A Combination of Blood Lymphocytes and AST Levels Distinguish Patients with Small Hepatocellular Carcinomas from Non Cancer Patients.

PurposeHCC patients typically present at an advanced tumor stage, in which surgical therapies cannot be used. Screening ultrasound exams can increase the numbers of patients diagnosed with small tumors, but are often not used in patients at risk for HCC. We evaluated clinically-available and cheap potential blood tests as biomarkers for screening patients at risk for HCC.MethodsA comparison was made of commonly used blood count and liver function parameters in a group of patients (n=101) with small HCCs (<3cm) or without HCC (n=275), who presented for liver transplantation in our institute. ResultsSignificant differences were found for blood lymphocytes and AST levels. This 2-parameter combination was found to be significantly different between patients with small HCCs versus no HCC. Using the combination of lymphocytes and AST levels to dichotomize the HCC patients, only blood levels of alpha-fetoprotein amongst the tumor characteristics, were found to be significantly different amongst the 2 HCC groups, as well as levels of blood total bilirubin, ALKP and PLR ratio. The results were confirmed using a separate smaller cohort of non-transplanted small size HCC patients.ConclusionThe combination of elevated blood levels of lymphocyte counts and AST levels holds promise for screening of patients with chronic liver disease who are at risk for HCC.

Association between Prothrombin Induced by Vitamin K Absence-II (PIVKA-II) and Barcelona Clinic Liver Cancer (BCLC) Stage, Tumor Size, Portal Venous Thrombosis in Hepatocellular Carcinoma Patients

Hepatocellular carcinoma is one of the major cancer problems in the world because of the low early screening awareness in patients. Serum alpha-fetoprotein is not adequate as a single screening tool, especially for small HCCs, thus, prothrombin induced by vitamin K absence-II (PIVKA-II) can help in detecting small HCCs. Barcelona Clinic Liver Cancer (BCLC) stage remains to be the preferred HCC classification because it can predict the outcome and help in choosing available treatment options according to stages. This study aims to investigate the association between PIVKA-II levels with BCLC stage, tumor size, portal venous thrombosis in HCC patients. We enrolled patients with newly diagnosed HCC at the Adam Malik General Hospital, Medan, Indonesia from January to December 2018. Patients with HCC were classified according to BCLC stages, findings of portal venous thrombosis and tumor size from triphasic CT scan were noted, and serum PIVKA-II levels were measured. Sixty patients were included in this study. There were significant differences in serum PIVKA-II levels with different stages of BCLC (p < 0.001). Significantly higher serum PIVKA-II levels were detected in patients with portal venous thrombosis (p < 0.001) and larger size tumors (p < 0.003). Our study shows that serum PIVKA-II levels can help to diagnose, differentiate between stages of BCLC, and determine the prognosis in patients with HCC.

Stereotactic body radiation therapy for small (≤5 cm) hepatocellular carcinoma not amenable to curative treatment: Results of a single-arm, phase II clinical trial

Background/Aims: Stereotactic body radiation therapy (SBRT) is used as an alternative ablative treatment in patients with hepatocellular carcinoma (HCC) not suitable for curative treatments. The purpose of this prospective study was to evaluate the long-term efficacy of SBRT for small (≤5 cm) HCCs.Methods: A phase II, single-arm clinical trial on SBRT for small HCCs was conducted at an academic tertiary care center. The planned SBRT dose was 45 Gy with a fraction size of 15-Gy over 3 consecutive days. The primary endpoint was 2-year local control rate. Radiologic responses were assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) and the modified RECIST criteria.Results: Between 2013 and 2016, 50 patients (53 lesions) were enrolled, with a median follow-up period of 47.8 months (range, 2.9–70.6). Patients’ age ranged from 41 to 74 years, and 80% were male. Median tumor size was 1.3 cm (range, 0.7–3.1). The 2- and 5-year local control rates were 100% and 97.1%, respectively. The 5-year overall survival rate was 77.6%. Six months after SBRT, radiologic responses were evident in 44 lesions (83%) according to the RECIST criteria and 49 (92.4%) according to the modified RECIST criteria. None of the patients showed grade ≥3 adverse events.Conclusions: SBRT showed excellent results as an ablative treatment for patients with small HCCs while showing minimal toxicities. SBRT can be a good alternative for both curative and salvage intents in patients with HCCs that are unsuitable for curative treatments.

Indian Society of Vascular and Interventional Radiology Expert Consensus Statements for Ablation in Hepatocellular Carcinoma: Part I

Locoregional therapies play an important role in the management of hepatocellular carcinoma (HCC). Percutaneous ablation is one of the most commonly employed nonsurgical methods for treating very early and early HCC. For small HCCs, ablation is potentially curative and competes with surgical resection. The widespread availability and the spectrum of ablative techniques mandate uniform approach among interventional radiologists. Thus, it is desirable to have a consensus regarding various aspects of liver ablation. This article represents a consensus document of the experts from the Indian Society of Vascular and Interventional Radiology involved in the care of patients with HCC. The statements are presented in two parts.

