A Multi-Institutional Natural Language Processing Pipeline to Extract Performance Status From Electronic Health Records.

PURPOSE: Performance status (PS), an essential indicator of patients' functional abilities, is often documented in clinical notes of patients with cancer. The use of natural language processing (NLP) in extracting PS from electronic medical records (EMRs) has shown promise in enhancing clinical decision-making, patient monitoring, and research studies. We designed and validated a multi-institute NLP pipeline to automatically extract performance status from free-text patient notes. PATIENTS AND METHODS: We collected data from 19,481 patients in Harris Health System (HHS) and 333,862 patients from veteran affair's corporate data warehouse (VA-CDW) and randomly selected 400 patients from each data source to train and validate (50%) and test (50%) the proposed pipeline. We designed an NLP pipeline using an expert-derived rule-based approach in conjunction with extensive post-processing to solidify its proficiency. To demonstrate the pipeline's application, we tested the compliance of PS documentation suggested by the American Society of Clinical Oncology (ASCO) Quality Metric and investigated the potential disparity in PS reporting for stage IV non-small cell lung cancer (NSCLC). We used a logistic regression test, considering patients in terms of race/ethnicity, conversing language, marital status, and gender. RESULTS: The test results on the HHS cohort showed 92% accuracy, and on VA data demonstrated 98.5% accuracy. For stage IV NSCLC patients, the proposed pipeline achieved an accuracy of 98.5%. Furthermore, our analysis revealed a documentation rate of over 85% for PS among NSCLC patients, surpassing the ASCO Quality Metrics. No disparities were observed in the documentation of PS. CONCLUSION: Our proposed NLP pipeline shows promising results in extracting PS from free-text notes from various health institutions. It may be used in longitudinal cancer data registries.

Treatment approach, hospital practice patterns, and receipt of multimodality therapy as measures of quality for locally advanced gastric cancer.

BACKGROUND: Adequate lymphadenectomy (AL) during surgical resection and delivery of multimodality therapy (MMT) are considered important for optimizing oncologic outcomes in patients with locally advanced gastric cancer. Both neoadjuvant and adjuvant approaches to MMT delivery are considered acceptable treatment strategies. Our goal was to evaluate the association between MMT treatment approach, hospital practice patterns, and survival and to explore whether AL and MMT might represent measures of quality for locally advanced gastric cancer. METHODS: A national cohort study of 5433 patients with locally advanced gastric cancer (≥cT2 and/or cN+) treated at 987 hospitals within the National Cancer Database (2006-2015). Patients were categorized as receiving a neoadjuvant therapy (NT) or adjuvant therapy (AT) approach. Patients were also categorized based on receipt of AL (≥15 nodes) and MMT (surgery with any preoperative, perioperative, or postoperative AT). Hospitals were stratified based on the predominant treatment approach and the proportion of patients that achieved performance benchmarks (AL ≥ 80%; MMT ≥ 75%). Multivariable Cox shared frailty modeling was used to evaluate the association with the overall risk of death. RESULTS: Overall, 54.5% of patients were treated with an AT and 45.6% with an NT approach. Relative to surgery alone, receipt of MMT by either approach was associated with decreased risk of death (NT-hazard ratio [HR]: 0.75, 95% confidence interval: [0.65-0.86]; AT-HR: 0.80 [0.71-0.90]). Relative to care at mixed pattern hospitals, care at predominantly AT hospitals was associated with an increased risk of death (HR: 1.28 [1.12-1.47]). Relative to patients whose care achieved no quality measures, AL (HR: 0.75, [0.67-0.82]) and MMT (HR: 0.68 [0.60-0.76]) were each associated with a reduced risk of death. Receipt of both measures was associated with an even greater reduction (HR: 0.47 [0.40-0.56]). Hospital performance on AL, MMT, or both measures was not associated with the risk of death. CONCLUSION: Because over half of patients are treated with surgery first (many having surgery alone) and care at hospitals favoring a surgery first approach is associated with worse outcomes, quality improvement (QI) efforts should focus on increasing the use of NT strategies. Furthermore, delivery of AL and MMT together may represent an actionable, generalizable target for gastric cancer QI efforts because it improves survival and is unrelated to the context in which care is provided.

Hospital clinical staging accuracy for upper gastrointestinal malignancy.

