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1. Prognostic value of total tumor volume in patients with colorectal liver metastases: A secondary analysis of the randomized CAIRO5 trial with external cohort validation

Author

Hart- en Vaatziekten Team A, Epi Kanker Team B, Cancer, MS CGO, Zorgeenheid Kinderchirurgie Medisch, Researchgr. Beeldg. Moleculaire Interv., Michiel Zeeuw, J., Wesdorp, Nina J., Ali, Mahsoem, Bakker, Anne Joëlle J.J., Voigt, Kelly R., Starmans, Martijn P.A., Roor, Joran, Kemna, Ruby, van Waesberghe, Jan Hein T.M., van den Bergh, Janneke E., Nota, Irene M.G.C., Moos, Shira I., van Dieren, Susan, van Amerongen, Martinus J., Bond, Marinde J.G., Chapelle, Thiery, van Dam, Ronald M., Engelbrecht, Marc R.W., Gerhards, Michael F., van Gulik, Thomas M., Hermans, John J., de Jong, Koert P., Klaase, Joost M., Kok, Niels F.M., Leclercq, Wouter K.G., Liem, Mike S.L., van Lienden, Krijn P., Quintus Molenaar, I., Patijn, Gijs A., Rijken, Arjen M., Ruers, Theo M., de Wilt, Johannes H.W., Verpalen, Inez M., Stoker, Jaap, Grunhagen, Dirk J., Swijnenburg, Rutger Jan, Punt, Cornelis J.A., Huiskens, Joost, Verhoef, Cornelis, Kazemier, Geert, Hart- en Vaatziekten Team A, Epi Kanker Team B, Cancer, MS CGO, Zorgeenheid Kinderchirurgie Medisch, Researchgr. Beeldg. Moleculaire Interv., Michiel Zeeuw, J., Wesdorp, Nina J., Ali, Mahsoem, Bakker, Anne Joëlle J.J., Voigt, Kelly R., Starmans, Martijn P.A., Roor, Joran, Kemna, Ruby, van Waesberghe, Jan Hein T.M., van den Bergh, Janneke E., Nota, Irene M.G.C., Moos, Shira I., van Dieren, Susan, van Amerongen, Martinus J., Bond, Marinde J.G., Chapelle, Thiery, van Dam, Ronald M., Engelbrecht, Marc R.W., Gerhards, Michael F., van Gulik, Thomas M., Hermans, John J., de Jong, Koert P., Klaase, Joost M., Kok, Niels F.M., Leclercq, Wouter K.G., Liem, Mike S.L., van Lienden, Krijn P., Quintus Molenaar, I., Patijn, Gijs A., Rijken, Arjen M., Ruers, Theo M., de Wilt, Johannes H.W., Verpalen, Inez M., Stoker, Jaap, Grunhagen, Dirk J., Swijnenburg, Rutger Jan, Punt, Cornelis J.A., Huiskens, Joost, Verhoef, Cornelis, and Kazemier, Geert

Published
2024

2. Prognostic value of total tumor volume in patients with colorectal liver metastases:A secondary analysis of the randomized CAIRO5 trial with external cohort validation

Author

Michiel Zeeuw, J., Wesdorp, Nina J., Ali, Mahsoem, Bakker, Anne Joëlle J.J., Voigt, Kelly R., Starmans, Martijn P.A., Roor, Joran, Kemna, Ruby, van Waesberghe, Jan Hein T.M., van den Bergh, Janneke E., Nota, Irene M.G.C., Moos, Shira I., van Dieren, Susan, van Amerongen, Martinus J., Bond, Marinde J.G., Chapelle, Thiery, van Dam, Ronald M., Engelbrecht, Marc R.W., Gerhards, Michael F., van Gulik, Thomas M., Hermans, John J., de Jong, Koert P., Klaase, Joost M., Kok, Niels F.M., Leclercq, Wouter K.G., Liem, Mike S.L., van Lienden, Krijn P., Quintus Molenaar, I., Patijn, Gijs A., Rijken, Arjen M., Ruers, Theo M., de Wilt, Johannes H.W., Verpalen, Inez M., Stoker, Jaap, Grunhagen, Dirk J., Swijnenburg, Rutger Jan, Punt, Cornelis J.A., Huiskens, Joost, Verhoef, Cornelis, Kazemier, Geert, Michiel Zeeuw, J., Wesdorp, Nina J., Ali, Mahsoem, Bakker, Anne Joëlle J.J., Voigt, Kelly R., Starmans, Martijn P.A., Roor, Joran, Kemna, Ruby, van Waesberghe, Jan Hein T.M., van den Bergh, Janneke E., Nota, Irene M.G.C., Moos, Shira I., van Dieren, Susan, van Amerongen, Martinus J., Bond, Marinde J.G., Chapelle, Thiery, van Dam, Ronald M., Engelbrecht, Marc R.W., Gerhards, Michael F., van Gulik, Thomas M., Hermans, John J., de Jong, Koert P., Klaase, Joost M., Kok, Niels F.M., Leclercq, Wouter K.G., Liem, Mike S.L., van Lienden, Krijn P., Quintus Molenaar, I., Patijn, Gijs A., Rijken, Arjen M., Ruers, Theo M., de Wilt, Johannes H.W., Verpalen, Inez M., Stoker, Jaap, Grunhagen, Dirk J., Swijnenburg, Rutger Jan, Punt, Cornelis J.A., Huiskens, Joost, Verhoef, Cornelis, and Kazemier, Geert

