Association between Time to Local Tumor Control and Treatment Outcomes Following Repeated Loco-Regional Treatment Session in Patients with Hepatocellular Carcinoma: A Retrospective, Single-Center Study
Abstract
:1. Introduction
2. Materials and Methods
3. Results
3.1. Patient Characteristics
3.2. Treatment Outcomes in Patients with No LTC
3.3. Treatment Outcomes in Patients LTC
3.4. Time to LTC as a Prognostic Factor
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Marrero, J.A.; Kulik, L.M.; Sirlin, C.B.; Zhu, A.X.; Finn, R.S.; Abecassis, M.M.; Roberts, L.R.; Heimbach, J.K. Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology 2018, 68, 723–750. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vogel, A.; Cervantes, A.; Chau, I.; Daniele, B.; Llovet, J.; Meyer, T.; Nault, J.C.; Neumann, U.; Ricke, J.; Sangro, B.; et al. Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2018, 29, iv238–iv255. [Google Scholar] [CrossRef] [PubMed]
- Heimbach, J.K.; Kulik, L.M.; Finn, R.S.; Sirlin, C.B.; Abecassis, M.M.; Roberts, L.R.; Zhu, A.X.; Murad, M.H.; Marrero, J.A. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 2018, 67, 358–380. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tang, A.; Bashir, M.R.; Corwin, M.T.; Cruite, I.; Dietrich, C.F.; Do, R.K.G.; Ehman, E.C.; Fowler, K.J.; Hussain, H.K.; Jha, R.C.; et al. Evidence supporting LI-RADS major features for CT- and MR imaging-based diagnosis of hepatocellular carcinoma: A systematic review. Radiology 2018, 286, 29–48. [Google Scholar] [CrossRef] [Green Version]
- Forner, A.; Ayuso, C.; Varela, M.; Rimola, J.; Hessheimer, A.J.; De Lope, C.R.; Reig, M.; Bianchi, L.; Llovet, J.M.; Bruix, J. Evaluation of tumor response after locoregional therapies in hepatocellular carcinoma: Are response evaluation criteria in solid tumors reliable? Cancer 2009, 115, 616–623. [Google Scholar] [CrossRef] [PubMed]
- Mähringer-Kunz, A.; Wagner, F.; Hahn, F.; Weinmann, A.; Brodehl, S.; Schotten, S.; Hinrichs, J.B.; Düber, C.; Galle, P.R.; dos Santos, D.P.; et al. Predicting survival after transarterial chemoembolization for hepatocellular carcinoma using a neural network: A Pilot Study. Liver Int. 2020, 40, 694–703. [Google Scholar] [CrossRef] [Green Version]
- Wang, W.; Zhao, Y.; Bai, W.; Han, G. Response assessment for HCC patients treated with repeated TACE: The optimal time-point is still an open issue. J. Hepatol. 2015, 63, 1530–1531. [Google Scholar] [CrossRef]
- Georgiades, C.; Geschwind, J.F.; Harrison, N.; Hines-Peralta, A.; Liapi, E.; Hong, K.; Wu, Z.; Kamel, I.; Frangakis, C. Lack of response after initial chemoembolization for hepatocellular carcinoma: Does it predict failure of subsequent treatment? Radiology 2012, 265, 115–123. [Google Scholar] [CrossRef]
- Kim, B.K.; Kim, S.U.; Kim, K.A.; Chung, Y.E.; Kim, M.J.; Park, M.S.; Park, J.Y.; Kim, D.Y.; Ahn, S.H.; Kim, M.D.; et al. Complete response at first chemoembolization is still the most robust predictor for favorable outcome in hepatocellular carcinoma. J. Hepatol. 2015, 62, 1304–1310. [Google Scholar] [CrossRef]
