Management and mechanism of calciphylaxis in a patient treated with the FGFR inhibitor pemigatinib-a case report.

Background: Small molecule fibroblast growth factor receptor (FGFR) inhibitors, such as pemigatinib, have been developed for the treatment of cholangiocarcinoma (CCA) with rearrangements or fusions in the FGFR2. FGFR inhibitors (FGFRis) have dermatologic side effects such as dry skin or nail bed damage. However, in very rare instances, a life-threatening vascular calcification disease known as calciphylaxis has been linked to these therapies. Case Description: We report a patient with metastatic CCA, who developed calciphylaxis following the start of their pemigatinib treatment. Calciphylaxis is associated with skin lesions and affects the dermal microvasculature in addition to the vascular calcification. This case focuses on the management strategy used for this rare adverse event (AE) as well as the pathology and complicated mechanism of calciphylaxis. We highlight the unclear pathophysiology behind this disease by identifying key players in the signaling and molecular pathways in the microenvironment that are needed to trigger this pathology. Conclusions: Calciphylaxis is normally associated with advanced renal failure in the setting of high phosphate and calcium. However, the patient we present here did not have advanced renal failure or high calcium levels and calcium dysregulation. As FGFRi use becomes more widespread, the more important it becomes to identify and have a treatment strategy for this rare AE.

Risk factors for early-onset pancreatic ductal adenocarcinoma: A systematic literature review.

BACKGROUND: Emerging cancer trends suggest an increase in pancreatic cancer incidence in individuals younger than its typical age of onset, potentially reflecting changes in population exposures and lifestyles. PATIENTS AND METHODS: We conducted a PRISMA-standard systematic literature review to identify non-heritable risk factors for early-onset pancreatic ductal adenocarcinoma (PDAC) (PROSPERO number: CRD42022299397). Systematic searches of MEDLINE and Embase bibliographic databases were performed (January 2022), and publications were screened against predetermined eligibility criteria; data were extracted using standardised data fields. The STROBE checklist was used to assess the completeness of reporting as a proxy for publication quality. Data were categorised by risk factor and analysed descriptively. RESULTS: In total, 24 publications were included. All publications reported observational study data; thresholds for age group comparisons ranged between 40 and 65 years. Lifestyle factors investigated included smoking, alcohol consumption, obesity, physical inactivity, meat intake, socioeconomic status and geographical residence. Clinical factors investigated included pancreatitis, diabetes/insulin resistance, prior cancer and cancer stage at diagnosis, hepatitis B infection, metabolic syndrome and long-term proton pump inhibitor exposure. Publication STROBE scores were 6-21 (maximum, 22). Eight studies reported results adjusted for confounders. Potential non-heritable risk factors for early-onset PDAC that warrant further investigation included smoking, alcohol consumption, pancreatitis and hepatitis B infection. CONCLUSION: Evidence for non-heritable risk factors for early-onset PDAC is heterogeneous, but four factors were identified that might aid the identification of at-risk individuals who may benefit from screening and risk reduction strategies.

NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial.

BACKGROUND: Pancreatic ductal adenocarcinoma remains one of the most lethal malignancies, with few treatment options. NAPOLI 3 aimed to compare the efficacy and safety of NALIRIFOX versus nab-paclitaxel and gemcitabine as first-line therapy for metastatic pancreatic ductal adenocarcinoma (mPDAC). METHODS: NAPOLI 3 was a randomised, open-label, phase 3 study conducted at 187 community and academic sites in 18 countries worldwide across Europe, North America, South America, Asia, and Australia. Patients with mPDAC and Eastern Cooperative Oncology Group performance status score 0 or 1 were randomly assigned (1:1) to receive NALIRIFOX (liposomal irinotecan 50 mg/m2, oxaliplatin 60 mg/m2, leucovorin 400 mg/m2, and fluorouracil 2400 mg/m2, administered sequentially as a continuous intravenous infusion over 46 h) on days 1 and 15 of a 28-day cycle or nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2, administered intravenously, on days 1, 8, and 15 of a 28-day cycle. Balanced block randomisation was stratified by geographical region, performance status, and liver metastases, managed through an interactive web response system. The primary endpoint was overall survival in the intention-to-treat population, evaluated when at least 543 events were observed across the two treatment groups. Safety was evaluated in all patients who received at least one dose of study treatment. This completed trial is registered with ClinicalTrials.gov, NCT04083235. FINDINGS: Between Feb 19, 2020 and Aug 17, 2021, 770 patients were randomly assigned (NALIRIFOX, 383; nab-paclitaxel-gemcitabine, 387; median follow-up 16·1 months [IQR 13·4-19·1]). Median overall survival was 11·1 months (95% CI 10·0-12·1) with NALIRIFOX versus 9·2 months (8·3-10·6) with nab-paclitaxel-gemcitabine (hazard ratio 0·83; 95% CI 0·70-0·99; p=0·036). Grade 3 or higher treatment-emergent adverse events occurred in 322 (87%) of 370 patients receiving NALIRIFOX and 326 (86%) of 379 patients receiving nab-paclitaxel-gemcitabine; treatment-related deaths occurred in six (2%) patients in the NALIRIFOX group and eight (2%) patients in the nab-paclitaxel-gemcitabine group. INTERPRETATION: Our findings support use of the NALIRIFOX regimen as a possible reference regimen for first-line treatment of mPDAC. FUNDING: Ipsen. TRANSLATION: For the plain language summary see Supplementary Materials section.

