Assessing the use of anti-PD1 monotherapy as adjuvant therapy and determinants of treatment choice in stage III cutaneous melanoma in the US.

BACKGROUND: The objective of this study was to describe real-world adjuvant therapy (AT) use by disease substage and assess determinants of treatment choice among patients with stage III melanoma. METHODS: This non-interventional retrospective study included survey responses and data from patient records provided by US medical oncologists. Survey responses, patient demographic/clinical characteristics, treatment utilization, and reasons for treatment were reported descriptively. The association between patient and disease characteristics and AT selection was assessed using logistic and multinomial regression models, overall and stratified by AJCC8 substage (IIIA vs. IIIB/C/D) and type of AT received (anti-PD1 monotherapy, BRAF/MEK, no AT), respectively. RESULTS: In total 152 medical oncologists completed the survey and reviewed the charts of 507 patients (168 stage IIIA; 339 stages IIIB/IIIC/IIID); 405 (79.9%) patients received AT (360/405 (88.9%) received anti-PD1 therapy; 45/405 (11.1%) received BRAF/MEK therapy). Physicians reported clinical guidelines (61.2%), treatment efficacy (37.5%), and ECOG performance status (31.6%) as drivers of AT prescription. Patient-level data confirmed that improving patient outcomes (79%) was the main reason for anti-PD1 prescription; expected limited treatment benefit (37%), patient refusal (36%), and toxicity concerns (30%) were reasons for not prescribing AT. In multivariable analyses stage IIIB/IIIC/IIID disease significantly increased the probability of receiving AT (odds ratio [OR] 1.74) and anti-PD1 therapy (OR 1.82); ECOG 2/3 and Medicaid/no insurance decreased the probability of AT receipt (OR 0.37 and 0.42, respectively) and anti-PD1 therapy (OR 0.41 and 0.42, respectively) among all patients and patients with stage IIIA disease. CONCLUSION: Most patients were given AT with a vast majority treated with an anti-PD1 therapy. Physician- and patient-level evidence confirmed the impact of disease substage on AT use, with stage IIIA patients, patients without adequate insurance coverage, and worse ECOG status having a lower probability of receiving AT.

New Model to Predict Recurrence After Endoscopic Mucosal Resection of Non-pedunculated Colonic Polyps ≥ 20 mm.

BACKGROUND: Polyp recurrence is common after endoscopic mucosal resection (EMR) of non-pedunculated colonic polyps ≥ 20 mm. Two models haven been published for polyp recurrence prediction: Sydney EMR recurrence tool (SERT) and the size, morphology, colonic site, and access to target (SMSA) score. None of these models have been evaluated in a real-world United States (U.S.) cohort. We aimed to evaluate the external validity of these two models and develop a new model. METHODS: Retrospective cohort study of patients with non-pedunculated polyps ≥ 20 mm that underwent EMR between 1/1/2012 and 6/30/2020. Univariate and multivariate analysis were performed to identify predictors of polyp recurrence to build a new model. Receiver Operating Characteristic (ROC) curves for the new model, SERT and a modified version of SMSA were derived and compared. RESULTS: A total of 461 polyps from 461 unique patients were included for analysis. The average polyp size was 29.1 ± 12.4 mm. Recurrence rate at first or second surveillance colonoscopy was 29.0% at a 15.6 months median follow up (IQR 12.3-17.4). A model was created with 4 variables from index colonoscopy: size > 40 mm, tubulovillous adenoma histology, right colon location and piecemeal resection. ROC curves showed that the Area Under the ROC (AUC) for the new model was 0.618, for SERT 0.538 and for mSMSA 0.550. CONCLUSION: SERT score and mSMSA have poor external validity to predict polyp recurrence after EMR of non-pedunculated polyps > 20 mm. Our new model is simpler and performs better in this multiethnic, non-referral cohort from the U.S.

Survival outcomes in veterans with hepatocellular carcinoma, with and without HIV infection.

