Background/AimIndices based on the white blood cell (WBC) count and WBC differential count are simple and can be easily calculated using routine blood tests. Many studies have examined the usefulness of these indices for predicting prognosis for various cancers, including lung cancer. However, no studies have focused on the relationships between indices based solely on WBC and WBC differential counts and the prognosis of patients with extensive-stage small cell lung cancer (ES-SCLC). The aim of this study was to evaluate the prognostic value of indices based on WBC and WBC differential counts in patients with ES-SCLC treated with platinum-doublet chemotherapy.Patients and MethodsThe pretreatment neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), neutrophil-to-monocyte ratio (NMR), monocyte-to-lymphocyte ratio (MLR), neutrophil-to-WBC ratio (NWR), lymphocyte-to-WBC ratio (LWR), monocyte-to-WBC ratio (MWR), neutrophil-to-eosinophil ratio (NER), lymphocyte-to-eosinophil ratio (LER), monocyte-to-eosinophil ratio (MER), eosinophil*neutrophil-to-lymphocyte ratio (ENLR), systemic inflammation response index (SIRI), and inflammatory related ratio (IRR) of patients with ES-SCLC who were treated with platinum-doublet chemotherapy as first-line treatment at Kainan Hospital were retrospectively analyzed.ResultsData from 102 patients were analyzed. On multivariate analysis, patients with low MLR, MWR, NER, MER, and IRR values had significantly longer overall survival (OS) than patients with high MLR, MWR, NER, MER, and IRR values. In addition, patients with low WBC and monocyte counts had significantly longer OS than patients with high WBC and monocyte counts.ConclusionIndices based on WBC and WBC differential counts, especially monocyte-related indices, may be useful markers for predicting the prognosis of patients with ES-SCLC treated with platinum-doublet chemotherapy.

Thoracic radiotherapy plus maintenance durvalumab after first line carboplatin and etoposide plus durvalumab in extensive-stage disease small cell lung cancer (ES-SCLC) - A multicenter single arm open label phase II trial (SAKK 15/19).

Consolidative thoracic radiotherapy (RT) following chemo-immunotherapy is increasingly used in extensive-stage small cell lung cancer (ES-SCLC). This study investigates the prognostic value of the estimated radiation dose to immune cells (EDRIC) and its determinants in these patients. This retrospective study included 173 ES-SCLC patients between 2020 and 2023. EDRIC was calculated as a function of the number of fractions and the average doses to the lungs, heart, and remaining body. Kaplan-Meier and Cox regression analyses were performed to evaluate overall survival (OS) and progression-free survival (PFS). GTV, PTV, and N stage were positively correlated with EDRIC (r = 0.2577, p = 0.0006; r = 0.3541, p < 0.01; r = 0.2259, p = 0.0028), while lymphocyte nadir was negatively correlated (r = -0.2190, p = 0.0038). Median OS and PFS were longer in the EDRIC ≤4.68 Gy group (OS: 24.9 vs. 17.4 months, p = 0.003; PFS: 12.4 vs. 10.1 months, p = 0.038). Patients in the EDRIC ≤4.68 Gy group had significantly better OS (HR = 0.56, p = 0.003) and PFS (HR = 0.68, p = 0.039). Bone metastasis was associated with worse OS (HR = 1.88, p = 0.002), and liver metastasis with shorter PFS (HR = 2.05, p = 0.001). EDRIC is an independent predictor of OS and PFS in ES-SCLC. These findings highlight the need to optimize radiation exposure to the immune system in cancer treatment.

Low-dose Radiation Therapy Concurrent With Atezolizumab and Chemotherapy as First-Line Treatment for Extensive-Stage Small Cell Lung Cancer: 3-Year Follow-up of a Multicenter, Single-arm, Phase 2 Trial (MATCH).

This first IPD meta-analysis evaluating RMST and RMTL as alternative endpoints in ES-SCLC demonstrates that these measures generally align with HR, with some exceptions. Given their clinical interpretability and ability to quantify survival benefit, RMST and RMTL should be considered as endpoints in future ES-SCLC trials.

