Chemotherapy for colorectal cancer in the elderly

Colorectal cancer(CRC) is one of the leading causes of cancer-related death in the elderly.However,elderly patients with CRC tend to be under-presented in clinical trials and undertreated in clinical practice.Advanced age alone should not be the only criteria to preclude effective therapy in elderly patients with CRC.The best guide about optimal cancer treatment can be provided by comprehensive geriatric assessment.Elderly patients with stage Ⅲ colon cancer can enjoy the same benefit from adjuvant chemotherapy with 5-fluorouracil/leucovorin or capecitabine as younger patients,without a substantial increase in toxicity.With conflicting results of retrospective studies and a lack of data available from randomized studies,combined modality treatment should be used with great caution in elderly patients with locally advanced rectal cancer.Combination chemotherapy can be considered for older patients with metastatic CRC.For elderly patients who are frail or vulnerable,however,monotherapy or a stopand-go strategy may be desirable.The use of targeted therapies in older patients with metastatic CRC appears to be promising in view of their better efficacy and toxicity.Treatment should be individualized based on the nature of the disease,the physiologic or functional status,and the patient's preference.

Hepatitis B reactivation in chronic myeloid leukemia patients receiving tyrosine kinase inhibitor

Hepatitis B virus(HBV) reactivation is a well-recognized complication in patients with chronic HBV infection receiving cytotoxic or immunosuppressive chemotherapy.Imatinib mesylate and nilotinib are selective Bcr/Abl tyrosine kinase inhibitors,which are now widely used in the treatment of patients with chronic myeloid leukemia.Although HBV reactivation induced by imatinib mesylate has been reported,nilotinib-related HBV reactivation has not been reported in the English literature.We report here 2 cases of HBV reactivation in chronic myeloid leukemia patients receiving imatinib mesylate and a novel case of nilotinib related HBV reactivation.

Profile of the breast cancer susceptibility marker rs4245739 identifies a role for miRNAs

Objective:To determine the influence of the single nucleotide polymorphism(SNP)rs4245739 on the binding and expression of micro RNAs and subsequent MDM4 expression and the correlation of these factors with clinical determinants of ER-negative breast cancers.Methods:Find Tar and miRanda were used to detect the manner in which potential micro RNAs are affected by the SNP rs4245739-flanking sequence.RNA sequencing data for ER-negative breast cancer from The Cancer Genome Atlas(TCGA)were used to compare the expression of miR-184,miR-191,miR-193a,miR-378,and MDM4 in different rs4245739 genotypes.Results:Comparison of ER-negative cancer patients with and without the expression of miR-191 as well as profile micro RNAs(miR-184,miR-191,miR-193a and miR-378 altogether)can differentiate the expression of MDM4 among different rs4245739 genotypes.Although simple genotyping alone did not reveal significant clinical relationships,the combination of genotyping and micro RNA profiles was able to significantly differentiate individuals with larger tumor size and lower number of involved lymph nodes(P<0.05)in the risk group(A allele).Conclusions:We present two novel methods to analyze SNPs within 3′UTRs that use:(i)a single miRNA marker expression and(ii)an expression profile of miRNAs predicted to bind to the SNP region.We demonstrate that the application of these two methods,in particular the miRNA profile approach,permits detection of new molecular and clinical features related to the rs4245739 variant in ER-negative breast cancer.

Glasgow prognostic score after concurrent chemoradiotherapy is a prognostic factor in advanced head and neck cancer

Objective: This study aims to evaluate the impact and potential prognostic roles of the pre- and post-treatment Glasgow prognostic score (GPS) and the change thereof in patients with advanced head and neck cancer undergoing concurrent chemoradiotherapy (CCRT). Methods: We collected GPS and clinicopathological data of 139 stage III, IVA, and IVB head and neck cancer patients who underwent CCRT between 2008 and 2011. Their GPSs pre- and post-CCRT and the change thereof were analyzed for correlations with recurrence and survival. Results: The GPS changed in 72 (51.8%) patients, with worse scores observed post-CCRT in 65 (90.3%) of the GPS changed patients. Patients in the improved GPS group showed a tendency toward better survival. From the multivariate analysis, the post-CCRT GPS level was an independent prognostic factor in addition to tumor stage. Conclusions: After CCRT, a high GPS was revealed to be an important predictor of survival for advanced head and neck cancer.

Comprehensive Nutrition Intervention with Omega-3 Fatty Acid, Micronutrient, and Probiotic-Enriched Regimens Improves Malnutrition in Patients with Head and Neck Cancers

Malnutrition is a common and unavoidable medical issue in patients with head and neck cancer during and after the treatment period, which deserves an intensive medical attention since nutrition status is often related with patients’ prognosis and treatment outcomes. In review of literature and our recent research, we found that an early and intensive nutrition intervention, including nasogastric tube feeding, minimized body weight loss, reduced treatmentinduced adverse effects, and increased survival benefits. Patients with BMI < 19 kg/m2 and were received the Ethanwell/ Ethanzyme regimen enriched with omega-3 fatty acids, micronutrients, and probiotics showed significantly less body weight loss. Patients with the malnourished status at the time of 3 months after treatment completion showed early recurrence and had significant negative effect on overall survival. In conclusion, comprehensive nutrition intervention should be started as early as the treatment begins and be continued following therapy completion, in order to prevent or overcome malnutrition in patients with head and neck cancer.

