Artificial Intelligence-Powered Prediction of ALK Gene Rearrangement in Patients With Non-Small-Cell Lung Cancer.

PURPOSE: Several studies reported the possibility of predicting genetic abnormalities in non-small-cell lung cancer by deep learning (DL). However, there are no data of predicting ALK gene rearrangement (ALKr) using DL. We evaluated the ALKr predictability using the DL platform. MATERIALS AND METHODS: We selected 66 ALKr-positive cases and 142 ALKr-negative cases, which were diagnosed by ALKr immunohistochemical staining in our institution from January 2009 to March 2019. We generated virtual slide of 300 slides (150 ALKr-positive slides and 150 ALKr-negative slides) using NanoZoomer. HALO-AI was used to analyze the whole-slide imaging data, and the DenseNet network was used to build the learning model. Of the 300 slides, we randomly assigned 172 slides to the training cohort and 128 slides to the test cohort to ensure no duplication of cases. In four resolutions (16.0/4.0/1.0/0.25 µm/pix), ALKr prediction models were built in the training cohort and ALKr prediction performance was evaluated in the test cohort. We evaluated the diagnostic probability of ALKr by receiver operating characteristic analysis in each ALKr probability threshold (50%, 60%, 70%, 80%, 90%, and 95%). We expected the area under the curve to be 0.64-0.85 in the model of a previous study. Furthermore, in the test cohort data, an expert pathologist also evaluated the presence of ALKr by hematoxylin and eosin staining on whole-slide imaging. RESULTS: The maximum area under the curve was 0.73 (50% threshold: 95% CI, 0.65 to 0.82) in the resolution of 1.0 µm/pix. In this resolution, with an ALKr probability of 50% threshold, the sensitivity and specificity were 73% and 73%, respectively. The expert pathologist's sensitivity and specificity in the same test cohort were 13% and 94%. CONCLUSION: The ALKr prediction by DL was feasible. Further study should be addressed to improve accuracy of ALKr prediction.

Optimising tissue acquisition and the molecular testing pathway for patients with non-small cell lung cancer: A UK expert consensus statement.

Targeted therapy against actionable variants has revolutionised the treatment landscape for non-small cell lung cancer (NSCLC). Approximately half of NSCLC adenocarcinomas have an actionable variant, making molecular testing a critical component of the diagnostic process to personalise therapeutic options, optimise clinical outcomes and minimise toxicity. Recently, genomic testing in England has undergone major changes with the introduction of Genomic Laboratory Hubs, designed to consolidate and enhance existing laboratory provision and deliver genomic testing as outlined in the National Genomic Test Directory. Similar changes are ongoing in Scotland, Wales and Northern Ireland. However, multiple challenges exist with current tissue acquisition procedures and the molecular testing pathway in the UK, including quantity and quality of available tissue, adequacy rates, test availability among genomic laboratories, turnaround times, multidisciplinary team communication, and limited guidance and standardisation. The COVID-19 pandemic has added an extra layer of complexity. Herein, we summarise best practice recommendations, based on expert opinion, to overcome existing challenges in the UK. The least invasive biopsy technique should be undertaken with the aim of acquiring the greatest quality and quantity of tissue. Use of sedation should be considered to improve patient experience. Rapid on-site evaluation may also be useful to help guide adequate sampling, and liquid biopsy may be beneficial in some instances. Sample processing should be appropriate to facilitate biomarker testing, in particular, next-generation sequencing for comprehensive genomic information. Steps to optimise tissue utilisation and turnaround times, such as planning of tissue usage, limiting immunohistochemistry, tumour enrichment, and reflex testing at diagnosis, should be implemented. Guidelines for tissue acquisition and sample processing may help to improve sample adequacy to perform downstream testing. Communication among genomic laboratories will help to standardise test availability across England and local auditing could identify further areas for optimisation, including ways to improve turnaround times and adequacy rates.

Impact of the SARS-CoV-2 pandemic on female breast, colorectal and non-small cell lung cancer incidence, stage and healthcare pathway to diagnosis during 2020 in Wales, UK, using a national cancer clinical record system.

