Central Line Patency: Management With Normal Saline Flushes for Adult Patients With Cancer.

BACKGROUND: Central venous catheter (CVC) maintenance is critical in administering chemotherapy, transfusions, and high-frequency laboratory draws. Although normal saline (NS) flushes have been associated with similar incidences of irreversible port occlusions as heparin among adult patients with cancer and ports, additional research is needed regarding NS efficacy in other central line maintenance within large populations with cancer. OBJECTIVES: The aim of this study was to analyze changes in reported CVC line patency via tissue plasminogen activator (tPA) administration rates in ports and other central lines because of an institutional switch from heparin to NS as preferred flushes in adult ambulatory patients with cancer. METHODS: Retrospective data were collected from patients with ports (3,706 prepolicy, 3,402 postpolicy) and nonport CVCs (816 prepolicy, 694 postpolicy). FINDINGS: Patients with nonport CVCs experienced similar tPA usage pre- versus postpolicy, versus an increased rate of tPA usage for ports. This policy resulted in institutional savings of $28,695.92. NS flushes are as effective as heparin for maintaining patency in ports and other CVCs for adult outpatients with cancer and address safety concerns with heparin-associated complications.

Mocetinostat in Combination With Durvalumab for Patients With Advanced NSCLC: Results From a Phase I/II Study.

BACKGROUND: Histone deacetylase (HDAC) inhibitors have potential to augment the effectiveness of immune checkpoint inhibitors and overcome treatment resistance. This dose-escalation/expansion study (NCT02805660) investigated mocetinostat (class I/IV HDAC inhibitor) plus durvalumab in patients with advanced non-small cell lung cancer (NSCLC) across cohorts defined by tumor programmed death-ligand 1 (PD-L1) expression and prior experience with anti-programmed cell death protein-1 (anti-PD-1) or anti-PD-L1 regimens. PATIENTS AND METHODS: Sequential cohorts of patients with solid tumors received mocetinostat (starting dose: 50 mg TIW) plus durvalumab at a standard dose (1500 mg Q4W) to determine the recommended phase II dose (RP2D: phase I primary endpoint), based on the observed safety profile. RP2D was administered to patients with advanced NSCLC across 4 cohorts grouped by tumor PD-L1 expression (none or low/high) and prior experience with anti-PD-L1 /anti-PD-1 agents (naïve, clinical benefit: yes/no). The phase II primary endpoint was objective response rate (ORR, RECIST v1.1). RESULTS: Eighty-three patients were enrolled (phase I [n = 20], phase II [n = 63]). RP2D was mocetinostat 70 mg TIW plus durvalumab. ORR was 11.5% across the phase II cohorts, and responses were durable (median 329 days). Clinical activity was observed in NSCLC patients with disease refractory to prior checkpoint inhibitor treatment: ORR 23.1%. Across all patients, fatigue (41%), nausea (40%), and diarrhea (31%) were the most frequent treatment-related adverse events. CONCLUSION: Mocetinostat 70 mg TIW plus durvalumab at the standard dose was generally well tolerated. Clinical activity was observed in patients with NSCLC unresponsive to prior anti-PD-(L)1 therapy.

Development of Neuropathic Arthropathy With Entrectinib: Case Report.

TRK inhibition can lead to on-target neurologic adverse events. Two cases illustrate the development of neuropathic arthropathy as a side effect of entrectinib. After starting entrectinib, both patients developed foot pain, swelling, and sensory changes with magnetic resonance imaging revealing marrow edema. Providers should have a low threshold to investigate foot pain or gait abnormalities thoroughly with magnetic resonance imaging and referral to specialists to aid in the diagnosis of neuropathic arthropathy, with consideration to transition to an alternative agent.

Prognostic Value of Early Fluorodeoxyglucose-Positron Emission Tomography Response Imaging and Peripheral Immunologic Biomarkers: Substudy of a Phase II Trial of Risk-Adaptive Chemoradiation for Unresectable Non-Small Cell Lung Cancer.

