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Context.--Precision therapies for patients with driver mutations can offer deep and durable responses that correlate with diagnosis, metastasis prognosis, and improvement in survival. The use of such targeted therapies will continue to increase, pushing us to change our traditional approaches. We needed to search for new tools to effectively integrate technological advancements into our practices because of their capability to improve the efficiency and accuracy of our diagnostic and treatment approaches. Perhaps nothing is as relevant as identifying and implementing new workflows for processing pathologic specimens and for improving communication of critical laboratory information to and from clinicians for appropriate care of patients in an efficient and timely manner. Objectives.--To define the gold standard in delivering the best care for patients, to identify gaps in the process, and to identify potential solutions that would improve our process, including gaps related to knowledge, skills, attitudes, and practices. Design.--We assembled a multidisciplinary team to systematically perform a gap analysis study to clarify the discrepancy between the current reality in pathology specimen processing and the desired optimal situation to deliver the results intended for patient care. Results.--A practical collaborative workflow for specimen management that seeks the cooperation of stakeholders in each medical discipline to provide guidelines in specimen collection, delivery, processing, and reporting of results with the ultimate goal of improving patient outcomes is provided. Conclusions.--New tools are required to effectively integrate data-driven approaches in specimen processing to meet the new demands. (Arch Pathol Lab Med. 2022;146:603-610; doi: 10.5858/arpa.2021-0089-OA), As changes in the new standard of care are upon us, health care providers are faced with numerous complex challenges to establish systematic and data-driven approaches to meet the new [...]

