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Zhang L, Zhang X, Li Q, Makamure J, Liu Z, Zhao D, Li X, Shi H, Zheng C, Liu F, Liang B. Transarterial chemoembolization failure in patients with hepatocellular carcinoma: Incidence, manifestation and risk factors. Clin Res Hepatol Gastroenterol 2023; 47:102071. [PMID: 36539181 DOI: 10.1016/j.clinre.2022.102071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2022] [Revised: 11/16/2022] [Accepted: 12/16/2022] [Indexed: 12/23/2022]
Abstract
BACKGROUND To identify the incidence, manifestation and risk factors of transarterial chemoembolization (TACE) failure defined as untreatable progression (UP) in patients with hepatocellular carcinoma (HCC) on short-term observation. METHODS Patients from two hospitals with HCC treated with TACE were considered. According to the definition of UP, TACE failure was considered to be present in at least one of the following situations: situation I, failure to achieve objective response in the targeted tumor after at least two initial TACE treatments; situation II, failure to achieve objective response in local tumor progression or new intrahepatic tumor after another TACE session; situation III, presence of major progression; and situation IV, presence of impaired liver function or performance status that contraindicates TACE treatment. Patients were assessed for TACE failure on follow-up visits after two or three TACE sessions. Risk factors for TACE failure were evaluated with logistic regression analysis. RESULTS A total of 206 patients were included. TACE failure occurred in 42 (42/206, 20.4%) patients, of whom 21, 1, 4, 0 and 16 patients manifested as situation I, II, III, IV alone, and combination of situation I with the others, respectively. Multivariate analysis showed that tumor without complete capsule (P < .001) and non-smooth margin (P = .004) were independent predictors of the presence of TACE failure. CONCLUSIONS TACE failure was uncommon in patients with HCC, which manifested predominantly as failure of treatment response of the initial intrahepatic tumor. Non-smooth tumor margin and tumors without complete capsule were associated with the presence of TACE failure.
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Affiliation(s)
- Lijie Zhang
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China; Department of Interventional Radiology, The Fifth Medical Center of Chinese, PLA General Hospital, Beijing 100039, PR China
| | - Xin Zhang
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China
| | - Qing Li
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China
| | - Joyman Makamure
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China
| | - Ziyi Liu
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China
| | - Dan Zhao
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China
| | - Xin Li
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China
| | - Heshui Shi
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China
| | - Chuansheng Zheng
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China
| | - Fengyong Liu
- Department of Interventional Radiology, The Fifth Medical Center of Chinese, PLA General Hospital, Beijing 100039, PR China.
| | - Bin Liang
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China.
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Ren Y, Liu Z, Makamure J, Kan X, Song S, Liu Y, Qian K, Zheng C, Liang B. Addition of Camrelizumab to Transarterial Chemoembolization in Hepatocellular Carcinoma With Untreatable Progression. Technol Cancer Res Treat 2022; 21:15330338221131385. [PMID: 36259117 PMCID: PMC9583233 DOI: 10.1177/15330338221131385] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Purpose: The present retrospective study aimed to evaluate the efficacy and safety of camrelizumab addition to transarterial chemoembolization (TACE) in the treatment of hepatocellular carcinoma (HCC) with TACE-related untreatable progression (UP). Methods: Patients with HCC who received addition of camrelizumab due to UP after initial TACE treatment were enrolled at our institution between May 2019 and January 2021. Patients were assessed for tumor response, progression-free survival (PFS), and adverse events (AEs). Risk factors for PFS were evaluated with logistic regression analysis. Results: A total of 41 patients were included. The objective response rates (ORR) and disease control rates (DCR) were 24.4% and 61.0% at 2 to 3 months, and 12.2% and 58.5% at 6 months, respectively. The median PFS of the patients were 6 months (95% confidence interval [CI]: 3.8 months, 8.2 months). Of the 41 patients, 23 received camrelizumab combined with TACE (hereafter, camrelizumab-TACE) on whom 52 combined TACE procedures were performed, with a median of 2 procedures (range: 1-6) per patient. The remaining 18 patients received camrelizumab alone due to TACE contraindications. Multivariable analysis indicated that camrelizumab-TACE was an independent prognostic factor for PFS. Subgroup analysis showed a median PFS of 8 months in the camrelizumab-TACE group and 3 months in the camrelizumab monotherapy group (P < .001). No treatment-related mortalities occurred. Seventeen patients (41.5%) developed at least 1 type of AE after treatment with camrelizumab, with reactive cutaneous capillary endothelial proliferation (RCCEP) (n = 14, 34.1%) being the most common AE. Conclusion: Addition of camrelizumab to TACE offered an effective and safe treatment for HCC with UP.
