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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.

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.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 SMI41 cmIn 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.Our findings suggests that sarcopenia is significantly associated with treatment-related toxicity. Further studies with larger sample sizes are warranted.

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.

Supplementary Figures 1-4, Methods and Materials from DNA Methyltransferase 1 and 3B Activate BAG-1 Expression via Recruitment of CTCFL/BORIS and Modulation of Promoter Histone Methylation

In a previous genomic analysis, using somatic methyltransferase (DNMT) knockout cells, we showed that hypomethylation decreased the expression of as many genes as were observed to increase, suggesting a previously unknown mechanism for epigenetic regulation. To address this idea, the expression of the BAG family genes was used as a model. These genes were used because their expression was decreased in DNMT1−/−, DNMT3B−/−, and double knockout cells and increased in DNMT1-overexpressing and DNMT3B-overexpressing cells. Chromatin immunoprecipitation analysis of the BAG-1 promoter in DNMT1-overexpressing or DNMT3B-overexpressing cells showed a permissive dimethyl-H3-K4/dimethyl-H3-K9 chromatin status associated with DNA-binding of CTCFL/BORIS, as well as increased BAG-1 expression. In contrast, a nonpermissive dimethyl-H3-K4/dimethyl-H3-K9 chromatin status was associated with CTCF DNA-binding and decreased BAG-1 expression in the single and double DNMT knockout cells. BORIS short hairpin RNA knockdown decreased both promoter DNA-binding, as well as BAG-1 expression, and changed the dimethyl-H3-K4/dimethyl-H3-K9 ratio to that characteristic of a nonpermissive chromatin state. These results suggest that DNMT1 and DNMT3B regulate BAG-1 expression via insulator protein DNA-binding and chromatin dynamics by regulating histone dimethylation. [Cancer Res 2008;68(8):2726–35]

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.

Background: The first invasive disease-free survival event in patients (pts) with estrogen receptor (ER)+ early-stage breast cancer (BC) is often contralateral BC, as reflected in the TAILORx data. We analyzed the CHS registry to study differences in RS results and clinicopathological characteristics between the primary and second primary BC. Methods: This exploratory analysis included all ER+ HER2-negative BC pts who underwent RS testing through CHS between 1/2006 and 12/2020 and for whom ≥2 RS results were identified which were >1 year apart. Results: In this timeframe, 11,040 RS assays were ordered through CHS for 10,659 unique patients. The current analysis included 62 pts for whom multiple RS assays were performed >1 year apart. All 62 pts were females; their median (interquartile [IQR]) age at diagnosis was 56 (44-63) yrs, and 77% were initially diagnosed with node-negative disease. The median (IQR) time between the first and the latest RS assay was 5.3 (3.1-7.6) yrs. Tumor characteristics for the first and subsequent (second/third) primary BC tumors are presented (Table). Clinicopathologic characteristics were overall similar between the first and second/third primary BC tumors. The RS results, however, were statistically significantly higher in the second/third primary BC (P=0.0002), and the RS distribution was also significantly different with more tumors in the RS 26-100 category in the second/third primary BC (P=0.0036) (Table). The median (IQR) difference in the RS results between the first and latest RS assay for all 62 pts was 6 (-0.25-11.25). In 46 pts, (74%), the latest BC tumor had higher RS (a median [IQR] difference of 9 [5-13]) compared to the first BC tumor, and in 15 pts (24%) it had lower RS (a median [IQR] difference of -6 [-10 to -3]). One pt (2%) had the same RS result in both tumors. In 42 pts (68%), the latest primary BC was ipsilateral and in 20 pts (32%), it was contralateral. A higher RS result was observed in 33/42 (79%) of pts with ipsilateral second primary BC, and in 13/20 (65%) of pts with contralateral second primary BC (P=NS, Chi-square test). Conclusions: In ER+ HER2-negative BC pts, the characteristics of the first and second/third primary BC tumors were overall similar except for the RS result which was generally higher in the second/third primary BC. First BC; 62 tumorsSecond/third BC; 65 tumorsMedian (IQR) tumor size in the greatest dimension, cm1.55 (1.0-2.2)1.5 (1.0-1.95)Tumor size category, n (%)≤1 cm16 (25.8%)18 (27.7%)>1 - 2 cm28 (45.2%)33 (50.8%)>218 (29.0%)10 (15.4%)Unknown0 (0%)4 (6.2%)Tumor grade category, n (%)Grade 19 (14.5%)6 (9.2%)Grade 232 (51.6%)39 (60.0%)Grade 311 (17.7%)10 (15.4%)Not applicable/Unknown10 (16.1%)10 (15.4%)Histology, n (%)Invasive ductal carcinoma49 (79.0%)51 (78.5%)Invasive lobular carcinoma8 (12.9%)11 (16.9%)Mucinous/colloid/papillary2 (3.2%)2 (3.1%)Other/unknown3 (4.8%)1 (1.5%)Recurrence Score Mean (SD)a 18 (10)24 (12)Median (IQR)17 (13-22)23 (17-30)RS categoryb, n (%)0-1525 (40.3%)13 (20.0%)16-2528 (45.2%)27 (41.5%)26-1009 (14.5%)25 (38.5%)aP = 0.0002 (Mann–Whitney test); bP = 0.0036 (Chi-square test) Citation Format: Shlomit Strulov Shachar, Michelle Leviov, Rinat Yerushalmi, Karen Drumea, Margarita Tokar, Lior Soussan-Gutman, Avital Bareket-Samish, Amir Sonnenblick, Noa Efrat Ben-Baruch, Shani Paluch-Shimon, Gil Bar Sela, Salomon M Stemmer. Differences in Recurrence Score (RS) results between primary and second primary breast cancer (BC): Exploratory analysis of the Clalit Health Services (CHS) registry [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 P1-08-14.

