新版實體瘤療效評價標(biāo)準(zhǔn)：修訂的recist指南（11版本）

1、New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1) 新版 新版實體瘤療效評價標(biāo)準(zhǔn)：修訂的 實體瘤療效評價標(biāo)準(zhǔn)：修訂的 RECIST 指南（ 指南（1.1 版本） 版本） Abstract 摘要 Background 背景介紹 Assessment of the change in tumour burden

2、 is an important feature of the clinical evaluation of cancer therapeutics: both tumour shrinkage (objective response) and disease progression are useful endpoints in clinical trials. Since RECIST was published in 2000,

3、many investigators, cooperative groups, industry and government authorities have adopted these criteria in the assessment of treatment outcomes. However, a number of questions and issues have arisen which have led to the

4、 development of a revised RECIST guideline (version 1.1). Evidence for changes, summarised in separate papers in this special issue, has come from assessment of a large data warehouse (>6500 patients), simulation stud

5、ies and literature reviews. 臨床上評價腫瘤治療效果最重要的一點就是對腫瘤負(fù)荷變化的評估：瘤體皺縮（目標(biāo)療效）和病情惡化在臨床試驗中都是有意義的判斷終點。自從 2000 年 RECIST 出版以來，許多研究人員、企業(yè)團體、行業(yè)和政府當(dāng)局都采納了這一標(biāo)準(zhǔn)來評價治療效果。但是，隨之涌現(xiàn)出的一些問題導(dǎo)致了本修訂版的出版（1.1 版） 。修正之處（請見各章的專題）源自于對大型數(shù)據(jù)庫（超過 6500 例患者） 、模擬研究

6、以及文獻綜述的評估。 Highlights of revised RECIST 1.1 1.1 版 RECIST 的重要修訂之處 Major changes include: Number of lesions to be assessed: based on evidence from numerous trial databases merged into a data warehouse for analysis purposes

7、, the number of lesions required to assess tumour burden for response determination has been reduced from a maximum of 10 to a maximum of five total (and from five to two per organ, maximum). Assessment of pathological l

8、ymph nodes is now incorporated: nodes with a short axis of 15 mm are considered measurable and assessable as target lesions. The short axis measurement should be included in the sum of lesions in calculation of tumour re

9、sponse. Nodes that shrink to <10 mm short axis are considered normal. Confirmation of response is required for trials with response primary endpoint but is no longer required in randomised studies since the control ar

10、m serves as appropriate means of interpretation of data. Disease progression is clarified in several aspects: in addition to the previous definition of progression in target disease of 20% increase in sum, a 5 mm absolut

11、e increase is now required as well to guard against over calling PD when the total sum is very small. Furthermore, there is guidance offered on what constitutes ?unequivocal progression‘ of non-measurable/non-target dise

12、ase, a source of confusion in the original RECIST guideline. Finally, a section on detection of new lesions, including the interpretation of FDG-PET scan assessment is included. Imaging guidance: the revised RECIST inclu

13、des a new imaging appendix with updated recommendations on the optimal anatomical assessment of lesions. 主要的修訂之處有：病灶數(shù)目的判定：為了方便分析，很多小型試驗數(shù)據(jù)庫的證據(jù)被合并成一個大型數(shù)據(jù)庫。根據(jù)該數(shù)據(jù)庫，為判斷療效對腫瘤負(fù)荷進行評估所需病灶的總數(shù)由原來的最多 10 個減至現(xiàn)在的 5 個（每個器官由最多 5 個減至 2 個）

14、 。病理性淋巴結(jié)的判定現(xiàn)在也合并為：短軸值 15mm 的淋巴結(jié)現(xiàn)在也被認(rèn)為是可檢測和評估的目標(biāo)病灶。計算腫瘤療效時， （結(jié)節(jié)性病灶的）短軸值必須包括在病灶（半徑的）總和中。結(jié)節(jié)皺縮至短軸值<10mm 時可以認(rèn)為是正常的。療效的確認(rèn)因為控制限已用作解釋數(shù)據(jù)的合適均值，試驗所必需的療效最初的終關(guān)鍵詞：療效評估標(biāo)準(zhǔn)；實體瘤；指南 1. Background 1 背景 1.1. History of RECIST criteria 1.

15、1 RECIST 標(biāo)準(zhǔn)的歷史 Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics. Both tumour shrinkage (objective response) and time to the development of disease progre

16、ssion are important endpoints in cancer clinical trials. The use of tumour regression as the endpoint for phase II trials screening new agents for evidence of anti-tumour effect is supported by years of evidence suggesti

17、ng that, for many solid tumours, agents which produce tumour shrinkage in a proportion of patients have a reasonable (albeit imperfect) chance of subsequently demonstrating an improvement in overall survival or other tim

18、e to event measures in randomised phase III studies (reviewed in [1], [2], [3] and [4]). At the current time objective response carries with it a body of evidence greater than for any other biomarker supporting its utili

19、ty as a measure of promising treatment effect in phase II screening trials. Furthermore, at both the phase II and phase III stage of drug development, clinical trials in advanced disease settings are increasingly utilisi

20、ng time to progression (or progression-free survival) as an endpoint upon which efficacy conclusions are drawn, which is also based on anatomical measurement of tumour size. 評價腫瘤負(fù)荷的改變是癌癥治療的臨床評價的一個重要特征。腫瘤縮小（客觀反應(yīng)）和疾病進展的時間都

21、是癌癥臨床試驗中的重要端點。為了篩查新的抗腫瘤藥物，腫瘤縮小作為 II 期試驗端點被多年研究的證據(jù)所支持。這些研究提示對于多種實體腫瘤來說，促使部分病人腫瘤縮小的藥物以后都有可能（盡管不完美）被證實可提高病人的總體生存期或在隨機Ⅲ期試驗中有進入事件評價的其他機會。 目前在Ⅱ期篩查試驗中評價治療效果的指標(biāo)中，客觀反應(yīng)比任何其他生物標(biāo)記更可靠。而且，在Ⅱ和Ⅲ期藥物試驗中，進展期疾病中的臨床試驗正越來越利用疾病進展的時間（無進展生存）作為得出

22、有治療效果結(jié)論的端點，而這些也是建立在腫瘤大小的基礎(chǔ)上。 However, both of these tumour endpoints, objective response and time to disease progression, are useful only if based on widely accepted and readily applied standard criteria based on anatomi

23、cal tumour burden. In 1981 the World Health Organisation (WHO) first published tumour response criteria, mainly for use in trials where tumour response was the primary endpoint. The WHO criteria introduced the concept of

24、 an overall assessment of tumour burden by summing the products of bidimensional lesion measurements and determined response to therapy by evaluation of change from baseline while on treatment.5 However, in the decades t

25、hat followed their publication, cooperative groups and pharmaceutical companies that used the WHO criteria often ?modified‘ them to accommodate new technologies or to address areas that were unclear in the original docum

26、ent. This led to confusion in interpretation of trial results6 and in fact, the application of varying response criteria was shown to lead to very different conclusions about the efficacy of the same regimen.7 In respons

27、e to these problems, an International Working Party was formed in the mid 1990s to standardise and simplify response criteria. New criteria, known as RECIST (Response Evaluation Criteria in Solid Tumours), were published

28、 in 2000.8 Key features of the original RECIST include definitions of minimum size of measurable lesions, instructions on how many lesions to follow (up to 10; a maximum five per organ site), and the use of unidimensiona

29、l, rather than bidimensional, measures for overall evaluation of tumour burden. These criteria have subsequently been widely adopted by academic institutions, cooperative groups, and industry for trials where the primary