Abstract

Background:This study aimed to assess the prognostic value of total tumor volume (TTV) for early recurrence (within 6 months) and overall survival (OS) in patients with colorectal liver metastases (CRLM), treated with induction systemic therapy followed by complete local treatment.Methods: Patients with initially unresectable CRLM from the multicenter randomized phase 3 CAIRO5 trial (NCT02162563) who received induction systemic therapy followed by local treatment were included. Baseline TTV and change in TTV as response to systemic therapy were calculated using the CT scan before and the first after systemic treatment, and were assessed for their added prognostic value. The findings were validated in an external cohort of patients treated at a tertiary center. Results:In total, 215 CAIRO5 patients were included. Baseline TTV and absolute change in TTV were significantly associated with early recurrence (P = 0.005 and P = 0.040, respectively) and OS in multivariable analyses (P = 0.024 and P = 0.006, respectively), whereas RECIST1.1 was not prognostic for early recurrence (P = 0.88) and OS (P = 0.35). In the validation cohort (n = 85), baseline TTV and absolute change in TTV remained prognostic for early recurrence (P = 0.041 and P = 0.021, respectively) and OS in multivariable analyses (P < 0.0001 and P = 0.012, respectively), and showed added prognostic value over conventional clinicopathological variables (increase C-statistic, 0.06; 95 % CI, 0.02 to 0.14; P = 0.008). Conclusion: Total tumor volume is strongly prognostic for early recurrence and OS in patients who underwent complete local treatment of initially unresectable CRLM, both in the CAIRO5 trial and the validation cohort. In contrast, RECIST1.1 did not show prognostic value for neither early recurrence nor OS.

Published
2024

3. Deep learning models for automatic tumor segmentation and total tumor volume assessment in patients with colorectal liver metastases

Author

Wesdorp, Nina J., Zeeuw, J. Michiel, Postma, Sam C.J., Roor, Joran, van Waesberghe, Jan Hein T.M., van den Bergh, Janneke E., Nota, Irene M., Moos, Shira, Kemna, Ruby, Vadakkumpadan, Fijoy, Ambrozic, Courtney, van Dieren, Susan, van Amerongen, Martinus J., Chapelle, Thiery, Engelbrecht, Marc R.W., Gerhards, Michael F., Grunhagen, Dirk, van Gulik, Thomas M., Hermans, John J., de Jong, Koert P., Klaase, Joost M., Liem, Mike S.L., van Lienden, Krijn P., Molenaar, I. Quintus, Patijn, Gijs A., Rijken, Arjen M., Ruers, Theo M., Verhoef, Cornelis, de Wilt, Johannes H.W., Marquering, Henk A., Stoker, Jaap, Swijnenburg, Rutger Jan, Punt, Cornelis J.A., Huiskens, Joost, Kazemier, Geert, Wesdorp, Nina J., Zeeuw, J. Michiel, Postma, Sam C.J., Roor, Joran, van Waesberghe, Jan Hein T.M., van den Bergh, Janneke E., Nota, Irene M., Moos, Shira, Kemna, Ruby, Vadakkumpadan, Fijoy, Ambrozic, Courtney, van Dieren, Susan, van Amerongen, Martinus J., Chapelle, Thiery, Engelbrecht, Marc R.W., Gerhards, Michael F., Grunhagen, Dirk, van Gulik, Thomas M., Hermans, John J., de Jong, Koert P., Klaase, Joost M., Liem, Mike S.L., van Lienden, Krijn P., Molenaar, I. Quintus, Patijn, Gijs A., Rijken, Arjen M., Ruers, Theo M., Verhoef, Cornelis, de Wilt, Johannes H.W., Marquering, Henk A., Stoker, Jaap, Swijnenburg, Rutger Jan, Punt, Cornelis J.A., Huiskens, Joost, and Kazemier, Geert

