Abstract
Purpose:
Currently, the anti-epidermal-growth-factor-receptor (EGFR) agents have shown encouraging treatment benefits in patients with various types of solid tumors including non-small-cell ...lung cancer (NSCLC). Despite these advances, radiological complete response to these therapies is rare. We meta-analyze the incidence of complete response (CR) in advanced NSCLC patients treated with anti-EGFR agents and controls in randomized controlled trials (RCTs).
Methods:
PubMed, Web of Science, Embase and Cochrane library databases were reviewed for phase III RCTs with EGFR-targeted agents vs. non-EGFR-targeted agents in patients with advanced NSCLC. We calculated the odds ratio of CR in patients assigned to anti-EGFR agents compared to controls.
Results:
A total of 11,568 patients from 17 RCTs were included for analysis. The incidence of CR in patients treated with anti-EGFR agents was 1.1% (95% CI, 0.7-1.7%) compared to 0.6% (95% CI, 0.4-0.9%) in control arms. Comparing the different types of anti-EGFR agents, the incidence of CR was 1.9% for gefitinib (95% CI: 1.4-2.6%), 1.4% for cetuximab (95% CI: 0.8-2.7%) and 0.9% for erlotinib (95% CI: 0.6-1.5%), respectively. The use of anti-EGFR agents significantly increased the odds ratio of obtaining a CR (OR 2.12, 95% CI: 1.28-3.49, p = 0.003) compared to controls. This was found to be higher in treatment arms involving more than 50% of: female patients, patients who had never smoked tobacco, patients of Asian descent or patients with adenocarcinoma or EGFR mutation. No significant differences in ORs were observed in any prespecified sub-groups.
Conclusion:
Although a CR is rare in advanced NSCLC patients receiving anti-EGFR agents, these drugs significantly increase the OR of a CR compared to controls, especially for patients with EGFR mutations. Further studies are needed to investigate whether the increase of CR with anti-EGFR therapy would be translated into survival benefits.
Comprehensive Summary
A novel schinortriterpenoid (SNT), schinensilactone A (1), characterized by a unique 7,8‐seco‐1,8‐cyclo‐schisanartane scaffold, was isolated from the leaves of Schisandra ...chinensis (Turcz.) Baill, together with a new SNT (schinensilactone B, 2) and two known (3, 4). Their structures were elucidated using spectroscopy and X‐ray diffraction. Furthermore, a hypothetical biosynthetic pathway for 1 was postulated due to its novel carbon skeleton. In addition, 1 exhibited significant anti‐proliferative activity against Caco‐2 cells originating from five different tumor cell lines, and its preliminary mechanism of action was investigated with respect to the expression of apoptosis‐related proteins, including P53, Caspase 3, Bax, PUMA, and Bcl2. These biological activities would further our understanding of the food function of Schisandra chinensis leaves.
A novel schinortriterpenoid (SNT), schinensilactone A (1), characterized by a unique 7,8‐seco‐1,8‐cyclo‐schisanartane scaffold, was isolated from the leaves of Schisandra chinensis (Turcz.) Baill. In addition, 1 exhibited significant anti‐proliferative activity against Caco‐2 cells originating from five different tumor cell lines, and its preliminary mechanism of action was investigated with respect to the expression of apoptosis‐related proteins, including P53, Caspase 3, Bax, PUMA, and Bcl2.
Abstract Background The purpose of this meta-analysis is to evaluate the efficacy and safety of altered radiation fraction size on outcomes for early breast cancer patients. Methods A search of ...MEDLINE, EMBASE, WEB OF SCIENCE, Cochrane Library and ClinicalTrials.gov was conducted. Quality of the randomized controlled trials (RCTs) or non-RCTs were evaluated according to Cochrane's risk of bias tool or Methodological Index for non-Randomized Studies (MINORS). Pooled risk ratio (RR) and 95% confidence interval (CI) were calculated. Subgroup analysis was applied according to different fraction dose and sensitivity analysis was performed according to RCTs or non-RCTs. Results 23 studies were included in this systematic review. Meta-analysis demonstrated hypofractionation radiotherapy (HFRT) was associated with decreased grade 2/3 acute skin reactions compared with conventional fraction RT (CFRT), either 2.5–3.0 Gy per fraction or 5.0–6.5 Gy per fraction. HFRT with 2.5–3.0 Gy per fraction significantly decreased moderate/marked photographic changes in breast appearance compared with CFRT RR = 0.80, 95% CI (0.70, 0.91), P = 0.001, while HFRT with more than 3.0 Gy per fraction significantly increased moderate/marked photographic changes RR = 1.21, 95% CI (1.06, 1.38), P = 0.004. In addition HFRT cost one-third lower than CFRT. Regarding to local regional recurrence, distant metastasis, overall survival, disease free survival, excellent/good cosmetic comes, symptomatic radiation pneumonitis, ischemic heart disease and symptomatic rib fracture, there was no significant difference between two arms. Conclusions Based on available evidence, HFRT with 2.5–3.0 Gy per fraction should be the better choice for treatment of early breast cancer patients.