Purpose: We sought to examine the prognostic value of fluorodeoxyglucose-positron emission tomography (PET) imaging during chemoradiation for unresectable non-small cell lung cancer for survival and hypothesized that tumor PET response is correlated with peripheral T-cell function. Methods and Materials: Forty-five patients with American Joint Committee on Cancer version 7 stage IIB-IIIB non-small cell lung cancer enrolled in a phase II trial and received platinum-doublet chemotherapy concurrent with 6 weeks of radiation (NCT02773238). Fluorodeoxyglucose-PET was performed before treatment start and after 24 Gy of radiation (week 3). PET response status was prospectively defined by multifactorial radiologic interpretation. PET responders received 60 Gy in 30 fractions, while nonresponders received concomitant boosts to 74 Gy in 30 fractions. Peripheral blood was drawn synchronously with PET imaging, from which germline DNA sequencing, T-cell receptor sequencing, and plasma cytokine analysis were performed. Results: Median follow-up was 18.8 months, 1-year overall survival (OS) 82%, 1-year progression-free survival 53%, and 1-year locoregional control 88%. Higher midtreatment PET total lesion glycolysis was detrimental to OS (1 year 87% vs 63%, P < .001), progression-free survival (1 year 60% vs 26%, P = .044), and locoregional control (1 year 94% vs 65%, P = .012), even after adjustment for clinical/treatment factors. Twenty-nine of 45 patients (64%) were classified as PET responders based on a priori definition. Higher tumor programmed death-ligand 1 expression was correlated with response on PET (P = .017). Higher T-cell receptor richness and clone distribution slope were associated with improved OS (P = .018-0.035); clone distribution slope was correlated with PET response (P = .031). Conclusions: Midchemoradiation PET imaging is prognostic for survival; PET response may be linked to tumor and peripheral T-cell biomarkers.

Performance status (PS) as a predictor of poor response to immune checkpoint inhibitors (ICI) in recurrent/metastatic head and neck cancer (RMHNSCC) patients.

BACKGROUND: Anti-PD1 checkpoint inhibitors (ICI) represent an established standard-of-care for patients with recurrent/metastatic head and neck squamous cell carcinoma (RMHNSCC). Landmark studies excluded patients with ECOG performance status (PS) ≥2; the benefit of ICI in this population is therefore unknown. METHODS: We retrospectively reviewed RMHNSCC patients who received 1+ dose of ICI at our institution between 2013 and 2019. Demographic and clinical data were obtained; the latter included objective response (ORR), toxicity, and any unplanned hospitalization (UH). Associations were explored using uni- and multivariate analysis. Overall survival (OS) was estimated using a Cox proportional hazards model; ORR, toxicity, and UH were evaluated with logistic regression. RESULTS: Of the 152 patients, 29 (19%) had an ECOG PS ≥2. Sixty-six (44%) experienced toxicity; 54 (36%) had a UH. A multivariate model for OS containing PS, smoking status, and HPV status demonstrated a strong association between ECOG ≥2 and shorter OS (p < 0.001; HR = 3.30, CI = 2.01-5.41). An association between OS and former (vs. never) smoking was also seen (p < 0.001; HR = 2.17, CI = 1.41-3.35); current smoking did not reach statistical significance. On univariate analysis, poor PS was associated with inferior ORR (p = 0.03; OR = 0.25, CI = 0.06-0.77) and increased UH (p = 0.04; OR = 2.43, CI = 1.05-5.71). There was no significant association between toxicity and any patient characteristic. CONCLUSIONS: We observed inferior OS, ORR, and rates of UH among ICI-treated RMHNSCC patients with ECOG 2/3. Our findings help frame discussion of therapeutic options in this poor-risk population.

Impact of Diagnostic Delays on Lung Cancer Survival Outcomes: A Population Study of the US SEER-Medicare Database.

PURPOSE: Time from diagnosis to treatment has been associated with worse survival outcomes in non-small-cell lung cancer (NSCLC). However, little is known about the impact of delay in time to diagnosis. We aimed to evaluate the impact of time from radiographic suspicion to histologic diagnosis on survival outcomes using the US SEER-Medicare population database. METHODS: We identified patients from the SEER-Medicare data set diagnosed with any stage NSCLC between January 1, 2011, and December 31, 2015, who received stage-appropriate treatment and had a computed tomography scan within 1 year of diagnosis. Time to confirmation was determined as the interval between most recent computed tomography imaging and date of histologic diagnosis. Our primary outcome was overall survival (OS). RESULTS: In total, 10,824 eligible patients were identified. The median time to confirmation was 20 (range 0-363) days. Using multivariate Cox regression models, longer time to confirmation was associated with improved OS in all comers driven by stage IV patients after adjustment for age, sex, diagnosis year, histology, and comorbidity index. In a separate landmark analysis excluding patients deceased within 6 months of diagnosis, the association between time to diagnosis and survival was no longer evident. CONCLUSION: Time to confirmation of NSCLC was inversely associated with OS in this US SEER population study. This association was lost when patients deceased within 6 months of diagnosis were excluded, suggesting that retrospective registry-claims databases may not be the optimal data source to study time to diagnosis as a quality metric because of the unaccounted confounding effects of tumor behavior. Prospective evaluations of clinically enriched data sources may better serve this purpose.

