Zie ook literatuurlijst niet-toxische middelen en behandelingen specifiek bij darmkanker van arts-bioloog drs. Engelbert Valstar

7 april 2022: Bron: JAMA Surg. Published online March 30, 2022

Hoewel het niet gebruikelijk is om darmkankerpatiënten met leveruitzaaiingen alsnog te opereren blijkt uit een kleine studie dat dit toch bij geselecteerde patiënten zinvol kan zijn. Uit een groep van 91 patiënten met inoperabele in de lever uitgezaaide darmkanker werden 10 patiënten geselecteerd. Deze patiënten hadden aantoonbaar alleen inoperabele leveruitzaaiingen en kregen een complete leveroperatie (hepatectomie) gevolgd door een levertransplantatie via levende donoren. Van de 10 patiënten leefde iedereen nog 1,5 tot 2 jaar na de levertransplantatie, waarvan 6 van de 10 patiënten kankervrij. 

De prospectieve studie werd uitgevoerd door Roberto Hernandez-Alejandro, M.D., van het University of Rochester Medical Center in New York, en collega's. Zij onderzochten de overlevingsresultaten van levertransplantatie via levende donoren voor darmkankerpatiënten met inoperabele, alleen in de lever uitgezaaid. De 10 patiënten ondergingen een levende donoren levertransplantatie tussen juli 2017 en oktober 2020 en werden gevolgd tot 1 mei 2021.

De onderzoekers ontdekten dat zeven van de 10 levende donoren mannelijk waren, met een mediane leeftijd van 40,5 jaar. De Kaplan-Meier-schattingen waren respectievelijk 62 en 100 procent voor recidiefvrije en algehele overleving na 1,5 jaar na de levertransplantatie. 

De 3 patiënten die een recidief kregen, werden behandeld met palliatieve systemische therapie en 1 van deze patiënten stierf aan de ziekte. Deze resultaten werden bereikt terwijl het donorrisico en de morbiditeit adequaat werden afgewogen; alle 10 donoren werden 4 tot 7 dagen na de operatie uit het ziekenhuis ontslagen en herstelden volledig.

De resultaten suggereren dat een levende donoren levertransplantatie een levensvatbare behandelingsoptie kan zijn voor geselecteerde patiënten met inoperabele leveruitzaaiingen vanuit darmkanker ontstaan met gunstige tumorbiologie.

"Zorgvuldige patiëntenselectie blijft wel de sleutel tot aanvaardbare oncologische resultaten voor deze ziekte", schrijven de onderzoekers..

In het volledige studierapport wordt tot in detail beschreven hoe de onderzoekers te werk zijn gegaan. Klik op de titel van het abstract voor het volledige studierapport:

editorial comment icon 
Editorial
Comment
Key Points

Question  What are the estimated overall and recurrence-free survival outcomes after living-donor liver transplant (LDLT) in patients with liver-confined, unresectable colorectal cancer liver metastasis (CRLM)?

Findings  In this cohort study of 10 adults with CRLM who received LDLT, Kaplan-Meier estimates of recurrence-free and overall survival at a median follow-up of 1.5 years were 62% and 100%, respectively. Perioperative outcomes for both recipients and donors were consistent with established benchmarks.

Meaning  The results suggest that LDLT may be a viable treatment option for select patients with unresectable CRLMs with favorable tumor biology.

Abstract

Importance  Colorectal cancer is a leading cause of cancer-related death, and nearly 70% of patients with this cancer have unresectable colorectal cancer liver metastases (CRLMs). Compared with chemotherapy, liver transplant has been reported to improve survival in patients with CRLMs, but in North America, liver allograft shortages make the use of deceased-donor allografts for this indication problematic.

Objective  To examine survival outcomes of living-donor liver transplant (LDLT) for unresectable, liver-confined CRLMs.

