Open Access Open Access  Restricted Access Subscription Access

Clinical Effectiveness of Preoperative Neoadjuvant Chemotherapy for Patients with Borderline Resectable Pancreatic Cancer:An Updated Meta-Analysis`


Affiliations
1 Department of Hepatobiliary Surgery, and Pancreas Disease Institute, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
2 Pancreas Disease Institute, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
 

The benefit of preoperative neoadjuvant chemotherapy (CT) to borderline resectable pancreatic cancer (BRPC) is still not well known. This study aims to define the benefits of neoadjuvant CT for BRPC patients. By searching databases (PubMed, Embase, Cochrane Library) from 1966 to 2015, all prospective studies were analysed, where preoperative neoadjuvant CT or chemoradiotherapy was given to patients with BRPC. Laparotomy and resection rates were the primary outcomes. Secondary outcome was therapyinduced toxicity, tumour response, and overall survival. Data were shown as weighted frequency with 95% confidence interval. Fifteen studies with a total of 356 patients were included. All patients had BRPC and received neoadjuvant CT. Following the preoperative therapy, 78.1% of evaluable patients underwent laparotomy and 76.3% of laparotomy patients were performed resection. Also, 86% of specimens were deemed microscopically negative (R0) resection margins. At restaging following treatment, weighted frequencies for complete/partial response were 23.0%, 54.3% for stable disease 23.4% for progressive disease and 23.6% for treatment-related grade 3-4 toxicity. The mean of overall survial amounted to 21.8 months for the resected patients, and 11.6 months for the unresected ones. This meta-analysis indicates that a benefit of preoperative neoadjuvant CT could be to spare surgery to BRPC patients with progressive disease during CT is administered. But downstaging of the lesion following treatment is uncommon.

Keywords

Borderline Resectable, Chemotherapy, Meta-Analysis, Neoadjuvant, Pancreatic Cancer.
User
Notifications
Font Size

