Biologic and Immunotherapy Developments in Advanced Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver, and the second leading cause of cancer-related mortality worldwide with a very poor 5-year survival. Treatment for HCC includes surgery, liver-directed therapies and systemic therapies. Until 2008, no effective systemic therapy was available for advanced HCC. Sorafenib is the first drug to show improvement in overall survival among patients with advanced HCC in comparison to placebo, and it is approved by U.S. Food and Drug Administration (FDA) as a first-line treatment of advanced HCC. After sorafenib approval, several targeted and immune therapies were tested and showed efficacy in advanced HCC. Lenvatinib has been shown to be non-inferior to sorafenib as first-line treatment. Both nivolumab and regorafenib showed improvement in overall survival among patients with advanced HCC as a second line treatment after progression on sorafenib, and both are FDA approved for this indication. There is a limited role for cytotoxic agents in the treatment of advanced HCC

Clinical Outcome of Ampullary Carcinoma: Single Cancer Center Experience

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Ampullary cancers represent a subset of periampullary cancers, comprising only 0.2% all gastrointestinal cancers. Localized disease is primarily managed by a surgical intervention, called pancreaticoduodenectomy (PD), followed in many cases by the administration of adjuvant chemotherapy (CT) or chemoradiation therapy (CRT). However, there are no clear evidence-based guidelines to aid in selecting both the modality and regimen of adjuvant therapy for resected Ampullary carcinoma. Methods. We retrospectively analyzed 54 patients at KU Cancer Center, who had undergone endoscopic resection or pancreaticoduodenectomy (PD) for Ampullary cancer from June 2006 to July 2016. We obtained patients’ baseline characteristics, clinical presentation, pathology, treatment modality, recurrence pattern, and survival outcomes. The time-to-events data were compared using Kaplan-Meier methods. A univariate and multivariate Cox proportional hazards regression was performed to evaluate factors associated with overall survival (OS) and generate hazard ratios (HR). Results. The mean age of the 54 patients was 68 (37-90). 38 (70%) were males and 16 (30%) were females. Most of the patients were Caucasian (76%). Approximately half of all patients had a history of smoking, 20% had alcohol abuse, and 13% had pancreatitis. Among the 54 patients with localized cancers, 9 (16%) were treated definitively with nonoperative therapies, usually due to a prohibitive comorbidity profile, performance status, or unresectable tumor. 45 out of 54 patients (83%) underwent surgery. Of the 45 patients who underwent surgery, 18 patients (40% of the study cohort) received adjuvant therapy due to concerns for advanced disease as determined by the treating physician. 13 patients (24%) received adjuvant CT and 5 patients (9.2%) received CRT. The remaining 27 patients (50%) underwent surgery alone. The median OS for the entire study cohort was 30 months. When compared to surgery alone, adjuvant therapy with either CT or CRT had no statistically significant difference in terms of progression-free survival (p=0.56) or overall survival (p=0.80). In univariate Cox proportional hazards regression analysis, high-risk features like peripancreatic extension (16%) and perineural invasion (26%) were found to be associated with poor OS. Lymph node metastasis (29%) did not significantly affect OS (HR 1.42, 95% CI 0.73-1.86; p=0.84). Lymphovascular invasion (29%) was not associated with poor OS (HR 1.22, 95% CI 0.52, 2.96; p=0.76). In multivariate Cox regression analysis, only age group>70 years was significantly associated with OS , while other factors, including the receipt of adjuvant therapy, lymph nodes, positive margin, and lymphovascular, perineural, and peripancreatic involvement, were not significantly associated with OS. These results are likely due to small sample size. Conclusions. Despite numerous advances in both cancer care and research, efforts in rare malignancies such as Ampullary cancer remain very challenging with a clear lack of an evidence-based standard of care treatment paradigm. Although adding adjuvant therapies such as chemotherapy or chemoradiotherapy is likely to improve survival in high-risk disease, there is no standardized regimen for the treatment of Ampullary cancer. More research is required to elucidate whether statistically and clinically relevant differences exist that may warrant a change in the current adjuvant treatment strategies

The Biological Process of Aging and the Impact of Ionizing Radiation

Ionizing radiation is used to create models of accelerated aging because the processes of aging and radiation injury share common elements. In this chapter we review the biological processes of aging and the similarities and impact of ionizing radiation on those processes. The information draws on data from laboratory studies and from epidemiology studies of radiation exposure victims. The chapter reviews the effects of radiation on DNA, cells, and organs systems on aged adults. The science of aging and the effect of radiation on the aging process are areas of active research and our understanding is evolving

Predictors of Toxicity Among Older Adults with Cancer

An increasing number of cancer patients are of advanced age as the incidence of cancer increases with age. In this article, the clinical predictors of toxicity that may help in treatment selection are addressed, as well as mitigators of toxicity. The potential of artificial intelligence to enable further progress in the understanding of the interaction of age and tolerance to radiation is reviewed. The final section reviews the literature on patient-related outcomes for older patients