Published papers

BACKGROUND: Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate targeting HER2-positive gastric cancer or gastroesophageal junction cancer (GC/GEJC). Although effective, T-DXd has notable toxicities, including interstitial lung disease (ILD). This study evaluated the efficacy, safety, and prognostic factors associated with T-DXd for GC/GEJC. METHODS: A retrospective observational study was conducted at our institution by reviewing medical records of patients treated with T-DXd until September 2023. Eligible patients had unresectable advanced or recurrent GC/GEJC, HER2 status of IHC 3 + or IHC 2 + /ISH-positive, and prior treatment with trastuzumab-containing regimen. RESULTS: Among the 101 patients analyzed, the initial T-DXd dose was 6.4 mg/kg in 77 patients and 5.4 mg/kg in 24 patients. The objective response rate was 54.3%, with a median PFS of 5.4 months and a median OS of 11.4 months. The significant prognostic factors for shorter PFS and OS included ECOG PS ≥ 1, presence of primary lesion, and peritoneal metastasis but not the initial T-DXd dose. ILD occurred in 14.9% of patients. Notably, higher T-DXd dose and smaller tumor burden were associated with a higher incidence of ILD. CONCLUSIONS: Several factors were associated with prognosis after T-DXd treatment in patients with GC/GEJC. Tumor burden is a potential risk factor for T-DXd-related ILD. Further studies are needed to optimize dosing based on tumor burden and to improve the therapeutic index.

BACKGROUND: Unplanned subgroup analyses from several studies have suggested primary tumor sidedness (PTS) as a potential prognostic and predictive parameter in metastatic colorectal cancer (mCRC). We aimed to investigate the impact of PTS on outcomes of mCRC patients. METHODS: PTS data of 9277 mCRC patients from 12 first-line randomized trials in the ARCAD database were pooled. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier and Cox models adjusting for age, sex, performance status, prior radiation/chemotherapy, and stratified by treatment arm. Predictive value was tested by interaction term between PTS and treatment (cetuximab plus chemotherapy vs chemotherapy alone). All statistical tests were 2-sided. RESULTS: Compared with right-sided metastatic colorectal cancer patients (n = 2421, 26.1%), left-sided metastatic colorectal cancer patients (n = 6856, 73.9%) had better OS (median = 21.6 vs 15.9 months; adjusted hazard ratio [HRadj] = 0.71, 95% confidence interval [CI] = 0.67 to 0.76; P < .001) and PFS (median = 8.6 vs 7.5 months; HRadj = 0.80, 95% CI = 0.75 to 0.84; P < .001). Interaction between PTS and KRAS mutation was statistically significant (Pinteraction < .001); left-sidedness was associated with better prognosis among KRAS wild-type (WT) (OS HRadj = 0.59, 95% CI = 0.53 to 0.66; PFS HRadj =0.68, 95% CI = 0.61 to 0.75) but not among KRAS mutated tumors. Among KRAS-WT tumors, survival benefit from anti-EGFR was confirmed for left-sidedness (OS HRadj = 0.85, 95% CI = 0.75 to 0.97; P = .01; PFS HRadj = 0.77, 95% CI = 0.67 to 0.88; P < .001) but not for right-sidedness. CONCLUSIONS: The prognostic value of PTS is restricted to the KRAS-WT population. PTS is predictive of anti-EGFR efficacy, with a statistically significant improvement of survival for left-sidedness mCRC patients. These results suggest treatment choice in mCRC should be based on both PTS and KRAS status.

