Comparison of efficacy, safety, and quality of life between sorafenib and sunitinib as first.line therapy for Chinese patients with metastatic renal cell carcinoma

Background: Sorafenib and sunitinib are widely used as first-line targeted therapy for metastatic renal cell carcinoma(mRCC) in China.This study aimed to compare the efficacy, safety, and quality of life(QoL) in Chinese mRCC patients treated with sorafenib and sunitinib as first-line therapy.Methods: Clinical data of patients with mRCC who received sorafenib(400 mg twice daily; 4 weeks) or sunitinib(50 mg twice daily; on a schedule of 4 weeks on treatment followed by 2 weeks off) were retrieved. Primary outcomes were overall survival(OS), progression-free survival(PFS), adverse events(AEs), and QoL(SF-36 scores), and secondary outcomes were associations of clinical characteristics with QoL.Results: Medical records of 184 patients(110 in the sorafenib group and 74 in the sunitinib group) were reviewed.PFS and OS were comparable between the sorafenib and sunitinib groups(both P > 0.05).The occurrence rates of leukocytopenia, thrombocytopenia, and hypothyroidism were higher in the sunitinib group(36.5% vs. 10.9%,P< 0.001; 40.5% vs. 10.9%, P < 0.001; 17.6% vs. 3.6%, P = 0.001), and that of diarrhea was higher in the sorafenib group(62.7% vs. 35.2%, P < 0.001). There was no significant difference in SF-36 scores between the two groups. Multivariate analysis indicated that role-physical and bodily pain scores were associated with the occurrence rate of grade 3 or 4 AEs(P = 0.017 and 0.005).Conclusions: Sorafenib has comparable efficacy and lower toxicity profile than sunitinib as first-line therapy for mRCC. Both agents showed no significant impact on QoL of patients.

Surface-enhanced Raman spectroscopy of serum predicts sensitivity to docetaxel-based chemotherapy in patients with metastatic castration-resistant prostate cancer

Docetaxel-based chemotherapy,as the first-line treatment for metastatic castration-resistant prostate cancer(mCRPC),has succeeded in helping quite a number of patients to improve quality of life and prolong survival time.However,almost half of mCRPC patients are not sensitive to docetaxel chemotherapy initially.This study aimed to establish models to predict sensitivity to docetaxel chemotherapy in patients with mCRPC by using serum surface-enhanced Raman spectroscopy(SERS).A total of 32 mCPRC patients who underwent docetaxel chemo-therapy at our center from July 2016 to March 2018 were included in this study.Patients were dichotomized in prostate-specific antigen(PSA)response group(n=17)versus PSA failure group(n=15)according to the response to docetaxel.In total 64 matched spectra from 32 mCRPC patients were obtained by using SERS of serum at baseline(q0)and after 1 cycle of docetaxel chemotherapy(ql).Comparing Raman peaks of serum samples at baseline(q0)be-tween two groups,significant differences revealed at the peaks of 638,810,890(p<0.05)and 1136cm^(-1)(p<0.01).The prediction models of peak 1363 cm^(-1)and principal component anal-ysis and linear discriminant analysis(PCA-LDA)based on Raman data were established,re-spectively.The sensitivity and specificity of the prediction models were 71%,80%and 69%,78%through the way of leave-one-out cross-validation.According to the results of five-cross-valida-tion,the PCA-LDA model revealed an accuracy of 0.73 and AUC of 0.83.

