Dataset Information

Cancer organoid-based diagnosis reactivity prediction (CODRP) index-based anticancer drug sensitivity test in ALK-rearrangement positive non-small cell lung cancer (NSCLC).

ABSTRACT:

Background

Recently, cancer organoid-based drug sensitivity tests have been studied to predict patient responses to anticancer drugs. The area under curve (AUC) or IC₅₀ value of the dose-response curve (DRC) is used to differentiate between sensitive and resistant patient's groups. This study proposes a multi-parameter analysis method (cancer organoid-based diagnosis reactivity prediction, CODRP) that considers the cancer stage and cancer cell growth rate, which represent the severity of cancer patients, in the sensitivity test.

Methods

On the CODRP platform, patient-derived organoids (PDOs) that recapitulate patients with lung cancer were implemented by applying a mechanical dissociation method capable of high yields and proliferation rates. A disposable nozzle-type cell spotter with efficient high-throughput screening (HTS) has also been developed to dispense a very small number of cells due to limited patient cells. A drug sensitivity test was performed using PDO from the patient tissue and the primary cancer characteristics of PDOs were confirmed by pathological comparision with tissue slides.

Results

The conventional index of drug sensitivity is the AUC of the DRC. In this study, the CODRP index for drug sensitivity test was proposed through multi-parameter analyses considering cancer cell proliferation rate, the cancer diagnosis stage, and AUC values. We tested PDOs from eight patients with lung cancer to verify the CODRP index. According to the anaplastic lymphoma kinase (ALK) rearrangement status, the conventional AUC index for the three ALK-targeted drugs (crizotinib, alectinib, and brigatinib) did not classify into sensitive and resistant groups. The proposed CODRP index-based drug sensitivity test classified ALK-targeted drug responses according to ALK rearrangement status and was verified to be consistent with the clinical drug treatment response.

Conclusions

Therefore, the PDO-based HTS and CODRP index drug sensitivity tests described in this paper may be useful for predicting and analyzing promising anticancer drug efficacy for patients with lung cancer and can be applied to a precision medicine platform.

SUBMITTER: Lee SY

PROVIDER: S-EPMC10664561 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Publications

Cancer organoid-based diagnosis reactivity prediction (CODRP) index-based anticancer drug sensitivity test in ALK-rearrangement positive non-small cell lung cancer (NSCLC).

Lee Sang-Yun SY Cho Hyeong Jun HJ Choi Jimin J Ku Bosung B Moon Seok Whan SW Moon Mi Hyoung MH Kim Kyung Soo KS Hyun Kwanyong K Kim Tae-Jung TJ Sung Yeoun Eun YE Hwang Yongki Y Lee Eunyoung E Ahn Dong Hyuck DH Choi Joon Young JY Lim Jeong Uk JU Park Chan Kwon CK Kim Sung Won SW Kim Seung Joon SJ Koo In-Seong IS Jung Woo Seok WS Lee Sang-Hyun SH Yeo Chang Dong CD Lee Dong Woo DW

Journal of experimental & clinical cancer research : CR 20231122 1

<h4>Background</h4>Recently, cancer organoid-based drug sensitivity tests have been studied to predict patient responses to anticancer drugs. The area under curve (AUC) or IC<sub>50</sub> value of the dose-response curve (DRC) is used to differentiate between sensitive and resistant patient's groups. This study proposes a multi-parameter analysis method (cancer organoid-based diagnosis reactivity prediction, CODRP) that considers the cancer stage and cancer cell growth rate, which represent the ...[more]