Purpose The COVID-19 pandemic presents specific challenges for cancer patients attending oncology treatment. Using a mixed-methods design (convergent parallel design), we aimed to assess the experience, perceptions, and reactions of cancer patients during the COVID-19 pandemic. Methods Participants were cancer patients receiving treatment at the hospital during the pandemic (July to August 2020). In study 1, 95 participants filled out a questionnaire measuring COVID-19 experiences and perceptions, psychological distress, and intolerance of uncertainty. In study 2, in-depth interviews were conducted with 10 cancer patients, probing their experience during the COVID-19 period. Results Most participants experienced the COVID-19 pandemic as a major threat that would affect future health, most attended all or most of their scheduled treatments, and their mean level of psychological distress was low. A mild decrease in social support was reported, and remote contacts and support from the community had not compensated for decreased person-to person contacts. In addition, intolerance of uncertainty was related to higher psychological distress, which was partially mediated by perceptions of threat. The analysis of in-depth interviews strengthened the quantitative findings by elucidating the experience of fear of contagion alongside determination to continue treatment. Conclusions and Implications for Cancer Survivors The mixed-methods design enabled us to examine the responses of cancer patients attending treatment. The findings suggest that in times of extreme uncertainty such as COVID-19, health experts need to screen cancer patients and survivors for emotional and instrumental support needs and identify patients and survivors with high intolerance of uncertainty as a risk factor for psychological distress.

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.

PURPOSE: Emergency cancer care constitutes a significant health care and patient burden. The purpose of this study was to identify characteristics of patients most fitting for treatment in an oncology-dedicated emergency department (OED). METHODS: Electronic files of patients with cancer seeking emergency services between April and June 2017 were retrospectively obtained from the hospital registry. Efficacy parameters were compared between patients treated in the OED and those treated in the general emergency department (GED). Using descriptive statistics and logistic regressions, patient- and treatment-related factors were correlated with effective care in the OED. RESULTS: More than half of the total 799 patients presented initially to the OED, of which 10.4% required GED referral. Treatment in the GED was associated with a higher rate of consultations, imaging, and hospitalization ( P < .001), with the cost of imaging alone four times that of the OED ($23,263 US dollars difference). The relative proportion of patients with cancer visiting the GED was reduced after founding the OED. In the OED, patient diagnoses included lung (33%), GI, and breast cancer, of which 85% were metastatic. Frequent chief complaints were pain (45%), GI, malaise, and respiratory symptoms. Referral to the GED was significant in those with genitourinary cancer, back pain ( P < .001), and neurologic symptoms, on biologic therapy, and with suspected oncological emergencies; conversely, disease symptoms (30% admissions) were well-controlled in the OED ( P = .003). CONCLUSION: Using minimal resources, the OED provides efficacious, cancer-focused care, suitable for the majority of acute admissions. Careful triage is recommended, as high-risk patients should be referred to the GED, where advanced multidisciplinary management is more readily available.

