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Supplementary Methods, Figure Legend from Optical Detection of Buccal Epithelial Nanoarchitectural Alterations in Patients Harboring Lung Cancer: Implications for Screening

We have recently developed a novel optical technology, partial wave spectroscopic (PWS) microscopy, which is exquisitely sensitive to the nanoarchitectural manifestation of the genetic/epigenetic alterations of field carcinogenesis. Our approach was to screen for lung cancer by assessing the cheek cells based on emerging genetic/epigenetic data which suggests that the buccal epithelium is altered in lung field carcinogenesis. We performed PWS analysis from microscopically normal buccal epithelial brushings from smokers with and without lung cancer (n = 135). The PWS parameter, disorder strength of cell nanoarchitecture (Ld), was markedly (>50%) elevated in patients harboring lung cancer compared with neoplasia-free smokers. The performance characteristic was excellent with an area under the receiver operator characteristic curve of >0.80 and was equivalent for both disease stage (early versus late) and histologies (small cell versus non–small cell lung cancers). An independent data set validated the findings with only a minimal degradation of performance characteristics. Our results offer proof of concept that buccal PWS may potentially herald a minimally intrusive prescreening test that could be integral to the success of lung cancer population screening programs. Cancer Res; 70(20); 7748–54. ©2010 AACR.

Supplementary Figure 1 from Optical Detection of Buccal Epithelial Nanoarchitectural Alterations in Patients Harboring Lung Cancer: Implications for Screening

BACKGROUND: COVID-19 represents a grave risk to residents in skilled nursing facilities (SNFs). OBJECTIVE: To determine whether establishment of an appropriate-use committee was associated with a reduction in SNF utilization. DESIGNS, SETTING, AND PARTICIPANTS: Retrospective cohort study at NorthShore University HealthSystem, a multihospital integrated health system in northern Illinois. Participants were patients hospitalized from March 19, 2019, to July 16, 2020. INTERVENTION: Creation of a multidisciplinary committee to assess appropriateness of discharge to SNF following hospitalization. MAIN OUTCOME AND MEASURES: Primary outcome was total discharges to SNFs. Secondary outcomes were new discharges to SNFs, readmissions, length of stay (LOS), and COVID-19 incidence following discharge. RESULTS: Matched populations pre and post intervention were each 4424 patients. Post intervention, there was a relative reduction in total SNF discharges of 49.7% (odds ratio [OR], 0.42; 95% CI, 0.38-0.47) and in new SNF discharges of 66.9% (OR, 0.29; 95% CI, 0.25-0.34). Differences in readmissions and LOS were not statistically significant. For patients discharged to a SNF, 2.99% (95% CI, 1.59%-4.39%) developed COVID-19 within 30 days, compared with 0.26% (95% CI, 0.29%-0.93%) of patients discharged to other settings (P < .001). CONCLUSION: Implementing a review committee to assess for appropriateness of SNF use after a hospitalization during the COVID-19 pandemic is highly effective. There was no negative impact on safety or efficiency of hospital care, and reduced SNF use likely prevented several cases of COVID-19. This model could serve as a template for other hospitals to reduce the risks of COVID-19 in SNFs and as part of a value-based care strategy.

Purpose This study aims to develop a multi-gene assay predictive of the clinical benefits of chemotherapy in non-small cell lung cancer (NSCLC) patients, and substantiate their protein expression as potential therapeutic targets. Patients and methods The mRNA expression of 160 genes identified from microarray was analyzed in qRT-PCR assays of independent 337 snap-frozen NSCLC tumors to develop a predictive signature. A clinical trial JBR.10 was included in the validation. Hazard ratio was used to select genes, and decision-trees were used to construct the predictive model. Protein expression was quantified with AQUA in 500 FFPE NSCLC samples. Results A 7-gene signature was identified from training cohort (n = 83) with accurate patient stratification (P = 0.0043) and was validated in independent patient cohorts (n = 248, P, Highlights • This paper develops a RT-PCR based 7-gene assay to predict the clinical benefits of chemotherapy for precision oncology • This work discovers a prognostic protein biomarker ZNF71 using AQUA technique as a potential companion test and therapeutic target • This research identifies prognostic mRNA and protein biomarker CD27 with implications in immunotherapy The results from this paper will help clinicians to select NSCLC patients who might benefit from chemotherapy. The identified prognostic protein biomarkers might also be new therapeutic targets in chemotherapy and immunotherapy.

