Molecular Testing Guideline Research Articles

Abstract C021: Racial and socioeconomic disparities in molecular diagnostics for NSCLC patients

Abstract Background: Targeted therapies have substantially changed the landscape of non-small cell lung cancer (NSCLC) outcomes. These drugs work by inhibiting specific molecular pathways, such as the epidermal growth factor receptor (EGFR) tyrosine kinase, the anaplastic lymphoma kinase (ALK), KRAS, and BRAF oncogenic pathways. Approximately 30% of NSCLC patients will have tumors with eligible targetable mutations, but a molecular test must be conducted to assess eligibility to these treatments. Disparities in molecular testing could be partially responsible for the disproportionate utilization of targeted therapy across race and socioeconomic status (SES). Methods: Surveillance, Epidemiology and End Results (SEER)-Medicare linked data was queried for NSCLC patients diagnosed from 2013 (the first year that standard guidelines for molecular testing in lung cancer were available) to 2016. Patients were limited to age over 66 years at diagnosis with continuous Part A and B coverage and no Part C coverage, for 1 year prior and 90 days post-diagnosis. The primary outcome was receipt of a molecular test based on claims data. Race, defined as white, Black or other, was the primary predictor variable. Demographic and clinical characteristics of those receiving vs not receiving a molecular test were compared using χ2 tests for categorical variables and t-tests for continuous variables. We also performed multivariable logistic regression to assess the association of molecular testing with race adjusting for sex, age, marital status, Charlson comorbidity index, histology, tumor site, stage, and census-level poverty indicator. Results: There were 28,511 NSCLC patients, of which 9,639 (33.8%) received some type of molecular testing. Black patients were significantly less likely than white patients to have received a molecular test (p<0.0001). Only 23.9% of Black patients underwent any molecular testing, compared to 34.6% of white patients. Patients living in census tracts with at least 10% of residents living in poverty were also less likely to receive a molecular test (p<0.0001). Patients who were female (p<0.0001), married (p<0.0001), with fewer comorbidities (p<0.0001), adenocarcinoma histology (p<0.0001), tumors located in the lower lobe (p<0.0001), diagnosed at a later stage (p=0.0001) were more likely to have molecular testing. After adjustment, Black patients (ORadj [odds ratio]: 0.65; 95% CI [confidence interval]: 0.59-0.72) and those living in areas with greater poverty (ORadj: 0.87; 95% CI: 0.82-0.91) were statistically significantly less likely to have received molecular testing. Conclusions: Disparities exist in comprehensive molecular diagnostics, and could explain, at least in part, the high mortality observed among Black NSCLC patients. Addressing barriers to molecular testing could increase uptake of targeted therapy treatment, decreasing disparities and improving patient outcomes. Citation Format: Stephanie Tuminello, Wiley Turner, Matthew Untalan, Raja Flores, Emaneula Taioli. Racial and socioeconomic disparities in molecular diagnostics for NSCLC patients [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C021.

NSCLC Digital PCR Panel Returns Low-Input Sample Results Where Sequencing Fails

Molecular diagnostics has drastically improved the survival rate of patients diagnosed with non-small cell lung cancer (NSCLC) over the last 10 years. Despite advancements in molecular testing, targeted therapies, and national guideline recommendations, more than half of NSCLC patients in the United States either never receive testing or patient care is not informed via molecular testing. Here, we sought to explore the relationship between DNA/RNA input, the molecular testing method, and test success rates. On a shared set of low-input reference test materials (n = 3), we ran both a hybrid capture-based, next-generation sequencing (NGS) assay and a multiplexed digital PCR (dPCR) panel. The dPCR panel was highly sensitive and specific for low-input samples in dilution studies ranging from 40 to 1 ng DNA and from 20 to 2.5 ng RNA, while NGS had up to an 86% loss in sensitivity as contrived sample inputs were serially diluted. The dPCR panel also demonstrated a high PPA (>95%) at diluted inputs as low as 15/7.5 ng DNA/RNA on 23 banked clinical samples with the same NGS hybrid capture assay at a high input. These data suggest that digital PCR is an accurate and effective way of identifying clinically relevant NSCLC mutations at low nucleotide input and quality.

