Trends in breast, colon, pancreatic, and uterine cancers in women during the COVID-19 pandemic in North Carolina.

IMPORTANCE: The COVID-19 pandemic led to reductions in primary care and cancer screening visits, which may delay detection of some cancers. The impact on incidence has not been fully quantified. We examined change in cancer incidence to determine how the COVID-19 pandemic may have altered the characteristics of cancers diagnosed among women. METHODS: This study included female patients aged ≥18 years and diagnosed with breast (n = 9489), colon (n = 958), pancreatic (n = 669), or uterine (n = 1991) cancer at three hospitals in North Carolina. Using interrupted time series, we compared incidence of cancers diagnosed between March 2020 and November 2020 (during pandemic) with cancers diagnosed between January 2016 and February 2020 (pre-pandemic). RESULTS: During the pandemic, incidence of breast and uterine cancers was significantly lower than expected compared to pre-pandemic (breast-18%, p = 0.03; uterine -20%, p = 0.05). Proportions of advanced pathologic stage and hormone receptor-negative breast cancers, and advanced clinical stage and large size uterine cancers were more prevalent during the pandemic. No significant changes in incidence were detected for pancreatic (-20%, p = 0.08) or colon (+14%, p = 0.30) cancers. CONCLUSION AND RELEVANCE: In women, the COVID-19 pandemic resulted in a significant reduction in the incidence of breast and uterine cancers, but not colon or pancreatic cancers. A change in the proportion of poor prognosis breast and uterine cancers suggests that some cancers that otherwise would have been diagnosed at an earlier stage will be detected in later years. Continued analysis of long-term trends is needed to understand the full impact of the pandemic on cancer incidence and outcomes.

Sensory Mechanisms of Parent-Offspring Recognition in Fishes, Amphibians, and Reptiles.

Parental care is important for offspring survival and success. Recognition of offspring by parents is critical to ensure parents direct care behaviors at related offspring and minimize energy lost by caring for unrelated young. Offspring recognition of parents prevents possible aggressive interactions between young and unrelated adults and allows offspring to direct begging behaviors toward the correct adult. Despite its importance and widespread nature, much of the current research has focused on a small range of species, particularly mammals and birds. We review the existing literature on the sensory mechanisms of parent-offspring recognition in fishes, amphibians, and reptiles. Within these groups, there is diversity in the presence and strategies for parent-offspring recognition. Future studies should continue to identify these mechanisms, as well as the neural and endocrine underpinnings in non-model organisms to expand our knowledge of this behavior and inform our understanding of the evolution of parent-offspring recognition.

Qualitative evaluation of barriers and facilitators to hepatocellular carcinoma care in North Carolina.

BACKGROUND: Many patients with hepatocellular carcinoma (HCC) never receive cancer-directed therapy. In order to tailor interventions to increase access to appropriate therapy, we sought to understand the barriers and facilitators to HCC care. METHODS: Patients with recently diagnosed HCC were identified through the University of North Carolina (UNC) HCC clinic or local hospital cancer registrars (rapid case ascertainment, RCA). Two qualitative researchers conducted in-depth, semi-structured interviews. Interviews were audiotaped, transcribed, and coded. RESULTS: Nineteen interviews were conducted (10 UNC, 9 RCA). Key facilitators of care were: physician knowledge; effective communication regarding test results, plan of care, and prognosis; social support; and financial support. Barriers included: lack of transportation; cost of care; provider lack of knowledge about HCC; delays in scheduling; or poor communication with the medical team. Participants suggested better coordination of appointments and having a primary contact within the healthcare team. LIMITATIONS: We primarily captured the perspectives of those HCC patients who, despite the challenges they describe, were ultimately able to receive HCC care. CONCLUSIONS: This study identifies key facilitators and barriers to accessing care for HCC in North Carolina. Use of the RCA system to identify patients from a variety of settings, treated and untreated, enabled us to capture a broad range of perspectives. Reducing barriers through improving communication and care coordination, assisting with out-of-pocket costs, and engaging caregivers and other medical providers may improve access. This study should serve as the basis for tailored interventions aimed at improving access to appropriate, life-prolonging care for patients with HCC.

