Tertiary lymphoid structures in pancreatic cancer are structurally homologous, share gene expression patterns and B-cell clones with secondary lymphoid organs but show increased T-cell activation.

Tertiary lymphoid structures (TLS) in cancer are considered ectopic hotspots for immune activation that are similar to lymphoid follicles in secondary lymphoid organs (SLO). This study elucidates shared and TLS/SLO-specific features in pancreatic ductal adenocarcinoma (PDAC). TLS abundance was related to superior survival and T-cell abundance in 110 treatment-naïve PDAC samples, underlining their clinical relevance.

Tumor-intrinsic kinome landscape of pancreatic cancer reveals new therapeutic approaches.

Effective therapies for pancreatic ductal adenocarcinoma (PDAC) have been largely elusive. Here, we perform Multiplexed kinase Inhibitor Bead Mass Spectrometry on 102 patient derived xenografts derived from 14 unique primary PDAC to define the tumor-intrinsic kinome landscape. Our findings uncover three kinome subgroups making up two tumor-intrinsic kinome subtypes that we call kinotypes.

Alternating gemcitabine plus nab-paclitaxel and gemcitabine alone versus continuous gemcitabine plus nab-paclitaxel after induction treatment of metastatic pancreatic cancer (ALPACA): a multicentre, randomised, open-label, phase 2 trial.

Background: A standardised dose-reduction strategy has not been established for the widely used gemcitabine plus nab-paclitaxel regimen in patients with metastatic pancreatic ductal adenocarcinoma. We aimed to investigate the efficacy and tolerability of alternating treatment cycles of nab-paclitaxel-gemcitabine combination therapy and gemcitabine alone versus continuous treatment with the nab-paclitaxel-gemcitabine combination.

Methods: ALPACA was a randomised, open-label, phase 2 trial conducted at 29 study centres across Germany.

Nanoliposomal irinotecan and fluorouracil plus leucovorin versus fluorouracil plus leucovorin in patients with cholangiocarcinoma and gallbladder carcinoma previously treated with gemcitabine-based therapies (AIO NALIRICC): a multicentre, open-label, randomised, phase 2 trial.

Background: There is an unmet need for effective therapies in pretreated advanced biliary tract cancer. We aimed to evaluate the efficacy of nanoliposomal irinotecan and fluorouracil plus leucovorin compared with fluorouracil plus leucovorin as second-line treatment for biliary tract cancer.

Methods: NALIRICC was a multicentre, open-label, randomised, phase 2 trial done in 17 German centres for patients aged 18 years or older, with an Eastern Cooperative Oncology Group performance status of 0-1, metastatic biliary tract cancer, and progression on gemcitabine-based therapy.

Unresectable biliary tract cancer: Current and future systemic therapy.

For decades, treatment of advanced biliary tract cancer (BTC) was confined to the use of chemotherapy. In recent years however, the number of therapeutic options available for patients with unresectable BTC have drastically increased, with immunotherapy and targeted treatment gradually joining the ranks of guideline-recommended treatment regimens. The aim of the present review is to summarise the current knowledge on unresectable BTC focusing on epidemiology, anatomical distribution and current strategies for systemic treatment.

Changes over time in the course of advanced pancreatic cancer treatment with systemic chemotherapy: a pooled analysis of five clinical trials from two decades of the German AIO study group.

Background: Over the past two decades, our group has conducted five multicenter trials focusing on first-line systemic therapy for patients with advanced pancreatic cancer. The current pooled analysis was designed to evaluate prognosis over time and the impact of clinical characteristics on survival.

Patients And Methods: Individual patient data were derived from five prospective, controlled, multicenter trials conducted by the 'Arbeitsgemeinschaft Internistische Onkologie' (AIO): 'Gem/Cis', 'Ro96', 'RC57', 'ACCEPT' and 'RASH', which recruited patients between December 1997 and January 2017.

Gemcitabine and nab-paclitaxel combined with afatinib in metastatic pancreatic cancer - Results of a phase 1b clinical trial.

