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.

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.

Prevalence, Patterns, and Predictors of Venous Thromboembolic Events in Patients Undergoing Salvage Chemotherapy and Autologous Stem Cell Transplantation for Relapsed Lymphomas.

BACKGROUND AND OBJECTIVES: Almost 25% of patients with lymphoma may have relapse or develop refractory disease, and a majority of such patients undergo salvage chemotherapy and autologous stem cell transplantation (ASCT). Data on venous thromboembolism (VTE) in this setting are scarce. This study aimed to investigate the prevalence and factors that may increase the risk of VTE in such patients. PATIENTS AND METHODS: Adult patients who were diagnosed with lymphoma and received salvage chemotherapy and ASCT were included in the study, and the subgroup with radiologically confirmed VTE were identified. Correlations between different clinical and laboratory variables and VTE were evaluated. RESULTS: A total of 216 patients (median age, 31 [range, 19-60] years) were enrolled in the study. Most patients (n = 140, 64.8%) had Hodgkin's lymphoma, while 54 (25.0%) had diffuse large B-cell lymphoma. A total of 36 (16.7%) patients had VTE, mostly as upper extremity deep vein thrombosis (n = 28, 77.8%); 18 (50%) of the cases were related to central venous catheter insertion. Thrombosis rates were higher among patients with high lactate dehydrogenase (LDH) level (29.2% vs. 5.9%, p < 0.001), those with mediastinal involvement (25.9% vs. 11.5%, p = 0.025). and those with longer hospital stay (22.3% vs.9.5%, p = 0.036). In the multivariate analysis, high LDH level (odds ratio (OR), 6.53; p < 0.001), mediastinal involvement (OR, 2.70; p = 0.005) and hospital stay ≥24 days (OR, 2.71; p = 0.007) were all associated with significantly higher VTE rates. CONCLUSION: Patients with relapsed lymphoma undergoing salvage chemotherapy and ASCT are at higher risk for VTE, especially in those with high LDH level, mediastinal involvement, and prolonged hospital stay. If no contraindications exist, thromboprophylaxis might be considered in these settings.

The impact of having a relative or a friend with cancer on person's modifiable cancer-related risk factors.

BACKGROUND: It is known that targeting cancer-related modifiable risk factors is the best way to fight cancer. Behavioral and lifestyle changes can significantly reduce the burden of cancer. AIMS: We aim to assess the impact of having a relative/friend with cancer on the number of cancer-related modifiable risk factors a participant might have. METHODS: A survey-based cross-sectional study was conducted at King Hussein Cancer Center from June 2020 until July 2020. The survey was distributed via social media platforms, where we targeted adults who have never been diagnosed with cancer. We asked about modifiable cancer-related risk factors and compared between participants with and without relatives or friends with cancer. RESULTS: A total of 1486 participants were considered for analysis, with a mean age of 30.62 (SD 11.19) years. Participants who had a relative with cancer had a mean of 0.31 (p = 0.007; 95% CI: 0.08-0.54) fewer risk factors, with smoking and extra sun exposure were significantly lower among participants with a cancer relative. No significant difference in modifiable risk factors was found between participants with a friend who have cancer and those who do not (p = 0.193). CONCLUSION: People who have relatives with cancer had less modifiable risk factors, which might reflect on their willingness to modify their cancer-related risk factors.

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.

A Durable Response of Primary Advanced Colonic Plasmacytoma Using a Combination of Surgical Resection and Adjuvant Bortezomib: A Case Report and Literature Review.

Background: Primary isolated extra-medullary plasmacytoma (EMP) is a rare entity that most commonly involves the nasopharynx or upper respiratory tract. Only 10% of cases involve the gastrointestinal tract, mainly the small intestine and the stomach. Involvement of the colon is extremely rare with less than 40 reported cases worldwide. Case Presentation: We report a case of a 57-year-old man who was presented with a 3-week history of fresh bleeding from the rectum. Colonoscopy showed a polypoidal mass arising from the ascending colon; biopsy showed clonal plasmacytosis and a primary colonic solitary EMP diagnosis was made after exclusion of multiple myeloma (MM). Accordingly, the patient underwent a right hemicolectomy, followed by 6 cycles of bortezomib, cyclophosphamide, and dexamethasone (VCD). The patient continued to be disease-free 30 months after the completion of his chemotherapy. Conclusion: To our knowledge, this is the first reported case of primary colonic plasmacytoma managed with surgical resection followed by an adjuvant bortezomib-based regimen with a durable response.