  • Hidalgo, M., Pancreatic cancer. N. Engl. J. Med., 2010, 362, 1605–1617. PMID: 20427809.
  • Bittoni, A., Santoni, M., Lanese, A., Pellei, C., Andrikou, K. and Stefano, C., Neoadjuvant therapy in pancreatic cancer: an emerging strategy. Gastroenterol. Res. Pract., 2014, 2014, 183852. PMID: 25101123.
  • Varadhachary, G. R. et al., Borderline resectable pancreatic cancer: definitions, management, and role of preoperative therapy. Ann. Surg. Oncol., 2006, 13, 1035–1046. PMID: 16865597.
  • Pancreatic Adenocarcinoma. In NCCN, National Comprehensive Cancer Network guidelines; www.nccn.org/professionals/ physician_gls/f_guidelines.htm
  • Callery, M. P., Chang, K. J., Fishman, E. K., Talamonti, M. S., William Traverso, L. and Linehan, D. C., Pretreatment assessment of resectable and borderline resectable pancreatic cancer: expert consensus statement. Ann. Surg. Oncol., 2009, 16, 1727–1733. PMID: 19396496.
  • Festa, V. et al., Neoadjuvant chemo-radiotherapy for patients with borderline resectable pancreatic cancer: a meta-analytical evaluation of prospective studies. J. Pancreas, 2013, 14, 618–625. PMID: 24216547.
  • Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G. and Group, P., Preferred reporting items for systematic reviews and metaanalyses: the PRISMA statement. PLoS Med., 2009, 6, e1000097. PMID: 19621072.
  • Moher, D., Cook, D. J., Eastwood, S., Olkin, I., Rennie, D. and Stroup, D. F., Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of reporting of meta-analyses. Lancet, 1999, 354, 1896–1900. PMID: 10584742.
  • Morley, P. T. et al., Part 3: Evidence evaluation process: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Circulation, 2010, 122, S283–S290. PMID: 20956251.
  • Therasse, P. et al., New guidelines to evaluate the response to treatment in solid tumours. J. Natl. Cancer Inst., 2000, 92, 205– 216. PMID: 10655437.
  • Greenland, S., Quantitative methods in the review of epidemiologic literature. Epidemiol. Rev., 1987, 9, 1–30. PMID: 3678409.
  • Deeks, J. J., Higgins, J. P. T. and Altman, D. G., Analysing and presenting results. In Cochrane Handbook for Systematic Reviews of Interventions 4.2.6; Section 8 (eds Higgins, J. P. T. and Green, S.), The Cochrane Library, Issue 4, John Wiley, Chichester, UK, 2006.
  • Higgins, J. P. and Thompson, S. G., Quantifying heterogeneity in a meta-analysis. Stat. Med., 2002, 21, 1539–1558. PMID: 12111919.
  • Egger, M., Davey Smith, G., Schneider, M. and Minder, C., Bias in meta-analysis detected by a simple, graphical test. BMJ, 1997, 315, 629–634. PMID: 9310563.
  • van Houwelingen, H. C., Arends, L. R. and Stijnen, T., Advanced methods in meta-analysis: multivariate approach and metaregression. Stat. Med., 2002, 21, 589–624. PMID: 11836738.
  • Mehta, V. K. et al., Preoperative chemoradiation for marginally resectable adenocarcinoma of the pancreas. J. Gastrointest. Surg., 2001, 5, 27–35. PMID: 11309645.
  • Magnin, V. et al., Neoadjuvant preoperative chemoradiation in patients with pancreatic cancer. Int. J. Radiat. Oncol. Biol. Phys., 2003, 55, 1300–1304. PMID: 12654441.
  • Le Scodan, R. et al., Preoperative chemoradiation in potentially resectable pancreatic adenocarcinoma: feasibility, treatment effect evaluation and prognostic factors, analysis of the SFRO-FFCD 9704 trial and literature review. Ann. Oncol., 2009, 20, 1387– 1396. PMID: 19502533.
  • Massucco, P. et al., Pancreatic resections after chemoradiotherapy for locally advanced ductal adenocarcinoma: analysis of preoperative outcome and survival. Ann. Surg. Oncol., 2006, 13, 1201–1208. PMID: 16955382.
  • Sahora, K., Kuehrer, I., Schindl, M., Koelblinger, C., Goetzinger, P. and Gnant, M., NeoGemTax: gemcitabine and docetaxel as neoadjuvant treatment for locally advanced nonmetastasized pancreatic cancer. World J. Surg., 2011, 35, 1580–1589. PMID: 21523499.
  • Pipas, J. M. et al., Docetaxel/gemcitabine followed by gemcitabine and external beam radiotherapy in patients with pancreatic adenocarcinoma. Ann. Surg. Oncol., 2005, 12, 995–1004. PMID: 16252135.
  • Sahora, K. et al., NeoGemOx: gemcitabine and oxaliplatin as neoadjuvant treatment for locally advanced, nonmetastasized pancreatic cancer. Surgery, 2011, 149, 311–320. PMID: 20817204.
  • Small, J. W. et al., Phase II trial of full-dose gemcitabine and bevacizumab in combination with attenuated three-dimensional conformal radiotherapy in patients with localized pancreatic cancer. Int. J. Radiat. Oncol. Biol. Phys., 2011, 80, 476–482. PMID: 20598452.
  • Leone, F. et al., Induction gemcitabine and oxaliplatin therapy followed by a twice-weekly infusion of gemcitabine and concurrent external-beam radiation for neoadjuvant treatment of locally advanced pancreatic cancer: a single institutional experience. Cancer, 2013, 119, 277–284. PMID: 22778019.
  • Lee, J. L. et al., Prospective efficacy and safety study of neoadjuvant gemcitabine with capecitabine combination chemotherapy for borderline-resectable or unresectable locally advanced pancreatic adenocarcinoma. Surgery, 2012, 152, 851–862. PMID: 22682078.
  • Sahora, K. et al., A phase II trial of two durations of Bevacizumab added to neoadjuvant gemcitabine for borderline and locally advanced pancreatic cancer. Anticancer Res., 2014, 34, 2377– 2384. PMID: 24778046.
  • Kobayashi, M. et al., Gemcitabine-based chemoradiotherapy followed by surgery for borderline resectable and locally unresectable pancreatic ductal adenocarcinoma: significance of the CA19-9 reduction rate and intratumoural human equilibrative nucleoside transporter 1 expression. Pancreas, 2014, 43, 350–360. PMID: 24622063.
  • Mahaseth, H. et al., Modified FOLFIRINOX regimen with improved safety and maintained efficacy in pancreatic adenocarcinoma. Pancreas, 2013, 42, 1311–1315. PMID: 24152956.
  • Takahashi, H. et al., Preoperative gemcitabine-based chemoradiation therapy for resectable and borderline resectable pancreatic cancer. Ann. Surg., 2013, 258, 1040–1050. PMID: 23799421.
  • Ferrone, C. R. et al., Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann. Surg., 2015, 261, 12–17. PMID: 25599322.
  • Gillen, S., Schuster, T., Meyer Zum Buschenfelde, C., Friess, H. and Kleeff, J., Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med., 2010, 7, e1000267. PMID: 20422030.
  • Assifi, M. M., Lu, X., Eibl, G., Reber, H. A., Li, G. and Hines, O. J., Neoadjuvant therapy in pancreatic adenocarcinoma: a metaanalysis of phase II trials. Surgery, 2011, 150, 466–473. PMID: 21878232.
  • Katz, M. H. et al., Response of borderline resectable pancreatic cancer to neoadjuvant therapy is not reflected by radiographic indicators. Cancer, 2012, 118, 5749–5756. PMID: 22605518.
  • Zhang, Y., Huang, J., Chen, M. and Jiao, L. R., Preoperative vascular evaluation with computed tomography and magnetic resonance imaging for pancreatic cancer: a meta-analysis. Pancreatology, 2012, 12, 227–233. PMID: 22687378.

