Meta-analysis of the impact of neoadjuvant therapy on patterns of recurrence in pancreatic ductal adenocarcinoma

Schorn, Stefan; Demir, Ihsan Ekin; Samm, Nicole; Scheufele, Florian; Calavrezos, Lenika; Sargut, Mine; Schirren, Rebekka; Frieß, Helmut; Ceyhan, Güralp O.

doi:10.1002/bjs5.46

Cited by 32 publications

(21 citation statements)

References 30 publications

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“…The recurrence rate of pancreatic cancer after neoadjuvant therapy followed by resection or upfront resection was 53.5% and 88% in other studies; 4,16,17 however, the recurrence rate in the current study was 66.0% for patients with BRPC after neoadjuvant treatment and surgery. Interestingly, the recurrence rate was different after gemcitabine and FOLFIRINOX treatment (82.4 % vs 57.6%; p=0.013).…”

Section: Discussioncontrasting

confidence: 67%

Comparison of Clinical Outcomes of Borderline Resectable Pancreatic Cancer According to the Neoadjuvant Chemo-Regimens: Gemcitabine versus FOLFIRINOX

et al. 2021

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Background/Aims: Although many studies have reported the promising effect of neoadjuvant treatment for borderline resectable pancreatic cancer (BRPC) to increase resectability, only a few studies have recommended the use of firstline chemotherapeutic agents as neoadjuvant treatment for BRPC. The current study compared clinical outcomes between gemcitabine and FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) in patients with BRPC. Methods: In this single-center retrospective study, 100 BRPC patients treated with neoadjuvant chemotherapy and resection from 2008 to 2018 were reviewed. Clinical outcomes included overall survival, resectability, and recurrence patterns after gemcitabine or FOLFIRINOX treatment. Results: For neoadjuvant chemotherapy, gemcitabine was administered to 34 patients and FOLFIRINOX to 66. Neoadjuvant radiotherapy was administered to 27 patients (79.4%) treated with gemcitabine and 19 (28.8%) treated with FOL-FIRINOX (p<0.001). The 2-and 5-year survival rates (YSRs) were significantly higher after FOLFIRINOX (2YSR, 72.2%; 5YSR, 46.0%) than after gemcitabine (2YSR, 58.4%; 5YSR, 19.1%; p=0.041). The margin negative rate was comparable (gemcitabine, 94.1%; FOLFIRINOX, 92.4%; p=0.753), and the tumor size change in percentage showed only a marginal difference (gemcitabine, 20.5%; FOLFIRINOX, 29.0%; p=0.069). Notably, the metastatic recurrence rate was significantly lower in the FOLFIRINOX group (n=20, 52.6%) than in the gemcitabine group (n=22, 78.6%; p=0.001). The rate of adverse events after chemotherapy was significantly higher with FOLFIRINOX than with gemcitabine (43.9%, 20.6%, respectively; p=0.037). Conclusions: FOLFIRINOX provided more clinical and oncological benefit than gemcitabine, with significantly higher overall survival and lower cumulative recurrence rates in BRPC. However, since FOLFIRINOX causes more adverse effects, the regimen should be individualized based on patient's general condition and clinical status.

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Section: Discussioncontrasting

confidence: 67%

Comparison of Clinical Outcomes of Borderline Resectable Pancreatic Cancer According to the Neoadjuvant Chemo-Regimens: Gemcitabine versus FOLFIRINOX

et al. 2021

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“…Recently published and ongoing trials clearly hint at a benefit for neoadjuvant therapy in non-metastasized PDAC [34–36]. A national cancer database query identified 15,237 patients with resectable PDAC; 13,000 underwent upfront surgery and 2000 underwent neoadjuvant treatment.…”

Section: Discussionmentioning

confidence: 99%

Proposal for a definition of "Oligometastatic disease in pancreatic cancer"