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Affiliation(s)
- Yanqiao Ren
- Department of Radiology, Union Hospital, Tongji Medical College,
Huazhong University of Science and Technology, Wuhan, China,Hubei Provinve Key Laboratory of Molecular Imaging, Wuhan,
China
| | - Ziyi Liu
- Department of Radiology, Union Hospital, Tongji Medical College,
Huazhong University of Science and Technology, Wuhan, China,Hubei Provinve Key Laboratory of Molecular Imaging, Wuhan,
China
| | - Joyman Makamure
- Department of Radiology, Union Hospital, Tongji Medical College,
Huazhong University of Science and Technology, Wuhan, China,Hubei Provinve Key Laboratory of Molecular Imaging, Wuhan,
China
| | - Xuefeng Kan
- Department of Radiology, Union Hospital, Tongji Medical College,
Huazhong University of Science and Technology, Wuhan, China,Hubei Provinve Key Laboratory of Molecular Imaging, Wuhan,
China
| | - Songlin Song
- Department of Radiology, Union Hospital, Tongji Medical College,
Huazhong University of Science and Technology, Wuhan, China,Hubei Provinve Key Laboratory of Molecular Imaging, Wuhan,
China
| | - Yiming Liu
- Department of Radiology, Union Hospital, Tongji Medical College,
Huazhong University of Science and Technology, Wuhan, China,Hubei Provinve Key Laboratory of Molecular Imaging, Wuhan,
China
| | - Kun Qian
- Department of Radiology, Union Hospital, Tongji Medical College,
Huazhong University of Science and Technology, Wuhan, China,Hubei Provinve Key Laboratory of Molecular Imaging, Wuhan,
China
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College,
Huazhong University of Science and Technology, Wuhan, China,Hubei Provinve Key Laboratory of Molecular Imaging, Wuhan,
China,Chuansheng Zheng, Department of Radiology,
Union Hospital, Tongji Medical College, Huazhong University of Science and
Technology, Wuhan 430022, China.
| | - Bin Liang
- Department of Radiology, Union Hospital, Tongji Medical College,
Huazhong University of Science and Technology, Wuhan, China,Hubei Provinve Key Laboratory of Molecular Imaging, Wuhan,
China,Bin Liang, Department of Radiology, Union
Hospital, Tongji Medical College, Huazhong University of Science and Technology,
Wuhan 430022, China.
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Hsu SJ, Xu X, Chen MP, Zhao ZY, Wang Y, Yin X, Zhang L, Ge NL, Chen Y, Wang YH, Luo JF, Ren ZG, Chen RX. Hepatic Arterial Infusion Chemotherapy with Modified FOLFOX as an Alternative Treatment Option in Advanced Hepatocellular Carcinoma Patients with Failed or Unsuitability for Transarterial Chemoembolization. Acad Radiol 2021; 28 Suppl 1:S157-S166. [PMID: 33653656 DOI: 10.1016/j.acra.2021.01.024] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 01/09/2021] [Accepted: 01/15/2021] [Indexed: 02/07/2023]
Abstract
OBJECTIVE This study aimed to assess the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) with modified FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) as an alternative treatment option in advanced hepatocellular carcinoma (HCC) patients with failed or unsuitability for transarterial chemoembolization (TACE). MATERIALS AND METHODS: From September 2018 to January 2020, 87 advanced HCC patients who progressed on TACE or were not eligible for TACE received HAIC treatment with modified FOLFOX. The primary endpoint was overall survival (OS) and secondary endpoints included progression-free survival (PFS), tumor response assessed by Response Evaluation Criteria in Solid Tumors 1.1, and adverse events graded according to CTCAE 5.0. Based on prognostic factors determined by multivariate analysis, a nomogram was developed to predict patient survival. RESULTS The median OS and PFS were 9.0 months (95%CI 7.6-10.4) and 3.7 months (95%CI 3.1-4.3), respectively. The objective response rate was 13.8%, with a disease control rate of 48.3%. Grade 3 adverse events were observed, such as infection (9.2%), thrombocytopenia (5.7%), hyperbilirubinemia (3.4%), abdominal pain (2.3%) and alanine aminotransferase increase (2.3%). Albumin, AST, and extrahepatic metastasis were incorporated to construct a new nomogram that could stratify patients into three prognostic subgroups, including low-, intermediate-, and high-risk groups, with significant differences in 9-month OS rates (71%, 42% and 6%, respectively; p< 0.001). The nomogram was better than the Okuda, AJCC, and CLIP staging systems for OS prediction. CONCLUSION These findings support the feasibility of HAIC with modified FOLFOX as an alternative treatment strategy for advanced HCC when TACE is ineffective or unsuitable.
