Outcomes of extracranial stereotactic body radiation therapy for induced oligometastatic non-small cell lung cancer on novel systemic therapy.

Background: Stereotactic body radiation therapy (SBRT) is often delivered in patients with oligometastatic disease (OMD). However, the specific subset of patients with polymetastatic non-small cell lung cancer (NSCLC) on novel systemic therapies who develop induced oligopersistant disease (OpersisD) or oligoprogressive disease (OprogD), as defined by the European Organisation for Research and Treatment of Cancer (EORTC) OMD classification, has not been well described. This study explores the outcomes of patients treated with this strategy. Methods: Patients with stage IV NSCLC being treated with osimertinib or immune checkpoint inhibitors (ICIs) who received extracranial SBRT for OpersisD or OprogD were identified in our retrospective analysis. Outcomes reported include progression-free survival (PFS), time to change of systemic treatment (TTCST), overall survival (OS), local control (LC) and treatment-related toxicity. Results: Forty-nine patients received SBRT for OpersisD (34.7%) or OprogD (65.3%) at a median of 5.8 and 15.3 months after start of systemic therapy, respectively. 55.1% received concurrent osimertinib and 44.9% received ICI. Seventy-seven extracranial lesions were treated with various fractionation schemas. At a median of 18.8 months follow-up from first SBRT, LC was achieved in 92.2% of total lesions treated (71). The 1-year OS was 91.7% for OpersisD and 83.3% for OprogD. OpersisD compared to OprogD had a longer median PFS (18.3 vs. 6.1 months) and longer median TTCST (23.6 vs. 13.5 months), median OS was not reached for either cohort. On multivariate analysis, patients treated with osimertinib had shorter PFS (HR: 2.20; 95% CI: 1.01-4.82; P=0.048) and shorter TTCST (HR: 2.83; 95% CI: 1.09-7.33; P=0.032). One patient (2%) experienced grade 3 pneumonitis after SBRT, and no grade 4-5 toxicities were reported with SBRT treatment. Conclusions: This study indicates that SBRT for OpersisD or OprogD in Stage IV NSCLC patients on osimertinib or ICIs is safe, very well tolerated, and may prolong the time before needing a shift in systemic therapy. Further prospective research is needed to validate and expand upon these findings.

Multimodal Machine Learning for Prediction of 30-Day Readmission Risk in Elderly Population.

BACKGROUND: Readmission within 30 days is a prevalent issue among elderly patients, linked to unfavorable health outcomes. Our objective was to develop and validate multimodal machine learning models for predicting 30-day readmission risk in elderly patients discharged from internal medicine departments. METHODS: This was a retrospective cohort study which included elderly patients aged 75 or older, who were hospitalized at the Hadassah Medical Center internal medicine departments between 2014 and 2020. Three machine learning algorithms were developed and employed to predict 30-day readmission risk. The primary measures were predictive model performance scores, specifically area under the receiver operator curve (AUROC), and average precision. RESULTS: This study included 19,569 admissions. Of them, 3258 (16.65%) resulted in 30-day readmission. Our 3 proposed models demonstrated high accuracy and precision on an unseen test set, with AUROC values of 0.87, 0.89, and 0.93, respectively, and average precision values of 0.76, 0.78, and 0.81. Feature importance analysis revealed that the number of admissions in the past year, history of 30-day readmission, Charlson score, and admission length were the most influential variables. Notably, the natural language processing score, representing the probability of readmission according to a textual-based model trained on social workers' assessment letters during hospitalization, ranked among the top 10 contributing factors. CONCLUSIONS: Leveraging multimodal machine learning offers a promising strategy for identifying elderly patients who are at high risk for 30-day readmission. By identifying these patients, machine learning models may facilitate the effective execution of preventive actions to reduce avoidable readmission incidents.

Effects of aquatic exercise program versus on-land exercise program on cancer-related fatigue, neuropathy, activity and participation, quality of life, and return to work for cancer patients: study protocol for a randomized controlled trial.

