Response Evaluation Criteria in Solid Tumors

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Response Evaluation Criteria In Solid Tumors ( RECIST ), for example criteria for evaluating the response to treatment in solid tumors , is a collection of published rules that aim to objectify the evaluation of the treatment success of cancer in medical research studies. The rules define exactly when a cancer disease declines (“responds”), remains unchanged (stable) or progresses ( progression ) under therapy . The criteria were published in February 2000 by an international working group which u. a. the EORTC and the study groups of the national cancer institutes in the USA and Canada, and the Netherlands-based NDDO-Oncology .

The current version 1.1 is from January 2009. Most clinical studies on cancer therapies now use RECIST. The revision concerns some simplifications and clarifications, for example for measurements on lymph nodes .

Patient suitability

  • In study protocols that evaluate the objective response rate, only patients should be included who have a measurable disease at the beginning , i. H. at least one measurable lesion (tumor, metastasis, etc.). If there is only a single lesion, it should be confirmed as a malignant neoplasm by cytodiagnosis or histology .
  • Measurable lesions ( measurable lesions ) are those whose size in one dimension at least at least 20 mm (in the conventional imaging ) or at least 10 mm (in the helical CT is) and can be specified exactly. All other lesions are considered immeasurable in the sense of RECIST; z. B. bone metastases , meninges , ascites , pleura and pericardium , inflammatory breast cancer , lymph vessel involvement of the skin or lungs, cystic lesions, and masses in the abdominal cavity that are not confirmed by imaging procedures.
  • All measured values ​​should be recorded metrically with a measuring stick or caliper . The initial values ​​should be recorded as close as possible to the start of therapy, at least four weeks in advance.
  • The same method and technique as at the beginning should always be used to assess the progression of each individual lesion.
  • Purely clinically documented lesions are only considered measurable when they are superficial, d. H. in the skin or in palpable lymph nodes . It is recommended to document skin lesions with color photos, on which a measuring stick is shown for size comparison.

Measurement methods

  • Computed tomography and magnetic resonance imaging (MR) are currently the best available and reproducible methods to measure the selected target lesions. Conventional CT and MR should deliver slices no thicker than 10 mm, and spiral CT 5 mm thick reconstructions, both without a slice gap. This refers to tumors in the chest, abdomen, and pelvis. Tumors in the head and neck area and extremities usually require special examination protocols.
  • X-ray lesions of the lungs are acceptable if they are surrounded by ventilated lung tissue and can be clearly demarcated. Even then, however, a CT is preferable.
  • If the primary endpoint of a study is objective therapy efficacy, lesions should not be measured solely with ultrasound . Ultrasound is a possible alternative to clinical measurements on superficial, palpable lymph nodes, nodes in the subcutaneous tissue, and in the thyroid gland. It can also document the complete disappearance of superficial lesions that have previously been clinically examined.
  • Reflections and laparoscopy have not yet been finally validated as a means of objectifying the size of the tumor. This application requires excellent equipment and training of the users, which are only available in some centers. Therefore, these methods of measuring objective tumor response should be reserved for specialized centers. However, they can serve to ensure a complete remission biopsy.
  • The effectiveness of the therapy cannot be assessed with tumor markers alone. If, however, the markers were elevated before the start of therapy, they must fall within the normal range in order to determine a complete remission, even if all the visible lesions have already disappeared.
  • In individual cases, only cytology and histology can differentiate between partial and complete remission. B. if benign masses remain after the treatment, such as germ cell tumors .

Initial documentation of the target and non-target lesions

  • All measurable lesions, up to a maximum of two lesions per organ and five lesions in total, representative of all affected organs, should be identified as target lesions and measured before starting treatment.
  • The largest lesions should be selected, if any, or those best suited for repeated accurate measurement.
  • The longest diameters (LD) of all target lesions are added up and recorded as the starting LD sum. This value will later be used as a reference when quantifying the tumor mass.
  • All other lesions (or diseased regions) are identified as non-target lesions and should also be documented at the beginning. Such lesions do not need to be measured, but their presence or absence should be noted during the observation period.

Criteria of addressing

Target lesions

  • Complete response (Engl. Complete response / remission , CR) all target lesions have disappeared.
  • Partial remission (PR): The total LD ​​of the target lesions has decreased by at least 30% compared to the base value.
  • Stable disease ( stable disease , SD): Neither PR nor PD
  • Progression ( progressive disease , PD): The total LD ​​has increased by at least 20% compared to the lowest value reached, or new lesions have formed.

