Primary bone lymphoma: tunisian multicentric retrospective study about 32 cases.

AIM: To report the epidemiologic, clinical features, treatment modalities and prognosis of primary bone lymphomas (PBL) within a retrospective Tunisian series. METHODS: We collected cases of histologically confirmed PBL in 3 medical oncology departments from northern and central Tunisia andwe analyzed their characteristics. RESULTS: From January 1990 to July 2014, we collected 32 patients with histologically proven PBL, having a median age of 53 years. They affected mainly the long bones and diagnosed at early stages. 91% of the PBL were large cell B lymphoma. All patients received CHOP or CHOP-likeChemotherapy (CT), associated to Rituximab in the last 9 cases, with 14/32 patients received loco-regional radiotherapy and one patient had a resection-reconstruction surgery. We observed 90% of objective responses after primary CT.With a median follow-up of 38.5 months (1 to 192), the 5-year overall survival OS rate was 63%.18 patients relapsed and 14 remain alive in complete remission. CONCLUSION: PBL remains a rare disease lately diagnosed in Tunisia. However, most of the patients had early stages tumors. Furthermore, the efficacy of CT and introduction of Rituximab leads to a high rate of complete/objective responses, improving the survival rate.

Clonal Evolutionary Analysis during HER2 Blockade in HER2-Positive Inflammatory Breast Cancer: A Phase II Open-Label Clinical Trial of Afatinib +/- Vinorelbine.

BACKGROUND: Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer associated with HER2 amplification, with high risk of metastasis and an estimated median survival of 2.9 y. We performed an open-label, single-arm phase II clinical trial (ClinicalTrials.gov NCT01325428) to investigate the efficacy and safety of afatinib, an irreversible ErbB family inhibitor, alone and in combination with vinorelbine in patients with HER2-positive IBC. This trial included prospectively planned exome analysis before and after afatinib monotherapy. METHODS AND FINDINGS: HER2-positive IBC patients received afatinib 40 mg daily until progression, and thereafter afatinib 40 mg daily and intravenous vinorelbine 25 mg/m2 weekly. The primary endpoint was clinical benefit; secondary endpoints were objective response (OR), duration of OR, and progression-free survival (PFS). Of 26 patients treated with afatinib monotherapy, clinical benefit was achieved in 9 patients (35%), 0 of 7 trastuzumab-treated patients and 9 of 19 trastuzumab-naïve patients. Following disease progression, 10 patients received afatinib plus vinorelbine, and clinical benefit was achieved in 2 of 4 trastuzumab-treated and 0 of 6 trastuzumab-naïve patients. All patients had treatment-related adverse events (AEs). Whole-exome sequencing of tumour biopsies taken before treatment and following disease progression on afatinib monotherapy was performed to assess the mutational landscape of IBC and evolutionary trajectories during therapy. Compared to a cohort of The Cancer Genome Atlas (TCGA) patients with HER2-positive non-IBC, HER2-positive IBC patients had significantly higher mutational and neoantigenic burden, more frequent gain-of-function TP53 mutations and a recurrent 11q13.5 amplification overlapping PAK1. Planned exploratory analysis revealed that trastuzumab-naïve patients with tumours harbouring somatic activation of PI3K/Akt signalling had significantly shorter PFS compared to those without (p = 0.03). High genomic concordance between biopsies taken before and following afatinib resistance was observed with stable clonal structures in non-responding tumours, and evidence of branched evolution in 8 of 9 tumours analysed. Recruitment to the trial was terminated early following the LUX-Breast 1 trial, which showed that afatinib combined with vinorelbine had similar PFS and OR rates to trastuzumab plus vinorelbine but shorter overall survival (OS), and was less tolerable. The main limitations of this study are that the results should be interpreted with caution given the relatively small patient cohort and the potential for tumour sampling bias between pre- and post-treatment tumour biopsies. CONCLUSIONS: Afatinib, with or without vinorelbine, showed activity in trastuzumab-naïve HER2-positive IBC patients in a planned subgroup analysis. HER2-positive IBC is characterized by frequent TP53 gain-of-function mutations and a high mutational burden. The high mutational load associated with HER2-positive IBC suggests a potential role for checkpoint inhibitor therapy in this disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT01325428.

