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ObjectiveLittle is known about the association between neighborhood characteristics and non-adherence to attending scheduled ophthalmology appointments. The purpose of this study was to examine the association between neighborhood-level social vulnerability and adherence to scheduled ophthalmology appointments.DesignRetrospective cohort study.ParticipantsAdults aged 18 years and older with scheduled ophthalmology appointments between September 12, 2020, and February 8, 2021.MethodsA single-center study was conducted at the University of Illinois Chicago Illinois Eye and Ear Infirmary, an urban tertiary care referral center in Chicago, Illinois. Primary exposure is neighborhood-level Social Vulnerability Index (SVI), based on the patient’s address of residence. The SVI ranks (possible range 0 to 1) each census tract on 15 social factors into four related themes (socioeconomic status, household composition & disability, minority status & language, and housing type & transportation). Higher SVI rankings indicate higher levels of social vulnerability. The overall SVI ranking and rankings for each of the four themes were analyzed separately as the primary exposure of interest in multivariable logistic regression models that controlled for age, sex, status (new or established appointment), race, and distance from clinic.Main Outcome MeasureNon-adherence to attending scheduled ophthalmology appointments, defined as missing more than 25% of scheduled appointments.ResultsA total of 8,322 unique patients (41% non-Hispanic Black, 24% Hispanic, 22% non-Hispanic White) had scheduled appointments during the five-month study period (range 1 to 23 appointments). Of those, 28% of patients were non-adherent to appointments. In multivariable logistic regression models, non-adherence to appointments was associated with living in higher SVI ranking neighborhoods (socioeconomic status: (adjusted odds ratio [95% confidence interval]) 2.38 [1.94, 2.91]; household composition/disability: 1.51 [1.26, 1.81]; minority status/language: 2.03 [1.55, 2.68]; housing type/transportation: 1.41 [1.16, 1.73]; and overall SVI: 2.46 [1.99, 3.06]).ConclusionsNeighborhood-level measures of social vulnerability are associated with greater risk of non-adherence to scheduled ophthalmology appointments. Studies to better understand these neighborhood-level vulnerabilities are needed to inform the design and evaluation of multi-level (individual and neighborhood) strategies to reduce disparities in access to ophthalmology care.

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Thirteen patients were enrolled and underwent at least one cycle of therapy.

Screening with drugs targeting sunitinib related receptor tyrosine kinases (RTK) or MAPK pathway were performed in PC9TMEM87A-RASGRF1 clone 1. Relative viability compared with control (treated with DMSO) was shown. A modest inhibitory effect was seen for gilteritinib without control osimertinib, suggesting the off-target toxic effect of the drug rather than on-target inhibition.

Purpose:We pursued genomic analysis of an exceptional responder with non–small cell lung cancer (NSCLC) through a multi-platform effort to discover novel oncogenic targets.Experimental Design:In this open-label, single-arm phase II study (NCT01829217), an enriched cohort of patients with advanced NSCLC was treated with the multi-kinase inhibitor sunitinib. The primary endpoint was objective response rate. Tissue was collected for multi-platform genomic analysis of responders, and a candidate oncogene was validated using in vitro models edited by CRISPR-Cas9.Results:Of 13 patients enrolled, 1 patient (8%), a never smoker, had a partial response lasting 33 months. Genomic analysis of the responder identified no oncogenic variant using multi-platform DNA analysis including hotspot allelotyping, massively parallel hybrid-capture next-generation sequencing, and whole-exome sequencing. However, bulk RNA-sequencing (RNA-seq) revealed a novel fusion, TMEM87A–RASGRF1, with high overexpression of the fusion partners. RASGRF1 encodes a guanine exchange factor which activates RAS from GDP-RAS to GTP-RAS. Oncogenicity was demonstrated in NIH/3T3 models with intrinsic TMEM87A–RASGRF1 fusion. In addition, activation of MAPK was shown in PC9 models edited to express this fusion, although sensitivity to MAPK inhibition was seen without apparent sensitivity to sunitinib.Conclusions:Sunitinib exhibited limited activity in this enriched cohort of patients with advanced NSCLC. Nonetheless, we find that RNA-seq of exceptional responders represents a potentially underutilized opportunity to identify novel oncogenic targets including oncogenic activation of RASGRF1.

Post-baseline toxicity incidence.

