LI-RADS Treatment Response Algorithm: Performance and Diagnostic Accuracy With Radiologic-Pathologic Explant Correlation in Patients With SBRT-Treated Hepatocellular Carcinoma.

PURPOSE: Our purpose was to evaluate the accuracy of LI-RADS Treatment Response Algorithm (LR-TRA) for assessing the viability of hepatocellular carcinoma (HCC) treated with stereotactic body radiation therapy (SBRT), using explant pathology as the gold standard. METHODS AND MATERIALS: This retrospective study included patients who underwent SBRT for locoregional treatment of HCC between 2008 and 2019 with subsequent liver transplantation. Five radiologists independently assessed all treated lesions by using the LR-TRA. Imaging and posttransplant histopathology were compared. Lesions were categorized as either completely (100%) or incompletely (<100%) necrotic, and performance characteristics and predictive values for the LR-TR viable and nonviable categories were calculated for each reader. Interreader reliability was calculated using the Fleiss kappa test. RESULTS: A total of 40 treated lesions in 26 patients (median age, 63 years [interquartile range, 59.4-65.5]; 23 men) were included. For lesions treated with SBRT, sensitivity for incomplete tumor necrosis across readers ranged between 71% and 86%, specificity between 85% and 96%, and positive predictive value between 86% and 92%, when the LR-TR equivocal category was treated as nonviable, accounting for subject clustering. When the LR-TR equivocal category was treated as viable, sensitivity of complete tumor necrosis for lesions treated with SBRT ranged from 88% to 96%, specificity from 71% to 93%, and negative predictive value from 85% to 96%. Interreader reliability was fair (k = 0.22; 95% confidence interval, 0.13-0.33). Although a loss of arterial phase hyperenhancement (APHE) was highly correlated with pathologically nonviable tumor on explant, almost half of the patients with APHE had pathologically nonviable tumor on explant. CONCLUSIONS: LR-TRA v2018 performs well for predicting complete and incomplete necrosis in HCC treated with SBRT. In contrast to other locoregional therapies, the presence of APHE after SBRT does not always indicate viable tumor and suggests that observation may be an appropriate strategy for these patients.

Long term outcomes of stereotactic body radiation therapy for hepatocellular carcinoma without macrovascular invasion.

BACKGROUND: Stereotactic Body Radiation Therapy (SBRT) is a non-invasive ablative treatment for hepatocellular carcinoma (HCC). This report aimed to address the limited availability of long-term outcomes after SBRT for HCC from North America. METHODS: Localized HCC patients without vascular invasion, who were ineligible for other liver-directed therapies and treated with SBRT at the University of Toronto or University of Michigan, were pooled to determine overall survival (OS), cumulative recurrence rates, and ≥ grade-3 toxicity. Multivariable analysis determined factors affecting OS and local recurrence rates. RESULTS: In 297 patients with 436 HCCs (42% > 3 cm), one-, three- and five-year OS was 77·3%, 39·0% and 24·1%, respectively. On Cox proportional hazards regression analysis, liver transplant after SBRT, Child-Pugh A liver function, alpha-fetoprotein ≤ 10 ng/ml, and Eastern Co-operative Oncology Group performance status 0 significantly improved OS (hazard ratio [HR] = 0·06, 95% confidence interval [CI- 0·02-0·25; p<0·001; HR = 0·42, 95% CI = 0·29-0·60, p<0·001; HR = 0·61, 95% CI- 0·44-0·83; p=0·002 and HR = 0·71, 95% CI = 0·51-0·97, p=0·034, respectively). Cumulative local recurrence was 6·3% (95% CI = 0.03-0.09) and 13·3% (95% CI = 0.06-0.21) at one and three years, respectively. Using Cox regression modelling, local control was significantly higher using breath-hold motion management and in HCC smaller than 3 cm (HR = 0.52, 95% CI = 0.58-0.98; p=0.042 and HR = 0.53, 95% CI = 0.26-0.98; p=0.042, respectively). Worsening of Child-Pugh score by ≥2 points three months after SBRT was seen in 15.9%. CONCLUSIONS: SBRT confers high local control and long-term survival in a substantial proportion of HCC patients unsuitable for, or refractory to standard loco-regional treatments. Liver transplant should be considered if appropriate downsizing occurs after SBRT.

