Trajectories of immune-related serum proteins and quality of life in patients with pancreatic and other periampullary cancer: the CHAMP study.

BACKGROUND: There is still a profound lack of efficient therapeutic strategies against pancreatic and other periampullary adenocarcinoma. Surgery is seldom possible, leaving palliative chemotherapy the only option for most patients. Chemotherapy treatment is however often accompanied by serious side-effects, and the identification of biomarkers for early prediction of disease and treatment-associated symptoms could help alleviate patient suffering. This study investigated the dynamic interrelationship between immune-related serum proteins, routine biomarkers, and health-related quality of life (HRQoL) factors during chemotherapy treatment of patients enrolled in the prospective, observational study Chemotherapy, Host response And Molecular dynamics in Periampullary cancer (CHAMP). METHODS: Proximity extension assay was applied to analyse 92 immune-associated proteins in longitudinal serum samples from 75 patients, 18 treated with curative and 57 with palliative intent. HRQoL data were available from all patients at baseline (BL), from 41 patients at three months, and from 23 patients at six months. Information on routine laboratory parameters albumin, CA19-9, CEA and CRP were collected from medical charts. RESULTS: In total nine proteins; chemokine (C-C motif) ligand 23 (CCL23), cluster of differentiation 4 (CD4), cluster of differentiation 28 (CD28), decorin (DCN), galectin-1 (Gal-1), granzyme B (GZMB), granzyme H (GZMH), matrix metallopeptidase 7 (MMP7), and monocyte chemotactic protein-1 (MCP-1) were strongly correlated (Spearman's Rho ≤ -0.6 or ≥ 0.6) with either cognitive functioning (DCN), emotional functioning (DCN, MCP-1), dyspnoea (CD28, GZMB, GZMH) or insomnia (CCL23, CD4, Gal-1, MMP7) during treatment. Associations between routine laboratory parameters (CA 19-9, CA-125, CRP, CEA and albumin) and HRQoL factors were overall weaker. None of the investigated proteins were associated with pain. CONCLUSIONS: This is, to our knowledge, the first study exploring associations between serum biomarkers and HRQoL in patients with pancreatic or other periampullary cancer, and some findings merit further validation. The associations of DCN and MCP-1with impaired cognitive and/or emotional functioning are of particular interest, given their established link to various neurodegenerative conditions. Chemotherapy is known to cause persistent cognitive dysfunction with effects on memory and executive function, referred to as "chemo brain". It would therefore be of great value to identify biomarkers for early detection and management of this debilitating condition. TRIAL REGISTRATION: Clinical Trial Registration: NCT03724994.

High Infiltration of CD68+/CD163- Macrophages Is an Adverse Prognostic Factor after Neoadjuvant Chemotherapy in Esophageal and Gastric Adenocarcinoma.

Tumor-associated macrophages (TAMs) have emerged as key players in tumor immunology but demonstrate a continuum of functional states being either tumor suppressive or promoting. Moreover, chemotherapeutic agents have been shown to alter the tumor microenvironment. Perioperative chemotherapy is a standard treatment option for resectable esophageal and gastric (EG) adenocarcinoma. The aim of this study was to investigate the influence of neoadjuvant chemotherapy (NAC) on TAMs to improve the prognostication and treatment course for these patients. The study cohort comprised 148 patients, all of whom were diagnosed with resectable EG adenocarcinoma and treated with NAC. Immunohistochemistry was applied to assess the total infiltration and infiltration into tumor nests (TN) of CD68+/CD163-, CD68+/CD163+, and MARCO+ TAMs, on paired biopsies from primary tumors (PT) pre-NAC, and resected PT and lymph node metastases post-NAC. In pre-NAC specimens, high CD68+/CD163+ infiltration into TN was an unfavorable prognostic factor. No association was found between TAM density in PT pre-NAC and histopathological regression. The density of CD68+/CD163+ TAMs was increased in PT post-NAC, while the density of MARCO+ TAMs was decreased. CD68+/CD163- TAM density was not altered. In post-NAC specimens, higher total as well as TN infiltration of CD68+/CD163- TAMs were adverse prognostic factors. In conclusion, these results suggest that NAC may alter certain TAM subsets in EG adenocarcinoma, along with their functional properties and thus their prognostic value.