Background: The phase 1/2 KEYMAKER-U02 substudy 02C (NCT04303169) is evaluating neoadjuvant pembro + investigational agents or pembro alone followed by adjuvant pembro in stage IIIB-D melanoma. Results from patients treated with neoadjuvant pembro (anti-PD-1) + vibo (anti-TIGIT; arm 1), pembro + geba (coxsackievirus A21; arm 2), or pembro alone (arm 3) are presented. Methods: Eligible patients were ≥18 y with resectable stage IIIB, IIIC, or IIID melanoma per AJCC 8th ed criteria, ≥1 measurable lesion per RECIST v1.1, and ECOG PS ≤1. Patients were randomly allocated across open investigational arms. Before resection, patients in arm 1 received 2 administrations of pembro 200 mg Q3W + vibo 200 mg Q3W (cycle 1, day 1; cycle 2, day 1); patients in arm 2 received 1 administration of pembro 400 mg (cycle 1, day 8) + 5 administrations of geba at a fixed dose of 3 × 108 tissue culture infectious dose 50% during cycle 1 (days 1, 3, 5, 8, and 22); and patients in arm 3 received 1 administration of pembro 400 mg. Surgical resection was performed at week 6. At week 12, patients started adjuvant pembro 400 mg Q6W for ≤8 administrations (total treatment duration, ~1 y). Primary end points were safety and tolerability and pCR rate by central review. Secondary end points were near pCR rate and pPR rate by central review and RFS by investigator review. ORR per RECIST v1.1 and EFS by investigator review were exploratory. Results: At data cutoff (September 9, 2022), 66 patients had been assigned to treatment (arm 1 [pembro + vibo], n = 26; arm 2 [pembro + geba], n = 25; arm 3 [pembro alone], n = 15). Median follow-up was 14.1 mo (range, 8.0-26.1). Treatment-related AEs occurred in 92% of patients in arm 1, 84% in arm 2, and 80% in arm 3. Grade 3/4 treatment-related AEs occurred in 8%, 24%, and 7% of patients, respectively, with no grade 5 treatment-related AEs. 3 patients (12%) in arm 1, 5 (20%) in arm 2, and 0 in arm 3 discontinued any drug because of treatment-related AEs. Immune-mediated AEs or infusion reactions were reported in 31% of patients in arm 1, 32% in arm 2, and 27% in arm 3. The pCR rate was 38% (95% CI, 20-59) in arm 1, 28% (12-49) in arm 2, and 40% (16-68) in arm 3; the near pCR rate was 12% (2-30), 12% (3-31), and 7% ( Conclusions: Neoadjuvant pembro + vibo, pembro + geba, and pembro alone followed by adjuvant pembro had manageable safety and promising antitumor activity in patients with stage IIIB-D melanoma. Of the combination treatments, pembro + vibo showed the most promise. Citation Format: Reinhard Dummer, Caroline Robert, Richard A. Scolyer, Janis M. Taube, Michael T. Tetzlaff, Andrew Hill, Jean-Jacques Grob, David C. Portnoy, Celeste Lebbe, Muhammad A. Khattak, Jonathan Cohen, Gil Bar-Sela, Inderjit Mehmi, Ronnie Shapira Frommer, Nicolas Meyer, Yixin Ren, Mizuho Fukunaga-Kalabis, Clemens Krepler, Georgina V. Long. KEYMAKER-U02 substudy 02C: neoadjuvant pembrolizumab (pembro) + vibostolimab (vibo) or gebasaxturev (geba) or pembro alone followed by adjuvant pembro for stage IIIB-D melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT002.