// Shalin Shah 1, * , Kevin Wood 2, * , Brian Labadie 2 , Brian Won 2 , Ryan Brisson 2 , Theodore Karrison 3 , Thomas Hensing 2 , Mark Kozloff 2 , Riyue Bao 4 , Jyoti D. Patel 2 and Jason J. Luke 2 1 Department of Medicine, NorthShore University HealthSystems, Chicago, IL, USA 2 Department of Medicine, University of Chicago, Chicago, IL, USA 3 Department of Public Health Sciences, University of Chicago, Chicago IL, USA 4 Center for Research Informatics and Department of Pediatrics, University of Chicago, Chicago, IL, USA * These authors contributed equally to this work Correspondence to: Jason J. Luke, email: jluke@medicine.bsd.uchicago.edu Keywords: non-small cell lung cancer; anti-PD-1/PD-L1 therapy; acquired resistance; immunotherapy; innate resistance Received: September 04, 2017 Accepted: December 08, 2017 Published: December 15, 2017 ABSTRACT Hypothesis: The majority of non-small cell lung cancer (NSCLC) patients treated with anti-PD-1/PD-L1 therapy develop either innate or acquired resistance. Across tumor types, the "T cell-inflamed" tumor microenvironment correlates with clinical response to immunotherapy. We hypothesize that clinical characteristics may be predictive of resistance and that "T cell-inflamed" NSCLC tumors can be identified by gene expression profiling. Results: Of 93 patients, 36 (38.7%) had innate resistance and 57 (61.3%) had initial benefit to immunotherapy. Innate resistance was associated with non-smokers ( p = 0.013), more involved disease sites ( p = 0.011), more prior therapy ( p = 0.001), and a lower albumin level ( p = 0.014). Among patients with initial benefit, factors associated with subsequent progression-free survival included higher Karnofsky Performance Status (KPS) ( p = 0.004) and lower depth of response to anti-PD-1 therapy ( p = 0.003). A "T cell-inflamed" microenvironment was identified in 42% of TCGA adenocarcinoma samples versus 21.0% of squamous cell. Discussion: Specific clinical characteristics appear to be predictive of either innate or acquired resistance to anti-PD-1/PD-L1 therapy. A "T cell-inflamed" tumor was more common in adenocarcinoma than squamous histology. Methods: A retrospective review of NSCLC patients treated with anti-PD-1/PD-L1 monotherapy. Patients with innate resistance to anti-PD-1/PD-L1 therapy (defined as progression at first CT evaluation) were compared to patients with initial clinical benefit. Among those with initial clinical benefit, we identified prognostic factors for time to progression (acquired resistance) or death. To further corroborate our findings on limited numbers, immune gene expression profiling of all NSCLC samples from the TCGA database was also pursued.

As epidermal growth factor receptor (EGFR) is overexpressed in approximately 90% of squamous cell carcinomas of the head and neck (SCCHN), several therapeutic agents that target EGFR have been evaluated for the treatment of SCCHN. Although patients with SCCHN derive clinical benefit from anti-EGFR agents, most notably the EGFR monoclonal antibody cetuximab, these patients eventually become resistant to EGFR-based therapies; preclinical studies have shown activation of secondary signaling pathways that lead to resistance to EGFR inhibition and, as such, serve as potential therapeutic targets to overcome resistance to EGFR inhibitors.This review summarizes the results of recently completed trials of anti-EGFR agents in SCCHN, highlights the various mechanisms that drive resistance to EGFR inhibitors in SCCHN, and focuses on several novel targeted agents that could potentially help overcome resistance to EGFR-based therapies in SCCHN. Expert commentary: Due to the development of resistance to EGFR-targeted therapies, novel treatment approaches to overcome resistance are a key unmet need for SCCHN.

This study reviews extensive genetic analysis in advanced non-small cell lung cancer (NSCLC) patients in order to: describe how targetable mutation genes interrelate with the genes identified as variants of unknown significance; assess the percentage of patients with a potentially targetable genetic alterations; evaluate the percentage of patients who had concurrent alterations, previously considered to be mutually exclusive; and characterize the molecular subset of KRAS. Thoracic Oncology Research Program Databases at the University of Chicago provided patient demographics, pathology, and results of genetic testing. 364 patients including 289 adenocarcinoma underwent genotype testing by various platforms such as FoundationOne, Caris Molecular Intelligence, and Response Genetics Inc. For the entire adenocarcinoma cohort, 25% of patients were African Americans; 90% of KRAS mutations were detected in smokers, including current and former smokers; 46% of EGFR and 61% of ALK alterations were detected in never smokers. 99.4% of patients, whose samples were analyzed by next-generation sequencing (NGS), had genetic alterations identified with an average of 10.8 alterations/tumor throughout different tumor subtypes. However, mutations were not mutually exclusive. NGS in this study identified potentially targetable genetic alterations in the majority of patients tested, detected concurrent alterations and provided information on variants of unknown significance at this time but potentially targetable in the future.

