Author: Peking University cancer hospital renal cell melanoma Sheng XinanIn recent ten years, the treatment of advanced renal cell carcinoma
Author: Peking University cancer hospital renal cell melanoma Sheng Xinan
In recent ten years, the treatment of advanced renal cell carcinoma has developed rapidly. Since 2005, Sola Fini has approved the listing, there are 7 kinds of targeted drugs for the treatment of advanced renal cell carcinoma, anti angiogenesis targeted therapy is becoming the main treatment of advanced renal cell carcinoma, tumor of renal cell carcinoma is all solid tumors using drugs targeting the most. Anti tumor therapy to the era of chemotherapy application based solid tumor efficacy evaluation standard: RECIST, because can not fully meet the targeting characteristics, constantly under rated efficiency standards for new challenges, such as the Choi standard, MASS standard. With the end of 2015, the immunosuppressive agent nivolumab monoclonal antibody approved for the treatment of advanced renal cell carcinoma, the irRC standard for immunotherapy has also been used in the field of renal cell carcinoma. In this paper, the author will discuss the advantages and disadvantages of these standards, and how to use the content.
Before the emergence of targeted drugs, renal cell carcinoma as other solid tumors, by relying on the cytotoxic drug era established WHO (WHO) to evaluate the efficacy of cancer treatment standard; subsequently improved by 2000, the European Organization for research and treatment of cancer in American National Cancer Institute and the National Cancer Institute of Canada launched a joint evaluation entity in the standard (RECIST), revised in 2009 as we currently use RECIST version 1.1. Although the RECIST standard established in the era of chemotherapy, the tumor size was measured to evaluate the imaging condition, but this is the focal point of tumor treatment center, so for the targeted treatment of advanced renal cell carcinoma, RECIST is still the main standard of curative effect evaluation. At present, the clinical efficacy of all targeted drugs, including nivolumab, were evaluated by RECIST standard.
However, for the treatment of renal cell carcinoma targeted drugs, the main mechanism is anti angiogenesis, but not directly kill the tumor, so most of the role is reflected in inhibiting the growth of tumor cells, the tumor, the tumor size may be stable, no change. So the first targeted therapy of advanced renal cell carcinoma, obtained complete remission (CR) rate is very low, and stable disease (SD) is close to 50%, or even individual drugs such as Sola Fini effect based on SD, reached about 70%, according to the RECIST standard to evaluate whether the treatment with CR or partial remission (PR) as the representative of the efficiency can not fully reflect the degree of benefit brought by the illness.
In addition, Sola Fini, sunitinib, targeted drug therapy often causes central tumor necrosis or cystic cavity formation, without causing tumor size reduction, these conditions often lead to an underestimate of the effect evaluation. Some of the most extreme manifestations, such as intra tumor hemorrhage, are characterized by an increase in the volume of the tumor, and RECIST criteria may be used to assess the progression of the disease (PD). Therefore, it is necessary to evaluate the curative effect of targeted drugs for renal cell carcinoma.
Choi standard and MASS standard
Introduction of CT value as the measurement index of tumor efficacy evaluation criteria
The process of Choi in gastrointestinal stromal tumor received imatinib treatment, the tumor size and density changes occur without obvious changes or even increased, according to the RECIST standard can not be considered effective, and may determine the treatment progress. In order to improve this defect, in 2007, Choi, an American scholar, put forward the standard of evaluating the effect of the combination of tumor size and density on the quality of Choi (Table 1).
Choi standard considers the change of tumor density caused by targeted drug therapy, so it has been applied to the targeted therapy of advanced renal cell carcinoma. In the sunitinib in the treatment of patients with metastatic renal cell carcinoma, Choi efficacy evaluation criteria is beneficial to early recognition from sunitinib benefit in patients with RECIST than the standard of progression free survival (PFS) and overall survival (OS) has a better predictive value. Similarly, a retrospective analysis found that sunitinib or sorafenib treated patients, the assessment results obtained with PR Choi standard, the PFS and OS benefit was significantly better than SD or PD patients, according to the RECIST standard, PR patients compared with other patients failed to obtain significant survival benefit, suggesting that Choi standard can better reflect the remission bring survival benefit.