High End-of-Life Health Care Utilization in a Contemporary Cohort of Head and Neck Cancer Patients Treated with Immune Checkpoint Inhibitors.

Background/Objective: End-of-life health care utilization (EOLHCU) is largely uncharacterized among patients with recurrent/metastatic head and neck squamous cell carcinomas (RMHNSCC), particularly now that immune checkpoint inhibitors (ICI) have been introduced to the treatment landscape. We examined this in a single-institution, retrospective study. Design/Settings: We utilized a database of deceased, ICI-treated RMHNSCC patients to obtain demographic and EOLHCU data, the latter of which included advanced care plan documentation (ACPD) and systemic therapy or emergency room (ER)/hospital/intensive care unit (ICU) admission within 30 days of death (DOD). This was compared with a cohort of deceased thoracic malignancy (TM) patients in an exploratory analysis. Multivariate analysis was performed to examine for association between patient factors (such as age, Eastern Cooperative Oncology Group (ECOG) performance status, or smoking status) and overall survival (OS); associations between the said patient factors and EOLHCU were also evaluated. This study was conducted at an academic, tertiary center in the United States. Results: The RMHNSCC patients (n = 74) were more likely to have ACPD (p < 0.01), an emergency department visit (p < 0.01), and/or hospital admission (p < 0.01) within 30 DOD relative to the TM group. There was no difference in ICU admissions, ICU deaths, or systemic therapy at end of life (EOL). The OS declined in association with ECOG performance status (PS) and smoking. No association was observed between patient factors and any EOLHCU metric. Conclusions: At our center, patients with ICI-treated RMHNSCC have higher rates of both ACPD and EOLHCU, suggesting high symptom burden and representing opportunities for further study into supportive care augmentation.

Adaptive Fluorodeoxyglucose-Positron Emission Tomography Based Chemotherapy Selection for Metastatic Non-small Cell Lung Cancer.

Objectives The change in tumor fluorodeoxyglucose (FDG) uptake by positron emission tomography (PET) scan after one cycle of platinum-based chemotherapy has been shown to predict progression-free and overall survival (PFS and OS) among advanced non-small cell lung cancer (NSCLC) patients. Using early FDG-PET response to determine subsequent chemotherapy, we aim to evaluate the role that adaptive chemotherapy regimens have on later CT response, PFS, and OS in patients with advanced NSCLC. Materials and Methods Chemotherapy-naïve patients with metastatic NSCLC received carboplatin and paclitaxel (CP) on day one and repeated FDG-PET on day 18. PET-responding patients continued CP chemotherapy for a total of four cycles. PET non-responders were switched to alternate docetaxel and gemcitabine (DG) for three additional cycles. The primary outcome was the CT Response Evaluation Criteria in Solid Tumors (RECIST 1.0) response. Secondary endpoints included PFS and OS. Results  Forty-six patients initiated treatment with chemotherapy on trial and were evaluable by PET/CT. Of these, 19 (41%) met the FDG-PET criteria for the response after a single cycle of CP. Only one non-responding patient had a CT response. Despite the lack of CT response in the DG arm, no trend for worse PFS or OS was seen between the two arms. Conclusions This work demonstrates that changing chemotherapy in the event of non-response by PET did not lead to improved CT RECIST response. However, non-responding patients who switched chemotherapy had similar PFS and OS to those who responded by PET and continued the same regimen.

Timing of postoperative radiation therapy and survival in resected salivary gland cancers: Long-term results from a single institution.