Aim: Compare healthcare costs for patients with epidermal growth factor receptor mutated (EGFRm) metastatic non-small-cell lung cancer (mNSCLC) with and without progression and estimate costs of progression. Materials & methods: Retrospective claims analysis (2015–2020) from adults with EGFRm mNSCLC initiating EGFR tyrosine kinase inhibitors. Adjusted costs for 12 months were compared (with vs without progression) and cumulative costs for early versus late progression were predicted over 36 months. Results: A total of 228 patients with EGFRm mNSCLC were included. Patients with progression within 12 months incurred significantly higher total costs despite lower treatment costs (vs without progression). Medical costs were significantly higher among early versus late progressors. Conclusion: These data may aid providers aiming to administer quality care in a cost-efficient way. Plain Language Summary Lung cancer is the leading cause of cancer death among both men and women in the US. Among US patients with adenocarcinoma histology, approximately 17% have epidermal growth factor activating mutations (EGFRm) that include exon 19 deletions or L858R mutations. These common mutations make up approximately 85% of all EGFR mutations. The aim of this study was to compare healthcare resource utilization and costs for patients with EGFRm metastatic non-small-cell lung cancer with and without disease progression within the first 12 months following first-line treatment initiation using data from insurance claims. The results suggest that patients with EGFRm metastatic non-small-cell lung cancer with disease progression in the first 12 months (after treatment initiation) have significantly higher costs compared with patients without disease progression in the first 12 months (and highest in the first 6 months). These data may help inform oncology providers aiming to administer high quality cancer care in a cost-efficient way. Article highlights Patients with non-small-cell lung cancer face a high burden of healthcare costs, especially when the disease progresses. This was a retrospective study using administrative claims data of 228 adult patients with epidermal growth factor receptor mutated (EGFRm) metastatic non-small-cell lung cancer (mNSCLC) that initiated a first-line EGFR tyrosine kinase inhibitor (TKI) between 2015 and 2020. Healthcare costs were captured during the first 12 months after treatment initiation in patients with and without disease progression, and cumulative costs were predicted over 36 months for patients with early (post initiation months 0–6) versus late (post initiation months 7–12) disease progression. There were 152 (66.7%) patients whose disease progressed at any time during the 12 months after treatment initiation; 101 (66.4%) patients had early progression and 51 (34.2%) had late progression. Patients with any disease progression had greater healthcare resource utilization compared with patients whose disease did not progress during follow-up. Adjusted mean total healthcare costs were statistically significantly higher for patients with any progression compared with those without progression, mainly driven by inpatient costs. Adjusted monthly predicted cumulative costs were significantly higher among patients who progressed early compared with those that progressed late. Study limitations include lack of biomarker and histology data from claims data, misclassification of metastatic disease status and specific EGFR mutations based on coding errors and limited generalizability. This studies provides real-world costs of patients with EGFRm mNSCLC that initiate a TKI whose disease progresses in a 12-month time period; the cost burden was highest among patients with disease progression in the first 6 months after treatment initiation. This study highlights the importance of delaying EGFRm mNSCLC disease progression in a timely manner. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) and poly (ADP-ribose) polymerase (PARP) inhibitors have shown efficacy in various tumors. A significant therapeutic challenge with either ICIs or PARP inhibitors as monotherapy is treatment failure from intrinsic primary resistance or the development of secondarily acquired resistance after a period of responsiveness. The combination of PARP inhibitors and ICIs could mitigate this by potentiating treatment response. We describe an 83-year-old male patient who initially presented with abdominal pain, and weight loss along with alternating constipation and diarrhea. Imaging and biopsy revealed metastatic esophageal adenocarcinoma. Genomic testing revealed germline BRCA2 mutation. The patient initially underwent a few cycles of chemoimmunotherapy. However, due to intolerance to chemotherapy, the patient's case was discussed at a multidisciplinary molecular tumor board. He was switched to PARP inhibitor olaparib and ICI nivolumab. This combination led to a durable complete response. A combination of poly-ADP ribose polymerase inhibitor (PARPi) plus ICI may work in synergy through various mechanisms including enhanced neoantigen expression, release of immune-activating cytokines, and increased programmed death-ligand 1 expression. This may culminate in accentuated efficacy outcomes with a manageable safety profile. This exceptional response with ICI and PARPi in our case is consistent with the synergistic value of this combination, and prospective studies are warranted to definitively characterize clinical utility. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune-related adverse events (irAEs) are one of the most common complications after cancer treatment caused by immune checkpoint inhibitors (ICIs). We performed an extensive review of the potential tests to predict irAEs in patients who receive ICIs. Approximately 40% of patients who receive ICIs experience irAEs. Despite this, only thyroid function tests are currently in mainstream use for predicting who will experience the adverse effects (namely, thyroid function abnormalities) from ICI treatment. A significant amount of research has paved the way for further potential tests that can be used in the clinic, but none have been meaningfully implemented in clinical practice. Nonetheless, further research on identifying these tests and incorporating them into clinical practice to help predict irAEs for patients with cancer will be significant in the field of ICI therapy. Immune-related adverse events (irAEs) are the most common complication of immune checkpoint inhibitor (ICI) therapy. With the widespread use of ICIs in patients with solid tumors, up to 40% of the patients develop irAEs within five months of treatment, and 11% develop severe irAEs requiring interventions. A predictive test for irAEs would be a crucial tool for monitoring for complications during and after ICI therapy. We performed an extensive review of potential predictive biomarkers for irAEs in patients who received ICI therapy. Currently, only thyroid-stimulating hormone is utilized in common clinical practice. This is due to the unavailability of commercial tests and unclear predictive values from various studies. Given the lack of single strong predictive biomarkers, some novel approaches using composite scores using genomic, transcriptomics, cytokine levels, or clinical parameters appear appealing. Still, these have yet to be validated and incorporated into clinical practice. Further research conducted to validate the models before implementing them into real-world settings will be of the utmost importance for irAE prediction. [ABSTRACT FROM AUTHOR]

