OBJECTIVE: The aim of this study was to determine the role of site-specific metastatic patterns over time and assess factors associated with extended survival in metastatic PDAC. Half of all patients with pancreatic ductal adenocarcinoma (PDAC) present with metastatic disease. The site of metastasis plays a crucial role in clinical decision making due to its prognostic value.
METHODS: We examined 56,757 stage-IV PDAC patients from the National Cancer Database (2016-2019), categorizing them by metastatic site: multiple, liver, lung, brain, bone, carcinomatosis, or other. The site-specific prognostic value was assessed using log-rank tests while time-varying effects were assessed by Aalen\'s linear hazards model. Factors associated with extended survival (>3years) were assessed with logistic regression.
RESULTS: Median overall survival (mOS) in patients with distant lymph node-only metastases (9.0 months) and lung-only metastases (8.1 months) was significantly longer than in patients with liver-only metastases (4.6 months, p < 0.001). However, after six months, the metastatic site lost prognostic value. Logistic regression identified extended survivors (3.6 %) as more likely to be younger, Hispanic, privately insured, Charlson-index <2, having received chemotherapy, or having undergone primary or distant site surgery (all p < 0.001).
CONCLUSIONS: While synchronous liver metastases are associated with worse outcomes than lung-only and lymph node-only metastases, this predictive value is diminished after six months. Therefore, treatment decisions beyond this time should not primarily depend on the metastatic site. Extended survival is possible in a small subset of patients with favorable tumor biology and good conditional status, who are more likely to undergo aggressive therapies.

Health-related quality of life is a key contributor to overall well-being, and this is becoming an increasingly prominent factor when making therapeutic choices in the management of ANCA-associated vasculitis (AAV). Progress in available therapeutic strategies for AAV has resulted in this historically acute disease with a potentially fatal short-term outcome, becoming a relapsing-remitting chronic disorder. This new perspective on AAV means that patient survival should no longer be considered as the only major treatment target. Additional outcomes in this context that should be portrayed in order to consider a therapeutic approach as successful include patient quality of life, as well as the burden of treatment-induced morbidity. Comorbidities and impaired quality of life in patients with AAV, as with many other autoimmune diseases, may be a consequence of the disease itself as well as a result of the therapy employed. The AAV disease process may induce organ damage, including kidney failure and structural lung damage, and increase the risk of cardiovascular disease. On top of this, treatments employed to manage the disease may contribute further to the overall comorbidities burden. Furthermore, pre-existing comorbidities can increase AAV severity and may also be contraindications that limit potential therapeutic options. Quality of life is another central topic that can have a huge impact on patient wellbeing as well as adherence to treatment. Ongoing monitoring of comorbidity risk and of quality of life is thus key for successful AAV management. This process, however, may be complicated; the identification of the correct parameters on which to focus is not always straightforward and, more importantly, it is sometimes the symptoms that may appear trivial to physicians that are most detrimental to a patient\'s quality of life. With these shifts in treatment capabilities and understanding of patient burden, it is necessary to adjust the treatment paradigm accordingly. Treatment success is no longer defined solely by the control of disease activity; treatment success requires holistic improvement determined through the assessment of all aspects of the disease, ranging from disease control to comorbidity risk through to the assessment of health-related quality of life. This review explores the burden of AAV itself as well as treatment-related side effects with a special focus on the tools available to measure outcomes. The management of AAV has entered a new era with a strong focus on both the management and prevention of comorbidities as well as patient-reported outcomes, both of which are now considered key factors in defining treatment success.

