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Purpose of Review: The concept of mutually exclusive oncogenic driver alterations has prevailed over the past decade, but recent reports have stressed the possible occurrence of dual-positive non-small-cell lung cancer (NSCLC) and even triple-positive disease for these oncogenes. This entity presents novel prognostic and therapeutic challenges. The present review highlights the available data in an effort to clarify the clinical and pathological significance of coexisting mutations as well as the subsequent therapeutic consequences., Recent Findings: Patients with a known driver oncogene can be successfully treated with the appropriate tyrosine kinase inhibitor, which will provide them with significant responses and lesser toxicities compared with cytotoxic therapy. Unfortunately, most patients will eventually progress. Although some resistance mechanisms have been identified, others remain to be determined but the emergence of secondary oncogenes could be part of the answer., Summary: Approximately 20-25% of NSCLC harbor treatable driver mutations/rearrangements; epidermal growth factor receptor mutation, anaplastic lymphoma kinase and ROS-1 gene rearrangements are the main alterations for which a Food and Drug Administration-approved tyrosine kinase inhibitor can be used.Because of recent technological advances, high sensitivity assays with a broad range of genomic targets have become more easily accessible in clinical practice, which has led to an increased detection of coexisting driver alterations in patients with advanced NSCLC. The prognostic/predictive and therapeutic implications of this novel entity are still unsettled for the time being. Randomized trials specifically designed to address this subset of patients will soon be necessary to help determine the optimal therapeutic agent to administer.

Metastatic melanoma has long been considered to have a very poor prognosis and to be chemo-resistant. However, a subgroup of patients with metastatic melanoma presents remarkable responses to chemotherapeutic agents, even in the absence of a response to modern targeted therapies and immunotherapies; accordingly, determining predictive biomarkers of the response to chemotherapies for metastatic melanoma remains a priority to guide treatment in these patients. We report a case study of a patient with B-Raf proto-oncogene serine/threonine kinase-mutated metastatic melanoma harbouring many genetic mutations. The patient did not respond to prior targeted therapies or immunotherapies but experienced a dramatic objective radiological and clinical response to subsequent dacarbazine-based chemotherapy. In the era of targeted therapies and immunotherapies for metastatic melanoma, cytotoxic chemotherapies may still represent an interesting therapeutic weapon in a well-defined subgroup of patients presenting with specific genetic and molecular features.

Background: Taxanes are drugs used in various chemotherapeutical protocols to treat solid tumors. They have multiple systemic adverse effects, such as bone marrow suppression, alopecia, nausea, and vomiting, and may rarely cause ocular symptoms. In the past decade, a few reported cases have shown the occurrence of a cystoid macular edema with significant visual loss after the use of a taxane-based chemotherapy. The aim of this study was to compare the central macular thickness (CMT) before and after the initiation of a taxane-based therapy in visually asymptomatic patients and to elucidate the possible impact of these drugs on the vision of cancer patients., Methods: Patients with a confirmed diagnosis of a solid tumor were screened for any ophthalmic disease before inclusion and had a baseline macular spectral domain optical coherence tomography (OCT; RTVue-100; Optovue Inc., Fremont, CA, USA) before the initiation of a taxane-based chemotherapy according to different protocols, such as 4EC-4T, 3FEC/3T, or 4TC. OCT was repeated after 4 cycles (or 3 months) of treatment, and CMT was compared to baseline. Patients presenting diabetic retinopathy, age-related macular degeneration or any condition that causes macular edema confirmed by ophthalmic examination were excluded., Results: Fifty eyes of 25 patients were included; 92% of the subjects were female with a mean age of 48.52 years, 88% were diagnosed with breast cancer, 8% with esophageal cancer, and 4% with ovarian cancer. Docetaxel was the taxane administered to 92% of the patients. The received dose of docetaxel ranged between 110 and 160 mg. The other patients had paclitaxel in their protocols. No significant macular edema or drop in visual acuity were noted in any patient. Nevertheless, the mean CMT was found to be increased, particularly in the parafoveal and perifoveal areas (mean difference of +2.22 μm; p = 0.001)., Conclusion: Taxane-based chemotherapy regimens seem to increase macular thickness, with a relative sparing of the fovea, in patients without significant macular edema. Further research is required to better explain the pathophysiology and possible impact of this phenomenon., (© 2017 S. Karger AG, Basel.)

Pancreatic cancer is one of the deadliest cancers, ranking fourth among cancer-related deaths. Despite all the major molecular advances and treatment breakthroughs, mainly targeted therapies, the cornerstone treatment of metastatic pancreatic cancer (mPC) remains cytotoxic chemotherapy. In 2016, more than 40 years after the introduction of gemcitabine in the management of mPC, the best choice for first-line treatment has not yet been fully elucidated. Two main strategies have been adopted to enhance treatment efficacy. The first strategy is based on combining non-cross resistant drugs, while the second option includes the development of newer generations of chemotherapy. More recently, two new regimens, FOLFIRINOX and gemcitabine/nab-paclitaxel (GNP), have both been shown to improve overall survival in comparison with gemcitabine alone, at the cost of increased toxicity. Therefore, the best choice for first line therapy is a matter of debate. For some authors, FOLFIRINOX should be the first choice in patients with an Eastern Cooperative Oncology Group score (0-1) given its lower hazard ratio. However, others do not share this opinion. In this paper, we review the main comparison points between FOLFIRINOX and GNP. We analyze the two pivotal trials to determine the similarities and differences in study design. In addition, we compare the toxicity profile of the two regimens as well as the impact on quality of life. Finally, we present studies revealing real life experiences and review the advantages and disadvantages of possible second-line therapies including their cost effectiveness., Competing Interests: Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.

