7. Qualitätsindikatoren – Hepatozelluläres Karzinom und biliäre Karzinome
Qualitätsindikatoren sind Messgrößen, deren Erhebung der Beurteilung der Qualität der zugrunde liegenden Strukturen, Prozesse bzw. Ergebnisse dient. Qualitätsindikatoren sind ein wichtiges Instrument des Qualitätsmanagements. Ziel ihres Einsatzes ist die stetige Verbesserung der Versorgung, indem die Ergebnisse der Versorgung dargestellt, kritisch reflektiert und wenn nötig verbessert werden. Die vorliegende Auswahl von Qualitätsindikatoren wurde gemäß der Methodik des Leitlinienprogramms Onkologie erstellt [826]. Für den Ableitungsprozess konstituierte sich eine „Arbeitsgruppe Qualitätsindikatoren“ (AG QI). Diese erstellte das finale Set der Qualitätsindikatoren auf Grundlage der bereits bestehenden Qualitätsindikatoren der Leitlinie HCC 2013, der neuen starken Empfehlungen („soll“) der aktualisierten Leitlinie HCC/CCA, der Ergebnisse der bestehenden Qualitätsindikatoren aus den zertifizierten Leberkrebszentren (nur HCC) der Deutschen Krebsgesellschaft sowie der Ergebnisse der Recherche nach bestehenden nationalen und internationalen Qualitätsindikatoren. Die genaue Vorgehensweise und die Zusammensetzung der AG QI sind im Leitlinienreport dargelegt.
Im Rahmen des Leitlinien-Updates (Version 5.01) wurden die Empfehlungen der Qualitätsindikatoren QI 3 und QI 5 modifiziert. Auf Basis der Modifikationen wurden die Qualitätsindikatoren geprüft, der Nenner des Qualitätsindikators 5 angepasst und im schriftlichen Umlaufverfahren angenommen.
Hinweis zur folgenden Tabelle:
Der Zähler ist stets eine Teilmenge des Nenners.
Die Qualitätsindikatoren 1, 3 und 4 sind mit dem onkologischen Basisdatensatz der Krebsregister zu dokumentieren (Stand: 05/2024).
Typisierung nach WHO-Klassifikation (seit 2013; in 2020 ergänzt)
Zähler
Patienten des Nenners mit Typisierung nach aktueller WHO-Klassifikation
Nenner
N1: Alle Patienten mit histologisch gesichertem HCC N2: Alle Patienten mit histologisch gesichertem CCA
Qualitätsziel / Referenzbereich
EK (Konsens) (3.17)
EK (Konsens) (4.9)
Qualitätsziel: Möglichst häufig Typisierung nach WHO
Referenz-Empfehlungen
Die Typisierung des HCCs soll sich nach der aktuellen WHO-Klassifikation richten.
Hierbei sollten zum einen Sonderformen (z.B. fibrolamelläres HCC und mischdifferenzierte Tumoren (kombiniertes HCC/iCCA)) und wenn möglich auch das frühe HCC vom progredienten HCC und prämalignen Läsionen unterschieden werden.
Es sollte eine sichere Unterscheidung von Sonderformen des intrahepatischen Cholangiokarzinoms, Lebermetastasen und auch benignen Lebertumoren erfolgen.
- Konsens
- Konsens
Die Typisierung der Karzinome der Gallenwege und der Gallenblase soll nach der anatomischen Lokalisation (intrahepatisch, perihilär, distale Gallenwege, Gallenblase) und gemäß der histologischen Differenzierung nach der aktuellen WHO-Klassifikation erfolgen. Bei intrahepatischen Cholangiokarzinomen sollte eine Unterscheidung von ‚small duct‘ und ‚large duct‘ Typ erfolgen.
- Konsens
- Starker Konsens
Inhalt Befundberichte HCC (seit 2013)
Zähler
Patienten des Nenners mit Befundberichten mit Angabe zu: • Staging (nach TNM-Klassifikation) • Typing (nach WHO-Klassifikation) • Grading • Resektionsrand • Status der Umgebungsleber
Nenner
Alle Patienten mit HCC und Leberresektion oder Leberexplantation
Qualitätsziel / Referenzbereich
EK (starker Konsens)
Qualitätsziel: Möglichst häufig vollständige Befundberichte
Referenz-Empfehlungen
Die Bearbeitung und Befundung eines Resektats oder Explantats soll die Ausdehnung des Tumors (Staging) gemäß der aktuellen TNM-Klassifikation, seinen Typ (Typing) und Differenzierungsgrad (Grading) und den Status des Resektatrandes (R-Klassifikation) sowie den Status der nichttumorösen Leber ermitteln.
