European Real-World Assessment of the Clinical Validity of a CE-IVD Panel for Ultra-Fast Next-Generation Sequencing in Solid Tumors.

Molecular profiling of solid tumors facilitates personalized, targeted therapeutic interventions. The ability to perform next-generation sequencing (NGS), especially from small tissue samples, in a short turnaround time (TAT) is essential to providing results that enable rapid clinical decisions. This multicenter study evaluated the performance of a CE in vitro diagnostic (IVD) assay, the Oncomine Dx Express Test, on the Ion Torrent Genexus System for detecting DNA and RNA variants in solid tumors. Eighty-two archived formalin-fixed paraffin embedded (FFPE) tissue samples from lung, colorectal, central nervous system, melanoma, breast, gastric, thyroid, and soft tissue cancers were used to assess the presence of single nucleotide variants (SNVs), insertions and deletions (indels), copy number variations (CNVs), gene fusions, and splice variants. These clinical samples were previously characterized at the various academic centers using orthogonal methods. The Oncomine Dx Express Test showed high performance with 100% concordance with previous characterization for SNVs, indels, CNVs, gene fusions, and splice variants. SNVs and indels with allele frequencies as low as 5% were correctly identified. The test detected all the expected ALK, RET, NTRK1, and ROS1 fusion isoforms and MET exon 14-skipping splice variants. The average TAT from extracted nucleic acids to the final variant report was 18.3 h. The Oncomine Dx Express Test in combination with the Ion Torrent Genexus System is a CE-IVD-compliant, performant, and multicenter reproducible method for NGS detection of actionable biomarkers from a range of tumor samples, providing results in a short TAT that could support timely decision- making for targeted therapeutic interventions.

Assessment of Different Circulating Tumor Cell Platforms for Uveal Melanoma: Potential Impact for Future Routine Clinical Practice.

Liquid biopsy and circulating tumor cell (CTC) screening has gained interest over the last two decades for detecting almost all solid malignancies. To date, the major limitation in terms of the applicability of CTC screening in daily clinical practice is the lack of reproducibility due to the high number of platforms available that use various technologies (e.g., label-dependent versus label-free detection). Only a few studies have compared different CTC platforms. The aim of this study was to compare the efficiency of four commercially available CTC platforms (Vortex (VTX-1), ClearCell FX, ISET, and Cellsearch) for the detection and identification of uveal melanoma cells (OMM 2.3 cell line). Tumor cells were seeded in RPMI medium and venous blood from healthy donors, and then processed similarly using these four platforms. Melan-A immunochemistry was performed to identify tumor cells, except when the Cellsearch device was used (automated identification). The mean overall recovery rates (with mean recovered cells) were 39.2% (19.92), 22.2% (11.31), 8.9% (4.85), and 1.1% (0.20) for the ISET, Vortex (VTX-1), ClearCell FX, and CellSearch platforms, respectively. Although paramount, the recovery rate is not sufficient to assess a CTC platform. Other parameters, such as the purpose for using a platform (diagnosis, genetics, drug sensitivity, or patient-derived xenograft models), reproducibility, purity, user-friendliness, cost-effectiveness, and ergonomics, should also be considered before they can be used in daily clinical practice and are discussed in this article.

Ultrafast Gene Fusion Assessment for Nonsquamous NSCLC.

Introduction: Gene fusion testing of ALK, ROS1, RET, NTRK, and MET exon 14 skipping mutations is guideline recommended in nonsquamous NSCLC (NS-NSCLC). Nevertheless, assessment is often hindered by the limited availability of tissue and prolonged next-generation sequencing (NGS) testing, which can protract the initiation of a targeted therapy. Therefore, the development of faster gene fusion assessment is critical for optimal clinical decision-making. Here, we compared two ultrafast gene fusion assays (UFGFAs) using NGS (Genexus, Oncomine Precision Assay, Thermo Fisher Scientific) and a multiplex reverse-transcriptase polymerase chain reaction (Idylla, GeneFusion Assay, Biocartis) approach at diagnosis in a retrospective series of 195 NS-NSCLC cases and five extrapulmonary tumors with a known NTRK fusion. Methods: A total of 195 NS-NSCLC cases (113 known gene fusions and 82 wild-type tumors) were included retrospectively. To validate the detection of a NTRK fusion, we added five NTRK-positive extrathoracic tumors. The diagnostic performance of the two UFGFAs and standard procedures was compared. Results: The accuracy was 92.3% and 93.1% for Idylla and Genexus, respectively. Both systems improved the sensitivity for detection by including a 5'-3' imbalance analysis. Although detection of ROS1, MET exon 14 skipping, and RET was excellent with both systems, ALK fusion detection was reduced with sensitivities of 87% and 88%, respectively. Idylla had a limited sensitivity of 67% for NTRK fusions, in which only an imbalance assessment was used. Conclusions: UFGFA using NGS and reverse-transcriptase polymerase chain reaction approaches had an equal level of detection of gene fusion but with some technique-specific limitations. Nevertheless, UFGFA detection in routine clinical care is feasible with both systems allowing faster initiation of therapy and a broad degree of screening.

