Outcome of inflammatory breast cancer in Moroccan patients: clinical, molecular and pathological characteristics of 219 cases from the National Oncology Institute (INO).

BACKGROUND: Usually misdiagnosed, Inflammatory Breast Cancer (IBC) is the most aggressive form of non-metastatic breast cancer. This orphan disease is more frequent in North Africa. Despite intensive treatment, the survival rate remains very low. METHODS: We have retrospectively studied all breast cancer cases diagnosed at the National Oncology Institute (INO), Rabat between 2005 and 2010. We have collected 219 cases of women with metastatic and non-metastatic IBC. Data have been obtained from patients' personal medical files over a follow-up period of 5 years. We have described IBC's clinicopathological features and analyzed its clinical outcome using SPSS software. HR (hazard Ratio) was calculated using Cox regression analysis. RESULTS: The frequency of IBC cases is 4.05%. The majority of our patients (65.3%) were under 50 years old. The most prevalent molecular subtype was Luminal A (38.7%) followed by Luminal B HER2+ (27.9%) and Triple negative (21.6%). During the follow-up period, 72 patients (32.9%) had recurrence and 40 patients (18.3%) died. The 3-year OS (Overall Survival) and EFS (Event Free Survival) of non-metastatic patients were 70.4 and 46.5% respectively, while in the metastatic disease, the 3-year OS was only 41.9%. In non-metastatic women, we observed a higher rate of EFS associated to Selective estrogen receptor modulation treatment (p = 0.01), and a lower rate EFS in triple negative breast cancer patients (p = 0.02). In univariate analysis, we found that EFS rate is lower in patients presenting Triple Negative tumors when compared to other molecular subtypes (HR: 3.54; 95%CI: 1.13-11.05; p = 0.02). We also found that Selective estrogen receptor modulation treatment is associated with higher EFS rate (HR: 0.48; 95%CI: 0.07-0.59; p = 0.01). CONCLUSIONS: IBC in Morocco shows similar characteristics to those in North African countries; however, survival rates are still the highest when compared with neighboring countries. Collaborative studies with prospective aspects are warranted to establish the epidemiological profile and understand the high frequencies of IBC in North Africa. More studies on molecular markers are also needed to improve IBC patients' management and eventually their survival rate.

Quality of life of early stage colorectal cancer patients in Morocco.

BACKGROUND: A multicentre cohort study was held in Morocco, designed to evaluate the quality of life of cancer patients. The aim of this paper is to report the assessment of the quality of life of early colorectal cancer patients, before and after cancer treatment, to identify other factors which are related to this quality of life. METHODS: We used the third version of the QLQ-C30 questionnaire of the European organization for Research and treatment of Cancer (EORTC) after a transcultural validation. The Data collection was done at inclusion and then every twelve weeks to achieve one year of follow up. RESULTS: Overall 294 patients presented with early colorectal cancer, the median age was 56 years (range: 21-88). The male-female sex ratio was 1.17. At inclusion, the global health status was the most affected functional dimension. For symptoms: financial difficulties and fatigue scores were the highest ones. Emotional and social functions were significantly worse in rectal cancer. Most symptoms were more present in rectal cancer. At inclusion, global health status score was significantly worse in stage III. Anorexia was significantly more important among colorectal female patients. For Patients over 70 years-old, the difference was statistically significant for the physical function item which was lower. Overall, Functional dimensions scores were improved after chemotherapy. The symptoms scores did not differ significantly for patients treated by radiotherapy, between inclusion and at one year. CONCLUSION: Our EORTC QLQ C30 scores are overall comparable to the reference values. Neither chemotherapy, nor radiotherapy worsened the quality of life at one year.

Ovarian cancer revealed by paraneoplastic cerebellar degeneration: a case report.

The prevalence of paraneoplastic cerebellar degeneration (PCD) associated with gynecological cancer is rare. Here, we reported the first case of ovarian cancer revealed by PCD in our institute. we describe a 80-year-old Moroccan female presented with subacute vestibular and cerebellar syndromes, she had an inguinal lymphadenopathy,with high levels of Anti-YO. Rapid progression and absence of known etiologies point towards a probable paraneoplastic origin of the syndrome in this patient. The exact incidence of PNS among those diagnosed with cancer remains uncertain, it is important to report this cases in the literature to help early diagnosis and appropriate treatment, which are able to stabilize the neurological symptoms.

Conjonctival melanoma metastatic to the breast: a case report.

