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Pancreatic ductal adenocarcinoma cancer (PDAC) is a highly lethal malignancy requiring efficient detection when the primary tumor is still resectable. We previously developed the MxPancreasScore comprising 9 analytes and serum carbohydrate antigen 19-9 (CA19-9), achieving an accuracy of 90.6%. The necessity for 5 different analytical platforms and multiple analytical runs, however, hindered clinical applicability. We therefore aimed to develop a simpler single-analytical run, single-platform diagnostic signature.We evaluated 941 patients (PDAC, 356; chronic pancreatitis [CP], 304; nonpancreatic disease, 281) in 3 multicenter independent tests, and identification (ID) and validation cohort 1 (VD1) and 2 (VD2) were evaluated. Targeted quantitative plasma metabolite analysis was performed on a liquid chromatography-tandem mass spectrometry platform. A machine learning-aided algorithm identified an improved (i-Metabolic) and minimalistic metabolic (m-Metabolic) signatures, and compared them for performance.The i-Metabolic Signature, (12 analytes plus CA19-9) distinguished PDAC from CP with area under the curve (95% confidence interval) of 97.2% (97.1%-97.3%), 93.5% (93.4%-93.7%), and 92.2% (92.1%-92.3%) in the ID, VD1, and VD2 cohorts, respectively. In the VD2 cohort, the m-Metabolic signature (4 analytes plus CA19-9) discriminated PDAC from CP with a sensitivity of 77.3% and specificity of 89.6%, with an overall accuracy of 82.4%. For the subset of 45 patients with PDAC with resectable stages IA-IIB tumors, the sensitivity, specificity, and accuracy were 73.2%, 89.6%, and 82.7%, respectively; for those with detectable CA19-92 U/mL, 81.6%, 88.7%, and 84.5%, respectively; and for those with CA19-937 U/mL, 39.7%, 94.1%, and 76.3%, respectively.The single-platform, single-run, m-Metabolic signature of just 4 metabolites used in combination with serum CA19-9 levels is an innovative accurate diagnostic tool for PDAC at the time of clinical presentation, warranting further large-scale evaluation.

Introduction: Studies on pancreatic neuroendocrine tumors (PanNETs) regarding loss of ATRX, DAXX, or frequency of microsatellite instability (MSI) show inconclusive results. So far, data on corresponding metastaseshave not been published. Methods: We performed immunohistochemistry (IHC) of ATRX, DAXX, MSH2, MSH6, MLH1, and PMS2 on 74 PanNETs and 19 metastases. ATRX- and DAXX-negative PanNETs were further sequenced for mutations. We used polymerase chain reaction for MSI on cases with IHC loss of MSH2, MSH6, MLH1, and PMS2. Results: Immunohistochemical loss of DAXX and ATRX was observed in 8/74 (11%) and 6/74 (8%) PanNETs. Loss of DAXX immunoreactivity was statistically associated with higher tumor grade and showed a tendency toward a decreased overall survival. Sequencing of DAXX- (7/11 [64%]) and ATRX-negative (5/11 [45%]) PanNETs revealed a mutation in 6/7 (86%) and 2/5 (40%). The specificity of immunohistochemical loss of DAXX and ATRX for mutation was 80% and 67%, respectively. The expression status of DAXX compared to primary tumor differs in 2/12 (17%) lymph node metastases. We further identified 3/74 (4%) tumors as MSI, associated with a poor prognosis. Discussion/Conclusion: Our study supports the hypothesis that a loss of DAXX immunoreactivity can identify a more aggressive subtype of PanNET with high confidence, while ATRX loss is a weaker indicator. Our results also strengthen the role of DAXX immunolabeling as a prognostic marker. We could show that ATRX might be less suitable as a surrogate for sequencing. Our results indicate that IHC of DAXX and ATRX may identify PanNET subtypes as targets for more aggressive therapy.