The Impact of a Family-Based Assessment and Intervention Healthy Lifestyle Programme on Health Knowledge and Beliefs of Children with Obesity and Their Families.

Objective: To determine the impact of a family-based assessment-and-intervention healthy lifestyle programme on health knowledge and beliefs of children and families affected by obesity. Second, to compare the health knowledge of the programme cohort to those of a national cohort in Aotearoa/New Zealand (NZ). Design: This mixed-methods study collected health knowledge and health belief data in a questionnaire at baseline and 12-, 24-, and 60-month follow-up assessments. Health knowledge over time was compared with baseline knowledge and with data from a nationally representative survey. A data-driven subsumption approach was used to analyse open-text responses to health belief questions across the study period. Setting: Taranaki region, a mixed urban−rural setting in NZ. Participants: Participants (caregiver/child dyads) from the Whanau Pakari randomised trial. Results: A greater proportion of the cohort correctly categorised foods and drinks as healthy or unhealthy at 12 months compared to baseline for most questionnaire items. Retention of this health knowledge was evident at 24- and 60-month follow-ups. More than twice as many participants correctly reported physical activity recommendations at follow-up compared to baseline (p < 0.001). Health knowledge of participants was similar to the national survey cohort at baseline, but surpassed it at 12 and 24 months. Participant beliefs around healthy lifestyles related to physical functioning, mental and emotional wellbeing, and enhancement of appearance, and gained greater depth and detail over time. Conclusions: This study demonstrates the important role that community-level healthy lifestyle programmes can have in knowledge-sharing and health promotion.

Daily Practice Assessment of KRAS Status in NSCLC Patients: A New Challenge for the Thoracic Pathologist Is Right around the Corner.

KRAS mutations are among the most frequent genomic alterations identified in non-squamous non-small cell lung carcinomas (NS-NSCLC), notably in lung adenocarcinomas. In most cases, these mutations are mutually exclusive, with different genomic alterations currently known to be sensitive to therapies targeting EGFR, ALK, BRAF, ROS1, and NTRK. Recently, several promising clinical trials targeting KRAS mutations, particularly for KRAS G12C-mutated NSCLC, have established new hope for better treatment of patients. In parallel, other studies have shown that NSCLC harboring co-mutations in KRAS and STK11 or KEAP1 have demonstrated primary resistance to immune checkpoint inhibitors. Thus, the assessment of the KRAS status in advanced-stage NS-NSCLC has become essential to setting up an optimal therapeutic strategy in these patients. This stimulated the development of new algorithms for the management of NSCLC samples in pathology laboratories and conditioned reorganization of optimal health care of lung cancer patients by the thoracic pathologists. This review addresses the recent data concerning the detection of KRAS mutations in NSCLC and focuses on the new challenges facing pathologists in daily practice for KRAS status assessment.

Perspectives and Issues in the Assessment of SMARCA4 Deficiency in the Management of Lung Cancer Patients.