BACKGROUND: HIV infection has been associated with survival disparities among persons with hepatocellular carcinoma (HCC). However, most studies examining survival do not control for provider (e.g. type of HCC treatment given) or individual-level factors (e.g. homelessness, substance use) that could impact survival. In this study, we evaluate the effect of HIV status on survival among persons with HCC, in a comprehensive model that accounts for key individual, provider, and systems-level factors. METHODS: We conducted a retrospective cohort study of persons with HIV (PWH) matched 1 : 1 to HIV-negative controls based on age and year of HCC diagnosis in the national Veterans Administration (VA) health system. The primary outcome was survival. We used Cox regression models to evaluate the effect of HIV status on risk of death. RESULTS: This cohort included 200 matched pairs diagnosed with HCC between 2009 and 2016. A total of 114 PWH (57.0%) and 115 HIV-negative patients (57.5%) received guideline-concordant therapy ( P  = 0.92). Median survival was 13.4 months [95% confidence interval (CI) 8.7-18.1] among PWH and 19.1 months (95% CI 14.6-24.9) for HIV-negative patients. In adjusted models, older age, homelessness, advanced Barcelona Clinic Liver Cancer (BCLC) stage, and not receiving any HCC treatment predicted risk of death. HIV status was not associated with risk of death [adjusted hazard ratio (aHR) 0.95; 95% CI 0.75-1.20; P  = 0.65]. CONCLUSION: HIV status was not associated with worse survival among HCC patients, in a single-payer, equal access healthcare system. These results suggest that HIV infection alone should not exclude PWH from receiving standard therapy.

Derivation and Validation of a Clinical Risk Assessment Model for Cancer-Associated Thrombosis in Two Unique US Health Care Systems.

PURPOSE: Venous thromboembolism (VTE), especially pulmonary embolism (PE) and lower extremity deep vein thrombosis (LE-DVT), is a serious and potentially preventable complication for patients with cancer undergoing systemic therapy. METHODS: Using retrospective data from patients diagnosed with incident cancer from 2011-2020, we derived a parsimonious risk assessment model (RAM) using least absolute shrinkage and selection operator regression from the Harris Health System (HHS, n = 9,769) and externally validated it using the Veterans Affairs (VA) health care system (n = 79,517). Bootstrapped c statistics and calibration curves were used to assess external model discrimination and fit. Dichotomized risk strata using integer scores were created and compared against the Khorana score (KS). RESULTS: Incident VTE and PE/LE-DVT at 6 months occurred in 590 (6.2%) and 437 (4.6%) patients in HHS and 4,027 (5.1%) and 3,331 (4.2%) patients in the VA health care system. Assessed at the time of systemic therapy initiation, the new RAM included components of the KS with the modified cancer subtype, cancer staging, systemic therapy class, history of VTE, history of paralysis/immobility, recent hospitalization, and Asian/Pacific Islander race. The c statistic was 0.71 in HHS and 0.68 in the VA health care system (compared with 0.65 and 0.60, respectively, for KS). Furthermore, the new RAM appropriately reclassified 28% of patients and increased the proportion of VTEs in the high-risk group from 37% to 68% in the validation data set. CONCLUSION: The novel RAM stratified patients with cancer into a high-risk group with 8%-10% cumulative incidence of VTE and 7% PE/LE-DVT at 6 months (v 3% and 2%, respectively, in the low-risk group). The model had improved performance over the original KS and doubled the number of VTE events in the high-risk stratum. We encourage additional external validation from prospective studies.[Media: see text].

Developing and optimizing a computable phenotype for incident venous thromboembolism in a longitudinal cohort of patients with cancer.