Introduction: Studies on mind-body approaches in patients with advanced pancreatic ductal adenocarcinoma (PDAC) are rare. We performed a pilot study with follow-up until one year to explore changes in pain, quality of life (QoL), stress, and negative emotions in patients with advanced PDAC, who regularly practiced a standardized form of spiritual meditation in addition to standard medical care. Methods: At baseline and every two months for a maximum of one year, global pain, QoL (global, SEIQoL, FACT-G), spiritual well-being (FACIT-Sp), perceived stress (PSQ-20), anxiety and depression (HADS), and diurnal cortisol secretion (cortisol slope) were assessed. Changes from baseline were explored by pairwise comparisons of available cases. Results: 20 participants (11 women, 62 ± 9.9 SD years) participated in the study, of whom 9 patients survived the study year. Pairwise comparisons revealed transient improvements of pain after 4 and 6 months (both p-values < .05), of global QoL after 4, 6, 8, 10 months (all p-values < .05), of SeiQoL scores after 4 months (p < .05), of FACT-G scores after 6 months (p < .05), and of FACIT-Sp scores after 2 and 6 months (both p-values < .05). Furthermore, overall stress levels (PSQ-20) decreased from baseline to 2, 6, and 8 months (all p-values < .05), and anxiety declined from baseline to 6 months (p < .05). Depression scores and the cortisol slope did not change. Conclusion: This pilot study demonstrated the acceptability and feasibility of studies on spiritual meditation in patients with advanced PDAC. Randomized controlled trials are warranted to study the effects of spiritual meditation and other mind-body interventions on pain, quality of life, and emotional well-being in this patient population.

ZusammenfassungAufgrund einer steigenden Inzidenz nehmen Pankreasneoplasien, welche hauptsächlich Adenokarzinome, neuroendokrine und zystische Neoplasien umfassen, im klinischen Alltag eine zunehmende Relevanz ein.Auf Grundlage einer systematischen Literaturrecherche wurden von Pankreasexperten im Auftrag der DGAV zur Verbesserung der Indikationsqualität evidenzbasierte Empfehlungen zur Indikationsstellung bei Pankreasneoplasien erarbeitet.Eine eindeutige Operationsindikation besteht bei primär oder sekundär resektablen Pankreaskarzinomen ohne Metastasierung, bei funktionell aktiven sowie über 2 cm großen funktionell inaktiven neuroendokrinen Neoplasien und bei symptomatischen oder malignitätsverdächtigen zystischen Pankreasneoplasien einschließlich intraduktaler papillär-muzinöser Neoplasien (IPMN) vom Hauptgang und vom Mischtyp, muzinös-zystischer Neoplasien (MCN) > 4 cm und solid pseudopapillärer Neoplasien (SPN). Eine Operation kann bei Pankreaskarzinomen mit isolierter arterieller Gefäßinfiltration oder über längere Zeit stabiler Oligometastasierung im Rahmen von neuroendokrinen Neoplasien zur Metastasen- oder Debulkingchirurgie sowie bei Seitengang-IPMN mit Risikokriterien und MCN < 4 cm indiziert sein. Keine primäre Operationsindikation ergibt sich bei lokal fortgeschrittenen und metastasierten Pankreaskarzinomen oder serös-zystischen Neoplasien (SCN).Insgesamt sollte die Operationsindikationsstellung individualisiert unter Berücksichtigung von Alter, Komorbiditäten und Patientenwunsch erfolgen.

