Breast cancer insights from Northern Israel: a comprehensive analysis of survival rates among Jewish and Arab women.

This study investigates breast cancer survival rates between 2000 and 2022 in northern Israel, focusing on ethnicity, socioeconomic status, age at diagnosis, and the Charlson Comorbidity Index. Analyzing data from Clalit Health Services, we studied 8,431 breast cancer patients (6,395 Jewish, 2,036 Arab). We compared five- and ten-year survival rates across different demographics. Ethnicity showed a minor impact on survival (OR 1.12, 95% CI: 0.93 - 1.35). Socioeconomic status had a significant effect, with a higher level of improving survival (OR 2.50, 95% CI: 2.04 - 3.08). Age was crucial; women 18-39 had better survival than 60-100, but no significant difference was found between the 18-39 and 40-59 age groups [OR (CI 0.90 - 1.53, p = 0.231)]. For the Charlson Comorbidity Index, women with scores of 3-10 showed lower survival compared to scores of 0 and 1-2. There was a notable improvement in five-year survival rates among patients aged 18-59 diagnosed from 2009-2018 (90.7%) compared to 2000-2008 (86.9%) (p = 0.0046), but not in patients aged 60-100. The study highlights that socioeconomic status, age, and comorbidity scores are significant in determining survival rates for breast cancer. The improvement in survival rates for younger patients diagnosed more recently reflects advancements in treatment and care. This research provides valuable insights into the factors affecting breast cancer survival rates, underscoring the role of socioeconomic status, age, and comorbidities while also highlighting the progress in breast cancer treatment over recent years.

Nuclear localization of heparanase 2 (Hpa2) attenuates breast carcinoma growth and metastasis.

Unlike the intense research effort devoted to exploring the significance of heparanase in cancer, very little attention was given to Hpa2, a close homolog of heparanase. Here, we explored the role of Hpa2 in breast cancer. Unexpectedly, we found that patients endowed with high levels of Hpa2 exhibited a higher incidence of tumor metastasis and survived less than patients with low levels of Hpa2. Immunohistochemical examination revealed that in normal breast tissue, Hpa2 localizes primarily in the cell nucleus. In striking contrast, in breast carcinoma, Hpa2 expression is not only decreased but also loses its nuclear localization and appears diffuse in the cell cytoplasm. Importantly, breast cancer patients in which nuclear localization of Hpa2 is retained exhibited reduced lymph-node metastasis, suggesting that nuclear localization of Hpa2 plays a protective role in breast cancer progression. To examine this possibility, we engineered a gene construct that directs Hpa2 to the cell nucleus (Hpa2-Nuc). Notably, overexpression of Hpa2 in breast carcinoma cells resulted in bigger tumors, whereas targeting Hpa2 to the cell nucleus attenuated tumor growth and tumor metastasis. RNAseq analysis was performed to reveal differentially expressed genes (DEG) in Hpa2-Nuc tumors vs. control. The analysis revealed, among others, decreased expression of genes associated with the hallmark of Kras, beta-catenin, and TNF-alpha (via NFkB) signaling. Our results imply that nuclear localization of Hpa2 prominently regulates gene transcription, resulting in attenuation of breast tumorigenesis. Thus, nuclear Hpa2 may be used as a predictive parameter in personalized medicine for breast cancer patients.

Cannabis and Cannabinoids in Adults With Cancer: ASCO Guideline.

PURPOSE: To guide clinicians, adults with cancer, caregivers, researchers, and oncology institutions on the medical use of cannabis and cannabinoids, including synthetic cannabinoids and herbal cannabis derivatives; single, purified cannabinoids; combinations of cannabis ingredients; and full-spectrum cannabis. METHODS: A systematic literature review identified systematic reviews, randomized controlled trials (RCTs), and cohort studies on the efficacy and safety of cannabis and cannabinoids when used by adults with cancer. Outcomes of interest included antineoplastic effects, cancer treatment toxicity, symptoms, and quality of life. PubMed and the Cochrane Library were searched from database inception to January 27, 2023. ASCO convened an Expert Panel to review the evidence and formulate recommendations. RESULTS: The evidence base consisted of 13 systematic reviews and five additional primary studies (four RCTs and one cohort study). The certainty of evidence for most outcomes was low or very low. RECOMMENDATIONS: Cannabis and/or cannabinoid access and use by adults with cancer has outpaced the science supporting their clinical use. This guideline provides strategies for open, nonjudgmental communication between clinicians and adults with cancer about the use of cannabis and/or cannabinoids. Clinicians should recommend against using cannabis or cannabinoids as a cancer-directed treatment unless within the context of a clinical trial. Cannabis and/or cannabinoids may improve refractory, chemotherapy-induced nausea and vomiting when added to guideline-concordant antiemetic regimens. Whether cannabis and/or cannabinoids can improve other supportive care outcomes remains uncertain. This guideline also highlights the critical need for more cannabis and/or cannabinoid research.Additional information is available at www.asco.org/supportive-care-guidelines.

