Advanced Cancer Disease Research Articles

The Impact of Psychedelic Drugs on Anxiety and Depression in Advanced Cancer or other Life-threatening Disease: A Systematic Review With Meta-analysis.

Life-threatening cancer or other diseases can induce anxiety and depressive symptoms. We performed a systematic review with meta-analyses of randomized controlled trials assessing patients with cancer or other life-threatening diseases using validated anxiety and depression scales. PubMed was searched up to November 15, 2022 and citations were applied to prespecified inclusion criteria. Disease rating scales for anxiety or depression included the State-Trait Anxiety Inventory (STAI) (STAI Trait [STAI-T], STAI-State [STAI-S]), Beck Depression Inventory (BDI), Hospital Anxiety and Depression Scale (HADS) (HADS-Anxiety [HADS-A]; HADS-Depression [HADS-D]), Profile of Mood States (POMS), and the Hamilton Rating Scale for Depression (HAM-D or GRID-HAM-D-17). Safety outcomes included assessments of blood pressure and heart rate. Five trials, predominantly in cancer patients, had data assessing anxiety and depressive symptoms. These trials found promising results for psychedelics versus placebo in several anxiety and depression scales but increases in blood pressure and heart rate also occurred. There were some concerns of risk of bias because it is difficult to truly randomize a psychedelic trial and there was a high percentage of patients in the trials who had used psychedelics in the past. There was high heterogeneity for all analyses that we could not explain. Although the results are promising, future trials are needed to assess the optimal psychedelic, dose, number of sessions required, and how psychedelic naïve patients would respond both psychologically and hemodynamically before this therapy can be considered for widescale clinical use.

Profile of emergency department overuse in hospitalized patients with pulmonary disease and its impact on mortality

Introduction and objectivesPortugal is one of the countries with the highest number of visits to the emergency department (ED), 31% classified as “non-urgent” or “avoidable.” The objectives of our study were to evaluate the size and characteristics of patients with pulmonary disease who overuse the ED, and identify factors associated with mortality. Materials and methodsA retrospective cohort study was conducted, based on the medical records of ED frequent users (ED-FU) with pulmonary disease who attended a university hospital center in the northern inner city of Lisbon from January 1 to December 31, 2019. To evaluate mortality, a follow-up until December 31, 2020 was performed. ResultsOver 5,567 (4.3%) patients were identified as ED-FU and 174 (0.14%) had pulmonary disease as the main clinical condition, accounting for 1,030 ED visits. 77.2% of ED visits were categorized as “urgent/very urgent.” A high mean age (67.8 years), male gender, social and economic vulnerability, high burden of chronic disease and comorbidities, with a high degree of dependency, characterized the profile of these patients. A high proportion (33.9%) of patients did not have a family physician assigned and this was the most important factor associated with mortality (p<0.001; OR: 24.394; CI 95%: 6.777–87.805). Advanced cancer disease and autonomy deficit were other clinical factors that most determined the prognosis. ConclusionsPulmonary ED-FU are a small group of ED-FU who constitute an aged and heterogeneous group with a high burden of chronic disease and disability. The lack of an assigned family physician was the most important factor associated with mortality, as well as advanced cancer disease and autonomy deficit.

Outcome following nivolumab treatment in patients with advanced non-small cell lung cancer and comorbid interstitial lung disease in a real-world setting.

Up to 10% of patients with advanced non-small cell lung cancer (aNSCLC) have pre-existing interstitial lung disease (ILD). These patients are usually excluded from immunotherapy clinical trials. Consequently, knowledge on outcomes following nivolumab treatment in these patients remains limited. The primary objective of this study was to evaluate survival outcome following nivolumab treatment in ILD patients with pre-treated aNSCLC in the real-world setting. The study included all patients with aNSCLC recorded in the French hospital database, starting nivolumab in 2015-2016. Patients were stratified by pre-existing ILD and three subgroups were studied [auto-immune or granulomatous (AI/G) ILD, other known causes ILD and idiopathic ILD]. Time to discontinuation of nivolumab treatment [time to treatment duration (TTD)] and overall survival (OS) were estimated using Kaplan-Meier survival analysis. Of 10,452 aNSCLC patients initiating nivolumab, 148 (1.4%) had pre-existing ILD. Mean age at nivolumab initiation was 64.6 ± 9.4 years in ILD and 63.8 ± 9.6 years in non-ILD. Compared to non-ILD, patients in the ILD group were more frequently men (p < 0.05) and had more comorbidities (p < 0.001). There was no significant difference between ILD and non-ILD groups for median TTD (2.5 versus 2.8 months; p = 0.6) or median OS (9.6 versus 11.9 months; p = 0.1). Median OS in AI/G ILD (n = 14), other known causes ILD (n = 75), and idiopathic ILD (n = 59) were 8.6, 10.7, and 9.6 months, respectively. In this large cohort of aNSCLC patients with ILD, outcomes are similar to those obtained in the non-ILD population. Immunotherapy could be beneficial for these patients.