BACKGROUND: Breast metastasis is fairly uncommon and prognosis is dismal. Breast metastasis might be the first symptom or may occur during the course of other malignancies dominantly arising from the contralateral breast. Leukemia, lung cancer and conjunctival melanoma may spread to the breast. CASE PRESENTATION: A 43-year-old female patient was operated on for conjunctival melanoma. After two years the disease progressed quickly and cutaneous nodes appeared on the back and paraumbilical region. Physical and radiological examination showed a breast mass. No palpable lymph's nodes were noted. She underwent an open biopsy. Histopathologic examination and immunohistochemistry confirmed breast metastases from melanoma. During post-operative staging multiple nasopharyngeal and oropharyngeal lesions were also objective. The patient was given palliative dacarbazine (250 mg/m2 per day for 4 days) for 4 cycles. She died 4 months after the diagnosis of breast metastases. CONCLUSION: Histopathological evaluation should be mandatory in patients with medical history of malignancies in order to differentiate new primary tumors, metastases, and benign tumors.

Frequency and Spectrum of KRAS Mutations in Moroccan Patients with Lung Adenocarcinoma.

Background. In lung adenocarcinoma, the frequency of KRAS mutations is ethnicity dependent with a higher proportion in African Americans and white Caucasians than in Asians. The prevalence of these mutations among North Africans patients is unknown. The objective of this study was to report the frequency and spectrum of KRAS mutations in a group of Moroccan lung adenocarcinoma patients. Methods. Tumor specimens from 117 Moroccan patients with lung adenocarcinoma were selected to determine frequency and spectrum of KRAS mutations. KRAS mutations in codons 12 and 13 of exon 2 were analyzed using conventional DNA sequencing. Results. The overall frequency of the KRAS mutations was 9% (11/117). In the population with KRAS mutations, there was a trend towards more male (P = 0.06) and more smokers (P = 0.08) compared to patients with wild type KRAS. KRAS mutations were located at codon 12 in 10 out of 11 patients (91%). The G12C mutation was the most frequent KRAS mutation (73%). Conclusion. This is the first study to date examining the frequency and spectrum of KRAS mutations in lung adenocarcinomas in North African and Arab populations. KRAS mutation frequency in Moroccan patients was comparable with the frequency observed in East-Asian population. KRAS mutations are more likely observed in males and smokers and to be transversions. Further studies, in larger numbers of patients, are needed to confirm these findings.

Demographic, clinical, pathological, molecular, treatment characteristics and outcomes of nonmetastatic inflammatory breast cancer in Morocco: 2007 and 2008.

We analyze the epidemiological characteristics and outcomes of 72 patients diagnosed with non-metastatic inflammatory breast cancer (IBC) at National Institute of Oncology of Rabat in Morocco, between January 2007 and December 2008. IBC patients represent 5% of all breast cancers (90/1800). The median age of patients was 47 years. Thirty eight patients (53%) had premenoposal status and 69% of the cases had clinical lymph nodes. The dominant pathological funding was infiltrating ductal carcinoma (96%). Most patients had high grade II/III (77.8%), 43.4% of the cases were ER negative and 47.4% of the tumors overexpress the HER2/neu receptor on IHC. Only 48.6% of the patients received completed treatment (chemotherapy [CT], surgery and radiotherapy [RT]) and all patients received anthracycline based neoadjuvant CT, 51.4% of whom received Taxane. Seventy one% of the patients underwent surgery and 54% received RT. The clinical response to CT was 68%. Only 1 (1.4%) patient has pathological complete response (pCR) in the breast and 5 (7%) had pathologically negative lymph-nodes. Patient who achieved pCR was disease free at 27 months. LRRFS, EFS and OS rates at 1-2 years were 90.8%-78.1%, 81.7%-57.5%, and 94.3%-74.6%, respectively. Patients with ER-negative status (EFS: P = 0.043) had poorer outcomes and RT was associated with highly significant increase in LRRFS, EFS and OS (P < 0.0001, P < 0.001 and P = 0.017).

Frequency and type of epidermal growth factor receptor mutations in moroccan patients with lung adenocarcinoma.

INTRODUCTION: Epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer predict response to tyrosine kinase inhibitors. The frequency of EGFR mutations is ethnicity-dependent, with a higher proportion in Asian populations than in whites. The prevalence of these mutations among North African patients is unknown. The objective of this study was to report the frequency and spectrum of EGFR mutations in a group of Moroccan patients with lung adenocarcinoma (AC). METHODS: Tumor specimens from 137 Moroccan patients with lung AC were selected to determine frequency and spectrum of EGFR mutations. Mutation detection techniques were polymerase chain reaction amplification and sequencing of exons 18, 19, 20, and 21. RESULTS: The overall frequency of the EGFR mutation was 21%. Mutations were mainly detected in the exon 19 (69%), followed by exon 21 (21%) and exon 20 (7%), whereas mutations in the exon 18 were rare (3%). EGFR mutation rate was significantly higher in women and in never smokers. CONCLUSION: Some one fifth of lung AC tumors in Moroccan patients harbor EGFR mutations. This mutation frequency is higher than that found in whites but lower than in Asian population. Further studies, in larger numbers of patients, are needed to confirm these findings.