- Gillmore, R.; Stuart, S.; Kirkwood, A.; Hameeduddin, A.; Woodward, N.; Burroughs, A.K.; Meyer, T. EASL and mRECIST responses are independent prognostic factors for survival in hepatocellular cancer patients treated with transarterial embolization. J. Hepatol. 2011, 55, 1309–1316. [Google Scholar] [CrossRef] [PubMed]
- Kim, C.J.; Kim, H.J.; Park, J.H.; Park, D., II; Cho, Y.K.; Sohn, C., II; Jeon, W.K.; Kim, B.I.; Kim, M.J. Radiologic response to transcatheter hepatic arterial chemoembolization and clinical outcomes in patients with hepatocellular carcinoma. Liver Int. 2014, 34, 305–312. [Google Scholar] [CrossRef]
- Tacher, V.; Lin, M.; Duran, R.; Yarmohammadi, H.; Lee, H.; Chapiro, J.; Chao, M.; Wang, Z.; Frangakis, C.; Sohn, J.H.; et al. Comparison of Existing Response Criteria in Patients with Hepatocellular Carcinoma Treated with Transarterial Chemoembolization Using a 3D Quantitative Approach. Radiology 2016, 278, 275–284. [Google Scholar] [CrossRef]
- Kim, J.H.; Sinn, D.H.; Shin, S.W.; Cho, S.K.; Kang, W.; Gwak, G.Y.; Paik, Y.H.; Lee, J.H.; Koh, K.C.; Paik, S.W.; et al. The role of scheduled second TACE in early-stage hepatocellular carcinoma with complete response to initial TACE. Clin. Mol. Hepatol. 2017, 23, 42–50. [Google Scholar] [CrossRef] [Green Version]
- Jianyong, L.; Jinjing, Z.; Yefang, L.; Lunan, Y.; Jinqiang, Z.; Wentao, W.; Bo, L.; Tianfu, W.; Jiaying, Y. Response to transarterial chemoembolization may serve as selection criteria for hepatocellular carcinoma liver transplantation. Oncotarget 2017, 8, 91328–91342. [Google Scholar] [CrossRef]
- Ciftciler, R.; Demiroglu, H.; Haznedaroglu, I.C.; Sayınalp, N.; Aksu, S.; Ozcebe, O.; Goker, H.; Aydın, M.S.; Buyukasık, Y. Impact of Time between Induction Chemotherapy and Complete Remission on Survival Outcomes in Patients with Acute Myeloid Leukemia. Clin. Lymphoma Myeloma Leuk. 2019, 19, 729–734. [Google Scholar] [CrossRef] [PubMed]
- Walter, R.B.; Sandmaier, B.M.; Storer, B.E.; Godwin, C.D.; Buckley, S.A.; Pagel, J.M.; Sorror, M.L.; Deeg, H.J.; Storb, R.; Ap-pelbaum, F.R. Number of Courses of Induction Therapy Independently Predicts Outcome after Allogeneic Transplantation for Acute Myeloid Leukemia in First Morphological Remission. Biol. Blood Marrow Transplant. 2015, 21, 373–378. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vitale, A.; Trevisani, F.; Farinati, F.; Cillo, U. Treatment of Hepatocellular Carcinoma in the Precision Medicine Era: From Treatment Stage Migration to Therapeutic Hierarchy. Hepatology 2020, 72, 2206–2218. [Google Scholar] [CrossRef] [PubMed]
- European Association For The Study Of The Liver. EASL-EORTC clinical practice guidelines: Management of hepatocellular carcinoma. J. Hepatol. 2012, 56, 908–943. [Google Scholar] [CrossRef] [Green Version]
- Chernyak, V.; Fowler, K.J.; Kamaya, A.; Kielar, A.Z.; Elsayes, K.M.; Bashir, M.R.; Kono, Y.; Do, R.K.; Mitchell, D.G.; Singal, A.G.; et al. Liver Imaging Reporting and Data System (LI-RADS) version 2018: Imaging of hepatocellular carcinoma in at-risk pa-tients. Radiology 2018, 289, 816–830. [Google Scholar] [CrossRef]
- Berenguer, M.; Herreras, J.; Di Maira, T.; Vinaixa, C.; Juan, F.S.; Rubín, Á. Milan-out Criteria and Worse Intention-to-Treat Outcome Postliver Transplantation. Transplantation 2019, 5, e487. [Google Scholar] [CrossRef]
