Blood-Based Surveillance Monitoring of Circulating Tumor DNA From Patients With SCLC Detects Disease Relapse and Predicts Death in Patients With Limited-Stage Disease

Iams, Wade T.; Kopparapu, Prasad; Yan, Yingjun; Muterspaugh, Anel; Zhao, Zhiguo; Chen, Heidi; Cann, Christopher; York, Sally J.; Horn, Leora; Ancell, Kristin K.; Wyman, Kenneth; Bertucci, Caterina; Shaffer, Tristan; Hodsdon, Lauren; Garg, Kavita D.; Hosseini, Seyed Ali; Lim, Lee P.; Lovly, Christine M.

doi:10.1016/j.jtocrr.2020.100024

Cited by 13 publications

(16 citation statements)

References 24 publications

(54 reference statements)

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“…In line with our results, it's well reported that cancer patients present higher cfDNA levels than healthy controls (46,47) but few studies have investigated the possible prognostic and predictive value of total cfDNA quantification in patients with SCLC. In contrast, the ctDNA, the tumor-derived fraction of this cfDNA, has been reported as a prognostic and predictive biomarker in several works (48)(49)(50)(51)(52). Almodovar et al reported that changes in the mutant allele frequencies on ctDNA were associated with response to treatment and relapse.…”

Section: Discussionmentioning

confidence: 99%

Plasma cell-free DNA and circulating tumor cells as prognostic biomarkers in small cell lung cancer patients

Mondelo‐Macía¹,

García‐González²,

Abalo³

et al. 2022

Transl Lung Cancer Res

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Background: Lack of biomarkers for treatment selection and monitoring in small-cell lung cancer (SCLC) patients with the limited therapeutic options, result in poor outcomes. Therefore, new prognostic biomarkers are needed to improve their management. The prognostic value of cell-free DNA (cfDNA) and circulating tumor cells (CTCs) have been less explored in SCLC.Methods: We quantified cfDNA in 46 SCLC patients at different times during first-line of chemotherapy or chemo-immunotherapy. Moreover, CTCs were analyzed in 21 patients before therapy onset using CellSearch ® system. The possible association between both biomarkers and patients' outcomes was investigated in order to develop a prognostic model.Results: High cfDNA levels before therapy were associated with shorter progression-free survival (PFS) and overall survival (OS). Furthermore, cfDNA levels at 3 weeks and at progression disease were also associated with patients' outcomes. Multivariate analyses confirmed the independence of cfDNA levels as a prognostic biomarker. Finally, the three-risk category prognostic model developed included Eastern Cooperative Oncology Group Performance Status (ECOG PS), gender and baseline cfDNA levels was associated with a higher risk of progression and death. Conclusions:We confirmed the prognostic utility of cfDNA quantitative analysis in SCLC patients before and during therapy. Our novel risk prognostic model in clinical practice will allow to identify patients who could benefit with actual therapies.

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Section: Discussionmentioning

confidence: 99%

Plasma cell-free DNA and circulating tumor cells as prognostic biomarkers in small cell lung cancer patients

Mondelo‐Macía¹,

García‐González²,

Abalo³

et al. 2022

Transl Lung Cancer Res

View full text Add to dashboard Cite

show abstract

“…Moreover, the authors observed a higher percentage of alterations in APC and AR in samples obtained at relapse. Recently, it has been hypothesized that the detection of ctDNA in patients with LS-SCLC after definitive therapy would predict disease relapse and death, after showing that residual ctDNA can be detected prior to radiographic relapse [ 76 ]. Overall, all of these studies demonstrate that cfDNA analyses constitute a powerful tool for SCLC diagnosis, therapy selection and monitoring that can be a key element to improve this tumor management in the close future.…”

Section: Liquid Biopsy As a Clinical Tool In Sclcmentioning

confidence: 99%

Current Status and Future Perspectives of Liquid Biopsy in Small Cell Lung Cancer

et al. 2021

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Approximately 19% of all cancer-related deaths are due to lung cancer, which is the leading cause of mortality worldwide. Small cell lung cancer (SCLC) affects approximately 15% of patients diagnosed with lung cancer. SCLC is characterized by aggressiveness; the majority of SCLC patients present with metastatic disease, and less than 5% of patients are alive at 5 years. The gold standard of SCLC treatment is platinum and etoposide-based chemotherapy; however, its effects are short. In recent years, treatment for SCLC has changed; new drugs have been approved, and new biomarkers are needed for treatment selection. Liquid biopsy is a non-invasive, rapid, repeated and alternative tool to the traditional tumor biopsy that could allow the most personalized medicine into the management of SCLC patients. Circulating tumor cells (CTCs) and cell-free DNA (cfDNA) are the most commonly used liquid biopsy biomarkers. Some studies have reported the prognostic factors of CTCs and cfDNA in SCLC patients, independent of the stage. In this review, we summarize the recent SCLC studies of CTCs, cfDNA and other liquid biopsy biomarkers, and we discuss the future utility of liquid biopsy in the clinical management of SCLC.

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“…In line with our results, it's well reported that cancer patients present higher cfDNA levels than healthy controls (38,39) but few studies have investigated the possible prognostic and predictive value of total cfDNA quantification in patients with SCLC. In contrast, the ctDNA, the tumor-derived fraction of this cfDNA, has been reported as a prognostic and predictive biomarker in several works (40)(41)(42)(43)(44). Almodovar et al reported that changes in the mutant allele frequencies on ctDNA were associated with response to treatment and relapse.…”

Section: Discussionmentioning

confidence: 99%

Plasma cell-free DNA as a prognostic biomarker in small cell lung cancer patients

Mondelo‐Macía

García‐González

Abalo

et al. 2022

Preprint

View full text Add to dashboard Cite

Background: Lack of biomarkers for treatment selection and monitoring in small-cell lung cancer (SCLC) patients with the limited therapeutic options, result in poor outcomes. Therefore, new prognostic biomarkers are needed to improve their management. The prognostic value of cell-free DNA (cfDNA) and circulating tumor cells (CTCs) have been less explored in SCLC. Methods: We quantified cfDNA in 46 SCLC patients at different times during therapy. Moreover, CTCs were analyzed in 21 patients before therapy onset using CellSearch system. Both biomarkers were associated with patients outcomes and a prognostic model was developed. Results: High cfDNA levels before therapy were associated with shorter progression-free survival and overall survival. Furthermore, changes in cfDNA levels between baseline and 3 weeks and cfDNA levels at progression disease were also associated with patients outcomes. Multivariate analyses confirmed the independence of cfDNA levels as a prognostic biomarker. Finally, the three-risk category prognostic model developed included ECOG Performance Status, gender and baseline cfDNA levels was associated with a higher risk of progression and death. Conclusions: We confirmed the prognostic utility of cfDNA in SCLC patients before and during therapy. Our novel risk prognostic model in clinical practice will allow to identify patients who could benefit with actual therapies.

show abstract

Blood-Based Surveillance Monitoring of Circulating Tumor DNA From Patients With SCLC Detects Disease Relapse and Predicts Death in Patients With Limited-Stage Disease

Cited by 13 publications

References 24 publications

Plasma cell-free DNA and circulating tumor cells as prognostic biomarkers in small cell lung cancer patients

Plasma cell-free DNA and circulating tumor cells as prognostic biomarkers in small cell lung cancer patients

Current Status and Future Perspectives of Liquid Biopsy in Small Cell Lung Cancer

Plasma cell-free DNA as a prognostic biomarker in small cell lung cancer patients

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