Background: Research on venous thromboembolism (VTE) that relies only on the International Classification of Diseases (ICD) can misclassify outcomes. Our study aims to discover and validate an improved VTE computable phenotype for people with cancer. Methods: We used a cancer registry electronic health record (EHR)-linked longitudinal database. We derived three algorithms that were ICD/medication based, natural language processing (NLP) based, or all combined. We then randomly sampled 400 patients from patients with VTE codes (n = 1111) and 400 from those without VTE codes (n = 7396). Weighted sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated on the entire sample using inverse probability weighting, followed by bootstrapped receiver operating curve analysis to calculate the concordance statistic (c statistic). Results: Among 800 patients sampled, 280 had a confirmed acute VTE during the first year after cancer diagnosis. The ICD/medication algorithm had a weighted PPV of 95% and a weighted sensitivity of 81%, with a c statistic of 0.90 (95% confidence interval [CI], 0.89-0.91). Adding Current Procedural Terminology codes for inferior vena cava filter removal or early death did not improve the performance. The NLP algorithm had a weighted PPV of 80% and a weighted sensitivity of 90%, with a c statistic of 0.93 (95% CI, 0.92-0.94). The combined algorithm had a weighted PPV of 98% at the higher cutoff and a weighted sensitivity of 96% at the lower cutoff, with a c statistic of 0.98 (95% CI, 0.97-0.98). Conclusions: Our ICD/medication-based algorithm can accurately identify VTE phenotype among patients with cancer with a high PPV of 95%. The combined algorithm should be considered in EHR databases that have access to such capabilities.

Surgery or active surveillance for pNETs < 2 cm: Preliminary results from a single center Brazilian cohort.

BACKGROUND AND OBJECTIVES: Incidence of pancreatic neuroendocrine tumors (pNETS) seems to be rising over the years, with many cases incidentally diagnosed. Surgery and active surveillance are current treatment modalities for small pNETS. We review our institutional series and compare outcomes for small asymptomatic and nonfunctioning tumors. METHODS: This retrospective cohort study included patients with 2 cm or less and well differentiated pNETS at a single Brazilian Cancer Center. From 2002 to 2020, patients received active surveillance or surgery as a treatment strategy. Short and long-term results were compared. RESULTS: Sixty-four patients were included, 41 in surgical strategy and 23 in the active surveillance approach. Baseline group characteristics were comparable. More patients on active surveillance underwent abdominal magnetic resonance imaging (MRI) and had tumors located in the pancreatic head (41% vs. 17%, p = 0.038). Minimally invasive procedure was chosen in 80.1% of the surgical patients. No patient died after surgery. Median follow-up period was 38.6 and 46.4 months for active surveillance and surgery cohorts, respectively. No difference in disease progression rate was observed. CONCLUSION: Both approaches seem to be safe for small pNETs. Long-term outcome and quality of life should be considered when discussing such options with patients.

PD-L1 expression in gastric and gastroesophageal junction cancer patients treated with perioperative chemotherapy.

BACKGROUND AND OBJECTIVES: The incidence, predictive, and prognostic impact of programmed cell death (PD-L1) expression in gastric (GC) and gastroesophageal junction tumors (GEJC) treated with perioperative chemotherapy is poorly understood. We aimed to assess PD-L1 expression by immunohistochemistry (IHC) in both pre and posttreatment specimens evaluating its impact on pathological response and survival outcomes. METHODS: Retrospective cohort of patients with GC and GEJ tumors treated in a single western cancer center between 2007 and 2017. PD-L1 expression was assessed by IHC before and after neoadjuvant chemotherapy, in surgical samples, and reported as combined positive score (CPS). CPS > 1% was tested for its association with pathological response and overall survival (OS). RESULTS: We were able to assess PD-L1 expression in at least one tissue sample from 155 subjects. PD-L1 positivity rate was 20%. In 74 paired samples, a 21% discordance between PD-L1 expression in biopsy sample and surgical specimen was observed. With a median follow-up period of 60.3 months, 5-years disease-free survival was 60.5% with a median OS not reached. PD-L1 expression was neither associated with pathological response or survival outcomes. CONCLUSIONS: PD-L1 expression in the setting of locally advanced GC tumors was relatively low and can vary considering the tissue sample analyzed. This expression had no association with survival or pathological response in this population.

