Middle East and North Africa Registry to Characterize Rate of RAS Testing Status in Newly Diagnosed Patients with Metastatic Colorectal Cancer.

BACKGROUND: Rat sarcoma virus mutational status guides first-line treatment in metastatic colorectal cancer. This study was a multi center, multi-country ambispective, observational study in the Middle East and North Africa assessing regional rat sarcoma virus testing practices in newly diagnosed patients. METHODS: The retrospective arm (2011-2014) included adults with metastatic colorectal cancer who had initiated first-line therapy with ≥1 post-baseline visit and survival data. The prospective arm (2014-2019) enrolled newly diagnosed patients with histologically proven metastatic colorectal cancer with ≥1 measurable lesion per Response Evaluation Criteria in Solid Tumors, and tissue availability for biomarker analysis. Data look-back and follow-up were 2 years; the rate of RAS mutation was evaluated. RESULTS: RAS testing was ordered for patients in retrospective (326/417) and prospective (407/500) studies. In the former, testing was typically prescribed after first-line treatment initiation, significantly more in patients with stage IV disease (P < .005), resulting in the addition of targeted therapy (41.8% anti-epidermal growth factor receptor, 30.2% anti-vascular endothelial growth factor) in wild-type metastatic colorectal cancer, and significantly impacted the treatment of left-sided tumors (P = .037). In the latter, 58.4% were RAS wild-type; 41.6% were RAS mutant. Non-prescription of RAS testing was attributed to test unavailability, financial, or medical rea sons; predictors of testing prescription were older age, primary tumor in ascending colon, and high tumor grade. RAS status knowledge resulted in the addition of anti-vascular endothelial growth factor (20.4%) or anti-epidermal growth factor receptor therapy (21.2%). CONCLUSION: Before 2014, RAS testing in patients with colorectal cancer in the Middle East and North Africa was often performed after first-line treatment. Testing is more routine in newly diagnosed patients, potentially shifting early treatment patterns.

Response to Induction Neoadjuvant Hormonal Therapy Using Upfront 21-Gene Breast Recurrence Score Assay-Results From the SAFIA Phase III Trial.

PURPOSE: Luminal, human epidermal growth factor receptor 2-negative breast cancer represents the most common subtype of breast malignancies. Neoadjuvant strategies of operable breast cancer are mostly based on chemotherapy, whereas it is not completely understood which patients might benefit from neoadjuvant hormone therapy (NAHT). MATERIALS AND METHODS: The SAFIA trial is a prospective multicenter, international, double-blind, neoadjuvant phase III trial, using upfront 21-gene Oncotype DX Breast Recurrence Score assay (recurrence score [RS] < 31) to select operable luminal human epidermal growth factor receptor 2-negative patients, for induction hormonal therapy HT (fulvestrant 500 mg with or without goserelin) before randomly assigning responding patients to fulvestrant 500 mg (with or without goserelin) plus either palbociclib (cyclin-dependent kinase 4/6 inhibitor) or placebo. The objectives of this interim analysis were to assess the feasibility of upfront RS determination on core biopsies in the Middle-East and North Africa region and evaluate the efficacy of induction NAHT in patients with an RS < 31. RESULTS: At the time of this interim analysis, 258 patients with relative risk were accrued, including 202 patients (RS < 31% to 78.3%) treated with induction NAHT and 182 patients evaluable so far for response. The feasibility of performing the Oncotype DX assays on core biopsy specimens was optimal in 96.4% of cases. Overall, 93.4% of patients showed hormone sensitivity and no difference in NAHT efficacy was noticed between RS 0-10, 11-25, and 26-30. Interestingly, patients with high RS (26-30) showed a trend toward a higher major response rate (P = .05). CONCLUSION: The upfront 21-gene assay performed on biopsies is feasible in our population and has allowed us to select patients with high hormone sensitivity (RS < 31). This approach could be an alternative to upfront surgery without significant risk of progression, particularly during pandemic times.

Incidence of lung cancer in males and females in Algeria: The lung cancer registry in Algeria (LuCaReAl).

BACKGROUND: Lung cancer is a major cause of death worldwide. However, few data on incidence, histologic types and mortality rates of lung cancer were available for Algeria. METHODS: LuCaReAl is an ongoing descriptive, non-interventional, national, multicenter, prospective and longitudinal study conducted in Algeria, among oncologists and pulmonologists in public community and university hospitals. Median and interquartile ranges are displayed. RESULTS: Between July 2016 and July 2017, 897 patients were included. Overall incidence of lung cancer was 3.4 [3.2;3.6] cases per 100,000 inhabitants; overall incidence by sex was 5.8 [5.4;6.2] for males and 1.0 [0.8;1.1] for females. Adenocarcinoma was the most common histologic type of cancer. Most tumors were diagnosed at Stage IV. CONCLUSION: The first results from the LuCaReAl study in Algeria showed that most patients are diagnosed with lung cancer at an advanced stage. The ongoing follow-up will next provide data on the survival and mortality rates.

