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.

Rosai-Dorfman disease masquerading as Uveal Melanoma: Case report and review of literature.

OBJECTIVE/BACKGROUND: Intra ocular Rosai-Dorfman disease (RDD) is an extremely rare disease. We are reporting the first case of RDD presenting as ciliary body mass mimicking ciliary body melanoma, and we are reviewing the English literature reporting on cases of RDD presented with intraocular disease. METHODS: An 18-year-old lady presented with loss of vision in the right eye, and was found to have intraocular mass lesion. She was diagnosed clinically and radiologically as a case of ciliary body melanoma associated with total retinal detachment. RESULTS: Histopathological sections and stains proved to be intraocular RDD. Review of the literature revealed three cases of intraocular RDD; two of them had choroid thickening associated with serous retinal detachment, and one presented with intraocular mass mimicking choroid melanoma. Two of the three cases were enucleated. Our case is the first case in English literature of intraocular ciliary body RDD, mimicking ciliary body melanoma. CONCLUSION: RDD can present as an intraocular mass that mimics ciliary body melanoma. This case emphasizes the importance of diagnostic biopsy before considering the final therapy in unclear cases, mainly when associated with unusual systemic features like lymphadenopathy.

Characteristics, management, and outcome of squamous carcinoma of the conjunctiva in a single tertiary cancer center in Jordan.

AIM: To evaluate the features and outcome of management of malignant conjunctival squamous tumors in King Hussein Cancer Center (a referral tertiary cancer center in the Middle East). METHODS: Retrospective case series of 31 eyes for 31 patients with conjunctival squamous neoplasia. Main outcome measures included: age, gender, laterality, tumor location, pathological features, tumor stage, treatment modality, and outcome. RESULTS: Twenty (65%) patients were males and median age was 58y. Twenty-two (71%) eyes had the tumor in the nasal quadrant. Tumor invasion to nearby structures was seen in 19 (61%) eyes, including the cornea, fornix, eyelid, and orbit in 17 (55%), 1 (3%), 2 (6%), and 3 (10%) eyes, respectively. Eye salvage was achieved by surgical excision with cryotherapy followed by topical chemotherapy in 28 (90%) eyes, and orbital exenteration was necessary in 3 (10%) eyes due to orbital tumor invasion. Tumor recurrence was seen in 7 (23%) eyes, and the significant predictive factors for recurrence were tumor extension onto the nearby structures (P=0.04), tumor invasiveness (P=0.038), and tumor TNM stage (P=0.031). No significant change in visual acuity was seen, and disease related mortality was 6% (2 patients, both had orbital invasion by invasive squamous carcinoma). CONCLUSION: Conjunctival squamous carcinoma is more common in males. Advanced American Joint Committee on Cancer (AJCC) T-stage, tumor local invasion, more pathologically aggressive tumors, and surgical treatment alone (without adjuvant therapy) are associated with higher risk for recurrence, and orbital invasion is the most important poor prognostic factor for metastasis and death. Treatment strategies should be affected by tumor characteristics at presentation.

Undifferentiated Endometrial Carcinoma, an Immunohistochemical Study Including PD-L1 Testing of a Series of Cases From a Single Cancer Center.

Undifferentiated endometrial carcinoma (UEC) is a rare and poorly recognized entity, associated with a poor outcome. The clinical, pathologic, and immunohistochemical features of 17 cases diagnosed at our center are described. The median age was 60 yr. Postmenopausal bleeding was the most common presenting symptom (76.9%). Most patients presented with advanced stage (64.7%). Total hysterectomy with bilateral salpingo-oophorectomy was the commonly offered surgical treatment (80.0%). Nine (52.9%) patients received adjuvant treatment. The median overall survival was 11 mo. Pure UEC was seen in 8 cases (47.0%), while dedifferentiated carcinoma in 5 cases (29.4%). The epithelial component was part of carcinosarcoma or was mixed with serous carcinoma in 2 cases (11.8%) each. Positivity for one or more of the cytokeratin cocktails, mostly as strong focal staining, was evident in 16 cases (94.1%). PAX-8 was negative in 13 cases (86.7%). BRG-1/SMARCA4 was lost in 3 cases (20.0%). Eleven cases (64.7%) were MLH1/PMS2 deficient. Ten cases (66.7%) were positive for programmed death ligand 1, with positivity in 10%, 20%, and 100% of tumor cells detected in a single case each. Only 2 of 11 (18.2%) referral cases were correctly diagnosed as UEC. UEC is a rare tumor that is frequently misdiagnosed. A panel of immunostains is necessary to make the correct diagnosis. The range of positivity for programmed death ligand 1 testing suggests that immunotherapy might be considered in the adjuvant setting, especially with the poor response of this tumor to traditional therapies.