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Chen L, Yu CX, Zhong BY, Zhu HD, Jin ZC, Zhu GY, Zhang Q, Ni CF, Teng GJ. Development of TACE Refractoriness Scores in Hepatocellular Carcinoma. Front Mol Biosci 2021; 8:615133. [PMID: 33981722 PMCID: PMC8109267 DOI: 10.3389/fmolb.2021.615133] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Accepted: 01/27/2021] [Indexed: 12/11/2022] Open
Abstract
Purpose: To identify the independent risk factors for transarterial embolization (TACE) refractoriness and to develop a novel TACE refractoriness score and nomogram for predicting TACE refractoriness in patients with hepatocellular carcinoma (HCC). Methods: Between March 2006 and March 2016, HCC patients who underwent TACE monotherapy as initial treatment at two hospitals formed the study cohort and validation cohort. The criteria of TACE refractoriness followed the Japan Society of Hepatology 2014 version of TACE refractoriness. In the study cohort, the independent risk factors for TACE refractoriness were identified, and TACE refractoriness score and nomogram were then developed. The accuracy of the systems was validated externally in the validation cohort. Results: In total, 113 patients from hospital A formed the study cohort and 122 patients from hospital B formed the validation cohort. In the study cohort, 82.3% of the patients (n = 93) developed TACE refractoriness with a median overall survival (OS) of 540 days (95% CI, 400.8–679.1), and the remaining 20 patients in the TACE-non-refractory group had a median OS of 1,257 days (95% CI, 338.8–2,175.2) (p = 0.019). The median time for developing TACE refractoriness was 207 days (95% CI, 134.8–279.2), and a median number of two TACE procedures were performed after refractoriness developed. The independent risk factors for TACE refractoriness were the number of tumors and bilobular invasion of HCC. TACE refractoriness scores <3.5 indicated a lower incidence of TACE refractoriness, whereas scores >3.5 points indicated a higher incidence (p < 0.001). In the validation cohort, 77.9% of the patients (n = 95) developed TACE refractoriness with a median OS of 568 days (95% CI, 416.3–719.7), and a median OS of 1,324 days was observed in the TACE-non-refractory group (n = 27; 95% CI, 183.5–2,464.5). Conclusions: TACE refractoriness impairs the OS of HCC patients. The number of tumors and bilobular invasion status were independent risk factors for TACE refractoriness. The TACE refractoriness score can be an effective tool and easy approach to predict the risk of TACE refractoriness status.
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Affiliation(s)
- Li Chen
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Chen-Xi Yu
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Bin-Yan Zhong
- Department of Interventional Radiology, the First Affiliated Hospital of Soochow University, Suzhou, China
| | - Hai-Dong Zhu
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Zhi-Cheng Jin
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Guang-Yu Zhu
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Qi Zhang
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Cai-Fang Ni
- Department of Interventional Radiology, the First Affiliated Hospital of Soochow University, Suzhou, China
| | - Gao-Jun Teng
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
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Yoo SH, Kwon JH, Nam SW, Lee JY, Kim YW, Shim DJ, Lee SW, Jang JW. Transarterial Infusion of Epirubicin and Cisplatin Combined With Systemic Infusion of 5-Flurouracil Versus Sorafenib for Hepatocellular Carcinoma With Refractoriness of Transarterial Chemoembolization Using Doxorubicin. Cancer Control 2020; 27:1073274820935843. [PMID: 32583687 PMCID: PMC7318831 DOI: 10.1177/1073274820935843] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Revised: 03/05/2020] [Accepted: 05/29/2020] [Indexed: 12/14/2022] Open
Abstract
Transarterial chemoembolization using doxorubicin (TACE-DOX) is an effective therapy for advanced hepatocellular carcinoma (HCC). However, there are limited options for patients with TACE refractoriness. We compared the effectiveness between sorafenib and transarterial chemolipiodolization using epirubicin and cisplatin combined with systemic infusion of 5-fluorouracil (5-FU; TACL-ECF) in patients with previous TACE-DOX refractoriness. We retrospectively analyzed 742 consecutively enrolled cohort patients who received TACE-DOX as the first-line therapy for HCC. Among the 94 patients who failed with TACE-DOX, 49 patients were treated with TACL-ECF and 45 patients were treated with sorafenib as a rescue therapy. The TACL-ECF regimen comprised transarterial infusion of epirubicin and cisplatin combined with systemic infusion of 5-FU. Of the 94 patients, 22 and 72 patients were in Barcelona Clinic Liver Cancer stages B and C, respectively; 66% patients were classified as having Child-Pugh class A (CPC A). Overall survival (OS) after rescue therapy did not differ between the sorafenib and TACL-ECF groups (4.1 months vs 6.4 months, P = .355). Progression-free survival (PFS) did not differ between the sorafenib and TACL-ECF groups (2.8 months vs 3.5 months, P = .629). Adverse events of CTC grade 3/4 occurred more frequently in the sorafenib group than in the TACL-ECF group (P = .024). The present study showed that the OS and PFS did not differ between patients given rescue TACL-ECF therapy and those given sorafenib therapy. The TACL-ECF treatment was better tolerated than sorafenib. The TACL-ECF might be considered as an alternative therapy for the patients with TACE-DOX refractoriness, especially CPC B and sorafenib-intolerant patients.