Advance Care Planning aims to define the appropriate end-of-life care for cancer patients. It is designed to help patients acknowledge their preferences, values, and goals and to make decisions regarding their care accordingly. The process is beneficial for strengthening communication patterns and increasing quality of care; however, this process encounters several challenges such as patients’ difficulty in acknowledging the harsh existential truth regarding their mortality. Cultural perceptions and traditions, such as the idea of a “good death,” the role of family members, and attitudes regarding patient’s autonomy, have been found to significantly impact a person’s outlook toward end-of-life care. These values should be acknowledged and considered during Advance Care Planning in order to provide the most appropriate, culturally sensitive care.

Background: The RS assay is widely used in ER+ HER2-negative BC to guide treatment decisions. In TAILORx, RS distribution was similar in blacks vs whites and in Hispanics vs non-Hispanics. Also, TAILORx analyses revealed similar results across ethnic groups with endocrine therapy being consistently noninferior to chemotherapy (CT) plus endocrine therapy in RS 11-25 pts. We investigated RS distribution among Jewish vs Arab/Druze pts who underwent RS testing through Clalit Health Services (CHS), the largest HMO in Israel, as well as differences in CT use and clinical outcomes between these 2 ethnic groups. Methods: The RS distribution analysis included all CHS pts (regardless of nodal status) who were tested between 1/2006 and 2/2019. For the clinical outcomes analysis, we employed a dataset used in prior analyses (Stemmer et al, poster# 249, SG-BCC 2019) of node-negative pts who were tested between 1/2006 and 12/2009, and as such, it is a subset of the cohort used for the RS distribution analysis. The study was approved by the IRB of the CHS Community Division and was granted a waiver for obtaining pt consent. Results: The RS distribution analysis involved 9054 pts who were tested in the evaluated timeframe and for whom RS results and ethnicity information were available. These included 8223 (91%) Jews and 831 (9%) Arabs/Druze, approximately reflecting the proportion of BC cases diagnosed in the respective ethnic groups. The 2 groups were similar in their baseline pt/tumor characteristics except for age and tumor size (Table). RS distribution was also similar between the 2 ethnic groups (Table). The subset of node-negative pts for whom treatment and clinical outcomes are known included 1274 (93%) Jewish pts and 91 (7%) Arab/Druze pts. In this subset, the only statistically significant difference in pt/tumor characteristics between the ethnic groups was age (median [interquartile range]) of 60 [53-66] yrs in the Jewish pts vs 55 [48-63] yrs in the Arab/Druze pts; P=.0004), similar to the complete cohort. The RS distribution was similar to that in the larger cohort, with no significant differences between the ethnic groups (P=.75). Also, CT use was consistent with the RS result in both ethnic groups, and was overall somewhat higher among Arab/Druze pts (25% vs 19%), due primarily to higher CT use among Arabs/Druze pts in the largest RS category (11-25), in which significant differences with respect to age were noted (median [interquartile range], 59 [52-66] yrs in Jewish pts vs 52 [46-61] yrs in Arab/Druze pts; P Conclusions: RS distribution and clinical outcomes were similar in Jewish and Arab/Druze BC pts. Arab/Druze pts undergoing RS testing were overall younger than the Jewish pts, which may suggest under-diagnosis and/or under-testing in the older Arab/Druze pt population. Also, CT use seemed higher in the Arab/Druze pt population, possibly reflecting the differences in the age distribution between these ethnic groups. Table: Patient/tumor characteristics by ethnicityJewsArabs/DruzeP valuen = 8223n = 831Female, n (%)8132 (98.9%)825 (99.3%).3Median (interquartile range) age, years62 (53-68)55 (48-64)1 - 2 cm4233 (51.5%)411 (49.5%)>22153 (26.2%)302 (36.3%)Unknown123 (1.5%)6 (0.7%)Tumor grade category, n (%).12Grade 11109 (13.4%)123 (14.8%)Grade 24192 (51.0%)443 (53.3%)Grade 31389 (16.9%)120 (14.4%)Not applicable/Unknown1533 (18.6%)145 (17.4%)Histology, n (%).92IDC6530 (79.4%)665 (80.0%)ILC1113 (13.5%)113 (13.6%)Papillary79 (1.0%)10 (1.2%)Mucinous/colloid144 (1.8%)16 (1.9%)Other/unknown357 (4.3%)27 (3.2%)Recurrence Score category, n (%).170-101612 (19.6%)176 (21.2%)11-255091 (61.9%)522 (62.8%)26-1001520 (18.5%)133 (16.0%) Citation Format: Gil Bar Sela, Yousef Samih, Rinat Yerushalmi, Michelle Leviov, Noa Efrat Ben-Baruch, Iryna Kuchuk, Margarita Tokar, Tamar Peretz, Amir L Sonnenblick, Lior Soussan-Gutman, Avital Bareket-Samish, Georgeta Fried, Shani Paluch-Shimon, Bella Kaufman, Ariel Hammerman, Nicky Liebermann, Salomon M Stemmer. Ethnicity, recurrence score (RS) distribution, and clinical outcomes in ER+ HER2-negative breast cancer (BC) patients (pts) in Israel [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-10-16.

