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Purpose Cetuximab in combination with chemotherapy is a standard-of-care first-line treatment regimen for patients with RAS wild-type (wt) metastatic colorectal cancer (mCRC); however, the efficacy of cetuximab plus leucovorin, fluorouracil, and oxaliplatin (FOLFOX) has never before been proven in a controlled and randomized phase III trial. To our knowledge, the TAILOR trial ( ClinicalTrials.gov identifier: NCT01228734) is the first randomized, multicenter, phase III study of the addition of cetuximab to first-line FOLFOX prospectively choosing a RAS wt population and thus providing confirmative data for the efficacy and safety of cetuximab plus FOLFOX versus FOLFOX alone. Patients and Methods TAILOR is an open-label, randomized (1:1), multicenter, phase III trial in patients from China comparing FOLFOX-4 with or without cetuximab in RAS wt ( KRAS/ NRAS, exons 2 to 4) mCRC. The primary end point of TAILOR was progression-free survival time; secondary end points included overall survival time, overall response rate, and safety and tolerability. Results In the modified intent-to-treat population of 393 patients with RAS wt mCRC, adding cetuximab to FOLFOX-4 significantly improved the primary end point of progression-free survival time compared with FOLFOX-4 alone (hazard ratio, 0.69; 95% CI, 0.54 to 0.89; P = .004; median, 9.2 v 7.4 months, respectively), as well as the secondary end points of overall survival time (current assessment after 300 events: hazard ratio, 0.76; 95% CI, 0.61 to 0.96; P = .02; median, 20.7 v 17.8 months, respectively) and overall response rate (odds ratio, 2.41; 95% CI, 1.61 to 3.61; P < .001; 61.1% v 39.5%, respectively). Treatment was well tolerated, and there were no new or unexpected safety findings. Conclusion The TAILOR study met all of its objectives and relevant clinical end points, confirming cetuximab in combination with FOLFOX as an effective standard-of-care first-line treatment regimen for patients with RAS wt mCRC.

Knee osteoarthritis is the most common degenerative disease of the joints caused by articular cartilage injury, degradation of the joint edge and subchondral bone hyperplasia. Various treatments are used to alleviate the symptoms of patients with knee osteoarthritis, including analgesics and intra-articular injections. Platelet-rich plasma (PRP) is an autologous and multifunctional platelet concentrate of the blood, which stimulates the cartilage healing process and improves the damage caused by articular disease. Hyaluronic acid (HA) is an effective treatment for patients with knee osteoarthritis. In the current study, the effectiveness of PRP and HA combination therapy administered via intra-articular injections for patients with knee osteoarthritis was analyzed. A total of 360 patients with knee osteoarthritis were randomized into four different treatment groups as follows: Double-blind treatment with PRP (2-14 ml); double-blind treatment with HA (0.1-0.3 mg); combination therapy of PRP and HA; and placebo groups. Following treatment, all patients were evaluated using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Common Toxicity Criteria. The most common treatment-emergent adverse events were hypertension and proteinuria. The current study demonstrated that PRP and HA treatment significantly improved arthralgia, and PRP treatment was determined to be significantly more effective than HA treatment using the WOMAC pain score (P<0.05). PRP and HA combination treatment significantly improved arthralgia, reduced humoral and cellular immune responses and promoted angiogenesis, which improved the patients' histological parameters compared with PRP or HA treatment alone. These results suggested that PRP and HA combination treatment may be a potential treatment option for patients with knee osteoarthritis in the future.

BackgroundNext-generation sequencing (NGS) is an efficient and sensitive method to detect mutations from ctDNA. Many features and clinical conditions could significantly affect the concordance between ctDNA and corresponding tumor tissues. Our goal was to systematically investigate the critical factors contributing to different concordance between ctDNA and corresponding tumor tissues.MethodsWe recruited two groups of IIIB or IV lung cancer patients: The standard group to evaluate the accuracy of our method and the concordance between ctDNA and tumor tissues, and the study group with various clinical conditions. We applied our unique identification (UID) indexed capturing-based sequencing (UC-Seq) to ctDNA samples, and confirm the results by Droplet digital PCR (ddPCR).ResultsConsidering mutations detected from NGS of tumor tissues as golden standard, UC-Seq achieved overall 93.6% sensitivity for SNVs and Indels, and 0.8 Pearson correlation between tumor TMB and bTMB. Efficacious treatments, long sampling date (more than 2 weeks) between tumor tissues and ctDNA and low concentrations of cfDNA (less than 9 ng/ml) could significantly decrease the concordance between ctDNA and tumor tissues. About 84% mutations showed shorter mutant fragment length than that of wild-type fragments, and the AFs of mutations could be significantly enriched in small-size ctDNA.ConclusionsIn late-stage lung cancer patients, ctDNA generally has high concordance with tumor tissues. However it could be significantly affected by three clinical conditions which could dynamically change the content of ctDNA. Moreover, the detection limit could be further extended by enriching small-size ctDNA in the preparation of samples.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4199-7) contains supplementary material, which is available to authorized users.