On the road with OIRO: Taking Science to the supermarket

The SCRUM-MONSTAR Cancer-Omics Ecosystem: Striving for a Quantum Leap in Precision Medicine

Abstract The SCRUM-Japan MONSTAR-SCREEN consortium is a nationwide molecular profiling project employing artificial intelligence–driven multiomics analyses for patients with advanced malignancies, aiming to develop novel therapeutics and diagnostics and deliver effective drugs to patients. Concurrently, studies assessing molecular residual disease–based precision medicine for resectable solid tumors, including CIRCULATE-Japan, are ongoing. The substantial data generated by these platforms are stored within a state-of-the-art supercomputing infrastructure, VAPOR CONE. Since 2015, our project has registered over 24,000 patients as of December 2023. Among 16,144 patients with advanced solid tumors enrolled in MONSTAR-SCREEN projects, 5.0% have participated in matched clinical trials, demonstrating a 29.2% objective response rate and 14.8-month median survival (95% CI, 13.4–16.3) for patients treated in the matched clinical trials. Notably, patients who received matched therapy demonstrated significantly prolonged overall survival compared with those who did not (hazard ratio 0.77; 95% confidence interval, 0.71–0.83). Significance: Our nationwide molecular profiling initiative played pivotal roles in facilitating the enrollment of patients with advanced solid tumors into matched clinical trials and highlighted the substantial survival benefits of patients treated with matched therapy. We aim to facilitate an industry–academia data-sharing infrastructure ecosystem, fostering new drug discovery paradigms and precision medicine.

Supplementary Table 4 from The SCRUM-MONSTAR Cancer-Omics Ecosystem: Striving for a Quantum Leap in Precision Medicine

Summary of umbrella and basket trials evaluating the efficacy of targeted biomarker-driven therapies

Data from The SCRUM-MONSTAR Cancer-Omics Ecosystem: Striving for a Quantum Leap in Precision Medicine

<div>AbstractThe SCRUM-Japan MONSTAR-SCREEN consortium is a nationwide molecular profiling project employing artificial intelligence–driven multiomics analyses for patients with advanced malignancies, aiming to develop novel therapeutics and diagnostics and deliver effective drugs to patients. Concurrently, studies assessing molecular residual disease–based precision medicine for resectable solid tumors, including CIRCULATE-Japan, are ongoing. The substantial data generated by these platforms are stored within a state-of-the-art supercomputing infrastructure, VAPOR CONE. Since 2015, our project has registered over 24,000 patients as of December 2023. Among 16,144 patients with advanced solid tumors enrolled in MONSTAR-SCREEN projects, 5.0% have participated in matched clinical trials, demonstrating a 29.2% objective response rate and 14.8-month median survival (95% CI, 13.4–16.3) for patients treated in the matched clinical trials. Notably, patients who received matched therapy demonstrated significantly prolonged overall survival compared with those who did not (hazard ratio 0.77; 95% confidence interval, 0.71–0.83).Significance: Our nationwide molecular profiling initiative played pivotal roles in facilitating the enrollment of patients with advanced solid tumors into matched clinical trials and highlighted the substantial survival benefits of patients treated with matched therapy. We aim to facilitate an industry–academia data-sharing infrastructure ecosystem, fostering new drug discovery paradigms and precision medicine.</div>

Supplementary Figure 3 from The SCRUM-MONSTAR Cancer-Omics Ecosystem: Striving for a Quantum Leap in Precision Medicine

Design of the whole transcriptome sequencing–based clinical trial platform in MONSTAR-SCREEN-3

Supplementary Table 3 from The SCRUM-MONSTAR Cancer-Omics Ecosystem: Striving for a Quantum Leap in Precision Medicine

Cox multivariate analysis of overall survival

Supplementary Table 1 from The SCRUM-MONSTAR Cancer-Omics Ecosystem: Striving for a Quantum Leap in Precision Medicine

List of regulatory approvals for targeted therapies and associated clinical trials in SCRUM-Japan MONSTAR-SCREEN project

Supplementary Figure 2 from The SCRUM-MONSTAR Cancer-Omics Ecosystem: Striving for a Quantum Leap in Precision Medicine

Comparison of overall survival between patients receiving matched therapy vs. those not receiving matched therapy among patients with any targets recommended for matched therapy.

Supplementary Figure 1 from The SCRUM-MONSTAR Cancer-Omics Ecosystem: Striving for a Quantum Leap in Precision Medicine

Conceptual framework for virtual sequencing using deep learning.

