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The present study explored the risk factors associated with radiotherapy in seniors diagnosed with limited-stage small cell lung cancer (LS-SCLC) to construct and validate a prognostic nomogram. The study retrospectively included 137 elderly patients with LS-SCLC who previously received radiotherapy. Univariate and multivariate COX analyses were conducted to identify independent risk factors and determine optimal cut-off values. Kaplan–Meier survival curves and nomograms were constructed to predict survival. Calibration and receiver operating characteristic (ROC) curves were used to evaluate the accuracy and consistency of the nomogram. Illness rating scale-geriatric (CIRS-G) score, treatment strategy, lymphocyte-to-monocyte ratio (LMR), white blood cell-to-monocyte ratio (WMR), and prognostic nutritional index (PNI) were discovered to be independent prognostic factors. Based on the findings of our multivariate analysis, a risk nomogram was developed to assess patient prognosis. Internal bootstrap resampling was utilized to validate the model, and while the accuracy of the AUC curve at 1 year was modest at 0.657 (95% CI 0.458–0.856), good results were achieved in predicting 3- and 5 year survival with AUCs of 0.757 (95% CI 0.670–0.843) and 0.768 (95% CI 0.643–0.893), respectively. Calibration curves for 1-, 3-, and 5 year overall survival probabilities demonstrated good cocsistency between expected and actual outcomes. Patients with concurrent chemoradiotherapy, CIRS-G score > 5 points and low PNI, WMR and LMR correlated with poor prognosis. The nomogram model developed based on these factors demonstrated good predictive performance and provides a simple, accessible, and practical tool for clinicians to guide clinical decision-making and study design. [ABSTRACT FROM AUTHOR]

Introduction: Small cell lung cancer (SCLC) has recently been characterized as heterogeneous tumors due to consensus nomenclature for distinct molecular subtypes on the basis of differential expression of four transcription markers (ASCL1, NEUROD1, POU2F3, and YAP1). It is necessary to validate molecular subtype classification in primary SCLC tumors by immunohistochemical (IHC) staining and investigate its relevance to survival outcomes. Methods: Using a large number of surgically resected primary SCLC tumors, we assessed the mRNA and protein levels of the four subtype markers (ASCL1, NEUROD1, POU2F3 and YAP1) in two independent cohorts, respectively. Next, molecular subtypes defined by the four subtype markers was conducted to identify the association with clinicopathologic characteristics, survival outcomes, the expression of classic neuroendocrine markers, and molecules related to tumor immune microenvironment. Results: Samples were categorized into four subtypes based on the relative expression levels of the four subtype markers, yielding to ASCL1, NEUROD1, POU2F3 and YAP1 subtypes, respectively. The combined neuroendocrine differentiation features were more prevalent in either ASCL1 or NEUROD1 subtypes. Kaplan-Meier analyses found that patients with tumors of the YAP1 subtype and ASCL1 subtype obtained the best and worst prognosis on both mRNA and IHC levels, respectively. Based on multivariate Cox proportional-hazards regression model, molecular subtype classification determined by IHC was identified as an independent indicator for survival outcomes in primary SCLC tumors. Correlation analyses indicated that the four subtype markers in SCLC cancer cells were interacted with its tumor immune microenvironment. Specifically, tumors positive for YAP1 was associated with fewer CTLA4+ T cell infiltration, while more immune-inhibitory receptors (FoxP3,PD1, and CTLA4) and fewer immune-promoting receptor (CD8) were found in tumors positive for ASCL1. Conclusions: We validated the new molecular subtype classification and clinical relevance on both mRNA and protein levels from primary SCLC tumors. The molecular subtypes determined by IHC could be a pre-selected effective biomarker significantly influenced on prognosis in patients with SCLC, which warrants further studies to provide better preventative and therapeutic options for distinct molecular subtypes. [ABSTRACT FROM AUTHOR]

