Abstract
Although systemic treatment for hepatocellular carcinoma has advanced after the development of tyrosine kinase inhibitors such as sorafenib and lenvatinib, the effectiveness of a single tyrosine kinase inhibitor in survival extension of unresectable hepatocellular carcinoma is limited to a few months. Therefore, novel treatment options are required for unresectable hepatocellular carcinomas, including those with multiple lung metastases. This case report describes a hepatocellular carcinoma patient with a recurrence of multiple lung metastases, which was successfully treated with conversion pneumonectomy after treatment with tyrosine kinase inhibitors. A 79-year-old man underwent right hepatectomy for hepatocellular carcinoma, along with removal of the tumor thrombus in the inferior vena cava. Multiple lung metastases were detected 4 months after hepatectomy. Treatment with tyrosine kinase inhibitors, mainly lenvatinib, resulted in complete remission of the lung metastases, except for one lesion in segment 3 of the right lung which gradually enlarged. Twenty-three months after hepatectomy, partial resection of the right lung was performed using video-assisted thoracic surgery for this residual lesion in the right lung. The patient remained disease-free for 11 months after conversion pneumonectomy, without any adjuvant therapies. This is the first case report of multiple lung metastases originating from hepatocellular carcinoma which were successfully treated with conversion pneumonectomy after treatment with tyrosine kinase inhibitors. Conversion pneumonectomy after systemic therapy with tyrosine kinase inhibitors should be considered as a treatment strategy for patients with unresectable multiple lung metastases from hepatocellular carcinomas.
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References
Kudo M, Finn RS, Qin S et al (2018) Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet 391:1163–1173. https://doi.org/10.1016/S0140-6736(18)30207-1
Llovet JM, Ricci S, Mazzaferro V et al (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359:378–390. https://doi.org/10.1056/NEJMoa0708857
Abbas A, Medvedev S, Shores N et al (2014) Epidemiology of metastatic hepatocellular carcinoma, a nationwide perspective. Dig Dis Sci 59:2813–2820. https://doi.org/10.1007/s10620-014-3229-9
Uchino K, Tateishi R, Shiina S et al (2011) Hepatocellular carcinoma with extrahepatic metastasis: clinical features and prognostic factors. Cancer 117:4475–4483. https://doi.org/10.1002/cncr.25960
Kojima Y, Ueno H, Okusaka T et al (2009) 6610 Hepatocellular carcinoma presenting with lung metastasis: clinical characteristics and prognostic factors. Eur J Cancer Suppl 7:393. https://doi.org/10.1016/S1359-6349(09)71331-X
Zhang S-M, Zeng Z-C, Tang Z-Y et al (2008) Prognostic analysis of pulmonary metastases from hepatocellular carcinoma. Hepatol Int 2:237–243. https://doi.org/10.1007/s12072-008-9052-7
Kuo S-W, Chang Y-L, Huang P-M et al (2007) Prognostic factors for pulmonary metastasectomy in hepatocellular carcinoma. Ann Surg Oncol 14:992–997. https://doi.org/10.1245/s10434-006-9217-3
Han KN, Kim YT, Yoon J-H et al (2010) Role of surgical resection for pulmonary metastasis of hepatocellular carcinoma. Lung Cancer 70:295–300. https://doi.org/10.1016/j.lungcan.2010.02.014
Lee CY, Bae MK, Park IK et al (2010) Surgical resection for pulmonary metastasis from hepatocellular carcinoma: analysis of prognosis in relation to primary control. J Surg Oncol 101:239–243. https://doi.org/10.1002/jso.21487
Yoon YS, Kim HK, Kim J et al (2010) Long-term survival and prognostic factors after pulmonary metastasectomy in hepatocellular carcinoma. Ann Surg Oncol 17:2795–2801. https://doi.org/10.1245/s10434-010-1073-5
Kitano K, Murayama T, Sakamoto M et al (2012) Outcome and survival analysis of pulmonary metastasectomy for hepatocellular carcinoma. Eur J Cardiothorac Surg 41:376–382. https://doi.org/10.1016/j.ejcts.2011.05.052
Kow AWC, Kwon CHD, Song S et al (2015) Clinicopathological factors and long-term outcome comparing between lung and peritoneal metastasectomy after hepatectomy for hepatocellular carcinoma in a tertiary institution. Surgery 157:645–653. https://doi.org/10.1016/j.surg.2014.07.024
Maeda Y, Shinohara T, Nagatsu A et al (2016) Long-term outcomes of conversion hepatectomy for initially unresectable colorectal liver metastases. Ann Surg Oncol 23:S242–S248. https://doi.org/10.1245/s10434-015-4460-0
Folprecht G, Grothey A, Alberts S et al (2005) Neoadjuvant treatment of unresectable colorectal liver metastases: correlation between tumour response and resection rates. Ann Oncol 16:1311–1319. https://doi.org/10.1093/annonc/mdi246
