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BACKGROUND: 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 in this highly symptomatic patient collective. PATIENTS AND METHODS: 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. RESULTS: One hundred and seventeen mPC patients with ascites were included in this study. Median time from mPC to ascites diagnosis was 8.9 months (range 0-99 months) and median overall survival (OS) after ascites diagnosis was 27.4 days (range 21.3-42.6 days). Identified prognostic factors at ascites diagnosis independently associated with an impaired OS were presence of liver metastases [hazard ratio (HR): 2.07, 95% confidence interval (CI) 1.13-3.79, P = 0.018), peritoneal carcinomatosis (HR: 1.74, 95% CI 1.11-2.71, P = 0.015), and portal vein obstruction (HR: 2.52, 95% CI 1.29-4.90, P = 0.007). Compared with best supportive care, continuation of systemic therapy after ascites diagnosis was independently associated with survival (HR: 0.35, 95% CI 0.20-0.61, P < 0.001) with a median OS of 62 days (95% CI 51-129 days, P < 0.001) versus 16 days (95% CI 11-24 days), respectively. CONCLUSIONS: Liver and peritoneal metastases as well as portal vein obstruction 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 quality-of-life assessment.
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Neoplasias Hepáticas , Neoplasias Pancreáticas , Humanos , Estudios Retrospectivos , Ascitis/etiología , Ascitis/patología , Calidad de Vida , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológicoRESUMEN
BACKGROUND: Malignant ascites is common in metastatic pancreatic cancer (mPC) and its management still remains a clinical challenge. Early identification of patients at risk for ascites development may support and guide treatment decisions. MATERIALS AND METHODS: Data of patients treated for mPC at the Medical University of Vienna between 2010 and 2019 were collected by retrospective chart review. Ascites was defined as clinically relevant accumulation of intraperitoneal fluid diagnosed by ultrasound or computer tomography scan of the abdomen. We investigated the association between general risk factors, metastatic sites, liver function, systemic inflammation as well as portal vein obstruction (PVO) and ascites development. RESULTS: Among 581 patients with mPC included in this study, 122 (21.0%) developed ascites after a median of 8.7 months after diagnosis of metastatic disease. The occurrence of ascites led to an 8.9-fold increased risk of death [confidence interval (CI) 7.2-11, P < 0.001] with a median overall survival of 1 month thereafter. Clinical risk factors for ascites were male sex [hazard ratio (HR) 1.71, CI 1.00-2.90, P = 0.048], peritoneal carcinomatosis (HR 6.79, CI 4.09-11.3, P < 0.001), liver metastases (HR 2.16, CI 1.19-3.91, P = 0.011), an albumin-bilirubin (ALBI) score grade 3 (HR 6.79, CI 2.11-21.8, P = 0.001), PVO (HR 2.28, CI 1.15-4.52, P = 0.019), and an elevated C-reactive protein (CRP) (HR 4.19, CI 1.58-11.1, P = 0.004). CONCLUSIONS: Survival after diagnosis of ascites is very limited in mPC patients. Male sex, liver and peritoneal metastases, impaired liver function, PVO, as well as systemic inflammation were identified as independent risk factors for ascites development in this uniquely large real-life patient cohort.
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Ascitis , Neoplasias Pancreáticas , Humanos , Masculino , Femenino , Estudios Retrospectivos , Ascitis/etiología , Ascitis/epidemiología , Ascitis/patología , Factores de Riesgo , Inflamación/complicaciones , Neoplasias Pancreáticas/tratamiento farmacológicoRESUMEN
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.
