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Esophageal cancer remains a highly aggressive malignancy with a poor prognosis, despite ongoing advancements in treatments such as immunotherapy. The tumor microenvironment, particularly cancer-associated fibroblasts (CAF), plays a crucial role in driving the aggressiveness of esophageal cancer. In a previous study utilizing human-derived xenograft models, we successfully developed a novel cancer treatment that targeted CAFs with near-infrared photoimmunotherapy (NIR-PIT), as an adjuvant therapy. In this study, we sought to translate our findings toward clinical practice by employing patient-derived xenograft (PDX) models and utilizing humanized mAbs, specifically sibrotuzumab, which is an antihuman fibroblast activation protein (FAP) Ab and already being investigated in clinical trials as monotherapy. PDX models derived from patients with esophageal cancer were effectively established, preserving the expression of key biomarkers such as EGFR and FAP, as observed in primary tumors. The application of FAP-targeted NIR-PIT using sibrotuzumab, conjugated with the photosensitizer IR700DX, exhibited precise binding and selective elimination of FAP-expressing fibroblasts in vitro. Notably, in our in vivo investigations using both cell line-derived xenograft and PDX models, FAP-targeted NIR-PIT led to significant inhibition of tumor progression compared with control groups, all without inducing adverse events such as weight loss. Immunohistologic assessments revealed a substantial reduction in CAFs exclusively within the tumor microenvironment of both models, further supporting the efficacy of our approach. Thus, our study demonstrates the potential of CAF-targeted NIR-PIT employing sibrotuzumab as a promising therapeutic avenue for the clinical treatment of patients with esophageal cancer., (©2024 American Association for Cancer Research.)

The first case is a 62-year-old female who complained of painful left axillary lymph node swelling. Six months later, a CT scan revealed multiple lung nodules. Biopsies of the axillary lymph node and lung showed metastatic carcinoma from breast cancer. However, no breast tumor was found. She was diagnosed with occult breast cancer with metastasis to the axillary lymph node and lung. ER(+), PgR(±), HER2(1+). Letrozole was administered, and effective control was achieved for 20 months. The second case is a 62-year-old female who presented with back pain. A CT scan revealed left axillary lymph node swelling and multiple osteolytic changes in the thoracolumbar spine and rib. Biopsies of the axillary lymph node and thoracic spine showed metastatic carcinoma from breast cancer. However, no breast tumor was found. She was diagnosed with occult breast cancer with metastasis to the axillary lymph nodule and bone. ER(+), PgR(+), HER2(1+). Fulvestrant and denosumab were administered. However, after 6 months, she discontinued the treatment. Our results suggested that effective control could be achieved through systemic therapy and local therapy was not necessary for Stage Ⅳ occult breast cancer.

This case was observed in a man in his 70s. Although symptomatic treatment was performed for epigastralgia, endoscopic examination revealed a type 3 tumor on the fornix of the stomach to the lesser curvature of the body just above the esophagogastric junction, and the patient was diagnosed with moderately differentiated tubular adenocarcinoma(cT4bN3aM0, cStage ⅣA). As esophageal and diaphragmatic invasion was suspected based on CT findings, S-1 plus CDDP was started as preoperative chemotherapy. Although the primary lesion and lymph node metastasis decreased in size, chemotherapy was discontinued after one course due to stenosis symptoms, and total gastrectomy and D2 dissection were performed. Postoperative adjuvant chemotherapy with S-1 was started. However, 6 months after starting the treatment, para-aortic lymph node recurrence was observed, and the treatment strategy was changed to weekly PTX. After 5 courses of weekly PTX, the lymph nodes continued to increase in size, and chemotherapy was discontinued per the patient's request. The patient was followed up with CT and PET-CT; however, no new recurrent lesions were found in other sites for approximately 1 year. Therefore, para-aortic lymph node dissection was performed as the salvage surgery. Pathological findings showed that gastric cancer metastasis was present in 1 swollen lymph node only, as confirmed by PET. At present, 6 years have passed since the first operation, and there has been no recurrence. In general, para-aortic lymph node metastasis is considered to result in poor prognosis in gastric cancer. However, in the absence of other noncurative factors, a good prognosis may be obtained with combined therapeutic modalities.