Rates of Variants of Uncertain Significance Among Patients With Breast Cancer Undergoing Genetic Testing: Regional Perspectives.

Purpose: Contrary to BRCA pathogenic variants, recommendations for management of variants of uncertain significance (VUS) are not clear and focus more on the patient's family and personal history of cancer. Local and regional data on VUS are scarce. In this paper, we study patterns and frequency of VUS among breast cancer patients undergoing genetic testing. Patients and Methods: Patients with breast cancer at high risk for pathogenic variants, as per the National Comprehensive Cancer Network (NCCN) guidelines, were tested at reference laboratories. Related surgical interventions were reviewed. Results: Among a group of 1,197 patients with breast cancer who underwent genetic testing and counseling, 110 (9.2%) had VUS; most (n = 79, 71.8%) were in BRCA2. Median age (range) was 39 (25-66) years with 65 (59.1%) patients who were 40 years or younger at diagnosis. Among 103 patients with non-metastatic disease, 48 (46.6%) had breast-conserving surgery (BCS) while only 5 (4.9%) had bilateral mastectomies; all were due to bilateral disease and not prophylactic. VUS diagnosis was known prior to initial surgery in 34 (33.0%) patients; 11 (32.4%) of them had BCS only. Over the study period, only one VUS variant was upgraded to "likely positive." The recent introduction of multiple-gene panel testing had resulted in a surge in VUS rate (22.2%) in genes other than BRCA1 or BRCA2, like PALB2, CHEK2, and ATM. Conclusions: Rates of VUS are relatively high and increasing, mostly in non-BRCA1 or BRCA2, and this had no impact on the therapeutic or prophylactic surgical decisions. Adherence to guidelines is extremely important to avoid unnecessary procedures.

The efficacy of a comprehensive bone health program in maintaining bone mineral density in postmenopausal women with early-stage breast cancer treated with endocrine therapy: real-world data.

BACKGROUND: Aromatase inhibitors (AI) are the gold standard treatment option for hormone-sensitive postmenopausal women with breast cancer. Several studies had documented the accelerated bone loss associated with AI. AIMS: In this study, we present real-world data describing the efficacy of implementing a comprehensive bone health program to maintain bone mineral density (BMD) in postmenopausal patients with early-stage breast cancer treated with AI. METHODS: A comprehensive bone health program that includes counseling, exercise, nutritional advice, vitamin D supplements and, when needed, intravenous bisphosphonate infusion was implemented following the initiation of endocrine therapy with AI. Postmenopausal women with hormone-sensitive, early-stage breast cancer treated with endocrine therapy using AI were retrospectively identified. All patients had BMD measurements before and at least 1 year after ET initiation. RESULTS: A total of 210 patients were included, median (range) age 67 (43-86) years. At baseline, osteoporosis was documented in 38 (18.1%) and osteopenia in 101 (48.1%) patients. Despite the known negative effect of AI, 32 (84.2%) patients with baseline osteoporosis and 69 (68.3%) of those with osteopenia, had a stable or better BMD. On the other hand, 41 (57.7%) of those with normal baseline BMD had a drop in their follow up BMD, p < 0.001. Vertebral fractures were reported in 3 (11.1%) patients with osteoporosis compared to none in patients with normal BMD, p = 0.021. CONCLUSIONS: Despite the known negative effect of ET on bone health of breast cancer patients, implementing a comprehensive bone health program stabilized or improved BMD.

From clinical trials to clinical practice: the use of everolimus and exemestane in the treatment of hormone receptor-positive metastatic breast cancer: real-world data.

Everolimus combined with exemestane can modulate endocrine resistance. The combination showed significant improvement in progression-free survival (PFS) in phase III clinical trials for hormone receptor positive metastatic breast cancer patients. It also showed serious adverse events. We evaluate the efficacy and prevalence of serious adverse events in a real-world setting. We retrospectively examined 91 breast cancer patients; all were previously treated with chemotherapy and fulvestrant (84% and 59%, respectively). After a 13-month median follow-up, 29% had a partial response, and 32% had stable disease. The PFS was 7.8 months. Due to adverse events, 19% of patients stopped the treatment, while 31% required a dose reduction. Despite enrolling heavier-pretreated patients, our real-world outcome for the efficacy and safety of the exemestane and everolimus match those of the clinical trials. Such results should assure clinicians and lead to wider adoption of this oral, chemotherapy-sparing regimen.

