Management of breast cancer patients with BRCA gene mutations in Jordan: perspectives and challenges.

BACKGROUND: This paper explores and discusses local challenges oncologists face for diagnosing and managing breast cancer patients with BRCA gene mutations in Jordan. METHODS: A task force involving key opinion leaders, experts in the management of breast cancer, and stakeholders in healthcare systems where genetic testing is available in Jordan discussed current evidence and local real-life practice. The task force then formulated recommendations to achieve better patient outcomes and satisfaction based on evidence-based medicine and their clinical experience in BRCA-mutated breast cancer management. RESULTS AND CONCLUSION: Eligibility of patients for genetic testing, physician acceptance and willingness to integrate genetic testing into routine practice is encouraging but remains restricted by testing availability and financial coverage. Until more data is available, genetic testing should be targeted for breast cancer patients based on tumor subtypes, as well as family and personal history of cancer, as per international guidelines. Whenever possible, genetic testing should aim to detect all actionable genes through a multigene panel including BRCA1/2. Major challenges faced in clinical practice in Jordan include fear of genetic discrimination and social stigmatization, as well as hesitancy toward risk-reducing surgery. Pre-testing counseling is therefore critical to promote acceptance of genetic testing. Since geneticists are in short supply in Jordan, genetic counseling can be offered through a specially trained genetic counselor or through a hybrid system that includes oncologist-based counselling. In addition to cancer prevention, germline genetic testing may assist in the selection of specific anti-cancer therapy, such as PARP inhibitors, in patients with BRCA1/2 mutation. Nationwide initiatives are also needed to ensure access to PARP inhibition therapy and provide financial coverage for genetic screening, mastectomies and reconstructive surgery across Jordan.

The first Middle East and North Africa expert consensus recommendations for the management of advanced colorectal cancer.

Colorectal cancer (CRC) is ranked as the third most prevalent and the second deadliest cancer worldwide. In the Middle East and North Africa (MENA) region, the number of CRC cases increased over the past decades and will nearly double by 2030. The lack of clear MENA guidelines for the management of patients with CRC represents a step backwards in the fight against this burden. Therefore a panel of 24 MENA experts in the field of gastrointestinal oncology developed, using a Delphi process, the first consensus recommendations for the management of patients with advanced CRC. Forty-seven different statements were formulated in the areas of epidemiology, screening, biomarkers and treatment. These recommendations will guide, standardize and unify the management of this cancer in the MENA region.

Generic Imatinib Therapy Among Jordanians: An Observational Assessment of Efficacy and Safety in Routine Clinical Practice.

INTRODUCTION: Generic imatinib therapy is being globally considered owing to cost considerations. However, evidence of its efficacy and safety in Middle Eastern clinical settings is scarce. PATIENTS AND METHODS: The efficacy and safety of generic imatinib (Cemivil) were assessed among Jordanian patients diagnosed with chronic myeloid leukemia using an observational, multicenter, prospective study design. Responses were defined using European LeukemiaNet 2009 guidelines and assessed by complete blood counts, fluorescence in situ hybridization, and real-time quantitative polymerase chain reaction. RESULTS: All patients (N = 91) were adults with chronic myeloid leukemia treated with generic imatinib 400 mg/day. Thirty-three patients received generic imatinib as first-line therapy, and 58 switched from patented imatinib to generic imatinib after a median of 4.5 years (range, 0.5-13.6 years) of imatinib therapy. The majority (85%; n = 28) of the first-line patients achieved complete hematologic response within 3 months of starting generic imatinib therapy (100% after 6 months [n = 33]). The 12-month major molecular response rate in the intention-to-treat population was 45%. The 12-month major molecular response rate was 88% for patients who switched therapy. The 12-month progression-free and overall survival rates were 92% and 100%, respectively. Most (85%; n = 144) adverse events were mild. Frequencies of drug-related adverse events were similar to patented imatinib. CONCLUSION: This study suggests that the efficacy and safety of generic imatinib in this Middle Eastern population in routine clinical practice are comparable to patented imatinib, and to that of the global population.