Some differences between social work, spiritual care, and psychology: Content variance in end-of-life conversations.

OBJECTIVES: Within the multidisciplinary team, there can sometimes be lack of clarity as to the specific different contributions of each of the psycho-social-spiritual professionals: social workers, psychologist, and spiritual caregivers. This study examined the content of their end-of-life conversations with patients. METHODS: A total of 180 patients with terminal cancer received standard multidisciplinary care, including conversations with a social worker, psychologist, and spiritual caregiver. After each patient's death, these professionals reported using a structured tool which content areas had arisen in their conversations with that patient. RESULTS: Across all content areas, there were significant differences between social work and spiritual care. The difference between social work and psychology was slightly smaller but still quite large. Psychology and spiritual care were the most similar, though they still significantly differed in half the content areas. The differences persisted even among patients who spoke with more than 1 kind of professional. The 6 content areas examined proved to subdivide into 2 linked groups, where patients speaking about 1 were more likely to speak about the others. One group, "reflective" topics (inner and transpersonal resources, interpersonal relationships, one's past, and end of life), included all those topics which arose more often with spiritual caregivers or psychologists. The second group, "decision-making" topics (medical coping and life changes), was comprised of those topics which arose most commonly with social workers, bridging between the medical and personal aspects of care and helping patients navigate their new physical, psychological, and social worlds. SIGNIFICANCE OF RESULTS: These findings help shed light on the differences, in practice, between patients' conversations with social workers, psychologists, and spiritual caregivers and the roles these professionals are playing; can aid in formulating individualized care plans; and strengthen the working assumption that all 3 professions contribute in unique, complementary ways to improving patients' and families' well-being.

Challenges in Implementing Guideline on Integrative Oncology and Pain: The Israeli Perspective.

CONTEXT AND OBJECTIVES: To explore the feasibility of implementing the joint guideline on integrative medicine for pain management in oncology, published by the Society for Integrative Oncology (SIO) and the American Society of Clinical Oncology (ASCO), for integrative oncology (IO) services in supportive and palliative care. METHODS: A qualitative research methodology was co-designed by the SIO-ASCO guideline committee, with the Society for Complementary Medicine, Israel Medical Association (IMA). A questionnaire with five open-ended questions exploring barriers and enablers to implementing the guideline was distributed to chairs and board members of nine IMA-affiliated medical societies; four deans of Israeli medical schools; and nurses from the Israeli Society for Oncology Nursing. Respondent narratives were qualitatively analyzed using ATLAS.Ti software for systematic coding. RESULTS: Questionnaires were completed by 52 physicians and nurses from medical oncology, hematology, gynecological oncology, pediatric oncology, palliative medicine, pain, family medicine, internal medicine, and integrative medicine. The SIO-ASCO guidelines were endorsed by nine IMA-affiliated societies. The domains identified included the importance of guideline implementation in clinical practice; barriers and facilitators to implementation; practical aspects required for this implementation (e.g., IO training); clinical indications for referral; budget-related issues; and clinical and administrative models enabling practical implementation of the guideline. CONCLUSION: We found across-the-board consensus among the nine IMA-affiliated societies supporting the current guideline. This, while identifying potential facilitators and barriers in order to address the implementation of the SIO-ASCO guideline recommendations.

Too Much of a Good Thing: The Association of Elevated Vitamin B12 Levels and Outcomes in Patients With Cancer Treated With Immunotherapy.

