The Utility of Liquid Biopsies in Radiation Oncology

Michino, Steven De; Aparnathi, Mansi K.; Rostami, Ariana; Lok, Benjamin H.; Bratman, Scott V.

doi:10.1016/j.ijrobp.2020.05.008

Cited by 14 publications

(8 citation statements)

References 156 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We acknowledge that this pilot study may be underpowered to detect these differences. For instance, while tumour response to neoadjuvant radiotherapy corresponds to lower cfDNA and ctDNA levels in other malignancies, 29 , 30 an association was not detected in this work (p = 0.705). To our knowledge, only two prior studies have examined cfDNA in patients with sarcoma.…”

Section: Discussioncontrasting

confidence: 70%

Detection and utility of cell-free and circulating tumour DNA in bone and soft-tissue sarcomas

Tsoi

Gökgöz

Darville-O'Quinn

et al. 2021

Bone & Joint Research

View full text Add to dashboard Cite

Aims Cell-free DNA (cfDNA) and circulating tumour DNA (ctDNA) are used for prognostication and monitoring in patients with carcinomas, but their utility is unclear in sarcomas. The objectives of this pilot study were to explore the prognostic significance of cfDNA and investigate whether tumour-specific alterations can be detected in the circulation of sarcoma patients. Methods Matched tumour and blood were collected from 64 sarcoma patients (n = 70 samples) prior to resection of the primary tumour (n = 57) or disease recurrence (n = 7). DNA was isolated from plasma, quantified, and analyzed for cfDNA. A subset of cases (n = 6) underwent whole exome sequencing to identify tumour-specific alterations used to detect ctDNA using digital droplet polymerase chain reaction (ddPCR). Results Cell-free was present in 69 of 70 samples above 0.5 ng/ml. Improved disease-free survival was found for patients with lower cfDNA levels (90% vs 48% at one-year for ≤ 6 ng/ml and > 6 ng/ml, respectively; p = 0.005). Digital droplet PCR was performed as a pilot study and mutant alleles were detectable at 0.5% to 2.5% of the wild type genome, and at a level of 0.25 ng tumour DNA. Tumour-specific alterations (ctDNA) were found in five of six cases. Conclusion This work demonstrates the feasibility and potential utility of cfDNA and ctDNA as biomarkers for bone and soft-tissue sarcomas, despite the lack of recurrent genomic alterations. A larger study is required to validate these findings. Cite this article: Bone Joint Res 2021;10(9):602–610.

show abstract

Section: Discussioncontrasting

confidence: 70%

Detection and utility of cell-free and circulating tumour DNA in bone and soft-tissue sarcomas

Tsoi

Gökgöz

Darville-O'Quinn

et al. 2021

Bone & Joint Research

View full text Add to dashboard Cite

show abstract

“…Serial ctDNA monitoring during treatment can provide insight into underlying biological factors that can potentially be used to predict response, treatment efficacy, and long-term outcomes ( 7 – 11 ). In practice however, ctDNA levels can appear erratic across time points and are often inconsistent between patients with similar disease and treatment.…”

Section: Introductionmentioning

confidence: 99%

Blood, Toil, and Taxoteres: Biological Determinants of Treatment-Induced ctDNA Dynamics for Interpreting Tumor Response

Boniface¹,

Spellman²

2022

Pathol. Oncol. Res.

View full text Add to dashboard Cite

Collection and analysis of circulating tumor DNA (ctDNA) is one of the few methods of liquid biopsy that measures generalizable and tumor specific molecules, and is one of the most promising approaches in assessing the effectiveness of cancer care. Clinical assays that utilize ctDNA are commercially available for the identification of actionable mutations prior to treatment and to assess minimal residual disease after treatment. There is currently no clinical ctDNA assay specifically intended to monitor disease response during treatment, partially due to the complex challenge of understanding the biological sources of ctDNA and the underlying principles that govern its release. Although studies have shown pre- and post-treatment ctDNA levels can be prognostic, there is evidence that early, on-treatment changes in ctDNA levels are more accurate in predicting response. Yet, these results also vary widely among cohorts, cancer type, and treatment, likely due to the driving biology of tumor cell proliferation, cell death, and ctDNA clearance kinetics. To realize the full potential of ctDNA monitoring in cancer care, we may need to reorient our thinking toward the fundamental biological underpinnings of ctDNA release and dissemination from merely seeking convenient clinical correlates.

show abstract

“…To test that hypothesis, we used radiotherapy (RT) as a modality to induce tumor cell death because RT can be delivered to a well-defined anatomical target region. From the perspective of radiation oncology, personalized radiotherapeutic approaches based on biomarkers are now under development, and ctDNA could be a biomarker for radiation response, the detection of minimal/molecular residual disease (MRD), and the early detection of tumor recurrence [5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Targeted Liquid Biopsy Using Irradiation to Facilitate the Release of Cell-Free DNA from a Spatially Aimed Tumor Tissue

et al. 2022

View full text Add to dashboard Cite

We investigated the feasibility of using an anatomically localized, target-enriched liquid biopsy (TLB) in mouse models of lung cancer. Materials and MethodsAfter irradiating xenograft mouse with human lung-cancer cell lines, H1299 (NRAS protooncogene, GTPase (NRAS) Q61K) and HCC827 (EGFR E746-750del), ctDNA levels were monitored with quantitative PCR (qPCR) on human long interspersed nuclear element-1 (LINE-1) and cell line-specific mutations. We checked dose-dependency at 6, 12, or 18 Gy to each tumor-bearing mouse leg using 6-MV photon beams. We also analyzed ctDNA of lung cancer patients by LiquidSCAN, a targeted deep sequencing to validated the clinical performances of TLB method. ResultsIrradiation could enhance the detection sensitivity of NRAS Q61K in the plasma sample of H1299-xenograft mouse to 4.5-fold. While cell-free DNA (cfDNA) level was not changed at 6 Gy, ctDNA level was increased upon irradiation. Using double-xenograft mouse with H1299 and HCC827, ctDNA PCR analysis with local irradiation in each region could specify mutation type matched to transplanted cell types, proposing an anatomically localized, target-enriched liquid biopsy. Furthermore, when we performed targeted deep sequencing of cfDNA to monitor ctDNA level in 11 patients with lung cancer who underwent radiotherapy, the average ctDNA level was increased within a week after the start of radiotherapy. ConclusionTLB using irradiation could temporarily amplify ctDNA release in xenograft mouse and lung cancer patients, which enables us to develop theragnostic method for cancer patients with accurate ctDNA detection.

show abstract

The Utility of Liquid Biopsies in Radiation Oncology

Cited by 14 publications

References 156 publications

Detection and utility of cell-free and circulating tumour DNA in bone and soft-tissue sarcomas

Detection and utility of cell-free and circulating tumour DNA in bone and soft-tissue sarcomas

Blood, Toil, and Taxoteres: Biological Determinants of Treatment-Induced ctDNA Dynamics for Interpreting Tumor Response

Targeted Liquid Biopsy Using Irradiation to Facilitate the Release of Cell-Free DNA from a Spatially Aimed Tumor Tissue

Contact Info

Product

Resources

About