BACKGROUND: Breast cancer (BC) patients with extended survival show a higher incidence of frailty. This study aimed to develop and validate a novel model combining sociodemographic factors (SF) and disease-related factors (DRF) to identify frailty in BC patients with extended survival.
METHODS: This cross-sectional study examined data from 1167 patients admitted to a large urban academic medical centre. Three types of predictive models were constructed in the training set (817 patients): the SF model, the DRF model, and the SF + DRF model (combined model). The model performance and effectiveness were assessed using receiver operating characteristic (ROC) curves, calibration plots and decision curves analysis (DCA). Then the model was subsequently validated on the validation set.
RESULTS: The incidence of frailty in BC patients with extended survival was 35.8%. We identified six independent risk factors including age, health status, chemotherapy, endocrine therapy, number of comorbidities and oral medications. Ultimately, we constructed an optimal model (combined model C) for frailty. The predictive model showed significantly high discriminative accuracy in the training set AUC: 0.754, (95% CI, 0.719-0.789; sensitivity: 76.8%, specificity: 62.2%) and validation set AUC: 0.805, (95% CI, 0.76-0.85), sensitivity: 60.8%, specificity: 87.1%) respectively. A prediction nomogram was constructed for the training and validation sets. Calibration and DCA were performed, which indicated that the clinical model presented satisfactory calibration and clinical utility. Ultimately, we implemented the prediction model into a mobile-friendly web application that provides an accurate and individualized prediction for BC.
CONCLUSIONS: The present study demonstrated that the prevalence of frailty in BC patients with extended survival was 35.8%. We developed a novel model for screening frailty, which may provide evidence for frailty screening and prevention.

Glioblastoma is the most frequent type of primary brain tumors. Despite the advanced therapy, most of the patients die within 2 years after the diagnosis. The tumor has a typical appearance on MRI: a central hypointensity surrounded by an inhomogeneous, ring-shaped contrast enhancement along its border. Too small to be recognized by MRI, detached individual tumor cells migrate along white matter fiber tracts several centimeters away from the edge of the tumor. Usually these cells are the source of tumor recurrence. If the infiltrated brain areas could be identified, longer survival time could be achieved through supratotal resection and individually planned radiation therapy. Probabilistic tractography is an advanced imaging method that can potentially be used to identify infiltrated pathways, thus the real extent of the glioblastoma. Our study consisted of twenty high grade glioma patients. Probabilistic tractography was started from the tumor. The location of tumor recurrence on follow-up MRI was considered as the primary infiltrated white matter tracts. The results of probabilistic tractography were evaluated at thirteen different thresholds. The overlap with the tumor recurrence of each threshold level was then defined to calculate the sensitivity and specificity. In the group level, sensitivity (81%) and specificity (90%) were the most reliable at 5% threshold level. There were two outliers in the study group, both with high specificity and very low sensitivity. According to our results, probabilistic tractography can help to define the true extent of the glioblastoma at the time of diagnosis with high sensitivity and specificity. Individually planned surgery and irradiation could provide a better chance of survival in these patients.

The development of treatment protocols that result in a complete response to chemotherapy has been hampered by free drug toxicity and the low bioavailability of nano-formulated drugs. Here, we explore the application of temperature-sensitive liposomes that have been formulated to enhance stability in circulation. We formed a pH-sensitive complex between doxorubicin (Dox) and copper (CuDox) in the core of lysolipid-containing temperature-sensitive liposomes (LTSLs). The complex remains associated at neutral pH but dissociates to free Dox in lower pH environments. The resulting CuDox-LTSLs were injected intravenously into a syngeneic murine breast cancer model (6 mg Dox/kg body weight) and intravascular release of the drug was triggered by ultrasound. The entire tumor was insonified for 5 min prior to drug administration and 20 min post drug injection. A single-dose administration of CuDox-LTSLs combined with insonation suppressed tumor growth. Moreover, after twice per week treatment over a period of 28 days, a complete response was achieved in which the NDL tumor cells and the tumor interstitium could no longer be detected. All mice treated with ultrasound combined with CuDox-LTSLs survived, and tumor was undetectable 8 months post treatment. Iron and copper-laden macrophages were observed at early time points following treatment with this temperature sensitive formulation. Systemic toxicity indicators, such as cardiac hypertrophy, leukopenia, and weight and hair loss were not detected with CuDox-LTSLs after the 28-day therapy.