BACKGROUND: Decisions about multimodality treatment for upper gastrointestinal malignancies are largely predicted on clinical staging information. However, hospital-level accuracy of clinical staging is currently unknown. METHODS: A national cohort study of patients with adenocarcinoma of the esophagus, stomach, or pancreas in the NCDB (2006-2015) who were treated with upfront resection. Hospital-level staging accuracy (ascertained by comparing clinical stage to pathologic stage) was calculated. Within hospital correlation of staging accuracy across disease sites was evaluated using risk and reliability adjustment. RESULTS: Overall, 1246 hospitals were evaluated. Median hospital T-staging accuracy was 77.5%, 73.7%, and 60.8% for esophageal, gastric, and pancreatic cancer, respectively. Median hospital N-staging accuracy was 80.2%, 72.9%, and 61.8%, respectively. For T-stage, over-staging was most frequently observed in esophageal patients (11.2%) while under-staging was most frequent in pancreatic patients (36.1%). For N-stage, over-staging was infrequent for all three, while under-staging was most common in pancreatic patients (37.4%). Correlation across disease sites was weak for both T- (best observed, r = .34) and N-stages (r = .30). When high volume hospitals were evaluated, correlation improved but accuracy rates were similar. CONCLUSIONS: Despite the importance of clinical staging in multimodality treatment planning, hospitals inaccurately stage 20-40% of patients, with low correlation across disease sites.

Impact of the Treating Hospital on Care Outcomes for Hepatocellular Carcinoma.

Multidisciplinary hepatocellular carcinoma (HCC) treatment is associated with optimal outcomes. There are few data analyzing the impact of treating hospitals' therapeutic offerings on survival. We performed a retrospective cohort study of patients aged 18-70 years with HCC in the National Cancer Database (2004-2012). Hospitals were categorized based on the level of treatment offered (Type I-nonsurgical; Type II-ablation; Type III-resection; Type IV-transplant). Associations between overall risk of death and hospital type were evaluated with multivariable Cox shared frailty modeling. Among 50,381 patients, 65% received care in Type IV hospitals, 26% in Type III, 3% in Type II, and 6% in Type I. Overall 5-year survival across modalities was highest at Type IV hospitals (untreated: Type IV-13.1% versus Type I-5.7%, Type II-7.0%, Type III-7.4% [log-rank, P < 0.001]; chemotherapy and/or radiation: Type IV-18.1% versus Type I-3.6%, Type II-4.6%, Type III-7.7% [log-rank, P < 0.001]; ablation: Type IV-33.3% versus Type II-13.6%, Type III-23.6% [log-rank, P < 0.001]; resection: Type IV-48.4% versus Type III-39.1% [log-rank, P < 0.001]). Risk of death demonstrated a dose-response relationship with the hospital type-Type I (ref); Type II (hazard ratio [HR] 0.81, 95% confidence interval [0.73-0.90]); Type III (HR 0.67 [0.62-0.72]); Type IV hospitals (HR 0.43 [0.39-0.47]). Conclusion: Although care at hospitals offering the full complement of HCC treatments is associated with decreased risk of death, one third of patients are not treated at these hospitals. These data can inform the value of health policy initiatives regarding regionalization of HCC care.

Prognostic Value of Nodal Response After Preoperative Treatment of Gastric Adenocarcinoma.

Background: Pathologically positive lymph nodes (ypN+) after preoperative chemotherapy are associated with poor survival in patients with gastric cancer. Little is known about the association between response to preoperative therapy and the benefit of postoperative therapy. Methods: This retrospective cohort study of the National Cancer Database included patients with clinically node-positive (cN+) gastric cancer treated with preoperative therapy followed by surgery (2006-2014). Preoperative treatment modality was categorized as the inclusion of radiation therapy (RT) or chemotherapy alone. Pretreatment clinical and pathologic stages were used to determine pathologic treatment response rates. The association between overall risk of death and preoperative treatment, disease response, and adjuvant therapy use was evaluated using multivariable Cox regression. Results: Preoperative RT was used in 53.6% of 1,976 patients with cN+ gastric cancer, (74.3% cardia and 10.1% noncardia). The nodal response rate was 38.9% and was higher with RT than with chemotherapy alone (cardia, 46.0% vs 29.1%; P<.001; noncardia, 43.8% vs 31.9%; P=.06). Preoperative RT was associated with an approximate 2-fold increase in the odds of pathologic response compared with chemotherapy. Overall, use of adjuvant therapy was not associated with a decreased risk of death. A primary tumor response with residual nodal disease was not associated with survival (hazard ratio [HR], 1.03; 95% CI, 0.66-1.60). However, a nodal response with residual primary disease was significantly associated with survival (HR, 0.54; 95% CI, 0.44-0.65). Conclusions: More than one-third of node-positive gastric cancers showed pathologic nodal response with preoperative treatment. RT is associated with a higher response than chemotherapy. Patients with ypN+ disease have worse survival, regardless of whether they receive postoperative therapy. Future gastric cancer trials should evaluate the role of preoperative RT and individualize postoperative therapy use.

