Chronic Diseases and Translational Medicine
Volume 03 · Issue 01 · 2017
Chron Dis Transl Med
- Sections
- Editorial
- Perspective
- Meta Analysis
- Original Article
近年来,肺癌一直是全球最常诊断的癌症;2012年全球有160万人死于肺癌,使肺癌成为癌症相关死亡的主要原因。
After the introduction of trastuzumab, a monoclonal antibody that binds to human epidermal growth factor receptor 2 (HER2), the overall survival (OS) among patients with HER2-positive breast cancer has been substantially improved. However, among these patients, the incidence of brain metastases (BM) has been increasing and an increased proportion of them have died of intracranial progression, which makes HER2-positive breast cancer brain metastases (BCBM) a critical issue of concern. For local control of limited BM, stereotactic radiosurgery (SRS) and surgical resection are available modalities with different clinical indications. Postoperative or preoperative radiation is usually delivered in conjunction with surgical resection to boost local control. Adjuvant whole-brain radiotherapy (WBRT) should be deferred for limited BM because of its impairment of neurocognitive function while having no benefit for OS. Although WBRT is still the standard treatment for local control of diffuse BM, SRS is a promising treatment for diffuse BM as the technique continues to improve. Although large molecules have difficulty crossing the blood brain barrier, trastuzumab-containing regimens are critical for treating HER2-positive BCBM patients because they significantly prolong OS. Tyrosine kinase inhibitors are more capable of crossing into the brain and they have been shown to be beneficial for treating BM in HER2-positive patients, especially lapatinib combined with capecitabine. The antiangiogenic agent, bevacizumab, can be applied in the HER2-positive BCBM scenario as well. In this review, we also discuss several strategies for delivering drugs into the central nervous system and several microRNAs that have the potential to become biomarkers of BCBM.
Anti-angiogenesis therapy, by blocking formation of new blood vessels in tumors, is the standard-of-care therapy for various cancer types. The classic concept of anti-angiogenesis is expected to turn a tumor into a "dormant" disease. However, the combination of anti-angiogenesis agents with conventional therapeutics has generally produced only modest survival benefits for cancer patients in clinical trials. Therefore, the concept and applications of anti-angiogenesis have evolved dramatically along with lessons learned from recent clinical experience. In this article, we will discuss the revised concept of anti-angiogenesis therapy and the applications of anti-angiogenesis drugs, and focus particularly on how to utilize current anti-angiogenesis agents and develop new approaches to provide more benefits to patients with cancer.
Radiological imaging plays an important role in oncological trials to provide imaging biomarkers for disease staging, stratifying patients, defining dose setting, and evaluating the safety and efficacy of new candidate drugs and innovative treatment. This paper reviews the techniques of most commonly used quantitative magnetic resonance imaging (qMRI) biomarkers (dynamic contrast enhanced, dynamic susceptibility contrast, and diffusion weighted imaging) and their applications in oncological trials. Challenges of incorporating qMRI biomarkers in oncological trials are discussed including understanding biological mechanisms revealed by MRI biomarkers, consideration of rigorous trial design and standardized implementation of qMRI protocols.
To compare the efficacy of axillary radiotherapy (ART) with that of completion axillary lymph node dissection (cALND) in clinically node-negative breast cancer patients with a positive sentinel lymph node.
A literature search was performed in PubMed, EMBASE and Cochrane Library by using the search terms "breast cancer" , "sentinel lymph node biopsy" , "axillary radiotherapy" or "regional node irradiation" for articles published between 2004 and 2016. Only randomized controlled trials that included patients with positive sentinel nodes were included in the meta-analysis.
Two randomized controlled trials and three retrospective studies were identified. The reported overall survival rate (hazard ratio [HR] = 1.09, 95% confidence interval [CI]: 0.75—1.43, P = 0.365), disease-free survival rate (HR = 1.01, 95% CI: 0.58—1.45, P = 0.144), and axillary recurrence rate (1.2% and 0.4%, and 1.3% and 0.8%, respectively) were similar in both groups. The absence of knowledge on the extent of nodal involvement in the ART group appeared to have no major impact on the administration of adjuvant systemic therapy.
ART is not inferior to cALND in the patients with clinically node-negative breast cancer who had a positive sentinel lymph node. Information obtained by using cALND after SLNB may have no major impact on the administration of adjuvant systemic therapy.
Recent studies have reported increased mortality for right-sided colon cancers; however, the results are conflicting for different stage tumors. We examined the differences in clinicopathology between right- and left-sided colon cancers and the relationships between colon cancer location (right- and left-side) and 5-year disease-free survival (DFS) and overall survival (OS).
We identified patients from 2005 to 2008 with stage II/III colon cancer who underwent surgery for curative intent. We explored the impact of the tumor location on the postoperative DFS and OS using univariate and multivariate analyses.
