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

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

doi:10.1016/j.ejca.2024.114185

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

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

^*Corresponding author for this work

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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.

Original language	English
Article number	114185
Journal	European Journal of Cancer
Volume	207
Early online date	23 Jun 2024
DOIs	https://doi.org/10.1016/j.ejca.2024.114185
Publication status	Published - Aug 2024

Keywords

Colorectal cancer
Liver metastases
Systemic therapy
Local treatment tumor volume
Prognostic marker

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PIIS0959804924008414Final published version, 2.72 MBLicence: CC BY

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Michiel Zeeuw, J., Wesdorp, N. J., Ali, M., Bakker, A. J. J. J., Voigt, K. R., Starmans, M. P. A., Roor, J., Kemna, R., van Waesberghe, J. H. T. M., van den Bergh, J. E., Nota, I. M. G. C., Moos, S. I., van Dieren, S., van Amerongen, M. J., Bond, M. J. G., Chapelle, T., van Dam, R. M., Engelbrecht, M. R. W., Gerhards, M. F., ... Kazemier, G. (2024). Prognostic value of total tumor volume in patients with colorectal liver metastases: A secondary analysis of the randomized CAIRO5 trial with external cohort validation. European Journal of Cancer, 207, Article 114185. https://doi.org/10.1016/j.ejca.2024.114185

@article{0ec4583739374dfea025a40c942dab95,

title = "Prognostic value of total tumor volume in patients with colorectal liver metastases: A secondary analysis of the randomized CAIRO5 trial with external cohort validation",

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.",

keywords = "Colorectal cancer, Liver metastases, Systemic therapy, Local treatment tumor volume, Prognostic marker",

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

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2024",

month = aug,

doi = "10.1016/j.ejca.2024.114185",

language = "English",

volume = "207",

journal = "European Journal of Cancer",

issn = "0959-8049",

publisher = "Elsevier Limited",

}

Michiel Zeeuw, J, Wesdorp, NJ, Ali, M, Bakker, AJJJ, Voigt, KR, Starmans, MPA, Roor, J, Kemna, R, van Waesberghe, JHTM, van den Bergh, JE, Nota, IMGC, Moos, SI, van Dieren, S, van Amerongen, MJ, Bond, MJG, Chapelle, T, van Dam, RM, Engelbrecht, MRW, Gerhards, MF, van Gulik, TM, Hermans, JJ, de Jong, KP, Klaase, JM, Kok, NFM, Leclercq, WKG, Liem, MSL, van Lienden, KP, Quintus Molenaar, I, Patijn, GA, Rijken, AM, Ruers, TM, de Wilt, JHW, Verpalen, IM, Stoker, J, Grunhagen, DJ, Swijnenburg, RJ, Punt, CJA, Huiskens, J, Verhoef, C & Kazemier, G 2024, 'Prognostic value of total tumor volume in patients with colorectal liver metastases: A secondary analysis of the randomized CAIRO5 trial with external cohort validation', European Journal of Cancer, vol. 207, 114185. https://doi.org/10.1016/j.ejca.2024.114185

TY - JOUR

T1 - Prognostic value of total tumor volume in patients with colorectal liver metastases

T2 - A secondary analysis of the randomized CAIRO5 trial with external cohort validation

AU - Michiel Zeeuw, J.

AU - Wesdorp, Nina J.

AU - Ali, Mahsoem

AU - Bakker, Anne Joëlle J.J.

AU - Voigt, Kelly R.

AU - Starmans, Martijn P.A.

AU - Roor, Joran

AU - Kemna, Ruby

AU - van Waesberghe, Jan Hein T.M.

AU - van den Bergh, Janneke E.

AU - Nota, Irene M.G.C.

AU - Moos, Shira I.

AU - van Dieren, Susan

AU - van Amerongen, Martinus J.

AU - Bond, Marinde J.G.

AU - Chapelle, Thiery

AU - van Dam, Ronald M.

AU - Engelbrecht, Marc R.W.

AU - Gerhards, Michael F.

AU - van Gulik, Thomas M.

AU - Hermans, John J.

AU - de Jong, Koert P.

AU - Klaase, Joost M.

AU - Kok, Niels F.M.

AU - Leclercq, Wouter K.G.

AU - Liem, Mike S.L.

AU - van Lienden, Krijn P.

AU - Quintus Molenaar, I.

AU - Patijn, Gijs A.

AU - Rijken, Arjen M.

AU - Ruers, Theo M.

AU - de Wilt, Johannes H.W.

AU - Verpalen, Inez M.

AU - Stoker, Jaap

AU - Grunhagen, Dirk J.

AU - Swijnenburg, Rutger Jan

AU - Punt, Cornelis J.A.

AU - Huiskens, Joost

AU - Verhoef, Cornelis

AU - Kazemier, Geert

PY - 2024/8

Y1 - 2024/8

N2 - 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.

AB - 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.

KW - Colorectal cancer

KW - Liver metastases

KW - Systemic therapy

KW - Local treatment tumor volume

KW - Prognostic marker

UR - http://www.scopus.com/inward/record.url?scp=85196830712&partnerID=8YFLogxK

U2 - 10.1016/j.ejca.2024.114185

DO - 10.1016/j.ejca.2024.114185

M3 - Article

C2 - 38924855

SN - 0959-8049

VL - 207

JO - European Journal of Cancer

JF - European Journal of Cancer

M1 - 114185

ER -

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

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