Thalidomide for the Management of Gastrointestinal Bleeding in a Palliative Care Setting.

BACKGROUND: Palliative care patients frequently present with clinically significant gastrointestinal bleeding. Due to the existence of confounding comorbidities and a remarkably reduced state of general health in many cases, the management of gastrointestinal bleeding in this population is often challenging. SUMMARY: This review summarizes and discusses the role of thalidomide in gastrointestinal bleeding with a special focus on palliative care patients. In addition, an illustrative case report is presented. Thalidomide may be beneficial in gastrointestinal bleeding by exerting antiangiogenic effects. The drug has an acceptable safety profile. Side effects like neurotoxicity may limit its use but can be monitored safely. Due to thalidomide's thrombin generation potential, patients managed with thalidomide-containing regimes should be closely monitored for deep venous thrombosis. Given its teratogenicity, thalidomide should not be administered to women of childbearing potential who are not using adequate contraception. KEY MESSAGE: Physicians caring for patients in a palliative care setting should be aware of thalidomide as an effective therapeutic option when endoscopy fails to find a bleeding source or for those patients who cannot or refuse to undergo endoscopy but present with recurrent or obscure gastrointestinal bleeding.

Risk as a pattern over time: Delineation of time-dependent risk factors in biological, psychological, and social variables in cancer patients.

BACKGROUND: Survival in cancer patients is associated with a multitude of biological, social, and psychological factors. Although it is well established that all these factors add to overall mortality, it is not well understood how the predictive power of these parameters changes in a comprehensive model and over time. METHODS: Patients who attended the authors' outpatient clinic were invited to participate. The authors followed 5180 mixed cancer patients (51.1% female; mean age, 59.1 years [SD = 13.8]) for up to 16 years and analyzed biological (age, sex, cancer site, anemia), psychological (anxiety, depression), and social variables (marital status, education, employment status) potentially predicting overall survival in a Cox proportional hazards model. RESULTS: The median survival time for the entire sample was 4.3 years (95% confidence interval, 4.0-4.7). The overall survival probabilities for 1 and 10 years were 76.8% and 38.0%, respectively. Following an empirical approach, the authors split the time interval into five periods: acute, subacute, short-term, medium-term, and long-term. A complex pattern of variables predicted overall survival differently in the five periods. Biological parameters were important throughout most of the time, social parameters were either time-independent predictors or tended to be more important in the longer term. Of the psychological parameters, only depression was a significant predictor and lost its predictive power in the long-term. CONCLUSIONS: The findings of this study allow the development of comprehensive patient-specific models of risk and resilience factors addressing biopsychosocial needs of cancer patients, paving the way for a personalized treatment plan that goes beyond biomedical cancer care.

The impact of COVID-19 on cancer care of outpatients with low socioeconomic status.

Patients with low socioeconomic status (SES) are among the most underserved groups of people regarding cancer care. Analyzing the impact of the coronavirus-induced disease 2019 (COVID-19) pandemic on health care disparities and calling attention to inequalities in cancer care is crucial to justify and initiate adequate countermeasures. We aimed to determine whether the COVID-19 pandemic aggravated health care disparities of cancer outpatients related to their SES and analyzed patient data of the largest university center providing services for patients with hematologic and oncologic disorders in Austria from 2018 to 2021. SES was assessed using three indicators: monthly net household income, level of education and occupational prestige. In total, 1217 cancer outpatients (51.1% female) with a mean age of 59.4 years (SD = 14.2) participated. In the first year of the pandemic, the relative proportion of individuals with low income, low education level and low occupational prestige seeking cancer care at our outpatient center decreased significantly (P ≤ .015). The strongest indicator was income, with a consistent effect throughout the first pandemic year. Countermeasures and specific interventions to support cancer patients with low SES in their access to health care should be initiated and prioritized.

C-reactive protein and white blood cell count are adverse prognostic markers for patients with advanced cancer on parenteral nutrition in a palliative care unit setting: A retrospective cohort study.