Natural history of hepatocellular carcinoma after stereotactic body radiation therapy.

PURPOSE: To determine the long-term natural history of size change in SBRT-treated HCC to identify an imaging biomarker to help assess treatment response. METHODS: This was a retrospective cohort study of consecutive HCCs treated with SBRT from January 2008 to December 2016 with either 2 years post-treatment MRI follow-up or post-treatment resection histology. Size, major features for HCC, and mRECIST and LI-RADS v.2018 treatment response criteria were assessed at each post-treatment MRI. Local progression, distant progression, and survival were modeled with Kaplan Meier analyses. RESULTS: 56 HCCs met inclusion criteria. Mean baseline HCC diameter was 30 mm (range: 9-105 mm). At 3 months, 76% (N = 43) of treated HCCs decreased in size (mean reduction: 8 mm, range: 5-99 mm) and 0% (N = 0) increased in size. By 24 months, 11% (N = 5) had increased in size and were considered local progression. APHE remained in 77% (43/56) at 3 months, 38% (19/50) at 12 months, and 23% (11/47) at 24 months. mRECIST-defined viable disease was observed in 77% (43/56) at 3 months and 20% (9/47) at 24 months. LI-RADS v.2018 criteria identified viable or equivocal disease in 0% at 3 months and 10% (5/47) at 24 months. CONCLUSION: Gradual loss of APHE and slow decrease in size are normal findings in HCCs treated with SBRT, and persistent APHE does not indicate viable disease. mRECIST is not accurate in the assessment of HCC after SBRT due to an overreliance on APHE to define viable disease. Increasing mass size or new nodular APHE at the treatment site may indicate local progression.

Magnetic Resonance Imaging Evaluation of Hepatocellular Carcinoma Treated With Stereotactic Body Radiation Therapy: Long Term Imaging Follow-Up.

PURPOSE: To determine the natural history of imaging findings seen on magnetic resonance imaging (MRI) of hepatocellular carcinoma (HCC) treated with stereotactic body radiation therapy (SBRT). Although arterial hyperenhancement is a key feature of untreated HCC, our clinical experience suggested that tumors that never progressed could still show hyperenhancement. Therefore, we undertook a systematic study to test the hypothesis that persistent arterial phase hyperenhancement (APHE) after SBRT is an expected finding that does not suggest failure of treatment. METHODS AND MATERIALS: One hundred forty-six patients undergoing SBRT for HCC between January 1, 2007, and December 31, 2015, were screened retrospectively using an institutional review board-approved prospectively maintained registry. Inclusion criteria were (1) HCC treated with SBRT, (2) multiphasic MRI ≤3 months before SBRT, (3) up to 1 year of follow-up MRI post-SBRT, and (4) cirrhosis. The exclusion criterion was ≤3 months of locoregional therapy to the liver segment containing the SBRT-treated HCC. Pre- and post-SBRT MRI from up to 3 years were analyzed in consensus by independent pairs of subspecialty-trained radiologists to determine the temporal evolution of major features for HCC and imaging findings in off-target parenchyma. RESULTS: Sixty-two patients with 67 HCCs (Organ Procurement and Transplantation Network imaging criteria [OPTN] 5a [n = 26], OPTN 5b [n = 28], OPTN 5x [n = 7]; Liver Imaging Reporting Data System [LI-RAD]-M [n = 4] and LiRADs-4 [n = 2]) were studied. Tumor size either decreased (66% [44 of 67]) or remained unchanged (34% [23 of 67]) within the first 12 months. Post-SBRT APHE was common (58% [39 of 67]). When graded using modified Response Evaluation Criteria in Solid Tumors at 3 to 6 months, 25% (17 of 67) met criteria for complete response and 75% (50 of 67) met criteria for stable disease. CONCLUSIONS: SBRT is an effective locoregional treatment option for HCC. Persistent APHE is common and does not necessarily indicate viable neoplasm; thus, standard response assessment such as modified Response Evaluation Criteria should be used with caution, particularly in the early phases after SBRT therapy.