Predicting Acute Care Events Among Patients Initiating Chemotherapy: A Practice-Based Validation and Adaptation of the PROACCT Model.

PURPOSE: Acute care events (ACEs), comprising emergency department visits and hospitalizations, are a priority area for reduction in oncology. Prognostic models are a compelling strategy to identify high-risk patients and target preventive services, but have yet to be broadly implemented, partly because of challenges with electronic health record (EHR) integration. To facilitate EHR integration, we adapted and validated the previously published PRediction Of Acute Care use during Cancer Treatment (PROACCT) model to identify patients at highest risk for ACEs after systemic anticancer treatment. METHODS: A retrospective cohort of adults with a cancer diagnosis starting systemic therapy at a single center between July and November 2021 was divided into development (70%) and validation (30%) sets. Clinical and demographic variables were extracted, limited to those in structured format in the EHR, including cancer diagnosis, age, drug category, and ACE in prior year. Three logistic regression models of increasing complexity were developed to predict risk of ACEs. RESULTS: Five thousand one hundred fifty-three patients were evaluated (3,603 development and 1,550 validation). Several factors were predictive of ACEs: age (in decades), receipt of cytotoxic chemotherapy or immunotherapy, thoracic, GI or hematologic malignancy, and ACE in the prior year. We defined high-risk as the top 10% of risk scores; this population had 33.6% ACE rate compared with 8.3% for the remaining 90% in the low-risk group. The simplest Adapted PROACCT model had a C-statistic of 0.79, sensitivity of 0.28, and specificity of 0.93. CONCLUSION: We present three models designed for EHR integration that effectively identify oncology patients at highest risk for ACE after initiation of systemic anticancer treatment. By limiting predictors to structured data fields and including all cancer types, these models offer broad applicability for cancer care organizations and may offer a safety net to identify and target resources to this high risk.

Neural activation patterns associated with mouthbrooding, maternal care, infanticide and fry release in an African cichlid fish.

Parental care has evolved several times and is present across taxa. Parental care behaviors, such as food provisioning and protection, are critical for offspring success. However, infanticide can co-exist with parental care in the same species. The mechanisms underlying the switch from care to consumption and from offspring dependence to independence are relatively unknown, especially in fishes, the oldest and largest group of vertebrates. Mouthbrooding, an extreme example of parental care present in dozens of genera of fishes, provides an excellent opportunity to investigate the brain regions important for parental care. The maternal mouthbrooding African cichlid fish Astatotilapia burtoni broods developing young inside the mouth for approximately 14 days, then provides post-release maternal care by protecting fry inside the mouth when threatened. Following the post-release maternal care phase, females can exhibit infanticide and consume their own offspring. We used immunohistochemistry for the neural activation marker pS6 to identify differences in neural activation among mouthbrooding, maternal-care-providing and infanticide-exhibiting females, and between pre- and post-release fry. We identified five brain regions (Dc-5, ATn, nPPa, Vd-c and Dl-g) that are differentially activated among mouthbrooding, maternal care and infanticide females as well as six regions (Dm, Vv, Vd, Vs-m, TPp, PGZ and INL of retina) differentially activated between pre- and post-release fry. This study identifies both shared and distinct circuitry that may support transitions between parental care states and from care to infanticide, as well as regions in developed fry that support the transition from pre- to post-release.

Risk Factors for Return to the Emergency Department and Readmission in Patients With Hospital-Diagnosed Advanced Lung Cancer.