- Wehling, C.; Dill, M.T.; Olkus, A.; Springfeld, C.; Chang, D.-H.; Naumann, P.; Longerich, T.; Kratochwil, C.; Mehrabi, A.; Merle, U.; et al. Treatment stage migration and treatment sequences in patients with hepatocellular carcinoma: Drawbacks and opportunities. J. Cancer Res. Clin. Oncol. 2021, 147, 2471–2481. [Google Scholar] [CrossRef] [PubMed]
- Johnson, P.J.; Berhane, S.; Kagebayashi, C.; Satomura, S.; Teng, M.; Reeves, H.L.; O’Beirne, J.; Fox, R.; Skowronska, A.; Palmer, D.; et al. Assessment of liver function in patients with hepatocellular carcinoma: A new evidence-based approach—The albi grade. J. Clin. Oncol. 2015, 33, 550–558. [Google Scholar] [CrossRef] [PubMed]
- Forner, A.; Reig, M.; Bruix, J. Hepatocellular carcinoma. Lancet 2018, 391, 1301–1314. [Google Scholar] [CrossRef]
- Kadalayil, L.; Benini, R.; Pallan, L.; O’Beirne, J.; Marelli, L.; Yu, D.; Hackshaw, A.; Fox, R.; Johnson, P.; Burroughs, A.K.; et al. A simple prognostic scoring system for patients receiving transarterial embolisation for hepatocellular cancer. Ann. Oncol. 2013, 24, 2565–2570. [Google Scholar] [CrossRef]
- Park, C.; Chu, H.H.; Kim, J.H.; Kim, S.Y.; Alrashidi, I.; Gwon, D., II; Yoon, H.; Kim, N. Clinical significance of the initial and best responses after chemoembolization in the treatment of intermediate-stage hepatocellular carcinoma with pre-served liver function. J. Vasc. Interv. Radiol. 2020, 31, 1998–2006.e1. [Google Scholar] [CrossRef] [PubMed]
- Centonze, L.; Di Sandro, S.; Lauterio, A.; De Carlis, R.; Sgrazzutti, C.; Ciulli, C.; Vella, I.; Vicentin, I.; Incarbone, N.; Bagnardi, V.; et al. A retrospective single-centre analysis of the oncological impact of LI-RADS classification applied to Metroticket 2.0 calculator in liver transplantation: Every nodule matters. Transpl. Int. 2021, 34, 1712–1721. [Google Scholar] [CrossRef]
- Liu, L.; Wang, W.; Chen, H.; Zhao, Y.; Bai, W.; Yin, Z.; He, C.; Jia, J.; Yang, M.; Xia, J.; et al. EASL- and mRECIST-Evaluated Responses to Combination Therapy of Sorafenib with Transarterial Chemoembolization Predict Survival in Patients with Hepato-cellular Carcinoma. Clin. Cancer Res. 2014, 20, 1623–1631. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shim, J.H.; Lee, H.C.; Kim, S.O.; Shin, Y.M.; Kim, K.M.; Lim, Y.S.; Suh, D.J. Which response criteria best help predict survival of patients with hepatocellular carcinoma following chemoembolization? A validation study of old and new models. Radiology 2012, 262, 708–718. [Google Scholar] [CrossRef]
- Bartnik, K.; Podgórska, J.; Rosiak, G.; Korzeniowski, K.; Giziński, J.; Sajdek, M.; Wróblewski, T.; Zieniewicz, K.; Nyckowski, P.; Rowiński, O. Performance of initial LI-RADS 2018 treatment response in predicting survival of patients with hepatocellular carcinoma following TACE: A retrospective, single-center cohort study. J. Cancer Res. Clin. Oncol. 2021. [Google Scholar] [CrossRef]