The European Society for Medical Oncology (ESMO) is one of the leading societies of oncology professionals in the world. Approximately 30% of the 13 000 ESMO members are below the age of 40 and thus meet the society's definition of young oncologists (YOs). ESMO has identified the training and development of YOs as a priority and has therefore established a comprehensive career development programme. This includes a leadership development programme to help identify and develop the future leaders in oncology. Well-trained and highly motivated future generations of multidisciplinary oncologists are essential to ensure the optimal evolution of the field of oncology with the ultimate goal of providing the best possible care to patients with cancer. ESMO's career development portfolio is managed and continuously optimised by several dedicated committees composed of ESMO officers and is directly supervised by the ESMO Executive Board and the ESMO President. It offers unique resources for YOs at all stages of training and includes a broad variety of fellowship opportunities, educational courses, scientific meetings, publications and resources. In this article, we provide an overview of the activities and career development opportunities provided by ESMO to the next generation of oncologists., Competing Interests: Competing interests: None declared.

The choice of immunotherapy in the treatment of cancer has improved the prognosis of many patients affected by various malignancies. The high expectations foreseen with immunotherapy have led to fast approvals despite the incomplete understanding of the toxicity profiles in the different organs, including the kidneys. The high prevalence of chronic kidney disease in cancer patients complicates the issue further and requires a better knowledge of the renal safety profile to ensure an optimal safe treatment. This review summarizes the present knowledge of renal adverse events secondary to immune checkpoint inhibitors and discusses their pathophysiology, clinical presentation and adequate management. We also advocate the need for a multidisciplinary approach in patients with immune-related toxic adverse events.

Immune checkpoint inhibitors (ICI) represent a new revolutionary weapon in the armamentarium of anti-cancer therapies. The side effects of these new agents represent a new challenge for oncologists; they are usually unpredictable and sometimes life threatening, if not managed rapidly and adequately. The most frequent side effects are the dermatologic, but they are usually low grade side effects and consequently easily manageable. Rash, pruritus and vitiligo are the most frequent dermatologic side effects. We aimed in this review to describe first all the dermatologic side effects of ICI according to the subtype of ICI and combination therapies in the clinical trials, then to report all the rare case reports dermatologic side effects, and finally to present the management algorithm of these side effects.

Testicular Germ cell tumors (TGCT) represent the most common solid tumors affecting young men. They constitute a distinct entity because of their embryonic origin and their unique biological behavior. Recently, new preclinical data on genetic and epigenetic susceptibility profiles, biological signaling machinery as well as on molecular patterns of tumors and pathways of pathogenesis helped to elucidate the pathogenesis and the differentiation of TGCTs and to understand the mechanisms behind the development of resistance to treatment. In the present work, we have reviewed new clues to the development, differentiation and progression of TGCTs. We focus on the most important epigenetic and molecular biomarkers, and discussed their diagnostic and prognostic accuracy compared to the currently used biomarkers. The mechanisms underlying the development of resistance to cisplatin and commonly used chemotherapeutic agents are also discussed in detail. Finally, we summarize failed and ongoing clinical trials using targeted therapies in resistant TGCTs, and analyze the potential of new targeted therapies.

After the massive approval of checkpoint inhibitors in the treatment of numerous malignancies and settings, checkpoint inhibitors-based combination therapies are emerging as a new therapeutic modality. Nivolumab and pembrolizumab (anti-PD1 agents) were recently approved as second-line treatment in NSCLC after progression on platinum-doublets. In parallel, targeting EGFR/ALK in NSCLC using tyrosine kinase inhibitors (TKI) demonstrated remarkable outcomes and was approved as standard treatment, in patients with EGFR mutation or ALK rearrangement. Combining TKI targeting EGFR/ALK with checkpoint inhibitors seems a promising therapeutic option and is being evaluated in different trials. We aimed in this paper to elucidate the rationale behind this combination, to report the premilinary results of ongoing trials evaluating this association and finally, to discuss briefly the possible future indication of this treatment modality.

Ampullary carcinoma (AC) is a rare gastrointestinal tumor without clear treatment recommendations. The management of this tumor is usually extrapolated from the treatment of pancreatic, biliary duct and intestinal cancers. Few papers have studied the AC as an independent entity and yet succombs to several limitations. These studies were retrospective single institutional experiences with limited sample sizes recruited over a long period of time. Unlike metastatic ACs where chemotherapy is the only recommended option, localized AC once excised may be approached by either chemotherapy alone or concomitant chemoradiation therapy. In this review, we report the overall survival and recurrence factors of more than 1000 patients from all the studies treating exclusively ACs. We also review the medical treatment of this tumor and conclude to the necessity of multi-institutional randomized controlled studies for AC exclusively., Competing Interests: Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.

