Disease-free survival，Relapse-free survival和Recurrence-free survival的含义和一致性比较

一、定义

1. Disease-free survival（无疾病生存期）：随机定义开始至肿瘤复发或（任何原因）死亡的时间间隔

Disease-free survival (DFS) is defined as the time from randomization to recurrence of tumor or death, and it is typically used in the adjuvant treatment setting. In some settings DFS may also be a surrogate for OS, because patients who remain disease free for an extended period of time may be cured.

Ref: https://www.sciencedirect.com/topics/medicine-and-dentistry/disease-free-survival

DFS常用于根治性手术或放疗后辅助治疗的研究，目前是作为乳腺癌辅助性激素治疗、结肠癌辅助治疗以及乳腺癌的辅助化疗的主要审批基础。疾病复发需要认真的随访，而记录同样比较困难，且肿瘤患者常有并发症容易干扰 DFS 的判断。当患者死于院外时，没有预先记录肿瘤进展情况，此时又往往不能尸检，无法确定复发情况。

关于DFS的优缺点探讨可以进一步参考：

https://www.verywellhealth.com/disease-free-survival-dfs-2252148

2. Relapse-free survival（无复发生存期）：首次治疗至肿瘤复发的时间间隔

In cancer, the length of time after primary treatment for a cancer ends that the patient survives without any signs or symptoms of that cancer. In a clinical trial, measuring the relapse-free survival is one way to see how well a new treatment works. Also called DFS, disease-free survival, and RFS.

Ref: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/relapse-free-survival

与上述National Cancer Institute给出的解释略有不同，最近关于癌症中时间-事件终点评估的定义指出，Relapse-free survival的endpoint 不包含 death。

Relapse-free survival is defined as any disease recurrence (local, regional, or distant), but death is censored (not included).

Ref: Definition for the Assessment of Time-to-event Endpoints in Cancer, January 2022，DOI:10.13140/RG.2.2.23392.20483

https://www.researchgate.net/publication/357619646_Definition_for_the_Assessment_of_Time-to-event_Endpoints_in_Cancer

3. Recurrence-free survival

从字面上看Recurrence-free survival 和 Relapse-free survival 是一致的，但确实存在定义上的细微差别

National Cancer Institute 给出的Recurrence 含义：

Cancer that has recurred (come back), usually after a period of time during which the cancer could not be detected. The cancer may come back to the same place as the original (primary) tumor or to another place in the body. Also called recurrent cancer. Recurrence Free Survival is defined as the time interval between the day of reference in the study (date of randomization, date of diagnosis, etc.) and the date of local relapse/recurrence or regional relapse/recurrence or death (all causes) whichever occurs first.

Ref： http://www.360doc6.net/wxarticlenew/979574406.html

The primary endpoint was recurrence-free survival (RFS), which was calculated from the date of surgery to the date of first detected disease recurrence or metastasis by dynamic CT or MRI studies, censoring recurrence-free patients at the date of last follow-up and those who died of other causes.

Ref: EBioMedicine. 2019 Dec;50, PMID: 31735556

二、关于其异同

1. 按照National Cancer Institute 的 词典解释，Disease-free survival 和 Relapse-free survival的含义一致

In a clinical trial, measuring the relapse-free survival is one way to see how well a new treatment works. Also called DFS, disease-free survival, and RFS.

In a clinical trial, measuring the disease-free survival is one way to see how well a new treatment works. Also called DFS, relapse-free survival, and RFS.

Ref: Definition of relapse-free survival - NCI Dictionary of Cancer Terms - National Cancer Institute

2. 研究者支持Disease-free survival 和 Recurrence-free survival的含义一致

Technically they are the same. Disease- free survival studies notes the time to first documentation of relapse/recurrences mostly for comparing efficacy in trials, and recurrence-free survival studies focuses on the onset of recurrence local/regional or distant after a standard treatment.

无病生存研究指出，首次记录复发/复发的时间主要是为了在试验中比较疗效。无复发生存研究集中于标准治疗后局部/区域或远处复发的发生。

Ref: Researchgate: Are the disease-free survival and recurrence-free survival the same definitions in oncology studies?

Ref: What does relapse free survival mean? – Moorejustinmusic

3. Relapse-free survival 与 Recurrence-free survival 的区别在于endpoint是否包含death

In contrast, recurrence-free survival (RFS) includes all-cause death which relapse free-survival does not. It is defined as the time interval between the date of treatment initiation until (a) local or regional disease recurrence or (b) death due to any cause.

Ref: Definition for the Assessment of Time-to-event Endpoints in Cancer, January 2022，DOI:10.13140/RG.2.2.23392.20483

https://www.researchgate.net/publication/357619646_Definition_for_the_Assessment_of_Time-to-event_Endpoints_in_Cancer

小结：目前感觉这三者只具有极细微的差别，且更多体现在临床意义上（2.2中研究者所述），在乳腺癌的研究中更多出现这些不同的定义。通常情况下，生信分析是是基于前期收集的endpoint直接分析，但需要注意，Relapse-free survival 与 Recurrence-free survival 关于 endpoint 是否包含 death 的区别。