A phase II study was performed to investigate the efficacy and the safety of a 3-week schedule of paclitaxel (PTX) plus cisplatin (DDP) combined with concurrent radiotherapy for esophageal squamous ...cell cancer.
Patients with newly diagnosed esophageal squamous cell cancer who had histologic proof of local-regional carcinoma of the esophagus, a Karnofsky performance status of 80 or greater, and normal liver, renal, and bone marrow functions were enrolled in the phase II trial. Chemotherapy consisted of DDP (25 mg/m/d) for 3 days plus PTX (175 mg/m) given for 3 hours, every 3 weeks for 4 cycles. The total dose of concurrent radiation with 68.4 Gy/44 Fx (late course-accelerated radiotherapy) or 61.2 Gy/34 Fx (conventional radiotherapy) was given at the first day of chemotherapy.
Between July 2008 and November 2011, 76 patients were enrolled in this trial. The median age was 58 years (range, 37 to 74 y). The stages were stage II (21 patients), stage III (27 patients), and stage IV (28 patients). A total of 89.5% (68/76) and 63.2% (48/76) patients completed ≥2 cycles and all 4 cycles of chemotherapy, respectively. With the median follow-up of 36 months, the overall median survival time was 28.5 months and the progression-free survival time was 14.7 months. One- and 3-year survival rates were 75% and 41%, respectively. Neutropenia grade 3 and 4 occurred in 30.3% and 31.6% of the patients, respectively.
Radiotherapy concurrent with a 3-week schedule of PTX and DDP resulted in an encouraging overall survival rate, but a relatively higher hematological toxicity.
Triple-negative breast cancer (TNBC) is a heterogeneous disease with highest loco-regional recurrence among breast cancer subtypes. Radiotherapy is indispensable for TNBC loco-regional control. ...However, intrinsic radiosensitivity differences exist in TNBC patients and RT is still prescribed mainly based on conventional clinicopathologic features of patients without considering the differences. The purpose of the present study is to develop and validate a TNBC radiosensitive gene signature (RSGS) and to guide therapeutic decisions. In this study, we compared transcriptome profiles of 12 locally recurrent TNBCs to 20 non-locally recurrent TNBCs treated with surgery radio-chemotherapy and developed a seven-gene RSGS and a simplified three-gene RSGS by using pathway analysis, univariate Cox proportional hazards regression model and rank-based linear algorithm. They were validated by using transcriptome profiles of 166 TNBC patients. Two gene signatures specifically identified a radiosensitive population that had an improved recurrence-free survival in patients treated with surgery radio-chemotherapy (Radiosensitive patients vs radioresistant patients, for seven-gene RSGS:
P
= 0.024, HR = 0.35, 95 %CI 0.14–0.87 and for three-gene RSGS:
P
= 0.035, HR = 0.38, 95 %CI 0.15–0.94). In contrast, there was no significant difference in outcome between predicted radiosensitive and radioresistant patients that treated with other treatment modality. RSGSs provide a useful tool for identification of radiosensitive/radioresistant TNBC patients and they could lead to a better selection of patients for RT protocols.
Primary breast sarcomas (PBSs) are spectrum heterogeneous sarcomas in breast and the optimal treatment for them is still under discussion. Our study was to investigate clinical characteristics and ...identify potential prognostic factors for this rare malignancy. The authors retrospectively reviewed 38 patients with PBSs between October 2000 and February 2014 in FuDan University Shanghai Cancer Center. Local control rate and overall survival (OS) were determined by Kaplan-Meier actuarial method. Univariate analysis and Cox proportional hazards model were applied to identify potential prognostic factors. With median follow-up of 40.19 months, 14 patients (14/38) were found with local recurrence. Extensive operation like mastectomy was not superior to local resection (P = 0.167). Three-year recurrence-free survival and OS rate were 61.9% and 89%, respectively. Larger tumor size and local recurrence were indicated as unfavorable prognostic factors in univariate analysis. Cox model identified narrow interval of recurrence free survival as an unfavorable factor (P = 0.048). Surgery remains crucial treatment for PBSs. Mastectomy, however, is not routinely necessary if clear margin could be achieved by local excision. Early recurrence indicates a poor OS.
Heavy summer rainfall induces significant soil erosion and shallow landslide activity on the loess hillslopes of the Xining Basin at the northeast margin of the Qinghai-Tibet Plateau. This study ...examines the mechanical effects of five native shrubs that can be used to reduce shallow landslide activity. We measured single root tensile resistance and shear resistance, root anatomical structure and direct shear and triaxial shear for soil without roots and five rootsoil composite systems. Results show that
Atriplex canescens
(Pursh) Nutt. possessed the strongest roots, followed by
Caragana korshinskii
Kom.,
Zygophyllum xanthoxylon
(Bunge) Maxim.,
Nitraria tangutorum
Bobr. and
Lycium chinense
Mill. Single root strength and shear resistance relationships with root diameter are characterized by power or exponential relations, consistent with the Mohr-Coulomb law. Root mechanical strength reflects their anatomical structure, especially the percentage of phloem and xylem cells, and the degree and speed of periderm lignifications. The cohesion force of root-soil composite systems is notably higher than that of soil without roots, with increasing amplitudes of cohesion force for
A. canescens
,
C. korshinskii
,
Z. xanthoxylon
,
N. tangutorum
and
L. chinense
of 75.9%, 75.1%, 36.2%, 24.6% and 17.0 % respectively. When subjected to shear forces, the soil without root samples show much greater lateral deformation than the root-soil composite systems, reflecting the restraining effects of roots. Findings from this paper indicate that efforts to reduce shallow landslides in this region by enhancing root reinforcement will be achieved most effectively using
A. canescens
and
C. korshinskii
.