Characteristics, management, and outcome of patients with uveal melanoma treated by Iodine-125 radioactive plaque therapy in a single tertiary cancer center in Jordan.

OBJECTIVE: To evaluate King Hussein Cancer Center experience in using Iodine-125 COMS radioactive plaque for treatment of Uveal Melanoma in Jordan. METHODS: Retrospective case series of eyes with uveal melanoma treated by Iodine-125 COMS radioactive plaque therapy. Data collection required access to medical, radiology, Labs and pathology reports. Main outcomes studied includes: Demographics, tumor features, eye salvage, visual outcome, metastasis, and mortality. RESULTS: Between September 2008 and March 2015, 28 eyes for 28 patients had intraocular uveal melanoma and treated by Iodine-125 radioactive plaque therapy. The mean age at diagnosis was 48 years and 16(57%) were males. The mean tumor thickness was 8 mm (range: 4-13 mm), and 27(96%) patients had medium or large size tumor. The radioactive plaques used had a median size of 16 mm (range: 12-20 mm). The mean apical dose was 83.5 Gy (range 81-87 Gy), and the median radiation rate was 7.25 (range: 4.5-13). At median follow up of 2 years (range 0.5-7 years), eye salvage rate was 93%. Four (15%) patients had distance metastasis, and 3(11%) were dead. Fifty percent of patient had visual acuity better than 20/200 at the last date of follow up. CONCLUSION: Our preliminary results are encouraging and are comparable to another countries worldwide. The use of Iodine-125 COMs plaque therapy at the inspection of implementation of plaque therapy in the developing countries can lead to eye salvage in more than 90% of cases, and reserves functional vision in more than 50% of cases.

Management and Outcome of Uveal Melanoma in a Single Tertiary Cancer Center in Jordan.

OBJECTIVE: The aim of this study was evaluate the features and outcome of management of uveal melanoma in King Hussein Cancer Center as an example of a referral tertiary cancer center in the Middle East. MATERIAL AND METHOD: This was aetrospective, observational case series of 46 eyes of 46 patients with uveal melanoma. Data collection required access to medical records, radiology and pathology reports, and laboratory results. The main outcome measures included age at diagnosis, tumor location and dimensions, TNM stage, treatment modality, visual outcome, metastasis, and mortality. RESULTS: There was slight female preference, and the median age at diagnosis was 45 years. Eighteen (39%) eyes were treated by primary enucleation, and 28 (61%) eyes were treated by I-125 radioactive plaque. The melanoma was in the choroid in 40 (87%) eyes and in the ciliary body in 6 (13%) eyes, with no single tumor in the iris. According to the 7th edition of the American Joint Committee on Cancer staging system (UICC/AJCC); 8 (17%) were T1, 17 (36%) were T2, 16 (35%) were T3, and 5 (11%) were T4. One (2%) patient showed lymph node metastasis (N1), and 6 (13%) patients showed distant metastasis (M1). Pathologically, 2 (10%) of the enucleated eyes were spindle cell type, 4 (20%) were epithelioid cell type, and 14 (70%) were mixed type. Extrascleral extension was seen in three (15%) eyes, and optic nerve invasion in two (10%) eyes. After brachytherapy, 26 (93%) eyes were salvaged, and 2 eyes were consecutively enucleated; one for tumor recurrence, and one for uncontrolled painful neovascular glaucoma. The eye salvage rate post plaque was 93% (26/28), and the visual acuity for the salvaged eyes was equal or better than 0.5 in 11 (42%) eyes, 0.1-0.4 in 5 (19%) eyes, and less than 0.1 in 10 (38%) eyes. CONCLUSION: The incidence of uveal melanomas in our region is low compared to that in the West with a younger age at presentation. Candidate tumors for radioactive plaque therapy were successfully controlled in 93% of cases.

