Gastric neuroendocrine carcinoma presenting complete durable response by nivolumab treatment for multiple metastases and radiotherapy to oligoprogressive metastasis.

Gastric neuroendocrine carcinomas (NEC) are highly aggressive cancer with dismal prognosis. Platinum-based chemotherapy is used as the first-line treatment for this entity. However, there are no established therapeutic guidelines for platinum-resistant gastric NEC. We herein report a patient with metastatic gastric NEC who achieved durable and complete response to nivolumab with radiotherapy for oligoprogressive metastasis. A 70-year-old male patient had recurrences of resected gastric NEC, involving the liver and lymph nodes. His disease became refractory to cisplatin and etoposide combination therapy, after which he was treated with nivolumab. All the tumors showed marked shrinkage. However, 1 year after starting nivolumab, one metastatic lesion of the liver began to enlarge, and radiotherapy was performed to the lesion. Thereafter, a complete response was obtained, which has been maintained without any treatment for the past 2 years.

Relationship Between Safety and Cumulative Bevacizumab Dose in Patients With Metastatic Colorectal Cancer Who Received Long-term Bevacizumab Treatment.

BACKGROUND/AIM: Bevacizumab-based chemotherapy is the standard treatment for metastatic colorectal cancer (mCRC) but has several specific adverse events. The cumulative bevacizumab dose (CBD) increases with long-term treatment as it is often used beyond the first disease progression, based on existing evidence. However, the association between CBD and the frequency and severity of adverse events in mCRC patients who received bevacizumab for long-term treatment remains unclear. PATIENTS AND METHODS: Among the mCRC patients who received bevacizumab-based chemotherapy between March 2007 and December 2017 at the University of Tsukuba Hospital, those who continued treatment for more than 2 years were eligible for the study. The onset and worsening of proteinuria, hypertension, bleeding, and thromboembolic events were assessed to determine their relationship with CBD. RESULTS: Of the 109 patients who received bevacizumab-based chemotherapy, 24 were included in the study. Grade 3 proteinuria was observed in 21 (88%) and 9 (38%) patients. The severity of proteinuria markedly increased after administering >100 mg/kg of CBD and progressed to grade 3 at concentrations exceeding 200 mg/kg. Thromboembolic events were observed in three (13%) patients, and two of them developed acute myocardial infarction after receiving a CBD of >300 mg/kg. Grade 2 or higher hypertension and grade 1 bleeding were observed in 9 (38%) patients and in 6 (25%) patients, respectively, regardless of the CBD. CONCLUSION: Proteinuria and thromboembolic events occurred and worsened in mCRC patients when the bevacizumab dose exceeded the threshold dose.

Systemic chemotherapy combined with anti-epidermal growth factor receptor antibody therapy for RAS wild-type appendiceal signet-ring cell carcinoma: a series of three cases.

The effect of anti-epidermal growth factor receptor (EGFR) antibody-containing chemotherapy on appendiceal signet-ring cell carcinoma (SRCC) remains unknown. Herein, we report three patients, diagnosed as having synchronous metastases, who underwent this treatment for unresectable appendiceal SRCC with RAS wild type. Cases 1, 2, and 3 received FOLFOX with panitumumab, FOLFOX with cetuximab, and FOLFIRI with cetuximab, respectively, and their progression-free survival were 6.2, 7.2, and 18.7 months, respectively. The subsequent anti-vascular endothelial growth factor antibody-containing therapy was ineffective, and their overall survival was 8.2, 11.4, and 22.9 months, respectively. The anti-EGFR antibody-containing chemotherapy showed moderate efficacy for appendiceal SRCC. Further studies including molecular analysis should be needed.

Severe Gastrointestinal Disorder Due to Capecitabine Associated with Dihydropyrimidine Dehydrogenase Deficiency: A Case Report and Literature Review.

Dihydropyrimidine dehydrogenase (DPD) deficiency induces severe adverse events in patients receiving fluoropyrimidines. We encountered a 64-year-old DPD-deficient man with a severe capecitabine-related gastrointestinal disorder. He received capecitabine-containing chemotherapy after rectal cancer resection. During the first course of chemotherapy, he developed severe diarrhea, a fever, and hematochezia. Endoscopy revealed mucosal shedding with bleeding throughout the gastrointestinal tract. DPD deficiency was suspected because he developed many severe adverse events of capecitabine early and was finally confirmed based on the finding of a low DPD activity level in peripheral blood mononuclear cells. After one month of intensive care, hemostasis and mucosal healing were noted, although his gastrointestinal function did not improve, and he had persistent nutritional management issues.