Abstract Views: 266

PDF Views: 110




  • Clinical Effectiveness of Preoperative Neoadjuvant Chemotherapy for Patients with Borderline Resectable Pancreatic Cancer:An Updated Meta-Analysis`

Abstract Views: 266  |  PDF Views: 110

Authors

Yao Liu
Department of Hepatobiliary Surgery, and Pancreas Disease Institute, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
Shan-Miao Gou
Pancreas Disease Institute, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
Yong Tang
Department of Hepatobiliary Surgery, and Pancreas Disease Institute, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
Chi-Dan Wan
Department of Hepatobiliary Surgery, and Pancreas Disease Institute, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China

Abstract


The benefit of preoperative neoadjuvant chemotherapy (CT) to borderline resectable pancreatic cancer (BRPC) is still not well known. This study aims to define the benefits of neoadjuvant CT for BRPC patients. By searching databases (PubMed, Embase, Cochrane Library) from 1966 to 2015, all prospective studies were analysed, where preoperative neoadjuvant CT or chemoradiotherapy was given to patients with BRPC. Laparotomy and resection rates were the primary outcomes. Secondary outcome was therapyinduced toxicity, tumour response, and overall survival. Data were shown as weighted frequency with 95% confidence interval. Fifteen studies with a total of 356 patients were included. All patients had BRPC and received neoadjuvant CT. Following the preoperative therapy, 78.1% of evaluable patients underwent laparotomy and 76.3% of laparotomy patients were performed resection. Also, 86% of specimens were deemed microscopically negative (R0) resection margins. At restaging following treatment, weighted frequencies for complete/partial response were 23.0%, 54.3% for stable disease 23.4% for progressive disease and 23.6% for treatment-related grade 3-4 toxicity. The mean of overall survial amounted to 21.8 months for the resected patients, and 11.6 months for the unresected ones. This meta-analysis indicates that a benefit of preoperative neoadjuvant CT could be to spare surgery to BRPC patients with progressive disease during CT is administered. But downstaging of the lesion following treatment is uncommon.

Keywords


Borderline Resectable, Chemotherapy, Meta-Analysis, Neoadjuvant, Pancreatic Cancer.

References





DOI: https://doi.org/10.18520/cs%2Fv110%2Fi4%2F595-602