索拉非尼与舒尼替尼一线治疗中国转移性肾细胞癌患者的疗效、安全性和生活质量的比较

背景与目的在中国,索拉非尼和舒尼替尼是广泛应用于治疗转移性肾细胞癌(metastatic renal cell carcinoma,mRCC)的一线靶向药物。本研究旨在比较索拉非尼与舒尼替尼一线治疗中国mRCC患者的疗效、安全性和生活质量(quality of life,QoL)。方法收集接受索拉菲尼治疗(400 mg,每天2次;4周)或舒尼替尼(50 mg,每天2次;用药4周后停药2周)治疗的mRCC患者的临床资料。主要指标为总生存(overall survival,OS)、无进展生存(progression-free survival,PFS)、不良事件(adverse events,AEs)和QoL(SF-36评分),次要指标为临床特征与QoL的相关性。结果本研究回顾了184例患者(索拉非尼组110例和舒尼替尼组74例)的病历。索拉非尼和舒尼替尼组的PFS和OS无显著性差异(均P> 0.05)。舒尼替尼组中白细胞减少、血小板减少和甲状腺功能减退的发生率较高(36.5%vs. 10.9%,P <0.001;40.5%vs. 10.9%,P <0.001;17.6%vs. 3.6%,P=0.001),而索拉非尼组腹泻的发生率较高(62.7%vs. 35.2%,P <0.001)。两组的SF-36评分无显著性差异。多因素分析表明,躯体角色和躯体疼痛评分与3或4级AEs的发生率相关(P=0.017和0.005)。结论作为mRCC一线治疗药物的索拉非尼与舒尼替尼相比,疗效相当,毒性较低。两种药物对患者的QoL无显著影响。

Indications,strategies,and development on prostate targeted biopsy:Report of the Panjiayuan Consensus Conference 2022

Prostate biopsy is the gold standard for diagnosing prostate cancer(PCa).Prostate targeted biopsy(TB)having a higher rate of detecting clinically significant PCa(csPCa)than traditional systematic biopsy(SB)is supported by high-quality evidence.However,the TB indications and strategies are controversial.The National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences,invited a panel of recognized urology experts in PCa to address these topics at the Panjiayuan Consensus Conference 2022.The conference results on prostate TB are presented herein.The National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences identified 10 key areas of prostate biopsy:(1)selection of imaging examination;(2)indications of TB;(3)transperineal and transrectal prostate biopsy;(4)TB pathways;(5)TB and SB;(6)three techniques of TB;(7)the number of TB cores needed for one lesion;(8)core number for SB;(9)free-hand TB;(10)future development of TB/prostate diagnosis.Thus,a panel of 25 recognized urologists and 2 radiologists from China were invited to attend this conference.The panel voted anonymously on 14 predetermined questions.Voting was based on the panelists'clinical practice and opinion,rather than high-level evidence.The voting outcomes were supported by the panel unequally,and details of the voting results were reported.The voting results can help clinicians to decide on biopsy timing and proper strategies,for which guidelines are sparse.We also focused on the future development of TB and SB,such as the combined pathway of TB and SB,techniques of TB,biopsy cores,free-hand TB,and prostate-specific membrane antigen positron emission tomography/computed tomography.

LSD1 inhibition suppresses the growth of clear cell renal cell carcinoma via upregulating P21signaling

Histone lysine-specific demethylase 1(LSD1) has been implicated in the disease progression of several types of solid tumors. This study provides the first evidence showing that LSD1 overexpression occurred in 62.6%(224/358) of clear cell renal cell carcinomas(ccRCC). LSD1 expression was associated with the progression of ccRCC, as indicated by TNM stage(P ? 0.006), especially tumor stage(P ? 0.017) and lymph node metastasis(P ? 0.030). High LSD1 expression proved to be an independent prognostic factor for poor overall survival(Po0.001) and recurrence-free survival(Po0.001) of ccRCC patients. We further show that LSD1 inhibition by siRNA knockdown or using the small molecule inhibitor SP2509 suppressed the growth of ccRCC in vitro and in vivo. Mechanistically, inhibition of LSD1 decreased the H3 K4 demethylation at the CDKN1 A gene promoter, which was associated with P21 upregulation and cell cycle arrest at G1/S in ccRCC cells. Our findings provide new mechanistic insights into the role of LSD1 in cc RCC and suggest the therapeutic potential of LSD1 inhibitors in ccRCC treatment.