Systemic immune response induced by oxaliplatin-based neoadjuvant therapy favours survival without metastatic progression in high-risk rectal cancer

Erta Kalanxhi; Sebastian Meltzer; Jakob Vasehus Schou; Finn Ole Larsen; Svein Dueland; Kjersti Flatmark; Benny Vittrup Jensen; Knut Håkon Hole; Therese Seierstad; Kathrine Røe Redalen; Dorte Lisbet Nielsen; Anne Hansen Ree

doi:10.1038/s41416-018-0085-y

Systemic immune response induced by oxaliplatin-based neoadjuvant therapy favours survival without metastatic progression in high-risk rectal cancer

Erta Kalanxhi, Sebastian Meltzer, Jakob Vasehus Schou, Finn Ole Larsen, Svein Dueland, Kjersti Flatmark, Benny Vittrup Jensen, Knut Håkon Hole, Therese Seierstad, Kathrine Røe Redalen, Dorte Lisbet Nielsen, Anne Hansen Ree

Department of Clinical Medicine

14 Citations (Scopus)

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Abstract

Background: Systemic failure remains a challenge in rectal cancer. We investigated the possible systemic anti-tumour immune activity invoked within oxaliplatin-based neoadjuvant therapy. Methods: In two high-risk patient cohorts, we assessed the circulating levels of the fms-like tyrosine kinase 3 ligand (Flt3L), a factor reflecting both therapy-induced myelosuppression and activation of tumour antigen-presenting dendritic cells, at baseline and following induction chemotherapy and sequential chemoradiotherapy, both modalities containing oxaliplatin. The primary end point was progression-free survival (PFS). Results: In both cohorts, the median Flt3L level was significantly higher at completion of each sequential modality than at baseline. The 5-year PFS (most events being metastatic progression) was 68% and 71% in the two cohorts consisting of 33% and 52% T4 cases. In the principal cohort, a high Flt3L level following the induction chemotherapy was associated with low risk for a PFS event (HR: 0.15; P < 0.01). These patients also had available dose scheduling and toxicity data, revealing that oxaliplatin dose reduction during chemoradiotherapy, undertaken to maintain compliance to the radiotherapy protocol, was associated with advantageous PFS (HR: 0.47; P = 0.046). Conclusion: In high-risk rectal cancer, oxaliplatin-containing neoadjuvant therapy may promote an immune response that favours survival without metastatic progression.

Original language	English
Journal	British Journal of Cancer
Volume	118
Issue number	10
Pages (from-to)	1322-1328
Number of pages	7
ISSN	0007-0920
DOIs	https://doi.org/10.1038/s41416-018-0085-y
Publication status	Published - 1 May 2018

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Systemic immune response induced by oxaliplatin-based neoadjuvant therapy favours survival without metastatic progression in high-risk rectal cancerFinal published version, 387 KBLicence: CC BY

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Kalanxhi, E., Meltzer, S., Schou, J. V., Larsen, F. O., Dueland, S., Flatmark, K., Jensen, B. V., Hole, K. H., Seierstad, T., Redalen, K. R., Nielsen, D. L., & Ree, A. H. (2018). Systemic immune response induced by oxaliplatin-based neoadjuvant therapy favours survival without metastatic progression in high-risk rectal cancer. British Journal of Cancer, 118(10), 1322-1328. https://doi.org/10.1038/s41416-018-0085-y

Systemic immune response induced by oxaliplatin-based neoadjuvant therapy favours survival without metastatic progression in high-risk rectal cancer. / Kalanxhi, Erta; Meltzer, Sebastian; Schou, Jakob Vasehus et al.
In: British Journal of Cancer, Vol. 118, No. 10, 01.05.2018, p. 1322-1328.

Research output: Contribution to journal › Journal article › Research › peer-review

Kalanxhi, E, Meltzer, S, Schou, JV, Larsen, FO, Dueland, S, Flatmark, K, Jensen, BV, Hole, KH, Seierstad, T, Redalen, KR, Nielsen, DL & Ree, AH 2018, 'Systemic immune response induced by oxaliplatin-based neoadjuvant therapy favours survival without metastatic progression in high-risk rectal cancer', British Journal of Cancer, vol. 118, no. 10, pp. 1322-1328. https://doi.org/10.1038/s41416-018-0085-y

