IMPORTANCE: The recently released eighth edition of the American Joint Committee on Cancer TNM staging system for pancreatic cancer seeks to improve prognostic accuracy but lacks international ...validation. OBJECTIVE: To validate the eighth edition of the American Joint Committee on Cancer TNM staging system in an international cohort of patients with resected pancreatic ductal adenocarcinoma. DESIGN, SETTING, AND PARTICIPANTS: This international multicenter cohort study took place in 5 tertiary centers in Europe and the United States from 2000 to 2015. Patients who underwent pancreatoduodenectomy for nonmetastatic pancreatic ductal adenocarcinoma were eligible. Data analysis took place from December 2017 to April 2018. EXPOSURES: Patients were retrospectively staged according to the seventh and eighth editions of the TNM staging system. MAIN OUTCOMES AND MEASURES: Prognostic accuracy on survival rates, assessed by Kaplan-Meier and multivariate Cox proportional hazards analyses and concordance statistics. RESULTS: A total of 1525 consecutive patients were included (median IQR age, 66 (58-72) years; 802 (52.6%) male). Distribution among stages via the seventh edition was stage IA in 41 patients (2.7%), stage IB in 42 (2.8%), stage IIA in 200 (13.1%), stage IIB in 1229 (80.6%), and stage III in 12 (0.8%); this changed with use of the eighth edition to stage IA in 118 patients (7.7%), stage IB in 144 (9.4%), stage IIA in 22 (1.4%), stage IIB in 643 (42.2%), and stage III in 598 (39.2%). With the eighth edition, 774 patients (50.8%) migrated to a different stage; 183 (12.0%) were reclassified to a lower stage and 591 (38.8%) to a higher stage. Median overall survival for the entire cohort was 24.4 months (95% CI, 23.4-26.2 months). On Kaplan-Meier analysis, 5-year survival rates changed from 38.2% for patients in stage IA, 34.7% in IB, 35.3% in IIA, 16.5% in IIB, and 0% in stage III (log-rank P < .001) via classification with the seventh edition to 39.2% for patients in stage IA, 33.9% in IB, 27.6% in IIA, 21.0% in IIB, and 10.8% in stage III (log-rank P < .001) with the eighth edition. For patients who were node negative, the T stage was not associated with prognostication of survival in either edition. In the eighth edition, the N stage was associated with 5-year survival rates of 35.6% in N0, 20.8% in N1, and 10.9% in N2 (log-rank P < .001). The C statistic improved from 0.55 (95% CI, 0.53-0.57) for the seventh edition to 0.57 (95% CI, 0.55-0.60) for the eighth edition. CONCLUSIONS AND RELEVANCE: The eighth edition of the TNM staging system demonstrated a more equal distribution among stages and a modestly increased prognostic accuracy in patients with resected pancreatic ductal adenocarcinoma compared with the seventh edition. The revised T stage remains poorly associated with survival, whereas the revised N stage is highly prognostic.
Background
Textbook Outcome (TO) is a novel composite measure of clinical outcomes that can be used to measure the quality of surgical outcomes. TOs for pancreatic surgery were published by the Dutch ...Pancreatic Cancer Group (DPCG) in 2020. The aim of this study was to explore how a medium volume hepatopancreaticobiliary unit could use TO to benchmark local outcomes following pancreatic surgery.
Methods
Retrospective analysis of prospectively collected data from patients who underwent pancreaticoduodenectomy (PD) or distal pancreatectomy (DP) for all indications between March 2005 and February 2020 at Christchurch Hospital (CH). Analysis of TO items as defined by the DPCG was performed and compared to nationwide Dutch outcomes (2014–2017), including cumulative analysis using CuSum.
Results
In total, 273 patients were included (median age 63 years; 51% female) of which 182 (67%) underwent PD and 91 (33%) underwent DP (median annual volume 12 PDs/6 DPs). Overall, 58% of patients undergoing PD and 74% of patients undergoing DP achieved TO, compared with 58% and 67%, P = 0.944 and P = 0.231, respectively, for the Netherlands (median annual volume 33 PDs/8 DPs per hospital).
Conclusions
TO offers a useful quality measure to benchmark local outcomes following pancreatic surgery against an external nationwide analysis. The results show that as a medium volume centre performance was comparable to previously published Dutch results, which included high volume centres. Applying CuSum methodology to the TO metric allows a continuous measure of performance. This offers the potential to provide feedback for quality improvement strategies.
Retrospective study analysing Textbook Outcomes (TO) following pancreatic surgery performed at Christchurch Hospital, NZ and comparing these outcomes to those from the Netherlands nationwide analysis to determine potential benchmarking benefit. Also incorporating CuSum analysis of TO to assess TO as a potential quality assurance measure.