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Monocitos , Neoplasias , Humanos , Monocitos/metabolismo , Macrófagos/metabolismo , Macrófagos/patología , Neoplasias/terapia , Inmunoterapia , Fenotipo , Microambiente TumoralRESUMEN
BACKGROUND: Following a European Society for Medical Oncology Women for Oncology (ESMO W4O) survey in 2016 showing severe under-representation of female oncologists in leadership roles, ESMO launched a series of initiatives to address obstacles to gender equity. A follow-up survey in October 2021 investigated progress achieved. MATERIALS AND METHODS: The W4O questionnaire 2021 expanded on the 2016 survey, with additional questions on the impact of ethnicity, sexual orientation and religion on career development. Results were analysed according to respondent gender and age. RESULTS: The survey sample was larger than in 2016 (n = 1473 versus 482), especially among men. Significantly fewer respondents had managerial or leadership roles than in 2016 (31.8% versus 51.7%). Lack of leadership development for women and unconscious bias were considered more important in 2021 than in 2016. In 2021, more people reported harassment in the workplace than in 2016 (50.3% versus 41.0%). In 2021, ethnicity, sexual orientation and religion were considered to have little or no impact on professional career opportunities, salary setting or related potential pay gap. However, gender had a significant or major impact on career development (25.5% of respondents), especially in respondents ≤40 years of age and women. As in 2016, highest ranked initiatives to foster workplace equity were promotion of work-life balance, development and leadership training and flexible working. Significantly more 2021 respondents (mainly women) supported the need for culture and gender equity education at work than in 2016. CONCLUSIONS: Gender remains a major barrier to career progression in oncology and, although some obstacles may have been reduced since 2016, we are a long way from closing the gender gap. Increased reporting of discrimination and inappropriate behaviour in the workplace is a major, priority concern. The W4O 2021 survey findings provide new evidence and highlight the areas for future ESMO interventions to support equity and diversity in oncology career development.
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Oncología Médica , Condiciones de Trabajo , Humanos , Masculino , Femenino , Factores Sexuales , Encuestas y CuestionariosRESUMEN
BACKGROUND: Gastroesophageal adenocarcinoma is a major contributor to global disease burden with poor prognosis even in resectable, regionally limited stages. Feasible prognostic tools are crucial to improve patient management, yet scarce. PATIENTS AND METHODS: Disease-related symptoms, patient, tumour, treatment as well as laboratory parameters at initial diagnosis and overall survival (OS) of patients with stage II and III gastroesophageal adenocarcinoma, who were treated between 1990 and 2020 at the Medical University of Vienna, were evaluated in a cross-validation model to develop a feasible risk prediction score. RESULTS: In total, 628 patients were included in this single-centre analysis. The final score ranked from 0 to 10 and included the factors sex (female +1), age, years (30-59 +1, >60 +2), underweight classified by body mass index (+2), location of the tumour (stomach +1), stage (III +2), stenosis in endoscopy (+1) and weight loss (+1). The score was grouped into low- (0-3), medium- (4-6) and high-risk (7+) subgroups. The median OS were 70.3 [95% confidence interval (CI) 51.2-111.8], 23.4 (95% CI 21.2-26.7) and 12.6 (7.0-16.1) months, respectively. The 1-year survival probabilities were 0.88 (95% CI 0.83-0.93), 0.75 (95% CI 0.70-0.79) and 0.54 (95% CI 0.39-0.74), whereas the 5-year survival probabilities were 0.57 (95% CI 0.49-0.66), 0.24 (95% CI 0.20-0.28) and 0.09 (95% CI 0.03-0.28), respectively. CONCLUSIONS: The VIennese risk prediction score for Oesophagogastric Localized Adenocarcinoma (VIOLA) risk prediction score poses a feasible tool for the estimation of OS in patients with regionally limited gastroesophageal adenocarcinoma and, thus, may improve patient management in clinical routine. Prospective analyses should be carried out to confirm our findings.
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Adenocarcinoma , Neoplasias Gástricas , Viola , Femenino , Humanos , Pronóstico , Estudios ProspectivosRESUMEN
BACKGROUND: Exploratory research showed that female oncologists are frequently under-represented in leadership roles. European Society for Medical Oncology (ESMO) Women for Oncology (W4O) therefore implemented gender equality programs in career development and established international studies on female representation at all stages of the oncology career pathway. METHODS: For 2017-2019, data were collected on (i) first and last authorship of publications in five major oncology journals and (ii) representation of women in leadership positions in oncology-as invited speakers at National/International congresses, board members or presidents of National/International societies and ESMO members. The 2015/2016 data from the first published W4O Study were incorporated for comparisons. RESULTS: Across 2017-2019, female oncologists were significantly more likely to be first than last authors (P < 0.001). The proportion of female first authors was similar across years: 38.0% in 2017, 37.1% in 2018, 41.0% in 2019 (P = 0.063). The proportion of female last authors decreased from 30.4% in 2017 to 24.2% in 2018 (P = 0.0018) and increased to 28.5% in 2019 (P = 0.018). Across 2015-2019, invited speakers at International/National oncology congresses were significantly less likely to be female than male (P < 0.001; 29.7% in 2015 to 36.8% in 2019). Across 2016-2019, board members of International/National oncology societies were significantly less likely to be female than male (P < 0.001; 26.8% in 2016 to 35.8% in 2019). There were statistically significant increasing trends in female speakers and board members across the study periods (P < 0.001 for both). Societies with a female president had a higher proportion of female board members across these periods (P = 0.026). CONCLUSIONS: Reported progress towards gender equality in career development in oncology is real but slow. Women in leadership positions are essential for encouraging young women to aspire to and work towards similar or greater success. Therefore, continued monitoring is needed to inform ESMO W4O initiatives to promote gender balance at all stages of the career pathway.