BACKGROUND: Parenteral nutrition is controversial in patients with advanced cancer. Nevertheless, this treatment is common practice near the end of life. AIM: We aimed to identify factors which were associated with the outcome of patients on parenteral nutrition at an academic tertiary palliative care unit. DESIGN: In this retrospective cohort study patients were assigned to two groups according to parenteral nutrition treatment. Inferential statistics were used to assess whether the dynamics of laboratory variables over 2 weeks of parenteral nutrition were associated with survival. SETTING/PARTICIPANTS: Patients admitted to the Department of Palliative Medicine at the Medical University of Vienna between 2016 and 2018 were included in this study. RESULTS: Of 443 patients, 113 patients received parenteral nutrition. Patients had a lower body mass index, lower levels of bilirubin, γ-glutamyltransferase, alkaline phosphatase, and were of younger age compared to patients which did not receive parenteral nutrition. No difference in survival as measured from admission to death was found when comparing the two groups. Levels for γ-glutamyltransferase, alkaline phosphatase, and C-reactive protein significantly increased during 2 weeks of parenteral nutrition. Among patients with parenteral nutrition, an increase in C-reactive protein or white blood cell count levels was associated with lower survival. CONCLUSION: Patients who responded with an increase of C-reactive protein or white blood cell count during 2 weeks after reinitiation or start of parenteral nutrition had a worse survival. Our findings might support clinicians and patients in their decision to forgo parenteral nutrition in a palliative care setting.

A higher ctDNA fraction decreases survival in regorafenib-treated metastatic colorectal cancer patients. Results from the regorafenib's liquid biopsy translational biomarker phase II pilot study.

The predictive effect of circulating tumor DNA (ctDNA) in colorectal cancer (CRC) treatment is still highly discussed. The primary objective of our study was to investigate a possible prognostic/predictive value of ctDNA under regorafenib treatment. This prospective multicenter translational biomarker phase II pilot study enrolled 30 metastatic CRC patients (67% men, 33% women) treated with regorafenib. ctDNA was assessed in plasma before treatment start and at defined time points during administration. Measurement of tumor fraction as well as mutation and copy number analysis of CRC driver genes were performed by next-generation sequencing approaches. Multivariate analyses for survival and treatment efficacy were adjusted to age, gender and Eastern Cooperative Oncology Group. Disease control rate was 30%. Median tumor fraction at baseline was 18.5% (0-49.9). Mutations in CRC driver genes or genes involved in angiogenesis were identified in 25 patients (83.3%). KRAS mutations were detected in 13 of 14 KRAS-positive tumors; in three patients without KRAS mutation in the respective tumors, acquired mutations as a consequence of prior anti-EGFR treatment were detected. In a subset of patients, novel occurring mutations or focal amplifications were detected. A tumor fraction of 5% and higher at baseline was significantly associated with a decreased OS (P = .022; hazard ratio 3.110 (95% confidence interval: 1.2-8.2). ctDNA is detectable in a high proportion of mCRC patients. Higher ctDNA levels are associated with survival among regorafenib treatment. Moreover, our data highlight the benefit of a combined evaluation of mutations and somatic copy number alterations in advanced cancer patients.

Prevalence of pain and its association with symptoms of post-traumatic stress disorder, depression, anxiety and distress in 846 cancer patients: A cross sectional study.

OBJECTIVE: Pain depicts a severe physical symptom but its relationship to mental health problems is not well studied in cancer patients. The aim of this study was to investigate the prevalence of pain and its correlation with symptoms of post-traumatic stress disorder (PTSD), depression, anxiety and psychological distress in a large sample of cancer patients. METHODS: From 2010 to 2019, cancer patients who received outpatient treatment at the Medical University of Vienna were assessed with the Post-Traumatic Symptom Scale (PTSS-10) and the Hospital Anxiety and Depression Scales. A visual analogue scale was used to assess pain perception. For statistical analysis, linear regression models were applied to log-transformed data. RESULTS: Of the 846 cancer patients included in the study, 63.5% experienced pain (mild 43.5%, moderate 13.6%, severe 6.4%). About a third (31.2%) of the total sample presented with significant PTSD symptoms. Significant symptoms of depression, anxiety and distress were present in 13.9%, 15.1% and 25.3%, respectively. Women more often reported symptoms of PTSD, anxiety and distress. Pain scores were significantly related to symptoms of PTSD, depression and psychological distress (all with p < .001), but not to anxiety. CONCLUSIONS: Results show a high prevalence of experienced pain and indicate a clear association of elevated pain levels with psychiatric symptoms in oncological patients in a large Austrian sample. In order to decrease experienced pain and to enable better treatment of mental health problems in cancer patients, diagnostic procedures and interventions based on a biopsychosocial model need to be intensified.