Abstract

Background: We developed models for tumor segmentation to automate the assessment of total tumor volume (TTV) in patients with colorectal liver metastases (CRLM). Methods:In this prospective cohort study, pre- and post-systemic treatment computed tomography (CT) scans of 259 patients with initially unresectable CRLM of the CAIRO5 trial (NCT02162563) were included. In total, 595 CT scans comprising 8,959 CRLM were divided into training (73%), validation (6.5%), and test sets (21%). Deep learning models were trained with ground truth segmentations of the liver and CRLM. TTV was calculated based on the CRLM segmentations. An external validation cohort was included, comprising 72 preoperative CT scans of patients with 112 resectable CRLM. Image segmentation evaluation metrics and intraclass correlation coefficient (ICC) were calculated. Results:In the test set (122 CT scans), the autosegmentation models showed a global Dice similarity coefficient (DSC) of 0.96 (liver) and 0.86 (CRLM). The corresponding median per-case DSC was 0.96 (interquartile range [IQR] 0.95–0.96) and 0.80 (IQR 0.67–0.87). For tumor segmentation, the intersection-over-union, precision, and recall were 0.75, 0.89, and 0.84, respectively. An excellent agreement was observed between the reference and automatically computed TTV for the test set (ICC 0.98) and external validation cohort (ICC 0.98). In the external validation, the global DSC was 0.82 and the median per-case DSC was 0.60 (IQR 0.29–0.76) for tumor segmentation. Conclusions: Deep learning autosegmentation models were able to segment the liver and CRLM automatically and accurately in patients with initially unresectable CRLM, enabling automatic TTV assessment in such patients. Relevance statement: Automatic segmentation enables the assessment of total tumor volume in patients with colorectal liver metastases, with a high potential of decreasing radiologist’s workl

Published
2023

4. Intersurgeon Variability in Local Treatment Planning for Patients with Initially Unresectable Colorectal Cancer Liver Metastases:Analysis of the Liver Expert Panel of the Dutch Colorectal Cancer Group

Author

Bond, Marinde J.G., Kuiper, Babette I., Bolhuis, Karen, Komurcu, Aysun, van Amerongen, Martinus J., Chapelle, Thiery, Dejong, Cornelis H.C., Engelbrecht, Marc R.W., Gerhards, Michael F., Grünhagen, Dirk J., van Gulik, Thomas, Hermans, John J., de Jong, Koert P., Klaase, Joost M., Kok, Niels F.M., Leclercq, Wouter K.G., Liem, Mike S.L., van Lienden, Krijn P., Molenaar, I. Quintus, Neumann, Ulf P., Patijn, Gijs A., Rijken, Arjen M., Ruers, Theo M., Verhoef, Cornelis, de Wilt, Johannes H.W., Kazemier, Geert, May, Anne M., Punt, Cornelis J.A., Swijnenburg, Rutger Jan, Bond, Marinde J.G., Kuiper, Babette I., Bolhuis, Karen, Komurcu, Aysun, van Amerongen, Martinus J., Chapelle, Thiery, Dejong, Cornelis H.C., Engelbrecht, Marc R.W., Gerhards, Michael F., Grünhagen, Dirk J., van Gulik, Thomas, Hermans, John J., de Jong, Koert P., Klaase, Joost M., Kok, Niels F.M., Leclercq, Wouter K.G., Liem, Mike S.L., van Lienden, Krijn P., Molenaar, I. Quintus, Neumann, Ulf P., Patijn, Gijs A., Rijken, Arjen M., Ruers, Theo M., Verhoef, Cornelis, de Wilt, Johannes H.W., Kazemier, Geert, May, Anne M., Punt, Cornelis J.A., and Swijnenburg, Rutger Jan