251 Background: A significant number of cancer-directed therapies are associated with cardiotoxicity. This adverse effect is well-established in anthracyclines and anti-HER2 agents. At our ambulatory oncology practice, the recent availability of echocardiograms with strain imaging has prompted an evaluation of current practices for cardiotoxicity monitoring. A review of the electronic health record (EHR) in 2019 found that although our institution maintains high rates of baseline monitoring, follow-up monitoring is not standardized and not consistent between different practices. Methods: A multidisciplinary team was formed to conduct a quality improvement project with the aim of increasing the rate of follow-up monitoring in patients who receive anthracyclines or infusional anti-HER2 agents. A survey of providers identified the potential reasons that follow-up cardiac monitoring was not completed. A Pareto chart showed that lack of familiarity with clinical necessity and appropriate timing were the most common barriers to follow-up monitoring. Our first plan-do-study-act focused on addressing these barriers, and a pilot in breast cancer treatment plans was started. Cardiac monitoring orders were added to curative intent protocols containing doxorubicin, trastuzumab, or pertuzumab. Education was provided to physician and nursing teams regarding utility and timing of cardiotoxicity monitoring. Collaboration with the cardiology group ensured timely access and result turnaround time. Results: An initial review of the EHR was conducted to identify current trends in cardiac monitoring. The review showed that there was an increase in the use of echocardiograms with strain imaging for baseline and follow-up monitoring in our patients. From January to April 2020, there was a total of 102 echocardiogram orders which was a 23% increase compared to the same timeframe in the previous year. The majority (61%) of those echocardiogram orders included strain imaging compared to 8% in the previous year. Review of treatment plan utilization and appropriate timing of cardiac monitoring in breast cancer patients is ongoing. Conclusions: This quality improvement project suggests that efforts to standardize cardiac monitoring practices can be achieved through provider education and workflow modifications. Further long-term review of the EHR will be needed to determine whether the timing of follow-up monitoring is appropriate and to identify what changes to the intervention should be made.

There have been significant advances in the understanding of the biology and treatment of non-small cell lung cancer (NSCLC) over the past few years. A number of molecularly targeted agents are in the clinic or in development for patients with advanced NSCLC (Table 1). We are beginning to understand the mechanisms of acquired resistance following exposure to tyrosine kinase inhibitors in patients with oncogene addicted NSCLC. The advent of next generation sequencing has enabled to study comprehensively genomic alterations in lung cancer. Finally, early results from immune checkpoint inhibitors are very encouraging. This review summarizes recent advances in the area of cancer genomics, targeted therapies and immunotherapy.

e14128 Background: Immune checkpoint inhibitors (ICIs) are changing the landscape of treatment in oncology. The use of ICIs is growing rapidly as the indications for these medications broaden and new ICIs become approved. Given the rapid growth and relative infancy of the use of ICIs, much information stands to be gained on their use in the clinical practice setting, especially regarding toxicity. Methods: The primary objective of this project was to examine the incidence and severity of immune-related adverse events (irAEs), after treatment with single-agent or combination ICIs at a multi-site community cancer center. A retrospective chart review was conducted on all patients who had received ipilimumab, nivolumab, pembrolizumab, atezolizumab, or ipilimumab plus nivolumab from May 1, 2011 to June 30, 2017. Data collected included patient demographics, disease state, treatment information, preexisting autoimmune disease, previous immunotherapy, and adverse event details. The results were analyzed using descriptive statistics. Results: Data was collected on 383 patients. Dermatologic irAEs were common across single agent ICIs (overall incidence 23%). Diarrhea and/or colitis incidence was highest with CTLA-4 inhibitor ipilimumab (26% at 3 mg/kg and 22% at 10 mg/kg) versus the other monotherapy PD-1/PDL-1 inhibitors. Endocrinopathies were most common with ipilimumab 10 mg/kg (55%) and pneumonitis incidence was highest with nivolumab (6%). ICI toxicity occurred in 63% of patients with preexisting autoimmune disease versus 54% of those without a baseline autoimmune disease. Incidence of hospitalization and treatment holds due to irAEs was higher with combination therapy (57% and 66%, respectively) than with monotherapy (10% and 24%, respectively). Conclusions: Overall, there was increased incidence in ICI toxicity in patients at this oncology institution versus what has been reported in clinical trials. Patients with preexisting autoimmune diseases appeared to have mainly low-grade toxicities with slightly increased incidence of irAE compared with those without pre-existing autoimmune disease. Treatment holds and hospitalizations were higher in patients treated with combination therapy ICIs compared to monotherapy ICIs.