Cardiac safety of the adjuvant Trastuzumab in a Moroccan population: observational monocentric study of about 100 patients.

BACKGROUND: Trastuzumab is a humanized monoclonal antibody that binds to the extracellular domain of the human epidermal growth factor receptor 2 (HER 2) and inhibits carcinoma cellular proliferation. Its use as an adjuvant for a period of one year is currently an internationally recognised standard for the treatment of localized breast cancer. Its use is generally well tolerated, with the most salient side effect being a particular cardiotoxicity that is typically manifested by an asymptomatic decrease in the left ventricular ejection fraction (LVEF) requiring careful monitoring before and during treatment. To evaluate the cardiac safety of trastuzumab we conducted a retrospective observational study of patients with HER2-positive localized breast cancer treated with trastuzumab between May 2008 and May 2010 in Morocco. FINDINGS: The study comprised of 100 patients. The average in LVEF before the start of trastuzumab was 70%, and at the end of treatment 66%, a decrease in absolute terms of 4%; this difference was statistically significant. 38% of the patients exhibited cardiotoxicity. 97% of our patients have completed treatment, of whom 23% with a provisional arrest because of a regressive fall in LVEF. A final arrest has been made in 3% of cases due to a non regressive reduction in LVEF. A symptomatic heart failure was found in three patients. Analysis of risk factors toxicity found a baseline LVEF higher in the patients who met cardiotoxicity than the rest of our sample. CONCLUSIONS: The cardiac safety in our study seems comparable with the literature data but located in the upper range of levels of toxicity. Cardiotoxicity is the major complication of Trastuzumab, of which LV dysfunction is the most common. Most instances are transient, asymptomatic and reversible.

Triple negative breast cancer in Moroccan women: clinicopathological and therapeutic study at the National Institute of Oncology.

BACKGROUND: Triple-negative breast cancer (TNBC) is defined by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression. This is an aggressive malignancy with a poor prognosis despite the high rates of response to chemotherapy. The aim of this study is to determine the clinicopathological, therapeutic features and outcomes associated with this type of breast cancer. METHODS: This is a retrospective study of confirmed triple negative breast cancer females collected at the National institute of oncology of Rabat in Morocco, between January 2007 and December 2008. Epidemiological, clinical, histological, therapeutic and evolutive data were analyzed. OS and DFS rates were estimated by Kaplan-Meier analysis. RESULTS: A total of one 152 patients with breast cancer, were identified as having triple-negative breast cancer (16,5%). The median age at diagnosis was 46 years. 130 patients (86%) had infiltrating ductal carcinoma and thirteen had medullar carcinoma (9%). 84 cases (55%) were grade III Scarff-Bloom-Richardson (SBR). 48 % had positive lymph nodes, and 5 % had distant metastases at diagnosis. According TNM staging, 12 patients (8%) had stage I, 90 patients (60%) had stage II and the 43(28%) had stage III. 145 patients received surgery. 41 (28%) had conservative surgery and 104 (72%) received radical mastectomy with axillary lymph nodes dissection. 14 patients with advanced tumors or inflammatory breast cancer have received neoadjuvant chemotherapy and four patients (28%) had complete pathologic response. From 131 patients how received adjuvant chemotherapy, 99 patients (75,5%) had Anthracycline based chemotherapy) and 27 patients (20,6%) had sequential Anthracycline and docetaxel,. Seven patients with metastatic disease received anthracycline-based regimen in the first line metastatic chemotherapy. The median follow-up time was 46 months (range 6,1 -60 months). Overall survival at 5 years for all patients was 76,5%. CONCLUSION: These results suggest that most TNBC characteristics in Moroccan patients are in accordance with literature data, especially concerning young age at diagnosis high grade tumors, advanced stage at diagnosis, and short time to relapse. Although the high response rate to chemotherapy, the overall prognosis of this subset of tumors remains poor.

Management of stage one and two-E gastric large B-cell lymphoma: chemotherapy alone or surgery followed by chemotherapy?