BACKGROUND: Exercise has shown positive effects on fatigue, exhaustion, neuropathy, and quality of life in cancer patients. While on-land exercises have been studied, the aquatic environment offers unique advantages. Water's density and viscosity provide resistance, enhancing muscle strength, while hydrostatic pressure improves venous return. This trial aims to investigate the effect of aquatic exercises on time to return to work, work hours, work-related difficulties, daily life activity and participation, quality of life, exhaustion, fatigue, and neuropathy among cancer patients, compared to on-land exercise intervention group and a non-exercise group. METHODS: This randomized controlled trial will include 150 cancer patients aged 18-65 years with stage III colon cancer or breast cancer patients with lymph node involvement. Participants in the aquatic exercise intervention group will undergo an 8-week, twice-weekly group-based Ai-Chi program, while the on-land exercise group will perform identical exercise. The control group will not engage in any exercise. The primary outcome will be assessed using an employment barriers questionnaire, capturing return to work date and working hours and daily life participation and activity and quality of life. Secondary outcomes include exhaustion, fatigue, and neuropathy. Data will be collected at baseline, post-intervention (8 weeks), and at 3,12, and 24 months. Mixed variance analyses will explore relationships among groups and over time for independent variables, with separate analyses for each dependent variable. DISCUSSION: The potential benefits include an earlier return to work for patients, reducing their need for social and economic support. The study's implications on socio-economic policies are noteworthy, as a successful intervention could offer a cost-effective and non-invasive solution, improving patients' quality of life and increasing their participation in daily activities. This, in turn, could lead to a faster return to work, contributing to both personal well-being and broader societal interests by reducing reliance on social services. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov NCT05427344 (22 June 2022).

A clinical evaluation of an ex vivo organ culture system to predict patient response to cancer therapy.

Introduction: Ex vivo organ cultures (EVOC) were recently optimized to sustain cancer tissue for 5 days with its complete microenvironment. We examined the ability of an EVOC platform to predict patient response to cancer therapy. Methods: A multicenter, prospective, single-arm observational trial. Samples were obtained from patients with newly diagnosed bladder cancer who underwent transurethral resection of bladder tumor and from core needle biopsies of patients with metastatic cancer. The tumors were cut into 250 µM slices and cultured within 24 h, then incubated for 96 h with vehicle or intended to treat drug. The cultures were then fixed and stained to analyze their morphology and cell viability. Each EVOC was given a score based on cell viability, level of damage, and Ki67 proliferation, and the scores were correlated with the patients' clinical response assessed by pathology or Response Evaluation Criteria in Solid Tumors (RECIST). Results: The cancer tissue and microenvironment, including endothelial and immune cells, were preserved at high viability with continued cell division for 5 days, demonstrating active cell signaling dynamics. A total of 34 cancer samples were tested by the platform and were correlated with clinical results. A higher EVOC score was correlated with better clinical response. The EVOC system showed a predictive specificity of 77.7% (7/9, 95% CI 0.4-0.97) and a sensitivity of 96% (24/25, 95% CI 0.80-0.99). Conclusion: EVOC cultured for 5 days showed high sensitivity and specificity for predicting clinical response to therapy among patients with muscle-invasive bladder cancer and other solid tumors.

Clinical Characteristics, Response to Platinum-Based Chemotherapy and Poly (Adenosine Phosphate-Ribose) Polymerase Inhibitors in Advanced Lung Cancer Patients Harboring BRCA Mutations.

The oncogenic role and clinical relevance of BRCA mutations in NSCLC remain unclear. We aim to evaluate the characteristics and clinical outcomes of patients with NSCLC harboring BRCA mutations treated at Hadassah Medical Center (HMC). We retrospectively assessed all patients with advanced NSCLC who underwent next-generation sequencing (NGS) and were found to have pathogenic somatic BRCA mutations (p-BRCA). We compared clinical outcomes in NSCLC patients with wild-type BRCA (wt-BRCA) matched by age, stage, gender, smoking, PDL-1 and driver mutations. Between 2015 and 2022, we evaluated 598 patients with advanced NSCLC using NGS and found 26 patients with p-BRCA, of whom 17 (65.4%) were carriers of germline BRCA variants and represented 1% of all BRCA carriers HMC. The median age of diagnosis was 67 years old (40-78), 13 patients (50%) had a history of smoking and 9 patients (34.6%) had additional driver mutations (EGFR, ALK, BRAF, MET or ERBB2). Objective response rate and median progression-free survival (PFS) for first-line platinum-based chemotherapy in the p-BRCA group compared to wt-BRCA controls were 72.2% and 16 months (CI 95%, 5-22), compared to 47.4% and 7 months (CI 95%, 5-9), respectively, and HR for PFS was 0.41 (CI 95%, 0.17-0.97). Six patients in the p-BRCA group were treated with advanced-line poly (adenosine-phosphate-ribose) polymerase inhibitors (PARPi), with a durable response observed in four patients (66%). In this cohort, patients with NSCLC harboring p-BRCA exhibit high-sensitivity PARPi and a prolonged response to platinum, suggesting some oncogenic role for BRCA mutations in NSCLC. The results support further prospective trials of the treatment of NSCLC harboring p-BRCA with PARPi.