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Liderazgo , Oncólogos , Autoria , Femenino , Humanos , Masculino , Oncología Médica , Sociedades MédicasRESUMEN
BACKGROUND: Brain metastases (BM) are a rare complication in colorectal cancer (CRC) patients and associated with an unfavorable survival prognosis. Primary tumor side (PTS) was shown to act as a prognostic and predictive biomarker in several trials including metastatic CRC (mCRC) patients. Here, we aim to investigate whether PTS is also associated with the outcome of CRC patients with BM. METHODS: Patients treated for CRC BM between 1988 and 2017 at an academic care center were included. Right-sided CRC was defined as located in the appendix, cecum and ascending colon and left-sided CRC was defined as located in the descending colon, sigma and rectum. RESULTS: Two hundred and eighty-one CRC BM patients were available for this analysis with 239/281 patients (85.1%) presenting with a left-sided and 42/281 patients (14.9%) with a right-sided primary CRC. BM-free survival (BMFS) was significantly longer in left-sided compared with right-sided CRC patients (33 versus 20 months, P = 0.009). Overall survival from CRC diagnosis as well as from diagnosis of BM was significantly longer in patients with a left-sided primary (42 versus 25 months, P = 0.002 and 5 versus 4 months, P = 0.005, respectively). In a multivariate analysis including graded prognostic assessment, PTS remained significantly associated with prognosis after BM (hazard ratio 0.65; 95% confidence interval: 0.46-0.92 months, P = 0.0016). CONCLUSIONS: PTS was associated with survival times after the rare event of BM development in CRC patients. Therefore, its prognostic value remains significant even thereafter.
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Neoplasias Encefálicas , Neoplasias del Colon , Neoplasias Colorrectales , Humanos , Pronóstico , Modelos de Riesgos ProporcionalesRESUMEN
BACKGROUND: European Society for Medical Oncology Women for Oncology (ESMO W4O) research has previously shown under-representation of female oncologists in leadership roles. As early reports suggested disproportionate effects of the COVID-19 pandemic on women, the ESMO W4O Committee initiated a study on the impact of the pandemic on the lives of female and male oncologists. METHODS: A questionnaire was sent to ESMO members and put on the ESMO website between 8 June 2020 and 2 July 2020. Questions focused on the working (hospital tasks, laboratory tasks, science) and home (household management, childcare, parent care, personal care) lives of oncologists during and after COVID-19-related lockdowns. RESULTS: Of 649 respondents, 541 completed the questionnaire. Of these, 58% reported that COVID-19 had affected their professional career, 83% of whom said this was in a negative way (85% of women versus 76% of men). Approximately 86% reported that COVID-19 had changed their personal life and 82% their family life. Women were again significantly more affected than men: personal life (89% versus 78%; P = 0.001); family life (84% versus 77%; P = 0.037). During lockdowns, women reported increased time spent on hospital and laboratory tasks compared with men (53% versus 46% and 33% versus 26%, respectively) and a significantly higher proportion of women than men spent less time on science (39% versus 25%) and personal care (58% versus 39%). After confinement, this trend remained for science (42% versus 23%) and personal care (55% versus 36%). CONCLUSIONS: The COVID-19 pandemic has adversely affected the professional and home lives of oncologists, especially women. Reduced research time for female oncologists may have long-lasting career consequences, especially for those at key stages in their career. The gender gap for promotion to leadership positions may widen further as a result of the pandemic.
