Construction Of A Prognostic Prediction Model For Small Cell Lung Cancer Patients In First-line Treatment With The Intervention Of Traditional Chinese Medicine

BackgroundLung cancer is a kind of malignant diseases with very high morbidity and mortality domestically and globally,and small cell lung cancer(SCLC)accounts for about 10%-15% of all,commonly happened in the long-run smoking males.SCLC is typical neuroendocrine cancer,and most patients have been found with distantly metastasis at the first diagnosis.Compared with the option of surgery which is limited to SCLC in the very early stage,chemotherapy has been the cornerstone of the first-line treatment of SCLC in the long term.In recent years,chemotherapy in combination with immunotherapy have become the first-line option for SCLC.Radiotherapy is mostly used for adjuvant,preventive or palliative purposes in the management of SCLC.Although SCLC has a high response rate to the standard first-line radiotherapy and chemotherapy,most patients still inevitably relapse within 2 year and the subsequent treatments often have no better response than the first-line therapy.The long-term survival prognosis is extremely poor with the 5-year survival is less than 10%.Traditional Chinese medicine(TCM)has played an important role in the comprehensive management of SCLC.To explore the prognostic characteristics of the intervention of Chinese medicine in the first-line treatment of SCLC and to construct the prediction model about the therapeutic effect can provide us with guidances for the whole management of SCLC with the integration of Chinese and Western medicine in the future,and besides,to distinguish the long-term prognosis of different risk SCLC groups can provide clinicians with more decision-making references and evidence for determining the first-line treatment regimen,which will be helpful for the personalized cancer medicine and bring about more survival benefits to the SCLC patients.PurposesBoth to establish a prediction model for the prognosis of SCLC patients taking the first-line therapy combined with TCM and to explore the prognostic role of TCM in SCLC.Furtherly,to provide references for doctors’ clinical decisions and practices.MethodsBased on a real-world retrospective cohort,patients receiving the first-line treatment of SCLC who were hospitalized at the Cancer Center in Guangzhou University of Chinese Medicine from January 1,2013 to December 31,2019 were included.The demographic characteristics,clinical characteristics,first-line treatment regimens,and follow-up information of the cohort were collected.The collected data will be used for statistical analysis using R project and the major procedures include the description of cohort baseline characteristics as well as the survival data,the screening of variables for predictive model,the construction of a predictive model and a nomogram,the verification and evaluation of the predictive model,and the development of online calculators for our nomogram.At the same time,the relationship between the time of taking Chinese medicine and the overall survival was described and explored.Results(1)The study finally included 146 patients,of which 108 cases had follow-up events(deaths),with a median overall survival time of 21 months and a median follow-up time of 44 months.The majority of the population was non-elderly(58.9%)while 91.1% were men.The median smoking index was 600.Most patients were diagnosed with locally advanced or systemically advanced SCLC,with lesions on the right side slightly more than those on the left side,and lung metastases were more frequently found compared with other organs.Pleural effusion had happened to 43.8% patients.The general KPS scores were greater than 70 points,and most people haved received 4 durations or more of the EP regimen.32.2% cases had received radiotherapy.The Chinese medicine syndrome was frequently characterized by the qi deficiency of lung and spleen or the blockage of phlegm and heat in the lung.The median time of taking Chinese medicine was about 9 months.(2)The multivariate stepwise Cox regression finally found out the best model with 9 variables including age,smoking index,uric acid,primary tumor side,CA125,CA153,lactate dehydrogenase(LDH),red blood cell,and lymphocyte based on the smallest AIC value.(3)In terms with clinical and statistical perspectives,the study finally established a predictive model of 10 variables including age,smoking index,uric acid,primary tumor side,CA125,CA153,LDH,red blood cell,lymphocyte,the classifications of TCM syndrome and so on.The calibration curve indicated that the prediction accuracy of the model was good.The AIC value(878.32),the C index(0.723)and the area under the time-dependent ROC curve also indicate that the prediction performance of this model was significantly better than the TNM staging and the VALSG staging.The DCA curve also showed that the prediction model was of better clinical value.An online calculator was also developed on the website(https://canfeng000.shinyapps.io/Dyn Nomapp/).(4)According to the nomogram scores,the population could be divided into high-risk and low-risk groups with the cutoff value of 253.The OS of the two groups had significant statistical differences,suggesting that the nomogram scores could be well served as an independent predictor of the prognosis of SCLC.(5)The overall time of benefits from taking TCM was about 30 months in this study cohort.The staged III population benefited longest from taking TCM,which is about 36 months while the high-risk group gained the shortest benefit from taking TCM,which is about 16-17 months.Conclusions:Through the review of the real-world data of our cancer center,the characteristics of the first-line treatment population as well as survival figures of SCLC with the intervention of TCM have been well clarified,and the initial prognosis predictive model of SCLC after the first-line treatment with the intervention of TCM has been constructed,which is a more suitable tool in terms of our center settings.The predictive efficiency of the model is found significantly better than the current SCLC staging systems.In addition,the length of benefit of taking TCM as well as the advantage subgroup are initially explored,which would provide some references for clinical practice.However,in view of limitations such as the retrospective design with the single-center samples,and lack of external cohort verification,relevant conclusions and the model are still needed to be continuously evaluated and optimized in the future clinical practice.