Using cfRNA as a tool to evaluate clinical treatment outcomes in patients with metastatic lung cancers and other tumors.

Aim: We report an exploratory analysis of cfRNA as a biomarker to monitor clinical responses in non-small cell lung cancer (NSCLC), breast cancer, and colorectal cancer (CRC). An analysis of cfRNA as a method for measuring PD-L1 expression with comparison to clinical responses was also performed in the NSCLC cohort. Methods: Blood samples were collected from 127 patients with metastatic disease that were undergoing therapy, 52 with NSCLC, 50 with breast cancer, and 25 with CRC. cfRNA was purified from fractionated plasma, and following reverse transcription (RT), total cfRNA and gene expression of PD-L1were analyzed by real-time polymerase chain reaction (qPCR) using beta-actin expression as a surrogate for relative amounts of cfDNA and cfRNA. For the concordance study of liquid biopsies and tissue biopsies, the isolated RNA was analyzed by RNAseq for the expressions of 13 genes. We had to close the study early due to a lack of follow-up during the Covid-19 pandemic. Results: We collected a total of 373 blood samples. Mean cfRNA PCR signals after RT were about 50-fold higher than those of cfDNA. cfRNA was detected in all patients, while cfDNA was detected in 88% of them. A high concordance was found for the expression levels of 13 genes between blood and solid tumor tissue. Changes in cfRNA levels followed over the course of treatments were associated with response to therapy, increasing in progressive disease (PD) and falling when a partial response (PR) occurred. The expression of PD-L1 over time in patients treated with immunotherapy decreased with PR but increased with PD. Pre-treatment levels of PD-L1 were predictive of response in patients treated with immunotherapy. Conclusion: Changes in cfRNA correlate with clinical response to the therapy. Total cfRNA may be useful in predicting clinical outcomes. PD-L1 gene expression may provide a biomarker to predict response to PD-L1 inhibition.

PD-L1-negative non-small cell lung cancer harbouring a rare BRAF mutation with successful treatment of first-line pembrolizumab plus chemotherapy: A case report and review the literature.

BRAF mutations are uncommon in non-small cell lung cancer (NSCLC), accounting for less than 5% of all NSCLC cases. The utilization of targeted therapies in non-V600E BRAF mutant NSCLC is considered controversial, although non-V600E genotype is reported in ~50% of all BRAF mutant patients. We document the case of a 63-year-old patient with NSCLC harbouring a rare BRAF E501Q mutation, who had prolonged response to immunotherapy combined with chemotherapy in Vietnam. The patient was diagnosed with metastatic PD-L1-negative lung adenocarcinoma and received pembrolizumab plus chemotherapy as first-line treatment. After completing 35 cycles of pembrolizumab and pemetrexed, his disease has remained stable during the treatment-free follow-up period, and he is alive 38 months after treatment initiation at the latest follow-up. Immune-based therapy is an appropriate option for lung adenocarcinoma with rare non-V600E BRAF mutation. Further clinical studies are necessary to determine the effectiveness of using immune-based therapy in this specific population.

The Effects of GCSF Primary Prophylaxis on Survival Outcomes and Toxicity in Patients with Advanced Non-Small Cell Lung Cancer on First-Line Chemoimmunotherapy: A Sub-Analysis of the Spinnaker Study.

GCSF prophylaxis is recommended in patients on chemotherapy with a >20% risk of febrile neutropenia and is to be considered if there is an intermediate risk of 10−20%. GCSF has been suggested as a possible adjunct to immunotherapy due to increased peripheral neutrophil recruitment and PD-L1 expression on neutrophils with GCSF use and greater tumour volume decrease with higher tumour GCSF expression. However, its potential to increase neutrophil counts and, thus, NLR values, could subsequently confer poorer prognoses on patients with advanced NSCLC. This analysis follows on from the retrospective multicentre observational cohort Spinnaker study on advanced NSCLC patients. The primary endpoints were OS and PFS. The secondary endpoints were the frequency and severity of AEs and irAEs. Patient information, including GCSF use and NLR values, was collected. A secondary comparison with matched follow-up duration was also undertaken. Three hundred and eight patients were included. Median OS was 13.4 months in patients given GCSF and 12.6 months in those not (p = 0.948). Median PFS was 7.3 months in patients given GCSF and 8.4 months in those not (p = 0.369). A total of 56% of patients receiving GCSF had Grade 1−2 AEs compared to 35% who did not receive GCSF (p = 0.004). Following an assessment with matched follow-up, 41% of patients given GCSF experienced Grade 1−2 irAEs compared to 23% of those not given GCSF (p = 0.023). GCSF prophylaxis use did not significantly affect overall or progression-free survival. Patients given GCSF prophylaxis were more likely to experience Grade 1−2 adverse effects and Grade 1−2 immunotherapy-related adverse effects.

