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IMPORTANCE: Few clinical trials have been specifically designed for elderly patients with advanced non–small cell lung cancer (NSCLC), and the anticipated increase in the number of such patients has prompted a search for new treatment options that provide a greater palliative benefit. OBJECTIVE: To determine whether treatment with carboplatin plus pemetrexed followed by pemetrexed maintenance is noninferior compared with docetaxel monotherapy with regard to overall survival (OS) for elderly patients with advanced nonsquamous NSCLC. DESIGN, SETTING, AND PARTICIPANTS: This open-label, multicenter, noninferiority phase 3 randomized clinical trial was conducted at 79 institutions in Japan. Cytotoxic chemotherapy–naive patients with advanced nonsquamous NSCLC, an Eastern Cooperative Oncology Group performance status of 0 or 1, and age of 75 years or older were enrolled between August 2013 and February 2017. Data were analyzed from November 2018 to February 2019. INTERVENTIONS: Patients were randomized to receive either docetaxel monotherapy (60 mg/m(2)) every 3 weeks or 4 cycles of carboplatin (area under the curve of 5) plus pemetrexed (500 mg/m(2)) administered every 3 weeks followed by maintenance therapy with the same dose of pemetrexed for 3 weeks. MAIN OUTCOMES AND MEASURES: The primary end point was OS analyzed on an intention-to-treat basis with a noninferiority margin of 1.154 for the upper limit of the 95% CI of the hazard ratio (HR) estimated with a stratified Cox regression model. RESULTS: Of the 433 enrolled patients, 250 (57.7%) were male, and the median (range) age was 78 (75-88) years. The median OS was 15.5 months (95% CI, 13.6-18.4) in the docetaxel group (n = 217) and 18.7 months (95% CI, 16.0-21.9) in the carboplatin-pemetrexed group (n = 216), with a stratified HR for OS of 0.850 (95% CI, 0.684-1.056; P for noninferiority = .003). Progression-free survival was also longer in the carboplatin-pemetrexed group (unstratified HR, 0.739; 95% CI, 0.609-0.896). Compared with those in the docetaxel group, those in the carboplatin-pemetrexed had lower rates of leukopenia (60 of 214 [28.0%] vs 147 of 214 [68.7%]) and neutropenia (99 of 214 [46.3%] vs 184 of 214 [86.0%]) of grade 3 or 4 and of febrile neutropenia (9 of 214 [4.2%] vs 38 of 214 [17.8%]) and higher rates of thrombocytopenia (55 of 214 [25.7%] vs 3 of 214 [1.4%]) and anemia (63 of 214 [29.4%] vs 4 of 214 [1.9%]) of grade 3 or 4. Dose reductions were less frequent with carboplatin-pemetrexed. CONCLUSION AND RELEVANCE: Carboplatin-pemetrexed treatment followed by pemetrexed maintenance is a valid option for first-line treatment of elderly patients with advanced nonsquamous NSCLC. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry Identifier: UMIN000011460

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Small Cell Lung Cancer (SCLC) provide recommended management for patients with SCLC, including diagnosis, primary treatment, surveillance for relapse, and subsequent treatment. This selection for the journal focuses on metastatic (known as extensive-stage) SCLC, which is more common than limited-stage SCLC. Systemic therapy alone can palliate symptoms and prolong survival in most patients with extensive-stage disease. Smoking cessation counseling and intervention should be strongly promoted in patients with SCLC and other high-grade neuroendocrine carcinomas. The “Summary of the Guidelines Updates” section in the SCLC algorithm outlines the most recent revisions for the 2022 update, which are described in greater detail in this revised Discussion text.

