The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study

E. Rangelova; T. F. Stoop; T. M.E. van Ramshorst; European Consortium on Minimally Invasive Pancreatic Surgery (E-MIPS); International Consortium on Advanced Pancreatic Surgery; M. Ali; E. A. van Bodegraven; A. A. Javed; D. Hashimoto; E. Steyerberg; A. Banerjee; A. Jain; A. Sauvanet; A. Serrablo; A. Giani; A. Giardino; A. Zerbi; A. Arshad; A. G. Wijma; A. Coratti; A. Zironda; A. Socratous; A. Rojas; A. Halimi; A. Ejaz; A. Oba; B. Y. Patel; B. Björnsson; B. N. Reames; B. Tingstedt; B. K.P. Goh; C. Payá-Llorente; C. D. Del Pozo; C. González-Abós; C. Medin; C. H.J. van Eijck; C. de Ponthaud; C. Takishita; D. S. Silva; E. Moltzer; E. Verkolf; F. Daams; G. Kazemier; J. Chen; M. Ramaekers; M. A. van Dam; C. Zhang; O. R. Busch; S. Festen; V. E. de Meijer; Y. Cho; S. H. Choi

doi:10.1016/j.annonc.2024.12.015

The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study

E. Rangelova^*, T. F. Stoop, T. M.E. van Ramshorst, European Consortium on Minimally Invasive Pancreatic Surgery (E-MIPS), International Consortium on Advanced Pancreatic Surgery, M. Ali, E. A. van Bodegraven, A. A. Javed, D. Hashimoto, E. Steyerberg, A. Banerjee, A. Jain, A. Sauvanet, A. Serrablo, A. Giani, A. Giardino, A. Zerbi, A. Arshad, A. G. Wijma, A. CorattiA. Zironda, A. Socratous, A. Rojas, A. Halimi, A. Ejaz, A. Oba, B. Y. Patel, B. Björnsson, B. N. Reames, B. Tingstedt, B. K.P. Goh, C. Payá-Llorente, C. D. Del Pozo, C. González-Abós, C. Medin, C. H.J. van Eijck, C. de Ponthaud, C. Takishita, D. S. Silva, E. Moltzer, E. Verkolf, F. Daams, G. Kazemier, J. Chen, M. Ramaekers, M. A. van Dam, C. Zhang, O. R. Busch, S. Festen, V. E. de Meijer, Y. Cho, S. H. Choi

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Abstract

Background: Left-sided pancreatic cancer is associated with worse overall survival (OS) compared with right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with resectable pancreatic cancer (RPC), current randomized trials included mostly patients with right-sided RPC. The purpose of this study was to assess the association between neoadjuvant therapy and OS in patients with left-sided RPC compared with upfront surgery. Patients and methods: This was an international multicenter retrospective study including consecutive patients after left-sided pancreatic resection for pathology-proven RPC, either after neoadjuvant therapy or upfront surgery in 76 centers from 18 countries on 4 continents (2013-2019). The primary endpoint was OS from diagnosis. Time-dependent Cox regression analysis was carried out to investigate the association of neoadjuvant therapy with OS, adjusting for confounders at the time of diagnosis. Adjusted OS probabilities were calculated. Results: Overall, 2282 patients after left-sided pancreatic resection for RPC were included of whom 290 patients (13%) received neoadjuvant therapy. The most common neoadjuvant regimens were (m)FOLFIRINOX (38%) and gemcitabine-nab-paclitaxel (22%). After upfront surgery, 72% of patients received adjuvant chemotherapy, mostly a single-agent regimen (74%). Neoadjuvant therapy was associated with prolonged OS compared with upfront surgery (adjusted hazard ratio 0.69, 95% confidence interval 0.58-0.83) with an adjusted median OS of 53 versus 37 months (P = 0.0003) and adjusted 5-year OS rates of 47% versus 35% (P = 0.0001) compared with upfront surgery. Interaction analysis demonstrated a stronger effect of neoadjuvant therapy in patients with a larger tumor (P_interaction = 0.003) and higher serum carbohydrate antigen 19-9 (CA19-9; P_interaction = 0.005). In contrast, the effect of neoadjuvant therapy was not enhanced for splenic artery (P_interaction = 0.43), splenic vein (P_interaction = 0.30), retroperitoneal (P_interaction = 0.84), and multivisceral (P_interaction = 0.96) involvement. Conclusions: Neoadjuvant therapy in patients with left-sided RPC was associated with improved OS compared with upfront surgery. The impact of neoadjuvant therapy increased with larger tumor size and higher serum CA19-9 at diagnosis. Randomized controlled trials on neoadjuvant therapy specifically in patients with left-sided RPC are needed.