Patterns of venous thromboembolism risk, treatment, and outcomes among patients with cancer from uninsured and vulnerable populations.

The epidemiology of cancer-associated thrombosis (CAT) among uninsured and vulnerable populations in the US is not well-characterized. We performed a retrospective cohort study for patients with newly diagnosed cancer from 2011 to 2020 at Harris Health System, which cares for uninsured residents in the Houston metropolitan area. Patient demographics, NCI comorbidity index, area of deprivation index (ADI), cancer histology, staging, and systemic therapy data were extracted. CAT included overall venous thromboembolism (VTE) or pulmonary embolism +/- lower extremity deep vein thrombosis (PE/LE-DVT) within 1 year of diagnosis. We used multivariable Fine-Gray models to assess the associations with CAT accounting for death as a competing risk. Among 15 342 patients, 74% were uninsured and 84% lived in socioeconomically disadvantaged neighborhoods. There were 16% Non-Hispanic White (NHW), 28% Non-Hispanic Black (NHB), 50% Hispanic (27% Mexican), and 6% Asian/Pacific Islanders (API). The 1-year CAT incidence rate was 14.6%. Overall VTE was lower for Hispanics versus NHW (SHR 0.87 [0.76-0.99]) and API versus NHW (SHR 0.58 [0.44-0.77]). PE/LE-DVT was higher for NHB versus NHW (SHR 1.18 [1.01-1.39]). CAT was also associated with chemotherapy-based regimens (+/- immunotherapy), age, obesity, cancer type/staging, VTE history, and recent hospitalization. NCI comorbidity and ADI scores were associated with mortality but not CAT. In a large cohort of underserved patients with cancer, we identified an elevated incidence of CAT with known and novel risk predictors. Hispanics had lower adjusted rates of CAT and mortality. Our findings highlight the need to investigate and incorporate vulnerable populations in clinical trials.

Sociodemographic and Facility-Related Disparities in the Delivery of Guideline-Concordant Therapy Among Patients With Esophageal Adenocarcinoma.

PURPOSE: Evidence on health disparities among patients treated with multimodality therapy protocols is still limited. We aimed to evaluate the associations between patient-level and system-level factors and the receipt of guideline-concordant therapy among patients with esophageal adenocarcinoma (EA). METHODS: This is a national cohort study of patients with stage I-III EA in the National Cancer Database (2006-2018) treated with either upfront resection or neoadjuvant therapy followed by surgery. Clinical and pathologic staging data were used for defining guideline-concordant therapy. Logistic regression models were built to identify independent associations between deviations from treatment guidelines and clinical, sociodemographic, and hospital-related factors. RESULTS: Among 18,803 patients with EA treated at 1,049 hospitals, 4,511 had an endoscopic resection, 4,866 had upfront resection, and 9,426 had neoadjuvant therapy followed by surgery. A total of 16,002 patients (85.1%) received guideline-concordant therapy. Patients who were age 70 years or older (odds ratio [OR] 1.35; 95% CI, 1.14 to 1.60), had a Charlson-Deyo modified score of ≥ 1, and were treated at hospitals with a safety-net burden of ≥ 10% (OR 1.13; 95% CI, 1.02 to 1.25) had higher risk of deviations from guidelines, whereas treatment at high-volume facilities (OR 0.84; 95% CI, 0.74 to 0.95) and diagnosis after 2011 decreased this risk. Relative to cT0-1N0 patients, those with cT2N0 disease had the highest risk of deviations from guideline-concordant therapy (OR 3.76; 95% CI, 3.30 to 4.29). Among patients treated at high-volume facilities, safety-net burden over 10% increased the risk of deviations (OR 1.26; 95% CI, 1.01 to 1.57). CONCLUSION: The delivery of guideline-concordant therapy among patients with EA varies significantly across clinical stage groups and is associated with several sociodemographic disparities. This knowledge should be a resource for future quality improvement strategies intended to address inequitable care within vulnerable populations.

Increasing Incidence of Gallbladder Cancer among Non-Hispanic Blacks in the United States: A Birth Cohort Phenomenon.