Age-related macular degeneration (AMD) is a leading cause of severe vision loss. With our aging population, it may affect 288 million people globally by the year 2040. AMD progresses from an early and intermediate dry form to an advanced one, which manifests as choroidal neovascularization and geographic atrophy. Conversion to AMD-related exudation is known as progression to neovascular AMD, and presence of geographic atrophy is known as progression to advanced dry AMD. AMD progression predictions could enable timely monitoring, earlier detection and treatment, improving vision outcomes. Machine learning approaches, a subset of artificial intelligence applications, applied on imaging data are showing promising results in predicting progression. Extracted biomarkers, specifically from optical coherence tomography scans, are informative in predicting progression events. The purpose of this mini review is to provide an overview about current machine learning applications in artificial intelligence for predicting AMD progression, and describe the various methods, data-input types, and imaging modalities used to identify high-risk patients. With advances in computational capabilities, artificial intelligence applications are likely to transform patient care and management in AMD. External validation studies that improve generalizability to populations and devices, as well as evaluating systems in real-world clinical settings are needed to improve the clinical translations of artificial intelligence AMD applications.

68Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) is a useful tool for diagnosing and staging neuroendocrine neoplasms (NEN). Unlike other PET tracers like FDG, the meaningfulness and use of standardized uptake values (SUVs) of 68Ga-DOTATATE is not well-established. This study aimed to determine if a correlation exists between intensity of 68Ga-DOTATATE uptake and markers of cellular proliferation. This retrospective study included 79 patients with positive 68Ga-DOTATATE PET/CT and Ki-67 and/or mitotic index (MI) available on pathology report. SUVmax of the most intense lesion and the most intense organ-matched lesion were determined. Demographics and pathology results for Ki-67 and MI were collected from the electronic medical record. Correlations and trends for correlations of SUVmax to Ki-67 and MI were performed using Kruskal–Wallis and Cuzick trend tests. A trend for an association between SUVmax and Ki-67 grade was found; median SUVmax of Ki-67 20% was 35.2, 31.8, and 12.8 (p = 0.077), respectively. There was also a trend between SUVmax and Ki-67 categories in organ-matched lesions (p = 0.08). The median organ-matched SUVmax of MI 20 lesions was 34.2, 18, and 21.7, respectively, (Cuzick trend test p = 0.066). The median SUVmax for small bowel, pancreatic, and other primary locations was 27.6, 46.9, and 9.3 (p

IntroductionThis study evaluated the effect of a surgical opioid-avoidance protocol (SOAP) on postoperative pain scores. The primary goal was to demonstrate that the SOAP was as effective as the pre-existing non-SOAP (without opioid restriction) protocol by measuring postoperative pain in a diverse, opioid-naive patient population undergoing inpatient surgery across multiple surgical services.MethodsThis prospective cohort study was divided into SOAP and non-SOAP groups based on surgery date. The non-SOAP group had no opioid restrictions (n=382), while the SOAP group (n=449) used a rigorous, opioid-avoidance order set with patient and staff education regarding multimodal analgesia. A non-inferiority analysis assessed the SOAP impact on postoperative pain scores.ResultsPostoperative pain scores in the SOAP group compared with the non-SOAP group were non-inferior (95% CI: −0.58, 0.10; non-inferiority margin=−1). The SOAP group consumed fewer postoperative opioids (median=0.67 (IQR=15) vs 8.17 morphine milliequivalents (MMEs) (IQR=40.33); pDiscussionThe SOAP was as effective as the non-SOAP group in postoperative pain scores across a diverse patient population and associated with lower postoperative opioid consumption and discharge prescription opioids.

Purpose: We pursued genomic analysis of an exceptional responder with non–small cell lung cancer (NSCLC) through a multi-platform effort to discover novel oncogenic targets. Experimental Design: In this open-label, single-arm phase II study (NCT01829217), an enriched cohort of patients with advanced NSCLC was treated with the multi-kinase inhibitor sunitinib. The primary endpoint was objective response rate. Tissue was collected for multi-platform genomic analysis of responders, and a candidate oncogene was validated using in vitro models edited by CRISPR-Cas9. Results: Of 13 patients enrolled, 1 patient (8%), a never smoker, had a partial response lasting 33 months. Genomic analysis of the responder identified no oncogenic variant using multi-platform DNA analysis including hotspot allelotyping, massively parallel hybrid-capture next-generation sequencing, and whole-exome sequencing. However, bulk RNA-sequencing (RNA-seq) revealed a novel fusion, TMEM87A–RASGRF1, with high overexpression of the fusion partners. RASGRF1 encodes a guanine exchange factor which activates RAS from GDP-RAS to GTP-RAS. Oncogenicity was demonstrated in NIH/3T3 models with intrinsic TMEM87A–RASGRF1 fusion. In addition, activation of MAPK was shown in PC9 models edited to express this fusion, although sensitivity to MAPK inhibition was seen without apparent sensitivity to sunitinib. Conclusions: Sunitinib exhibited limited activity in this enriched cohort of patients with advanced NSCLC. Nonetheless, we find that RNA-seq of exceptional responders represents a potentially underutilized opportunity to identify novel oncogenic targets including oncogenic activation of RASGRF1.