Late life depression and concepts of aging: an emerging paradigm.

Late life depression (LLD) is an emerging challenge, and recognized as a significant barrier to long-term healthy aging. Viewed within the context of the medical/biological model, advances in brain sciences over the last several decades have led to a deeper understanding of the biology of LLD. These advances in current knowledge include the description of aging brain pathophysiology; the biology and biochemistry of neurotransmitters; the correspondence between changes in neurological structure, function, and neural network; the description of neural, hormonal and inflammatory biomarkers; and identification of typical phenotypic subtypes of LLD. Despite these advances, current treatment of LLD, which remains largely pharmacological with accompanying cognitive and behavioral interventions, has poor success rate for long-term remission among older people. A wider perspective, in keeping with several emerging aging concepts, is suggested as an alternative framework within which to view LLD. A growing body of research supports the important role in LLD of frailty, resilience, intrinsic capacity, and functional integrity. Similarly, important social determinants need to be addressed in the etiology of LLD, rooted largely in negative stereotypes of aging, with consequent repercussions of reduced participation and inclusion, growing social isolation, with loss of identity, meaning and hope. This perspective suggests the importance of a wider integrative conceptualization of depression, set against a background of emerging aging concepts.

Paclitaxel Delivery to the Brain for Glioblastoma Treatment.

The development of paclitaxel-loaded polymeric nanoparticles for the treatment of brain tumors was investigated. Poly(lactide-glycolide) (PLGA) nanoparticles containing 10% w/w paclitaxel with a particle size of 216 nm were administered through intranasal and intravenous routes to male Sprague-Dawley rats at a dose of 5 mg/kg. Both routes of administration showed appreciable accumulation of paclitaxel in brain tissue, liver, and kidney without any sign of toxicity. The anti-proliferative effect of the nanoparticles on glioblastoma tumor cells was comparable to that of free paclitaxel.

Comparing end-of-life care of hematologic malignancy versus solid tumor patients in a tertiary care center.

OBJECTIVES: To compare end-of-life (EOL) care for solid tumor and hematologic malignancy (HM) patients. METHODS: We collected data on the last 100 consecutive deceased HM and 100 consecutive deceased solid tumor patients who died prior to June 1st 2020, treated at a single center. We compared demographic parameters, cause of death as ascertained by review of medical records by two independent investigators, and EOL quality indicators including: place of death, use of chemotherapy or targeted/biologic treatment, emergency department visits as well as hospital, inpatient hospice and Intensive Care Unit admissions and the time spent as inpatient over the last 30 days of life; mechanical ventilation and use of blood products during the last 14 days of life. RESULTS: In comparison with solid tumor patients, HM patients more commonly died from treatment complications (13% vs. 1%) and unrelated causes (16% vs. 2%, p < .001 for all comparisons). HM patients died more frequently than solid tumor patients in the intensive care unit (14% vs. 7%) and the emergency department (9% vs. 0%) and less frequently in hospice (9% vs. 15%, p = .005 for all comparisons). In the 2 weeks prior to death HM patients were more likely than solid tumor patients to undergo mechanical ventilation (14% vs. 4%, p = .013), receive blood (47% vs. 27%, p = .003) and platelet transfusions (32% vs. 7%, p < .001); however, no statistical difference was found in use of either of chemotherapy (18% vs. 13%, p = .28) or targeted treatment (10% vs. 5%, p = .16). CONCLUSIONS: HM patients were more likely than solid tumor patients to undergo aggressive measures at EOL. Rarity of HM deaths, frequently caused by complications of treatment and unrelated causes, may affect treatment choices at EOL.