Background: Most patients with unresectable advanced digestive cancers require placement of a fully implantable venous access port to facilitate safe delivery of anti-cancer drugs. Anti-VEGF therapies are commonly used even though they increase the risk of thrombosis. The objective of this study was to assess the incidence of radiologically confirmed catheter-related thrombosis(CRT)in patients with advanced digestive cancers., Methods: We retrospectively reviewed 88 patients with advanced digestive cancers who had adapted implantable ports placed in our institution for chemotherapy., Results: Thirty-nine patients were diagnosed with colorectal cancer, 26 with gastric cancer, 12 with pancreatic cancer, 8 with esophageal cancer, and 3 with other cancers. During follow-up, 22 patients(25%)received anti-VEGF therapies, while 66 patients(75%)did not. Four out of 88 patients(4.5%)had asymptomatic CRT. The incidence of CRT was the same(4.5%)regardless of whether the patient received anti-VEGF therapy., Conclusions: In patients with digestive cancers who had implantable venous access ports, the incidence of the CRT was 4.5% with no association with anti-VEGF therapies.

A 66-year-old woman underwent distal gastrectomy because of gastric cancer(stage ⅠB)and received no adjuvant chemotherapy. Eight years after the operation, computed tomography showed a small nodule in the right breast. Mammography did not reveal any abnormalities. Ultrasound sonography showed a diffuse and gradual non-mass-like low echoic lesion. Core needle biopsy indicated a malignancy. Partial resection of the right breast was performed to obtain a diagnosis. On postoperative histopathological examination, signet-ring cells were found in the tumor, and immunohistochemical analysis showed that both the breast tumor and the gastric carcinoma were MUC5AC-positive and MUC1-negative. We diagnosed this breast tumor as metastasis from gastric cancer. The patient has received chemotherapy with no subsequent metastatic tumors, and good control has been achieved for 21 months after the detection of the breast metastasis.

A 76-year-old female underwent breast-conserving surgery of the right breast and sentinel lymph node biopsy for primary breast cancer. Three years later, mammography and ultrasonography showed a small nodule in the right breast. There was nothing abnormal in the left breast. Three months later, she complained of a huge and rapid growing mass in the left breast. Malignant cells were obtained on fine needle aspiration biopsy in the right breast tumor. But it was not possible to diagnose whether the left breast tumor was benign or malignant on fine needle aspiration biopsy and needle biopsy. Bilateral mastectomy and sentinel lymph node biopsy of the right side were performed. Pathological diagnosis were squamous cell carcinoma of the right breast and spindle cell carcinoma of the left breast. Although the patient was treated with adjuvant chemotherapy, she had an early relapse with pleural, lung and bone metastases. The patient died approximately 8 months after operation. Spindle cell carcinoma presents many problems about therapy and prognosis. Further accumulation analysis is necessary.

Current treatment guidelines for locally advanced breast cancers recommend multimodality therapy consisting of chemotherapy followed by local treatment(surgery and radiotherapy). We retrospectively analyzed 35 cases oflocally advanced breast cancer at our institution between January 2004 and December 2014. Nine patients(25.7%)were treated with multimodality therapy consisting ofchemotherapy, surgery, and radiotherapy. Nineteen patients(54%)had disease recurrence and 9(26%)died. Factors that were significantly associated with recurrence were premenopausal, T1-3, and 4 or more lymph node metastases, and the number oflymph node metastases remained significant in the multivariable analysis. The median relapse-free survival was 1,147 days and the 5-year relapse-free survival rate was 49.7%. Survival rates were influenced by menopausal state and the number oflymph node metastases on the univariate analysis, but not in the multivariable analysis. Our results indicate that multimodality therapy is necessary particularly for patients with 4 or more lymph node metastases.