- Konsens
- Starker Konsens
Vorstellung Tumorkonferenz (seit 2013, geprüft 2024) (QI 4 entsprechend Langversion)
Zähler
Patienten des Nenners mit prätherapeutischer Vorstellung in der Tumorkonferenz
Nenner
Alle Patienten mit HCC
Qualitätsziel / Referenzbereich
EK (starker Konsens)
Qualitätsziel: Möglichst häufig prätherapeutische Vorstellung in der Tumorkonferenz
Anmerkung
- Teilnehmer TK: Gastroenterologe, Pathologe, interventioneller Radiologe, Viszeralchirurg
- Videokonferenzen sind möglich
Referenz-Empfehlungen
Patienten mit einem Hepatozellulären Karzinom sollen vor einer Behandlung und bei Änderung der Therapiestrategie in einer interdisziplinären Tumorkonferenz vorgestellt werden.
- Konsens
- Starker Konsens
Änderungshinweis
Patienten mit einem Hepatozellulären Karzinom sollen in einer interdisziplinären Tumorkonferenz vorgestellt werden.Vorstellung Tumorkonferenz nach TACE (modifiziert 2020) (QI 6 entsprechend Langversion)
Zähler
Patienten des Nenners mit Vorstellung in der Tumorkonferenz nach zwei Behandlungszyklen
Nenner
Alle Patienten mit HCC und TACE
Qualitätsziel / Referenzbereich
EK (Konsens)
Qualitätsziel: Möglichst häufig Vorstellung in der Tumorkonferenz nach TACE
Referenz-Empfehlungen
Die Indikation zur Fortführung der TACE soll nach zwei Behandlungszyklen im Tumorboard überprüft werden.
- Konsens
- Konsens
mRECIST-/EASL/LI-RADS-TR-Klassifikation nach TACE (modifiziert 2024) (QI 7 entsprechend Langversion)
Zähler
Patienten des Nenners mit Beurteilung der Remission mittels mRECIST-, EASL- oder LI-RADS-TR-Klassifikation
Nenner
Alle Patienten mit HCC und TACE
Qualitätsziel / Referenzbereich
EK (starker Konsens)
Qualitätsziel: Möglichst häufig Verwendung der mRESCIST-, EASL- oder LI-RADS-TR-Klassifikation nach TACE
Referenz-Empfehlungen
Die Remissionsbeurteilung nach Ablation / TACE / TARE soll nach standardisierten Kriterien erfolgen (mRECIST, EASL oder LI-RADS-TR).
- Konsens
- Starker Konsens
Änderungshinweis
Die Remissionsbeurteilung nach Ablation/TACE/TARE soll nach mRECIST/EASL erfolgen.Bridging-Therapie (neu 2020) (QI 8 entsprechend Langversion)
Zähler
Patienten des Nenners, die eine Bridging-Therapie erhalten haben
Nenner
Alle Patienten mit HCC (BCLC A), Child A auf der Transplantationswarteliste
Qualitätsziel / Referenzbereich
A, LoE 1
Qualitätsziel: Möglichst häufig Bridging-Therapie bei Patienten mit HCC (BCLC A) innerhalb der Mailand-Kriterien
Anmerkung
- Bridging: Lokalablation, Resektion, oder transarterielle Verfahren (TACE, TARE)
- BCLC A:
- ECOG (PS): 0-2
- Child-Pugh A bis C
- Singulärer Tumor > 2cm oder frühe multifokale Erkrankung mit bis zu 3 Tumoren < 3cm
Referenz-Empfehlungen
Patienten mit HCC (BCLC A) innerhalb der Mailand-Kriterien sollen eine Bridging-Therapie erhalten, sofern es die Leberfunktion zulässt.
