Vollständiges pathologisches Ansprechen auf Pembrolizumab nach Ex-vivo-Leberresektion bei einer Patientin mit Lebermetastasen eines kolorektalen Karzinoms

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Abstract

Fortschritte bei der systemischen Behandlung des kolorektalen Karzinoms im Stadium IV mit Lebermetastasen haben zu höheren Überlebensraten geführt, nachdem die Prognose für die Patienten zuvor verheerend war. Ein vollständiges Ansprechen laut histopathologischem Befund (pCR) ist bei chemotherapeutisch behandelten Lebermetastasen eines kolorektalen Karzinoms jedoch weiterhin selten, und auch seine Bedeutung ist noch nicht vollständig geklärt. Wir beschreiben hier den Fall einer Patientin, die nach neoadjuvanter Immuntherapie mit Pembrolizumab und linksseitiger Ex-vivo-Hemihepatektomie ein pCR erreichte.

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Most cited references 15

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Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial

Bernard Nordlinger, Halfdan Sorbye, Bengt Glimelius … (2008)

Summary Background Surgical resection alone is regarded as the standard of care for patients with liver metastases from colorectal cancer, but relapse is common. We assessed the combination of perioperative chemotherapy and surgery compared with surgery alone for patients with initially resectable liver metastases from colorectal cancer. Methods This parallel-group study reports the trial's final data for progression-free survival for a protocol unspecified interim time-point, while overall survival is still being monitored. 364 patients with histologically proven colorectal cancer and up to four liver metastases were randomly assigned to either six cycles of FOLFOX4 before and six cycles after surgery or to surgery alone (182 in perioperative chemotherapy group vs 182 in surgery group). Patients were centrally randomised by minimisation, adjusting for centre and risk score. The primary objective was to detect a hazard ratio (HR) of 0·71 or less for progression-free survival. Primary analysis was by intention to treat. Analyses were repeated for all eligible (171 vs 171) and resected patients (151 vs 152). This trial is registered with ClinicalTrials.gov, number NCT00006479. Findings In the perioperative chemotherapy group, 151 (83%) patients were resected after a median of six (range 1–6) preoperative cycles and 115 (63%) patients received a median six (1–8) postoperative cycles. 152 (84%) patients were resected in the surgery group. The absolute increase in rate of progression-free survival at 3 years was 7·3% (from 28·1% [95·66% CI 21·3–35·5] to 35·4% [28·1–42·7]; HR 0·79 [0·62–1·02]; p=0·058) in randomised patients; 8·1% (from 28·1% [21·2–36·6] to 36·2% [28·7–43·8]; HR 0·77 [0·60–1·00]; p=0·041) in eligible patients; and 9·2% (from 33·2% [25·3–41·2] to 42·4% [34·0–50·5]; HR 0·73 [0·55–0·97]; p=0·025) in patients undergoing resection. 139 patients died (64 in perioperative chemotherapy group vs 75 in surgery group). Reversible postoperative complications occurred more often after chemotherapy than after surgery (40/159 [25%] vs 27/170 [16%]; p=0·04). After surgery we recorded two deaths in the surgery alone group and one in the perioperative chemotherapy group. Interpretation Perioperative chemotherapy with FOLFOX4 is compatible with major liver surgery and reduces the risk of events of progression-free survival in eligible and resected patients. Funding Swedish Cancer Society, Cancer Research UK, Ligue Nationale Contre le Cancer, US National Cancer Institute, Sanofi-Aventis.

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Effect of surgical margin status on survival and site of recurrence after hepatic resection for colorectal metastases.