Background: Mutations in kinases are the most frequent genetic alterations in cancer; however, experimental evidence establishing their cancerous nature is available only for a small fraction of these mutants. Aims: Predicition analysis of kinome mutations is the primary aim of this study. Further objective is to compare the performance of various softwares in pathogenicity prediction of kinase mutations. Materials and methods: We employed a set of computational tools to predict the pathogenicity of over forty‐two thousand mutations and deposited the kinase‐wise data in Mendeley database (Estimated Pathogenicity of Kinase Mutants [EPKiMu]). Results: Mutations are more likely to be drivers when being present in the kinase domain (vs. non‐kinase domain) and belonging to hotspot residues (vs. non‐hotspot residues). We identified that, while predictive tools have low specificity in general, PolyPhen‐2 had the best accuracy. Further efforts to combine all four tools by consensus, voting, or other simple methods did not significantly improve accuracy. Discussion: The study provides a large dataset of kinase mutations along with their predicted pathogenicity that can be used as a training set for future studies. Furthermore, a comparative sensitivity and selectivity of commonly used computational tools is presented. Conclusion: Primary‐structure‐based in silico tools identified more cancerous/deleterious mutations in the kinase domains and at the hot spot residues while having higher sensitivity than specificity in detecting deleterious mutations. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have revolutionized treatment for patients with non-small lung cancer (NSCLC). Currently approved ICIs are monoclonal antibodies that target programmed death receptor 1 (PD-1), its ligand PD-L1, or CTLA-4. With ICIs comes a novel collection of toxicities: immune-related adverse events (IRAEs). Management of IRAEs requires multidisciplinary expertise. We review the biology of IRAEs and their management in patients with squamous NSCLC. We review the pathophysiology of ICIs and IRAEs. For IRAEs related to squamous NSCLC, Cochrane Central, EMBASE, and PubMed were queried for trials with patients with squamous cell carcinoma or adenocarcinoma histology, who were assessed for incidence rates of IRAEs. Thirteen trials met inclusion criteria. National guidelines are reviewed to outline management strategies for IRAEs. IRAEs are unique compared to standard chemotherapy. As the role of ICIs expand across all stages of squamous cell NSCLC and with different combinations of antineoplastics, management of IRAEs will become crucial. Optimal management of IRAEs requires multidisciplinary teamwork. Further investigation into the pathophysiology of IRAEs can enhance current management strategies. [ABSTRACT FROM AUTHOR]

Chemotherapy‐induced myelosuppression is an acute, dose‐limiting toxicity of chemotherapy regimens used in the treatment of extensive‐stage small cell lung cancer (ES‐SCLC). Trilaciclib protects haematopoietic stem and progenitor cells from chemotherapy‐induced damage (myeloprotection). To assess the totality of the myeloprotective benefits of trilaciclib, including analysis of several clinically relevant but low‐frequency events, an exploratory composite endpoint comprising five major adverse haematological events (MAHE) was prospectively defined: all‐cause hospitalisations, all‐cause chemotherapy dose reductions, febrile neutropenia (FN), prolonged severe neutropenia (SN) and red blood cell (RBC) transfusions on/after Week 5. MAHE and its individual components were assessed in three randomised, double‐blind, placebo‐controlled Phase 2 trials in patients receiving a platinum/etoposide or topotecan‐containing chemotherapy regimen for ES‐SCLC and in data pooled from the three trials. A total of 242 patients were randomised across the three trials (trilaciclib, n = 123; placebo, n = 119). In the individual trials and the pooled analysis, administering trilaciclib prior to chemotherapy resulted in a statistically significant reduction in the cumulative incidence of MAHE compared to placebo. In the pooled analysis, the cumulative incidences of all‐cause chemotherapy dose reductions, FN, prolonged SN and RBC transfusions on/after Week 5 were significantly reduced with trilaciclib vs placebo; however, no significant difference was observed in rates of all‐cause hospitalisations. Additionally, compared to placebo, trilaciclib significantly extended the amount of time patients remained free of MAHE. These data support the myeloprotective benefits of trilaciclib and its ability to improve the overall safety profile of myelosuppressive chemotherapy regimens used to treat patients with ES‐SCLC. [ABSTRACT FROM AUTHOR]

Introduction: Non-small cell lung cancer (NSCLC), which accounts for the majority of lung cancer diagnoses in the United States, has many known driver mutations, including MET exon 14 skipping mutation (METex14). The detection of oncogenic driver mutations in NSCLC and the development of drugs to target these alterations, including METex14, has created the need for accurate and reliable testing, of which next-generation sequencing (NGS) is the gold standard. However, detection of METex14 in patients with NSCLC can be challenging due to the complex biology of METex14 and the abilities of different NGS platforms to detect METex14. Areas covered: This review provides an overview of METex14 biology, discusses the optimal platforms for the detection of METex14 in NSCLC, and provides an overview of the use of NGS in the community setting. Expert opinion: Broad molecular testing is crucial for identifying actionable oncogenic drivers in NSCLC. METex14 is a complex oncogenic driver mutation requiring carefully optimized platforms for proper detection. To identify patients eligible for targeted therapies – including therapies targeting novel oncogenic drivers, such as MET inhibitors – community oncologists need to be aware of both the use of NGS platforms and the differences in their capabilities to detect certain oncogenic drivers. [ABSTRACT FROM AUTHOR]