Metabolic pathways may regulate responses to cancer immunotherapy (IO). Due to its immunomodulatory properties, we sought to examine the association between serum vitamin B12 (VitB12) and survival in individuals with cancer treated with immune checkpoint inhibitors, compared with biological and chemotherapy. We collected data on patients with advanced cancer initiating intravenous antineoplastic treatment and a concomitant VitB12 measurement (elevated: >820 ng/L), between January 2010 and January 2022. Patients on IO and other regimens (control) were compared using the Mann-Whitney test for continuous variables, χ 2 test or Fisher test for categorical variables, and multivariate Cox regression models assessed the effect of VitB12 on overall survival and progression-free survival, adjusting for confounders. Patient groups (control: n = 408; IO: n = 93) were balanced for the treatment line and VitB12 (elevated 29.9% vs 23.7%; mean 762.4 vs 687.6 ng/L). In multivariate analysis, overall survival in all patients was negatively associated with VitB12 [control: hazard ratio (HR): 1.4, 95% CI: 1.01-1.96, P = 0.04, false discovery rate (FDR): 0.069; IO: HR: 2.74 as sum of linear baseline and interaction effects, log scale], age (HR: 1.03, 95% CI: 1.02-1.04, P < 0.01), male sex (HR: 0.66, 95% CI: 0.50-0.88, P < 0.01), and neutrophil-to-lymphocyte ratio (HR: 1.05, 95% CI: 0.48-0.99, P = 0.01). However, VitB12 was significantly negatively associated with progression-free survival only in the IO group ( P < 0.001, FDR < 0.001, calculated HR: 8.34; biological treatment P = 0.08; FDR: 0.111; neutrophil-to-lymphocyte ratio, P = 0.07; FDR: 0.09). Taken together, elevated VitB12 was a negative predictor for outcomes on IO, independently of other known prognostic factors. Further research is needed to elucidate the immune-metabolic interplay and its interaction with the gut microbiome, as well as interventional strategies to enhance IO responses.

Linkage between Psychological Factors and Response to Immune Checkpoint Inhibitor Therapy: A Preliminary Study.

Substantial evidence has accumulated showing that psychological distress affects immune regulation, the response to cancer treatment, and survival. The effect of psychological parameters on the effectiveness of immune checkpoint inhibitor (ICI) treatment has not yet been studied. This preliminary study aimed to (a) examine the associations between psychological factors and responses to ICI treatment and (b) assess the associations between psychological factors and blood measures of sPD-1, sCTLA-4, and cytokines that may alter the effect of ICI treatment. The participants were 62 individuals with advanced cancer, aged 18 years or older, who were candidates for ICI treatment as a new line of treatment. The participants answered questionnaires and provided blood samples and medical data prior to the start of ICI treatment and 3 months after. Perceived health status was positively associated with better responses to ICI treatment. In the subsample of participants with biomarkers, worse health-related quality of life was associated with higher IL-6 and sCTLA-4; emotional distress and sleep difficulties were associated with higher sCTLA-4; and better perceived health was associated with lower IL-6 and TNFα. sPD-1 was not associated with psychological measures. This preliminary study found for the first time that some psychological measures could be linked to responses to cancer treatment, possibly via pro-inflammatory cytokines and sCTLA-4.

Second breast cancer: recurrence score results, clinicopathologic characteristics, adjuvant treatments, and outcomes-exploratory analysis of the Clalit registry.

Data on using the 21-gene Recurrence Score (RS) testing on second breast cancer (BC; second primary or local recurrence) are lacking. This cohort study examined patients with first and second BC, who underwent 21-gene testing both times. It included a 'study-cohort' (60 N0/N1mi/N1 ER + HER2‒ BC patients with ≥2 RS results >1 year apart) and a 'general 21-gene-tested BC-cohort' (2044 previously described N0/N1mi/N1 patients). The median time between the first and second BC was 5.2 (IQR, 3.1-7.1) years; the second BC was ipsilateral in 68%. Patient/tumor characteristics of the first- and second-BC in the 'study-cohort' were similar, except for the RS which was higher in the second BC (median [IQR]: 23 [17-30] vs 17 [14-22], p < 0.001). Overall, 56 patients had follow-up data, of whom 5 experienced distant recurrence (2 RS 11-25 patients and 3 RS 26-100 patients). Studies exploring the prognostic utility of the RS in this setting are warranted.

Associations Between Psycho-Social-Spiritual Interventions, Fewer Aggressive End-of-Life Measures, and Increased Time After Final Oncologic Treatment.