Non-target lesions

  • Complete remission (CR): All non-target lesions have disappeared, all tumor marker concentrations are back in the normal range.
  • Incomplete remission / stable disease (SD): One or more non-target lesions have remained and / or tumor marker concentrations remain elevated.
  • Progression (PD): one or more new lesions, and / or definite increase in size of existing non-target lesions

Overall response

The overall response is determined after evaluating the target, non-target, and any new lesions.

Target lesions Non-target lesions New lesions Overall response
CR CR No CR
CR SD No PR
PR Non-PD No PR
SD Non-PD No SD
PD (no matter) (no matter) PD
(no matter) PD (no matter) PD
(no matter) (no matter) Yes PD
  • The best overall response is the best response achieved in the period from the start of treatment to progression. As a rule, this information is secured by additional controls.
  • If the general condition of a patient deteriorates to such an extent that the therapy has to be discontinued without there being any objective progression, a “ symptomatic deterioration ” is noted. Even after discontinuation of treatment, objective criteria for progression should still be sought.

validation

  • Sometimes it is difficult to distinguish remaining tumor tissue from normal tissue (scar, etc.). If the classification as complete remission depends on it, it is recommended that the lesion be clarified by means of a biopsy or fine-needle biopsy.
  • The objective response must be ensured in order not to overestimate the response rate of the treatment. Unsecured data should be disclosed as such upon publication.
  • To achieve PR or CR status, the corresponding measurements must be repeated after four weeks at the earliest. Longer periods may be appropriate and will be specified in the study protocol.
  • For an SD, the corresponding measurements must adhere to a minimum interval specified in the study protocol; at least 6–8 weeks are usual.

rating

  • The duration of the overall response is the time from the first achievement of the criteria for CR or PR to the date on which PD or a relapse of the disease are objectively documented. PD is always seen on the basis of the lowest measured values ​​in the entire course of treatment.
  • The duration of SD is calculated from the start of treatment to progression.
  • The clinical significance of such periods of time depends on the particular cancer disease. It is therefore strongly recommended that the study protocol specify the minimum distance between two measurements, taking into account the expected clinical benefit of a status "SD" for the patient.
  • If the response rate is the study endpoint, it is highly recommended that any responses be reviewed by independent experts, preferably using medical records and x-rays.
  • All patients once enrolled in the study must be evaluated, even if they do not meet the entry criteria or if there were gross deviations from the treatment protocol. Each patient is assigned to one of the following categories: 1) complete remission, 2) partial remission, 3) stable disease, 4) progression, 5) early death from cancer, 6) early death from side effects of therapy, 7) early death from other reasons , or 9) History unknown (not available, incomplete data, etc. The use of the number “9” for such data categories is common). Precise definitions of categories 1-7 and 9 are a matter of the study protocol.
  • All cases that meet the study criteria should be included in the calculation of the response rate, categories 4–9 as non-responses. Treatment errors do not result in the case being excluded from the evaluation.
  • The conclusions should be based on the complete data. Although sub-analyzes may be carried out with selected patients, e.g. B. without those in whom the treatment was stopped early or carried out differently than planned, without the deaths for other reasons, etc., but these sub-analyzes cannot be used to make statements about the effectiveness of the treatment. The reasons for excluding some patients from these analyzes must be specified.
  • The 95% confidence intervals should be given.

Sources and individual references

  1. ↑ Therasse P, Arbuck SG, et al .: New Guidelines to Evaluate the Response to Treatment in Solid tumor. Journal of the National Cancer Institute 2000 92 (3): 205-216] doi : 10.1093 / jnci / 92.3.205
  2. ↑ Eisenhauer EA, Therasse P, Bogaerts J, et al. : New response evaluation criteria in solid tumors: revised RECIST guideline (version 1.1) . In: Eur. J. Cancer . 45, No. 2, January 2009, pp. 228-47. doi : 10.1016 / j.ejca.2008.10.026 . PMID 19097774 .
  3. ↑ Therasse P, Eisenhauer EA, Verweij J: RECIST revisited: a review of validation studies on tumor assessment . In: Eur. J. Cancer . 42, No. 8, May 2006, pp. 1031-9. doi : 10.1016 / j.ejca.2006.01.026 . PMID 16616487 .

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