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COVID-19 , Adulto , Control de Enfermedades Transmisibles , Femenino , Humanos , Masculino , Oncología Médica , Persona de Mediana Edad , Oncólogos , Pandemias , SARS-CoV-2 , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: Tumor mutational burden (TMB) and density of tumor-infiltrating lymphocytes (TIL) have been postulated as predictive biomarkers for immunotherapy. Therefore, we investigated the concordance of TMB and TIL of primary/extracranial renal cell carcinoma (RCC) specimens and matched brain metastases (BM). PATIENTS AND METHODS: Twenty specimens from 10 patients were retrieved from the Vienna Brain Metastasis Registry (6/10 primary tumor, 4/10 lung metastasis, 10/10 matched BM). TMB was assessed using the TruSight Oncology 500 gene panel with libraries sequenced on a NextSeq instrument. TIL subsets (CD3+, CD8+, CD45RO+, FOXP3+, PD-L1+) were investigated using immunohistochemistry (Ventana Benchmark Ultra system) and automated tissue analysis (Definiens software). RESULTS: No significant difference in TMB, CD3+, CD8+, CD45RO+, FOXP3+ or PD-L1+ expression was observed between extracranial and matched intracranial specimens (P > 0.05). Higher CD8+ TIL (P = 0.053) and CD45RO+ TIL (P = 0.030) densities in the primary tumor compared with the intracranial samples were observed in specimens collected after exposure to systemic treatment. Neither extracranial sample origin (lung metastasis versus primary RCC) nor extracranial disease status at BM diagnosis (progressive versus stable disease) were significantly associated with TMB or TIL densities in extracranial and intracranial samples (P > 0.05). No significant correlation was found between the median differences of TMB or TIL densities from extracranial to intracranial samples and BM-free survival. CONCLUSION: The comparable immunological microenvironment of extra- and intracranial tumor samples in our study underscores the immunological activation also in BM from RCC, and therefore, supports the development of immune modulatory treatments also in patients with brain metastatic RCC.
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Neoplasias Encefálicas , Carcinoma de Células Renales , Neoplasias Renales , Biomarcadores de Tumor , Neoplasias Encefálicas/genética , Humanos , Linfocitos Infiltrantes de Tumor , Microambiente TumoralRESUMEN
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.
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Neoplasias/terapia , Femenino , Objetivos , Humanos , Masculino , Persona de Mediana Edad , Percepción , Estudios ProspectivosRESUMEN
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.
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Neoplasias Gástricas/sangre , Tiroxina/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias Gástricas/mortalidad , Análisis de SupervivenciaRESUMEN
Symptomatic brain metastases (BM) are a frequent and late complication in cancer patients. However, a subgroup of cancer patients presents with BM as the first symptom of metastatic cancer. Here we aimed to analyze the clinical course and prognostic factors of this particular BM patient population. Patients presenting with newly diagnosed BM without a history of metastatic cancer were identified from the Vienna Brain Metastasis Registry. Clinical characteristics and overall survival were retrieved by chart review. 459/2419 (19.0%) BM patients presented with BM as first symptom of advanced cancer. In 374/459 (81.5%) patients, an extracranial primary tumor, most commonly lung cancer, could be identified within 3 months after BM diagnosis. In 85/459 (18.5%) patients no extracranial primary tumor could be identified despite comprehensive diagnostic workup within the first 3 months after diagnosis of BM. Survival of patients with identified extracranial tumor differed only numerically from patients with cancer of unknown primary (CUP), however patients receiving targeted therapy after molecular workup showed significantly enhanced survival (20 months vs. 7 months; p = 0.003; log rank test). The GPA score showed a statistically significant association with median overall survival times in the CUP BM patients (class I: 46 months; class II: 7 months; class III: 4 months; class IV: 2 months; p < 0.001; log rank test). The GPA score has a strong prognostic value in patients with CUP BM and may be useful for patient stratification in the clinical setting. Comprehensive diagnostic workup including advanced imaging techniques and molecular tissue analyses appears to benefit patients by directing specific molecular targeted therapies.
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Neoplasias Encefálicas/secundario , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida , Pronóstico , Estudios Retrospectivos , Centros de Atención TerciariaRESUMEN
Ovarian cancer represents the most common gynaecological malignancy and has the highest mortality of all female reproductive cancers. It has a rare predilection to develop brain metastases (BM). In this study, we evaluated the mutational profile of ovarian cancer metastases through Next-Generation Sequencing (NGS) with the aim of identifying potential clinically actionable genetic alterations with options for small molecule targeted therapy. Library preparation was conducted using Illumina TruSight Rapid Capture Kit in combination with a cancer specific enrichment kit covering 94 genes. BRCA-mutations were confirmed by using TruSeq Custom Amplicon Low Input Kit in combination with a custom-designed BRCA gene panel. In our cohort all eight sequenced BM samples exhibited a multitude of variant alterations, each with unique molecular profiles. The 37 identified variants were distributed over 22 cancer-related genes (23.4%). The number of mutated genes per sample ranged from 3 to 7 with a median of 4.5. The most commonly altered genes were BRCA1/2, TP53, and ATM. In total, 7 out of 8 samples revealed either a BRCA1 or a BRCA2 pathogenic mutation. Furthermore, all eight BM samples showed mutations in at least one DNA repair gene. Our NGS study of BM of ovarian carcinoma revealed a significant number of BRCA-mutations beside TP53, ATM and CHEK2 mutations. These findings strongly suggest the implication of BRCA and DNA repair malfunction in ovarian cancer metastasizing to the brain. Based on these findings, pharmacological PARP inhibition could be one potential targeted therapeutic for brain metastatic ovarian cancer patients.