Patient-reported tolerability of adjuvant ipilimumab (3 or 10 mg/kg) versus high-dose interferon alfa-2b for resected high-risk stage III-IV melanoma in phase III trial E1609.

PURPOSE: Trial E1609 demonstrated superior overall survival with ipilimumab 3 mg/kg (ipi3) compared to high-dose interferon (HDI) for patients with resected high-risk melanoma. To inform treatment tolerability, we compared health-related quality of life (HRQoL), gastrointestinal (GI), and treatment-specific physical and cognitive/emotional symptoms. We also compared treatment-specific concerns between all arms. METHODS: We assessed HRQoL using the Functional Assessment of Cancer Therapy-General, physical and cognitive/emotional concerns using the FACT-Biologic Response Modifier subscale, and GI symptoms with the Functional Assessment of Chronic Illness Therapy-Diarrhea subscale pre-treatment and every 3 months. The primary outcome was the difference in HRQoL at 3 months between ipi3/ipi10 vs. HDI. RESULTS: 549 patients (n = 158 ipi3; n = 191 ipi10; n = 200 HDI) were analyzed. 3-month completion was 58.7%. Compared to HDI, ipilimumab patients reported better HRQoL (ipi3 = 87.5 ± 14.6 vs. HDI = 74.7 ± 15.4, p < .001; ipi10 = 84.9 ± 16.5 vs. HDI, p < .001) and fewer physical (ipi3 = 22.3 ± 4.6 vs. HDI = 17.1 ± 5.4, p < .001; ipi10 = 21.8 ± 5.0 vs. HDI p < .001) and cognitive/emotional (ipi3 = 18.6 ± 4.4 vs. HDI = 15.0 ± 5.3, p < .001; ipi10 = 17.7 ± 4.8 vs. HDI p < .001) concerns, but worse GI symptoms (ipi3 = 40.8 ± 5.0 vs. HDI = 42.2 ± 2.9, p = .011; ipi10 = 39.5 ± 7.0 vs. HDI, p < .001). Fewer ipilimumab patients reported worsening treatment-specific concerns (e.g., 52% of ipi3 and 58% of ipi10 reported worsening fatigue vs. 82% HDI, p's < .001). CONCLUSION: PROs demonstrated less toxicity of ipi3 compared to HDI and ipi10. Priorities for symptom management among patients receiving ipilimumab include GI toxicities, fatigue, weakness, appetite loss, arthralgia, and depression. TRIAL REGISTRATION: NCT01274338, January 11, 2011 (first posted date) https://clinicaltrials.gov/ct2/show/NCT01274338?term=NCT01274338&draw=2&rank=1 .

Pharmacotherapeutic options for pancreatic ductal adenocarcinoma.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy projected to be the 2nd leading cause of cancer related death in the USA by 2030. This manuscript discusses current and evolving treatment approaches in patients with pancreatic cancer. AREAS COVERED: PDAC is classified as: a) resectable, b) borderline resectable, c) unresectable (locally advanced and metastatic). The standard of care for patients who present with resectable pancreatic adenocarcinoma is six months of adjuvant modified (m) FOLFIRINOX, gemcitabine plus capecitabine, or single agent gemcitabine. For many reasons, there has been a paradigm shift to employing neoadjuvant chemotherapy. For resectable and borderline resectable patients, we generally start with systemic therapy and reevaluate resectability with subsequent scans specifically when the tumor is located in the head or body of the pancreas. Combined chemoradiation therapy can be employed in select patients. The standard of care for metastatic PDAC is FOLFIRINOX or gemcitabine and nab-paclitaxel. Germline and somatic genomic profiling should be obtained in all patients. Patients with a germline BRCA mutation can receive upfront gemcitabine and cisplatin. EXPERT OPINION: Thorough understanding of molecular pathogenesis in PDAC has opened various therapeutic avenues. We remain optimistic that future treatment modalities such as targeted therapies, cellular therapies and immunotherapy will further improve survival in PDAC.

