Tony Ibrahim

Systemic Versus Local Therapies for Colorectal Cancer Pulmonary Metastasis: What to Choose and When?

BackgroundLung is the second most common site of colorectal cancer metastasis. Treatment is based mainly on systemic therapy which has largely evolved lately, but outcome remains relatively poor. The place of locoregional therapies as curative strategies is still debated.MethodA systematic literature review was performed by the authors for systemic therapy, surgery, radiofrequency ablation (RFA), and stereotactic body radiation therapy (SBRT). The highest level of evidence for each strategy was presented. Major findings were addressed in a summarized and clinically relevant manner.ResultsAll reported studies were descriptive non comparative reports except for one retrospective study comparing surgery to SBRT. The highest level of evidence for each therapeutic strategy are presented as follows: three large meta-analyses for surgery as well as seven and three prospective trials for RFA and SBRT, respectively.DiscussionSurgery has the highest level of evidence for cure followed by RFA and SBRT. However, careful patient selection and complete resection of all metastasis are the main principles behind the efficacy of local therapies in the curative setting. Despite encouraging results, randomized trials are still needed.

Comparison between a second and a third generation parathyroid hormone assay in hemodialysis patients

OBJECTIVE Third generation parathyroid hormone (PTH) assays are new generation assays that do not recognize the PTH7-84 fragment whereas second generation assays detect both PTH1-84 and PTH7-84 fragments. Despite the excellent correlation between both assays in chronic renal failure (CRF) subjects, the mean PTH levels are typically 50% lower with the third compared to the second generation assays. The assessment of third generation PTH assays has not been extensively studied in hemodialysis subjects. The purpose of our study was to compare a third generation PTH assay to a second generation one in a population of hemodialysis subjects. MATERIALS AND METHODS 92 haemodialysis subjects (36 women and 56 men) with a mean age of 67±12.9 years were included in this study. Anthropometric and clinical parameters (Body Mass Index (BMI) and blood pressure) were measured. Second and third generation PTH assays (Cis biomedical and Diasorin respectively) were performed in each subject. In addition, the following biochemical tests were measured: 25-hydroxyvitamin D (25-(OH)D), 1,25-hydroxyvitamin D (1,25-(OH)2D), crosslaps and alkaline phosphatase. RESULTS The mean second and third generation PTHs are respectively 211±205 pg/ml and 151±164 pg/ml. The mean third generation PTH values are 28.4% lower compared to the second generation ones. Both methods are strongly correlated (r=0.923, p<0.001). This correlation persisted without any significant difference after controlling for gender, age, BMI and Blood Pressure. However, the difference between both methods increases when baseline PTH increases. Each of the second and third generation method is significantly correlated with hemodialysis duration (p<0.01), crosslaps (p<0.001), alkaline phosphatase (p<0.05), but not with age, BMI, Blood Pressure, 25-(OH)D or 1,25-(OH) 2D levels. CONCLUSION Our results show that both second and third generation PTH methods are strongly correlated in hemodialysis patients mainly when PTH values are low. However, the difference between both methods increases when PTH values are high. More research is needed to establish which method is the gold standard when PTH values are high.

Dilemma of first line regimens in metastatic pancreatic adenocarcinoma

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.

Efficacy of a Silicon Based Continuous Scalp Cooling System with Thermostat on Chemotherapy Induced Alopecia

Introduction: Alopecia although reversible, is one of the most distressing side effects of chemotherapy. Preventive measures mainly focus on scalp cooling with variable and unpredictable efficacy reported in the literature. The objective of this work is to test the tolerance and effectiveness of a new silicon based cooling technique in preventing chemotherapy induced alopecia (CIA) after each of six cycles of chemotherapy. Method: This is a one center prospective descriptive study. Included patients were females receiving Taxanes and/or Adriamycin based regimens at the oncology department of Hotel-Dieu de France University Hospital. Cooling was done using the Orbis-Paxman scalp cooling system. Hair loss severity was evaluated using the World Health Organization (WHO) grading system. Failure or success of cooling was defined on the basis of wig or head cover use. Independent factors like age, type of hair, type and dose of chemotherapy, total and post infusion cooling time hemoglobin and creatinine at each course. Results: 81 patients were included. Success ranged between 84.8% and 96% for the repeated cycles. No association was found with the independent factors, except for the dose of chemotherapy in the first course with higher doses of Adriamycin (99 mg v/s 77 mg, p value 0.037) as well as taxanes (140 mg v/s 122 mg, p value 0.035) in patients experiencing failure. Conclusion: Scalp cooling has proved to be a successful and well tolerated prevention method for CIA in breast cancer patients treated by Taxanes and Adriamycin.

