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Importance: The effect of adjuvant chemotherapy following resection of pancreatic adenocarcinoma after preoperative (m)FOLFIRINOX (combination leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin in full or modified dosing) chemotherapy on overall survival (OS) is unclear because current studies do not account for the number of cycles of preoperative chemotherapy and adjuvant chemotherapy regimen.

Objective: To investigate the association of adjuvant chemotherapy following resection of pancreatic adenocarcinoma after preoperative (m)FOLFIRINOX with OS, taking into account the number of cycles of preoperative chemotherapy and adjuvant chemotherapy regimen.

Design, Setting, and Participants: This retrospective cohort study included patients with localized pancreatic adenocarcinoma treated with 2 to 11 cycles of preoperative (m)FOLFIRINOX followed by resection across 48 centers in 20 countries from 2010 to 2018. Patients who died within 3 months after surgery were excluded (landmark). Data were analyzed from February 1 to December 31, 2023.

Exposures: Preoperative (m)FOLFIRINOX chemotherapy followed by resection and eventually followed by adjuvant chemotherapy.

Main Outcomes and Measures: The primary outcome was OS, calculated from the 3-month landmark. Cox regression analysis, including interaction analyses, was performed to investigate the association of adjuvant chemotherapy with OS.

Results: Overall, 767 patients were included after resection of pancreatic adenocarcinoma (median [IQR] age, 62 [55-67] years; 404 [52.7%] male). Adjuvant chemotherapy was independently associated with prolonged OS (hazard ratio [HR], 0.66; 95% CI, 0.49-0.87), confirmed by adjusted OS curves. The interaction analysis to assess estimated treatment effect across subgroups was not statistically significant. The forest plot and interaction test suggest that the association of adjuvant chemotherapy was lower among patients receiving 8 or more cycles of preoperative (m)FOLFIRINOX, those who had radiological response, and those with ypNO disease. Compared to no adjuvant chemotherapy, both adjuvant (m)FOLFIRINOX (HR, 0.57; 95% CI, 0.40-0.80) and other multiagent adjuvant regimens (HR, 0.61; 95% CI, 0.41-0.92) were associated with prolonged OS, whereas single-agent adjuvant chemotherapy was not (HR, 0.75; 95% CI, 0.55-1.03).

Conclusions and Relevance: In this cohort study, adjuvant (m)FOLFIRINOX and other multiagent chemotherapy regimens were associated with improved OS following resection of localized pancreatic adenocarcinoma after preoperative (m)FOLFIRINOX, whereas single-agent adjuvant chemotherapy was not. The impact of adjuvant chemotherapy on OS may be lower in subgroups such as patients with 8 or more preoperative cycles of (m)FOLFIRINOX, those having radiological response, and those with ypNO.

Intraductal papillary mucinous neoplasms (IPMNs) resection margins are assessed intraoperatively using frozen section (IFS) pathology. We conducted a systematic review to evaluate the concordance of IFS with permanent histopathology and the association between IFS margin status and recurrence. A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We queried PubMed, Embase, Scopus, and Google Scholar for studies reporting IFS in patients undergoing resection for IPMN. Data, including IFS margin status, recurrence rates, and final pathology, were extracted. Positive margins were defined as high-grade dysplasia or invasive cancer. Seven studies, with a total of 706 patients, met the inclusion criteria. Positive IFS margins were reported in 9.4% of cases, with a high correlation (98%) between IFS and final pathology. Recurrence occurred in 15.4% of patients. Fifty-nine of 85 (69.4%) patients with recurrence of IPMN or intraductal papillary mucinous carcinoma (IPMC) had negative IFS margins. IFS accurately predicts final pathology and is a valuable tool for guiding intraoperative decision-making. A sizeable number of patients experienced recurrence despite negative margins, highlighting the need for adjunct diagnostic modalities and continued surveillance following resection, regardless of margin status.