Background
Conditional survival is the survival probability after already surviving a predefined time period. This may be informative during follow-up, especially when adjusted for tumor ...characteristics. Such prediction models for patients with resected pancreatic cancer are lacking and therefore conditional survival was assessed and a nomogram predicting 5-year survival at a predefined period after resection of pancreatic cancer was developed.
Methods
This population-based study included patients with resected pancreatic ductal adenocarcinoma from the Netherlands Cancer Registry (2005–2016). Conditional survival was calculated as the median, and the probability of surviving up to 8 years in patients who already survived 0–5 years after resection was calculated using the Kaplan–Meier method. A prediction model was constructed.
Results
Overall, 3082 patients were included, with a median age of 67 years. Median overall survival was 18 months (95% confidence interval 17–18 months), with a 5-year survival of 15%. The 1-year conditional survival (i.e. probability of surviving the next year) increased from 55 to 74 to 86% at 1, 3, and 5 years after surgery, respectively, while the median overall survival increased from 15 to 40 to 64 months at 1, 3, and 5 years after surgery, respectively. The prediction model demonstrated that the probability of achieving 5-year survival at 1 year after surgery varied from 1 to 58% depending on patient and tumor characteristics.
Conclusions
This population-based study showed that 1-year conditional survival was 55% 1 year after resection and 74% 3 years after resection in patients with pancreatic cancer. The prediction model is available via
www.pancreascalculator.com
to inform patients and caregivers.
Histopathologically scoring the response of pancreatic ductal adenocarcinoma (PDAC) to neoadjuvant treatment can guide the selection of adjuvant therapy and improve prognostic stratification. ...However, several tumor response scoring (TRS) systems exist, and consensus is lacking as to which system represents best practice. An international consensus meeting on TRS took place in November 2019 in Amsterdam, The Netherlands. Here, we provide an overview of the outcomes and consensus statements that originated from this meeting. Consensus (≥80% agreement) was reached on a total of seven statements: (1) TRS is important because it provides information about the effect of neoadjuvant treatment that is not provided by other histopathology-based descriptors. (2) TRS for resected PDAC following neoadjuvant therapy should assess residual (viable) tumor burden instead of tumor regression. (3) The CAP scoring system is considered the most adequate scoring system to date because it is based on the presence and amount of residual cancer cells instead of tumor regression. (4) The defining criteria of the categories in the CAP scoring system should be improved by replacing subjective terms including “minimal” or “extensive” with objective criteria to evaluate the extent of viable tumor. (5) The improved, consensus-based system should be validated retrospectively and prospectively. (6) Prospective studies should determine the extent of tissue sampling that is required to ensure adequate assessment of the residual cancer burden, taking into account the heterogeneity of tumor response. (7) In future scientific publications, the extent of tissue sampling should be described in detail in the “Materials and methods” section.
Pancreatic acinar cell carcinoma is relatively rare (1 to 2% of pancreatic malignancies) but may be under-recognized. In contrast to pancreatic ductal adenocarcinoma, most acinar cell carcinomas lack ...mutations in KRAS, DPC, CDKN2A or TP53, but appear to have a high incidence of gene rearrangements, with up to 20% reported to be driven by BRAF fusions. With the development of a new class of RET-specific tyrosine kinase inhibitors, which appear to have particularly strong activity against RET gene rearranged tumours, there is now considerable interest in identifying RET gene rearrangements across a wide range of cancers. RET rearrangements have been reported to occur at a very low incidence (<1%) in all pancreatic carcinomas. We postulated that given its unique molecular profile, RET gene rearrangements may be common in acinar cell carcinomas. We performed fluorescent in-situ hybridization (FISH) studies on a cohort of 40 acinar cell spectrum tumours comprising 36 pure acinar cell carcinomas, three pancreatoblastomas and one mixed acinar-pancreatic neuroendocrine tumour. RET gene rearrangements were identified in 3 (7.5%) cases and BRAF gene rearrangements in 5 (12.5%). All gene rearranged tumours were pure acinar cell carcinomas. Our findings indicate that amongst all pancreatic carcinomas, acinar carcinomas are highly enriched for potentially actionable gene rearrangements in RET or BRAF. FISH testing is inexpensive and readily available in the routine clinical setting and may have a role in the assessment of all acinar cell carcinomas-at this stage to recruit patients for clinical trials of new targeted therapies, but perhaps in the near future as part of routine care.
Background and Objectives
Patients with locally advanced pancreatic cancer (LAPC) are increasingly treated with FOLFIRINOX, resulting in improved survival and resection of tumors that were initially ...unresectable. It remains unclear, however, which specific patients benefit from FOLFIRINOX. Two nomograms were developed predicting overall survival (OS) and resection at the start of FOLFIRINOX for LAPC.
