Clinicogenomic factors and treatment patterns among patients with advanced non-small cell lung cancer with or without brain metastases in the United States.

BACKGROUND: This retrospective, real-world study evaluated the prevalence of brain metastases, clinicodemographic characteristics, systemic treatments, and factors associated with overall survival among patients with advanced non-small cell lung cancer (aNSCLC) in the US. We also described the genomic characterization of 180 brain metastatic specimens and frequency of clinically actionable genes. MATERIALS AND METHODS: De-identified electronic health records-derived data of adult patients diagnosed with aNSCLC between 2011 and 2017 were analyzed from a US-nationwide clinicogenomic database. RESULTS: Of 3257 adult patients with aNSCLC included in the study, approximately 31% (n = 1018) had brain metastases. Of these 1018 patients, 71% (n = 726) were diagnosed with brain metastases at initial NSCLC diagnosis; 57% (n = 583) of patients with brain metastases received systemic treatment. Platinum-based chemotherapy combinations were the most common first-line therapy; single-agent chemotherapies, epidermal growth factor receptor tyrosine kinase inhibitors, and platinum-based chemotherapy combinations were used in second line. Patients with brain metastases had a 1.56 times greater risk of death versus those with no brain metastases. In the brain metastatic specimens (n = 180), a high frequency of genomic alterations in the p53, MAPK, PI3K, mTOR, and cell-cycle associated pathways was observed. CONCLUSION: The frequency of brain metastases at initial clinical presentation and associated poor prognosis for patients in this cohort underscores the importance of early screening for brain metastasis in NSCLC. Genomic alterations frequently identified in this study emphasize the continued need for genomic research and investigation of targeted therapies in patients with brain metastases.

Real-world maintenance therapy and survival outcomes for pembrolizumab plus pemetrexed and platinum for non-small-cell lung cancer in USA.

Aim: To evaluate treatment patterns and overall survival (OS) in real world metastatic non-squamous non-small-cell lung cancer (NSQ-NSCLC) patients that received pembrolizumab plus pemetrexed-platinum (pembro+pem+plat) aligned with KEYNOTE-189. Materials & methods: OS was evaluated for the overall cohort and maintenance therapy (MT) subgroups and analyzed using Kaplan-Meier estimates and Cox proportional hazards model. Results: Of 2488 patients that received first-line treatment, 45.1% received less than four cycles of pembro+pem+plat, 43.9% received four cycles plus MT with pembro and/or pem, and 11.1% received four cycles without continuing on MT. The median OS was 21.0 months and 9.1 months in patients that continued and did not continue MT. Conclusion: Real world patients that received KEYNOTE-189-aligned treatment had similar OS benefits.

What is this article about? KEYNOTE-189 was a research study (i.e., clinical trial) that compared two different combinations of medicine to treat patients with advanced non-squamous (NSQ) non-small-cell lung cancer (NSCLC). This was the first treatment after being diagnosed for all patients, and they received one of two combinations ­ either pembrolizumab, pemetrexed, plus a platinum-based chemotherapy (pembro+pem+plat) or placebo plus pemetrexed plus a platinum-based chemotherapy. After receiving these combinations four-times, patients were switched to maintenance therapy with pembro and/or pem. In general, patients first treated with pembro+pem+plat survived longer than those treated with placebo plus pemetrexed-platinum. In the current study, researchers wanted to learn if the same results can be expected for patients being treated in the community. What are the results? Patients who completed four sessions of pembro+pem+plat and continued on maintenance therapy survived for 21.0 months and those who completed four sessions of pembro+pem+plat but did not continue on maintenance therapy survived for 9.1 months. What do the results of the study mean? Patients in the community who were treated with pembro+pem+plat and continued on maintenance therapy survived as long as those in the KEYNOTE-189 study.

Real-world comparison between weekly versus biweekly dosing of cetuximab for metastatic colorectal cancer.

