One Cycle of Concurrent Chemotherapy vs. Two Cycles of Concurrent Chemotherapy With Radiation Therapy in Patients With Limited-Stage Small Cell Lung Cancer

Yu, Hao; Zhang, Jiaqi; Zhang, Zhen; Wang, Youyou; Xu, Guangying; Xu, Liming; Liu, Ningbo; Zhao, Lujun; Wang, Ping

doi:10.3389/fonc.2021.785022

Cited by 3 publications

(3 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SCLCs are highly aggressive and malignant which lead to poor prognosis and hard to predict prognosis, even in LS-SCLC. Our research group has conducted numerous studies on the timing of radiotherapy [ 24 ], the target area of radiotherapy [ 25 , 26 ], radiotherapy techniques [ 27 ], treatment sequencing [ 28 ] and the number of cycles of chemotherapy [ 29 ] during chemoradiotherapy, as well as prophylactic cranial irradiation(PCI) [ 30 ] for SCLC. Our findings reveal the difficulty in accurately predicting the prognosis of LS-SCLC from a purely clinical standpoint.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of CT radiomic features combined with clinical factors in predicting prognosis in patients with limited-stage small cell lung cancer

Wu,

Zhou,

et al. 2024

BMC Cancer

Self Cite

View full text Add to dashboard Cite

Background The prognosis of SCLC is poor and difficult to predict. The aim of this study was to explore whether a model based on radiomics and clinical features could predict the prognosis of patients with limited-stage small cell lung cancer (LS-SCLC). Methods Simulated positioning CT images and clinical features were retrospectively collected from 200 patients with histological diagnosis of LS-SCLC admitted between 2013 and 2021, which were randomly divided into the training (n = 140) and testing (n = 60) groups. Radiomics features were extracted from simulated positioning CT images, and the t-test and the least absolute shrinkage and selection operator (LASSO) were used to screen radiomics features. We then constructed radiomic score (RadScore) based on the filtered radiomics features. Clinical factors were analyzed using the Kaplan–Meier method. The Cox proportional hazards model was used for further analyses of possible prognostic features and clinical factors to build three models including a radiomic model, a clinical model, and a combined model including clinical factors and RadScore. When a model has prognostic predictive value (AUC > 0.7) in both train and test groups, a nomogram will be created. The performance of three models was evaluated using area under the receiver operating characteristic curve (AUC) and Kaplan–Meier analysis. Results A total of 1037 features were extracted from simulated positioning CT images which were contrast enhanced CT of the chest. The combined model showed the best prediction, with very poor AUC for the radiomic model and the clinical model. The combined model of OS included 4 clinical features and RadScore, with AUCs of 0.71 and 0.70 in the training and test groups. The combined model of PFS included 4 clinical features and RadScore, with AUCs of 0.72 and 0.71 in the training and test groups. T stages, ProGRP and smoke status were the independent variables for OS in the combined model, whereas T stages, ProGRP and prophylactic cranial irradiation (PCI) were the independent factors for PFS. There was a statistically significant difference between the low- and high-risk groups in the combined model of OS (training group, p < 0.0001; testing group, p = 0.0269) and PFS (training group, p < 0.0001; testing group, p < 0.0001). Conclusion Combined models involved RadScore and clinical factors can predict prognosis in LS-SCLC and show better performance than individual radiomics and clinical models.

show abstract

Section: Discussionmentioning

confidence: 99%

Effectiveness of CT radiomic features combined with clinical factors in predicting prognosis in patients with limited-stage small cell lung cancer

Wu,

Zhou,

et al. 2024

BMC Cancer

Self Cite

View full text Add to dashboard Cite

show abstract

“…SCLC is highly sensitive to radiotherapy in the early stages of treatment, but radioresistance inevitably develops in a significant proportion of patients [ 32 , 33 ]. Cancer radioresistance is an intricate phenomenon that has attracted a lot of attention, and there are two main hypotheses to explain it [ 34 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

PI3K/mTOR inhibitors promote G6PD autophagic degradation and exacerbate oxidative stress damage to radiosensitize small cell lung cancer

