on imaging modalities, genetic, metabolic and other molecular markers and the subsequent outcomes in post-Y 90 treatment will be presented. How these biomarkers and future biomarker research can inform locoregional treatment decisions in the clinical setting of metastatic colorectal cancer lesions of the liver will be explored. There are opportunities for personalized cancer treatment in the setting of Y 90 radioembolization. The ability to predict tumor response after Ytrium-90 radioembolization therapy can greatly impact clinical decision making and enhance treatment outcomes, therefore further research into the field is needed.

Aim: To simulate effects of the new Organ Procurement and Transplantation Network/United Network for Organ Sharing policy on the patients’ characteristics and post orthotopic liver transplantation (OLT) outcome. Materials & methods: The United Network for Organ Sharing database was used to identify patients with hepatocellular carcinoma who were listed for OLT 2002–2014. All patients (actual group) versus simulated group with new 6-month delay in assigning Model for End-Stage Liver Disease score exception and Model for End-Stage Liver Disease exception cap of 34 were compared. Results & conclusion: With the new policy, 7,745 (30.4%) of the transplanted patients would have received a delayed transplantation or not be transplanted. The simulated group also showed significantly higher mean overall survival after OLT (p

Background To investigate the neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), and systemic immune‐inflammation index (SII) as prognostic biomarkers in intrahepatic cholangiocarcinoma (ICC) with a focus on viral hepatitis and liver status. Methods In this retrospective cohort study, patients from the institutional cancer registry with ICC from 2005 to 2016 were stratified by treatment group. Baseline inflammatory markers were dichotomized at the median. Overall survival (OS) was assessed via Kaplan‐Meier curves and Cox proportional hazard models. Multiple patient, liver, and tumor factors were included in the multivariable analysis (MVA). Results About 131 patients (median age 65 years, 52% male, 76% Caucasian) had a median OS of 13.0 months. Resection/interventional oncology with/without systemic therapy had improved survival vs systemic therapy alone in Child‐Pugh A patients (P, The neutrophil‐to‐lymphocyte ratio (NLR) has the strongest impact as a prognostic marker in intrahepatic cholangiocarcinoma (ICC) versus the platelet‐to‐lymphocyte ratio and systemic immune‐inflammation index, and increased NLR is associated with decreased survival in ICC. The NLR has decreased prognostic utility in patients with advanced liver disease.

Novel approaches with checkpoint inhibitors in immunotherapy continue to be essential in the treatment of non-small cell lung cancer (NSCLC). However, the low rate of primary response and the development of acquired resistance during the immunotherapy limit their long-term effectiveness. The underlying cause of acquired resistance is poorly understood; potential management strategies for patients with acquired resistance are even less clear. Here, we report the case of a 75-year-old female smoker with cough, fatigue, and weight loss that was found to have an 8.6 cm right upper lobe lung lesion with local invasion, adenopathy, and a malignant pericardial effusion. This lesion was biopsied and identified to be cT3N3M1b squamous cell cancer of the lung without any recognizable PD-L1 expression on tumor cells. For her metastatic NSCLC, the patient underwent two lines of conventional chemotherapy before initiation of combination immunotherapy with an anti-PD-L1 and anti-CTLA-4 antibody. Though she initially achieved a response, she thereafter progressed and developed immunotherapy resistant lymph nodal metastasis. While cervical lymph nodes could be surgically removed, another metastasis in an aortocaval area required a more sensitive therapy like thermal ablation. The aortocaval node was partially treated with a single treatment of cryotherapy and demonstrated durable complete response. Cryotherapy for checkpoint immunotherapy resistant metastasis appears to be a safe and feasible treatment for treating metastatic disease in non-small cell lung cancer. The prospect of cryotherapy adjuvancy may enable local control of metastatic disease after initial response to immune checkpoint immunotherapy and may impact on overall outcomes. CA extern

