Purpose: To design a simple and reproducible method with minimum uncertainty for evaluating the stereotactic accuracy of Computed Tomography imaging and Magnetic Resonance Imaging and to compare the results.

Methods: 3D phantom has been designed with 1 mm diameter targets in eight sectors for stereotactic MR imaging and CT imaging. The phantom was connected to Leksell stereotactic frame and the images obtained are exported to treatment planning system. Leksell stereotactic coordinates (X, Y, Z) of the holes are determined in each slice and mean maximum errors were calculated along with 3D vector distances from center of stereotactic coordinate system (100,100,100) to five known Targets. The target volumes are calculated independently for each image data sets.

Results: The mean of maximum absolute error estimated for MR images from the Siemens Magnetom vision MR unit were 0.46 mm (X-Axis), 1.66 mm (Y-Axis) and 2.11 mm (Z-Axis). Mean of absolute maximum error estimated using CT images from the Philips Brilliance 16 CT scanner were 0.29mm (X-axis), 0.51mm (Y-Axis) and 0.90mm (Z-Axis). 3D vector calculations were 0.38 mm for CT and 0.72 mm for MRI. No significant variation is noticed in volume calculations from both image data sets.

Conclusion: This study showed that accuracy and quality of stereotactic CT- imaging and MR-imaging are limited by localization devices and their designs in frame based Radiosur-gery. This method is simple, direct and economical with good resolution and high reproduci-bility.

Keywords: Stereotactic accuracy, Computed Tomography, Magnetic Resonance Imaging, frame based Radiosurgery

Objective: The aim of this report is to address treatment outcomes of patients with early-stage seminoma in a developing country with special reference to patients with history of surgical violation of the scrotum and the potential predictors of disease relapse.

Patients and Methods: Seventy four patients with pure seminoma were treated at King Hussein Cancer Center (Amman, Jordan) between 2003 and 2010. All patients underwent orchiectomy. All but 3 patients received adjuvant radiotherapy. Patients who underwent surgical violation of the scrotum prior to referral were managed by further excision or irradiation of the scrotal scar. The follow-up ranged from 1 to 200 months (mean, 33 months).

Results: At the time of follow-up; all but one patient remain alive. The 3-year relapse-free survival for the entire cohort was 95.9%. Three patients were burdened by relapse, all of whom received adjuvant irradiation following inguinal orchiectomy and initially harbored tumors larger than 4cm upon pathological examination. Median time to relapse was 14 months (range, 8-25 months). None were associated with elevated tumor markers prior to detection of relapse. All but one patient were successfully salvaged by chemotherapy.

Conclusions: Our results confirm the excellent prognosis for patients with early-stage seminoma treated by orchiectomy and adjuvant radiotherapy in a developing country. Although all patients burdened by relapse demonstrated adverse pathological findings upon initial assessment, no consistent predictor of relapse was found. Scrotal scar re-excision or irradiation in patients with prior history of surgical violation of the scrotum is effective in preventing local failure.

Keywords: Seminoma; stage I; radiotherapy; scrotal violation; developing country; management

c-MET overexpression as a prognostic biomarker in colorectal adenocarcinoma  

Background: There is a need for informative molecular markers that provide prognostic information over and above that given by conventional pathologic parameters. This study examined the expression and potential prognostic value of c-MET in colorectal adenocarcinoma.

Material and Methods: Two-hundred and thirty cases were evaluable after tissue microarray construction and evaluated for c-MET expression by immunohistochemistry. The results were correlated with standard clinicopathologic prognostic factors. Cases were followed up for 5 years.

Results: c-MET was highly expressed in 138 of 230 cases (60%). In normal tissues a negative or weak reaction was observed. Significantly higher c-MET expression was found in the metastatic group (p=0.04). No significant association was found in relation to age, sex, tumor site, tumor size, histological type, or tumor grade (p > 0.05). The 5-year disease free survival for patients with low levels of expression was significantly higher than that for patients with high levels (64% versus 45%, p=0.04).

Conclusion: c-MET seems to be a valuable biomarker in colorectal adenocarcinoma; overexpression is a useful prognostic indicator for metastasis and patient outcome.

Keywords: c-MET, prognosis, colorectal adenocarcinoma, tissue microarray.

Clinical prognostic factors in locally advanced nasopharyngeal carcinoma in Moroccan population 

Background: Nasopharyngeal carcinoma is a distinct cancer of head and neck by its pathology, etiology, epidemiology and clinical behavior. Morocco is considered an endemic region with intermediate incidence. The aim of our report is to underline some clinical determinants of survival in locally advanced disease.

Patients and Methods: We conducted a retrospective study from January 2003 to December 2005. All patients with undifferentiated nasopharyngeal carcinoma treated in the National Institute of Oncology of Rabat, Morocco were recorded. Classified stage II to IVB disease according to TNM classification adopted by the AJCC (American Joint Committee of Cancer) 6th edition.

