論文

Background: The phase 3 BEACON CRC study demonstrated the survival benefits of encorafenib and cetuximab, with or without binimetinib (the BEACON triplet or doublet regimen), for BRAFV600E-mutant metastatic colorectal cancer (mCRC). This expanded access program (EAP) and subsequent follow-up study assessed the efficacy and safety of the BEACON triplet regimen in Japanese patients with BRAFV600E-mutant mCRC. Materials and Methods: The EAP was an open-label, single-arm study including Japanese patients with BRAFV600E-mutant mCRC whose disease progressed after 1 to 2 prior regimens. The patients received the BEACON triplet regimen with 28-day cycles. The subsequent follow-up study assessed the survival outcomes following EAP completion. Safety was assessed only during the EAP. Results: Among the 86 enrolled patients, 81 received the BEACON triplet regimen. The objective response rate and median progression-free survival were 27.6% (95% confidence interval [CI], 18.0%-39.1%) and 5.26 (95% CI, 4.14-5.52) months, respectively. Grade 3 to 4 adverse events and treatment-related adverse events occurred in 43.2% and 28.4% of patients, respectively. No new safety signals were observed during the EAP. Among 58 patients with confirmed survival at EAP completion, 57 were included in the follow-up study. With a median observation period of 9.17 months through the EAP and follow-up study, the median overall survival was 10.38 (95% CI, 9.00-16.16) months. Conclusion: The efficacy and safety of the BEACON triplet regimen in Japanese patients with BRAFV600E-mutant mCRC were consistent with those reported in the BEACON CRC trial, supporting its use as a standard treatment for pretreated patients with BRAFV600E-mutant mCRC.

As the number of scientific papers continues to grow, there is a demand for approaches that can effectively convey research findings, with posters serving as a key medium for presenting paper contents. Poster layouts determine how effectively research is communicated and understood, highlighting their growing importance. In particular, a gap remains in understanding how papers correspond to the layouts that present them, which calls for datasets with paired annotations at scale. To bridge this gap, we introduce SciPostGen, a large-scale dataset for understanding and generating poster layouts from scientific papers. Our analyses based on SciPostGen show that paper structures are associated with the number of layout elements in posters. Based on this insight, we explore a framework, Retrieval-Augmented Poster Layout Generation, which retrieves layouts consistent with a given paper and uses them as guidance for layout generation. We conducted experiments under two conditions: with and without layout constraints typically specified by poster creators. The results show that the retriever estimates layouts aligned with paper structures, and our framework generates layouts that also satisfy given constraints. The dataset and code are publicly available at https://omron-sinicx.github.io/paper2layout/.

Recently, the first case of a novel DEK-AFF2 fusion has been identified in nonkeratinizing squamous cell carcinoma (SCC) of the sinonasal tract with an exceptional response to pembrolizumab. Here we present the case of a 71-year-old female with metastatic poorly differentiated SCC of the sinonasal cavity with a DEK-AFF2 fusion. She initially received pembrolizumab monotherapy as first-line treatment, but the disease progressed after two months. Subsequent treatment with paclitaxel plus cetuximab also led to disease progression after two months. She was enrolled in the SCRUM-Japan MONSTAR-SCREEN-2, a nationwide molecular profiling project. Tumor tissue samples were analyzed using whole exome and transcriptome sequencing (WETS). WETS of a pretreatment tissue specimen revealed DEK-AFF2 fusion and APC pathogenic variant (p.G1677fs), and HLA genotype HLA-A*02:06/24:02, HLA-B*39:04/54:01, and HLA-C*01:02/07:02. Third-line therapy with 5-FU, carboplatin, and pembrolizumab achieved a partial response, but disease progression occurred after nine months. In tissues obtained from pancreatic metastases, acquired amplification of MYC (copy number 8.7) was detected in addition to DEK-AFF2 fusion and APC mutation. These findings suggest that the lack of benefit from pembrolizumab despite the presence of DEK-AFF2 fusion may be due to the HLA haplotype being different from one reported to be associated with efficacy. Additionally, acquired MYC amplification may contribute to resistance to chemotherapy and pembrolizumab. These findings underscore the importance of personalized treatment strategies in SCC patients with specific genomic alterations.