Driver mutation characteristics of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) in advanced non-small cell lung cancer.

OBJECTIVES: The identification and targeting of actionable genomic alterations (AGA) have revolutionized the treatment of cancer in general and mostly for non-small cell lung cancer (NSCLC). We investigated whether in NSCLC patients PIK3CA mutations are actionable. MATERIALS AND METHODS: Chart review was performed of advanced NSCLC patients. PIK3CA mutated patients were analyzed as two groups: Group A: without any non-PIK3CA established AGA; Group B: with coexisting AGA. Group A was compared to a cohort of non-PIK3CA patients (group C), using t-test and chi-square. To evaluate the impact of PIK3CA mutation on outcome, we compared Group A survival to age/sex/histology matched cohort of non-PIK3CA mutated patients (group D) by Kaplan-Meier method. A patient with a PIK3CA mutation was treated with a PI3Ka-isoform selective inhibitor BYL719 (Alpelisib). RESULTS: Of a cohort of 1377 patients, 57 are PIK3CA mutated (4.1%). Group A: n-22, group B: n-35. Group A median age is 76 years, 16 (72.7%) men, 10 (45.5%) squamous, 4 (18.2%) never smokers. Two never-smoker female adenocarcinoma patients had solitary PIK3CA mutation. One of them was treated with a PI3Ka-isoform selective inhibitor BYL719 (Alpelisib), with rapid clinical and partial radiological improvement. Group B, compared with Group A, included younger patients (p = 0.030), more females (p = 0.028) and more adenocarcinoma cases (p < 0.001). Compared to group C, group A patients were older (p = 0.030) and had more squamous histology (p = 0.011). CONCLUSION: In a small minority of NSCLC patients with PIK3CA mutation there are no additional AGA. PIK3CA mutations may be actionable in these cases.

Preclinical In-Vivo Safety of a Novel Thyrotropin-Releasing Hormone-Loaded Biodegradable Nanoparticles After Intranasal Administration in Rats and Primates.

Thyrotropin-releasing hormone (TRH) and TRH-like peptides carry a therapeutic potential for neurological conditions. Nanoparticles (NP) made of the biodegradable polymer, Poly(Sebacic Anhydride) (PSA), have been developed to carry TRH, intended for intranasal administration to patients. There is limited information on the safety of biodegradable polymers when given intranasally, and therefore, we have performed two preclinical safety and toxicity studies in cynomolgus monkeys and rats using TRH-PSA nanoparticles. The rats and monkeys were dosed intranasally for 42 days or 28 days, respectively, and several animals were followed for additional 14 days. Animals received either placebo, vehicle (PSA), or different concentrations of TRH-PSA. No systemic adverse effects were seen. Changes in T3 or T4 concentrations were observed in some TRH-PSA-treated animals, which did not have clinical or microscopic correlates. No effect was seen on TSH or prolactin concentrations. In the monkey study, microscopic changes in the nasal turbinates were observed, which were attributed to incidental mechanical trauma caused during administration. Taken together, the TRH-loaded PSA NPs have proven to be safe, with no local or systemic adverse effects attributed to the drug loaded nanoparticles. These findings provide additional support to the growing evidence of the safety of peptide-loaded NPs for intranasal delivery and pave the way for future clinical trials in humans.

UNcommon EGFR Mutations: International Case Series on Efficacy of Osimertinib in Real-Life Practice in First-LiNe Setting (UNICORN).