Supplementary Table 2 from The SCRUM-MONSTAR Cancer-Omics Ecosystem: Striving for a Quantum Leap in Precision Medicine

List of regulatory approvals for companion diagnostic therapeutics in SCRUM-Japan MONSTAR-SCREEN project

Clinical utility of BRCA and ATM mutation status in circulating tumour DNA for treatment selection in advanced pancreatic cancer

Supplementary Figure 1 from Colorectal Cancer Recurrence Prediction Using a Tissue-Free Epigenomic Minimal Residual Disease Assay

Supplementary Figure 1. Sample Collection and Imaging Schedule.

Supplementary Table 6 from Colorectal Cancer Recurrence Prediction Using a Tissue-Free Epigenomic Minimal Residual Disease Assay

Supplementary Table 6. Risk of recurrence based on ctDNA detection following adjuvant chemotherapy in patients with stage II or higher CRC. Tables to accompany Figure 5A-B.

Supplementary Figure 6 from Colorectal Cancer Recurrence Prediction Using a Tissue-Free Epigenomic Minimal Residual Disease Assay

Supplementary Figure 6. Patterns of recurrence in the Longitudinal Analysis population.

Data from Colorectal Cancer Recurrence Prediction Using a Tissue-Free Epigenomic Minimal Residual Disease Assay

<div>AbstractPurpose:Posttreatment detection of ctDNA is strongly predictive of recurrence. Most minimal/molecular residual disease assays require prior tissue testing to guide ctDNA analysis, resulting in lengthy time to initial results and unevaluable patients.Experimental Design:We assessed a tissue-free assay (Guardant Reveal) that bioinformatically evaluates >20,000 epigenomic regions for ctDNA detection in 1,977 longitudinally collected postoperative plasma samples from 342 patients with resected colorectal cancer.Results:We observed sensitive and specific detection of minimal/molecular residual disease associated with clinically meaningful differences in recurrence-free intervals at each time point evaluated with a median lead time of 5.3 months. The longitudinal sensitivity in stage II or higher colon cancer was 81%. Sensitivity increased with serial measurement and varied by recurrence site: higher for liver (100%) versus lung (53%) and peritoneal (40%). Sensitivity among patients with rectal cancer was 60% owing to a high proportion of lung metastases. Specificity was 98.2% among 1,461 posttreatment samples (99.1% among those with follow-up longer than the upper IQR of the lead time observed in this study).Conclusions:Our data demonstrate the potential clinical utility of ctDNA as a tool to improve the management of stage II and higher colorectal cancer with a methodology that is noninvasive, accessible, and allows for rapid evaluation to inform clinical decisions.</div>

Supplementary Figure 8 from Colorectal Cancer Recurrence Prediction Using a Tissue-Free Epigenomic Minimal Residual Disease Assay

Supplementary Figure 8. Patterns of recurrence based on ctDNA detection 28 days post-surgery.

Supplementary Figure 4 from Colorectal Cancer Recurrence Prediction Using a Tissue-Free Epigenomic Minimal Residual Disease Assay

Supplementary Figure 4. ctDNA kinetics among 15 recurrence patients with more than one positive sample.

Supplementary Table 7 from Colorectal Cancer Recurrence Prediction Using a Tissue-Free Epigenomic Minimal Residual Disease Assay

Supplementary Table 7. Risk of recurrence based on ctDNA detection early on adjuvant chemotherapy in patients with stage II or higher CRC, Tables to accompany Supplementary Figure 9A-B.

Supplementary Figure 7 from Colorectal Cancer Recurrence Prediction Using a Tissue-Free Epigenomic Minimal Residual Disease Assay

Supplementary Figure 7. Risk of recurrence based on ctDNA detection 28 days post-surgery by pathologic stage.

Supplementary Table 3 from Colorectal Cancer Recurrence Prediction Using a Tissue-Free Epigenomic Minimal Residual Disease Assay

Supplementary Table 3. ctDNA Positive Rate in the 1,902 samples from 334 Patients in the Longitudinal Surveillance Analysis by Stage.

Supplementary Table 1 from Colorectal Cancer Recurrence Prediction Using a Tissue-Free Epigenomic Minimal Residual Disease Assay

Supplementary Table 1. Clinicopathologic Characteristics of the 342 Enrolled Patients with Clinical Stage I-III CRC.

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