Background: To determine the anatomical and functional outcomes and possible complications after pars plana vitrectomy (PPV) with silicone oil (SO) tamponade in primary uncomplicated rhegmatogenous retinal detachments., Methods: This is a prospective observational study. Overall, 62 consecutive patients who underwent surgical repair by PPV and SO injection for primary uncomplicated rhegmatogenous retinal detachment between January 01, 2006 and April 30, 2012 were followed. In general, PPV was chosen over scleral buckling when a significant cataract or a vitreous hemorrhage prevented adequate fundus visualization. Silicone oil was chosen over gas tamponade in patients living at 1,000 meters above the sea level, where SF6 or C3F8 tamponade could not be performed because of the risk of acute increase of intraocular pressure (IOP). One thousand centistokes SO was used in all eyes. At all visits, patients had a detailed ocular history and thorough bilateral evaluation, including best-corrected visual acuity, anterior segment examination, and IOP measurements by aplanation and fundus examination. Outcomes were assessed at 1 day, 1 week, 1 month, 3 months, 6 months, and every 6 months thereafter. Increased IOP was defined as an IOP of more than 21 mmHg., Results: Anatomical success rate, final best-corrected visual acuity, IOP elevation, cataract formation, and other complications were the main outcome measures. This study included 62 eyes of 62 patients (41 men and 21 women) that underwent retinal detachment repair by PPV and SO injection. The age at the time of intervention was 57.6 ± 10.5 years (mean ± standard deviation; range, 34-79 years). All patients were whites. Mean follow-up was 24.5 ± 17.3 months (range, 6-70 months). Anatomical success rate defined as retinal reattachment 6 months after SO removal was 93.5%. Final BCVA was improved in 55 eyes (88.7%), with a mean of 4 Snellen lines, unchanged in 5 (8.1%), and worse in 2 eyes (3.2%), with a mean of 3 Snellen lines. Mean duration of SO tamponade was 5.12 ± 2.37 months (range, 2-12 months). From the 30 eyes that were still phakic after vitrectomy, 24 eyes (80.0%) underwent cataract surgery within a period of 7.37 ± 3.00 months (range, 2-13 months). Thirty-five eyes (56.5%) had an increase in IOP during the follow-up period. Thirty-one patients had transient ocular hypertension requiring topical treatment during the immediate postoperative period (one month). Only 1 eye (2.9%) required filtrating drainage surgery for IOP control. No eyes developed optic neuropathy secondary to IOP elevation., Conclusion: Pars plana vitrectomy with SO injection seems to be a safe and efficient surgical approach in the treatment of primary uncomplicated rhegmatogenous retinal detachment in patients living in high altitude (>1,000 m). Also, PPV and SO injection are associated with good anatomical and functional outcomes in our series. Reattachment rates are high, and rates of proliferative vitreoretinopathy are low. Cataract formation and elevated IOP represent frequent but successfully controlled complications.

Bleeding diathesis is a rare manifestation of monoclonal gammopathies that is often attributed to a dysfunction of the coagulation pathway. Patients usually present with a severe bleeding disorder attributed to an acquired factor inhibitor, most commonly factor VIII inhibitor. Data are sparse concerning this disease, and subsequently the best course of action is not yet defined in such clinical instances. In this article, we report the case of a patient, known to have a monoclonal gammopathy of unknown significance, who was followed for over two decades for a bleeding disorder attributed to an acquired thrombin inhibitor. We describe also the different modalities used as maintenance and event treatments as the patient presented repetitive cataclysmic bleedings.

The involvement of the female genital tract in transitional cell carcinoma (TCC) has not been fully elucidated in women, although involvement is usually associated with a poor prognosis. The vagina, in particular, is considered to be the most commonly affected gynecological organ, with an incidence of 4% of total TCC cases. The pathogenesis of vaginal TCC is challenging to determine, although it is essential for the adequate management of the tumor and to determine the appropriate treatment. The present study reports a case of bladder TCC and metachronous vaginal TCC. The patient had a history of high risk non muscle invasive bladder cancer treated by BCG and presented with a recurrent carcinoma in situ . A novel cycle of BCG was initiated but the patient had a persistent disease and a palpable mass on bimanual examination. Radical anterior pelvectomy and bilateral pelvic and inguinal lymph node dissection was performed revealing the presence of TCC of the bladder neck and the invasion into the anterior vaginal wall. The differences between local vaginal invasion and the metastatic spread from a primary bladder TCC, the occurrence of a second primary vaginal tumor and the direct implantation of TCC via urine that contains transitional cancer cells were reviewed and analyzed. Finally, a management plan was determined.

Beside its poor prognosis and its late diagnosis, pancreatic cancer remains one of the most painful malignancies. Optimal management of pain in this cancer represents a real challenge for the oncologist whose objective is to ensure a better quality of life to his patients. We aimed in this paper to review all the treatment modalities incriminated in the management of pain in pancreatic cancer going from painkillers, chemotherapy, radiation therapy and interventional techniques to agents under investigation and alternative medicine. Although specific guidelines and recommendations for pain management in pancreatic cancer are still absent, we present all the possible pain treatments, with a progression from medical multimodal treatment to radiotherapy and chemotherapy then interventional techniques in case of resistance. In addition, alternative methods such as acupuncture and hypnosis can be added at any stage and seems to contribute to pain relief.