9088 Background: KEYNOTE-024 established single-agent P as a 1st-line option for pts with metastatic NSCLC without targetable alterations and PD-L1 tumor proportion score (TPS) ≥ 50%. KEYNOTE-189 and 407 established concurrent C + P as a treatment option irrespective of PD-L1 expression. In this randomized phase II selection trial, we explored sequencing of C and P in this pt. population. Methods: Eligible pts were randomized 1:1 to (arm A) C (carboplatin (AUC 6) + pemetrexed 500 mg/m2 (non-squamous) or paclitaxel 200 mg/m2 (squamous)) x 4 cycles followed by P 200 mg x 4 cycles, or the reverse sequence (arm B) of P x 4 cycles followed by C x 4 cycles. After 8 cycles, pts on both arms were eligible to receive maintenance P for up to 24 months. Primary endpoint was objective response rate (ORR) per RECIST 1.1 by independent review. Secondary endpoints included progression free survival (PFS) per RECIST 1.1 and overall survival (OS). Efficacy endpoints were also evaluated by PD-L1 expression. Results: 89 pts (47 arm B & 42 arm A) were enrolled and are included in the analysis (PD-L1 TPS 0/1-49%/≥50% = 24 pts (34%)/25 pts (36%)/21 pts (30%)). There was no significant difference in ORR (36% vs 38%, p = 0.829), median PFS (2.7 vs 5.5 months (mo), HR 1.25, 95% CI 0.77-2.02, p = 0.363) or OS (13.1 vs 19.8 mo, HR 1.25, 95% CI 0.69-2.25, p = 0.4573), arm B (Px4→C) vs arm A (Cx4→P). Multivariable Cox regression analysis demonstrated significant interaction between treatment and PD-L1 TPS ( < 50% vs ≥ 50%) for PFS (HR 6.76, 95% CI 2.14-21.35, p = 0.0011) and a trend for OS (HR 5.02, 95% CI 0.92-27.55, p = 0.0632), arm B vs arm A. Incidence of grade ≥3 adverse events was 71% for arm A and 65% for arm B. No new safety signals were observed. Conclusions: In pts with stage IV NSCLC and PD-L1 TPS ≥ 50% there was an observed improvement in PFS and OS in favor of C followed by P vs P x 4 followed by C. Given small # of pts and trial design, this observation should be considered hypothesis-generating, but supports further exploration of sequential C + P in this setting. Support:Merck Sharp & Dohme Corp.; https://acknowledgments.alliancefound.org Clinical trial information: NCT02591615.

e14088 Background: The checkpoint inhibitor (CPI) immunotherapy class of drugs is redefining how we treat cancer. The US FDA has approved CPI drugs as 1st, 2nd or salvage line after progression on conventional chemotherapy (CTX) for multiple cancers including melanoma, lung, bladder and other cancers. However, many questions remain regarding optimal treatment post-progression. Indeed, it has been noted that the patterns of response and relapse to CPI agents are quite different from those of standard cytotoxic agents and that response to CTX AFTER CPI may be different than in the de novo setting. The purpose of this retrospective analysis is to evaluate the activity (response rate (RR), response duration (DOR) and progression free survival (PFS)) of subsequent CTX after disease progression following treatment with CPI. Methods: In this analysis, patients (pts) were enrolled under an IRB approved waiver of consent. We identified pts treated with CPI agents between Jan, 2011 and Dec, 2018 at a multi-site community cancer program who received subsequent CTX as a result of disease progression (PD). We assessed the RECIST RR to subsequent therapy, DOR from onset of response, and PFS from the onset of post CPI CTX, identifying index lesions from the most recent pre-treatment anatomic scan. Results: A total of 47 cases satisfying the above criteria were found; 31 NSCLC, 8 melanoma, 1 SCLC, 1 GEJ, 1 gastric, 2 head/neck, 1 large cell neuroendocrine tumor, 2 bladder cancer. 25 pts had PD as best response to post-CPI CTX. 9 pts (19%) achieved a partial response (PR) with a median DOR of 99 days. 22 pts achieved a PR or stable disease (SD) for a clinical benefit (CB) rate of 47%. The median duration of CB was 92 days. Of the 9 patients who achieved PR, 5/6 had achieved response to CTX prior to CPI . The median PFS for the entire cohort was 97 days. Conclusions: While an expected RR could not be calculated in this heterogenous group of pts, the number and degree of responses suggests CPI possible “priming” that may enhance response to CTX. Post-CPI CTX may be of value and in this retrospective study of a heterogenous group of pts, responses may be more frequent than expected. A larger further study is warranted.