Targeted precision Strike in Extensive-Stage small cell lung Cancer: Current advances and future Perspectives for Antibody–Drug conjugates

A multi-institutional perspective on tarlatamab administration and management of CRS/ICANS.

Background and purposeCurrent evidence is insufficient to define the value of thoracic radiotherapy (TRT) following chemoimmunotherapy (CT‐IO) in extensive‐stage small‐cell lung cancer (ES‐SCLC). We aimed to ascertain whether incorporating immunotherapy (IO) could improve survival and explore the efficacy of TRT in combination with CT‐IO among patients with ES‐SCLC.MethodsClinical data were retrospectively analyzed. Patients were classified into two groups: IO and chemoradiotherapy (CRT). Within the IO group, we further defined two subgroups: CT‐IO and chemoradioimmunotherapy (CRT‐IO) groups.ResultsA total of 206 patients were enrolled in this study. The median overall survival was 22.2 months in the CRT‐IO group, which was longer than the 16.0 months observed in the CT‐IO group (P = 0.002) and 19.0 months noted in the CRT group (P = 0.208). The objective response rate (ORR) in the CRT‐IO group (69.8%) was better than that in the CT‐IO (68.9 %, P = 0.929) and CRT (59.3 %, P = 0.227) groups.ConclusionsConsidering the trend toward prolonged survival and a higher ORR in the CRT‐IO group, TRT may be feasible in IO era. Considering the economic factors and physical conditions, CRT may be an option for patients with ES‐SCLC.

BackgroundThe NCT04878016 trial evaluated the efficacy and safety of socazolimab in combination with carboplatin/etoposide as a first-line treatment for extensive-stage small cell lung cancer (ES-SCLC). This study aims to analyze the cost-effectiveness of this combination regimen from the perspective of the Chinese healthcare system.MethodA Markov model with three health states was constructed. The model simulated a time horizon of 10 years with a cycle length of 3 weeks. Costs and utilities were discounted at 5% annually. The primary outcomes were total costs, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER). One-way sensitivity analysis and probabilistic sensitivity analysis were conducted to assess the robustness of the results.ResultsThe base-case analysis showed that the ICER for the socazolimab group compared to the chemotherapy-alone group was 355,316.95 yuan/QALY, which exceeds three times China’s per capita GDP in 2024 as the willingness-to-pay (WTP) threshold. One-way sensitivity analysis revealed that PD utility, PFS utility, socazolimab cost, and neutropenia management cost had significant impacts on model results. Probabilistic sensitivity analysis indicated that the probability of socazolimab combined with chemotherapy being cost-effective was 21.9%.ConclusionAt China’s WTP threshold, socazolimab combined with chemotherapy is not cost-effective versus chemotherapy alone for ES-SCLC.

The NCT04878016 trial evaluated the efficacy and safety of socazolimab in combination with carboplatin/etoposide as a first-line treatment for extensive-stage small cell lung cancer (ES-SCLC). This study aims to analyze the cost-effectiveness of this combination regimen from the perspective of the Chinese healthcare system. A Markov model with three health states was constructed. The model simulated a time horizon of 10 years with a cycle length of 3 weeks. Costs and utilities were discounted at 5% annually. The primary outcomes were total costs, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER). One-way sensitivity analysis and probabilistic sensitivity analysis were conducted to assess the robustness of the results. The base-case analysis showed that the ICER for the socazolimab group compared to the chemotherapy-alone group was 355,316.95 yuan/QALY, which exceeds three times China's per capita GDP in 2024 as the willingness-to-pay (WTP) threshold. One-way sensitivity analysis revealed that PD utility, PFS utility, socazolimab cost, and neutropenia management cost had significant impacts on model results. Probabilistic sensitivity analysis indicated that the probability of socazolimab combined with chemotherapy being cost-effective was 21.9%. At China's WTP threshold, socazolimab combined with chemotherapy is not cost-effective versus chemotherapy alone for ES-SCLC.