Background: Pancreatic Ductal Adenocarcinoma (PDAC) lacks effective treatment options beyond chemotherapy. Although molecular subtypes such as classical and QM (quasi-mesenchymal)/basal-like with transcriptome-based distinct signatures have been identified, deduced therapeutic strategies and targets remain elusive. Gene expression data show enrichment of glycolytic genes in the more aggressive and therapy resistant QM subtype. However, whether the glycolytic transcripts are translated into functional glycolysis that could further be explored for metabolic targeting in QM subtype is still not known. Methods: We used different patient-derived PDAC model systems (conventional and primary patient derived cells, patient derived xenografts (PDX) and patient FFPE samples) and performed transcriptional and functional metabolic analysis. These included: RNAseq and Illumina HT12 bead array, in vitro Seahorse metabolic flux assays and metabolic drug targeting, and in vivo hyperpolarized [1-13C]pyruvate and [1-13C]lactate magnetic resonance spectroscopy (HP-MRS) in PDAC xenografts. Results: We found that glycolytic metabolic dependencies are not unambiguously functionally exposed in all QM PDACs. Metabolic analysis demonstrated functional metabolic heterogeneity in patient-derived primary cells and less so in conventional cell lines independent of molecular subtype. Importantly, we observed that the glycolytic product lactate is actively imported in the PDAC cells and used in mitochondrial oxidation in both classical and QM PDAC cells, although more actively in the QM cell lines. By using hyperpolarized 13C-magnetic resonance spectroscopy (HP-MRS), we were able to non-invasively identify highly glycolytic PDAC xenografts by detecting the last glycolytic enzymatic step and prominent intra-tumoral [1‑13C]pyruvate and [1-13C]lactate interconversion in vivo.Conclusion: Our study adds functional metabolic phenotyping to transcriptome-based analysis and proposes a functional approach to identify highly glycolytic PDACs as candidates for anti-metabolic therapeutic avenues.

694 Background: Perioperative chemotherapy (CTX) in resectable pancreatic adenocarcinoma (rPDAC) is still not considered SoC and data regarding efficacy but also quality of life (QoL) are limited. NEONAX is a prospective, randomized phase II trial in patients with rPDAC with two independent experimental arms examining perioperative (2 pre- and 4 postoperative cycles, arm A) or adjuvant (6 cycles, arm B) of Gem (1000mg/m2) and nab-P (125mg/m2) on days 1,8,15 of a 28-day cycle. The primary endpoint DFS at 18 mo. as well as DFS, OS and safety have already been reported. Here we present the QoL data of the NEONAX trial. Methods: QoL was evaluated by EORTC QLQ-C30, EORTC QLQ-PAN26 and HADS-D questionnaires at baseline, at the beginning of each CTX cycle (neoadj. and adj. in arm A, only adj. in arm B), after neoadj. treatment in arm A as well as prior and post resection and after 6 cycles of CTX. Results: Global health status score (GHS-score) (QLQ-C30) showed no difference between baseline (t1) and the timepoint after 6 cycles of CTX (t2) in the perioperative arm A (66.7/100 at both timepoints). Here patients experienced the lowest GHS-score pre- and postoperatively (50/100 in both cases). Adjuvant arm B showed a deterioration in the GHS-score of 12.5 points from timepoint 1 to 2 (62.5/100 to 50.0/100). Here the lowest GHS-score was observed within 4 weeks post-surgery (41.7/100). Physical function score (QLQ-C30) was decreased by 6.7 points (86.7/100 to 80/100) in perioperative arm A and by 26.7 points (86.7/100 to 60/100) in arm B between both timepoints. Role function (QLQ-C30) was reduced by 16.7 points (83.3/100 to 66.7/100) in arm A and by 33.3 points (83.3/100 to 50/100) in arm B between both timepoints. In the remaining subscales of the used questionnaires the two arms of the trial showed comparable median scores over the whole study period. The number of submitted questionnaires at each timepoint varied but was at large comparable in both arms. Conclusions: QoL was largely preserved in the perioperative as well as the adjuvant arm of the NEONAX trial. GHS-score was lower pre-and postoperatively in arm A. The lowest GHS-score was observed postoperatively in the adjuvant arm B. QoL was restored at the end of the treatment period in the perioperative arm A and remained slightly reduced in arm B suggesting that QoL is not substantially impaired by perioperative treatment in rPDAC. Clinical trial information: NCT02047513 . [Table: see text]