Aim: This real-world study aims to compare overall survival (OS) associated with biweekly (Q2W) versus weekly (Q1W) cetuximab dosing regimens for metastatic colorectal cancer (mCRC) treatment in the US. Methods: Adult patients with KRAS wild-type mCRC who received cetuximab ± chemotherapy from 2013 to 2019 were selected using Flatiron Health's electronic health records database. Propensity score matching was used to balance Q2W and Q1W cohorts on baseline patient characteristics. The Kaplan-Meier method was used for survival analyses. Several sensitivity analyses were conducted to assess the robustness of findings from the main analysis. Results: Of 1075 patients in the study, 60.7% received cetuximab Q1W and 39.3% Q2W. Median OS (95% confidence interval) in months was 17.2 (15.3, 18.8) for Q2W versus 14.3 (12.8, 16.0) for Q1W; p = 0.246. Similar OS between the dosing cohorts was observed in sensitivity analyses. Conclusion: Weekly and biweekly cetuximab had comparable effectiveness in this real-world study.

Comparative Effectiveness of First-Line Selpercatinib versus Standard Therapies in Patients with RET-Activated Cancers: An Exploratory Interpatient Analysis of LIBRETTO-001.

Selpercatinib is indicated for locally advanced/metastatic RET-activated solid tumors after progression or following prior systemic therapies. Until the recently published data from LIBRETTO-431 and LIBRETTO-531, there were limited effectiveness data comparing selpercatinib with other first-line treatments in RET-activated non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC), and thyroid cancer (TC). This study analyzed patient data from LIBRETTO-001 and compared the outcomes (time to treatment discontinuation {TTD}, time to next treatment or death {TTNT-D}, time to progression {TTP}, and the objective response rate {ORR}) of first-line selpercatinib (selpercatinib arm) use with the outcomes of first-line standard therapies in patients who then received selpercatinib in later lines of treatment (comparator arm). Overall, the first-line selpercatinib arm had a longer TTD, TTNT-D, and TTP versus the first-line comparator arm. The hazard ratios (HRs) for TTD were 0.29 (NSCLC), 0.15 (MTC), 0.08 (TC); for TTNT-D, the HRs were 0.48 (NSCLC), 0.11 (MTC), 0.09 (TC); and for TTP, the HRs were 0.54 (NSCLC), 0.15 (MTC), and 0.12 (TC). The ORR was higher for first-line selpercatinib versus the first-line comparator (NSCLC: 85.3% vs. 39.7%; MTC: 82.6% vs. 15.2%; and TC: 81.8% vs. 31.8%). First-line selpercatinib use is associated with improved outcomes compared to first-line comparator therapies for patients with advanced/metastatic RET-activated cancers.

Biomarker Testing for Patients With Advanced/Metastatic Nonsquamous NSCLC in the United States of America, 2015 to 2021.

Introduction: NSCLC is a solid tumor with a growing number of actionable biomarkers that may inform treatment. Current guidelines recommend a broad, panel-based approach be taken to identify actionable markers. This retrospective study used a deidentified electronic health records database in the United States to evaluate utilization of various testing modalities. Methods: Data from all adult patients diagnosed with having advanced/metastatic nonsquamous NSCLC between January 2015 and March 2021 were eligible if there was evidence of systemic therapy within 90 days of diagnosis. Results: Records from a total of 17,513 patients (91.6% from community-based practices) were eligible with 83,064 genomic biomarker tests recorded from 2015 to 2021. The proportion of patients who received biomarker testing by next-generation sequencing (NGS)-based methods ranged from 28.3% in 2015 to 68.1% in 2020. The proportion of biomarker testing methods with inconclusive or unsuccessful results ranged from 3.4% for NGS to 9.7% for fluorescence in situ hybridization. The median time to receive results ranged from 4.0 days for polymerase chain reaction-based tests to 10.0 days for immunohistochemistry- and NGS-based tests. Median time to receive results was 8 days for academic and 9 days for community practices. Conclusions: These real-world data suggest increased adoption of NGS-based testing, yet nearly one-third of all patients with advanced/metastatic nonsquamous NSCLC still did not receive broad-based genomic testing by 2020.

Comprehensive population-based survey of migraine in Japan: results of the ObserVational Survey of the Epidemiology, tReatment, and Care Of MigrainE (OVERCOME [Japan]) study.