Heterogeneity of Hepatocellular Carcinoma on Imaging

Tumor heterogeneity in hepatocellular carcinomas (HCC) occurs at different levels. On conventional imaging modalities, the spectrum of tumor heterogeneity is evident in the dynamic enhancement pattern, where the characteristic wash-in and wash-out is present in only 60% of small HCCs. In larger HCCs, heterogeneity within the tumor, known as the mosaic pattern, can reflect the presence of different grades of HCC differentiation. The advent of functional imaging techniques has not improved the diagnostic sensitivity of imaging techniques for the diagnosis of HCC. However, the combination of conventional and functional imaging techniques potentially allows the identification of heterogeneity in tumor vascularity, cellularity, and molecular expression.

Low Alpha-Fetoprotein HCC and the Role of GGTP

Background HCC patients are heterogeneous in terms of both tumor and liver factors. Alpha-fetoprotein (AFP) is an important prognostic tumor marker for those patients with elevated AFP levels. Aims To examine the differences in HCC patients with high or low AFP levels in blood and evaluate the prognostic parameters in low AFP patients. Methods A cohort of 2,440 HCC patients from 11 Italian medical centers was studied. AFP-positive patients were compared to AFP-negative ones, and the blood and tumor parameters of AFP-negative patients were examined. Results Low blood AFP levels were found in 58% of the total cohort, in 64% of patients with small HCCs, and in 51% of patients with large HCCs. In patients with large tumors, platelet and gamma glutamyl transpeptidase (GGTP) levels, tumor multifocality and portal vein thrombosis (PVT) incidence were all greater than in patients with small tumors, regardless of AFP status. Patients with higher AFP levels had worse survival rates than those with low AFP in each tumor size group. In patients with small tumors, the elevated AFP was associated with significantly increased PVT and worse survival. In patients with large tumors, the elevated AFP was associated with significantly higher GGTP, ALKP, and bilirubin levels, as well as with increased PVT and multifocality, and worse survival. Low-AFP patients with high GGTP levels had worse survival than patients with low GGTP levels. Conclusion Patients with low AFP were the majority in this cohort, and patients with elevated GGTP had worse prognosis than those with low GGTP. GGTP may be a useful tumor and prognosis marker in low-AFP patients. AFP-negative patients are important to identify due to their enhanced survival.

Disconnect between earlier presentation patterns and application of curative treatments in HCC.

187 Background: In the U.S., a greater proportion of small hepatocellular carcinomas are being diagnosed. The extent to which patients with small HCCs are receiving potentially curative therapies is unclear. Methods: Receipt of liver transplantation, resection, radiofrequency ablation, and other or unspecified surgery/ablation as first therapy was examined among HCC cases in the NCI SEER18 cancer registries during the years 2000 to 2010. Survival of HCC by treatment modality was also examined. Results: The diagnosis of small tumors (≤5 cm) significantly increased between 2000 and 2010, surpassing diagnosis of larger tumors beginning in 2005. Among patients diagnosed during 2007-2010 with complete data available, 57% had small tumors and more than three quarters had a single tumor, however fewer than one third received surgical or ablative treatment. Incidence rates of resection, ablation and transplantation (therapies with curative intent) increased 17.6% per year between 2000 and 2005, then decreased by -2.9% per year through 2010. Resection was the leading treatment followed by radiofrequency ablation and transplantation. The number of patients treated with curative intent decreased as tumor size or tumor number increased; 42% of patients with single tumors ≤5 cm in size were treated with curative intent compared to 20% with single tumors >5 cm. While radiofrequency ablation was used to treat small tumors, resection was used to treat both small and large tumors. Patients who received transplants had the best five-year survival rate (71%), followed by patients who received resection (42%) and radiofrequency ablation (30%). Five-year survival of patients who did not receive surgery or ablation was 6%. Conclusions: Despite more patients being diagnosed with small tumors, the US-SEER database analysis demonstrates a recent decrease in the use of curative treatments. Treatment guidelines suggest that early diagnosis HCC cases are eligible for treatment with curative intent. Investigations of reasons for the limited treatment are recommended with the goal of improving outcomes.

Identification of two HCC phenotypes based on thrombocytopenia.

e14720 Background: Clinical phenotypes of small and larger HCCs are not well characterized. Aims. To characterize small HCC phenotypes. Methods: A cohort of 430 small HCCs that were diagnosed through screening, were dichotomized by size of < 3cm or > 3cm maximum tumor diameter and compared for radiologic and blood test parameters and analyzed by Chi-square test for categorical variables and Mann-Whitney test for continuous variables. Results: Significant differences between the tumor size groups included AFP values and platelet counts, with thrombocytopenia and elevated bilirubin levels being associated with smaller tumors. In comparing PVT+ and PVT- patients, AFP levels and platelet counts were also significantly different between the 2 groups. Conclusions: Larger tumors were associated with normal platelets and bilirubin levels, compared to smaller tumors that were more typically found in the presence of thrombocytopenia, suggesting that smaller and larger HCCs might have different developmental pathways.