The Application of the ThroLy Risk Assessment Model to Predict Venous Thromboembolism in Patients with Diffuse Large B-Cell Lymphoma.

BACKGROUND: Patients with aggressive lymphomas are at higher risk for venous thromboembolism (VTE). ThroLy is a risk assessment model (RAM) derived to predict the occurrence of VTE in various types of lymphomas. In this study, we assess the clinical application of ThroLy RAM in a unified group of patients with diffuse large B-cell lymphoma (DLBCL). METHODS: Hospital databases were searched for patients with DLBCL and radiologically-confirmed VTE. Items in the ThroLy RAM, including prior VTE, reduced mobility, obesity, extranodal disease, mediastinal involvement, neutropenia and hemoglobin < 10.0 g/dL, were retrospectively reviewed. RESULTS: A total of 524 patients, median age 49 (range: 18-90) years were included. Patients had high disease burden; 57.3% with stage III/IV and 34.0% with bulky disease. All were treated on unified guidelines; 63 (12.0%) had primary refractory disease. Venous thromboembolic events were reported in 71 (13.5%) patients. Among 121 patients with high (> 3) ThroLy score, 22.3% developed VTE compared to 8.4% and 12.4% in those with low and intermediate risk scores, respectively (P = .014). Simplifying the ThroLy model into two risk groups; high-risk (score ≥ 3) and low risk (score < 3) can still segregate patients; VTE developed in 44 (17.2%) high-risk patients (n = 256) compared to 27 (10.1%) in the low-risk group (n = 268), P = .038. Neutropenia, a component of the ThroLy, was encountered in only 14 (2.7%) patients. CONCLUSIONS: ThroLy RAM can identify patients with DLBCL at high risk for VTE. Model can be modified by dividing patients into two, rather than three risk groups, and further simplified by omitting neutropenia.

Prevalence and predictors of germline BRCA1 and BRCA2 mutations among young patients with breast cancer in Jordan.

BRCA1 and BRCA2 mutations are not uncommon in breast cancer patients. Western studies show that such mutations are more prevalent among younger patients. This study evaluates the prevalence of germline mutations in BRCA1 and BRCA2 among breast cancer patients diagnosed at age 40 or younger in Jordan. Blood samples of patients with breast cancer diagnosed at age 40 years or younger were obtained for DNA extraction and BRCA sequencing. Mutations were classified as benign/likely benign (non-carrier), pathogenic/likely pathogenic variant (carrier) and variant of uncertain significance (VUS). Genetic testing and counseling were completed on 616 eligible patients. Among the whole group, 75 (12.2%) had pathogenic or likely pathogenic variants; two of the BRCA2 mutations were novel. In multivariate analysis, triple-negative disease (Odd Ratio [OR]: 5.37; 95% CI 2.88-10.02, P < 0.0001), breast cancer in ≥ 2 family members (OR: 4.44; 95% CI 2.52-7.84, P < 0.0001), and a personal history ≥ 2 primary breast cancers (OR: 3.43; 95% CI 1.62-7.24, P = 0.001) were associated with higher mutation rates. In conclusion, among young Jordanian patients with breast cancer, mutation rates are significantly higher in patients with triple-negative disease, personal history of breast cancer and those with two or more close relatives with breast cancer.

Differences in clinicopathological characteristics, treatment, and survival outcomes between older and younger breast cancer patients.

