Neoadjuvant therapy affects margins and margins affect all: perioperative and survival outcomes in resected pancreatic adenocarcinoma

Geus, Susanna W.L. de; Kasumova, Gyulnara G.; Sachs, Teviah E.; Ng, Sing Chau; Kent, Tara S.; Moser, A. James; Vahrmeijer, Alexander L.; Callery, Mark P.; Tseng, Jennifer F.

doi:10.1016/j.hpb.2017.12.004

Cited by 24 publications

(21 citation statements)

References 46 publications

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“…As only 2 of these studies were phase II trials 29,30 , one of which was randomized 29 all studies were therefore included in the network meta-analysis. 4 studies were prospective 31–34 and 3 studies were retrospective 35–37 (Supplementary Table 1a; Supplementary Fig. 2).…”

Section: Resultsmentioning

confidence: 99%

“…31 did not report this outcome separately for resectable only cases but included borderline cases also in reporting the outcomes of response to NAT (complete response: 5/45; partial response: 13/45; stable disease 5/45). 6 studies (n = 17596) reported the number of patients in the SFadj pathway who received adjuvant therapy 31–33,35–37 giving a pooled proportion of 63.01% (95% CI: 59.452–66.489).…”

Section: Resultsmentioning

confidence: 99%

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Upfront Surgery versus Neoadjuvant Therapy for Resectable Pancreatic Cancer: Systematic Review and Bayesian Network Meta-analysis

Bradley

Meer

2019

Sci Rep

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Current treatment recommendations for resectable pancreatic cancer support upfront resection and adjuvant therapy. Randomized controlled trials offering comparison with the emerging neoadjuvant approach are lacking. This review aims to compare both treatment strategies for resectable pancreatic cancer. PubMed, MEDLINE, Embase, Cochrane Database and Cochrane Databases were searched for studies comparing neoadjuvant and surgery-first with adjuvant therapy for resectable pancreatic cancer. A Bayesian network meta-analysis was conducted using the Markov chain Monte Carlo method. Cochrane Collaboration’s risk of bias, ROBINS-I and GRADE tools were used to assess quality and risk of bias of included trials. 9 studies compared neoadjuvant therapy and surgery-first with adjuvant therapy (n = 22,285). Aggregate rate (AR) of R0 resection for neoadjuvant therapy was 0.8008 (0.3636–0.9144) versus 0.7515 (0.2026–0.8611) odds ratio (O.R.) 1.27 (95% CI 0.60–1.96). 1-year survival AR for neoadjuvant therapy was 0.7969 (0.6061–0.9500) versus 0.7481 (0.4848–0.8500) O.R. 1.38 (95% CI 0.69–2.96). 2-year survival AR for neoadjuvant therapy was 0.5178 (0.3000–0.5970) versus 0.5131 (0.2727–0.5346) O.R. 1.26 (95% CI 0.94–1.74). 5-year AR survival for neoadjuvant therapy was 0.2069 (0.0323–0.3300) versus 0.1783 (0.0606–0.2300) O.R. 1.19 (95% CI 0.65–1.73). In conclusion neoadjuvant therapy may offer benefit over surgery-first and adjuvant therapy. However, further randomized controlled trials are needed.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Upfront Surgery versus Neoadjuvant Therapy for Resectable Pancreatic Cancer: Systematic Review and Bayesian Network Meta-analysis

Bradley

Meer

2019

Sci Rep

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“…Therefore, clinicians should consider more aggressive postoperative treatments or neoadjuvant therapy first, rather than upfront surgery in these cases. Neoadjuvant chemoradiation, which has the advantage of increased R0 rates, is widely performed recently when it is deemed difficult to obtain sufficient surgical margin [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Oncologic outcomes according to the location and status of resection margin in pancreas head cancer: role of radiation therapy in R1 resection