Purpose To investigate if accounting for a cup-to-disc ratio (CDR) genetic risk score (GRS) modified the association between large CDR and cognitive function among women. Design This was a retrospective study using data from the Women’s Health Initiative. Methods Patients with glaucoma or ocular hypertension were excluded. Large CDR was defined as ≥ 0.6 in either eye. Cognitive function was measured by the Modified Mini-Mental State Examination (3MSE). We used the combined effects from 13 single nucleotide polymorphisms (SNPs) to formulate the GRS for CDR. We used logistic regression to investigate associations between weighted GRS and large CDR, then a linear regression to assess the association between weighted GRS and 3MSE scores, and between weighted GRS, CDR, and 3MSE scores, adjusted for demographic and clinical characteristics. Results Final analyses included 1,196 White women with mean age of 69.60 ± 3.62 years and 7.27% with large CDR. Mean GRS in women with and without large CDR was 1.51 ± 0.31 vs. 1.41 ± 0.36, respectively (p = 0.004). The odds of large CDR for a one unit increase in GRS was 2.30 (95% CI: (1.22, 4.36), p = 0.011). Adding the CDR GRS in the model with CDR and 3MSE, women with large CDR still had statistically significantly lower 3MSE scores than those without large CDR, yielding a predicted mean difference in 3MSE scores of 0.84 (p = 0.007). Conclusions Independent of the CDR GRS, women with large CDR had a lower cognitive function.

Patient Adherence to Immunosuppressive Therapy for Chronic Inflammatory Eye Disease To investigate adherence rates to immunosuppressive therapy (IMT) for treatment of noninfectious inflammatory eye disease (IED), adherence and disease control, and factors associated with nonadherence. Retrospective review of medical charts from 2015 to 2020 was conducted on patients with IED at 6 months, 1 and 2 years after initiation of IMT. Of 183 patients, adherence rates at 6 months and 1 year were 70% and 58% by 2 years. Eighty-two percent, 78%, and 65% of patients with disease quiescence were adherent at 6 months, 1 and 2 years, respectively. Adherent patients have 1.86 (95% CI 1.09, 3.20) times greater likelihood for disease control compared to nonadherent. Primary reason for nonadherence was patient self-discontinuation. No specific factors were associated with nonadherence. Patients on IMT for IED had steady adherence rates up to 1 year, with decreased adherence at 2 years. Adherence to IMT significantly correlates with disease quiescence.

Objective: Compare FDG-PET/CT, CT, and bone scan for detecting and monitoring bone metastases’ response in metastatic renal cell cancer (mRCC). Methods: Patients with mRCC prospectively underwent FDG-PET/CT, CT, and bone scans at baseline and after 8 weeks of therapy. Tumor visibility and metabolic activity were retrospectively recorded. Response was evaluated by PERCIST, RECIST, and MD Anderson bone criteria. Kaplan-Meier methodology estimated event-time distributions for PFS, OS, and time to symptomatic skeletal event (SSE). Log-rank test tested differences in event-time distributions between response at 8 weeks by response criteria. Results: Sixteen patients (n = 30; 53%) were evaluable. Baseline FDG-PET/CT detected more osseous metastases (n = 55) than CT (n = 45) or bone scan (n = 34). From baseline to 8 weeks, metabolic activity of lesions decreased >20%, while qualitative and quantitative CT and bone scan parameters were unchanged for most patients. Partial metabolic responders by PERCIST had longer PFS and OS (n = 5, 20+ months) versus those with stable (n = 9; PFS = 9.2 mos, OS = 8.7 mos) and progressive (n = 2; PFS = 5.4 mos, OS = 12.1 mos) metabolic disease, p = 0.09 and 0.42, respectively. By RECIST, longer PFS and OS was seen for stable (n = 12, PFS = 8.3 mos, OS = 17.7 mos) versus progressive (n = 4; PFS = 3.7 mos, OS = 7.5 mos) disease, p = 0.16, 0.02, respectively. OS was not reached, but estimated ≥20 mos, for 4 patients with RECIST SD and PERCIST PMR, compared to OS of 17.7 mos for other patients with RECIST SD. Conclusions: FDG-PET/CT identified more bone metastases and greater numbers of quantitative and qualitative treatment responses in mRCC compared to CT and bone scan. FDG-PET/CT also may identify a sub-group of patients with better outcomes than predicted by standard imaging modalities.

