COMPASS-CAT versus Khorana risk assessment model for predicting venous thromboembolic events in patients with non-small cell lung cancer on active treatment with chemotherapy and/or immunotherapy, the CK-RAM study.

Cancer patients are at higher risk for venous thromboembolism (VTE). Several risk assessment models (RAM), including the Khorana and COMPASS-CAT, were developed to help predict the occurrence of VTE in cancer patients on active anti-cancer therapy. We aim to study the prevalence and predictors of VTE among patients with non-small cell lung cancer (NSCLC) and compare both RAMs in predicting VTE in patients with NSCLC were retrospectively reviewed. Variables known to increase the risk of VTE were collected and risk of VTE was assessed using both Khorana and COMPASS-CAT RAM. A total of 508 patients (mean age ± SD, 58.4 ± 12.2 years) were enrolled. Most (n = 357, 70.3%) patients had adenocarcinoma, and 333 (65.6%) patients had metastatic disease. VTE were confirmed in 76 (15.0%) patients. Rates were higher among patients with metastatic disease (19.8%, p < 0.001), adenocarcinoma (17.4%, p = 0.01) and those treated with immunotherapy (23.5%, p = 0.014). VTE rates were 21.2%, 14.1% and 13.9% among those with high (n = 66), intermediate (n = 341) and low (n = 101) Khorana risk scores, respectively (p = 0.126). On the other hand, 190 (37.4%) were classified as high risk by the COMPASS-CAT RAM; 52 (27.4%) of them had VTE compared to 24 (7.5%) of the remaining 318 (62.6%) classified as Low/Intermediate risk level, p < 0.001. In conclusion, patients with NSCLC are at high risk for VTE, especially those with adenocarcinoma, metastatic disease and when treated with immunotherapy. Compared to Khorana RAM, COMPASS-CAT RAM was better in identifying more patients in high-risk group, with higher VTE rate.

Differences in Treatment Outcomes Between Patients with HER2-Low versus HER2-Zero, Hormone Receptor-Positive Advanced-Stage Breast Cancer Treated with Ribociclib.

Background: Metastatic breast cancers (MBC) with no expression of human epidermal growth factor receptor-2 (HER2) are recently classified into two groups; HER2-zero [HER2-immunohistochemistry (IHC) score of 0 (IHC-0)] and HER2-low, defined as those with IHC score of 1+ or 2+ with negative in situ hybridization (ISH) assay. We investigate differences in treatment outcomes between both groups treated with endocrine therapy (ET) and the CDK4/6 inhibitor ribociclib. Methods: Data were retrospectively collected for patients with HR-positive+/HER2-negative MBC who received ribociclib with an aromatase inhibitor (AI) or fulvestrant and were divided into two groups: HER2-zero and HER2-low. Results: A total of 257 patients, median age 48 (22-87) years, all with MBC who were treated with ET and ribociclib were enrolled. One hundred and thirty-seven (53.3%) patients had de novo MBC, and majority (n = 162, 63.0%) received ribociclib as a first-line therapy. In total, 114 (44.4%) patients had HER2-zero (IHC-0), while 143 (55.6%) others had HER2-low disease. The overall response rate (ORR) was 52.0% for the HER2-zero group compared to 39.4% for the HER2-low group, p = 0.005. The median PFS was 22.2 (95% confidence interval [CI], 19.4-NR) months for HER2-zero versus 17.3 (95% CI, 14.1-20.6) months for HER2-low, P = 0.0039. In multivariable analysis, HER2-low expression remained significant determinant of inferior PFS after adjusting for other factors, including the site of metastasis, prior chemotherapy, and the line of treatment. Conclusion: In patients with MBC treated with ET and ribociclib, level of HER2 negativity may affect treatment outcomes; patients with HER2-zero had better response rate and PFS compared to those with HER2-low disease. These findings, if confirmed in larger studies, may help oncologists select patients with HER2-low for better treatment options.

Prevalence and clinical implications of germline mutations among Jordanian patients with ovarian cancer. The Jordanian exploratory cancer genetics (Jo-ECAG) ovarian study.