Narrowing the therapeutic window?-A case-control study on the influence of the COVID-19 pandemic on the primary UICC stage of NSCLC.

Background: General clinical perception suggests a decline in the diagnosis and treatment of lung cancer during the SARS-CoV-2 pandemic. Early diagnosis of non-small cell lung cancer (NSCLC) is crucial in therapeutic regimes as early stages are potentially curable by operation alone or with combined therapy. Pandemic-triggered overload of the healthcare system may have prolonged the diagnosis of NSCLC, possibly leading to higher tumor stages at first diagnosis. This study aims to identify how COVID-19 affected the distribution of the Union for International Cancer Control (UICC) stage in NSCLC at first diagnosis. Methods: A retrospective case-control study was conducted, including all patients receiving their first diagnosis of NSCLC in the regions of Leipzig and Mecklenburg-Vorpommern (MV) between January 2019 and March 2021. Patient data were retrieved from the clinical cancer registries of the city of Leipzig and the federal state of MV. Ethical approval for this retrospective evaluation of archived, anonymized patient data was waived by the Scientific Ethical Committee at the Medical Faculty, Leipzig University. Three investigation periods were defined to study the effects of high incidences of SARS-COV-2: the curfew period as an enacted security measure, the period of high incidence rates and the period of the aftermath of high incidences. Differences in the UICC stages between these pandemic periods were studied by Mann-Whitney-U-Test. Pearson's correlation was calculated to examine changes in operability. Results: The number of patients diagnosed with NSCLC dropped substantially during investigation periods. There was a significant difference in the UICC status in the aftermath of high incidences and imposed security measures in Leipzig (P=0.016). N-status differed significantly in the aftermath of high incidences and imposed security measures (P=0.022) with a decrease of N0- and an increase of N3-status, respectively, while N1- and N2-status remained relatively unaffected. No pandemic phase showed a significant difference in operability. Conclusions: The pandemic led to a delay in the diagnosis of NSCLC in the two examined regions. This resulted in higher UICC stages upon diagnosis. However, no increase in inoperable stages was shown. It remains to be seen, how this will affect the overall prognosis of the involved patients.

Meta-analysis of Lung Cancer Patients in COVID-19

Background: Lung cancer patients have a higher chance of getting infected and showing severe outcomes from coronavirus disease 2019 (COVID-19). This infection influences the respiratory system, albeit other organs are also involved with high risk related to health. The blend of COVID-19 disease and lung cancer predicts a higher mortality rate and more serious clinical results. Objective(s): This research reports the Systematic Review and Meta-analysis correlation between COVID-19 patients with lung cancer and comprehensive proof with regards to the mortality of these patients. Method(s): A systematic review and meta-analysis were planned to evaluate the data from a PubMed systematic search on Lung Cancer Patients reported by COVID-19, as well as an efficient literature review and information research from 2019 to 2021. Result(s): 22 out of 3639 review and research literature assessments were gathered, and 10951 patients were COVID +ve and suffering from can-cer, with 21% of the patients suffering from SCLC and NSCLC, and lung cancer accounting for 6% of the mortality. Conclusion(s): Lung cancer patients who are suffering from COVID-19 additionally reflected the se-riousness of the illness and higher rates of intensive care unit confirmations and mechanical ventila-tion. COVID-19 in patients with lung cancer is related to extreme disease and expanded mortality compared with patients with different tumours. There is conflicting proof of explicit lung cancer therapies' results. Until more conclusive data is available, lung cancer-coordinated therapy should be restarted as soon as possible in mild to moderate cases to avoid decline and cancer-related mor-tality.Copyright © 2023 Bentham Science Publishers.

Identification of phytochemical compounds of Fagopyrum dibotrys and their targets by metabolomics, network pharmacology and molecular docking studies.

