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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.

Keywords Non-small cell Lung cancer (NSCLC), High-throughput screening (HTS), Cancer Organoid-based diagnosis
reactivity prediction (CODRP) platform, Patient-derived Organoid (PDO), 3D cell culture