BACKGROUND: Little is known about the impact of spiritual caregivers, psychologists, and social workers on desired end-of-life (EoL) medical outcomes, such as reduced use of aggressive care in the final 2 weeks of life, having more time between the last active oncological treatment and death, and increased hospice use. PATIENTS AND METHODS: We conducted a prospective study of 180 patients with cancer and their families, their interactions with social work, psychology, and spiritual care, and the above three treatment outcomes. RESULTS: We found that having one or more spiritual care visits (adjusted odds ratio (AOR) = 2.02; P = .04), having more quality visits with the psychologist (P = .01), and speaking with someone about one's inner resources (AOR = 2.25; P = .03) all correlated with reduced EoL aggressive care. The key interventions correlating with increased time after final treatment were more visits with the spiritual caregiver or the social worker (AOR = 1.30; P < .001), and speaking about the medical treatment (AOR = 1.54; P < .001) and about interpersonal relationships (AOR = 2.28; P < .001). A subjectively good-quality connection with the spiritual caregiver correlated with increased hospice use (AOR = 10.00; P = .01). CONCLUSIONS: Patients with cancer who availed themselves of the spiritual care, psychology, and social work services, each profession in distinct ways, had significantly different outcomes in their EoL medical treatment, including undergoing fewer futile aggressive measures, having more time after their last active treatment, and using hospice services more. These outcomes directly bear on improved quality of life and reduced costs.

Avelumab for the treatment of locally advanced or metastatic Merkel cell carcinoma-A multicenter real-world experience in Israel.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare and aggressive malignancy of the skin, affecting predominantly the fair-skinned older population exposed to high levels of ultraviolet light. Immune suppression is considered a significant risk factor. With the recent advances in the field of immunotherapy, the treatment paradigm for advanced MCC, traditionally based on chemotherapy, has largely shifted to anti-PD-L1 and PD-1 agents such as avelumab and pembrolizumab, respectively. However, real-world data remain sparse. The aim of this study was to assess real-world evidence of the effectiveness of avelumab in a diverse group of patients with MCC in Israel. METHODS: The electronic databases of five university hospitals in Israel were searched for all consecutive patients with MCC treated with at least one dose of avelumab in 2018-2022. Data on baseline, disease-related, treatment-related, and outcome parameters were collected and analyzed. RESULTS: The cohort included 62 patients of whom 22% were immune-suppressed. The overall response rate to avelumab was 59%. The median progression-free survival was 8.1 months, and the median overall survival, 23.5 months, with no differences between immune-competent and immune-suppressed patients. Treatment was well tolerated; any-grade toxicity developed in 34% of patients, and grade 3-4 toxicity, in 14%. CONCLUSIONS: Avelumab was found to be effective and safe for the treatment of advanced MCC in a diverse group of patients, including some with immune suppression. Further studies are warranted to evaluate the optimal sequence and duration of treatment and to assess the potential role of avelumab for earlier stages of MCC.

The Humoral Response of Patients With Cancer to Breakthrough COVID-19 Infection or the Fourth BNT162b2 Vaccine Dose.

Since January 2022 in Israel, high-risk populations with underlying health conditions were advised to receive a fourth dose of the BNT162b2 vaccine (Pfizer-BioNTech) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We monitored vaccine-induced immunity among oncology patients undergoing systemic anti-cancer therapy before and after the 4th-BNT162b2-dose. Three groups of patients were included in the study: those who received 3rd-BNT162b2-dose and had no breakthrough infection (control), those who received 3rd-BNT162b2-dose and had the breakthrough infection, and those who received the 4th-BNT162b2-dose and had no breakthrough infection. Anti-SARS-CoV-2 immunoglobulin-G (IgG) levels of the control group exhibited a rapid decrease over time, whereas IgG titers of patients with breakthrough-infections or patients vaccinated with the 4th-BNT162b2-dose were considerably elevated, consistent with the capacity of the second booster to induce anti-SARS-CoV-2 IgG levels. Additionally, oncology patients' humoral immune response was significantly greater after breakthrough-infection than in response to the 4th dose of BNT162b2.

Endothelial Progenitor Cells Promote Osteosarcoma Progression and Invasiveness via AKT/PI3K Signaling.