Frequency of epidermal growth factor receptor mutations in Jordanian lung adenocarcinoma patients at diagnosis.

BACKGROUND: Somatic mutations of the epidermal growth factor receptor (EGFR) gene have been associated with tumor response to tyrosine kinase inhibitors (TKIs) and favorable outcome in patients with non-small-cell lung cancer (NSCLC). The activating mutations that confer sensitivity to EGFR TKIs are present in the TK domain of the EGFR gene. This study aims to report on the prevalence of EGFR mutations in NSCLC and non-squamous lung cancer patients at diagnosis, using genomic deoxyribonucleic acid (DNA) obtained from paraffin-embedded tissue samples. MATERIALS AND METHODS: We collected formalin.fixed, paraffin.embedded. (FFPE) tissue samples from 166. cases of lungadenocarcinomas referring to Jordan University Hospital and King Hussein Cancer Center between 2007 and first half of 2013. None of the patients met the definition of never smoker defined as those who smoked less than 100 cigarettes in their lifetime. We evaluated EGFR mutations by nested polymerase chain reaction. (PCR) followed by direct sequencing of the EGFR kinase domain from exon 18 to 21. RESULTS: Six different point mutations were detected in 24 patients (14.46%) of the study population. The resultant mutations were as follows: Ten patients have deletion in exon 19, sevenpatients have L858R, two patients have L861P, and one of each of the following: A735T, D770_N771 insY, L858P, L861Q, and G917C. CONCLUSION: The present study revealed that the EGFR mutations rate in Jordanian patients with adenocarcinoma of the lung was higher than in African-American, and some white Caucasian patients, and was lower than in patients in East Asia, and other countries of South Asia.

Efficacy of capecitabine and temozolomide combination in well-differentiated neuroendocrine tumors: Jordan experience.

OBJECTIVES: Options for the treatment of well-differentiated neuroendocrine tumors (NETs) are limited. We evaluated the efficacy of capecitabine and temozolomide combination in patients from Jordan. METHODS: A retrospective review was conducted of 21 patients with metastatic well-differentiated NETs who failed somatostatin analogues and chemotherapy. Patients received capecitabine and temozolomide regimen every 28 days, and evaluation was done every 2 cycles. RESULTS: Twelve patients (57%) achieved partial response, and 5 (23%) achieved stable disease. Median progression-free survival was 16.5 months (range, 14.8-18 months). Of the 7 carcinoid tumors, 2 had partial response, and 2 had stable disease. There were no grade 4 toxicities or treatment-related deaths. CONCLUSIONS: Capecitabine and temozolomide regimen is an effective and well-tolerated salvage option for well-differentiated NETs.

Intravenous iron monotherapy for the treatment of non-iron-deficiency anemia in cancer patients undergoing chemotherapy: a pilot study.

