Current Management and Progress in Radiotherapy for Small Cell Lung Cancer

Tjong, Michael C.; Mak, David; Shahi, Jeevin; Li, George J.; Chen, Hanbo; Louie, Alexander V.

doi:10.3389/fonc.2020.01146

Cited by 24 publications

(23 citation statements)

References 103 publications

(161 reference statements)

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“…Small-cell lung cancer (SCLC), which accounted for ~15% of all cases of lung cancer in the United States in 2020 ( 1 ), is a highly aggressive lung cancer tumor. The 5-year survival rate was <7% in the United States in 2017 ( 2 ).…”

Section: Introductionmentioning

confidence: 99%

“…Firstly, SCLC is characterized by rapid growth and metastasis and the lack of early detection means few cases can be treated by surgery ( 3 ). Secondly, the initial effects of chemotherapy quickly diminish, and the majority of patients relapse within the first year, worldwide ( 1 ), developing multidrug resistance. Finally, a lack of adequate surgical tissues and re-biopsy for molecular profiling results in few therapeutic options for SCLC compared with that in non-small-cell lung cancer (NSCLC).…”

Section: Introductionmentioning

confidence: 99%

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Effective ferroptotic small-cell lung cancer cell death from SLC7A11 inhibition by sulforaphane

et al. 2020

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Small-cell lung cancer (SCLC) is a highly aggressive cancer with poor prognosis, due to a lack of therapeutic targets. Sulforaphane (SFN) is an isothiocyanate derived from cruciferous vegetables and has shown anticancer effects against numerous types of cancer. However, its anticancer effect against SCLC remains unclear. The present study aimed to demonstrate the anticancer effects of SFN in SCLC cells by investigating cell death (ferroptosis, necroptosis and caspase inhibition). The human SCLC cell lines NCI-H69, NCI-H69AR (H69AR) and NCI-H82 and the normal bronchial epithelial cell line, 16HBE14o-were used to determine cell growth and cytotoxicity, evaluate the levels of iron and glutathione, and quantify lipid peroxidation following treatment with SFN. mRNA expression levels of cystine/glutamate antiporter xCT (SLC7A11), a key component of the cysteine/glutamate antiporter, were measured using reverse transcription-quantitative PCR, while the levels of SLC7A11 protein were measured using western blot analysis. Following the addition of SFN to the cell culture, cell growth was significantly inhibited, and cell death was shown in SCLC and multidrug-resistant H69AR cells. The ferroptotic effects of SFN were confirmed following culture with the ferroptosis inhibitor, ferrostatin-1, and deferoxamine; iron levels were elevated, which resulted in the accumulation of lipid reactive oxygen species. The mRNA and protein expression levels of SLC7A11 were significantly lower in SFN-treated cells compared with that in the control cells (P<0.0001 and P=0.0006, respectively). These results indicated that the anticancer effects of SFN may be caused by ferroptosis in the SCLC cells, which was hypothesized to be triggered from the inhibition of mRNA and protein expression levels of SLC7A11. In conclusion, the present study demonstrated that SFN-induced cell death was mediated via ferroptosis and inhibition of the mRNA and protein expression levels of SLC7A11 in SCLC cells. The anticancer effects of SFN may provide novel options for SCLC treatment.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effective ferroptotic small-cell lung cancer cell death from SLC7A11 inhibition by sulforaphane

et al. 2020

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“…Historically, RT was reserved for palliation in extensive-stage SCLC. [ 67 ] The fact that many patients had recurrent or progressive intrathoracic disease led to clinical trial investigations and other observational studies examining the role of consolidative TRT in this population. In the first RCT examining consolidative TRT following CT, TRT led to significant OS improvements.…”

Section: Discussionmentioning

confidence: 99%

A systematic literature review of real-world treatment outcomes of small cell lung cancer