Japanese Society of Medical Oncology clinical guidelines: Molecular testing for colorectal cancer treatment, 5th edition.

Molecular testing to determine optimal therapies is essential for managing patients with colorectal cancer (CRC). In October 2022, the Japanese Society of Medical Oncology published the 5th edition of the Molecular Testing Guideline for Colorectal Cancer Treatment. In this guideline, in patients with unresectable CRC, RAS/BRAF V600E mutational and mismatch repair tests are strongly recommended prior to first-line chemotherapy to select optimal first- and second-line therapies. In addition, HER2 testing is strongly recommended because the pertuzumab plus trastuzumab combination is insured after fluoropyrimidine, oxaliplatin, and irinotecan in Japan. Circulating tumor DNA (ctDNA)-based RAS testing is also strongly recommended to assess the indications for the readministration of anti-EGFR antibodies. Both tissue- and ctDNA-based comprehensive genomic profiling tests are strongly recommended to assess the indications for targeted molecular drugs, although they are currently insured in patients with disease progression after receiving standard chemotherapy (or in whom disease progression is expected in the near future). Mutational and mismatch repair testing is strongly recommended for patients with resectable CRC, and RAS/BRAF V600E mutation testing is recommended to estimate the risk of recurrence. Mutational and mismatch repair and BRAF testing are also strongly recommended for screening for Lynch syndrome. Circulating tumor DNA-based minimal residual disease (MRD) testing is strongly recommended for estimating the risk of recurrence based on clinical evidence, although MRD testing was not approved in Japan at the time of the publication of this guideline.

Impact of Online Tumor Board Simulation for Optimizing Testing and Treatment of Patients with BRAFV600E- mutant Metastatic Colorectal Cancer

Abstract Introduction/Objective Approximately 10% of patients with metastatic colorectal cancer (mCRC) have BRAF genetic mutations, 90% of which result in a V600E substitution. Although there are targeted therapies available, there has been confusion about new and emerging testing and treatment options for BRAFV600E-mutant mCRC. Methods/Case Report To meet these needs, ASCP designed a 60-minute, self-paced, CME/CMLE online tumor board simulation to: increase knowledge, skills, and competence of pathologists and laboratory professionals to ensure patients with mCRC are appropriately and efficiently tested for BRAF mutations in accordance with NCCN guidelines, and enable pathologists to guide medical oncologists in the appropriate diagnosis, testing, and treatment of patients with mCRC. In the simulation, an expert pathologist and oncologist presented patient cases involving BRAFV600E-mutant mCRC. Learners answered questions designed to help them carefully consider the nuances of each case, building their knowledge and skills related to the detection and optimal management of patients with BRAF-mutant mCRC. Results (if a Case Study enter NA) 250+ learners have participated, with results demonstrating greater understanding of the NCCN guidelines for molecular testing of patients with mCRC, the clinicopathologic characteristics of BRAF-mutant mCRC. The tumor board simulation also increased awareness of strategies for improving turnaround times in biomarker testing for patients with mCRC, as well as current and emerging treatment options for BRAFV600E-mutant mCRC, which were two of the main goals of the education. Conclusion This project advanced knowledge, skills, and competence among pathologists and laboratory professionals, particularly those in community practice, to help ensure that patients who may be eligible for new and emerging therapies for BRAFV600E-mutant mCRC receive effective, optimized, and timely biomarker testing and treatment. The education may be useful to learners who want an increased understanding of BRAF mutations and their role in treatment selection.

B-246 The Evaluation of Actionable Mutations By Multiplex Analysis Using IntelliPlex® Lung Cancer Panel for Non-Small Cell Cancer Management

