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The survival benefit of using neoadjuvant therapy for resectable and unresectable tumours in pancreatic cancer patients estimated with multi-centred real-world data of the PURPLE registry

Witmond, V. (2020) The survival benefit of using neoadjuvant therapy for resectable and unresectable tumours in pancreatic cancer patients estimated with multi-centred real-world data of the PURPLE registry.

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Abstract:Introduction: Pancreatic cancer (PC) is the fifth leading cause of cancer-related deaths in Australia. Moreover, the Australian five-year survival rate for PC remains less than 10%. Surgical resection of the tumour is considered as the only chance of cure. However, less than one-fifth of the PC patients is classified as surgical candidates. Neoadjuvant therapy has the potential advantage to improve the resection rate. Meta-analysis have observed the added value of neoadjuvant therapy, but multi-centred randomised trials have not been completed. Real-world data (RWD) are an alternative source of clinical data. This study aimed to analyse the potential survival benefit of using neoadjuvant therapy for resectable and unresectable tumours in PC patients by using multi-centred RWD of the PURPLE registry. Methods: Data of 1,492 PC patients from 27 hospitals across Australia, New Zealand and Singapore were obtained from PURPLE. The effects of neoadjuvant therapy were studied within three tumour resectability classifications of non-metastatic PCs: potential resectable (PR), borderline resectable (BR), and locally advanced unresectable (LA). The role of the type of therapy, the neoadjuvant regimen, and the therapy duration were analysed as well. Overall survival (OS) was determined as the primary outcome. Kaplan-Meier estimators and Cox Proportional Hazards models were applied as evaluation methods for investigating the role of neoadjuvant therapy to the OS. Backwards stepwise selection was applied for determination of the most valuable features in an attempt to develop a Cox regressive model. Results: This study identified 648 (43.4%) non-metastatic PC patients, whose tumours were classified as PR (n = 368), BR (n = 118), or LA (n = 162). Twelve (3.2%), 89 (75.4%), and 4 (2.5%) patients received neoadjuvant therapy, respectively. These neoadjuvant therapy patients (n = 105) were younger (P < 0.001) and had lower ECOG scores (P = 0.002) compared to the group without neoadjuvant therapy (n = 543). The median OS (mOS) was lower for the neoadjuvant therapy group compared to those without neoadjuvant therapy in case of PR tumours (22.7 months vs. 29.9 months P = 0.58) and BR tumours (21.6 months vs. 22.1 months; P = 0.80). The mOS was higher for LA cases treated with neoadjuvant therapy (17.1 months vs. 14.8; P = 0.49). This study was unable to conduct the survival analysis of neoadjuvant chemo-radiotherapy against neoadjuvant chemotherapy alone. FOLFIRINOX resulted in a higher mOS compared to gemcitabine nab-paclitaxel (22.0 months vs. 12.0 months; P < 0.001). Neoadjuvant therapy duration of at least 6 cycles had a mOS of 24.4 months and was therefore higher compared the 21.6 months for those with shorter therapy durations (P = 0.68). Multivariate Cox regression did not demonstrate neoadjuvant therapy as conclusive prognostic factor (HR: 0.91; P = 0.81) and was therefore not adopted as feature in any model proposal due to its insufficient regressive property to the OS. Discussion & conclusion: This RWD analysis did not provide conclusive evidence to support the hypothesis that neoadjuvant therapy contributes to better survival outcomes for PC patients with either PR, BR or LA classified tumours. Most observations were not supported with a significant statistical test result due to the limited number of patients in certain research arms, the relative short follow-up period, and the influence of potential confounders. However, if neoadjuvant therapy is used, FOLFIRINOX seemed to be the best chemotherapy regimen compared to gemcitabine nab-paclitaxel. We recommend clinicians to discuss neoadjuvant treatment as possible treatment option, which might potentially lead to more variation in PURPLE registry. If more data is available in PURPLE and the follow-up period is majorly increased, then we recommend a re-conduction of the survival analysis and a further identification of potential confounders.
Item Type:Essay (Master)
University of Melbourne, Melbourne, Australia
Faculty:BMS: Behavioural, Management and Social Sciences
Subject:44 medicine
Programme:Industrial Engineering and Management MSc (60029)
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