et al. 2022

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Background: Robust evidence from real-world studies is needed to aid decision-makers and other stakeholders in choosing the best treatment options for patients. The objective of this work was to assess real-world outcomes of treatment strategies for limited-and extensive-stage small cell lung cancer (SCLC) prior to the global introduction of immunotherapies for this disease.Methods: Searches were conducted in MEDLINE and Embase to identify articles published in English from October 1, 2015, through May 20, 2020. Searches were designed using a combination of Medical Subject Heading (Medline), Emtree (Embase subject headings), and free-text terms such as SCLC. Observational studies reporting data on outcomes of initial treatment strategies in patients with limited-and extensive-stage SCLC were included. Studies with limited sample sizes (<100 patients), enrolled all patients prior to 2010, or did not report outcomes for limited-and extensive-stage SCLC separately were excluded. Data were extracted into a predesigned template by a single researcher. All extractions were validated by a second researcher, with disagreements resolved via consensus.Results: Forty articles were included in this review. Most enrolled patients from the United States (n = 18 articles) or China (n = 12 articles). Most examined limited-stage (n = 27 articles) SCLC. All studies examined overall survival as the primary outcome. Articles investigating limited-stage SCLC reported outcomes for surgery, chemotherapy and/or radiotherapy, and adjuvant prophylactic cranial irradiation. In studies examining multiple treatment strategies, chemoradiotherapy was the most commonly utilized therapy (56%-82%), with chemotherapy used in 18% to 44% of patients. Across studies, median overall survival was generally higher for chemoradiotherapy (15-45 months) compared with chemotherapy alone (6.0-15.6 months). Studies of extensive-stage SCLC primarily reported on chemotherapy alone, consolidative thoracic radiotherapy, and radiotherapy for patients presenting with brain metastases. Overall survival was generally lower for patients receiving chemotherapy alone (median: 6.4-16.5 months; 3 years, 5%-14.9%) compared with chemotherapy in combination with consolidative thoracic radiotherapy (median: 12.1-18.0 months; 3 years, 15.0%-18.1%). Studies examining whole-brain radiotherapy for brain metastases reported lower median overall survival (5.6-8.7 months) compared with stereotactic radiosurgery (10.0-14.5 months).Conclusions: Under current standard of care, which has remained relatively unchanged over the past few decades, prognosis remains poor for patients with SCLC.

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“…Until now, the standard initial therapy remains concurrent chemoradiotherapy (CRT) in most limited stage SCLC cases ( 17 , 18 ). ARIE, as a frequent acute complication of CRT, can continuously reduce the quality of life of patients.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Epigallocatechin-3-Gallate as a Radioprotective Agent During Radiotherapy of Lung Cancer Patients: A 5-Year Survival Analysis of a Phase 2 Study

et al. 2021

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BackgroundPrevious analysis of the study (NCT02577393) had demonstrated the application of epigallocatechin-3-gallate (EGCG) could be safe and effective in the prevention and treatment of acute radiation esophagitis in patients with advanced lung cancer. EGCG seemed to improve the response rate of small cell lung cancer (SCLC) to radiotherapy in a subgroup analysis. This research continued to analyze the impact of EGCG application on cancer-radiation efficacy and patient survival.MethodsAll patients with SCLC in the NCT02577393 study were included. Patients were randomized into EGCG group or conventional therapy group as protocol. The primary endpoints of the study were radiation response rate and progression-free survival (PFS). Overall survival (OS) and the efficacy of EGCG in the treatment of esophagitis were assessed as secondary endpoints.ResultsA total of 83 patients with lung cancer in the NCT02577393 study were screened, and all 38 patients with SCLC were eligible for analysis. No significant differences with regard to baseline demographic and clinical characteristics were observed between the two groups. The objective response rate (ORR) was higher than that of conventionally treated patients (84.6 vs 50%, P = 0.045), while the median PFS and OS were not significantly prolonged. At data cut-off (1 January 2021), 5-year PFS was 33% with EGCG versus 9.3% with conventional treatment, and 5-year OS was 30.3% versus 33.3%, respectively. The mean adjusted esophagitis index and pain index of patients with EGCG application were lower than conventional treatment (5.15 ± 2.75 vs 7.17 ± 1.99, P = 0.030; 8.62 ± 5.04 vs 15.42 ± 5.04, P < 0.001).ConclusionThe study indicates EGCG may alleviate some esophagitis-related indexes in SCLC patients exposed to ionizing radiation without reducing survival. However, this conclusion should be confirmed by further studies with large sample size.

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Current Management and Progress in Radiotherapy for Small Cell Lung Cancer

Cited by 24 publications

References 103 publications

Effective ferroptotic small-cell lung cancer cell death from SLC7A11 inhibition by sulforaphane

Effective ferroptotic small-cell lung cancer cell death from SLC7A11 inhibition by sulforaphane

A systematic literature review of real-world treatment outcomes of small cell lung cancer

Evaluation of Epigallocatechin-3-Gallate as a Radioprotective Agent During Radiotherapy of Lung Cancer Patients: A 5-Year Survival Analysis of a Phase 2 Study

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