Background: The optimal number of concurrent chemotherapy cycles during thoracic radiotherapy (RT) in patients with limited stage-small cell lung cancer (LS-SCLC) is not well defined. The purpose of this study was to evaluate the impact of the number of concurrent chemotherapy cycles on prognosis of LS-SCLC. Material and Methods: Patients with LS-SCLC treated with concurrent chemo-radiotherapy from May 2008 to December 2020 in our hospital were retrospectively analyzed. The prescribed radiation dose was 60Gy administrated with conventional RT in 30 fractions within 6 weeks. The prognostic role of cycle number of chemotherapy administrated concurrently with RT were analyzed. All patients were followed up at one month after the treatment, then once every three months until two years after the treatment, and every six months thereafter. Propensity score matching (PSM) was performed to reduce confounding factors. The primary endpoint was overall survival (OS). Survival analysis was performed with Kaplan-Meier and multivariate analysis was performed with Cox regression model. Results: Among the 370 patients who received radical radiotherapy, 206 patients received concurrent chemo-radiotherapy and were included for the analysis. Multivariate analysis showed that stage and PCI were independent prognostic factors for OS. The median OS in patients who received one cycle and two cycles of chemotherapy concurrently with RT were 32.9 months and 31.6 months, respectively (P = 0.241). And the median PFS were 20.6 months and 18.4 months, respectively (P = 0.764). After PSM, no statistical differences in OS and PFS were observed between patients who received one cycle and those who received two cycles of concurrent chemotherapy. Conclusion: Two cycles of concurrent chemotherapy during RT were not necessarily superior compared to one cycle in LS-SCLC. The optimal cycle number of concurrent chemotherapy during RT needs to be further studied. [ABSTRACT FROM AUTHOR]

Background: Accumulated evidence for systemic inflammation response in several solid tumors prompts a possibility of prediction of patients' prognosis in a more accessible and valuable manner. However, the prognostic value of peripheral blood inflammatory markers in limited-stage small cell lung cancer (LS-SCLC) remains unclear. Therefore, we investigated the prognostic values of pretreatment inflammatory indexes in LS-SCLC patients. Methods: We retrospectively identified 334 patients with LS-SCLC and collected their pretreatment serum levels of neutrophil, platelet, lymphocyte, leukocyte, hemoglobin, and albumin, then neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic inflammation index (SII) were calculated. Patients were dichotomized as low-Risk or high-Risk group based on their corresponding cutoff values. Univariate and multivariate analyses were conducted with a Cox proportional hazards model. The least absolute shrinkage and selection operator (LASSO)-Cox regression analysis was performed to construct the inflammation-related prognostic scoring system named Risk for OS. Nomograms were established to provide prognostic information, allowing for more individualized prediction of survival. Results: Higher pretreatment platelet, lymphocyte, and albumin were indicators of favorable overall survival (OS), whereas higher NLR and SII were accompanied by inferior OS. The prognosis of patients with high Risk was significantly worse than that with low Risk in both the training group and the validation group (both p < 0.001). Comparable area under the curve (AUC) values between the training group and the validation group were observed, yielding 1-, 3-, and 5-year OS rates of 67.3% vs. 69.2%, 66.8% vs. 69.5%, and 66.7% vs. 71.4%, respectively. Multivariate analyses revealed that Risk [hazard ratio (HR) = 0.551, p < 0.001] was an independent negative prognostic indicator for OS, which was further verified in the validation set. The addition of Risk to nomogram (C-index = 0.643) harbored improved predictive accuracy for OS when compared with that of clinical factors alone (C-index = 0.606); the AUC values of 1-, 3-, and 5-year OS rates were 71.7% vs. 66.4%, 73.5% vs. 66.6%, and 71.9% vs. 65.6%, respectively. Conclusions: Pretreatment peripheral blood inflammatory indexes may be a noninvasive serum biomarker for poor prognosis in LS-SCLC. The addition of Risk to the nomogram model could serve as a more powerful, economical, and practical method to predict survival for patients with LS-SCLC. [ABSTRACT FROM AUTHOR]