BACKGROUND: Anemia in patients with cancer who are undergoing active therapy is commonly encountered and may worsen quality of life in these patients. The effect of blood transfusion is often temporary and may be associated with serious adverse events. Erythropoiesis-stimulating agents are not effective in 30%-50% of patients and may have a negative effect on overall survival. AIMS: To assess the efficacy and feasibility of intravenous iron therapy in patients with cancer who have non-iron-deficiency anemia and who are undergoing treatment with chemotherapy without the use of erythropoiesis-stimulating agents. METHODS: Adult patients with solid cancers and non-iron-deficiency anemia were included. Ferric sucrose at a dose of 200 mg was given in short intravenous infusions weekly for a total of 12 weeks. Hemoglobin level was measured at baseline, every 3 weeks, and 2 weeks after the last iron infusion (week 14). Adverse events related to intravenous iron were prospectively reported. RESULTS: Of 25 patients included, 19 (76.0%) completed at least three iron infusions and 14 (56.0%) finished the planned 12 weeks of therapy. The mean hemoglobin level of the 25 patients at baseline was 9.6 g/dL (median, 9.9 g/dL; range, 6.9 g/dL 10.9 g/dL). The mean change in hemoglobin level for the 15 patients who completed at least 9 treatments was 1.7 g/dL (median, 1.1 g/dL; range, -1.9 g/dL to 3.2 g/dL); it reached 2.1 g/dL (median, 1.3 g/dL; range, -0.2 g/dL to 4.6 g/dL; P = 0.0007) for the 14 patients who completed all 12 weekly treatments. Five (20.0%) patients were transfused and considered as treatment failures. No treatment-related adverse events were reported. CONCLUSION: Intravenous iron treatment alone is safe and may reduce blood transfusion requirements and improve hemoglobin level in patients with cancer who are undergoing anticancer therapy. Further randomized studies are needed to confirm these findings.

Acute lymphoblastic leukemia experience: epidemiology and outcome of two different regimens.

OBJECTIVES: Accurate data about adult acute lymphoblastic leukemia (ALL) are lacking. We aim to assess demographics, prognostic factors, and outcome of ALL therapy at King Hussein Cancer Center (KHCC) in Jordan, and to compare the efficacy of two protocols. METHODS: We reviewed medical records of adults diagnosed and treated for ALL at KHCC from January, 2007 to December, 2011. RESULTS: Over a 5-year period, 108 patients with ALL were treated (66 with the Hyper-CVAD regimen, and 42 with the CALGB 8811 regimen). Median age at diagnosis was 33 years, with 63% males. The most common immunophenotype was CD10-positive common ALL, and 16% have BCR-ABL translocation. Complete response (CR) rate was 88%. After a median follow-up of 32 months (range, 10-72 months), the median survival (MS) was 30 months, and CR duration (CRD) was 28 months. In the multivariate analysis, the presence of BCR-ABL translocation was the only poor prognostic factor with lower MS of 23 months (p<0.01). There was no difference in MS or CRD between the two used regimens. CONCLUSION: International protocols for adult ALL were successfully applied to our patients. There is no difference in efficacy between Hyper-CVAD and CALGB 8811 regimens. Future protocols for adult ALL should incorporate new targeted agents and minimal residual disease monitoring to improve outcome.

ABL kinase domain mutations in patients with chronic myeloid leukemia in Jordan.

Mutations of the BCR-ABL tyrosine kinase domain constitute a major cause of resistance to tyrosine kinase inhibitors in patients with chronic myelogenous leukemia (CML). In this study, we analyzed peripheral blood samples from 185 Jordanian CML patients for ABL mutations, who were on imatinib for a minimum of 6 months regardless of their disease status and over a period of 5 years. Mutations were detected by nested RT-polymerase chain reaction, followed by direct sequencing of the ABL kinase domain. Twelve different point mutations were detected 25 times in 21 patients. The resultant mutations were as follows: four patients have T315I, three of each of the following: L248V, F317L, and G250E, two of each of the following: H396R, M244V, and T277A, and one of each of the following: F311I, M318T, Q252H, F359A, F359I, and Y326H. After patient follow-up, the mutation had disappeared in 12 patients; 3 patients died; 3 patients were not retested; and 3 patients had persistent mutation. The finding of our study is in line with what has been described in the literature. Detecting ABL mutations in chronic phase may lead to positive outcome by modifying treatment.

Metastatectomy for extra-cranial extra-adrenal non-small cell lung cancer solitary metastases: systematic review and analysis of reported cases.