Pancreatic ductal adenocarcinoma (PDAC) is associated with a poor prognosis, and biomarkers to guide treatment decisions in PDAC are generally lacking. Intratumoural expression of dihydropyrimidine dehydroge- nase (DPD) is a potential prognostic parameter in patients with PDAC undergoing surgical resection and postoperative chemotherapy. In the present study, DPD was analysed by immunohistochemistry of a tissue microarray platform including a real-world cohort of 495 patients with PDAC who had undergone resection with curative intent at any of three tertiary centres, including Northern, Western and Southeastern regions of Sweden, between 1993 and 2019. DPD level (high/low) was analysed and overall survival associations were assessed in treatment subgroups using a multivariate Cox regression model accounting for potential confounders. In patients who had not received adjuvant chemotherapy (n=182), the median overall survival time was 11.6 months (95% CI 9.6-13.5), compared with 28.8 months (25.0-32.6) among those who had (n=313; log-rank P<0.001). The most common type of chemotherapy was gemcitabine single agent (Gem, n=239) followed by gemcitabine plus capecitabine (GemCape, n=39). Tumour-Node-Metastasis (TNM) stage and DPD expression were statistically significant prognostic parameters in the Gem group (HR 1.19, 95% CI 1.01-1.41, P=0.036), with high expres- sion of DPD linked with worse survival. In addition, tumour grade and TNM stage were statistically significant prognostic factors in the group that did not receive any chemotherapy (P≤0.001). No statistically significant parameters were iden- tified in the GemCape group. Taken together, intratumoural expression of DPD may be considered a prognostic marker for patients with PDAC treated with adjuvant gemcitabine following surgical resection, with low expression levels predicting better survival. Further studies in larger cohorts of patients receiving multi-drug or non-gemcitabine based regimens are warranted.

Objectives: Sleep apnea is suggested to be associated with cancer risk, but results are heterogenous, and few studies are population-based. We aimed to assess risk associations between self-reported witnessed apnea during sleep and specific cancers in a population-based cohort.

Methods: This retrospective cohort study analyzed questions on witnessed sleep apnea in relation to incident cancer in the Northern Sweden Health and Disease Study. Cancer diagnoses were derived from the Swedish Cancer Registry and characterized as 12 different cancer types. Cox regression models adjusted for age, sex, ever smoking, body mass index, and education were used to assess risk associations.

Results: In total, 82,059 participants were included, and 10,668 (13 %) reported witnessed sleep apnea. They were followed for 9.0 (SD 4.7) years and 4030 incident cancers were diagnosed. Self-reported witnessed sleep apnea was independently associated with incident lung cancer with an adjusted hazard ratio (aHR), 1.78 (95 %CI 1.16, 2.73) p = 0.008 and breast cancer aHR, 1.39 (95 %CI 1.04, 1.84) p = 0.023. The risk for lung cancer was driven by an association with lung adenocarcinoma aHR, 2.16 (95 %CI 1.19, 3.91) p = 0.01. There was a multiplicative effect on ever smoking and reporting witnessed apnea for lung cancer with an aHR, 5.27 (95 %CI 3.07, 9.05) p < 0.001.

Conclusions: Self-reported witnessed sleep apnea is associated with an increased risk of developing lung- and breast cancer. There is a multiplicative effect of reporting witnessed sleep apnea and ever-smoking with an over 5 times increase on the hazard for lung cancer.

Objective: To investigate whether tangential versus segmental portomesenteric venous resection (PVR) impacts surgical and oncological outcome in patients undergoing pancreatoduodenectomy for pancreatic cancer with portomesenteric vein (PMV) involvement.

Summary Background Data: Current comparative studies on tangential versus segmental PVR as part of pancreatoduodenectomy for pancreatic cancer include all degrees of PMV involvement, including cases where tangential PVR may not be a feasible approach, limiting the clinical applicability.

Methods: International retrospective study in 10 centers from 5 countries, including all consecutive patients after pancreatoduodenectomy with PVR for pancreatic cancer with ≤180° PMV involvement on cross-sectional imaging at diagnosis (2014-2020). Cox and logistic regression analyses were performed to investigate the association of tangential versus segmental PVR with overall survival (OS) from surgery, recurrence-free survival (RFS), locoregional recurrence, and in-hospital/30-day major morbidity, adjusting for potential confounders.

Results: Overall, 357 patients who underwent pancreatoduodenectomy with PVR were included (42% tangential PVR, 58% segmental PVR). The adjusted risk for in-hospital/30-day major morbidity was 23% (95%CI, 17-32) after tangential and 23% (95%CI, 17-30) after segmental PVR (P=0.98). After adjusting for confounders, PVR type was not associated with OS (HR=0.94 [95%CI, 0.69-1.30]), RFS (HR=0.94 [95% CI, 0.69 to 1.28), and locoregional recurrence (OR=0.76 [95%CI, 0.40-1.46]).