Introduction: Advanced pancreatic cancer (APC), one of the most aggressive tunors, was considered to be resistant to chemotherapy for decades. FOLFIRINOX (5-FU, leucovorin, iNinotecah and oxaliplatin) regimen showed an improvement of quality of life and overall sUrvival.ir APb patients with good performance status (ECOG < 2)., Material and Methods: Seven patients diagnosed with APO, during a six-month period, received FOLFIRINOX as first line treat- ment. Tumor measurement Was assesed every two months and CA 19-9, tHe specific tumor marker of pahcteatid can6er, was assessed every two wedks at every cycle., Results: Three patients ouf of seven receiving FOLFiRINOX dtpe- riented an early And transitory increase of CA 19-9 after th6 first two cybles resulting ih a considerable response with a median survival of 15 mnths and suggesting a fhdel of fdmor release syndrome., Conclusion: This phenoMenon of early and transitory increase of CA 19-9 in APC could reflect the high efficacy of FOLFIRINOX and could predict better out- come in these patients.

New concepts of trial design are being developed based on biomarkers, namely basket and umbrella trials. Basket trials appear optimally positioned to evaluate new molecular markers for testicular germ cell tumors, a rare heterogeneous disease with relatively few molecular alterations. However, not uncommonly, the "balls" fall outside the "basket". In this short communication, we discussed the different causes limiting the inclusion of TGCT in basket trials and we proposed a new design for trials suitable for this malignancy.

Introduction: Despite the availability of several potent HER2-directed targeted agents, primary and acquired resistance continues to influence patient outcomes in HER2-positive breast cancer. Neratinib is an irreversible pan-HER tyrosine kinase inhibitor in late-phase clinical development., Areas Covered: This review article focuses on neratinib in the treatment of HER2-positive breast cancer - early and metastatic stage - and HER2-mutant breast cancer, with particular emphasis on the pharmacokinetics and pharmacodynamics of the drug., Expert Opinion: The phase III ExteNET trial shows that neratinib improves 2-year invasive disease-free survival after trastuzumab-based adjuvant therapy in early-stage HER2-positive breast cancer, and in particular HER2+/HR+ tumors. Survival data are awaited. The investigational role of neratinib in high-risk patients or conversely in de-escalation dual regimens with other anti-HER2 therapies and without chemotherapy are of interest. Phase II trials show that neratinib has efficacy, either as monotherapy or in combination with other chemotherapeutic or endocrine agents, in patients with HER2-positive metastatic breast cancer and in tumors harboring HER2 mutations. The role of neratinib in therapeutic algorithms of HER2-positive patients, as well as delaying CNS events, awaits the results of ongoing trials such as NALA. Diarrhea, the main toxicity of neratinib, can be effectively managed with early loperamide prophylaxis.

Purpose of Review: The aim of this review is to draw the attention of the physicians and oncologists on the rare side-effects of checkpoint inhibitors not usually reported in clinical trials to treat them quickly and render their prognosis better., Recent Findings: Rare side-effects of checkpoint inhibitors are mainly neurologic, haematologic, rheumatologic, renal, and cardiac. The majority of reported side-effects are consequent of the treatment by ipilimumab in patients diagnosed with melanomas. Neurologic side-effects have poorer prognosis compared with other rare side-effects. There is no relationship between developing rare side-effects and the outcome of the disease., Summary: It is important to be aware, when treating patients with checkpoint inhibitors, to detect as early as possible the unpredictable and uncontrollable rare side-effects of these agents. The large spectrum of these rare side-effects should be well documented and reported to assure to the physicians a road map for the diagnosis and the management of these toxicities.

Purpose of Review: After the dramatic and often long-standing response rates of checkpoint inhibitors as single agents, the new era for checkpoint inhibitors is combined therapy (either with other checkpoint inhibitors, chemotherapies, targeted therapies or immunotherapies) that is aiming to do even better. Although one can speculate that these combinations will result in improved results, high cost and potential toxicity are limiting factors for their use. In this review, we plan to report on the different side-effects of the checkpoint inhibitor-based combination therapies and to discuss the future perspectives of these new modalities., Recent Findings: Many checkpoint inhibitor-based combinations are associated with high response rates (>50%) in melanomas and nonsmall cell lung cancers (NSCLCs). As a result, the combination of nivolumab and ipilimumab for metastatic melanoma was recently approved by the Food and Drug Administration; however, 30% of the patients had to discontinue this combination because of high toxicity. In NSCLC, the combination of chemotherapy and anti-programmed cell death protein 1 or anti-programmed cell death protein ligand 1 agents is leading to high response rate (exceeding 65%) but with more than 40% of the patients presenting grade 3/4 toxicities. Despite the discouraging results with the combination of ipilimumab (anti-cytotoxic T-lymphocyte-associated protein 4) with vemurafenib (anti-proto-oncogene protein B-raf-targeted therapy) due to hepatotoxicity, more recent trials are showing less frequent and severe toxicities with other combinations of checkpoint inhibitors and targeted therapies., Summary: Despite the high toxicity rates observed with some checkpoint inhibitor-based combination therapies, these combinations will likely become the new paradigm for the management of various malignancies, namely, melanomas, renal cell carcinomas and NSCLC, provided that their side-effects can be effectively managed.