Cross-sectional relationships between nocturia and sleep problems have been well evaluated but the risk association for each incidence is scarcely reported. This analysis included 8076 participants of the Nagahama study in Japan (median age 57, 31.0% male) and associations between nocturia and self-reported, sleep-related problems (poor sleep) were evaluated cross-sectionally. Causal effects on each new-onset case were analyzed longitudinally after 5 years. Three models were applied: univariable analysis, adjustment for basic variables (i.e., demographic and lifestyle variables) and full adjustment for basic and clinical variables. The overall prevalences of poor sleep and nocturia were 18.6% and 15.5%, while poor sleep was positively associated with nocturia (OR = 1.85, p < 0.001) and vice versa (OR = 1.90, p < 0.001). Among 6579 good sleep participants, 18.5% developed poor sleep. Baseline nocturia was positively associated with this incident poor sleep (OR = 1.49, p < 0.001, full adjustment). Among 6824 non-nocturia participants, the nocturia incidence was 11.3%. Baseline poor sleep was positively associated with this incident nocturia (OR = 1.26, p = 0.026); such associations were significant only in women (OR = 1.44, p = 0.004) and under-50-year-old groups (OR = 2.82, p < 0.001), after full adjustment. Nocturia and poor sleep associate with each other. Baseline nocturia can induce new-onset poor sleep while baseline poor sleep may induce new-onset nocturia only in women.

Background: Post-radical prostatectomy (RP) lymph node positivity (pN1) is associated with disease progression. However, the optimal treatment strategy for pN1 patients has remained unclear. This study aimed to establish a risk model for predicting survival outcomes in these patients. Methods: We retrospectively studied 528 eligible patients with pN1 undergoing RP with pelvic lymph node dissection between 2006 and 2019 at 33 participant institutions in the Japanese Urologic Oncology Study Group. Metastasis-free survival (MFS) was used to evaluate for survival outcome. A least absolute shrinkage and selection operator (LASSO)-penalized, multivariate Cox regression model for MFS was used to evaluate patients for their risk factors and establish a risk model with an associated nomogram. Results: Grade group (GGs 4–5 vs. GGs 1–3: HR, 7.35; 95% confidence intervals (CI), 1.76–30.7; p = 0.006), pathological T-stage (pT3b or more vs. pT2 to pT3a: HR, 2.01; 95% CI, 0.93–4.34; p = 0.075), number of positive lymph nodes (HR, 2.03; 95% CI, 0.83–4.96; p = 0.044), and positive lymph node diameter (> 2 mm vs. ≤ 2 mm: HR, 2.03; 95% CI, 1.09–9.00; p = 0.034) were identified as independent prognostic factors for predicting 60-month MFS. Conclusions: This study explored prognostic factors for pN1 prostate cancer patients for predicting their MFS and identified a risk model involving a nomogram. Randomized controlled trials are necessary in patients with pN1 prostate cancer to elucidate optimal postoperative treatment indications and selection.

Background: Several biomarkers have been established for metastatic colorectal cancer (mCRC). We investigated whether plasma angiogenesis factors could predict the efficacy of biologics combined with chemotherapy in first-line (1L) treatment in patients with RAS wild-type mCRC and the dynamics of plasma angiogenesis factors at progression during 1L treatment. Methods: In this multicenter prospective observational study, serial plasma samples were prospectively collected at pretreatment and progression stages; 17 plasma angiogenesis factors were analyzed using the multiplex assay with Luminex® technology. Interactions between the pretreatment measurements and treatment groups on progression-free survival (PFS) and overall survival (OS) in patients with RAS wild-type were assessed using the propensity-score weighted Cox proportional hazards model. Results: From February 2018 to September 2020, 202 patients were enrolled in the 1L cohort; 133 patients had RAS wild-type (chemotherapy plus bevacizumab [BEV group, n = 33] and plus anti-epidermal growth factor receptor monoclonal antibodies [aEGFR group, n = 100]). A trend of strong interaction on PFS was observed for interleukin-8 (IL-8) (p = 0.0752) and soluble vascular cell adhesion molecule-1 (sVCAM-1) (p = 0.0156). Regarding OS, IL-8 (p = 0.0283), soluble vascular endothelial growth factor-receptor-1 (sVEGFR-1) (p = 0.0777) and sVCAM-1 (p = 0.0011) tended to differentiate the treatment effect. In 112 patients, plasma samples were evaluable for dynamic analysis (57 and 55 from the BEV and aEGFR groups, respectively). In the BEV group, six factors significantly increased during progression, whereas two decreased. In the aEGFR group, three factors significantly increased, and six decreased. Conclusion: Pretreatment plasma IL-8 and sVCAM-1 levels could be predictive biomarkers to distinguish BEV and anti-EGFR mAbs when combined with chemotherapy in the 1L treatment of RAS wild-type mCRC. Several plasma angiogenesis factors showed significant change at progression in 1L chemotherapy plus biologics for RAS wild-type mCRC, which are potential biomarkers for selecting an optimal angiogenesis inhibitor in second-line treatment.