A registry-based study evaluating overall survival and treatment duration in Swedish patients with metastatic castration-resistant prostate cancer treated with enzalutamide.

Objective: This retrospective, single-centre, non-interventional, registry-based study evaluated patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide in daily clinical practice at Skåne University Hospital, Malmö, Sweden.Materials and methods: Registry data were reviewed for patients treated with enzalutamide pre- or post-chemotherapy initiated between December 2013 and June 2017. The primary endpoint was overall survival (OS) in post-chemotherapy patients. Secondary endpoints were enzalutamide treatment duration in the pre- and post-chemotherapy setting. This study was approved by the Lund regional Ethics Review Board (Dnr:2017/716) and is registered with ClinicalTrials.gov (NCT03328364).Results: A total of 102 pre-chemotherapy and 98 post-chemotherapy patients were included. Median age was higher in the pre- than in the post-chemotherapy group (77 vs 72 years, respectively). Median OS in post-chemotherapy patients from initiation of enzalutamide until death from any cause was 14.3 months [95% confidence interval (CI) = 11.00-18.20]. Median treatment duration was 13.8 months (95% CI = 11.4-20.2) and 7.6 months (95% CI = 6.3-10.2) for pre- and post-chemotherapy patients, respectively.Conclusion: Enzalutamide can be used to effectively treat mCRPC patients in daily clinical settings, despite the patients being older and less healthy than those enrolled in the previous randomised, clinical registration studies.

A Nordic registry-based study of drug treatment patterns in overactive bladder patients.

Aim: To describe treatment patterns in Denmark, Norway and Sweden for patients receiving overactive bladder (OAB) pharmacotherapy.Methods: This was a prospective, multinational, registry-based study involving three nationwide prescribed drug registries (sample size 6000 patients per country), performed between 1 January and 30 June 2014. Patients were followed prospectively for 12 months after first pick-up of index medication. The primary objective was to evaluate the proportion of patients picking up first refill of index medication. Secondary objectives included evaluation of the average number of pick-ups collected during 1 year and time to discontinuation of index medication.Results: A high proportion of patients in the three Nordic countries picked up a first refill of OAB medication: 64-75% for mirabegron and 84-95% for individual antimuscarinics. Amongst treatment-naïve patients, the proportion picking up their first mirabegron refill was 60-64%; for individual antimuscarinics it was 30-63%. Mean number of pick-ups during 1 year ranged from 3.5-5.0 for mirabegron across the countries and for individual antimuscarinics from 3.8-12.3. Median time to discontinuation for mirabegron ranged from 140 (Denmark) to 207 days (Norway) and, for individual antimuscarinics (solifenacin), from 182 (Denmark) to 355 days (Sweden). At 12 months, the proportion of patients still on treatment with mirabegron and antimuscarinics was 21% and 38%, respectively.Conclusions: Treatment patterns in patients with OAB picking up a mirabegron or antimuscarinic prescription in Denmark, Norway and Sweden indicate that persistence remains a challenge.

Patient-perceived effectiveness and impact on quality of life of solifenacin in combination with an α-blocker in men with overactive bladder in Sweden: a non-interventional study.

Treating male lower urinary tract symptoms (LUTS) by targeting the prostate would have limited effect on overactive bladder (OAB) symptoms. This study assessed perceived symptoms and quality of life (QoL) of male patients with OAB treated with an α-blocker plus solifenacin in daily clinical practice. Male patients aged ≥40 years were included after the decision was made to initiate treatment with an α-blocker for LUTS plus solifenacin for OAB symptoms. The primary endpoint was change in patient perception of bladder condition (PPBC) questionnaire score over 6 months. Other assessments included the OAB-questionnaire short form (OAB-q SF) and International Prostate Symptom Score (IPSS). Interpretation of the study data was hindered by not meeting the enrollment target and a high dropout rate. In 36 evaluable patients, mean (SD) PPBC score improved from 4.3 (0.93) at baseline ("moderate" to "severe" problems) to 3.5 (1.06) at month 6 ("minor" to "moderate" problems). OAB-q SF scores and total IPSS also improved. In this patient population, treatment with solifenacin and an α-blocker resulted in improvements in male patient perception of their LUTS and QoL, although the results should be interpreted with caution due to the low number of patients with complete data.