Yina Wang

Prognostic Significance of COX-2 Immunohistochemical Expression in Colorectal Cancer: A Meta-Analysis of the Literature

Background Cyclooxygenase-2 (COX-2) is believed to be an important enzyme in the pathogenesis of colorectal cancer (CRC). Correlations between the expression of COX-2 with tumor growth and distant metastasis have become an issue; thus, attention has been paid to COX-2 as a prognostic factor. Various studies examined the relationship between COX-2 immunohistochemistry (IHC) overexpression with the clinical outcome in patients with colorectal cancer, but yielded conflicting results. The prognostic significance of COX-2 overexpression in colorectal cancer remains controversial. Methods Electronic databases updated to October 2012 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between COX-2 overexpression and survival of patients with colorectal cancer. Survival data were aggregated and quantitatively analyzed. Results We performed a meta-analysis of 23 studies (n  =  4567 patients) that evaluated the correlation between COX-2 overexpression detected by IHC and survival in patients with colorectal cancer. Combined hazard ratios suggested that COX-2 overexpression had an unfavorable impact on overall survival (OS) (HR [hazard ratio]  =  1.193, 95% CI [confidence interval]: 1.02 ∼ 1.37), but not disease free survival (DFS) (HR  =  1.25, 95% CI: 0.99 ∼ 1.50) in patients with colorectal cancer. Conclusions Cox-2 overexpression in colorectal cancer detected by IHC appears to have slightly worse overall survival. However, the prognostic value of COX-2 on survival in colorectal cancer still needs further large-scale prospective trials to be clarified.

Compensatory acclimated mechanisms of photoprotection in a Xa mutant of Lycopersicon esculentum Mill

To probe the role of xanthophylls in non-photochemical quenching (NPQ) and the compensatory acclimated photoprotection mechanisms, a tomato (Lycopersicon esculentum Mill. cv. Ailsa Craig) Xa mutant with deficit in lutein (L) and neoxanthin (N) contents was used. The Xa mutant showed lowered NPQ, an increased degree of de-epoxidation state [(A+Z)/(V+A+Z)], and decreases of photosystem 2 (PS2) antenna size. Although the Xa mutant had a CO2 assimilation rate similar to that of Ailsa Craig, it exhibited a much larger stomatal conductance (gs) than Ailsa Craig. Decreased electron flux in PS2 (JPS2) for the Xa mutant was associated with electron flux for photorespiratory carbon oxidation (Jo) and alternative electron flux in PS2 (Ja) while electron flux for photosynthetic carbon reduction (Jc) was not different from Ailsa Craig. Moreover, the Xa mutant also exhibited higher activities of antioxidant enzymes, higher contents of ascorbate and glutathione, and lower contents of reactive oxygen species. Hence some compensatory acclimated mechanisms of photoprotection operated properly in the lack of NPQ and xanthophylls.

Incidence and relative risk of peripheral neuropathy in cancer patients treated with eribulin: a meta-analysis

Background Eribulin is a microtubule inhibitor, which is approved for the treatment of breast cancer. Peripheral neuropathy has been reported in the studies of eribulin, but the incidence and relative risk (RR) of eribulin-associated peripheral neuropathy varied greatly in cancer patients. The purpose of this meta-analysis was to determine the overall incidence and RR of eribulin-associated peripheral neuropathy in cancer patients. Materials and Methods Pubmed database and Embase and abstracts presented at the American Society of Clinical Oncology (ASCO) meetings were systematically reviewed for primary studies. Eligible studies included prospective clinical trials and expanded access programs of cancer patients treated with eribulin. Statistical analyses were performed to calculate the incidences, RRs, and 95% confidence intervals (CIs). Results Altogether, 4,849 patients from 19 clinical trials were selected for this meta-analysis. The incidences of all-grade and high-grade peripheral neuropathy were 27.5% (95% CI: 23.3–32.4%) and 4.7% (95% CI: 3.6–6.2%), respectively. The relative risks of peripheral neuropathy of eribulin compared to control were increased for all-grade (RR = 1.89, 95% CI: 1.10–3.25) but not statistically significant for high-grade (RR = 2.98, 95% CI: 0.71–12.42). Conclusions The use of eribulin is associated with an increased incidence of peripheral neuropathy. The RR is increased for all-grade peripheral neuropathy.

Incidence and relative risk of cutaneous squamous cell carcinoma with single-agent BRAF inhibitor and dual BRAF/MEK inhibitors in cancer patients: a meta-analysis

Background BRAF inhibitor and dual BRAF/MEK inhibitors have been approved for the treatment of BRAF-mutated melanoma. Cutaneous squamous cell carcinoma (cuSCC) is an adverse event associated with these drugs. The contribution of BRAF inhibitor and dual BRAF/MEK inhibitors to cuSCC are still unknown. We performed this meta-analysis to determine the overall incidence and relative risk of cuSCC in cancer patients treated with these drugs. Results A total of 7,442 patients from 24 primary studies were included. The incidences of all-grade and high-grade cuSCC in cancer patients treated with BRAF inhibitor were 12.5% (95% CI: 10.8–14.6%) and 11.6% (95% CI: 9.8–13.8%), and dual BRAF/MEK inhibitors were 3.0% (95% CI: 2.0–4.5%) and 2.8% (95% CI: 1.9–4.0%), respectively. On subgroup analysis and meta-regression, the incidence of cuSCC did not vary with tumor type, study design and specific drug used. The use of single agent BRAF inhibitor significantly increased the risk of developing cuSCC comparing with dual BRAF/MEK inhibitors for all-grade (RR 4.72, 95% CI: 2.42–9.20) and high-grade (RR 4.92, 95% CI: 2.64–9.16) in cancer patients. Materials and Methods The databases of PubMed, Embase and abstracts published in ASCO proceedings were searched for relevant studies from January 2000 to June 2017. Summary incidences, relative risks (RRs) and 95% confidence intervals (CIs) were calculated by using either random effects or fixed effect models according to the heterogeneity of included studies. Conclusions BRAF inhibitor significantly increases the risk of developing cuSCC compared with dual BRAF/MEK inhibitors in cancer patients. Clinicians should be aware of the risks of cuSCC with the administration of these drugs in cancer patients.