UNLABELLED: Management of localized primary gastric B lymphoma (PGL) remains controversial. The aim of this study is to compare two treatments: chemotherapy alone and surgery plus chemotherapy. MATERIALS: Records of all patients with a diagnosis of gastric lymphoma and which were treated in the National Institute of Oncology, between 1999 and 2006, were reviewed and patients fulfilling the following criteria were included in this study: histologically proven large-cell B lymphoma of the stomach; complete clinical information stage I/II disease according to the Musshoff staging; patients who received surgery followed by chemotherapy (group I) or chemotherapy alone (group II). RESULTS: This study included 82 patients who were treated for cancer in our Institute. All clinical and pathological features were similar between the two groups, except that patients of group-I had significantly more stage II disease (P = 0.023) than that of group II. Among the 52 patients who could be evaluated for response to chemotherapy, there were 45 who had complete response to treatment, 3 had partial response to the treatment and 4 had progressive disease. The projected 5-year relapse-free survival (RFS) and overall survival (OS) of group I were 86.69% (95% CI, 57.9 - 97.7%) and 90.0% (95% CI, 58.0 - 97.8%), respectively. And the projected 5-year relapse-free survival RFS and OS of group II were 86.67% (95% CI, 57.0 - 88.2%) and 93.33% (95% CI, 73.3 - 98.7%) respectively. There were no statistically significant differences in RFS (P = 0.485) and OS (P = 0.551) between the two groups. CONCLUSION: Our data suggest that chemotherapy alone may be a reasonable alternative treatment for stage I/II gastric large-cell lymphoma but this result must be confirmed by prospective randomized clinical trials.

Primary nasopharyngeal Hodgkin's disease: case report and literature review.

INTRODUCTION: Primary Hodgkin's disease of the nasopharynx is a rare and uncommon event. It has a relatively favorable prognosis and represents less than 1% of all documented cases of Hodgkin's disease. CASE PRESENTATION: A 40-year-old Arabic man presented initially with bilateral nasal obstruction, which was then followed by a significant involvement of his bilateral cervical lymph nodes. His nasopharyngeal biopsy together with immunohistochemistry analysis showed negative expressions of CD15, CD20 and CD3, but positive expressions of CD30 and epithelial membrane antigen. This confirmed the diagnosis of nasopharyngeal Hodgkin's disease of a mixed cellularity subtype. The disease was at stage IIEA. Our patient received four cycles of chemotherapy, which yielded a 75% response. This was followed by irradiation of his Waldeyer's ring and supraclavicular lymph nodes. He remains in good local control after 30 months of follow-up. CONCLUSION: The literature review and our case report discuss the optimal management of this rare and atypical localization of Hodgkin's disease, which should be differentiated from lymphoproliferations associated with Epstein-Barr virus and non-Hodgkin's lymphoma.

Advanced adenoid cystic carcinoma of the cervix: a case report and review of the literature.

INTRODUCTION: Adenoid cystic carcinoma is a malignant epithelial neoplasm derived from the salivary glands. Primary adenoid cystic carcinoma of the cervix is extremely rare, accounting for less than 1% of all cervical carcinomas. In this paper we report a case of primary adenoid cystic carcinoma and a review of the related literature. CASE PRESENTATION: A 68 year-old woman was admitted with signs and symptoms suggestive of a cervical cancer. The radiological and pathological investigations confirmed the diagnostic of primary adenoid cystic carcinoma of the cervix at Stage IIIB according to the International Federation of Gynaecology and Obstetrics classification. The patient was managed successfully by concurrent chemo-radiotherapy. CONCLUSION: The optimal management of adenoid cystic carcinoma cannot be established for certain. From our case and from the literature, it appears that combined treatment (surgery, radiotherapy, and chemotherapy) is necessary for achieving a long-term remission. Concurrent chemo-radiotherapy appears to be a logical option for locally advanced disease.

Role of chemotherapy in the management of primary rectal lymphoma: a case report and review of the literature.

INTRODUCTION: Primary rectal lymphoma is a rare disease. In this paper we present an unusual case of primary rectal lymphoma which was managed with chemotherapy and discussed by a thorough review of the related literature. CASES PRESENTATION: An 85-years-male patient was diagnosed in Sidi Mohammed Ben Abdellah Hospital as having diffuse large B-cell lymphoma of the rectum at a bulky stage two. This patient was managed successfully with 8 treatment cycles of Cyclophosphamide 750 mg/m2 at day 1 of each cycle, Doxorubicin (50 mg/m2 in the first 4 cycles and 25 mg/m2 in the subsequent cycles) at day 1 of each cycle, Vincristine 1.4 mg/m(2 )at day 1 of each cycle, and prednisone 50 mg/m(2 )at day 1 to 5 of each cycle. CONCLUSION: The optimal treatment of primary rectal lymphoma needs more research studying to be achieved.