Abstract

Background: Consensus on resectability criteria for colorectal cancer liver metastases (CRLM) is lacking, resulting in differences in therapeutic strategies. This study evaluated variability of resectability assessments and local treatment plans for patients with initially unresectable CRLM by the liver expert panel from the randomised phase III CAIRO5 study. Methods: The liver panel, comprising surgeons and radiologists, evaluated resectability by predefined criteria at baseline and 2-monthly thereafter. If surgeons judged CRLM as resectable, detailed local treatment plans were provided. The panel chair determined the conclusion of resectability status and local treatment advice, and forwarded it to local surgeons. Results: A total of 1149 panel evaluations of 496 patients were included. Intersurgeon disagreement was observed in 50% of evaluations and was lower at baseline than follow-up (36% vs. 60%, p < 0.001). Among surgeons in general, votes for resectable CRLM at baseline and follow-up ranged between 0–12% and 27–62%, and for permanently unresectable CRLM between 3–40% and 6–47%, respectively. Surgeons proposed different local treatment plans in 77% of patients. The most pronounced intersurgeon differences concerned the advice to proceed with hemihepatectomy versus parenchymal-preserving approaches. Eighty-four percent of patients judged by the panel as having resectable CRLM indeed received local treatment. Local surgeons followed the technical plan proposed by the panel in 40% of patients. Conclusion: Considerable variability exists among expert liver surgeons in assessing resectability and local treatment planning of initially unresectable CRLM. This stresses the value of panel-based decisions, and the need for consensus guidelines on resectability criteria and technical approach to prevent unwarranted variability in clinical practice.

Published
2023

5. The role of tumour biological factors in technical anatomical resectability assessment of colorectal liver metastases following induction systemic treatment:An analysis of the Dutch CAIRO5 trial

Author

Bolhuis, Karen, Bond, Marinde J.G., Van Amerongen, Martin J., Komurcu, Aysun, Chapelle, Thiery, Dejong, Cornelis H.C., Engelbrecht, Marc R.W., Gerhards, Michael F., Grünhagen, Dirk J., van Gulik, Thomas M., Hermans, John J., De Jong, Koert P., Kazemier, Geert, Klaase, Joost M., Kok, Niels F.M., Leclercq, Wouter K.G., Liem, Mike S.L., van Lienden, Krijn P., Molenaar, I. Quintus, Neumann, Ulf P., Patijn, Gijs A., Rijken, Arjen M., Ruers, Theo M., Verhoef, Cornelis, de Wilt, Johannes H.W., May, Anne M., Punt, Cornelis J.A., Swijnenburg, Rutger Jan, Bolhuis, Karen, Bond, Marinde J.G., Van Amerongen, Martin J., Komurcu, Aysun, Chapelle, Thiery, Dejong, Cornelis H.C., Engelbrecht, Marc R.W., Gerhards, Michael F., Grünhagen, Dirk J., van Gulik, Thomas M., Hermans, John J., De Jong, Koert P., Kazemier, Geert, Klaase, Joost M., Kok, Niels F.M., Leclercq, Wouter K.G., Liem, Mike S.L., van Lienden, Krijn P., Molenaar, I. Quintus, Neumann, Ulf P., Patijn, Gijs A., Rijken, Arjen M., Ruers, Theo M., Verhoef, Cornelis, de Wilt, Johannes H.W., May, Anne M., Punt, Cornelis J.A., and Swijnenburg, Rutger Jan

