Predictive Dosimetry and Outcomes of Hepatocellular Carcinoma Treated by Yttrium-90 Resin Microsphere Radioembolization: A Retrospective Analysis Using Technetium-99m Macroaggregated Albumin SPECT/CT and Planning Software.

PURPOSE: To characterize estimated mean absorbed tumor dose (ADT), objective response (OR), and estimated target dose of hepatocellular carcinoma (HCC) after resin microsphere yttrium-90 (90Y) radioembolization using partition dosimetry. MATERIALS AND METHODS: In this retrospective, single-center study, multicompartment dosimetry of index tumors receiving 90Y radioembolization between October 2015 and June 2022 was performed using a commercial software package and pretreatment technetium-99m macroaggregated albumin single photon emission computed tomography (SPECT)/computed tomography (CT). In total, 101 patients with HCC underwent 102 treatments of 127 index tumors. Patients underwent imaging every 2-3 months after treatment to determine best response per modified Response Evaluation Criteria in Solid Tumors (mRECIST). Best response was defined as the greatest response category per mRECIST and categorized as OR or nonresponse (NR). A Cox proportional hazards model evaluated the probability of tumor OR and progression-free survival using ADT. RESULTS: The median follow-up period was 148 days (interquartile range [IQR], 92-273 days). The median ADT of OR was 141.9 Gy (IQR, 89.4-215.8 Gy) compared with the median ADT of NR treatments of 70.8 Gy (IQR, 42.0-135.3 Gy; P < .001). Only ADT was predictive of response (hazard ratio = 2.79 [95% confidence interval {CI}: 1.44-5.40]; P = .003). At 6 months, an ADT of 157 Gy predicted 90.0% (95% CI: 41.3%-98.3%) probability of OR. At 1 year, an ADT of 157 Gy predicted 91.6% (95% CI: 78.3%-100%) probability of progression-free survival. Partition modeling and delivered activity were predictive of progression (P = .021 and P = .003, respectively). CONCLUSIONS: For HCC treated with resin microspheres, tumors receiving higher ADT exhibited higher rates of OR. An ADT of 157 Gy predicted 90.0% OR at 6 months.

Predictive Partition Dosimetry and Outcomes after Yttrium-90 Resin Microsphere Radioembolization of Colorectal Cancer Metastatic to the Liver: A Retrospective Analysis.

PURPOSE: To characterize estimated absorbed tumor dose (ADT), objective response (OR), and estimated target dose of liver metastatic colorectal cancer (mCRC) after resin microsphere yttrium-90 (90Y) radioembolization using partition dosimetry. MATERIALS AND METHODS: In this retrospective, single-center study, multicompartment dosimetry of index tumors undergoing 90Y radioembolization from October 2013 to July 2022 was performed using MIM SurePlan and pretreatment technetium-99m macroaggregated albumin infusion data. Thirty-eight patients with mCRC underwent treatments for 59 index tumors. Patients were imaged every 2-3 months after treatment and then every 3-6 months after disease control to determine the best response per Response Evaluation Criteria in Solid Tumors 1.1. Responses were categorized as OR or nonresponse (NR). A Cox proportional hazards model evaluated the probability of tumor OR and local progression-free survival (LPFS) based on ADT. RESULTS: Patients had a median follow-up of 116 days (interquartile range [IQR], 69-231 days). The ADT was higher for OR patients than for NR patients (median, 130.8 [IQR, 85.6-239.0] vs 40.6 [IQR, 26.0-66.3] Gy; P < .001). A greater percentage of OR than NR patients were treated with activities calculated by partition modeling (54% vs 12%; P = .005). Only ADT predicted response (P = .032). At 6 months, an ADT of 120 Gy predicted a 55% (95% CI, 0.0%-89%) probability of OR. Only ADT (P = .010) and female sex (P = .014) predicted LPFS. At 1 year, an ADT of 120 Gy predicted a 70% (95% CI, 35%-100%) probability of LPFS. CONCLUSIONS: Tumor dose was the strongest predictor of OR for mCRC. Administration of an estimated 120 Gy to mCRC predicted 55% OR with 90Y resin microspheres at 6 months.

Partition Dosimetry and Outcomes of Metastatic Neuroendocrine Tumors after Yttrium-90 Resin Microsphere Radioembolization.