How the Tumor Micromilieu Modulates the Recruitment and Activation of Colorectal Cancer-Infiltrating Lymphocytes.

The successful treatment of advanced colorectal cancer disease still represents an insufficiently solved clinical challenge, which is further complicated by the fact that the majority of malignant colon tumors show only relatively low immunogenicity and therefore have only limited responsiveness to immunotherapeutic approaches, such as, for instance, the use of checkpoint inhibitors. As it has been well established over the past two decades that the local tumor microenvironment and, in particular, the quantity, quality, and activation status of intratumoral immune cells critically influence the clinical prognosis of patients diagnosed with colorectal cancer and their individual benefits from immunotherapy, the enhancement of the intratumoral accumulation of cytolytic effector T lymphocytes and other cellular mediators of the antitumor immune response has emerged as a targeted objective. For the future identification and clinical validation of novel therapeutic target structures, it will thus be essential to further decipher the molecular mechanisms and cellular interactions in the intestinal tumor microenvironment, which are crucially involved in immune cell recruitment and activation. In this context, our review article aims at providing an overview of the key chemokines and cytokines whose presence in the tumor micromilieu relevantly modulates the numeric composition and antitumor capacity of tumor-infiltrating lymphocytes.

2,4-Dinitrophenol as an Uncoupler Augments the Anthracyclines Toxicity against Prostate Cancer Cells.

One of the strategies for the treatment of advanced cancer diseases is targeting the energy metabolism of the cancer cells. The compound 2,4-DNP (2,4-dinitrophenol) disrupts the cell energy metabolism through the ability to decouple oxidative phosphorylation. The aim of the study was to determine the ability of 2,4-DNP to sensitize prostate cancer cells with different metabolic phenotypes to the action of known anthracyclines (doxorubicin and epirubicin). The synergistic effect of the anthracyclines and 2,4-DNP was determined using an MTT assay, apoptosis detection and a cell cycle analysis. The present of oxidative stress in cancer cells was assessed by CellROX, the level of cellular thiols and DNA oxidative damage. The study revealed that the incubation of LNCaP prostate cancer cells (oxidative phenotype) with epirubicin and doxorubicin simultaneously with 2,4-DNP showed the presence of a synergistic effect for both the cytostatics. Moreover, it contributes to the increased induction of oxidative stress, which results in a reduced level of cellular thiols and an increased number of AP sites in the DNA. The synergistic activity may consist of an inhibition of ATP synthesis and the simultaneous production of toxic amounts of ROS, destroying the mitochondria. Additionally, the sensitivity of the LNCaP cell line to the anthracyclines is relatively higher compared to the other two (PC-3, DU-145).

Lower expression of NINJ1 (Ninjurin 1), a mediator of plasma membrane rupture, is associated with advanced disease and worse prognosis in serous ovarian cancer.

Gasdermin proteins (GSDMs) form pores in cell membranes upon various stimuli, leading to the release of certain proinflammatory molecules such as IL-1β and IL-18, and this ultimately results in pyroptotic cell death. NINJ1 (Ninjurin 1) has recently been identified as a cell membrane protein responsible for the final complete plasma membrane rupture following lytic cell death mechanisms including pyroptosis, causing the release of relatively larger molecules such as HMGB1 and LDH. In this study, we reported the presence of higher GSDMD and lower GSDME protein levels in ovarian tumors compared to surrounding non-malignant stromain the tumor microenvironment. GSDME protein levels are also lower in the tumorsof theomentum compared to adjacentstromal cells.We found that NINJ1 expression decreases from early to late stage in serous ovarian cancer, and the percentage of NINJ1 copy number loss events is the highest in ovarian cancer among other cancers. Moreover, we showed that low expression of NINJ1 is associated with shorter overall survival of patients with ovarian cancer. In support of the findings showing that low NINJ1 expression contributes to worse prognosis in this most lethal gynecological malignancy, NINJ1 expression was found to be lower in cisplatin-resistant ovarian cancer cells compared to cisplatin-sensitive counterparts in vitro. We suggest that the members of gasdermin family might have distinct functions in serous ovarian cancer, and low levels of NINJ1 might contribute, at least in part, to the progression and poorer prognosis of ovarian cancer. A complete picture of how pyroptosis and subsequent plasma membrane rupture are involved in ovarian cancer will be of high importance in order to identify actionable therapeutic vulnerabilities within this newly identified group of proteins.