Lung cancers are ranked third among the cancer incidence in France in the year 2020, with adenocarcinomas being the commonest sub-type out of ~85% of non-small cell lung carcinomas. The constant evolution of molecular genotyping, which is used for the management of lung adenocarcinomas, has led to the current focus on tumor suppressor genes, specifically the loss of function mutation in the SMARCA4 gene. SMARCA4-deficient adenocarcinomas are preponderant in younger aged male smokers with a predominant solid morphology. The importance of identifying SMARCA4-deficient adenocarcinomas has gained interest for lung cancer management due to its aggressive behavior at diagnosis with vascular invasion and metastasis to the pleura seen upon presentation in most cases. These patients have poor clinical outcome with short overall survival rates, regardless of the stage of disease. The detection of SMARCA4 deficiency is possible in most pathology labs with the advent of sensitive and specific immunohistochemical antibodies. The gene mutations can be detected together with other established lung cancer molecular markers based on the current next generation sequencing panels. Sequencing will also allow the identification of associated gene mutations, notably KRAS, KEAP1, and STK11, which have an impact on the overall survival and progression-free survival of the patients. Predictive data on the treatment with anti-PD-L1 are currently uncertain in this high tumor mutational burden cancer, which warrants more groundwork. Identification of target drugs is also still in pre-clinical testing. Thus, it is paramount to identify the SMARCA4-deficient adenocarcinoma, as it carries worse repercussions on patient survival, despite having an exceptionally low prevalence. Herein, we discuss the pathophysiology of SMARCA4, the clinicopathological consequences, and different detection methods, highlighting the perspectives and challenges in the assessment of SMARCA4 deficiency for the management of non-small cell lung cancer patients. This is imperative, as the contemporary shift on identifying biomarkers associated with tumor suppressor genes such as SMARCA4 are trending; hence, awareness of pathologists and clinicians is needed for the SMARCA4-dNSCLC entity with close follow-up on new management strategies to overcome the poor possibilities of survival in such patients.

EGFR Status Assessment for Better Care of Early Stage Non-Small Cell Lung Carcinoma: What Is Changing in the Daily Practice of Pathologists?

The recent emergence of novel neoadjuvant and/or adjuvant therapies for early stage (I-IIIA) non-small cell lung carcinoma (NSCLC), mainly tyrosine kinase inhibitors (TKIs) targeting EGFR mutations and immunotherapy or chemo-immunotherapy, has suddenly required the evaluation of biomarkers predictive of the efficacy of different treatments in these patients. Currently, the choice of one or another of these treatments mainly depends on the results of immunohistochemistry for PD-L1 and of the status of EGFR and ALK. This new development has led to the setup of different analyses for clinical and molecular pathology laboratories, which have had to rapidly integrate a number of new challenges into daily practice and to establish new organization for decision making. This review outlines the impact of the management of biological samples in laboratories and discusses perspectives for pathologists within the framework of EGFR TKIs in early stage NSCLC.

The cost of investigating weight-related comorbidities in children and adolescents in Aotearoa/New Zealand.

AIM: Expert recommendations for child/adolescent obesity include extensive investigation for weight-related comorbidities, based on body mass index (BMI) percentile cut-offs. This study aimed to estimate the cost of initial investigations for weight-related comorbidities in children/adolescents with obesity, according to international expert guidelines. METHODS: The annual mean cost of investigations for weight-related comorbidities in children/adolescents was calculated from a health-funder perspective using 2019 cost data obtained from three New Zealand District Health Boards. Prevalence data for child/adolescent obesity (aged 2-14 years) were obtained from the New Zealand Health Survey (2017/2018), and prevalence of weight-related comorbidities requiring further investigation were obtained from a previous New Zealand study of a cohort of children with obesity. RESULTS: The cost of initial laboratory screening for weight-related comorbidities per child was NZD 28.36. Based on national prevalence data from 2018/2019 for children with BMI greater than the 98th percentile (obesity cut-off), the total annual cost for initial laboratory screening for weight-related comorbidities in children/adolescents aged 2-14 years with obesity was estimated at NZD 2,665,840. The cost of further investigation in the presence of risk factors was estimated at NZD 2,972,934. CONCLUSIONS: Investigating weight-related comorbidities in New Zealand according to international expert guidelines is resource-intensive. Ways to further determine who warrants investigation with an individualised approach are required.

The Importance of STK11/LKB1 Assessment in Non-Small Cell Lung Carcinomas.