OBJECTIVE: The ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE study in Japan (OVERCOME [Japan]) aimed to provide an up-to-date assessment of migraine epidemiology in Japan. METHODS: OVERCOME (Japan) was a cross-sectional, population-based web survey of Japanese adults recruited from consumer panels. People with active migraine (met modified International Classification of Headache Disorders, 3rd edition [ICHD-3] criteria or had a self-reported physician diagnosis of migraine) answered questions about headache features, physician consultation patterns, and migraine medication use. The burden and impact of migraine were assessed using Migraine Disability Assessment (MIDAS) and Work Productivity and Activity Impairment scales. RESULTS: In total, 231,747 respondents accessed the screener, provided consent, and were eligible for the survey. The migraine group included 17,071 respondents (mean ± SD age 40.7 ± 13.0 years; 66.5% female). ICHD-3 migraine criteria were met by 14,033 (82.2%) respondents; 9667 (56.6%) self-reported a physician diagnosis of migraine. The mean number of monthly headache days was 4.5 ± 5.7 and pain severity (0-10 scale) was 5.1 ± 2.2. In the migraine group, 20.7% experienced moderate to severe migraine-related disability (MIDAS score ≥ 11). Work productivity loss was 36.2% of work time missed, including 34.3% presenteeism. Only 57.4% of respondents had ever sought medical care for migraine/severe headache. Most respondents (75.2%) were currently using over-the-counter medications for migraine; 36.7% were using prescription nonsteroidal anti-inflammatory drugs, and only 14.8% were using triptans. Very few (9.2%) used preventive medications. CONCLUSIONS: Unmet needs for migraine health care among people with migraine in Japan include low rates of seeking care and suboptimal treatment.

Efficacy of immune checkpoint inhibitor therapy in patients with RET fusion-positive non-small-cell lung cancer.

Aim: To describe outcomes of patients with rearraned during transfection (RET) fusion-positive non-small-cell lung cancer (NSCLC) who received immune checkpoint inhibitor (ICI)-based treatments in the US. Patients & methods: Using de-identified Flatiron Health-Foundation Medicine NSCLC Clinico-Genomic and Guardant Health databases, treatment patterns and outcomes of 69 patients with advanced/metastatic RET fusion-positive NSCLC who received ICI-based treatment were described. Results: Median real-world progression-free survival and overall survival months were 4.2 (95% CI: 1.4-8.4) and 19.1 (6.9-not reached), respectively, among patients in Clinico-Genomic database (n = 17) receiving first-line ICI-based therapy. In the Guardant Health database, progression-free survival was unavailable, and the median overall survival was not reached (n = 29). Conclusion: Outcomes associated with ICI-based treatments in the first-line setting among patients with RET fusion-positive NSCLC are consistent with unselected populations reported in literature.

Lay abstract Treatment options are rapidly expanding for patients who are diagnosed with advanced/metastatic non-small-cell lung cancer. The current standard of care for patients who do not have an actionable genomic alteration includes immune checkpoint inhibitor (ICI)-based therapy. However, the role of ICI-based therapy is not well understood in patients with rearranged during transfection (RET) fusions. In this study, the survival outcomes observed in patients with RET fusion-positive non-small-cell lung cancer who received first-line ICI-based therapy were comparable with published data from patients without genomic alterations. This study is limited due to the small sample size.

Characteristics and outcomes of patients with RET-fusion positive non-small lung cancer in real-world practice in the United States.

