Combination immunotherapy with anti-programmed cell death1-ligand1 (PD-L1) and anti-vascular endothelial growth factor (VEGF) antibodies has become the standard treatment for patients with unresectable HCC (u-HCC). However, limited patients obtain clinical benefits. Cell-free DNA (cfDNA) in peripheral blood contains circulating tumor DNA (ctDNA) that reflects molecular abnormalities in tumor tissue. We investigated the potential of cfDNA/ctDNA as biomarkers for predicting the therapeutic outcome in u-HCC patients treated with anti-PD-L1/VEGF therapy. We enrolled a multicenter cohort of 85 HCC patients treated with atezolizumab and bevacizumab (Atezo/Bev) between 2020 and 2021. Pretreatment plasma was collected, and cfDNA levels were quantified. Ultradeep sequencing of cfDNA was performed with a custom-made panel for detecting mutations in 25 HCC-related cancer genes. We evaluated the association of cfDNA/ctDNA profiles and clinical outcomes. Patients with high plasma cfDNA levels showed a significantly lower response rate and shorter progression-free survival and overall survival (OS) than those with low cfDNA levels. ctDNA detected in 55% of HCC patients included the telomerase reverse transcriptase (TERT) promoter in 31% of these patients, tumor protein 53 (TP53) in 21%, catenin beta 1 (CTNNB1) in 13% and phosphatase and tensin homolog (PTEN) in 7%. The presence or absence of ctDNA did not predict the efficacy of Atezo/Bev therapy. Twenty-six patients with a TERT mutation had significantly shorter OS than those without. The presence of a TERT mutation and alpha-fetoprotein (AFP) ≥ 400 ng/mL were independent predictors of poor OS according to multivariate Cox proportional hazard analysis and could be used to stratify patients treated with Atezo/Bev therapy based on prognosis. In conclusion, pretreatment cfDNA/ctDNA profiling may be useful for predicting the therapeutic outcome in u-HCC patients treated with anti-PD-L1/VEGF therapy.

An optimal therapeutic strategy for unresectable locally advanced pancreatic cancer (UR-LAPC) has not been established. This study investigated the therapeutic efficacy of chemoradiotherapy (CRT) following induction chemotherapy with gemcitabine plus nab-paclitaxel (GnP) (CRT group) compared with systemic chemotherapy alone (CTx group) in patients with UR-LAPC. This was a retrospective study of 63 consecutive patients with UR-LAPC treated at our department in a Japanese cancer referral center between February 2015 and July 2018. We excluded patients who underwent other regimens and those enrolled in another prospective study. The CRT group (n = 25) exhibited significantly better progression-free survival (PFS) and overall survival (OS) than the CTx group (n = 20, PFS 17.9 vs. 7.6 months, p = 0.044; OS 29.2 vs. 17.4 months, p < 0.001). In the multivariate analyses, CRT following induction chemotherapy was identified as an independent prognostic factor for OS. Seven (15.6%) patients underwent conversion surgery, all of whom were in the CRT group. The R0 resection rate was 85.7% (6/7). In summary, patients with UR-LAPC experienced favorable treatment outcomes after receiving GnP as the first-line chemotherapy, especially when receiving additional CRT. Thus, this treatment strategy represents a promising treatment option for selected patients with UR-LAPC.

Although comprehensive genomic profiling (CGP) tests have been covered under the Japanese national health insurance program since 2018, the utility and issues of CGP tests have not been clarified. We retrospectively reviewed 115 patients with incurable pancreatic cancer (IPC) who underwent CGP tests in a Japanese cancer referral center from November 2019 to August 2021. We evaluated the results of CGP tests, treatments based on CGP tests, and survival time. Eight cases (6.9%) were diagnosed as tumor mutation burden-high (TMB-H) and/or microsatellite instability-high (MSI-H). The gene mutation rates of KRAS/TP53/CDKN2A/SMAD4 were 93.0/83.0/53.0/25.2%, respectively. Twenty-five patients (21.7%) had homologous recombination deficiency (HRD)-related genetic mutations. Four patients (3.5%) having TMB-H and/or MSI-H were treated with pembrolizumab, and only two patients (1.7%) participated in the clinical trials. Patient characteristics were not significantly different between patients with and without HRD-related gene mutations. The median OS was significantly longer in the HRD (+) group than in the HRD (−) group (749 days vs. 519 days, p = 0.047). In multivariate analysis, HRD-related gene mutation was an independent prognostic factor associated with favorable OS. CGP tests for patients with IPC have the potential utility of detecting HRD-related gene mutations as prognostic factors as well as a therapeutic search.

Background and Aim: To investigate the outcomes in eight Japanese patients with cancer treated with mycophenolate mofetil (MMF) and corticosteroids for immune checkpoint inhibitor treatment‐induced severe immune‐related hepatitis (ir‐hepatitis) and the efficacy and safety of MMF.Methods: We retrospectively examined patient background, treatment course, as well as examination and imaging data using electronic medical records.Results: The ratio of male to female patients was 7:1, and the median age was 60 years (27–72 years). There were five and two cases of kidney cancer and malignant melanoma, respectively, and one case of lung cancer. The median number of days until MMF administration in addition to systemic corticosteroid therapy after the onset of ir‐hepatitis was 14.5 (2–42). The patients were categorized as four “good responders” who showed an improvement in the liver function tests following MMF treatment and four “poor responders” who did not. Furthermore, the time from the onset of ir‐hepatitis to initial MMF administration was significantly shorter in good responders (median 3 days, range 2–15 days) than in poor responders (median 25.5 days, range 14–42 days) (P = 0.042). No significant intergroup difference was observed in other clinical factors. No serious adverse events caused by MMF were observed in any case.Conclusions: According to these findings, early recognition of corticosteroid refractoriness and the use of MMF may be beneficial in patients with ir‐hepatitis.

Background: Pancreatic cancer is associated with a high thromboembolism risk. We investigated the significance of early venous thromboembolism (VTE) detection in patients with unresectable metastatic pancreatic cancer (UR-MPC) who received first-line chemotherapy with gemcitabine plus nab-paclitaxel (GnP). Methods: This single-center retrospective study enrolled 174 patients with UR-MPC who underwent GnP as a first-line chemotherapy from April 2017 to March 2020. The early detection of VTE (deep venous thrombosis and pulmonary thromboembolism) was defined as diagnosis by the first follow-up CT scan after the initiation of chemotherapy. We compared the patients with early detection of VTE (VTE (+) group) with the others (VTE (-) group). We examined overall survival (OS), progress free survival (PFS), severe adverse events, and predictors associated with OS using the Cox proportional hazards model. Results: Early detection of VTE was observed in 17 patients (9.8%). Thirteen patients were diagnosed with VTE at treatment initiation, and four patients were diagnosed after treatment initiation. The median time to diagnosis after treatment initiation was 55 days (range: 31–71 days). Only 3 patients were symptomatic. The VTE (+) group exhibited worse OS and PFS than the VTE (-) group (OS: 259 days vs. 400 days, P < 0.001; PFS: 120 days vs. 162 days, P = 0.008). The frequency of grade 3–4 adverse events was not significantly different. Although the performance status was poorer in the VTE (+) group, VTE was identified as a statistically significant independent predictor for OS in multivariate analyses (HR, 1.87; 95% CI, 1.02–3.44; P = 0.041). Conclusions: Early VTE detection is a predictor of a poor prognosis in UR-MPC patients who receive GnP as first-line chemotherapy, suggesting that screening VTE for patients with UR-MPC is crucial, even if patients are asymptomatic.