BACKGROUND: Gallbladder cancer incidence varies among racial/ethnic subgroups in the United States (US). We investigated trends in gallbladder cancer incidence rates in 50 states from 2001 to 2018. METHODS: Age-adjusted incidence rates and trends in adults were calculated using data from the US Cancer Statistics registry. We used joinpoint regression to compute annual percentage of changes (APC). We analyzed incidence trends by time periods, age groups, and birth cohorts through age-period-cohort modeling. RESULTS: Overall, age standardized incidence rates for gallbladder cancer decreased by 0.3% annually between 2001 and 2018 [95% confidence interval (CI) -0.5% to -0.1%]. However, secular trends varied by race/ethnicity. Although gallbladder cancer rates declined in other racial/ethnic groups, rates increased by 1.4% annually among non-Hispanic Blacks (NHB) between 2001 and 2018 (APC = 1.4%; 95% CI, 0.9%-2.0%). We found evidence for period and birth cohort effects with increasing rates among successive birth cohorts of NHBs. Relative to NHB cohorts born circa 1946, gallbladder cancer rates were 85% higher in NHB cohorts born circa 1971 [incidence rate ratio (IRR), 1.85; 95% CI, 1.26-2.72). The rates among NHBs in South region were higher in cohorts born circa 1971 (IRR, 2.17; 95% CI, 1.27-3.73) relative to those born circa 1946. CONCLUSIONS: The incidence of gallbladder cancer has consistently increased in the US among NHBs. A notable increase in incidence was observed among NHBs with evidence of birth cohort effects in South, Northeast, and Midwest regions. IMPACT: The cohort effect observed among NHBs with increasing rates in different US regions suggests that gallbladder cancer rates will continue to rise in the US in the near future.

Trends in the incidence of early-onset colorectal cancer in all 50 United States from 2001 through 2017.

BACKGROUND: The rate of change in the incidence of colorectal cancer (CRC) among persons younger than 50 years in the United States appears to vary by demographics, tumor location, and geography. This study analyzed data from all 50 states to examine recent changes in the incidence of CRC among persons younger than 50 years and to identify key subgroups with disproportionate risk. METHODS: Annual incidence rates for CRC, colon cancer, and rectal cancer in persons aged 20 to 49 years were extracted from the US Cancer Statistics for the period 2001-2017. Secular trends were examined overall and by age group, sex, race/ethnicity, stage, and state. Joinpoint regression was used to compute annual percent changes and average annual percent changes (AAPCs) as well as corresponding 95% confidence intervals (95% CIs). RESULTS: The incidence of CRC increased by 1.27% (95% CI, 0.95%-1.60%) annually from 2001 to 2012 and by 3.00% (95% CI, 2.06%-3.95%) annually from 2012 to 2017. AAPCs for the period 2001-2017 were higher among persons aged 20 to 24 years (AAPC, 6.62%; 95% CI, 3.86%-9.45%) in comparison with other age groups and higher among non-Hispanic Whites (AAPC, 2.38%; 95% CI, 1.98%-2.79%) in comparison with other racial/ethnic groups. In 2001-2002, only 1 state had an age-standardized incidence rate > 13.0 per 100,000, but this number increased to 32 states by 2016-2017. CONCLUSIONS: CRC rates among US adults aged 20 to 49 years increased from 2001 to 2017, with the fastest increases observed from 2012 to 2017. Increases were observed among the youngest age groups, among non-Hispanic Whites, and in states in the West, Midwest, and Rocky Mountain regions. Increasing rates across all tumor stages suggest a real increase in CRC incidence.

Symptomatic Recurrence and Survival Outcomes After Curative Treatment of Gastric Cancer: Does Intensive Follow-up Evaluation Improve Survival?

