Cancer in People Living With HIV, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology.

People living with HIV (PLWH) are diagnosed with cancer at an increased rate over the general population and generally have a higher mortality due to delayed diagnoses, advanced cancer stage, comorbidities, immunosuppression, and cancer treatment disparities. Lack of guidelines and provider education has led to substandard cancer care being offered to PLWH. To fill that gap, the NCCN Guidelines for Cancer in PLWH were developed; they provide treatment recommendations for PLWH who develop non-small cell lung cancer, anal cancer, Hodgkin lymphoma, and cervical cancer. In addition, the NCCN Guidelines outline advice regarding HIV management during cancer therapy; drug-drug interactions between antiretroviral treatments and cancer therapies; and workup, radiation therapy, surgical management, and supportive care in PLWH who have cancer.

Phase I and Preliminary Phase II Study of TRC105 in Combination with Sorafenib in Hepatocellular Carcinoma.

Purpose: Endoglin (CD105) is an endothelial cell membrane receptor highly expressed on proliferating tumor vasculature, including that of hepatocellular carcinoma (HCC), and is associated with poor prognosis. Endoglin is essential for angiogenesis, and its expression is induced by hypoxia and VEGF pathway inhibition. TRC105 is a chimeric IgG1 CD105 mAb that inhibits angiogenesis and causes antibody-dependent cellular cytotoxicity and apoptosis of proliferating endothelium.Experimental Design: Patients with HCC (Child-Pugh A/B7), ECOG 0/1, were enrolled in a phase I study of TRC105 at 3, 6, 10, and 15 mg/kg every 2 weeks given with sorafenib 400 mg twice daily. Correlative biomarkers included DCE-MRI and plasma levels of angiogenic factors, including soluble endoglin. Pharmacokinetics were assessed in serum.Results: Twenty-six patients were enrolled, of whom 25 received treatment, 15 with cirrhosis. Hep B/C: 3/15; M:F 19:6; mean age of 60 (range, 18-76); 1 DLT (grade 3 AST) occurred at 10 mg/kg. The most frequent toxicity was low-grade epistaxis, a known toxicity of TRC105. One patient experienced an infusion reaction and was replaced. One patient with coronary stenosis developed a fatal myocardial infarction, and one patient developed G3 cerebral tumor hemorrhage. MTD was not established and DL4 (15 mg/kg) was expanded. The overall response rate in 24 evaluable patients at all 4 dose levels was 21% [95% confidence interval (CI), 7.1-42.2], and 25% (95% CI, 8.7-49.1) in patients with measureable disease. Four patients had confirmed stable disease, one of whom was treated for 22 months. Median progression-free survival (PFS) for 24 patients evaluable for PFS was 3.8 months (95% CI, 3.2-5.6 months); median overall survival was 15.5 months (95% CI, 8.5-26.3 months).Conclusions: TRC105 combined with sorafenib was well tolerated at the recommended single agent doses of both drugs. Encouraging evidence of activity to date (PR rate 25%) was observed, and the study is now continuing to recruit in the phase II stage as a multicenter study to confirm activity of the combination. Clin Cancer Res; 23(16); 4633-41. ©2017 AACR.

The case for immune-based approaches in biliary tract carcinoma.

Biliary tract cancers (BTC) comprise a group of uncommon malignancies in which the standard therapies are minimally effective and evolve slowly. Like the majority of gastrointestinal cancers, with some notable exceptions, the impact of immune-based approaches has yet to be seen. However, the etiological background of BTC-overlapping in almost every known causative or associated factor with inflammation-provides a strong clue that these approaches may have an impact in this group of diseases. This review covers what we currently know about the role of the immune system in the etiology of BTC, highlighting differences by subtype, and pointing to the therapeutic opportunities currently entering the clinic or about to do so. (Hepatology 2016;64:1785-1791).

Pancreatic Squamous Cell Carcinoma: A Population-Based Study of Epidemiology, Clinicopathologic Characteristics and Outcomes.

OBJECTIVES: Squamous metaplasia is commonly detected in pancreatic parenchyma; however, primary pancreatic squamous cell carcinoma (SCC) is a rare malignancy with unknown incidence and unclear prognosis. METHODS: Surveillance, Epidemiology, and End Results (SEER) registries were examined identifying pancreatic SCC and adenocarcinoma cases from 2000 to 2012. Age-adjusted incidence rates were calculated. Patients with SCC versus adenocarcinoma were compared by clinical features and relative survival outcomes. RESULTS: We identified 214 patients with SCC and 72,860 with adenocarcinoma. For SCC, incidence rates tripled between 2000 and 2012. Significantly higher SCC incidence rates were observed in older age groups, blacks, and males. Greater proportion of patients with SCC than those with adenocarcinoma had poorly differentiated histology (73.0% vs 43.7%, P < 0.001). In both subtypes, majority of patients had stage IV disease, 59.0% for adenocarcinoma versus 62.6% for SCC. The 1- and 2-year relative survival rate was significantly lower in patients with SCC versus adenocarcinoma. The 1-year relative survival was 14.0% (95% confidence interval, 9.5%-19.4%) for SCC, compared with 24.5% (95% confidence interval, 24.2%-24.8%) for adenocarcinoma. CONCLUSIONS: Although primary pancreatic SCC is a rare neoplasm, incidence rates for this subtype are increasing. Relative to adenocarcinoma, pancreatic SCC is characterized by poorly differentiated histology and worse survival.