To investigate comparative effectiveness of drug-eluting bead transarterial chemoembolization (DEB-TACE) versus Yttrium-90 (90Y)-radioembolization for hepatocellular carcinoma (HCC). Studies comparing conventional (c)TACE versus 90Y-radioembolization or DEB-TACE for HCC treatment were identified using PubMed/Medline, Embase, and Cochrane databases. The adjusted indirect meta-analytic method for effectiveness comparison of DEB-TACE versus 90Y-radioembolization was used. Wilcoxon rank-sum test was used to compare baseline characteristics. A priori defined sensitivity analysis of stratified study subgroups was performed for primary outcome analyses. Publication bias was tested by Egger’s and Begg’s tests. Fourteen studies comparing DEB-TACE or 90Y-radioembolization with cTACE were included. Analysis revealed a 1-year overall survival benefit for DEB-TACE over 90Y-radioembolization (79 % vs. 54.8 %; OR: 0.57; 95 %CI: 0.355-0.915; p = 0.02; I-squared: 0 %; p > 0.5), but not for the 2-year (61 % vs. 34 %; OR: 0.65; 95%CI: 0.294-1.437; p = 0.29) and 3-year survival (56.4 % vs. 20.9 %; OR: 0.713; 95 % CI: 0.21-2.548; p = 0.62). There was significant heterogeneity in the 2- and 3-year survival analyses. The pooled median overall survival was longer for DEB-TACE (22.6 vs. 14.7 months). There was no significant difference in tumour response rate. DEB-TACE and 90Y-radioembolization are efficacious treatments for patients suffering from HCC; DEB-TACE demonstrated survival benefit at 1-year compared to 90Y-radioembolization but direct comparison is warranted for further evaluation. • This meta-analysis shows greater 1-year survival benefit for DEB-TACE over 90 Y-radioembolization. • DEB-TACE has a favourable 2- & 3-year survival benefit trend over 90 Y-radioembolization. • No significant difference for tumour response was detected. • Direct comparison of these methods for a more robust evaluation is warranted.

To investigate survival outcomes following radioembolization with Yttrium-90 (Y90) for neuroendocrine tumor liver metastases (NETLMs). This study was designed to assess the efficacy of Y90 radioembolization and to evaluate lung shunt fraction (LSF) as a predictor for survival.A single-center, prospective study of 44 consecutive patients (median age: 58.5 years, 29.5 % male) diagnosed with pancreatic (52.3 %) or carcinoid (47.7 %) NETLMs from 2006 to 2012 who underwent Y90 radioembolization was performed. Patients' baseline characteristics, including LSF and median overall survival (OS) from first Y90 radioembolization, were recorded and compared between patients with high (≥10 %) and low (10 %) LSF. Baseline comparisons were performed using Fisher's exact tests for categorical and Mann-Whitney U test for continuous variables. Survival was calculated using the Kaplan-Meier method. Univariate (Wilcoxon rank-sum test) and multivariate analyses (Cox Proportional Hazard Model) for risk factor analysis were performed.There was no statistically significant difference in age, gender, race, tumor properties, or previous treatments between patients with high (n = 15) and low (n = 29) LSF. The median OS was 27.4 months (95 %CI 12.73-55.23), with 4.77 months (95 %CI 2.87-26.73) for high and 42.77 months (95 %CI 18.47-59.73) for low LSF (p = 0.003). Multivariate analysis identified high LSF (p = 0.001), total serum bilirubin1.2 mg (p = 0.016), and lack of pretreatment with octreotide (p = 0.01) as independent prognostic factors for poorer survival. Tumor type and total radiation dose did not predict survival.LSF ≥10 %, elevated bilirubin levels, and lack of pretreatment with octreotide were found to be independent prognostic factors for poorer survival in patients with NETLMs.