Abstract Background Understanding the genetic alterations which occur in genes associated with various cancers can improve therapy outcomes by promoting tailored treatments for each patient. Molecular profiling is therefore a crucial tool for precision medicine and enables for a personalized approach to cancer management. Current guidelines for molecular testing of Non-Small Cell Lung Cancer (NSCLC) patients involves treatment selection of a targeted Tyrosine Kinase Inhibitor based on the minimal testing of EGFR, ALK and ROS1 genes and strongly recommending the additional testing of KRAS, BRAF, MET, RET, NTRK and ERBB2 (Her2) genes to fully evaluate the patient’s mutational status. Method The IntelliPlex Lung Cancer Panel, based on PlexBio’s multiplexing πCode® technology, is an in vitro molecular amplification assay intended for the qualitative identification of 74 DNA mutations in the KRAS, NRAS, PIK3CA, BRAF, EGFR, HER2, MEK1 and AKT1 genes and 28 gene variants of the ALK, ROS1, RET, NTRK1 and MET genes. The assay is suitable for the use with formalin-fixed paraffin-embedded (FFPE) tumor tissues from NSCLC patients. The performance of IntelliPlex Lung Cancer Panel was evaluated on FFPE specimens by comparing the results with two commercially available molecular amplification assays. Discrepant samples were resolved by a corresponding digital PCR method kit. Results The IntelliPlex Lung Cancer Panel can detect DNA mutations at very low allele frequencies (as low as 0.1%) while only requiring DNA quantities of 10ng. Most RNA rearrangements are detected with 10 or more copies present in the sample while only low RNA input quantities (50 ng) are required. The IntelliPlex Lung Cancer Panel can analyze the mutational status of 102 targets in less than 5.5 h from sample to results and allows screening of up to 48 samples in parallel. Among 50 FFPE DNA specimens tested, the overall agreement for EGFR and KRAS mutations between IntelliPlex system and the comparison method were both found to be 98%. And the overall agreement after resolved the discrepancies by digital PCR was 100%. Conclusion The multiplex amplification and detection capabilities of the IntelliPlex Lung Cancer Panel provides a comprehensive and efficient way to evaluate the individual mutational status from lung cancer patients with high sensitivity and specificity. Accurate genetic analysis provides valuable information which can support precision medicine decisions for better cancer management. This can also be used further with non-invasive whole blood sampling (i.e., “liquid biopsy”) for subsequent treatment monitoring.

OS12.7.A IMPLEMENTATION OF A NATIONAL AYA MOLECULAR TUMOR BOARD: REPORT FROM THE CANADIAN AYA NEURO-ONCOLOGY NETWORK

Abstract BACKGROUND The adolescent and young adult (AYA) population (15-39 years) is a unique and understudied population within neuro-oncology, and their care requires expertise across pediatric and adult-type brain tumors. Current challenges in AYA neuro-oncology include fragmented care across pediatric and adult hospitals, low inclusion in clinical trials, unique survivorship considerations and a lack of standard-of-care therapies for this population. MATERIAL AND METHODS We report on a two-year national effort from the Canadian AYA Neuro-Oncology Network (CANON) to implement national AYA rounds. The aims of the rounds are to discuss challenging cases, encourage and review the utility standardized molecular testing, and provide point-of-care multidisciplinary recommendations benefiting from the expertise of pediatric and adult providers across several tertiary and community centers. RESULTS Since April 2021, the Canadian national AYA rounds have occurred biweekly on a virtual secure platform. Over 2 years, 138 cases have been discussed; 23% of patients were 15-20 years old, 33% were 21-30 years old and 26% were 31-40 years old. Cases discussed included low grade gliomas (39%), followed by high grade gliomas (33%), ependymomas (6.5%), medulloblastomas (6.5%) and others (9.4%). A total of 240 participants across 25 institutions across Canada have attended the rounds, spanning adult and pediatric neurosurgery, neuro-pathology, neuro-oncology, radiation oncology and radiology. A prospective database of cases presented at our AYA rounds, matching molecular characterization, choice of therapies and relevant clinical outcomes has been initiated and interim data will be presented at the meeting. CONCLUSION Virtual national AYA-neuro-oncology multi-disciplinary rounds have raised awareness of current gaps and possible nation-wide solutions to improve the care of AYA brain tumors. Leveraging this network, our group has published guidelines for molecular testing in AYA brain tumors and is employing this platform for ongoing research and clinical collaborations.

Advances in Molecular Profiling and Their Potential Influence on the Extent of Surgery in Well-Differentiated Thyroid Carcinoma (WDTC).