Design, Setting, and Participants  This prospective cohort study included patients at 3 North American liver transplant centers with established LDLT programs, 2 in the US and 1 in Canada. Patients with liver-confined, unresectable CRLMs who had demonstrated sustained disease control on oncologic therapy met the inclusion criteria for LDLT. Patients included in this study underwent an LDLT between July 2017 and October 2020 and were followed up until May 1, 2021.

Exposures  Living-donor liver transplant.

Main Outcomes and Measures  Perioperative morbidity and mortality of treated patients and donors, assessed by univariate statistics, and 1.5-year Kaplan-Meier estimates of recurrence-free and overall survival for transplant recipients.

Results  Of 91 evaluated patients, 10 (11%) underwent LDLT (6 [60%] male; median age, 45 years [range, 35-58 years]). Among the 10 living donors, 7 (70%) were male, and the median age was 40.5 years (range, 27-50 years). Kaplan-Meier estimates for recurrence-free and overall survival at 1.5 years after LDLT were 62% and 100%, respectively. Perioperative morbidity for both donors and recipients was consistent with established standards (Clavien-Dindo complications among recipients: 3 [10%] had none, 3 [30%] had grade II, and 4 [40%] had grade III; donors: 5 [50%] had none, 4 [40%] had grade I, and 1 had grade III).

Conclusions and RelevanceThis study’s findings of recurrence-free and overall survival rates suggest that select patients with unresectable, liver-confined CRLMs may benefit from total hepatectomy and LDLT.

Conclusions

This cohort study found that selected patients with unresectable, liver-confined CRLMs may benefit from total hepatectomy and LDLT, with encouraging rates of recurrence-free and overall survival. Unresectable CRLMs with favorable tumor biology may become an acceptable indication for LT. Careful patient selection remains the key for ensuring acceptable oncologic outcomes for this disease. As more centers begin to use this novel treatment approach, prospective multicenter collaborations must be established to continue to understand and refine the selection and treatment-response criteria. It is time for a North American registry for centers performing LT for unresectable CRLMs. Such a registry will provide a platform for data acquisition in what remains a rare indication for LT, and it may improve understanding of gaps in treatment and of the natural history of posttransplant recurrence and survival. However, LT for CRLMs should be adopted with great caution and only by centers with experienced multidisciplinary teams that include gastrointestinal oncology, transplant oncology, hepatobiliary surgery, and liver transplant. The field of transplant oncology should move toward unified criteria that may facilitate the incorporation of selected patients with CRLMs into the standard organ-allocation systems.

Back to top
Article Information

Accepted for Publication: January 9, 2022.

Published Online: March 30, 2022. doi:10.1001/jamasurg.2022.0300

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Hernandez-Alejandro R et al. JAMA Surgery.

Corresponding Author: Gonzalo Sapisochin, MD, PhD, MSc, Abdominal Transplant & HPB Surgical Oncology, Ajmera Transplant Center, Division of General Surgery, Toronto General Hospital, University of Toronto, 585 University Ave, 11PMB184, Toronto, M5G 2N2, ON, Canada (gonzalo.sapisochin@uhn.ca).

Author Contributions: Drs Hernandez-Alejandro and Ruffolo had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Hernandez-Alejandro, Ruffolo, Sasaki, Tomiyama, Dokus, McGilvray, Ghanekar, Gallinger, Burkes, Hashimoto, Fujiki, Quintini, Menon, Aucejo, Sapisochin.

Acquisition, analysis, or interpretation of data: Hernandez-Alejandro, Ruffolo, Sasaki, Tomiyama, Orloff, Pineda-Solis, Nair, Errigo, Dokus, Cattral, Selzner, Claasen, Fujiki, Estfan, Kwon, Sapisochin.

Drafting of the manuscript: Hernandez-Alejandro, Ruffolo, Sasaki, Errigo, Cattral, Claasen, Menon.

Critical revision of the manuscript for important intellectual content: Hernandez-Alejandro, Ruffolo, Sasaki, Tomiyama, Orloff, Pineda-Solis, Nair, Dokus, Cattral, McGilvray, Ghanekar, Gallinger, Selzner, Claasen, Burkes, Hashimoto, Fujiki, Quintini, Estfan, Kwon, Aucejo, Sapisochin.