- Empfehlungsgrad
- A: Starke Empfehlung für oder gegen ein Maßnahme - verwendete Ausdrucksweise = soll/soll nicht
- Evidenzlevel
- 1
- Konsens
- Starker Konsens
- Literatur
- [196] [197] [198]
Evidenztabellen (1)
HCC Bridging-TherapieInhalt Befundberichte CCA (neu 2020) (QI 9 entsprechend Langversion)
Zähler
Patienten des Nenners, bei denen ein histopathologischer Befundbericht mit folgenden Angaben vorliegt: • Staging (TNM-Klassifikation) • Typing (WHO-Klassifikation) • Grading • Resektionsrand (R-Klassifikation) • Bei intrahepatischen Cholangiokarzinomen (C22.1): Status der nicht-tumorösen Leber
Nenner
Alle Patienten mit CCA und Resektion oder Explantation
Qualitätsziel / Referenzbereich
EK (starker Konsens)
Qualitätsziel: Möglichst häufig vollständige Befundberichte
Referenz-Empfehlungen
Die Bearbeitung und Befundung eines Resektats soll die Ausdehnung des Tumors (Staging) gemäß der aktuellen TNM-Klassifikation, seinen Typ (Typing) und Differenzierungsgrad (Grading) und den Status des Resektatrandes (R-Klassifikation) sowie bei intrahepatischen Cholangiokarzinomen den Status der nichttumorösen Leber ermitteln. Bei Präparaten mit prämalignen Läsionen soll durch genaue Aufarbeitung ein möglicher Übergang in ein invasives Karzinom abgeklärt werden.
- Konsens
- Starker Konsens
Evidenztabellen
HCC Bridging-Therapie
Schlüsselfrage:
Profitieren Patienten mit HCC inside Milano von Bridging-Therapien?
Inhalt: 5 Literaturstellen
| Literaturstelle | Evidenzlevel | Studientyp |
|---|---|---|
| Agopian, V. G. 2017 | 2 | Multicentric cohort/registry, 20 US centers, HCC Transplant Consortium (UMHTC) |
| Huang, X. 2017 | 1 | Systematic review and Meta-Analysis. 12 studies Preoperative locoregional therapy on recurrence and survival in HCC. |
| Kulik, L. 2018 | 1 | Systematic review and meta-analysis. Effectiveness of LRT in the management of HCC patients on the LT waitlist. |
| Salem, R. 2016 | 2 | RCT, open-label, singlecenter, investigator initiated phase 2 Prospective Chemoembolization vs Radioembolization for the Treatment of Hepatocellular Carcinoma. |
| Sneiders, D. 2018 | 1 | Systematic review and meta-analysis. 14 retrospective studies. HCC undergoing preliver transplantation TACE. |
OXFORD (2011) Appraisal Sheet: Systematic Reviews: 3 Bewertung(en)
| Huang, X. et al. Impact of preoperative locoregional therapy on recurrence and patient survival following liver transplantation for hepatocellular carcinoma: a meta-analysis. Scand J Gastroenterol. 52. 143-149. 2017 | ||||
|---|---|---|---|---|
| Evidence level/Study Types | P - I - C | Outcomes/Results | Literature References | |
| Evidence level: 1 Study type: Systematic review and Meta-Analysis. 12 studies Preoperative locoregional therapy on recurrence and survival in HCC. Databases: PubMed, EMBASE, Google Scholar, the Cochrane Library, the China National Knowledge Infrastructure whole-article database (CNKI), and the VIP Chinese Journals Database Search period: Inception-04/2014 Inclusion Criteria: Study patients who had undergone preoperative locoregional therapy prior to liver transplantation, an intervention with locoregional therapy and a control group, the reporting of survival results, and a sufficiently long follow-up period (e.g., five years). Studies could be designed as randomized control trials (RCTs) or non-RCTs. Exclusion Criteria: Reviews and case reports were excluded. |
Population: HCC patients. 12 studies, n=35-200, predominantly US studies. Intervention: Preoperative locoregional therapy including TACE, RFA, PEI and combination of these treatments. Comparison: No treatment |
Primary: five-year survival and five-year recurrence-free survival Secondary: - Results: Locoregional therapy and 5-year survival rate :10 studies (n = 1,235). Only one study showed statistical significance; pooled results preoperative locoregional therapy was not associated with a decreased risk of five-year survival (HR = 1.06; 95% CI = 0.82–1.38). In random-effects model HR of 1.04 (95% CI = 0.74–1.45). Locoregional therapy and 5-year recurrence-free survival rate 6 studies found that preoperative locoregional therapy had no association with five-year recurrence-free survival rates, same was true for pooled results (pooled HR = 1.02, 95% CI = 0.70-1.50. Author's Conclusion: Meta-analysis suggests that preoperative locoregional therapy has no association with survival following liver transplantation for HCC. However, the majority of included studies were performed via retrospective analysis and/or examined small numbers of patients at single centers. Therefore, we believe that a multi-center prospective study with a longer follow-up period and more clearly defined parameters would be the best way to study this issue in the future. |