Purpose: This study aims to examine the impact of sleep deprivation on individual cognitive reappraisal ability using a standardized behavioral paradigm. Methods: A randomized pretest-posttest ...control group design was conducted. Thirty-nine participants were eventually enrolled and randomly assigned to receive either the sleep control (SC: n = 17) or the sleep deprivation (SD: n = 22). Both of them were required to perform a standardized behavioral paradigm of measuring cognitive reappraisal ability one time under sleep-rested condition and another time under the condition of different sleep manipulation a week later. Results: Mean valence ratings of SD group were more negative than SC group's (p < 0.05) and mean arousal ratings of SD group were higher than SC group's (p < 0.01). Conclusion: Sleep deprivation may impair individual cognitive reappraisal ability and could potentially undermine the efficacy of cognitive therapy in terms of emotion regulation. Keywords: sleep deprivation, emotion regulation, cognitive reappraisal, IAPS, CRA
Background: Ramucirumab, a fully human immunoglobulin G1 (IgG1) monoclonal antibody targeting vascular endothelial growth factor receptor-2 (VEGFR-2), has been approved for the treatment of advanced ...gastric cancer or gastroesophageal junction adenocarcinoma. Hypertension has been described as a common adverse event with ramucirumab, but the incidence and risk have not been well determined. We conduct this meta-analysis to investigate the overall incidence and risk of developing hypertension associated with use of ramucirumab.
Materials and Methods: Databases from PubMed, Web of Science, and abstracts presented at the American Society of Clinical Oncology (ASCO) meeting up to May 31, 2014, were searched to identify relevant studies. Eligible studies included prospective phase II and III trials evaluating ramucirumab in cancer patients with adequate data on hypertension. Statistical analyses were conducted to calculate the summary incidence, relative risk (RR), and 95% confidence intervals (CIs) by using either random--effect or fixed--effect models according to the heterogeneity of included studies.
Results: A total of 2,649 patients with a variety of solid tumors from eight prospective clinical trials were included in our analysis. The incidence of all--grade and high-grade hypertension associated with ramucirumab was 16.4% (95%CI: 11.9-22.3%) and 9.8% (95%CI: 7.2-13.0%), respectively. Patients treated with ramucirumab had a significantly increased risk of developing all-grade (RR: 2.28, 95%CI: 1.61-3.24, P < 0.001) and high-grade (RR: 3.59, 95%CI: 2.32-5.53, P < 0.001) hypertension compared with patients treated with control medication. No evidence of publication bias was observed.
Conclusions: The use of ramucirumab is associated with a significantly increased risk of developing hypertension when compared with controls. Close monitoring and appropriate managements are recommended during the therapy.
A retrospective analysis of diagnoses was performed in patients with phyllodes tumors of the breast (PTB) who received preoperative core needle biopsy (CNB) and had breast surgery at Fudan University ...Shanghai Cancer Center from January 1, 2002 to April 1, 2013. The resulting data allowed us to compare the accordance between CNB and excision diagnoses of PTB patients and evaluate the accuracy of CNB in preoperative diagnosis.
Data from 128 patients with PTB who had undergone preoperative CNB and breast surgery were retrospectively analyzed. We reviewed the medical history, clinical follow-up data, and CNB diagnostic data. A diagnostic test was used to evaluate the sensitivity and specificity of CNB in diagnosing benign, borderline, and malignant phyllodes tumors.
The accuracy of CNB for diagnosing PTB was 13.3% (17/128). Of the remaining patients, 98 (75.5% of the PTB patients) were diagnosed with fibroadenoma or fibroepithelial lesions. The sensitivity of CNB at diagnosing benign, borderline, and malignant phyllodes tumors were 4.9% (2/41), 4.2% (3/71), and 25.0% (4/16), respectively, whereas the corresponding specificity were 92.0%, 98.2%, and 100%, respectively. Some clinical features, such as large tumor size, rapid growth, or surgical history of fibroadenomas, were indicative of an increased possibility of PTB.
CNB provides a pathological basis for the preoperative diagnosis of PTB, but it has a poor accuracy and offers limited guidance for surgical decisions. Considering CNB along with multiple histologic features may improve the ability to accurately diagnose PTB. An integrated assessment using CNBs in combination with clinical data and imaging features is suggested as a reliable strategy to assist PTB diagnosis.
PDF