Statistical analysis: Hernandez-Alejandro, Ruffolo, Fujiki, Quintini.

Administrative, technical, or material support: Hernandez-Alejandro, Ruffolo, Orloff, Nair, Errigo, Dokus, McGilvray, Ghanekar, Selzner, Claasen, Burkes.

Supervision: Hernandez-Alejandro, Ruffolo, Sasaki, Tomiyama, Pineda-Solis, Gallinger, Menon, Aucejo, Sapisochin.

Conflict of Interest Disclosures: Dr Kwon reported receiving grants from Medtronic, Integra LifeSciences, Olympus, Fujifilm, and Ethicon outside the submitted work. Dr Sapisochin reported receiving grants from Roche and Bayer and personal fees from Integra, Roche, AstraZeneca, and Novartis outside the submitted work. No other disclosures were reported.

References
1.
Steele  G  Jr, Ravikumar  TS.  Resection of hepatic metastases from colorectal cancer. Biologic perspective.   Ann Surg. 1989;210(2):127-138. doi:10.1097/00000658-198908000-00001PubMedGoogle ScholarCrossref
2.
Bray  F, Ferlay  J, Soerjomataram  I, Siegel  RL, Torre  LA, Jemal  A.  Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.   CA Cancer J Clin. 2018;68(6):394-424. doi:10.3322/caac.21492PubMedGoogle ScholarCrossref
3.
Bismuth  H, Adam  R, Lévi  F,  et al.  Resection of nonresectable liver metastases from colorectal cancer after neoadjuvant chemotherapy.   Ann Surg. 1996;224(4):509-520. doi:10.1097/00000658-199610000-00009PubMedGoogle ScholarCrossref
4.
Garden  OJ, Rees  M, Poston  GJ,  et al.  Guidelines for resection of colorectal cancer liver metastases.   Gut. 2006;55(suppl 3):iii1-iii8. doi:10.1136/gut.2006.098053PubMedGoogle ScholarCrossref
5.
Cremolini  C, Casagrande  M, Loupakis  F,  et al.  Efficacy of FOLFOXIRI plus bevacizumab in liver-limited metastatic colorectal cancer: a pooled analysis of clinical studies by Gruppo Oncologico del Nord Ovest.   Eur J Cancer. 2017;73:74-84. doi:10.1016/j.ejca.2016.10.028PubMedGoogle ScholarCrossref
6.
Dueland  S, Guren  TK, Hagness  M,  et al.  Chemotherapy or liver transplantation for nonresectable liver metastases from colorectal cancer?   Ann Surg. 2015;261(5):956-960. doi:10.1097/SLA.0000000000000786PubMedGoogle ScholarCrossref
7.
Scientific Registry of Transplant Recipients. OPTN/SRTR 2019 annual data report: liver. Health Resources and Services Administration. Accessed July 15, 2021. https://srtr.transplant.hrsa.gov/annual_reports/2019/Liver.aspx
8.
Kwong  AJ, Kim  WR, Lake  JR,  et al.  OPTN/SRTR 2019 Annual Data Report: Liver.   Am J Transplant. 2021;21(suppl 2):208-315. doi:10.1111/ajt.16494PubMedGoogle ScholarCrossref
9.
Ishaque  T, Massie  AB, Bowring  MG,  et al.  Liver transplantation and waitlist mortality for HCC and non-HCC candidates following the 2015 HCC exception policy change.   Am J Transplant. 2019;19(2):564-572. doi:10.1111/ajt.15144PubMedGoogle ScholarCrossref
10.
Reichman  TW, Katchman  H, Tanaka  T,  et al.  Living donor versus deceased donor liver transplantation: a surgeon-matched comparison of recipient morbidity and outcomes.   Transpl Int. 2013;26(8):780-787. doi:10.1111/tri.12127PubMedGoogle ScholarCrossref
11.
Lai  Q, Sapisochin  G, Gorgen  A,  et al.  Evaluation of the intention-to-treat benefit of living donation in patients with hepatocellular carcinoma awaiting a liver transplant.   JAMA Surg. 2021;156(9):e213112. Published online September 8, 2021. doi:10.1001/jamasurg.2021.3112