BACKGROUND: Advanced lung cancer (ALC) is a symptomatic disease often diagnosed in the context of hospitalization. The index hospitalization may be a window of opportunity to improve care delivery. OBJECTIVES: We examined the patterns of care and risk factors for subsequent acute care utilization among patients with hospital-diagnosed ALC. RESEARCH DESIGN, SUBJECTS, AND MEASURES: In Surveillance, Epidemiology, and End Results-Medicare, we identified patients with incident ALC (stage IIIB-IV small cell or non-small cell) from 2007 to 2013 and an index hospitalization within 7 days of diagnosis. We used a time-to-event model with multivariable regression to identify risk factors for 30-day acute care utilization (emergency department use or readmission). RESULTS: More than half of incident ALC patients were hospitalized around the time of diagnosis. Among 25,627 patients with hospital-diagnosed ALC who survived to discharge, only 37% ever received systemic cancer treatment. Within 6 months, 53% had been readmitted, 50% had enrolled in hospice, and 70% had died. The 30-day acute care utilization was 38%.Small cell histology, greater comorbidity, precancer acute care use, length of index stay >8 days, and prescription of a wheelchair were associated with higher risk of 30-day acute care utilization. Age >85 years, female sex, residence in South or West regions, palliative care consultation, and discharge to hospice or a facility were associated with lower risk. CONCLUSIONS: Many patients with hospital-diagnosed ALC experience an early return to the hospital and most die within 6 months. These patients may benefit from increased access to palliative and other supportive care during index hospitalization to prevent subsequent health care utilization.

A phase II single-arm trial of memantine for prevention of cognitive decline during chemotherapy in patients with early breast cancer: Feasibility, tolerability, acceptability, and preliminary effects.

BACKGROUND: Cognitive difficulties have been described after chemotherapy for breast cancer, but there is no standard of care to improve cognitive outcomes in these patients. This trial examined the feasibility, tolerability, acceptability, and preliminary effects of memantine to prevent cognitive decline during chemotherapy for breast cancer. METHODS: Patients with stage I-III breast cancer, scheduled for neo/adjuvant chemotherapy, completed a cognitive battery prior to and 4 weeks after completing chemotherapy. Memantine (10 mg BID) was administered concurrent with chemotherapy. Our primary cognitive outcome was visual working memory assessed by the Delayed Matching to Sample test. We used the Brief Medication Questionnaire to assess acceptability. RESULTS: Of 126 patients approached, 56 (44%) enrolled. Forty-five (80%) received ≥1 dose of memantine and completed pre-post assessments. Seventy-six percent reported taking ≥90% of scheduled doses. Participants were mean age of 56, 77% White, and 57% had stage I disease. Sixty-four percent had stable or improved Delayed Matching to Sample test scores. Stable or improved cognition was observed in 87%-91% across objective cognitive domain composite measures. Sixty-six percent self-reported stable or improved cognitive symptoms. There were seven greater than or equal to grade 3 adverse events; two were possibly related to memantine. Only 5% reported that taking memantine was a disruption to their lives. CONCLUSIONS: Memantine was well-tolerated and consistently taken by a large majority of patients receiving breast cancer chemotherapy. The majority demonstrated stable or improved cognition from pre- to post-assessment. Randomized trials are needed to determine memantine's efficacy to ameliorate cognitive loss. TRIAL REGISTRATION: ClinicalTrials.gov NCT04033419.

A bioresorbable peripheral nerve stimulator for electronic pain block.

Local electrical stimulation of peripheral nerves can block the propagation of action potentials, as an attractive alternative to pharmacological agents for the treatment of acute pain. Traditional hardware for such purposes, however, involves interfaces that can damage nerve tissue and, when used for temporary pain relief, that impose costs and risks due to requirements for surgical extraction after a period of need. Here, we introduce a bioresorbable nerve stimulator that enables electrical nerve block and associated pain mitigation without these drawbacks. This platform combines a collection of bioresorbable materials in architectures that support stable blocking with minimal adverse mechanical, electrical, or biochemical effects. Optimized designs ensure that the device disappears harmlessly in the body after a desired period of use. Studies in live animal models illustrate capabilities for complete nerve block and other key features of the technology. In certain clinically relevant scenarios, such approaches may reduce or eliminate the need for use of highly addictive drugs such as opioids.

Behavior and neural activation patterns of non-redundant visual and acoustic signaling during courtship in an African cichlid fish.

