Once daily (OD) versus twice-daily (BID) chemoradiation for limited stage small cell lung cancer (LS-SCLC): A meta-analysis of randomized clinical trials

Viani, Gustavo Arruda; Gouveia, Andre G; Matsuura, Fernando Konjo; Jacinto, Alexandre Arthur; Moraes, Fábio Ynoe de

doi:10.1016/j.radonc.2022.01.032

Cited by 14 publications

(4 citation statements)

References 27 publications

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“…Moreover, modifying the amount and timing of PCI treatment can significantly reduce the risk of side effects. 42,48 Our analysis, in line with previous findings, 49,50 showed that the dose of PCI had no significant impact on the efficacy of PCI, suggesting that patients could benefit from lower doses while experiencing fewer side effects.…”

Section: Discussionsupporting

confidence: 88%

Prophylactic cranial irradiation effect on survival in patients with small cell lung cancer: a comprehensive systematic review and meta-analysis

Maroufi,

Fallahi,

Kankam

et al. 2023

Neurosurgical Focus

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OBJECTIVE Prophylactic cranial irradiation (PCI) is a companion treatment option for small cell lung cancer (SCLC) patients. However, its efficacy and associated risk factors have not been clearly defined. In this study, the authors aimed to systematically assess the effectiveness and role of PCI in the treatment plan of SCLC. METHODS The PubMed, Scopus, Web of Science, and Cochrane databases were searched using the following key terms and their equivalents: "brain," "radiotherapy," "metastases," "prophylactic," and "small cell lung cancer." Studies comparing overall survival (OS), progression-free survival (PFS), brain metastasis–free survival (BMFS), and incidence of brain metastases between patients receiving PCI and those not receiving it were considered eligible. Risk of bias was assessed using the Risk of Bias in Non-Randomized Studies–of Interventions (ROBINS-I) tool. Meta-analysis was conducted on the mentioned outcomes with subgrouping based on different factors. RESULTS The authors identified 74 studies published between 1983 and 2022 with 31,551 SCLC patients, of whom 26.7% received PCI. The studies were a mix of prospective randomized and retrospective observational studies. Patients with limited-stage disease receiving PCI had better OS, PFS, and BMFS than those not receiving PCI. Patients receiving PCI also had significantly longer OS times and developed brain metastases significantly later. However, findings regarding extensive-stage SCLC were not as promising. CONCLUSIONS PCI is an effective option for limited-stage SCLC patients. It improves OS and PFS, delays brain metastases, and reduces the incidence of brain metastases. However, it might not benefit patients with extensive-stage SCLC under adequate follow-up with MRI surveillance. Finally, the heterogeneity of the included studies and publication bias were the main limitations of this study.

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Section: Discussionsupporting

confidence: 88%

Prophylactic cranial irradiation effect on survival in patients with small cell lung cancer: a comprehensive systematic review and meta-analysis

Maroufi,

Fallahi,

Kankam

et al. 2023

Neurosurgical Focus

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“…Alternative approaches to improve the efficacy of TRT include studying the use of hypofractionated regimens (once-daily, higher-dose radiotherapy 13 Data from the National Cancer Database, [14][15][16] suggest that hypofractionated radiation does not appear to be worse than standard radiotherapy. Furthermore, in a meta-analysis based on the latest pooled phase II trial, 17 hypofractionated radiotherapy was associated with an improvement in OS compared to HFRT (p = 0.03). Additional randomized phase III trials are required to explore the efficacy of hypofractionated radiotherapy.…”

Section: Trt For Ls-stage Sclcmentioning

confidence: 99%

Progress in radiotherapy for small‐cell lung cancer

Yang,

Zhao

2023

Precision Radiation Oncology

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Small‐cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumor that is prone to spread extensively. Compared to non‐small‐cell lung cancer (NSCLC), SCLC treatment progresses slowly. Although SCLC is highly sensitive to chemotherapy during the initial treatment, most patients still experience resistance and recurrence after receiving chemotherapy. A meta‐analysis demonstrated that thoracic radiotherapy (TRT) improves overall survival in SCLC. The results of the CALGB and CONVERT trials provide evidence for the efficacy of once‐daily high‐dose TRT. TRT at 60 Gy administered twice daily significantly improved survival without increasing toxicity. The long‐standing debate over the optimal timing of radiotherapy has not been fully resolved. SBRT has excellent local control rates and is a safe and effective treatment option for patients with stage I or II SCLC. Prophylactic cranial irradiation (PCI) is used to reduce treatment‐related neurotoxicity to the extent that there has been a recent discussion on whether magnetic resonance imaging (MRI) monitoring can replace PCI. Radiotherapy combined with immunotherapy significantly improves the survival rate of patients with NSCLC; however, its clinical effectiveness has not been systematically explored in patients with SCLC. Therefore, we summarize the evolving therapeutic strategies, (TRT for limited stage‐SCLC and consolidative TRT for extensive stage‐SCLC) and improved radiotherapy techniques (role of SBRT in stage I or II node‐negative SCLC, progress of PCI, and stereotactic radiosurgery), and discuss the possibilities and prospects of radiotherapy combined with immunotherapy for SCLC.

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“…SCLC is divided into limited-stage (LS-SCLC) and extensive-stage (ES-SCLC). The standard treatment for LS-SCLC remains concurrent chemoradiotherapy (CCRT) [ 2 , 3 ]. Although CCRT is effective in early treatment, resistance to chemoradiotherapy always develops in most SCLC patients, followed by progression and relapse [ 4 , 5 ].…”

Section: Introductionmentioning

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

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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.

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Once daily (OD) versus twice-daily (BID) chemoradiation for limited stage small cell lung cancer (LS-SCLC): A meta-analysis of randomized clinical trials

Cited by 14 publications

References 27 publications

Prophylactic cranial irradiation effect on survival in patients with small cell lung cancer: a comprehensive systematic review and meta-analysis

Prophylactic cranial irradiation effect on survival in patients with small cell lung cancer: a comprehensive systematic review and meta-analysis

Progress in radiotherapy for small‐cell lung cancer

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

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