183Background: In pts with CRC, the clinical usefulness of ctDNA testing after curative resection has been strongly suggested. Prognostic biomarkers are also needed for pts with resectable metastases to identify high-risk patients who may be spared unnecessary surgery or local ablation. We aimed to create a prediction model to estimate the risk of post-operative recurrence using an integrated analysis of preoperative ctDNA level and radiographic imaging. Methods: The GALAXY study (UMIN000039205) included 645 pts with newly diagnosed or recurrent CRC with resectable metastatic lesions. Pts without liver or lung metastases and those who had received chemotherapy within 3 months prior to ctDNA measurement were excluded. We used the ratio of preoperative ctDNA levels [mean tumor molecules (MTM)/mL] to tumor metastasis volume (mL) from radiographic imaging (ctDNA/volume) to predict recurrence. Cutoff ctDNA/volume values were determined from receiver operating characteristic curves using Youden index. Pts with above and below the cutoff values were defined as high and low risk, respectively. Disease-free survival (DFS) was calculated from the date of definitive surgical resection to first recurrence or death. Results: In this cohort of 110 pts with liver metastases and 24 with lung metastases, the median follow-up was 13.2 months (range: 0.7-30.9). The cutoff values for the ctDNA/volume model were 0.837 (liver) and 0.496 (lung) MTM/mL2. Among the pts with liver metastases, the high-risk group predicted by the ctDNA/volume model had a median DFS of 14.7 months (95% CI: 6.1–not reached) versus not reached (95% CI: not reached–not reached) in the low-risk group (HR = 3.6, P = 0.021). Among the pts with lung metastases, the median DFS was 2.9 months (95% CI: 2.1–not reached) in the high-risk group versus 21.8 months (95% CI: 21.8–not reached) in the low-risk group (HR = 21.0, P < 0.0001). The high-risk group had a significantly higher cumulative recurrence at 6 months (17% and 67% in pts with liver and lung metastases, respectively) versus the low-risk group (0%, P = 0.012 and 6%, P < 0.001 in pts with liver and lung metastases, respectively) considering death as a competing risk. Conclusions: The ctDNA/volume model was able to predict postoperative recurrence in CRC pts with liver and lung metastases. Ongoing and future studies will further optimize the model by incorporating other clinicopathologic factors associated with postoperative CRC recurrence. [Table presented]

Background: Undetectable circulating tumor DNA (ctDNA) is an obstacle to performing comprehensive genomic profiling in daily practice to identify genomic alterations. We investigated the associations between clinicopathological factors and undetectable ctDNA using a commercially available comprehensive genomic profiling assay in metastatic prostate cancer. Patients and methods: Patients treated with systemic treatment for metastatic prostate cancer were included. ctDNA was analyzed by FoundationOne®Liquid CDx at enrollment. The associations between clinicopathological characteristics and ctDNA detection were analyzed. Results: The number of bone metastasis was associated with ctDNA detection (odds ratio [95% confidence interval], 13.6 [1.71–108], P = 0.014). An algorithm predicting ctDNA detection using clinicopathological parameters was created. If ≥ 4 bone metastases were observed, ctDNA detection was estimated to be 98.9%. Among the patients with < 4 bone metastases, if two or three features among ISUP grade group 5, PSA level ≥ 10 ng/ml, and castration resistance were present, the ctDNA detection rate was 96.7% while the ctDNA detection rate was 86.3% if no or only one feature was present. Conclusions: An algorithm created in this study is helpful in determining when to undertake comprehensive genomic profiling assay using blood.