In developing countries, breast cancer is diagnosed at a much younger age. In this study we investigate the dichotomies between older and young breast cancer patients in our region. The study involved two cohorts; older patients (≥ 65 years, n = 553) and younger ones (≤ 40 years, n = 417). Statistical models were used to investigate the associations between age groups, clinical characteristics and treatment outcomes. Compared to younger patients, older patients were more likely to present with advanced-stage disease (20.6% vs. 15.1%, p = .028). However, among those with non-metastatic disease, younger patients tended to have more aggressive pathological features, including positive axillary lymph nodes (73.2% vs. 55.6%, p < .001), T-3/4 (28.2% vs. 13.8%, p < .001) and HER2-positive disease (29.3% vs. 16.3%, p < .001). The 5-year overall survival (OS) rate was significantly better for the younger (72.1%) compared to the older (67.6%), p = .035. However, no significant difference was observed in disease-free survival (DFS) between the two groups.In conclusion, younger patients with breast cancer present with worse clinical and pathological features, albeit a better OS rate. The difference in DFS between the two groups was not insignificant, suggesting that older women were more likely to die from non-cancer related causes.

Predictors of Venous Thromboembolism in Patients With Testicular Germ Cell Tumors: A Retrospective Study.

Malignancy, including testicular tumors, significantly increases the risk of venous thromboembolism (VTE). In this study, we search for predictors that may help identify subgroups of patients at higher risk of VTE. Patients with confirmed diagnosis of testicular germ cell tumor and proven VTE were identified. Clinical and pathological features possibly associated with VTE were reviewed. A total of 322 patients, median age (range) 31 (18-76) years were identified. Tumors were mostly non-seminoma (n = 194, 60.2%), node-positive (n = 130, 40.4%) and 58 (18.0%) had metastatic disease at diagnosis. Venous thromboembolism were confirmed in 27 (8.4%) patients; however, rates were significantly higher (P < 0.001) in patients with node-positive (18.5%), metastatic disease (22.4%), and those with high lactate dehydrogenase (LDH) (21.3%). Rates were also significantly higher among those who received multiple lines of chemotherapy (27.5%) compared to those who received one line (13.8%) or none (<1.0%), P < 0.001. Patients with testicular tumors and high tumor burden, including nodal involvement, high LDH or metastatic disease, and those treated with multiple lines of chemotherapy have significantly higher rates of VTE.

The Application of the Lymphoma International Prognostic Index to Predict Venous Thromboembolic Events in Diffuse Large B-Cell Lymphoma Patients.

BACKGROUND: Venous thromboembolic events (VTE) are commonly encountered in patients with lymphoma. Several risk assessments models (RAM) had attempted to identify higher risk patients with varying success. The International Prognostic Index (IPI) is a clinicopathological tool developed to help predict both response to treatment and prognosis of patients with diffuse large B-cell lymphoma (DLBCL). OBJECTIVE: In this study, we utilize the IPI index to identify group of patients with DLBCL at higher risk for VTE. PATIENTS/METHODS: Patients with pathologically-confirmed diagnosis of DLBCL and with image-confirmed VTE, treated and followed at our institution were included. Rates of VTE was calculated for each risk category. RESULTS: A total of 373 patients, median age 49 (range: 18-90) years were included. VTE were reported in 56 (15.0%) patients; 51 (91.1%) had active disease while 29 (51.8%) were ambulatory at time of VTE diagnosis. VTE rates were particularly high among patients with poor performance status (26.2%, P=0.028) and high LDH (19.0%, P=0.023). Applying the age-adjusted IPI separated patients into two risk categories; VTE were diagnosed in 9.7% in patients with "low and low-intermediate" scores compared to 19.8% in patients with "high and high-intermediate" scores, P=0.020. CONCLUSIONS: The original IPI and its modified versions, routinely used at diagnosis as a prognostic and predictive tool for patients with DLBCL, can also be utilized to define high risk patients for VTE; the risk of whom might be high enough to recommend thromboprophylaxis even in the ambulatory settings. More work is needed to refine and improve currently available RAMs.

Patterns and Prevalence of BRCA1 and BRCA2 Germline Mutations Among Patients with Triple-Negative Breast Cancer: Regional Perspectives.