The next decade in cancer therapy will be marked by the expansion of immunotherapies, namely immune checkpoint inhibitors. The increasing number and combination of checkpoint inhibitors and the variety of their mechanisms of action and indications will most likely multiply the side effects associated with these therapies and make their management more complicated and diversified. Given the growing rate of approval of different checkpoint inhibitors in different cancers in multiple settings, a review summarizing the major side effects of the new agents in use today and their management seems to be appropriate. Highlighting these adverse events and their management in a single review might help the daily practice of the physicians and consequently contribute the patient's safety and quality of life.

Small cell carcinoma (SCC) is most commonly associated with lung cancer. Extra-pulmonary SCC can originate in virtually any organ system, with the gastrointestinal tract being the most common site of involvement. We review the clinical presentation, pathogenesis, histology, imaging modalities and optimal therapeutic management of PSCC in light of available evidence., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Introduction: Despite worldwide trends toward optimizing full disclosure of information (DOI), the prevailing belief that cancer diagnosis should be concealed from patients, for their own good, has endured for a substantial period of time in Middle Eastern communities., Objectives: This study would assess the reliability of the Arabic translated version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-INFO 25). The study was also designed to quantify DOI to Lebanese cancer patients and determine patient satisfaction with this DOI. Moreover, we compared the differences in the level of information among groups based on clinical and biographical variables., Methods: A sample of patients, being treated for a variety of malignancies, was prospectively evaluated. A physician interviewed patients using the Arabic version of the EORTC QLQ-INFO 25, on the day of hospitalization for chemotherapy, before treatment was administered., Results: In total 201 patients were interviewed. The translated version of the EORTC QLQ-INFO 25 showed high reliability when assessed using Cronbach's alpha coefficients for internal consistency with values scoring higher than 0.7 for all scales and the full questionnaire. There was a considerable lack of information provided to the participants with 38.8 % being unaware of their diagnosis and more than half being uninformed about the extent of their disease. Paradoxically, 86.5 % of patients expressed their satisfaction about the amount of information they received and 89.5 % believe the information provided was helpful. Further analysis showed no significant association between gender, marital status, cancer site and stage and the amount of information received. However, age and level of education were associated with DOI such as younger and more educated patients received more information. Older patients were also found to be the most satisfied with the information they received, despite having less access to information., Conclusions: Although a high proportion of patients were not properly informed about their diagnosis, the overwhelming majority were satisfied with the amount of information they received and believed it was useful, reflecting the complexity of Middle Eastern cultural influences on cancer patients' perspectives.

2015 was marked by the tsunami of immune checkpoint inhibitors revealed by numerous FDA approvals, publications and abstracts in relation with these drugs in different cancers and settings. First, we reported all new indications of anti-CTLA4 and anti-PD1 approved by the FDA, the positive clinical trials published and the abstracts with promising results at important scientific meetings during 2015. Then, we discussed different critical issues of these new agents going from their predictive factors, combination therapies, tumor response patterns, efficacy in particular settings, side effect management to cost and economic burden., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Next to janus kinase 2 (JAK2) and myeloproliferative leukemia protein, calreticulin (CALR) is a recently discovered mutation present in > 20% of patients diagnosed with primary myelofibrosis (PMF)., Materials and Methods: Six studies published from December 2013 to December 2014 met the inclusion criteria for the present meta-analysis: 2 of an Asian and 4 of a non-Asian population. We assessed the biologic characteristics at diagnosis and investigated overall survival. The analyses were stratified by ethnic origin (Asian vs. non-Asian)., Results: A total of 816 patients with the JAK2 mutation and 307 patients with the CALR mutation were included. The patients with the JAK2 mutation were older than those with the CALR mutation, and no statistically significant difference was noted in the gender distribution of the patients with PMF with the JAK2 versus CALR mutation. Patients with JAK2-mutated PMF had a higher white blood cell count, but no statistically significant evidence was found for a difference in the platelet count or hemoglobin level. No difference was found in thrombosis risk or acute leukemic transformation in those 2 populations. Major differences were found between the Asian and non-Asian populations. The difference in characteristics between JAK2 and CALR was larger in the Asian population than in the non-Asian population (P = .007). Also, in the non-Asian population, those with JAK2 mutation had lower platelet counts than the Asians (P = .06). In the non-Asian population, the patients diagnosed with JAK2-positive PMF had worse overall survival than the patients with CALR-positive PMF, with a combined hazard ratio of 2.43 (95% confidence interval, 1.83-3.22)., Conclusion: The results of the present meta-analysis have confirmed the role of the CALR mutation in the diagnosis of, and as a prognostic tool for, PMF. Our results suggest that patients with the CALR mutation will have better overall survival than patients with the JAK2 mutation in a non-Asian population., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Choroidal metastasis from prostate cancer is very rare and usually presents late during the disease. Since 2010, many new drugs were approved in the treatment of castrationresistant prostate cancer, including Abiraterone acetate. We report a case of bilateral choroidal metastases from prostate cancer 3 months after the initiation of Abiraterone. Abiraterone was not efficient in controlling the progression of the disease in this case, especially the choroidal metastasis. More case reports are essential in order to evaluate the role of Abiraterone in controlling choroidal metastases from prostate adenocarcinoma.