ArticlePubMedGoogle Scholar
12.
Bonney  GK, Chew  CA, Lodge  P,  et al.  Liver transplantation for non-resectable colorectal liver metastases: the International Hepato-Pancreato-Biliary Association consensus guidelines.   Lancet Gastroenterol Hepatol. 2021;6(11):933-946. doi:10.1016/S2468-1253(21)00219-3PubMedGoogle ScholarCrossref
13.
Dueland  S, Syversveen  T, Solheim  JM,  et al.  Survival following liver transplantation for patients with nonresectable liver-only colorectal metastases.   Ann Surg. 2020;271(2):212-218. doi:10.1097/SLA.0000000000003404PubMedGoogle ScholarCrossref
14.
Hagness  M, Foss  A, Line  PD,  et al.  Liver transplantation for nonresectable liver metastases from colorectal cancer.   Ann Surg. 2013;257(5):800-806. doi:10.1097/SLA.0b013e3182823957PubMedGoogle ScholarCrossref
15.
Fong  Y, Fortner  J, Sun  RL, Brennan  MF, Blumgart  LH.  Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases.   Ann Surg. 1999;230(3):309-318. doi:10.1097/00000658-199909000-00004PubMedGoogle ScholarCrossref
16.
Line  P-D, Dueland  S.  Liver transplantation for secondary liver tumours: The difficult balance between survival and recurrence.   J Hepatol. 2020;73(6):1557-1562. doi:10.1016/j.jhep.2020.08.015PubMedGoogle ScholarCrossref
17.
Dueland  S, Grut  H, Syversveen  T, Hagness  M, Line  P-D.  Selection criteria related to long-term survival following liver transplantation for colorectal liver metastasis.   Am J Transplant. 2020;20(2):530-537. doi:10.1111/ajt.15682PubMedGoogle ScholarCrossref
18.
Dankner  M.  Targeted therapy for colorectal cancers with non-V600 BRAF mutations: perspectives for precision oncology.   JCO Precis Oncol. 2018;2(2):1-12. doi:10.1200/PO.18.00195PubMedGoogle Scholar
19.
Amaki-Takao  M, Yamaguchi  T, Natsume  S,  et al.  Colorectal cancer with BRAF D594G mutation is not associated with microsatellite instability or poor prognosis.   Oncology. 2016;91(3):162-170. doi:10.1159/000447402PubMedGoogle ScholarCrossref
20.
Pomfret  EA, Lodge  JPA, Villamil  FG, Siegler  M.  Should we use living donor grafts for patients with hepatocellular carcinoma? ethical considerations.   Liver Transpl. 2011;17(suppl 2):S128-S132. doi:10.1002/lt.22356PubMedGoogle ScholarCrossref
21.
Sapisochin  G, Hibi  T, Toso  C,  et al.  Transplant oncology in primary and metastatic liver tumors: principles, evidence, and opportunities.   Ann Surg. 2021;273(3):483-493. doi:10.1097/SLA.0000000000004071PubMedGoogle ScholarCrossref

 








Plaats een reactie ...

Reageer op "Complete leveroperatie en levertransplantatie via levende donor geeft bij vooraf geselecteerde darmkankerpatienten met beperkte leveruitzaaiingen hele goede resultaten"


Gerelateerde artikelen
 

Gerelateerde artikelen

Personalised medicin en gerichte >> Studiepublicaties van niet-toxische >> ESMO 2022. Aanbevolen abstracten >> UEG oktober 2020: Abstracten >> ASCO 2020: aanbevolen abstracten >> Aanvullende niet toxische >> Aflibercept (Zaltrap) toegevoegd >> Avastin - bevacizumab de >> Bestraling - radiotherapie >> Chemo bij darmkanker: een >>