PURPOSE: To characterize estimated mean tumor-absorbed dose (ADT) and objective response of metastatic neuroendocrine tumor (NET) after resin microsphere yttrium-90 (90Y) hepatic radioembolization using partition dosimetry. MATERIALS AND METHODS: In this retrospective, single-center study, multicompartment dosimetry of index tumors receiving 90Y radioembolization between 2013 and 2022 involved the use of Sureplan (MIM Software, Cleveland, Ohio) and technetium-99m macroaggregated albumin single photon emission computed tomography (SPECT) combined with computed tomography. Thirty-six patients with NET underwent treatment of 56 index tumors. Patients underwent imaging every 3-6 months after treatment to determine best response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and modified RECIST (mRECIST) criteria. Responses were categorized as objective response (OR) or nonresponse (NR). Wilcoxon rank sum test evaluated differences in continuous variables, and Pearson χ2 test evaluated differences in categorical variables. RESULTS: Median follow-up was 582 days (IQR, 187-1,227 days). Per RECIST 1.1, 27 patients (75%) experienced OR and 9 patients experienced (25%) NR. Of the 36 patients, 33 (92%) showed hypervascular, mRECIST-evaluable tumors. Among them, 28 patients (85%) showed mRECIST OR and 5 patients (15%) showed NR. The mRECIST OR group received a higher ADT than the NR group (median, 107 Gy; IQR, 95.1-154 Gy vs median, 70.4 Gy; IQR, 62.9-87.6 Gy; P = .048). All tumors receiving at least 120 Gy showed mRECIST OR. CONCLUSIONS: In hypervascular metastatic NET treated by 90Y resin microsphere radioembolization, higher tumor dose was associated with better tumor response per mRECIST. Doses of ≥120 Gy led to OR.

Six-Year Evaluation of Same-Day Discharge following Conventional Transarterial Chemoembolization of Hepatocellular Carcinoma.

PURPOSE: To evaluate whether same-day discharge increased the incidence of 30-day readmission (30dR) after conventional transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) at a single institution. MATERIALS AND METHODS: In this retrospective study, 253 patients with HCC underwent 521 transarterial chemoembolization procedures between 2013 and 2020. TACE was performed with 50-mg doxorubicin/10-mg mitomycin C/5-10-mL ethiodized oil/particles. Patients not requiring intravenous pain medications were discharged after a 3-hour observation, and 30dR was tracked. The primary objective was to determine the incidence of 30dR in same-day discharge patients versus patients admitted for observation using the chi-square test. Secondary objectives assessed factors associated with overnight admission and factors predictive of 30dR using generalized estimated equation calculations and logistic regression. RESULTS: In the cohort, 24 readmissions occurred within 30 days (4.6%). Same-day discharge was completed after 331 TACE procedures with sixteen 30dRs (4.8%). Patients admitted overnight were readmitted 8 times after 190 TACE procedures (4.2%). This difference was not statistically significant (P = .4). Factors predicting overnight admission included female sex (58/190 [30.5%] vs 58/331 [17.5%], P < .001) and tumor size of ≥3.8 cm (104/190 [55%] vs 85/190 [45%]). Factors predicting 30dR included female sex (10/116 [8.6%] vs 14/405 [0.2%]) and younger age (median [interquartile range], 63 years [55-65 years] vs 65 years [59-71 years]). At regression, factors predictive of 30dR were Child-Pugh Class B/C (odds ratio [OR], 2.1; P = .04) and female sex (OR, 2.9; P = .004). CONCLUSIONS: Same-day discharge after conventional TACE is a safe and effective strategy with 30dR rate of <5%, similar to overnight observation.

Neutrophil/Lymphocyte Ratio Predicts Increased Risk of Immediate Progressive Disease following Chemoembolization of Hepatocellular Carcinoma.

PURPOSE: To demonstrate that patients with hepatocellular carcinoma (HCC) and elevated baseline neutrophil/lymphocyte ratio (NLR) have a significantly greater risk of progressive disease following initial transarterial chemoembolization. MATERIALS AND METHODS: A total of 190 HCC patients (149 male/41 female) treated with transarterial chemoembolization between July 2013 and July 2017 were reviewed. Mean patient age was 62. Child-Pugh grades were 132 A, 61 B, and 4 C. Tracked criteria included etiology of cirrhosis, tumor number, Barcelona Clinic Liver Cancer score, diameter of the largest 2 tumors, and presence of portal vein thrombosis. Complete blood count with differential before the procedure was used for NLR calculation. Follow-up imaging was performed 2 months after treatment. The modified response evaluation criteria in solid tumors were used to assess response. The association between baseline NLR and tumor response (ordinal modified response evaluation criteria in solid tumors categories) on 2-month follow-up imaging was evaluated using the proportional odds logistic regression model. RESULTS: A total of 194 patients (76.6%) patients had a preprocedural NLR <3.5, and 59 (23%) patients had a preprocedural NLR ≥3.5. There was a statistically significant association between baseline NLR and immediate progression on 2-month follow-up imaging (mean NLR 4.10, 2.76, 2.72, and 2.48 for progressive and stable disease and partial and complete response, respectively; odds ratio 2.1, P = .04). NLR (P = .021) and tumor multiplicity (P = .011) predicted progressive disease at 2-month imaging. CONCLUSIONS: Elevated baseline NLR is associated with higher rates of HCC tumor progression at 2-month follow-up imaging after transarterial chemoembolization.