Metastatic pancreatic cancer (MPC) is one of the most aggressive malignancies, known to be chemo-resistant and have been recently considered resistant to some targeted therapies (TT). Erlotinib combined to gemcitabine is the only targeted therapy that showed an overall survival benefit in MPC. New targets and therapeutic approaches, based on new-TT, are actually being evaluated in MPC going from immunotherapy, epigenetics, tumor suppressor gene and oncogenes to stromal matrix regulators. We aim in this paper to present the major causes rendering MPC an untargetable malignancy and to focus on the new therapeutic modalities based on TT in MPC.

Background: Neuroendocrine tumors represent 20% of primary lung neoplasms in some registries. According to the WHO classification of 2004, reconsidered for 2015, these lung tumors are divided into 4 groups: typical and atypical carcinoid, small cell and large cell neuroendocrine carcinomas. We report in this paper, for the first time in Lebanon, the distribution and the population characteristics of these tumors., Materials and Methods: This descriptive retrospective study concerned all the pulmonary neuroendocrine tumors (NET) with their characteristics diagnosed in Hotel Dieu de France in Beirut, Lebanon from 2001 to 2012, with attention to features like age, gender and subgroup., Results: Of 194 patients with pulmonary NET, 12.4% were typical carcinoid tumors, 3.6% atypical carcinoid, 66.5% small cell lung cancer, 7.7% combined small cell carcinomas and 9.8% large cell neuroendocrine tumors. The mean ages of patients were respectively 51.2 years in typical carcinoid, 64 years in atypical carcinoid, 64.2 years in small cell lung cancers, 67.2 in combined small cell lung cancer and 66.9 in large cells neuroendocrine tumors. The M/F sex ratios were respectively 0.3, 1.3, 1.4, 2.7 and 2.2., Conclusions: The characteristics of lung neuroendocrine tumors in our Lebanese institution are comparable to those reported in the literature.

Background: Research in the field of informational needs of breast cancer patients is scarce. In the few published articles, these needs were usually not satisfied. The main objective of this study was to evaluate satisfaction regarding informational needs in women with breast cancer. The long-term goal was to guide physician-patient communication to meet these needs., Materials and Methods: A survey with 21 questions was completed by 84 female patients receiving chemotherapy in a one-day hospital in Beirut, Lebanon. All patients were aware of their disease and agreed to participate in the survey., Results: The doctor was the major source of information for patients followed by media (radio and television). The level of knowledge of patients concerning their disease was proportional to the number of information sources. Women aged younger than 45 years, diagnosed during the last three months before the survey and certified from high school were less satisfied with information given by the oncologist. The missing information was in relation with the steps of the treatment after the chemotherapy regimen, the risk of a family member (sisters and daughters) of developing the disease and management of lymphedema., Conclusions: This study generated a scale for the degree of satisfaction of information received by women with breast cancer from their oncologist. The physician can use this scale to improve his or her skills of communication to patients and diminish their level of fear and anxiety.

Background: Chronic lymphocytic leukemia (CLL) is the most frequent form of leukemia in Europe and North America, and it mainly affects older individuals. Many approaches are implemented in the management of CLL from a watch and wait (WandW) strategy to chemotherapeutic regimens. We here reviewed our clinical practice for the relevance of the W and W strategy in Lebanese CLL patients., Materials and Methods: A total of 95 patients with CLL diagnosed in four institutions in Lebanon, between 1992 and 2013, were selected and their files were reviewed. Characteristics of these patients were noted including age, sex, RAI and Binet scores, CBC values, presence of hepatomegaly or splenomegaly, performance of bone marrow biopsy or peripheral blood flux cytometry for diagnosis, adoption of W and W strategy, different chemotherapeutic regimens and the indications for treatment., Results: Some 38 patients (40%) diagnosed with CLL were women and 57 (60%) were men with a mean age of 65.1 years [36-89]. Of the total, 50.5%, 17.2%, 14%, 7.5% and 10.8% had an RAI score at diagnosis of 0, 1, 2, 3 and 4, respectively, while 65.6%, 17.2% and 17.2% had Binet scores of I, II and III. The mean lymphocyte count at diagnosis was 39885/mm3 [1596-290000], the mean hemoglobin level was 12.7 g/dl [6.2-17] and the mean platelet count was 191255/mm3 [14000-458000]. While 26.3% of patients with CLL had splenomegaly, only 7.4% had hepatomegaly. Some 33.7% had undergone a bone marrow biopsy, 66.3% flow cytometry of circulating blood and 5.3% a lymph node biopsy. Overall, the W and W was adopted in 62.4% (58) of patients with a mean duration of 37.7 months [3-216]. The W and W was used in 82.6%, 73.3%, 46.2%, 14.3% and 0% of patients having RAI scores of 0, 1, 2, 3 and 4, respectively, and, it was used in 80%, 46.7% and 6.25% with Binet scores of I, II and III. The most frequent indication for treatment was anemia and thrombocytopenia, accounting for 32.7% of cases. The most frequently used chemotherapeutical regimens were chlorambucil until the end of the last century and flufarabine-cyclophosphamide-rituximab during the last decade., Conclusions: This retrospective review of CLL clinical practice showed an important implementation of the W and W strategy with a long duration, especially in early stage cases with low RAI or Binet scores.

