Identification of factors associated with survival after ascites diagnosis in metastatic pancreatic cancer (mPC) patients may guide treatment decisions and help to maintain quality of life (QoL) in ...this highly symptomatic patient collective.
All patients treated for mPC at the Medical University of Vienna between 2010 and 2019 developing ascites throughout their course of disease were identified by retrospective chart review. General risk factors, metastatic sites, systemic inflammation and liver function parameters, as well as type of treatment after ascites diagnosis were investigated for associations with survival.
117 mPC patients with ascites were included in this study. Median time from mPC to ascites diagnosis was 8.9 months (range 0 to 99) and median overall survival (OS) after ascites diagnosis was 27.4 days (range 21.3 to 42.6). Identified prognostic factors at ascites diagnosis independently associated with an impaired OS were presence of liver metastases (HR: 2.07, CI: 1.13-3.79, p=0.018), peritoneal carcinomatosis (HR: 1.74, CI: 1.11-2.71, p=0.015), and portal vein obstruction (PVO) (HR: 2.52, CI: 1.29-4.90, p=0.007). Compared to best supportive care (BSC), continuation of systemic therapy after ascites diagnosis was independently associated with survival (HR: 0.35, CI: 0.20-0.61, p<0.001) with a median OS of 62 days (CI: 51-129 days, p<0.001) versus 16 days (CI: 11-24 days), respectively.
Liver and peritoneal metastases as well as PVO were found to be prognostic factors after ascites diagnosis in mPC patients. Continuation of systemic therapy after ascites diagnosis was associated with a longer OS, which needs to be evaluated in larger clinical trials including QoL assessment.
•Ascites development represents an end-stage condition in mPC patients•Liver and peritoneal metastases as well as portal vein obstruction are prognosticators for survival in mPC patients with ascites•Continued systemic therapy may improve outcome in these patients compared to BSC alone
Microbial community metabolic balance (i.e., the ratio between photosynthesis and community respiration) is critical for assessing the strength of the biological carbon pump and its importance for ...the marine food web. This study aimed at characterizing the microbial community metabolic balance (hereinafter referred to as metabolic balance) in the Beagle Channel (BC, 54°S, 68° W), a sub-Antarctic environment that connects the Pacific and Atlantic Oceans at the southernmost extreme of South America. During a binational Chilean-Argentinian cruise along the eastern BC in the austral spring (November 2019), oxygen production and consumption rates were estimated in vitro after 12-h light and dark incubations. Phytoplankton primary productivity was additionally assessed using in vivo active fluorescence techniques. Environmental conditions (temperature, salinity, nutrients, dissolved oxygen, carbonate system and light) and the composition of the plankton community (i.e., phytoplankton and bacteria) were analyzed to assess the factors controlling productivity in the BC. Finally, we explored the role of the microbial community metabolic balance in modulating CO2 uptake by means of high-resolution underway CO2 fugacities (fCO2). Results showed a highly dynamic and rapidly changing system, with gross primary production (GPP) rates presenting a west-east gradient, with minimum values in the western portion of the study area (0.63 ± 0.12 mmol O2 m−3 d−1) and maximum values towards the Atlantic (13.87 ± 2.00 mmol O2 m−3 d−1). Community respiration rates were high (mean: 2.81 mmol O2 m−3 d−1) and positively correlated with GPP. Although net community production (NCP) was relatively low (0.25–3.27 mmol O2 m−3d−1), the P:R ratio suggests the prevalence of autotrophic communities, dominated by chain forming diatoms, mainly in the eastern portion (NCP : 3.27 mmol O2 m−3 d−1). Thermohaline conditions played a key role in regulating the productive capacity of the BC and in the sea-air CO2 exchange, except in the most productive stations, where biological production fueled fCO2 dynamics.
•In November 2019, eastern Beagle Channel plankton showed a net autotrophic metabolism.•Diatoms dominated the microbial community biomass during spring.•Temperature triggered the spring bloom in the Channel under optimal light conditions.•Microbial metabolism affects CO2 uptake during spring.