Despite the recent implementation of immunotherapy as a single treatment or in combination with chemotherapy for first-line treatment of advanced non-small cell lung cancer (NSCLC), many patients do not benefit from this regimen due to primary treatment resistance or toxicity. Consequently, there is an urgent need to develop efficient biomarkers that can select patients who will benefit from immunotherapy thereby providing the appropriate treatment and avoiding toxicity. One of the biomarkers recently described for the stratification of NSCLC patients undergoing immunotherapy are mutations in STK11/LKB1, which are often associated with a lack of response to immunotherapy in some patients. Therefore, the purpose of this review is to describe the different cellular mechanisms associated with STK11/LKB1 mutations, which may explain the lack of response to immunotherapy. Moreover the review addresses the co-occurrence of additional mutations that may influence the response to immunotherapy and the current clinical studies that have further explored STK11/LKB1 as a predictive biomarker. Additionally this work includes the opportunities and limitations to look for the STK11/LKB1 status in the therapeutic strategy for NSCLC patients.

Setting-Up a Rapid SARS-CoV-2 Genome Assessment by Next-Generation Sequencing in an Academic Hospital Center (LPCE, Louis Pasteur Hospital, Nice, France).

Introduction: Aside from the reverse transcription-PCR tests for the diagnosis of the COVID-19 in routine clinical care and population-scale screening, there is an urgent need to increase the number and the efficiency for full viral genome sequencing to detect the variants of SARS-CoV-2. SARS-CoV-2 variants assessment should be easily, rapidly, and routinely available in any academic hospital. Materials and Methods: SARS-CoV-2 full genome sequencing was performed retrospectively in a single laboratory (LPCE, Louis Pasteur Hospital, Nice, France) in 103 SARS-CoV-2 positive individuals. An automated workflow used the Ion Ampliseq SARS-CoV-2 panel on the Genexus Sequencer. The analyses were made from nasopharyngeal swab (NSP) (n = 64) and/or saliva (n = 39) samples. All samples were collected in the metropolitan area of the Nice city (France) from September 2020 to March 2021. Results: The mean turnaround time between RNA extraction and result reports was 30 h for each run of 15 samples. A strong correlation was noted for the results obtained between NSP and saliva paired samples, regardless of low viral load and high (>28) Ct values. After repeated sequencing runs, complete failure of obtaining a valid sequencing result was observed in 4% of samples. Besides the European strain (B.1.160), various variants were identified, including one variant of concern (B.1.1.7), and different variants under monitoring. Discussion: Our data highlight the current feasibility of developing the SARS-CoV-2 next-generation sequencing approach in a single hospital center. Moreover, these data showed that using the Ion Ampliseq SARS-CoV-2 Assay, the SARS-CoV-2 genome sequencing is rapid and efficient not only in NSP but also in saliva samples with a low viral load. The advantages and limitations of this setup are discussed.

Two-year outcomes of Whanau Pakari, a multi-disciplinary assessment and intervention for children and adolescents with weight issues: A randomized clinical trial.

OBJECTIVE: To determine whether 12-month BMI SDS reductions persisted at 24 months in a multi-disciplinary assessment and intervention program for children and adolescents with obesity, and whether secondary outcomes improved. METHODS: This was a community-based 12-month RCT in Aotearoa/New Zealand. Eligible participants were aged 5 to 16 years with BMI ≥98th centile or BMI >91st centile with weight-related comorbidities. The low-intensity control received comprehensive home-based baseline assessments and advice, and 6-monthly follow-up. The high-intensity intervention received the same assessments and advice, but also weekly multidisciplinary sessions. Primary outcome was BMI SDS at 12 months. Secondary outcomes included cardiovascular and metabolic markers. RESULTS: 121 participants (60% of participants at baseline) were assessed at 24 months. BMI SDS reduction at 12 months was lost at 24 months in the modified intention-to-treat analysis [Control -0.03 (95%CI -0.14, 0.09) and Intervention -0.02 (-0.12, 0.08); P = .93]. However, sweet drink intake was reduced, water intake increased, and there were improvements in cardiovascular fitness in the high-intensity intervention. ≥70% attendance in the high-intensity intervention resulted in a persistent BMI SDS reduction of -0.22 after 24 months (95%CI -0.38, -0.06). CONCLUSIONS: This trial was negative in terms of primary outcome at 24 months. However, high engagement led to sustained treatment effect, and there were multiple improvements in health measures.

What affects programme engagement for Maori families? A qualitative study of a family-based, multidisciplinary healthy lifestyle programme for children and adolescents.

