•This Clinical Practice Guideline provides management recommendations for patients with brain metastases from solid tumours.•The guideline covers clinical and pathological diagnosis, staging and risk ...assessment, treatment and follow-up.•Treatment and management algorithms are provided.•The author panel encompasses a multidisciplinary group of experts from different institutions and countries in Europe.•Recommendations are based on available scientific data and the authors’ collective expert opinion.
Purpose
Misconceptions regarding activity and toxicity of therapeutic interventions are common among cancer patients. There is little knowledge about the factors that contribute to a more realistic ...perception by patients.
Methods
This pilot study was designed as a prospective questionnaire survey and included 101 therapy-naïve patients treated at the Division of Oncology, Medical University of Vienna. After obtaining written informed consent, patients’ expectations about treatment aims, side effects and the satisfaction with their oncologic consultation were interrogated before the first treatment cycle by questionnaires.
Results
Of 101 patients, 53 (53%) were female and 67/101 (66%) were treated with curative attempt in an adjuvant or neo-adjuvant setting. The most common diagnoses were lung cancer (31%) and breast cancer (30%). Although 92% of patients were satisfied with the information given by their oncologist, palliative patients were more likely to declare that not everything was explained in an intelligible manner (
p
= 0.01). Patients with a first language other than German stated more often that their physician did not listen carefully enough (
p
= 0.02). Of 30 patients, 26 (87%) receiving chemotherapy with palliative intent believed that their disease was curable. Concerning adverse events, female patients anticipated more frequently hair loss (
p
= 0.003) and changes in taste (
p
= 0.001) compared to men. Patients under curative treatment were more likely to expect weight loss (
p
= 0.02) and lack of appetite (
p
= 0.01) compared to patients with palliative treatment intent.
Conclusion
In conclusion, cancer patients were satisfied with the patient-doctor communication. This prospective study aggregated patients’ concerns on side effects and the perception of therapeutic goals in therapy-naïve patients. Of note, the majority of patients treated in the palliative setting expected their treatment to cure the disease.
The introduction of immune checkpoint inhibitors (ICIs) for the treatment of solid cancers dramatically turned the tables in clinical routine. However, therapy success is still limited with up to 70% ...of non-responders in patients with ICI treatment. Traditionally, most immunotherapy approaches aim at directly stimulating anti-tumor T cell responses. More recently, tumor-associated macrophages have come into focus due to their predominance in solid tumors. Intensive cross-talk with tumor cells and immune as well as stromal cells within the tumor microenvironment can drive either pro- or anti-tumorigenic macrophage phenotypes. In turn, tumor-associated macrophages strongly shape cytokine and metabolite levels in the tumor microenvironment and thus are central players in anti-tumor immunity. Thus, ambivalent macrophage populations exist which raises therapeutic possibilities to either enhance or diminish their functionality. However, molecular signals controlling tumor-associated macrophage polarization are incompletely understood. Gaining in-depth understanding of monocyte/macrophage properties both in circulation and within distinct tumor microenvironments would (i) allow the development of new therapeutic approaches, and (ii) could additionally aid our understanding of underlying mechanisms limiting current therapy with the option of combinatorial therapies to increase efficacy. In this review, we summarize recent data addressing heterogeneity of tumor-associated macrophage populations and we discuss strategies to target macrophages using known molecular pathways with the potential for straight-forward clinical application.
•Single-cell sequencing reveals enormous macrophage complexity.•Strong functional imprinting of tumor-associated macrophages by tumor microenvironment.•Suspected active role of monocytes in hyperprogression.•Several, potential targets on monocytes and tumor-associated macrophages under investigation.