PURPOSE: Advanced esophageal squamous cell carcinoma (ESCC) has a poor prognosis, and current treatments provide limited survival benefits. This study aimed to identify prognostic biomarkers and therapeutic targets by genomic profiling of advanced ESCC using circulating tumor DNA (ctDNA). METHODS: The SCRUM-MONSTAR GOZILA study is a nationwide, plasma-based molecular profiling project using Guardant360, involving 31 core cancer institutions in Japan. We evaluated the genomic landscape of advanced ESCC and investigated associations between specific alterations and overall survival (OS). The correlation between blood tumor mutation burden (bTMB) and clinical outcomes in patients with PD-1 inhibitors was also assessed using multiple cutoff values (2, 4, 6, 8, and 10 mutations/Mb). RESULTS: Among 313 patients, alterations predominantly consisted of single nucleotide variants (SNVs, 68.9%) and copy number alterations (20.7%). TP53 was the most frequent alterations (88.5%), followed by PIK3CA (36.4%), NFE2L2 (24.3%), CCND1 (22.4%), and EGFR (20.1%). Amplifications in PIK3CA, FGFR1, CCND1, and EGFR, as well as mutations in NFE2L2, FGFR1, and RB1 were associated with worse OS (any P < .05). Multivariable analysis confirmed mutations in NFE2L2 or FGFR1 and amplifications in EGFR or PIK3CA as independent poor prognostic factors (all P < .05). In 142 patients treated with PD-1 inhibitors, no significant differences in objective response rate or progression-free survival were observed at different bTMB cutoff values (all P > .1). CONCLUSION: ctDNA analysis identified key genomic alterations linked to poor outcomes in advanced ESCC, revealing potential prognostic biomarkers and therapeutic targets. In contrast, bTMB did not show predictive value for the efficacy of PD-1 inhibitors in this study.

Background: In biliary tract cancer (BTC), TP53 is the most commonly altered gene and may co-occur with KRAS alteration. The presence of a co-alterations in of TP53 and KRAS is associated with poor prognosis in many cancers. In patients (pts) with advanced BTC, the prognostic implications of such co-alterations have not been fully investigated. Methods: This is a pooled analysis of SCRUM-Japan GOZILA and MONSTAR-SCREEN-1 and -2 studies. Genomic profiling was conducted with Guardant360 for plasma in GOZILA, FoundationOne CDx for tissue and FoundationOne Liquid CDx for plasma in MONSTAR-SCREEN-1, and CARIS MI Profile for tissue in MONSTAR-SCREEN-2. Pts with advanced BTC receiving systemic therapy were included in this study. Results: Among 636 pts with advanced BTC, 85 had TP53/KRAS co-alteration, 293 had TP53, 44 had KRAS, and 214 had neither KRAS nor TP53 alteration (WT/WT). Tumors with TP53 alteration had significantly higher level of tumor mutation burden (TMB) compared to the other groups (3.8 mut/Mb for TP53/KRAS, 5.0 mut/Mb for TP53, 2.8 mut/Mb for KRAS, and 2.5 mut/Mb for WT/WT, respectively, P<0.001). In addition, the frequency of microsatellite instability-high (MSI-High) in the TP53/KRAS group (11.0%) was significantly higher compared to the TP53 group (3.1%, P<0.05), and the WT/WT group (0.6%, P<0.001), respectively. The objective response rate of first-line therapy in the TP53/KRAS group (8.2%) was significantly lower than in the other groups (20.8% for TP53, 23.3% for KRAS, and 19.7% for WT/WT groups, P=0.035). There was no pts treated with durvalumab plus gemcitabine and cisplatin. Two pts with TP53/KRAS alteration and MSI-High received pembrolizumab monotherapy, and partial response was achieved with a progression-free survival of 9.4 and 22.0 months. The median overall survival (OS) for pts treated with first-line therapy of the TP53/KRAS, KRAS, TP53, and WT/WT groups were 13.6 (95% confidence interval [CI], 11.5-15.5), 14.3 (95%CI, 9.7-25.9), 18.8 (95%CI, 16.9-20.6), and 22.7 months (95%CI, 20.4-25.9), respectively. Multivariate analysis identified TP53/KRAS alteration (hazard ratio [HR] 2.14, 95%CI 1.43-3.22, P<0.001), number of detected variants (≥2) (HR 1.50, 95%CI 1.04-2.16, P=0.029), locally advanced (HR 1.72, 95%CI 1.05-2.83, P=0.033), and metastatic status (HR 1.78, 95%CI 1.39-2.28, P<0.001) as independent prognostic factors for shorter OS. Conclusions: Patients with advanced BTC with co-occurring TP53/KRAS alterations have worse prognosis. Interestingly, the presence of these co-alterations was associated with a higher likelihood of MSI-High phenotype.