Original language	English
Pages (from-to)	529-542
Number of pages	14
Journal	Annals of Oncology
Volume	36
Issue number	5
DOIs	https://doi.org/10.1016/j.annonc.2024.12.015
Publication status	E-pub ahead of print - 13 Jan 2025

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Rangelova, E., Stoop, T. F., van Ramshorst, T. M. E., European Consortium on Minimally Invasive Pancreatic Surgery (E-MIPS), International Consortium on Advanced Pancreatic Surgery, Ali, M., van Bodegraven, E. A., Javed, A. A., Hashimoto, D., Steyerberg, E., Banerjee, A., Jain, A., Sauvanet, A., Serrablo, A., Giani, A., Giardino, A., Zerbi, A., Arshad, A., Wijma, A. G., ... Choi, S. H. (2025). The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study. Annals of Oncology, 36(5), 529-542. Advance online publication. https://doi.org/10.1016/j.annonc.2024.12.015

@article{85b2dcbbceec4047a67348317d4ab4ee,

title = "The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study",

abstract = "Background: Left-sided pancreatic cancer is associated with worse overall survival (OS) compared with right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with resectable pancreatic cancer (RPC), current randomized trials included mostly patients with right-sided RPC. The purpose of this study was to assess the association between neoadjuvant therapy and OS in patients with left-sided RPC compared with upfront surgery. Patients and methods: This was an international multicenter retrospective study including consecutive patients after left-sided pancreatic resection for pathology-proven RPC, either after neoadjuvant therapy or upfront surgery in 76 centers from 18 countries on 4 continents (2013-2019). The primary endpoint was OS from diagnosis. Time-dependent Cox regression analysis was carried out to investigate the association of neoadjuvant therapy with OS, adjusting for confounders at the time of diagnosis. Adjusted OS probabilities were calculated. Results: Overall, 2282 patients after left-sided pancreatic resection for RPC were included of whom 290 patients (13\%) received neoadjuvant therapy. The most common neoadjuvant regimens were (m)FOLFIRINOX (38\%) and gemcitabine-nab-paclitaxel (22\%). After upfront surgery, 72\% of patients received adjuvant chemotherapy, mostly a single-agent regimen (74\%). Neoadjuvant therapy was associated with prolonged OS compared with upfront surgery (adjusted hazard ratio 0.69, 95\% confidence interval 0.58-0.83) with an adjusted median OS of 53 versus 37 months (P = 0.0003) and adjusted 5-year OS rates of 47\% versus 35\% (P = 0.0001) compared with upfront surgery. Interaction analysis demonstrated a stronger effect of neoadjuvant therapy in patients with a larger tumor (Pinteraction = 0.003) and higher serum carbohydrate antigen 19-9 (CA19-9; Pinteraction = 0.005). In contrast, the effect of neoadjuvant therapy was not enhanced for splenic artery (Pinteraction = 0.43), splenic vein (Pinteraction = 0.30), retroperitoneal (Pinteraction = 0.84), and multivisceral (Pinteraction = 0.96) involvement. Conclusions: Neoadjuvant therapy in patients with left-sided RPC was associated with improved OS compared with upfront surgery. The impact of neoadjuvant therapy increased with larger tumor size and higher serum CA19-9 at diagnosis. Randomized controlled trials on neoadjuvant therapy specifically in patients with left-sided RPC are needed.",

author = "E. Rangelova and Stoop, \{T. F.\} and \{van Ramshorst\}, \{T. M.E.\} and \{European Consortium on Minimally Invasive Pancreatic Surgery (E-MIPS)\} and \{International Consortium on Advanced Pancreatic Surgery\} and M. Ali and \{van Bodegraven\}, \{E. A.\} and Javed, \{A. A.\} and D. Hashimoto and E. Steyerberg and A. Banerjee and A. Jain and A. Sauvanet and A. Serrablo and A. Giani and A. Giardino and A. Zerbi and A. Arshad and Wijma, \{A. G.\} and A. Coratti and A. Zironda and A. Socratous and A. Rojas and A. Halimi and A. Ejaz and A. Oba and Patel, \{B. Y.\} and B. Bj{\"o}rnsson and Reames, \{B. N.\} and B. Tingstedt and Goh, \{B. K.P.\} and C. Pay{\'a}-Llorente and \{Del Pozo\}, \{C. D.\} and C. Gonz{\'a}lez-Ab{\'o}s and C. Medin and \{van Eijck\}, \{C. H.J.\} and \{de Ponthaud\}, C. and C. Takishita and Silva, \{D. S.\} and E. Moltzer and E. Verkolf and F. Daams and G. Kazemier and J. Chen and M. Ramaekers and \{van Dam\}, \{M. A.\} and C. Zhang and Busch, \{O. R.\} and S. Festen and \{de Meijer\}, \{V. E.\} and Y. Cho and Choi, \{S. H.\}",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s)",