BACKGROUND: Among all subtypes, patients with triple-negative (TN) breast cancer is known for their poor outcome and their higher risk of harboring BRCA1 or BRCA2 pathogenic mutations. Identification of such mutations has clinical impact on breast and ovarian cancer prevention and treatment decisions. We here report on patterns and prevalence of BRCA1 and BRCA2 mutations among Arab patients diagnosed with TN subtype. PATIENTS AND METHODS: Patients with TN-breast cancer (n=197) were enrolled regardless of their age or family history. Following a detailed genetic counseling, BRCA1/2 testing was performed at reference labs. BRCA1 and BRCA2 variants were classified as negative, pathogenic/likely pathogenic (positive) and variants of uncertain significance (VUS). RESULTS: Median age of enrolled patients was 42 (range, 19-74) years and 27 (13.7%) were non-Jordanian Arabs. Among the study group, 50 (25.4%) were tested positive for BRCA1 (n=36, 18.3%) or BRCA2 (n=14, 7.1%), while 14 (7.1%) others had VUS. Compared to older ones, mutation rates were higher among patients <40 years (32.9%, P= 0.034), those with close relatives with breast, ovarian, pancreatic or prostate cancer (37.8%, P=0.002) and those with two or more breast cancers (41.4%, P=0.032). Among eligible patients, 23 (63.9%) patients underwent prophylactic mastectomy, while 19 (52.8%) patients had risk-reducing salpingo-oophorectomy. None of the patients with VUS underwent any prophylactic surgery. CONCLUSION: Arab patients with TN-breast cancer have relatively high BRCA1 or BRCA2 mutation rates. Young age at diagnosis and personal and family history of breast cancer further increase this risk.

Late presentation and suboptimal treatment of breast cancer among Syrian refugees: a retrospective study.

OBJECTIVES: The crisis in Syria has had a profound impact on the entire region. In this study, we report the patterns of presentation and management of Syrian patients with breast cancer treated at our institution. METHODS: We retrospectively collected data on Syrian refugees treated for breast cancer over the past 10 years at our center. Management was compared against our approved clinical practice guidelines. RESULTS: A total of 113 patients were eligible and included. The median age (range) at diagnosis was 47 (21-84) years and most women presented with locally advanced or metastatic disease (n = 74, 65.5%). Breast-conserving surgery and breast reconstruction were performed in 27 (33.8%) and 11 (35.4%) patients, respectively. Only a few patients received targeted (35.5%) or advanced endocrine therapy (30.0%). In total, 37 (32.7%) patients had considerable deviations from our institutional treatment guidelines and had worse outcomes. CONCLUSIONS: Syrian refugees with breast cancer present late, have more advanced-stage disease, and are more likely to receive delayed and suboptimal therapy. An international systematic approach for cancer care among such vulnerable populations is urgently needed.

Thrombosis and Anticoagulant Therapy Among Pediatric Cancer Patients: Real-Life Data.

BACKGROUND: Venous thromboembolism (VTE) in children is relatively rare, and more so among those with cancer. In this study, we report the characteristics and outcomes of children with cancer-associated thrombosis. METHODS: We reviewed institutional databases for all children with cancer and a diagnosis of VTE at King Hussein Cancer Center in Jordan. Variables reviewed are patients' clinical characteristics, treatment for cancer, and anticoagulation therapy. RESULTS: Between January 2011 and December 2018, a total of 45 patients fulfilled the inclusion criteria, and the median age was 10.4 (0.8-17.9) years. The most common underlying diagnosis was acute lymphoblastic leukemia (n = 13, 29%). At the time of VTE, 29 (64.4%) patients were receiving chemotherapy, and eight (17.8%) had a central venous catheter (CVC). The majority of patients (n = 37, 82%) developed VTE within 30 days of hospitalization. Thrombosis mostly involved the extremities (n = 23, 51%) and sagittal vein (n = 12, 26.7%). All patients were treated with low-molecular-weight heparin (LMWH), complicated by bleeding in three (6.6%) patients. CONCLUSION: In contrast to adults, VTE in pediatric cancer patients is more associated with chemotherapy and recent hospitalization. LMWH is a safe and effective therapy for children with cancer who develop VTE.

Effect of level of hormone-receptor expression on treatment outcomes of "triple-positive" early-stage breast cancer.