• 12% of EGFRm NSCLC patients treated with 1L 1st/2nd-generation EGFR-TKIs had SAEs. • SAEs with the largest burden in healthcare costs were MAHA, hepatotoxicity and ILD. • The economic burden of SAEs due to 1st/2nd-generation EGFR-TKIs is substantial. • Awareness is needed among treating oncologists about the risk of SAEs in NSCLC. • EGFR-TKIs with more favorable safety profiles may ease the burden of managing NSCLC. Clinical trials with first- and second-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) reported severe adverse events (SAEs) in 6%–49% of patients with EGFR-mutated non-small cell lung cancer. This study describes incremental healthcare resource utilization (HRU) and costs associated with real-world management of AEs in this population, with a focus on SAEs. Patients receiving erlotinib, gefitinib, or afatinib as first-line (1L) monotherapy were identified from IQVIA™ Real-World Data Adjudicated Claims–US database (04/01/2012–03/31/2017). Relevant AEs were selected from corresponding prescribing information; SAEs were identified from hospitalization claims. HRU and cost per-patient-per-month (PPPM) were assessed during 1L treatment and compared for patients with and without each AE using multivariate Poisson and linear regression, respectively, adjusting for baseline characteristics. Of 1646 patients, 86.9% were treated with erlotinib, 12.1% with afatinib, and 1.0% with gefitinib. In 1L, 12.2% of patients had ≥1 acute SAE (220.1/1000 patient-years). Patients with any SAE had higher PPPM costs than patients without SAEs (cost difference = $4700, p < 0.001). Incremental costs ranged from $2604 PPPM for diarrhea to $10,143 PPPM for microangiopathic hemolytic anemia (MAHA), and were statistically significant for all SAEs (all p < 0.001) except MAHA (p < 0.0528). Patients with any SAEs had higher rates of HRU relative to patients without SAEs (hospitalization rate ratio = 6.15; outpatient visits rate ratio = 1.21; all p < 0.001). More than one-tenth of patients experienced SAEs, resulting in sizeable economic burden with respect to HRU and costs. EGFR-TKIs with more favorable safety profiles may reduce the burden of managing this population. [ABSTRACT FROM AUTHOR]

The oncogenic role ERBB2 amplification is well established in breast and gastric cancers. This has led to the development of a well‐known portfolio of monoclonal antibodies and kinase inhibitors targeting the ERBB2 kinase. More recently, activating mutations in the ERBB2 gene have been increasingly reported in multiple solid cancers and were shown to play an oncogenic role similar to that of ERBB2 amplification. Thus, ERBB2 mutations define a distinct molecular subtype of solid tumors and serve as actionable targets. However, efforts to target ERBB2 mutation has met with limited clinical success, possibly because of their low frequency, inadequate understanding of the biological activity of these mutations, and difficulty in separating the drivers from the passenger mutations. Given the current impetus to deliver molecularly targeted treatments for cancer, there is an important need to understand the therapeutic potential of ERBB2 mutations. Here we review the distribution of ERBB2 mutations in different tumor types, their potential as a novel biomarker that defines new subsets in many cancers, and current data on preclinical and clinical efforts to target these mutations. Implications for Practice: A current trend in oncology is to identify novel genomic drivers of solid tumors and developing precision treatments that target them. ERBB2 amplification is an established therapeutic target in breast and gastric cancers, but efforts to translate this finding to other solid tumors with ERBB2 amplification have not been effective. Recently the focus has turned to targeting activating ERBB2 mutations. The year 2018 marked an important milestone in establishing ERBB2 mutation as an important actionable target in multiple cancer types. There have been several recent preclinical and clinical studies evaluating ERBB2 mutation as a therapeutic target with varying success. With increasing access to next‐generation sequencing technologies in the clinic, oncologists are frequently identifying activating ERBB2 mutations in patients with cancer. There is a significant need both from the clinician and bench scientist perspectives to understand the current state of affairs for ERBB2 mutations. Considering the current impetus to deliver molecularly targeted treatments for cancer, a better understanding of the therapeutic potential of ERBB2 mutations is needed. This article reviews the distribution of ERBB2 mutations in different tumor types, focusing on potential as a novel biomarker. [ABSTRACT FROM AUTHOR]