We aimed to analyse the impact of breast cancer (BC) subtypes on the clinical course of disease with special emphasis on the occurrence of brain metastases (BM) and outcome in an elderly BC ...population. A total number of 706 patients ≥65 years receiving treatment for BC from 2007 to 2011 were identified from a BC database. 62 patients diagnosed with DCIS and 73 patients with incomplete datasets were excluded, leaving 571 patients for this analysis. Patient characteristics, biological tumour subtypes, and clinical outcome including overall survival (OS) were obtained by retrospective chart review. 380/571 (66, 5 %) patients aged 65–74 years were grouped among the young-old, 182/571 (31.9 %) patients aged 75–84 years among the old–old, and 29/571 (5.1 %) patients aged ≥85 years among the oldest-old. 392/571 (68.8 %) patients presented with luminal BC, 119/571 (20.8 %) with HER2-positive, and 59/571 (10.3 %) with triple-negative BC (TNBC). At 38 months median follow-up, 115/571 (20.1 %) patients presented with distant recurrence. A higher recurrence rate was observed in the HER2-positive subtype (43/119 (36.1 %)), as compared to TNBC (15/59 (25.4 %)) and luminal BC (57/392 (14.5 %);
p
< 0.001). BM were detected at a significantly higher rate in HER2-positive BC patients (9/119 (7.6 %)), as compared to TNBC (2/59 (3.4 %)) and luminal BC patients (6/392 (1.5 %);
p
= 0.003). Diagnosis of metastatic disease (HR 7.7; 95 % CI 5.2–11.4;
p
< 0.001) as well as development of BM (HR 3.5; 95 % CI 1.9–6.4;
p
< 0.001) had a significantly negative impact on OS in a time-dependent covariate cox regression model. In contrast to younger BC patients, outcome in this large cohort of elderly patients suggests that HER2-positive disease—not TNBC—featured the most aggressive clinical course with the highest rates of metastatic spread and BM. In-depth analysis regarding a potentially distinct biology of TNBC in elderly is therefore warranted.
Brain metastases (BM) are frequently diagnosed in metastatic Her2-positive breast cancer. Local treatment remains the standard of care but lapatinib plus capecitabine was recently established as ...systemic therapy option. Due to a disruption of the blood–brain/tumour-barrier at metastatic sites, even large molecules may penetrate into the central nervous system (CNS). Here, we report on the activity of T-DM1 in Her2-positive breast cancer BM. T-DM1 was administered at a dose of 3.6 mg once every 3 weeks as primary systemic therapy for BM or upon documented CNS progression after initial local treatment. Thus, this study allowed for the appraisal of T-DM1 activity in BM. Restaging was conducted every 12 weeks with MRI or whenever symptoms of disease progression occurred. Ten patients were included; in two asymptomatic subjects, T-DM1 was administered as primary therapy, while eight had progressive BM. All patients had received prior treatment with trastuzumab, six had already received lapatinib, and three pertuzumab as well. Three patients had partial remission of BM, and two patient had stable disease lasting for ≥6 months; two further patients had stable disease for <6 months while three progressed despite treatment. At 8.5 months median follow-up, intracranial PFS was 5 months, and median OS from initiation of T-DM1 was not reached. Local treatment of BM remains the standard of care; lapatinib plus capecitabine is currently the best established systemic therapy option. Still, T-DM1 apparently offers relevant clinical activity in BM and further investigation is warranted.
Aim
We aimed to characterize angiogenesis and proliferation and their correlation with clinical characteristics in a large brain metastasis (BM) series.
Methods
Ki67 proliferation index, ...microvascular density (MVD) and hypoxia‐inducible factor 1 alpha (HIF‐1 alpha) index were determined by immunohistochemistry in BM and primary tumour specimens.
Results
Six hundred thirty‐nine BM specimens of 639 patients with lung cancer (344/639; 53.8%), breast cancer (105/639; 16.4%), melanoma (67/639; 10.5%), renal cell carcinoma (RCC; 52/639; 8.1%) or colorectal cancer (CRC; 71/639; 11.1%) were available. Specimens of the corresponding primary tumour were available in 113/639 (17.7%) cases. Median Ki67 index was highest in CRC BM and lowest in RCC BM (P < 0.001). MVD and HIF‐1 alpha index were both highest in RCC BM and lowest in melanoma BM (P < 0.001). Significantly higher Ki67 indices, MVD and HIF‐1 alpha indices in the BM than in matched primary tumours were observed for breast cancer, non‐small cell lung cancer (NSCLC) and CRC. Correlation of tissue‐based parameters with overall survival in individual tumour types showed a favourable and independent prognostic impact of low Ki67 index hazard ratio (HR) 1.015; P < 0.001 in NSCLC BM and of low Ki67 index (HR 1.027; P = 0.008) and high angiogenic activity (HR 1.877; P = 0.002) in RCC.
Conclusion
Our data argue for differential pathobiological and clinical relevance of Ki67 index, HIF1‐alpha index and MVD between primary tumour types in BM patients. An independent prognostic impact of tissue‐based characteristics was observed in patients with BM from NSCLC and RCC, supporting the incorporation of these tissue‐based parameters into diagnosis‐specific prognostic scores.
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