Methods
From our multicenter, prospective LAPC registry in 14 Dutch hospitals, LAPC patients starting first‐line FOLFIRINOX (April 2015–December 2017) were included. Stepwise backward selection according to the Akaike Information Criterion was used to identify independent baseline predictors for OS and resection. Two prognostic nomograms were generated.
Results
A total of 252 patients were included, with a median OS of 14 months. Thirty‐two patients (13%) underwent resection, with a median OS of 23 months. Older age, female sex, Charlson Comorbidity Index ≤1, and CA 19.9 < 274 were independent factors predicting a better OS (c‐index: 0.61). WHO ps >1, involvement of the superior mesenteric artery, celiac trunk, and superior mesenteric vein ≥ 270° were independent factors decreasing the probability of resection (c‐index: 0.79).
Conclusions
Two nomograms were developed to predict OS and resection in patients with LAPC before starting treatment with FOLFIRINOX. These nomograms could be beneficial in the shared decision‐making process and counseling of these patients.
Various prognostic factors are associated with overall survival (OS) after resection of distal cholangiocarcinoma (dCCA). The objective of this study was to develop and validate a prediction model ...for 3-year OS after pancreatoduodenectomy for dCCA.
The derivation cohort consisted of all patients who underwent pancreatoduodenectomy for dCCA in the Netherlands (2009-2016). Clinically relevant variables were selected based on the Akaike information criterion using a multivariate Cox proportional hazards regression model, with model performance being assessed by concordance index (C-index) and calibration plots. External validation was performed using patients from the Belgium Cancer Registry (2008-2016), and patients from two university hospitals of Southampton (U.K.) and Verona (Italy).
Independent prognostic factors for OS in the derivation cohort of 454 patients after pancreatoduodenectomy for dCCA were age (HR 1.02, 95% CI 1.01-1.03), pT (HR 1.43, 95% CI 1.07-1.90) and pN category (pN1: HR 1.78, 95% CI 1.37-2.32; pN2: HR 2.21, 95% CI 1.63-3.01), resection margin status (HR 1.79, 95% CI 1.39-2.29) and tumour differentiation (HR 2.02, 95% CI 1.62-2.53). The prediction model was based on these prognostic factors. The optimism-adjusted C-indices were similar in the derivation cohort (0.69), and in the Belgian (0.66) and Southampton-Verona (0.68) validation cohorts. Calibration was accurate in the Belgian validation cohort (slope = 0.93, intercept = 0.12), but slightly less optimal in the Southampton-Verona validation cohort (slope = 0.88, intercept = 0.32). Based on this model, three risk groups with different prognoses were identified (3-year OS of 65.4%, 33.2% and 11.8%).
The prediction model for 3-year OS after resection of dCCA had reasonable performance in both the derivation and geographically external validation cohort. Calibration slightly differed between validation cohorts. The model is readily available via www. pancreascalculator.com to inform patients from Western European countries on their prognosis, and may be used to stratify patients for clinical trials.
Background
The prognostic value of four proposed modifications to the 8th American Joint Committee on Cancer (AJCC) TNM staging system has yet to be evaluated. This study aimed to validate five ...proposed modifications.
Methods
Patients who underwent pancreatic ductal adenocarcinoma resection (2014–2016), as registered in the prospective Dutch Pancreatic Cancer Audit, were included. Stratification and prognostication of TNM staging systems were assessed using Kaplan–Meier curves, Cox proportional hazard analyses, and C-indices. A new modification was composed based on overall survival (OS).
Results
Overall, 750 patients with a median OS of 18 months (interquartile range 10–32) were included. The 8th edition had an increased discriminative ability compared with the 7th edition {C-index 0.59 (95% confidence interval CI 0.56–0.61) vs. 0.56 (95% CI 0.54–0.58)}. Although the 8th edition showed a stepwise decrease in OS with increasing stage, no differences could be demonstrated between all substages; stage IIA vs. IB (hazard ratio HR 1.30, 95% CI 0.80–2.09;
p
= 0.29) and stage IIB vs. IIA (HR 1.17, 95% CI 0.75–1.83;
p
= 0.48). The four modifications showed comparable prognostic accuracy (C-index 0.59–0.60); however, OS did not differ between all modified TNM stages (ns). The new modification, migrating T3N1 patients to stage III, showed a C-index of 0.59, but did detect significant survival differences between all TNM stages (
p
< 0.05).
Conclusions
The 8th TNM staging system still lacks prognostic value for some categories of patients, which was not clearly improved by four previously proposed modifications. The modification suggested in this study allows for better prognostication in patients with all stages of disease.
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