Background: Randomized clinical trials provide the best evidence for the effects of a new treatment. However, the use of a placebo control arm may present practical and ethical concerns for enrolled patients and treating providers. The CRC ARCAD global database includes a total of 1,673 individual patient data (IPD) treated with placebo plus best supportive care in a salvage-line setting for refractory mCRC. By using placebo IPD, we have proposed to construct a synthetic control arm for clinical trials (Yoshino T. et al., Nature Medicine 2023). Methods: From 40,889 IPD from 59 studies in ARCAD mCRC database, 723 placebo pts were selected from 4 placebo-controlled randomized studies in a salvage-line setting (CORRECT, RECOURSE, CONCUR and TERRA). We analyzed the impact of baseline patient characteristics and various prognostic factors on outcome in the placebo control. Results: The adjusted hazard ratios (HRs) (95% confidence interval [CI]) were 0.52 (0.40-0.67) for the number of metastatic sites (1 vs 2+), 0.71 (0.59-0.84) for ECOG performance status (PS) (0 vs 1), 0.54 (0.45-0.66) for liver metastases (No vs Yes), 0.54 (0.40-0.71) for peritoneal metastases (No vs Yes), and 0.51 (0.38-0.70) for Royal Marsden Hospital (RMH) Score (consisting of albumin level, number of metastatic sites, and LDH level) (0-1 vs 2-3). Conclusions: Number of metastatic sites, ECOG PS, liver metastasis, peritoneal metastasis and RMH Score were significant prognostic factors in patients with mCRC receiving placebo in a salvage-line setting. Further prognostic factors should be investigated to increase the accuracy of the proposed synthetic control arm.

PURPOSE: Oxaliplatin-based adjuvant chemotherapy in patients with stage III colon cancer (CC) for 6 months remains a standard in high-risk stage III patients. Data are lacking as to whether early discontinuation of all treatment (ETD) or early discontinuation of oxaliplatin (EOD) could worsen the prognosis. MATERIALS AND METHODS: We studied the prognostic impact of ETD and EOD in patients with stage III CC from the ACCENT/IDEA databases, where patients were planned to receive 6 months of infusional fluorouracil, leucovorin, and oxaliplatin or capecitabine plus oxaliplatin. ETD was defined as discontinuation of treatment and EOD as discontinuation of oxaliplatin only before patients had received a maximum of 75% of planned cycles. Association between ETD/EOD and overall survival and disease-free survival (DFS) were assessed by Cox models adjusted for established prognostic factors. RESULTS: Analysis of ETD and EOD included 10,447 (20.9% with ETD) and 7,243 (18.8% with EOD) patients, respectively. Compared with patients without ETD or EOD, patients with ETD or EOD were statistically more likely to be women, with Eastern Cooperative Oncology Group performance status ≥ 1, and for ETD, older with a lower body mass index. In multivariable analyses, ETD was associated with a decrease in disease-free survival and overall survival (hazard ratio [HR], 1.61, P < .001 and HR, 1.73, P < .001), which was not the case for EOD (HR, 1.07, P = .3 and HR, 1.13, P = .1). However, patients who received < 50% of the planned cycles of oxaliplatin had poorer outcomes. CONCLUSION: In patients treated with 6 months of oxaliplatin-based chemotherapy for stage III CC, ETD was associated with poorer oncologic outcomes. However, this was not the case for EOD. These data favor discontinuing oxaliplatin while continuing fluoropyrimidine in individuals with significant neurotoxicity having received > 50% of the planned 6-month chemotherapy.

