Sequencing of treatment in metastatic colorectal cancer:Where to fit the target?

Colorectal cancer is a lethal disease if not discovered early.Even though appropriate screening and preventive strategies are in place in many countries,a significant number of patients are still diagnosed at late stages of the disease.The management of metastatic colorectal cancer remains a significant clinical challenge to oncologists worldwide.While cytotoxic regimens constitute the main treatment of choice in this patient population,addition of the five biologics(bevacizumab,cetuximab,aflibercept,panitumumab and regorafenib)to these regimens has improved clinical outcomes.The most commonly used cytotoxic regimens include doublet combinations(FOLFOX/XELOX or FOLFIRI).Many clinical trials have been published and others are underway to compare the biologic agents with one another in order to prove the superiority of one regimen over another.Metastatic colorectal cancer patients have many treatment options;however,the optimal use and sequence of targeted agents remain to be determined.This review entails concise and updated clinical data on the management of metastatic colorectal cancer.The aim of the review is to determine where to fit the five biologic targets into the treatment algorithm of metastatic colorectal cancer patients and to derive treatment sequences that would achieve best clinical outcome based on the current available data.

Survey on physicians' opinions of post-mastectomy radiotherapy for breast cancer in Guangdong province

Objective:The aim of our study was to comprehensively access current status of radiotherapy physicians' opinions in post-mastectomy radiotherapy(PMRT) for breast cancer in Guangdong province.Methods:From June 2007 to June 2008,questionnaires on the clinical value,sequencing with chemotherapy and endocrine therapy,indications and irradiated targets for PMRT were sent to physicians of all radiotherapy departments registering at Radiotherapy Professional Committee of Guangdong Anti-cancer Association.Results:There were 126 physicians joining this investigation.Proportions of physicians who accepted the views that PMRT could merely improve local control or can improve both local control and overall survival were 100% and 25.2%.The most common sequences of PMRT and chemotherapy or endocrine therapy were "sandwich" and sequential modes,performed 46.9% and 59.5% respectively.The median interval of surgery and PMRT was 8 weeks.Proportions of physicians who accepted T3-4 diseases,or four or more axillary lymph nodes metastasis,or T1-2 with 1-3 positive lymph nodes,or T1-2N0 with primary tumor located in the center or inner quadrant as the indications of PMRT were 97.6%,100%,46.8%,13.5%,respectively.Proportions of physicians who accepted chest wall,supraclavicular region,internal mammary chain or axilla as irradiated targets were 86.5%,100%,49.2% and 38.9% respectively.Conclusion:For Radiotherapy physicians of Guangdong Province,there is still lacking of consensus in the opinions of whether PMRT can improve survival,and optimal sequencing with chemotherapy or endocrine therapy,and how to make decision for patients with T1-2 with 1-3 positive lymph nodes,and rational irradiated targets,which requires advanced professional training for physicians and further prospective clinical trial evidences to guide clinical practice.

Sequencing of high-efficacy disease-modifying therapies in multiple sclerosis： perspectives and approaches

Multiple sclerosis（MS） is characterized by chronic inflammation in conjunction with neurodegeneration within the central nervous system. Most individuals with MS begin with a relapsing remitting course that later transitions to secondary progressive MS. Currently available disease-modifying therapies（DMTs） for relapsing MS have been demonstrated to reduce disease activity, however most patients require a change in therapy over the course of their disease. Treatment goals include the prevention of relapses and disability accumulation and to achieve this objective requires careful planning. Sequencing of DMTs for individual patients should be designed in such a way to maximize disease control and minimize risk based on the mechanism of action, pharmacokinetic and pharmacodynamic properties of each therapy. This includes the DMT patients are being switched from to those they are being switched to. The reversibility of immune system effects should be a key consideration for DMT sequence selection. This feature varies across DMTs and should factor more prominently in decision making as newer treatments become available for the prevention of disability accumulation in patients with progressive MS. In this short review, we discuss the landscape of existing therapies with an eye to the future when planning for optimal DMT sequencing. While no cure exists for MS, efforts are being directed toward research in neuroregeneration with the hope for positive outcomes.

Effect of post-bond heat treatment on the microstructure and high temperature mechanical property of a TLP bonded γ'-strengthened co-based single crystal superalloy

Post-bond heat treatment(PBHT) applied to a transient liquid phase(TLP) bonding joint is an effective approach to remove the brittle borides and improve its properties.Herein,we proposed two types of PBHT strategies to obtain a TLP bonded γ'-strengthened Co-based single crystal superalloy,and the microstructural characteristics and tensile properties of the two heat treated joints were compared to identify the optimal PBHT strategy.The evolution of the brittle boride in the joint after the PBHT was studied by using in-situ microscopy.The experimental results allowed to provide a theoretic model to quantitatively evaluate the distribution of the brittle phase after the optimal PBHT and analyze the joint fractures to understand the failure mechanisms.The obtained results revealed that a post-bond solid solution treatment performed to the joint at a high temperature(over 1275℃) could decrease the area fraction of the boride from 7.2 % to 1.4 % and increase the elongation from 1.9 % to 7.8 %.This work emphasizes the relevance of solid solution temperature when a PBHT strategy is applied.

Characterization of cancer genomic heterogeneity by next-generation sequencing advances precision medicine in cancer treatment

Cancer is a heterogeneous disease with unique genomic and phenotypic features that differ between individual patients and even among individual tumor regions.In recent years,large-scale genomic studies and new next-generation sequencing technologies have uncovered more scientifc details about tumor heterogeneity,with significant implications for the choice of specific molecular biomarkers and clinical decision making Genomic heterogeneity signifcantly contributes to the generation of a diverse cell population during tumor development and progression,representing a determining factor for variation in tumor treatment response.It has been considered a prominent contributor to therapeutic failure,and increases the likelihood of resistance to future therapies in most common cancers.The understanding of molecular heterogeneity in cancer is a fundamental component of precision oncology,enabling the identification of genomic alteration of key genes and pathways that can be targeted therapeutically.Here,we review the emerging knowledge of tumor genomics and heterogeneity,as well as potential implications for precision medicine in cancer treatment and new therapeutic discoveries.An analysis and interpretation of the TCGA database was included.