A review of the international early recommendations for departments organization and cancer management priorities during the global COVID-19 pandemic: applicability in low- and middle-income countries.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a new virus that has never been identified in humans before. COVID-19 caused at the time of writing of this article, 2.5 million cases of infections in 193 countries with 165,000 deaths, including two-third in Europe. In this context, Oncology Departments of the affected countries had to adapt quickly their health system care and establish new organizations and priorities. Thus, numerous recommendations and therapeutic options have been reported to optimize therapy delivery to patients with chronic disease and cancer. Obviously, while these cancer care recommendations are immediately applicable in Europe, they may not be applicable in certain emerging and low- and middle-income countries (LMICs). In this review, we aimed to summarize these international guidelines in accordance with cancer types, making a synthesis for daily practice to protect patients, staff and tailor anti-cancer therapy delivery taking into account patients/tumour criteria and tools availability. Thus, we will discuss their applicability in the LMICs with different organizations, limited means and different constraints.

Optimizing cancer pain management in resource-limited settings.

PURPOSE: Adequate cancer pain management (CPM) is challenging in resource-limited settings, where current international guideline recommendations are difficult to implement owing to constraints such as inadequate availability and accessibility of opioids, limited awareness of appropriate opioid use among patients and clinicians, and lack of guidance on how to translate the best evidence into clinical practice. The multinational and multidisciplinary CAncer Pain managEment in Resource-limited settings (CAPER) Working Group proposes a two-step initiative to bridge clinical practice gaps in CPM in resource-limited settings. METHODS: A thorough review of the literature, a steering committee meeting in February 2017, and post-meeting teleconference discussions contributed to the development of this initiative. As a first step, we developed practical evidence-based CPM algorithms to support healthcare providers (HCPs) in tailoring treatment according to availability of and access to resources. The second part of the initiative proposes a framework to support an effective implementation of the CPM algorithms that includes an educational program, a pilot implementation, and an advocacy plan. RESULTS: We developed CPM algorithms for first-line use, breakthrough cancer pain, opioid rotation, and refractory cancer pain based on the National Comprehensive Cancer Network guidelines and expert consensus. Our proposed educational program emphasizes the practical elements and illustrates how HCPs can provide optimal CPM according to evidence-based guidelines despite varied resource limitations. Pilot studies are proposed to demonstrate the effectiveness of the algorithms and the educational program, as well as for providing evidence to support a draft advocacy document, to lobby policymakers to improve availability and accessibility of analgesics in resource-limited settings. CONCLUSIONS: These practical evidence-informed algorithms and the implementation framework represent the first multinational step towards achieving optimal CPM in resource-limited settings.

Molecular and epidemiological characteristics of inflammatory breast cancer in Algerian patients.

Inflammatory breast cancer (IBC) shows a high incidence in Tunisia and Egypt but epidemiological and molecular characteristics have not been described in Algeria. We compared 117 IBC and 59 non-IBC locally advanced breast cancers (LABC), for estrogen and progesterone receptors, HER2, and EGFR protein expression by immunohistochemistry, and HER2 gene amplification by chromogenic in situ hybridization. Demographic, clinico-pathological, and molecular variables were compared with chi-square and Fisher's exact tests to test for significance (P < 0.05, two-tailed). Overall survival (OS) and disease-free survival (DFS) were plotted using Kaplan-Meier curves and compared using the log-rank test. Tumor emboli were detected in 77% of IBC. Palpable masses were found in all LABC but only in 32% of IBC (P < 0.001). Recurrences were higher in LABC than in IBC (48 vs. 35%; P = 0.14) but OS was worse in IBC (68 vs. 71%; P = 0.06). There were no significant differences between IBC and LABC by demographics or by clinico-pathological parameters. The majority of IBC and LABC tumors were luminal A (62 and 64%), followed by basal (~18%, each), triple negative (~18%, each), and HER2+ (~10%, each) subtypes. In multivariate analyses, grade was associated with worse OS (P = 0.04), and DFS (P < 0.001) in IBC; chemo- and radio-therapy were associated with improved OS and DFS, respectively (P < 0.05 for each) in LABC. In conclusion, IBC in Algeria shows similar characteristics to IBC described for Egypt and Tunisia with subtle molecular differences. Current therapeutic treatments were not very effective in this population and new approaches are much needed.