BACKGROUND: Osteosarcoma (OS) mortality is attributed to lung metastases. Endothelial progenitor cells (EPCs) mediate the angiogenic switch in several cancers. The spatial proximity between EPCs and OS in the bone led to the hypothesis that EPCs-osteosarcoma interactions may possibly promote OS progression and aggressiveness. METHODS: A PI3K inhibitor, Bevacizumab (an anti-VEGF-A antibody), and an anti-FGF2 antibody were added to the EPCs' conditioned medium (EPC-CM), and their impacts on OS cell (U2-OS and 143B) proliferation, migration, invasion, MMP9 expression, and AKT phosphorylation were determined. The autocrine role of VEGF-A was assessed using Bevacizumab treatment and VEGF-A silencing in OS cells. Toward this end, an orthotopic mouse OS model was established. Mouse and human tumors were immunolabeled with antibodies to the abovementioned factors. RESULTS: EPC-CM enhanced osteosarcoma MMP9 expression, invasiveness, and migration via the PI3K/AKT pathway. The addition of Bevacizumab and an anti-FGF2 antibody to the EPC-CM diminished OS cell migration. The autocrine role of VEGF-A was assessed using Bevacizumab and VEGF-A silencing in OS cells, resulting in decreased AKT phosphorylation and, consequently, diminished invasiveness and migration. Consistently, OS xenografts in mice displayed high VEGF-A and FGF2 levels. Remarkably, lung metastasis specimens derived from OS patients exhibited marked immunolabeling of CD31, VEGF-A, and FGF2. Conclusions: EPCs promote OS progression not only by physically incorporating into blood vessels, but also by secreting cytokines, which act via paracrine signaling. EPCs induced in vitro MMP9 overexpression, invasion, and migration. Additional animal studies are warranted to further expand these results. These findings may pave the way toward the development of novel EPCs-targeted therapeutics aimed at blocking OS metastasis.

Positive affect and fatigue as predictors of anti-inflammatory IL-10 concentrations among colorectal cancer patients during adjuvant chemotherapy.

OBJECTIVES: (1) To examine the relationships of positive and negative affect and symptoms of depression, anxiety, and fatigue at baseline with the anti-inflammatory cytokine IL-10 concentrations in serum at three points in colorectal cancer patients; and (2) to assess the relationship between these factors and disease recurrence or mortality after a median follow-up of 24 months. METHODS: In a prospective trial, 92 stage II or III colorectal cancer patients scheduled to receive standard chemotherapy were enrolled. Blood samples were collected prior to start of chemotherapy onset (T0), 3 months later (T1), and upon chemotherapy completion (T2). RESULTS: IL-10 concentrations were similar across the time points. Linear mixed-effects model analysis showed that controlling for confounders, higher positive affect and lower fatigue pretreatment (T0) predicted IL-10 concentrations across the time points (estimate = 0.18, SE = 0.08, 95% CI = 0.03, 0.34, p < .04 and estimate = -0.25, SE = 0.12, 95% CI = -0.50, 0.01, p < .04, respectively). Depression at T0 significantly predicted higher disease recurrence and mortality (estimate = 0.17, SE = 0.08, adjusted OR = 1.18, 95% CI = 1.02, 1.38, p = .03). CONCLUSIONS: We report on associations not previously assessed between positive affect and fatigue and the anti-inflammatory cytokine IL-10. Results add to previous findings suggesting that positive affect and fatigue could have a role in anti-inflammatory cytokine dysregulation.

Oncology-Led Early Identification of Nutritional Risk: A Pragmatic, Evidence-Based Protocol (PRONTO).