Cancer-related cognitive impairment and associated factors in a sample of older male oral-digestive cancer survivors.

OBJECTIVE: This study examines the demographic and clinical variables associated with cancer-related cognitive impairment (CRCI) in a sample of older, male, oral-digestive cancer survivors at VA Medical Centers in Boston and Houston. METHODS: A two-time point, longitudinal design was used, with cognitive assessment conducted at 6 and 18 months post-diagnosis. Using ANCOVA, the cognitive functioning of 88 older adults with head and neck, esophageal, gastric, or colorectal cancers was compared with that of 88 healthy controls. Paired t-tests examined cognitive change over time in the cancer group. Hierarchical linear regression examined variables potentially associated with cognitive impairment at 18 months. RESULTS: Forty-eight percent of cancer patients exhibited cognitive impairment 6 months post-cancer diagnosis, and 40% at 18 months. Cancer survivors were impaired relative to controls on measures of sustained attention, memory, and verbal fluency at 18 months, controlling for age. Older age, low hemoglobin, and cancer-related PTSD were associated with worse cognition at 18 months. CONCLUSIONS: CRCI is more frequent in older adults than reported in studies of younger adults and may be more frequent in men. Potential areas of intervention for CRCI include psychotherapy for cancer-related PTSD, treatment of anemia, and awareness of particularly vulnerable cognitive domains such as sustained attention, memory, and verbal fluency.

National Trends in Multimodality Therapy for Locally Advanced Gastric Cancer.

BACKGROUND: Multimodality therapy (MMT) is recommended for patients with resectable gastric cancer, but no single approach has been established as standard. Little is presently known about current national practice patterns and sequencing of MMT. METHODS: Retrospective cohort study of patients with gastric cancer aged 18 to 80 y in the National Cancer Database (2006-2014) with ≥T2 and/or node-positive disease (i.e., stage Ib to III) treated with MMT. Clinical nodal staging accuracy was ascertained among those treated with upfront surgery by comparing clinical and pathologic nodal staging. Multivariable Cox regression was used to evaluate the association between overall risk of death and MMT approach (i.e., radiation used versus not and treatment sequence). RESULTS: Among 5817 patients, 16.1% received perioperative MMT, 50.6% preoperative only, and 33.3% postoperative only. The sensitivity, specificity, positive predictive value, and negative predictive values of clinical nodal staging were 68.4%, 88.8%, 91.1%, and 62.7%, respectively. Current clinical nodal staging modalities understage 37.3% of clinically node-negative patients. Over time, radiation utilization decreased (74.3% in 2006 versus 53.9% in 2014; trend test, P < 0.001), perioperative MMT increased (8.9% versus 22.2%%; trend test, P < 0.001), and postoperative MMT decreased (43.1% versus 21.0%; trend test, P < 0.001). Neither type of MMT nor treatment sequence is associated with risk of death. CONCLUSIONS: One-third of patients with gastric cancer who are candidates to receive MMT are treated with upfront surgery. Given the high false negative rate of clinical nodal staging and high noncompletion rate of postoperative treatment, efforts should be directed at improving and optimizing preoperative therapy utilization.

The role of surgery and adjuvant therapy in lymph node-positive cancers of the gallbladder and intrahepatic bile ducts.

BACKGROUND: Lymph node metastasis is a poor prognostic factor for biliary tract cancers (BTCs). The optimal management of patients who have BTC with positive regional lymph nodes, including the impact of surgery and adjuvant therapy (AT), is unclear. METHODS: This was a retrospective cohort study of patients who had T1-T3N1M0 gallbladder cancer (GBC) and intrahepatic cholangiocarcinoma (IHC) in the National Cancer Database (2004-2012). Patients were classified by treatment approach (nonoperative, surgery, surgery plus AT). Associations between the overall risk of death and treatment strategy were evaluated with multivariable Cox regression. RESULTS: Rates of surgical resection were 84.1% for patients with GBC (n = 1335) and 36.6% for those with IHC (n = 1009). The median overall survival of patients in the nonoperative, surgery, and surgery plus AT group was 11.6, 13.3, and 19.6 months, respectively, for those with GBC (log-rank P < .001), and 12.7, 16.2, and 22.6 months, respectively, for those with IHC (log-rank P < .001), respectively. Compared with nonoperative therapy, surgery with or without AT was associated with a lower risk of death from GBC (surgery with AT: hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.48-0.73; surgery without AT: HR, 0.71; 95% CI, 0.56-0.89) and from IHC (surgery with AT: HR, 0.52; 95% CI, 0.42-0.63; surgery without AT: HR, 0.70; 95% CI, 0.56-0.87). AT that included radiation was associated with a lower risk of death relative to surgery alone for patients with GBC regardless of margin status (margin-negative resection: HR, 0.66; 95% CI, 0.52-0.84; margin-positive resection: HR, 0.54; 95% CI, 0.39-0.75), but adjuvant chemotherapy alone was not. For patients with IHC, no survival benefit was detected with adjuvant chemotherapy or radiation for those who underwent either margin-positive or margin-negative resection. CONCLUSIONS: The best outcomes for patients who have lymph node-positive BTCs are associated with margin-negative resection and, in those who have GBC, the inclusion of adjuvant chemotherapy with radiation regardless of margin status. Cancer 2018;124:74-83. © 2017 American Cancer Society.