AIM: It is important that intervention programmes are accessible and acceptable for groups most affected by excess weight. This study aimed to understand the barriers to and facilitators of engagement for Maori in a community-based, assessment-and-intervention healthy lifestyle programme (Whanau Pakari). METHODS: Sixty-four in-depth, home-based interviews were conducted with past service users. Half of these were with families with Maori children and half with non-Maori families. The interviews were thematically analysed with peer debriefing for validity. RESULTS: Maori families experienced barriers due to racism throughout the health system and society, which then affected their ability to engage with the programme. Key barriers included the institutionalised racism evident through substantial structural barriers and socio-economic challenges, the experience of interpersonal racism and its cumulative impact with weight stigma, and internalised racism and beliefs of biological determinism. Responses to these barriers were distrust of health services, followed by renewed engagement or complete disengagement. Participants identified culturally appropriate care as that which was compassionate, respectful, and focused on relationship building. CONCLUSIONS: While Whanau Pakari is considered appropriate due to the approach of the delivery team, this is insufficient to retain some Maori families who face increased socio-economic and structural barriers. Past instances of weight stigma and racism have enduring effects when re-engaging with future health services, and inequities are likely to persist until these issues are addressed within the health system and wider society.

Real-world assessment of the BRAF status in non-squamous cell lung carcinoma using VE1 immunohistochemistry: A single laboratory experience (LPCE, Nice, France).

INTRODUCTION: International guidelines recommend BRAF mutational status assessment in treatment-naive advanced non-squamous non-small cell lung carcinoma (NSCLC) patients since the presence of a BRAFV600 mutation enables specific BRAF inhibitor treatment. For this purpose, the mutational status needs to be obtained in 10 working days. Herein, we prospectively evaluated the feasibility of systematic assessment of the BRAF status using immunohistochemistry (IHC) in a single institution (LPCE, Nice) at baseline for NSCLC diagnosed. METHODS: 1317 NSCLC were evaluated using BRAF IHC from 2011 to 2019. Initially the BRAF status was prospectively assessed using NGS and/or pyrosequencing in 618 consecutively diagnosed NSCLC patients from 2012 to 2016; BRAFV600E and BRAF nonV600E mutated tumors detected in this cohort were retrospectively evaluated using BRAF IHC. Secondarily, 699 biopsies of NSCLC were prospectively analyzed between 2017 and 2019 using BRAF IHC. BRAF IHC positive tumors were tested using a rapid BRAF specific PCR based assay. RESULTS: Initially, 21/618 (3%) of tumors (15 early and 6 late stage tumors) were BRAFV600E mutated according to the results of NGS and/or pyrosequencing. BRAF IHC was positive in 21/21 of these cases and negative in 51/51 (100 %) BRAF non V600E mutated cases. In the prospective BRAF IHC tested cohort of patients, 24/699 (3%) tumors (13 early and 11 late stage tumors) were positive with VE1 IHC. The BRAF PCR assay was positive in 20/24 (83 %) of these cases. CONCLUSION: BRAFV600E IHC screening of treatment-naïve NSCLC patients is a rapid, specific and very sensitive method which can lead in advanced stage positive NSCLC tumors to a BRAF inhibitor treatment. This test can be routinely integrated into mandatory predictive biomarker 'testing of NSCLC. According to the organization of patient care and the physician's request, this practice can be proposed as an alternative to NGS-based tissue biopsy made at baseline.

Comparison of Three Sequencing Panels Used for the Assessment of Tumor Mutational Burden in NSCLC Reveals Low Comparability.

