Preoperative chemoradiotherapy may improve the radical resection rate for resectable or borderline resectable pancreatic cancer, but the overall benefit is unproven.
In this randomized phase III ...trial in 16 centers, patients with resectable or borderline resectable pancreatic cancer were randomly assigned to receive preoperative chemoradiotherapy, which consisted of 3 courses of gemcitabine, the second combined with 15 × 2.4 Gy radiotherapy, followed by surgery and 4 courses of adjuvant gemcitabine or to immediate surgery and 6 courses of adjuvant gemcitabine. The primary end point was overall survival by intention to treat.
Between April 2013 and July 2017, 246 eligible patients were randomly assigned; 119 were assigned to preoperative chemoradiotherapy and 127 to immediate surgery. Median overall survival by intention to treat was 16.0 months with preoperative chemoradiotherapy and 14.3 months with immediate surgery (hazard ratio, 0.78; 95% CI, 0.58 to 1.05;
= .096). The resection rate was 61% and 72% (
= .058). The R0 resection rate was 71% (51 of 72) in patients who received preoperative chemoradiotherapy and 40% (37 of 92) in patients assigned to immediate surgery (
< .001). Preoperative chemoradiotherapy was associated with significantly better disease-free survival and locoregional failure-free interval as well as with significantly lower rates of pathologic lymph nodes, perineural invasion, and venous invasion. Survival analysis of patients who underwent tumor resection and started adjuvant chemotherapy showed improved survival with preoperative chemoradiotherapy (35.2
19.8 months;
029). The proportion of patients who suffered serious adverse events was 52% versus 41% (
096).
Preoperative chemoradiotherapy for resectable or borderline resectable pancreatic cancer did not show a significant overall survival benefit. Although the outcomes of the secondary end points and predefined subgroup analyses suggest an advantage of the neoadjuvant approach, additional evidence is required.
The benefit of neoadjuvant chemoradiotherapy in resectable and borderline resectable pancreatic cancer remains controversial. Initial results of the PREOPANC trial failed to demonstrate a ...statistically significant overall survival (OS) benefit. The long-term results are reported.
In this multicenter, phase III trial, patients with resectable and borderline resectable pancreatic cancer were randomly assigned (1:1) to neoadjuvant chemoradiotherapy or upfront surgery in 16 Dutch centers. Neoadjuvant chemoradiotherapy consisted of three cycles of gemcitabine combined with 36 Gy radiotherapy in 15 fractions during the second cycle. After restaging, patients underwent surgery followed by four cycles of adjuvant gemcitabine. Patients in the upfront surgery group underwent surgery followed by six cycles of adjuvant gemcitabine. The primary outcome was OS by intention-to-treat. No safety data were collected beyond the initial report of the trial.
Between April 24, 2013, and July 25, 2017, 246 eligible patients were randomly assigned to neoadjuvant chemoradiotherapy (n = 119) and upfront surgery (n = 127). At a median follow-up of 59 months, the OS was better in the neoadjuvant chemoradiotherapy group than in the upfront surgery group (hazard ratio, 0.73; 95% CI, 0.56 to 0.96;
= .025). Although the difference in median survival was only 1.4 months (15.7 months
14.3 months), the 5-year OS rate was 20.5% (95% CI, 14.2 to 29.8) with neoadjuvant chemoradiotherapy and 6.5% (95% CI, 3.1 to 13.7) with upfront surgery. The effect of neoadjuvant chemoradiotherapy was consistent across the prespecified subgroups, including resectable and borderline resectable pancreatic cancer.
Neoadjuvant gemcitabine-based chemoradiotherapy followed by surgery and adjuvant gemcitabine improves OS compared with upfront surgery and adjuvant gemcitabine in resectable and borderline resectable pancreatic cancer.
Auditing is an important tool to identify practice variation and ‘best practices’. The Dutch Pancreatic Cancer Audit is mandatory in all 18 Dutch centers for pancreatic surgery.
Performance ...indicators and case-mix factors were identified by a PubMed search for randomized controlled trials (RCT's) and large series in pancreatic surgery. In addition, data dictionaries of two national audits, three institutional databases, and the Dutch national cancer registry were evaluated. Morbidity, mortality, and length of stay were analyzed of all pancreatic resections registered during the first two audit years. Case ascertainment was cross-checked with the Dutch healthcare inspectorate and key-variables validated in all centers.
