Adjuvant Chemotherapy in the Treatment of Intraductal Papillary Mucinous Neoplasms of the Pancreas: Systematic Review and Meta-Analysis

Abstract Background The present systematic review aimed to compare survival outcomes of invasive intraductal papillary mucinous neoplasms (IIPMNs) treated with adjuvant chemotherapy versus surgery alone and to identify pathologic features that may predict survival benefit from adjuvant chemotherapy. Method A systematic search of MEDLINE, PubMed, Scopus, and EMBASE was performed using the PRISMA framework. Studies comparing adjuvant chemotherapy and surgery alone for patients with IIPMNs were included. Primary endpoint was overall survival (OS). A narrative synthesis was performed to identify pathologic features that predicted survival benefits from adjuvant chemotherapy. Results Eleven studies and 3393 patients with IIPMNs were included in the meta-analysis. Adjuvant chemotherapy significantly reduced the risk of death in the overall cohort (HR 0.57, 95% CI 0.38–0.87, p = 0.009) and node-positive patients (HR 0.29, 95% CI 0.13–0.64, p = 0.002). Weighted median survival difference between adjuvant chemotherapy and surgery alone in node-positive patients was 11.6 months (95% CI 3.83–19.38, p = 0.003) favouring chemotherapy. Adjuvant chemotherapy had no impact on OS in node-negative patients (HR 0.53, 95% CI 0.20–1.43, p = 0.209). High heterogeneity (I2 > 75%) was observed in pooled estimates of hazard ratios. Improved OS following adjuvant chemotherapy was reported for patients with stage III/IV disease, tumour size > 2 cm, node-positive status, grade 3 tumour differentiation, positive margin status, tubular carcinoma subtype, and presence of perineural or lymphovascular invasion. Conclusion Adjuvant chemotherapy was associated with improved OS in node-positive IIPMNs. However, the findings were limited by marked heterogeneity. Future large multicentre prospective studies are needed to confirm these findings and explore additional predictors of improved OS to guide patient selection for adjuvant chemotherapy.

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P-P23 Adjuvant chemotherapy in the treatment of intraductal papillary mucinous neoplasms of the pancreas: systematic review and meta-analysis

British Journal of Surgery ◽

10.1093/bjs/znab430.246 ◽

2021 ◽

Vol 108 (Supplement_9) ◽

Author(s):

Eric Jing Fu Chong ◽

Bathiya Ratnayake ◽

Bobby V M Dasari ◽

Benjamin PT Loveday ◽

Ajith K Siriwardena ◽

...

Keyword(s):

Systematic Review ◽

Adjuvant Chemotherapy ◽

Meta Analysis ◽

Intraductal Papillary Mucinous Neoplasms ◽

Tubular Carcinoma ◽

Risk Of Death ◽

Node Positive ◽

Survival Difference ◽

Pathologic Features ◽

Mucinous Neoplasms

Abstract Background The present systematic review aimed to compare survival outcomes of invasive intraductal papillary mucinous neoplasms (IIPMNs) treated with adjuvant chemotherapy versus surgery alone and to identify pathologic features that may predict survival benefit from adjuvant chemotherapy. Methods A systematic search of Medline, Pubmed, Scopus, and EMBASE was performed using the PRISMA framework. Studies comparing adjuvant chemotherapy and surgery alone for patients with IIPMNs were included. Primary endpoint was overall survival (OS). A narrative synthesis was performed to identify pathologic features that predicted survival benefits from adjuvant chemotherapy. Results Eleven studies and 3393 patients with IIPMNs were included in the meta-analysis. Adjuvant chemotherapy significantly reduced risk of death in the overall cohort (HR 0.57, 95%-CI:0.38-0.87, p = 0.009) and node-positive patients (HR 0.29, 95%-CI:0.13-0.64, p = 0.002). Weighted median survival difference between adjuvant chemotherapy and surgery alone in node-positive patients was 11.6 months (95%-CI:3.83-19.38, p = 0.003) favouring chemotherapy. Adjuvant chemotherapy had no impact on OS in node-negative patients (HR 0.53, 95%-CI:0.20-1.43, p = 0.209). High heterogeneity (I2>75%) was observed in pooled estimates of hazard ratios. Improved OS following adjuvant chemotherapy were reported for patients with stage III/IV disease, tumour size >2 cm, node-positive status, grade 3 tumour differentiation, positive margin status, tubular carcinoma subtype, and presence of perineural or lymphovascular invasion. Conclusions Adjuvant chemotherapy was associated with improved OS in node-positive IIPMNs. However, the findings were limited by marked heterogeneity. Future large multicentre prospective studies are needed to confirm these findings and explore additional predictors of improved OS to guide patient selection for adjuvant chemotherapy.

