Despite an aging population and underrepresentation of elderly patients in clinical trials, studies on elderly patients with metastatic pancreatic cancer are scarce. This study investigated the use ...of chemotherapy and survival in elderly patients with metastatic pancreatic cancer. From the Netherlands Cancer Registry, all 9407 patients diagnosed with primary metastatic pancreatic adenocarcinoma in 2005–2013 were selected to investigate chemotherapy use and overall survival (OS), using Kaplan–Meier and Cox proportional hazard regression analyses. Over time, chemotherapy use increased in all age groups (<70 years: from 26 to 43%, 70–74 years: 14 to 25%, 75–79 years: 5 to 13%, all P < 0.001, and ≥80 years: 2 to 3% P = 0.56). Median age of 2,180 patients who received chemotherapy was 63 years (range 21–86 years, 1.6% was ≥80 years). In chemotherapy‐treated patients, with rising age (<70, 70–74, 75–79, ≥80 years), microscopic tumor verification occurred less frequently (91‐88‐87‐77%, respectively, P = 0.009) and OS diminished (median 25‐26‐19‐16 weeks, P = 0.003). After adjustment for confounding factors, worse survival of treated patients ≥75 years persisted. Despite limited chemotherapy use in elderly age, suggestive of strong selection, elderly patients (≥75 years) who received chemotherapy for metastatic pancreatic cancer exhibited a worse survival compared to younger patients receiving chemotherapy.
Data on elderly patients with metastatic pancreatic cancer are scarce. With rising age, palliative chemotherapy use decreased until <5% in octogenarians. Following chemotherapy, patients over 75 years of age had a worse survival.
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.
Objective:
This study compared median OS after resection of LAPC after upfront FOLFIRINOX versus a propensity-score matched cohort of LAPC patients treated with FOLFIRINOX-only (ie, without ...resection).
Background:
Because the introduction of FOLFIRINOX chemotherapy, increased resection rates in LAPC patients have been reported, with improved OS. Some studies have also reported promising OS with FOLFIRINOX-only treatment in LAPC. Multicenter studies assessing the survival benefit associated with resection of LAPC versus patients treated with FOLFIRINOX-only are lacking.
Methods:
Patients with non-progressive LAPC after 4 cycles of FOLFIRINOX treatment, both with and without resection, were included from a prospective multicenter cohort in 16 centers (April 2015–December 2019). Cox regression analysis identified predictors for OS. One-to-one propensity score matching (PSM) was used to obtain a matched cohort of patients with and without resection. These patients were compared for OS.
Results:
Overall, 293 patients with LAPC were included, of whom 89 underwent a resection. Resection was associated with improved OS (24 vs 15 months,
P
< 0.01), as compared to patients without resection. Before PSM, resection, Charlson Comorbidity Index, and Response Evaluation Criteria in Solid Tumors (RECIST) response were predictors for OS. After PSM, resection remained associated with improved OS Hazard Ratio (HR) 0.344, 95% confidence interval (0.222–0.534),
P
< 0.01, with an OS of 24 versus 15 months, as compared to patients without resection. Resection of LAPC was associated with improved 3-year OS (31% vs 11%,
P
< 0.01).
Conclusions:
Resection of LAPC after FOLFIRINOX was associated with increased OS and 3-year survival, as compared to propensity-score matched patients treated with FOLFIRINOX-only.
The relation between type of postoperative complication and not receiving chemotherapy after resection of pancreatic ductal adenocarcinoma (PDAC) is unclear. The aim was to investigate which patient ...factors and postoperative complications were associated with not receiving adjuvant chemotherapy.
Patients who underwent resection (2014–2017) for PDAC were identified from the nationwide mandatory Dutch Pancreatic Cancer Audit. The association between patient-, tumor-, center-, treatment characteristics, and the risk of not receiving adjuvant chemotherapy was analyzed with multivariable logistic regression.
Overall, of 1306 patients, 24% (n = 312) developed postoperative Clavien Dindo ≥3 complications. In-hospital mortality was 3.5% (n = 46). Some 433 patients (33%) did not receive adjuvant chemotherapy. Independent predictors (all p < 0.050) for not receiving adjuvant chemotherapy were older age (odds ratio (OR) 0.96), higher ECOG performance status (OR 0.57), postoperative complications (OR 0.32), especially grade B/C pancreatic fistula (OR 0.51) and post-pancreatectomy hemorrhage (OR 0.36), poor tumor differentiation grade (OR 0.62), and annual center volume of <40 pancreatoduodenectomies (OR 0.51).