BACKGROUND: Although patients with stage IV non-small cell lung cancer (NSCLC) have a poor prognosis, a subset of patients with solitary brain or adrenal metastasis have more favorable outcome following surgical resection. Nevertheless, the outcome and predictive factors for survival following metastatectomy for patients with other metastatic sites are not well defined. METHODS: We performed a systematic review using PUBMED database for all articles which included patients with NSCLC and solitary metastasis to sites other than the adrenal gland or the brain who had undergone resection of their metastasis and definitive treatment of the primary lung cancer. Potential prognostic factors on survival including age, sex, histology, T and N stage of the primary tumor, synchronous vs. metachronous presentation, visceral vs. non-visceral metastasis and the use of perioperative chemotherapy were analyzed using multi-variable Cox proportional hazard model. RESULTS: 62 cases were eligible for the analysis. The 5-year survival rate was 50% for the entire cohort. Mediastinal lymph node involvement was independently predictive of inferior outcome; 5-year survival rate 0% vs. 64% in favor of no involvement, p<0.001. Similarly, patients with intra-thoracic stage III disease had an inferior outcome compared to patients with stage II and stage I disease: 5-year survival rate 0% vs. 77% and 63%, respectively, p<0.001. Other factors have no effect on outcome. CONCLUSION: Selected patients with distant metastatic NSCLC can achieve long term survival following metastatectomy and definitive treatment of the primary tumor. Mediastinal lymph node involvement is associated with poor prognosis.

Prognostic Factors in Advanced Non-Small-Cell Lung Cancer Patients: Patient Characteristics and Type of Chemotherapy.

Eleven prognostic factors were retrospectively analyzed in 270 newly diagnosed patients with advanced non-small-cell lung cancer including age, sex, performance status, histology, stage, smoking status, hemoglobin level, forced expiratory volume in one second (FEV1), weight loss >5% in 3 months preceding therapy, number of involved organs, and type of first-line chemotherapy. Response rate was 35.6%, and median survival was 8.2 months (95% CI, 7.8 to 8.7) for the whole group. Age ≤60 years (P = .016), FEV1 ≥ 2L (P = .03), and the use of platinum/docetaxel (P < .0001) were significantly associated with an improved survival. Histology did not affect outcome in the absence of targeted therapies.

Myeloid sarcoma: clinicopathologic, cytogenetic, and outcome analysis of 21 adult patients.

Myeloid sarcoma (MS) is a neoplasm of immature granulocytes, monocytes, or both involving any extramedullary site. Twenty one patients with MS at diagnosis who were treated at King Hussein Cancer Center in Jordan were included in this retrospective study with a male to female ratio of 2 : 1. The most common site was the reticuloendothelial system. The most common morphology subtype was M2 (38%) and the most frequent chromosomal abnormality was trisomy 8. Twenty patients received induction chemotherapy; only 14 (70%) achieved complete remission. Median survival time was 24.7 months for the whole group and 58.6 months for patients who underwent allogenic bone marrow transplant. This paper showed that MS has frequent M2 morphology, carries chromosomal aberrations other than t(8;21), and requires aggressive therapy as a front line approach.

Advanced gastric cancer in jordan from 2004 to 2008: a study of epidemiology and outcomes.