Basal cell carcinoma (BCC) is a cancer that arises from the basal layer of the epidermis and is most often caused by exposure to UV radiation. Most BCCs are localized and can be fully treated by surgical removal or topical treatment. In the last decade, it has been found that the hedgehog pathway, a signaling pathway that regulates embryonic development, has a pivotal role in the pathogenesis of BCC in adults. Therefore, two drugs that inhibit the hedgehog pathway have been developed. These drugs, indicated for metastatic or locally advanced BCC, may cause a rapid clinical and imaging response, but have an adverse reaction that includes muscle spasms, alopecia, dysgeusia and fatigue, and often leads to drug discontinuation. Due to the high rates of treatment discontinuation, the possibility of administering the drug intermittently was examined and, indeed, a decrease in adverse reactions together with tumor response was observed. Additionally, it seems that patients who discontinue treatment may benefit from long-term remission. These cases indicate the possibility of changing the schedule of administration of the drug. We hereby report two cases of patients who were treated with radiation therapy for ringworm in their childhood and developed BCC. The patients were treated with a hedgehog pathway inhibitor with complete tumor regression. After treatment was discontinued due to adverse reactions, no recurrence of the tumor was observed over a period of almost two years.

Additional file 1: Fig S1. Comparison of neutrophil isolation methods shows the superiority and advantage of negative selection cell sorting. (A) Flow cytometry analysis of cell pellets population separated using dextran, Max exp, or Stem Cell kits. The left column show neutrophil content of lysed whole blood start sample. The Center column shows the final isolated cell pellets of CD16+ cells, and the right column shows an analysis of isolated cell pellets with CD16 and CD66b. The CD16high CD66bhigh cell population is defined as neutrophils, and CD16low CD66bhigh as eosinophils. (B) Yields and kits efficiency of isolated neutrophil cells per ml blood. (C) Representative measurements of neutrophils' baseline activation result from the isolation/sorting technique. The extent of extracellular ROS release assessed baseline activation before and after stimulation with PMA. Fig. S2. (A) Distributions of gene type annotations of differentially expressed genes in HD Upregulated genes (DEG_UP) and HD downregulated genes (DEG_Down). (B) Heatmap of significant differentially expressed HD upregulated genes on all 14 HC and HD samples. The expression level is normalized from 0 (no expression) to 1 (highest expression). Fig. S3. No difference in uninduced neutrophil cells of HC and HD patients over 4h. Image analysis of uninduced (with no stimulation) neutrophil cells n=6 donors from each group (e.g., HC or HD). HC and HD cells showed no difference in the distribution of nuclei architecture or any signs of spontaneous NETosis after Incubation of 4h. Neutrophils taken from HD patients and stimulated with LPS generated less intracellular free radicals than HC donors. (B) live-cell measurement of global ROS levels and superoxide in neutrophils induced with 100ng/ml LPS. Profiling ROS formation by fluorescence microscopy was performed with highly pure neutrophils from HC and HD patients, loaded with ROS/Superoxide detection reagents, and activated with LPS. General oxidative stress levels were monitored in the green channel, while the orange/Red channel detected superoxide production. Snapshots were taken in indicated time points (e.g., 0, 15, 45 min). (C) Neutrophils were isolated from whole blood samples of HC and HD. The kinetics of extracellular ROS release was performed with L-012 (20mM) with or without PMA (100nM) stimulation. The kinetics of extracellular ROS release was measured for 30 min using an ELISA plate reader. Results are presented as means ± S.E. of RLU of six independent donors from each group. Neutrophils induced with PMA were a positive control for extracellular ROS release.