Purpose: Thoracic radiotherapy (TRT) is the recommended therapeutic regimen for extensive-stage small cell lung cancer (ES-SCLC). Little is known about TRT benefits in elderly populations. The aim of this study was to evaluate TRT effects on the prognosis of elderly patients with ES-SCLC. Patients and methods: This retrospective analysis reviewed the records of patients over 65 years of age with metastatic ES-SCLC treated between 2010 and 2016. Enrolled patients received standard chemotherapy regimens (etoposide plus cisplatin or carboplatin). A total of 93 eligible patients were subjected to propensity score matching, which led to 40 patients being assigned to the TRT group and 40 to the no thoracic radiotherapy (noTRT) group. The cohort of 80 patients (67 males) had the median age of 69 years (range, 65–85 years), with a median of 4 chemotherapy cycle (range, 1–8 cycles), and a median chest irradiation dose of 50 Gy (range, 30–60 Gy). We analyzed overall survival (OS), progression-free survival (PFS), and local recurrence-free survival (LRFS) as endpoints; survival rates were determined by the Kaplan–Meier method and compared across groups with log-rank tests. Multivariate prognostic analysis was performed with Cox regression modeling, and categorical variables were analyzed with Chi-square tests. Results: In all patients, the 1-year OS, PFS, and LRFS rates were 38.3%, 16%, and 17.9%, respectively. The TRT group had superior survival outcomes compared to the noTRT group: their 1-year OS, PFS, and LRFS rates were 55% vs. 25% (P < 0.001), 32.1% vs. 0% (P < 0.001), and 31% vs. 2.6% (P < 0.001), respectively. TRT did not increase the incidence of adverse reactions (P = 0.431). Conclusion: TRT can improve chest tumor control and survival time in elderly ES-SCLC patients. Large-scale studies to further assess the benefits of TRT are warranted. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the prognosis of patients with extensive-stage small-cell lung cancer (ES-SCLC) that may be associated with timing of thoracic radiotherapy (TRT).Methods: ES-SCLC patients (n = 232) without progression were retrospectively analyzed after first-line induction chemotherapy. Patients in the TRT group were stratified as early-TRT (ERT; ≤3 cycles of induction chemotherapy received prior to TRT, n = 65) or late-TRT (LRT; >3 cycles, n = 122). To avoid selection bias, we conducted Propensity Score Matching (PSM) for patients. Overall survival (OS), progression-free survival (PFS), and locoregional recurrence-free survival (LRRFS) were assessed and compared.Results: Overall, the median survival time, PFS, and LRRFS were 13.2, 8.7, and 14.6 months, respectively. After matching by PSM, there were 45 patients total in the TRT/non-TRT groups, and 56 patients total in the ERT/LRT groups. OS, PFS, and LRRFS were significantly longer in the TRT group than the non-TRT group (P < 0.001, all). However, between the ERT and LRT groups these survival parameters were similar (P > 0.05, all).Conclusion: For ES-SCLC patients without progression, the addition of TRT after first-line chemotherapy benefited survival greatly. Early TRT showed no significant benefit over late TRT. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: To evaluate the risk factors for radiation-induced lung toxicity (RILT) from post-operative radiation therapy (PORT) in patients with non-small cell lung cancer (NSCLC). Material and methods: Ninety NSCLC patients who received PORT with or without chemotherapy from November 2002 to March 2006 were retrospectively analyzed. Each individual''s radiotherapy plans were reviewed to determine the percentage of the whole lung volume that received more than a specific dose of irradiation (Vdose). The endpoint was RILT of grade 2 or higher. Data of potential risk factors for RILT were extracted from the medical records and evaluated by logistic regression modeling, the t-test, and the Chi-square test. Results: A total of 20 patients received pneumonectomy, while the remaining 70 received lobectomy. In the lobectomy group, 9 patients (10%) developed ≥grade 2 RILT. Among the clinical factors, only adjuvant chemotherapy was significantly correlated with RILT (p =0.039). For lung dosimetric factors, V20 through V40 were all significantly higher in the RILT group than in the non-RILT group. In the lobectomy group, the incidence of RILT was 27.3% in patients who received adjuvant chemotherapy and whose V20 was greater than 20%. It was 9.7% in lobectomy patients with one of the risk factors, and 0.0% in those with no risk factors (p =0.032). Conclusions: The lung toxicity of PORT was found to be acceptably low. Adjuvant chemotherapy and lung dosimetric factors of V20–V40 were significantly correlated with RILT risk in NSCLC patients. [Copyright &y& Elsevier]