The application of artificial intelligence (AI) in diagnosing and managing ocular disease has gained popularity as research highlights the utilization of AI to improve personalized medicine and healthcare outcomes. The objective of this study is to describe current optometric perspectives of AI in eye care.Members of the American Academy of Optometry were sent an electronic invitation to complete a 17-item survey. Survey items assessed perceived advantages and concerns regarding AI using a 5-point Likert scale ranging from "strongly agree" to "strongly disagree."A total of 400 optometrists completed the survey. The mean number of years since optometry school completion was 25 ± 15.1. Most respondents reported familiarity with AI (66.8%). Though half of optometrists had concerns about the diagnostic accuracy of AI (53.0%), most believed it would improve the practice of optometry (72.0%). Optometrists reported their willingness to incorporate AI into practice increased from 53.3% before the COVID-19 pandemic to 65.5% after onset of the pandemic (p0.001).In this study, optometrists are optimistic about the use of AI in eye care, and willingness to incorporate AI in clinical practice also increased after the onset of the COVID-19 pandemic.

68Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) is a useful tool for diagnosing and staging neuroendocrine neoplasms (NEN). Unlike other PET tracers like FDG, the meaningfulness and use of standardized uptake values (SUVs) of 68Ga-DOTATATE is not well-established. This study aimed to determine if a correlation exists between intensity of 68Ga-DOTATATE uptake and markers of cellular proliferation.This retrospective study included 79 patients with positive 68Ga-DOTATATE PET/CT and Ki-67 and/or mitotic index (MI) available on pathology report. SUVA trend for an association between SUVThe association between 68Ga-DOTATATE SUV

PURPOSE: We pursued genomic analysis of an exceptional responder with non-small cell lung cancer (NSCLC) through a multi-platform effort to discover novel oncogenic targets. METHODS: In this open-label, single-arm phase II study (NCT01829217), an enriched cohort of patients with advanced NSCLC were treated with the multi-kinase inhibitor sunitinib. The primary endpoint was objective response rate. Tissue was collected for multi-platform genomic analysis of responders, and a candidate oncogene was validated using in vitro models edited by CRISPR-Cas9. RESULTS: Of 13 patients enrolled, one patient (8%), a never-smoker, had a partial response lasting 33 months. Genomic analysis of the responder identified no oncogenic variant using multi-platform DNA analysis including hotspot allelotyping, massively parallel hybrid-capture next-generation sequencing, and whole exome sequencing. However, bulk RNA sequencing revealed a novel fusion, TMEM87A-RASGRF1, with high overexpression of the fusion partners. RASGRF1 encodes a guanine exchange factor which activates RAS from GDP-RAS to GTP-RAS. Oncogenicity was demonstrated in NIH/3T3 models with intrinsic TMEM87A-RASGRF1 fusion. Additionally, activation of MAPK was shown in PC9 models edited to express this fusion, though sensitivity to MAPK inhibition was seen without apparent sensitivity to sunitinib. CONCLUSIONS: Sunitinib exhibited limited activity in this enriched cohort of patients with advanced NSCLC. Nonetheless, we find that RNA sequencing of exceptional responders represents a potentially under-utilized opportunity to identify novel oncogenic targets including oncogenic activation of RASGRF1.