It is recognized that certain primary immune deficiencies are associated with increased risk of specific pathogens and this has led to a greater understanding of the role of individual genes in mediating host defense against these pathogens. In a similar fashion, the increased risk of cancers associated with primary immune deficiencies provides us with insight about immune protections from malignancies. The immune system has the ability to identify and eradicate developing cancers, a phenomenon termed “cancer immunosurveillance” (Schumacher and Schreiber, 2015). The notion of the normal immune system preventing cancer development through immune surveillance is supported by the increased risk of cancers in immunocompromized patients, including persons with AIDS (Patel et al., 2008; Shiels et al., 2010; Shiels et al., 2011; Simard et al., 2010), hematopoietic stem cell transplant recipients (Majhail, 2011; Majhail et al., 2011), and solid organ transplant recipients (Engels et al., 2011). In these secondary immune deficiencies, multiple factors can influence the risk of cancer including impaired immunosurveillance as well as therapy-related genotoxicity (Olivero et al., 2007). In contrast, patients with primary immune deficiencies provide the opportunity to more directly delineate the role of immune protection from cancer at the level of specific genes and pathways. The goals of this chapter are to review immune deficient conditions in which the occurrence of cancer is strikingly high and describe the insights we gain regarding the role of the immune system in protecting from incident cancer. We will also discuss implications for cancer screening, gaps in knowledge, and future directions in research.

Background Proper approach to symptom control in cancer patients requires a good understanding of the prevalence of the various symptoms these patients have. Aim This study aims at assessing the Lebanese oncologists’ point of view concerning the symptom burden among cancer patients of Lebanon and comparing their opinions to the real complaints of patients themselves. Methods A cross-sectional study was conducted among a representative sample of the Lebanese medical oncologists. Thirty-six physicians filled out a questionnaire regarding their demographics as well as the symptom profile of their patients. Those results were compared to the ones obtained from our previous study about symptom profile as reported by patients. Results Fatigue was the symptom most our patients suffered from according to their physicians (64.167%). Also, a good percentage of physicians agreed that patients suffer from appetite loss, pain, weight loss, and nausea. When compared to the patients’ reports of their own symptoms, a statistically significant difference existed between the two profiles for the majority of symptoms (14 out of 19). Also, for the majority of symptoms, physicians were found to underestimate the percentage of patients suffering from each symptom. Conclusion This study shows that there is a statistically significant difference between the physicians’ and the patients’ perspectives on most of the common distressing symptoms. This entails more detailed questioning of the cancer patients about their distressing symptoms.

[Background] PD-L1 immunohistochemistry (IHC) has been traditionally used for predicting clinical responses to immune checkpoint inhibitors (ICIs). However, there are at least 4 different assays and antibodies used for PD-L1 IHC, each developed with a different ICI. We set to test if next generation RNA sequencing (RNA-seq) is a robust method to determine PD-L1 mRNA expression levels and furthermore, efficacy of predicting response to ICIs as compared to routinely used, standardized IHC procedures., [Methods] A total of 209 cancer patients treated on-label by FDA-approved ICIs, with evaluable responses were assessed for PD-L1 expression by RNA-seq and IHC, based on tumor proportion score (TPS) and immune cell staining (ICS). A subset of serially diluted cases was evaluated for RNA-seq assay performance across a broad range of PD-L1 expression levels., [Results] Assessment of PD-L1 mRNA levels by RNA-seq demonstrated robust linearity across high and low expression ranges. PD-L1 mRNA levels assessed by RNA-seq and IHC (TPS and ICS) were highly correlated (p, [Conclusions] Measurement of PD-L1 mRNA expression by RNA-seq is comparable to PD-L1 expression by IHC both analytically and clinically in predicting ICI response. RNA-seq has the added advantages of being amenable to standardization and avoidance of interpretation bias. PD-L1 by RNA-seq needs to be validated in future prospective ICI clinical studies across multiple histologies., This research was funded by OmniSeq, Inc. (Buffalo, NY).

Introduction. Accurate evaluation of estrogen and progesterone receptors and HER2 is critical when diagnosing invasive breast cancer for optimal treatment. The current evaluation method is via immunohistochemistry (IHC). In this paper, we compared results of ER, PR, and HER2 from microarray gene expression to IHC in 81 fresh breast cancer specimens. Methods. Gene expression profiling was performed using the GeneChip Human Genome U133 Plus 2.0 arrays (Affymetrix Inc). Immunohistochemical staining for estrogen receptor, progesterone receptor, and HER2 status was performed using standard methods at a CAP-accredited pathology laboratory. Concordance rates, agreement measures, and kappa scores were calculated for both methods. Results. For ER, Kappa score was 0.918 (95% CI, 0.77.3–1.000) and concordance rate was 97.5% (95% CI, 91.4%–99.7%). For PR, Kappa score was 0.652 (95% CI, 0.405–0.849) and concordance rate was 86.4% (95% CI, 77%–93%). For HER2, Kappa score was 0.709 (95% CI, 0.428–0.916) and concordance rate was 97.5% (95% CI, 91.4%–99.7%). Conclusion. Our results are in line with the available evidence with the concordance rate being the lowest for the progesterone receptor. In general, microarray gene expression and IHC proved to have high concordance rates. Several factors can increase the discordance rate such as differences in sample processing.