Abstract

Background: Large inter-surgeon variability exists in technical anatomical resectability assessment of colorectal cancer liver-only metastases (CRLM) following induction systemic therapy. We evaluated the role of tumour biological factors in predicting resectability and (early) recurrence after surgery for initially unresectable CRLM. Methods: 482 patients with initially unresectable CRLM from the phase 3 CAIRO5 trial were selected, with two-monthly resectability assessments by a liver expert panel. If no consensus existed among panel surgeons (i.e. same vote for (un)resectability of CRLM), conclusion was based on majority. The association of tumour biological (sidedness, synchronous CRLM, carcinoembryonic antigen and RAS/BRAFV600E mutation status) and technical anatomical factors with consensus among panel surgeons, secondary resectability and early recurrence (<6 months) without curative-intent repeat local treatment was analysed by uni- and pre-specified multivariable logistic regression. Results: After systemic treatment, 240 (50%) patients received complete local treatment of CRLM of which 75 (31%) patients experienced early recurrence without repeat local treatment. Higher number of CRLM (odds ratio 1.09 [95% confidence interval 1.03–1.15]) and age (odds ratio 1.03 [95% confidence interval 1.00–1.07]) were independently associated with early recurrence without repeat local treatment. In 138 (52%) patients, no consensus among panel surgeons was present prior to local treatment. Postoperative outcomes in patients with and without consensus were comparable. Conclusions: Almost a third of patients selected by an expert panel for secondary CRLM surgery following induction systemic treatment experience an early recurrence only amenable to palliative treatment. Number of CRLM and age, but no tumour biological factors are predictive, suggesting that until there are better biomarkers; resectability assessment remains primarily a technical anatomical de

Published
2023

6. Deep learning models for automatic tumor segmentation and total tumor volume assessment in patients with colorectal liver metastases

Author

MS CGO, Cancer, Epi Kanker Team B, Wesdorp, Nina J., Zeeuw, J. Michiel, Postma, Sam C.J., Roor, Joran, van Waesberghe, Jan Hein T.M., van den Bergh, Janneke E., Nota, Irene M., Moos, Shira, Kemna, Ruby, Vadakkumpadan, Fijoy, Ambrozic, Courtney, van Dieren, Susan, van Amerongen, Martinus J., Chapelle, Thiery, Engelbrecht, Marc R.W., Gerhards, Michael F., Grunhagen, Dirk, van Gulik, Thomas M., Hermans, John J., de Jong, Koert P., Klaase, Joost M., Liem, Mike S.L., van Lienden, Krijn P., Molenaar, I. Quintus, Patijn, Gijs A., Rijken, Arjen M., Ruers, Theo M., Verhoef, Cornelis, de Wilt, Johannes H.W., Marquering, Henk A., Stoker, Jaap, Swijnenburg, Rutger Jan, Punt, Cornelis J.A., Huiskens, Joost, Kazemier, Geert, MS CGO, Cancer, Epi Kanker Team B, Wesdorp, Nina J., Zeeuw, J. Michiel, Postma, Sam C.J., Roor, Joran, van Waesberghe, Jan Hein T.M., van den Bergh, Janneke E., Nota, Irene M., Moos, Shira, Kemna, Ruby, Vadakkumpadan, Fijoy, Ambrozic, Courtney, van Dieren, Susan, van Amerongen, Martinus J., Chapelle, Thiery, Engelbrecht, Marc R.W., Gerhards, Michael F., Grunhagen, Dirk, van Gulik, Thomas M., Hermans, John J., de Jong, Koert P., Klaase, Joost M., Liem, Mike S.L., van Lienden, Krijn P., Molenaar, I. Quintus, Patijn, Gijs A., Rijken, Arjen M., Ruers, Theo M., Verhoef, Cornelis, de Wilt, Johannes H.W., Marquering, Henk A., Stoker, Jaap, Swijnenburg, Rutger Jan, Punt, Cornelis J.A., Huiskens, Joost, and Kazemier, Geert

Published
2023

7. ASO Visual Abstract: Intersurgeon Variability in Local Treatment Planning for Patients with Initially Unresectable Colorectal Cancer Liver Metastases-Analysis of the Liver Expert Panel of the Dutch Colorectal Cancer Group