BACKGROUND: Contradictory and limited data are available about the presentation and outcomes of patients with RET-fusion positive metastatic NSCLC as compared to patients without RET fusions. This observational study utilizing a linked electronic health records (EHR) database to genomics testing results was designed to compare characteristics, tumor response, progression-free (PFS) and overall survival (OS) outcomes by RET fusion status among patients with metastatic NSCLC treated with standard therapies. METHODS: Adult patients with metastatic NSCLC with linked EHR and genomics data were eligible who received systemic anti-cancer therapy on or after January 1, 2011. Adjusted, using all available baseline covariates, and unadjusted analyses were conducted to compare tumor response, PFS and OS between patients with RET-fusion positive and RET-fusion negative disease as detected by next-generation sequencing. Tumor response outcomes were analysed using Fisher's exact test, and time-to-event analyses were conducted using Cox proportional hazards model. RESULTS: There were 5807 eligible patients identified (RET+ cohort, N = 46; RET- cohort, N = 5761). Patients with RET fusions were younger, more likely to have non-squamous disease and be non-smokers and had better performance status (all p < 0.01). In unadjusted analyses, there were no significant differences in tumor response (p = 0.17) or PFS (p = 0.06) but OS was significantly different by RET status (hazard ratio, HR = 1.91, 95% CI:1.22-3.0, p = 0.005). There were no statistically significant differences by RET fusion status in adjusted analyses of either PFS or OS (PFS HR = 1.24, 95% CI:0.86-1.78, p = 0.25; OS HR = 1.52, 95% CI: 0.95-2.43, p = 0.08). CONCLUSIONS: Patients with RET fusions have different baseline characteristics that contribute to favorable OS in unadjusted analysis. However, after adjusting for baseline covariates, there were no significant differences in either OS or PFS by RET status among patients treated with standard therapy prior to the availability of selective RET inhibitors.

Clinical Characteristics, Treatments, and Concurrent Mutations in Non-Small Cell Lung Cancer Patients With NF1 Mutations.

OBJECTIVES: Metastatic non-small cell lung cancer (mNSCLC) is characterized by complex genomic alterations. NF1 mutations may confer distinct clinical characteristics within NSCLC, and real-world evidence on concurrent mutations, treatment patterns, and health outcomes is lacking. MATERIALS AND METHODS: This retrospective study was performed in patients with mNSCLC treated in the Flatiron Health network who underwent the FoundationOne tumor-sequencing. Anticancer therapies, concurrent mutations, real-world progression-free survival (rwPFS), and overall survival (OS) were assessed. RESULTS: Of the 1663 patients, 103 patients were identified with NF1 mutation. Concurrent mutations with Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (16.5%) and epidermal growth factor receptor fusion (6.8%) were the most frequent. In patients with NF1 mutation only (n = 57), 42% were women, 86% patients had smoking history, and 70% had non-squamous cell carcinoma type. Most (51%) of the patients with NF1 mutations received a single line of therapy versus other mutations and the overall treated population (44%). Platinum-based chemotherapy was the predominant first-line therapy, with programmed cell death-1/programmed cell death-ligand-1 inhibitors as subsequent lines of therapy. The NF1 mutation only group had numerically the shortest median rwPFS (82 days) than other mutation groups. Median OS for the NF1 mutation group in first, second, and third lines of therapy was 321, 498, and 210 days, respectively. CONCLUSIONS: NF1 mutations confer distinct clinical characteristics in patients with mNSCLC. These patients may have different trajectories for progression and survival than seen for other mutations, experience less systemic therapy after first-line therapy, and may have shorter survival.

Pulmonary Carcinosarcoma: A Surveillance, Epidemiology, and End Results (SEER) Analysis.

INTRODUCTION: Pulmonary carcinosarcoma (PC) is a rare malignant neoplasm composed of epithelial and mesenchymal components. It accounts for < 1% of thoracic cancers and is not fully understood. This study examined Surveillance, Epidemiology, and End Results (SEER) data to describe demographic and clinical characteristics of patients with PC and assessed survival outcomes by treatment modality and stage. PATIENTS AND METHODS: SEER data were reviewed to identify patients diagnosed with primary PC (1973-2012). Overall survival (OS) and disease-specific survival (DSS) were analyzed by univariate/multivariable Cox proportional hazards models and Kaplan-Meier methods. RESULTS: A total of 411 patients were included. Median age was 67 (range, 24-96) years. Disease stage at the time of initial diagnosis was known for 74.7% of the identified patients (307/411). Of these patients, 23.1% had localized disease. Survival was significantly better for patients with localized disease (OS: 31 vs. 6 months, P < .001; DSS: 54 vs. 8 months, P < .001). Additionally, patients who received surgery alone had significantly improved OS (20 months; P < .001) and DSS (32 months; P < .001) compared to patients who received combined surgery and radiotherapy (OS: 7 months; DSS: 8 months) or radiotherapy alone (OS: 4 months; DSS: 4 months). CONCLUSION: Treatment with surgery alone resulted in superior survival outcomes compared to other treatment modality combinations, regardless of patient age and disease stage. Within the limitations of this study, providers may wish to consider these findings when devising patient treatment plans.