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Affiliation(s)
- Sun Hong Yoo
- Department of Internal Medicine, The Catholic University of Korea, Incheon St. Mary’s Hospital, Incheon, South Korea
- Division of Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Jung Hyun Kwon
- Department of Internal Medicine, The Catholic University of Korea, Incheon St. Mary’s Hospital, Incheon, South Korea
- Division of Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Soon Woo Nam
- Department of Internal Medicine, The Catholic University of Korea, Incheon St. Mary’s Hospital, Incheon, South Korea
- Division of Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Jong Yul Lee
- Department of Internal Medicine, The Catholic University of Korea, Incheon St. Mary’s Hospital, Incheon, South Korea
| | - Young Woon Kim
- Department of Internal Medicine, The Catholic University of Korea, Incheon St. Mary’s Hospital, Incheon, South Korea
| | - Dong Jae Shim
- Department of Radiology, The Catholic University of Korea, Incheon St. Mary’s Hospital, Incheon, South Korea
| | - Sung Won Lee
- Division of Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Jeong Won Jang
- Division of Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
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Marisi G, Cucchetti A, Ulivi P, Canale M, Cabibbo G, Solaini L, Foschi FG, De Matteis S, Ercolani G, Valgiusti M, Frassineti GL, Scartozzi M, Casadei Gardini A. Ten years of sorafenib in hepatocellular carcinoma: Are there any predictive and/or prognostic markers? World J Gastroenterol 2018; 24:4152-4163. [PMID: 30271080 PMCID: PMC6158485 DOI: 10.3748/wjg.v24.i36.4152] [Citation(s) in RCA: 133] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2018] [Revised: 08/06/2018] [Accepted: 08/24/2018] [Indexed: 02/06/2023] Open
Abstract
Sorafenib has been considered the standard of care for patients with advanced unresectable hepatocellular carcinoma (HCC) since 2007 and numerous studies have investigated the role of markers involved in the angiogenesis process at both the expression and genetic level and clinical aspect. What results have ten years of research produced? Several clinical and biological markers are associated with prognosis. The most interesting clinical parameters are adverse events, Barcelona Clinic Liver Cancer stage, and macroscopic vascular invasion, while several single nucleotide polymorphisms and plasma angiopoietin-2 levels represent the most promising biological biomarkers. A recent pooled analysis of two phase III randomized trials showed that the neutrophil-to-lymphocyte ratio, etiology and extra-hepatic spread are predictive factors of response to sorafenib, but did not identify any predictive biological markers. After 10 years of research into sorafenib there are still no validated prognostic or predictive factors of response to the drug in HCC. The aim of the present review was to summarize 10 years of research into sorafenib, looking in particular at the potential of associated clinical and biological markers to predict its efficacy in patients with advanced HCC.
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Affiliation(s)
- Giorgia Marisi
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola 47014, Italy
| | - Alessandro Cucchetti
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna 40126, Italy
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, Forlì 47121, Italy
| | - Paola Ulivi
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola 47014, Italy
| | - Matteo Canale
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola 47014, Italy
| | - Giuseppe Cabibbo
- Section of Gastroenterology, DI.BI.M.I.S., University of Palermo, Palermo 35628, Italy
| | - Leonardo Solaini
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna 40126, Italy
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, Forlì 47121, Italy
| | - Francesco G Foschi
- Department of Internal Medicine, Degli Infermi Hospital, Faenza 48018, Italy
| | - Serena De Matteis
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola 47014, Italy
| | - Giorgio Ercolani
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna 40126, Italy
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, Forlì 47121, Italy
| | - Martina Valgiusti
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola 47014, Italy
| | - Giovanni L Frassineti
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola 47014, Italy
| | - Mario Scartozzi
- Department of Medical Oncology, University of Cagliari, Cagliari 45698, Italy
| | - Andrea Casadei Gardini
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola 47014, Italy
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