Results: The study included 339 patients, 122 women and 217 men (sex-ratio: 1.7). Mean age was 43 years old (range: 6-91years). Median duration to diagnosis was 6 months (range: 1-72) presenting symptoms at diagnosis were predominantly cervical lymph node in 79%. Forty- two patients have T1 tumors, 159 = T2 tumors, 64 = T3 tumors and 69 = T4 tumors. Sixty-five patients do not have lymph-node involvement, 49 have N1, 128 have N2 and 95 have N3. Three patients were at stage IIA, 57 patients were at stage IIB, 40 patients were at stage III, and 57 patients were at stage IVA and the remaining 96 patients were at stage IVB. Eighty-seven percent of patients underwent sequential chemoradiation and 17% underwent  concurrent chemo-radiation (CTR). Response to induction chemotherapy was assessed in 235 patients. There were 31 patients with complete response and 59 patients have partial response. Complete response to radiotherapy was reached in 235 patients. Mean overall survival (OS) was 66.2%. Gender was a prognostic factor of OS (p=0.045) and DFS favoring women. Age wasn’t a prognostic factors determining the outcome with no difference between patients aged more than 40 years old and patients younger. Tumor size was not a determinant of survival with a non-significant p in OS and DFS (0.27 and 0.46 respectively) but T4 stage patients appear to have a worse prognosis. Lymph node involvement was significantly determining the outcome either in OS and DFS (p=0.001 and 0.009 respectively). TNM stage was also a significant prognostic factor in OS but not in DFS favoring those with early stage (p= 0, 004 and p= 0, 13 respectively) The treatment strategy was not a significant prognostic factor with no difference between patients who underwent sequential or concurrent chemoradiation (OS p= 0, 48 and DFS p= 0, 9). In multivariate analysis, lymph-node involvement is the most significant factor.

Conclusion: Our findings were mostly concordant with the literature data in endemic areas for TNM staging; however we are limited by the bias of retrospective studies. Prospective studies would be more accurate to define those prognostic factors in our population.

Keywords: UCNT, prognostic factors, endemic areas, lymph node involvement

BRCA1 gene Molecular Alterations in Omani Breast Cancer Patients 

Background: Breast cancer (BC) is the most common cancer reported in females in Oman and usually occurs at a relatively younger age, presents at an advanced stage and behaves aggressively. BC occurs in hereditary and sporadic forms. Although germ-line mutations in BRCA1 and BRCA2 genes are rare in sporadic cases compared with hereditary cases, molecular alterations, such as loss of heterozygosity, and CpG methylation, are common. In this study, we investigated the types of molecular alterations associated with hereditary and sporadic BRCA1-associated BC in Omani patients.

Methods: We obtained clinical data and samples from 43 sporadic BC patients. The selection of cases was made based on the following criteria: aged ≤ 40 years, or bilateral breast cancer, or estrogen and progesterone receptor negative status, and HER-2/neu negative (Triple Negative phenotype) status. Screening for molecular alterations was performed by direct sequencing, multiplex ligation-dependent probe amplification (MLPA).

Results: Genomic deletions and duplication in the BRCA1 gene were identified in four female patients. Two patients carried exon 1 and 2 deletions and two showed exon 1 and 2 duplication. Screening for mutation by direct sequencing revealed three polymorphisms in exon 11. Two of these polymorphisms are nonsynonymous (rs1800704, rs799917) and one is synonymous (rs1800740).

Conclusion: The current pilot study detected previously described gene rearrangements and polymorphisms involving the BRCA1 gene and no seemingly pathogenic missense mutations were elucidated.

Keywords: BRCA1, breast cancer, mutation, polymorphism, Omani, Arab

Rituximab, a chimeric monoclonal antibody (MoAb) targeting CD20 has been widely used in the management of B-cell lympho-proliferative disorders.(1-3) The usual recommended schedule of regular administration over 3 to 4 hours requires considerable healthcare resources and oftentimes inconvenient for patients. Literature shows the availability of published reports proving the safety and feasibility of rapid infusion of rituximab. This study explored the safety and tolerability of rituximab infusion over a shorter total infusion time. A total of 24 patients diagnosed with CD20+ Non-Hodgkin’s lymphoma and planned to receive rituximab at a dose of 375mg/m2 in combination with standard chemotherapy regimens were included in the study from January 2009 to December 2009. The administration of first rituximab dose was unaltered and given as per standard practice of 3-4 hours infusion. The second and subsequent doses were delivered over a total infusion time of only 90 minutes (20% of dose in the first 30 minutes, remaining 80% over the next 60 minutes). These patients, aged between 15 and 79 years, received a total of 152 rituximab infusions with an average of 6.33 (+/-2.37) infusions per patient. Grade 1 infusion related toxicity was reported in 5 infusions (3.2%), and there were no acute reactions or G3/4 toxicity in any infusion episode. A rapid infusion of rituximab is well tolerated, feasible and safe when administered as second and subsequent infusions in the course of therapy for those who tolerate the first dose without significant infusion related toxicity. This shortened infusion method results in a substantial reduction in resource utilization. Our institution has now adopted this as a routine practice.