Purpose Although programmed death (PD)-1 pathway inhibitors are now used in nearly all patients with advanced non–small-cell lung cancer (NSCLC), the large number of patients with NSCLC and concurrent autoimmune disease (AID) have been universally excluded from immunotherapy clinical trials. Therefore, the safety of PD-1 and PD-ligand 1 (PD-L1) inhibitors in patients with NSCLC and underlying AID is currently unknown. Methods As part of a multi-institutional effort, we retrospectively collected clinicopathologic data from patients with NSCLC and a history of AID who received monotherapy with either a PD-1 or a PD-L1 (herein referred to as PD-[L]1) inhibitor. Qualifying AIDs included but were not limited to: rheumatologic, neurologic, endocrine, GI, and dermatologic conditions. Results We identified 56 patients with NSCLC and an AID who received a PD-(L)1 inhibitor. At the time of treatment initiation, 18% of patients had active AID symptoms and 20% were receiving immunomodulatory agents for their AID. A total of 55% of patients developed an AID flare and/or an immune-related adverse event (irAE). Exacerbation of the AID occurred in 13 patients (23% of the whole cohort), four of whom required systemic corticosteroids. Immune-related adverse events occurred in 21 patients (38%). Among irAEs, 74% were grade 1 or 2 and 26% were grade 3 or 4; eight patients required corticosteroids for irAE management. PD-(L)1 therapy was permanently discontinued in eight patients (14%) because of irAEs. The overall response rate to immunotherapy in this population was 22%. Conclusion In patients with NSCLC with AID treated with a PD-(L)1 inhibitor, exacerbation of AID occurred in a minority of patients. The incidence of irAEs was similar to reported rates in clinical trials where patients with AID were excluded. Adverse events were generally manageable and infrequently led to permanent discontinuation of immunotherapy.

Background Programmed cell death protein 1 inhibitors increasingly are being used to treat patients with advanced lung carcinomas. Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) in tumor cells (TCs) and tumor-infiltrating immune cells (ICs) is used to select patients for programmed cell death protein 1 inhibition, but few studies have evaluated PD-L1 IHC in cytology specimens. The objective of the current study was to compare PD-L1 IHC in cytology cell blocks and matched surgical specimens. Methods A total of 56 cytology specimens obtained between 2013 and 2016 with matching surgical specimens were stained with anti-PD-L1. Membranous positivity was scored as a percentage of the TCs and ICs by 2 pathologists. Results were compared between cytology and surgical specimens, and interobserver concordance was assessed. Results The average PD-L1 positivity rate was 28% in TCs and 5% in ICs in surgical specimens (standard deviations of 37% and 7%, respectively), and 21% in TCs and 8% in ICs in cytology specimens (standard deviations of 33% and 15%, respectively). Interobserver concordance was high for TCs in surgical and cytology specimens (intraclass correlation coefficients of 0.96 and 0.96, respectively), and was moderate for ICs in surgical and cytology specimens (intraclass correlation coefficients of 0.47 and 0.67, respectively). There was moderate to high correlation between PD-L1 positivity in TCs between surgical and cytology specimens (Spearman correlation coefficient [Spearman r], 0.69), particularly among fine-needle aspiration specimens (Spearman r, 0.78), but not between PD-L1 positivity in ICs in surgical and cytology specimens (Spearman r, 0.14), including among fine-needle aspiration specimens (Spearman r, 0.23). Conclusions Tumor PD-L1 IHC positivity in cytology specimens appears to correlate strongly with results obtained from matching surgical specimens. PD-L1 IHC in ICs within cytology specimens does not reflect results in matched surgical specimens and should not be used in clinical decision making. Cancer Cytopathol 2018;126:253-63. © 2018 American Cancer Society.

Background Clinically-available biomarkers to identify the fraction of patients with small cell lung cancer (SCLC) who respond to immune-checkpoint inhibitors (ICIs) are lacking. High nonsynonymous tumor mutational burden (TMB), as assessed by whole exome sequencing, correlates with improved clinical outcomes for patients with SCLC treated with ICIs. Whether TMB as assessed by targeted next generation sequencing (NGS) is associated with improved efficacy of ICIs in patients with SCLC is currently unknown. Here we determined whether TMB by targeted NGS is associated with efficacy of ICIs in patients with SCLC. Methods We collected clinicopathologic data from patients with relapsed or refractory SCLC which underwent targeted NGS with TMB assessment by the Dana-Farber Cancer Institute OncoPanel platform. The relationship between TMB and clinical outcomes after treatment with ICIs was investigated. Results Among the 52 patients treated with ICIs, we found no significant difference in the objective response rate (ORR) between patients with a TMB above the 50th percentile (“TMB high”) and those with a TMB at or below the 50th percentile (“TMB low”). The median progression-free survival (mPFS) and median overall survival (mOS) were significantly longer in patients with a high TMB compared to those with a low TMB (mPFS: 3.3 versus 1.2 months, HR: 0.37 [95% CI: 0.20–0.69], P