- Biolato, M.; Gallusi, G.; Iavarone, M.; Cabibbo, G.; Racco, S.; De Santis, A.; Corte, C.D.; Maida, M.; Attili, A.F.; Sangio-Vanni, A.; et al. Prognostic ability of BCLC-B Subclassification in Patients with Hepatocellular Carcinoma Undergoing Transarteri-al Chemoembolization. Ann. Hepatol. 2018, 17, 110–118. [Google Scholar] [CrossRef]
- Burrel, M.; Reig, M.; Forner, A.; Barrufet, M.; de Lope, C.R.; Tremosini, S.; Ayuso, C.; Llover, J.M.; Real, M.I.; Bruix, J. Survival of patients with hepatocellular carcinoma treated by transarterial chemoembolisation (TACE) using Drug Eluting Beads. Im-plications for clinical practice and trial design. J. Hepatol. 2012, 56, 1330–1335. [Google Scholar] [CrossRef]
- Han, G.; Berhane, S.; Toyoda, H.; Bettinger, D.; Elshaarawy, O.; Chan, A.W.H.; Kirstein, M.; Mosconi, C.; Hucke, F.; Palmer, D.; et al. Prediction of Survival Among Patients Receiving Transarterial Chemoembolization for Hepatocellular Carcinoma: A Response-Based Approach. Hepatology 2020, 72, 198–212. [Google Scholar] [CrossRef] [PubMed]
- Zhang, R.; Shen, L.; Zhao, L.; Guan, Z.; Chen, Q.; Li, W. Combined transarterial chemoembolization and microwave ablation versus transarterial chemoembolization in BCLC stage B hepatocellular carcinoma. Diagn. Interv. Radiol. 2018, 24, 219–224. [Google Scholar] [CrossRef] [Green Version]
- Yen, C.; Sharma, R.; Rimassa, L.; Arizumi, T.; Bettinger, D.; Choo, H.Y.; Pressiani, T.; Burlone, M.E.; Pirisi, M.; Giordano, L.; et al. Treatment Stage Migration Maximizes Survival Outcomes in Patients with Hepatocellular Carcinoma Treated with Soraf-enib: An Observational Study. Liver Cancer 2017, 6, 313–324. [Google Scholar] [CrossRef]
Variable | No LTC | LTC | p Value |
---|---|---|---|
N of patients | 57 | 82 | - |
Age (years) | |||
<60 | 17 (30%) | 21 (26%) | 0.56 |
>60 | 39 (70%) | 61 (74%) | |
Gender | |||
Male | 46 (81%) | 58 (71%) | 0.23 |
Female | 11 (19%) | 24 (29%) | |
BCLC stage | |||
A | 16 (28%) | 51 (62%) | <0.001 |
B | 41 (72%) | 31 (38%) | |
Child Turcotte Pugh Class | |||
A | 48 (84%) | 75 (91%) | 0.27 |
B | 9 (16%) | 7 (9%) | |
Serum AFP | |||
<200 ng/mL | 32 (56%) | 64 (78%) | 0.01 |
≥200 ng/mL | 25 (44%) | 18 (22%) | |
ALBI | |||
1 | 27 (47%) | 51 (62%) | 0.16 |
2 | 26 (46%) | 29 (35%) | |
3 | 4 (7%) | 2 (2%) | |
Albumin, g/L | 3.95 (2.5–5.0) | 4.1 (2.0–5.2) | 0.17 |
Creatinine | 0.87 (0.56–1.56) | 0.91 (0.54–1.97) | 0.65 |
Total bilirubin (umol/L) | 0.98 (0.3–5.6) | 1.05 (0.21–4.04) | 0.14 |
INR | 1.15 (0.91-1.66) | 1.15 (0.92–2.45) | 0.82 |
ALT, IU/L | 47 (12–348) | 49 (19–303) | 0.69 |
AST, IU/L | 65 (18–408) | 50 (20–423) | 0.02 |
N of treated HCC lesions | |||
1 | 22 (39%) | 55 (67%) | 0.003 |
2 | 17 (30%) | 19 (23%) | |
≥3 | 18 (31%) | 4 (10%) | |
Tumor size | |||
<30 mm | 9 (16%) | 32 (39%) | 0.002 |
30–50 mm | 20 (35%) | 31 (38%) | |
>50 mm | 28 (49%) | 19 (23%) | |
Fulfilled Milan criteria | |||
Yes | 6 (11%) | 21 (26%) | 0.03 |
No | 51 (89%) | 61 (74%) |
Variable | 2 Sessions | 3 Sessions | >3 Sessions | p Value |
---|---|---|---|---|
N of patients | 42 | 26 | 14 | - |
Age (years) | ||||
<60 | 13 (31%) | 5 (19%) | 3 (21%) | 0.59 |
>60 | 29 (69%) | 21 (81%) | 11 (79%) | |
Gender | ||||
Male | 27 (64%) | 22 (85%) | 9 (64%) | 0.16 |
Female | 15 (36%) | 4 (15%) | 5 (36%) | |