Introduction: Epidermal growth factor receptor (EGFR) mutations are well-described drivers of non-small cell lung cancer (NSCLC) and EGFR tyrosine kinase inhibitors (TKIs) have become key components of the NSCLC front-line treatment landscape. Tumors inevitably develop resistance to these agents, and development efforts continue to focus on identifying mechanisms of resistance and drugs to target these mechanisms. Areas covered: With several EGFR TKIs approved for use in the first-line or in later-line settings, an understanding of the efficacy and safety of these inhibitors in various populations is warranted. Furthermore, given the frequent emergence of drug resistance in NSCLC, examination of tumor tissue throughout the disease course provides the opportunity to select treatments based on the tumor's mutation profile. Here, we discuss: key efficacy and safety findings for approved and investigational EGFR TKIs; known mechanisms of resistance, particularly the T790M acquired EGFR mutation; and recent advances in EGFR mutational testing that may facilitate less invasive tissue testing and guide treatment selection. Expert commentary: The expanding armamentarium of EGFR TKIs, improvements in the understanding of resistance mechanisms and technological developments in the molecular analysis of tumors may help render EGFR mutation-positive NSCLC a chronic disease in many patients by facilitating optimal sequential therapy. [ABSTRACT FROM AUTHOR]

The standard of care treatment for locally advanced nasopharyngeal carcinoma (NPC) includes both chemotherapy and definitive radiation. However, there are limited data on the optimal management of stage II NPC. We performed a retrospective analysis of the National Cancer Database to analyze the treatment patterns and role of chemotherapy in patients with stage II NPC. We identified 611 patients diagnosed with T1‐2, N0‐1, M0 NPC, from 2004 to 2013. Five‐year survival was calculated using Kaplan Meier (KM) analysis. Multivariable analysis and propensity matched analysis were performed to analyze the impact of chemotherapy on overall survival. Of the 611 patients, 527 underwent concurrent chemoradiation (CCRT) and 84 received radiation only. Unadjusted KM analysis showed improved 5‐year survival in the CCRT group compared to radiation only (80.5% vs 65.7%; P = 0.0021). Multivariable analysis also showed improved survival with the addition of chemotherapy (Hazard ratio [HR] 0.59; 95 CI 0.39‐0.89; P = 0.0124). Propensity matched analysis confirmed a significant clinical benefit from the addition of chemotherapy to radiation. Age ≥ 65 years (HR 2.41; 95% CI 1.71‐3.4; P = <0.0001), Charlson‐Deyo comorbidity index >1 (HR 2.82; 95% CI 1.49‐5.31; P = 0.0014) and positive lymph node status (HR 1.6; 95% CI 1.04‐2.46; P = 0.0340) were associated with worse survival. In this retrospective analysis, patients with stage II NPC had improved survival with CCRT compared to definitive radiation only. Elderly patients with comorbidities had worse outcomes. [ABSTRACT FROM AUTHOR]

The first biosimilar of bevacizumab was approved by the US FDA; other potential biosimilars of bevacizumab are in late-stage clinical development. Their availability offers opportunity for increased patient access across a number of oncologic indications. The regulatory pathway for biosimilar approval relies on the totality of evidence that includes a comprehensive analytical assessment, and a clinical comparability study in a relevant disease patient population. Extrapolation of indications for a biosimilar to other eligible indications held by the originator, in the absence of direct clinical comparison, frequently forms part of the regulatory judgment. Herein, we consider the evidence required to demonstrate biosimilarity for bevacizumab biosimilars, with particular focus on the rationale for extrapolation across oncologic indications. [ABSTRACT FROM AUTHOR]