Stockland, A.H., et al., Preoperative chemoembolization in patients with hepato- cellular carcinoma undergoing liver transplantation: influence of emergent versus elective procedures on patient survival and tumor recurrence rate. Cardiovasc Intervent Radiol, 2007. 30(5): p. 888-93. Bharat, A., et al., Pre-Liver Transplantation Locoregional Adjuvant Therapy for Hepatocellular Carcinoma as a Strategy to Improve Longterm Survival. Journal of the American College of Surgeons, 2006. 203(4): p. 411–420 Seehofer, D, et al., impact of neoadjuvant TACE on tumor recurrence and patient survival after liver transplantation for HCC: 2613. Transplantation, 2010. 90. DuBay DA, et al. Radiofrequency ablation of hepatocellular carcinoma as a bridge to liver transplantation. HPB (Oxford), 2011. 13(1): p. 24-32. Yao, F.Y., et al., The impact of pre-operative loco-regional therapy on outcome after liver transplantation for hepatocellular carcinoma. Am J Transplant, 2005. 5(4 Pt 1): p. 795-804. Kim, JM, et al., Effectiveness of Locoregional Therapy Before Living Donor Liver Transplantation in Patients With Hepatocellular Carcinoma Who Meet the Milan Criteria. Transplantation Proceedings, 2012. 44(2): p. 403–408. Lao, O.B., J. Weissman, and J.D. Perkins, Pre-transplant therapy for hepato-cellular carcinoma is associated with a lower recurrence after liver trans- plantation. Clin Transplant, 2009. 23(6): p. 874-81. Porrett, P.M., et al., Lack of benefit of pre-transplant locoregional hepatic therapy for hepatocellular cancer in the current MELD era. Liver Transpl, 2006. 12(4): p. 665-73. Kim, P.T., et al., Tumor biology and pre-transplant locoregional treatments determine outcomes in patients with T3 hepatocellular carcinoma undergoing liver transplantation. Clin Transplant, 2013. 27(2): p. 311-8. S.L., et al., Transarterial chemoembolization for HCC in patients with extensive liver transplantation waiting times. Angiology, 2012. 63(3): p.206-12. Decaens, T., et al., Impact of pretransplantation transarterial chemo embolization on survival and recurrence after liver transplantation for hepato- cellular carcinoma. Liver Transpl, 2005. 11(7): p. 767-75 Heckman, J.T., et al., Bridging locoregional therapy for hepatocellular carcinoma prior to liver transplantation. Ann Surg Oncol, 2008. 15(11): p. 3169-77. |
|
| Methodical Notes | ||||
| Funding Sources: "we thank all those persons, organizations and funds that have provided us with any help." COI: The authors have declared that no competing interest exists. Study Quality: "We used the Newcastle-Ottawa Scale (NOS) to assess the quality of the studies included in our analysis....The studies included in the MA were deemed to have moderate to high overall quality, with all of the included studies ranking ≥5 stars on the modified NOS which meant a relative high quality." Heterogeneity: "If the heterogeneity was not obvious, HRs were pooled using a fixed effects model. Otherwise, we used a random effects model to pool the HRs. We also conducted a sensitivity analysis to examine the stability of the pooled results. There was no significant heterogeneity among the studies." Publication Bias: "Publication bias was detected using the funnel plot of the meta-analysis results. ..The plots are relatively symmetric, suggesting that there is no significant publication bias in the reports of five-year survival rates." Notes: |
||||
| Kulik, L. et al. Therapies for patients with hepatocellular carcinoma awaiting liver transplantation: A systematic review and meta-analysis. Hepatology. 67. 381-400. 2018 | ||||
|---|---|---|---|---|
| Evidence level/Study Types | P - I - C | Outcomes/Results | Literature References | |
| Evidence level: 1 Study type: Systematic review and meta-analysis. Effectiveness of LRT in the management of HCC patients on the LT waitlist. Databases: Ovid Medline In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, and Scopus Search period: inception to April 25, 2016. Inclusion Criteria: studies that enrolled adults with cirrhosis awaiting LT and treated with bridging or down-staging therapies before transplant. Therapies included TACE,transarterial radioembolization (TARE), ablation, and radiotherapy. We included both comparative and noncomparative studies with no language restrictions. Exclusion Criteria: studies with patients enrolled before 1996, case reports, cohorts with fewer than 5 patients, reviews, letters, errata, commentaries, and studies published only as abstracts. |