Animals evolve mechanisms to send and receive communication signals through multiple sensory channels during crucial behavioral contexts such as aggression and reproduction. This ensures the transmission of important context-dependent signals that supply either the same (redundant) or different (non-redundant) information to the receiver. Despite the importance of multimodal communication, there are relatively few species in which information on sender signals and receiver responses are known. Further, little is known about where context-dependent unimodal and multimodal information is processed in the brain to produce adaptive behaviors. We used the African cichlid, Astatotilapia burtoni, to investigate how unimodal and multimodal signals are processed within the female brain in a reproductive context. During courtship, dominant males produce low frequency sounds in conjunction with visual displays (quivers) directed towards receptive gravid females. We compared affiliation behaviors and neural activation patterns in gravid females exposed to visual, acoustic and visual-acoustic signals from courting dominant males. Females displayed reduced affiliation in auditory-only conditions, but similar affiliation during visual and visual-acoustic conditions, demonstrating that visual-acoustic signaling from males is non-redundant but vision dominates. Using the neural activation marker cfos, we identified differential activation in specific socially relevant brain nuclei between unimodal and multimodal conditions and distinct neural co-activation networks associated with each sensory context. Combined with our previous work on chemosensory signaling, we propose that A. burtoni represents a valuable vertebrate model for studying context-dependent behavioral and neural decision making associated with non-redundant multimodal communication.

Incidence of Severe Acute Respiratory Syndrome Coronavirus 2 and Subsequent Mortality in a Multisite Cohort of Patients With Cancer in the CancerLinQ Discovery Database.

PURPOSE: Understanding risks for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and subsequent mortality among patients with cancer may help inform treatment decisions during the COVID-19 pandemic. METHODS: CancerLinQ is an electronic health record database from US oncology practices. We identified a cohort of patients with malignancy and 2+ encounters at CancerLinQ practices in the 12 months before the study period (January 1, 2020-January 31, 2021). We identified a SARS-CoV-2 subcohort as having a positive SARS-CoV-2 test or International Classification of Diseases, 10th Revision, code. We examined predictors of SARS-CoV-2 infection and mortality including sex, race, ethnicity, age, malignancy type, and prior therapy. Unadjusted and adjusted incidence rate ratios (aIRRs) and 95% CIs were estimated from Poisson regression models for SARS-CoV-2 infections and mortality. RESULTS: The cancer cohort included 629,128 patients, and the SARS-CoV-2 subcohort included 12,300 patients. Higher incidence of SARS-CoV-2 was seen among patients who were male (incidence rate ratio [IRR], 1.14; 95% CI, 1.10 to 1.18), Black (IRR, 1.48; 95% CI, 1.41 to 1.56), Hispanic (IRR, 2.02; 95% CI, 1.91 to 2.14), age < 50 years (IRR, 1.34; 95% CI, 1.26 to 1.42), with hematologic malignancies (IRR, 1.07; 95% CI, 1.02 to 1.12), and with recent chemotherapy (IRR, 1.30, 95% CI, 1.22 to 1.40). In the adjusted analysis, higher incidence was seen in patients who were male (aIRR, 1.17; 95% CI, 1.13 to 1.21), Hispanic (aIRR, 2.01; 95% CI, 1.88 to 2.14), and with recent chemotherapy (aIRR, 1.17; 95% CI, 1.09 to 1.25). There were 182 all-cause deaths within the SARS-CoV-2 subcohort. Higher mortality was seen among patients who were male (IRR, 1.39; 95% CI, 1.04 to 1.86), unknown race (IRR, 2.64; 95% CI, 1.42 to 4.91), other/unknown ethnicity (IRR, 1.99; 95% CI, 1.20 to 3.29), age 60-69 years (IRR, 2.76; 95% CI, 1.23 to 6.19), age 70-79 years (IRR, 5.28; 95% CI, 2.42 to 11.5), age 80+ years (IRR, 7.31; 95% CI, 3.31 to 16.1), or with recent chemotherapy (IRR, 1.52, 95% CI, 1.01 to 2.29). In the adjusted analysis, higher mortality was seen with increased age and receipt of chemotherapy. CONCLUSION: Patients with increased risk of SARS-CoV-2 infection must balance the competing risks of their cancer diagnosis/treatment and SARS-CoV-2 infection.