Objectives Although dramatic responses to MET inhibitors have been reported in patients with MET exon 14 (METex14) mutant non-small cell lung cancer (NSCLC), the impact of these treatments on overall survival in this population is unknown. Methods We conducted a multicenter retrospective analysis of patients with METex14 NSCLC to determine if treatment with MET inhibitors impacts median overall survival (mOS). Event-time distributions were estimated using the Kaplan-Meier method and compared with the log-rank test. Multivariable Cox models were fitted to estimate hazard ratios. Results We identified 148 patients with METex14 NSCLC; the median age was 72; 57% were women and 39% were never smokers. Of the 34 metastatic patients who never received a MET inhibitor, the mOS was 8.1 months; those in this group with concurrent MET amplification had a trend toward worse survival compared to cancers without MET amplification (5.2 months vs 10.5 months, P = 0.06). Of the 27 metastatic patients who received at least one MET inhibitor the mOS was 24.6 months. A model adjusting for receipt of a MET inhibitor as first- or second-line therapy as a time-dependent covariate demonstrated that treatment with a MET inhibitor was associated with a significant prolongation in survival (HR 0.11, 95% CI 0.01-0.92, P = 0.04) compared to patients who did not receive any MET inhibitor. Among 22 patients treated with crizotinib, the median progression-free survival was 7.4 months. Discussion For patients with METex14 NSCLC, treatment with a MET inhibitor is associated with an improvement in overall survival.

Highlights • Tumor growth rate of ALK-rearranged NSCLC treated with crizotinib was assessed. • Overall growth rate after nadir was 0.04/month for the logarithm of tumor volume. • The study provides objective reference values for ALK-directed treatment decisions., Purpose The purpose of the study is to investigate volumetric tumor burden dynamics and tumor growth rates in ALK-rearranged advanced NSCLC patients during crizotinib monotherapy. Methods The study included 44 ALK-rearranged advanced NSCLC patients treated with crizotinib monotherapy as their initial ALK-directed therapy, who had at least one measurable lung lesion and at least two follow-up CT scans, and experienced tumor volume increase while on crizotinib. The tumor volume (in mm3) of the dominant lung lesion was measured on serial CT scans during therapy for analysis of tumor growth rates after the volume nadir. Results A total of 231 volume measurements from the nadir to the end of crizotinib therapy or the last follow-up in 44 patients were analyzed in a linear mixed-effects model, fitting time (in months since baseline) as a random effect. When measured from the volume nadir, the tumor growth rate of the logarithm of tumor volume (logeV) was 0.04/month (SE = 0.012, P = 0.0011) in the unadjusted model. When adjusted for the baseline volume (logeV0), the growth rate was again 0.04/month (SE = 0.011, P = 0.0004). When adjusted for clinical variables and logeV0, the growth rate was 0.045/month (SE = 0.012, P = 0.0002), indicating that the tumor growth rate after nadir in this cohort remains very close to 0.04/month regardless of logeV0 or clinical factors. Conclusions Tumor volume growth rate after nadir in ALK-rearranged NSCLC patients treated with crizotinib was obtained, providing objective reference values that can inform physicians when deciding to keep their patients on ALK directed therapy with slowly progressing lung cancer.

Purpose Genomic profiling for personalized targeted therapy has become standard of care. We report the success of genomic profiling of non-small cell lung cancer (NSCLC) obtained by trans-thoracic needle biopsy (TTNB) in a single center experience. Materials and methods Patients with NSCLC who underwent TTNB for genomic were identified. Pathology specimens were evaluated for tumor adequacy and then analyzed for selected exons of epidermal growth factor receptor, KRAS, BRAF, PIK3CA, and ERBB2. ALK rearrangements were detected with fluorescence in situ hybridization and/or immunohistochemistry. Technical success was recorded and the factors affecting successful profiling were evaluated. Complications (pneumothorax, hemorrhage, and admission) were recorded. Comparison of yield and complications were done between the two groups (core biopsy and fine needle aspiration only group). Utility of PET-CT to guide the needle track for optimized yield was assessed in a subset of patients. Results Between December 6, 2009, and December 30, 2016, 765 patients with NSCLC underwent TTNB. Five-hundred and seventy-seven of 765 (75%) of all TTNB were profiled, for genomic analysis. Five-hundred and eight of 577 (88%) were successfully profiled. The number of samples obtained ranged from 1 to 10 (1 to 2 cm, 18 to 20 G). Lesions biopsied ranged in size from 0.6 to 16 cm. No statistically significant difference was observed in the incidence of pneumothorax between two groups (P = 0.26). PET guidance was not found to be statistically significant ( P = 0.79) in the overall yield. Conclusion Computed tomographic guided TTNB is a safe and efficacious technique for genomic profiling, enables the acquisition of sufficient tissue for genetic mutation analyses allowing for personalized therapy with an acceptable complication rate.