S1417CD: A Prospective Multicenter Cooperative Group-Led Study of Financial Hardship in Metastatic Colorectal Cancer Patients.

BACKGROUND: Financial toxicity is a growing problem in oncology, but no prior studies have prospectively measured the financial impact of cancer treatment in a diverse national cohort of newly diagnosed cancer patients. S1417CD was the first cooperative group-led multicenter prospective cohort study to evaluate financial hardship in metastatic colorectal cancer (mCRC) patients. METHODS: Patients aged 18 years or older within 120 days of mCRC diagnosis completed quarterly questionnaires for 12 months. We estimated the cumulative incidence of major financial hardship (MFH), defined as 1 or more of increased debt, new loans from family and/or friends, selling or refinancing home, or 20% or more income decline. We evaluated the association between patient characteristics and MFH using multivariate cox regression and the association between MFH and quality of life using linear regression. RESULTS: A total of 380 patients (median age = 59.9 years) were enrolled; 77.7% were White, 98.0% insured, and 56.5% had annual income of $50 000 or less. Cumulative incidence of MFH at 12 months was 71.3% (95% confidence interval = 65.7% to 76.1%). Age, race, marital status, and income (split at $50 000 per year) were not statistically significantly associated with MFH. However, income less than $100 000 and total assets less than $100 000 were both associated with greater MFH. MFH at 3 months was associated with decreased social functioning and quality of life at 6 months. CONCLUSIONS: Nearly 3 out of 4 mCRC patients experienced MFH despite access to health insurance. These findings underscore the need for clinic and policy solutions that protect cancer patients from financial harm.

Tilsotolimod: an investigational synthetic toll-like receptor 9 (TLR9) agonist for the treatment of refractory solid tumors and melanoma.

INTRODUCTION: Cancer immunotherapy has seen tremendous strides in the past 15 years, with the introduction of several novel immunotherapeutic agents. Nevertheless, as clinical practice has shown, significant challenges remain with a considerable number of patients responding sub-optimally to available therapeutic options. Research has demonstrated the important immunoregulatory role of the tumor microenvironment (TME), with the potential to either hinder or promote an effective anti-tumor immune response. As such, scientific efforts have focused on investigating novel candidate immunomodulatory agents with the potential to alter the TME toward a more immunopotentiating composition. AREAS COVERED: Herein, we discuss the novel investigational toll-like receptor 9 agonist tilsotolimod currently undergoing phase II and III clinical trials for advanced refractory cancer, highlighting its mode of action, efficacy, tolerability, and potential future applications in the treatment of cancer. To this effect, we conducted an exhaustive Web of Science and PubMed search to evaluate available research on tilsotolimod as of August 2021. EXPERT OPINION: With encouraging early clinical results demonstrating extensive TME immunomodulation and abscopal effects on distant tumor lesions, tilsotolimod has emerged as a potential candidate immunomodulatory agent with the possibility to augment currently available immunotherapy and provide novel avenues of treatment for patients with advanced refectory cancer.

Tumor-Treating Fields: A fourth modality in cancer treatment, new practice updates.

Although major innovations in treatment are advancing, cancer persists as one of the leading causes of mortality. With the rising incidence of cancer and as we treat them, patients incur short term and long-term toxicities of current traditional therapies, including chemotherapy. This imposes a significant physical, emotional, and financial burden among patients, which affects their quality of life. Tumor-Treating Fields (TTFields) is a novel innovative new treatment modality that utilizes alternating electric fields at specific intermediate frequencies to diminish tumor growth by inhibiting mitosis and thus proliferation of malignant cells. The distinguishing feature of this new treatment modality is that it is noninvasive and tolerable. In fact, TTFields is currently FDA approved for the treatment of glioblastoma multiforme (GBM) as well as malignant pleural mesothelioma (MPM). Recently, TTFields have also been found to affect immunogenic cell death resulting in stronger anti-neoplastic effects. In this review, we discuss the mechanism of action of TTFields, the plethora of clinical trials being conducted in patients with GBM, pancreatic adenocarcinoma, ovarian cancer, non-small-cell-lung-cancer (NSCLC), brain metastasis from NSCLC, and MPM and toxicity profile.