Author

Epi Kanker Team B, Cancer, MS CGO, Epi Kanker, JC onderzoeksprogramma Kanker, Bond, Marinde J G, Kuiper, Babette I, Bolhuis, Karen, Komurcu, Aysun, van Amerongen, Martinus J, Chapelle, Thiery, Dejong, Cornelis H C, Engelbrecht, Marc R W, Gerhards, Michael F, Grünhagen, Dirk J, van Gulik, Thomas, Hermans, John J, de Jong, Koert P, Klaase, Joost M, Kok, Niels F M, Leclercq, Wouter K G, Liem, Mike S L, van Lienden, Krijn P, Quintus Molenaar, I, Neumann, Ulf P, Patijn, Gijs A, Rijken, Arjen M, Ruers, Theo M, Verhoef, Cornelis, de Wilt, Johannes H W, Kazemier, Geert, May, Anne M, Punt, Cornelis J A, Swijnenburg, Rutger-Jan, Epi Kanker Team B, Cancer, MS CGO, Epi Kanker, JC onderzoeksprogramma Kanker, Bond, Marinde J G, Kuiper, Babette I, Bolhuis, Karen, Komurcu, Aysun, van Amerongen, Martinus J, Chapelle, Thiery, Dejong, Cornelis H C, Engelbrecht, Marc R W, Gerhards, Michael F, Grünhagen, Dirk J, van Gulik, Thomas, Hermans, John J, de Jong, Koert P, Klaase, Joost M, Kok, Niels F M, Leclercq, Wouter K G, Liem, Mike S L, van Lienden, Krijn P, Quintus Molenaar, I, Neumann, Ulf P, Patijn, Gijs A, Rijken, Arjen M, Ruers, Theo M, Verhoef, Cornelis, de Wilt, Johannes H W, Kazemier, Geert, May, Anne M, Punt, Cornelis J A, and Swijnenburg, Rutger-Jan

Published
2023

8. Intersurgeon Variability in Local Treatment Planning for Patients with Initially Unresectable Colorectal Cancer Liver Metastases: Analysis of the Liver Expert Panel of the Dutch Colorectal Cancer Group

Author

Epi Kanker Team B, Cancer, MS CGO, Epi Kanker, JC onderzoeksprogramma Kanker, Bond, Marinde J G, Kuiper, Babette I, Bolhuis, Karen, Komurcu, Aysun, van Amerongen, Martinus J, Chapelle, Thiery, Dejong, Cornelis H C, Engelbrecht, Marc R W, Gerhards, Michael F, Grünhagen, Dirk J, van Gulik, Thomas, Hermans, John J, de Jong, Koert P, Klaase, Joost M, Kok, Niels F M, Leclercq, Wouter K G, Liem, Mike S L, van Lienden, Krijn P, Molenaar, I Quintus, Neumann, Ulf P, Patijn, Gijs A, Rijken, Arjen M, Ruers, Theo M, Verhoef, Cornelis, de Wilt, Johannes H W, Kazemier, Geert, May, Anne M, Punt, Cornelis J A, Swijnenburg, Rutger-Jan, Epi Kanker Team B, Cancer, MS CGO, Epi Kanker, JC onderzoeksprogramma Kanker, Bond, Marinde J G, Kuiper, Babette I, Bolhuis, Karen, Komurcu, Aysun, van Amerongen, Martinus J, Chapelle, Thiery, Dejong, Cornelis H C, Engelbrecht, Marc R W, Gerhards, Michael F, Grünhagen, Dirk J, van Gulik, Thomas, Hermans, John J, de Jong, Koert P, Klaase, Joost M, Kok, Niels F M, Leclercq, Wouter K G, Liem, Mike S L, van Lienden, Krijn P, Molenaar, I Quintus, Neumann, Ulf P, Patijn, Gijs A, Rijken, Arjen M, Ruers, Theo M, Verhoef, Cornelis, de Wilt, Johannes H W, Kazemier, Geert, May, Anne M, Punt, Cornelis J A, and Swijnenburg, Rutger-Jan

Published
2023

9. Interobserver Variability in CT-based Morphologic Tumor Response Assessment of Colorectal Liver Metastases

Author

MS CGO, Cancer, CTC, Wesdorp, Nina J., Kemna, Ruby, Bolhuis, Karen, van Waesberghe, Jan H.T.M., Nota, Irene M.G.C., Struik, Femke, Abdennabi, Ikrame Oulad, Phoa, Saffire S.K.S., van Dieren, Susan, van Amerongen, Martinus J., Chapelle, Thiery, Dejong, Cornelis H.C., Engelbrecht, Marc R.W., Gerhards, Michael F., Grünhagen, Dirk, van Gulik, Thomas M., Hermans, John J., de Jong, Koert P., Klaase, Joost M., Liem, Mike S.L., van Lienden, Krijn P., Molenaar, I Quintus, Patijn, Gijs A., Rijken, Arjen M., Ruers, Theo M., Verhoef, Cornelis, de Wilt, Johannes H.W., Swijnenburg, Rutger Jan, Punt, Cornelis J.A., Huiskens, Joost, Stoker, Jaap, Kazemier, Geert, MS CGO, Cancer, CTC, Wesdorp, Nina J., Kemna, Ruby, Bolhuis, Karen, van Waesberghe, Jan H.T.M., Nota, Irene M.G.C., Struik, Femke, Abdennabi, Ikrame Oulad, Phoa, Saffire S.K.S., van Dieren, Susan, van Amerongen, Martinus J., Chapelle, Thiery, Dejong, Cornelis H.C., Engelbrecht, Marc R.W., Gerhards, Michael F., Grünhagen, Dirk, van Gulik, Thomas M., Hermans, John J., de Jong, Koert P., Klaase, Joost M., Liem, Mike S.L., van Lienden, Krijn P., Molenaar, I Quintus, Patijn, Gijs A., Rijken, Arjen M., Ruers, Theo M., Verhoef, Cornelis, de Wilt, Johannes H.W., Swijnenburg, Rutger Jan, Punt, Cornelis J.A., Huiskens, Joost, Stoker, Jaap, and Kazemier, Geert