Acute lung injury (ALI) is a clinically severe lung illness with high incidence rate and mortality. Especially, coronavirus disease 2019 (COVID-19) poses a serious threat to world wide governmental fitness. It has distributed to almost from corner to corner of the universe, and the situation in the prevention and control of COVID-19 remains grave. Traditional Chinese medicine plays a vital role in the precaution and therapy of sicknesses. At present, there is a lack of drugs for treating these diseases, so it is necessary to develop drugs for treating COVID-19 related ALI. Fagopyrum dibotrys (D. Don) Hara is an annual plant of the Polygonaceae family and one of the long-history used traditional medicine in China. In recent years, its rhizomes (medicinal parts) have attracted the attention of scholars at home and abroad due to their significant anti-inflammatory, antibacterial and anticancer activities. It can work on SARS-COV-2 with numerous components, targets, and pathways, and has a certain effect on coronavirus disease 2019 (COVID-19) related acute lung injury (ALI). However, there are few systematic studies on its aerial parts (including stems and leaves) and its potential therapeutic mechanism has not been studied. The phytochemical constituents of rhizome of F. dibotrys were collected using TCMSP database. And metabolites of F. dibotrys' s aerial parts were detected by metabonomics. The phytochemical targets of F. dibotrys were predicted by the PharmMapper website tool. COVID-19 and ALI-related genes were retrieved from GeneCards. Cross targets and active phytochemicals of COVID-19 and ALI related genes in F. dibotrys were enriched by gene ontology (GO) and KEGG by metscape bioinformatics tools. The interplay network entre active phytochemicals and anti COVID-19 and ALI targets was established and broke down using Cytoscape software. Discovery Studio (version 2019) was used to perform molecular docking of crux active plant chemicals with anti COVID-19 and ALI targets. We identified 1136 chemicals from the aerial parts of F. dibotrys, among which 47 were active flavonoids and phenolic chemicals. A total of 61 chemicals were searched from the rhizome of F. dibotrys, and 15 of them were active chemicals. So there are 6 commonly key active chemicals at the aerial parts and the rhizome of F. dibotrys, 89 these phytochemicals's potential targets, and 211 COVID-19 and ALI related genes. GO enrichment bespoken that F. dibotrys might be involved in influencing gene targets contained numerous biological processes, for instance, negative regulation of megakaryocyte differentiation, regulation of DNA metabolic process, which could be put down to its anti COVID-19 associated ALI effects. KEGG pathway indicated that viral carcinogenesis, spliceosome, salmonella infection, coronavirus disease - COVID-19, legionellosis and human immunodeficiency virus 1 infection pathway are the primary pathways obsessed in the anti COVID-19 associated ALI effects of F. dibotrys. Molecular docking confirmed that the 6 critical active phytochemicals of F. dibotrys, such as luteolin, (+) -epicatechin, quercetin, isorhamnetin, (+) -catechin, and (-) -catechin gallate, can combine with kernel therapeutic targets NEDD8, SRPK1, DCUN1D1, and PARP1. In vitro activity experiments showed that the total antioxidant capacity of the aerial parts and rhizomes of F. dibotrys increased with the increase of concentration in a certain range. In addition, as a whole, the antioxidant capacity of the aerial part of F. dibotrys was stronger than that of the rhizome. Our research afford cues for farther exploration of the anti COVID-19 associated ALI chemical compositions and mechanisms of F. dibotrys and afford scientific foundation for progressing modern anti COVID-19 associated ALI drugs based on phytochemicals in F. dibotrys. We also fully developed the medicinal value of F. dibotrys' s aerial parts, which can effectively avoid the waste of resources. Meanwhile, our work provides a new strategy for integrating metabonomics, network pharmacology, and molecular docking techniques which was an efficient way for recognizing effective constituents and mechanisms valid to the pharmacologic actions of traditional Chinese medicine.

Early Hospital Discharge on Day Two Post Robotic Lobectomy with Telehealth Home Monitoring: A Pilot Study.