Background: A significant percentage of lung adenocarcinomas have a driver mutation. To date, there has been no assessment of the prevalence of such mutations in a Middle Eastern population. The present multicenter prospective study of formalin fixed paraffin embedded (FFPE) tissues from patients diagnosed with lung adenocarcinoma was performed to assess the prevalence of EGFR and ALK mutations in the Levant. Methods: Patients of Middle Eastern origin with lung adenocarcinomas at 10 sites in Lebanon, Jordan and Iraq were prospectively enrolled. Tumors were tested for EGFR by PCR and for EML4-ALK translocation by fluorescence in situ hybridization (FISH). Results: A total of 210 patients were enrolled, 139 (66.2%) males and 71 females (33.8%), with a mean age of 63.4 years. EGFR testing of 205 (97.6%) demonstrated the wild type in 173 (84.4%) and mutated forms in 32 (15.6%). Some 46.9% of EGFR positive patients were non-smokers and 62.5% were females as opposed to 22.4% and 33.8%, respectively, in the general population. As for the EML4-ALK translocation, testing in 157 (74.8%) cases gave negative results in 154 (98.1%), only 3 being positive (1.9%), 2 being females and 2 non-smokers. Conclusion: Our study established a 15.6% EGFR mutation rate in lung adenocarcinomas with ALK translocation mutations in only 1.9%, as compared to a 15-20% and 5%, respectively, in the Western literature.

Breast cancer is commonest cancer in women worldwide. Elucidation of underlying biology and molecular pathways is necessary for improving therapeutic options and clinical outcomes. Molecular alterations in breast cancer are complex and involve cross-talk between multiple signaling pathways. The aim of this study is to extract a unique mRNA fingerprint of breast cancer in Lebanese women using microarray technologies. Gene-expression profiles of 94 fresh breast tissue samples (84 cancerous/10 non-tumor adjacent samples) were analyzed using GeneChip Human Genome U133 Plus 2.0 arrays. Quantitative real-time PCR was employed to validate candidate genes. Differentially expressed genes between breast cancer and non-tumor tissues were screened. Significant differences in gene expression were established for COL11A1/COL10A1/MMP1/COL6A6/DLK1/S100P/CXCL11/SOX11/LEP/ADIPOQ/OXTR/FOSL1/ACSBG1 and C21orf37. Pathways/diseases representing these genes were retrieved and linked using PANTHER®/Pathway Studio®. Many of the deregulated genes are associated with extracellular matrix, inflammation, angiogenesis, metastasis, differentiation, cell proliferation and tumorigenesis. Characteristics of breast cancers in Lebanese were compared to those of women from Western populations to explain why breast cancer is more aggressive and presents a decade earlier in Lebanese victims. Delineating molecular mechanisms of breast cancer in Lebanese women led to key genes which could serve as potential biomarkers and/or novel drug targets for breast cancer.

Study objective To develop a competency model for emergency physicians from the perspective of nurses, juxtapose this model with the widely adopted Accreditation Council for Graduate Medical Education (ACGME) model, and identify competencies that might be unique to the nurses' perspective. Methods The study relied on secondary data originally collected as part of nurses' assessment of emergency physicians' nonclinical skills in the emergency department (ED) of an academic medical center in the Middle East. Participants were 36 registered nurses who had worked in the ED for at least 2 years and had worked for at least 2 shifts per month with the physician being evaluated. Results Through content analysis, a nurse-led competency model was identified, including 8 core competencies encompassing 33 subcompetencies. The 8 core competencies were emotional intelligence; problem-solving and decisionmaking skills; operations management; patient focus; patient care, procedural skills, and medical knowledge; professionalism; communication skills; and team leadership and management. When the developed model was compared with the ACGME model, the 2 models diverged more than they converged. Conclusion The nurses' perspective offered distinctive insight into the competencies needed for physicians in an emergency medicine environment, indicating the value of nurses' perspective and shedding light on the need for more systematic and more methodologically sound studies to examine the issue further. The differences between the models highlighted the competencies that were unique to the nurse perspective, and the similarities were indicative of the influence of different perspectives and organizational context on how competencies manifest.