A Durable Response after the Discontinuation of Nivolumab in an Advanced Gastric Cancer Patient.

A durable response after the discontinuation of immune checkpoint-inhibitor therapy has previously been reported in several cancers. We herein describe a patient with gastric cancer who maintained a durable response after the discontinuation of nivolumab. A 65-year-old man was treated with nivolumab as a sixth-line therapy for recurrent gastric cancer. After four cycles of nivolumab therapy, he showed a partial response. But the treatment was discontinued when two immune-related adverse events occurred after six cycles. Disease regression was sustained for approximately 2 years, without the re-administration of nivolumab. The characteristics leading to such responses are unclear, and further studies are warranted in this regard.

Retrospective analysis for the efficacy and safety of nivolumab in advanced gastric cancer patients according to ascites burden.

BACKGROUND: Nivolumab is a standard later-line therapy for advanced gastric cancer (AGC). However, few reports exist about its efficacy and safety in patients with massive ascites. METHODS: We retrospectively collected clinical data from 72 AGC patients who received nivolumab administration at least once from Oct 2017 to Feb 2019 and studied their clinical outcomes dividing into two groups: 50 patients with no or localized ascites in the pelvic cavity or liver surface (LAB: low ascites burden) and 22 patients with massive ascites (HAB: high ascites burden). RESULTS: Median overall survival (OS) was 5.3 months (95% CI 3.4-7.3) in the LAB group and 2.5 months (95% CI 0.0-5.0) in the HAB group. Multivariate Cox regression analysis for OS revealed blood neutrophil-to-lymphocyte ratio (hazard ratio 0.40, 95% CI 0.20-0.83, p = 0.013) as an independent prognostic factor. Response rates in the patients with measurable lesions were 16% (7/43) and 8% (1/12) in the LAB and HAB groups, respectively. Ascites decreased or disappeared in 6 HAB patients (27%) and these responders had a prolonged OS of median 9.7 months (95% CI 3.6-15.8). The median time to ascites response was 1.3 months (95% CI 0.8-1.9). These responders have lower neutrophil-to-lymphocyte ratios than 5.0 at the start of nivolumab. Immune-related adverse events occurred in 23% of HAB and 18% of LAB patients. CONCLUSIONS: Nivolumab could improve massive ascites and confer survival benefit for some AGC patients. Considering a similar incidence of immune-related adverse events, it would be a recommended treatment option for AGC with massive ascites.

[A case of acute respiratory failure in an elderly patient with elderly asthma-COPD overlap syndrome (ACOS) is differentiated from acute eosinophilic pneumonia].

We report a case of acute respiratory failure in a 77-year-old male with chronic obstructive pulmonary disease (COPD) who showed marked eosinophilia (61.5% of the peripheral total white blood cells [WBCs]; 13,200/mm(3)). The patient was an ex-smoker, but he had started smoking again one month previously, His forced expiratory volume in one second (FEV1) was low and dyspnea symptom was observed. Although rhonchi were detected, wheezing chest sounds were not detected. Chest X-radiography and computed tomography of the lung revealed diffuse bilateral pulmonary infiltrates and emphysematous changes. He was given intravenous methyl prednisolone (1,000 mg) for 3 consecutive days. The abnormal shadows on the chest X-ray film improved remarkably and the eosinophils in his peripheral blood were reduced. Furthermore, it was no longer necessary to administer oxygen to treat his hypoxemia. The symptomatic and clinical course mimicked to a case of acute eosinophilic pneumonia (AEP). However, transbronchial lung biopsy specimens did not reveal eosinophilic infiltration in the alveolar septa. The fraction of eosinophils in the patient's bronchoalveolar lavage was 4.4% and not greater than 25%. After hospitalization, 5-15 mg of prednisolone administered orally in combination with bronchodilators to better manage his clinical symptoms. This case was thus determined to correspond to elderly asthma-COPD overlap syndrome (ACOS).