Population attributable fractions of risk factors for hepatocellular carcinoma in the United States.

BACKGROUND: Hepatocellular carcinoma (HCC) incidence has been increasing in the United States for several decades; and, as the incidence of hepatitis C virus (HCV) infection declines and the prevalence of metabolic disorders rises, the proportion of HCC attributable to various risk factors may be changing. METHODS: Data from the Surveillance, Epidemiology, and End Results-Medicare linkage were used to calculate population attributable fractions (PAFs) for each risk factor over time. Patients with HCC (n = 10,708) who were diagnosed during the years 2000 through 2011 were compared with a 5% random sample of cancer-free controls (n = 332,107) residing in the Surveillance, Epidemiology, and End Results areas. Adjusted odds ratios (ORs) and PAFs were calculated for HCV, hepatitis B virus (HBV), metabolic disorders, alcohol-related disorders, smoking, and genetic disorders. RESULTS: Overall, the PAF was greatest for metabolic disorders (32%), followed by HCV (20.5%), alcohol (13.4%), smoking (9%), HBV (4.3%), and genetic disorders (1.5%). The PAF for all factors combined was 59.5%. PAFs differed by race/ethnicity and sex. Metabolic disorders had the largest PAF among Hispanics (PAF, 39.3%; 95% confidence interval [CI], 31.9%-46.7%) and whites (PAF, 34.8%; 95% CI, 33.1%-36.5%), whereas HCV had the largest PAF among blacks (PAF, 36.1%; 95% CI, 31.8%-40.4%) and Asians (PAF, 29.7%; 95% CI, 25.9%-33.4%). Between 2000 and 2011, the PAF of metabolic disorders increased from 25.8% (95% CI, 22.8%-28.9%) to 36% (95% CI, 33.6%-38.5%). In contrast, the PAFs of alcohol-related disorders and HCV remained stable. CONCLUSIONS: Among US Medicare recipients, metabolic disorders contribute more to the burden of HCC than any other risk factor, and the fraction of HCC caused by metabolic disorders has increased in the last decade. Cancer 2016;122:1757-65. Published 2016. This article is a U.S. Government work and is in the public domain in the USA..

The yin and yang of evasion and immune activation in HCC.

Current systemic treatment options for patients with hepatocellular carcinoma (HCC) are limited to sorafenib. With the recent FDA approval of the second PD1-PD-L1 pathway inhibitor, immunotherapy has gained even more interest as a potential novel treatment option for patients with HCC. This is due not only because of the failure of other treatment approaches in the past, but also because immunological mechanisms have been shown to play an important role during tumor development, growth, and treatment. Here we present a review of immunological mechanisms in the liver relevant for tumor progression and treatment. We summarize our current knowledge on immune activating and immune suppressing mechanisms during tumor initiation, development, and treatment. We try to explain the paradox of how inflammatory responses in a setting of chronic infection promote tumor development, while the primary aim of immunotherapy is to activate immunity. Finally we summarize recent advances in addition to providing an outlook for the immunotherapy of HCC.

Identification of active chemotherapy regimens in advanced biliary tract carcinoma: a review of chemotherapy trials in the past two decades.

Biliary tract carcinoma is a rare malignancy. We performed a comprehensive analysis of published prospective clinical trials in advanced biliary tract carcinoma in an attempt to identify active regimens in this setting. We searched PubMed and abstracts presented at the American Society of Clinical Oncology, Gastrointestinal Cancer Symposium, European Society of Medical Oncology and European Cancer Organization conferences for clinical trials in this disease. We found 83 trials. The effect of gemcitabine on overall survival benefit showed a strong trend (p = 0.014) and an improvement in progression-free survival (p = 0.003). Gemcitabine-based regimens containing 5-fluorouracil showed a trend toward an improved overall survival (p = 0.047) relative to platinum agents. Our findings support gemcitabine as the chemotherapy backbone for the treatment of patients with cholangiocarcinoma. Gemcitabine plus 5-fluorouracil combinations warrant further investigations.