Despite the adoption of enhanced recovery programs, the reported postoperative length of stay after robotic surgery is 4 days even in highly specialized centers. We report preliminary results of a pilot study for a new protocol of early discharge (on day 2) with telehealth home monitoring after robotic lobectomy for lung cancer. All patients with a caregiver were discharged on postoperative day 2 with a telemonitoring device if they satisfied specific discharge criteria. Teleconsultations were scheduled once in the afternoon of post-operative day 2, twice on postoperative day 3, and then once a day until the chest tube removal. Post-discharge vital signs were recorded by patients at least four times daily through the device and were available for consultation by two surgeons through phone application. In case of sudden variation of vital signs or occurrence of adverse events, a direct telephone line was available for patients as well as a protected re-hospitalization path. Primary outcome was the safety evaluated by the occurrence of post-discharge complications and readmissions. Secondary outcome was the evaluation of resources optimization (hospitalization days) maintaining the standard of care. During the study period, twelve patients satisfied all preoperative clinical criteria to be enrolled in our protocol. Two of twelve enrolled patients were successively excluded because they did not satisfy discharge criteria on postoperative day 2. During telehealth home monitoring a total of 27/427 vital-sign measurements violated the threshold in seven patients. Among the threshold violations, only 1 out of 27 was a critical violation and was managed at home. No postoperative complication occurred neither readmission was needed. A mean number of three hospitalization days was avoided and an estimated economic benefit of about EUR 500 for a single patient was obtained if compared with patients submitted to VATS lobectomy in the same period. These preliminary results confirm that adoption of telemonitoring allows, in selected patients, a safe discharge on postoperative day 2 after robotic surgery for early-stage NSCLC. A potential economic benefit could derive from this protocol if this data will be confirmed in larger sample.

Transcriptional profiles and common genes link lung cancer with the development and severity of COVID-19.

Lung cancer patients with COVID-19 present an increased risk of developing severe disease and, consequently, have poor outcomes. Determining SARS-CoV-2-host interactome in lung cancer cells and tissues, infected or uninfected with SARS-CoV-2, may reveal molecular mechanisms associated with COVID-19 development and severity in lung cancer patients. Here, we integrated transcriptome data of lung tumors from patients with small- or non-small cell lung cancer (SCLC and NSCLC) and normal lung and lung cancer cells infected with SARS-CoV-2. We aimed to characterize molecular mechanisms potentially associated with COVID-19 development and severity in lung cancer patients and to predict the SARS-CoV-2-host cell interactome. We found that the gene expression profiles of lung cell lines infected with SARS-CoV-2 resemble more primary lung tumors than non-malignant lung tissues. In addition, the transcriptomic-based interactome analysis of SCLC and NSCLC revealed increased expression of cancer genes BRCA1 and CENPF, whose proteins are known or predicted to interact with the SARS-CoV-2 spike glycoprotein and helicase, respectively. We also found that TRIB3, a gene coding a putative host-SARS-CoV-2 interacting protein associated with COVID-19 infection, is co-expressed with the up-regulated genes MTHFD2, ADM2, and GPT2 in all tested conditions. Our analysis identified biological processes such as amino acid metabolism and angiogenesis and 22 host mediators of SARS-CoV-2 infection and replication that may contribute to the development and severity of COVID-19 in lung cancers.

The Impact of COVID-19 on Lung Cancer Incidence in England: Analysis of the National Lung Cancer Audit 2019 and 2020 Rapid Cancer Registration Datasets.

BACKGROUND: The COVID-19 pandemic has caused significant disruption to health-care services and delivery worldwide. The impact of the pandemic and associated national lockdowns on lung cancer incidence in England have yet to be assessed. RESEARCH QUESTION: What was the impact of the first year of the COVID-19 pandemic on the incidence and presentation of lung cancer in England? STUDY DESIGN AND METHODS: In this retrospective observational study, incidence rates for lung cancer were calculated from The National Lung Cancer Audit Rapid Cancer Registration Datasets for 2019 and 2020, using midyear population estimates from the Office of National Statistics as the denominators. Rates were compared using Poisson regression according to time points related to national lockdowns in 2020. RESULTS: Sixty-four thousand four hundred fifty-seven patients received a diagnosis of lung cancer across 2019 (n = 33,088) and 2020 (n = 31,369). During the first national lockdown, a 26% reduction in lung cancer incidence was observed compared with the equivalent calendar period of 2019 (adjusted incidence rate ratio [IRR], 0.74; 95% CI, 0.71-0.78). This included a 23% reduction in non-small cell lung cancer (adjusted IRR, 0.77; 95% CI, 0.74-0.81) and a 45% reduction in small cell lung cancer (adjusted IRR, 0.55; 95% CI, 0.46-0.65) incidence. Thereafter, incidence rates almost recovered to baseline, without overcompensation (adjusted IRR, 0.96; 95% CI, 0.94-0.98). INTERPRETATION: The incidence rates of lung cancer in England fell significantly by 26% during the first national lockdown in 2020 and did not compensate later in the year.