Outpatient Transarterial Chemoembolization of Hepatocellular Carcinoma: Review of a Same-Day Discharge Strategy.

PURPOSE: To test the hypothesis that same-day discharge of selected transarterial chemoembolization patients would not increase 30-day readmission rate compared with overnight observation. MATERIALS AND METHODS: With institutional review board approval, 193 hepatocellular carcinoma patients who underwent transarterial chemoembolization from July 2013 to June 2016 were reviewed. Treatment was conventional/lipiodol transarterial chemoembolization with 50 mg doxorubicin/10 mg mitomycin-c/particles or drug-eluting embolics transarterial chemoembolization with 50-75 mg doxorubicin/vial. At 3 hours, patients tolerating oral intake and not requiring intravenous analgesics were considered for discharge. The primary outcome measure was 30-day readmission for observation versus discharge using chi-squared (χ2) analysis. The secondary aim was to identify baseline or treatment variables independently associated with readmission, including Child-Pugh class, medically managed encephalopathy or ascites, patient age (<65 vs ≥65), tumor number (1 or >1), and level of embolization (segmental vs lobar). RESULTS: Patients underwent 261 transarterial chemoembolization procedures. The 30-day readmission rate was not significantly different between observed patients (n = 179, 9.0%) and discharged patients (n = 82, 13.8%; P = .33). Readmission was not related to the selected agent (conventional/lipiodol-transarterial chemoembolization, 11.0% vs drug-eluting embolics transarterial chemoembolization, 7.5%; P = .36). Baseline variables associated with readmission were Child-Pugh B/C (χ2 = 7.9, P < .01), history of encephalopathy (χ2 = 15.4, P < 0.01), and ascites (χ2 = 4.4, P < .05). Patient age (<65 vs ≥65), tumor number (1 vs >1), and level of embolization (segmental vs lobar) were not predictive of readmission (all P > .05). CONCLUSIONS: Same-day discharge after transarterial chemoembolization does not increase the risk of 30-day readmission. Child-Pugh B/C patients, as well as those with ascites or encephalopathy, have the highest risk of readmission.

Are prophylactic antibiotics necessary prior to transarterial chemoembolization for hepatocellular carcinoma in patients with native biliary anatomy?

BACKGROUND AND OBJECTIVES: Prophylactic antibiotics are frequently administered for transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC). In patients without previous biliary instrumentation, infection risk from TACE is low. We hypothesized that there is a negligible rate of infection in these patients without prophylactic antibiotics. METHODS: We reviewed consecutive patients undergoing TACE between 7/1/2013-6/15/2016. All patients had an intact Sphincter of Oddi, received no peri-procedural antibiotics, and had 30+ days follow-up. Level of arterial selection was recorded. Baseline Child-Pugh (CP) and Barcelona Clinic Liver Cancer (BCLC) scores were recorded. The primary outcome measure was the absence of clinical or imaging findings of hepatic abscess within 30 days. RESULTS: A total of 171 patients underwent 235 TACE procedures. CP scores were A (n = 109), B (n = 47), and C (n = 15). BCLC scores were 0 (n = 1), A (n = 108), B (n = 47), and C (n = 15). TACE was performed segmentally (n = 208) or lobar (n = 27). Three patients died of non-infectious causes before 30 days. No hepatic abscesses developed in evaluable patients: 0/232 infusions. CONCLUSIONS: In patients with HCC and an intact Sphincter of Oddi, TACE was performed safely without prophylactic antibiotics. The majority of the patients were BCLC and CP A/B. Additional study of BCLC and CP C patients is warranted.

Neutrophil to lymphocyte ratio predicts disease progression following intra-arterial therapy of hepatocellular carcinoma.

BACKGROUND: Prospectively predicting response to intra-arterial therapy for hepatocellular carcinoma (HCC) is challenging. Neutrophil/lymphocyte ratio (NLR) is a serum biomarker that is associated with survival for multiple malignancies. It was hypothesized that increased NLR would be associated with early disease progression after intra-arterial therapy of HCC. METHODS: The outcomes of 86 treatment-naïve patients who had chemoembolization or radioembolization of HCC between July 2013-July 2014 were reviewed. Pre-treatment laboratory tests and imaging were used to measure NLR, Child-Pugh (CP) score, tumor number and tumor size. High/low NLR groups were defined as >3 and <3 respectively. Follow-up imaging at two months with assessed response using modified response criteria in solid tumors (mRECIST). RESULTS: NLR >3 was seen in 25/86 patients (range 3.0-21.6). NLR >3 patients had a significantly higher baseline CP score. Comorbidities were otherwise similar between groups as was tumor number/size. Disease control was significantly worse (p = 0.014) with NLR >3. Logistic regression for tumor response revealed NLR >3 as the best predictor of early progression (p < 0.0001). DISCUSSION: NLR may be a serologic biomarker of early progressive disease after intra-arterial therapy of HCC. Future research should focus on outcomes by treatment type or potentially combining arterial therapies with ablation and/or targeted biologic agents.