Timothy Pawlik, Charles R Scoggins, Daria Zorzi … (2005)

To evaluate the influence of surgical margin status on survival and site of recurrence in patients treated with hepatic resection for colorectal metastases. Using a multicenter database, 557 patients who underwent hepatic resection for colorectal metastases were identified. Demographics, operative data, pathologic margin status, site of recurrence (margin, other intrahepatic site, extrahepatic), and long-term survival data were collected and analyzed. On final pathologic analysis, margin status was positive in 45 patients, and negative by 1 to 4 mm in 129, 5 to 9 mm in 85, and > or =1 cm in 298. At a median follow-up of 29 months, the 1-, 3-, and 5-year actuarial survival rates were 97%, 74%, and 58%; median survival was 74 months. Tumor size > or =5 cm, >3 tumor nodules, and carcinoembryonic antigen level >200 ng/mL predicted poor survival (all P or =1 cm had similar overall recurrence rates (P > 0.05). Patients with positive margins were more likely to have surgical margin recurrence (P = 0.003). Adverse preoperative biologic factors including tumor number greater than 3 (P = 0.01) and a preoperative CEA level greater than 200 ng/mL (P = 0.04) were associated with an increased risk of positive surgical margin. A positive margin after resection of hepatic colorectal metastases is associated with adverse biologic factors and increased risk of surgical-margin recurrence. The width of a negative surgical margin does not affect survival, recurrence risk, or site of recurrence. A predicted margin of <1 cm after resection of hepatic colorectal metastases should not be used as an exclusion criterion for resection.

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Neoadjuvant treatment of unresectable colorectal liver metastases: correlation between tumour response and resection rates.

G Folprecht, A. Grothey, S. Alberts … (2005)

Long-term survival is reported in patients with liver metastases of colorectal cancer. Recently, an increased number of reports on liver resection following neoadjuvant chemotherapy in patients with initially unresectable liver metastases has been published. We analysed all published or presented trials and retrospective studies that report the rate of objective response and the rate of resection of initially unresectable metastases to correlate objective response and the rate of resection of metastases. In studies that enrolled patients with metastases confined to the liver, 24-54% of patients were resected following chemotherapy, compared to 1-26% of patients in trials that included non-selected patients with metastatic colorectal cancer. A strong correlation was found between response rates and the resection rate in studies with patients with isolated liver metastases (r = 0.96, P=0.002). Likewise, in studies with non-selected patients, the resection rate of metastases also was associated with the objective response rate (r = 0.74, P <0.001). Patient selection and efficacy of pre-operative chemotherapy are both strong predictors for resectability of liver metastases. Resectability is a novel endpoint focusing on the curative potential of treatment compared with classical endpoints of response or progression-free survival that are important if palliation is the aim. Therefore, patients with potentially resectable liver metastases should be investigated in special trials and interdisciplinary teams.

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Journal ID (publisher-id): KKO

Journal ID (doi): 10.1159/issn.2296-5416

Title: Karger Kompass Onkologie

Publisher: S. Karger AG

ISSN (Print): 2296-5416

ISSN (Electronic): 2296-5386

Publication date Subscription-year: 2019

Publication date (Print): May 2019

Publication date (Electronic): 27 May 2019

Volume: 6

Issue: 2

Pages: 115-119

Affiliations

^a Department of General Surgery, Carolinas Medical Center, Carolinas Healthcare Systems, Charlotte, NC, USA; ^bDepartment of Hepatopancreatobiliary Surgery, Carolinas Medical Center, Carolinas Healthcare Systems, Charlotte, NC, USA; ^cDepartment of Pathology, Carolinas Medical Center, Carolinas Healthcare Systems, Charlotte, NC, USA; ^dDepartment of Medical Oncology, Carolinas Medical Center, Carolinas Healthcare Systems, Charlotte, NC, USA; ^eDepartment of Transplant Surgery, Carolinas Medical Center, Carolinas Healthcare Systems, Charlotte, NC, USA

Article

Publisher ID: 500174 Other ID: Karger Kompass Onkol 2019;6:115-119

DOI: 10.1159/000500174

SO-VID: 85fed963-2c59-41aa-bda9-3826092d54f0

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Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

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Vollständiges pathologisches Ansprechen auf Pembrolizumab nach Ex-vivo-Leberresektion bei einer Patientin mit Lebermetastasen eines kolorektalen Karzinoms

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Most cited references 15

Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial

Effect of surgical margin status on survival and site of recurrence after hepatic resection for colorectal metastases.

Neoadjuvant treatment of unresectable colorectal liver metastases: correlation between tumour response and resection rates.

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