Population: Three research questions 1.) Adults with cirrhosis awaiting LT andT1 HCC 2.)Adults with cirrhosis awaiting LT and T2 HCC 3.)Adults with cirrhosis awaiting LT and beyond Milan (T3) HCC 63 studies were included (comparative and non-comparative). Intervention: three research questions. 1.) Observation versus any therapy (TACE,TARE, ablation, or radiotherapy) 2.)Transplant alone versus transplant with any bridging therapy (TACE, TARE, ablation, or radiotherapy) 3.) Transplant without down-staging versus transplant following down-staging to within Milan (T2) Comparison: - |
Primary: Waitlist dropout due to progression beyond transplant criteria, post-LT survival, recurrence. Secondary: - Results: 1.): For adults with T1 HCC and waiting for LT, there were only 2 nonrandomized comparative studies, both with a high risk of bias. In one series, the rate of dropout from all causes at 6 months in T1 HCC patients who underwent LRT was 5.3%, while in the other series of T1 HCC patients who did not receive LRT, the dropout rate at median follow-up of 2.4 years and the progression rate to T2 HCC were 30% and 88%, respectively. 2: For adults with T2 HCC awaiting LT, transplant with any bridging therapy showed a nonsignificant reduction in the risk of waitlist dropout due to progression (relative risk [RR], 0.32; 95%CI, 0.06-1.85; I2 5 0%) and of waitlist dropout from all causes (RR, 0.38; 95% CI, 0.060-2.370; I2 5 85.7%) compared to no therapy based on three comparative studies. The quality of evidence is very low due to high risk of bias, imprecision, and inconsistency. There were five comparative studies which reported on posttransplant survival rates and 10 comparative studiesvwhich reported on posttransplant recurrence, and there was no significant difference seen in either of these endpoints. 3.)For adults initially with stage T3 HCC who received LRT, there were three studies reporting on transplant with any downstaging therapy versus no downstaging, and this showed a significant increase in 1-year (two studies, RR, 1.11; 95% CI,1.01-1.23) and 5-year (1 study, RR, 1.17; 95% CI, 1.03-1.32) post-LT survival rates for patients who received LRT. The quality of evidence is very low due to serious risk of bias and imprecision Author's Conclusion: "In patients with HCC listed for LT, the use of LRT is associated with a non-significant trend toward improved waitlist and posttransplant outcomes, though there is a high risk of selection bias in the available evidence." |
see article, 63 references. | |
| Methodical Notes | ||||
| Funding Sources: not stated. COI: "Potential conflict of interest: Dr. Kulik advises Bayer." Study Quality: Modified Newcastle-Ottawa Scale was used to assess the risk of bias in observational studies. Quality of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methods. Quality of evidence was rated very low for all outcomes. Heterogeneity: "There was significant heterogeneity among the three studies that looked at down-staging for T3 HCC compared to transplant for T3 HCC without downstaging in terms of the comparative group" Publication Bias: Not investigated Notes: Publication bias not investigated. |
||||
| Sneiders, D. et al. Systematic Review and Meta-Analysis of Posttransplant Hepatic Artery and Biliary Complications in Patients Treated With Transarterial Chemoembolization Before Liver Transplantation. Transplantation. 102. 88-96. 2018 | ||||
|---|---|---|---|---|
| Evidence level/Study Types | P - I - C | Outcomes/Results | Literature References | |
| Evidence level: 1 Study type: Systematic review and meta-analysis. 14 retrospective studies. HCC undergoing preliver transplantation TACE. Databases: Embase, MEDLINE OvidSP, Web of Science, Google Scholar, and Cochrane Search period: Inception - March 2016. Inclusion Criteria: Studiey investigating posttransplant complications of the hepatic artery or biliary tract, in patients treated with TACE before deceased or living-donor liver transplantation, compared with liver transplantation recipients who had not undergone TACE. We included articles describing transarterial embolization or chemoinfusion alone, embolization with drug eluting beads or chemoembolization. Exclusion Criteria: Articles describing radioembolization. Case reports, letters, and editorials, pediatric and nonhuman studies. |
Population: 14 retrospective observational studies on HCC patients. n=1122 TACE patients. Intervention: TACE before liver transplantation Comparison: Liver transplantation without prior TACE |