BACKGROUND: Intensive surveillance after treatment of gastric cancer patients with curative intent may lead to an earlier diagnosis of disease recurrence, but its impact on survival is uncertain. This study aimed to evaluate whether early diagnosis of disease recurrence among asymptomatic patients was associated with long-term survival. METHODS: This retrospective study analyzed patients with stages 1 to 3C gastric adenocarcinoma treated between 1999 and 2018. All recurrence events were classified as symptomatic or asymptomatic (detected by follow-up tests), and their clinicopathologic characteristics, patterns of recurrence, and survival were analyzed. RESULTS: The cohort consisted of 669 patients treated with a total gastrectomy in 48.6% and a D2-lymphadenectomy in 88.8% of the cases. Most of the tumors were pT3-4 (46.5%), with 45.5% involving lymph node metastases and 42.3% manifesting a diffuse histology. During a median follow-up period of 80.1 months (95% confidence interval [CI], 75.3-84.8 months), 166 patients had recurrences (24.8%), 65.7% of which were symptomatic. The peritoneum was the main site of recurrence (37.2%), and peritoneal recurrence was associated with worse overall survival (OS) (hazard ratio, 1.69; 95%CI, 1.2-2.37). The median disease-free, post-recurrence survival, and OS periods in the asymptomatic and symptomatic groups were respectively 13.4 versus 17.2 months (p = 0.04), 11.9 versus 4.7 months (p < 0.001), and 29.9 versus 26.4 months (p = 0.21). When OS was analyzed among the patients with non-peritoneal recurrence, no difference was observed between the two groups (31.3 vs 31.1 months; p = 0.46). CONCLUSION: Early diagnosis of asymptomatic disease recurrence did not affect the OS of the gastric cancer patients treated with curative intent. The use of intensive surveillance strategies in this scenario still requires further evidence.

Impact of anticoagulation on recurrent thrombosis and bleeding after hematopoietic cell transplantation.

History of venous thromboembolism (VTE) is prevalent among patients undergoing hematopoietic cell transplantation (HCT). Management of anticoagulation is particularly challenging as most patients will have chemotherapy-induced thrombocytopenia while awaiting engraftment post-HCT. We conducted a retrospective study of autologous and allogeneic HCT recipients with prior VTE from 2006-2015 to 1) compare anticoagulant strategies on short-term VTE recurrence and bleeding and 2) assess predictors for VTE recurrence beyond 30 days. Patients with VTE were allocated to two cohorts based on anticoagulant strategy at thrombocytopenia onset and underwent inverse probability weighting to assess primary outcomes of VTE recurrence and bleeding within 30 days post-HCT. Subsequently, multivariable logistic regression model was used to assess the association of 100-day VTE recurrence by the HIGH-2-LOW VTE risk assessment score and whether patients resumed anticoagulation at platelet recovery. Thirteen percent of recipients had VTE prior to HCT; of those meeting inclusion criteria, 227 continued anticoagulation and 113 temporarily discontinued it. Anticoagulant strategy was not significantly associated with decreased risk of VTE recurrence within 30 days (3% vs 4%, p = 0.61); however, risk of overall bleeding was non-significantly higher in those who continued vs discontinued anticoagulation (41% vs 31%, p = 0.08). In a subgroup of 250 allogeneic HCT patients, every one-point increase of HIGH-2-LOW score was significantly associated with VTE recurrence at 100 days (OR 1.57 [95% CI 1.10-2.23]), while anticoagulation resumption upon platelet engraftment was associated with lower recurrent risk (OR 0.48 [0.20-1.14]). Temporarily withholding anticoagulation during thrombocytopenia may optimize risk-benefit tradeoffs, though additional strategies are essential to prevent VTE recurrence after hematopoietic recovery.

Brazilian Group of Gastrointestinal Tumours' consensus guidelines for the management of oesophageal cancer.