Screening for post-traumatic stress disorders in 1017 cancer patients and correlation with anxiety, depression, and distress.

OBJECTIVE: Post-traumatic stress disorder (PTSD) is a severe psychiatric disorder, which might develop after a traumatic event, like cancer diagnosis, and threatens the patient's psychological and/or physiological integrity. Anxiety, depression, and mental distress are known to be common in cancer patients; however, the frequency of PTSD was not investigated thoroughly in this patient group so far. Here, we aim to screen cancer patients for PTSD symptoms and determine a possible correlation with anxiety, depression, and distress. METHODS: The study was performed at the Divisions of Hematology and Oncology of the Medical University of Vienna from 2010 to 2018. Following written consent, patients were asked to fill out the validated self-assessment questionnaire for PTSS-10 and HADS. The study was approved by the institutional ethics committee of the Medical University of Vienna (EC Nr: 2255/2016). RESULTS: A total of 1017 adult cancer patients (513 male, 504 female) were included in a cross-sectional single-center study. Mean age was 57.6 years (SD 14.4 years); 31.7%, 14.6%, 13.2%, and 27.4% of patients outscored the predefined thresholds for self-assessed cases of PTSD, anxiety, depression, and distress, respectively. Compared with men, women showed a higher prevalence of symptoms for PTSD (38.9% vs 24.5%; P < .001) and anxiety (20.4% vs 8.6%; P < .001). The scores of HADS-A, HADS-D, and the combined HADS score (distress) were significantly correlated with PTSS-10 scores (P < .01). No differences in age were observed among the different score groups. CONCLUSION: The study shows a significant prevalence as well as a correlation of PTSD symptoms with anxiety, depression, and distress among cancer patients. Findings underscore the necessity of a serious screening for psychiatric disorders, especially in female patients. In order to enable multidisciplinary care for cancer patients and to reduce the burden for psychiatric disorders, interdisciplinary screening and treatment concepts, which take into account gender aspects, are urged.

Patients' attitude and knowledge towards resuscitation and advance care planning at the palliative care unit.

OBJECTIVE: There is a lack of information about patients' attitudes towards and knowledge of resuscitation and advance care planning (ACP) in the palliative care unit (PCU). The aims of this study were to examine (a) patients' attitudes towards and knowledge of the topic of resuscitation, (b) patients' level of education about their illness and (c) their concept of ACP. METHODS: This study used a qualitative methodology that involved semi-structured interviews with advanced cancer patients admitted to the PCU. Interviews were conducted during the first week after admission, recorded digitally and transcribed verbatim. Data were analysed through content analysis using NVivo 12. RESULTS: Eighteen interviews revealed the following themes: (a) ambivalence regarding preference for or refusal of resuscitation, (b) patient confidence concerning their level of education, (c) lack of information about ACP and (d) positive perception of the stay in the PCU. The data showed that a high percentage of PCU patients desired resuscitation even though education about their illness was mostly perceived as good. Many patients did not receive information about ACP. Patients perceived the stay in the PCU positively. CONCLUSION: The study results reveal that there is lack of knowledge about ACP and resuscitation in patients in the PCU.

Analysis of 10 Adrenocortical Carcinoma Patients in the Cohort of the Precision Medicine Platform MONDTI.