Purpose: To determine whether the effect of radiation dose varies with gross tumor volume (GTV) in patients with stage I/II non–small cell lung cancer (NSCLC). Methods and Materials: Included in the study were 114 consecutive patients with medically inoperable stage I/II NSCLC treated with three-dimensional conformal radiotherapy between 1992 and 2004. The median biologic equivalent dose (BED) was 79.2 Gy (range, 58.2–124.5 Gy). The median GTV was 51.8 cm3 (range, 2.1–727.8 cm3). The primary endpoint was overall survival (OS). Kaplan-Meier estimation and Cox regression models were used for survival analyses. Results: Multivariate analysis showed that there was a significant interaction between radiation dose and GTV (p < 0.001). In patients with BED ≤79.2 Gy (n = 68), the OS medians for patients with GTV >51.8 cm3 and ≤51.8 cm3 were 18.2 and 23.9 months, respectively (p = 0.015). If BED was >79.2 Gy (n = 46), no significant difference was found between GTV groups (p = 0.681). For patients with GTV >51.8 cm3 (n = 45), the OS medians in those with BED >79.2 Gy and ≤79.2 Gy were 30.4 and 18.2 months, respectively (p < 0.001). If GTV was ≤51.8 cm3 (n = 45), the difference was no longer significant (p = 0.577). Conclusion: High-dose radiation is more important for patients with larger tumors and may be effective in reducing the adverse outcome associated with large GTV. Further prospective studies are needed to confirm this finding. [Copyright &y& Elsevier]

Abstract: Background and purpose: To determine the dose to regional nodal stations in patients with T1–3N0M0 non-small cell lung cancer (NSCLC) treated with three-dimensional conformal radiation therapy (3DCRT) without intentional elective nodal irradiation (ENI). Materials and methods: Twenty-three patients with medically inoperable T1–3N0M0 NSCLC were treated with 3DCRT without ENI. Hilar and mediastinal nodal regions were contoured on planning CT. The prescription dose was normalized to 70Gy. Equivalent uniform dose (EUD) and other dosimetric parameters (e.g., V 40) were calculated for each nodal station. Results: The median EUD for the whole group ranged from 0.4 to 4.4Gy for all elective nodal regions. Gross tumor volume (GTV) and the relationship between GTV and hilum were significantly correlated with irradiation dose to ipsilateral hilar nodal regions (P <.05). For patients with GTV⩾30.2cm3 (diameter≈4cm) and or having any overlap with hilum, the median EUDs were 9.6, 22.6, and 62.9Gy for ipsilateral lower paratracheal, subcarinal, and ipsilateral hilar regions, respectively. The corresponding median V40 were 32.5%, 39.3%, and 97.6%, respectively. Conclusions: Although incidental nodal irradiation dose is low in the whole group, the dose to high-risk nodal regions is considerable in patients with T1–3N0 NSCLC when the primary is large and/or centrally located. [Copyright &y& Elsevier]

Purpose: The use of prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC) with surgical resection has not been fully identified. This study undertook to assess the factors affecting the risk of brain metastases in patients with stage I-III SCLC after surgical resection. The implications of PCI treatment for these patients are discussed. Methods and Materials: One hundred twenty-six patients treated with surgical resection for stage I-III SCLC from January 1998-December 2009 were retrospectively analyzed to elucidate the risk factors of brain metastases. Log-rank test and Cox regression model were used to determine the risk factors of brain metastases. Results: The median survival time for this patient population was 34 months, and the 5-year overall survival rate was 34.9%. For the whole group, 23.0% (29/126) of the patients had evidence of metastases to brain. Pathologic stage not only correlated with overall survival but also significantly affected the risk of brain metastases. The 5-year survival rates for patients with pathologic stages I, II, and III were 54.8%, 35.6%, and 14.1%, respectively (P=.001). The frequency of brain metastases in patients with pathologic stages I, II, and III were 6.25% (2/32), 28.2% (11/39), and 29.1% (16/55) (P=.026), respectively. A significant difference in brain metastases between patients with complete resection and incomplete resection was also observed (20.5% vs 42.9%, P=.028). The frequency of brain metastases was not found to be correlated with age, sex, pathologic type, induction chemotherapy, adjuvant chemotherapy, or adjuvant radiation therapy. Conclusions: Stage I SCLC patients with complete resection had a low incidence of brain metastases and a favorable survival rate. Stage II-III disease had a higher incidence of brain metastases. Thus, PCI might have a role for stage II-III disease but not for stage I disease. [ABSTRACT FROM AUTHOR]