INTRODUCTION: Approximately 10% of EGFR mutations (EGFRmuts) are uncommon (ucEGFRmuts). We aimed to collect real-world data about osimertinib for patients with ucEGFRmuts. METHODS: This is a multicenter, retrospective study of ucEGFRmut (exon 20 insertions excluded) metastatic NSCLC treated with osimertinib as first EGFR inhibitor. The Response Evaluation Criteria in Solid Tumors and response assessment in neuro-oncology brain metastases brain objective response rate (ORR) were evaluated by the investigators. Median progression-free survival (mPFS), median overall survival, and median duration of response (mDOR) were calculated from osimertinib initiation. Mutations found at resistance were collected. RESULTS: A total of 60 patients were included (22 centers, nine countries), with median age of 64 years, 75% females, and 83% Caucasian. The largest subgroups were G719X (30%), L861Q (20%), and de novo Thr790Met (T790M) (15%). The ORR was 61%, mPFS 9.5 months, mDOR 17.4 months, and median overall survival 24.5 months. Regarding patients with no concurrent common mutations or T790M (group A, n = 44), ORR was 60%, mPFS 8.6 months, and mDOR 11 months. For G719X, ORR was 47%, mPFS 8.8 months, and mDOR 9.1 months. For L861Q, ORR was 80%, mPFS 16 months, and mDOR 16 months. For de novo T790M, ORR was 44%, mPFS 12.7 months, and mDOR 46.2 months. Compound EGFRmut including common mutations had better outcome compared with only ucEGFRmut. For 13 patients with a response assessment in neuro-oncology brain metastases-evaluable brain metastases, brain ORR was 46%. For 14 patients, rebiopsy results were analyzed: four patients with additional EGFR mutation (C797S, D585Y, E709K), three with new TP53 mutation, one with c-Met amplification, one with PIK3CA mutation, and one with neuroendocrine transformation. CONCLUSIONS: Osimertinib was found to have an activity in ucEGFRmut with a high rate of disease control systemically and intracranially. Several resistance mechanisms were identified. This report comprises, to the best of our knowledge, the largest data set of its kind.

Liquid First Is "Solid" in Naïve Non-Small Cell Lung Cancer Patients: Faster Turnaround Time With High Concordance to Solid Next-Generation Sequencing.

Purpose: Molecular profiling is crucial in naïve non-small cell lung cancer (NSCLC). While tissue-based analysis is challenged by turnaround time and scarcity of tissue, there is increasing demand for liquid biopsy. We aimed to analyze the use of upfront liquid biopsy as a molecular profiling approach. Methods: This retrospective multicenter, non-interventional study compared findings and turnaround times of liquid vs. standard-of-care (SOC) tissue-biopsy molecular profiling. The study included naïve advanced NSCLC patients with available liquid biopsy (Guardant360 CDx). Results: A total of 42 consecutive patients (60% men; median age, 69.5 [39-87] years; 86% stage IV NSCLC) were identified between September 2017 and December 2020. Liquid-biopsy analysis provided results for all 42 patients, whereas the tissue-based analysis failed in 5 (12%) patients due to insufficient tumor samples. In 17 patients, 18 actionable driver mutations were identified. Eleven mutations were detected by both approaches (i.e., concordance of 61%), 4 only by liquid biopsy and 3 only by tissue biopsy. The median time from the molecular request to receiving the molecular solid report on the last biomarker was 21 (range: 5-66) days, whereas the median time from blood draw to the liquid-biopsy results was 10.5 (7-19) days. The median time between the availability of liquid-biopsy findings and that of the last biomarker was 5 days. Treatment changes following the liquid-biopsy results were observed in 3 (7%) patients. Conclusion: Performing liquid-biopsy upfront is feasible and accurate and allows a shorter time for treatment in NSCLC, especially when tumor tissue is scarce.

Breast Cancer with Low Recurrence Score on Oncotype DX©: Interplay Between Early Recurrence, Lobular Histology and BRCA Mutation.

INTRODUCTION: The 21-gene recurrence score assay Oncotype DX© (ODX) has clear prognostic and predictive value regarding adjuvant chemotherapy. However, recent studies have shown the clinical distinctiveness of both BRCA1/2-driven early breast cancer (EBC) and invasive lobular (ILC) breast cancers. We evaluated the association between BRCA1/2-driven EBC/ILC and Oncotype DX failure despite a recurrence score ≤ 20. METHODS: Here, we describe a small cohort of 16 patients from our center who, despite a low recurrence score (RS) ≤ 20, suffered from early disease recurrence. Clinical parameters of our cohort of patients were compared to a cohort from the general population of Clalit Health Service (CHS). RESULTS: Median age at diagnosis in our cohort was significantly younger. BRCA mutational status was available in 14 patients in our cohort. A high percentage of these patients had BRCA1/2 mutations (35.7%), either germline (in 3) or somatic (in 2). Half of our cohort was diagnosed with lobular carcinoma (ILC) relative to 10-15% in the general population of BC (p = 0.02). The median time to recurrence was 44 months. CONCLUSION: BRCA1/2 mutation and ILC are highly represented in this cohort. Although our cohort is small, these data may suggest that a RS ≤ 20 in these subgroups may not reflect a low risk of recurrence.