Patient-Reported Outcome Dashboards Within the Electronic Health Record to Support Shared Decision-making: Protocol for Co-design and Clinical Evaluation With Patients With Advanced Cancer and Chronic Kidney Disease.

BackgroundPatient-reported outcomes—symptoms, treatment side effects, and health-related quality of life—are important to consider in chronic illness care. The increasing availability of health IT to collect patient-reported outcomes and integrate results within the electronic health record provides an unprecedented opportunity to support patients’ symptom monitoring, shared decision-making, and effective use of the health care system.ObjectiveThe objectives of this study are to co-design a dashboard that displays patient-reported outcomes along with other clinical data (eg, laboratory tests, medications, and appointments) within an electronic health record and conduct a longitudinal demonstration trial to evaluate whether the dashboard is associated with improved shared decision-making and disease management outcomes.MethodsCo-design teams comprising study investigators, patients with advanced cancer or chronic kidney disease, their care partners, and their clinicians will collaborate to develop the dashboard. Investigators will work with clinic staff to implement the co-designed dashboard for clinical testing during a demonstration trial. The primary outcome of the demonstration trial is whether the quality of shared decision-making increases from baseline to the 3-month follow-up. Secondary outcomes include longitudinal changes in satisfaction with care, self-efficacy in managing treatments and symptoms, health-related quality of life, and use of costly and potentially avoidable health care services. Implementation outcomes (ie, fidelity, appropriateness, acceptability, feasibility, reach, adoption, and sustainability) during the co-design process and demonstration trial will also be collected and summarized.ResultsThe dashboard co-design process was completed in May 2020, and data collection for the demonstration trial is anticipated to be completed by the end of July 2022. The results will be disseminated in at least one manuscript per study objective.ConclusionsThis protocol combines stakeholder engagement, health care coproduction frameworks, and health IT to develop a clinically feasible model of person-centered care delivery. The results will inform our current understanding of how best to integrate patient-reported outcome measures into clinical workflows to improve outcomes and reduce the burden of chronic disease on patients and health care systems.International Registered Report Identifier (IRRID)DERR1-10.2196/38461

Discussing prognosis and the end of life with patients with advanced cancer or COPD: A qualitative study.

To explore patients' experiences and recommendations for discussions about their prognosis and end of life with their physicians. Patients with advanced cancer or advanced chronic obstructive pulmonary disease (COPD) were enrolled in qualitative interviews, which were analyzed with a phenomenological and thematic approach. During interviews with fourteen patients (median age 64 years), we identified the following themes for discussion about prognosis and the end of life: topics discussed, the timing, the setting, physician-patient relationship, responsibilities for clinicians, and recommendations. Patients preferred the physician to initiate such discussion, but wanted to decide about its continuation and content. The discussions were facilitated by an established physician-patient relationship or attendance of relatives. Patients with cancer had had discussions about prognosis at rather clear-cut moments of deterioration than patients with COPD. Patients with COPD did not consider end-of-life discussions a responsibility of the pulmonologist. Patients recommended an understandable message, involvement of relatives or other clinicians, sufficient time, and sensitive non-verbal communication. Patients appreciated open, sensitive, and negotiable discussions about prognosis and the end of life. Patients' recommendations could be used for communication training. Possible differences in the need for such discussions between patients with cancer or COPD warrant further research.

Impact of treatment line on risks and benefits of immune checkpoint inhibitor in patients with advanced non-small cell lung cancer and interstitial lung disease: a systematic review and meta-analysis of cohort studies.