OBJECTIVE: Adrenocortical carcinoma (ACC) is a rare disease with a dismal prognosis. We aimed to evaluate if a personalized medicine approach may be useful for matching patients with ACC to targeted therapies. METHODS: This is an analysis of 10 molecularly profiled ACCs that were progressing under standard of care treatment. The profile consisted of a 50-gene next-generation sequencing panel, immunohistochemistry (IHC), and fluorescence in situ hybridization for several proteins or chromosomal aberrations. RESULTS: In 6 (60%) tumor samples, no somatic mutation was detected, while in 3 (30%) tumors 1 mutation was detected and in 1 (10%) tumor 2 mutations were detected. These mutations were CTNNB1 (2 samples), TP53 (1 sample), RB1 (1 sample) and APC (1 sample). Expression of phospho-mTOR and of EGFR was commonly detected by IHC (87.5 and 62.5%). In 4 (50%) samples, IHC revealed a weak expression of progesterone receptor. Less frequent alterations were expression of PDGFR-α, c-KIT, and estrogen receptor, each in 1 case. CONCLUSIONS: Based on the molecular profile, no recommendation for targeted therapy was made by the multi-disciplinary team. Currently, ACC might not be suitable for a precision medicine approach according to our tests.

Vitamin "G"arden: a qualitative study exploring perception/s of horticultural therapy on a palliative care ward.

PURPOSE: In a palliative care setting, the preservation of quality of life is of particular importance. Horticultural therapy (HT) is reported as an excellent way to improve physical as well as psychological well-being, reduce levels of anxiety and depression, and promote social interaction. The use of horticultural interventions in palliative care has not yet been explored. The aim of this study was to explore the effects of HT in patients and team members on a palliative care ward. METHODS: This study was based on a qualitative methodology, comprising 20 semistructured interviews with 15 advanced cancer patients participating in HT and with 5 members of the palliative care team. Interviews were analyzed using NVivo 10 software based on thematic analysis. RESULTS: The results revealed the following themes: (1) well-being, (2) variation of clinical routine, (3) creation, and (4) building relationships. Patients experienced positive stimulation through HT, were distracted from daily clinical routines, enjoyed creative work, and were able to build relationships with other patients. HT was also welcomed by the members of the palliative care team. Thirty-six percent of the patients did not meet the inclusion criteria, and 45% could not participate in the second or third HT session. CONCLUSIONS: Our study showed that the availability of HT was highly appreciated by the patients as well as by the palliative care team. Nevertheless, the dropout rate was high, and therefore, it might be more feasible to integrate green spaces into palliative care wards.

Feasibility of personalized treatment concepts in gastrointestinal malignancies: Sub-group results of prospective clinical phase II trial EXACT.

OBJECTIVE: Advances in high-throughput genomic profiling and the development of new targeted therapies improve patient's survival. In gastrointestinal (GI) malignancies, the concept of personalized medicine (PM) was not investigated so far. The aim of this prospective study was to evaluate the efficacy of a personalized treatment in GI patients who failed standard treatment. METHODS: Out of the original prospective clinical phase II EXACT trial, 21 (38%) GI cancer patients who had no further treatment options were identified. A molecular profile (MP) via a 50 gene next generation sequencing (NGS) panel in combination with immunohistochemistry (IHC) was conducted using real-time biopsy tumor material. Results were discussed by a multidisciplinary team (MDT) to translate the individual MP in an experimental treatment. RESULTS: Of the 55 patients originally included in the EXACT trial, 21 (38%) suffered from GI malignancies. The final analysis showed that 15 (71%) patients had experienced a longer progression-free survival (PFS) upon experimental targeted treatment (124 d, quartiles 70/193 d), when compared with the PFS achieved by the previous conventional therapy (62 d, quartiles 55/83 d) (P=0.014). Thirteen (62%) patients receiving targeted treatment experienced a disease control according to Response Evaluation Criteria in Solid Tumors (RECIST). Median overall survival (OS) from the start of experimental therapy to time of censoring or death was 193 d (quartiles 115/374 d). CONCLUSIONS: PM was not investigated in GI malignancies so far in a prospective trial. This study shows that treatment based on real-time molecular tumor profiling led to a superior clinical benefit, and survival as well as response was significantly improved when compared with previous standard medications.

Effects of cilengitide in osteoclast maturation and behavior.