Background: Despite availability of novel therapies, namely JAK inhibitors and immunomodulatory agents, for treatment of myelofibrosis, the disease remains incurable unless eligible patients are offered an allogeneic hematopoietic cell transplant (allo-HCT). Available data supporting allo-HCT in myelofibrosis are limited to single-arm prospective or retrospective studies (including data from registries) or single-center case series. No randomized controlled trial (RCT) has ever been conducted comparing the impact of dose-intensity of the conditioning regimen on post-transplant outcomes in patients with myelofibrosis. Accordingly, we performed a systematic review/meta-analysis of the published literature using PubMed and EMBASE from date of inception until 12/16/2015. We restricted inclusion criteria to studies published only as peer-reviewed manuscripts which included more than 10 patients. Patients and methods: Our search strategy identified 907 publications, but only 29 (n=2,128 patients) met our inclusion criteria. Data were collected on treatment benefits (overall response rate (ORR), complete (CR) or partial response (PR), overall survival (OS)) and harms (grade 2-4 acute graft-versus-host disease (GVHD), 3-4 acute GVHD, chronic GVHD, non-relapse mortality (NRM), and graft failure) whenever available. We also assessed outcomes based on disease-risk stratification whenever possible. For the purposes of our analysis, low-risk encompassed (low-risk Lille/Dupriez/DIPSS), intermediate-risk (intermediate-risk Lille/Dupriez/int-1 DIPSS), and high-risk (high-risk Lille/Dupriez/Int-2 or high-DIPSS). All results are reported as pooled proportions. Results: When using reduced-intensity conditioning (RIC) regimens, 7 prospective (n=281 patients) and 11 retrospective (n=532 patients) studies were identified. Pooled (rates) outcomes of RIC prospective studies were as follow: ORR=65% (95%CI=26-95%), CR=51% (95%CI=18-84%), OS= 69% (95%CI=58-80%), grade 2-4 acute GVHD= 37% (95%CI=27-48%), grade 3-4 acute GVHD= 22% (95%CI=7-44%), chronic GVHD= 38% (95%CI=22-55%), NRM= 23% (95%CI=12-37%), and graft failure= 6% (95%CI=1-12%). Pooled outcomes of RIC retrospective studies were as follow: ORR= 100% (95%CI=86-100%), CR=100% (95%CI=86-100%), OS= 51% (95%CI=43-58%), grade 2-4 acute GVHD= 35% (95%CI=30-39%), grade 3-4 acute GVHD=19% (95%CI=11-29%), chronic GVHD= 47% (95%CI=41-52%), NRM= 20% (95%CI=13-27%), and graft failure= 15% (95%CI=9-22%). For myeloablative conditioning (MAC) regimens, 0 prospective and 5 retrospective (n=132 patients) studies were identified. Outcomes were as follow: ORR= 40% (95%CI=21-61%), CR=40% (95%CI=21-61%), OS=56% (95%CI=42-70%), grade 2-4 acute GVHD= 46% (95%CI=26-66%), grade 3-4 acute GVHD=13% (95%CI=4-26%), chronic GVHD= 57% (95%CI=26-86%), NRM= 26% (95%CI=16-38%), and graft failure= 9% (95%CI=0-32%). Furthermore, Survival outcomes based on disease-risk stratification showed OS rates of 78% (95%CI=69-86%) for low-risk, 60% (95%CI=48-70%) for intermediate-risk, and 42% (95%CI=36-48%) for high-risk cases. Conclusions: Notwithstanding the need of a RCT to help better understand the effect of dose-intensity of allo-HCT regimens (RIC vs. MAC) on outcomes, this systematic review/meta-analysis highlights encouraging OS rates of 51-69% when using RIC regimens with resulting pooled NRM rates of 20-23%. Rates of grade 2-4 acute and chronic GVHD appear, unsurprisingly, lower with RIC regimens; but high rates of graft failure remain a serious concern in myelofibrosis regardless of the intensity of the conditioning regimen. Disclosures Hamadani: Janssen: Consultancy; Celgene: Honoraria, Research Funding; Takeda Pharmaceuticals: Research Funding. Nishihori:Signal Genetics: Research Funding; Novartis: Research Funding.

e12648 Background: Recent evidence suggests that a significant percentage of lung adenocarcinomas have a driver mutation that is responsible for the development of the tumor and promotion of its gr...