BACKGROUND: Ovarian cancer is one of the most common gynecological malignancies. Due to the absence of effective screening methods, ovarian cancer is usually diagnosed at late stages. Patients with pathogenic and likely-pathogenic germline variants (PGVs) in BRCA1 or BRCA2 harbor elevated risk of developing both ovarian and breast cancers. Identifying PGVs may help in both cancer prevention and active disease treatment. Worldwide prevalence of PGVs varies and the matter is poorly addressed among Arab patients. METHODS: Patients with epithelial ovarian, fallopian tube or primary peritoneal cancers were offered the universal 20 or 84-multi-gene panel testing as per standard guidelines. Cascade family screening was also offered to all first and second-degree relatives of PGV positive patients. Genetic testing was done at a referral lab using a next generation sequencing (NGS)-based platform. RESULTS: During the study period, 152 patients, median age (range): 50 (18-79) years old, were tested. The majority (n = 100, 65.8%) had high-grade serous carcinoma, and 106 patients (69.7%) had metastatic disease at presentation. In total, 38 (25.0%) had PGVs, while 47 (30.9%) others had variants of uncertain significance (VUS). PGVs were mostly in BRCA1 (n = 21, 13.8%) and in BRCA2 (n = 12, 7.9%), while 6 (3.9%) others had PGVs in non-BRCA1/2 genes. PGV rates were significantly higher among 15 patients with a positive family history of ovarian cancer (60.0%, p = .022) and among 52 patients with a positive family history of breast cancer (40.4%, p = .017). CONCLUSIONS: PGVs are common among Jordanian women with ovarian cancer, and mostly occur in BRCA1/2. Given its clinical impact on disease prevention and precision therapy, universal testing should be routinely offered.

Guideline-Based, Multi-Gene Panel Germline Genetic Testing for at-Risk Patients with Breast Cancer.

Background: Genetic testing for at-risk patients with breast cancer should be routinely offered. Knowledge generated may influence both treatment decisions and cancer prevention strategies among the patients themselves and their relatives. In this study, we report on the prevalence and patterns of germline mutations, using commercially available next-generation sequencing (NGS)-based multi-gene panels (MGP). Patients and Methods: Consecutive at-risk breast cancer patients, as determined by international guidelines, were offered germline genetic testing using a 20-gene NGS-based panel at a reference lab. Samples of peripheral blood were obtained for DNA extraction and genetic variants were classified as benign/likely benign (negative), pathogenic/likely pathogenic (positive) or variants of uncertain significance (VUS). Results: A total of 1310 patients, median age (range) 43 (19-82) years, were enrolled. Age ≤45 years (n = 800, 61.1%) was the most common indication for testing. Positive family history of breast, ovarian, pancreatic or prostate cancers, and triple-negative disease were among the common indications. Among the whole group, 184 (14.0%) patients had pathogenic/likely pathogenic variants; only 90 (48.9%) were in BRCA1 or BRCA2, while 94 (51.9%) others had pathogenic variants in other genes; mostly in APC, TP53, CHEK2 and PALB2. Mutation rates were significantly higher among patients with positive family history (p = 0.009); especially if they were 50 years or younger at the time of breast cancer diagnosis (p < 0.001). Patients with triple-negative disease had relatively higher rate (17.5%), and mostly in BRCA1/2 genes (71.4%). Variants of uncertain significance (VUS) were reported in 559 (42.7%) patients; majority (90.7%) were in genes other than BRCA1 or BRCA2. Conclusion: Pathogenic mutations in genes other than BRCA1/2 are relatively common and could have been missed if genetic testing was restricted to BRCA1/2. The significantly high rate of VUS associated with multi-gene panel testing can be disturbing.

Pathogenic germline variants in patients with breast cancer: conversations across generations, practices and patients' attitude.

Background: Breast cancer susceptibility genes such as BRCA1, BRCA2, PALB2, CHEK2 and many others are increasingly recognized among our patient population. In addition to their impact on treatment decisions of tested patients themselves, identifying at-risk family members offer opportunities for cancer preventive measures. Methods: This is an observational cross-sectional study of adult breast cancer patients with positive breast-cancer-susceptibility germline variants who received treatment at our institution. Patients with variants of uncertain significance (VUS), or who refused to give consent, were excluded. The data was collected from an eligible sample of breast cancer patients using a structured questionnaire developed by the study team and tested for validity and reliability, as well as a clinical chart review form. Patients were invited to participate in the study during their scheduled oncology clinics visit. Results: 169 patients were enrolled, including 42 (24.9%) with pathogenic/likely pathogenic (P/LP) BRCA1 variants, 84 (49.7%) with BRCA2 and 43 (25.4%) with non-BRCA variants. All patients were female and the mean age was 45 ± 9.9 years. Among 140 eligible patients, 104 (74.3%) underwent prophylactic mastectomy, while 79 (59.0%) of 134 eligible patients had prophylactic bilateral salpingo-oophorectomy (BSO). Results were communicated with family members by majority (n = 160, 94.7%), including 642 first degree female relatives, and 286 (44.5%) of them have taken no action. Fear of positive test results, cost of testing, unwillingness to undergo preventive measures, and social stigma were cited as barriers to genetic testing in 54%, 50%, 34% and 15%, respectively. Conclusion: Risk-reducing interventions including mastectomy and BSO were carried by majority of patients with P/LP variants. However, though the rate of communication of genetic testing results with family members was high, proper preventive measures were relatively low. Cost and fear of cancer diagnosis, were the leading causes that prevented cascade testing in our cohort.