The incidence of pancreatic ductal adenocarcinoma is continuously increasing and will become the second leading cause of cancer-related death in Europe and the USA by 2030. With a 5-year overall survival rate of less than 10% the prognosis remains poor. So far surgical tumor resection remains the only curative treatment option, which is now partially supported by multimodal neoadjuvant and adjuvant therapy concepts. Due to the aggressive tumor biology patients with advanced pancreatic cancer in particular can profit from these multimodal therapy concepts. Additionally, in recent years surgical treatment was optimized, the criteria for tumor resectablity were defined and minimally invasive surgery was widely introduced. This review article summarizes the newest developments and the new German S3 guidelines concerning surgery of pancreatic cancer.Die Inzidenz des duktalen Adenokarzinoms des Pankreas steigt weiterhin und es wird bis 2030 zur zweithäufigsten krebsbedingten Todesursache in Europa und den USA aufsteigen. Mit einer 5‑Jahres-Überlebensrate von nur bis zu 10 % hat es weiterhin eine sehr schlechte Prognose. Die chirurgische Tumorresektion stellt die einzige kurative Therapieoption dar, die inzwischen zum Teil durch multimodale neoadjuvante und adjuvante Therapiekonzepte unterstützt wird. Aufgrund der aggressiven Tumorbiologie können Patienten insbesondere bei fortgeschrittenen Pankreaskarzinomen von diesen multimodalen Therapiekonzepten profitieren. Daneben wurden in den letzten Jahren die chirurgische Therapie optimiert, die Resektabilität anhand verschiedener Kriterien klarer definiert und minimal-invasive Operationen in der Breite eingeführt. Die aktuelle Übersichtsarbeit fasst die neuesten Entwicklungen und die neue S3-Leitlinie zum Thema Chirurgie beim Pankreaskarzinom zusammen.

BACKGROUND: Aberrant right hepatic arteries (aRHA) are frequently encountered during pancreaticoduodenectomy (PD). Their effects on surgical morbidity and resection margin are still debated. This study aimed to compare the short term and long term outcomes in patients with and without aRHA. METHODS: A single-center retrospective analysis of 353 consecutive PD during a 5-year period was done. The type of arterial supply was determined preoperatively by CT and confirmed at surgery. Hiatt types III–VI included some type of aRHA and comprised the study group. Hiatt types I and II were considered irrelevant for PD and used as controls. Primary endpoints were the rates of major postoperative complications and the rate of R0-resection in cases of malignant disease. Secondary endpoints included duration of surgery, postoperative stay, number of harvested lymph nodes and survival in patients with pancreatic cancer. Own results were compared to existent data using a systematic review of the literature. RESULTS: No aRHA had to be sacrificed or reconstructed. Surgical morbidity and specific complications such as post-pancreatectomy hemorrhage (PPH), pancreatic fistula and bile leak were the same in patients with and without aRHA. There was no significant difference in operative time, blood loss, length of ICU- and hospital stay. Patients with malignancy had similar high rates of R0-resection and identical number of harvested lymph nodes. Survival of patients with pancreatic cancer was not affected by aRHA. CONCLUSIONS: aRHA may be preserved in virtually all cases of PD for resectable pancreatic head lesions without increasing surgical morbidity and without compromising oncological radicality in patients with cancer, provided the variant anatomy is being recognised on preoperative CT and a meticulous surgical technique is used.

3626 Background: CRC still is one of the leading causes of cancer related death though prognosis has improved through guideline based management. The COVID-19 pandemic lead to re-allocation of resources subordinating all sections of care for CRC patients. We present data on changes of CRC care during the pandemic from 22 German AIO CC and our high volume Institute of Pathology (pathology). Methods: Data was collected retrospectively comparing the months (mo) of the first wave (fw) (4-6/2020) and second wave (sw) (11-12/2020) of the pandemic with corresponding periods (cp) in 2019 focusing on the number of precancerous (ICD-O/0+2) and malignant (ICD-O/3+6) colorectal lesions (CRL) diagnosed by our pathology, the number/stage of primary diagnoses (PD) and the number of surgeries (surg) at AIO CC. There, quality criteria of CRC care were also assessed (number of PD discussed within a multidisciplinary tumor board (tb), received social service (soc)/ psychological (psy) counseling or recruited into a clinical trial). Statistical analysis was performed using students t-test for paired data. Results: Numbers of CRL detected upon histology (row 1-3), number of cases, surg and quality criteria from AIO CC (row 4-9) are displayed in the table. We saw a dip in diagnosed CRL and number of surg (p=0.007) only during fw, whereas PD dipped significantly in both waves. A significant reduction in diagnosis of stage III CRC was detected for 2019 vs. 2020 (p=0.001), not for other stages. Quality criteria showed a significant reduction in clinical trial inclusion, a small dip in soc/psy counseling and persistently high tb presentation. Conclusions: We detected a significant decrease of premalignant lesions and primary cancers during the first year of the pandemic which may impact cancer mortality in the future. Certified German CC provided CRC care with significant reduction in clinical trial inclusion only, suggesting high stability of established certified cancer care infrastructure.[Table: see text]