Genomic classification of lung cancer: toward a personalized treatment.

Lung cancer is the first cause of death by cancer worldwide. In Tunisia, its incidence has increased from 17.6 cases per 100.000 persons in 1997 to 27.6 cases per 100.000 persons in 2003. Its prognosis has been improving thanks to the emergence of molecular targets. The first one is represented by EGFR (Epidermal growth factor receptor), which marks this (2014) its tenth anniversary. many other targets have been identified. the most famous and useful of them the fusion gene ALK-EML4 but other oncogenic pathways have been implicated and under investigations including HER2, BRAF, MET, RET... The relevant challenges encountered are represented by the difficulty to achieve a consensual decisional and therapeutic algorithm, the absence of standardized diagnostic techniques and unavoidable occurrence of secondary resistance due to the activation of other oncogenic pathways that must be explored and targeted. In this update, we tried to present the major pathways implicated and the most relevant practice routine strategies.

Exocrine Pancreatic carcinoma in Tunisia: A retrospective study about 158 cases.

BACKGROUND: Exocrine pancreatic carcinoma (EPC) occurs in the majority of cases with early locoregional spread and distant metastasis at diagnosis, leading to dismal prognosis and limited treatment options. Traditional cytotoxic chemotherapy provide only modest benefit to patients with EPC. Identification of different molecular pathways, overexpressed in pancreatic cancer cells, has provided the opportunity to develop targeted therapies with a crucial therapeutic role in this cancer setting. OBJECTIVE: Our aim is to study the epidemiological, clinicopathological characteristics, treatment modality and clinical outcome of pancreatic adenocarcinoma in Tunisian patients treated in the department of medical oncology Abderrahmane Mami Ariana. METHODS: This retrospective study concerned patients with exocrine pancreatic carcinoma treated between 2009 and 2012. We analysed the following data: Anamnesis, age, sex, delay to diagnosis(DD), symptoms, clinical exam, performance status, stage, therapeutic protocol and results. RESULTS: We collected 158 patients (113 males/45 females, SR 2.5) with a median age of 64 years (20-93). The median DD was 2 months (1-12). Abdominal pain, jaundice and weight loss were the most frequent symptoms, 88.6%, 43% and 55.1% of cases respectively. Performance status was < 2 in 56.9% (90 pts). Seric CA19-9 was increased in 86.6% of cases. Tumor was at stage III in 24.7% and stage IV in 58.2%. Surgery was done in 24.7% of cases (39pts), curative in 21 patients. Neoadjuvant chemotherapy(NACT) was administrated to 10.8% of patients, adjuvant to 13.9% (22 pts) and palliative chemotherapy(PCT) concerned 58.8% of patients. We used weekly Gemcitabine, Gemcitabine-CDDP, Gemcitabine-Oxaliplatine and LV5-FU2-CDDP in palliative setting respectively in 20%, 31.1%, 2.2 and 36.7% of cases. Median survival was 6 months (2-60) and the 1year overall survival at 38.8%. CONCLUSION: EPC remains a rare cancer in Tunisia. The prognosis is still grim worldwide and so does in our country. In this retrospective serie, we noted the predominance of locally advanced and metastatic cases with a long delay to diagnosis. Awareness campaigns have to be programmed to improve early diagnosis in EPC and improve outcomes.