Expression and localization of neuronal nitric oxide synthase in the brain and sensory tissues of the African cichlid fish Astatotilapia burtoni.

Nitric oxide (NO) produced by the enzyme neuronal nitric oxide synthase serves as an important neurotransmitter in the central nervous system that is involved in reproductive regulation, learning, sensory processing, and other forms of neural plasticity. Here, we map the distribution of nnos-expressing cells in the brain and retina of the cichlid fish Astatotilapia burtoni using in situ hybridization. In the brain, nnos-expressing cells are found from the olfactory bulbs to the hindbrain, including within specific nuclei involved in decision-making, sensory processing, neuroendocrine regulation, and the expression of social behaviors. In the retina, nnos-expressing cells are found in the inner nuclear layer, presumably in amacrine cells. We also used quantitative PCR to test for differences in nnos expression within the eye and olfactory bulbs of males and females of different reproductive states and social statuses. In the eye, males express more nnos than females, and socially dominant males express more nnos than subordinate males, but expression did not differ among female reproductive states. In the olfactory bulbs, dominant males had greater nnos expression than subordinate males. These results suggest a status-specific function for NO signaling in the visual and olfactory systems that may be important for sensory perception related to mating or territorial interactions to maintain the social hierarchy. The widespread distribution of nnos-expressing cells throughout the cichlid brain is similar to that in other teleosts, with some conserved localization patterns across vertebrates, suggesting diverse functions for this important neurotransmitter system.

Soft, bioresorbable coolers for reversible conduction block of peripheral nerves.

Implantable devices capable of targeted and reversible blocking of peripheral nerve activity may provide alternatives to opioids for treating pain. Local cooling represents an attractive means for on-demand elimination of pain signals, but traditional technologies are limited by rigid, bulky form factors; imprecise cooling; and requirements for extraction surgeries. Here, we introduce soft, bioresorbable, microfluidic devices that enable delivery of focused, minimally invasive cooling power at arbitrary depths in living tissues with real-time temperature feedback control. Construction with water-soluble, biocompatible materials leads to dissolution and bioresorption as a mechanism to eliminate unnecessary device load and risk to the patient without additional surgeries. Multiweek in vivo trials demonstrate the ability to rapidly and precisely cool peripheral nerves to provide local, on-demand analgesia in rat models for neuropathic pain.

Prevalence of Pathologic N2/N3 Disease in Postmenopausal Women with Clinical N0 ER+/HER2- Breast Cancer.

BACKGROUND: The RxPONDER trial demonstrated that the 21-gene recurrence score can be used to guide adjuvant systemic therapy decisions in postmenopausal women with pN1 ER+/HER2- breast cancer. As such, a sentinel lymph node biopsy (SLNB) may not provide systemic treatment-altering information for many patients, and omission of SLNB in patients with low probability of pN2/N3 disease could be considered. METHODS: Postmenopausal women (aged ≥ 50 years) diagnosed with cN0cM0, ER+/HER- breast cancer from 2013 to 2017 were identified in the National Cancer Database. The primary outcome was the prevalence of pN2/N3 disease. RESULTS: Of 325,692 postmenopausal women with cN0 ER+/HER2- breast cancer, 7106 (2.2%) were pN2/N3. In total, 81.7% had cT1 tumors, 16.8% T2, 1.3% T3, and 0.2% T4. In patients with T1 tumors, the prevalence of pN2/N3 disease was 1.2% compared with 17.2% in patients with T3/T4 tumors. In multivariable models, cT stage was the strongest predictor of pN2/N3 disease (adjusted odds ratio [aOR] 14.9 [12.1-18.4]). Lobular histology (aOR 2.4 [2.3-2.6]), higher grade (aOR 2.9 [2.6-3.1]), and young age (aOR 1.5 [1.3-1.7]) were also associated with increased prevalence of pN2/N3. We created a model using histology, grade, and T stage that stratifies patients with low prevalence of pN2/3 disease (< 1%) and those at high risk (> 20%). CONCLUSIONS: In postmenopausal women with cN0 ER+/HER2- breast cancer, the prevalence of pN2/N3 disease is low, indicating a potential opportunity to use the results of RxPONDER to extend criteria to omit SLNB. Prospective study is needed to determine safety, including risk of nodal recurrence, of omission of SLNB in carefully selected patients.