year = "2025",

month = jan,

day = "13",

doi = "10.1016/j.annonc.2024.12.015",

language = "English",

volume = "36",

pages = "529--542",

journal = "Annals of Oncology",

issn = "0923-7534",

publisher = "Elsevier Ltd.",

number = "5",

}

Rangelova, E, Stoop, TF, van Ramshorst, TME, European Consortium on Minimally Invasive Pancreatic Surgery (E-MIPS), International Consortium on Advanced Pancreatic Surgery, Ali, M, van Bodegraven, EA, Javed, AA, Hashimoto, D, Steyerberg, E, Banerjee, A, Jain, A, Sauvanet, A, Serrablo, A, Giani, A, Giardino, A, Zerbi, A, Arshad, A, Wijma, AG, Coratti, A, Zironda, A, Socratous, A, Rojas, A, Halimi, A, Ejaz, A, Oba, A, Patel, BY, Björnsson, B, Reames, BN, Tingstedt, B, Goh, BKP, Payá-Llorente, C, Del Pozo, CD, González-Abós, C, Medin, C, van Eijck, CHJ, de Ponthaud, C, Takishita, C, Silva, DS, Moltzer, E, Verkolf, E, Daams, F, Kazemier, G, Chen, J, Ramaekers, M, van Dam, MA, Zhang, C, Busch, OR, Festen, S, de Meijer, VE, Cho, Y & Choi, SH 2025, 'The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study', Annals of Oncology, vol. 36, no. 5, pp. 529-542. https://doi.org/10.1016/j.annonc.2024.12.015

TY - JOUR

T1 - The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer

T2 - an international multicenter study

AU - Rangelova, E.

AU - Stoop, T. F.

AU - van Ramshorst, T. M.E.

AU - European Consortium on Minimally Invasive Pancreatic Surgery (E-MIPS)

AU - International Consortium on Advanced Pancreatic Surgery

AU - Ali, M.

AU - van Bodegraven, E. A.

AU - Javed, A. A.

AU - Hashimoto, D.

AU - Steyerberg, E.

AU - Banerjee, A.

AU - Jain, A.

AU - Sauvanet, A.

AU - Serrablo, A.

AU - Giani, A.

AU - Giardino, A.

AU - Zerbi, A.

AU - Arshad, A.

AU - Wijma, A. G.

AU - Coratti, A.

AU - Zironda, A.

AU - Socratous, A.

AU - Rojas, A.

AU - Halimi, A.

AU - Ejaz, A.

AU - Oba, A.

AU - Patel, B. Y.

AU - Björnsson, B.

AU - Reames, B. N.

AU - Tingstedt, B.

AU - Goh, B. K.P.

AU - Payá-Llorente, C.

AU - Del Pozo, C. D.

AU - González-Abós, C.

AU - Medin, C.

AU - van Eijck, C. H.J.

AU - de Ponthaud, C.

AU - Takishita, C.

AU - Silva, D. S.

AU - Moltzer, E.

AU - Verkolf, E.

AU - Daams, F.

AU - Kazemier, G.

AU - Chen, J.

AU - Ramaekers, M.

AU - van Dam, M. A.

AU - Zhang, C.

AU - Busch, O. R.

AU - Festen, S.

AU - de Meijer, V. E.

AU - Cho, Y.

AU - Choi, S. H.