Purpose: Preoperative chemoradiotherapy (CRT) and surgical cohorts, respectively. While immune-related severe adverse events resection are the standard treatment for locally advanced rectal were observed in 3 patients, no treatment-related deaths were cancer (LARC). Combining immune checkpoint inhibitors with observed. In 38 patients with MSS who underwent surgery, pCR radiation suggests a promising approach for enhancing efficacy. We rates of 75% (6/8) and 17% (5/30; P = 0.004, Fisher exact test) were investigated the efficacy of CRT followed by nivolumab and surgery observed in those with programmed cell death ligand 1 (PD-L1) in patients with LARC. tumor proportion score ≥1% and <1%, respectively; IHC staining Patients and Methods: In phase I, we investigated the feasibility was performed using pre-CRT samples. In 24 patients with of sequentially combined CRT, 5 cycles of nivolumab, and radical MSS, pre-CRT samples were analyzed by flow cytometry; pCR surgery. In phase II, patients with microsatellite stable (MSS) and rates of 78% (7/9) and 13% (2/15; P = 0.003, Fisher exact test) microsatellite instability-high (MSI-H) LARC were evaluated. were observed for CD8þ T cell/effector regulatory T cell (CD8/Results: Three patients in phase I received full courses of CRT eTreg) ratios of ≥2.5 and <2.5, respectively, in tumor-infiltrating and nivolumab without dose modification; the schedule was recomlymphocytes. mended for phase II. A pathologic complete response (pCR) was Conclusions: CRT followed by consolidation nivolumab could centrally confirmed in 30% [11/37; 90% confidence interval (CI), increase pCR. PD-L1 expression and an elevated CD8/eTreg ratio 18%–44%] and 60% (3/5) of the MSS and exploratory MSI-H were positive predictors in patients with MSS LARC.

Circulating tumor DNA (ctDNA) testing in patients with colorectal cancer (CRC) has demonstrated clinical significance in various contexts, including post-curative resection. Therefore, we developed a predictive model integrating preoperative ctDNA levels with radiographic imaging to assess the risk of postoperative recurrence in patients with CRC. Patients with CRC from the GALAXY study with either newly diagnosed or recurrent, curatively resectable liver or lung metastases were enrolled between May 2020 and December 2022, and radiographic images were collected between February 2023 and January 2025. The ratio of preoperative ctDNA levels to tumor metastasis volume from radiographic imaging, ctDNA levels alone, and tumor volume alone was assessed. Overall, 181 and 48 patients from the GALAXY trial had liver and lung metastases, respectively. Among patients with liver metastases, the median progression-free survival (PFS) was 11.4 and 24 months in the high- and low-risk groups classified by the ctDNA model, respectively. Among patients with lung metastases, the median PFS was 12 months and not reached in the high- and low-risk groups classified by the ctDNA/volume model, respectively. Conclusively, incorporating radiological markers of necrosis and refining the tumor volume estimation may further improve model accuracy in liver metastasis settings.

Purpose: A systematic literature review was conducted to estimate the global prevalence of Kirsten rat sarcoma virus gene (KRAS) mutations, with an emphasis on the clinically significant KRAS G12C mutation, and to estimate the prognostic significance of these mutations in patients with colorectal cancer (CRC). Design: Relevant English-language publications in the Embase, MEDLINE, and the Cochrane Library databases (from 2009 to 2021) and congress presentations (from 2016 to 2021) were reviewed. Eligible studies were those that reported the prevalence and clinical outcomes of the KRAS G12C mutation in patients with CRC. Results: A total of 137 studies (interventional [n = 8], post hoc analyses of randomized clinical trials [n = 6], observational [n = 122], and longitudinal [n =1]) were reviewed. Sixty-eight studies reported the prevalence of KRAS mutations (KRASm) in 42 810 patients with CRC. The median global prevalence of KRASm was 38% (range, 13.3%-58.9%) and that of the KRAS G12C mutation (KRAS G12C) 3.1% (range, 0.7%-14%). Available evidence suggests that KRASm are possibly more common in tumors that develop on the right side of the colon. Limited evidence suggests a lower objective response rate and inferior disease-free/relapse-free survival in patients with KRAS G12C compared with patients with KRASwt or other KRASm. Conclusion: Our analysis reveals that KRAS G12C is prevalent in 3% of patients with CRC. Available evidence suggests a poor prognosis for patients with KRAS G12C. Right-sided tumors were more likely to harbor KRASm; however, their role in determining clinical outcomes needs to be investigated further.