Body mass index (BMI) is a prognostic factor in several cancer types. We investigated the prognostic role of BMI in a large patient cohort with newly diagnosed lung cancer brain metastases (BM) ...between 1990 and 2013. BMI at diagnosis of BM and graded prognostic assessment (GPA) were calculated. Definitions were underweight (BMI <18.50), weight within normal range (BMI 18.50–24.99) and overweight (BMI ≥ 25.00). A total of 624 patients (men 401/624 64.3%; women 223/624 35.7%; median age of 61 range 33–88) were analysed. Histology was non‐small cell lung cancer in 417/622 (66.8%), small cell lung cancer (SCLC) in 205/624 (32.9%) and not otherwise specified in 2/624 (0.3%) patients. About 313/624 (50.2%) had normal BMI, 272/624 (43.5%) were overweight and 39/624 (6.3%) were underweight. Underweight patients had shorter median overall survival (3 months) compared to patients with normal BMI (7 months) and overweight (8 months; p < .001; log rank test). At multivariate analysis, higher GPA class (HR 1.430; 95% cumulative incidence, CI 1.279–1.598; p < .001; Cox regression model), SCLC histology (HR 1.310; 95% CI 1.101–1.558) and presence of underweight (HR 1.845; 95% CI 1.317–2.585; p = .014; Cox regression model) were independent prognostic factors. Underweight at diagnosis of BM in lung cancer is associated with an unfavourable prognosis.
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
As endocrinological parameters such as thyroid hormones modulate proliferative, metabolic, and angiogenic pathways, it is surmised that their levels can be associated with cancer development and ...progression. Most patients with gastroesophageal cancer are diagnosed very late and have a poor prognosis, yet the association with endocrinological parameters has not been addressed so far. The aim of this study was to correlate hormones with the outcome, so new prognostic and potentially therapeutic markers can be defined. We analyzed clinical and endocrinological parameters including history of thyroid disorders and laboratory analyses of thyroid hormones and correlated these with the overall survival in a large European cohort of patients with inoperable locally advanced or metastatic gastroesophageal cancer treated between 2002 and 2018 at the Vienna General Hospital, Austria. In total, the survival outcome of 258 patients was evaluated. Higher levels of fT4 (
p
= 0.041, HR = 2.202) and lower levels of T3 (
p
= 0,003, HR = 0,141) were associated with significantly shorter survival. However, the overall survival of patients with known thyroid disorders did not differ significantly from euthyroid patients (euthyroid, 283 days; hyperthyroid, 354 days; hypothyroid, 284 days;
p
= 0.472). Elevated fT4 levels are associated with poorer overall survival of patients with gastroesophageal cancer in advanced stages. Since data on the correlation of endocrinological parameters and gastroesophageal cancer are scarce, this analysis is an important impulse for further studies concerning the impact of thyroxine on patients with cancer of the upper GI tract.
Summary
Background
It is important to know what drives and arrests melanocytic growth in vivo but observations linking oncogenic mutations to growth rates of melanocytic neoplasms in vivo are sparse.
...Objectives
To clarify the relationship between BRAFV600E mutations and p16 expression and the growth rate of melanocytic neoplasms in vivo.
Methods
We measured the growth rate of 54 melanocytic lesions (26 melanomas, 28 naevi) in vivo with digital dermatoscopy and correlated it with BRAFV600E and p16 expression, and with dermatoscopic and histological patterns.
Results
Melanomas grew faster than naevi (mean 2·7 vs. 0·8 mm2/year; P < 0·001) and the growth rate was faster in lesions with more nests (> 25% nests: 2·0 mm2/year vs. < 25% nests: 1·0 mm2/year; P = 0·036). Melanomas with the BRAFV600E mutation grew significantly faster than melanomas without the mutation (mean 3·36 vs. 1·60 mm2/year, P = 0·018). This effect of the BRAFV600E mutation on the growth rate was not observed in melanocytic naevi (mean 1·01 vs. 0·47 mm2/year, P = 0·274). Histopathologically, extensive nesting, larger nests and larger cell sizes were more common in melanocytic neoplasms with the BRAFV600E mutation than in those without the mutation. Melanomas expressing p16 had a slower growth rate than melanomas without p16 expression (2·27 vs. 4·34 mm2/year, P = 0·047). This effect was not observed in naevi (0·81 vs. 0·68 mm2/year, P = 0·836).
Conclusions
The expression of BRAFV600E and the loss of p16 accelerate the growth rate of early melanomas in vivo but not in melanocytic naevi. In comparison to melanocytic proliferations that lack the mutation, the epidermal melanocytes in lesions that harbour BRAFV600E mutations are larger and more frequently arranged in large nests.
What's already known about this topic?
Oncogenic BRAF mutations are common in melanoma and naevi but the biological significance of oncogenic BRAF regarding the growth rate of melanocytic proliferations in vivo is currently unknown.
What does this study add?
BRAFV600E and lack of p16 expression enhance the growth rate of early melanomas in vivo.
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