Thyroid cancer surgery has evolved dramatically with advances in our understanding of the biological behaviour of WDTC. Molecular profiling is shedding light on the subset that may behave aggressively. In an era when thyroid cancer management is becoming increasingly conservative, decision making regarding the extent of surgery must be objectively guided by molecular markers. The aim of the present article is to summarise the current published literature and provide possible practice recommendations. An online search for relevant published articles was performed using several databases. Title, abstract, and full-text screening, along with data extraction, was performed by two independent reviewers after the inclusion and exclusion criteria were defined. A total of 1241 articles were identified, and 82 relevant articles were extracted and scrutinised. BRAF V600E and TERT promoter mutations were found to be associated with an increased risk of disease recurrence and distant metastases. Several other mutations have been identified that enhance disease aggressiveness (such as RET/PTC, PTEN, and TP53). One of the most important determinants of the outcome in WDTC is the extent of surgical resection. The evolution of molecular testing has reached a stage of personalised incorporation into surgical practice. Guidelines for molecular testing and surgery in WDTC will need to be clearly defined, arguably representing the next chapter in the management of the disease.

What's new in bone and soft tissue pathology 2023: guidelines for molecular testing.

Our understanding of bone and soft tissue tumors has thoroughly evolved as a consequence of modern molecular techniques. DNA and RNA sequencing methods play an important diagnostic and therapeutic role in sarcoma pathology. Herein, we discuss current guidelines and best practices for molecular testing in bone and soft tissue tumors.

Real-World Data on EGFR and ALK Testing and TKI Usage in Norway—A Nation-Wide Population Study

Clinical studies have shown the efficacy of EGFR- and ALK-directed therapies in non-small cell lung cancer (NSCLC). Real-world data on, e.g., testing patterns, uptake, and duration of treatment are scarce. Reflex EGFR and ALK testing of non-squamous NSCLCs were implemented in Norwegian guidelines in 2010 and 2013, respectively. We present a complete national registry data on incidence, pathology procedures, and drug prescription in the period of 2013 to 2020. Test rates for both EGFR and ALK increased over time and were 85% and 89%, respectively, at the end of the study period, independent of age up to 85 years. The positivity rate for EGFR was higher among females and young patients, whereas no sex difference was observed for ALK. EGFR-treated patients were older than ALK-treated patients (71 vs. 63 years at start, p < 0.001). Male ALK-treated patients were significantly younger than females at the start of treatment (58 vs. 65 years, p = 0.019). The time from the first dispensation to the last dispensation of TKI (as a surrogate for progression-free survival) was shorter for EGFR- than for ALK-TKI, and survival for both EGFR- and ALK-positive patients was substantially longer than for non-mutated patients. We found a high adherence to molecular testing guidelines, good concordance of mutation positivity and treatment, and the real-world replication of findings in clinical trials, indicating that the relevant patients are provided substantially life-prolonging therapy.

Implementation Challenges and Disparities in Molecular Testing for Patients With Stage IV NSCLC: Perspectives from an Urban Safety-Net Hospital

The advent of next-generation sequencing (NGS), including both tissue assays and circulating tumor DNA (ct-DNA), has been pivotal in improving outcomes for patients with non-small cell lung cancer (NSCLC). Although molecular testing is standard of care for advanced NSCLC, challenges still exist in its implementation. This Perspective examines barriers to the widespread implementation of NGS from the vantage point of a single urban safety-net institution, with a particular focus on examining racial disparities in NGS completion. We conducted a review of patients at our institution from January 2015 through January 2022 and examined molecular testing patterns before and after the publication of updated molecular testing guidelines from the International Association for the Study of Lung Cancer (IASLC), Association for Molecular Pathology (AMP), and College of American Pathologists (CAP) in March of 2018. While NGS increased over time, we found that 43% of patients in the March 2018 through January 2022 group still did not receive NGS, and the most common reasons for the absence of testing included a lack of physician ordering and insufficient tissue on biopsy. We did not note any racial disparities in completion or time-to-adoption of NGS. Patients with squamous cell carcinoma (SCC) histology were noted to receive liquid NGS markedly less often than patients with non-squamous histology in the March 2018 through January 2022 period. Based on our own data and a review of findings from colleagues in the field, we advocate for additional physician educational programming, increased use of ct-DNA biopsy, automated (reflexive) NGS tissue testing on receipt of biopsy, and consideration for the broader molecular profiling of patients with SCC histology.

