DISCUSSION
NSCLC, SCLC, tumor, cancer, hematological malignancies, inflammation, SD, non‐neoplastic diseases, lung cancer, PD, malignant tumor, tumors, PD‐L1
TUMOR, SCLC, INFLAMMATION, HEMATOLOGICAL MALIGNANCIES, CANCER, HYPONATREMIA, LUNG CANCER, NSCLC, MALIGNANT TUMOR, TUMORS, COMPLICATIONS
We developed and internally validated two nomograms for predicting OS and PFS of SCLC patients based on inflammatory markers and other clinicopathological variables. To the best of our knowledge, this was a real‐world study of maximum sample size using nomograms, ROC and DCA to ascertain the prognostic factors of Chinese SCLC patients. Also, the two prognostic nomogram models were the first to include multiple inflammatory biomarkers in SCLC and showed good predictive abilities. Recent studies indicated that, except for some traditional clinical prognostic factors, inflammation could also be critical in the initiation and progression of tumors.But the CRP/ALB ratio (CAR), a novel biomarker, can reflect both systemic inflammation and nutritional status, and calculate using the above two continuous variables, which can reduce the possibility of overestimation or underestimation and stratifies patients to more accurately predict survival. CAR has been proved to be a significant and convenient factor in predicting the short survival of patients with hematological malignancies and solid cancer.Immune cells can easily affect the occurrence and development of cancer. NLR and PLR are also markers indicative of inflammation and immune status, and have been reported to be closely related to the efficacy of immune checkpoint inhibitors in non small‐cell lung cancer (NSCLC) patients.In the last step of the aerobic glycolysis process of malignant tumor cells, LDH is responsible for the catabolism of pyruvate into lactic acid, so the level of LDH symbolizes the activity of tumor cells.Inflammatory markers such as lymphocyte/CRP ratio (LCR) have never been reported in predicting survival in SCLC. Our study showed LCR was only significant in the univariate analysis of OS and PFS. Other factors such as LMR and RDW were not significant prognostic factors in SCLC. Consistent with previous studies, hyponatremia, extensive stage, SD + PD for the best efficacy of first‐line chemotherapy and high NSE level were independently negative prognostic factors both in OS and PFS in our present study. In our study, cut‐off values of the above inflammatory markers were calculated using the survival and survminer packages in R software, while other studies may determine cut‐off values by using X‐tile, ROC curves, or log‐rank statistics, which may lead to different results. In addition, because there will be differences in factors such as region and ethnicity of the included population, and the sample size differs, which may also cause different results between these inflammatory markers.Compared with Xie's and Zhou's studies, we included not only some known prognostic factors of SCLC, such as the level of LDH, NSE, and CEA, but also other inflammatory factors to build more comprehensive nomograms both for OS and PFS. Also, we conducted AUC to determine the discrimination of the nomograms and used DCA to estimate the value of the nomograms with respect to competing benefits and problems. Compared with traditional VALG staging and TNM staging, the nomograms have better prognostic predictive value, which could show better prospects in clinical application. Compared with Qie'sThere are some limitations in our study. First, this was a retrospective study and certain biases were inevitable. A prospective study is warranted to evaluate the nomogram models in the prognostic prediction of the SCLC patients in the future. Also, the nomograms in this study were established and validated internally which should be validated externally on a larger number of patients at multiple institutions. Second, the NCCN Guidelines for SCLC have approved that the PD‐L1 inhibitors combining chemotherapy could be a new standard first‐line treatment for ES‐SCLC patients, but owing to the inaccessibility of drugs or lack of reimbursement by medical insurance companies in China, only 22 SCLC patients received PD‐L1 inhibitors combined with chemotherapy in this study. Whether these prognostic markers are able to predict the efficacy and prognosis of immunotherapeutic patients remains to be further explored. Third, other clinical information such as history of non‐neoplastic diseases and complications were not recorded in our study which may inevitably lead to a certain bias. Finally, our nomograms were mainly built and validated based on the whole 612 SCLC patients. It is well known that there is a difference in survival rate between patients with ES‐SCLC and LS‐SCLC. These predictors may have some bias between SCLC patients of different VALG stages. In spite of these shortcomings, our nomograms were established based on the large sample real‐world evidence of survival of Chinese SCLC patients, and the nomogram models were found to have better stability and accuracy in validation.In conclusion, we constructed and validated nomogram to predict OS and PFS for patients with SCLC. The two nomograms outperform the traditional VALG staging system and provide more accurate prediction for the survival of SCLC patients. Inflammatory markers such as CAR, NLR, and AGR should be used widely to identify SCLC patients who could benefit from immunotherapy and better guide clinical treatment. The two proposed survival prognostic models could be helpful to better guide individualized treatment surveillance and decision.