Red Flags, Pitfalls, and Cautions in Y90 Radiotherapy.

Radioembolization with yttrium-90 (Y90) microspheres is increasingly used to palliate patients with liver-dominant malignancy. With appropriate patient selection, this outpatient treatment is efficacious with limited toxicity profile. This article reviews common scenarios that can present in daily practice including evaluation of liver functions, evaluation of previous therapies, integrating Y90 into ongoing systemic therapy, determining performance status, and considering retreatment for patients who have already undergone Y90 who have hepatic dominant progression. Finally, we address the importance of evaluating tumors in potential watershed zones to maximize treatment response by using c-arm computed tomography. Many of these potential variables can overlap in an individual patient. By considering these factors individually, the consulting Interventional Radiologist can present a thorough treatment plan with a full description of expected outcomes and toxicities to clinic patients.

Interventional Oncology Service Development.

Interventional oncology is rapidly expanding its suite of oncologic therapies, providing unique proven therapeutic benefits. To grow a practice alongside other oncology specialties, knowledge of cancer fundamentals is required. Areas of interest include methods to assess disease stage, treatment toxicity, and response. Additionally, techniques to leverage opportunities and resources available at one's institution toward practice development and efficiency will be reviewed.

Procedural Impact of a Dedicated Interventional Oncology Service Line in a National Cancer Institute Comprehensive Cancer Center.

PURPOSE: We tested the hypothesis that establishing a dedicated interventional oncology (IO) clinical service line would increase clinic visits and procedural volumes at a single quaternary care academic medical center. METHODS: Two time periods were defined: July 2012 to June 2013 (pre-IO clinic) and July 2013 to June 2014 (first year of dedicated IO service). Staff was recruited, and clinic space was provided in the institution's comprehensive cancer center. Clinic visits and procedure numbers were documented using the institution's electronic medical record and billing forms. IO procedures included were transarterial chemoembolization, Y-90 radioembolization, perfusion mapping for Y-90, portal vein embolization, and bland embolization. We compared changes in clinic visit and procedure numbers using paired t tests. Changes after IO initiation were compared to 1-year changes in the Medicare 5% Limited Data Set by cross-referencing Current Procedure Terminology and International Classification of Diseases codes in 2012 and 2013. RESULTS: Clinic visits increased from 9 to 204 (P = .003, t = 8.89, df = 3). Procedures increased from 60 to 239 (P = .018, t = 3.85, df = 4). Procedural volumes increased at least 150% for each subtype. The volumes in the 5% Limited Data Set did not change significantly over the 2-year period (443 to 385, P > .05). CONCLUSIONS: The establishment of a dedicated IO service significantly increased clinic visits and procedural volumes. National trends were unchanged, suggesting that the impact of our program was not part of a sudden increase of IO procedures.

Five percent dextrose maximizes dose delivery of Yttrium-90 resin microspheres and reduces rates of premature stasis compared to sterile water.

Resin Yttrium-90 (Y90) microspheres have historically been infused using sterile water (H2O). In 2013, recommendations expanded to allow delivery with 5% dextrose in water (D5W). In this retrospective study, we hypothesized that D5W would improve Y90 delivery with a lower incidence of stasis. We reviewed 190 resin Y90 infusions using H2O (n=137) or D5W (n=53). Y90 dosimetry was calculated using the body surface area method. Infusion was halted if intra-arterial stasis was fluoroscopically identified prior to clearing the vial. Differences between H2O and D5W groups were calculated for activity prescription, percentage of cases reaching stasis, and percentage delivery of prescribed activity using z- and t-test comparisons, with α=0.05. Thirty-one of 137 H2O infusions developed stasis compared to 2 of 53 with D5W (z=3.07, p=1.05E-03). D5W also had a significantly higher prescribed activity than H2O [28.2 millicuries (mCi) vs. 20.4 mCi, respectively; t=5.0, p=1.1E-6]. D5W had a higher delivery percentage of the prescribed dose compared to H2O (101.5 vs. 92.7%, respectively; t=3.8, p=1.92E-4). In conclusion, resin microsphere infusion utilizing D5W has a significantly lower rate of stasis than H2O and results in more complete dose delivery. D5W is preferable to H2O for resin microsphere infusion.