Published
2022

10. Short-Term Outcomes of Secondary Liver Surgery for Initially Unresectable Colorectal Liver Metastases following Modern Induction Systemic Therapy in the Dutch CAIRO5 Trial

Author

Bolhuis, Karen, Grosheide, Lodi, Wesdorp, Nina J., Komurcu, Aysun, Chapelle, Thiery, Dejong, Cornelis H.C., Gerhards, Michael F., Grünhagen, Dirk J., Van Gulik, Thomas M., Huiskens, Joost, De Jong, Koert P., Kazemier, Geert, Klaase, Joost M., Liem, Mike S.L., Molenaar, I. Quintus, Patijn, Gijs A., Rijken, Arjen M., Ruers, Theo M., Verhoef, Cornelis, De Wilt, Johannes H.W., Punt, Cornelis J.A., Swijnenburg, Rutger Jan, Bolhuis, Karen, Grosheide, Lodi, Wesdorp, Nina J., Komurcu, Aysun, Chapelle, Thiery, Dejong, Cornelis H.C., Gerhards, Michael F., Grünhagen, Dirk J., Van Gulik, Thomas M., Huiskens, Joost, De Jong, Koert P., Kazemier, Geert, Klaase, Joost M., Liem, Mike S.L., Molenaar, I. Quintus, Patijn, Gijs A., Rijken, Arjen M., Ruers, Theo M., Verhoef, Cornelis, De Wilt, Johannes H.W., Punt, Cornelis J.A., and Swijnenburg, Rutger Jan

Abstract

Objective: To present short-term outcomes of liver surgery in patients with initially unresectable colorectal liver metastases (CRLM) downsized by chemotherapy plus targeted agents. Background: The increase of complex hepatic resections of CRLM, technical innovations pushing boundaries of respectability, and use of intensified induction systemic regimens warrant for safety data in a homogeneous multicenter prospective cohort. Methods: Patients with initially unresectable CRLM, who underwent complete resection after induction systemic regimens with doublet or triplet chemotherapy, both plus targeted therapy, were selected from the ongoing phase III CAIRO5 study (NCT02162563). Short-term outcomes and risk factors for severe postoperative morbidity (Clavien Dindo grade ≥ 3) were analyzed using logistic regression analysis. Results: A total of 173 patients underwent resection of CRLM after induction systemic therapy. The median number of metastases was 9 and 161 (93%) patients had bilobar disease. Thirty-six (20.8%) 2-stage resections and 88 (51%) major resections (>3 liver segments) were performed. Severe postoperative morbidity and 90-day mortality was 15.6% and 2.9%, respectively. After multivariable analysis, blood transfusion (odds ratio [OR] 2.9 [95% confidence interval (CI) 1.1-6.4], P = 0.03), major resection (OR 2.9 [95% CI 1.1-7.5], P = 0.03), and triplet chemotherapy (OR 2.6 [95% CI 1.1-7.5], P = 0.03) were independently correlated with severe postoperative complications. No association was found between number of cycles of systemic therapy and severe complications (r = -0.038, P = 0.31). Conclusion: In patients with initially unresectable CRLM undergoing modern induction systemic therapy and extensive liver surgery, severe postoperative morbidity and 90-day mortality were 15.6% and 2.7%, respectively. Triplet chemotherapy, blood transfusion, and major resections were associated with severe postoperative morbidity.

Published
2021

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