Due to its rising incidence, pancreatic neoplasia, which mainly include adenocarcinomas, neuroendocrine and cystic neoplasia of the pancreas, is becoming increasingly relevant in everyday clinical practice.Based on a systematic literature search, a working group of pancreatic experts developed evidence-based recommendations for surgical indications in pancreatic neoplasia to improve the quality.There is a clear surgical indication for primary or secondary resectable pancreatic carcinomas without metastasis, for functionally active, symptomatic and functionally inactive neuroendocrine neoplasia of more than 2 cm in size and for cystic neoplasm with symptoms or signs of malignancy including all intraductal papillary-mucinous neoplasia (IPMN) of the main duct and mixed type, all mucinous-cystic neoplasia (MCN)4 cm and all solid pseudopapillary neoplasia (SPN). Surgery can be indicated for pancreatic carcinomas with isolated arterial vascular infiltration or for long periods of stable oligometastasis, regarding neuroendocrine neoplasias for metastasis or debulking surgery as well as for branch-duct IPMN with risk criteria and MCN4 cm. There is no primary indication for surgery in locally advanced and metastatic pancreatic cancer or asymptomatic serous-cystic neoplasia (SCN).The indication for surgery should always be individualized taking into account age, comorbidities and patient wishes.Aufgrund einer steigenden Inzidenz nehmen Pankreasneoplasien, welche hauptsächlich Adenokarzinome, neuroendokrine und zystische Neoplasien umfassen, im klinischen Alltag eine zunehmende Relevanz ein.Auf Grundlage einer systematischen Literaturrecherche wurden von Pankreasexperten im Auftrag der DGAV zur Verbesserung der Indikationsqualität evidenzbasierte Empfehlungen zur Indikationsstellung bei Pankreasneoplasien erarbeitet.Eine eindeutige Operationsindikation besteht bei primär oder sekundär resektablen Pankreaskarzinomen ohne Metastasierung, bei funktionell aktiven sowie über 2 cm großen funktionell inaktiven neuroendokrinen Neoplasien und bei symptomatischen oder malignitätsverdächtigen zystischen Pankreasneoplasien einschließlich intraduktaler papillär-muzinöser Neoplasien (IPMN) vom Hauptgang und vom Mischtyp, muzinös-zystischer Neoplasien (MCN)4 cm und solid pseudopapillärer Neoplasien (SPN). Eine Operation kann bei Pankreaskarzinomen mit isolierter arterieller Gefäßinfiltration oder über längere Zeit stabiler Oligometastasierung im Rahmen von neuroendokrinen Neoplasien zur Metastasen- oder Debulkingchirurgie sowie bei Seitengang-IPMN mit Risikokriterien und MCN4 cm indiziert sein. Keine primäre Operationsindikation ergibt sich bei lokal fortgeschrittenen und metastasierten Pankreaskarzinomen oder serös-zystischen Neoplasien (SCN).Insgesamt sollte die Operationsindikationsstellung individualisiert unter Berücksichtigung von Alter, Komorbiditäten und Patientenwunsch erfolgen.

