Zie ook literatuurlijst van niet-toxische middelen en behandelingen specifiek bij longkanker van arts-bioloog drs. Engelbert Valstar

24 juli 2023: zie ook dit artikel: https://kanker-actueel.nl/circulerend-tumor-dna-ctdna-voorspelt-ziekteprogressie-bij-patienten-met-niet-kleincellige-longkanker-egfr-mutatie-die-worden-behandeld-met-tyrosinekinaseremmers.html

30 maart 2023: zie ook dit artikel: https://kanker-actueel.nl/circulerend-tumor-dna-ctdna-regelmatig-meten-en-combineren-met-een-weefselanalyse-biopt-geeft-beduidend-meer-informatie-over-veranderde-mutaties-bij-patienten-met-uitgezaaide-gevorderde-kleincellige-longkanker.html

24 juli 2023: Bron: Nature 21 november 2021

Meting van circulerend tumor-DNA (ctDNA) is een sterke voorspeller van al of niet een optreden van een recidief bij patiënten met niet-kleincellige longkanker. Wanneer het ctDNA een positieve uitslag geeft van overgebleven kankercellen dan is een verwacht recidief een heel stuk meer dan voor de patiënten die negatief scoorden in de ctDNA testen. ctDNA metingen werden gedaan direct na de operatie en gedurende de behandeling met chemotherapie en ook werden die ctDNA metingen gedaan bij patiënten die geen chemotherapie hadden gehad. 

Dat blijkt uit een Chinese studie bij 103 operabele longkankerpatiënten stadium II/III waarbij gedurende een bepaalde periode regelmatig ctDNA is getest. Bij stadium II-III-patiënten heeft de postoperatieve ctDNA-positieve groep baat bij aanvullende chemotherapie als de ctDNA test positief was, terwijl ctDNA-negatieve patiënten een laag risico op een recidief hebben, ongeacht of er wel of geen chemotherapie is toegediend. Tijdens ziekte controle gaat ctDNA-positiviteit mediaan 88 dagen vooraf aan een radiologisch aantoonbaar recidief.

In onderstaande grafiek de verschillen grafisch weergegeven:

figure 2


a Kaplan–Meier curve of recurrence-free survival (RFS) in patients stratified by postsurgical ctDNA status. p-value was calculated by the log-rank test. b Kaplan–Meier curve of RFS in patients stratified by post-ACT ctDNA status. p-value was calculated by the log-rank test. c Kaplan–Meier curve of RFS in stage II–III patients stratified by both ACT treatment and postsurgical ctDNA status. p-value was calculated by the log-rank test for each comparison without adjustments. d Kaplan–Meier curve of RFS in patients stratified by longitudinal ctDNA status. p-value was calculated by the log-rank test.

Het studieverslag, gepubliceerd in Nature geeft een gedetailleerd beeld van hoe is er getest en hoe de onderzoekers de verkregen gegevens hebben toegepast in deze studie. En hoe een ctDNA test van waarde kan zijn voor een vervolg behandeling na de operatie. Of juist geen behandeling om overbehandeling te voorkomen.

Het volledige studierapport is gratis in te zien. Klik op de titel voor het volledige studierapport: 

Dynamic recurrence risk and adjuvant chemotherapy benefit prediction by ctDNA in resected NSCLC

Nature Communications volume 12, Article number: 6770 (2021) Cite this article


Abstract

Accurately evaluating minimal residual disease (MRD) could facilitate early intervention and personalized adjuvant therapies. Here, using ultradeep targeted next-generation sequencing (NGS), we evaluate the clinical utility of circulating tumor DNA (ctDNA) for dynamic recurrence risk and adjuvant chemotherapy (ACT) benefit prediction in resected non-small cell lung cancer (NSCLC). Both postsurgical and post-ACT ctDNA positivity are significantly associated with worse recurrence-free survival. In stage II-III patients, the postsurgical ctDNA positive group benefit from ACT, while ctDNA negative patients have a low risk of relapse regardless of whether or not ACT is administered. During disease surveillance, ctDNA positivity precedes radiological recurrence by a median of 88 days. Using joint modeling of longitudinal ctDNA analysis and time-to-recurrence, we accurately predict patients’ postsurgical 12-month and 15-month recurrence status. Our findings reveal longitudinal ctDNA analysis as a promising tool to detect MRD in NSCLC, and we show pioneering work of using postsurgical ctDNA status to guide ACT and applying joint modeling to dynamically predict recurrence risk, although the results need to be further confirmed in future studies.

Data availability

All raw targeted DNA-sequencing data have been deposited in the National Genomics Data Center (NGDC) under the accession code HRA001346. The deposited and publicly available data are compliant with the regulations of the Ministry of Science and Technology of the People’s Republic of China. The raw sequencing data contain information unique to individuals and are available under controlled access. Access to the data can be requested by completing the application form via GSA-Human System and is granted by the corresponding Data Access Committee. Additional guidance can be found at the GSA-Human System website [https://ngdc.cncb.ac.cn/gsa-human/document/GSA-Human_Request_Guide_for_Users_us.pdf]. Data used for survival analysis and joint model construction and evaluation are publicly available at https://github.com/cancer-oncogenomics/ctDNA-dynamic-prediction-lung-cancer. All specific mutation genomic locations and allele frequencies are available in Supplementary Data 2. Source data are provided with this paper.

Code availability

All analyses were performed using R version 4.0.2. R package survival (version 3.2-10) was used for survival analysis. R package JMbayes (version 0.8-85) was used for the construction and evaluation of joint models and cox models. Reference scripts to reproduce the results of this study is available at https://github.com/cancer-oncogenomics/ctDNA-dynamic-prediction-lung-cancer.

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Acknowledgements

We appreciate the support and participation of the physicians and patients in this study.

Author information

Author notes

  1. These authors contributed equally: Bin Qiu, Wei Guo.

Authors and Affiliations

  1. Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Bin Qiu, Wei Guo, Fan Zhang, Fang Lv, Ying Ji, Yue Peng, Fengwei Tan, Qi Xue, Shugeng Gao & Jie He

  2. Key Laboratory of Minimally Invasive Therapy Research for Lung Cancer, Chinese Academy of Medical Sciences, Beijing, China

    Bin Qiu, Wei Guo, Fengwei Tan, Qi Xue & Shugeng Gao

  3. Geneseeq Research Institute, Nanjing Geneseeq Technology Inc, Nanjing, China

    Xiaoxi Chen, Hua Bao, Yang Xu & Yang Shao

Contributions

B.Q. and S.G. conceived the study. B.Q., W.G., H.B., Y.S., F.T., Q.X. and S.G. provided project management and supervision. B.Q., W.G., F.Z., F.L., Y.J., Y.P. and F.T. provided or facilitated the accrual of patient samples, pathology, and/or clinical data. W.G., X.C. and H.B. performed bioinformatics and genomic analyses. B.Q., W.G., F.Z., F.L., Y.J. and Y.P. performed statistical analyses. W.G. and X.C. wrote the original draft, with input from all authors. B.Q., Y.X., H.B., S.G. and J.H. review and editing the manuscript.

Corresponding author

Correspondence to Shugeng Gao.

Ethics declarations

Competing interests

The following authors are employees of Nanjing Geneseeq Technology Inc. (Xiaoxi Chen, Hua Bao, Yang Xu, and Yang Shao). All remaining authors declare no competing interests.

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ctDNA, circulerend tumor-DNA, niet-kleincellige longkanker, voorspellende waarde, chemotherapie, minimale residuele ziekte, MRD


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