Sohn

Kim

et al. 2022

Ann Surg Treat Res

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Purpose The clinical significance of margin status in pancreatic head cancer is still controversial due to the nonstandardized definition of R status and pathologic reporting. This study aims to evaluate the impact of the margin status including location and the role of radiation therapy in pancreatic head cancer. Methods A total of 314 patients who underwent curative-intent surgery for pancreatic head cancer between 2010 and 2017 were analyzed. Demographics, survival, and local recurrences were compared according to 2 definitions: 0-mm R1 as direct involvement and 1-mm R1 as close resection margin less than 1 mm. The specific margins were divided into 4 groups according to the location around the pancreas: pancreas transection, anterior surface, posterior surface, and vessel (superior mesenteric artery/superior mesenteric vein) margin. Results The 0-mm R1-rate was 15.6%, and increased to 36.3% in 1-mm R1. The median overall survival rate of 0-mm R0 vs. R1 was 26 months vs. 16 months (P = 0.052) and that of 1-mm R0 vs. R1 was 27 months vs. 18 months, respectively (P = 0.016). In individual margins, posterior, anterior surface, and pancreas transection margin involvement were associated with poor outcome, and the 1 mm posterior surface involvement was an independent risk factor for disease-free survival (hazard ratio, 1.63). Adjuvant radiation therapy had oncologic benefits, especially in R1 patients (P = 0.011) compared to R0 patients (P = 0.088). Conclusion Margin status, especially 1-mm R1 status is an important predictive factor, and involved posterior surface has a clinical impact. Patients with positive margins should be considered adjuvant radiation therapy.

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“…25 and de Geus et al . 37 used the same NCD database and data collected during overlapping periods from 2006 to 2012. Furthermore, two other studies by Roland et al .…”

Section: Discussionmentioning

confidence: 99%

Neoadjuvant therapy versus upfront surgery in resectable pancreatic cancer according to intention-to-treat and per-protocol analysis: A systematic review and meta-analysis

Lee

Yang

et al. 2019

Sci Rep

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The effectiveness of neoadjuvant therapy (NAT) remains unclear in resectable pancreatic cancer (PC) as compared with upfront surgery (US). The aim of this study was to investigate the survival gain of NAT over US in resectable PC. PubMed and EMBASE were searched for studies comparing survival outcomes between NAT and US for resectable PC until June 2018. Overall survival (OS) was analyzed according to treatment strategy (NAT versus US) and analytic methods (intention-to-treat analysis (ITT) and per-protocol analysis (PP)). In 14 studies, 2,699 and 6,992 patients were treated with NAT and US, respectively. Although PP analysis showed the survival gain of NAT (HR 0.72, 95% CI 0.68–0.76), ITT analysis did not show the statistical significance (HR 0.96, 95% CI 0.82–1.12). However, NAT completed with subsequent surgery showed better survival over US completed with adjuvant therapy (HR 0.82, 95% CI 0.71–0.93). In conclusion, the supporting evidence for NAT in resectable PC was insufficient because the benefit was not demonstrated in ITT analysis. However, among the patients who completed both surgery and chemotherapy, NAT showed survival benefit over adjuvant therapy. Therefore, NAT could have a role of triaging the patients for surgery even in resectable PC.

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Neoadjuvant therapy affects margins and margins affect all: perioperative and survival outcomes in resected pancreatic adenocarcinoma

Cited by 24 publications

References 46 publications

Upfront Surgery versus Neoadjuvant Therapy for Resectable Pancreatic Cancer: Systematic Review and Bayesian Network Meta-analysis

Upfront Surgery versus Neoadjuvant Therapy for Resectable Pancreatic Cancer: Systematic Review and Bayesian Network Meta-analysis

Oncologic outcomes according to the location and status of resection margin in pancreas head cancer: role of radiation therapy in R1 resection

Neoadjuvant therapy versus upfront surgery in resectable pancreatic cancer according to intention-to-treat and per-protocol analysis: A systematic review and meta-analysis

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