PMID: 37993887

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Project description:IntroductionRadiotherapy (RT) is currently the main treatment for brain metastases (BMs) from non-small cell lung cancer (NSCLC). Due to the short survival time and obvious adverse reactions of RT, we urgently need more appropriate treatment. This network meta-analysis reviewed the efficacy and adverse effects of radiotherapy-based combination therapy for patients without targeted epidermal growth factor receptor (EGFR) mutations/anaplastic lymphoma kinase (ALK) gene rearrangement NSCLC BMs, to screen out the therapy with the best efficacy.MethodsPubMed, Embase, Web of Science, and Cochrane Library were searched from the earliest publication date available to 1 April 2022. STATA15.0 was used to conduct heterogeneity analysis, sensitivity analysis, forest plot analysis, and publication bias analysis.ResultsA total of 28 studies, involving 3707 patients were included in the Bayesian network meta-analysis. In the limited paired meta-analysis for head-to-head comparative trials, compared with RT-based combination therapy, RT combined with Immune checkpoint inhibitors (ICIs) showed significant overall survival (OS) benefit (HR 0.65, 95%CI 0.47-0.9, p<0.01), RT combined with ICIs showed a non-significant difference for intracranial progression-free survival (iPFS) (HR 0.76, 95%CI 0.27-2.27, p<0.01) and progression-free survival (PFS) (HR 0.9, 95%CI 0.36-2.37, p<0.01). In addition, according to the ranking results, compared with RT combined with chemotherapy(CT) or with targeted therapy(TT), RT combined with ICIs might be the best treatment mode for OS(ICIs+RT vs CT+RT vs TT+RT; 91.9% vs. 27.8% vs. 29.3%, iPFS (ICIs+RT vs CT+RT vs TT+RT, 46.9% vs 25.2% vs 25.6%) and PFS (ICIs+RT vs CT+RT vs TT+RT, 36.2% vs 31% vs 36.5%).ConclusionsRT combined with ICIs might be the best treatment mode to prolong the OS for BMs from NSCLC with non-EGFR mutation/ALK gene rearrangement.Review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022350065, identifier (CRD42022350065).

Project description:BackgroundAnaplastic lymphoma kinase (ALK) test in advanced non-small cell lung cancer (NSCLC) can help physicians provide target therapies for patients harboring ALK gene rearrangement. This study aimed to investigate the real-world test patterns and positive rates of ALK gene rearrangements in advanced NSCLC.MethodsIn this real-world study (ChiCTR2000030266), patients with advanced NSCLC who underwent an ALK rearrangement test in 30 medical centers in China between October 1, 2018 and December 31, 2019 were retrospectively analyzed. Interpretation training was conducted before the study was initiated. Quality controls were performed at participating centers using immunohistochemistry (IHC)-VENTANA-D5F3. The positive ALK gene rearrangement rate and consistency rate were calculated. The associated clinicopathological characteristics of ALK gene rearrangement were investigated as well.ResultsThe overall ALK gene rearrangement rate was 6.7% in 23,689 patients with advanced NSCLC and 8.2% in 17,436 patients with advanced lung adenocarcinoma. The quality control analysis of IHC-VENTANA-D5F3 revealed an intra-hospital consistency rate of 98.2% (879/895) and an inter-hospital consistency rate of 99.2% (646/651). IHC-VENTANA-D5F3 was used in 53.6%, real-time polymerase chain reaction (RT-PCR) in 25.4%, next-generation sequencing (NGS) in 18.3%, and fluorescence in-situ hybridization (FISH) in 15.9% in the adenocarcinoma subgroup. For specimens tested with multiple methods, the consistency rates confirmed by IHC-VENTANA-D5F3 were 98.0% (822/839) for FISH, 98.7% (1,222/1,238) for NGS, and 91.3% (146/160) for RT-PCR. The overall ALK gene rearrangement rates were higher in females, patients of ≤ 35 years old, never smokers, tumor cellularity of > 50, and metastatic specimens used for testing in the total NSCLC population and adenocarcinoma subgroup (all P < 0.05).ConclusionsThis study highlights the real-world variability and challenges of ALK test in advanced NSCLC, demonstrating a predominant use of IHC-VENTANA-D5F3 with high consistency and distinct clinicopathological features in ALK-positive patients. These findings underscore the need for a consensus on optimal test practices and support the development of refined ALK test strategies to enhance diagnostic accuracy and therapeutic decision-making in NSCLC.

Dataset Information

Cancer organoid-based diagnosis reactivity prediction (CODRP) index-based anticancer drug sensitivity test in ALK-rearrangement positive non-small cell lung cancer (NSCLC).

Background

Methods

Results

Conclusions

Publications

Cancer organoid-based diagnosis reactivity prediction (CODRP) index-based anticancer drug sensitivity test in ALK-rearrangement positive non-small cell lung cancer (NSCLC).

Similar Datasets

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