Background: Human epidermal growth factor receptor (HER) family plays a critical role in cancer pathogenesis. In the CALGB/SWOG 80405 trial, high HER2 expression was significantly good prognostic factor in patients with mCRC, and cetuximab improved overall survival (OS) in those with high HER2 expression compared to bevacizumab (Battaglin et al. ASCO2020; abstr 4086). Our study aimed to evaluate the prognostic impact of HER1/3/4 in the CALGB/SWOG 80405 and to corroborate it, including HER2, in the MONSTAR-SCREEN-2 in patients with mCRC, utilizing transcriptome expression data from both studies. Methods: In the CALGB/SWOG 80405 cohort, we assessed the prognostic potential of mRNA expressions of HER1, HER3, and HER4 from patients with KRAS exon 2 wild-type mCRC. Tumor tissue from 925 patients was tested for NanoString gene expression using an 800-gene panel. The results were validated through 398 mCRC patients according to RAS mutational status in the MONSTAR-SCREEN-2 cohort, employing whole-transcriptome sequencing with Caris MI profile. HER family expressions were classified into two or three groups, using the median or tertile expression values. The log-rank test was utilized to discern disparities in overall survival (OS). Results: In the CALGB/SWOG 80405 cohort, high HER3 expression significantly correlated with better OS (P=0.044), a trend particularly evident in patients undergoing cetuximab therapy (P=0.0048). HER1 and HER4 expression exhibited no significant association with OS, irrespective of treatment modality. In the corroborative analysis using the MONSTAR-SCREEN-2 cohort, high HER2expression demonstrated a significantly improved OS in the RAS wild-type population (hazard ratio [HR], 0.21; 95%CI, 0.06–0.71; P=0.0056), but no difference in OS compared to low HER2 expression in the RAS-mutant (HR, 1.11; 95%CI, 0.57–2.16; P=0.75). Elevated expressions of HER1 and HER3 were also significantly associated with better OS in RAS wild-type disease (HR, 0.22; 95%CI, 0.07–0.67; P=0.0034; and HR, 0.23; 95%CI, 0.07–0.70; P=0.0048, respectively), although there was no significant difference in RAS-mutant (HR, 0.83; 95%CI, 0.41–1.67; P=0.60; and HR, 0.76; 95%CI, 0.39–1.48; P=0.43, respectively). HER4expression exhibited no significant association with OS, irrespective of RAS mutational status. Conclusions: Our findings highlight the prognostic significance of HER1-3 gene expressions in RAS wild-type mCRC patients in the MONSTAR-SCREEN-2 cohort. These insights may contribute to the development of more efficacious treatment methodologies according to HER family transcriptome expression profiles. ClinicalTrials.gov Identifier: NCT00265850. Research Sponsor: P30CA014089, U10CA180821, U10CA180882, U10CA180888 (SWOG); Genentech. https://acknowledgments.alliancefound.org.

Purpose: Perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) is a standard treatment for locally advanced gastric/gastroesophageal junction cancer (GC/GEJC). The impact of biomarker status on the efficacy of perioperative FLOT remains unclear. This study evaluated the association between clinicopathological features, including biomarker status, and the efficacy of perioperative FLOT in patients with resectable GC/GEJC. Patients and Methods: A retrospective observational study was conducted by reviewing medical records of patients treated with perioperative FLOT between February 2020 and March 2024. Eligible patients had histologically confirmed adenocarcinoma, resectable disease at stages cT2-4a and/or N0-3, M0, and underwent biomarker testing. Results: Among 116 eligible patients, human epidermal growth factor receptor 2 (HER2) positivity was observed in 7.8%, whereas PD-L1 combined positive score (CPS) of ≥1, ≥5, and ≥10 was detected in 90.5%, 44.0%, and 15.5% of patients, respectively. Claudin-18 isoform 2 (CLDN18.2) positivity (2+/3+ in ≥75% of tumor cells) was observed in 30.2% of patients. Major pathological response (MPR) and pathological complete response (pCR) rates were 22.4% (95% CI, 15.3 to 31.0) and 8.6% (95% CI, 4.2 to 15.3), respectively. Diffuse-type histology was a negative indicator for pathological response. CLDN18.2 expression decreased significantly after preoperative FLOT, with the median H-score declining from 285.0 to 187.5 (P < .001) in patients with CLDN18.2 positivity at initiation. Maintained CLDN18.2 positivity was more frequently observed in patients without MPR compared with those with MPR (53.8% v 12.5%, P = .05). Conclusion: HER2, PD-L1, and CLDN18.2 statuses were not linked to pathological response to FLOT in resectable GC/GEJC. CLDN18.2 expression significantly decreased after preoperative FLOT but remained higher in patients without MPR, suggesting that CLDN18.2-targeted therapy may warrant investigation in the perioperative setting.