SERUM INSULIN-LIKE GROWTH FACTOR 1 IN LEBANESE SCHOOLCHILDREN AND ITS RELATION TO VITAMIN D AND FERRITIN LEVELS

OBJECTIVE The aims of our study were to establish reference values for insulin-like growth factor 1 (IGF-1) in Lebanese schoolchildren and to evaluate the relationship between IGF-1 and age, sex, body mass index (BMI), vitamin D, and ferritin. METHODS This cross-sectional study included 952 Lebanese schoolchildren (495 boys and 457 girls) aged 8 to 18 years. Blood samples were taken from children attending 10 schools with different socio-economic status (SES). Chemiluminescent immunoassays were used for IGF-1, 25 hydroxyvitamin D (25(OH)D), testosterone, and ferritin measurements. RESULTS The mean age was 13.46 ± 2.80 with no significant difference according to sex. IGF-1 was correlated with age in both sexes (P<.0001); it was higher in girls compared to boys (P = .007) and peaked at the ages of 14 and 12 for boys and girls, respectively. For each age group, the median IGF-1 value was higher compared to the values provided by the kit. IGF-1 was significantly correlated with BMI in boys (r = 0.16, P<.0001) but not girls. In both sexes, IGF-1 was inversely correlated with 25(OH)D and ferritin values. After adjustment for age, BMI, and height, the correlation between IGF-1 and 25(OH)D disappeared, whereas the relationship with ferritin persisted (P<.001 for boys, P = .002 for girls). For both sexes, multivariate regression analysis revealed independent associations between IGF-1 and height, Tanner stage, and ferritin. An association was also noted in boys for BMI and testosterone. CONCLUSION Our results showed higher and earlier peak IGF-1 values in the pediatric Lebanese population compared to western populations. In addition, an independent inverse relationship was observed between IGF-1 and ferritin. Further studies are needed to identify the reason(s) underlying these results. ABBREVIATIONS BMI = body mass index CRP = C-reactive protein CV = coefficient of variation GH = growth hormone IGF-1 = insulin-like growth factor 1 25(OH)D = 25 hydroxyvitamin D SES = socio-economic status TSH = thyroid-stimulating hormone.

Could contrast-enhanced CT detect STEMI prior to electrocardiogram?

We present here a case in which contrast-enhanced computed tomography (CT) was the first diagnostic tool to detect myocardial hypoperfusion in a patient with atypical symptoms and normal electrocardiogram (ECG) on admission. An ST-segment elevation was detected thereafter on a second ECG realized several minutes after CT with raised troponin levels. Percutaneous coronary intervention was performed after failure of thrombolysis and confirmed occlusion of the left anterior descending artery. Further studies are needed to evaluate the role of high-resolution contrast-enhanced CT with or without coronary angiography in the workup of suspected myocardial infarction in the setting of a normal ECG.

Colorectal cancer and brain metastases: An aggressive disease with a different response to treatment

Introduction: Brain metastases (BM) are rare in colorectal cancer (CRC) and are associated with a dismal prognosis. This work aims to report the rate of BM in CRC patients treated in a single institution, along with survival and prognostic factors. Methods: Medical charts for patients with histologically proven CRC were retrospectively reviewed. Results: A total of 538 patients were identified, of whom 33% developed any metastatic disease and 4.4% presented BM. Lung was the most frequently associated metastatic site (in 68% of the cases). The only factor independently associated with BM development was the presence of metastatic disease at the time of initial presentation. The median duration from initial diagnosis to BM development was 38.6 months (SD 29.1 months). Median survival after BM development was 62 days (95% confidence interval [CI] 56–68). Patients diagnosed with BM within 1 year of cancer diagnosis responded significantly better to treatment than those who acquired BM later, with a median survival after BM diagnosis of 261 days versus 61 days, respectively (p = .002). Patients with BM who received antiangiogenic therapy had an improved median survival compared to those who did not (151 days vs 59 days, p = 0.02; hazard ratio for death 0.29 [95% CI 0.09–0.94]). Conclusion: CRC with BM is an aggressive disease resistant to standard treatment and is associated with poor outcomes. Adding antiangiogenic therapy might be of value for those patients. Patients with BM developing early in the disease course might respond better to treatment.