Endocrine and neuroendocrine regulation of social status in cichlid fishes.

Position in a dominance hierarchy profoundly impacts group members' survival, health, and reproductive success. Thus, understanding the mechanisms that regulate or are associated with an individuals' social position is important. Across taxa, various endocrine and neuroendocrine signaling systems are implicated in the control of social rank. Cichlid fishes, with their often-limited resources of food, shelter, and mates that leads to competition, have provided important insights on the proximate and ultimate mechanisms related to establishment and maintenance of dominance hierarchies. Here we review the existing information on the relationships between endocrine (e.g., circulating hormones, gonadal and other tissue measures) and neuroendocrine (e.g., central neuropeptides, biogenic amines, steroids) systems and dominant and subordinate social rank in male cichlids. Much of the current literature is focused on only a few representative cichlids, particularly the African Astatotilapia burtoni, and several other African and Neotropical species. Many hormonal regulators show distinct differences at multiple biological levels between dominant and subordinate males, but generalizations are complicated by variations in experimental paradigms, methodological approaches, and in the reproductive and parental care strategies of the study species. Future studies that capitalize on the diversity of hierarchical structures among cichlids should provide insights towards better understanding the endocrine and neuroendocrine mechanisms contributing to social rank. Further, examination of this topic in cichlids will help reveal the selective pressures driving the evolution of endocrine-related phenotypic traits that may facilitate an individual's ability to acquire and maintain a specific social rank to improve survival and reproductive success.

Risk stratification and outreach to hematology/oncology patients during the COVID-19 pandemic.

PURPOSE: Cancer patients have many medical and psychosocial needs, which may increase during the COVID-19 pandemic. We sought to (1) risk-stratify hematology/oncology patients using general medicine and cancer-specific methods to identify those at high risk for acute care utilization, (2) measure the correlation between two risk stratification methods, and (3) perform a telephone-based needs assessment with intervention for high-risk patients. METHODS: Patients were risk-stratified using a general medical health composite score (HCS) and a cancer-specific risk (CSR) stratification based on disease and treatment characteristics. The correlation between HCS and CSR was measured using Spearman's correlation. A multi-disciplinary team developed a focused needs assessment script with recommended interventions for patients categorized as high-risk by either method. The number of patient needs identified and referrals for services made in the first month of outreach are reported. RESULTS: A total of 1697 patients were risk-stratified, with 17% high-risk using HCS and 22% high-risk using CSR. Correlation between HCS and CSR was modest (ρ = 0.41). During the first month of the pilot, 286 patients were called for outreach with 245 contacted (86%). Commonly identified needs were financial difficulties (17%), uncontrolled symptoms (15%), and interest in advance care planning (13%), resulting in referral for supportive services for 33% of patients. CONCLUSION: There is a high burden of unmet medical and psychosocial needs in hematology/oncology patients during the COVID-19 pandemic. A telephone-based outreach program results in the identification of and intervention for these needs; however, additional cancer-specific risk models are needed to improve targeting to high-risk patients.

Pleomorphic Invasive Lobular Carcinoma of the Breast With Extracellular Mucin and HER2 Amplification.

Invasive lobular carcinoma with extracellular mucin is an uncommon pattern of invasive breast carcinoma. The 5th Edition of the World Health Organization Classification of Breast Tumors states that it is unknown whether these tumors are a subtype of mucinous carcinoma or invasive lobular carcinoma. Invasive lobular carcinoma with extracellular mucin frequently presents as a palpable mass and may be more likely to be grade 2 to 3 and HER2-positive than classic invasive lobular carcinoma. This case of pleomorphic invasive lobular carcinoma with extracellular mucin was detected by imaging only and was HER2-amplified, suggesting that a subset of these tumors may be clinically occult with an aggressive phenotype. Invasive lobular carcinoma with extracellular mucin is infrequently encountered and awareness of this entity is helpful in avoiding misdiagnosis.