Bone metastasis is a common burden in many types of cancer and has a severe impact on the quality of life in patients. Hence, specific therapeutic strategies inhibiting tumor induced osteolysis are urgently needed. In this study, we aimed to interfere with integrin adhesion receptors, which are central players of the bone resorption process. For this purpose, we used cilengitide, a cyclic RGD peptide, which blocks integrin αVß3 and αVß5-ligand binding. Our results revealed that cilengitide blocked osteoclast maturation in a dose-dependent manner. In detail, pre-osteoclasts treated with cilengitide exhibited reduced cell spreading, cell migration and cell adhesion on RGD-containing matrix proteins, which are ligands of integrin αV. The activation of the most upstream signal transduction molecules of the integrin receptor-initiated pathway, FAK and c-Src, were consistently blocked by cilengitide. First evidence suggests that cilengitide might interfere with metastatic bone disease in vivo and this study describes a potential underlying mechanism of the inhibitory effect of cilengitide on αV-integrin expressing pre-osteoclasts by blocking integrin ligand binding and interfering with osteoclast maturation and cell behavior. In conclusion, our findings suggest that cilengitide, which interferes with αV-integrins on osteoclasts, may represent a novel therapeutic strategy in the treatment of malignant bone disease.

Integrins in the Spotlight of Cancer.

Integrins are heterodimeric cell surface receptors that bind to different extracellular ligands depending on their composition and regulate all processes which enable multicellular life. In cancer, integrins trigger and play key roles in all the features that were once described as the Hallmarks of Cancer. In this review, we will discuss the contribution of integrins to these hallmarks, including uncontrolled and limitless proliferation, invasion of tumor cells, promotion of tumor angiogenesis and evasion of apoptosis and resistance to growth suppressors, by highlighting the latest findings. Further on, given the paramount role of integrins in cancer, we will present novel strategies for integrin inhibition that are starting to emerge, promising a hopeful future regarding cancer treatment.

In vivo Tube Assay: An Optimised Protocol of the Directed in vivo Angiogenesis Assay by Implementing Immunohistochemistry.

BACKGROUND: Angiogenesis, the formation of new blood vessels, is an essential process under physiological and pathological conditions. METHOD: Here, we improved the directed in vivo angiogenesis assay (DIVAA®) test, which is based on the usage of small Matrigel-filled tubes that are implanted into mice subcutaneously for a period of up to 15 days. The subsequent ex vivo assessment of neoangiogenesis within the silicon tubes is then achieved by fluorometry. RESULTS: We showed that the immunohistochemical quantification of the ingrowth of endothelial cells, based on CD31, was superior to the fluorometric quantification advised in the manufacturer's instructions. We optimised the explantation procedure, ensuring the complete recovery of the ingrown vessels. Using this modified protocol, we investigated the effect of the length of stay of the implanted tubes as well as of the concentration of the growth factors VEGF and FGF on the assay. CONCLUSION: Our improved protocol offered an effective and reliable alternative to the original assay, which is expected to facilitate in vivo research on angiogenesis and, thus, might drive the development of novel therapeutic agents.

Baseline carcinoembryonic antigen (CEA) serum levels predict bevacizumab-based treatment response in metastatic colorectal cancer.

Carcinoembryonic antigen (CEA) affects tumorigenesis by enhancing tumor cell survival and by inducing tumor angiogenesis. This study aimed to evaluate baseline CEA serum levels to predict bevacizumab-based therapy effect and survival in patients with metastatic colorectal cancer (mCRC). Two hundred and ninety eight mCRC patients receiving chemotherapy plus either bevacizumab or cetuximab were analyzed in a retrospective study. Disease control (DC), progression-free survival (PFS), and overall survival were assessed and related to pretreatment CEA serum levels. Patients with baseline CEA serum levels below the statistical median of 26.8 ng/mL (group I) were compared with patients with higher CEA levels (group II). The cetuximab-based treatment cohort was analyzed for specificity assessment of CEA to predict the anti-vascular endothelial growth factor effect in mCRC. Baseline CEA serum levels inversely correlated with therapeutic response in patients receiving bevacizumab-based treatment (disease control rate, 84% vs 60%), inversely correlated with median PFS leading to a median PFS benefit of 2.1 months for patients in group I when compared with group II, as well as inversely correlated with median overall survival (37.5 months vs 21.4 months). In an independent cohort of 129 patients treated with cetuximab-based therapy, no association of therapeutic response or PFS with CEA serum levels was found. As expected, baseline CEA levels were prognostic for mCRC. These data give first evidence that baseline serum CEA levels might constitute an important predictor for the efficacy of first-line bevacizumab-based therapy in patients with mCRC.