[Metastatic non-small cell lung cancer: a Tunisian retrospective study about 100 cases]. / Cancers Broncho-pulmonaires non à petites cellules métastatiques : Etude tunisienne retrospective à propos de 100 cas.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common histologic form, leading causes of cancer death among masculine population. Half of CNPC was metastatic at diagnosis. AIM: To report the epidemiologic, anatomoclinic profile, therapeutic protocols and results of a retrospective study of non-small cell lung cancer (NSCLC) initially metastatic. METHODS: our retrospective study include patients with NSCLC histologically confirmed with inaugural metastasis collected from January 1999 to december 2012. We had analysed epidemiologic, anatomopathologic data (TNM 2009), therapeutic protocols and results in term of overall survival, median survival and event free survival. RESULTS: 100 case of NSCLC have been collected, mea nage was 57 years (22 to 81) and sex -ratio was 4,6. The majority of cases (74%) had a good performance statut (PS ≤ 2). Pathologic analysis leads to 81 cases of adenocarcinoma (ADK), 16 epidermoid carcinoma. 34% was stager T4 and 31% N2. Metastasis was located to bone in 36 cases, pleural in 26 cases, controlateral lung 26 cases, adrenal gland 17 cases and brain in 13 cases. 82% of patients underwent polychemotherapy as first line of treatment based on regimens conteined platine with mean number of 4 cycles. We have observed 4% of complete response, 61 of partial response, 20% of stabilisation, and 15% of progression. A palliatif radiotherapy of bone or brain metastasis was performed in 38 % of cases. With a median follow-up of 71 months (12 to 130 months), mean survival was 11 months; overall survival (Kaplan-Meier) at 1, 3 and 5 years was respectively 44, 13 and 0 %. CONCLUSION: Despite therapeutic progress in management of NSCLC, the prognosis of metastatic forms still reserved with a poor mean survival reported in litterature (12 years) valideted in our study. This push us to improve research mainly since advent of targeted therapy wich still a promising way in the management of these tumors.

Glioblastoma in Tunisia: A retrospective study about 41 cases.

BACKGROUND: Glioblastoma (GB) is the most common and lethal primary brain tumor in adults representing 25% of primary brain tumors in adults. The objective of our study was to report the epidemiologic, clinical and therapeutic features of GB in Tunisia. METHODS: Our retrospective study included 41 patients with histologically confirmed GB treated between 2006 and 2012 at the medical oncology departments of Abderrahmane Mami hospital in Ariana and the military hospital in Tunis. RESULTS: Median age was 54 years (13 to 72 years) and sex-ratio was 2.3. Karnofsky performance status (KPS) was <70% in 31.7% of cases, while Recursive partitioning analysis radiation therapy oncology group (RTOG-RPA) classification was III in 11 (26.8%), IV in 19 (46.3%), V in 10 (24.3%) and VI in 1 (2.4%) cases. Complete resection (CR) was achieved in 29 patients (70.7%), partial resection (PR) or tumor debulking in 5 patients (12.2%) and biopsy alone (BA) in 7 patients (17.1%). All patients received brain radiotherapy (RT) at a dose of 60 Gy combined with concurrent temozolomide (TMZ). Nineteen patients (46.3%) received adjuvant TMZ, 8 of them completed 6 cycles. Median overall survival (OS) was 12 months (2 to 56 months). Six, 12, 18 and 24-months OS rates were 84.6%, 57.6%, 35.4% and 20.7%, OS being correlated to age, KPS, RPA and quality of resection. CONCLUSION: Our retrospective study is the first African GB series. Despite it included predominantly poor prognosis patients with impaired neurocognitive function and adjuvant treatment discontinuation, our median OS was comparable to Stupp.

[Aromatases inhibitors for breast cancer in menopausal patients]. / Les inhibiteurs de l'aromatase dans le traitement adjuvant du cancer du sein de la femme ménopausée.