PurposeSmall cell lung cancer (SCLC) is a highly aggressive malignancy with poor prognosis. Studies capturing the impact of recently approved immunotherapies are limited, highlighting a knowledge gap regarding their real-world use and effectiveness. Patients and MethodsWe examined data from 29949 patients with extensive-stage (ES)-SCLC across observational studies from the United States, United Kingdom, Spain, Taiwan, South Korea, and Japan to describe the clinical course of ES-SCLC. Data sources included electronic health record databases, registries, and claims data over time periods ranging between 2013 and 2023. Patient characteristics, recent treatment patterns, and real-world overall survival (rwOS) were assessed in each country.ResultsThe most common first-line (1L) treatment was platinum plus etoposide without anti-PD-L1 agents (59–89%), followed by platinum plus etoposide with anti-PD-L1 agents (9–38%). Second-line (2L) and third-line (3L) treatments varied widely across countries. Median rwOS ranged from 8.1–11.3 months following 1L initiation, 4.8–6.9 months following 2L, and 4.1–5.5 months following 3L. Patients receiving compared to those not receiving 1L anti-PD-L1 therapy showed numerically higher median rwOS following 1L initiation, with no meaningful difference in rwOS following 2L or 3L therapy.ConclusionIn our evaluation of real-world treatment patterns and outcomes among patients with ES-SCLC from six countries, we found that rwOS in 1L, 2L and 3L was consistently poor across countries, despite differences in patient characteristics and treatment patterns. These findings may support the generalizability of clinical evidence across geographies and highlight the need for further research to optimize treatment strategies to improve patient outcomes globally.

Th7R is a novel Th1-like CD4+ T cell lineage characterized by TCF7 and IL-7 receptor expression, exhibiting distinct transcriptional and epigenetic profiles compared with classical Th1 cells. The clinical significance of Th7R, including the efficacy of immune checkpoint inhibitors and the prediction of postoperative disease-free survival, has been demonstrated in non–small cell lung cancer (NSCLC) but not in small cell lung cancer (SCLC). In this study, we investigated Th7R expression as a predictive marker in patients with extensive-stage SCLC (ES-SCLC) who received chemotherapy or chemo-immunotherapy (n = 47). Results showed that Th7R was positively correlated with progression-free survival (PFS) after treatment and that long-term PFS was observed only in patients with Th7Rhigh who were treated with anti-programmed cell death-1 ligand 1 (PD-L1) antibody combination therapy. Furthermore, high Th7R levels were associated with significantly better overall survival. Th7R showed a positive correlation with GZMB−GZMK+ precursor exhausted CD8+ T cells (Tpex), which are known target cells for PD-1 blockade therapy. These findings suggest the presence of the Th7R–Tpex axis. Th7R, which reflects antitumor T-cell immunity, is a useful predictive marker for treatment efficacy in ES-SCLC.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00262-025-04242-6.

Emerging evidence suggests that circadian timing influences the efficacy of immune checkpoint inhibitors (ICI), with morning infusions associated with improved therapeutic outcomes across various malignancies. However, the impact of ICI infusion timing on extensive-stage small cell lung cancer (ES-SCLC), a disease with poor prognosis and limited therapeutic advancements, remains unexplored. This retrospective study (LungTime-R02) analyzed 397 patients with ES-SCLC who received first-line anti-PD-L1 (atezolizumab or durvalumab) plus chemotherapy at our center between May 2019 and October 2023. The time of day of administration (ToDA) was calculated as the median infusion time for each patient's first four ICI treatment cycles. To assess its prognostic relevance, hazard ratios (HRs) of earlier progression or death were estimated across multiple ToDA thresholds (11:00-16:30). Propensity score matching (1:2) was applied to balance baseline characteristics. Of the 397 patients, the optimal ToDA cutoff for maximizing progression-free survival (PFS) benefit was identified as 15:00, with the lowest HR for PFS observed at this threshold. Patients who received immunochemotherapy before 15:00 exhibited significantly longer PFS and overall survival compared to those treated later, with results consistent across pooled and propensity score matching cohorts. Multivariable analysis confirmed early ToDA as an independent prognostic factor for both PFS (adjusted HR, 0.483; 95% CI, 0.357-0.654) and overall survival (adjusted HR, 0.373; 95% CI, 0.265-0.526). This study provides real-world evidence supporting the survival benefit of earlier immunochemotherapy administration in patients with ES-SCLC. These findings add to the growing body of knowledge on the clinical relevance of circadian timing in cancer treatment. Not applicable.