Identifiable Mutations in Pancreatic Adenocarcinoma in the Veteran Population: Molecular Testing Guidelines by NCCN 2020

Abstract Introduction/Objective In 2019 and 2020, the National Comprehensive Cancer Network (NCCN) advanced a recommendation that all patients with metastatic, recurrent, or locally advanced pancreatic adenocarcinoma should undergo tumor gene profiling (TGP). Prior to these recommendations, TGP in targeted patients have demonstrated a high frequency of KRAS (&amp;gt;90%), TP53 (60-70%), CDKN2A (&amp;gt;50%), SMAD4, TGF- βR1, and TGF- βR2 mutations or alterations. Even less frequent mutations such as the homologous recombination repair (HRR) genes impact treatment by predicting tumor response to platinum-based therapies. However, the literature is sparse for the frequency of these mutations in patients with pancreatic adenocarcinoma undergoing generalized testing as part of the standard of care per NCCN guidance, particularly for veterans. Methods/Case Report For a quality assurance study, a retrospective review was performed to identify patients with pancreatic adenocarcinoma at a tertiary medical center serving veterans from January 2019 to February 2021 with TGP performed as part of their care. All of the TGP had been sent to Foundation Medicine (Cambridge MA), and the identifiable tumor mutations from the test reports were recorded to document the frequency of KRAS, TP53, CDKN2A, SMAD4, TGF- βR1, TGF- βR2 and HRR mutations or alterations. Results (if a Case Study enter NA) There were a total of 11 patients with pancreatic adenocarcinoma who had a tumor specimen for TGP during the study period. All 11 patient tumors had KRAS mutation. 10 out of 11 had a mutation or alteration in TP53. 8 of 11 patients had a CDKN2A mutation or alteration. 7 of 11 patients had a mutation or alteration of SMAD4 though none had TGF- βR1 or TGF- βR2. 2 of 11 patients had HRR mutations (1 with FANCA and 1 with ATM). Conclusion Tumor mutations on generalized gene profiling per NCCN guidelines continue to identify important mutations in pancreatic adenocarcinoma for veteran patients.

ALK Gene Rearrangements in Lung Adenocarcinomas: Concordance of Immunohistochemistry, Fluorescence In Situ Hybridization, RNA In Situ Hybridization, and RNA Next-Generation Sequencing Testing

IntroductionThe 2018 updated molecular testing guidelines for patients with advanced lung cancer incorporated ALK immunohistochemistry (IHC) analysis as an equivalent to fluorescence in situ hybridization (FISH) method recommended in 2013. Nevertheless, no specific recommendation for alternative methods was proposed owing to insufficient data. The aim of this study was to compare the results of ALK IHC, FISH, RNA next-generation sequencing (NGS), and RNA in situ hybridization (ISH) with available clinical data. MethodsA search for lung carcinomas with ALK testing by greater than or equal to one modality (i.e., ALK IHC, FISH, NGS) was performed; a subset underwent RNA ISH. When available, clinical data were recorded. ResultsThe results were concordant among all performed testing modalities in 86 of 90 cases (95.6%). Of the four discordant cases, two were ALK positive by FISH but negative by IHC, RNA NGS, and RNA ISH. The remaining two cases failed RNA NGS testing, one was IHC negative, FISH positive, RNA ISH negative and the second was IHC positive, FISH positive, RNA ISH equivocal. RNA NGS identified one rare and one novel ALK fusion. Sufficient therapy data were available in 10 cases treated with tyrosine kinase inhibitors; three had disease progression, including one with discordant results (FISH positive, RNA NGS negative, IHC negative, RNA ISH negative) and two with concordant ALK positivity among all modalities. ConclusionsOur results reveal high concordance among IHC, RNA NGS, and RNA ISH. In cases of discordance with available RNA NGS, FISH result was positive whereas IHC and ISH results were negative. On the basis of our data, multimodality testing is recommended to identify discrepant results and patients (un)likely to respond to tyrosine kinase inhibitors.

NGS in Lung, Breast, and Unknown Primary Cancer in Colombia: A Multidisciplinary Consensus on Challenges and Opportunities.