OBJECTIVES: Timely administration of postoperative radiation therapy (PORT) impacts oncologic outcomes in resected squamous cell carcinomas of the head and neck. Salivary gland cancers (SGCs) are uncommon, and timing of PORT has not been extensively explored. We aimed to determine if the interval between surgery and PORT impacts outcomes in SGCs. MATERIALS AND METHODS: This is a retrospective study of patients with SGCs who underwent curative intent surgical resection followed by adjuvant PORT. Locoregional recurrence free survival (LRFS), disease free survival (DFS), and overall survival (OS) were estimated using the Kaplan Meier method. A multivariate analysis explored the association between demographics, tumor characteristics, and PORT timing with oncologic outcomes using a stepwise Cox proportional hazards model. RESULTS: 180 eligible patients were identified. The median time to PORT start was 61 (range 8-121) days. 169 (93.5%) of patients received neutron radiation. With a median follow up of 8.2 years in surviving patients, the 10-year OS and LRFS estimates were 61% and 53%. In a multivariate analysis, nodal involvement, histologic grade, and age at diagnosis were associated with OS, while nodal involvement, tumor size, and age at diagnosis were associated with LRFS and DFS. Time to PORT start or completion was not statistically associated with survival outcomes. CONCLUSION: SGC patients who underwent surgery in our tertiary institution received PORT within a median of 61 days after surgery. With long term follow up, PORT timing in this retrospective series was not associated with worse oncologic outcomes, and support timely administration of PORT.

Effect of Clinical Trial Participation on Costs to Payers in Metastatic Non-Small-Cell Lung Cancer.

PURPOSE: The costs associated with clinical trial enrollment remain uncertain. We hypothesized that trial participation is associated with decreased total direct medical costs to health care payers in metastatic non-small-cell lung cancer. METHODS: In this retrospective cohort study, we linked clinical data from electronic medical records to sociodemographic data from a cancer registry and claims data from Medicare and two private insurance plans. We used a difference-in-difference analysis to estimate mean per patient per month total direct medical costs for patients enrolled on a second-line (2L) trial versus patients receiving standard-of-care 2L systemic therapy. RESULTS: Among 70 eligible patients, the difference-in-difference of mean per patient per month total direct medical costs between 2L trial participants and nonparticipants was -$6,663 (P = .01), for a mean savings of $45,308 per patient for the duration of 2L trial therapy. In a secondary analysis by primary insurance payer, this difference-in-difference was -$5,526 (P = .26) for patients with commercial insurance and -$7,432 (P = .01) for patients with Medicare. CONCLUSION: Participation in a 2L trial was associated with a $6,663 per month cost savings to health care payers for the duration of trial participation. Further studies are necessary to elucidate differences in cost savings from trial participation for Medicare and commercial payers. If confirmed, these results support health care payer investment in programs to improve clinical trial access and enrollment.

A Phase II study of nab-Paclitaxel (nab-P) in patients with advanced non-small cell lung cancer with EGFR mutations after frontline tyrosine kinase inhibitor therapy.

BACKGROUND: Patients with metastatic non-small cell lung cancer (NSCLC) harboring a sensitizing EGFR mutation have effective targeted therapy options initially but most patients eventually progress and receive cytotoxic chemotherapy. In this single-institution phase II study, we evaluated the role of nab-paclitaxel monotherapy in this patient population. PATIENTS AND METHODS: Patients with metastatic NSCLC with an activating EGFR mutation whose disease progressed after frontline tyrosine kinase inhibitor therapy and who were chemotherapy naïve received nab-paclitaxel 125 mg/m2 on days 1, 8 and 15 in a 28-day cycle. The primary endpoint was response rate per RECIST 1.1 and secondary endpoints were duration of response, progression free survival, toxicity and overall survival. RESULTS: A total of 27 patients were enrolled and 21 patients were evaluable for response. Median age was 65 (range 52-81), 69% of patients were women, 42% of patients did not having a smoking history. 31% of patients had central nervous system (CNS) metastatic disease at baseline. Confirmed partial response was documented in 9 of 26 patients (35%, 95% CI 17-56) and disease control rate was 58% (95% CI 35-73). CNS was a common first site of progression. Median progression free survival was 4.0 months (95% CI 1.8-5.2). No new safety signals were observed. CONCLUSION: Single agent nab-paclitaxel showed modest antitumor activity in patients with EGFR mutation positive NSCLC and may be an option in patients who are platinum ineligible. Patients often progressed in the CNS and the results underscores the importance of CNS activity of systemic therapies in this patient population.