Peptide loaded polymeric nanoparticles by non-aqueous nanoprecipitation.

It is always a challenge to encapsulate water-soluble peptides in polymer nanoparticle (NP) systems. We establish and validate our newly developed non-aqueous nanoprecipitation method to encapsulate neuro-peptides drugs such as oxytocin and Luteinizing hormone-releasing hormone (LHRH) in poly(sebacic anhydride) (PSA) NPs. NPs were prepared by a solvent-antisolvent process under a strict anhydrous environment to obtain high drug loading and to avoid premature PSA degradation and drug release. Dynamic light scattering (DLS) and Scanning Electron Microscopy (SEM) reveal the size for both drug loaded PSA NPs to âˆ¼ 300 nm. The drug loaded NPs were dispersible and spherical in shape with uniform morphology. The in vitro release profile of oxytocin from PSA NPs occurs with the burst release of âˆ¼ 50% within the first hour in the aqueous release medium, whereas LHRH release is comparatively slow. Thus, looking into the fast degrading properties of PSA and drug release behavior, the developed NPs can be used for direct delivery of the neuropeptides to the olfactory epithelium using a refillable nasal atomizer that deposits mist onto the olfactory neuro-epithelium. We also applied our developed method to prepare NPs of poly(lactic-co-glycolic acid) (PLGA), polylactic acid (PLA), and poly(ε-caprolactone) (PCL). A Thyrotropin releasing hormone (TRH) was used as the sample neuropeptide drug to validate our non-aqueous method. The results reveal the formation of TRH loaded PLGA, PLA and PCL NPs with 100% drug loading. TEM analysis shows the formation of spherical NPs, having similar release properties as those of PSA NPs. Overall, we report that our developed method is suitable for co-encapsulating hydrophilic drugs in polymer NPs with high drug loading and release properties.

dNLR-Based Score Predicting Overall Survival Benefit for The Addition of Platinum-Based Chemotherapy to Pembrolizumab in Advanced NSCLC With PD-L1 Tumor Proportion Score ≥50.

INTRODUCTION: Both pembrolizumab (P) as a monotherapy or in combination with platinum-based chemotherapy (PCT) represent standard first-line treatment options for advanced non-small cell lung cancer (aNSCLC) with PD-L1 tumor proportion score (TPS)≥50%. No predictive biomarkers exist to guide treatment decisions. METHODS: 423 consecutive patients with EGFR/ALK/ROS1-wild-type PD-L1 TPS≥50% aNSCLC receiving P (n = 302) or PCT (n = 121) as a first-line treatment were identified in the electronic databases of 5 Israeli cancer centers. Overall survival (OS, months [mo]) was assessed in correlation with blood biomarkers (BB: NLR, dNLR, PLR, SII, LIPI, ALI); a predictive score was developed. RESULTS: In the propensity score matching analysis (n = 236; 118 patients in each group matched for age, sex and ECOG PS), mOS was 17.2mo (95% CI, 13.2-36.5) and 21.3mo (95% CI, 14.8-NR) in groups P and PCT, respectively (P = .44). In group P, NLR, dNLR, PLR, LIPI, and ALI significantly correlated with OS in uni- and multivariate COX regression analyses (P < .05), whereas in group PCT, none of the BB demonstrated a significant correlation. A predictive score was developed (each parameter receiving one point): age≥65, female sex, never-smoking status, adenocarcinoma histology, dNLR≥3. In patients with predictive score 3-5, OS was significantly longer with PCT as compared to P: mOS NR (95% CI, 15.3-NR) and 8.7mo (95% CI, 5.8-13.7) (P = .0005), while OS didn't differ significantly in patients with predictive score 0-2 (P = .61). CONCLUSION: With the limitations of the retrospective analysis, the proposed dNLR-based score appears to predict OS with P and PCT.

Combined intracranial Acriflavine, temozolomide and radiation extends survival in a rat glioma model.