BACKGROUND: COVID-19 pandemic responses impacted behaviour and health services. We estimated the impact on incidence, stage and healthcare pathway to diagnosis for female breast, colorectal and non-small cell lung cancers at population level in Wales. METHODS: Cancer e-record and hospital admission data linkage identified adult cases, stage and healthcare pathway to diagnosis (population ~2.5 million). Using multivariate Poisson regressions, we compared 2019 and 2020 counts and estimated incidence rate ratios (IRR). RESULTS: Cases decreased 15.2% (n = -1011) overall. Female breast annual IRR was 0.81 (95% CI: 0.76-0.86, p < 0.001), colorectal 0.80 (95% CI: 0.79-0.81, p < 0.001) and non-small cell lung 0.91 (95% CI: 0.90-0.92, p < 0.001). Decreases were largest in 50-69 year olds for female breast and 80+ year olds for all cancers. Stage I female breast cancer declined 41.6%, but unknown stage increased 55.8%. Colorectal stages I-IV declined (range 26.6-29.9%), while unknown stage increased 803.6%. Colorectal Q2-2020 GP-urgent suspected cancer diagnoses decreased 50.0%, and 53.9% for non-small cell lung cancer. Annual screen-detected female breast and colorectal cancers fell 47.8% and 13.3%, respectively. Non-smal -cell lung cancer emergency presentation diagnoses increased 9.5% (Q2-2020) and 16.3% (Q3-2020). CONCLUSION: Significantly fewer cases of three common cancers were diagnosed in 2020. Detrimental impacts on outcomes varied between cancers. Ongoing surveillance with health service optimisation will be needed to mitigate impacts.

Molecular Beacon for Detection miRNA-21 as a Biomarker of Lung Cancer.

Lung cancer (LC) is the leading cause of cancer-related death worldwide. Although the diagnosis and treatment of non-small cell lung cancer (NSCLC), which accounts for approximately 80% of LC cases, have greatly improved in the past decade, there is still an urgent need to find more sensitive and specific screening methods. Recently, new molecular biomarkers are emerging as potential non-invasive diagnostic agents to screen NSCLC, including multiple microRNAs (miRNAs) that show an unusual expression profile. Moreover, peripheral blood mononuclear cells' (PBMCs) miRNA profile could be linked with NSCLC and used for diagnosis. We developed a molecular beacon (MB)-based miRNA detection strategy for NSCLC. Following PBMCs isolation and screening of the expression profile of a panel of miRNA by RT-qPCR, we designed a MB targeting of up-regulated miR-21-5p. This MB 21-5p was characterized by FRET-melting, CD, NMR and native PAGE, allowing the optimization of an in-situ approach involving miR-21-5p detection in PBMCs via MB. Data show the developed MB approach potential for miR-21-5p detection in PBMCs from clinical samples towards NSCLC.

Defining comprehensive biomarker-related testing and treatment practices for advanced non-small-cell lung cancer: Results of a survey of U.S. oncologists.

BACKGROUND: An ASCO taskforce comprised of representatives of oncology clinicians, the American Cancer Society National Lung Cancer Roundtable (NLCRT), LUNGevity, the GO2 Foundation for Lung Cancer, and the ROS1ders sought to: characterize U.S. oncologists' biomarker ordering and treatment practices for advanced non-small-cell lung cancer (NSCLC); ascertain barriers to biomarker testing; and understand the impact of delays on treatment decisions. METHODS: We deployed a survey to 2374 ASCO members, targeting U.S. thoracic and general oncologists. RESULTS: We analyzed 170 eligible responses. For non-squamous NSCLC, 97% of respondents reported ordering tests for EGFR, ALK, ROS1, and BRAF. Testing for MET, RET, and NTRK was reported to be higher among academic versus community providers and higher among thoracic oncologists than generalists. Most respondents considered 1 (46%) or 2 weeks (52%) an acceptable turnaround time, yet 37% usually waited three or more weeks to receive results. Respondents who waited ≥3 weeks were more likely to defer treatment until results were reviewed (63%). Community and generalist respondents who waited ≥3 weeks were more likely to initiate non-targeted treatment while awaiting results. Respondents <5 years out of training were more likely to cite their concerns about waiting for results as a reason for not ordering biomarker testing (42%, vs. 19% with ≥6 years of experience). CONCLUSIONS: Respondents reported high biomarker testing rates in patients with NSCLC. Treatment decisions were impacted by test turnaround time and associated with practice setting and physician specialization and experience.