Frequency of unplanned surgery in patients with stage IV colorectal cancer receiving palliative chemotherapy with an intact primary: An analysis of SEER-Medicare.

BACKGROUND AND OBJECTIVES: Stage IV colorectal cancer is often treated with palliative chemotherapy with the primary tumor in place. Low rates of unplanned surgical intervention (due to obstruction or perforation) have been reported. We examined a large national dataset to determine the rate of unplanned surgical intervention in these patients. METHODS: Surveillance Epidemiology and End Results-Medicare were queried for patients with metastatic colorectal cancer receiving chemotherapy (1998-2013). Patient who underwent planned surgery to the primary or metastasectomy were excluded. The primary outcome was the need for nonelective surgery. Time to surgery or death was measured. Conditional analyses were performed to determine the risk of surgical intervention at 6-month, 1-, and 2-year after diagnosis. RESULTS: The analytic cohort consisted of 4692 patients (median age = 75). At 24 months, 80% of the patients had died. The overall unplanned intervention rate was 12%. The probability of requiring unplanned surgery between 6 and 12 months was 8.1%; 12 and 24 months = 6.7%, and >24 months = 5.3%. Males, those with right-sided tumors, and older patients were less likely to require surgery. CONCLUSIONS: Patients treated with palliative chemotherapy who are not resected upfront are unlikely to require unplanned surgery. Prophylactic surgery to reduce the risk of perforation or obstruction may not be necessary.

Treatment patterns and survival outcomes for patients receiving second-line treatment for metastatic colorectal cancer in the USA.

BACKGROUND: Colorectal cancer is the third most common cause of cancer death in the USA. It is important to identify patients who may experience poor outcomes from available treatments. METHODS: In this retrospective observational study, treatment patterns and survival outcomes were described among adult patients from the Flatiron Health electronic medical records database who were treated with at least two lines of therapy for metastatic colorectal cancer in the USA between January 2013 and May 2018. Patients with rapid progression were defined as those whose time from start of first- to second-line therapy was ≤ 183 days. RESULTS: A total of 14,315 patients formed the study cohort. The most common first-line treatments were FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) plus bevacizumab, received by 34.7% (n = 4962) of patients, followed by FOLFOX alone (17.1%, n = 2445). Of all patients, 6991 (48.9%) also received second-line anti-cancer therapy and of those, 3338 (47.7%) had rapid progression and 3653 (52.3%) did not. Median overall survival from the start of first- and second-line therapy was 20.8 months (95% CI 20.2-21.3) and 14.5 months (95% CI 13.9-15.0) for the entire study population, respectively. Median overall survival from the start of second-line therapy was 14.1 (95% CI 13.2-14.8) for patients with rapid progression and 14.6 months (95% CI 13.8-15.4) for patients without rapid progression. CONCLUSIONS: Patients diagnosed with metastatic colorectal cancer lived less than 2 years in this real-world database. While the time to initiation of second-line therapy was by definition longer among patients without rapidly progressing disease, survival outcomes were comparable from initiation of second-line therapy.

Effect of CYP3A4, CYP3A5, and ABCB1 Polymorphisms on Intravenous Tacrolimus Exposure and Adverse Events in Adult Allogeneic Stem Cell Transplant Patients.