However, Choi standard is still used in many cases of gastrointestinal stromal tumors, and it is lack of data and basis for large-scale application. In the Chinese society of Clinical Oncology (CSCO) used in previous RECIST standard evaluation for the progress of Choi standard reference formulation of the Committee of experts "China kidney" in the guidelines for the diagnosis and treatment of renal cell carcinoma and confirmed for the Choi benchmark is not up to the progress of patients still suggest that the original program continue to targeted therapy.
The MASS standard in 2010 American Smith (Smith), based on the standard of Choi, according to tumor size, CT value change and enhancement of the renal cell carcinoma targeted therapy of MASS (morphology, attenuation, size, and, structure) standard. The standard changed the efficacy of traditional RECIST four points, the efficacy of three into response (favorable response), stable (indeterminate response) and unfavorable. Compared with the previous Choi standards, MASS standards will be some special CT enhancement (first part of central necrosis appeared obvious enhancement; originally uniform enhancement of low CT value area of new enhancement) defined as progress.
The study found that MASS standard evaluation effect on clinical prognosis better (such as PFS for more than 250 days) the sensitivity of 87%, specificity of 100%; and compared to the RECIST standard, the sensitivity was 17%, specificity was 100%. Due to the strengthening factor, the CT enhanced scan has higher requirements, so the standard is higher than the Choi standard.
Immune related efficacy criteria (irRC)
In recent years, nivolumab monoclonal antibody (PD-1), which has been a breakthrough in the treatment of advanced renal cell carcinoma, has been recommended by the national comprehensive cancer network (NCCN) guidelines for second-line therapy for advanced renal cell carcinoma. Compared with the previous targeted drugs, immunotherapy onset time may be longer, and may appear in the traditional sense of the progress of disease, the interrupt is not suitable for immunotherapy, and also the emergence of new lesions do not represent ineffective treatment, so evaluating curative effect of immunotherapy should be devoted to the standard, but also
Immune related efficacy evaluation criteria (irRC). All the lesions were considered as a whole, and the appearance of new lesions was no longer regarded as the progression of the disease, but was evaluated as the total tumor burden. In 2009, the irRC standard based on double diameter measurement will be the progress and the effective threshold is set to 25% and 50%, and in the year of 2013 proposed a new standard based on single diameter measurement, its progress and effective threshold has been consistent with the RECIST standard.
The irRC standard has been raised since 2009, 71% (10/14) immunotherapy clinical research related to not be as the main standard of curative effect evaluation, still using the RECIST standard, just as the emergence of RECIST determination for the progress of clinicians reference factor. Most of the studies on the immune related efficacy evaluation data reported in the literature are used in the clinical study of melanoma immunotherapy. Clinical study of Nivolumab monoclonal antibody to the RECIST 1.1 standard is still carried out as the main effect of assessment standards, "2015 issue of the Journal of Clinical Oncology" (J Clin Oncol) nivolumab monoclonal antibody phase II clinical study published in the RECIST irRC standard and simultaneously announced the results, they obtain the objective response rate (ORR) were 21% and 23%, which only 3 cases (1.8%) with the emergence of the so-called "pseudoprogression", namely the RECIST criteria for the progress of irRC standard for assessing the effectiveness of effective, PFS and corresponding OS data has not been announced, but a number of other related irRC standard evaluation. The research samples are relatively low, it is difficult to analyze.
Although the RECIST standard evaluation to the curative effect in renal cell carcinoma target problems, but the Choi standard, MASS standard and irRC standard simply make up some defects, has not been widely used clinically, more in the exploration and practice stage increased, there is still no can completely replace the RECIST standard, so the evaluation standard of the primary efficacy study with the RECIST standard is still in clinical practice. Clinicians should according to the actual situation, the new standard and RECIST standard combined with flexible application, especially the change of cavity, cystic density occurs in the treatment of PD-1 and monoclonal antibody treatment stage of disease progression, should use the new standards to determine whether true progress is considered.
(Editor: Huang Leilei, China Medical Tribune)