On dying alone in prison and the social responsibility of medicine: a pilot interview study of physicians caring for terminally ill incarcerated patients in Austria and the United States.

BACKGROUND: This group of physicians is difficult to reach and small in number. While studies of palliative care and end-of-life (EOL) issues in prison have increased, especially in the United States and since the coronavirus disease 2019 (COVID-19) pandemic, they are still limited due to the constraints of carrying out research in carceral contexts. At present, there is very little knowledge of the experiences of physicians providing EOL care in prisons. The aim of this pilot study was to examine the experiences of doctors caring for terminally ill patients inside prisons. METHODS: Three expert qualitative interviews were conducted in March and April 2021 with physicians working in carceral institutions in New York State and Austria. The interviews were audio-recorded and transcribed verbatim. Braun and Clarke's thematic analysis was used to examine the data. RESULTS: The following five themes were found: (I) a lack of training and support; (II) interrupted relationships; (III) limitations on visits and saying one's goodbyes; (IV) security as a main concern; and (V) the possibility of release. CONCLUSIONS: The study reveals the difficulties physicians face when caring for dying incarcerated patients. Provider-patient relationships are hardly continuous. The findings represent a starting point for further research. Support from the medical and palliative care community is needed for adequate provision of EOL care within prisons, improved post-release conditions, and help for physicians working in existing structures.

Prevalence and biopsychosocial indicators of fatigue in cancer patients.

INTRODUCTION: Symptoms of cancer-related fatigue (CRF) can have a significant impact on patients' quality of life and treatment adherence. We aimed to investigate the relationship between CRF and multiple psychosocial and somatic indicators within a large mixed cancer sample. METHODS: In this cross-sectional study, N = 1787 outpatients with cancer were assessed for CRF, pain, anxiety, and depression using validated screening instruments. We further obtained clinical parameters (Hb, CRP, creatinine, leukocytes, ASAT, and ALAT), sociodemographic data (age, gender, income, education level, marital status, parenthood, and living area), and lifestyle factors. Multivariate linear regression models were applied to estimate the impact of each indicator on CRF. RESULTS: Overall, 90.6% of patients experienced some CRF, with 14.8% experiencing severe CRF. No gender difference was found in the prevalence of CRF. Patients with higher levels of pain, depressive symptoms, and lower Hb levels had significantly higher levels of CRF (ps <0.001). Lower levels of CRF were observed in patients who had children (p = 0.03), had less education (p < 0.001), and were physically active for more than 2 h per week before their oncological diagnosis (p = 0.014). The latter was only a significant indicator in the male subsample. CONCLUSION: The present results demonstrate a high prevalence of CRF and highlight that not only somatic and psychosocial factors, but also lifestyle factors prior to diagnosis appear to be associated with the etiology and persistence of CRF. To effectively treat CRF, a biopsychosocial, personalized approach is recommended.

CD98hc (SLC3A2) drives integrin-dependent renal cancer cell behavior.