Editorial: Global Regulatory Initiatives Deliver Accelerated Approval of the First Bispecific Therapeutic Monoclonal Antibody for Advanced Non-Small Cell Lung Cancer (NSCLC).

The coronavirus disease 2019 (COVID-19) pandemic has affected the number of completed clinical trials, particularly in oncology. Between 80-85% of all lung cancers are non-small cell lung cancer (NSCLC), and of these, between 2-3% have an EGFR exon 20 insertion, which is associated with increased cell proliferation, metastasis, and a lack of response to chemotherapy and epidermal growth factor receptor (EGFR) inhibitors. Until this year, there were no available targeted therapies for advanced NSCLC with this genetic subtype. However, in May 2021, the US Food and Drug Administration (FDA) granted accelerated approval for amivantamab-vmjw (Rybrevant®), a bispecific monoclonal antibody, targeting activating and resistant EGFR and MET mutations and amplifications. This FDA approval was for adult patients with locally advanced metastatic NSCLC, with disease progression on or following platinum-based chemotherapy. The FDA also approved the Guardant360® companion diagnostic, a next-generation sequencing platform for circulating tumor DNA (ctDNA), which is a liquid biopsy assay. In 2019, Project Orbis was launched by the FDA Oncology Center of Excellence as a global collaborative review program to facilitate rapid global access for patients to innovative cancer therapies. This Editorial aims to highlight how global regulatory initiatives from the FDA have delivered accelerated approval of the first bispecific therapeutic monoclonal antibody, amivantamab-vmjw (Rybrevant®), and a companion diagnostic for patients with advanced NSCLC with an EGFR exon 20 insertion.

Italian survey on the clinical management of non-small cell lung cancer patients during the COVID-19 pandemic: A lesson for the second wave.

This study investigated the clinical management of non small cell lung cancer (NSCLC) patients during the first wave of coronavirus disease 2019 (COVID-19) outbreak in Italy. A 29-questions survey was sent to 95 Italian thoracic oncologists, with 77 % of them declaring significant changes in the outpatients management and treatment. The results of this survey pointed out a significant delay of lung cancer diagnosis along with a relevant reduction of patients' accrual within clinical trials. Telemedicine emerged as a valid support for patient-healthcare interactions. Therapeutic indications followed the guidelines for adjuvant chemotherapy and concurrent chemo-radiation. Clinical indications to first-line therapies were largely confirmed, while major changes regarded the selection of second line treatment options as well as the management of elderly population. This work may represent a valid source of information to improve the clinical management of NSCLC patients during second wave of COVID-19 pandemic.

Development of a Model to Estimate the Association Between Delay in Cancer Treatment and Local Tumor Control and Risk of Metastases.