Child Turcotte Pugh Class | ||||
A | 40 (95%) | 24 (92%) | 11 (79%) | 0.16 |
B | 2 (5%) | 2 (8%) | 3 (23%) | |
BCLC Stage | ||||
A | 30 (71%) | 16 (62%) | 5 (36%) | 0.06 |
B | 12 (29%) | 10 (38%) | 9 (64%) | |
Serum AFP | ||||
<200 ng/mL | 32 (76%) | 21 (81%) | 11 (79%) | 0.94 |
≥200 ng/mL | 10 (24%) | 5 (19%) | 3 (21%) | |
ALBI | ||||
1 | 27 (64%) | 17 (65%) | 7 (50%) | 0.73 |
2 | 14(33%) | 8 (31%) | 7 (50%) | |
3 | 1 (3%) | 1 (4%) | 0 (0%) | |
Albumin, g/L | 4.15 (3.0–5.2) | 4.3 (2.0–5.2) | 3.9 (2.8–4.6) | 0.16 |
Creatinine | 0.89 (0.54–1.97) | 0.92 (0.65–1.35) | 0.89 (0.59–1.42) | 0.81 |
Total bilirubin (umol/L) | 0.85 (0.24–4.04) | 0.98 (0.43–2.0) | 1.01 (0.42–3.0) | 0.76 |
INR | 1.15 (0.92–2.45) | 1.16 (1.01–1.69) | 1.17 (0.97–1.43) | 0.97 |
ALT, IU/L | 49 (19–200) | 49 (20–303) | 55 (23–264) | 0.6 |
AST, IU/L | 42 (20–189) | 50 (22–243) | 72 (22–193) | 0.14 |
N of treated HCC lesions | ||||
1 | 32 (76%) | 16 (62%) | 7 (50%) | 0.31 |
2 | 7 (17%) | 8 (31%) | 4 (29%) | |
≥3 | 3 (7%) | 2 (7%) | 3 (21%) | |
Tumor size | ||||
<30 mm | 19 (45%) | 9 (35%) | 4 (29%) | 0.07 |
30–50 mm | 18 (43%) | 10 (38%) | 3 (21%) | |
>50 mm | 5 (12%) | 7 (27%) | 7 (50%) |
Variable | Hazard Ratio | 95% Confidence Interval | p Value |
---|---|---|---|
Overall survival | |||
LTC × 2 sessions | 1.00 | reference | |
LTC × 3 sessions | 0.96 | 0.76–2.36 | 0.41 |
LTC × >3 sessions | 1.74 | 1.00–1.01 | 0.16 |
Time to LTC (weeks) | 1.03 | 1.01–1.6 | 0.04 |
BCLC A | 1.00 | reference | |
BCLC B | 2.06 | 1.06–4.02 | 0.03 |
CPS A | 1.00 | reference | |
CPS B | 1.87 | 0.64–5.38 | 0.25 |
ALBI grade 1 | 1.00 | reference | |
ALBI grade 2 | 1.73 | 0.87–3.44 | 0.93 |
ALBI grade 3 | 3.25 | 0.42–24.84 | 0.38 |
Progression free survival | |||
LTC × 2 sessions | 1.00 | reference | |
LTC × 3 sessions | 0.92 | 0.49–1.75 | 0.76 |
LTC × >3 sessions | 0.69 | 0.30–1.61 | 0.43 |
Time to LTC (weeks) | 1.05 | 1.02–1.09 | 0.004 |
BCLC A | 1.00 | reference | |
BCLC B | 1.86 | 1.04–3.35 | 0.04 |
CPS A | 1.00 | reference | |
CPS B | 2.02 | 0.79–5.16 | 0.14 |
ALBI grade 1 | 1.00 | reference | |
ALBI grade 2 | 1.48 | 0.82–2.67 | 0.68 |
ALBI grade 3 | 3.16 | 0.74–13.41 | 0.19 |
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Bartnik, K.; Hołówko, W.; Rowiński, O. Association between Time to Local Tumor Control and Treatment Outcomes Following Repeated Loco-Regional Treatment Session in Patients with Hepatocellular Carcinoma: A Retrospective, Single-Center Study. Life 2021, 11, 1062. https://doi.org/10.3390/life11101062
Bartnik K, Hołówko W, Rowiński O. Association between Time to Local Tumor Control and Treatment Outcomes Following Repeated Loco-Regional Treatment Session in Patients with Hepatocellular Carcinoma: A Retrospective, Single-Center Study. Life. 2021; 11(10):1062. https://doi.org/10.3390/life11101062
Chicago/Turabian StyleBartnik, Krzysztof, Wacław Hołówko, and Olgierd Rowiński. 2021. "Association between Time to Local Tumor Control and Treatment Outcomes Following Repeated Loco-Regional Treatment Session in Patients with Hepatocellular Carcinoma: A Retrospective, Single-Center Study" Life 11, no. 10: 1062. https://doi.org/10.3390/life11101062