Oesophageal cancer is among the ten most common types of cancer worldwide. More than 80% of the cases and deaths related to the disease occur in developing countries. Local socio-economic, epidemiologic and healthcare particularities led us to create a Brazilian guideline for the management of oesophageal and oesophagogastric junction (OGJ) carcinomas. The Brazilian Group of Gastrointestinal Tumours invited 50 physicians with different backgrounds, including radiology, pathology, endoscopy, nuclear medicine, genetics, oncological surgery, radiotherapy and clinical oncology, to collaborate. This document was prepared based on an extensive review of topics related to heredity, diagnosis, staging, pathology, endoscopy, surgery, radiation, systemic therapy (including checkpoint inhibitors) and follow-up, which was followed by presentation, discussion and voting by the panel members. It provides updated evidence-based recommendations to guide clinical management of oesophageal and OGJ carcinomas in several scenarios and clinical settings.

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.

HIGH-2-LOW risk model to predict venous thromboembolism in allogeneic transplant patients after platelet engraftment.

Venous thromboembolism (VTE) after allogeneic hematopoietic cell transplantation (HCT) is a significant treatment-associated complication, although optimal timing of thromboprophylaxis remains uncertain when weighing concurrent risks of bleeding. We aimed to derive and internally validate a risk assessment model (RAM) using patients who underwent first allogeneic HCT from 2006 through 2015 (n = 1703). Index date was defined as the 30th day after transplant, at which point we estimated >75% of patients would have achieved platelet engraftment >50 × 109/L. Stepwise logistic regression modeling was used for model development, and internal validation was achieved by fitting a logistic regression model with 1000 bootstrapped resamples to estimate the optimism-corrected c-statistic. The final RAM, "HIGH-2-LOW," included 7 predictors obtained at 30 days after transplant: History of catheter-related deep venous thrombosis (DVT), Inpatient at day 30, Graft-versus-host disease grade 3 to 4, History of pulmonary embolism or lower-extremity DVT, Lymphoma diagnosis, Obesity with body mass index ≥35 kg/m2, and White blood cell count ≥11 × 109/L. Approximately 16% of patients were stratified as high risk, with incident VTE rate of 10.3% at 100 days compared with 1.5% for those at low risk. VTE odds ratios at 100 days were 5.87 (95% confidence interval [CI], 2.98-11.57) and 2.71 (95% CI, 1.38-5.35) in the high- and intermediate-risk vs low-risk groups, respectively. HIGH-2-LOW model serves as a novel and potentially clinically meaningful tool to identify high-risk allogeneic HCT patients who may benefit from early thromboprophylaxis after platelet engraftment.

Predictors of long-term survival in patients with hepatic resection of colorectal metastases: Analysis of a Brazilian Cancer Center Cohort.

BACKGROUND: Hepatic metastases are a major cause of death in patients with colorectal cancer. A comprehensive assessment of the prognostic factors associated with long-term survival could improve patient selection for surgical approaches and decrease morbidity and futile locoregional treatments. METHODS: We performed a retrospective analysis of patients who underwent hepatectomy for colorectal liver metastases at a single center from 2000 to 2012. RESULTS: To identify factors associated with 5- and 10-year overall (OS) and disease-free survival (DFS), we analyzed 280 patients and 150 patients in the 5- and 10-year cohorts, respectively. Only seven relapses occurred after 5 years of follow-up, and no relapses occurred after 10 years. Multivariable analysis indicated that bilobar disease and extra-hepatic disease before hepatectomy were independent 5- and 10-year predictors of OS, and major postoperative complications predicted OS in the 5-year survival cohort only. Our analysis indicated that prognostic factors associated with DFS included some confounders and was therefore inconclusive. CONCLUSIONS: Taken together, our results suggest that the predictors of 5- and 10-year OS rates of colorectal cancer patients with hepatic metastases are similar, differing only by postoperative complications that influenced exclusively 5-year survival. Since no relapse occurred 10 years after hepatic resection, oncological remission is likely.

Does hipec improve outcomes in gastric cancer patients treated with perioperative chemotherapy and radical surgery? A propensity-score matched analysis.