Glioblastomas have been historically difficult to treat with poor long-term survival. With novel strategies focused on targeting hypoxia-inducible factor (HIF) regulatory pathways, recent evidence has shown that Acriflavine (ACF) can effectively target glioma invasiveness and recurrence. However, local delivery of ACF and its combinatory effects with Temozolomide (TMZ) and radiation therapy (XRT) have not yet been optimized. In this study we test a novel polymeric matrix that can gradually release ACF at the tumor bed site in combination with systemic TMZ and XRT. In vitro cytotoxicity assays of ACF in combination with TMZ and XRT were performed on rodent and human cell lines with CCK-8 and flow cytometry. In vitro drug release was measured and intracranial safety was assessed in tumor-free animals. Finally, efficacy was assessed in an intracranial gliosarcoma model and combination therapy with TMZ and XRT evaluated. Combination therapy of ACF, TMZ, and XRT was able to reduce cell viability and induce apoptosis in glioma cells. In vitro and in vivo release of ACF was measured in benchtop and animal models. Efficacy was established in an in vivo gliosarcoma model in which intracranial ACF (p < 0.01) significantly improved median survival and the combination therapy of ACF, TMZ and XRT (p < 0.01) significantly improved median survival and led to long-term survival (LTS). We provide evidence that ACF, combined with TMZ and XRT, led to LTS in an intracranial model of rat gliosarcoma. These findings, in combination with the use of a novel polymeric matrix that allows more gradual drug delivery, constitute a first step in the translation of this novel strategy to human use.

Depression, hope and social support among older people with cancer: a comparison of Muslim Palestinian and Jewish Israeli cancer patients.

OBJECTIVES: Studies of depression in older Muslim Palestinians diagnosed with cancer are scarce. To gain insight into the psychological response and coping ability of this very large, globally distributed population, we collected data from older Muslim Palestinian people diagnosed with cancer concerning depression hope and perceived social support. Both hope and social support were selected because they can be manipulated through intervention and education, as shown in the geriatric literature. Data were compared to data collected from older Jewish Israeli people diagnosed with cancer. DESIGN: The study sample comprised 143 Muslim Palestinian and 110 Jewish Israeli people diagnosed with cancer, aged ≥ 65. All participants were either in treatment for active disease or within 6 months of such treatment. Self-administered measures included depression (the Five-Item Geriatric Depression Scale), perceived social support (Cancer Perceived Agents of Social Support Questionnaire) and hope (Snyder's Adult Hope Scale). RESULTS: Hope and depression were both found to be significantly higher among the Muslim Palestinian patients than in the Jewish Israeli participants. In both samples, higher levels of hope were associated with lower levels of depression, with this correlation stronger in the Jewish Israeli group. CONCLUSION: To improve the psychological wellbeing of patients, healthcare providers must exercise cultural sensitivity in their interactions, respecting the perspectives of both the patients and their families. Incorporating the concept of hope into the therapeutic dialogue and language may improve psychological wellbeing and synchronize the needs and expectations of patients, caregivers, and healthcare professionals, resulting in more equitable, effective and value-oriented care.

Informal caregivers of older Muslims diagnosed with cancer: A portrait of depression, social support, and faith.

OBJECTIVE: Islamic population constitute more than 20% of the world population and is growing rapidly. Nevertheless, data concerning informal caregiving to older Muslim patients diagnosed with cancer are scarce. Improving the well-being of caregivers is a vital step to optimal care for the patients themselves throughout the Muslim community and the world. This study focuses on a sample of Palestinian caregivers of older Muslim patients diagnosed with cancer living in East Jerusalem, the West Bank, and Gaza. The study aims to describe the socio-demographic characteristics of the caregivers and to understand their social support, and identify predictors of caregivers' depression. METHODS: A cross-sectional study of a convenience sample of 99 dyads of Palestinian patients (age ≥65) and their informal caregivers. Depression and social support were measured using the five items of the Geriatric Depression Scale and the Cancer Perceived Agents of Social Support questionnaire. RESULTS: Caregivers were most frequently adult children (52%) or spouses (32%), with male patients cared for by spouses (47.5%) or sons (32%), and female patients by daughters (50%). Clinical levels of depression were reported by 76% of the caregivers and 85% of patients. The significant predictors of caregiver depression were female gender, lower education, lower perceived social support from spouse and family, and higher perceived support from faith. SIGNIFICANCE OF RESULTS: Healthcare providers serving the study population should determine the position and role of the caregiver within the social and family structure surrounding the patients' families. This understanding may facilitate overcoming barriers to effective and meaningful social support.