Importance: The coronavirus disease 2019 (COVID-19) pandemic has led to treatment delays for many patients with cancer. While published guidelines provide suggestions on which cases are appropriate for treatment delay, there are no good quantitative estimates on the association of delays with tumor control or risk of new metastases. Objectives: To develop a simplified mathematical model of tumor growth, control, and new metastases for cancers with varying doubling times and metastatic potential and to estimate tumor control probability (TCP) and metastases risk as a function of treatment delay interval. Design, Setting, and Participants: This decision analytical model describes a quantitative model for 3 tumors (ie, head and neck, colorectal, and non-small cell lung cancers). Using accepted ranges of tumor doubling times and metastatic development from the clinical literature from 2001 to 2020, estimates of tumor growth, TCP, and new metastases were analyzed for various treatment delay intervals. Main Outcomes and Measures: Risk estimates for potential decreases in local TCP and increases in new metastases with each interval of treatment delay. Results: For fast-growing head and neck tumors with a 2-month treatment delay, there was an estimated 4.8% (95% CI, 3.4%-6.4%) increase in local tumor control risk and a 0.49% (0.47%-0.51%) increase in new distal metastases risk. A 6-month delay was associated with an estimated 21.3% (13.4-30.4) increase in local tumor control risk and a 6.0% (5.2-6.8) increase in distal metastases risk. For intermediate-growing colorectal tumors, there was a 2.1% (0.7%-3.5%) increase in local tumor control risk and a 2.7% (2.6%-2.8%) increase in distal metastases risk at 2 months and a 7.6% (2.2%-14.2%) increase in local tumor control risk and a 24.7% (21.9%-27.8%) increase in distal metastases risk at 6 months. For slower-growing lung tumors, there was a 1.2% (0.0%-2.8%) increase in local tumor control risk and a 0.19% (0.18%-0.20%) increase in distal metastases risk at 2 months, and a 4.3% (0.0%-10.6%) increase in local tumor control risk and a 1.9% (1.6%-2.2%) increase in distal metastases risk at 6 months. Conclusions and Relevance: This study proposed a model to quantify the association of treatment delays with local tumor control and risk of new metastases. The detrimental associations were greatest for tumors with faster rates of proliferation and metastasis. The associations were smaller, but still substantial, for slower-growing tumors.

Consensus statement: summary of the Quebec Lung Cancer Network recommendations for prioritizing patients with thoracic cancers in the context of the COVID-19 pandemic.

Background: The emergence of covid-19 has the potential to change the way in which the health care system can accommodate various patient populations and might affect patients with non-covid-19 problems. The Quebec Lung Cancer Network, which oversees thoracic oncology services in the province of Quebec under the direction of the Ministère de la Santé et des Services sociaux, convened to develop recommendations to deal with the potential disruption of services in thoracic oncology in the province of Quebec. The summary provided here has been adapted from the original document posted on the Programme québécois du cancer Web site at: https://www.msss.gouv.qc.ca/professionnels/documents/coronavirus-2019-ncov/PJ1_Recommandations_oncologie-thoracique-200415.pdf. Methods: Plans to optimize the health care system and potentially to prioritize services were discussed with respect to various levels of activity. For each level-of-activity scenario, suggestions were made for the services and treatments to prioritize and for those that might have to be postponed, as well as for potential alternatives to care. Results: The principal recommendation is that the cancer centre executive committee and the multidisciplinary tumour board always try to find a solution to maintain standard-of-care therapy for all patients with thoracic tumours, using novel approaches to treatment and the adoption of a network approach to care, as needed. Conclusions: The effect of the covid-19 pandemic on the health care system remains unpredictable and requires that cancer teams unite and offer the most efficient and innovative therapies to all patients under the various conditions that might be forced upon them.

Collateral effects of the coronavirus disease 2019 pandemic on lung cancer diagnosis in Korea.

BACKGROUND: The COVID-19 pandemic is predicted to significantly affect patients with lung cancer, owing to its rapid progression and high mortality. Studies on lung cancer diagnosis and treatment during an epidemic are lacking. We analyzed the impact of COVID-19 on lung cancer diagnosis in Korea, where lung cancer incidence continues to rise. METHODS: The number of newly diagnosed lung cancer cases in three university-affiliated hospitals during the pandemic and their clinical features were compared with lung cancer cases diagnosed during the same period in the past 3 years. The effectiveness of measures taken by the study hospitals to prevent nosocomial transmission was reviewed. RESULTS: A total of 612 patients were diagnosed with lung cancer from February through June, 2017-2020. During the pandemic, the number of patients who sought consultation at the division of pulmonology of study hospitals dropped by 16% from the previous year. Responding to the pandemic, the involved hospitals created physically isolated triage areas for patients with acute respiratory infection symptoms. Wide-range screening and preventive measures were implemented, thus minimizing the delay in lung cancer diagnosis. No patient acquired COVID-19 due to hospital exposure. The proportion of patients with stage III-IV non-small-cell lung cancer (NSCLC) significantly increased (2020: 74.7% vs. 2017: 57.9%, 2018: 66.7%, 2019: 62.7%, p = 0.011). The number of lung cancers diagnosed during this period and the previous year remained the same. CONCLUSIONS: The proportion of patients with advanced NSCLC increased during the COVID-19 pandemic.

