针对寡转移性透明细胞肾细胞癌 (ccRCC) 的转移灶定向放射治疗（不联合全身治疗）的 II 期试验及循环肿瘤 DNA (ctDNA) 研究.pdf

1、Phase 2 trial of metastasis directed radiotherapy without systemic therapy(MRWS)for oligometastatic clear cell renal cell carcinoma(ccRCC)and investigation of circulating tumor DNA(ctDNA)as a personalized biomarkerChad Tang,Alex Sherry,Aaron Seo,Kieko Hara,Haesun Choi,Suyu Liu,Xiaowen Sun,Anya Monto

2、ya,Ethan Ludmir,Amishi Y Shah,Eric Jonasch,Amado J Zurita,Craig Kovitz,Christopher J Battey,Sarah Ratzel,Giannicola Genovese,Kanishka Sircar,Jose Karam,Nizar Tannir,Pavlos MsaouelIntroduction:RCCDoublet IO/IO or TKISBRTCosts$150,000-300,000 per year$15,000-40,000 per roundToxicities45-85%grade 3+5-1

3、0%grade 3+Clinic VisitsAt least monthly infusions1-2 weeks per round Front line systemic therapy for metastatic RCC utilizes doublets with combination PD-1 and CTLA-4 inhibitors or TKI Metastatic RCC exhibits a spectrum of clinical behaviors including indolent low volume(oligometastatic)disease Limi

4、ted studies have investigated metastasis directed therapy(MDT)to defer systemic therapy in low volume metastatic RCC MDT without systemic therapy offers advantages in costs,toxicities,and clinic visits over frontline systemic therapiesIntroduction:ctDNA in RCC One of the greatest barriers to MDT wit

5、hout systemic therapy are prognostic markers ctDNA offers an accessible and quantitative solution.However,challenges exist for ctDNA in RCC,which are compounded by indolent low volume disease.Low shedding BiologyBettegowda Sci Trans Med 2014Intrapatient HeterogeneityGerlinger NEJM 2012Low Mutation B

6、urdenLawrence Nature 2013Trial DesignCo-Primary Endpoints:Progression free survival(PFS;RECIST 1.1)Systemic therapy free survival(STFS;start systemic therapy or death due to disease).Rini Lancet Oncology 2016 found surveillance was associated with 14.9 mo(95%CI:10.6-25 mo)STFS.Success defined as med