scholarly journals Circulating tumour cell and cell-free DNA kinetics during radiotherapy in patients with intact head and neck squamous cell carcinoma

Author(s):  
Sweet Ping Ng ◽  
Carolyn S Hall ◽  
Salyna Meas ◽  
Vanessa N Sarli ◽  
Houda Bahig ◽  
...  

AbstractHead and neck squamous cell carcinoma (HNSCC) treatment response relies heavily on macroscopic clinical findings. Blood monitoring of circulating markers during treatment may improve earlier detection of responders versus non-responders during radiotherapy. In this study, patients with intact tumour of HNSCC were enrolled in the prospective PREDICT-HN study. Pre-, after first treatment, weekly, and post-treatment blood samples were collected. CTC was enumerated using the CellSearch system. cfDNA was quantified from cfNA isolated at pre-, mid- and post-treatment timepoints. Blood samples were collected from 45 patients. Of the 339 samples analysed for CTC, 31% had detectable CTCs. Nine patients had detectable CTCs (1-3/7.5ml blood) in pre-treatment samples. After 1 fraction, 16 patients had CTCs detected, with 12 who had no pre-treatment CTC. Sixteen (36%) patients had detectable CTC in final week of treatment. There was no correlation between cancer stage, nodal status and tumour burden with CTC. cfDNA levels increased during treatment, with its highest level in the final week and lowest at post-treatment. Our results showed in HNSCC that CTCs can be detected during radiotherapy, suggesting mobilization into circulation during treatment, with as-yet-unknown viability. cfDNA kinetics during treatment correlated with CTC release, and may indicate apoptotic change.Simple SummaryHead and neck squamous cell carcinoma (HNSCC) treatment response relies heavily on macroscopic clinical findings. Blood monitoring of circulating markers such as circulating tumour cell (CTC) and cell-free DNA (cfDNA) during treatment may improve earlier detection of responders versus non-responders during definitive radiotherapy. Although the detection of CTCs and cfDNA in patients with HNSCC has been described, there is minimal data on the kinetics of CTC counts and cfDNA levels during radiotherapy in patients with HNSCC. Here, our study prospectively describes the changes in CTC and cfDNA enumeration during radiotherapy in patients with HNSCC. Our results showed, for the first time to our knowledge, in HNSCC, that CTCs can be detected during radiotherapy, suggesting mobilization into peripheral circulation during treatment, with as-yet-unknown viability. cfDNA kinetics during treatment correlated with CTC release, may indicate apoptotic change during radiotherapy. Combined cfDNA-CTC as an early marker of treatment response should be investigated further.

PLoS ONE ◽  
2015 ◽  
Vol 10 (12) ◽  
pp. e0144770 ◽  
Author(s):  
Ann D. King ◽  
Steven Kwok Keung Chow ◽  
Kwok-Hung Yu ◽  
Frankie Kwok Fai Mo ◽  
David K. W. Yeung ◽  
...  

PLoS ONE ◽  
2014 ◽  
Vol 9 (3) ◽  
pp. e90746 ◽  
Author(s):  
Amy T. Shah ◽  
Michelle Demory Beckler ◽  
Alex J. Walsh ◽  
William P. Jones ◽  
Paula R. Pohlmann ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Konstantin Hellwig ◽  
Stephan Ellmann ◽  
Markus Eckstein ◽  
Marco Wiesmueller ◽  
Sandra Rutzner ◽  
...  

ObjectivesTo assess the predictive value of multiparametric MRI for treatment response evaluation of induction chemo-immunotherapy in locally advanced head and neck squamous cell carcinoma.MethodsTwenty-two patients with locally advanced, histologically confirmed head and neck squamous cell carcinoma who were enrolled in the prospective multicenter phase II CheckRad-CD8 trial were included in the current analysis. In this unplanned secondary single-center analysis, all patients who received contrast-enhanced MRI at baseline and in week 4 after single-cycle induction therapy with cisplatin/docetaxel combined with the immune checkpoint inhibitors tremelimumab and durvalumab were included. In week 4, endoscopy with representative re-biopsy was performed to assess tumor response. All lesions were segmented in the baseline and restaging multiparametric MRI, including the primary tumor and lymph node metastases. The volume of interest of the respective lesions was volumetrically measured, and time-resolved mean intensities of the golden-angle radial sparse parallel-volume-interpolated gradient-echo perfusion (GRASP-VIBE) sequence were extracted. Additional quantitative parameters including the T1 ratio, short-TI inversion recovery ratio, apparent diffusion coefficient, and dynamic contrast-enhanced (DCE) values were measured. A model based on parallel random forests incorporating the MRI parameters from the baseline MRI was used to predict tumor response to therapy. Receiver operating characteristic (ROC) curves were used to evaluate the prognostic performance.ResultsFifteen patients (68.2%) showed pathologic complete response in the re-biopsy, while seven patients had a residual tumor (31.8%). In all patients, the MRI-based primary tumor volume was significantly lower after treatment. The baseline DCE parameters of time to peak and wash-out were significantly different between the pathologic complete response group and the residual tumor group (p < 0.05). The developed model, based on parallel random forests and DCE parameters, was able to predict therapy response with a sensitivity of 78.7% (95% CI 71.24–84.93) and a specificity of 78.6% (95% CI 67.13–87.48). The model had an area under the ROC curve of 0.866 (95% CI 0.819–0.914).ConclusionsDCE parameters indicated treatment response at follow-up, and a random forest machine learning algorithm based on DCE parameters was able to predict treatment response to induction chemo-immunotherapy.


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