Additional file 2.

ObjectiveIntegrating spiritual care into multidisciplinary care teams has seen both successful thoughtful collaboration and challenges, including feelings of competition and poor cross-disciplinary understanding. In Israel, where the profession is new, we aimed to examine how spiritual care is perceived by other healthcare professionals learning to integrate spiritual caregivers into their teams.MethodSemi-structured qualitative interviews of 19 professionals (seven physicians, six nurses, three social workers, two psychologists, and one medical secretary) working with spiritual caregivers in three Israeli hospitals, primarily in oncology/hematology. The interviews were transcribed and subjected to thematic analysis.ResultsRespondents’ overall experience with adding a spiritual caregiver was strongly positive. Beneficial outcomes described included calmer patients and improved patient–staff relationships. Respondents identified reasons for a referral not limited to the end of life. Respondents distinguished between the role of the spiritual caregiver and those of other professions and, in response to case studies, differentiated when and how each professional should be involved.ConclusionDespite its relative newness in Israel, spiritual care is well received by a wide variety of professionals at those sites where it has been integrated. Steps to improve collaboration should include improving multidisciplinary communication to broaden the range of situations in which spiritual caregivers and other professionals work together to provide the best possible holistic care.

The increased susceptibility of cancer patients to coronavirus disease-2019 (COVID-19) infections and complications calls for special precautions while treating cancer patients during COVID-19 pandemics. Thus, oncology departments have had to implement a wide array of prevention measures.To address issues associated with cancer care during the COVID-19 pandemic and to assess the implementation of measures aimed at containment of COVID-19 diffusion while allowing continuation of quality cancer care.A national survey among oncology departments in Israel was conducted between 12 April 2020 and 14 April 2020. Eighteen heads of hospital-based oncology departments completed a self-report questionnaire regarding their institute's preparedness for treatment of cancer patients during the COVID-19 pandemic.In this national survey, prevention measures against COVID-19 spread were taken prior to patients' arrival and at arrival or while staying in the departments. Most participants (78-89%) reported using a quick triage of patients and caregivers prior to their entrance to the oncology units, limiting the entrance of caregivers, and reducing unnecessary visits to the clinic. Switching to oral therapies rather than intravenous ones when possible was considered by 82% and shortage in personal protective equipment was reported by five (28%) heads of oncology departments. Some differences between large and small/medium sized medical centers were observed regarding issues related to COVID-19 containment measures and changes in treatment.Oncology departments in Israel were able to prepare and adapt their services to guidelines and requirements related to the COVID-19 pandemic with little harm to their treatment capacity.

Gaps between physician and patient perceptions may lead to misunderstandings and mismanage of treatment. There are sparse data about the differences in opinions toward medical cannabis (MC) between patients and health professionals. The aim of this study was to examine the attitudes toward MC, its perceived efficacy, side effects and risk of dependency, among patients, nurses and physicians. A cross-sectional study of samples of 430 patients, 65 nurses and 65 physicians in two large medical centers in Israel. Questionnaires were administered on attitudes, perceived efficacy, side-effects and perceived risks of dependency. Compared with nurses and physicians, patients who were using MC had the most positive attitudes toward MC (