Purpose: The combination of gemcitabine/nab-paclitaxel is an established standard treatment in the first-line treatment of metastatic ductal adenocarcinoma of the pancreas (mPDAC). Afatinib, an oral second-generation pan ErbB family tyrosine kinase inhibitor, has shown promising pre-clinical signs in the treatment of pancreatic cancer. The aim of this phase 1b trial was to determine the maximum tolerated dose (MTD) of afatinib in combination with gemcitabine/nab-paclitaxel in patients with mPDAC.

Three-month life expectancy as inclusion criterion for clinical trials in advanced pancreatic cancer: is it really a valid tool for patient selection?

Purpose: To analyze the 3-month life expectancy rate in pancreatic cancer (PC) patients treated within prospective trials from the German AIO study group.

Patients And Methods: A pooled analysis was conducted for patients with advanced PC that were treated within five phase II/III studies conducted between 1997 and 2017 (Gem/Cis, Ro96, RC57, ACCEPT, RASH). The primary goal for the current report was to identify the actual 3-month survival rate, a standard inclusion criterion in oncology trials.

A Retrospective Analysis of Biliary Tract Cancer Patients Presented to the Molecular Tumor Board at the Comprehensive Cancer Center Munich.

Background And Objective: With the rising importance of precision oncology in biliary tract cancer (BTC), the aim of this retrospective single-center analysis was to describe the clinical and molecular characteristics of patients with BTC who underwent comprehensive genomic profiling (CGP) and were discussed in the CCCMunich molecular tumor board (MTB).

Patients And Methods: In this single-center observational study, we included BTC patients with intrahepatic cholangiocarcinoma (iCCA), extrahepatic CCA (eCCA), and gallbladder cancer (GB), who had been discussed in the institutional MTB from May 29, 2017, to July 25, 2022. Patients were followed up until 31 January 2023.

Integrated Analysis of the RASH Study with the Use of the "Burden of Therapy" (BOTh) Methodology-A Novel Tool for Assessing Adverse Events in Metastatic Pancreatic Cancer.

This analysis of the RASH trial (NCT01729481) aimed at gaining a better understanding of the "Burden of Therapy" (BOTh) in pancreatic ductal adenocarcinoma (PDAC). In the RASH study, 150 patients with newly diagnosed metastatic PDAC were treated with gemcitabine plus erlotinib (gem/erlotinib) for four weeks. Patients who developed a skin rash during this four-week run-in phase continued with the gem/erlotinib treatment, while rash-negative patients were switched to FOLFIRINOX.

TPX2 expression as a negative predictor of gemcitabine efficacy in pancreatic cancer.

Background: Targeting protein for Xenopus kinesin-like protein 2 (TPX2) overexpression in human tumours is associated with increased malignancy. Its effect on gemcitabine resistance in pancreatic ductal adenocarcinoma (PDAC) has not been studied yet.

Methods: The prognostic impact of TPX2 expression was examined in the tumour tissue of 139 patients with advanced PDAC (aPDAC) treated within the AIO-PK0104 trial or translational trials and of 400 resected PDAC (rPDAC) patients.

Cancer of unknown primary (CUP) through the lens of precision oncology: a single institution perspective.

Purpose: For patients with cancer of unknown primary (CUP), treatment options are limited. Precision oncology, the interplay of comprehensive genomic profiling (CGP) and targeted therapies, aims to offer additional treatment options to patients with advanced and hard-to-treat cancers. We aimed to highlight the use of a molecular tumor board (MTB) in the therapeutic management of CUP patients.

Treatment of Mediastinal Endometrial Carcinoma Developed from Extragenital Endometriosis and Simultaneous Rectal Adenocarcinoma in a 55-year-old Woman.

Background/aim: Endometriosis is a common disorder in reproductive-age women leading to a broad range of symptoms and is associated with a higher risk for endometrioid ovarian carcinoma.

Case Report: We report the case of a 55 year-old woman with previously undiagnosed endometriosis presenting with a large mediastinal cancer of unknown primary (CUP) and synchronous Union Internationale Contre le Cancer (UICC) stage II rectal adenocarcinoma. Histopathologically the mediastinal tumor resembled endometrial carcinoma and laparoscopically endometriotic lesions on the patient's peritoneum were detected.

Precision Oncology in Pancreatic Cancer: Experiences and Challenges of the CCCMunich Molecular Tumor Board.

Background: In pancreatic cancer, systemic treatment options in addition to chemotherapy remain scarce, and so far only a small proportion of patients benefit from targeted therapies.