Keywords: Rituximab, Short infusion, Oman

The role of sentinel lymph-node biopsy in managing lip squamous cell carcinoma patients without clinical evidence of nodal metastasis 

Aim: Squamous cell carcinoma (SCC) of the lip is a common oral malignancy. Lymph node metastasis occurs lately in the natural history of the disease but it is associated with poor outcome. Sentinel lymph node biopsy (SLNB) is an option that determines the potentially affected lymph nodes especially in clinically negative-node patients. The study aims to determine the feasibility of SLNB as a reliable staging tool in N0 stage lip SCC patients.

Methods: Eighteen patients with N0 stage lip SCC were enrolled in the study. They were subjected to SLNB using the injection of the radiocolloid material and the Blue dye. The procedure was followed by bilateral supraomohyoid neck dissection in all patients. The pathological results of the harvested sentinel lymph nodes (SLNs) were compared with that of the dissection specimen in each patient.

Results: The patent blue dye could localize the SLN in 15/18 patients whilst the radioisotope scanning could successfully identify it in 17/18 patents. On average, 1.8 SLNs were harvested from each patient. Two of seventeen patients with identified SLNs (11.8%) have positive nodal metastases. One of them has two SLNs and the other has only one. No false negativity was reported in the study as all the excised SLNs reflected correctly the status of the lymph node basin.

Conclusion: Sentinel lymphadenectomy is a safe and feasible procedure in managing neck of patients with node-negative lip SCC. It can accurately stage these patients.

Keywords: sentinel lymph node, lip, cancer

The development of advanced radiation treatment techniques such as intensity modulated radiation therapy (IMRT) and volumetric intensity modulated arc therapy (VMAT) require more accurate dose calculation algorithms within the treatment planning systems (TPS) considering that the human body is composed of tissues of widely differing radiological properties and the characteristics of a therapeutic radiation treatment beam along a heterogeneous path will be different. The objective of this study was to evaluate the accuracy of 2D-isodose distributions predicted by pencil beam convolution algorithm (PBC) and anisotropic analytic algorithm (AAA) in a heterogeneous slab phantom composed of media equivalent to air, water and bone density. The measurements were done by using the films at multiple depths in the phantom for open field sizes 5 × 5 cm2 and 10 × 10 cm2. The results from this study indicated that the AAA had better agreement with the measurement compared to PBC for both the test field sizes at all selected depths; however, the limitation of AAA in predicting doses within and beyond low-density medium was observed, especially for a smaller field size (up to 32.7% and 34.0% for AAA and PBC, respectively). Furthermore, discrepancies up to -4.8% for AAA and -14.6% for PBC was seen in the high-density medium as well. Dose prediction errors by the AAA and PBC were more pronounced for a smaller test field size, especially in the low-density medium.

Keywords: IMRT, dose calculation algorithms, Anisotropic Analytical Algorithm (AAA), Pencil Beam Convolution (PBC), Varian’s Eclipse treatment planning system

Hepatocellular Carcinoma in Qatar

Objective: The main aim of this study was to report and discuss epidemiological, etiological, type of treatment and data on survival of the patients with each mode of treatment using available data for patients with hepatocellular carcinoma (HCC) who have been diagnosed at Hamad Medical Corporation during the period March 2004-December 2010 inclusive.

Materials and Methods: Retrospective analysis of 150 patient’s data had been done, including demographic, epidemiological, etiological disease status assessment with child Pugh criteria, modes of treatment and treatment related outcome. Patient’s various characteristics such as demographic, epidemiological, and other clinical characteristics were summarized using an appropriate descriptive statistics. Univariate Kaplan-Meier survival curve analysis was performed to estimate overall and group wise survival at different time points. Furthermore, the log-rank test was applied to determine any statistical difference in survival among various subgroups. In addition, the multivariate Cox regression method was used to assess the significant effects of various prognostic factors on outcome survival time.

Results: The mean age of the studied HCC patients was 58.8 years (31-87years) with a male: female ratio of 3:1 (76% Male 24% Female). There were 48 (32%) Qatari and 102 (62%) non- Qatari patients. The underlying etiology HCV was the most common (45%) similar to Western European countries, HBV in (27%), alcoholic liver disease only in 6 (4%), Child-Pugh assessment was A in (33%), B in (37%) and C in (30%), nearly half of the patients (53%) were in advanced stage and had palliative treatment, the other half had chemoembolization in (17%), systemic therapy sorafenib in (13%), surgery (liver resection or transplantation) in (12%) and local ablation in (5%).