Pharmacogenetics influences oral tacrolimus exposure; however, little data exist regarding i.v. tacrolimus. We investigated the impact of genetic polymorphisms in CYP3A4, CYP3A5, and ABCB1 on i.v. tacrolimus exposure and toxicity in adult patients receiving an allogeneic hematopoietic stem cell transplant for hematologic malignancies. Germline DNA was extracted from buccal swabs and genotyped for CYP3A4, CYP3A5, and ABCB1 polymorphisms. Continuous i.v. infusion of tacrolimus .03 mg/kg/day was initiated on day +5 post-transplant, and steady-state blood concentrations were measured 4days later. We evaluated the association between phenotypes and prevalence of nontherapeutic target concentrations (below or above 5 to 15 ng/mL) as well as tacrolimus-related toxicities. Of 63 patients, 28.6% achieved the target concentration; 71.4% were >15ng/mL, which was more common in CYP3A4 intermediate/normal metabolizers (compared with rapid) and those with at least 1 ABCB1 C2677T loss-of-function allele (P < .05). ABCB1 C2677T was significantly associated with concentrations >15ng/mL (odds ratio, 6.2; 95% confidence interval, 1.8 to 23.6; P = .004) and tacrolimus-related toxicities (odds ratio, 7.5; 95% confidence interval, 1.6 to 55.2; P = .02). ABCB1 C2677T and CYP3A4 are important determinants of i.v. tacrolimus exposure, whereas ABCB1 C2677T also impacts tacrolimus-related toxicities in stem cell transplants.

Reporting of mitotic rate in cutaneous melanoma: A study using the national cancer data base.

BACKGROUND: The seventh edition of the American Joint Commission on Cancer staging manual (AJCC7, published 2009), updated thin cutaneous melanoma staging protocols with the incorporation of mitotic rate (MR). In these patients, higher MR is associated with decreased survival. This study utilizes the National Cancer Data Base (NCDB) to evaluate MR reporting since AJCC7. METHODS: The NCDB was queried for patients with primary cutaneous melanoma from 1998 to 2013. Because MR reporting was infrequent prior to implementing AJCC7, records from 2010 to 2013 were analyzed. Categorical variables were compared with chi-square tests; univariate and multivariate logistic regression models were constructed to determine the effects of covariates on MR reporting. RESULTS: A total of 107,134 patients met inclusion criteria. From 2010 to 2013, MR reporting increased dramatically (64.3-80.9%). On multivariate analysis, factors significantly related to increased MR reporting include later diagnosis year, T-classification (T1a and b vs. T1), facility type (academic vs. other specified types of cancer programs), facility volume, patient income, level of education, and county population (metropolitan vs. urban and rural). CONCLUSIONS: MR reporting increased dramatically after the introduction of AJCC7; however, disparities in reporting remain across facility types. Further investigation of procedures performed in academic settings that may influence reporting of MR is warranted. J. Surg. Oncol. 2017;115:281-286. © 2017 Wiley Periodicals, Inc.

Pediatric and Adolescent Melanoma: A National Cancer Data Base Update.

BACKGROUND: Studies suggest that the biology of pediatric and adolescent melanoma differs from that of adult disease. We report the largest series to date examining the natural history of pediatric and adolescent melanoma. We aim to elucidate the natural history of pediatric and adolescent melanoma and to examine the appropriateness of diagnostic and therapeutic modalities developed for adults and that are currently being used in children. METHODS: A retrospective cohort study was conducted of patients with an index diagnosis of cutaneous non-metastatic melanoma from 1998 to 2011 using the National Cancer Data Base (NCDB; n = 420,416). Three age-based cohorts were analyzed: 1-10 years (pediatric), 11-20 years (adolescent), and ≥21 years (adult). Multivariate analyses were used to identify factors associated with overall survival (OS). RESULTS: Pediatric melanoma patients have longer OS than their adolescent (hazard ratio [HR] 0.50, 95 % CI 0.25-0.98) and adult counterparts (HR 0.11, 95 % CI 0.06-0.21). Adolescents have longer OS than adults. No difference was found in OS in pediatric patients who are node-positive versus node-negative. In pediatric patients, sentinel lymph node biopsy and completion lymph node dissection are not associated with increased OS. In adolescents, nodal positivity is a significant negative prognostic indicator (HR 4.82, 95 % CI 3.38-6.87). CONCLUSIONS: Age-based differences in melanoma outcomes warrant different considerations for diagnostic and therapeutic approaches in each group in order to maximize quality of life while minimizing complications and costs. Prospective, multicenter studies should evaluate the role of diagnostic procedures for pediatric patients.

National Trends in Utilization of Endoscopic Ultrasound for Gastric Cancer: a SEER-Medicare Study.