BACKGROUND: Delayed gastric emptying (DGE) is one of the most common complications after pancreatic head resection. It leads to increased length of hospital stay, high costs for healthcare systems and reduced quality of life. The primary aim of the study was to assess the impact of pylorus preservation, respectively resection on the occurrence of DGE in patients undergoing pancreaticoduodenectomy (PD). METHODS: All cases of pylorus-resecting PD (PRPD) and pylorus-preserving PD (PPPD) entered in the StuDoQ|Pancreas nationwide registry of the German Society of General and Visceral Surgery from 01/01/2014 until 31/12/2018 including demographics, surgical techniques, histopathological and perioperative data were retrospectively analyzed. This study was approved by the ethics committee of the Ruhr-University Bochum, Germany. RESULTS: Data of 5,080 patients were enrolled. PPPD was the method of choice (70.4%). Pylorus preservation had no impact on the occurrence of DGE (20.3% vs. 21.5%, P=0.33), but further risk factors could be identified. The comparison of PPPD and PRPD groups showed statistically significant differences in the surgical approach (primary open approach, 94.8% vs. 98.0%, P

Postpancreatectomy haemorrhage (PPH) is a rare but potentially fatal complication after pancreatoduodenectomy. Preventive strategies are lacking with scarce data for support. The aim of this study was to investigate whether a prophylactic falciform ligament wrap around the hepatic and gastroduodenal artery can prevent PPH from these vessels.In a randomized, controlled, multicentre trial, patients who were scheduled for elective open partial pancreatoduodenectomy with pancreatojejunostomy between 5 November 2015 and 2 April 2020 were randomly allocated in a 1 : 1 ratio to undergo pancreatoduodenectomy with (intervention) or without (control) a falciform ligament wrap around the hepatic artery. The primary endpoint was the rate of clinically relevant PPH from the hepatic artery or gastroduodenal artery stump within 3 months after pancreatoduodenectomy. Secondary endpoints were the rates of associated postoperative complications, for example postoperative pancreatic fistula (POPF) and PPH.Altogether, 445 patients were randomized with 222 and 223 in each group. Among the patients included in modified intention-to-treat analysis (207 in the intervention group and 210 in the control group), the primary endpoint was observed in six of 207 in the intervention group compared with 15 of 210 in the control group (2.9 versus 7.1 per cent respectively; odds ratio 0.39 (95 per cent c.i. 0.15 to 1.02); P = 0.071). Per protocol analysis showed a significant reduction in the intervention group (odds ratio 0.26 (95 per cent c.i. 0.09 to 0.80); P = 0.017). A soft pancreas texture (43 per cent) and the rate of a clinically relevant POPF were evenly (20 per cent) distributed between the groups. The rate of any clinically relevant PPH including the primary endpoint and other bleeding sites was not significantly different between intervention and control groups (9.7 versus 14.8 per cent respectively).A falciform ligament wrap may reduce PPH from the hepatic artery or gastroduodenal artery stump and should be considered during pancreatoduodenectomy.NCT02588066 (http://www.clinicaltrials.gov).

4008 Background: Chemotherapy (CT) is the standard of care in nonresectable locally advanced pancreatic cancer. The CONKO-007 trial studied the role of sequential CT and chemoradiotherapy (CRT). Methods: In this randomized multicenter phase III trial resectability was judged by an independent surgical board. Patients (pts) received induction chemotherapy (IC) for 3 months (3 cycles gemcitabine (Gem, 1000 mg/m² d1, 8, 15, q4w) or FOLFIRINOX (6 cycles, q2w)). After IC pts without progression were randomized to either continuing CT for another 3 months or receiving CRT (cumulative dose of 50.4Gy, single dose 1.8Gy + Gem 300 mg/m² weekly, followed by 1 cycle of Gem 1000 mg/m² at d1, 8, 15). The primary endpoint of the study was overall survival (OS) since the begin of IC. Determination of sample size calculated 590 pts to be randomized. Due to the exclusion of pts with progressive disease after IC a total of 830 pts should be enrolled. Due to delayed patient accrual the primary endpoint was changed to R0 resection rate resulting in an estimated sample size of 525 pts. Results: Between 04/2013 and 02/2021 a total of 525 pts were enrolled in 47 sites. 402 pts received IC with FOLFIRINOX and 93 pts with Gem. After IC 190 pts were excluded due to progression or toxicity, 335 were randomized, their median FU was 16 months. Hematological toxicities were significantly increased in the CRT arm, non-hematological toxicities were comparable. R0 CRM- resection rate and pCR rate was significantly higher in the CRT arm. R1-resections occurred significantly more often in the CT arm. Median progression-free survival (PFS) (HR 0.919, 95% CI 0.702-1.203, p=0.540) and OS (HR 0.964, 95% CI 0.760-1.225, p=0.766) did not differ significantly in both arms, whereas the PFS rate tended to be higher in the CRT arm after 2 years. OS rates for CRM- R0 surgery with 87.5. ± 0.05% (1y) and 67.2 ± 0.05% (2y) were significantly higher (p