Prognostic value of neoadjuvant treatment response in locally advanced rectal cancer.

BACKGROUND: For locally advanced rectal cancer, response to neoadjuvant radiation has been associated with improved outcomes but has not been well characterized in general practice. The goals of this study were to describe disease response rates after neoadjuvant treatment and to evaluate the association between disease response and survival. MATERIALS AND METHODS: Retrospective cohort study of patients aged 18-80 y with clinical stage II and III rectal adenocarcinoma in the National Cancer Database (2006-2012). All patients underwent radical resection after neoadjuvant treatment. Treatment responses were defined as follows: no tumor response; intermediate-T and/or N downstaging with residual disease; and complete-ypT0N0. Multivariable, multinomial regression was used to evaluate the association between neoadjuvant radiation use and disease response. Multivariable Cox regression was used to evaluate the association between disease response and overall risk of death. RESULTS: Among 12,024 patients, 12% had a complete and 30% an intermediate response. Neoadjuvant chemotherapy alone was less likely to achieve an intermediate (relative risk ratio: 0.70 [0.56-0.88]) or a complete response (relative risk ratio: 0.59 [0.41-0.84]) relative to neoadjuvant radiation. Tumor response was associated with improved 5-y overall survival (complete = 90.2%, intermediate = 82.0%, no response = 70.5%; log-rank, P < 0.001). Complete and intermediate pathologic responses were associated with decreases in risk of death (hazard ratio: 0.40 [0.34-0.48] and 0.63 [0.57-0.69], respectively) compared to no response. Primary tumor and nodal response were independently associated with decreased risk of death. CONCLUSIONS: Neoadjuvant radiation is associated with treatment response, and pathologic response is associated with improved survival. Pathologic response may be an early benchmark for the oncologic effectiveness of neoadjuvant treatment.

Determinants and Outcomes of Hospice Utilization Among Patients with Advance-Staged Hepatocellular Carcinoma in a Veteran Affairs Population.

BACKGROUND: Hospice provides integrative palliative care for advance-staged hepatocellular carcinoma (HCC) patients, but hospice utilization in HCC patients in the USA is not clearly understood. AIMS: We examined hospice use and subsequent clinical course in advance-staged HCC patients. METHODS: We conducted a retrospective study on a national, Veterans Affairs cohort with stage C or D HCC. We evaluated demographics, clinical factors, treatment, and clinical course in relation to hospice use. RESULTS: We identified 814 patients with advanced HCC, of whom 597 (73.3%) used hospice. Oncologist management consistently predicted hospice use, irrespective of HCC treatment [no treatment: OR 2.25 (1.18-4.3), treatment: OR 1.80 (1.10-2.95)]. Among patients who received HCC treatment, hospice users were less likely to have insurance beyond VA benefits (47.2 vs. 60.0%, p = 0.01). Among patients without HCC treatment, hospice users were older (62.2 [17.2] vs. 60.2 [14.0] years, p = 0.05), white (62.1 vs. 52.9%, p = 0.01), resided in the Southern USA (39.5 vs. 31.8%, p = 0.05), and had a performance score ≥ 3 (41.9 vs. 31.8%, p = 0.01). The median time from hospice entry to death or end of study was 1.05 [2.96] months for stage C and 0.53 [1.18] months for stage D patients. CONCLUSIONS: 26.7% advance-staged HCC patients never entered hospice, representing potential missed opportunities for improving end-of-life care. Age, race, location, performance, insurance, and managing specialty can predict hospice use. Differences in managing specialty and short-term hospice use suggest that interventions to optimize early palliative care are necessary.

Utility of Adjuvant Chemotherapy After Neoadjuvant Chemoradiation and Esophagectomy for Esophageal Cancer.