Purpose To investigate baseline and early apparent diffusion coefficients (ADC) derived from diffusion-weighted imaging (DWI) as a predictor of objective response (OR) and survival in unresectable hepatocellular carcinoma (HCC) treated with doxorubicin drug-eluting bead (DEB) transcatheter arterial chemoembolization. Materials and Methods In a prospective study, 57 patients underwent DEB chemoembolization. Dynamic contrast-enhanced magnetic resonance imaging and DWI were performed at baseline and 1 and 3 months after DEB chemoembolization. OR was evaluated per modified Response Evaluation Criteria In Solid Tumors (mRECIST) and European Association for the Study of the Liver (EASL) guidelines. Baseline ADCs of tumors that showed OR at 1 and 3 months were compared with nonresponding tumor ADCs by two-sample t test and receiver operating characteristic curves. Additionally, ADC changes at 30 days were correlated with OR. Finally, Kaplan–Meier analysis was used to compare survival between patients with lesions demonstrating more restricted baseline diffusion and others. Results At 1 month, 33 patients (60%) showed OR (21 complete responses and 12 partial responses). At baseline, tumors with OR at 1 month showed significantly more restricted diffusion (0.731 × 10 −3 mm 2 /s) compared with others (1.057 × 10 −3 mm 2 /s; P = .031). No difference between response rates at 1 and 3 months according to mRECIST and EASL was observed. For an area under the curve of 0.965, the sensitivity and specificity of predicting objective tumor response at 1 month using a baseline HCC ADC of 0.83 × 10 −3 mm 2 /s were 91% and 96%, respectively. In addition, patients with lesions with a baseline ADC −3 mm 2 /s showed prolonged survival compared with others ( P Conclusions In unresectable HCC, a baseline ADC −3 mm 2 /s is a predictor of survival and treatment response at 1 and 3 months after DEB chemoembolization with high sensitivity and specificity.

Reliable response criteria are critical for the evaluation of therapeutic response in hepatocellular carcinoma (HCC). Current response assessment is mainly based on: (1) changes in size, which is at times unreliable and lag behind the result of therapy; and (2) contrast enhancement, which can be difficult to quantify in the presence of benign post-procedural changes and in tumors presenting with a heterogeneous pattern of enhancement. Given these challenges, functional magnetic resonance imaging (MRI) techniques, such as diffusion-weighted imaging (DWI) have been recently investigated, aiding specificity to locoregional therapy response assessment and outcome prediction. Briefly, DWI quantifies diffusion of water occurring naturally at a cellular level (Brownian movement), which is restricted in multiple neoplasms because of high cellularity. Disruption of cellular integrity secondary to therapy results in increased water diffusion across the injured membranes. This review will provide an overview of the current literature on DWI therapy response assessment and outcome prediction in HCC following treatment with locoregional therapies.

Background: Biosensor imaging of redundant deviation in shifts (BIRDS) is a non-invasive MR imaging modality that maps extracellular pH (pHe) by directly detecting paramagenetically shifted non-exchangeable protons of exogeneous agents. Previously it has been used to characterize various tumors in the rat brain and to monitor the response to loco-regional treatment of liver cancer. The purpose of this study was to investigate the feasibility of utilizing pHe mapping with BIRDS to differentiate ablated and non-ablated tumors in the setting of systemic immunotherapy of murine colorectal cancer (CRC). Materials and Methods: Eight BALB/c mice (Charles River Laboratories, Wilmington, MA, USA) were implanted with bilateral flank injections of 0.5 × 106 CT26.WT colorectal cancer cells (CRL- 2638; ATCC, Manassas, VA). Mice were randomly assigned into 3 treatment groups; group 1 received injections of sham antibodies (InVivoMAb IgG controls), group 2 was treated with dual anti-PD-1 and anti-CTLA-4 antibodies (Clone J43 & Clone 9D9; BioXcell, West Lebanon, NH, USA), III). Group 3 received cryoablation in combination with systemic injections of dual checkpoint inhibitors. Mapping of pHe was performed between 3-10 days after the initiation of treatment and was immediately followed by sacrifice. Results: The mean pHe of untreated, control tumors was significantly lower than the average pHe of tumors treated with immuno-thermal ablations (6.6 vs 6.96; p0.05). Conclusions: BIRDS MR quantification was feasible for imaging murine CRC model. BIRDS quantification of pHe could serve as an imaging non-invasive biomarker for metabolic changes of the tumor microenvironment in a murine CRC model with Immuno-Thermal Ablation Therapy. Significance at a GlanceTreatment GroupMean Extracellular pHSignificant DifferencesControl6.6Vs Target Ablated Tumors (p Citation Format: Ryan J. Slovak, Daniel Coman, Johannes M. Ludwig, Hyun S. Kim. Mapping the extracellular pH gradient of colorectal cancer after immuno-thermal ablation [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2778.