Novel biomarkers for cholangiocarcinoma: how can it enhance diagnosis, prognostication, and investigational drugs? Part-1.

INTRODUCTION: The development of novel biomarkers for cancer has exploded over the last decade with advances in novel technologies. Cholangiocarcinoma (CCA), a cancer of the bile ducts, has a dearth of strong disease and pathophysiology biomarkers, making early detection and prognostication a difficult task. AREAS COVERED: In this comprehensive review, we discuss the spectrum of biomarkers for CCA diagnosis and prognostication. We elaborate on novel biomarker discovery through a comprehensive multi-omics approach. We also cover, how certain biomarkers may also serve as unique and potent targets for therapeutic development. EXPERT OPINION: Despite the relatively poor diagnostic and prognostic performance of existing biomarkers for CCA, there is a vast range of novel biomarkers with exquisite diagnostic and prognostic performance for CCA in the pipeline. Moreover, these biomarkers may serve as potential targets for precision medicine. Existing strategies to target unique biomolecular classes are discussed, within the context of an overall 'omics' focused profiling strategy. Omics profiling will simultaneously allow for enhanced biomarker development and identification of unique subtypes of cholangiocarcinoma and how they are influenced by an individual's unique context. In this manner, patient management strategy and clinical trial design can be optimized to the individual.

KEYNOTE-921: Phase III study of pembrolizumab plus docetaxel for metastatic castration-resistant prostate cancer.

Despite recent advances, treatment options for men with metastatic castration-resistant prostate cancer (mCRPC) progressing after next-generation hormonal agents (NHAs) are limited and provide only modest survival benefit. Thus, an unmet need remains for mCRPC patients after treatment with targeted endocrine therapy or NHA therapy. Pembrolizumab, a humanized monoclonal antibody for PD-1, has been found to have activity as monotherapy in patients with mCRPC and as combination therapy in a Phase Ib/II study with docetaxel and prednisone/prednisolone for patients previously treated with enzalutamide or abiraterone acetate. The aim of the randomized, double-blind, Phase III KEYNOTE-921 study is to evaluate the efficacy and safety of pembrolizumab plus docetaxel in patients with mCRPC who were previously treated with an NHA. Clinical trial registration: NCT03834506 (ClinicalTrials.gov).

Clinical complexity of utilizing FGFR inhibitors in cancer therapeutics.

INTRODUCTION: Fibroblast growth factor receptors (FGFR 1-4) are a highly conserved family of receptor tyrosine kinases, involved in several physiological processes. Genetic aberrations of FGFRs and their ligands, fibroblast growth factors (FGFs) are involved in several pathological processes including cancer. The FGF-FGFR axis has emerged as a treatment target in oncology. Because these aberrations drive cancer progression, the development of FGFR targeted therapies have been accelerated. AREAS COVERED: In this comprehensive review, we evaluate molecular pathology and targeted therapies to FGFRs. We reviewed the evidence for safety and efficacy from preclinical and clinical studies (phase I-III) of FGFR targeted therapies. We also discuss potential challenges in bringing these targeted therapies from bench to bedside and the potential opportunities. EXPERT OPINION: Despite the challenges of the clinical development of FGFR targeted therapies, two FGFR small-molecule inhibitors, namely Erdafitinib and Pemigatinib, are FDA approved for urothelial cancer and cholangiocarcinoma, respectively. Understanding and detection of FGFR genomic aberrations, protein overexpression and the development of isoform-specific inhibitors are factors in the clinical success of these therapies. An enhanced understanding of patient selection based on a gene signatures or biomarkers is key to success of FGFR targeted therapies.

Survival trends of metastatic small intestinal neuroendocrine tumor: a population-based analysis of SEER database.