Top Ten Tips Palliative Care Clinicians Should Know About Caring for Serious Illness in Pregnancy.

Palliative care (PC) teams are increasingly being called upon to provide care earlier and more remote from end of life. Because much of the field has grown out of hospice and geriatric care, most teams have little to no experience caring for pregnant women or their fetuses when serious or life-threatening illness strikes. This article, written by a team of oncologists (gynecologic, medical, and radiation) and PC providers, seeks to demystify the care of seriously ill pregnant women and their fetuses by exploring the diagnostic, treatment, prognostication, symptom management, and communication needs of these patients. Truly comprehensive PC extends throughout the life span, from conception to death, regardless of age. Accordingly, increased knowledge of the unique needs of these vulnerable groups will enhance our ability to provide care across this continuum.

Assessing the Impact of a Novel Integrated Palliative Care and Medical Oncology Inpatient Service on Health Care Utilization before Hospice Enrollment.

BACKGROUND: Evidence increasingly supports the integration of specialist palliative care (PC) into routine cancer care. A novel, fully integrated PC and medical oncology inpatient service was developed at Duke University Hospital in 2011. OBJECTIVE: To assess the impact of PC integration on health care utilization among hospitalized cancer patients before hospice enrollment. METHODS: Retrospective cohort study. Patients in the solid tumor inpatient unit who were discharged to hospice between September 1, 2009, and June 30, 2010 (pre-PC integration), and September 1, 2011, to June 30, 2012 (postintegration). Cohorts were compared on the following outcomes from their final hospitalization before hospice enrollment: intensive care unit days, invasive procedures, subspecialty consultations, radiographic studies, hospital length of stay, and use of chemotherapy or radiation. Cohort differences were examined with descriptive statistics and nonparametric tests. RESULTS: Two hundred ninety-six patients were included in the analysis (133 pre-PC integration; 163 post-PC integration). Patient characteristics were similar between cohorts. Health care utilization was relatively low in both groups, although 26% and 24% were receiving chemotherapy at the time of admission or during hospitalization in the pre- and post-PC integration cohorts, respectively, and 6.8% in each cohort spent time in an intensive care unit. We found no significant differences in utilization between cohorts. DISCUSSION: PC integration into an inpatient solid tumor service may not impact health care utilization during the final hospitalization before discharge to hospice. This likely reflects the greater benefits of integrating PC farther upstream from the terminal hospitalization, if one hopes to meaningfully impact utilization near the end of life.

Optimal therapy for patients with hepatocellular carcinoma and resistance or intolerance to sorafenib: challenges and solutions.

The only US Food and Drug Administration (FDA)-approved first-line systemic therapy for hepatocellular carcinoma (HCC) is sorafenib; however, resistance or intolerance to sorafenib is unfortunately common. In this review, we briefly describe systemic therapies that can be considered for patients with HCC who show resistance or intolerance to sorafenib. For all patients with HCC who need systemic therapy, we strongly advocate for participation in clinical trials. Cytotoxic chemotherapy plays a minor role in the treatment of advanced HCC, with some data supporting the use of FOLFOX (infusional fluorouracil, leucovorin, and oxaliplatin) and GEMOX (gemcitabine-oxaliplatin). Multi-target kinase inhibitors such as lenvantinib and regorafenib have recently met their primary endpoints as first- and second-line therapy, respectively, with regorafenib now representing the only FDA-approved drug for second-line treatment of HCC. Other targeted therapies remain under investigation, but results so far have not significantly changed clinical practice. Immunotherapy is an interesting area of research in the treatment of HCC with preclinical and early clinical data demonstrating exciting results; thus numerous investigational studies are currently focusing on immunotherapy in the treatment of HCC. While systemic treatment options in HCC remain a challenge for providers, in this review, we summarize the current literature and highlight areas of progress with respect to the treatment of patients with HCC and resistance or intolerance to sorafenib.