et al. 2019

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BackgroundTo date, patients with metastasized pancreatic ductal adenocarcinoma (PDAC M1) are regarded as a uniform collective. We hypothesize the existence of oligometastatic disease (OMD): a state of PDAC M1 disease with better tumor biology, limited metastasis, and increased survival.MethodsData of 128 PDAC M1 patients treated at the University of Cologne between 2008 and 2018 was reviewed. Interdependence between clinical parameter was calculated using the Mann-Whitney U-Test. Survival curves were generated using the Kaplan-Meier method and analyzed using the log-rank test.ResultsEighty-one (63%) patients had metastases confined to one organ (single organ metastasis, SOG) whereas the remaining 47 (37%) showed multiple metastatic sites (multi-organ metastasis, MOG). Survival analysis revealed a median overall survival (OS) of 12.2 months for SOG vs 4.5 months for MOG (95% CI 5.7–9.8; p < 0.001). We defined limited disease by the presence of ≤4 metastases in liver or lung. Limited disease together with CA 19–9 baseline < 1000 U/ml and response or stable disease after first-line chemotherapy defined OMD. We identified 8 patients with hepatic metastases and 2 with pulmonary metastases matching all OMD criteria. This group of 10 (7.8%) had a median overall survival of 19.4 vs 7.2 months compared to the remaining patients (95% CI 5.7–9.8; p = 0.009).ConclusionWe propose a definition of oligometastatic disease in PDAC including anatomical criteria and biological criteria reflecting better tumor biology. The 10 OMD patients (7.8%) survived significantly longer and might even benefit from surgical resection in the future.

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“…A first relevant subgroup is patients receiving neoadjuvant therapy versus those having upfront surgery. Neoadjuvant therapy alters many histopathological prognostic factors (such as decreased risk of larger tumour size, positive lymph nodes and poor differentiation), and is associated with changes in outcomes including tumour recurrence patterns and survival. Second, the location of the pancreatic cancer (head or tail) should be distinguished; although there are conflicting results on the influence of location on outcomes, tail cancers have been shown to have more aggressive tumour biology.…”

Section: Discussionmentioning

confidence: 99%

Systematic review of clinical prediction models for survival after surgery for resectable pancreatic cancer

Strijker

Chen

Mungroop

et al. 2019

British Journal of Surgery

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Background: As more therapeutic options for pancreatic cancer are becoming available, there is a need to improve outcome prediction to support shared decision-making. A systematic evaluation of prediction models in resectable pancreatic cancer is lacking.Methods: This systematic review followed the CHARMS and PRISMA guidelines. PubMed, Embase and Cochrane Library databases were searched up to 11 October 2017. Studies reporting development or validation of models predicting survival in resectable pancreatic cancer were included. Models without performance measures, reviews, abstracts or more than 10 per cent of patients not undergoing resection in postoperative models were excluded. Studies were appraised critically.Results: After screening 4403 studies, 22 (44 319 patients) were included. There were 19 model development/update studies and three validation studies, altogether concerning 21 individual models. Two studies were deemed at low risk of bias. Eight models were developed for the preoperative setting and 13 for the postoperative setting. Most frequently included parameters were differentiation grade (11 of 21 models), nodal status (8 of 21) and serum albumin (7 of 21). Treatment-related variables were included in three models. The C-statistic/area under the curve values ranged from 0⋅57 to 0⋅90. Based on study design, validation methods and the availability of web-based calculators, two models were identified as the most promising. Conclusion: Although a large number of prediction models for resectable pancreatic cancer have been reported, most are at high risk of bias and have not been validated externally. This overview of prognostic factors provided practical recommendations that could help in designing easily applicable prediction models to support shared decision-making.Prediction models enable clinicians and patients to calculate the risks of a specific endpoint individualized to a patient, using combinations of predictors. Such models are used widely in some fields, including the CHADS 2 -VASc score for estimation of stroke risk in atrial fibrillation 3 , and the Acute Physiology and Chronic Health Evaluation (APACHE) score 4 for mortality in intensive care. In breast cancer, the PREDICT 5 and Adjuvant! 6 models have been employed in the decision-making process to determine adjuvant treatment administration. Data analysisData extraction was performed independently by two authors. Articles were categorized into development/model update studies and validation studies 12 .

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Meta-analysis of the impact of neoadjuvant therapy on patterns of recurrence in pancreatic ductal adenocarcinoma

Cited by 32 publications

References 30 publications

Comparison of Clinical Outcomes of Borderline Resectable Pancreatic Cancer According to the Neoadjuvant Chemo-Regimens: Gemcitabine versus FOLFIRINOX

Comparison of Clinical Outcomes of Borderline Resectable Pancreatic Cancer According to the Neoadjuvant Chemo-Regimens: Gemcitabine versus FOLFIRINOX

Proposal for a definition of "Oligometastatic disease in pancreatic cancer"

Systematic review of clinical prediction models for survival after surgery for resectable pancreatic cancer

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