BACKGROUND: Circulating tumor DNA (ctDNA) is a promising tool for diagnosing and predicting cancer prognosis. However, its clinical utility in metastatic renal cell carcinoma (mRCC) remains unclear, particularly in terms of clinical prognosis. METHODS: We enrolled 124 patients with mRCC in the MONSTAR-SCREEN study (UMIN 000036749) between August 2019 and February 2022, a national observational ctDNA-based screening study, and performed ctDNA sequencing before and at the time of resistance to systemic therapy. RESULTS: ctDNA were assessed in 178 samples containing 432 mutations. The most frequently altered genes at baseline were VHL (25.0%), PBRM1 (10.9%), TERT2 (8.7%), BAP1 (8.7%), and MTOR (7.6%). Patients receiving first-line therapy with tumor fraction (TF) < 1.2% showed significantly better progression-free survival than those with TF ≥ 1.2% (Hazard ratio (HR) = 0.467; 95% CI 0.229-0.979; p = 0.0425). BAP1 mutational status of ctDNA at baseline led to poor OS (HR = 0.4867; 95% CI 0.322-0.736; p = 0.0003). Serial ctDNA analysis showed that 46.8% of patients developed new ctDNA mutations at disease progression, which was linked to shorter time to progression (p = 0.046). CONCLUSIONS: Our findings demonstrated that ctDNA profiling is feasible in mRCC and can predict disease progression after treatment.

Kato T., Shiota M., Nishimoto K., et al. Prognostic significance of circulating tumor DNA alterations in advanced renal cell carcinoma from SCRUM-Japan MONSTAR-SCREEN: a nationwide genomic profiling project: Genetics and Genomics. British Journal of Cancer, e2200653 (2025); https://doi.org/10.1038/s41416-025-02985-8.

Background: This study investigated the prognostic factors of recurrent colorectal liver metastasis (r-CRLM) and the indications for repeat liver resection (RLR). Methods: In total, 485 patients underwent initial liver resection (ILR) for CRLM. Among them, 98 with resectable r-CRLM were included in this study. Recurrence-free interval (RFI) was defined as the time between ILR and r-CRLM diagnosis. Long-term outcomes were assessed using overall survival (OS) and time to surgical failure (TSF) as endpoints. Results: Eighty-two patients underwent RLR, and 16 received chemotherapy alone. RLR (P = 0.019, hazard ratio [HR] 0.37) was an independent better prognostic factor for OS in 98 patients. In 82 patients who underwent RLR, the presence of ≥ 3 tumors (P = 0.011, HR 2.28), tumor size ≥ 20 mm (P = 0.004, HR 2.41), and RFI < 180 days (P = 0.006, HR 2.28) were independent prognostic factors for TSF. A score of 1 for each factor could stratify the prognosis of patients who underwent RLR (score 0 group: reference, score 1 group: HR—3.20, and score 2–3 group: HR—6.69). Patients who underwent RLR with scores of 2–3 and those who received chemotherapy alone did not significantly differ in prognosis (P = 0.173). Conclusions: RFI < 180 days, presence of ≥ 3 tumors, and tumor size ≥ 20 mm have a prognostic impact on patients with resectable r-CRLM. The RLR indications should be cautiously considered in patients with these risk factors.