INTRODUCTION: Tumor mutational burden (TMB) has been proposed as a novel predictive biomarker for the stratification of patients with NSCLC undergoing immune checkpoint inhibitor (ICI) treatment. The assessment of TMB has recently been established using large targeted sequencing panels, and numerous studies are ongoing to harmonize TMB assessment. "Correlation" or the coefficient of determination has generally been used to evaluate the association between different panels. We hypothesized that these metrics might overestimate the comparability, especially for lower TMB values. METHODS: A total of 30 samples from patients with NSCLC undergoing ICI treatment were consecutively sequenced using the following three large, targeted sequencing panels: FoundationOne, Oncomine TML, and QiaSeq TMB. The TMB values were compared in the whole patient population and in a subset of patients in which the TMB assessed by FoundationOne was between 5 and 25 mutations/Mb. Prediction of durable clinical benefit (>6 mo with no progression) was assessed using receiver operator characteristics, and optimal cutoff values were calculated using the Youden J statistic. RESULTS: Correlation between the three targeted sequencing panels was strong in the whole patient population (R2 > 0.79) but was dramatically reduced in the subset of patients with TMB of 5 to 25 mutations/Mb. The agreement assessed using the Bland-Altman method was also very low. All panels were able to predict durable clinical benefit in the TMB-high population. CONCLUSIONS: Assessment of TMB using the three targeted sequencing panels was possible and predictive of response to ICI treatment, but correlation was an inappropriate measurement to assess the association between the respective panels.

Targeted Assessment of the EGFR Status as Reflex Testing in Treatment-Naive Non-Squamous Cell Lung Carcinoma Patients: A Single Laboratory Experience (LPCE, Nice, France).

BACKGROUND: Assessment of actionable EGFR mutations is mandatory for treatment-naïve advanced or metastatic non-squamous lung carcinoma (NSLC), but the results need to be obtained in less than 10 working days. For rapid EGFR testing, an EGFR-specific polymerase chain reaction (PCR) assay is an alternative and simple approach compared to next generation sequencing (NGS). Here, we describe how a rapid EGFR-specific PCR assay can be implemented in a single laboratory center (LPCE, Nice, France) as reflex testing in treatment-naïve NSLC. METHODS: A total of 901 biopsies from NSLC with more than 10% of tumor cells were prospectively and consecutively evaluated for EGFR mutation status between November 2017 and December 2019 using the Idylla system (Biocartis NV, Mechelen, Belgium). NGS was performed for nonsmokers with NSLC wild type for EGFR, ALK, ROS1, and BRAF and with less than 50% PD-L1 positive cells using the Hotspot panel (Thermo Fisher Scientific, Waltham, MA, USA). RESULTS: Results were obtained from 889/901 (97%) biopsies with detection of EGFR mutations in 114/889 (13%) cases using the Idylla system. Among the 562 EGFR wild type tumors identified with Idylla, NGS detected one actionable and one nonactionable EGFR mutation. CONCLUSIONS: Rapid and targeted assessment of EGFR mutations in treatment-naïve NSLC can be implemented in routine clinical practice. However, it is mandatory to integrate this approach into a molecular algorithm that allows evaluation of potentially actionable genomic alterations other than EGFR mutations.

Critical Assessment in Routine Clinical Practice of Liquid Biopsy for EGFR Status Testing in Non-Small-Cell Lung Cancer: A Single-Laboratory Experience (LPCE, Nice, France).

BACKGROUND: The introduction of liquid biopsy using PCR-based assays into routine practice has had a strong impact on the treatment of EGFR-mutated lung adenocarcinoma and is now commonly used for routine testing of EGFR mutations in certain clinical settings. To assess whether the claimed benefits of PCR-based assays hold true in daily practice at a multicenter clinical institution, we assessed how treatment decisions are affected by PCR-based assays for the analysis of EGFR mutations from plasma samples in a centralized laboratory (LPCE, Nice, France). PATIENTS AND METHODS: A total of 345 samples were analyzed using the US Food and Drug Administration-approved Cobas EGFR Mutation Test v2 and 103 using the Therascreen EGFR Plasma RGQ PCR Kit over 3 years (395 samples from 324 patients). Eleven plasma samples were validated independently using Cobas at 3 institutions, and 130 samples were analyzed using Stilla digital PCR. Clinical data were collected for 175 (54%) of 324 patients. RESULTS: Cobas was superior to the Therascreen assay and demonstrated 100% reproducibility. Digital PCR showed only 48%, 83%, and 58% concordance with Cobas for exon 19 deletions, L858R mutations, and T790M mutations, respectively. Liquid biopsies helped inform and change treatment when resistance occurred and enabled the detection of EGFR mutations in patients when biopsy tissue results were unavailable. CONCLUSION: PCR-based assays are a fast and convenient test, allowing the detection of primary and secondary EGFR mutations from plasma. Cobas proved to be a reliable test, whereas digital PCR produced too many inconclusive results to be currently recommended as a principal testing device.

