Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Identification of CT Attenuation Values that Could be Predictive of Necrosis (N-CTav) in Hepatocellular Carcinoma Tumors after Lenvatinib Treatment and the Association between the N-CTav Occupancy Rate in the Tumor and Maintenance of Complete Response with Lenvatinib Treatment

Version 1 : Received: 11 February 2022 / Approved: 18 February 2022 / Online: 18 February 2022 (04:05:18 CET)

A peer-reviewed article of this Preprint also exists.

Chuma, M.; Yokoo, H.; Hiraoka, A.; Ueda, K.; Yokoyama, T.; Tsuji, K.; Shimada, N.; Uojima, H.; Kobayashi, S.; Hattori, N.; Okubo, T.; Atsukawa, M.; Ishikawa, T.; Takaguchi, K.; Tsutsui, A.; Toyoda, H.; Tada, T.; Saito, Y.; Hirose, S.; Tanaka, T.; Takeda, K.; Otani, M.; Sekikawa, Z.; Watanabe, T.; Hidaka, H.; Morimoto, M.; Numata, K.; Kagawa, T.; Sakamoto, M.; Kumada, T.; Maeda, S. Identification of CT Values That Could Be Predictive of Necrosis (N-CTav) in Hepatocellular Carcinoma after Lenvatinib Treatment. Curr. Oncol. 2022, 29, 3259-3271. Chuma, M.; Yokoo, H.; Hiraoka, A.; Ueda, K.; Yokoyama, T.; Tsuji, K.; Shimada, N.; Uojima, H.; Kobayashi, S.; Hattori, N.; Okubo, T.; Atsukawa, M.; Ishikawa, T.; Takaguchi, K.; Tsutsui, A.; Toyoda, H.; Tada, T.; Saito, Y.; Hirose, S.; Tanaka, T.; Takeda, K.; Otani, M.; Sekikawa, Z.; Watanabe, T.; Hidaka, H.; Morimoto, M.; Numata, K.; Kagawa, T.; Sakamoto, M.; Kumada, T.; Maeda, S. Identification of CT Values That Could Be Predictive of Necrosis (N-CTav) in Hepatocellular Carcinoma after Lenvatinib Treatment. Curr. Oncol. 2022, 29, 3259-3271.

Journal reference: Curr. Oncol. 2022, 29, 266
DOI: 10.3390/curroncol29050266

Abstract

Purpose: To assess the utility of measurement of the computed tomography (CT) attenuation value (CTav) in predicting tumor necrosis in hepatocellular carcinoma (HCC) patients who achieve a complete response (CR), defined using modified Response Evaluation Criteria in Solid Tumors (mRECIST), after lenvatinib treatment. Method: We compared CTav in arterial phase CT images with postoperative histopathology in four patients who underwent HCC resection after lenvatinib treatment, to determine CTav thresholds indicative of histological necrosis (N-CTav). Next, we confirmed the accuracy of the determined N-CTav in 15 cases with histopathologically proven necrosis in surgical specimens. Furthermore, the percentage of the tumor with N-CTav, i.e. the N-CTav occupancy rate, assessed using Image J software in 30 tumors in 12 patients with CR out of 571 HCC patients treated with lenvatinib, and its correlation with local recurrence following CR were examined. Results: Receiver operating characteristic (ROC) curve analysis revealed an optimal cut-off value of CTav of 30.2 HU, with 90.0% specificity and 65.0% sensitivity in discriminating between pathologically identified necrosis and degeneration, with a CTav of less than 30.2 HU indicating necrosis after lenvatinib treatment (N30-CTav). Furthermore, the optimal cut-off value of 30.6% for the N30-CTav occupancy rate by ROC analysis was a significant indicator of local recurrence following CR with 76.9% specificity and sensitivity (area under the ROC curve; 0.939), with the CR group with high N30-CTav occupancy (>30.6%) after lenvatinib treatment showing significantly lower local recurrence (8.3% at 1 year) compared with the low (<30.6%) N30-CTav group (P<0.001, 61.5% at 1 year). Conclusion: The cut-off value of 30.2 HU for CTav (N30-CTav) might be appropriate for identifying post-lenvatinib necrosis in HCC, and an N30-CTav occupancy rate of >30.6% might be a predictor of maintenance of CR. Use of these indicators have the potential to impact systemic chemotherapy for HCC.

Keywords

hepatocellular carcinoma; lenvatinib; molecular targeted agents; complete response; CT value

Subject

MEDICINE & PHARMACOLOGY, Gastroenterology

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