Role of Neoadjuvant Chemotherapy in Non-small Cell Lung Cancer in the COVID-19 Pandemic.

Introduction Cancer patients are among the groups at high risk in the COVID-19 pandemic. Here, we aimed to determine the effectiveness of neoadjuvant chemotherapy (NACT) during the pandemic period and examine the prognostic factors in patients with non-small cell lung cancer (NSCLC). Method Patients with stage I-III NSCLC were treated in our hospitals between 2020-2022. Treatment responses were evaluated in patients who underwent NACT. Prognostic factors and the nutritional and inflammatory indexes were investigated. Results Thirty-eight patients received NACT. 57.9% of patients were stage-III. The objective response rate was 57.9%. Pathological complete response was obtained in 10.5% of patients. No prognostic role of inflammatory indices was determined. 21.1% of patients developed a COVID-19 infection. Disease-free survival was 19 months. Survival decreased with large tumor size and presence of metastasis. Conclusion NACT has high response rates. NACT can be used as bridging therapy in suitable patients whose surgery is postponed during the pandemic period.

Dysregulated Metabolism in EGFR-TKI Drug Resistant Non-Small-Cell Lung Cancer: A Systematic Review.

Drug resistance is a common barrier to continued effective treatment in cancer. In non-small-cell lung cancer (NSCLC), tyrosine kinase inhibitors that target the epidermal growth factor receptor (EGFR-TKIs) exhibit good efficacy in cancer treatment until acquired resistance occurs. It has been observed that drug resistance is accompanied by numerous molecular-level changes, including significant shifts in cellular metabolism. The purpose of this study was to critically and systematically review the published literature with respect to how metabolism differs in drug-resistant compared to drug-sensitive NSCLC. Understanding the differences between resistant and sensitive cells is vital and has the potential to allow interventions that enable the re-sensitisation of resistant cells to treatment, and consequently reinitiate the therapeutic effect of EGFR-TKIs. The main literature search was performed using relevant keywords in PubMed and Ovid (Medline) and reviewed using the Covidence platform. Of the 1331 potentially relevant literature records retrieved, 27 studies were subsequently selected for comprehensive analysis. Collectively, the literature revealed that NSCLC cell lines resistant to EGFR-TKI treatment possess characteristic metabolic and lipidomic phenotypic signatures that differentiate them from sensitive lines. Further exploration of these reported differences suggests that drug-resistant cell lines are differentially reliant on cellular energy sources and that modulation of relative energy production pathways may lead to the reversal of drug resistance.

Coronavirus Disease 2019 Outcomes, Patient Vaccination Status, and Cancer-Related Delays During the Omicron Wave: A Brief Report From the TERAVOLT Analysis.

Introduction: The Thoracic Centers International coronavirus disease 2019 (COVID-19) Collaboration (TERAVOLT) registry found approximately 30% mortality in patients with thoracic malignancies during the initial COVID-19 surges. Data from South Africa suggested a decrease in severity and mortality with the Omicron wave. Our objective was to assess mortality of patients with thoracic malignancies with the Omicron-predominant wave and evaluate efficacy of vaccination. Methods: A prospective, multicenter observational study was conducted. A total of 28 institutions contributed data from January 14, 2022, to February 4, 2022. Inclusion criteria were any thoracic cancer and a COVID-19 diagnosis on or after November 1, 2021. End points included mortality, hospitalization, symptomatic COVID-19 infection, asymptomatic COVID-19 infection, and delay in cancer therapy. Analysis was done through contingency tables and a multivariable logistic model. Results: We enrolled a total of 346 patients. Median age was 65 years, 52.3% were female, 74.2% were current or former smokers, 86% had NSCLC, 72% had stage IV at time of COVID-19 diagnosis, and 66% were receiving cancer therapy. Variant was unknown for 70%; for those known, Omicron represented 82%. Overall mortality was 3.2%. Using multivariate analysis, COVID-19 vaccination with booster compared with no vaccination had a protective effect on hospitalization or death (OR = 0.30, confidence interval: 0.15-0.57, p = 0.0003), whereas vaccination without booster did not (OR = 0.64, confidence interval: 0.33-1.24, p = 0.1864). Cancer care was delayed in 56.4% of the patients. Conclusions: TERAVOLT found reduced patient mortality with the most recent COVID-19 surge. COVID-19 vaccination with booster improved outcomes of hospitalization or death. Delays in cancer therapy remain an issue, which has the potential to worsen cancer-related mortality.

