@article{956d116f4e0146ea81ed3b98995d851e,
title = "Association between adjuvant therapy and survival in colorectal cancer patients according to metabolic Warburg-subtypes",
abstract = "PurposeTumor location and tumor node metastasis (TNM) stage guide treatment decisions in colorectal cancer (CRC) patients. However, patients with the same disease stage do not benefit equally from adjuvant therapy. Hence, there remains an urgent clinical need to identify prognostic and/or predictive biomarker(s) to personalize treatment decisions. In this exploratory study, we investigated whether our previously defined metabolic Warburg-subtypes can predict which CRC patients might derive survival benefit from adjuvant therapy.MethodsInformation regarding treatment (surgery only: n = 1451; adjuvant radiotherapy: n = 82; or adjuvant chemotherapy: n = 260) and Warburg-subtype (Warburg-low: n = 485, -moderate: n = 641, or -high: n = 667) was available for 1793 CRC patients from the Netherlands Cohort Study (NLCS). Kaplan-Meier curves and Cox regression models were used to investigate survival benefit from adjuvant therapy compared to surgery-only for the different Warburg-subtypes.ResultsPatients with Warburg-moderate CRC (HRCRC-specific 0.64; 95% CI 0.47-0.86, HRoverall 0.61; 95% CI 0.47-0.80), and possibly Warburg-high CRC (HRCRC-specific 0.86; 95% CI 0.65-1.14, HRoverall 0.82; 95% CI 0.64-1.05), had survival benefit from adjuvant therapy. No survival benefit was observed for patients with Warburg-low CRC (HRCRC-specific 1.07; 95% CI 0.76-1.52, HRoverall 0.95; 95% CI 0.70-1.30). There was a significant interaction between Warburg-subtype and adjuvant therapy for CRC-specific survival (p = 0.049) and overall survival (p = 0.035).ConclusionOur results suggest that Warburg-subtypes may predict survival benefit from adjuvant therapy in CRC patients. A survival benefit from adjuvant therapy was observed for patients with Warburg-moderate and possibly Warburg-high CRC, but not for patients with Warburg-low CRC. Future prospective studies are necessary to validate our findings.",
keywords = "Warburg-effect, Colorectal cancer, Survival, Chemotherapy, Radiotherapy, Adjuvant therapy, COLON-CANCER, RESISTANCE, REQUIREMENTS, NETHERLANDS, BIOMARKERS",
author = "K. Offermans and J.C.A. Jenniskens and C.C.J.M. Simons and I. Samarska and G.E. Fazzi and K.M. Smits and L.J. Schouten and M.P. Weijenberg and H.I. Grabsch and {van den Brandt}, P.A.",
note = "Funding Information: This project was funded by The Dutch Cancer Society (KWF 11044 to P.A. van den Brandt). The sponsors of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. Funding Information: The authors would like to thank the participants and staff of the Netherlands Cohort Study (NLCS), the Netherlands Cancer Registry, and the Dutch Pathology Registry. They are grateful to Ron Alofs and Harry van Montfort for data management and programming assistance; to Jaleesa van der Meer, Edith van den Boezem, and Peter Moerkerk for TMA construction; and to Jakob Kather (University Hospital Aachen, Germany) for scanning of TMA slides. The Rainbow-TMA consortium was financially supported by BBMRI-NL, a Research Infrastructure financed by the Dutch government (NWO 184.021.007, to P.A. van den Brandt), and Maastricht University Medical Center, University Medical Center Utrecht, and Radboud University Medical Centre, the Netherlands. The authors would like to thank all investigators from the Rainbow-TMA consortium project group [P.A. van den Brandt, A. zur Hausen, H. Grabsch, M. van Engeland, L.J. Schouten, J. Beckervordersandforth (Maastricht University Medical Center, Maastricht, Netherlands); P.H.M. Peeters, P.J. van Diest, H.B. Bueno de Mesquita (University Medical Center Utrecht, Utrecht, Netherlands); J. van Krieken, I. Nagtegaal, B. Siebers, B. Kiemeney (Radboud University Medical Center, Nijmegen, Netherlands); F.J. van Kemenade, C. Steegers, D. Boomsma, G.A. Meijer (VU University Medical Center, Amsterdam, Netherlands); F.J. van Kemenade, B. Stricker (Erasmus University Medical Center, Rotterdam, Netherlands); L. Overbeek, A. Gijsbers (PALGA, the Nationwide Histopathology and Cytopathology Data Network and Archive, Houten, Netherlands)] and collaborating pathologists [Amongst others: A. de Bru{\"i}ne (VieCuri Medical Center, Venlo); J.C. Beckervordersandforth (Maastricht University Medical Center, Maastricht); J. van Krieken, I. Nagtegaal (Radboud University Medical Center, Nijmegen); W. Timens (University Medical Center Groningen, Groningen); F.J. van Kemenade (Erasmus University Medical Center, Rotterdam); M.C.H. Hogenes (Laboratory for Pathology OostNederland, Hengelo); P.J. van Diest (University Medical Center Utrecht, Utrecht); R.E. Kibbelaar (Pathology Friesland, Leeuwarden); A.F. Hamel (Stichting Samenwerkende Ziekenhuizen Oost-Groningen, Winschoten); A.T.M.G. Tiebosch (Martini Hospital, Groningen); C. Meijers (Reinier de Graaf Gasthuis/ S.S.D.Z., Delft); R. Natt{\'e} (Haga Hospital Leyenburg, The Hague); G.A. Meijer (VU University Medical Center, Amsterdam); J.J.T.H. Roelofs (Academic Medical Center, Amsterdam); R.F. Hoedemaeker (Pathology Laboratory Pathan, Rotterdam); S. Sastrowijoto (Orbis Medical Center, Sittard); M. Nap (Atrium Medical Center, Heerlen); H.T. Shirango (Deventer Hospital, Deventer); H. Doornewaard (Gelre Hospital, Apeldoorn); J.E. Boers (Isala Hospital, Zwolle); J.C. van der Linden (Jeroen Bosch Hospital, Den Bosch); G. Burger (Symbiant Pathology Center, Alkmaar); R.W. Rouse (Meander Medical Center, Amersfoort); P.C. de Bruin (St. Antonius Hospital, Nieuwegein); P. Drillenburg (Onze Lieve Vrouwe Gasthuis, Amsterdam); C. van Krimpen (Kennemer Gasthuis, Haarlem); J.F. Graadt van Roggen (Diaconessenhuis, Leiden); S.A.J. Loyson (Bronovo Hospital, The Hague); J.D. Rupa (Laurentius Hospital, Roermond); H. Kliffen (Maasstad Hospital, Rotterdam); H.M. Hazelbag (Medical Center Haaglanden, The Hague); K. Schelfout (Stichting Pathologisch en Cytologisch Laboratorium West-Brabant, Bergen op Zoom); J. Stavast (Laboratorium Klinische Pathologie Centraal Brabant, Tilburg); I. van Lijnschoten (PAMM laboratory for Pathology and Medical Microbiology, Eindhoven); K. Duthoi (Amphia Hospital, Breda)]. Publisher Copyright: {\textcopyright} 2023, The Author(s).",
year = "2023",
month = aug,
doi = "10.1007/s00432-023-04581-w",
language = "English",
volume = "149",
pages = "6271--6282",
journal = "Journal of Cancer Research and Clinical Oncology",
issn = "0171-5216",
publisher = "Springer, Cham",
number = "9",
}