Background: Next generation sequencing tests (NGS) are usually performed on relatively small core biopsy or fine needle aspiration (FNA) samples. Data is limited on what amount of tumor by volume or minimum number of FNA passes are needed to yield sufficient material for running NGS. We sought to identify the amount of tumor for running the PCDx NGS platform. Methods: 2,723 consecutive tumor tissues of all cancer types were queried and reviewed for inclusion. Information on tumor volume, success of performing NGS, and results of NGS were compiled. Assessment of sequence analysis, mutation calling and sensitivity, quality control, drug associations, and data aggregation and analysis were performed. Results: 6.4% of samples were rejected from all testing due to insufficient tumor quantity. The number of genes with insufficient sensitivity make definitive mutation calls increased as the percentage of tumor decreased, reaching statistical significance below 5% tumor content. The number of drug associations also decreased with a lower percentage of tumor, but this difference only became significant between 1–3%. The number of drug associations did decrease with smaller tissue size as expected. Neither specimen size or percentage of tumor affected the ability to pass mRNA quality control. A tumor area of 10 mm2 provides a good margin of error for specimens to yield adequate drug association results. Conclusions: Specimen suitability remains a major obstacle to clinical NGS testing. We determined that PCR-based library creation methods allow the use of smaller specimens, and those with a lower percentage of tumor cells to be run on the PCDx NGS platform. [ABSTRACT FROM AUTHOR]

Follicular lymphoma (FL) is the second most common type of non-Hodgkin's lymphoma. FL is an incurable disease with treatment options ranging from a "watch-and-wait" approach to localized therapy with radiation or systemic therapy with rituximab in combination with chemotherapy regimens. This review summarizes the role of rituximab across the spectrum of FL treatment and the evolving therapeutic landscape with the emergence of novel agents currently in clinical development. Despite the prospect of new agents on the horizon, it is widely accepted that rituximab will remain as the cornerstone of therapy because of its established long-term efficacy. Many biologics, including rituximab, have lost exclusivity of composition-of-matter patent or will do so in the next few years, which is a concern for patients and physicians alike. Moreover, access to rituximab is challenging, particularly in countries with restricted resources. Together, these concerns have fueled the development of safe and effective biosimilars. The term "biosimilar" refers to a biologic product that is highly similar to an approved reference (or originator) product, notwithstanding minor differences in clinically inactive components, and for which there are no clinically meaningful differences in purity, potency, or safety. Biosimilars are developed to treat the same condition(s) using the same treatment regimens as an approved reference biologic, and have the potential to increase access to more affordable treatment of FL. Herein, we also discuss the potential benefits of eagerly awaited rituximab biosimilars, which may mitigate the impact of the lack of access to rituximab. [ABSTRACT FROM AUTHOR]

The article explores the impact of lung cancer on never-smokers in the U.S. It cites recent and relevant studies in lung cancer in never smokers that constitutes a small proportion of patients with lung cancer due to better response rates with epidermal growth factor receptor-tyrosine kinase (EGFR-TK) inhibitors as compared to smokers with lung cancer. Moreover, it shows potential enhancement on knowledge of lung cancer biology.

Summary: A 65-year-old male with 40-pack year smoking history presented with exertional dyspnea and was subsequently diagnosed with bronchiolo-alveolar carcinoma (BAC). He did not respond to first line therapy with geftinib, but he achieved disease stabilization with gemcitabine and carboplatin for 4 months before developing symptomatic worsening requiring oxygen supplementation. He responded dramatically to bortezomib with rapid symptom improvement. The follow-up computerized tomography revealed partial response that was maintained for 11 months. Based on observations like this and those seen in phase I studies with bortezomib, this agent is being studied now in patients with bronchio-alevolar cancer. [Copyright &y& Elsevier]

Tumor heterogeneity, especially intratumoral heterogeneity, is a primary reason for treatment failure. A single biopsy may not reflect the complete genomic architecture of the tumor needed to make therapeutic decisions. Circulating tumor DNA (ctDNA) is believed to overcome these limitations. We analyzed concordance between ctDNA and whole-exome sequencing/whole-genome sequencing (WES/WGS) of tumor samples from patients with breast (n = 12), gastrointestinal (n = 20), lung (n = 19), and other tumor types (n = 13). Correlation in the driver, hotspot, and actionable alterations was studied. Three cases in which more-in-depth genomic analysis was required have been presented. A total 58% (37/64) of patients had at least one concordant mutation. Patients who had received systemic therapy before tissue next-generation sequencing (NGS) and ctDNA analysis showed high concordance (78% (21/27) vs. 43% (12/28) p = 0.01, respectively). Obtaining both NGS and ctDNA increased actionable alterations from 28% (18/64) to 52% (33/64) in our patients. Twenty-one patients had mutually exclusive actionable alterations seen only in either tissue NGS or ctDNA samples. Somatic hotspot mutation analysis showed significant discordance between tissue NGS and ctDNA analysis, denoting significant tumor heterogeneity in these malignancies. Increased tissue tumor mutation burden (TMB) positively correlated with the number of ctDNA mutations in patients who had received systemic therapy, but not in treatment-naïve patients. Prior systemic therapy and TMB may affect concordance and should be taken into consideration in future studies. Incorporating driver, actionable, and hotspot analysis may help to further refine the correlation between these two platforms. Tissue NGS and ctDNA are complimentary, and if done in conjunction, may increase the detection rate of actionable alterations and potentially therapeutic targets. [ABSTRACT FROM AUTHOR]