Objective: The patients with pancreatic cancer discussed in the CCCMunich Molecular Tumor Board were reviewed to gain a better real-world understanding of the challenges and chances of precision oncology in this hard-to-treat cancer.

Methods: Patients with pancreatic cancer who received comprehensive genomic profiling and were discussed in the interdisciplinary Molecular Tumor Board between May 2017 and July 2022 were included.

Exploring Pain, Quality of Life, and Emotional Well-Being in Patients with Advanced Pancreatic Cancer Practicing Spiritual Meditation: A Pilot Study.

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 1 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 2 months for a maximum of 1 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.

Comparison of somatostatin receptor expression in patients with neuroendocrine tumours with and without somatostatin analogue treatment imaged with [F]SiTATE.

Purpose: Somatostatin analogues (SSA) are frequently used in the treatment of neuroendocrine tumours. Recently, [F]SiTATE entered the field of somatostatin receptor (SSR) positron emission tomography (PET)/computed tomography (CT) imaging. The purpose of this study was to compare the SSR-expression of differentiated gastroentero-pancreatic neuroendocrine tumours (GEP-NET) measured by [18F]SiTATE-PET/CT in patients with and without previous treatment with long-acting SSAs to evaluate if SSA treatment needs to be paused prior to [18F]SiTATE-PET/CT.

Regional hyperthermia with cisplatin added to gemcitabine versus gemcitabine in patients with resected pancreatic ductal adenocarcinoma: The HEAT randomised clinical trial.

Background: Regional hyperthermia (RHT) with cisplatin added to gemcitabine showed efficacy in gemcitabine-pre-treated patients with advanced pancreatic ductal adenocarcinoma. We conducted a randomised clinical trial to investigate RHT with cisplatin added to gemcitabine (GPH) compared with gemcitabine (G) in the adjuvant setting of resected pancreatic ductal adenocarcinoma.

Methods: This randomised, multicentre, open-label trial randomly assigned patients to either GPH (gemcitabine 1000 mg/m on day 1, 15 and cisplatin 25 mg/m with RHT on day 2, 3 and 15,16) or to G (gemcitabine 1000 mg/m on day 1,8,15), four-weekly over six cycles.

Clinical Impact of Structured Post-Operative Surveillance in Resected Pancreatic Adenocarcinoma: Results from a Retrospective Cohort Study.

Introduction: To this date, surgery remains the only potentially curative approach in the treatment of pancreatic cancer. To analyse the clinical impact of a structured post-operative follow-up programme, we retrospectively analysed a cohort of resected pancreatic adenocarcinoma patients treated at LMU Munich.

Methods: Pancreatic adenocarcinoma patients who underwent resection and presented for regular follow-up visits at our centre between 2002 and 2017 were identified from two existing study cohorts.

Robust Preanalytical Performance of Soluble PD-1, PD-L1 and PD-L2 Assessed by Sensitive ELISAs in Blood.

The interaction between programmed death-1 receptor PD-1 and its ligands PD-L1 and PD-L2 is involved in self-tolerance, immune escape of cancer, cardiovascular diseases, and COVID-19. As blood-based protein markers they bear great potential to improve oncoimmunology research and monitoring of anti-cancer immunotherapy. A variety of preanalytical conditions were tested to assure high quality plasma sample measurements: (i) different time intervals and storage temperatures before and after blood centrifugation; (ii) fresh samples and repeated freeze-thaw-cycles; (iii) different conditions of sample preparation before measurement.

High Quality Performance of Novel Immunoassays for the Sensitive Quantification of Soluble PD-1, PD-L1 and PD-L2 in Blood.

Programmed death-1 receptor PD-1(CD279) and its corresponding ligands PD-L1(CD274, B7-H1) and PD-L2(CD273, B7-DC) play important roles in physiological immune tolerance and for immune escape in cancer disease. Hence, the establishment and analytical validation of a novel enzyme-linked immunosorbent assay (ELISA) to measure soluble PD-1, PD-L1 and PD-L2 in blood samples according to high quality standards is required. Antibody pairs were used to establish novel highly sensitive ELISAs for all three markers on an open electrochemiluminescence Quickplex platform.