OBJECTIVE: To determine whether adjuvant chemotherapy (AC) after neoadjuvant chemoradiation and esophagectomy is associated with improved overall survival for patients with locally advanced esophageal cancer, and to evaluate how pathologic disease response to neoadjuvant treatment impacts this effect. BACKGROUND: Neoadjuvant chemoradiation is currently the preferred management approach for locoregional esophageal cancer. Although there is interest in the use of AC, the benefit of systemic therapy after neoadjuvant chemoradiation and esophagectomy is unclear. METHODS: Retrospective cohort study of patients with esophageal cancer treated with neoadjuvant chemoradiation and esophagectomy in the National Cancer Data Base (2006-2012). RESULTS: Among 3592 patients with esophageal cancer (84.7% adenocarcinoma, 15.2% squamous cell carcinoma), 335 (9.3%) were treated with AC. AC was not associated with a significantly lower risk of death among patients with no residual disease (ypT0N0) or residual non-nodal disease (ypT+N0). Among patients with residual nodal disease (ypTanyN+), AC was associated with a 30% lower risk of death in the overall cohort [hazard ratio (HR) 0.70, (0.57-0.85)] and among those with adenocarcinoma [HR 0.69 (0.57-0.85)]. Using a 90-day postoperative landmark, findings were similar. Among patients with postoperative length of stay ≤10 days and no unplanned readmission, AC was associated with approximately 40% lower risk of death among patients with residual nodal disease [overall cohort, HR 0.63 (0.48-0.84); adenocarcinoma, HR 0.66 (0.49-0.88)]. CONCLUSIONS: AC after neoadjuvant chemoradiation and esophagectomy is associated with improved survival in patients with residual nodal disease. Our findings suggest AC may provide additional benefit for esophageal cancer patients, and merits further investigation.

National Quality Forum Colon Cancer Quality Metric Performance: How Are Hospitals Measuring Up?

OBJECTIVE: To evaluate the impact of care at high-performing hospitals on the National Quality Forum (NQF) colon cancer metrics. BACKGROUND: The NQF endorses evaluating ≥12 lymph nodes (LNs), adjuvant chemotherapy (AC) for stage III patients, and AC within 4 months of diagnosis as colon cancer quality indicators. Data on hospital-level metric performance and the association with survival are unclear. METHODS: Retrospective cohort study of 218,186 patients with resected stage I to III colon cancer in the National Cancer Data Base (2004-2012). High-performing hospitals (>75% achievement) were identified by the proportion of patients achieving each measure. The association between hospital performance and survival was evaluated using Cox shared frailty modeling. RESULTS: Only hospital LN performance improved (15.8% in 2004 vs 80.7% in 2012; trend test, P < 0.001), with 45.9% of hospitals performing well on all 3 measures concurrently in the most recent study year. Overall, 5-year survival was 75.0%, 72.3%, 72.5%, and 69.5% for those treated at hospitals with high performance on 3, 2, 1, and 0 metrics, respectively (log-rank, P < 0.001). Care at hospitals with high metric performance was associated with lower risk of death in a dose-response fashion [0 metrics, reference; 1, hazard ratio (HR) 0.96 (0.89-1.03); 2, HR 0.92 (0.87-0.98); 3, HR 0.85 (0.80-0.90); 2 vs 1, HR 0.96 (0.91-1.01); 3 vs 1, HR 0.89 (0.84-0.93); 3 vs 2, HR 0.95 (0.89-0.95)]. Performance on metrics in combination was associated with lower risk of death [LN + AC, HR 0.86 (0.78-0.95); AC + timely AC, HR 0.92 (0.87-0.98); LN + AC + timely AC, HR 0.85 (0.80-0.90)], whereas individual measures were not [LN, HR 0.95 (0.88-1.04); AC, HR 0.95 (0.87-1.05)]. CONCLUSIONS: Less than half of hospitals perform well on these NQF colon cancer metrics concurrently, and high performance on individual measures is not associated with improved survival. Quality improvement efforts should shift focus from individual measures to defining composite measures encompassing the overall multimodal care pathway and capturing successful transitions from one care modality to another.

Effectiveness of surveillance for hepatocellular carcinoma in clinical practice: A United States cohort.