BACKGROUND: Incidence of small intestinal neuroendocrine tumors (SNETs) is increasing and they now comprise the most common types of small intestinal cancer. SNETs frequently present with distant metastasis. Significant uncertainty prevails with regards to the surgical management strategies in metastatic SNETs. Therefore, we aim to analyze survival trends in metastatic SNET patients stratified by type of surgical treatment. METHODS: We analyzed the data from the SEER database: Incidence - SEER 18 Regs Research Data + Hurricane Katrina Impacted Louisiana Cases, Nov 2016 Sub (1973-2014 varying). Relative survival rates (RSRs) and hazard ratios (HRs) were measured for patients diagnosed with metastatic SNET between 2000 and 2014. Treatment received was divided into two broad categories; surgical resection and no surgery and further subcategorized into local resection (LR) (surgery of the primary tumor only) and radical resection (RR) (surgery for primary tumor and metastasectomy). RESULTS: We identified 1,138 metastatic SNET cases. Median age was 61 years. Median survival was 41 months and 5 year RSR was 72%. Age >50 years (HR 2.10, P<0.001), poorly differentiated histology (HR 3.50, P<0.001) and tumor size >2 cm (HR 1.27, P=0.07), showed poor outcome. The group which did not receive any tumor directed surgery showed the worst survival (5 years RSR 45.30% vs. 76%, respectively for no surgery vs. surgery group, P<0.001). We found no significant difference in survival between LR and RR (HR 1.01, 95% CI: 0.73-1.40, P=0.92). Upon further stratification, surgery significantly improved survival on patients who were >50 years (HR 0.37), and for primary tumor location in the duodenum (HR 0.13). CONCLUSIONS: Surgery for the primary tumor (LR or RR) significantly improved 5-year survival even in the presence of distant metastasis irrespective of primary tumor size, grade, or histology. Poor prognostic factors include, age >50 years, duodenal primary, tumor size >2 cm, and poorly differentiated histology.

A Multidisciplinary Evaluation of Barriers to Enrolling Cancer Patients into Early Phase Clinical Trials: Challenges and Patient-centric Recommendations.

Introduction: Early phase clinical trials are the first clinical research step to bringing new cancer therapeutics to patients. At this stage, a new drug's safety, dosing, and scheduling profiles are established as the main endpoints. However, excellent responses due to biomarker-guided and immune checkpoint trials in early phase have resulted in direct approvals of new anti-cancer drugs. Despite doubling of the success rate of new drug approvals, many barriers exist to expeditiously bring active new drugs to the clinic. Areas covered: This review covers roles of members of the early phase program and the challenges they face in enrolling advanced cancer patients to trials. Practical solutions are provided from the perspective of the investigators, regulatory, investigational pharmacy, research nurses, clinical research coordinators, budgets, contracts, and data management. Expert opinion: We are witnessing a burgeoning era in drug development with rapid approval of efficacious drugs. This is achieved by a strong collaboration between investigators, academic institutions, pharmaceutical sponsors, scientists, Food and Drug Administration (FDA), and community practices. Herein, we discuss some of the challenges faced by early phase clinical trials programs and discuss methods of improvement.

Everolimus for the treatment of advanced pancreatic ductal adenocarcinoma (PDAC).

Introduction: PDAC is a lethal malignancy with a clear unmet need; almost all patients fail 1st, 2nd, and 3rd line multi-agent cytotoxic chemotherapy. The mammalian target of rapamycin (mTOR) has been identified as a key signaling node enhancing tumor survival and drug resistance in PDAC; hence, it is considered a promising therapeutic target. Areas covered: We comprehensively reviewed the evidence from preclinical and phase I and II clinical trials, based on the authors'clinical experience and a PubMed, Cochrane library, Embase, and Google Scholar search everolimus + pancreatic cancer. Expert opinion: Everolimus has not demonstrated efficacy in PDAC; however, an mTOR inhibitor in combination with stroma-targeted therapies may be a promising area to explore in clinical trials.

First-in-Human, First-in-Class Phase I Trial of the Anti-CD47 Antibody Hu5F9-G4 in Patients With Advanced Cancers.