Deng,

Chen,

Wang

et al. 2023

Cell Death Dis

View full text Add to dashboard Cite

Our previous study revealed that PI3K/AKT/mTOR signaling was associated with SCLC radioresistance. SBC2 cells were used as primary radioresistance models, while H446 cells were continuously exposed to ionizing radiation (IR) to develop acquired radioresistance. Cell viability and apoptosis assays were used to investigate synergistic effects of BEZ235/GSK2126458 and IR in vitro, while immunoblotting, metabolite quantitative analysis and bioinformatic analyses were utilized to explore the underlying mechanism. Both genetically engineered mouse models (GEMM) and subcutaneous tumor models were used to confirm the synergistic effect in vivo. Key molecules of PI3K/AKT/mTOR signaling were upregulated after IR, which was correlated with primary radioresistance, and they were more expressed in acquired radioresistant cells. BEZ235/GSK2126458 effectively enhanced the cytotoxic effects of IR. BEZ235/GSK2126458 plus IR elevated γ-H2AX and p-Nrf2 expression, suggesting DNA and oxidative stress damage were intensified. Mechanistically, BEZ235/GSK2126458 plus IR significantly reduced the expression of G6PD protein, the rate-limiting enzyme of the pentose phosphate pathway (PPP). In detail, PI3K/mTOR inhibitors reinforced interaction between G6PD and HSPA8/HSC70, and G6PD was degraded by chaperone-mediated autophagy processes. Their metabolites (NADPH and R-5P) were decreased, and ROS levels were indirectly elevated, both of which exacerbated cell death. PI3K/AKT/mTOR signaling activator, insulin, enhanced SCLC radioresistance, while the synergistic effect of BEZ235/GSK2126458 and IR can be attenuated by N-acetylcysteine, and enhanced by 6-amino niacinamide. GEMM and allograft transplantation assays further confirmed their synergistic effect in vivo. This study provided insights into the connection between PI3K/AKT/mTOR signaling and the PPP underlying radioresistance and provided evidence of mechanisms supporting PI3K/mTOR inhibitors as possible therapeutic strategies to abrogate SCLC radioresistance.

show abstract

“…The major challenge remains how many cycles of IC gives the best outcome. Yu et al [ 14 ] compared 1 versus 2 cycles of concurrent chemo-radiotherapy in 370 patients with limited stage NSCLC and concluded that 2 cycles of concurrent chemotherapy during RT were not necessarily superior compared to 1 cycle. Chen et al [ 15 ] meanwhile assessed the association between the number of cycles of IC, and radiation therapy dose with overall survival in 227 unresectable stage III NSCLC patients, and concluded that number of cycles of IC did not interfere with survival, but 3 or more cycles induced more grade 3 to 4 hematological toxicities.…”

Section: Introductionmentioning

confidence: 99%

Optimum cycles of induction chemotherapy in concurrent chemo-radiotherapy management of unresectable stage III non-small cell lung cancer: Results from a single institutional database

et al. 2023

View full text Add to dashboard Cite

Induction chemotherapy (IC) prior to concurrent chemo-radiotherapy is the recommended treatment for unresectable stage III non-small cell lung cancer (NSCLC). However, the optimum number of IC cycles for improved survival outcomes is still not known. Here, we assessed the efficacy of 2 or more cycles of IC for unresectable stage III NSCLC patients from our hospital. Data on unresectable stage III NSCLC patients treated with IC + concurrent chemo-radiotherapy at our hospital between 2018 and 2022 were retrieved and analyzed, and survival outcomes compared between IC = 2 and IC > 2 patients. Univariate and multivariate Cox regression, and Chi-square or Fisher exact test were used to assess prognosis and acute toxicity profiles. One hundred twenty-six patients were recruited; 90 for IC = 2 and 36 for IC > 2. Median follow-up time was 26 months [IQR 16-38]. Three-year overall survival was not statistically significant between the 2 groups (77.8% vs 75.0%, P = .453). Distant metastasis free survival, loco-regional recurrence free survival and progression free survival were also not significant, (90.0% vs 86.1%, P = .068), 97.8% vs 97.2%, P = .056), and (73.3% vs 66.7%, P = .446) respectively. Univariate and multivariate Cox regression analysis revealed smoking, T_stage, N_stage, and IC_regimen as independent prognostic factor for overall survival, while drinking and T_stage were risk factors for progression free survival. In summary, 2 cycles of platinum-based IC was effective for stage III unresectable NSCLC and adding more than 2 cycles did not offer extra survival benefits.

show abstract

One Cycle of Concurrent Chemotherapy vs. Two Cycles of Concurrent Chemotherapy With Radiation Therapy in Patients With Limited-Stage Small Cell Lung Cancer

Cited by 3 publications

References 23 publications

Effectiveness of CT radiomic features combined with clinical factors in predicting prognosis in patients with limited-stage small cell lung cancer

Effectiveness of CT radiomic features combined with clinical factors in predicting prognosis in patients with limited-stage small cell lung cancer

PI3K/mTOR inhibitors promote G6PD autophagic degradation and exacerbate oxidative stress damage to radiosensitize small cell lung cancer

Optimum cycles of induction chemotherapy in concurrent chemo-radiotherapy management of unresectable stage III non-small cell lung cancer: Results from a single institutional database

Contact Info

Product

Resources

About