BACKGROUND & AIMS: The effectiveness of surveillance for hepatocellular carcinoma (HCC) in reducing cancer related mortality among patients with cirrhosis is largely unknown. The objective of this study was to study the effectiveness of HCC surveillance in the national Veterans Administration (VA) clinical practice. METHODS: We conducted a retrospective cohort study of patients with HCC during 2005-2010 by reviewing patients' medical records to determine receipt of HCC surveillance in the 2years prior to HCC diagnosis. We determined association of HCC surveillance with overall mortality adjusting for age, risk factors, model for end-stage liver disease (MELD) score, comorbidity index, alpha-fetoprotein levels, healthcare utilization, Barcelona Clinic Liver Cancer (BCLC) stage, and treatment. We accounted for lead and length time biases. RESULTS: Of 887 patients with HCC, only 412 (46.5%) received any surveillance prior to HCC diagnosis. Patients who received surveillance were significantly more likely to have early stage disease HCC (BCLC stage 0/A 27.2% vs. 11.6%) and receive potentially curative (20.9% vs. 11.6%) or palliative (59.2% vs. 45.5%) treatments compared to those without HCC surveillance. Receipt of HCC surveillance was associated with 38% reduction in mortality risk (unadjusted hazard ratios (HR) 0.62, 95% confidence intervals (CI) 0.54-0.71) that declined to 20% (HR 0.80, 95% CI 0.69-0.94) after adjusting for HCC stage and treatment, compared to those without HCC surveillance. CONCLUSIONS: Among patients with HCC, pre-diagnosis HCC surveillance is associated with a significant 38% reduction in overall mortality. The reduction in mortality risk with surveillance is mediated via stage migration and receipt of HCC specific treatment. LAY SUMMARY: Surveillance for liver cancer leads to earlier detection of cancer and increases chances of getting curative treatment. This ultimately leads to increased longevity in patients with liver cancer.

Hepatocellular Carcinoma in the Absence of Cirrhosis in United States Veterans is Associated With Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) can develop in individuals without cirrhosis. We investigated risk factors for development of HCC in the absence of cirrhosis in a U.S. METHODS: We identified a national cohort of 1500 patients with verified HCC during 2005 to 2010 in the U.S. Veterans Administration (VA) and reviewed their full VA medical records for evidence of cirrhosis and risk factors for HCC. Patients without cirrhosis were assigned to categories of level 1 evidence for no cirrhosis (very high probability) or level 2 evidence for no cirrhosis (high probability), which were based on findings from histologic analyses, laboratory test results, markers of fibrosis from noninvasive tests, and imaging features. RESULTS: A total of 43 of the 1500 patients with HCC (2.9%) had level 1 evidence for no cirrhosis, and 151 (10.1%) had level 2 evidence for no cirrhosis; the remaining 1203 patients (80.1%) had confirmed cirrhosis. Compared with patients with HCC in presence of cirrhosis, greater proportions of patients with HCC without evidence of cirrhosis had metabolic syndrome, nonalcoholic fatty liver disease (NAFLD), or no identifiable risk factors. Patients with HCC without evidence of cirrhosis were less likely to have abused alcohol or have hepatitis C virus infection than patients with cirrhosis. Patients with HCC and NAFLD (unadjusted odds ratio, 5.4; 95% confidence interval, 3.4-8.5) or metabolic syndrome (unadjusted odds ratio, 5.0; 95% confidence interval, 3.1-7.8) had more than 5-fold risk of having HCC in the absence of cirrhosis, compared with patients with HCV-related HCC. CONCLUSIONS: Approximately 13% of patients with HCC in the VA system do not appear to have cirrhosis. NAFLD and metabolic syndrome are the main risk factors for HCC in the absence of cirrhosis.

Transarterial bland versus chemoembolization for hepatocellular carcinoma: rethinking a gold standard.

BACKGROUND: Transarterial chemoembolization (TACE) is the most common procedure for the treatment of hepatocellular carcinoma (HCC). However, HCC is generally considered chemoresistant and data demonstrating the superiority of TACE over bland embolization (TAE) are lacking. MATERIALS AND METHODS: A nationwide, retrospective cohort study of HCC patients treated with first-line TACE or TAE within the Veterans Affairs health care system (2005-2012) was performed. The primary outcome was overall survival. Risk of death by treatment type (TACE or TAE) was evaluated using multivariate (adjusted for age, presence of cirrhosis, Barcelona Clinic Liver Cancer stage, and Charlson comorbidity score) and propensity score-adjusted Cox regression. RESULTS: The cohort included 405 patients treated with first-line transarterial embolization. Among these patients, 32 (7.9%) underwent TAE. Most of the patients (76.8%) had intermediate or advanced stage at presentation. Similar proportions of patients (TACE 53.3% versus TAE 43.7%; P = 0.30) received more than one embolization procedure. There was no difference in median survival (20.1 versus 23.1 mo, respectively; log-rank P = 0.84). Compared to TACE, there was no difference in risk of death associated with TAE after multivariate (hazard ratio [HR] 0.92; 95% CI, 0.61-1.37) and propensity score adjustment (HR = 0.86; 95% CI = 0.58-1.29). CONCLUSIONS: There is no clear benefit associated with chemotherapy infusion over bland embolization for HCC treatment. Given the rising incidence of HCC in the United States and considering the added costs associated with TACE compared to TAE, future work comparing these competing management strategies is needed.