AIMS: To analyze the litterature data concerning the results of the main international randomized trials of adjuvant Aromarase Inhibitors (AI) in adjuvant setting for early breast cancer and the impact on daily practice in the management of breast cancer. METHODS: We selected through a litterature review 30 publications concerned the topic of AI RESULTS: They concerned the large ATAC, BIG, MA17 and IES concerning anastrozole, letrozole and exemestane . AI have been compared to tamoxifen in upfront of swich intents and showed a superiority to reduce, mortality rate, controlateral breast cancer risk, a better tolerance profile compared to tamoxifen and a sigificant benefit in term of disease-free survival. These results made a revolution in the adjuvant BC treatment, leading to the systematic use of upfront AI in menopaused patients. CONCLUSION: Adjuvant hormonotherapy in menopaused patients is now based on AI and proved its superiority to tamoxifen in term of distant, controlateral risks reduction and disease-free survival, less for overall survival.

Sternal or parasternal involvement from breast cancer: a misleading clinical sign.

BACKGROUND: Sternal arch is a nonspecific clinical signs wich may arise during following of breast cancer, this sign reveals an involvement of internal mammary nodes secondary to breast cancer. AIM: To report a rare event such as a loco-regional sternal or parasternal invasion secondary to locally advanced cases of breast cancer (BC) about a Tunisian series. METHODS: We collected retrospectively from 1988 to 2012, 11 cases of BC treated at the Institut Salah Azaiez (ISA) of Tunis, with presence during the disease evolution (initial or at relapse) of a sternal or parasternal swelling. We analyzed their clinical history, clinical and imaging data (CT-scan and/or MRI), stage, time of occurrence, treatment and evolution RESULTS: All patients were females and their mean age was 46 years varying from 24 to 75 years. The sternal or parasternal swelling was found at diagnosis in 5 cases and on recurrence in 6 patients after a mean free interval of 24 months, > 12 months in 5 cases. The mean clinical tumor size of the primitive BC was 38 mm (24-75 mm) and lesions located in external quadrants in 3 cases and internal or central in 6 cases. Sternal involvement related to large Intrammmary Chain (IMC) adenopathies was diagnosed by CT-scan. 7 patients had synchronous metastases. 9 out of the 11 patients received a locoregional RT and two received chemotherapy (CT). CONCLUSION: Sternal or parasternal swelling is a clinical apparent symptom of advanced internal mammary lymph nodes in breast cancer. The first etiologic diagnosis in this context is an advanced internal mammary chain (IMC) node involvement from breast cancer.

Breast Cancer in the Arabian Gulf Countries.

Breast cancer stands as the prevailing malignancy across all six Gulf Cooperation Council (GCC) nations. In this literature review, we highlighted the incidence and trend of breast cancer in the GCC. Most of the studies reported a consistent increase in breast cancer incidence over the past decades, which was particularly attributed to the adoption of a Westernized lifestyle in the region and the implications of emerging risk factors and other environmental and societal factors, the increase in screening uptake, as well as the improvement in data collection and reporting in the GCC. The data on breast cancer risk factors in the GCC were limited. In this geographic region, breast cancer frequently manifests with distinctive characteristics, including an early onset, typically occurring before the age of 50; an advanced stage at presentation; and a higher pathological grade. Additionally, it often exhibits more aggressive features such as human epidermal growth factor receptor 2 (HER2) positivity or the presence of triple-negative (TN) attributes, particularly among younger patients. Despite the growing body of literature on breast cancer in the GCC, data pertaining to survival rates are, regrettably, meager. Reports on breast cancer survival rates emanating from the GCC region are largely confined to Saudi Arabia and the United Arab Emirates (UAE). In the UAE, predictive modeling reveals 2-year and 5-year survival rates of 97% and 89%, respectively, for the same period under scrutiny. These rates, when compared to Western counterparts such as Australia (89.5%) and Canada (88.2%), fall within the expected range. Conversely, Saudi Arabia reports a notably lower 5-year survival rate, standing at 72%. This disparity in survival rates underscores the need for further research directed toward elucidating risk factors and barriers that hinder early detection and screening. Additionally, there is a pressing need for expanded data reporting on survival outcomes within the GCC. In sum, a more comprehensive and nuanced understanding of breast cancer dynamics in this region is imperative to inform effective strategies for prevention, early detection, and improved patient outcomes.