Of 627 patients, 50.6% (317/627) had right-sided colon cancer. These patients were more likely to have weight loss, second primary tumor, elevated preoperative carbohydrate antigen 19-9 (CA19-9), increased incidence of non-adenocarcinoma, more poorly differentiated tumors, vascular invasion, defective mismatch repair, and a lighter smoking history (P < 0.05). Right-sided colon cancer had a higher recurrence incidence compared with left-sided cancer (30.6% vs. 23.2%, P = 0.037), particularly with multiple metastatic sites in the first recurrence (17.5% vs. 5.6%, P = 0.020). Kaplan—Meier survival curves demonstrated a significant difference in the 5-year DFS rate between right- and left-sided cancers across all stages (68.1% vs. 75.2%, P = 0.043). However, there was no significant difference in the 5-year OS rate between the two groups (73.8% vs. 79.0%, P = 0.103). Subgroup analysis demonstrated that patients with left-sided colon cancer had a significantly better 5-year DFS and OS rates compared with those with right-sided disease at stage III (64.3% vs. 46.8%, P = 0.002; 69.5% vs. 53.5%, P = 0.006, respectively); there were no significant differences in the 5-year DFS and OS rates at stage II (85.2% vs. 85.9%, P = 0.819; 89.8% vs. 88.5%, P = 0.803, respectively). Adjusted Cox regression analysis showed no significant differences in the 5-year OS and DFS rates for stage II [hazard ratio (HR) = 1.203, 95% confidence interval (CI): 0.605—2.391, P = 0.598; HR = 0.980, 95% CI: 0.542—1.774, P = 0.948, respectively] or all stages combined (HR = 0.867, 95% CI: 0.613—1.227, P = 0.421; HR = 0.832, 95% CI: 0.606—1.142, P = 0.255, respectively). However, stage III left-sided cancer had higher 5-year OS and DFS rates (HR = 0.626, 95% CI: 0.414—0.948, P = 0.027; HR = 0.630, 95% CI: 0.428—0.926, P = 0.019, respectively).
We found that right- and left-sided colon cancers had significantly different clinicopathological characteristics. Right-sided colon cancer had a higher incidence of recurrence than left-sided disease. Patients with stage III right-sided colon cancer had a worse prognosis compared with those with stage III left-sided colon cancer.
To analyze the clinical epidemiological characteristics of patients with gallbladder carcinoma recruited from 17 hospitals in five northwestern provinces of China (Shaanxi Province, Gansu Province, Qinghai Province, Ningxia Hui Autonomous Region, and Xinjiang Uygur Autonomous Region) from 2009 to 2013, and to summarize the clinical diagnosis and treatment data of gallbladder carcinoma.
Clinical information of 2379 patients with gallbladder carcinoma from 17 hospitals in five northwestern provinces of China was retrospectively collected and analyzed using the "Questionnaire for Gallbladder Carcinoma Patients in Northwestern Area of China." All information was verified with EpiData software and analyzed with SPSS 13.0 software.
(1) Gallbladder carcinoma accounted for 2.7% (2379/86,609) of all biliary tract diseases during the study period, which was significantly higher than that from 1986 to 1998 (P < 0.001). (2) Gallbladder carcinoma was more prone to occur in elderly women. The male:female incidence ratio was 1.0:2.1, the average age of onset of disease was 63.7 ± 11.3 years, and the incidence was higher in farmers than in other occupational groups. (3) A total of 57.2% (1360/2379) of patients with gallbladder carcinoma also had gallstones. (4) Abdominal pain (1796/2379, 75.5%) and jaundice (727/2379, 30.6%) were the most common clinical manifestations, 81.2% (1527/1881) were positive in those receiving B ultrasound examinations and 90.7% (1567/1727) were positive in those undergoing computed tomography, and 64.5% (1124/1742) of patients with gallbladder carcinoma were positive for carbohydrate antigen (CA) 19-9. (5) The pathological type of gallbladder carcinoma was mainly moderately and poorly differentiated adenocarcinoma with a high degree of malignancy. At admission, 55.1% (1091/1981) of patients had stage IV cancer among patients with TNM staging information; 55.9% (1331/2379) had lymphatic metastasis, 29.7% (706/2379) had bile duct metastasis, and 53.1% (1263/2379) had liver metastasis. (6) A total of 283 patients (283/2379, 11.9%) had incidentally detected gallbladder carcinoma. (7) The rate of radical surgical resection was 30.4% (723/2379).
The proportion of gallbladder carcinoma in biliary tract diseases in the northwestern area of China was significantly higher from 2009 to 2013 than from 1986 to 1998. Gallbladder carcinoma was common in older women and mainly diagnosed at an advanced stage. Compared with other surveys in different regions, the rate of metastasis in this survey was high, leading to a low resection rate. Populations at high risk should undergo B-ultrasound examinations at regular follow-up intervals to increase the rate of early diagnosis of gallbladder carcinoma.
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