BACKGROUND: Overexpression of CD98hc (SLC3A2) occurs in a variety of cancers and is suspected to contribute to tumor growth. CD98, a heterodimeric transmembrane protein, physically associates with certain integrin ß subunit cytoplasmic domains via its heavy chain, CD98hc. CD98hc regulates adhesion-induced intracellular signal transduction via integrins, thereby, affecting cell proliferation and clonal expansion. Disruption of CD98hc led to embryonic lethality in mice (E 3.5 and E 9.5) and CD98hc -/- embryonic stem cell transplantation failed to form teratomas, while CD98hc over-expression in somatic cells resulted in anchorage-independent growth. However, it is unclear whether interference with CD98hc expression tumor cell behavior. METHODS: Renal cell cancer cell lines have been used to determine the effect of CD98hc expression on cancer cell behavior using cell adhesion, cell trans-migration and cell spreading assays. Flow cytometric analysis was performed to study the rate of apoptosis after detachment or serum starvation. shRNA-lentiviral constructs were used to stably knockdown or reconstitute full length or mutated CD98hc. The role of CD98 as a promotor of tumorigenesis was evaluated using an in in vivo tumor transplantation animal model. Immunohistochemical analysis was performed to analyze cell proliferation and CD98 expression in tumors. RESULTS: This report shows that CD98hc silencing in clear cell renal cancer cells reverts certain characteristics of tumorigenesis, including cell spreading, migration, proliferation and survival in vitro, and tumor growth in vivo. Acquisition of tumorigenic characteristics in clear cell renal cancer cells occurred through the integrin binding domain of CD98hc. A CD98hc/integrin interaction was required for adhesion-induced sustained FAK phosphorylation and activation of the major downstream signaling pathways PI3k/Akt and MEK/ERK, while overexpression of a constitutive active form of FAK rescued the CD98hc deficiency. CONCLUSIONS: In this study we demonstrate that loss of CD98hc blocks tumorigenic potential in renal cell cancer.

Interactions of EGFR/PTEN/mTOR-Pathway Activation and Estrogen Receptor Expression in Cervical Cancer.

(1) Objective: Late-line chemotherapy rechallenge in recurrent cervical cancer is associated with modest therapy response but significant side effects. As mTOR pathways modulate cellular growth via estrogen receptor (ER) signaling and combined mTOR and ER inhibition previously demonstrated survival benefits in breast cancer, this exploratory study evaluates mTOR pathway and ER expression interactions in a preclinical cervical cancer model. (2) Methods: Immunostaining of a 126-tumor core tissue microarray was performed to assess phosphorylated-mTOR and ER expression. To identify tumor subsets with different clinical behavior, expression results were matched with clinicopathologic patient characteristics, and both univariate and multivariable survival statistics were performed. (3) Results: phosphorylated-mTOR correlates with ER (r = 0.309, p < 0.001) and loss of PTEN expression (r = -2.09, p = 0.022) in tumor samples across stages but not in matched negative controls. Positive ER expression is observed significantly more often in phosphorylated-mTOR positive samples (30.0% vs. 6.3%, p = 0.001). In the subgroup of phosphorylated-mTOR positive tumors (n = 60), ER expression is associated with improved survival (p = 0.040). (4) Conclusion: ER expression appears closely intertwined with EGFR/PTEN/mTOR-pathway activation and seems to define a subgroup with clinically distinct behavior. Considering limited therapeutic options in recurrent cervical cancer, further validation of combined mTOR and ER inhibition in selected patients could appear promising.

Routine laboratory parameters to support decision on parenteral nutrition in palliative care.

Introduction: Parenteral nutrition (PN) is widely used in palliative care (PC), but there is limited evidence to support its use at the end of life (EOL). This aim of this was to investigate the relationship between routine laboratory parameters and survival in patients receiving PN, and to develop a decision tree model to support clinicians decide whether to start or forgo PN. Methods: The laboratory parameters of 113 patients with advanced diseases who were admitted to a specialized palliative care unit (PCU) were analyzed at two points in time: T0 = before PN, T1 = two weeks after initiation of PN. Univariate Mann-Whitney U-tests and multivariate linear regression models, as well as a decision tree analysis were computed; all in relation to survival time. Results: The final regression model was significant with p = 0.001 (adjusted R2 = 0.15) and included two predictors for survival time after PN initiation: the CRP/albumin ratio and urea at T1 (ps = 0.019). Decision tree analysis revealed three important predictors for classification of survival time after PN initiation: CRP, urea, and LDH (all at T0). Discussion: The decision tree model may help to identify patients likely to benefit from PN, thus supporting the clinical decision whether or not to start PN.