4133 Background: Perioperative chemotherapy (CTX) in resectable pancreatic ductal adenocarcinoma (PDAC) is still not considered standard of care and data are limited. The NEONAX trial examined gemcitabine (Gem) plus nab-paclitaxel (nab-P), in the perioperative or adjuvant therapy of resectable PDAC (NCCN criteria). Methods: NEONAX is a prospective, randomized phase II trial with two independent experimental arms. 127 resectable PDAC patients in 22 German centers were randomized 1:1 to perioperative (2 pre- and 4 postoperative cycles, arm A) or adjuvant (6 cycles, arm B) of Gem (1000mg/m2) and nab-P (125mg/m2) on days 1,8,15 of a 28-day cycle. Results: We previously reported the primary endpoint disease free survival (DFS) at 18 mo. in the modified intention-to-treat (ITT)-population (defined as R0/R1 resected pts. that either started neoadjuvant (A) or adjuvant (B) CTX. The pre-defined DFS rate of 55% at 18 mo. was not reached in both arms (A: 32.2%, B: 41.4%). Here we present the final results of the secondary endpoints median overall survival (mOS), pN0-resection rate, perioperative morbidity/mortality and safety in the ITT-population. Most common grade ≥3 treatment emergent adverse events in the safety population were neutropenia (arm A 21.1%, arm B 12.3%), fatigue (arm A 8.8%, arm B 5.3%) and anemia (arm A 10.5%, arm B 1.8%). The most frequent post-/perioperative complications of all grades in pts. undergoing resection were infections (arm A: 24.4%, arm B: 8.8%), pancreatic fistulas (arm A: 14.6%; arm B: 13.3%) and bleedings (arm A: 9.7%; arm B: 6.7%). Perioperative mortality was 2.4% in the neoadjuvant and 6.7% in the upfront surgery setting. The median number of resected lymph nodes was comparable in both arms (A: n = 21, B: n = 26). The pN0-resection rate was 33.3% in the neoadjuvant/perioperative arm A and 29.5% in the upfront surgery arm B. R0 resection rates were 87.8% in arm A and 67.4% in arm B, respectively. Median OS as a key secondary endpoint in the ITT population was 25.2 mo. in arm A and 16.7 mo. for upfront surgery, a difference of 8.5 mo. This difference corresponds to a mDFS of 11.5 mo. in arm A and 5.9 mo. in arm B. 91.5% of pts. in arm A started and 84.7% completed neoadjuvant CTX but only 42.4% of pts. in arm B started adjuvant CTX. Conclusions: Perioperative treatment with Gem/nab-P was well tolerated and showed an encouraging mOS of 25.2 mo., this is well in the range of the data in SWOG 1505 (23.6 mo.) or PREOPANC (15.7 mo.). The corresponding mOS in the upfront surgery arm was 16.7 mo. The 8.5 mo. difference may be explained by the fact that many pts. in arm B did not receive adjuvant treatment whereas the vast majority of pts. in arm A completed at least preoperative CTX. Neoadjuvant/perioperative treatment is a promising novel option for pts. with resectable PDAC. The optimal treatment regimen is subject of current clinical trials. Clinical trial information: NCT02047513.