[Trastuzumab (herceptin) for the medical treatment of breast cancer]. / Trastuzumab (herceptine) dans le traitement medical des cancers du sein.

BACKGROUND: Trastuzumab is humanized monoclonal antibody targeting her 2 neu receptor, overexpressed in 20% of breast cancers and part of the complex of Epidermal Growth Factor Receptor. AIM: To review new advances in the knowledge of the practical use of "trastuzumab (Herceptin ®)" in breast cancer. METHODS: Review of literature using medical data bases (Medline, Science direct) with the following key words: breast cancer, targeted therapy, HER2 neu, transtuzumab/herceptine RESULTS: Trastuzumab represent an important advance in breast cancer treatment with an improvement of median survival in metastatic setting and overall and disease-free survival in adjuvant setting in association with chemotherapy. Herceptin remain well tolerated with a low and rare risk of cardiac failure. CONCLUSION: Trastuzumab is a new therapeutic tool very interesting to ameliorate prognosis of breast cancer.

Establishment of the First Comprehensive Adult and Pediatric Hematopoietic Stem Cell Transplant Unit in the United Arab Emirates: Rising to the Challenge.

Hematopoietic stem cell transplantation (HSCT) is increasingly indicated for various malignant and non-malignant diseases. In the United Arab Emirates (UAE), patients that could benefit from the procedure commonly need to seek medical care abroad in view of the lack of a comprehensive HSCT facility that could offer the full spectrum of interventions and monitoring protocols. This comes with considerable challenges related to coverage and logistics of travel. It also limits the continuity of clinical care, and presents inconvenience to patients who come from a different cultural background. In this article, we share our experiences and lessons learned during the establishment of the first comprehensive adult and pediatric HSCT unit in the UAE that is designed to cater for local citizens and residents, as well as neighboring countries facing similar availability challenges.

Rituximab-induced interstitial lung disease: case report and literature review.

Rituximab, a chimeric monoclonal antibody against CD20, very rarely causes lung toxicity. Toxicity may present as interstitial lung disease, alveolar hemorrhage and adult respiratory distress syndrome. Sixteen cases of rituximab-induced interstitial lung disease (R-ILD) have been reported. With this case and a review of all other cases reported in the literature, we will try to identify the features of R-ILD, its treatment and why the early diagnosis of this complication is important.

[Superior vena cava syndrome and internal mammary nodes in breast cancer: two cases]. / Syndrome cave superieur avec atteinte de la chaine mammaire interne au cours d'un cancer du sein: a propos de deux observations.

BACKGROUND: The association of superior vena cava syndrome with involvement of the internal mammary lymph nodes in breast cancer has not been reported in the literature. AIM: To report two cases of association of superior vena cava with involvement of the internal mammary lymph nodes in breast cancer. CASES REPORT: We report two observations in two patients 45 and 52 years with breast cancer classified T4N2M0 and T3N2M0 treated. Both patients had clinical features compatible with the diagnosis of superior vena cava confirmed by the initial clinical appearance (observation 1) and after treatment (observation 2) to the CT scan. CONCLUSION: The combination of superior vena cava with the achievement of the internal mammary chain in breast cancer worse prognosis.

The State of Cancer Care in the United Arab Emirates in 2020: Challenges and Recommendations, A report by the United Arab Emirates Oncology Task Force.

With cancer being the third leading cause of mortality in the United Arab Emirates (UAE), there has been significant investment from the government and private health care providers to enhance the quality of cancer care in the UAE. The UAE is a developing country with solid economic resources that can be utilized to improve cancer care across the country. There is limited data regarding the incidence, survival, and potential risk factors for cancer in the UAE. The UAE Oncology Task Force was established in 2019 by cancer care providers from across the UAE under the auspices of Emirates Oncology Society. In this paper we summarize the history of cancer care in the UAE, report the national cancer incidence, and outline current challenges and opportunities to enhance and standardize cancer care. We provide recommendations for policymakers and the UAE Oncology community for the delivery of high-quality cancer care. These recommendations are aligned with the UAE government's vision to reduce cancer mortality and provide high quality healthcare for its citizens.