Conclusion: HCC is more common in males (ratio M:F 3:1). HCV is the most common underlying cause, similar to the pattern in western European countries. The survivals in our patient were comparable to other studies reported in the literature. Patients who had chemoembolization had the longest median survival [Median = 27 months, 95% CI (20.27- 33.72). Majority of cases (53%) were diagnosed at advanced stage. To improve the outcome of treatment of HCC patients, the number of early and very early stage diagnosis should be increased by improving the implementation and effectiveness of the strategic screening program.

Keywords: Hepatocellular carcinoma, chemoembolization, radiofrequency, sorafenib, hepatitis C, Hepatitis B.

MALT lymphomas - Treated with chemotherapy or radiotherapy: Clinical Features, Prognostic factors and Survival 

Objective: MALT lymphomas are a group of extranodal indolent lymphomas that usually present as stage IE. To clarify clinical features, treatment alternatives and outcomes, we evaluated 38 patients treated with chemotherapy or radiotherapy between 2000 and 2011.

Patients and Methods: MALT lymphoma patients identified according to WHO classification and treated at KCCC between 2000 and 2011 were included in this study. Demographic and clinical data are presented as means or medians. Overall survival was estimated using the Kaplan-Meier method. Survival rates were compared using the log-rank test. A p value < 0.05 was considered significant.

Results: The median age of the patients was 49 years and the male to female ratio was 2:1. Gastric MALT accounted for 63% of all patients and the most common presenting symptom was abdomen pain and dyspepsia. The common extra gastric sites were salivary glands, lung and orbit. 90% of the patients presented with early stage disease. Two patients had history of pre-existing autoimmune disease. Even among patients who had failed prior antibiotic therapy for Helicobacter pylori, treatment with chemotherapy achieved good results with 5 year survival of 80%.

Conclusion: MALT lymphomas are indolent neoplasm’s with excellent long term outcome. There is no significant difference in survival between gastric and extra-gastric MALT lymphoma.

Keywords: MALT lymphoma, Gastric Neoplasm, H. pylori

Z. Adriana, S. Al Bahar, R. Pandita

Kuwait Cancer Control Center, Department of Hematology, Laboratory of Cancer Genetics, Kuwait

We describe a rare presentation of acute lymphoblastic leukemia in a young adult male who at the beginning of the disease lacked the Philadelphia chromosome in bone marrow and blood cells and fluorescence in situ hybridization was negative for the presence of a clone with the BCR-ABL1 rearrangement. The patient initially had pancytopenia with a blast cell count of 5% in the peripheral blood that evolved to a phase with progressive leukocytosis and a sudden rise in blast cells 7 months later. At this time, his bone marrow aspirate showed the presence of a neartriploid karyotype containing two Philadelphia chromosomes. The multiple karyotypic changes observed in our patient support the notion that leukemic progression involves several cytogenetic evolutionary processes, the first step of which may not necessarily involve acquisition of the Philadelphia chromosome.

Keywords: Late-appearing Philadelphia chromosome, adolescent ALL, BCR-ABL1, dasarinib

A case of isolated cutaneous Rosai-Dorfman-Syndrome

Rosai-Dorfman Syndrome (RDD) is a rare, benign, self-limiting disorder which is characterized by the non-malignant proliferation of distinctive histiocytic cell within lymphatic system. RDD has been described as a dynamic entity in the spectrum of histiocytosis with non-Langerhans cell histiocytosis at one end and Langerhans cell histiocytosis at the other. The exact etiology of this disease is uncertain despite widespread search for infectious or immunological reasons. We present a case of purely cutaneous Rosai-Dorfman Syndrome presenting as abdominal wall swelling.

Keywords: Rosai-Dorfman Disease, Lymphoma

Cutaneous Metastasis from Breast Carcinoma: A brief report of a rare variant and proposed morphological classification

Background: Breast carcinoma is the second commonest cancer in women after non-melanoma skin cancers and, excluding melanoma, the most common tumor to metastasize to the skin in women. Cutaneous metastasis from breast cancer has varied presentations but there is no well-established classification which includes them all.

Objective and Conclusion: We report a 69 year-old lady with advanced primary ductal carcinoma of right breast (cT4cN1cM0) who presented five months after radical mastectomy with very extensive cutaneous metastases in absence of distant spread. Skin involvement was in the form of nodules and purpuric papulo-vesicles on a background of erythema which clinically mimicked lymphatic malformation. We also propose a morphological classification of the cutaneous metastasis from breast cancer.

Keywords: Breast Carcinoma, Cutaneous metastasis, lymphatic malformation.