Published papers

We have grown Ce-doped (La,Y)$_2$Si$_2$O$_7$ single crystal by micro-pulling-down method and investigated its optical and scintillation properties. We have successfully prepared the single crystal with (Ce$_{0.015}$La$_{0.600}$Y$_{0.385}$)$_2$Si$_2$O$_7$ composition. The observed thermal quenching process could be characterized by the quenching temperature (T50%) of 526 K and its activation energy was determined to be 0.62 eV. Further considering the thermal quenching factors, it was found that the thermal quenching was caused by at least the thermal ionization and maybe also by classical thermal quenching. The light output and scintillation decay time were evaluated to be ~12,000 photons/MeV and ~42 ns, respectively. These results indicate that (Ce$_{0.015}$La$_{0.600}$Y$_{0.385}$)$_2$Si$_2$O$_7$ has a great potential for application in scintillation materials.

The interim analysis of the CIRCULATE-Japan GALAXY observational study demonstrated the association of circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) detection with recurrence risk and benefit from adjuvant chemotherapy (ACT) in resectable colorectal cancer (CRC). This updated analysis with a 23-month median follow-up, including 2,240 patients with stage II-III colon cancer or stage IV CRC, reinforces the prognostic value of ctDNA positivity during the MRD window with significantly inferior disease-free survival (DFS; hazard ratio (HR): 11.99, P < 0.0001) and overall survival (OS; HR: 9.68, P < 0.0001). In patients who experienced recurrence, ctDNA positivity correlated with shorter OS (HR: 2.71, P < 0.0001). The significantly shorter DFS in MRD-positive patients was consistent across actionable biomarker subsets. Sustained ctDNA clearance in response to ACT was an indicator of favorable DFS and OS compared to transient clearance (24-month DFS: 89.0% versus 3.3%; 24-month OS: 100.0% versus 82.3%). True spontaneous clearance rate with no clinical recurrence was 1.9% (2/105). Overall, our findings provide evidence for the utility of ctDNA monitoring for post-resection recurrence and mortality risk stratification that could be used for guiding adjuvant therapy.

3555Background: Wnt/β-catenin signaling is activated by loss-of-function mutations in the adenomatous polyposis coli (APC) gene and plays a key role in tumorigenesis in colorectal cancer (CRC). Tankyrase inhibitors, which cause degradation of β-catenin, are expected to have a promising therapeutic effect for CRC, and the short-form APC mutations predict the sensitivity of CRC cells to tankyrase inhibitors (Tanaka et al. Mol Cancer Ther 2017; Chen et al. Br J Cancer, in press).However, clinicopathological characteristics and survival in metastatic CRC (mCRC) with short-form APCmutations remain unclear. Methods: Patients with mCRC who were treated with chemotherapy between 2010 and 2021 and have tissue or circulating tumor DNA-based next-generation sequencing results were enrolled. Short-form APC mutations were defined as those truncated at amino acid 1, 256 or shorter, lacking all seven 20-amino acid repeat (20-AAR) regions. Non-short-form APC mutations were defined as those possess more than one 20-AAR. Short-form and non-short-form heterozygous mutations were classified as non-short-form APC mutations. We confirmed incidence of mCRC with short-form APC mutations and compared clinicopathological characteristics and overall survival (OS) between mCRC patients with short-form and non-short-form APCmutations. Results: Of 177 patients (median age, 56.0 years) included in this study, 44 (25%) and 79 (45%) had short-form and non-short-form APC mutations, respectively. Patients with short-form APC mutations were not likely to have lung metastasis (P = 0.15). Logistic regression multivariate analysis, lung metastasis was related to mCRC patients with short-form APC mutations (Odds ratio: 0.46, P = 0.047). Patients with short-form APC mutations had significantly shorter overall survival (OS) than did those without (n = 133), with a median OS of 34.7 vs 50.5 months (PLog-rank= 0.035, hazard ratio (HR), 1.59; 95% confidence interval (CI), 1.03-2.45). In multivariate analysis, short-form APC mutation was independent factor related to OS (hazard ratio (HR): 1.68, P = 0.02), as well as the BRAF V600E mutation, liver metastasis and peritoneal metastasis. Conclusions: Short-form APC mutation is more common in mCRC patients without lung metastases and is independently associated with a short prognosis.

Despite decreased incidence rates in average-age onset patients in high-income economies, colorectal cancer is the third most diagnosed cancer in the world, with increasing rates in emerging economies. Furthermore, early onset colorectal cancer (age ≤50 years) is of increasing concern globally. Over the past decade, research advances have increased biological knowledge, treatment options, and overall survival rates. The increase in life expectancy is attributed to an increase in effective systemic therapy, improved treatment selection, and expanded locoregional surgical options. Ongoing developments are focused on the role of sphincter preservation, precision oncology for molecular alterations, use of circulating tumour DNA, analysis of the gut microbiome, as well as the role of locoregional strategies for colorectal cancer liver metastases. This overview is to provide a general multidisciplinary perspective of clinical advances in colorectal cancer.

PURPOSE: 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.

OBJECTIVE: To investigate the association between perioperative ctDNA status and prognosis in patients with esophageal squamous cell carcinoma (ESCC). BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for assessing molecular residual disease (MRD) in various malignancies. However, there are limited studies evaluating the utility of ctDNA for predicting recurrence risk in patients with ESCC. METHODS: We prospectively enrolled patients with locally advanced ESCC who were scheduled to receive neoadjuvant chemotherapy (NAC) followed by surgery. This report retrospectively analyzed ctDNA with a personalized, tumor-informed 16-plex mPCR-NGS assay at multiple time points: pre-NAC, post-NAC but before surgery, postoperatively, and longitudinally during follow-up. RESULTS: A total of 28 patients who underwent curative surgery, and had successful whole-exome sequencing analysis of tumor tissue samples were included in this report. At the pre-NAC time point, ctDNA was detected in 50% of patients with stage I and 100% of those with stages II, III, and IV. Post-NAC but before surgery, ctDNA was detected in 33.3% of patients. The recurrence rate was 77.8% in ctDNA-positive patients compared to 27.8% in ctDNA-negative patients, with significantly worse recurrence-free survival (RFS) for ctDNA-positive patients vs. ctDNA-negative patients (HR: 4.56, P =0.01). In patients analyzed during the MRD window (2-16 weeks post-surgery), the recurrence rate was 100% in ctDNA-positive patients compared to 30.4% in ctDNA-negative patients, with significantly worse RFS (HR: 30.99, P <0.0001). Similarly, during surveillance (>16 weeks post-surgery), detectable ctDNA was significantly associated with poor RFS (HR: 27.34, P =0.003). CONCLUSION: This study suggests that ctDNA-based MRD assessment may be valuable for evaluating patients with ESCC, particularly in post-NAC and postsurgical settings.