Nutritional issues, including malnutrition, low muscle mass, sarcopenia (i.e., low muscle mass and strength), and cachexia (i.e., weight loss characterized by a continuous decline in skeletal muscle mass, with or without fat loss), are commonly experienced by patients with cancer at all stages of disease. Cancer cachexia may be associated with poor nutritional status and can compromise a patient's ability to tolerate antineoplastic therapy, increase the likelihood of post-surgical complications, and impact long-term outcomes including survival, quality of life, and function. One of the primary nutritional problems these patients experience is malnutrition, of which muscle depletion represents a clinically relevant feature. There have been recent calls for nutritional screening, assessment, treatment, and monitoring as a consistent component of care for all patients diagnosed with cancer. To achieve this, there is a need for a standardized approach to enable oncologists to identify patients commencing and undergoing antineoplastic therapy who are or who may be at risk of malnutrition and/or muscle depletion. This approach should not replace existing tools used in the dietitian's role, but rather give the oncologist a simple nutritional protocol for optimization of the patient care pathway where this is needed. Given the considerable time constraints in day-to-day oncology practice, any such approach must be simple and quick to implement so that oncologists can flag individual patients for further evaluation and follow-up with appropriate members of the multidisciplinary care team. To enable the rapid and routine identification of patients with or at risk of malnutrition and/or muscle depletion, an expert panel of nutrition specialists and practicing oncologists developed the PROtocol for NuTritional risk in Oncology (PRONTO). The protocol enables the rapid identification of patients with or at risk of malnutrition and/or muscle depletion and provides guidance on next steps. The protocol is adaptable to multiple settings and countries, which makes implementation feasible by oncologists and may optimize patient outcomes. We advise the use of this protocol in countries/clinical scenarios where a specialized approach to nutrition assessment and care is not available.

Primary cemiplimab treatment for orbital squamous cell carcinoma is effective and may alleviate the need for orbital exenteration.

PURPOSE: To evaluate the effectiveness of cemiplimab, a Programmed-cell-death-1(PD-1) protein inhibitor, for the treatment of cutaneous periocular-locally-advanced squamous-cell-carcinoma (POLA-SCC) with orbital-invasion. METHODS: Multicentre real-world retrospective study. Demographic and clinical data were collected and analysed for patients with biopsy-proven POLA-SCC(AJCC-T4) with orbital-invasion who were treated with cemiplimab at one of four tertiary medical centres in 2019-2022. RESULTS: The cohort included 13 patients, 8 males and 5 females, of median age 76 years (IQR65-86). The median duration of treatment was 5.0months (IQR3.5-10.5) and the median follow-up time, 15.0 months (IQR10.5-30). The overall response rate was 69.2%. Complete response was documented in seven patients (53.8%), partial response in two (15.4%), stable disease in one (7.7%), and progressive disease in two (15.4%); in one patient (7.7%), response was not evaluable. Six complete responders (46.1% of the cohort) received no further treatment and did not have a recurrence during an average follow-up of 6.14 (±6.9) months from treatment cessation. None of the patients underwent orbital-exenteration. The majority of adverse events were mild (grade-1), except for a moderate increase in creatinine level (grade-2), severe bullous dermatitis (grade-3), and myocarditis (grade-5) in one patient each. Four patients (30.7%) died during the follow-up period, all of whom had an Eastern-Cooperative-Oncology-Group score of 4 at presentation. CONCLUSIONS: To our knowledge, this is the largest study to date on cemiplimab therapy for cutaneous POLA-SCC with orbital-invasion. Treatment was shown to be effective, with an overall response rate of 69.2%. Cemiplimab holds promise for the treatment of patients with tumours invading the orbit as it may alleviate the need for orbital exenteration.

Rhabdomyolysis Induced by the Interaction Between Ribociclib and Statins- Case Report and Literature Review.

Cyclin-dependent kinase (CDK) 4/6 inhibitors given with endocrine therapy are standard of care for the treatment of women with advanced hormone receptor (HR) positive and human epidermal growth factor receptor 2 (HER-2) negative breast cancer. Ribociclib is a CDK 4/6 inhibitor with moderate to solid inhibition of CYP3A4, a member of the cytochrome P450 family oxidase system, which may lead to interactions with medicinal substrates that are metabolized via CYP3A4. Statins are among the most widely prescribed medications worldwide, predominantly metabolized by the CYP3A4 isoenzyme. Rhabdomyolysis is a known rare side effect of statins, commonly triggered by drug interactions. We report a case of a 73-year-old woman with metastatic HR-positive and HER-2 negative breast cancer who developed rhabdomyolysis and acute kidney injury due to interaction between simvastatin and ribociclib with a literature review.

Advance Care Planning and Attainment of Cancer Patients' End-of-Life Preferences: Relatives' Perspective.