Practical steps for establishing ocular plaque therapy in developing countries.

INTRODUCTION: Retinoblastoma and uveal melanoma are the most common ocular tumors in children and adults, respectively. Enucleation and external beam radiation therapy are integral in the management of ocular tumors. However, these tumors could also be treated effectively by plaque therapy, which has the potential of preserving the globe and maintaining vision. METHODS AND MATERIALS: We reviewed our experience with the introduction of this technique to our center. Furthermore, we highlighted the critical role of a specialized multidisciplinary team in the successful implementation of this procedure. DISCUSSION: This review represents a detailed report addressing the practical steps for successfully establishing plaque therapy in developing countries. RESULTS: Plaque therapy was successfully implemented at our center in 1.5 years. Integration with an advanced cancer center is crucial for the correct transfer of this complex technology. CONCLUSION: Complex brachytherapy procedures could be successfully established and implemented in developing countries.

Resolution of extensive leptomeningeal metastasis and clinical spinal cord compression from breast cancer using weekly docetaxel chemotherapy.

Metastatic breast cancer to the leptomeninges is a late event in the disease course and is associated with significant morbidity and a grave prognosis. Treatment typically involves direct intrathecal injection of chemotherapy into the cerebrospinal fluid compartment since systemic chemotherapy penetrates poorly to the central nervous system. Here we report an interesting clinical observation involving a patient presenting with leptomeningeal spread of breast cancer causing extensive spinal cord compression with obliteration of the subarachnoid space, thus precluding the use of direct intrathecal chemotherapy. We administered systemic chemotherapy using weekly docetaxel with complete radiographic resolution of her disease and recovery from clinical spinal cord compression. While this is a single clinical observation, weekly administration of docetaxel in this circumstance may have been associated with improved drug "escape" into the central nervous system and better antitumor effect. Because leptomeningeal disease is typically a late event in metastatic breast cancer, resistance to therapeutic intervention may reflect intrinsically resistant disease in the setting of extensive prior therapy rather than a routine problem with systemic drug delivery to the CNS. Studying patterns of disease relapse in patients who had received adjuvant weekly taxanes may provide insights into this hypothesis.

Enucleation for retinoblastoma: the experience of a single center in Jordan.

Despite multiple advances in the management of retinoblastoma, enucleation remains an essential therapeutic modality. We studied patients who underwent enucleation at the King Hussein Cancer Center in Jordan. We retrospectively reviewed medical records of children with retinoblastoma who were treated at our center from June 2002 to February 2008. Twenty-eight eyes from 27 patients were enucleated. Median age at diagnosis was 1.1 years (range, 0.3-6.3 years). Twenty-six eyes (93%) had advanced disease (RE groups IV and V). Seventeen patients (61%) had unilateral retinoblastoma, and 11 (39%) had bilateral retinoblastoma. The median time from diagnosis to enucleation was 0.45 months (range, 0-45 months; mean, 4.4 months) and was longer for patients with bilateral retinoblastoma (median, 2.2 vs. 0.2 months; P = 0.034). Twenty enucleated eyes (71%) did not show high-risk pathologic features. Seventeen eyes with advanced intraocular disease were enucleated at the time of presentation, whereas chemoreduction was attempted for the other 19 eyes with advanced intraocular disease. Enucleation was then recommended for nine (47%) of those eyes. Enucleation at the time of diagnosis was feasible for most patients with advanced disease. Attempted salvage of eyes with advanced disease is justified, particularly in patients with bilateral disease. We were able to salvage almost half of these eyes. We hope our study provides new insights for counseling patients.