Lessons Learned Adding docetaxel to the modified FOLFOX7 backbone (DOF) is a feasible three-drug combination therapy for advanced gastric cancer with high activity, providing evidence that leucovorin is not necessary in this setting. The DOF regimen represents an alternative to the FLOT (5-FU 2,600 mg/m2 as 24-hour infusion with leucovorin 200 mg/m2, oxaliplatin 85 mg/m2, and docetaxel 50 mg/m2) regimen that can be considered in select patients with advanced gastric cancer and is a potential choice in the curative setting. Background The combination of docetaxel, cisplatin, and 5-fluorouracil (5-FU) demonstrates high response rates in advanced gastric cancer, albeit with increased toxicity. Given the efficacy of platinum-taxane-fluoropyrimidine regimens, this phase II study evaluated the efficacy and toxicity of docetaxel, oxaliplatin, and 5-FU (DOF) for the treatment of metastatic or unresectable gastric or gastroesophageal junction (GEJ) adenocarcinoma. Methods Patients with metastatic or unresectable gastric or GEJ adenocarcinoma with no prior therapy for metastatic disease received docetaxel 50 mg/m2 on day 1, oxaliplatin 85 mg/m2 on day 1, and 5-FU 2,400 mg/m2 continuous intravenous infusion over 46 hours; cycles were repeated every 2 weeks. The primary endpoint was overall response rate (ORR). Results Forty-four patients were enrolled. Assessment of treatment response and toxicity was feasible in 41 and 43 patients, respectively. ORR was 73.2% (68.3% partial response; 4.9% complete response). Therapy was discontinued for progressive disease in 53%, toxicity in 26%, and death on treatment in 16%. Two patients underwent surgical resection. Thirty-three patients (76.7%) received at least seven cycles (7–34). Grade 3–4 toxicities occurred in 31 patients (72.1%), including neutropenia (23.3%), neurologic (20.9%), and diarrhea (14.0%). Median overall survival was 10.3 months. Conclusion DOF demonstrates a high response rate, expected safety profile, and prolonged survival and remains an option for select patients with unresectable or metastatic gastric or GEJ adenocarcinoma.

Objective: An increasing amount of clinical data is available to biomedical researchers, but specifically designed database and informatics infrastructures are needed to handle this data effectively. Multiple research groups should be able to pool and share this data in an efficient manner. The Chicago Thoracic Oncology Database Consortium (CTODC) was created to standardize data collection and facilitate the pooling and sharing of data at institutions throughout Chicago and across the world. We assessed the CTODC by conducting a proof of principle investigation on lung cancer patients who took erlotinib. This study does not look into epidermal growth factor receptor (EGFR) mutations and tyrosine kinase inhibitors, but rather it discusses the development and utilization of the database involved. Methods: We have implemented the Thoracic Oncology Program Database Project (TOPDP) Microsoft Access, the Thoracic Oncology Research Program (TORP) Velos, and the TORP REDCap databases for translational research efforts. Standard operating procedures (SOPs) were created to document the construction and proper utilization of these databases. These SOPs have been made available freely to other institutions that have implemented their own databases patterned on these SOPs. Results: A cohort of 373 lung cancer patients who took erlotinib was identified. The EGFR mutation statuses of patients were analyzed. Out of the 70 patients that were tested, 55 had mutations while 15 did not. In terms of overall survival and duration of treatment, the cohort demonstrated that EGFR-mutated patients had a longer duration of erlotinib treatment and longer overall survival compared to their EGFR wild-type counterparts who received erlotinib. Discussion: The investigation successfully yielded data from all institutions of the CTODC. While the investigation identified challenges, such as the difficulty of data transfer and potential duplication of patient data, these issues can be resolved with greater cross-communication between institutions of the consortium. Conclusion: The investigation described herein demonstrates the successful data collection from multiple institutions in the context of a collaborative effort. The data presented here can be utilized as the basis for further collaborative efforts and/or development of larger and more streamlined databases within the consortium.