Conclusions: In patients undergoing pancreatoduodenectomy for pancreatic cancer with ≤180° PMV involvement, the type of PVR (i.e., tangential vs. segmental) was not associated with differences in surgical and oncological outcome. This suggest that if both procedures are technically feasible, surgeons can choose the type of PVR based on their preference.

Background: Left-sided pancreatic cancer is associated with worse overall survival (OS) compared with right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with resectable pancreatic cancer (RPC), current randomized trials included mostly patients with right-sided RPC. The purpose of this study was to assess the association between neoadjuvant therapy and OS in patients with left-sided RPC compared with upfront surgery.

Patients and methods: This was an international multicenter retrospective study including consecutive patients after left-sided pancreatic resection for pathology-proven RPC, either after neoadjuvant therapy or upfront surgery in 76 centers from 18 countries on 4 continents (2013-2019). The primary endpoint was OS from diagnosis. Time-dependent Cox regression analysis was carried out to investigate the association of neoadjuvant therapy with OS, adjusting for confounders at the time of diagnosis. Adjusted OS probabilities were calculated.

Results: Overall, 2282 patients after left-sided pancreatic resection for RPC were included of whom 290 patients (13%) received neoadjuvant therapy. The most common neoadjuvant regimens were (m)FOLFIRINOX (38%) and gemcitabine-nab-paclitaxel (22%). After upfront surgery, 72% of patients received adjuvant chemotherapy, mostly a single-agent regimen (74%). Neoadjuvant therapy was associated with prolonged OS compared with upfront surgery (adjusted hazard ratio 0.69, 95% confidence interval 0.58-0.83) with an adjusted median OS of 53 versus 37 months (P = 0.0003) and adjusted 5-year OS rates of 47% versus 35% (P = 0.0001) compared with upfront surgery. Interaction analysis demonstrated a stronger effect of neoadjuvant therapy in patients with a larger tumor (Pinteraction = 0.003) and higher serum carbohydrate antigen 19-9 (CA19-9; Pinteraction = 0.005). In contrast, the effect of neoadjuvant therapy was not enhanced for splenic artery (Pinteraction = 0.43), splenic vein (Pinteraction = 0.30), retroperitoneal (Pinteraction = 0.84), and multivisceral (Pinteraction = 0.96) involvement.

Conclusions: Neoadjuvant therapy in patients with left-sided RPC was associated with improved OS compared with upfront surgery. The impact of neoadjuvant therapy increased with larger tumor size and higher serum CA19-9 at diagnosis. Randomized controlled trials on neoadjuvant therapy specifically in patients with left-sided RPC are needed.

Background: Adjuvant therapy is associated with improved pancreatic cancer survival after neoadjuvant chemotherapy and surgery. However, whether adjuvant treatment should include radiotherapy is unclear in this setting.

Methods: This study queried the National Cancer Database for pancreatic adenocarcinoma patients who underwent curative resection after multiagent neoadjuvant chemotherapy between 2010 and 2019 and received adjuvant treatment. Adjuvant chemotherapy plus radiotherapy (external beam, 45–50.4 gray) was compared with adjuvant chemotherapy alone. Uni- and multivariable Cox regression was used to assess survival associations. Analyses were repeated in a propensity score-matched subgroup.

Results: Of 1983 patients who received adjuvant treatment after multiagent neoadjuvant chemotherapy and resection, 1502 (75.7%) received adjuvant chemotherapy alone and 481 (24.3%) received concomitant adjuvant radiotherapy (chemoradiotherapy). The patients treated with adjuvant chemoradiotherapy were younger, were treated at non-academic facilities more often, and had higher rates of lymph node metastasis (ypN1-2), positive resection margins (R1), and lymphovascular invasion (LVI+). The median survival was shorter for the chemoradiotherapy-treated patients according to the unadjusted analysis (26.8 vs 33.2 months; p = 0.0017). After adjustment for confounders, chemoradiotherapy was associated with better outcomes in the multivariable model (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.61–0.93; p = 0.008). The association between chemoradiotherapy and improved outcomes was stronger for the patients with grade III tumors (HR, 0.53; 95% CI, 0.37–0.74) or LVI+ tumors (HR, 0.58; 95% CI, 0.44–0.75). In a subgroup of 396 propensity-matched patients, chemoradiotherapy was associated with a survival benefit only for the patients with LVI+ or grade III tumors.

Conclusion: After multiagent neoadjuvant chemotherapy and resection for pancreatic cancer, additional adjuvant chemoradiotherapy versus adjuvant chemotherapy alone is associated with improved survival for patients with LVI+ or grade III tumors.