This study demonstrated that a third of patients do not receive chemotherapy after resection of PDAC. Next to higher age, worse performance status and lower annual surgical volume, this is mostly related to surgical complications, especially postoperative pancreatic fistula and post-pancreatectomy hemorrhage.
IMPORTANCE: Implementation of new cancer treatment strategies as recommended by evidence-based guidelines is often slow and suboptimal. OBJECTIVE: To improve the implementation of guideline-based ...best practices in the Netherlands in pancreatic cancer care and assess the impact on survival. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, stepped-wedge cluster randomized trial compared enhanced implementation of best practices with usual care in consecutive patients with all stages of pancreatic cancer. It took place from May 22, 2018 through July 9, 2020. Data were analyzed from April 1, 2022, through February 1, 2023. It included all patients in the Netherlands with pathologically or clinically diagnosed pancreatic ductal adenocarcinoma. This study reports 1-year follow-up (or shorter in case of deceased patients). INTERVENTION: The 5 best practices included optimal use of perioperative chemotherapy, palliative chemotherapy, pancreatic enzyme replacement therapy (PERT), referral to a dietician, and use of metal stents in patients with biliary obstruction. A 6-week implementation period was completed, in a randomized order, in all 17 Dutch networks for pancreatic cancer care. MAIN OUTCOMES AND MEASURES: The primary outcome was 1-year survival. Secondary outcomes included adherence to best practices and quality of life (European Organisation for Research and Treatment of Cancer EORTC global health score). RESULTS: Overall, 5887 patients with pancreatic cancer (median age, 72.0 IQR, 64.0-79.0 years; 50% female) were enrolled, 2641 before and 2939 after implementation of best practices (307 during wash-in period). One-year survival was 24% vs 23% (hazard ratio, 0.98, 95% CI, 0.88-1.08). There was no difference in the use of neoadjuvant chemotherapy (11% vs 11%), adjuvant chemotherapy (48% vs 51%), and referral to a dietician (59% vs 63%), while the use of palliative chemotherapy (24% vs 30%; odds ratio OR, 1.38; 95% CI, 1.10-1.74), PERT (34% vs 45%; OR, 1.64; 95% CI, 1.28-2.11), and metal biliary stents increased (74% vs 83%; OR, 1.78; 95% CI, 1.13-2.80). The EORTC global health score did not improve (area under the curve, 43.9 vs 42.8; median difference, −1.09, 95% CI, −3.05 to 0.94). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, implementation of 5 best practices in pancreatic cancer care did not improve 1-year survival and quality of life. The finding that most patients received no tumor-directed treatment paired with the poor survival highlights the need for more personalized treatment options. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03513705
Periampullary adenocarcinoma consists of pancreatic adenocarcinoma (PDAC), distal cholangiocarcinoma (DC), ampullary cancer (AC), and duodenal adenocarcinoma (DA). The aim of this study was to assess ...treatment modalities and overall survival by tumor origin.
Patients diagnosed with non-metastatic periampullary cancer in 2012–2018 were identified from the Netherlands Cancer Registry. OS was studied with Kaplan–Meier analysis and multivariable Cox regression analyses, stratified by origin.
Among the 8758 patients included, 68% had PDAC, 13% DC, 12% AC, and 7% DA. Resection was performed in 35% of PDAC, 56% of DC, 70% of AC, and 59% of DA. Neoadjuvant and/or adjuvant therapy was administered in 22% of PDAC, 7% of DC, 7% of AC, and 12% of DA. Three-year OS was highest for AC (37%) and DA (34%), followed by DC (21%) and PDAC (11%). Adjuvant therapy was associated with improved OS among PDAC (HR = 0.62; 95% CI 0.55–0.69) and DC (HR = 0.69; 95% CI 0.48–0.98), but not AC (HR = 0.87; 95% CI 0.62–1.22) and DA (HR = 0.85; 95% CI 0.48–1.50).
This retrospective study identified considerable differences in treatment modalities and OS between the four periampullary cancer origins in daily clinical practice. An improved OS after adjuvant chemotherapy could not be demonstrated in patients with AC and DA.
In recent years, new treatment options have become available for pancreatic ductal adenocarcinoma (PDAC) including 5-fluorouracil, leucovorin, irinotecan and oxaliplatin. The impact hereof has not ...been assessed in nationwide cohort studies. This population-based study aimed to investigate nationwide trends in incidence, treatment and survival of PDAC.
