1.Measurement of tumor lesions (1) Definition of tumor lesion baseline Tumor lesion baseline is divided into measurable lesions ( at least one measurable lesion ): lesions that can be accurately measured with conventional techniques, lesion diameter length ³20mm or spiral CT ³10mm. Non-measurable lesions: all other lesions (including small lesions i.e. conventional techniques with length diameter <20mm or spiral CT <10mm ) including bone lesions, meningeal lesions, ascites, pleural fluid, pericardial effusion, inflammatory breast cancer, cancerous lymphangitis of the skin or lung, abdominal masses and cystic lesions that cannot be diagnosed and followed up by imaging. Yu-Dong Wang, Department of Gynecology, International Peace Maternity and Child Health Hospital (2) Measurements The same techniques and methods were applied to assess lesions at baseline and follow-up. (a) Clinically superficial lesions such as palpable lymph nodes or skin nodules can be used as measurable lesions, and color photographs with scale size should be used for skin lesions. (b) Chest X-rays: Clearly defined lesions can be used as measurable lesions, but CT scans are preferred. (c) CT and MRI: For determining measurable target lesions to evaluate the efficacy, CT and MRI are currently the best and repeatable follow-up methods. For the thorax, abdomen and pelvis, CT and MRI are scanned with 10 mm or thinner layers, spiral CT is scanned continuously with 5 mm layers, while special protocols are used for the head and neck and special sites. (d) Ultrasound pick-up: When the end poinst of the study is objective tumor efficacy, ultrasound cannot be used to measure tumor lesions, but only superficially palpable lymph nodes, subcutaneous nodules and thyroid nodules, and can be used to confirm the complete disappearance of superficial lesions after clinical examination. (e) Endoscopy and laparoscopy: as objective tumor efficacy evaluation has not been widely and adequately used so far, only in controversial lesions or in high level research centers with clear validation purposes. Biopsy specimens obtained by this method can confirm CR on pathological tissues. (f) Tumor markers: cannot be applied alone to determine efficacy. However, when tumor markers are higher than normal levels before treatment, all markers need to return to normal when CR is clinically evaluated. The requirement for disease progression is that an increase in tumor markers must be accompanied by visible lesion progression. (g) Cytology and pathological histology: In a few cases, cytology and pathological histology can be used to differentiate between CR and PR and to distinguish between benign or residual malignant lesions after treatment. Cytology is needed to differentiate tumor remission, stability and progression for any exudate that occurs during treatment. 2. Evaluation of tumor remission (1) Evaluation of tumor lesions at baseline To establish the total tumor load at baseline, which is compared in subsequent measurements, at least one measurable target lesion, such as a limited number of curved lesions needs to be confirmed histopathologically. (a) Measurable target lesions: All organs involved should be represented, with a maximum of 5 lesions per organ and a maximum of 10 total lesions as target lesions, which should be measured and recorded at baseline. Target lesions should be selected based on lesion length and diameter size and accurate repeatability of measurement. The sum of the lengths of all target lesions is used as the reference baseline for effective remission recording. (b) Non-target lesions: All other lesions should be treated as non-target lesions and recorded at baseline, and lesions that do not require measurement should be noted for their presence or absence during follow-up. (2) Criteria for remission Evaluation of target lesions CR : All target lesions disappeared. PR : Total reduction in the length diameter of the baseline lesions ³ 30%. SD: Reduction in the total length of the baseline lesions but not PR or increase but not PD. PD: Increase in the total length of the baseline lesions ³ 20% or appearance of new lesions. Evaluation of non-target lesions CR: All non-target lesions disappeared and tumor marker levels were normal. PD: One or more new lesions or/and the presence of non-target lesion progression. SD: One or more non-target lesions and/or tumor markers above normal persist. (1) Best remission assessment Best remission assessment refers to the minimum measurement recorded after the start of treatment until disease progression/recurrence (minimum measurement recorded as a reference for progression); those who discontinue treatment due to systemic deterioration, although there is no evidence of PD, should have "symptomatic deterioration" and detailed documentation of tumor progression after discontinuation of treatment. Objective progression. Patients with early progression, early death, and those who cannot be evaluated should be identified. In some cases, it is difficult to distinguish between residual tumor lesions and normal tissues. When evaluating CR, a fine needle aspiration or biopsy should be used to examine the residual lesions before confirmation after 4 weeks. (2) Frequency of tumor re-evaluation The frequency of tumor re-evaluation is determined by the treatment plan. In fact, the benefit time of treatment is unclear, and re-evaluation every 2 cycles (6-8 weeks) is reasonable, which should be adjusted to shorter or longer time in special cases. After the end of treatment, the tumor needs to be re-evaluated to determine the end points of the clinical trial, whether it is the remission rate or the time to event (Time to event, TTE) i.e. time to progression/time to death (Time to progression, TTP/Time to death, TTD) If it is TTP/TTD then a routine repeat evaluation is needed. There are no strict rules for the interval between second assessments. (3) Confirmation The objective of objective efficacy confirmation is to avoid high RR, and changes in CR and PR tumor measurements must be confirmed by repeated judgments and must be reviewed and confirmed at least 4 weeks after the first evaluation, and longer confirmation determined by the trial protocol is also appropriate. patients with SD have at least one SD for lesion measurements at a minimum interval of 6-8 weeks after treatment. for patients with progression-free survival ( For clinical studies with end points of Progression-free survival (PFS) and Overall survival (OS), repeated confirmations of tumor size changes are not required. (4) Remission period is from the first measurement of CR or PR until the first disease recurrence or progression. (5) Stable phase is the time from the start of treatment to disease progression. The clinical relevance of SD phase varies with different tumor types and degrees of differentiation. The remission stage, stable stage and PFS are influenced by the frequency of follow-up after baseline evaluation. Due to the influence of various factors such as the type of disease, stage, treatment cycle and clinical practice, the basic frequency of follow-up can not be determined yet, which affects the accuracy of the trial end points to some extent. (6) PFS/TTP In some cases (such as brain tumor or non-cytotoxic drug studies) PFS/TTP can be considered as end points of the study, especially for the initial evaluation of biological drugs with non-cytotoxic mechanisms of action. (7) Independent expert committee For CR, PR is the main end points of the study, it is emphasized that all remissions must be examined by an independent expert committee outside the study. 4. Outcome reporting All patients in the trial including those who deviated from the treatment regimen or failed must be judged for efficacy to treatment (Intend to treatment, ITT) and each patient must be classified as follows CR, PR, SD, PD, died of tumor, died of toxicity, died of other tumor, unknown (not enough information to assess). All patients meeting the criteria for eligibility should be included in the analysis of RR, and all PD and death should be considered as treatment failure. Conclusions are based on patients meeting the criteria, and subsequent further analyses can be performed in different subgroups of patients and provide a 95% confidence limit interval.