Given the benefits and likely future applications, there is an urgent need to expand the use of next-generation sequencing (NGS) in breast, lung, and unknown primary cancers in Colombia. The objective of this review is to address the barriers limiting access to the use of NGS in Colombia, specifically for patients with breast, lung, and unknown primary cancers in the public health care system. A selected Panel of Colombian experts in NGS were provided with a series of relevant questions to address in a multiday conference. Each narrative was discussed and edited by the Panel through numerous drafts and rounds of discussion until consensus was achieved. There are limitations to the widespread adoption of innovative technology inherent to the Colombian health care system. Barriers identified to implementing NGS in Colombia include availability, accessibility, and affordability; limited infrastructure; training and awareness of health personnel; quality-control procedures; and collection of local data. Stakeholders must align to adapt the implementation of NGS to the constraints of resource-limited environments. Diagnostic algorithms were developed to guide molecular testing for lung, breast, and unknown primary cancers. Recommendations on overcoming the barriers to the widespread adoption of NGS include country-specific molecular testing guidelines, creating a national genetic registry, improving infrastructure, and creating health policy that favors the adoption of innovative technology.

Molecular biomarker testing for non-small cell lung cancer: consensus statement of the Korean Cardiopulmonary Pathology Study Group.

Molecular biomarker testing is the standard of care for non–small cell lung cancer (NSCLC) patients. In 2017, the Korean Cardiopulmonary Pathology Study Group and the Korean Molecular Pathology Study Group co-published a molecular testing guideline which contained almost all known genetic changes that aid in treatment decisions or predict prognosis in patients with NSCLC. Since then there have been significant changes in targeted therapies as well as molecular testing including newly approved targeted drugs and liquid biopsy. In order to reflect these changes, the Korean Cardiopulmonary Pathology Study Group developed a consensus statement on molecular biomarker testing. This consensus statement was crafted to provide guidance on what genes should be tested, as well as methodology, samples, patient selection, reporting and quality control.

Scoping the Problem

Scoping the Problem

Systematic Literature Review of the Epidemiology of Advanced Prostate Cancer and Associated Homologous Recombination Repair Gene Alterations.

To characterize the global epidemiology of metastatic castration-sensitive prostate cancer (mCSPC), nonmetastatic castration-resistant prostate cancer (nmCRPC) and metastatic castration-resistant prostate cancer (mCRPC). Additionally, to assess the prevalence of homologous recombination repair gene alterations (HRRm) and their prognostic impact in advanced disease setting. A systematic literature review of real-world evidence published from January 2009 through May 2019 was conducted to assess global epidemiology and clinical practice trends for mCSPC, nmCRPC, mCRPC and HRRm; 4,732 papers were systematically screened for inclusion. Ten conference proceedings from 2014 through 2019 were reviewed. Of the screened articles 22 relevant publications were identified for this paper. Six publications reported global epidemiology of advanced prostate cancer. The prevalence of nmCRPC was estimated as 1.1% to 12.3% of prostate cancer cases and for mCRPC 1.2% to 2.1% of prostate cancer cases. No mCSPC prevalence was captured. Sixteen publications investigated HRRm prevalence in advanced prostate cancer with the majority conducted in mCRPC assessed using next-generation sequencing of tissue and germline samples. In mCRPC, the highest prevalence HRRm in both germline (3.3%-6.0%) and somatic (5.0%-15.1%) was BRCA2. Five publications reported the prognostic impact of HRRm in advanced prostate cancer. Published real-world evidence quantifying the prevalence of advanced prostate cancer and HRRm beyond mCRPC is sparse. Published data on HRRm, specifically BRCA2, are consistent with published clinical trial data for poly (ADP-ribose) polymerase inhibitors in mCRPC. In mCRPC, real-world evidence suggests that patients with HRRm have different clinical outcomes to noncarriers. More data are needed to better understand real-world patient segmentation and clinical outcomes for biomarkers given increasing interest in profiling.

Japanese Society of Medical Oncology Clinical Guidelines: Molecular Testing for Colorectal Cancer Treatment, 4th edition.