BackgroundThere is no clear consensus regarding the safety and efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced non-small cell lung cancer (NSCLC) and pre-existing interstitial lung disease (ILD). We aimed to elucidate the impact of ICIs on pre-existing ILD.MethodsWe systematically queried PubMed-MEDLINE, Embase-Scopus, and ISI Web of Science databases up to January 10, 2022. The pooled any-grade and grade 3–5 ICI-associated pneumonitis (ICIP) rate and objective response rate (ORR) in patients with pre-existing ILD were mainly evaluated. The relative risk (RR) was also evaluated for pre-existing ILD and usual interstitial pneumonia (UIP) patterns. Sensitivity and subgroup analyses were performed to assess the heterogeneity.ResultsIn total, 17 studies involving 5,529 patients were included in the meta-analysis. The pooled ICIP rate was 30% [95% confidence interval (CI): 24–36%]; it was found to be significantly higher in patients with pre-existing ILD relative to those without (RR =3.05, 95% CI: 2.53–3.69; I2=0.0%). The pooled grade 3–5 ICIP rate was 12% (95% CI: 9–15%); this was also significantly higher in patients with pre-existing ILD (RR =3.19, 95% CI: 2.32–4.38; I2=0.0%). According to subgroup analysis, these ICIP rates were not significantly different among the treatment lines (first, ≥ second, and mixed) (P=0.33) whereas the pooled ORR was 36% (95% CI: 24–48%; I2=53.7%) with a significant difference among the treatment lines (P=0.027). The pooled ICIP rate was independent of the UIP pattern (RR =1.06, 95% CI: 0.86–1.32; I2=0.0%).ConclusionsOverall, ICIs should be administered cautiously in patients with pre-existing ILD, regardless of the treatment line. Moreover, the risks of ICIP may outweigh ICI benefits, especially in second-or later-line treatment. These results need to be further confirmed by meta-analyses including more observational cohort studies in clinical setting.

1275P Chemotherapy at the end of life: The reality of an oncological centre

In advanced and incurable cancer disease, chemotherapy may be recommended if it improves the quality of life, even if it does not increase survival. However, in an end-of-life setting, the use of chemotherapy is controversial, with less clear indications and more individualized decisions. This study aimed to evaluate patients who received chemotherapy within the last three months of life, an indicator of the quality of care provided.

Geographic variation in attitudes regarding management of locally advanced pancreatic cancer

BackgroundRecent literature suggests wide variations exist in the international management of locally advanced pancreatic cancer. This study sought to evaluate how geography contributes to variations in management of locally advanced pancreatic cancer. MethodsAn electronic survey investigating preferences for the evaluation and management of locally advanced pancreatic cancer was distributed to an international cohort of pancreatic surgeons. Surgeons were classified according to geographic location of practice, and survey responses were compared across locations. ResultsA total of 153 eligible responses were received from 4 continents: North and South America (n = 94, 61.4%), Europe (n = 25, 16.3%), and Asia (n = 34, 22.2%). Preferences for the use and duration of neoadjuvant chemotherapy and radiotherapy varied widely. For example, participants in Asia commonly preferred 2 months of neoadjuvant chemotherapy (61.8%), whereas North and South American participants preferred 4 months (52.1%), and responses in Europe were mixed (P = .006). Participants in Asia were less likely to consider isolated liver or lung metastases contraindications to exploration and consequently had a greater propensity to consider exploration in a vignette of oligometastatic disease (56.7% vs North and South America: 25.6%, Europe: 43.5%; P = .007). ConclusionIn an international survey of pancreatic surgeons, attitudes regarding locally advanced pancreatic cancer and metastatic disease management varied widely across geographic locations. Better evidence is needed to define optimal management of locally advanced pancreatic cancer.

Financial Toxicity Related to Advanced Cancer Patients’ Care: Case study of Selected Households of Kiambu County, Kenya

Purpose : The aim of this study is to investigate family caregiver’s experiences on household financial burden related to cancer treatment/care following referral to a palliative care unit in Kenya. Methodology: Case study approach was used to collect data from caregivers of advanced cancer patients following referral to a palliative care unit at Kijabe Mission Hospital in Kenya. This approach is best suited to gain insight into economic implication of the rising cost of cancer treatment which has put a considerable financial strain on affected families, leading to adverse outcomes of caring for patients with advanced cancer. Semi-structured in-depth interviews, documentary data and field notes, observations were used to collect information relating to financial and economic impact of the careburden experiences from theoretical sample of 12 caregivers. This approach enabled an in-depth, multifaceted explorations of complex issues related to in their real-world contexts. The case study method was particularly chosen because of its richness to gain an in-depth understanding of an issue, event, or phenomenon of interest in its natural real-life context. A socio-technical coding matrix was used to analyze qualitative data thematically, along with additional themes that emerged from the data. All ethical considerations were observed accordingly. Findings – Four (4) male and eight (8) female caregivers interviewed were between 18 to 67 years. The study reports families facing enormous financial strain and difficulties treating their patient with advanced cancer patient. Treating patient with advanced cancer is reported to drain resources threatening to bring vicious cycle of poverty and financial stability. Family members get frustrated at their inability to meet growing demands related to care, treatment and management of their patient in advanced stage of cancer. Financial concerns, catastrophic health expenditure (CHE) and distress financing (DF as part of devastating effects of cancer, limited health insurance coverage and gaps in financing are among the key concerns identified. Unique contributions to theory, practice and policy : This study builds evidence towards social and conomic consequences of treating advanced cancer diseases that affect household families and impact on life of patients with advanced cares. Hence, seeks to shape how multidisciplinary cancer care teams’ practices to become more aware of the costs of their clinical decisions. Findings of this study also form basis of review of already existing policies related to insurance coverage provided by state agency to tailor it to chronic diseases. Further research is required to mitigate financial toxicity and additional financial safety nets Key words : financial burden, cancer, economics, Kenya DOI: 10.7176/JHMN/101-06 Publication date: June 30 th 2022