Sixteen RCT's and three large series were found. Sixteen indicators and 20 case-mix factors were included in the audit. During 2014–2015, 1785 pancreatic resections were registered including 1345 pancreatoduodenectomies. Overall in-hospital mortality was 3.6%. Following pancreatoduodenectomy, mortality was 4.1%, Clavien–Dindo grade ≥ III morbidity was 29.9%, median (IQR) length of stay 12 (9–18) days, and readmission rate 16.0%. In total 97.2% of >40,000 variables validated were consistent with the medical charts.
The Dutch Pancreatic Cancer Audit, with high quality data, reports good outcomes of pancreatic surgery on a national level.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Novel definitions suggest that resectability status for pancreatic ductal adenocarcinoma (PDAC) should be assessed beyond anatomical criteria, considering both biological and conditional ...factors. This has, however, yet to be validated on a nationwide scale. This study evaluated the prognostic value of biological and conditional factors for staging of patients with resectable PDAC.
Patients and Methods
A nationwide observational cohort study was performed, including all consecutive patients who underwent upfront resection of National Comprehensive Cancer Network resectable PDAC in the Netherlands (2014–2019) with complete information on preoperative carbohydrate antigen (CA) 19-9 and Eastern Cooperative Oncology Group (ECOG) performance status. PDAC was considered biologically unfavorable (R
B+
) if CA19-9 ≥ 500 U/mL and favorable (R
B−
) otherwise. ECOG ≥ 2 was considered conditionally unfavorable (R
C+
) and favorable otherwise (R
C−
). Overall survival (OS) was assessed using Kaplan–Meier and Cox-proportional hazard analysis, presented as hazard ratios (HRs) with 95% confidence interval (CI).
Results
Overall, 688 patients were analyzed with a median overall survival (OS) of 20 months (95% CI 19–23). OS was 14 months (95% CI 10 months—median not reached) in 20 R
B+C+
patients (3%; HR 1.61, 95% CI 0.86–2.70), 13 months (95% CI 11–15) in 156 R
B+C−
patients (23%; HR 1.86, 95% CI 1.50–2.31), and 21 months (95% CI 12–41) in 47 R
B−C+
patients (7%; HR 1.14, 95% CI 0.80–1.62) compared with 24 months (95% CI 22–27) in 465 patients with R
B−C−
PDAC (68%; reference).
Conclusions
Survival after upfront resection of anatomically resectable PDAC is worse in patients with CA19-9 ≥ 500 U/mL, while performance status had no impact. This supports consideration of CA19-9 in preoperative staging of resectable PDAC.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract Background Beyond demographic and immune factors, metabolic considerations, particularly metformin’s recognized impact in oncology, warrant exploration in treating pancreatic cancer. This ...study aimed to investigate the influence of metformin on patient survival and its potential correlation with distinct immune profiles in pancreatic ductal adenocarcinoma (PDAC) tumors. Methods We included 82 upfront resected and 66 gemcitabine-based neoadjuvant chemoradiotherapy (nCRT)-treated patients from the PREOPANC randomized controlled trial (RCT). Transcriptomic NanoString immunoprofiling was performed for a subset of 96 available resected specimens. Results Disparities in survival outcomes and immune profiles were apparent between metformin and non-metformin users in upfront resected patients but lacking in nCRT-treated patients. Compared to non-metformin users, upfront resected metformin users showed a higher median overall survival (OS) of 29 vs 14 months and a better 5-year OS rate of 19% vs 5%. Furthermore, metformin use was a favorable prognostic factor for OS in the upfront surgery group (HR = 0.56; 95% CI = 0.32 to 0.99). Transcriptomic data revealed that metformin users significantly underexpressed genes related to pro-tumoral immunity, including monocyte to M2 macrophage polarization and activation. Furthermore, the relative abundance of anti-inflammatory CD163+ MRC1+ M2 macrophages in non-metformin users and immune-activating CD1A+ CD1C+ dendritic cells in metformin users was heightened (P < .001). Conclusion This study unveils immune profile changes resulting from metformin use in upfront resected pancreatic cancer patients, possibly contributing to prolonged survival outcomes. Specifically, metformin use may decrease the abundance and activity of pro-tumoral M2 macrophages and increase the recruitment and function of tumor-resolving DCs, favoring antitumor immunity. PREOPANC trial EudraCT: 2012-003181-40
PDF
