Advanced hepatocellular carcinoma and sorafenib: Diagnosis, indications, clinical and radiological follow-up

Advanced stage hepatocellular carcinoma(HCC) is a category of disease defined by radiological, clinical and hepatic function parameters, comprehending a wide range of patients with different general conditions. The main therapeutic option is represented by sorafenibtreatment, a multi-kinase inhibitor with anti-proliferative and anti-angiogenic effect. Trans-arterial Radio Embolization also represents a promising new approach to intermediate/advanced HCC. Post-marketing clinical studies showed that only a portion of patients actually benefits from sorafenib treatment, and an even smaller percentage of patients treated shows partial/complete response on follow-up examinations, up against relevant costs and an incidence of drug related adverse effects. Although the treatment with sorafenib has shown a significant increase in mean overall survival in different studies, only a part of patients actually shows real benefits, while the incidence of drug related significant adverse effects and the economic costs are relatively high. Moreover, only a small percentage of patients also shows a response in terms of lesion dimensions reduction. Being able to properly differentiate patients who are responding to the therapy from non-responders as early as possible is then still difficult and could be a pivotal challenge for the future; in fact it could spare several patients a therapy often difficult to bear, directing them to other second line treatments(many of which are at the moment still under investigation). For this reason, some supplemental criteria to be added to the standard modified Response Evaluation Criteria in Solid Tumors evaluation are being searched for. In particular, finding some parameters(cellular density, perfusion grade and enhancement rate) able to predict the sensitivity of the lesions to anti-angiogenic agents could help in stratifying patients in terms of treatment responsiveness before the beginning of the therapy itself, or in the first weeks of sorafenib treatment. This would bring a strongly desirable help in clinical managements of these patients.

Cancer-related microangiopathic hemolytic anemia in patients with advanced gastric cancer: A retrospective single-center analysis

BACKGROUND Microangiopathic hemolytic anemia(MAHA) with thrombocytopenia and organ failure caused by tumor-associated thrombotic microangiopathy(TMA) is a lifethreatening oncological emergency. Rapid diagnosis and precise distinction from other forms of TMA is crucial for appropriate therapy, which aims at treating the underlying malignancy. However, the prognosis of patients with cancer-related(CR)-MAHA is limited. To date, less than 50 patients with gastric cancer and CRMAHA have been reported, mainly as single case reports, and detailed information on treatment strategies and outcome are scarce. We analyzed the characteristics and outcomes data of CR-MAHA patients with gastric cancer treated at our center between 2012 and 2019.AIM To gain knowledge about CR-MAHA and the course of disease.METHODS We retrospectively analyzed patients using an institutional prospectively maintained database. Patients who had CR-MAHA but other cancer types or cancer of unknown primary were excluded. The basic requirements for inclusion were: Histologically proven gastric adenocarcinoma;and clinical diagnosis of hemolytic anemia with schistocytes with or without thrombocytopenia. The observation period for each patient started with the first day of documented symptoms. The follow-up period for this analysis ended on February 1, 2020.RESULTS We identified eight patients with a median age of 54 years. Histologically, all patients had(partial) diffuse subtypes of gastric adenocarcinoma with partial or complete signet cell morphology. All patients had metastatic disease and one patient had a microsatellite instability-high(MSI-H) tumor. In three patients, clinical signs of MAHA preceded the diagnosis of cancer, and in two patients, CRMAHA indicated recurrent disease. All patients had severe hemolytic anemia and thrombocytopenia. Six patients experienced severe bone pain, and five patients had dyspnea. Systemic, 5-fluorouracil-based combination chemotherapy was initiated in six patients, which resulted in rapid initial response with significant improvement of clinical symptoms and blood values. Progression-free survival(PFS) of the whole cohort was 1.9 wk and median overall survival(OS) was 1.9 wk. For patients with chemotherapy, PFS was 9.0 wk and OS was 10.3 wk. The patient with the MSI-H tumor has been undergoing immunotherapy for more than 3 years.CONCLUSION The benefit of chemotherapy in CR-MAHA patients is limited. Immunotherapy for patients with MSI-H tumors may lead to long-term tumor control even in CRMAHA patients.

Gemcitabine and Docetaxel as a Second-Line Treatment in Advanced Soft Tissue Sarcomas

OBJECTIVE Promising anti-tumor activity in patients with metastatic or unresectable soft tissue sarcomas has been reported with gemcitabine and/or docetaxel. METHODS Forty patients with advanced soft tissue sarcomas refractory to first-line chemotherapy treatment were enrolled. They received combination of gemcitabine at dose of 900 mg/m2 on days 1 and 8 and docetaxel at dose of 100 mg/m2 on day 8, and had this regimen repeated every 3 weeks. If the patients had received the pelvic irradiation in advance, gemcitabine dose was reduced to 675 mg/m2 on days 1 and 8 and docetaxel to 75 mg/m2 on day 8, and had it repeated every 3 weeks. RESULTS Gemcitabine/docetaxel combination was well tolerated by the patients with an overall response of 20%. After median follow-up of 15 months, a median overall survival time was 12 months （95% CI 7.042-16.958） and a median progression free survival time was 6 months （95% CI 5.445-6.545）. The most common hematologic toxicity was neutropenia （47.5%） while mucositis was the most common nonhematologic toxicity （45%）. The 1- and 2- year survival rates were 50% and 15%, respectively. CONCLUSION This regimen of gemcitabine/docetaxel combination as second-line treatment for the patients with advanced soft tissue sarcomas is effective with acceptable toxicities. These results should be evaluated in a large phase III trial.