碳离子治疗肿瘤的临床进展研究

碳离子束拥有独特的物理学及生物学优势,在肿瘤治疗过程中具有高效性和低毒性,并且整体治疗周期短,因此被认为是21世纪最理想的肿瘤放射治疗射线。但是碳离子中心建设及设备运营费用昂贵,目前世界范围内,仅有日本、德国、中国、意大利、奥地利等极少数国家将碳离子应用于临床。自1994年以来,日本一直应用碳离子束治疗恶性肿瘤,治疗效果较好。截至2022年底,全球范围内超过46800例患者接受了碳离子治疗,其中包括头颈部恶性肿瘤、肺癌、肝癌、胰腺癌等。本文总结近20年来碳离子在临床应用中的经验、治疗效果、最新发展及其作为一种新兴癌症治疗方式的优点,并将碳离子治疗与传统的光子放疗疗效及不良反应进行比较,可以帮助临床进一步了解碳离子治疗的优势及进展,并且指导关于新的碳离子治疗中心的建设,从而更好地服务于肿瘤患者。

Bevacizumab biosimilar LY01008 compared with bevacizumab(Avastin)as first-line treatment for Chinese patients with unresectable,metastatic,or recurrent non-squamous non-small-cell lung cancer:A multicenter,randomized,double-blinded,phase Ⅲ trial

Background:Previous studies have demonstrated the preclinical pharmacological and toxicological consistency,and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab(Avastin).This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first-line treatment of Chinese patients with advanced or recurrent non-squamous non-small cell lung cancer(NSCLC).Methods:StageⅢB-ⅣNSCLC patients with evaluable lesions,good physical status,and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin(combined treatment)for 4-6 cycles,followed by maintenance monotherapy with LY01008 until disease progression,intolerable toxicity,or death.The primary endpoint was objective response rate(ORR)in accordance with Response Evaluation Criteria in Solid Tumors(RECIST)version 1.1 confirmed by independent radiological review committees(IRRC).Secondary endpoints included disease control rate(DCR),duration of response(DoR),progression-free survival(PFS),overall survival(OS),and safety.This study was registered in Clinical Trials.gov(NCT03533127).Results:Between December 15^(th),2017,and May 15^(th),2019,a total of 649 patients were randomized to the LY01008(n=324)or Avastin(n=325)group.As of September 25th,2019 for primary endpoint analysis,589 patients received ORR evaluation,with a median number of combined treatment cycles of 5(range 1-6)andmedian duration of treatment of 3.0(range 0.0-5.1)months.ORRof responseevaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%,respectively.The stratified ORR ratio was 0.91(90%CI 0.80-1.04,within the prespecified equivalence margin of 0.75-1.33).Up to May 15^(th),2020,with a median follow-up of 13.6(range 0.8-28.4)months,no notable differences in DCR,median DoR,median PFS,median OS,and 1-year OS rate were observed between the LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,or recurrent non-squamous NSCLC patients in the first-line setting.

A preliminary study on effect of carbon ion radiotherapy on bone marrow suppression

Objective:To explore the effect of carbon ion radiotherapy(CIRT)on the bone marrow adjacent to or within the treatment fields,and to observe the bone marrow toxicities after CIRT alone.Methods:Twenty-one patients with malignant tumors of different body parts and treated with CIRT in Heavy Ion Center,Wuwei Cancer Hospital were analyzed retrospectively.The data of white blood cells,neutrophils,hemoglobin,platelets,lymphocytes and globulin before treatment,7,14 and 28 d during treatment,and 1 and 3 months after treatment were collected.Hematological toxicities were measured according to the Common Terminology Criteria for Adverse Events(CTCAE,Version 4.03)criteria.Dose-volume histogram parameters were obtained for all patients and analyzed for their correlation with myelosuppression.Univariate analysis was performed for patients’sex,age group,tumor site,radiation dose,and Karnofsky performance score(KPS)was used as an independent factor to find predictors factors for the risk of myelosuppression.Results:CIRT minimized the dose radiated to the bone marrow.Overall,volume receiving 3 GyE(V3)or more of the bone marrow were less than 0.5%,especially V5 less than 0.1%.No patients treated with carbon ion radiotherapy developed grade III or IV myelosuppression.Seven patients(33.3%)developed grade I myelosuppression and one patient(4.8%)developed grade II myelosuppression,and most of them showed reduced white blood cell counts.There were no significant differences in hemoglobin and globulin levels before and after CIRT.Univariate analysis did not find any statistically significant predictors for myelosuppression.Conclusions:CIRT is effective in preserving bone marrow function regardless of tumor site.Patients receiving CIRT alone have a low incidence of grade III myelosuppression and a mild effect on globulins.There was no significant correlation between occurrence of myelosuppression and the dose and site irradiated by CIRT.