Tomasello G, Petrelli F, Ghidini M et al (2017) FOLFOXIRI plus bevacizumab as conversion therapy for patients with initially unresectable metastatic colorectal cancer: a systematic review and pooled analysis. JAMA Oncol 3:e170278. https://doi.org/10.1001/jamaoncol.2017.0278
Kinoshita J, Yamaguchi T, Moriyama H et al (2021) Current status of conversion surgery for stage IV gastric cancer. Surg Today 51:1736–1754. https://doi.org/10.1007/s00595-020-02222-0
Morgagni P, Solaini L, Framarini M et al (2018) Conversion surgery for gastric cancer: a cohort study from a western center. Int J Surg 53:360–365. https://doi.org/10.1016/j.ijsu.2018.04.016
Takahashi K, Kim J, Takahashi A et al (2021) Conversion hepatectomy for hepatocellular carcinoma with main portal vein tumour thrombus after lenvatinib treatment: a case report. World J Hepatol 13:384–392. https://doi.org/10.4254/wjh.v13.i3.384
Yokoo H, Takahashi H, Hagiwara M et al (2020) Successful hepatic resection for recurrent hepatocellular carcinoma after lenvatinib treatment: a case report. World J Hepatol 12:1349–1357. https://doi.org/10.4254/wjh.v12.i12.1349
Tomonari T, Sato Y, Tanaka H et al (2020) Conversion therapy for unresectable hepatocellular carcinoma after lenvatinib: three case reports. Medicine (Baltimore) 99:e22782. https://doi.org/10.1097/MD.0000000000022782
Ohya Y, Hayashida S, Tsuji A et al (2020) Conversion hepatectomy for advanced hepatocellular carcinoma after right portal vein transection and lenvatinib therapy. Surg Case Rep 6:318. https://doi.org/10.1186/s40792-020-01078-3
Matsuki R, Kawai K, Suzuki Y et al (2020) Pathological complete response in conversion hepatectomy induced by lenvatinib for advanced hepatocellular carcinoma. Liver Cancer 9:358–360. https://doi.org/10.1159/000506202
Sato N, Beppu T, Kinoshita K et al (2019) Conversion hepatectomy for huge hepatocellular carcinoma with arterioportal shunt after chemoembolization and lenvatinib therapy. Anticancer Res 39:5695–5701. https://doi.org/10.21873/anticanres.13768
Takahashi A, Moriguchi M, Seko Y et al (2019) Impact of relative dose intensity of early-phase lenvatinib treatment on therapeutic response in hepatocellular carcinoma. Anticancer Res 39:5149–5156. https://doi.org/10.21873/anticanres.13710
Schlumberger M, Tahara M, Wirth LJ et al (2015) Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med 372:621–630. https://doi.org/10.1056/NEJMoa1406470
Liu SQ, Zhang XJ, Xue Y et al (2021) A case of lenvatinib therapy-induced unilateral interstitial pneumonia and cavity formation in advanced liver cancer (in Chinese). Zhonghua Gan Zang Bing Za Zhi 29:1109–1110. https://doi.org/10.3760/cma.j.cn501113-20201208-00646
Kotani K, Enomoto M, Okada M et al (2019) Interstitial pneumonia suspected during regorafenib administration and exacerbated by subsequent therapy with lenvatinib for unresectable hepatocellular carcinoma. Clin J Gastroenterol 12:355–360. https://doi.org/10.1007/s12328-019-00983-x
Imakura T, Sato S, Tomonari T et al (2022) Lenvatinib-induced interstitial pneumonia in a patient with hepatocellular carcinoma. Intern Med 61:1211–1217. https://doi.org/10.2169/internalmedicine.7300-21
Kimura-Tsuchiya R, Sasaki E, Nakamura I et al (2018) A case of squamous cell carcinoma of unknown primary that responded to the multi-tyrosine kinase inhibitor lenvatinib. Case Rep Oncol 11:75–80. https://doi.org/10.1159/000486569
Zheng H, Pomyen Y, Hernandez MO et al (2018) Single-cell analysis reveals cancer stem cell heterogeneity in hepatocellular carcinoma. Hepatology 68:127–140. https://doi.org/10.1002/hep.29778
Al-Batran S-E, Hartmann JT, Heidel F et al (2007) Focal progression in patients with gastrointestinal stromal tumors after initial response to imatinib mesylate: a three-center-based study of 38 patients. Gastric Cancer 10:145–152. https://doi.org/10.1007/s10120-007-0425-8
Kobayashi S, Boggon TJ, Dayaram T et al (2005) EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med 352:786–792. https://doi.org/10.1056/NEJMoa044238
Jackman DM, Holmes AJ, Lindeman N et al (2006) Response and resistance in a non-small-cell lung cancer patient with an epidermal growth factor receptor mutation and leptomeningeal metastases treated with high-dose gefitinib. J Clin Oncol 24:4517–4520. https://doi.org/10.1200/JCO.2006.06.6126
Shindoh J, Kawamura Y, Kobayashi Y et al (2021) Prognostic Impact of Surgical Intervention After Lenvatinib Treatment for Advanced Hepatocellular Carcinoma. Ann Surg Oncol 28:7663–7672. https://doi.org/10.1245/s10434-021-09974-0
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Sano, S., Asahi, Y., Kamiyama, T. et al. Conversion surgery after lenvatinib treatment for multiple lung metastases from hepatocellular carcinoma. Int Canc Conf J 12, 7–13 (2023). https://doi.org/10.1007/s13691-022-00567-6
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DOI: https://doi.org/10.1007/s13691-022-00567-6