Long-Term Outcome of Critically Ill Advanced Cancer Patients Managed in an Intermediate Care Unit.

Background: To analyze the long-term outcomes for advanced cancer patients admitted to an intermediate care unit (ImCU), an analysis of a do not resuscitate orders (DNR) subgroup was made. Methods: A retrospective observational study was conducted from 2006 to January 2019 in a single academic medical center of cancer patients with stage IV disease who suffered acute severe complications. The Simplified Acute Physiology Score 3 (SAPS 3) was used as a prognostic and severity score. In-hospital mortality, 30-day mortality and survival after hospital discharge were calculated. Results: Two hundred and forty patients with stage IV cancer who attended at an ImCU were included. In total, 47.5% of the cohort had DNR orders. The two most frequent reasons for admission were sepsis (32.1%) and acute respiratory failure (excluding sepsis) (38.7%). Mortality in the ImCU was 10.8%. The mean predicted in-hospital mortality according to SAPS 3 was 51.9%. The observed in-hospital mortality was 37.5% (standard mortality ratio of 0.72). Patients discharged from hospital had a median survival of 81 (30.75–391.25) days (patients with DNR orders 46 days (19.5–92.25), patients without DNR orders 162 days (39.5–632)). The observed mortality was higher in patients with DNR orders: 52.6% vs. 23.8%, p 0 < 0.001. By multivariate logistic regression, a worse ECOG performance status (3–4 vs. 0–2), a higher SAPS 3 Score and DNR orders were associated with a higher in-hospital mortality. By multivariate analysis, non-invasive mechanical ventilation, higher bilirubin levels and DNR orders were significantly associated with 30-day mortality. Conclusion: For patients with advanced cancer disease, even those with DNR orders, who suffer from acute complications or require continuous monitoring, an ImCU-centered multidisciplinary management shows encouraging results in terms of observed-to-expected mortality ratios.

Abstract 530: UMAP- Personalized lung cancer monitoring platform

Abstract Lung cancer is the leading cause of cancer death, accounting for 1.6 million deaths per year. The prognosis for newly diagnosed cases is overall poor and strongly influenced by clinical stage at time of diagnosis, with dismal survival rates for cases diagnosed at a late stage. However, molecular profiling at diagnosis and advances in precision medicine has vastly improved the clinical management of lung cancer patients. An efficient evaluation of treatment response and early detection of recurrent disease can further improve survival rates. However, response evaluation during treatment is still limited to either radiological evaluation at fixed intervals or the risk-associated trans-thoracic biopsies that cannot be performed frequently. Therefore, there is an imperative need to identify minimally invasive, personalised biomarkers that can longitudinally monitor treatment response as well as early detect and map emerging resistance mechanisms leading to relapse. Employing liquid biopsy platforms to analyse tumor biomarkers in circulating nucleic acids, especially circulating tumor DNA (ctDNA), is a promising approach for longitudinal disease monitoring as it is less invasive and quantitative. Here we present the Umeå Molecular Adaptive Platform (UMAP) aimed for developing personalised tumor biomarkers for disease monitoring of individual lung cancer patients following curative treatment. The UMAP employs matched diagnostic tumor tissue and plasma samples from Swedish lung cancer patients (retrieved from Uppsala-Umeå Comprehensive Cancer Consortium, Sweden) and entails mutational profiling of tumor tissue, specifically identifying disease-associated large structural variants (SVs) and single nucleotide variants (SNVs) by long read sequencing using Oxford Nanopore Technology (ONT) and Illumina TST170 target enrichment sequencing, respectively. Individualized SVs and SNVs biomarker assays are then developed for droplet digital PCR (ddPCR) -based analysis and quantification in ctDNA isolated from corresponding plasma samples. This tailored, patient-specific panel can then be used to longitudinally monitor disease evolution and treatment response during the entire therapy regimen using blood-based sampling. The UMAP workflow has been optimised by mutational profiling of 3 lung cancer cell lines (H1299, H1975 and H2228) and fresh frozen tumor tissues from 12 lung cancer patients using ONT and Illumina TST170 panel followed by development of robust, highly sensitive ddPCR assays for targeting candidate SNVs and SVs with minimal hands-on time and with detection limit as low as 0.001%. Impact of this tailored approach on improving survival can be evaluated by implementing UMAP in a prospective clinical trial with patients with advanced lung cancer disease. Citation Format: Zahra Haider, Linda Köhn, Nicholas Karlowatz, Mikael B. Johansson, Jonas A. Nilsson. UMAP- Personalized lung cancer monitoring platform [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 530.