INTRODUCTION In rectal cancer, neoadjuvant chemoradiation (NCRT) is preferred because of toxicity profile, improved resectability and sphincter preservation, although with no impact on overall survival. Pathologic complete response (pCR) to NCRT has been linked with longer disease-free survival (DFS). The study purpose was to evaluate an association between clinical factors and treatment schedule with tumor response and treatment outcome, among patients with locally advanced rectal cancer. PATIENTS AND METHODS In this single-center retrospective study, conducted over 9 years (2011 to 2020), patients with stage II to III rectal cancer who had received NCRT were enrolled. The standard radiotherapy was 45 Gy to the pelvis, with a simultaneous integrated 50 Gy boost to the primary tumor. Continuous 5-Fluorouracil or oral capecitabine was administered concurrently. Surgery was preplanned within 6 to 8 weeks. Multinomial logistic regressions for evaluation of clinical factors, Kaplan-Meier method for DFS estimation, and receiver operating characteristic analysis for determination of the optimal timeframe were used. RESULTS Of 279 cases, pCR was observed in 72 (25.8%). In 207 cases, pTis-4N-negative was obtained in 137 (66.2%), pT0N-positive in 6 (2.9%), and pTis-4N-positive in 64 (30.9%). The pCR group had shorter diagnosis-NCRT time (P

The first evidence that cannabinoids may have in vitro and in vivo antineoplastic activity against tumor cell lines and animal tumor models was published in the Journal of the National Cancer Institute nearly 50 years ago. Cannabinoids appear to induce apoptosis in rodent brain tumors by way of direct interaction with the cannabinoid receptor. They may inhibit angiogenesis and tumor cell invasiveness. Despite preclinical findings, attempts to translate the benefits from bench to bedside have been limited. This session provides a review of the basic science supporting the use of cannabinoids in gliomas, paired with the first randomized clinical trial of a cannabis-based therapy for glioblastoma multiforme. Another preclinical presentation reports the effects of cannabinoids on triple-negative breast cancer cell lines and how cannabidiol may affect tumors. The session’s second human trial raises concerns about the use of botanical cannabis in patients with advanced cancer receiving immunotherapy suggesting inferior outcomes.

Myoepithelial tumor is a rare form of cancer, mainly arising from the salivary glands and extremities. Due to its rarity, no formal treatment guidelines exist. Here we report a case of a male patient diagnosed with metastatic myoepithelial tumor which was successfully treated with an androgen-receptor (AR) antagonist (bicalutamide), based on the results of molecular testing. Six years after the initiation of bicalutamide, patient was diagnosed with metastatic prostate cancer. To our knowledge, this is the first case described in literature that demonstrate the effectiveness of anti-androgens in treating myoepithelial tumor. Vigilance should be maintained when screening these patients for prostate cancer as their 'true' prostate specific antigen levels might be masked by the ongoing endocrine therapy.

Background: The European Organisation for Research and Treatment of Cancer (EORTC) 1325/KEYNOTE-054 trial assessed pembrolizumab versus placebo in patients with resected high-risk stage III melanoma. At 15-month median follow-up, pembrolizumab improved recurrence-free survival (hazard ratio [HR] 0·57 [98·4% CI 0·43–0·74], p1 mm), IIIB, or IIIC (without in-transit metastasis), and with an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible. Patients were randomly assigned (1:1) via a central interactive voice response system to receive intravenous pembrolizumab 200 mg or placebo every 3 weeks for up to 18 doses or until disease recurrence or unacceptable toxicity. Randomisation was stratified according to disease stage and region, using a minimisation technique, and clinical investigators, patients, and those collecting or analysing the data were masked to treatment assignment. The two coprimary endpoints were recurrence-free survival in the intention-to-treat (ITT) population and in patients with PD-L1-positive tumours. The secondary endpoint reported here was distant metastasis-free survival in the ITT and PD-L1-positive populations. This study is registered with ClinicalTrials.gov, NCT02362594, and EudraCT, 2014-004944-37. Findings: Between Aug 26, 2015, and Nov 14, 2016, 1019 patients were assigned to receive either pembrolizumab (n=514) or placebo (n=505). At an overall median follow-up of 42·3 months (IQR 40·5–45·9), 3·5-year distant metastasis-free survival was higher in the pembrolizumab group than in the placebo group in the ITT population (65·3% [95% CI 60·9–69·5] in the pembrolizumab group vs 49·4% [44·8–53·8] in the placebo group; HR 0·60 [95% CI 0·49–0·73]; p