Intratumoral nanoplexed poly I:C BO-112 in combination with systemic anti-PD-1 for patients with anti-PD-1-refractory tumors.

Intratumoral therapies, especially Toll-like receptor agonists, can trigger both the innate and adaptive immune systems. BO-112 is a nanoplexed form of polyinosinic:polycytidylic acid (poly I:C) that induces local and systemic immunotherapeutic effects in mouse models. In a multicenter phase 1 clinical trial, repeated intratumoral administrations of BO-112 induced an increase in tumor cell necrosis and apoptosis, as well as augmented immune reactivity according to gene expression profiling. The first three cohorts receiving BO-112 as a monotherapy resulted in a recommended dose of 1 mg that could be safely repeated. Two grade 3 to 4 adverse reactions in the form of reversible thrombocytopenia were reported. In a fourth cohort of 28 patients with tumors that had primary resistance to anti-programmed cell death protein-1 (PD-1), the combination of intratumoral BO-112 with nivolumab or pembrolizumab was also well tolerated, and 3 patients (2 with melanoma and 1 with renal cell carcinoma) achieved partial responses, with 10 more patients having stable disease at 8 to 12 weeks. Thus, local BO-112 combined with a systemic anti-PD-1 agent might be a strategy to revert anti-PD-1 resistance.

Maintenance with Trabectedin in the Treatment of Platinum-Sensitive Recurrent Ovarian Cancer.

Ovarian cancer is the seventh most common type of cancer and the fifth leading cause of cancer death among women worldwide. The current usual therapeutic approach in this disease includes optimal cytoreductive therapy followed by platinum-based adjuvant chemotherapy, along with neoadjuvant chemotherapy prior to surgery in selected cases. The platinum-free interval (PFI) continues to be the most useful tool to assist in the selection of the subsequent therapy and to predict response to treatment. The combination of trabectedin and pegylated liposomal doxorubicin (PLD) is useful in patients with partially platinum-sensitive recurrent ovarian cancer, in patients who have previously received two or more platinum-based chemotherapy regimens, in patients who have already experienced a platinum-induced hypersensitivity reaction and in patients who have previously failed to respond to a platinum-based treatment. CASE PRESENTATION: A 64-years-old postmenopausal woman with pain, abdominal distension, and an altered intestinal transit and with partially platinum-sensitive recurrent ovarian cancer, was successfully treated with a second line of trabectedin chemotherapy in combination with PLD, followed by trabectedin in monotherapy. This case proves the effectiveness of the combination of trabectedin and PLD and demonstrates how the administration of trabectedin, even in monotherapy, allows to maintain an adequate clinical response with good tolerance to the treatment during more than two years of drug administration.

Gastric ischaemia as an unusual presentation of median arcuate ligament compression syndrome.

Median arcuate ligament compression syndrome is an anatomical and clinical entity defined by a combination of extrinsic compression of the coeliac axis by the median arcuate ligament and clinical manifestations. The majority of patients with features of compression experience no symptoms. The most common clinical symptoms when present are epigastric pain, nausea, vomiting and weight loss. Hypertrophy of the median arcuate ligament is a rare cause of chronic abdominal pain. We present a case of an elderly male patient who presented with acute epigastric pain, and gastric and intrahepatic portal pneumatosis on CT imaging. Emphysematous gastritis, caustic ingestion and other causes of this imaging presentation were ruled out. Imaging also showed chronic compression of the coeliac axis with compensatory hypertrophy of the gastroduodenal artery. Gastric ischaemia is a rare presentation of this syndrome, which occurs owing to the failure of compensatory mechanisms and resultant ischaemic injury to a virtual watershed vascular territory of the gastric wall. Conservative management was performed, including volume restoration, intravenous proton pump inhibitor therapy, broad-spectrum antibiotic therapy and blood transfusion. No surgical or endovascular interventional procedures were carried out. The patient showed clinical improvement soon after the initiation of treatment. Disappearance of the imaging findings was documented 2 weeks after treatment. Complete endoscopic recovery and absence of clinical alterations were observed during follow-up after 3 months.