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) has been associated with improved survival when compared with surgery alone for non-metastatic gastric cancer patients in randomized trials and meta-analyses. However, little evidence is available regarding the use of HIPEC in nonmetastatic patients who are treated with perioperative chemotherapy and radical surgery. The aim of this study was to investigate the putative survival benefit of HIPEC in the subgroup of gastric cancer patients treated with perioperative chemotherapy and surgery. PATIENTS AND METHODS: This was a retrospective cohort study that included gastroesophageal junction and gastric cancer patients who were treated with perioperative chemotherapy and curative resection in a single cancer center in the period between 2006 and 2017. In this time period, younger patients with diffuse-type tumors and serosa invasion or positive lymph node disease were often offered an adjuvant HIPEC protocol. This study compared the survival outcomes of these patients to the ones of those who received only perioperative chemotherapy and resection. A 2:1 propensity-score matched analysis for the two groups was also performed, and variables used were postchemotherapy T (ypT) and N (ypN) stages, histology and tumor site. RESULTS: The study population comprised 269 subjects, 241 treated with chemotherapy and surgery and 28 who also received HIPEC. The mean age was 59 years old (standard deviation: 12.2) and 60% of all individuals were male. A total gastrectomy was performed in 137 patients and a distal resection in 132, with a D2-lymphadenectomy in 97.4% of the sample. Overall 60-day morbidity and mortality rates were 35.3% and 3.3%, respectively. In the HIPEC group, patients were younger, and more frequently had American Society of Anesthesiologists (ASA) 1 to 2 classification, tumors located in the gastric body, had diffuse histology, and ypN+ disease. Overall survival (OS; 5 years) results in the HIPEC and no HIPEC group were 59.5% vs 68.7% (P = .453), and disease-free survival (DFS) ones were 49.5% and 65.8% (P = .060), respectively. In the multivariable Cox regression model, ypT and ypN were independent overall and DFS predictors; also, ASA 3 to 4 classification and diffuse histology were associated with worse OS. In the matched analysis, HIPEC did not improve either overall (53.5% vs 59.5%; P = .517) or DFS (50.0% vs 49.5%; P = .993). CONCLUSION: Treatment with HIPEC in patients who received perioperative chemotherapy and a D2-resection did not improve survival outcomes. Both ypT and ypN stages remained as the most important survival predictors in this cohort.

Trends in the Incidence of Pancreatic Adenocarcinoma in All 50 United States Examined Through an Age-Period-Cohort Analysis.

BACKGROUND: Pancreatic ductal adenocarcinoma is a major contributor to cancer-related mortality in the United States. We aimed to investigate trends in incidence rates from all 50 states from 2001 to 2016, overall and by race, sex, and state and using age-period-cohort analyses. METHODS: Age-adjusted incidence rates and trends in adults aged 35 years and older were calculated using data from the US Cancer Statistics registry. We used joinpoint regression to compute annual percent changes (APC) and average annual percent changes. We also analyzed incidence trends by age groups and birth cohorts through age-period-cohort modeling. RESULTS: Age-standardized incidence rates increased by 1.23% (95% confidence interval [CI] = 0.92% to 1.54%) annually between 2001 and 2008 but were stable between 2008 and 2016 (APC = 0.11%, 95% CI = -0.13% to 0.35%). APCs and inflection points were no different for men and women. Rates increased statistically significantly among non-Hispanic whites (NHW) and non-Hispanic blacks between 2001 and 2007 and between 2001 and 2008, respectively, but, in later years, rates increased slowly among NHWs (APC = 0.36%, 95% CI = 0.12% to 0.60%), and were stable among non-Hispanic blacks (APC = -0.40%, 95% CI = -0.89% to 0.10%). The number of states with age-standardized incidence rates no less than 20.4 per 100 000 increased from 16 in 2001-2003 to 40 by 2015-2016. We found a strong birth cohort effect in both men and women and increasing rates among successive birth cohorts of NHWs. CONCLUSIONS: The incidence of pancreatic ductal adenocarcinoma has consistently increased in the United States, albeit at slower rates recently. We observed notable increases among NHWs and in some states in the central and southern part of the country.