Right-sided colon cancer (RCC) has worse prognosis compared to left-sided colon cancer (LCC) and rectal cancer. The reason for this difference in outcomes is not well understood. We performed comparative somatic and proteomic analyses of RCC, LCC and rectal cancers to understand the unique molecular features of each tumor sub-types. Utilizing a novel in silico clonal evolution algorithm, we identified common tumor-initiating events involving APC, KRAS and TP53 genes in RCC, LCC and rectal cancers. However, the individual role-played by each event, their order in tumor development and selection of downstream somatic alterations were distinct in all three anatomical locations. Some similarities were noted between LCC and rectal cancer. Hotspot mutation analysis identified a nonsense mutation, APC R1450* specific to RCC. In addition, we discovered new significantly mutated genes at each tumor location, Further in silico proteomic analysis, developed by our group, found distinct central or hub proteins with unique interactomes among each location. Our study revealed significant differences between RCC, LCC and rectal cancers not only at somatic but also at proteomic level that may have therapeutic relevance in these highly complex and heterogeneous tumors. [ABSTRACT FROM AUTHOR]

• There are no specific recommendations available for the treatment of > 80 years old patients with metastatic NSCLC. • Only 29% of > 80 years old patients received chemotherapy with improved survival even in patients with high CDCI ≥ 3. • 80 years and older patients are 50% less likely to receive chemotherapy compared to patients age < 80 years. • The elderly patients should be evaluated for chemotherapy based on functional status and comorbidities rather than age. • Despite improved survival, chemotherapy use remained unchanged overtime in > 80 years old patients with advanced NSCLC. There are limited data on the role for chemotherapy in patients > 80 years old with advanced stage non-small cell lung carcinoma (NSCLC). We used the National Cancer Database (NCDB) to evaluate treatment patterns and outcomes for patients ≥80 years old with advanced NSCLC. We identified patients diagnosed with metastatic NSCLC between 2004 and 2014. We divided them into two groups: < 80 years old (n = 218,365) and ≥ 80 years old (n = 33,352). Patient characteristics including median age at diagnosis, gender, ethnicity, histology, chemotherapy status, tumor grade, treatment center, insurance status, income, education, and Charlson-Deyo co-morbidity index were collected. Continuous variables were compared using t -test and categorical variables were compared using chi-square or Fisher's exact test. Multivariable (MV) and propensity matched analyses were performed to analyze the impact of chemotherapy on overall survival. We identified 33,352 patients > 80 years old diagnosed with advanced NSCLC. Only 29 % received chemotherapy, those who received chemotherapy had improved median overall survival of 8 months compared to 2 months in patients not receiving chemotherapy; adjusted hazards ratio (HR) 0.46; confidence interval (CI) 0.45−0.47; p <.001. MV analysis showed benefit of chemotherapy in all age subgroups (80–84 years, 85–89 years and 90+ years; p <.0001) and it was confirmed by propensity matched analysis. Patients receiving multiagent chemotherapy had improved 1-year survival of 35.5 % compared to 32.8 % with single agent chemotherapy (adjusted HR 0.92; CI 0.88−0.96; p <.001). Despite benefit from chemotherapy, the proportion of patients age ≥ 80 years receiving chemotherapy did not change over time. Chemotherapy improved overall survival in ≥80 years old patients with advanced stage NSCLC. Despite improved survival and an increase in the proportion of ≥80 years old patients diagnosed with advanced NSCLC, less than one-third receive chemotherapy. [ABSTRACT FROM AUTHOR]