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abstract = "Background: Systemic failure remains a challenge in rectal cancer. We investigated the possible systemic anti-tumour immune activity invoked within oxaliplatin-based neoadjuvant therapy. Methods: In two high-risk patient cohorts, we assessed the circulating levels of the fms-like tyrosine kinase 3 ligand (Flt3L), a factor reflecting both therapy-induced myelosuppression and activation of tumour antigen-presenting dendritic cells, at baseline and following induction chemotherapy and sequential chemoradiotherapy, both modalities containing oxaliplatin. The primary end point was progression-free survival (PFS). Results: In both cohorts, the median Flt3L level was significantly higher at completion of each sequential modality than at baseline. The 5-year PFS (most events being metastatic progression) was 68% and 71% in the two cohorts consisting of 33% and 52% T4 cases. In the principal cohort, a high Flt3L level following the induction chemotherapy was associated with low risk for a PFS event (HR: 0.15; P < 0.01). These patients also had available dose scheduling and toxicity data, revealing that oxaliplatin dose reduction during chemoradiotherapy, undertaken to maintain compliance to the radiotherapy protocol, was associated with advantageous PFS (HR: 0.47; P = 0.046). Conclusion: In high-risk rectal cancer, oxaliplatin-containing neoadjuvant therapy may promote an immune response that favours survival without metastatic progression.",

author = "Erta Kalanxhi and Sebastian Meltzer and Schou, {Jakob Vasehus} and Larsen, {Finn Ole} and Svein Dueland and Kjersti Flatmark and Jensen, {Benny Vittrup} and Hole, {Knut H{\aa}kon} and Therese Seierstad and Redalen, {Kathrine R{\o}e} and Nielsen, {Dorte Lisbet} and Ree, {Anne Hansen}",

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T1 - Systemic immune response induced by oxaliplatin-based neoadjuvant therapy favours survival without metastatic progression in high-risk rectal cancer

AU - Kalanxhi, Erta

AU - Meltzer, Sebastian

AU - Schou, Jakob Vasehus

AU - Larsen, Finn Ole

AU - Dueland, Svein

AU - Flatmark, Kjersti

AU - Jensen, Benny Vittrup

AU - Hole, Knut Håkon

AU - Seierstad, Therese

AU - Redalen, Kathrine Røe

AU - Nielsen, Dorte Lisbet

AU - Ree, Anne Hansen

PY - 2018/5/1

Y1 - 2018/5/1

N2 - Background: Systemic failure remains a challenge in rectal cancer. We investigated the possible systemic anti-tumour immune activity invoked within oxaliplatin-based neoadjuvant therapy. Methods: In two high-risk patient cohorts, we assessed the circulating levels of the fms-like tyrosine kinase 3 ligand (Flt3L), a factor reflecting both therapy-induced myelosuppression and activation of tumour antigen-presenting dendritic cells, at baseline and following induction chemotherapy and sequential chemoradiotherapy, both modalities containing oxaliplatin. The primary end point was progression-free survival (PFS). Results: In both cohorts, the median Flt3L level was significantly higher at completion of each sequential modality than at baseline. The 5-year PFS (most events being metastatic progression) was 68% and 71% in the two cohorts consisting of 33% and 52% T4 cases. In the principal cohort, a high Flt3L level following the induction chemotherapy was associated with low risk for a PFS event (HR: 0.15; P < 0.01). These patients also had available dose scheduling and toxicity data, revealing that oxaliplatin dose reduction during chemoradiotherapy, undertaken to maintain compliance to the radiotherapy protocol, was associated with advantageous PFS (HR: 0.47; P = 0.046). Conclusion: In high-risk rectal cancer, oxaliplatin-containing neoadjuvant therapy may promote an immune response that favours survival without metastatic progression.

AB - Background: Systemic failure remains a challenge in rectal cancer. We investigated the possible systemic anti-tumour immune activity invoked within oxaliplatin-based neoadjuvant therapy. Methods: In two high-risk patient cohorts, we assessed the circulating levels of the fms-like tyrosine kinase 3 ligand (Flt3L), a factor reflecting both therapy-induced myelosuppression and activation of tumour antigen-presenting dendritic cells, at baseline and following induction chemotherapy and sequential chemoradiotherapy, both modalities containing oxaliplatin. The primary end point was progression-free survival (PFS). Results: In both cohorts, the median Flt3L level was significantly higher at completion of each sequential modality than at baseline. The 5-year PFS (most events being metastatic progression) was 68% and 71% in the two cohorts consisting of 33% and 52% T4 cases. In the principal cohort, a high Flt3L level following the induction chemotherapy was associated with low risk for a PFS event (HR: 0.15; P < 0.01). These patients also had available dose scheduling and toxicity data, revealing that oxaliplatin dose reduction during chemoradiotherapy, undertaken to maintain compliance to the radiotherapy protocol, was associated with advantageous PFS (HR: 0.47; P = 0.046). Conclusion: In high-risk rectal cancer, oxaliplatin-containing neoadjuvant therapy may promote an immune response that favours survival without metastatic progression.

U2 - 10.1038/s41416-018-0085-y

DO - 10.1038/s41416-018-0085-y

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C2 - 29695770

SN - 0007-0920

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EP - 1328

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 10

ER -

Systemic immune response induced by oxaliplatin-based neoadjuvant therapy favours survival without metastatic progression in high-risk rectal cancer

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