Clinical courses and outcomes of five patients with primary lung cancer surgically treated while affected by Severe acute respiratory syndrome coronavirus 2.

OBJECTIVES: There is currently a lack of clinical data on the novel beta-coronavirus infection [caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] and concomitant primary lung cancer. Our goal was to report our experiences with 5 patients treated for lung cancer while infected with SARS-CoV-2. METHODS: We retrospectively evaluated 5 adult patients infected with SARS-CoV-2 who were admitted to our thoracic surgery unit between 29 January 2020 and 4 March 2020 for surgical treatment of a primary lung cancer. Clinical data and outcomes are reported. RESULTS: All patients were men with a mean age of 74.0 years (range 67-80). Four of the 5 patients (80%) reported chronic comorbidities. Surgery comprised minimally invasive lobectomy (2 patients) and segmentectomy (1 patient), lobectomy with en bloc chest wall resection (1 patient) and pneumonectomy (1 patient). Mean chest drain duration was 12.4 days (range 8-22); mean hospital stay was 33.8 days (range 21-60). SARS-CoV-2-related symptoms were fever (3 patients), persistent cough (3 patients), diarrhoea (2 patients) and syncope (2 patients); 1 patient reported no symptoms. Morbidity related to surgery was 60%; 30-day mortality was 40%. Two patients (1 with a right pneumonectomy, 74 years old; 1 with a lobectomy with chest wall resection and reconstruction, 70 years old), developed SARS-CoV-2-related lung failure leading to death 60 and 32 days after surgery, respectively. CONCLUSIONS: Lung cancer surgery may represent a high-risk factor for developing a severe case of coronavirus disease 2019, particularly in patients with advanced stages of lung cancer. Additional strategies are needed to reduce the risk of morbidity and mortality from SARS-CoV-2 infection during treatment for lung cancer.

Management of Lung Nodules and Lung Cancer Screening During the COVID-19 Pandemic: CHEST Expert Panel Report.

BACKGROUND: The risks from potential exposure to coronavirus disease 2019 (COVID-19), and resource reallocation that has occurred to combat the pandemic, have altered the balance of benefits and harms that informed current (pre-COVID-19) guideline recommendations for lung cancer screening and lung nodule evaluation. Consensus statements were developed to guide clinicians managing lung cancer screening programs and patients with lung nodules during the COVID-19 pandemic. METHODS: An expert panel of 24 members, including pulmonologists (n = 17), thoracic radiologists (n = 5), and thoracic surgeons (n = 2), was formed. The panel was provided with an overview of current evidence, summarized by recent guidelines related to lung cancer screening and lung nodule evaluation. The panel was convened by video teleconference to discuss and then vote on statements related to 12 common clinical scenarios. A predefined threshold of 70% of panel members voting agree or strongly agree was used to determine if there was a consensus for each statement. Items that may influence decisions were listed as notes to be considered for each scenario. RESULTS: Twelve statements related to baseline and annual lung cancer screening (n = 2), surveillance of a previously detected lung nodule (n = 5), evaluation of intermediate and high-risk lung nodules (n = 4), and management of clinical stage I non-small cell lung cancer (n = 1) were developed and modified. All 12 statements were confirmed as consensus statements according to the voting results. The consensus statements provide guidance about situations in which it was believed to be appropriate to delay screening, defer surveillance imaging of lung nodules, and minimize nonurgent interventions during the evaluation of lung nodules and stage I non-small cell lung cancer. CONCLUSIONS: There was consensus that during the COVID-19 pandemic, it is appropriate to defer enrollment in lung cancer screening and modify the evaluation of lung nodules due to the added risks from potential exposure and the need for resource reallocation. There are multiple local, regional, and patient-related factors that should be considered when applying these statements to individual patient care.