Background: Mesotheliomas are relatively rare tumors in Lebanon. The only previous study goes back to 14 years ago, when we published epidemiological characteristics of mesotheliomas in Lebanon, showing that the pleural location accounted for the vast majority of cases, with clear evidence of asbestos exposure from the Eternit factory of Chekka region. The objective of this current study was to estimate the incidence of mesothelioma in the past decade and to identify its epidemiological, clinical and therapeutic characteristics, making comparisons with our first study published in 2001., Materials and Methods: Between 2002 and 2014, patients diagnosed with malignant mesothelioma at Hotel-Dieu de France University Hospital were investigated. Epidemiological data focusing on asbestos exposure history were collected from medical records and interviews with the families., Results: A total of 26 patients were diagnosed with mesothelioma, 21 of which were successfully investigated. The mean age of these 21 patients is 62.5 (19-82). Only 3 (14.29%) are women. 18 (85.71%) were smokers. Among the 21 available mesotheliomas, 15 (71.4%) are pleural, while 5 (23.8%) are peritoneal and 1 (4.8%) pericardial. Only 60% of patients with pleural mesothelioma and 50% of those with an obvious exposure to asbestos lived and/or worked in Chekka region. The mean time of asbestos exposure in patients with mesothelioma is 24.5 (1-50) years and the mean latency is 37.4 (4-61) years. Of the 21 patients, 10 (47.6%) underwent surgery during their treatment, 16 (76.2%) received chemotherapy and 3 (14.3%) received best supportive care., Conclusions: Compared to the previous study (1991-2000), substantial changes in the epidemiology of mesothelioma in Lebanon were observed, such as an increase in peritoneal localizations and a lower correlation with Chekka region asbestos contamination.

Background: Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NEN) are relatively rare tumors, not equally distributed in the gastrointestinal system. In 2010, a revised version of the WHO classification of GEP-NENs was published. This study reports for the first time the distribution and characteristics of GEP-NENs in a Lebanese population., Materials and Methods: This descriptive retrospective study concerns all the digestive neuroendocrine tumors with their characteristics diagnosed in Hotel Dieu de France in Beirut, Lebanon from 2001 to 2012, all the pathology reports being reanalyzed according to the latest WHO 2010 classification. The characteristics and features of GEP-NEN analyzed in this study were age, gender, grade and site., Results: A total of 89 GEP-NENs were diagnosed, representing 28.2% of all neuroendocrine tumors. The mean age of GEP-NEN patients was 58.7 years and the M/F sex ratio was 1.2. The primary localization was as follows: 21.3%(19) pancreatic, 18% (16) gastric, 15.7% (14) duodenal, 11.2% (10) appendix, 10.1% (9) intestinal, 10.1% (9) colorectal (7.9% colonic and 2.2% rectal), 5.6% (4) hepatic, 2.2% (2) ampulla, 1.1% (1) esophageal and 7.9%(5) NOS digestive (metastatic with unknown primary). Of the 89 patients with GEP-NEN, 56.2% (50) were diagnosed as grade I, 11.2% (10) as grade II, 20.2% (18) as grade III and 12.4% (11) were considered as mixed adeno-neuroendocrine carcinomas (MANEC)., Conclusions: This study, one of the rare examples based on the 2010 WHO classification of neuroendocrine tumors in the literature, indicates that in the Lebanese population, all duodenal and appendicular tumors are G1 and the majority of MANEC tumors are gastric and pancreatic tumors. Moreover, more duodenal tumors and fewer rectal tumors were encountered in our study compared to European reports.