Molecular testing to select the appropriate targeted and standard of care therapies is essential for managing patients with colorectal cancer (CRC). The Japanese Society of Medical Oncology previously published clinical guidelines for molecular testing in CRC. In the third edition published in 2018, RAS and BRAF V600E mutations should be tested prior to first‐line chemotherapy to assess the benefit of anti–epidermal growth factor receptor (EGFR) antibody therapy in patients with unresectable CRC. Microsatellite instability (MSI) testing was recommended in patients with curatively resected stage II CRC because deficient mismatch repair is associated with low risk of recurrence. MSI testing was also recommended in patients with CRC suspected to be Lynch syndrome. The main aim of this fourth edition is to reflect recent advances in comprehensive genomic profiling (CGP) tests and liquid biopsy. Here, CGP tests performed on tumor tissues are strongly recommended to assess the benefit of molecular targeted drugs in patients with CRC. Circulating tumor DNA (ctDNA)‐based CGP tests are also proposed. ctDNA testing is recommended to determine the optimal treatment based on the risk of recurrence for curatively resected CRC and evaluate the suitability and monitor the therapeutic effects of anti–EGFR antibodies in patients with unresectable CRC. While both MSI testing and immunohistochemistry are strongly recommended to determine the indication of immune checkpoint inhibitors in patients with unresectable CRC, next‐generation sequencing‐based tests are weakly recommended because these tests have not been validated in clinical trials.

EMQN best practice guidelines for molecular genetic testing and reporting of 21-hydroxylase deficiency

Molecular genetic testing for congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is offered worldwide and is of importance for differential diagnosis, carrier detection and adequate genetic counseling, particularly for family planning. In 2008 the European Molecular Genetics Quality Network (EMQN) for the first time offered a European-wide external quality assessment scheme for CAH (due to 21-OH deficiency). The interest was great and over the last years at about 60 laboratories from Europe, USA and Australia regularly participated in that scheme. These best practice guidelines were drafted on the basis of the extensive knowledge and experience got from those annually organized CAH-schemes. In order to obtain the widest possible consultation with practicing laboratories the draft was therefore circulated twice by EMQN to all laboratories participating in the EQA-scheme for CAH genotyping and was updated by that input. The present guidelines address quality requirements for diagnostic molecular genetic laboratories, as well as criteria for CYP21A2 genotyping (including carrier-testing and prenatal diagnosis). A key aspect of that article is the use of appropriate methodologies (e.g., sequencing methods, MLPA (multiplex ligation dependent probe amplification), mutation specific assays) and respective limitations and analytical accuracy. Moreover, these guidelines focus on classification of variants, and the interpretation and standardization of the reporting of CYP21A2 genotyping results. In addition, the article provides a comprehensive list of common as well as so far unreported CYP21A2-variants.

The International Association for the Study of Lung Cancer Global Survey on Molecular Testing in Lung Cancer.

Access to targeted therapies for lung cancer depends on the accurate identification of patients' biomarkers through molecular testing. The International Association for the Study of Lung Cancer (IASLC) conducted an international survey to evaluate perceptions on current practice and barriers to implementation of molecular testing. We distributed the survey to IASLC members and other health care professionals around the world. The survey included a seven-question introduction for all respondents, who then answered according to one of three tracks: (1) requesting tests and treating patients, (2) performing and interpreting assays, or (3) tissue acquisition. Barriers to implementing molecular testing were provided in free-response fields. The chi-square test was used for regional comparisons. A total of 2537 respondents from 102 countries participated. Most respondents who test and treat patients believe that less than 50% of patients with lung cancer in their country receive molecular testing, but reported higher rates within their own practice. Although many results varied by region, the five most frequent barriers cited in all regions were cost, quality and standards, access, awareness, and turnaround time. Many respondents expressed dissatisfaction with the current state of molecular testing for lung cancer, including 41% of those performing and interpreting assays. Issues identified included trouble understanding results (37%) and the quality of the samples (23% reported >10% rejection rate). Despite concerns regarding the quality of testing, 47% in the performing and interpreting track stated there is no policy or strategy to improve quality in their country. In addition, 33% of respondents who request tests and treat patients were unaware of the most recent College of American Pathologists, IASLC, and Association for Molecular Pathology guidelines for molecular testing. Adoption of molecular testing for lung cancer is relatively low across the world. Barriers include cost, access, quality, turnaround time, and lack of awareness.

ES07.04 Predictive Molecular Testing on Small Biopsy Samples

ES07.04 Predictive Molecular Testing on Small Biopsy Samples