Background: KRAS mutations in metastatic colorectal cancer (mCRC) are a factor of poor prognosis, partly because of associated resistance to anti-EGFR therapies. Liver metastases (LM) were also described as a factor of poor prognosis. This study aims to compare the outcomes of patients treated in third-line setting with placebo or Trifluridine/Tipiracil or regorafenib (TToR) and to assess the impact of LM and KRAS mutations on prognosis. Methods: Data were pooled from five placebo-controlled randomized trials of the ARCAD CRC database (CORRECT, RECOURSE, CONCUR, TERRA, and J003). Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan–Meier estimates and adjusted Cox models. Interaction tests were conducted to evaluate the combined effects of LM and KRAS mutations. Results: The study included 2,207 patients: 1,464 treated with TToR and 743 with placebo. A total of 73% had LM and 51% had KRAS mutations. Patients with LM had significantly lower OS and PFS compared to those without LM in both TToR (HR = 0.48 for OS; HR = 0.55 for PFS) and placebo groups (HR = 0.49 for OS; HR = 0.58 for PFS). Patients with KRAS mutations had worse OS compared to wild-type KRAS in TToR-treated patients (HR = 1.18), but not in placebo-treated patients (HR = 1.03). Interaction tests were not significant between LM and KRAS status in both TToR and placebo groups. Conclusions: In patients with refractory mCRC, LM are a major poor prognosis factor, while KRAS mutations have no clinically relevant additive impact. These results underline the importance to stratify clinical trials on liver metastases rather than on RAS status in latter lines.

BACKGROUND: The liver is the most frequent site of metastases in colorectal cancer (CRC). This study aimed to assess the response rate and survival outcomes in metastatic CRC patients with non-liver metastases (NLM) compared to those with liver metastases (LM) across different lines of treatment. METHODS: A total of 17,924 mCRC patients included in 26 trials from the ARCAD CRC database were analyzed. The analysis was conducted based on the presence or absence of LM across different treatment groups: chemotherapy (CT) alone, CT + anti-VEGF, CT + anti-EGFR in KRAS wild-type tumors, within the first-line (1 L) and second-line (2 L), and patients enrolled in third-line (≥3 L) trials treated with trifluridine/tipiracil or regorafenib or placebo. The endpoints were overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). RESULTS: Out of the 17,924 patients, 14,066 had LM (30.6 % with only liver involvement and 69.4 % with liver and other metastatic sites), while 3858 patients had NLM. In the CT alone and CT + anti-VEGF subgroups, NLM patients showed better OS and PFS in the 1 L and 2 L settings. However, in the CT + anti-EGFR 1 L and 2 L subgroups, there was no significant difference in OS and PFS between NLM and LM patients. In the ≥ 3 L subgroups, better OS and PFS were observed in NLM patients. ORRs were higher in LM patients than in NLM patients across all cohorts treated in the 1 L and only in the anti-EGFR cohort in the 2 L. CONCLUSION: LM is a poor prognostic factor for mCRC increasing from 1 L to ≥ 3 L except for patients in 1 L and 2 L receiving CT+anti-EGFR. These data justify using LM as a stratification factor in future trials for patients with unresectable mCRC.

BACKGROUND: This study aimed to create a prognostic model to predict disease recurrence among patients with lymph node involvement but no prostate-specific antigen (PSA) persistence and to explore its clinical utility. METHODS: The study analyzed patients with lymph node involvement after pelvic lymph node dissection with radical prostatectomy in whom no PSA persistence was observed between 2006 and 2019 at 33 institutions. Prognostic factors for recurrence-free survival (RFS) were analyzed by the Cox proportional hazards model. RESULTS: Among 231 patients, 127 experienced disease recurrence. The factors prognostic for RFS were PSA level at diagnosis (≥ 20 vs. < 20 ng/mL: hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.09-2.52; P = 0.017), International Society of Urological Pathology grade group at radical prostatectomy (RP) specimen (group ≥ 4 vs. ≤ 3: HR, 1.63; 95% CI 1.12-2.37; P = 0.010), pathologic T-stage (pT3b/4 vs. pT2/3a: HR, 1.70; 95% CI 1.20-2.42; P = 0.0031), and surgical margin status (positive vs. negative: HR, 1.60; 95% CI 1.13-2.28; P = 0.0086). The prognostic model using four parameters were associated with RFS and metastasis-free survival. CONCLUSION: The prognostic model in combination with postoperative PSA value and number of lymph nodes is clinically useful for discussing treatment choice with patients.