38 Background: To meet Commission on Cancer accreditation requirements, cancer programs must implement processes to monitor the dissemination of survivorship care plans (SCP) for patients with Stages I-III cancers who were treated with curative intent and completed active therapy. Challenges of SCP delivery across disease sites include lack of designated/trained staff, time burden, knowledge of current evidence-based guidelines, and sustainability. We describe the challenges NorthShore University HealthSystem Kellogg Cancer Center (NKCC) and their Living in the Future (LIFE) Cancer Survivorship Program faced in meeting this standard and how evolving the SCP delivery process has resulted in a sustainable model. Methods: LIFE implemented a technology-based SCP tool using a centralized consultative model led by a nurse practitioner (NP) with specialized survivorship training. Physicians referred eligible patients to the survivorship clinic for an education visit where they received a SCP from the NP. Since the centralized model was dependent on one person for delivery, a more sustainable model was needed. NKCC transitioned to a decentralized process, moving SCP creation and delivery responsibility to all oncology care providers (OCPs). Although not all OCPs had specialized survivorship training, care quality was supported by automated SCP creation based on evidence-based care recommendations embedded in the technology. Results: To date, 143 evidence-based SCPs have been delivered since tool implementation in April 2017. During the centralized model (April 25– June 30) 67 SCPs were created by the lead LIFE NP; 76 were created during the decentralized process while the lead NP was on leave (July 3 – Oct 1). By using a technology-based SCP, OCPs incorporated SCP delivery into their workflow and no longer had to refer patients to a separate clinic. Conclusions: This project demonstrates the feasibility of a sustainable, decentralized process using a technology-based SCP as an option for augmenting centralized SCP delivery. A comparable number of patients received a SCP during both processes with an equivalent number of SCPs being delivered via the decentralized model by OCPs supported by evidence-based technology.

For patients with non-small cell lung cancer (NSCLC) to benefit from ALK inhibitors, sensitive and specific detection of ALK genomic rearrangements is needed. ALK break-apart fluorescence in situ hybridization (FISH) is the U.S. Food and Drug Administration approved and standard-of-care diagnostic assay, but identification of ALK rearrangements by other methods reported in NSCLC cases that tested negative for ALK rearrangements by FISH suggests a significant false-negative rate. We report here a large series of NSCLC cases assayed by hybrid-capture-based comprehensive genomic profiling (CGP) in the course of clinical care.Hybrid-capture-based CGP using next-generation sequencing was performed in the course of clinical care of 1,070 patients with advanced lung cancer. Each tumor sample was evaluated for all classes of genomic alterations, including base-pair substitutions, insertions/deletions, copy number alterations and rearrangements, as well as fusions/rearrangements.A total of 47 patients (4.4%) were found to harbor ALK rearrangements, of whom 41 had an EML4-ALK fusion, and 6 had other fusion partners, including 3 previously unreported rearrangement events: EIF2AK-ALK, PPM1B-ALK, and PRKAR1A-ALK. Of 41 patients harboring ALK rearrangements, 31 had prior FISH testing results available. Of these, 20 were ALK FISH positive, and 11 (35%) were ALK FISH negative. Of the latter 11 patients, 9 received crizotinib based on the CGP results, and 7 achieved a response with median duration of 17 months.Comprehensive genomic profiling detected canonical ALK rearrangements and ALK rearrangements with noncanonical fusion partners in a subset of patients with NSCLC with previously negative ALK FISH results. In this series, such patients had durable responses to ALK inhibitors, comparable to historical response rates for ALK FISH-positive cases.Comprehensive genomic profiling (CGP) that includes hybrid capture and specific baiting of intron 19 of ALK is a highly sensitive, alternative method for identification of drug-sensitive ALK fusions in patients with non-small cell lung cancer (NSCLC) who had previously tested negative using standard ALK fluorescence in situ hybridization (FISH) diagnostic assays. Given the proven benefit of treatment with crizotinib and second-generation ALK inhibitors in patients with ALK fusions, CGP should be considered in patients with NSCLC, including those who have tested negative for other alterations, including negative results using ALK FISH testing.

Fractals are mathematical constructs that show self-similarity over a range of scales and non-integer (fractal) dimensions. Owing to these properties, fractal geometry can be used to efficiently estimate the geometrical complexity, and the irregularity of shapes and patterns observed in lung tumour growth (over space or time), whereas the use of traditional Euclidean geometry in such calculations is more challenging. The application of fractal analysis in biomedical imaging and time series has shown considerable promise for measuring processes as varied as heart and respiratory rates, neuronal cell characterization, and vascular development. Despite the advantages of fractal mathematics and numerous studies demonstrating its applicability to lung cancer research, many researchers and clinicians remain unaware of its potential. Therefore, this Review aims to introduce the fundamental basis of fractals and to illustrate how analysis of fractal dimension (FD) and associated measurements, such as lacunarity (texture) can be performed. We describe the fractal nature of the lung and explain why this organ is particularly suited to fractal analysis. Studies that have used fractal analyses to quantify changes in nuclear and chromatin FD in primary and metastatic tumour cells, and clinical imaging studies that correlated changes in the FD of tumours on CT and/or PET images with tumour growth and treatment responses are reviewed. Moreover, the potential use of these techniques in the diagnosis and therapeutic management of lung cancer are discussed.