Patients with PDAC (1997–2016) were included from the Netherlands Cancer Registry. Results were categorised by treatment and by period of diagnosis (1997–2000, 2001–2004, 2005–2008, 2009–2012 and 2013–2016). Kaplan–Meier survival analysis was used to calculate overall survival.
In a national cohort of 36,453 patients with PDAC, the incidence increased from 12.1 (1997–2000) to 15.3 (2013–2016) per 100,000 (p < 0.001), whereas median overall survival increased from 3.1 to 3.8 months (p < 0.001). Over time, the resection rate doubled (8.3%–16.6%, p-trend<0.001), more patients received adjuvant chemotherapy (3.0%–56.2%, p-trend<0.001) and 3-year overall survival following resection increased (16.9%–25.4%, p < 0.001). Over time, the proportion of patients with metastatic disease who received palliative chemotherapy increased from 5.3% to 16.1% (p-trend<0.001), whereas 1-year survival improved from 13.3% to 21.2% (p < 0.001). The proportion of patients who only received supportive care decreased from 84% to 61% (p-trend<0.001).
The incidence of PDAC increased in the past two decades. Resection rates and use of adjuvant or palliative chemotherapy increased with improved survival in these patients. In all patients with PDAC, however, the survival benefit of 3 weeks is negligible because the majority of patients only received supportive care.
•The incidence of pancreatic ductal adenocarcinoma increased from 1997 to 2016.•Resection rates and use of adjuvant or palliative chemotherapy increased.•The majority of patients still received supportive care only.•Survival improved in patients who underwent resection or systemic treatment.•The survival of all patients improved with only 3 weeks.
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.
Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis of all common cancers. However, divergent outcomes exist between patients, suggesting distinct underlying tumor biology. Here, we ...delineated this heterogeneity, compared interconnectivity between classification systems, and experimentally addressed the tumor biology that drives poor outcome. RNA-sequencing of 90 resected specimens and unsupervised classification revealed four subgroups associated with distinct outcomes. The worst-prognosis subtype was characterized by mesenchymal gene signatures. Comparative (network) analysis showed high interconnectivity with previously identified classification schemes and high robustness of the mesenchymal subtype. From species-specific transcript analysis of matching patient-derived xenografts we constructed dedicated classifiers for experimental models. Detailed assessments of tumor growth in subtyped experimental models revealed that a highly invasive growth pattern of mesenchymal subtype tumor cells is responsible for its poor outcome. Concluding, by developing a classification system tailored to experimental models, we have uncovered subtype-specific biology that should be further explored to improve treatment of a group of PDAC patients that currently has little therapeutic benefit from surgical treatment.
To investigate the association between perineural invasion (PNI) and overall survival (OS) in a nationwide cohort of patients with resected pancreatic ductal adenocarcinoma (PDAC), stratified for ...margin negative (R0) or positive (R1) resection and absence or presence of lymph node metastasis (pN0 or pN1-N2, respectively).
Patients with R0 and pN0 resected PDAC have a relatively favorable prognosis. As PNI is associated with worse OS, this might be a useful factor to provide further prognostic information for patients counselling.
A nationwide observational cohort study was performed including all patients who underwent PDAC resection in the Netherlands (2014-2019) with complete information on relevant pathological features (PNI, R status, and N status). OS was assessed using Kaplan-Meier curves, and Cox-proportional hazard analyses were performed to calculate hazard ratio's (HR) with corresponding 95% confidence intervals (CI).
In total, 1630 patients were included with a median follow-up of 43 (interquartile range 33-58) months. PNI was independently associated with worse OS in both R0 patients (HR 1.49 95%CI 1.18-1.88; P<0.001) and R1 patients (HR 1.39 95% CI 1.06-1.83; P=0.02), as well as in pN0 patients (HR 1.75 95%CI 1.27-2.41; P<0.001) and pN1-N2 patients (HR 1.35 95% CI 1.10-1.67; P<0.01). In 315 patients with R0N0, multivariable analysis showed that PNI was the strongest predictor of OS (HR 2.24 95% CI 1.52-3.30; P<0.001).
PNI is strongly associated with worse survival in patients with resected PDAC, in particular in patients with relatively favorable pathological features. These findings may aid patient stratification and counselling and help guide treatment strategies.
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