PURPOSE: The purpose of this study is to determine which element of advance care planning (ACP) - an advance directives (AD) document or an end-of-life discussion between patient and family (DwF), if any-improves the likelihood of cancer patients' attaining their preferences regarding treatments in the last month of life and dying in the place they prefer. METHODS: First-degree relatives of deceased cancer patients, interviewed by telephone, were asked if the treatments the patients received in their last month of life and their place of death corresponded to the patients' preferences. Nominal logistic regression analyses were conducted in search of significant association between having an AD document and/or conducting a DwF and patients' treatment and place of death in accordance with their preferences. RESULTS: 491 deceased patients were included in the study. Their average age was 68; 52% were women. According to 32% of the relatives, the patients' treatment in the last month of life was aligned with their preferences and 55% said the patients had died in their preferred place. Only 16.5% had an AD document, 58.5% only discussed their treatment preferences with relatives, and 25% did neither. DwF and ability to speak until last week of life were significantly related to receiving treatment consistent with patients' preferences. Dying where the patient prefers is significantly associated with having an AD and a DwF, with an AD yielding higher odds. CONCLUSION: A multifaceted interconnection exists between the two elements of ACP in attaining cancer patients' wishes and abetting better end of life care.

Deep learning-based image analysis predicts PD-L1 status from H&E-stained histopathology images in breast cancer.

Programmed death ligand-1 (PD-L1) has been recently adopted for breast cancer as a predictive biomarker for immunotherapies. The cost, time, and variability of PD-L1 quantification by immunohistochemistry (IHC) are a challenge. In contrast, hematoxylin and eosin (H&E) is a robust staining used routinely for cancer diagnosis. Here, we show that PD-L1 expression can be predicted from H&E-stained images by employing state-of-the-art deep learning techniques. With the help of two expert pathologists and a designed annotation software, we construct a dataset to assess the feasibility of PD-L1 prediction from H&E in breast cancer. In a cohort of 3,376 patients, our system predicts the PD-L1 status in a high area under the curve (AUC) of 0.91 - 0.93. Our system is validated on two external datasets, including an independent clinical trial cohort, showing consistent prediction performance. Furthermore, the proposed system predicts which cases are prone to pathologists miss-interpretation, showing it can serve as a decision support and quality assurance system in clinical practice.

The association between geriatric assessment, muscle measures, and treatment-related toxicity in older adults with cancer: An Israeli prospective study.

INTRODUCTION: We investigated the associations among frailty, as determined via the comprehensive geriatric assessment (CGA), muscle measures (i.e., sarcopenia), and treatment-related toxicity in older adults with cancer in Israel. MATERIALS AND METHODS: This prospective cohort study enrolled patients ≥65 years with newly-diagnosed stage IV lung, breast, or genitourinary cancer. Patients were enrolled and completed CGA before their first line of systemic therapy (chemotherapy, biologic therapy, immunologic therapy, or a combination thereof). CGA was used to classify patients as robust, pre-frail, or frail, and routine pre-treatment computed tomography (CT) images were used to quantify skeletal muscle index (SMI) and skeletal muscle density (SMD) at L3 cross-section. Two sarcopenia definitions were used: i. for women SMI <41 cm2/m2 regardless of body mass index (BMI), and for men SMI <43 cm2/m2 for those with BMI of <25 and < 53 cm2/m2 for those with BMI ≥25; and ii. SMI <38 cm2/m2 for women and < 41 cm2/m2 for men, regardless of BMI. The associations between frailty and muscle measures with the occurrence of at least one adverse event (AE) grade ≥ 2 were examined using the chi-square test, and logistic regression to determine odds ratio (OR) and 95% confidence interval (CI). RESULTS: In total, 51 patients were included in the analysis. The median (interquartile range) age was 72 (68-76) years, 30 (59%) were male, and 26 (51%) had lung cancer. CGA data were available for 48 patients: fifteen (31%), thirteen (27%), and twenty (42%) were defined as robust, pre-frail, and frail, respectively. Overall, 33 (65%) were sarcopenic by the first aforementioned definition, and sixteen (31%) by the second. No statistically significant associations were identified between frailty and having at least one AE grade ≥ 2, or between frailty and sarcopenia. Statistically significant associations were found between having sarcopenia (the second definition) and having at least one AE grade ≥ 2 (P = 0.0217). The corresponding odds ratio (95% CI) was 4.2 (1.2-15.0), P = 0.026. DISCUSSION: Our findings suggests that sarcopenia is significantly associated with treatment-related toxicity. Further studies with larger sample sizes are warranted.