Primary: postoperative hepatic artery Secondary: biliary complications Results: Hepatic Artery Complications: Posttransplant hepatic artery complications occurred more frequently in TACE recipients (76/837) compared with non-TACE recipients (145/2294). WWe observed a significant association between preliver transplantation TACE and posttransplantation occurrence of hepatic artery complications, including thrombosis, stenosis, and (pseudo)- aneurysms (OR, 1.57; 95% CI, 1.09-2.26; P = 0.016; I2 = 0%) No evidence of an association between pretransplant TACE and posttransplant occurrence of hepatic artery thrombosis, alone, was found (OR, 1.31; 95% CI, 0.74-2.35; I2 = 0%) Biliary Tract Complications No strong evidence of a significant association was observed between preliver transplantation TACE and occurrence of biliary tract complications posttransplantation (OR, 1.30; 95% CI, 0.96-1.76; P = 0.087; I2 = 0%) Author's Conclusion: "Patients treated with TACE before liver transplantation may be at increased risk for development of hepatic artery complications after liver transplantation." |
Casadaban L, et al. Presurgical transarterial chemoembolization does not increase biliary stricture incidence in orthotopic liver transplant patients. Transplant Proc. 2014;46:1413–1419. Goel A, et al. Hepatic artery and biliary complications in liver transplant recipients undergoing pretransplant transarterial chemoembolization. Liver Transpl. 2014;20:1221–1228. Kanakadandi V, et al. Chemoembolization therapy of hepatocellular carcinoma prior to liver transplant is associated with the development of post-transplant biliary anastomotic strictures. Hepatology. 2012;56:475A–476A. Li H, et al. Preoperative transarterial chemoembolization does not increase hepatic artery complications after liver transplantation: a single center 12-year experience. Clin Res Hepatol Gastroenterol.2015;39:451–457. Lin TS, et al. Intimal dissection of the hepatic artery following transarterial embolization for hepatocellular carcinoma: an intraoperative problem in adult living donor liver transplantation. Liver Transpl.2009;15:1553–1556. Majno PE, et al. Influence of preoperative transarterial lipiodol chemo-embolization on resection and transplantation for hepatocellular carcinoma in patients with cirrhosis. Ann Surg. 1997;226:688–701. Mekeel KL, et al. The risk of hepatic arterial complications associated with trans-arterial chemoembolization prior to liver transplantation for hepato-cellular carcinoma. Transplantation. 2010;90(Suppl 1):781. Panaro F, et al. Hepatic artery complications following liver transplantation. Does preoperative chemoembolization impact the postoperative course? Clin Transplant. 2014;28:598–605. Pravisani R, et al. Transarterial chemoembolization does not harm the hepatic artery at transplantation. Transplant Int. 2015;28:212. Ramanathan M, et al. Downstaging or bridging therapy of hepatocellular cancer does not increase incidence of biliary complications after liver trans-plantation. Hepatology. 2015;62:833A. Richard HM 3rd, et al. Hepatic arterial complications in liver transplant recipients treated with pretransplantation chemoembolization for hepatocellular carcinoma. Radiology. 2000;214:775–779. Saborido BP, et al. Is transarterial chemoembolization necessary before liver transplantation for hepatocellular carcinoma?Am J Surg. 2005;190:383–387. Shiani A, et al. Incidence of biliary stricture after transarterial chemoembolization for hepatocellular carcinoma in orthotopic liver transplant patients. Am J Gastroenterol. 2015;110:S907–S908. Shiani A, et al. Vascular complications after transarterial chemoembolization in orthotopic liver transplant patients.Am J Gastroenterol. 2015;110:S906. |
|
| Methodical Notes | ||||
| Funding Sources: not stated. COI: "The authors declare no conflicts of interest." Study Quality: Quality assessment of studies was done by the validated checklist of Downs and Black. Therefore, the quality of all included studies according to GRADE is low to very low. Heterogeneity: "Potential heterogeneity between studies was assessed with I2 tests... There was no significant heterogeneity between studies in both analyses." Publication Bias: Not investigated. Notes: Publication bias not investigated. |
||||
(T32GM008152 to A.C.G.) with support for research provided by an Allied
Scientist grant from the Society of Interventional Radiology Foundation.
COI: "These authors disclose the following: Robert J. Lewandowski, Laura Kulik, and
Riad Salem serve as advisors to BTG International. The remaining authors
disclose no conflicts.
Randomization: Prospective randomization 1:1 to conventional chemoembolization (cTACE; control arm) or radioembolization (Y90; test arm). Method not described.
Blinding: No blinding of patients, open label.