PY - 2025/1/13

Y1 - 2025/1/13

N2 - Background: Left-sided pancreatic cancer is associated with worse overall survival (OS) compared with right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with resectable pancreatic cancer (RPC), current randomized trials included mostly patients with right-sided RPC. The purpose of this study was to assess the association between neoadjuvant therapy and OS in patients with left-sided RPC compared with upfront surgery. Patients and methods: This was an international multicenter retrospective study including consecutive patients after left-sided pancreatic resection for pathology-proven RPC, either after neoadjuvant therapy or upfront surgery in 76 centers from 18 countries on 4 continents (2013-2019). The primary endpoint was OS from diagnosis. Time-dependent Cox regression analysis was carried out to investigate the association of neoadjuvant therapy with OS, adjusting for confounders at the time of diagnosis. Adjusted OS probabilities were calculated. Results: Overall, 2282 patients after left-sided pancreatic resection for RPC were included of whom 290 patients (13%) received neoadjuvant therapy. The most common neoadjuvant regimens were (m)FOLFIRINOX (38%) and gemcitabine-nab-paclitaxel (22%). After upfront surgery, 72% of patients received adjuvant chemotherapy, mostly a single-agent regimen (74%). Neoadjuvant therapy was associated with prolonged OS compared with upfront surgery (adjusted hazard ratio 0.69, 95% confidence interval 0.58-0.83) with an adjusted median OS of 53 versus 37 months (P = 0.0003) and adjusted 5-year OS rates of 47% versus 35% (P = 0.0001) compared with upfront surgery. Interaction analysis demonstrated a stronger effect of neoadjuvant therapy in patients with a larger tumor (Pinteraction = 0.003) and higher serum carbohydrate antigen 19-9 (CA19-9; Pinteraction = 0.005). In contrast, the effect of neoadjuvant therapy was not enhanced for splenic artery (Pinteraction = 0.43), splenic vein (Pinteraction = 0.30), retroperitoneal (Pinteraction = 0.84), and multivisceral (Pinteraction = 0.96) involvement. Conclusions: Neoadjuvant therapy in patients with left-sided RPC was associated with improved OS compared with upfront surgery. The impact of neoadjuvant therapy increased with larger tumor size and higher serum CA19-9 at diagnosis. Randomized controlled trials on neoadjuvant therapy specifically in patients with left-sided RPC are needed.

AB - Background: Left-sided pancreatic cancer is associated with worse overall survival (OS) compared with right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with resectable pancreatic cancer (RPC), current randomized trials included mostly patients with right-sided RPC. The purpose of this study was to assess the association between neoadjuvant therapy and OS in patients with left-sided RPC compared with upfront surgery. Patients and methods: This was an international multicenter retrospective study including consecutive patients after left-sided pancreatic resection for pathology-proven RPC, either after neoadjuvant therapy or upfront surgery in 76 centers from 18 countries on 4 continents (2013-2019). The primary endpoint was OS from diagnosis. Time-dependent Cox regression analysis was carried out to investigate the association of neoadjuvant therapy with OS, adjusting for confounders at the time of diagnosis. Adjusted OS probabilities were calculated. Results: Overall, 2282 patients after left-sided pancreatic resection for RPC were included of whom 290 patients (13%) received neoadjuvant therapy. The most common neoadjuvant regimens were (m)FOLFIRINOX (38%) and gemcitabine-nab-paclitaxel (22%). After upfront surgery, 72% of patients received adjuvant chemotherapy, mostly a single-agent regimen (74%). Neoadjuvant therapy was associated with prolonged OS compared with upfront surgery (adjusted hazard ratio 0.69, 95% confidence interval 0.58-0.83) with an adjusted median OS of 53 versus 37 months (P = 0.0003) and adjusted 5-year OS rates of 47% versus 35% (P = 0.0001) compared with upfront surgery. Interaction analysis demonstrated a stronger effect of neoadjuvant therapy in patients with a larger tumor (Pinteraction = 0.003) and higher serum carbohydrate antigen 19-9 (CA19-9; Pinteraction = 0.005). In contrast, the effect of neoadjuvant therapy was not enhanced for splenic artery (Pinteraction = 0.43), splenic vein (Pinteraction = 0.30), retroperitoneal (Pinteraction = 0.84), and multivisceral (Pinteraction = 0.96) involvement. Conclusions: Neoadjuvant therapy in patients with left-sided RPC was associated with improved OS compared with upfront surgery. The impact of neoadjuvant therapy increased with larger tumor size and higher serum CA19-9 at diagnosis. Randomized controlled trials on neoadjuvant therapy specifically in patients with left-sided RPC are needed.

UR - http://www.scopus.com/inward/record.url?scp=85217968624&partnerID=8YFLogxK

U2 - 10.1016/j.annonc.2024.12.015

DO - 10.1016/j.annonc.2024.12.015

M3 - Article

C2 - 39814200

AN - SCOPUS:85217968624

SN - 0923-7534

VL - 36

SP - 529

EP - 542

JO - Annals of Oncology

JF - Annals of Oncology

IS - 5

ER -

Rangelova E, Stoop TF, van Ramshorst TME, European Consortium on Minimally Invasive Pancreatic Surgery (E-MIPS), International Consortium on Advanced Pancreatic Surgery, Ali M et al. The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study. Annals of Oncology. 2025 Jan 13;36(5):529-542. Epub 2025 Jan 13. doi: 10.1016/j.annonc.2024.12.015

The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study

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