Temporal trends of nonalcoholic fatty liver disease-related hepatocellular carcinoma in the veteran affairs population.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is a risk factor for hepatocellular carcinoma (HCC). However, no systemic studies from the United States have examined temporal trends, HCC surveillance practices, and outcomes of NAFLD-related HCC. METHODS: We identified a national cohort of 1500 patients who developed HCC from 2005 through 2010 from Veterans Administration (VA) hospitals. We reviewed patients' full VA medical records; NAFLD was diagnosed based on histologic evidence for, or the presence of, the metabolic syndrome in the absence of hepatitis C virus (HCV) infection, hepatitis B, or alcoholic liver disease. We compared annual prevalence values for the main risk factors (NAFLD, alcohol abuse, and HCV), as well a HCC surveillance and outcomes, among HCC patients. RESULTS: NAFLD was the underlying risk factor for HCC in 120 patients (8.0%); the annual proportion of NAFLD-related HCC remained relatively stable (7.5%-12.0%). In contrast, the proportion of HCC cases associated with HCV increased from 61.0% in 2005 (95% confidence interval, 53.1%-68.9%) to 74.9% in 2010 (95% confidence interval, 69.0%-80.7%). The proportion of HCC cases associated with only alcohol abuse decreased from 21.9% in 2005 to 15.7% in 2010, and the annual proportion of HCC cases associated with hepatitis B remained relatively stable (1.4%-3.5%). A significantly lower proportion of patients with NAFLD-related HCC had cirrhosis (58.3%) compared with patients with alcohol- or HCV-related HCC (72.4% and 85.6%, respectively; P < .05). A significantly higher percentage of patients with NAFLD-related HCC did not receive HCC surveillance in the 3 years before their HCC diagnosis, compared with patients with alcohol- or HCV-associated HCC. A lower proportion of patients with NAFLD-related HCC received HCC-specific treatment (61.5%) than patients with HCV-related HCC (77.5%; P < .01). However, the 1-year survival rate did not differ among patients with HCC related to different risk factors. CONCLUSIONS: NAFLD is the third most common risk factor for HCC in the VA population. The proportion of NAFLD-related HCC was relatively stable from 2005 through 2010. Although patients with NAFLD-related HCC received less HCC surveillance and treatment, a similar proportion survive for 1 year, compared with patients with alcohol-related or HCV-related HCC.

Referral and receipt of treatment for hepatocellular carcinoma in United States veterans: effect of patient and nonpatient factors.

UNLABELLED: The delivery of treatment for hepatocellular carcinoma (HCC) could be influenced by the place of HCC diagnosis (hospitalization versus outpatient), subspecialty referral following diagnosis, as well as physician and facility factors. We conducted a study to examine the effect of patient and nonpatient factors on the place of HCC diagnosis, referral, and treatment in Veterans Administration (VA) hospitals in the United States. Using the VA Hepatitis C Clinical Case Registry, we identified hepatitis C virus (HCV)-infected patients who developed HCC during 1998-2006. All cases were verified and staged according to Barcelona Clinic Liver Cancer (BCLC) criteria. The main outcomes were place of HCC diagnosis, being seen by a surgeon or oncologist, and treatment. We examined factors related to these outcomes using hierarchical logistic regression. These factors included HCC stage, HCC surveillance, physician specialty, and facility factors, in addition to risk factors, comorbidity, and liver disease indicators. Approximately 37.2% of the 1,296 patients with HCC were diagnosed during hospitalization, 31.0% were seen by a surgeon or oncologist, and 34.3% received treatment. Being seen by a surgeon or oncologist was associated with surveillance (adjusted odds ratio [aOR] = 1.47; 95% CI: 1.20-1.80) and varied by geography (1.74;1.09-2.77). Seeing a surgeon or oncologist was predictive of treatment (aOR = 1.43; 95% CI: 1.24-1.66). There was a significant increase in treatment among patients who received surveillance (aOR = 1.37; 95% CI: 1.02-1.71), were seen by gastroenterology (1.65;1.21-2.24), or were diagnosed at a transplant facility (1.48;1.15-1.90). CONCLUSION: Approximately 40% of patients were diagnosed during hospitalization. Most patients were not seen by a surgeon or oncologist for treatment evaluation and only 34% received treatment. Only receipt of HCC surveillance was associated with increased likelihood of outpatient diagnosis, being seen by a surgeon or oncologist, and treatment.