ObjectiveThis study aimed to explore the value of clinical-radiomics features for predicting response to immunotherapy in extensive-stage small cell lung cancer (ES-SCLC).MethodsThis retrospective study enrolled patients with ES-SCLC who received immunotherapy as first-line treatment from two centers. Patients were divided into a training and an external test cohort. Chest Computed Tomography (CT) images were obtained at baseline and after 2–3 cycles of immunotherapy. Each lesion was segmented based on intratumoral regions (ITR) in the plain scan (PS) and venous phase (VP) CT images. Radiomic features, including absolute and relative delta features were extracted. Four signatures were established by the least absolute shrinkage and selection operator (LASSO) after selecting relevant features. Multivariable logistic regression incorporating signature scores and clinical predictors was used to generate a nomogram. The performance of the nomogram was evaluated through area under the curves (AUC) analysis, calibration curves, and decision curve analysis (DCA). Tertiary lymphoid structures (TLS) and the tumor immune microenvironment (TIME) of tumors were investigated via multiplex immunohistochemistry (mIHC). Kaplan-Meier curves were constructed to illustrate Overall Survival (OS) in different patients groups.ResultsThe nomogram was built based on two radiomics signatures (ITR before treatment; relative delta radiomics) and two clinical factors (age; node). This model showed powerful predictive ability for both training and external test sets with AUCs of 0.919 and 0.839, respectively. Calibration curves and DCA showed a favorable predictive performance of the nomogram.ConclusionThe nomogram that included ITR, delta radiomic features, and clinical risk factors had the best performance in predicting prognosis for patients with ES-SCLC who received immunotherapy compared to models relying solely on radiomic features or clinical risk factors, and has the potential to assist clinicians in making personalized treatment decisions.

Consolidative thoracic radiotherapy in the immunotherapy era for extensive-stage small cell lung cancer: a systematic review and meta-analysis with emphasis on brain and liver metastases.

PurposeTo investigate the predictive value of peripheral blood neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), neutrophil percentage-to-albumin-ratio (NPAR), and D-dimer in the efficacy and prognosis of immunotherapy for extensive-stage small cell lung cancer (ES-SCLC).Patients and MethodsA total of 70 ES-SCLC were included. The diagnostic performance of inflammatory indexes and D-dimer in predicting the efficacy and prognosis of immunotherapy was evaluated using receiver operating characteristic curve (ROC). Disease control rate (DCR) was used as the assessment indicator for immunotherapy efficacy, and progression free survival (PFS) > 6 months was used as the judgement indicator for better prognosis. Using Lasso regression and logistic multivariate analysis to predict the efficacy and prognosis of immunotherapy, and the optimal cut-off value was determined according to the area under the ROC curve. Kaplan-Meier survival analysis was applied to compare survival differences between groups.ResultsAt baseline, PLR can predict the efficacy of immunotherapy in ES-SCLC patients, but cannot predict their prognosis. After two cycles of immunotherapy, NLR can not only predict the efficacy and prognosis of immunotherapy, but also be identified as an independent predictor of long-term PFS in multivariate analysis (P<0.01). The long-term PFS rate of the low NLR2 group (<2.2) was significantly higher than that of the high NLR2 group (≥ 2.2) (P<0.001), with median PFS of 4.83 months vs 9.9 months, respectively, P<0.001.ConclusionAfter two cycles of chemotherapy combined with immunotherapy, the efficacy and prognosis of NLR and ES-SCLC immunotherapy are closely related and can serve as effective and reliable predictive indicators.