Nutritional Therapy for Head and Neck Cancer

Patients with head and neck cancer face great challenges in maintaining optimal nutrition since both the disease itself and treatments,especially surgery and concurrent chemoradiotherapy,have a significant negative impact on the nutritional status.A fundamental understanding of the nutrient metabolism of patients with head and neck cancer will aid in treatment selection.In this review,metabolic abnormalities presented in patients with head and neck cancer are discussed,together with methods of nutritional support,dietary intervention,and potential roles of phytonutrients,probiotics,and exercise in nutritional therapy for head and neck cancer patients.

Comprehensive review into the challenges of gastrointestinal tumors in the Gulf and Levant countries

Although gastrointestinal stromal tumors(GISTs)are rare,with an incidence of 1/100000 per year,they are the most common sarcomas in the peritoneal cavity.Despite considerable progress in the diagnosis and treatment of GIST,about half of all patients are estimated to experience recurrence.With only two drugs,sunitinib and regorafenib,approved by the Food and Drug Administration,selecting treatment options after imatinib failure and coordinating multidisciplinary care remain challenging.In addition,physicians across the Middle East face some additional and unique challenges such as lack of published local data from clinical trials,national disease registries and regional scientific research,limited access to treatment,lack of standardization of care,and limited access to mutational analysis.Although global guidelines set a framework for the management of GIST,there are no standard local guidelines to guide clinical practice in a resource-limited environment.Therefore,a group of 11 experienced medical oncologists from across the Gulf and Levant region,part of the Rare Tumors Gastrointestinal Group,met over a period of one year to conduct a narrative review of the management of GIST and to describe regional challenges and gaps in patient management as an essential step to proposing local clinical practice recommendations.

Time to Progression of AFP(TPA)as a Predictor of Survival in Hepatocellular Carcinoma Treated with Sorafenib(SOR)

Background: The standard therapy in advanced hepatocellular carcinoma (HCC) is sorafenib (SOR), which has the inconvenience of toxicity and discontinuation. Patient selection and the use of early markers are critical for optimizing the potential benefit of SOR. Alpha-fetoprotein (AFP) has an established role in HCC prognosis. The objective was to evaluate whether AFP variation during SOR treatment reflects the lack of progression to SOR and can be used as a prognostic factor. Methods: AFP levels were prospectively analyzed in 114 patients to determine whether the time to progression of AFP (TPA) at 3 months had a prognostic value for survival. Results: Between July 2007 and October 2012, 114 patients were included (mean age 64 years, 97 male, 96 with cirrhosis). Etiology was alcohol 47 (41%) and hepatitis C virus (HCV) 31 (27%). According to the Barcelona Clinic Liver Cancer (BCLC) staging system: A (one case), B (24 cases) and C (89 cases). The Child-Pugh was Class A in 89 cases. The general condition of the patient according to ECOG-PS was 0 in 73 cases. The median duration of treatment was 5 months (3.47 - 6.53, 95% CI). The median overall survival (OS) was 9.23 months. The standard dose was maintained in 26 patients (22.8%). Sixty-seven percent of patients experienced at least one adverse event grade 3-4. The time to progression of AFP lower or higher than 3 months was an independent prognostic factor of OS (univariate and multivariate analysis): 8.10 vs. 18.85 months, P < 0.001. Conclusion: HCC treated with SOR with TPA > 3 months had longer OS, and TPA was an independent prognostic factor.

Design,synthesis,and biological evaluation of novel chrysin derivatives as poly(ADP-ribose)polymerase 1(PARP1)inhibitors for the treatment of breast cancer

In this study,we reported the discovery and structure-activity relationship analysis of chrysin derivatives as a new class of inhibitors targeting poly(ADP-ribose)polymerase 1(PARP1).Among these derivatives,compound 5d emerged as the most effective chrysin-based inhibitor of PARP1,with an IC50 value of 108 nmol·L^(-1).This compound significantly inhibited the proliferation and migration of breast cancer cell lines HCC-1937 and MDA-MB-436 by inducing DNA damage.Furthermore,5d induced apoptosis and caused an extended G1/S-phase in these cell lines.Molecular docking studies revealed that 5d possesses a strong binding affinity toward PARP1.In vivo,in a xenograft model,5d effectively reduced tumor growth by downregulating PARP1 expression.Overall,compound 5d shows promise as a potential therapeutic agent for the treatment of BRCA wild-type breast cancer.