Background: Oxaliplatin-based chemotherapy is a standard adjuvant therapy for stage II or stage III colorectal cancer (CRC); however, its use is limited by chemotherapy-induced peripheral neuropathy (CIPN), which reduces the quality of life of patients and often persists for months or years after chemotherapy ends. Compared with superoxide dismutase (SOD), lecithinized SOD (PC-SOD) exhibits much longer stability in plasma, thus reducing oxidative stress, which is a key mechanism of CIPN. A randomized phase II trial (jRCT2031210466) of PC-SOD compared with placebo in patients with CRC who received adjuvant mFOLFOX6 therapy showed promising results regarding its CIPN-preventive effect and safety. Furthermore, PC-SOD suppressed oxaliplatin allergy. Design: PROSPER (Pc-sod for the pRevention Of Sensory PERipheral neuropathy) is a multicenter, randomized, double-blind, placebo-controlled, phase III study designed to investigate the efficacy of PC-SOD for CIPN in patients with CRC who receive adjuvant mFOLFOX6 therapy. Key eligibility criteria include curative resection of stage II or stage III colorectal adenocarcinoma and 12 planned cycles of mFOLFOX6. The primary endpoint is the time to onset of grade ≥2 CIPN (Common Terminology Criteria for Adverse Events). Key secondary endpoints include the time to onset of grade ≥2 CIPN (Neurotoxicity Criteria of Debiopharm) and oxaliplatin allergy.

A multicenter study of nonmetastatic castration-resistant prostate cancer (nmCRPC) was conducted to identify the optimal cut-off value of prostate-specific antigen (PSA) doubling time (PSADT) that correlated with the prognosis in Japanese nmCRPC. Of the 515 patients diagnosed and treated for nmCRPC at 25 participating Japanese Urological Oncology Group centers, 450 patients with complete clinical information were included. The prognostic values of clinical factors were evaluated with respect to prostate specific antigen progression-free (PFS), cancer-specific survival (CSS), and overall survival (OS). The optimal cutoff value of PSADT was identified using survival tree analysis by Python. The Median PSA and PSADT at diagnosis of nmCRPC were 3.3 ng/ml, and 5.2 months, respectively. Patients treated with novel hormonal therapy (NHT) showed significantly longer PFS (HR: hazard ratio 0.38, p < 0.0001) and PFS2 (HR 0.45, p < 0.0001) than those treated with vintage nonsteroidal antiandrogen agent (Vintage). The survival tree identified 4.65 months as the most prognostic PSADT cutoff point. Among the clinical and pathological factors PSADT of < 4.65 months remained an independent prognostic factor for OS (HR 2.96, p = 0.0003) and CSS (HR 3.66, p < 0.0001). Current data represented optimal cut-off of PSADT 4.65 months for a Japanese nmCRPC.

Multigene panel testing (MGPT) is increasingly used for diagnosing hereditary cancers; however, its application in cascade testing remains limited, and the psychological impact on unaffected relatives is not well understood. This multicenter study in Japan recruited 123 first-degree relatives without a personal history of cancer to evaluate psychological responses before (T0) and two weeks after (T1) MGPT result disclosure. Participants completed the Japanese version of the Cancer Worry Scale (CWS-J) at both time points and the Impact of Event Scale-Revised (IES-R) at T1. Two weeks after disclosure, 6.5% of relatives met the threshold for clinically significant distress. Mean IES-R scores were higher among carriers of pathogenic variants (mean 8.2) than among those with negative results (mean 4.8) or variants of uncertain significance (mean 2.4). In contrast, multivariate analysis revealed no independent association between test result and post-disclosure distress. In contrast, higher baseline CWS-J scores were strongly associated with elevated IES-R scores after disclosure (p < 0.001). Children and relatives who frequently discussed cancer risk within their families exhibited higher distress levels than other subgroups. Overall, CWS-J scores showed no significant change from pre- to post-disclosure, with 41% of relatives maintaining persistently high worry. Across both time points, unaffected relatives consistently reported lower CWS-J scores than individuals with cancer (p < 0.0001). These findings suggest that MGPT has minimal psychological impact on unaffected relatives undergoing cascade testing, although those with higher preexisting cancer worry may require additional psychosocial support.