239 Background: Assessment of the clinical outcome and prognostic factors of patients receiving Y90 radioembolization to treat colorectal liver metastases. Methods: Multi-institution retrospective study of patients with CRLM who received Y-90 radioembolization after undergoing molecular testing was performed. Patients treated between 2008 and 2019 were included from 7 institutions within the United States and Europe. Patient demographics, systemic therapy regimens, tumor characteristics, laboratory values and overall survival were analyzed between patients with differing histopathologic and genomic status. Genomic profiling was obtained for KRAS, BRAF, PIK3CA, AKT, MEK, NRAS and MMR genes. Kaplan-Meier survival estimation and multivariate Cox regression were analyzed. Results: 445 patients treated with Y90 radioembolization fulfilled the inclusion criteria. Of the total cohort, 430 patients were available who had documented KRAS mutation status. Average age at diagnosis was found to be 58.4 years for all patients (57.6% male, 42.4% female). Decreased survival post Y90 treatment was shown in those patients with mutant KRAS. The median survival in patients with mutated KRAS was 5.7 months, as compared to 8.0 months in those patients with wild-type KRAS (p< 0.0001). Patient demographics including age, gender and race were not shown to be significant in overall survival post-Y90 treatment (p-values >0.05). The average number of systemic chemotherapy treatments prior to Y90 was 2.15 and was similar between KRAS groups (mutant vs wild type.) KRAS status persisted as a significant predictor of survival on multivariate analysis (p< 0.0001; HR 2.1 CI: 1.54-2.85). Conclusions: KRAS status is shown as a significant prognostic factor in patients with colorectal liver metastases receiving Y90 radioembolization.

160 Background: Checkpoint inhibitors have demonstrated significant clinical impact in colorectal cancer with deficient mismatch repair (MMR) and high microsatellite instability. However, most patients have disease with stable microsatellites and typically respond poorly to most immunotherapies. The purpose of this study was to quantify the immune responses induced by mono versus dual immune checkpoint blockade (DICB) in a MMR proficient model of colorectal cancer. Methods: A MMR proficient model of colorectal cancer was established in 30 BALB/c mice via bilateral subcutaneous flank injections of 0.5x106 CT26.WT murine colorectal cancer cells (CRL- 2638; ATCC, Manassas, VA). Mice were assigned to receive either sham antibodies (InVivoMAb IgG controls), monotherapy with anti-PD-1 antibodies (Clone J43; BioXcell, West Lebanon, NH, USA), or DICB with anti-PD-1 and anti-CTLA-1 antibodies (Clone 9D9; BioXcell). Tumor growth was monitored over time and mice were sacrificed at either 7 or 14 days post-treatment. Single cell suspensions of harvested tumors and spleens were analyzed using FACS. The number of CD8+ and CD4+ T cells as well as the expression of co-inhibitory surface molecules PD-1, LAG3, and TIM3 was quantified in each sample. Results: DICB was associated with a reduction in tumor volume as compared to either mono PD-1 inhibition or control (p < 0.05). Neither monotherapy nor DICB significantly affected tumor infiltration by lymphocytes. Tumor infiltrating CD8+ T cells in the DICB treatment group demonstrated less expression of PD-1 and LAG3 compared to the control and monotherapy groups (PD-1: 1723±90.5 [Mean fluorescence intensity ± SEM] vs 2489±119.9 & 2404±117.9; p < 0.05) (LAG3: 453.8±21.58 vs 664.1±53.21 & 719.7±14.25; p < 0.05). The DICB group also showed increased expression of TIM3 (11,779±1271 vs 2832±380.9 & 4081±426.6; p < 0.05). Conclusions: These results suggest dual therapy with anti-CTLA and anti-PD-1 antibodies inhibits the growth of stable microsatellite colorectal cancer by suppressing key immunosuppressive checkpoints. Upregulation of TIM3 represents a potential escape mechanism that could be a target for future combination immunotherapies.