Harnessing physical activity monitoring and digital biomarkers of frailty from pendant based wearables to predict chemotherapy resilience in veterans with cancer.

This study evaluated the use of pendant-based wearables for monitoring digital biomarkers of frailty in predicting chemotherapy resilience among 27 veteran cancer patients (average age: 64.6 ± 13.4 years), undergoing bi-weekly chemotherapy. Immediately following their first day of chemotherapy cycle, participants wore a water-resistant pendant sensor for 14 days. This device tracked frailty markers like cadence (slowness), daily steps (inactivity), postural transitions (weakness), and metrics such as longest walk duration and energy expenditure (exhaustion). Participants were divided into resilient and non-resilient groups based on adverse events within 6 months post-chemotherapy, including dose reduction, treatment discontinuation, unplanned hospitalization, or death. A Chemotherapy-Resilience-Index (CRI) ranging from 0 to 1, where higher values indicate poorer resilience, was developed using regression analysis. It combined physical activity data with baseline Eastern Cooperative Oncology Group (ECOG) assessments. The protocol showed a 97% feasibility rate, with sensor metrics effectively differentiating between groups as early as day 6 post-therapy. The CRI, calculated using data up to day 6 and baseline ECOG, significantly distinguished resilient (CRI = 0.2 ± 0.27) from non-resilient (CRI = 0.7 ± 0.26) groups (p < 0.001, Cohen's d = 1.67). This confirms the potential of remote monitoring systems in tracking post-chemotherapy functional capacity changes and aiding early non-resilience detection, subject to validation in larger studies.

Malignant Insulinoma Arising From Nonfunctioning Pancreatic Neuroendocrine Tumor.

Pancreatic neuroendocrine tumors are rare neoplasms characterized into nonfunctioning (NF-PNET) and functioning (F-PNET) subtypes. F-PNETs typically involve overt symptoms related to excessive hormone secretion but may rarely present first as NF-PNETs with delayed transformation. We present a patient with known NF-PNET with liver metastases who developed hypoglycemia 2 years after initial diagnosis due to malignant insulinoma. Hypoglycemia was refractory to continuous dextrose but improved temporarily after diazoxide and hepatic artery embolization. Malignant insulinomas are usually metastatic at presentation and portend poor prognosis. Hypoglycemia may be medically managed with steroids, somatostatin analogues, and diazoxide, along with therapies to reduce tumor burden.

Study protocol: maintaining preventive care during public health emergencies through effective coordination.

BACKGROUND: Screening lies at the heart of preventive care. However, COVID-19 dramatically disrupted routine screening efforts, resulting in excess mortality not directly attributable to COVID-19. Screening rates during COVID varied markedly by facility and clinical condition, suggesting susceptibilities in screening and referral process workflow. To better understand these susceptibilities and identify new practices to mitigate interrupted care, we propose a qualitative study comparing facilities that exhibited high, low, and highly variable performance (respectively) in screening rates before and during the pandemic. We will be guided by Weaver et al.'s multi-team systems (MTS) model of coordination, using cancer and mental health screening rates as exemplars. METHOD: Qualitative analysis of interviews and focus groups with primary care personnel, leadership, and patients at 10 VA medical centers. We will select sites based on rurality, COVID-19 caseload at the beginning of the pandemic, and performance on five outpatient clinical performance indicators of cancer and mental health screening. Sites will be categorized into one of five screening performance groups: high performers, low performers, improvers, plummeters, and highly variable. We will create process maps for each performance measure to create a workflow baseline and then interview primary care leadership to update the map at each site. We will clinician conduct focus groups to elicit themes regarding clinician coordination patterns (e.g., handoffs), strategies, and barriers/facilitators to screening during COVID. We will also conduct patient interviews to examine their screening experience during this period, for context. All interviews and focus groups will be audio-recorded, transcribed, and enhanced by field notes. We will analyze clinician transcripts and field notes using iterative, rapid analysis. Patient interviews will be analyzed using inductive/deductive content analysis. DISCUSSION: Our study represents a unique opportunity to inform the multi-team systems literature by identifying specific forms of information exchange, collective problem solving, and decision-making associated with higher and improved clinical performance. Specifically, our study aims to detect the specific points in the screening and referral process most susceptible to disruption and coordination processes that, if changed, will yield the highest value. Findings apply to future pandemics or any event with the potential to disrupt care.