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Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundario , Mutación , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Adulto , Anciano , Proteínas de la Ataxia Telangiectasia Mutada/genética , Proteína BRCA1/genética , Proteína BRCA2/genética , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/tratamiento farmacológico , Estudios Retrospectivos , Proteína p53 Supresora de Tumor/genéticaRESUMEN
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.
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Neoplasias Encefálicas/secundario , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Neoplasias Pulmonares/mortalidad , Sobrepeso/epidemiología , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Delgadez/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Carcinoma de Pulmón de Células no Pequeñas/secundario , Comorbilidad , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Carcinoma Pulmonar de Células Pequeñas/secundario , Tasa de SupervivenciaRESUMEN
Colorectal brain metastases (BM) are rare (1-2%) and a late-stage disease manifestation. Molecular mechanisms for BM development are not well understood. We tested whether variants within genes involved in overcoming the blood-brain barrier (BBB) are associated with BM susceptibility and survival in patients with BM. Germline single-nucleotide polymorphisms (SNPs, n=17) in seven genes (CXCR4, MMP9, ST6GALNAC5, ITGAV, ITGB1, ITGB3, KLF4) were analyzed from germline DNA in patients with resected BM (n=70) or no clinical evidence of BM after at least 24 months from diagnosis (control group, n=45). SNPs were evaluated for association with BM susceptibility and overall survival (OS) from BM diagnosis. ST6GALNAC5 rs17368584 and ITGB3 rs3809865 were significantly associated with BM susceptibility. In multivariable analysis adjusted for patient characteristics, KLF4 rs2236599, ITGAV rs10171481, ST6GALNAC5 rs1883778, CXCR4 rs2680880 and ITGB3 rs5918 were significant for OS. This study shows for the first time that variants within genes involved in breaching the BBB are associated with BM susceptibility and survival. These findings warrant further validation to develop better screening guidelines and to identify novel therapy targets for patients with BM.
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Biomarcadores de Tumor/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundario , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Barrera Hematoencefálica/patología , Neoplasias Encefálicas/mortalidad , Distribución de Chi-Cuadrado , Neoplasias Colorrectales/mortalidad , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Heterocigoto , Homocigoto , Humanos , Estimación de Kaplan-Meier , Factor 4 Similar a Kruppel , Masculino , Persona de Mediana Edad , Análisis Multivariante , Fenotipo , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Factores de TiempoRESUMEN
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.
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Neoplasias Encefálicas/secundario , Neoplasias de la Mama/clasificación , Receptor ErbB-2/metabolismo , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Pronóstico , Estudios RetrospectivosRESUMEN
The comprehensive assessment of symptoms is the basis for effective, individualised palliative treatment. Established scoring systems provide in-depth information but are often lengthy and hence unsuitable. We introduce the PERS(2) ON score as a short and practically feasible score to evaluate symptom burden. Fifty patients admitted to a Palliative Care Unit rated seven items, i.e. pain, eating (loss of appetite/weight loss), rehabilitation (physical impairment), social situation (possibility for home care), suffering (anxiety/burden of disease/depression), O2 (dyspnoea) and nausea/emesis, on a scale ranging from 0 (absence) to 10 (worst imaginable), resulting in a score ranging from 0 to 70. Assessments were performed at admission, 7 days after admission and at the day of discharge. Symptom intensity scores were calculated, and change over time was evaluated. A significant improvement was observed from the PERS²ON score between admission and 7 days (P < 0.001; paired t-test). Significant improvement from baseline evaluation to evaluation on the day of discharge was observed (P = 0.001; paired t-test). This study provides initial evidence that the PERS²ON score is both feasible and sensitive to changes of the most prominent symptoms in palliative care. It may be useful in clinical practice to direct palliative treatment strategies and provide targeted symptom management.