The LIFE Cancer Survivorship Program at NorthShore University HealthSystem provides risk-adapted visits (RAV) facilitated by an oncology nurse during which a survivorship care plan (SCP) is provided and discussed. In this report, we describe and evaluate RAV in promoting individualized health care and self-management during survivorship transition. Patients complete a post-RAV questionnaire at their RAV and another ≥1 year after their RAV. One thousand seven hundred thirteen (1713) RAVs, majority for breast cancer, occurred from January 2007 to March 2014. One thousand six hundred fifteen (1615) “day-of” post-RAV questionnaires were completed. Respondents scaled statements as strongly agree/agree/disagree/strongly disagree. Combined strongly agree/agree ratings are 94 % felt more confident in communicating information about their treatments to other health care providers, 90 % felt more comfortable recognizing signs/symptoms to report to providers, and 98 % had a better appreciation for community programs/services. Of 488 respondents (RAV January 2007 to December 2012 n = 1366) to a questionnaire at least 1 year after the RAV, nearly 100 % found SCP useful to summarize medical information, 97 % to reinforce follow-up, 85 % to recognize symptoms of recurrence, 93 % to identify healthy lifestyle practices, 91 % to assist in identifying resources for support, 72 % discussed their SCP with their healthcare provider, and 97 % made at least one positive lifestyle change. Participation in LIFE RAV following treatment helps survivors to guide future self-care behavior. Data suggest that benefits may persist 1 year after the visit and support the feasibility of a nurse-led RAV to establish a SCP in cancer survivors. Combined provision and discussion of SCPs help survivors construct a useful understanding of their cancer experience and may promote long-term self-management.

114 Background: Due to escalating cost of cancer care, patients (PTs) with cancer are at increased risk for financial toxicity (FTOX) that can exacerbate disparities in care and lead to clinically relevant adverse PT outcomes; including quality of life; symptom burden; adherence; and survival. A review of our informed consent (IC) process demonstrated that PTs were not routinely informed of financial risks of high-cost (HC) cancer therapies at the time of IC. Methods: A multidisciplinary team was formed to conduct a rapid-cycle quality improvement project with the aim of reducing FTOX through improvement in patient education at the time of IC. Because of HC and increased utilization, the initial pilot focused on treatment with immune checkpoint inhibitors (ICI). A cause and effect diagram identified the potential causes that FTOX was not addressed during the IC process. Diagnostic data were obtained through staff surveys and querying our EMR from June to August, 2016. A Pareto chart identified lack of educational (ED) tools at the time of IC and a poorly understood prior authorization (PA) process as the most common causes for not addressing risk of FTOX during IC. Plan-do-study-act (PDSA) #1 began with development of a PT ED tool to be used during IC. The tool was approved by the Patient Advisory Board. Staff from clinical teams utilizing ICI for approved indication completed training on its use and a pilot study was initiated. PDSA#2 focused on optimizing the PA process and PDSA#3 focused on PT distress and FTOX monitoring through the NCCN distress and a validated patient-reported-outcome tools (COST), respectively. Results: The utilization of the PT ED tool reached the project aim (administer to > 65% of pts during IC) during initial phase of PDSA#1, although accrual is ongoing. A revised PA process (PDSA#2) was developed, staff were educated and the updated PA process was initiated. Work on PDSA#3 is ongoing. Conclusions: This QI project suggests that it is feasible to address FTOX through PT ED during IC for HC cancer therapies. However, the impact of this intervention on PT distress, overall FTOX and treatment disparities will need to be monitored closely.

97 Background: Node positive disease (N+) is frequent (~40%) following neoadjuvant therapy (NAT) and esophagectomy, yet limited data exist regarding the efficacy of adjuvant chemotherapy (AC) in this setting. There are no randomized studies addressing this question and single-institution, retrospective studies have reported mixed findings. Methods: A retrospective analysis was conducted using the National Cancer Database. 2,258 N+ patients were identified who had received NAT (83.3% chemoradiation and 17.7% chemotherapy alone) followed by esophagectomy. Patients with either incomplete staging or treatment data were excluded, as were those who died within 90 days following esophagectomy. Multivariate logistic regression was used to test for differences in patient characteristics between those who did (AC+) or did not (AC-) receive AC. Overall survival (OS) after surgery, by AC status, was analyzed using Cox regression in a sample propensity matched on relevant demographic and clinical factors. Results: 433/2258 patients received AC (19.2%). Patients who received AC tended to be younger (OR 0.98 per 1-year increase, P = .03) and had a higher socioeconomic status (SES) (OR 1.47 for high vs. low SES, P = .01). Although there were no significant differences in comorbidity (P = .32), AC+ patients had significantly shorter hospital stays after surgery (OR 0.98 per 1-day increase, P = .03). Pathologic T classification was unrelated to the likelihood of receiving AC (P = .39), however patients with a higher pathologic N stage were more likely receive AC (OR 2.12 for pN3 vs. pN1, P < .001). Those receiving AC had demonstrably longer OS from the time of surgery than those who did not (HR 0.78, P = .004). Median OS for the entire cohort was 22.6 months, whereas the administration of AC was associated with an improvement in median OS of 6.2 months (26.3 vs. 20.1 months). Conclusions: This retrospective analysis indicates that AC is associated with a significant improvement in OS (median 6.2 months) in N+ patients following NAT and esophagectomy. Further studies are needed to clarify the optimal role of AC in this setting.