BACKGROUND: WE REPORT THE EPIDEMIOLOGIC FEATURES AND THE TREATMENT EXPERIENCE OF ADVANCED GASTRIC CANCER (GC) AT KING HUSSEIN CANCER CENTER (KHCC) IN JORDAN, AND WE RETROSPECTIVELY COMPARE OUTCOMES OF TWO DIFFERENT REGIMENS: DCF (docetaxel/cisplatin/5-fluorouracil) vs. ECF (epirubicin/cisplatin/5-fluorouracil). METHODS: Charts of 162 patients with inoperable GC treated between January 2004 and December 2008 were reviewed. A total 143 patients received chemotherapy (ECF = 113; DCF = 30). Choice of regimen was changed from ECF to DCF on January 2008 according to KHCC guidelines. RESULTS: The median patient age was 59 years, with a male:female ratio of 1.8:1. Lymph nodes (67.9%) and liver (49.4%) were the most common sites of metastasis. Primary disease site was stomach in 78.4%, gastroesophageal junction in 16.7%, lower esophagus in 4.9%. Poorly differentiated histology was predominant (46.9%). Anemia (53.7%), pain (48.1%), and reflux (44.4%) were the most common presenting symptoms. Helicobacter pylori infection was present in 79%. Average time between initial symptom and diagnosis was 6.0 months. The overall response rate (ORR) was 59.3% with DCF and 32.6% with ECF (P = .01). Time to tumor progression (TTP) was 6.9 months with DCF and 5.9 months with ECF (P = .005). Median survival was 11.0 months with DCF and 10.2 months with ECF (P = .17). CONCLUSION: Some epidemiologic features of GC in Jordan mimic those of high-risk areas. Our outcomes of chemotherapy are comparable to internationally reported data and suggest superiority of DCF over ECF in terms of ORR and TTP.

Ectopic pancreatic tissue in the thoracic cavity: report of two cases.

Ectopic pancreas in the thoracic cavity is uncommon. We report 2 patients who had large cystic or cystic-solid masses containing pancreatic tissue in the thorax. Their clinical presentation, imaging, and pathologic findings are described. Both patients underwent total surgical resection of the masses, with no recurrence.

A positive antinuclear antibody test predicts for a poor response to initial steroid therapy in adults with idiopathic thrombocytopenic purpura.

Adult idiopathic thrombocytopenic purpura (ITP) is an acquired autoimmune disease that may be associated with other autoimmune disorders and a positive antinuclear antibody (ANA). This pilot study aimed to determine the clinical significance of a positive ANA test on the presentation and response to steroids. The medical records of 46 patients aged 15 years or older who were diagnosed with ITP at King Abdullah University Hospital from January, 2004 to December, 2006 were retrospectively analyzed. ANA results were available for 41 patients, and only 10 patients had a positive test. The study showed no association between the ANA and any of the patients' characteristics at presentation. This included the age, sex, presence of autoimmune diseases, a family history of autoimmune diseases, platelet count, hemoglobin level, and erythrocyte sedimentation rate (ESR). It is interesting to note that the mean platelet count after 2 weeks of steroids was 99,323 per cu/ml in patients with a negative ANA, and 32,800 per cu/ml in those with a positive ANA (P = 0.006). The difference in mean platelet count between positive and negative ANA-tested patients remained significant after adjusting for sex, age, and ESR (P = 0.001). Also, patients with a positive ANA were 6.25 times more likely of not achieving a complete response defined as a platelet count of 100,000 per cu/ml or more for a minimum of 3 months after discontinuation of therapy. In conclusion, the ANA test could be a useful screening test that predicts initial response to steroid therapy. Patients who test positive are expected to have lower response and should be monitored closely.

Palliative ethanol injections of unresectable advanced esophageal carcinoma combined with chemoradiation.

Combined chemoradiation therapy has proven to be an effective treatment for unresectable esophageal cancer. Nonsurgical endoscopic palliation of local disease has become feasible with neodymium:yttrium-aluminum-garnet laser, BICAP tumor probe, and metallic stents. Alternatively, endoscopic injections of ethanol are safe, inexpensive, and useful for palliation of malignant dysphagia. Two patients with unresectable squamous cell carcinoma of the esophagus were treated with 1 mL of absolute (95 g/L) alcohol injections once a week for 4 weeks, followed by chemoradiation therapy consisting of concomitant 5-fluorouracil 300 mg/m/d and radiation therapy (total of 60 Gy over 6 weeks). One patient had a complete response but died of alcoholism 25 months after diagnosis without evidence of tumor recurrence. The other patient had a partial response but died 16 months after diagnosis from disease progression. We conclude that tumor ablation by ethanol injection for palliation combined with chemoradiation may be a low-cost alternative for advanced unresectable esophageal cancer.