INTRODUCTION: Accurate preoperative staging is important for patients with gastric cancer. This study identifies the rate of utilization of endoscopic ultrasound (EUS) and its associated factors in Medicare patients with gastric adenocarcinoma. METHODS: The linked Surveillance, Epidemiology, and End Results (SEER)-Medicare claims database was queried from 1996 to 2009 for patients with gastric cancer who underwent gastric resection. Analysis with univariate, multivariate, and Cochran-Armitage trend tests were performed. RESULTS: In 5826 patients with gastric cancer with an average age of 76.9 ± 6.62 years, 59.1% had regionalized spread of cancer. EUS utilization increased significantly during the study period from 2.6% to 22% (p < 0.0001). EUS patients were more likely to be male, white, married, have higher education and income quartiles, and live in large metropolitan areas compared to non-EUS patients (p < 0.0001). Even after controlling for confounding factors, patients who underwent EUS were more likely to have >15 lymph nodes examined (odds ratio (OR) 1.26, 95% confidence interval (CI) 1.04-1.53) and have the administration of both pre- and postoperative chemotherapy (OR 1.27, 95% CI 1.03-1.57). CONCLUSION: EUS is currently under-utilized but increasing. Patients who underwent EUS (12.9%) were more likely to receive other NCCN-recommended care, including perioperative chemotherapy and adequate nodal retrieval.

Margin re-excision and local recurrence in invasive breast cancer: A cost analysis using a decision tree model.

BACKGROUND: SSO-ASTRO recently published guidelines defining adequate margins in breast conservation therapy (BCT) as no tumor on ink based on studies demonstrating little difference in local recurrence (LR) with wider margins. We hypothesize that not routinely re-excising close margins results in decreased costs without compromising care. METHODS: A decision tree model was developed for the management of margins after BCT for invasive cancer. Patients were compared among three margin status groups: positive, close (≤2 mm) and negative (>2 mm). Ten publications provided re-excision rates (RER) and LR rates. The model assumed 140,000 BCT/year. Sensitivity analyses determined the most cost-effective strategy. Surgical costs were estimated using 2013 Medicare reimbursement rates. RESULTS: Re-excising close margins was significantly more costly than the alternative, $233.1 million versus $214.3 million, per year in the United States. Total surgical cost was most sensitive to re-excision of close margins-increasing the RER from 0% to 100% resulted in an $18.8 million cost difference. CONCLUSIONS: The strategy of re-excising close margins resulted in a predicted cost of $18.8 million per year. This does not include hospital costs, the cost of surgical complications after re-excision, and underestimates the potential savings by using Medicare reimbursement rates.

Customized versus Population Fetal Growth Norms and Adverse Outcomes Associated with Small for Gestational Age Infants in a High-Risk Cohort.

OBJECTIVE: To compare population versus customized fetal growth norms in identifying neonates at risk for adverse perinatal and neonatal outcomes (AOs) associated with small for gestational age (SGA) in high-risk women. DESIGN: Secondary analysis to a multicenter treatment trial of pregnant women at high risk for preeclampsia using low-dose aspirin versus placebo. The associations between SGA by population (SGApop) and customized (SGAcust) norms and AOs were evaluated. RESULTS: A total of 2,289 mother/infant pairs were included in the analysis. The rates of SGA in the aspirin and placebo groups were similar by the customized (22.8% vs 23.9%; p = 0.55) or population (8.7% vs 7.5%; p = 0.54) norms; however, they were lower using population norms compared with customized norms (p < 0.001). SGAcust, but not SGApop, was associated with spontaneous preterm birth (odds ratio [OR]: 1.44, 95% confidence interval [CI]: 1.15-1.81; p < 0.001), preterm premature rupture of membranes (OR 1.42 95% CI 1.05-1.92; p = 0.02), and cesarean delivery (OR: 1.35, 95% CI: 1.11-1.64; p = 0.002). Both SGAcust and SGApop were associated with the composite neonatal outcome, indicated preterm delivery before 32, 35, and 37 weeks, oligohydramnios, fetal distress, as well as decreased risk of oxygen requirement. Neither was associated with preeclampsia. CONCLUSION: Customized approach for assessment of fetal growth was associated with higher SGA rates and better identification of SGA neonates at risk for AOs.