Neoadjuvant therapy in pancreatic cancer: what is the true oncological benefit?

Ren, Lei; Reyes, Carmen Mota; Frieß, Helmut; Demir, Ihsan Ekin

doi:10.1007/s00423-020-01946-4

Cited by 7 publications

(7 citation statements)

References 52 publications

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“…The therapeutic goal is to be able to select the patients with a favorable tumor biology, to justify cumbersome surgery with prospects of an oncologic and survival benefit. The obvious necessity to find biomarkers to assess the aggressivity of the tumor beyond anatomical landmarks and beyond the conventional radiological findings is the instigator to start a prospective study evaluating the role of radiomics, genomics and proteomics in the selection of patients with BR and LA after neoadjuvant FOLFIRINOX (PeRFormanCe Trial, NCT05298722) [ 33 – 37 ].…”

Section: Discussionmentioning

confidence: 99%

Predictive factors for survival in borderline resectable and locally advanced pancreatic cancer: are these really two different entities?

de Carvalho,

Gryspeerdt,

Rashidian

et al. 2023

BMC Surg

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Background The treatment of borderline resectable (BR) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC) has evolved with a wider application of neoadjuvant chemotherapy (NACHT). The aim of this study was to identify predictive factors for survival in BR and LA PDAC. Methods Clinicopathologic data of patients with BR and LA PDAC who underwent surgical exploration between January 2011 and June 2021 were retrospectively collected. Survival from the date of surgery was estimated using the Kaplan-Meier method. Simple and multiple Cox proportional hazards models were fitted to identify factors associated with survival. Surgical resection was analyzed in combination with the involvement of lymph nodes as this last was only known after a formal resection. Results Ninety patients were surgically explored (BR: 45, LA: 45), of which 51 (57%) were resected (BR: 31, LA: 20). NACHT was administered to 43 patients with FOLFIRINOX being the most frequent regimen applied (33/43, 77%). Major complications (Clavien-Dindo grade III and IV) occurred in 7.8% of patients and 90-day mortality rate was 3.3%. The median overall survival since surgery was 16 months (95% CI 12-20) in the group which underwent surgical resection and 10 months (95% CI 7-13) in the group with an unresectable tumor (p=0.001). Cox proportional hazards models showed significantly lower mortality hazard for surgical resection compared to no surgical resection, even after adjusting for National Comprehensive Cancer Network (NCCN) classification and administration of NACHT [surgical resection with involved lymph nodes vs no surgical resection (cHR 0.49; 95% CI 0.29-0.82; p=0.007)]. There was no significant difference in survival between patients with BR and LA disease (cHR= 1.01; 95% CI 0.63-1.62; p=0.98). Conclusions Surgical resection is the only predictor of survival in patients with BR and LA PDAC, regardless of their initial classification as BR or LA. Our results suggest that surgery should not be denied to patients with LA PDAC a priori. Prospective studies including patients from the moment of diagnosis are required to identify biologic and molecular markers which may allow a better selection of patients who will benefit from surgery.

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Section: Discussionmentioning

confidence: 99%

Predictive factors for survival in borderline resectable and locally advanced pancreatic cancer: are these really two different entities?

de Carvalho,

Gryspeerdt,

Rashidian

et al. 2023

BMC Surg

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“…Although conventional neoadjuvant therapy has been able to downstage tumors in locally advanced and borderline resectable tumors, multi-omics tumor profiling of tumor biopsies before targeted neoadjuvant treatment has shown great promise and may result in optimal patient selection for systemic therapies, less-extensive surgical procedures due to maximized tumor shrinkage, or even lead, in the long term, to a wait-and-see approach in patients with PDAC with complete response to molecular-driven therapies [3]. We have recently reviewed and summarized the currently ongoing trials employing neoadjuvant therapy in human PDAC [17].…”

Section: Improving the Outcome Of Resectable Pdac Through Molecular Subtypingmentioning

confidence: 99%

Molecular Profiling in Pancreatic Cancer: Current Role and Its Impact on Primary Surgery

et al. 2021

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Background: The advent of next-generation sequencing technologies has enabled the identification of molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) with different biological traits and clinically targetable features. Summary: Although current chemotherapy trials are currently exploiting this knowledge, these molecular subtypes have not yet sufficiently caught the attention of surgeons. In fact, integration of these molecular subtypes into the timing of surgery can in theory improve patient outcome. Here, we present the molecular subtypes of PDAC from the surgeon’s perspective and a clinically applicable algorithm that integrates the molecular subtyping of PDAC preoperatively into the decision of primary surgery versus neoadjuvant therapy. Furthermore, we point out the potential of “tailored” (in addition to conventional) neoadjuvant treatment for exploiting the molecular subtypes of PDAC. Key Messages: We believe that for surgeons, the preoperative knowledge on the subtype of PDAC can properly guide in deciding between upfront surgery versus neoadjuvant treatment for improving patient outcome.

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“…Downloaded from Pancreas antitumour abilities. [20][21][22][23] Multiple studies have consistently reported better response rates and prolonged survival among women undergoing anticancer treatments, including nCRT. [24][25][26][27][28][29] Inititally, these beneficial outcomes were ascribed to reduced exposure to risk factors or enhanced pharmacokinetic drug handling.…”

Section: Introductionmentioning

confidence: 99%

Enhanced antitumour immunity following neoadjuvant chemoradiotherapy mediates a favourable prognosis in women with resected pancreatic cancer

van Eijck,

Mustafa,

Vadgama

et al. 2023

Gut

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BackgroundThis study investigates sex disparities in clinical outcomes and tumour immune profiles in patients with pancreatic ductal adenocarcinoma (PDAC) who underwent upfront resection or resection preceded by gemcitabine-based neoadjuvant chemoradiotherapy (nCRT).MethodsPatients originated from the PREOPANC randomised controlled trial. Upfront surgery was performed in 82 patients, and 66 received nCRT before resection. The impact of sex on overall survival (OS) was investigated using Cox proportional hazards models. The immunological landscape within the tumour microenvironment (TME) was mapped using transcriptomic and spatial proteomic profiling.ResultsThe 5-year OS rate differed between the sexes following resection preceded by nCRT, with 43% for women compared with 22% for men. In multivariate analysis, the female sex was a favourable independent prognostic factor for OS only in the nCRT group (HR 0.19; 95% CI 0.07 to 0.52). Multivariate heterogeneous treatment effects analysis revealed a significant interaction between sex and treatment, implying increased nCRT efficacy among women with resected PDAC. The TME of women contained fewer protumoural CD163+MRC1+M2 macrophages than that of men after nCRT, as indicated by transcriptomic and validated using spatial proteomic profiling.ConclusionPDAC tumours of women are more sensitive to gemcitabine-based nCRT, resulting in longer OS after resection compared with men. This may be due to enhanced immunity impeding the infiltration of protumoral M2 macrophages into the TME. Our findings highlight the importance of considering sex disparities and mitigating immunosuppressive macrophage polarisation for personalised PDAC treatment.

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Neoadjuvant therapy in pancreatic cancer: what is the true oncological benefit?

Cited by 7 publications

References 52 publications

Predictive factors for survival in borderline resectable and locally advanced pancreatic cancer: are these really two different entities?

Predictive factors for survival in borderline resectable and locally advanced pancreatic cancer: are these really two different entities?

Molecular Profiling in Pancreatic Cancer: Current Role and Its Impact on Primary Surgery

Enhanced antitumour immunity following neoadjuvant chemoradiotherapy mediates a favourable prognosis in women with resected pancreatic cancer

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