CT, MRT Scans (for outcome assesment) were reviewed in a blinded manner by 2
board-certified radiologists.
Dropout Rate/ITT-Analysis: Intention to treat analysis was performed.
Notes:
Time to initial treatment different between groups. A lot of censored datasets due to transplants.
| Salem, R. et al. Y90 Radioembolization Significantly Prolongs Time to Progression Compared With Chemoembolization in Patients With Hepatocellular Carcinoma. Gastroenterology. 151. 1155-1163.e2. 2016 | |||
|---|---|---|---|
| Population | Intervention - Comparison | Outcomes/Results | |
| Evidence level: 2 Study type: RCT, open-label, singlecenter, investigator initiated phase 2 Prospective Chemoembolization vs Radioembolization for the Treatment of Hepatocellular Carcinoma. Number of Patient: 45 randomized (21 cTACE, 24 Y90) Recruitung Phase: 2009-2015 Inclusion Criteria: Image/biopsy-proven HCC by guidelines, unablatable/unresectable disease, no vascular invasion, Child–Pugh A/B, bilirubin level of 2.0 mg/dL or less, and aspartate aminotransferase/alanine aminotransferase 5 times the upper limit of normal or less. Exclusion Criteria: Infiltrative/bulk disease (≥70% tumor burden), 50% or more tumor burden with albumin level less than 3 g/dL, cardiac comorbidities, major surgery within the past 4 weeks, or active infection. |
Intervention: cTACE. Chemoembolization was performed with 75 mg/ m2 (maximum, 150 mg) dosing. The drug/lipiodol combination was followed by embolic microspheres. Comparison: Y90. Angiography and technetium-99m scintigraphy were used to estimate lung shunting, identify extrahepatic perfusion, and perform coil embolization if necessary. Glass microspheres were used at a 120-Gy dose, with treatment on an outpatient basis. |
Primary: Time to progression (TTP) Secondary: safety, rate of response (based on tumor size and necrosis criteria), and Kaplan–Meier survival time. Results: Population: n=45 (cTACE 21, Y90 =24). For all 45 patients, the median length of followup evaluation was 17.2 months (range, 1.4–62.1 mo). Primary: Time to progression The median TTP was significantly longer in the Y90 group: 6.8 months for cTACE vs not reached for Y90 (>26 mo; P ¼ .0012; HR, 0.122; 95% CI, 0.027–0.557; P = .007). Competing risk analysis: Y90 again showed a significantly reduced hazard of progression compared with cTACE (subdistribution HR, 0.13; 95% CI, 0.03–0.57; P = .006), with transplant/death as competing events. By IPCW analysis, risk reduction of progression in the Y90 group was more pronounced (HR, 0.071; 95% CI, 0.008–0.645; P = .019). Secondary outcomes Imaging outcomes: Primary index lesions (n = 43) were defined in 184 reviewed studies (mean, 4.3 scans/patient), with follow-up imaging available in 42 of 43 patients (98%). WHO response was 12 of 19 (63%) for cTACE vs 12 of 23 (52%) for Y90 (P = .542), with comparable median times with PR by group (7.3 mo; 95% CI, 3.9–12.6 after cTACE vs 7.6 mo. Overall survival: KM curves (censored to liver transplantation) showing the median of 17.7 months (95% CI, 8.3–not calculable) and 18.6 months (95% CI, 7.4–32.5) OS for cTACE and Y90, respectively (P = .99) Author's Conclusion: "In a randomized phase 2 study of patients with HCC of BCLC stages A or B, we found Y90 radioembolization to provide significantly longer TTP than cTACE. Y90 radioembolization provides better tumor control and could reduce drop-out from transplant waitlists." |
|
| Methodical Notes | |||
| Agopian, V. G. et al. Impact of Pretransplant Bridging Locoregional Therapy for Patients With Hepatocellular Carcinoma Within Milan Criteria Undergoing Liver Transplantation: Analysis of 3601 Patients From the US Multicenter HCC Transplant Consortium. Ann Surg. 266. 525-535. 2017 | |||
|---|---|---|---|
| Evidence level | Methodical Notes | Patient characteristics | Interventions |
| Evidence level: 2 Study type: Multicentric cohort/registry, 20 US centers, HCC Transplant Consortium (UMHTC) |
Funding sources: not described. Conflict of Interests: The authors report no conflicts of interest. Randomization: - Blinding: - Dropout rates: - |