Checkpoint Inhibitors: Conquering Cancer with a Little (T)-Help from Our Microbial Friends

Checkpoint inhibitors (CPIs) are a new class of drugs designed to block either the cytotoxic T-lymphocyte antigen 4 (CTLA-4) or the programmed cell death protein-1 (PD-1), which are used by cancer cells to evade host immune system. Blocking these proteins increases recognition of cancer cells by the immune system with consequent eradication by activated effector T cells [1]. CTLA4 and PD(L)1-directed monoclonal antibodies (mAb) are approved for the therapy of several types of cancers regardless of the patient’s age, based on the results of clinical trials. In addition to their effectiveness, these therapies are associated with serious adverse events that differ from those associated with conventional chemotherapy, since CPIs activate the immune system against the self [2]. The gut microbiota is considered a “hidden” organ, comprised of 1014 organisms/gm feces composed primarily of the phyla Firmicutes and Bacteroidetes followed by Cyanobacteria, Fusobacteria, Actinobacteria, Verrucomicrobia, and Proteobacteria. Some species are abundant in patients with cancer such as Fusobacterium nucleatum, Bacteroides fragilis, and Escherichia coli as opposed to other organisms, specifically Faecalibacterium prausnitzii [3, 4]. Alterations of the composition of the gut microbiota are associated with variations of the response to chemotherapy and the incidence and severity of chemotherapy-related toxicity [5]. Alteration of the microbiota is an important predictive marker of efficacy and toxicity to CPIs in cancer [1, 3]. Several recent studies document that CPIs alter the host microbiota, which in turn affect treatment outcomes [6]. In animal models, the CPI ipilimumab amplifies the abundance of specific gut bacterial species, specifically B. fragilis, Bacteroides thetaiotaomicron, and Burkholderia cepacia, alterations that presumably improve its anticancer effect through enhancement of T cell-mediated immune mechanisms [3, 7, 8]. Regarding the mechanism of action of CPIs and the contribution of the intestinal flora, CTLA-4 antibodies activate intestinal epithelial lymphocytes, which promote apoptosis of intestinal epithelial cells, leading to dysbiosis and accumulation of B. fragilis in the inner mucus layer. The CD11b+ dendritic cells of the lamina propria migrate to lymph nodes where they produce IL-12 after ingesting Bacteroides and their products, which activates T-helper (TH)1 cells [7]. Moreover, the amount of IL-12 secreted by dendritic cells production is highly influenced by the composition of the microbiota [7, 8], especially by the polysaccharide capsule of bacteroides [1]. Other types of bacteria, including bifidobacterium species, also enhance the efficacy of anti-PDL-1 by activating dendritic cells as well as CD8+ T cells, with consequent accumulation in the tumor microenvironment [9]. The pharmacological mechanisms by which the intestinal microbiota influences immunotherapy efficacy could be summed up in the acronym: TIMER (Translocation, Immunomodulation, Metabolism, Enzymatic degradation, and Reduced diversity and ecological variation) [5]. The contribution of commensal bacteria toward the regulation of antitumor immunity was confirmed by in vivo studies [7]. In mice, the antitumor effect of anti-CTLA4 * Tony Ibrahim tony.ibrahim@gustaveroussy.fr

Abridged geriatric assessment is a better predictor of overall survival than the Karnofsky Performance Scale and Physical Performance Test in elderly patients with cancer

OBJECTIVES Comprehensive geriatric assessment (CGA) is a complex and interdisciplinary approach to evaluate the health status of elderly patients. The Karnofsky Performance Scale (KPS) and Physical Performance Test (PPT) are less time-consuming tools that measure functional status. This study was designed to assess and compare abridged geriatric assessment (GA), KPS and PPT as predictive tools of mortality in elderly patients with cancer. MATERIALS AND METHODS This prospective interventional study included all individuals aged >70years who were diagnosed with cancer during the study period. Subjects were interviewed directly using a procedure that included a clinical test and a questionnaire composed of the KPS, PPT and abridged GCA. Overall survival (OS) was the primary endpoint. The log rank test was used to compare survival curves, and Coxs regression model (forward procedure) was used for multivariate survival analysis. RESULTS One hundred patients were included in this study. Abridged GA was the only tool found to predict mortality [median OS for unfit patients (at least two impairments) 467days vs 1030days for fit patients; p=0.04]. Patients defined as fit by mean PPT score (>20) had worse median OS (560 vs 721days); however, this difference was not significant (p=0.488 on log rank). Although median OS did not differ significantly between patients with low (≤80) and high (>80) KPS scores (467 and 795days, respectively; p=0.09), survival curves diverged after nearly 120days of follow-up. Visual and hearing impairments were the only components of abridged GA of prognostic value. CONCLUSION Neither KPS nor PPT were shown to predict mortality in elderly patients with cancer whereas abridged GA was predictive. This study suggests a possible role for visual and hearing assessment as screening for patients requiring CGA.

PULMONARY ARTERY ACCELERATED FLOW REVEALING HODGKIN'S LYMPHOMA.

We present a case in which transthoracic echocardiography was the first diagnostic tool to suspect mediastinal Hodgkins lymphoma by revealing a change in the hemodynamic of left pulmonary artery flow, and it was used as a follow-up method for monitoring treatment efficacy by demonstrating a normalization of pulmonary artery hemodynamics.