Nitric-Oxide Synthase trafficking inducer (NOSTRIN) is an emerging negative regulator of colon cancer progression

BackgroundNOSTRIN, abundantly expressed in colon, was reported to be anti-angiogenic, anti-invasive and anti-inflammatory. NOSTRIN expression was inversely related to survival of pancreatic ductal adeno-carcinoma patients. Yet its function and regulatory mechanism in CRC remains elusive.MethodsNOSTRIN’s influence on EMT of CRC cells were analysed using realtime PCR array containing the functional EMT-transcriptome followed by western blotting. Regulation of oncogenic potential of CRC cells by NOSTRIN was elucidated using soft agar colony formation, trans-well invasion, wound healing and colonosphere formation assays. Biochemical assays were used to reveal mechanism of NOSTRIN function. Human CRC tissue array was used to test NOSTRIN mark in control and CRC disease stages.ResultsWe showed here that CRC cell lines with less NOSTRIN expression has more invasive and migratory potential. NOSTRIN affected EMT-associated transcriptome of CRC cells by down regulating 33 genes that were functionally annotated to transcription factors, genes important for cell growth, proliferation, migration, cell adhesion and cytoskeleton regulators in CRC cells. NOSTRIN over-expression significantly reduced soft agar colony formation, wound healing and cell invasion. In line with this, RNA interference of Nostrin enhanced metastatic potential of CRC cells. Furthermore, stable overexpression of NOSTRIN in CRC cell line not only curtailed its ability to form colonosphere but also decreased expression of stemness markers CD133, CD44 and EpCAM. NOSTRIN’s role in inhibiting self-renewal was further confirmed using BrdU incorporation assay. Interestingly, NOSTRIN formed immune-complex with Cdk1 in CRC cells and aided in increase of inhibitory Y15 and T14 phosphorylation of Cdk1 that halts cytokinesis. These ex vivo findings were substantiated using human colon cancer tissue array containing cDNAs from patients’ samples with various stages of disease progression. Significant decrease in NOSTRIN expression was found with initiation and progression of advanced colon cancer disease stages.ConclusionWe illustrate function of a novel molecule, NOSTRIN in curtailing EMT and maintenance of CRC cell stemness. Our data validates importance of NOSTRIN mark during onset and disease progression of CRC indicating its diagnostic potential.

Laboratory breakpoints for assessing high level gentamicin resistance in Streptococcus agalactiae: it is the time for a consensus

Group B streptococcus (GBS, Streptococcus agalactiae) is the most frequent cause of meningitis and a notable cause of sepsis in the first 3 months of life [1]. In adults, GBS is an occasional pathogen, mostly associated with genitourinary infection, but it can also cause invasive infections in those with certain predisposing conditions, particularly advanced age, diabetes, cancer, HIV, and liver disease [2].

Rintatolimod (Ampligen®) Enhances Numbers of Peripheral B Cells and Is Associated with Longer Survival in Patients with Locally Advanced and Metastasized Pancreatic Cancer Pre-Treated with FOLFIRINOX: A Single-Center Named Patient Program.

