Hyperprogressive Disease in Patients With Urothelial Carcinoma or Renal Cell Carcinoma Treated With PD-1/PD-L1 Inhibitors

BackgroundA rapid progression pattern called hyperprogressive disease (HPD) has been observed during early cycles of programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor therapy. Data regarding HPD in patients with genitourinary cancer are limited.Patients and MethodsWe included 203 patients with genitourinary cancer treated with PD-1/PD-L1 inhibitors between February 2015 and June 2018. HPD was defined as a greater than 50% increase in tumor burden, greater than 2-fold increase in tumor growth rate, or development of extensive (10 or more) new lesions.ResultsPatients (n = 102) with renal cell carcinoma (RCC) and patients (n = 101) with urothelial carcinoma (UC) were included. HPD was observed in 13 (6.4%) patients. The median overall survival for patients with progressive disease and HPD was 7.3 months and 3.5 months, respectively. HPD occurred more frequently in patients with UC than in those with RCC (11.9% vs. 0.9%; P = .01). Multivariate analysis showed that UC and creatinine above 1.2 mg/dL were independent predictive factors for HPD. A 30% increase in lymphocyte number following PD-1/PD-L1 inhibitor treatment was a negative predictor of HPD. The incidence of HPD in patients with UC treated with paclitaxel-based chemotherapy was one-third of those treated with PD-1/PD-L1 inhibitors.ConclusionHPD developed predominantly in patients with UC, and the incidence of HPD in patients with RCC was negligible. Treatment with PD-1/PD-L1 inhibitors should be prescribed with caution in patients with UC and creatinine above 1.2 mg/dL.     

Targeting DNA Repair in Ovarian Cancer Treatment Resistance

Most patients with advanced high-grade serous ovarian cancer (HGSOC) develop recurrent disease within 3 years and succumb to the disease within 5 years. Standard treatment for HGSOC is cytoreductive surgery followed by a combination of platinum (carboplatin or cisplatin) and taxol (paclitaxel) chemotherapies. Although initial recurrences are usually platinum-sensitive, patients eventually develop resistance to platinum-based chemotherapy. Accordingly, one of the major problems in the treatment of HGSOC and disease recurrence is the development of chemotherapy resistance. One of the causes of chemoresistance may be redundancies in the repair pathways involved in the response to DNA damage caused by chemotherapy. These pathways may be acting in parallel, where if the repair pathway that is responsible for triggering cell death after platinum chemotherapy therapy is deficient, an alternative repair pathway compensates and drives cancer cells to repair the damage, leading to chemotherapy resistance. In addition, if the repair pathways are epigenetically inactivated by DNA methylation, cell death may not be triggered, resulting in accumulation of mutations and DNA damage. There are novel and existing therapies that can drive DNA repair pathways towards sensitivity to platinum chemotherapy or targeted therapy, thus enabling treatment-resistant ovarian cancer to overcome chemotherapy resistance.     

Colitis following the use of immune checkpoint inhibitors: A real-world analysis of spontaneous reports submitted to the FDA adverse event reporting system

BackgroundAlthough colitis has been reported in patients treated with immune checkpoint inhibitors (ICIs), associations between colitis and ICIs had not been thoroughly assessed in real-world studies. Here, we identified and characterized significant colitis-associated with ICIs.MethodsBased on the Food and Drug Administration Adverse Event Reporting System (FAERS) from January 2004 to December 2019, the disproportionality analysis and Bayesian analysis, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN) and the multi-item gamma Poisson shrinker (MGPS) algorithms were adopted to data mining of the suspected adverse events of colitis after ICIs administrating. Clinical characteristics of patients with ICIs-associated colitis and the time to onset of colitis following different ICI regimens were collected.ResultsA total of 3786 reports of colitis adverse events were identified with ICIs. Seven ICI monotherapies were associated with the reporting of colitis. Statistically significant ROR, PRR, information component (IC), and empirical Bayesian geometric mean (EBGM) emerged for all ICI monotherapies and combination therapies. ICIs-associated colitis affected mostly male (53.51%), with a wide mean age range (60.65 to 72 years). Colitis adverse events were commonly reported in patients with melanoma and lung cancer. Adverse outcomes of colitis concerning ICI were mainly outcomes of hospitalization-initiated or prolonged and other serious. Among colitis cases, 17.43% cases of colitis concerning ICI lead to death. The adverse event of colitis occurred earliest in ipilimumab monotherapy with a median time to onset of 64.21 days (IQR: 27–69 days) among all monotherapies.ConclusionsICI may lead to severe and disabling ICIs-associated colitis during therapy. Analysis of FAERS data identified signals for adverse events of colitis with ICI regimens. Practitioners should consider the factors that may increase the likelihood of colitis. The findings support a continued surveillance and risk factor identification studies.     

Composites with AIEgens for Temperature Sensing and Strain Measurement

Traditional fluorescent molecules are easily quenched in most solid applications. Materials with aggregation‐induced emission (AIE) characteristics offer a new way to solve this problem. In this paper, polymer composites consisting of tetraphenylethene (TPE) with AIE properties and polydimethylsiloxane (PDMS) are developed by a simple blending method. The prepared material shows a variable fluorescent emission with different TPE concentrations in the polymer matrix. Such a unique phenomenon arises mainly from the transition of the AIEgen from the crystal to the amorphous state. Interestingly, the fluorescent emission of composites is strongly affected by external factors, such as temperature and mechanical conditions, thus giving the material a stimuli‐sensitive fluorescence property. Specifically, the fluorescence intensity of composites decreases with an increasing temperature, and the same response exhibits when the mechanical force is applied to the material. The excellent response of composites to the temperature and mechanical deformation guarantees the sensory applications of the developed material.     

TACE对原发性肝癌患者的疗效及NLR、PLR的影响研究

目的研究经导管动脉化疗栓塞(TACE)对原发性肝癌患者的疗效及中性粒细胞/淋巴细胞计数比(NLR)、血小板/淋巴细胞计数比(PLR)的影响。方法选择2015年6月～2019年1月我院接诊的原发性肝癌患者80例作为研究对象,采用随机数表法将患者分为两组,每组各40例。对照组予传统肝切除术治疗,观察组采用TACE治疗。对比两组治疗后的临床效果,NLR、PLR、癌胚抗原(CEA)、可溶性B7-H4、可溶性白细胞介素-2受体(sIL-2R)及并发症发生情况。结果治疗后,两组患者的总有效率分别为75.00%和52.50%,观察组高于对照组,差异有统计学意义(P0.05);治疗前,两组患者NLR、PLR水平对比,差异无统计学意义(P0.05);治疗后,患者NLR、PLR水平下降,观察组低于对照组,差异有统计学意义(P0.05);治疗前,两组患者CEA、B7-H4、sIL-2R水平对比,差异无统计学意义(P0.05);治疗后,两组患者CEA、B7-H4、sIL-2R水平下降,观察组低于对照组,差异有统计学意义(P0.05);两组患者并发症发生率分别为17.50%、40.00%,观察组低于对照组,差异有统计学意义(P0.05)。结论在原发性肝癌患者中使用TACE效果显著,可有效改善患者肿瘤标志物水平,减少并发症,值得推广应用。