Impact of Clinical Trial Participation on Survival of Patients with Metastatic Non-Small Cell Lung Cancer.

INTRODUCTION: The impact of clinical trial participation on overall survival is unclear. We hypothesized that enrollment in a therapeutic drug clinical trial is associated with longer overall survival in patients with metastatic non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: We linked electronic medical record and Washington State cancer registry data to identify patients with metastatic NSCLC diagnosed between January 1, 2007, and December 31, 2015 who received treatment at a National Cancer Institute-designated cancer center. The exposure was trial enrollment. The primary outcome was overall survival, defined as the date of second-line treatment initiation to date of death or last follow-up. We used a conditional landmark analysis starting at the date of second-line treatment initiation and propensity scores with inverse probability of treatment weighting to estimate the association between trial enrollment and survival. RESULTS: Of 215 patients, 40 (19%) participated in a second-line trial. Trial participants were more likely to be never smokers (45% vs 27%), have a good performance status (88% vs 77%) and have EGFR (48% vs 14%) and ALK mutations (8% vs 5%) than nonparticipants. Trial participants had similar overall survival to nonparticipants (HR 1.05; 95% CI, 0.72, 1.53; p = 0.81) after adjusting for sociodemographic and disease characteristics. CONCLUSION: Accounting for the immortal time bias and selection bias, trial participation does not appear detrimental to survival. This finding may be reassuring to patients and supports programs and policies to improve clinical trial access.

Combined lenvatinib and pembrolizumab as salvage therapy in advanced adrenal cortical carcinoma.

BACKGROUND: There is no effective systemic therapy for metastatic adrenal cortical carcinoma (ACC) after failure of platinum-based chemotherapy. The efficacies of single-agent oral multikinase inhibitors (MKIs) or salvage immune checkpoint inhibitors (CPIs) have been very limited. It is unknown whether combining CPIs, such as pembrolizumab (PEM), with other therapies, such as MKIs, could yield higher response rates in ACC, yet this combination has shown promise in other cancers. Herein, we describe the first case series using PEM in combination with the MKI lenvatinib (LEN) in patients with progressive, metastatic ACC. METHODS: A retrospective case series describing the use of LEN/PEM as salvage therapy in patients with progressive/metastatic ACC. RESULTS: Eight patients were treated with the LEN/PEM combination therapy. Half were female, and the median age at time of diagnosis was 38 years (range 21-49). Three (37.5%) patients had hormonally active ACC. The median number of prior lines of systemic therapy was 4 (range 2-9). Six (75%) patients had had disease progression on prior CPIs and five (62.5%) patients had progressed on prior MKI therapy. The median progression-free survival was 5.5 months (95% CI 1.8-not reached) and median duration of therapy was 8.5 months (range 2-22). Two (25%) patients had a partial response, one (12.5%) patient had stable disease, and five (62.5%) patients had progressive disease. None of the eight patients stopped therapy because of adverse events. CONCLUSIONS: In our small cohort of heavily pretreated patients with ACC, the combination of LEN/PEM was associated with objective responses in a subset of patients without significant toxicity. This combination should be formally investigated in phase II clinical trial with robust correlative studies to identify predictors for response.

MYCN drives chemoresistance in small cell lung cancer while USP7 inhibition can restore chemosensitivity.

Small cell lung cancer (SCLC) is an aggressive neuroendocrine cancer characterized by initial chemosensitivity followed by emergence of chemoresistant disease. To study roles for MYCN amplification in SCLC progression and chemoresistance, we developed a genetically engineered mouse model of MYCN-overexpressing SCLC. In treatment-naïve mice, MYCN overexpression promoted cell cycle progression, suppressed infiltration of cytotoxic T cells, and accelerated SCLC. MYCN overexpression also suppressed response to cisplatin-etoposide chemotherapy, with similar findings made upon MYCL overexpression. We extended these data to genetically perturb chemosensitive patient-derived xenograft (PDX) models of SCLC. In chemosensitive PDX models, overexpression of either MYCN or MYCL also conferred a switch to chemoresistance. To identify therapeutic strategies for MYCN-overexpressing SCLC, we performed a genome-scale CRISPR-Cas9 sgRNA screen. We identified the deubiquitinase USP7 as a MYCN-associated synthetic vulnerability. Pharmacological inhibition of USP7 resensitized chemoresistant MYCN-overexpressing PDX models to chemotherapy in vivo. Our findings show that MYCN overexpression drives SCLC chemoresistance and provide a therapeutic strategy to restore chemosensitivity.