Retrospective clinical data and laboratory studies point to metformin having a potential role in cancer treatment; however, the efficacy of this drug in cancer treatment therapy has not been validated in prospective trials. In particular, limited data evaluating the effects of metformin in lung cancer has been available. Responding to this need, a prospective phase II clinical trial was conducted, and this article evaluates response rate and progression‐free survival of platinum‐based doublet chemotherapy with or without metformin in chemotherapy‐naïive advanced or metastatic nonsquamous non‐small cell lung cancer., Background. In the absence of a targeted oncogenic driver mutation or high programmed death‐ligand 1 expression, systemic therapy with platinum‐based doublet chemotherapy with or without bevacizumab has been the standard treatment in advanced or metastatic non‐small cell lung cancer (NSCLC). Metformin has been shown to have antitumor effects via a variety of insulin‐dependent and insulin‐independent mechanisms and to be potentially synergistic with chemotherapy. Materials and Methods. This open‐label single‐center phase II study (NCT01578551) enrolled patients with chemotherapy‐naïve advanced or metastatic nonsquamous NSCLC and randomized them (3:1) to receive carboplatin, paclitaxel, and bevacizumab with (Arm A) or without (Arm B) concurrent metformin for four to six cycles followed by maintenance therapy with bevacizumab ± metformin continued until disease progression, intolerable toxicity, or study withdrawal. The primary outcome was 1‐year progression free survival (PFS). Secondary outcomes included overall survival, response to therapy, and toxicity. Results. A total of 25 patients were enrolled from August 2012 to April 2015, of whom 24 received at least one cycle of therapy administration. The study was stopped early due to slow accrual and changes in standard first‐line therapy of advanced NSCLC. The 1‐year PFS on Arm A (n = 18) was 47% (95% confidence interval [CI]: 25%–88%), which exceeded the historical control 1‐year PFS of 15%. Median overall survival of patients treated on Arm A was 15.9 months (95% CI: 8.4–not available [NA]) and 13.9 months (95% CI: 12.7–NA) on Arm B. There were no significant differences in toxicity between the study arms. Conclusion. To the authors' knowledge, this is the first study to show a significant benefit in PFS with the use of metformin in this patient population and is a signal of efficacy for metformin in advanced NSCLC. Implications for Practice. The anticancer effects of metformin continue to be elucidated. To the authors' knowledge, this is the first trial in nondiabetic advanced non‐small cell lung cancer patients to show a significant change in outcome with the addition of metformin to standard first‐line chemotherapy. Well tolerated and widely available, metformin is a drug that should be considered for further study in the lung cancer treatment landscape.

Programmed cell death protein 1 inhibitors increasingly are being used to treat patients with advanced lung carcinomas. Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) in tumor cells (TCs) and tumor-infiltrating immune cells (ICs) is used to select patients for programmed cell death protein 1 inhibition, but few studies have evaluated PD-L1 IHC in cytology specimens. The objective of the current study was to compare PD-L1 IHC in cytology cell blocks and matched surgical specimens.A total of 56 cytology specimens obtained between 2013 and 2016 with matching surgical specimens were stained with anti-PD-L1. Membranous positivity was scored as a percentage of the TCs and ICs by 2 pathologists. Results were compared between cytology and surgical specimens, and interobserver concordance was assessed.The average PD-L1 positivity rate was 28% in TCs and 5% in ICs in surgical specimens (standard deviations of 37% and 7%, respectively), and 21% in TCs and 8% in ICs in cytology specimens (standard deviations of 33% and 15%, respectively). Interobserver concordance was high for TCs in surgical and cytology specimens (intraclass correlation coefficients of 0.96 and 0.96, respectively), and was moderate for ICs in surgical and cytology specimens (intraclass correlation coefficients of 0.47 and 0.67, respectively). There was moderate to high correlation between PD-L1 positivity in TCs between surgical and cytology specimens (Spearman correlation coefficient [Spearman r], 0.69), particularly among fine-needle aspiration specimens (Spearman r, 0.78), but not between PD-L1 positivity in ICs in surgical and cytology specimens (Spearman r, 0.14), including among fine-needle aspiration specimens (Spearman r, 0.23).Tumor PD-L1 IHC positivity in cytology specimens appears to correlate strongly with results obtained from matching surgical specimens. PD-L1 IHC in ICs within cytology specimens does not reflect results in matched surgical specimens and should not be used in clinical decision making. Cancer Cytopathol 2018;126:253-63. © 2018 American Cancer Society.