Despite a good response to first-line chemotherapy, small-cell lung cancer (SCLC) has high relapse rates and a poor prognosis. We conducted a systematic review and meta-analysis to assess the role of immune checkpoint inhibitors (ICIs) in the treatment of extended stage SCLC (ES-SCLC), in different lines of therapy. Medline (PubMed), EMBASE, and Cochrane Library databases between January 2010 and March 2025 and conference proceedings between 2018 and 2025 were searched for RCTs assessing ICIs versus chemotherapy in patients with ES-SCLC. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR) and grade 3+ adverse events. Pooled hazard ratios (HR) for OS and PFS were meta-analyzed using the generic inverse variance method, and random-effect models were used to compute pooled estimates. Subgroup analyses compared survival by line of therapy, sex, age, and ECOG status. ICIs decreased risk of death by 19% (HR: 0.81, 95% CI: 0.76-0.86). OS benefit was regardless of age, sex, or ECOG, but only in first-line treatment. ICIs decreased the risk of disease progression by 22% (HR: 0.78, 95% CI: 0.67-0.91), with PFS benefit restricted to first-line treatment with a detrimental effect in the second line. ICIs improved ORR (OR: 0.79, 95% CI: 0.66-0.95), but were associated with increased grade 3+diarrhea (OR: 3.63, 95% CI: 1.46-9.02). ICIs conferred efficacy benefits and an acceptable safety profile in the treatment of patients with ES-SCLC in the first-line, but should not be used in the second-line as single agents. Biomarkers predicting long-term benefit are needed to further improve outcomes.

ObjectiveTo assess the cost-effectiveness of toripalimab plus etoposide and platinum (EP)-based chemotherapy as a first-line treatment for extensive-stage small cell lung cancer (ES-SCLC) from a Chinese healthcare system perspective, and to explore the impact of factors such as biomarker stratification, drug wastage, and drug donation on cost-effectiveness.MethodsA partitioned survival model was conducted to simulate the disease progression in ES-SCLC patients. Model parameters were derived from the EXTENTORCH clinical trial, public databases, and published literature. Key outcomes included total cost, quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), and incremental net monetary benefit (INMB). Drug wastage was quantified based on body surface area, and patients were stratified according to biomarkers. Sensitivity analysis and scenario analysis were conducted to assess model stability.ResultsOver a 10-year simulation period, the total cost of toripalimab plus EP was $28,551.37, with a QALYs of 0.75; the total cost of EP was $24,678.81, with a QALYs of 0.55. The ICER was $20,034.74/QALY, below China willingness-to-pay threshold of 2–3 times GDP. The sensitivity analysis demonstrated the stability of the conclusions and indicated that when the WTP is set at 2 times the GDP, toripalimab has an 89% probability of being cost-effective. The A11+/B62– genotype and the intratumor heterogeneity (ITH) low population achieve better efficacy and a lower ICER compared to the overall population. While drug wastage increases the treatment cost, it does not alter the conclusions.ConclusionCompared to EP alone, toripalimab plus EP is cost-effective as first-line treatment in Chinese ES-SCLC patients, particularly when considering genetic stratification and donation policies. The study results provide important reference for China medical insurance policy-making and clinical practice.

A nomogram predicting prognosis of extensive-stage small cell lung cancer patients receiving chemoradiotherapy

BackgroundSmall cell lung cancer (SCLC) accounts for approximately 15% of lung cancers and is characterized by rapid progression and early metastasis. The prognostic nutritional index (PNI), based on serum albumin and lymphocyte count, has emerged as a potential prognostic biomarker in various cancers.ObjectiveThis study aimed to evaluate the prognostic value of changes in pre- and post-treatment PNI levels in patients with extensive-stage SCLC.MethodsA total of 177 treatment-naïve patients with extensive-stage SCLC diagnosed between September 2018 and October 2022 were included. Kaplan–Meier survival analysis and ROC curve analysis were used to assess overall survival (OS) and progression-free survival (PFS) according to PNI categories.ResultsThe median OS was 10.3 months and median PFS was 7.5 months in the entire cohort. Patients with persistently low PNI values had the poorest outcomes (median OS 6.4 months, PFS 5.7 months), whereas those with consistently high PNI values had the best prognosis (median OS 14.6 months, PFS 8.4 months; p < 0.001).ConclusionsDynamic changes in PNI are significantly associated with prognosis in extensive-stage SCLC. Patients with low pre- and post-treatment PNI values exhibited worse outcomes, while consistently high PNI predicted better survival. This study is the first to evaluate PNI changes in this patient population.