The programmed death‐1/programmed death‐ligand 1 (PD‐L1) pathway is a negative feedback pathway that suppresses the activity of T cells. Previous studies reported that high PD‐L1 expression on tumor cells (TC) was associated with poor survival in patients with colorectal cancer; however, the prognostic evaluation of these studies was limited because they included patients at various disease stages. The purpose of the present study was to evaluate the relationship between PD‐L1 status in the immune microenvironment and the clinicopathological features of stage III colorectal cancer. Two hundred and thirty‐five patients were included in the analysis. PD‐L1 expression on TC and tumor‐infiltrating mononuclear cells (TIMC) was evaluated by immunohistochemistry. The median follow‐up of thisi study was 52.9 months. A total of 8.1% of stage III colorectal cancer showed high PD‐L1 expression on TC and 15.3% showed high PD‐L1 expression on TIMC. Patients with high PD‐L1 expression on TC had significantly shorter disease‐free survival (DFS) than patients with low expression (hazard ratio [HR] 2.36; 95% confidence interval [CI], 1.21–4.62; P = 0.012). In addition, patients with high PD‐L1 expression on TIMC were associated with longer DFS than patients with low expression (HR 0.40; 95% CI, 0.16–0.98; P = 0.046). These findings suggest that PD‐L1 expression status may be a new predictor of recurrence for stage III colorectal cancer patients and highlight the necessity of evaluating PD‐L1 expression on TC and TIMC separately in the tumor microenvironment.
In Japan, the social (medical) health‐care system is on the way to being developed to advance personalized medicine through the implementation of cancer genomic medicine, known as “cancer clinical sequencing,” which uses a next‐generation sequencer. However, no Japanese guidance for cancer genomic testing exists. Gene panel testing can be carried out to help determine patient treatment, confirm diagnosis, and evaluate prognostic predictions of patients with mainly solid cancers for whom no standard treatment is available. This guidance describes how to utilize gene panel testing according to the type of cancer: childhood cancer, rare cancer, carcinoma of unknown primary, and other cancers. The level of evidence classification for unified use in Japan is also detailed. This guidance establishes the basic principles of the quality control of specimens, requirements of medical institutions, informed consent, handling of data during the postanalysis stage, and treatment options based on the evidence level. In Japan, gene panel testing for cancer treatment and diagnosis is recommended to comply with this guidance. This is a collaborative work of the Japanese Society of Medical Oncology, Japan Society of Clinical Oncology, and the Japanese Cancer Association.
HER3 is overexpressed in several cancers, including colorectal cancer. Although therapies with anti-HER3 antibodies have been investigated, significant clinical benefits have not been reported. U3-1402 is a novel HER3-antibody-drug conjugate (ADC) composed of the HER3 antibody patritumab and a novel topoisomerase I inhibitor, DX-8951 derivative (DXd). The sensitivity of DXd was evaluated by a growth inhibition assay. The antitumor activity of U3-1402 was evaluated in a murine xenograft model in which its effects on cells, with a range of HER3 expression levels, were compared with those of patritumab alone, irinotecan, control-ADC, and saline. In the growth inhibition assay, all colorectal cancer cell lines were sensitive to DXd. In the tumor xenograft model, significant tumor regression with U3-1402 was observed both in the DiFi cell line (high HER3 expression; KRAS wild type) and in SW620 (high HER3 expression; KRAS mutation), but no treatment effect was observed in Colo320DM (low HER3 expression). Notably, SW620 tumor growth was significantly suppressed with U3-1402 compared with the saline-treated group (P < 0.001) and showed greater activity compared with the irinotecan group. By contrast, patritumab alone, control-ADC, and saline did not significantly differ in tumor growth inhibition. The antitumor activity of U3-1402 was dependent on HER3 expression level, but not on KRAS mutation status. These results support further investigation of development strategies for U3-1402 in patients with HER3-expressing colorectal cancer.
BackgroundEwing sarcoma is a rare tumor that occurs commonly in the long bones of children or adolescents that can also arise in soft tissues including the extremities, retroperitoneum, chest wall, and rarely in the liver as primary sites. We report a case of Ewing sarcoma arising primarily in the liver and, to our knowledge, this is the fourth reported case of Ewing sarcoma occurring in the liver.Case presentationA 27-year-old Japanese woman was admitted with sudden onset right upper abdominal pain. Clinical examination revealed a multilocular cystic mass consisting of thickened, irregular septa and nodal walls in the right hepatic lobe. Ultrasound-guided aspiration biopsy of the liver mass showed clusters of small atypical round cells and the clinical preoperative diagnosis was mucinous cystadenoma of the liver. The patient underwent an extended right hepatectomy and histopathological findings revealed sheet-like proliferation of small- to medium-sized round cells. Tumor cells were positive for periodic acid-Schiff reaction and immunoreactive for glycoprotein C99 and gene NKX2.2, as well as the neuroendocrine markers, CD56 and synaptophysin. EWS-FLI-1 fusion transcript type 1 was detected by reverse transcriptase polymerase chain reaction. Pathological and molecular analysis confirmed the diagnosis of Ewing sarcoma arising primarily in the liver and the patient received adjuvant systemic chemotherapy with vincristine, doxorubicin, and cyclophosphamide, alternating with ifosfamide and etoposide. We found no evidence of recurrence 15 months after completing chemotherapy.ConclusionWe present an extremely rare case of Ewing sarcoma arising primarily in the liver. To our knowledge, this is the fourth reported case of Ewing sarcoma occurring in the liver, and the first case with a multilocular cystic liver mass. Imaging examinations of the other three reported cases showed solid tumors and a diffuse enlarged liver without mass lesion. Clinicians should consider the possibility of Ewing sarcoma in young patients with a multilocular cystic mass with thick and/or irregular cyst walls in the liver.
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