Aggressiveness of Cancer Care at End of Life in Patients with Metastatic Breast Cancer in Jordan.

Background: Contrary to Western societies, more than 15% of patients with breast cancer in Jordan are diagnosed with stage IV disease. In this study, we evaluate the value of early palliative care integration in the end-of-life care of such patients. Methods: All consecutive adult patients who died between 2014 to 2018, while under the care of our institution, with a confirmed diagnosis of breast cancer at the time of death, irrespective of place of death, were retrospectively reviewed. Results: During the study period, a total of 433 patients, median age 51.6 years, were included in the analysis. Among the whole group, 102 (23.6%) were referred to palliative care service early (≥30 days prior to death), 182 (42.0%) had late referral (<30 days from death), while 149 (34.4%) were never referred and were followed up by their medical oncologists. During the last 30 days prior to death, patients who were never referred to palliative care were more likely to visit the Emergency Room (ER) more than once (OR 1.89, 95% CI 1.20-2.99, p = 0.006), more likely to be admitted to the hospital more than once (OR 2.27, 95% CI 1.38-3.73, p = 0.001), and more likely to be admitted to the intensive care unit (ICU) (OR 3.07, 95% CI 1.48-6.38, p = 0.0027). Fewer patients in the "no referral" group died with advance directives compared to those who had early or late referral; 60.8%, 75.0% and 82.5%, respectively, p = 0.0003. Survival of patients followed by medical oncologist was not better than those referred to palliative care, either late or early; median survival was 19.0, 19.1 and 23.8 months, respectively (p = 0.2338). Conclusion: Findings suggest that earlier palliative care referral is associated with less aggressive end-of-life care, leading to less frequent ER visits, hospital and ICU admissions during the last month of life, and does not compromise survival.

Clinical Characteristics, Prognostic Factors and Treatment Outcomes of Patients with Bone-Only Metastatic Breast Cancer.

Introduction: Bone is the most frequent site of breast cancer metastasis. Differences between those who present with de novo bone-only metastasis (BOM) and those who progress to bone-only disease following a diagnosis of early-stage breast cancer are not clear. Such differences in clinical course might have an impact on the aggressiveness of treatment. This study presents the clinical and pathological features, along with treatment outcomes, of breast cancer patients with BOM in relation to the timing and type of bone metastasis. Patients and Methods: Patients with breast cancer and BOM were retrospectively reviewed. De novo BOM was defined as bone metastasis diagnosed at presentation or within the first 4 months of follow-up. Treatment outcomes of patients with de novo, compared to those with subsequent BOM, are presented. Results: 242 patients, median age (range) at diagnosis was 52 (27-80) years were enrolled. The majority of the patients (77.3%) had de novo BOM with multiple sites of bone involvement (82.6%). At a median follow-up of 37.7 months, the median overall survival (OS) for patients with de novo BOM disease was significantly shorter than those who developed so subsequently; 40.8 months (95% CI, 51.1-184.1) compared to 80.9 months (95% CI, 36.4-47.9), p < 0.001. Tumor grade, hormone receptor status and type of bone lesions (lytic versus sclerotic) had a significant impact on survival outcomes. Conclusion: Breast cancer with de novo BOM is a distinct clinical entity with unfavorable prognosis and is associated with shorter survival. Several risk factors for poor outcomes were identified and might inform treatment plans.

Atrial Septal Defect Repair in Adolescent and Adult Patients, a Cross Sectional Study at Jordan University Hospital, a Tertiary Hospital in a Developing Country.

Objective: We aim to report our heart team's experience in repair of Secundum atrial septal defect (ASD) in adolescent and adult patients at Jordan University Hospital (JUH). Methodology: A retrospective observational study of 44 patients who underwent secundum ASD closure by transcatheter closure (TCC) or Minimally Invasive Cardiac Surgery (MICS) at JUH. Patients who were treated at an age of 14 years or older regardless of the age of diagnosis were included. SPSS and Microsoft Excel were used to analyze the data. Results: A total of 44 patients with secundum ASD were treated during the period of (January 2015 and December 2019). The mean age was 34.1 (±14.3) years. Thirty-four patients underwent TCC, 9 underwent surgical closure and one had a hybrid procedure. We had no mortality and 2 minor morbidities. After a mean follow-up period of 13.2-/+13.6 months, most patients experienced improved symptoms, and there was a significant reduction of right ventricular dimension from 33.1 (±8.74) to 24 (±4.67) mm (p=0.0001). Conclusion: ASD closure whether TCC or MICS is a safe procedure with very low morbidity. A heart team approach is a necessity in the era of advances in both MICS surgery and TCC approach. A heart team provides the patients with a variety of safe and cosmetic solutions that allow the patients to have a fast management and recovery phase in rapid time through providing the merits and avoiding the complications of each modality, the team allows low volume centers in developing countries to achieve an excellent outcome.