Simple SummarySurvival of patients with locally advanced and metastatic pancreatic cancer remains poor after standard care with FOLFIRINOX. It is not known whether treatment with rintatolimod, a TLR-3 agonist, would improve progression-free survival. We investigated the immunomodulatory effects of rintatolimod and its benefits regarding progression-free and overall survival in patients who had been pre-treated with FOLFIRINOX. In long-term survivors (11 patients), we observed that rintatolimod treatment resulted in a lowering of the systemic immune-inflammation index (SIII) as well as the neutrophil to lymphocyte ratio (NLR), whereas peripheral B-cell counts were higher, when compared to short-term survivors (16 patients). Of note, rintatolimod treatment was associated with a higher progression-free and overall survival when compared to matched controls. These results support the effectiveness of adding rintatolimod as a maintenance therapy after FOLFIRINOX treatment in patients with advanced pancreatic cancer. A randomized controlled trial to further determine the efficacy of the drug is recommended.Background: Treatment with the TLR-3 agonist rintatolimod may improve pancreatic cancer patients’ survival via immunomodulation, but the effect is unproven. Methods: In this single-center named patient program, patients with locally advanced pancreatic cancer (LAPC) or metastatic disease were treated with rintatolimod (six weeks total, twice per week, with a maximum of 400 mg per infusion). The primary endpoints were the systemic immune-inflammation index (SIII), the neutrophil to lymphocyte ratio (NLR), and the absolute counts of 18 different populations of circulating immune cells as measured by flow cytometry. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Subgroup analyses were performed in long-term survivors (>1-year overall survival after starting rintatolimod) and compared to short-term survivors (≤1 year). Results: Between January 2017 and February 2019, twenty-seven patients with stable LAPC or metastatic disease were pre-treated with FOLFIRINOX and treated with rintatolimod. Rintatolimod treatment was well-tolerated. The SIII and NLR values were significantly lower in the 11 long-term survivors, versus 16 short-term survivors. The numbers of B-cells were significantly increased in long-term survivors. Numbers of T cells and myeloid cells were not significantly increased after treatment with rintatolimod. Median PFS was 13 months with rintatolimod, versus 8.6 months in a subset of matched controls (n = 27, hazard ratio = 0.52, 95% CI = 0.28–0.90, p = 0.007). The median OS was 19 months with rintatolimod, versus 12.5 months in the matched control (hazard ratio = 0.51, 95% CI = 0.28–0.90, p = 0.016). Conclusions: Treatment with rintatolimod showed a favorable effect on the numbers of peripheral B cells in patients with pancreatic cancer and improved survival in pancreatic cancer, but additional evidence is required.

Abstract OT2-19-06: Phase 2 study of abemaciclib in combination with endocrine therapy with or without paclitaxel induction in patients with hormone receptor-positive, HER2-negative advanced breast cancer and aggressive disease criteria: ABIGAIL

Abstract Background: Endocrine therapy (ET) is the preferred therapy option for patients (pts) with hormone receptor-positive (HR[+]) advanced breast cancer (ABC), except for pts with visceral crisis who often receive chemotherapy to achieve rapid symptom control. Cyclin-dependent kinases 4/6 inhibitors have improved the effectiveness of ET across all subgroups of pts with ABC by targeting potential mechanisms of resistance. An exploratory analysis revealed that the addition of abemaciclib to ET conferred the largest benefit in pts with poor prognostic characteristics (liver metastases, high grade tumors, or progesterone receptor-negative status) [Di Leo, NPJ Breast Cancer 2018; 4: 41]. ABIGAIL aims to provide consistent evidence that abemaciclib plus ET is superior or non-inferior to paclitaxel in terms of early overall response as first-line regimen in HR[+], HER2-negative ABC pts with poor prognosis. Trial Design: This is a multicenter, randomized, open-label, phase 2 trial. Eligible participants are men and women of any menopausal status aged ≥18 years with HR[+], HER2-negative ABC who had no prior systemic therapy in the advanced setting and at least one of the following aggressive disease criteria: (i) Visceral disease; (ii) High histological grade and/or progesterone receptor-negative status; (iii) Lactate dehydrogenase &amp;gt;1.5 × the upper limit of normal; (iv) Relapse while on or within 36 months of completing adjuvant ET. Eastern Cooperative Oncology Group performance status of 0 or 1, measurable disease as per RECIST 1.1, and adequate organ function are also required. A total of 160 pts will be randomly assigned (1:1) to receive abemaciclib (300 mg/day orally during each 28-day cycle) plus ET as per investigator’s criteria (either letrozole [2.5 mg/day orally] or fulvestrant [500 mg intramuscularly on days 1, 15 of cycle 1, and on day 1 thereafter], or paclitaxel (90 mg/m² intravenously on days 1, 8, 15). Men and pre-/peri-menopausal women will receive a gonadotropin-releasing hormone agonist if randomized to abemaciclib plus ET. At investigator’s discretion, pts in the paclitaxel arm could receive abemaciclib plus ET at any point after the first 12 weeks or extend chemotherapy for a total of 6 cycles. Randomization will be stratified according to the presence of visceral disease and endocrine therapy. The primary endpoint is 12-week overall response rate (ORR) as per RECIST 1.1. Key secondary endpoints include ORR, clinical benefit rate, 12-week progression-free survival, progression-free survival, time to response, duration of response, overall survival, time to first subsequent therapy, time to second subsequent therapy, and time to first chemotherapy for pts in abemaciclib plus ET arm, patient-reported outcomes, and safety as per NCI-CTCAE 5.0. The sample size assumes the comparison of two proportions in an asymptotical normal test. We expect that 12-week ORR will be higher in the abemaciclib plus ET arm than paclitaxel arm (30% vs. 15%), with the assumption of a 5% non-inferiority margin. Based on a 10% dropout rate, a sample size of 160 pts is necessary to attain 80% power at nominal level of two-sided alpha of 0.05. We will test the superiority of abemaciclib plus ET as compared with paclitaxel if the non-inferiority is achieved. Both analyses, will be conducted with the Newcombe hybrid score method for confidence intervals. This trial was opened to accrual in May 2021. Citation Format: Antonio Llombart-Cussac, Joseph Gligorov, Serena Di Cosimo, Cinta Albacar, Patricia Cortez, Eduardo Martinez-De Dueñas, Ana López, Vicente Carañana, Jacques Medioni, Luigi Cavanna, Marina Elena Cazzaniga, Sofia Braga, Passos Coelho, Miguel Sampayo-Cordero, Andrea Malfettone, José Manuel Pérez-García, Javier Cortes. Phase 2 study of abemaciclib in combination with endocrine therapy with or without paclitaxel induction in patients with hormone receptor-positive, HER2-negative advanced breast cancer and aggressive disease criteria: ABIGAIL [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-19-06.