Total no. patients: 3601 with a known pre-LT diagnosis of HCC meeting MC Recruiting Phase: 2002 to 2013 Inclusion criteria: Consecutive, adult (≥18 years) HCC patients undergoing LT regardless of tumor size, requirement for MELD exception points, follow-up time, or non- HCC-related death. HCC diagnosis was based on pretransplant radiographic imaging, biopsy, or incidental discovery on explant pathology. Exclusion criteria: Patients with cholangiocarcinoma, mixed hepatocellular/ cholangiocarcinoma, fibrolamellar HCC, or hepatoblastoma were excluded. |
Interventions: pre liver transplant locoregional therapy (pre LT LRT) Comparison: LT without LRT |
| Notes: | Author's conclusion: "Bridging LRT in HCC patients within MC does not improve post-LT survival or HCC recurrence in the majority of patients who fail to achieve cPR. The need for increasing LRT treatments and lack of alphafetoprotein response to LRT independently predict post-LT recurrence, serving as a surrogate for underlying tumor biology which can be utilized for prioritization of HCC LT candidates" |
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| Outcome Measures/results | Primary Recurrence-free survival and post-LT recurrence Secondary |
Results: Population: Of 3601 patients in the UMHTC with a known pre-LT diagnosis of HCC meeting MC, 2854 (79.3%) received pre-LT LRT, 747 (20.7%) did not. At a median follow-up time of 46.7 months [IQR 24.2–76.2], 375 patients developed post-LT HCC recurrence (10.4%); median time to recurrence of 17.2 months (IQR 8.5–34.1). At time of last follow-up, 2433 (67.6%) were alive without recurrence, 95 (2.6%) had recurred but were alive, 279 (7.7%) had died of HCC recurrence, and 794 (22.1%) had non-HCC-related mortality. thermal ablation, 464 (12.9%) received ablation without TACE, 298 (8.3) received both TACE and ablation, and 170 recipients received Of 3601 HCC LT recipients, In the LT LRT group 1922 (53.4%) received TACE and not thermal ablation, 464 (12.9%) received ablation without TACE, 298 (8.3) received both TACE and ablation, and 170 recipients received other LRT without TACE or ablation (4.7%). Comparison LT and Pre-LT LRT Survival and recurrence:747 LT recipients not receiving LRT, 2854 receiving LRT had similar 1, 3, and 5-year recurrence-free survival (89%, 77%, 68% vs85%, 75%, 68%; P = 0.490) and 5-year post-LT recurrence (11.2% vs 10.1%; P = 0.474). Post-LT recurrence: Increasing LRT number [3 LRTs: hazard ratio (HR) 2.1, P < 0.001; 4þ LRTs: HR 2.5, P < 0.001), and unfavorable waitlist alphafetorotein trend significantly predicted post-LT recurrence, whereas LRT modality did not. Treated Stratification by by LRT modality: no significant differences in the 1, 3, and 5- year RFS. Complete Pathological response Treated patients achieving cPR had superior 5-year RFS (72%) and lower post-LT recurrence (HR 0.52, P < 0.001) compared with both untreated patients (69%; P ¼ 0.010; HR 1.0) and treated patients not achieving cPR (67%; P = 0.010; HR 1.31, P = 0.039). |
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Literaturhinweise
[826] Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF), Entwicklung von leitlinienbasierten Qualitätsindikatoren. Methodenpapier für das Leitlinienprogramm Onkologie, Version 2.1, 2017., https://www.leitlinienprogramm-onkologie.de/methodik/grundlegende-informationen-zur-methodik
[196] Huang, X., Lu, S., Impact of preoperative locoregional therapy on recurrence and patient survival following liver transplantation for hepatocellular carcinoma: a meta-analysis, Scand J Gastroenterol, 2017. 52(2): p. 143-149., https://www.tandfonline.com/doi/full/10.1080/00365521.2016.1236396
[197] Kulik, L., Heimbach, J. K., Zaiem, F., Almasri, J., Prokop, L. J., Wang, Z., et.al. Therapies for patients with hepatocellular carcinoma awaiting liver transplantation: A systematic review and meta-analysis, Hepatology, 2018. 67(1): p. 381-400., https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/hep.29485
[198] Sneiders, D., Houwen, T., Pengel, L. H. M., Polak, W. G., Dor, Fjmf, Hartog, H., Systematic Review and Meta-Analysis of Posttransplant Hepatic Artery and Biliary Complications in Patients Treated With Transarterial Chemoembolization Before Liver Transplantation, Transplantation, 2018. 102(1): p. 88-96.