PURPOSE: Breast cancer that overexpresses the human epidermal growth factor receptor-2 (HER2) and both estrogen (ER) and progesterone (PR) receptors is recently recognized as a subtype (triple-positive) with distinctive behavior and response to treatment. In this study, we investigate the treatment outcomes and the beneficial effect of anti-HER2 treatment in relation to level of hormone-receptor (HR) expression. METHODS: Consecutive breast cancer patients with triple-positive disease, diagnosed, treated and followed at our institution between 2006 and 2016 were enrolled. Disease-free survival (DFS) was studied in relation to the level of HR-positivity. RESULTS: During the study period, a total of 312 were enrolled; median age (range) was 47 (20-83) years. Fifty (16.0%) of the enrolled patients received adjuvant chemotherapy without trastuzumab (cohort A). All remaining patients were treated with both chemotherapy and trastuzumab and were divided into two groups: Cohort B with both ER and PR scores ≥ 50% (n = 130, 41.7%) and Cohort C with ER and/or PR < 50% (n = 132, 42.3%). After a median follow-up of 47 months, 14 (28.0%), 30 (23.1%) and 20 (15.2%) patients in cohorts A, B, and C had an event in a form of local/system relapse or death while disease-free. The estimated 5-year DFS was 56.2%, 75.4%, and 80.8%, respectively, and at 7 year was 56.2%, 67.1%, and 78.0%, respectively (p < 0.001). CONCLUSIONS: HER2-positive tumors are not homogeneous; stronger ER/PR co-expression may weaken the beneficial effect of anti-HER2 therapy. Such findings may have potential implication on modifying anti-HER2 treatment based on the strength of HR expression.

Patterns and predictors of thromboembolic events among patients with gastric cancer.

Patients with gastric cancer are at higher risk for venous thromboembolic events (VTE). Majority of such patients are treated in ambulatory settings where thromboprophylaxis is not routinely offered. In this study, we report on VTE rates and search for predictors that may help identify patients at higher risk to justify VTE-prophylaxis in ambulatory settings. Patients with pathologically-confirmed gastric adenocarcinoma were retrospectively reviewed for VTE detected by imaging studies. Clinical and pathological features known to increase the risk of VTE were studied. Khorana risk assessment model was applied on patients receiving chemotherapy. A total of 671 patients; median age 55 years, were recruited. VTE were diagnosed in 150 (22.4%) patients, including 42 (28.0%) pulmonary embolism and 18 (12.0%) upper extremity deep vein thrombosis (DVT). Majority (> 80%) developed VTE while in ambulatory settings and none had been on thromboprophylaxis. Rate was higher (27.1%) among 365 patients with metastatic compared to 16.7% among 306 patients with nonmetastatic disease, p = 0.001. Patients with metastatic disease who received multiple lines of chemotherapy (n = 85) had significantly higher rate of VTE compared to those who received a single line; 48.2% versus 19.4%, p < 0.001. Among the whole group, Khorana risk score, age, gender, smoking and obesity had no impact on VTE rates. Patients with metastatic gastric cancer, especially when treated with multiple lines of chemotherapy, are at a significantly higher risk of VTE. Khorana risk score had no impact on VTE rates. Thromboprophylaxis in ambulatory patients with metastatic gastric cancer worth studying.

Trends, Patterns, and Treatment Outcomes of Cancer Among Older Patients in Jordan: A Retrospective Analysis of National Cancer Registry and Institutional Outcome Data.

PURPOSE: Cancer is a leading cause of morbidity and the second leading cause of mortality in Jordan and worldwide. Because of their age and comorbidities, older patients may receive suboptimal cancer therapy. This article addresses trends in cancer incidence and reports key treatment outcomes in this age group. MATERIALS AND METHODS: This is a retrospective study using data obtained from the national Jordan Cancer Registry (JCR) and our institutional cancer registry. The first data set reports only on demographics, whereas the second data set reports also on treatment outcomes. Older patients were defined as those age 65 years or older at time of diagnosis. RESULTS: Between 2001 and 2015, a total of 19,397 older patients were diagnosed with cancer, representing 29.8% of the total 65,050 patients with cancer diagnosed during this time. More men than women developed cancer, and colorectal, breast, lung, prostate, and bladder cancers were the most commonly reported cancers. Among this age group over the 15-year study period, cancer diagnoses increased by a rate of 77%, much higher than the 55% increment among all ages during the same study period. The 5-year survival rate for all of the 3,821 older patients diagnosed, treated, and followed up at our institution was 33% but varied by stage (63% for stage I disease and 14% for stage IV disease). CONCLUSION: Cancer diagnoses among older patients are increasing at a rate higher than that of all ages and much higher than the witnessed increase in Jordanian population in same age group, which highlights the importance of looking for factors other than just aging to explain this increase. Strategies to offer better care for this rapidly expanding group are highly needed.