Importance Lung cancer is the leading cause of cancer deaths worldwide, with non–small-cell lung cancer (NSCLC) constituting more than 80% of all lung cancers. Non–small-cell lung cancer is a heterogenous disease, with multiple different oncogenic driver mutations representing possible therapeutic targets. The vi-Ki-ras2 Kirsten rat sarcoma viral oncogene ( KRAS ) represents one of the most common oncogenic driver mutations. Unfortunately, targeted therapies thus far have been unsuccessful. Objective To discuss current advancements in understanding the prognostic and predictive value of KRAS in NSCLC and explaining the treatment advancements in both the preclinical and clinical setting. Evidence Review PubMed, Cochrane Library, and Google Scholar databases were searched through February 1, 2016. English-language peer-reviewed articles published between 1964 and 2016 were found using the keywords “ RAS ,” “ KRAS ,” “NSCLC,” “synthetic lethality,” “oncogenic driver mutations,” “clinical trials,” and “phase 3 clinical trials.” Abstracts at scientific meetings were not excluded. Of 112 records idetified, 61 articles or studies were included in qualitative synthesis for this review. Findings The KRAS oncogenic driver mutation is noted in 15% to 25% of patients with NSCLC.While there has been limited success in inhibiting the protein directly, phase 2 and phase 3 clinical trials have demonstrated success in inhibiting downstream effectors, specifically MEK1 and/or MEK2 with selumetinib and trametinib (albeit with poor tolerability). Current clinical trials are evaluating inhibiting downstream effector pathways for improved efficacy. In the laboratory, the success of synthetic lethal approaches suggests another possible direction for future clinical trials. Conclusions and Relevance KRAS is one of the most common oncogenic driver mutations in NSCLC, with prior attempts at direct inhibition being unsuccessful. In recent years, there has been significant advancement in the understanding of the biology of KRAS and its downstream effectors. This has translated into a multitude of important preclinical studies and clinical trials that are currently underway to find effective therapeutic drugs for KRAS mutant lung cancer. Ultimately, better therapeutics need to be engineered to arrive at RAS -driven precision medicine.

8565Background: Small-cell lung cancer (SCLC) is the most aggressive subtype of lung cancer. Treatment options have not significantly changed over the past 3 decades and the 5-year survival has rem...

159 Background: Approval of new oral anticancer agents (OAA) continues to rise, accounting for 75% of new oncology drugs approved so far in 2015. OAA prescriptions generated at our institution demonstrate similar growth, as the prescription volume for OAA is approximately 200% greater than it was 8 years ago. Challenges of OAA, including safe prescribing, monitoring toxicities, and assessing adherence, continue to be an obstacle to providing quality care. In recognition of these challenges, our institution employed the electronic medical record (EMR) to develop tools to enhance safe prescribing, monitoring, and follow up for patients receiving OAA. Methods: Comprehensive, regimen-specific, OAA protocols were built in the EMR using the American Society of Clinical Oncology’s Quality Oncology Practice Initiative criteria as a guide. Protocols included OAA prescriptions, laboratory tests, monitoring communications, supportive care medications, plan for follow up, and a monitoring order. The monitoring order, dated 7 to 10 days after the start of each cycle, was utilized to identify patients for follow up, and as a documentation tool. During follow up calls, pharmacists provided education, addressed adherence and toxicities, and communicated findings to team members. The initial analysis focused on six of the most commonly prescribed OAA agents at our institution. Results: Cycle 1 follow up calls were placed for 115 new start OAA patients. Over half of the patients (56.5%) required an intervention (ex: symptom management, alerting the medical team, counseling). Eleven patients had barriers to adherence (ex: confusion, incorrect technique, cost, obtaining insurance coverage, and toxicity). Overall, 98% of patients verbalized appropriate adherence. There were 191 subsequent follow up efforts, after the cycle 1 follow up call, which resulted in 39 interventions (20%). Conclusions: OAA requires the same intensive monitoring and follow up as IV chemotherapy, but is more difficult to provide given the nature of administration of these medications. Utilizing the EMR to develop prescribing and monitoring tools can help address these challenges by providing a means for enhanced documentation and follow up.