Aldosterone-Secreting Adrenocortical Carcinoma Presenting With Cardiac Arrest.

Adrenocortical carcinoma (ACC) is a rare malignancy that usually is detected as a result of symptoms of hormone excess or mass effect. We describe a rare presentation of ACC with primary aldosterone production leading to profound hypokalemia and cardiac arrest. The patient was previously asymptomatic with low-grade, untreated hypertension and no documented electrolyte abnormalities. She had sudden cardiac arrest, and potassium levels were undetectable. After successful resuscitation, imaging showed a 6-cm left adrenal mass highly suspicious for malignancy. Biochemical workup revealed aldosterone excess as well as cortisol excess, despite the absence of Cushingoid symptoms. Histopathological examination after surgical resection demonstrated high-grade ACC. This case illustrates that the workup of cardiac arrest as a result of electrolyte abnormalities should include evaluation for adrenal pathology.

Targeting NOTCH activation in small cell lung cancer through LSD1 inhibition.

Small cell lung cancer (SCLC) is a recalcitrant, aggressive neuroendocrine-type cancer for which little change to first-line standard-of-care treatment has occurred within the last few decades. Unlike nonsmall cell lung cancer (NSCLC), SCLC harbors few actionable mutations for therapeutic intervention. Lysine-specific histone demethylase 1A (LSD1 also known as KDM1A) inhibitors were previously shown to have selective activity in SCLC models, but the underlying mechanism was elusive. Here, we found that exposure to the selective LSD1 inhibitor ORY-1001 activated the NOTCH pathway, resulting in the suppression of the transcription factor ASCL1 and the repression of SCLC tumorigenesis. Our analyses revealed that LSD1 bound to the NOTCH1 locus, thereby suppressing NOTCH1 expression and downstream signaling. Reactivation of NOTCH signaling with the LSD1 inhibitor reduced the expression of ASCL1 and neuroendocrine cell lineage genes. Knockdown studies confirmed the pharmacological inhibitor-based results. In vivo, sensitivity to LSD1 inhibition in SCLC patient-derived xenograft (PDX) models correlated with the extent of consequential NOTCH pathway activation and repression of a neuroendocrine phenotype. Complete and durable tumor regression occurred with ORY-1001-induced NOTCH activation in a chemoresistant PDX model. Our findings reveal how LSD1 inhibitors function in this tumor and support their potential as a new and targeted therapy for SCLC.

Long term follow-up of neoadjuvant chemotherapy for non-small cell lung cancer (NSCLC) investigating early positron emission tomography (PET) scan as a predictor of outcome.

BACKGROUND: Neoadjuvant chemotherapy is effective in improving survival of resectable NSCLC. Based on findings in the adjuvant and metastatic setting, FDG positron emission tomography (PET) scans may offer early prognostic or predictive value after one cycle of induction chemotherapy. METHODS: In this phase II non-randomized trial, patients with AJCC version 6 stage IB to IIIB operable NSCLC were treated with 3 cycles of cisplatin and pemetrexed neoadjuvant chemotherapy. Patients underwent FDG-PET scanning prior to and 18 to 21 days after the first cycle of chemotherapy. Investigators caring for patients were blinded to results, unless the scans showed evidence of disease progression. FDG-PET response was defined prospectively as a ≥ 20% decrease in the SUV of the primary lesion. RESULTS: Between October 2005 and February 2010, 25 patients enrolled. Fifty two percent were female, 88% white, and median age was 62 years. Histology was divided into adenocarcinoma 66%, not otherwise specified (NOS) 16%, squamous cell 12%, and large cell 4%. Stage distribution was: 16% IB, 4% IIB, and 79% IIIA. Treatment was well tolerated and only one patient had a grade 4 toxicity. The median follow up was 95 months. The 5 year progression free survival (PFS) and overall survival (OS) for the entire population were 54 and 67%, respectively. Eighteen patients had a baseline FDG-PET scan and a repeat scan at day 18-21 available for comparison. Ten patients (56%) were considered metabolic responders on the day 18-21 FDG-PET scan. Responders had a 5 year PFS and OS of 60 and 70%, respectively, while the percentage for non-responders was 63 and 75% (p = 0.96 and 0.85). CONCLUSIONS: This phase II trial did not demonstrate that a PET scan after one cycle of chemotherapy can predict survival outcomes of patients with NSCLC treated with neoadjuvant chemotherapy. TRIAL REGISTRATION: NCT00227539 registered September 28th, 2005.