Genomic profiling of synchronous triple primary tumors of the lung, thyroid and kidney in a young female patient: A case report

Synchronous multiple primary malignant tumors (MPMTs) are rare in young adults. Genomic profiling of synchronous MPMTs has not been systematically investigated to elucidate their genetic associations, but may be important to assist diagnosis and guide appropriate treatment strategy. In the present study, mutation profiling was performed using targeted next generation sequencing (NGS) on 416 cancer-related genes in synchronous triple primary tumors of the lung, kidney and thyroid in a 32-year-old female patient. The patient was diagnosed with moderately differentiated lung adenocarcinoma (T2aN0M0; stage IB), renal clear cell carcinoma (T1aN0M0; stage I), and thyroid papillary carcinoma (T1N1aM0, stage III) by pathological assessments. Clinically actionable mutations in EGFR and BRAF genes were identified in the lung and the thyroid lesions, respectively. Three tumors demonstrated distinct genomic profiles, suggesting that all tumors were independent primary tumors, which was consistent with histopathological assessment. Three potential germline cancer susceptibility mutations were shared between this patient and her father who was diagnosed with lung cancer. The present results demonstrated that, in the context of identical germline background and environmental exposure, multiple synchronous tumors in the same patient may have distinct mutation profiles and can be driven by distinct molecular events. Combination therapies may need to be considered during treatment decision-making.

Continuous EGFR tyrosine kinase inhibitor treatment with or without chemotherapy beyond gradual progression in non-small cell lung cancer patients

Background Several clinical studies have demonstrated that continuous administration of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) could provide additional survival benefit for advanced non-small cell lung cancer (NSCLC) patients who had benefited from prior EGFR TKI therapy. However, whether EGFR TKI combined with chemotherapy could further prolong survival in patients with gradual progression is still unclear. The present study was conducted to evaluate the clinical outcome of continuous EGFR TKI treatment in combination with chemotherapy (combination group) versus continuous EGFR TKI treatment only (monotherapy group) in such a clinical setting. Methods We designed a cohort study to collect all chart data of NSCLC patients treated with EGFR TKI in our institution from February 2012 to December 2015 retrospectively and followed up the clinical outcome of EGFR TKI monotherapy or therapy in combination with chemotherapy until April 2017 prospectively. All eligible patients had to meet the criteria of gradual progression. The time interval of progression-free survival 1 (PFS1, gradual progression or death) to PFS2 (off-EGFR TKI progression), and overall survival (OS) between the above 2 groups were used in survival analysis. Results In all, 50 patients were included in our study. Patients’ baseline characteristics were well balanced. Exon 19 deletion mutations and L858R point mutations were detected in 16 and 8 patients, respectively. Twenty, 22, and 8 patients were treated with EGFR TKI in the first, second, and third line setting, respectively. The time interval from PFS1 to PFS2 was 92 and 37 days (monotherapy vs combination), respectively (hazard ratio [HR] =1.16, 95% confidence interval [CI]: 0.61–2.21, P=0.652). The median OS in the monotherapy group and combination group was 696 and 799 days, respectively (HR =0.74, 95% CI: 0.33–1.71, P=0.501). There were no statistical differences between the 2 groups in terms of the time interval from PFS1 to PFS2 and OS. Conclusion Our results suggested that compared with EGFR TKI monotherapy, its combination with chemotherapy beyond gradual progression may not confer a significant survival benefit to NSCLC patients. Further prospective studies are warranted to reinforce the results of the study.

Icotinib combined with rapamycin in a renal transplant recipient with epidermal growth factor receptor‑mutated non‑small cell lung cancer: A case report

As kidney transplant recipients are at increased risk of developing cancer, regular monitoring should be undertaken to monitor the balance between immunosuppression and graft function and to identify malignancy. The present study reports the outcome of the treatment of adenocarcinoma of the lung (T1aN0M1a, stage IV) using the molecular-targeted therapy, icotinib, in a 66-year-old male renal transplant patient receiving rapamycin and prednisolone as ongoing renal immunosuppressive therapy. An initial partial response to icotinib was achieved, and graft function remained good. However, the patient subsequently developed interstitial pneumonitis. The plasma concentrations of rapamycin and icotinib were within the normal ranges, which excluded the possibility of a pharmacokinetic drug interaction and indicated that the interstitial pneumonitis was likely to be associated with the side-effects of icotinib. Drug therapy was discontinued and the patient underwent a segmentectomy. Tacrolimus was administered for ongoing renal graft immunosuppression. To the best of our knowledge, this is the first report of the concomitant administration of icotinib and rapamycin in post-transplant de novo lung cancer. It is also the first report of interstitial pneumonitis associated with icotinib in a post-transplant patient.