Background: The therapeutic role of pelvic lymph node dissection (PLND) during radical prostatectomy (RP) for prostate cancer is not established. In clinical practice, PLND is primarily performed in cases of high-risk prostate cancer. The detection of lymph node metastasis plays a crucial role in determining the need for subsequent treatments. This study aims to evaluate the prognosis of prostate cancer patients with lymph node involvement (LNI) by stratifying them based on postoperative prostate-specific antigen (PSA) levels to identify biomarkers that can guide postoperative treatment strategies. Methods: Analysis was conducted on 383 patients, selected from 572 initially eligible, who underwent RP with LNI across 33 Japanese Urological Oncology Group institutions from 2006 to 2019. Patients were grouped according to postoperative PSA levels and salvage treatments received. Follow-up focused on castration resistance-free survival (CRFS), metastasis-free survival (MFS), and overall survival (OS). Results: In the persistent PSA group (PSA ≥ 0.1 ng/mL), CRFS and MFS were significantly shorter compared to the non-persistent PSA group (PSA < 0.1 ng/mL), and there was a tendency for shorter OS. In the persistent PSA group, patients with postoperative PSA values above the median (PSA ≥ 0.52 ng/mL) showed shorter CRFS and MFS. Furthermore, in the PSA ≥ 0.52 group, androgen deprivation therapy (ADT) plus radiotherapy (RT) combination had prolonged CRFS and MFS compared with ADT alone. Conclusions: This study provides valuable insights into stratifying patients based on postoperative PSA levels to tailor postoperative treatment strategies, potentially improving the prognosis of prostate cancer patients with LNI.

Background: Docetaxel, cisplatin, and 5-fluorouracil (DCF) combination chemotherapy has been established as one of the standard neoadjuvant therapies for locally advanced esophageal squamous cell carcinoma (ESCC). However, little is known about prognostic factors in patients with residual pathological disease after neoadjuvant DCF followed by surgery for locally advanced ESCC who are candidates for adjuvant nivolumab. Objectives: This study aimed to investigate prognostic factors in patients with residual pathological disease after neoadjuvant DCF chemotherapy followed by surgery for locally advanced ESCC. Design: This was a retrospective cohort study. Methods: This retrospective cohort study included patients who received neoadjuvant DCF followed by surgery for locally advanced ESCC between June 2014 and January 2020 at the National Cancer Center Hospital East. Results: Among a total of 210 patients, 45 patients (21.4%) achieved a pathological complete response. The 3-year disease-free survival (DFS) rate was significantly lower in patients with residual pathological disease than in those with a pathological complete response [53.5% versus 74.5%; hazard ratio (HR): 2.09, 95% confidence interval (CI): 1.16–3.77, p = 0.01]. In patients with residual pathological disease (n = 165), multivariate analysis revealed that pathological node positivity (HR: 3.59, 95% CI: 1.92–6.71, p < 0.01), supraclavicular lymph node metastasis (HR: 2.15, 95% CI: 1.19–3.90, p = 0.01), and lymphovascular invasion (HR: 1.90, 95% CI: 1.14–3.17, p = 0.02) were significantly associated with poor DFS. Conclusion: In this largest-to-date cohort study, patients with residual pathological disease after neoadjuvant DCF followed by surgery for locally advanced ESCC had a poor prognosis. In these patients, pathological node positivity, including supraclavicular lymph node metastasis, and lymphovascular invasion were considered significant prognostic factors.