Characterizing Potentially Preventable Cancer- and Chronic Disease-Related Emergency Department Use in the Year After Treatment Initiation: A Regional Study.

PURPOSE: As new quality metrics and interventions for potentially preventable emergency department (ED) visits are implemented, we sought to compare methods for evaluating the prevalence and costs of potentially preventable ED visits that were related to cancer and chronic disease among a commercially insured oncology population in the year after treatment initiation. METHODS: We linked SEER records in western Washington from 2011 to 2016 with claims from two commercial insurers. The study included patients who were diagnosed with a solid tumor and tracked ED utilization for 1 year after the start of chemotherapy or radiation. Cancer symptoms from the Centers for Medicare & Medicaid Services metric and a patient-reported outcome intervention were labeled potentially preventable (PpCancer). Prevention Quality Indicators of the Agency for Healthcare Research and Quality were labeled potentially preventable-chronic disease (PpChronic). We reported the primary diagnosis, all diagnosis field coding (1 to 10), and 2016 adjusted reimbursements. RESULTS: Of 5,853 eligible patients, 27% had at least one ED visit, which yielded 2,400 total visits. Using primary diagnosis coding, 49.8% of ED visits had a PpCancer diagnosis, whereas 3.2% had a PpChronic diagnosis. Considering all diagnosis fields, 45.0%, 9.4%, and 18.5% included a PpCancer only, a PpChronic only, and both a PpCancer and a PpChronic diagnosis, respectively. The median reimbursement per visit was $735 (interquartile ratio, $194 to $1,549). CONCLUSION: The prevalence of potentially preventable ED visits was generally high, but varied depending on the diagnosis code fields and the group of codes considered. Future research is needed to understand the complex landscape of potentially preventable ED visits and measures to improve value in cancer care delivery.

Inflammatory Gene Polymorphisms in Lung Cancer Susceptibility.

INTRODUCTION: Chronic inflammation has been implicated in carcinogenesis, with increasing evidence of its role in lung cancer. We aimed to evaluate the role of genetic polymorphisms in inflammation-related genes in the risk for development of lung cancer. METHODS: A nested case-control study design was used, and 625 cases and 625 well-matched controls were selected from participants in the ß-Carotene and Retinol Efficacy Trial, which is a large, prospective lung cancer chemoprevention trial. The association between lung cancer incidence and survival and 23 polymorphisms descriptive of 11 inflammation-related genes (interferon gamma gene [IFNG], interleukin 10 gene [IL10], interleukin 1 alpha gene [IL1A], interleukin 1 beta gene [IL1B], interleukin 2 gene [IL2], interleukin 4 receptor gene [IL4R], interleukin 4 gene [IL4], interleukin 6 gene [IL6], prostaglandin-endoperoxide synthase 2 gene [PTGS2] (also known as COX2), transforming growth factor beta 1 gene [TGFB1], and tumor necrosis factor alpha gene [TNFA]) was evaluated. RESULTS: Of the 23 polymorphisms, two were associated with risk for lung cancer. Compared with individuals with the wild-type (CC) variant, individuals carrying the minor allele variants of the IL-1ß-511C>T promoter polymorphism (rs16944) (CT and TT) had decreased odds of lung cancer (OR = 0.74, [95% confidence interval (CI): 0.58-0.94] and OR = 0.71 [95% CI: 0.50-1.01], respectively, p = 0.03). Similar results were observed for the IL-1ß-1464 C>G promoter polymorphism (rs1143623), with presence of the minor variants CG and CC having decreased odds of lung cancer (OR = 0.75 [95% CI: 0.59-0.95] and OR = 0.69 [95% CI: 0.46-1.03], respectively, p = 0.03). Survival was not influenced by genotype. CONCLUSIONS: This study provides further evidence that IL1B promoter polymorphisms may modulate the risk for development of lung cancer.