Background Breast cancer patients are increasingly seeking Complementary and Alternative Medicine (CAM) therapies with the hope of alleviating the burden of the disease and improving their quality of life (QOL). The objective of this study was to assess the prevalence, types, socio-demographic and disease-related correlates as well as characteristics of CAM use (including disclosure to treating physicians) among breast cancer patients in Beirut, Lebanon. A secondary objective was to evaluate the association between CAM use and QOL. Methods A cross-sectional survey was conducted on breast cancer patients recruited from two major referral centers in Beirut: a philanthropic hospital and a private academic medical center. In face-to-face interviews, participants completed a questionnaire of three sections: socio-demographic and lifestyle characteristics, breast cancer condition, and CAM use. Three to four weeks following these interviews, the secondary QOL assessment was carried out via telephone using the Arabic version of the Functional Assessment of Cancer Therapy-Breast questionnaire. The main outcome in this study, CAM use, was defined as using CAM at least once after breast cancer diagnosis. Results A total of 180 breast cancer patients completed the survey (response rate: 94.6 %). Prevalence of CAM use was 40 %. Using multivariate logistic regression, CAM use was negatively associated with age (OR: 0.96, CI: 0.92-0.99), treatment at the philanthropic hospital (OR: 0.13, CI: 0.05-0.35) and was positively associated with an advanced stage of the disease (OR: 4.20, CI: 1.65-10.69). Among study participants recruited from both sites, the most commonly used CAM was ‘special food’ followed by ‘herbal teas’, ‘diet supplements’ and ‘Spiritual healing’. Only 4 % of CAM users cited health professionals as influencing their choice of CAM and only one in four patients disclosed CAM use to their treating physician. There was no significant association between CAM use and QOL. Conclusions The findings of this study revealed a prevalent CAM use among Lebanese breast cancer patients. Furthermore, physicians’ role in orienting CAM use was found to be marginal as patients relied mainly on family and media for their choice of CAM and were less likely to disclose CAM use to their treating physicians. Electronic supplementary material The online version of this article (doi:10.1186/s12906-015-0969-9) contains supplementary material, which is available to authorized users.

Background: Anthracycline adjuvant therapy has taken a particular role in the treatment of early stage breast cancer with an associated decrease in rates of both relapse and death. Their success however has been limited by their myelosuppression and their well-established risk of cardiac dysfunction. Guidelines have emerged that would limit the maximum lifetime dose of anthracyclines and make a baseline assessment and periodic monitoring of cardiac function part of the routine practice, which could be cumbersome, and may condemn the patient to an unwarranted modification of his/her regimen. Our study aimed at assessing the incidence of abnormal baseline echocardiography in asymptomatic women with breast cancer prior to anthracycline therapy and establishing risk criteria associated with abnormal echocardiograms at baseline. Methods: 220 Patients seen at AUBMC (American University of Beirut Medical Center) who had non- metastatic breast cancer, and had an echocardiography performed before starting anthracycline chemotherapy were chosen. Data about demographic characteristics, tumor characteristics, baseline echocardiography results, and change in clinical decision was collected. Patients with suboptimal (less than 50%) ejection fraction (EF) on baseline echocardiography were analyzed for the prevalence of cardiac risk factors. Results were compared to those among the overall study group using Fisher's Exact test. A p- value of = < 0.05 was used as reference for statistical significance. Results: All 220 of our patients had received a baseline echo prior to initiation of anthracycline therapy. 6.7% of these patients had already some abnormality in wall motion but only 2.7% had a suboptimal ejection fraction. 1.3% had a change in chemotherapy regimen based on ejection fraction. The patients with depressed EF had higher rates of CAD (coronary artery disease), diabetes, hypertension and dyslipidemia than the overall study group but without statistical significance. Conclusions: Our study, as well as the previous contingent studies raise the question about routine echocardiography prior to anthracycline therapy and might eventually lead to a modification of current practice guidelines., SCOPUS: ar.j, info:eu-repo/semantics/published