Introduction: In Lebanon, annual national breast awareness campaigns were started in 2002 during the international breast month of October to promote the utilization of mammography for women aged ≥ 40. The impact of the campaigns has been assessed periodically since 2003. Results of 2003-2005 campaigns have been published previously., Objectives: To measure the prevalence of two behavioral outcomes of interest: ever-use of mammography, and repeat mammography in the previous 12 months among ever-users. The prevalence was described by region and age group. The aim was to document the effectiveness of the program towards reaching a nationally defined goal of 80% screening coverage., Methods: The survey's sampling frame was developed incrementally, and since 2005 it has included women aged ≥ 40 from all areas of Lebanon. The sample size has also increased incrementally from 1200 in 2005 to 2400 in 2013. Results have been tabulated biannually and presented as historical trends with regional and demographic variations covering a 9-year period., Results: In all six consecutive surveys presented here, the mean age of participating women was about 50 years. Year-by-year increases in utilization indicators were detected, with consistent differences in favor of the more urban areas in and around the capital city Beirut and its suburbs (Greater Beirut or GB). By 2013, ever-utilization had reached 43% (41-45) and recent mammography 20% (18-22) nationwide. Utilization was significantly more important in the age group 50-59 compared with the age group 40-49 or ≥ 60. While recent rates have increased nationwide, they have reached a plateau of about 25% in GB and are tending to the same level in other areas., Discussion and Conclusions: While initial progress was slow, it has been accelerating in the last 4-5 years, indicating that the message is being accepted by a larger audience of targeted women at each iteration. However, concern remains that women between 40 and 50 and those >60 are not responding as well as desired to the screening message, for reasons currently under investigation., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Epidermal growth factor receptor (EGFR) represents an important molecular target in the treatment of lung adenocarcinomas; many anti-EGFR therapies are approved as first line and second-line treatment in patients having metastatic lung adenocarcinomas. The occurrence of this mutation varies in terms of race; it is around 10% in Caucasians and can reach 30% in Asians. Its prevalence in our Middle Eastern region is not well known., Methods: Patients diagnosed with non-squamous non-small cell lung carcinomas between March 2013 and March 2015 were included. This study was conducted at Hôtel-Dieu de France University Hospital, a tertiary medical center in Lebanon. EFGR mutations were analyzed using real time PCR technique on the Rotor-Gene Q using Scorpions and ARMS technologies. The following data was collected: the patients' characteristics (age, gender, smoking status, stage), the samples' characteristics (histology subtype, TTF-1 and Napsin A immunostainings, the site and the adequacy and the type of the sample), and the mutational EGFR status (presence and type of mutation). These variables were analyzed using SPSS 20., Results: 201 patients were included. The mean age was 65.2 years [31-87]; 40.2% were females. 78.1% of the included patients were smokers or ex-smokers. 12.9% of patients had a localized disease, 17.4% a locally advanced disease and 69.7% a metastatic disease. Adenocarcinoma was the main histologic subtype found in 90.5% of patients, followed by large cell carcinoma (3.5%), adenosquamous carcinoma (3.0%) and non-small cell carcinoma not otherwise specified (3.0%). 11.9% of patients had an EGFR mutation: 48% of them presented a deletion on exon 19, 40.0% a L858R mutation on exon 21, 4.0% a G719X mutation in exon 18, 4.0% an insertion in exon 20, and 4% a T790M mutation in exon 20. The presence of an EGFR mutation was significantly associated with the female gender (two-third) (p<0.05) and the non-smoking status (two-third) (p<0.05)., Conclusions: The prevalence of EGFR mutation (11.9%) detected in our Lebanese population is similar to that observed in the Caucasian population. This mutation is also significantly more frequent in females and non-smokers., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Osteonecrosis of the jaw (ONJ) is one of the most relevant and specific complication of biphosphonates. ONJ in patients receiving zoledronic acid every 3 to 4 weeks is frequently described, but the ONJ biyearly regimen used to reduce aromatase inhibitor associated bone loss (AIBL), is rarely reported. A literature review, focusing on the important trials using zoledronic acid to reduce AIBL, found that the mean risk of developing ONJ when zoledronic acid is used biyearly varies between 0.12% and 0.7%.

The factor XIII deficiency is a very rare disorder. We report here two cases of congenital deficiency of factor XIII, revealed by spontaneous intra-axial hemorrhage, one of them manifested with an intramedullary hemorrhage never described in the literature before. Our two patients were cousins from two consanguineous parents. We discuss in this study the clinical presentation, the diagnosis, the treatment, and the prevention of factor XIII deficiency coagulopathy. A mutation described only once before was confirmed and correlated again with a severe clinical presentation.

Major advances in cancer research in the last two decades have provided us with a better understanding of the dynamics of the cancer cell and its microenvironment. This has consequently led to the development of new therapies and treatment strategies either targeting the cancer cell or the tumor microenvironment. In this review we will discuss the major existing and promising future treatment approaches in medical oncology. Therapies targeting the cancer cell include hormonal therapies, small molecules, and monoclonal antibodies. They are used mostly in the advanced disease setting. Strategies developed more recently are antibody drug conjugates (trastuzumab emtansine and radioimmunotherapy) and oncolytic viruses. Molecular therapies targeting the tumor microenvironment include angiogenesis inhibitors and the new agents and approaches that interfere with the immune system (immune checkpoint inhibitors and adoptive cell therapy). The development of resistance (primary and acquired) to targeted therapies is unfortunately a common phenomenon that can be overcome or delayed using multiple strategies like the use of second- or third-generation molecular therapies targeting the emerging resistant mutations or genetic abnormalities, multitargeted drugs, and drug combinations targeting the same or different proteins, and/or the use of modern immunotherapy. Molecular targeted therapies have a distinct array of side effects that can be mechanism-based, but can also be unpredictable. Although the progress in research brings a vast amount of new information about cancer and its environment, it renders the field of oncologic research more and more complex with fragmentation of tumor entities. These are important challenges for future research and precision oncology.

Biliary tract cancers (BTCs) are highly fatal malignancies, which are often diagnosed at an advanced stage and have relatively poor prognosis. The treatment of patients with advanced BTC is systemic, based on chemotherapy or best supportive care, depending on their performance status. Despite clinical trials studying many chemotherapeutic regimens and targeted therapies for the treatment of BTC, the standard of care for advanced BTC remains the combination of gemcitabine with cisplatin. Many new molecules targeting proliferation and survival pathways, the immune response and angiogenesis are currently undergoing phase I and II trials for the treatment of advanced BTC with promising results.