Background Magnetic Resonance Imaging (MRI) relies on optimal scanning parameters to achieve maximal signal-to-noise ratio (SNR) and high contrast-to-noise ratio (CNR) between tissues resulting in high quality images. The optimization of such parameters is often laborious, time consuming, and user-dependent, making harmonization of imaging parameters a difficult task. In this report, we aim to develop and validate a computer simulation technique that can reliably provide "optimal in vivo scanning parameters" ready to be used for in vivo evaluation of disease models. Methods A glioblastoma murine model was investigated using several MRI imaging methods. Such MRI methods underwent a simulated and an in vivo scanning parameter optimization in pre- and post-contrast conditions that involved the investigation of tumor, brain parenchyma and cerebrospinal fluid (CSF) CNR values in addition to the time relaxation values of the related tissues. The CNR tissues information were analyzed and the derived scanning parameters compared in order to validate the simulated methodology as a reliable technique for "optimal in vivo scanning parameters" estimation. Results The CNRs and the related scanning parameters were better correlated when spin-echo-based sequences were used rather than the gradient-echo-based sequences due to augmented inhomogeneity artifacts affecting the latter methods. "Optimal in vivo scanning parameters" were generated successfully by the simulations after initial scanning parameter adjustments that conformed to some of the parameters derived from the in vivo experiment. Conclusion Scanning parameter optimization using the computer simulation was shown to be a valid surrogate to the in vivo approach in a glioblastoma murine model yielding in a better delineation and differentiation of the tumor from the contralateral hemisphere. In addition to drastically reducing the time invested in choosing optimal scanning parameters when compared to an in vivo approach, this simulation program could also be used to harmonize MRI acquisition parameters across scanners from different vendors.

9037Background: Among patients with NSCLC and a PD-L1 TPS ≥50%, the response rate to the PD-1 inhibitor pembrolizumab is ~45%. Whether certain subsets of patients with a PD-L1 TPS ≥50% are more lik...

8511 Background: Dramatic responses to MET inhibitors have been reported in patients with NSCLC harboring activating mutations that cause MET exon 14 ( METdel14) skipping. We conducted a multicenter retrospective analysis of pts with METdel14 NSCLC to determine if treatment with MET inhibitors impacts survival. Methods: We collected clinicopathologic data on pts with METdel14 NSCLC. Event-time distributions were estimated using Kaplan-Meier and compared with the log-rank test. Multivariable Cox models were fitted to estimate hazard ratios. Results: Of the 148 pts with METdel14 mutant NSCLC, the median age was 72 (range 43-88); 57% were women, and 41% were never smokers. The most common histologies were adenocarcinoma (77%) and pulmonary sarcomatoid carcinoma (14%). Overlap with oncogenic driver mutations in other genes was rare. At the time of diagnosis, 70% of pts had stage I-III disease, and 30% had stage IV disease. Of the 34 pts with metastastic disease who never received a MET inhibitor, the median overall survival (mOS) was 8.1 months. In this cohort, cancers that also had concurrent MET amplification had a trend toward worse survival compared to cancers without MET amplification (5.2 months vs 10.5 months, P = 0.06). Of the 27 pts with metastatic disease who received at least one MET inhibitor (including crizotinib, glesatinib, capmatinib, and ABBV-399), the mOS was 24.6 months. A model adjusting for receipt of a MET inhibitor as first- or second-line therapy as a time-dependent covariate demonstrated that treatment with a MET inhibitor was associated with a significant prolongation in survival (HR 0.11, 95% CI 0.01-0.92, P = 0.04). Among 22 patients treated with crizotinib, the median progression-free survival (PFS) was 7.36 months. Conclusions: Forpts with METdel14 NSCLC, treatment with a MET inhibitor is associated with an improvement in overall survival. The prognosis of pts who never received treatment with a MET inhibitor appears to be poor, particularly among METdel14 cancers with concurrent MET amplification.