Survey of Barriers and Facilitators to Engagement in a Multidisciplinary Healthy Lifestyles Program for Children.

OBJECTIVE: To understand facilitators and barriers to engagement in a multidisciplinary assessment and intervention program for children and adolescents with obesity, particularly for Maori, the Indigenous people of New Zealand. METHODS: Whanau Pakari participants and caregivers (n = 71, 21% response rate) referred to the family-based healthy lifestyles program in Taranaki, New Zealand, were asked to participate in a confidential survey, which collected self-reported attendance levels and agreement with statements around service accessibility and appropriateness and open-text comments identifying barriers and facilitators to attendance. RESULTS: Self-reported attendance levels were higher when respondents reported sessions to be conveniently located (P = .03) and lower when respondents considered other priorities as more important for their family (P = .02). Maori more frequently reported that past experiences of health care influenced their decision to attend (P = .03). Facilitators included perceived convenience of the program, parental motivation to improve child health, and ongoing support from the program. CONCLUSIONS AND IMPLICATIONS: Program convenience and parental and/or self-motivation to improve health were facilitators of attendance. Further research is required to understand the relationship between past experiences with health care and subsequent engagement with services.

The Desire to Better Understand Older Adults with Solid Tumors to Improve Management: Assessment and Guided Interventions-The French PACA EST Cohort Experience.

Todays challenge in geriatric oncology is to screen patients who need geriatric follow-up. The main goal of this study was to analyze factors that identify patients, in a large cohort of patients with solid tumors, who need more geriatric interventions and therefore specific follow-up. Between April 2012 and May 2018, 3530 consecutive patients were enrolled in the PACA EST cohort (France). A total of 3140 patients were finally enrolled in the study. A Comprehensive Geriatric Assessment (CGA) was performed at baseline. We analyzed the associations between factors at baseline (geriatric and oncologic factors) and the need to perform more than three geriatric interventions. The mean age of the population was 82 years old with 59% of patients aged older than 80 years old. A total of 8819 geriatric interventions were implemented for the 3140 patients. The percentage of patients with three or more geriatric interventions represented 31.8% (n = 999) of the population. In multivariate analyses, a Mini Nutritional assessment (MNA) <17, an MNA ≤23·5 and ≥17, a performans status (PS) >2, a dependence on Instrumental Activities of Daily Living (IADL), a Geriatric Depression Scale (GDS) ≥5, a Mini Mental State Examination (MMSE) <24, and a Screening tool G8 ≤14 were independent risk factors associated with more geriatric interventions. Factors associated with more geriatric interventions could assist practitioners in selecting patients for specific geriatric follow-up.

Tumor mutational burden assessment as a predictive biomarker for immunotherapy in lung cancer patients: getting ready for prime-time or not?

The emergence of immunotherapy as a first- or second-line of treatment has revolutionized the therapeutic management of lung cancer patients. However, not all lung cancer patients receive the same benefit from this treatment, leading to limitations in the number of patients who can receive anti-PD-1/PD-L1 checkpoint inhibitors because some secondary toxicity has been associated with immunotherapy, and because some patients would benefit more from chemotherapy. In this context, the selection of patients is currently based on PD-L1 immunohistochemistry (IHC), specifically on the percentage of PD-L1 positive tumor cells. To date, this is the only validated biomarker that is used as a companion diagnostic test for immunotherapy in non-small cell carcinoma lung (NSCLC) patients. However, this biomarker is not sufficiently robust and demonstrates many challenges. For example, some patients with more than 50% PD-L1 positive tumor cells are non-responders to anti-PD-1/PD-L1 treatment, while conversely, other patients with no PD-L1 positive tumor cells are good responders. The tumor mutation burden (TMB) or tumor mutation load (TML) emerged recently as a new predictive biomarker for immunotherapy response in NSCLC. However, this biomarker needs to be validated for routine clinical use and shares similar constraints with the PD-L1 IHC biomarker. PD-L1 IHC and TMB are currently the two best predictive biomarkers that could soon be used to systematically inform treatment decisions in advanced or metastatic NSCLC patients. The aim of this review is to consider the possible integration of TMB testing in daily practice through a pros- and cons-debate, and to establish sample quality-dependent algorithms and the main current constraints for laboratories considering TMB assessments.