Epidermal growth factor receptor (EGFR) abundance correlates with p53 and Bcl-2 accumulation and patient age in a small cohort of North African nasopharyngeal carcinoma patients.

In North Africa, nasopharyngeal carcinoma (NPC) is characterized by a bimodal distribution involving a juvenile (≤  30 years old) and an elder population (> 30 years old). The Epstein Barr virus oncogene LMP1, the anti-apoptotic Bcl-2 protein and the tumor suppressor p53 have recently emerged as biomarkers of the disease. EGFR/ErbB1 expression is detected in the majority of NPC tumors with advanced disease. To obtain greater insight into the potential oncogenic mechanisms specific to these two NPC populations, we examined the correlation between EGFR expression and patient age, and determined the molecular profiles of its associations with the biomarkers of NPC. We performed an immunohistochemical analysis of the latter molecules in NPC specimens from eleven Algerian patients (six patients  ≤  30 years of age and five patients > 30 years of age) using the LSAB method. Evaluation of the biopsies, based on the intensity of staining and the percentage of positive cells, showed that LMP1 expression was higher in patients under 30 years of age. Conversely, EGFR, like Bcl-2 and p53, was significantly up-regulated in tumors from elderly patients. Analysis of all tumors showed that EGFR expression was constantly (100%) associated with high p53 nuclear accumulation and Bcl-2 expression in LMP1-positive tissues. Biopsies negative for Bcl-2 staining were found to display low amounts of p53 (100%), and to be constantly negative for EGFR (100%). Molecular classification of all NPC tissues showed that the majority of patients displaying a EGFR+/LMP1+/Bcl-2+/p53-high molecular pattern were in the older age group. On the other hand, the most of the EGFR negative results were associated with the juvenile form of the disease and were characterized by an important diversity of molecular patterns. Our preliminary results suggest that in Algerian patients, the bimodal distribution of NPC might be related to distinct expression profiles of viral and cellular biomarkers of NPC.

Gemcitabine and treatment of diffuse large B-cell lymphoma in relapsed or refractory elderly patients: a prospective randomized trial in Algeria.

CONTEXT: Support for non-Hodgkin's lymphoma (NHL) with large cells that is refractory or relapsed after first-line chemotherapy poses a greater therapeutic problem with bone marrow transplant therapy or when old age is a contra-indication for high-dose chemotherapy, especially among developing countries such as Algeria. AIM: To show that the regimen, including gemcitabine, could be more effective in treating elderly patients with diffuse large B-cell lymphoma (DLBCL) in relapse / refractory, without complete remission, when compared with the ESHAP (etoposide, cisplatine, solumedrol, aracytine) regimen. MATERIALS AND METHODS: Ninety-six patients in the age group of 60-70 years were volunteers for a prospective randomized single-blind study, carried out for three years. Patients were divided into two groups by the drawing of lots. The first group (GA, n = 48, relapse; n = 27 [56.3%], refractory; n = 21 [43.7%]) received treatment with ESHAP protocol and the second one (GB, n = 48, relapse; n = 28 [58%], refractory; n = 20 [42%]) with GPD (gemcitabine, dexamethasone, cisplatine) protocol. RESULTS: The overall response rates and mean survival at three years were significantly higher among patients subjected to GPD treatment compared with those subjected to ESHAP treatment (63% vs. 55%, P = 0.01 and 20.5% [95% CI 16.5-24.5] vs. 11.8% [8.9-14.6], respectively). Additionally, three-year progression-free and event-free survival rates were 20.5% (16.3-24) and 19.7% (15.9-23.5), respectively, for the GPD regimen and 10.9% (8.2-13.7) and 11.1% (95% CI 8.5-13.7), respectively, for the ESHAP regimen. Moreover, the GPD regimen was associated with improving overall survival (RR=2.02, 95% CI 1.59-2.56; P = 0.000), event-free survival (2.03, 1.64-2.52; P < 0.001) and progression-free survival (1.86, 1.46-2.37; P < 0.001). CONCLUSION: In cases of contra-indication for high-dose chemotherapy for elderly patients with DLBCL, without complete remission, the Gemcitabine-based therapy protocol represents a more effective and less toxic than that of ESHAP.

A New Heterocyclic Multicomponent Reaction For the Combinatorial Synthesis of Fused 3-Aminoimidazoles.

When general and reliable, multicomponent reactions are among the most powerful tools in modern drug discovery. The principle of chemical ligation of reactive partners (see reaction scheme) has been employed to find a new, highly efficient synthesis of fused 3-aminoimidazoles.