Spiritual Interventions Delivered by Nurses to Address Patients' Needs in Hospitals or Long-Term Care Facilities: A Systematic Review.

Introduction: Despite increasing evidence of the benefits of spiritual care and nurses' efforts to incorporate spiritual interventions into palliative care and clinical practice, the role of spirituality is not well understood and implemented. There are divergent meanings and practices within and across countries. Understanding the delivery of spiritual interventions may lead to improved patient outcomes. Aim: We conducted a systematic review to characterize spiritual interventions delivered by nurses and targeted outcomes for patients in hospitals or assisted long-term care facilities. Methodology: The systematic review was developed following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, and a quality assessment was performed. Our protocol was registered on PROSPERO (Registration No. CRD42020197325). The CINAHL, Embase, PsycINFO, and PubMed databases were searched from inception to June 2020. Results: We screened a total of 1005 abstracts and identified 16 experimental and quasi-experimental studies of spiritual interventions delivered by nurses to individuals receiving palliative care or targeted at chronic conditions, such as advanced cancer diseases. Ten studies examined existential interventions (e.g., spiritual history, spiritual pain assessment, touch, and psychospiritual interventions), two examined religious interventions (e.g., prayer), and four investigated mixed interventions (e.g., active listening, presence, and connectedness with the sacred, nature, and art). Patient outcomes associated with the delivery of spiritual interventions included spiritual well-being, anxiety, and depression. Conclusion: Spiritual interventions varied with the organizational culture of institutions, patients' beliefs, and target outcomes. Studies showed that spiritual interventions are associated with improved psychological and spiritual patient outcomes. The studies' different methodological approaches and the lack of detail made it challenging to compare, replicate, and validate the applicability and circumstances under which the interventions are effective. Further studies utilizing rigorous methods with operationalized definitions of spiritual nursing care are recommended.

Chemotherapy at the End of Life – The Reality of an Oncological Centre

Background: In advanced and incurable cancer disease, chemotherapy may be recommended if it improves the quality of life, even if it does not increase survival. However, in an end-of-life setting, the use of chemotherapy is controversial, with less clear indications and more individualized decisions. This study aimed to evaluate patients who received chemotherapy within the last three months of life, an indicator of the quality of care provided. Methods: We analyzed data from patients receiving chemotherapy in the last 3 months of life and who died from January 2018 to December 2020, in our Oncology Department. Results: It was found that 391 patients received chemotherapy in the last 3 months of life. Most had metastatic disease at diagnosis (71%, n=276) and were treated in a first-line setting. A more detailed analysis revealed that 50% (n=193) underwent treatment in the last month and 22% (n=42) in the last week of life. Most patients died due to disease progression, with 79% of deaths occurring in the hospital. Conclusions: This work puts into figures the reality of an Oncology Centre, revealing the investment made in fighting the disease and providing greater longevity to patients, with quality of life.