PURPOSE: To evaluate the safety, pharmacokinetics, and pharmacodynamics of Hu5F9-G4 (5F9), a humanized IgG4 antibody that targets CD47 to enable phagocytosis. PATIENTS AND METHODS: Adult patients with solid tumors were treated in four cohorts: part A, to determine a priming dose; part B, to determine a weekly maintenance dose; part C, to study a loading dose in week 2; and a tumor biopsy cohort. RESULTS: Sixty-two patients were treated: 11 in part A, 14 in B, 22 in C, and 15 in the biopsy cohort. Part A used doses that ranged from 0.1 to 3 mg/kg. On the basis of tolerability and receptor occupancy studies that showed 100% CD47 saturation on RBCs, 1 mg/kg was selected as the priming dose. In subsequent groups, patients were treated with maintenance doses that ranged from 3 to 45 mg/kg, and most toxicities were mild to moderate. These included transient anemia (57% of patients), hemagglutination on peripheral blood smear (36%), fatigue (64%), headaches (50%), fever (45%), chills (45%), hyperbilirubinemia (34%), lymphopenia (34%), infusion-related reactions (34%), and arthralgias (18%). No maximum tolerated dose was reached with maintenance doses up to 45 mg/kg. At doses of 10 mg/kg or more, the CD47 antigen sink was saturated by 5F9, and a 5F9 half-life of approximately 13 days was observed. Strong antibody staining of tumor tissue was observed in a patient at 30 mg/kg. Two patients with ovarian/fallopian tube cancers had partial remissions for 5.2 and 9.2 months. CONCLUSION: 5F9 is well tolerated using a priming dose at 1 mg/kg on day 1 followed by maintenance doses of up to 45 mg/kg weekly.

Survival differences among patients with hepatocellular carcinoma based on the stage of disease and therapy received: pre and post sorafenib era.

BACKGROUND: The incidence of hepatocellular carcinoma (HCC) is increasing. Development of newer therapeutic modalities has changed the paradigm of HCC treatment in recent years. So, the aim of our study is to analyze the impact of these treatment modalities into the survival of HCC patients, based on the stage of HCC in real life practice. METHODS: We analyzed the data from the SEER database: Incidence - SEER 18 Regs Research Data + Hurricane Katrina Impacted Louisiana Cases, Nov 2015 Sub (1973-2013 varying). Relative survival rates (RSRs) and hazard ratios (HRs) were measured for patients diagnosed with HCC between 2001 and 2013. Rates were compared between pre sorafenib [2001-2007] and post sorafenib [2008-2013] eras. RESULTS: A total of 50,088 patients (21,435 in pre sorafenib era and 28,653 in the post-sorafenib era) were included with HCC from SEER database. The median relative survival for the entire population was 14 months with 5-year RSR of 21.20%; 11 months for those diagnosed in 2001-2007 with 5-year RSR 19.30% and 17 months for those diagnosed in 2008-2013 with 5-year RSR 22.40% (P<0.01). This survival improvement was largely limited to HCC patients with single nodule (5-year RSR; 35.1% vs. 37.00% for pre and post sorafenib era respectively; P value <0.01) and multiple nodules without vascular invasion (5-year RSR; 19.90% vs. 22.60% for pre and post sorafenib era respectively; P value <0.01). RSR remained extremely poor with no significant improvement for advanced stage HCC who had vascular invasion (P=0.37) or distant metastasis (P=0.10), respectively for pre and post sorafenib era in each category. Survival improved since 2008, for HCC patients who received either no surgical intervention (P<0.01) or received tumor-directed therapy (P<0.01), however, it remained significantly poor compared to the patients who received lobectomy or hepatectomy and transplant. Approximately 70% of patients from our study population did not receive any HCC directed surgical intervention and among this, more than 40% of patients were with single nodule in the liver. CONCLUSIONS: Survival in patients with HCC has improved since 2008, which is limited to early stage HCC. Survival of advanced stage HCC patients is extremely poor and has not shown any significant improvement since the approval of sorafenib, emphasizing the need for better therapeutic options. Not receiving any surgical intervention is associated with significantly poor prognosis. Large numbers of early stage HCC patients were not able to receive surgical interventions. This can impose a significant financial burden, as these patients would progress on to the advanced stage, where treatment options are very limited and not as cost-effective. This emphasizes the need for further research to identify various barriers and the possible need for healthcare policy changes.

Kytococcus schroeteri Bacteremia in a Patient with Hairy Cell Leukemia: A Case Report and Review of the Literature.

The Kytococcus genus formerly belonged to Micrococcus. The first report of a Kytococcus schroeteri infection was in 2002 in a patient diagnosed with endocarditis. We report a case of central line associated Kytococcus schroeteri bacteremia in a patient with underlying Hairy Cell Leukemia. Kytococcus schroeteri is an emerging infection in the neutropenic population and in patients with implanted artificial tissue. It is thought to be a commensal bacterium of the skin; however, attempts to culture the bacteria remain unsuccessful. There have been a total of 5 cases (including ours) of K. schroeteri bacteremia in patients with hematologic malignancies and neutropenia and only 18 documented cases in any population. Four of the cases of bacteria in neutropenic patients have been fatal, but early detection and treatment could make a difference in clinical outcomes.