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Association between pancreatic intraductal papillary mucinous neoplasms and extrapancreatic malignancies: A systematic review with meta-analysis

European Journal of Surgical Oncology ◽

10.1016/j.ejso.2021.09.018 ◽

2021 ◽

Author(s):

Antonio Facciorusso ◽

Stefano Francesco Crinò ◽

Daryl Ramai ◽

Giovanni Marchegiani ◽

Janice Lester ◽

...

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Intraductal Papillary Mucinous Neoplasms ◽

Mucinous Neoplasms

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Results of Non-Operative Management for Intraductal Papillary Mucinous Neoplasms with High-Risk Stigmata or Worrisome Features: A Systematic Review and Meta-Analysis

Gastroenterology ◽

10.1016/s0016-5085(17)32394-6 ◽

2017 ◽

Vol 152 (5) ◽

pp. S681-S682

Author(s):

Giuseppe Vanella ◽

Stefano Crippa ◽

Livia Archibugi ◽

Paolo Giorgio Arcidiacono ◽

GianfrancoDelle Fave ◽

...

Keyword(s):

Systematic Review ◽

High Risk ◽

Meta Analysis ◽

Operative Management ◽

Intraductal Papillary Mucinous Neoplasms ◽

Mucinous Neoplasms ◽

Non Operative Management

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Tu1237 Diagnostic Yield of Endoscopic Procedures to Distinguish Malignant and Benign Intraductal Papillary Mucinous Neoplasms - A Meta-Analysis and Systematic Review of Literatures

Gastroenterology ◽

10.1016/s0016-5085(13)62953-4 ◽

2013 ◽

Vol 144 (5) ◽

pp. S-799

Author(s):

Rei Suzuki ◽

Nirav Thosani ◽

Atsushi Irisawa ◽

Hiromasa Ohira ◽

Srinadh Annangi ◽

...

Keyword(s):

Systematic Review ◽

Diagnostic Yield ◽

Meta Analysis ◽

Intraductal Papillary Mucinous Neoplasms ◽

Endoscopic Procedures ◽

Mucinous Neoplasms

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The impact of time to adjuvant chemotherapy (AC) on survival in colorectal cancer (CRC): A systematic review and meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.364 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 364-364 ◽

Cited By ~ 4

Author(s):

J. J. Biagi ◽

M. Raphael ◽

W. D. King ◽

W. Kong ◽

W. J. Mackillop ◽

...

Keyword(s):

Systematic Review ◽

Prognostic Factors ◽

Adjuvant Chemotherapy ◽

Publication Bias ◽

Meta Analysis ◽

Disease Free Survival ◽

Significant Heterogeneity ◽

Risk Of Death ◽

The Impact ◽

The Relationship

364 Background: The optimal timing from CRC surgery to initiation of AC is unknown. We report a systematic review and meta-analysis to determine the relationship between time to adjuvant chemotherapy (TTAC) and survival. Methods: A systematic review of literature was done to identify studies that described the relationship between TTAC and survival. Studies were only included if the distribution of relevant prognostic factors was adequately described, and either comparative groups were balanced or results adjusted for the prognostic factors. Hazard ratio (HR) and TTAC for overall survival (OS) and disease free survival (DFS) from each study were converted to a regression coefficient (β) and standard error (SE) corresponding to a continuous representation per 4 weeks of TTAC. The adjusted β from individual studies were combined using a fixed-effect model. Inverse-variance (1/SE2) was used to weight individual studies. The possible effect of publication bias was investigated using the trim and fill approach. Results: We identified 9 eligible studies involving 14,357 patients (4 published articles, 5 abstracts). Two studies were randomized trials and 7 were cohort studies. Six studies reported TTAC as a binary variable and 3 reported TTAC as ≥3 categories. An estimate of HR for OS was derived from all 9 studies and estimate for DFS was derived from 5 studies. Meta-analysis demonstrated that a 4-week increase in TTAC was associated with a significant decrease in both OS (HR = 1.12, 95% CI 1.09-1.15), and DFS (HR = 1.15, 95% CI 1.11-1.20). The analysis showed no significant heterogeneity among studies. These TTAC associations remained significant after analysis for potential publication bias, and when the analysis was repeated excluding the two studies of largest weight. Conclusions: This study demonstrates a 12% increase in the risk of death for each 4 week of delay in the start of AC for CRC. These findings indicate the need for clinicians and health systems managers to take the steps necessary to keep TTAC as short as reasonably achievable. In addition, our results suggest there may be some benefit to AC after a 3-month TTAC delay. No significant financial relationships to disclose.

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