Correction to: Aromatase inhibitor-induced carpal tunnel syndrome: prevalence in daily practice.

The original version of this article unfortunately contained a mistake. The given name and family name were swapped.

First site of recurrence after breast cancer adjuvant treatment in the era of multimodality therapy: which imaging for which patient during follow-up?

PURPOSE: We evaluated the relation between first site of recurrence of early breast cancer and disease profile at presentation and reported survival results, suggesting a personalized diagnostic imaging guidance during follow up. METHODS: Among 1400 early breast cancer treated from 2000 to 2010, 324 relapses were divided into 4 groups according to first site: A-locoregional, B-bone, C-Brain and D-visceral. We analyzed redictive factors of each group compared to a control group of 100 non relapsing patients and the remaining groups matched. RESULTS: In group A, patients were more likely to have histological tumor size above >2 cm, grade 1-2, HR positive and 0-3 involved lymph nodes. In group B, patients had more commonly grade 2-3, 1-3 positive lymph nodes and HR positive tumors. In group C, patients were more frequently young, with large tumor size, grade3, positive lymph nodes and HER2 positive tumors. In group D, patients were more likely to have tumors>2 cm in size, with nodal involvement, grade 3, HR negative and HER2 positive tumors. Annual recurrence rate in group A, was stable ranging between 15%-18%, within the first 3 years and peaked at 19.4% in the interval [1-2]year in group B. Median survival was 46 months in group A, 43 months in group B, with no significant difference. CONCLUSION: Outcome of loco-regional and bone relapses was good, suggesting that both systematic mammography and bone-scan/CT scan for high risk patients (N+, gradeIII) during the first 2-3 years may represent a tailored relevant follow-up protocol for breast cancer patients.

Aggressive primary hepatic epithelioid hemangioendothelioma: a case report and literature review.

A new case of epithelioid hemangioendothelioma is reported to have occurred to a 67-year-old patient who consulted for right-sided chest pain. The work-up showed multiple right pulmonary lesions associated with bilateral moderate pleural effusion and left-sided pleural thickening and three hypodense nodules in the right lobe of the liver, peritoneal thickening, ascites, and multiple vertebral lytic lesions. The diagnosis of an epithelioid hemangioendothelioma was concluded through a histological examination of a computed tomography scan guided biopsy of the liver. The patient received a primary mono-chemotherapy with Adriamycin (75 mg/m2 every three weeks) and intravenous bisphosphonates without response and general status impairment. The patient died after 16 months of follow-up.

Aromatase inhibitor-induced carpal tunnel syndrome: prevalence in daily practice.

INTRODUCTION: We aim to evaluate prevalence and characteristics of CTS in routine daily practice over a 5-year period, with a review of the literature. METHODS: Patients treated with endocrine therapy (441) were retrospectively analyzed looking for CTS cases in aromatase inhibitors (219, 49.6%) and in tamoxifen (222, 50.3%) patients. We described patient's characteristics and CTS management. We also reviewed the literature reporting CTS in aromatase inhibitors clinical trials. RESULTS: Six cases of CTS were diagnosed, all in patients on aromatase inhibitors given in the adjuvant setting. Prevalence was 2.7%. Median age was 54 years. CTS occurred under anastrozole in four cases and letrozole in two cases. One patient had severe intensity presentation. Median time to symptoms onset was 14 months, and resolution was obtained within 4 months after a nonsurgical treatment. CONCLUSION: Aromatase inhibitor-induced CTS is rare. It should be recognized and treated in order to avoid endocrine therapy discontinuation.