A Pilot Study of Using Smartphone Application vs. Routine Follow-Up for Patient Care in Advanced Non-Small Cell Lung Cancer During the COVID-19 Pandemic Era.

Introduction: Cancer care monitoring should be adapted regarding COVID-19 pandemic preparedness plans. Lung Cancer Care application was a mobile application program to monitor adverse events and report outcomes. This study is aimed to invent a new mobile application evaluating patient-reported outcome (PRO) for patients with non-small cell lung cancer (NSCLC) and to evaluate the validity of a mobile application, particularly during the COVID-19 pandemic era. Methods: The validity of the application was tested, and Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaires were contained in the mobile application-based PRO. Patients were randomly assigned to use mobile application-based PRO vs. routine follow-up. The primary end point was to compare the quality of life (QoL) scores between two groups. A secondary end point was overall survival (OS) and the outcomes of progressive disease (PD) between the two groups. Results: In total, 33 patients with advanced NSCLC were enrolled. Patients in the mobile application group had higher FACT-L scores at 3 months than patients with a routine follow-up arm (106 ± 5.97 vs. 99.96 ± 5.74, p-value = 0.07). The median follow-up time was 5.43 months; patients with mobile application had an insignificant increase in median OS when compared with patients using routine follow-up (4.53 vs. 2.93 months, p-value = 0.85). The sensitivity, specificity, positive predictive value (PPV), and negative predictive (NPV) value of this application for predicting disease progression were 50, 83.3, 66.7, and 70%, respectively. Conclusion: Self-reported symptoms by Lung Cancer Care application improved QoL and were similar in monitoring outcomes to face-to-face follow-up. This tool is applicable for patients with cancer to make monitoring as safe as possible for physical distancing during the COVID-19 pandemic era.

Practical considerations of single-fraction stereotactic ablative radiotherapy to the lung.

Stereotactic ablative radiotherapy (SABR) is a well-established treatment for patients with medically inoperable early-stage non-small cell lung cancer (NSCLC) and pulmonary oligometastases. The use of single-fraction SABR in this setting is supported by excellent local control and safety profiles which appear equivalent to multi-fraction SABR based on the available data. The resource efficiency and reduction in hospital outpatient visits associated with single-fraction SABR have been particularly advantageous during the COVID-19 pandemic. Despite the increased interest, single-fraction SABR in subgroups of patients remains controversial, including those with centrally located tumours, synchronous targets, proximity to dose-limiting organs at risk, and concomitant severe respiratory illness. This review provides an overview of the published randomised evidence evaluating single-fraction SABR in primary lung cancer and pulmonary oligometastases, the common clinical challenges faced, immunogenic effect of SABR, as well as technical and cost-utility considerations.

Unmet needs in the management of unresectable stage III non-small cell lung cancer: a review after the 'radio talk' webinars.

INTRODUCTION: Stage III non-small cell lung cancer (NSCLC) is a variable entity, encompassing bulky primary tumors, nodal involvement, or both. Multidisciplinary evaluation is essential to discuss multiple treatment options, to outline optimal management, and to examine the main debated topics and critical issues not addressed by current trials and guidelines that influence daily clinical practice. AREAS COVERED: From March to 5 May 2021 ,meetings were scheduled in a webinar format titled 'Radio Talk' due to the COVID-19 pandemic; the faculty was composed of 6 radiation oncologists from 6 different Institutions of Italy, all of them were the referring radiation oncologist for lung cancer treatment at their respective departments and were or had been members of AIRO (Italian Association of Radiation Oncology) Thoracic Oncology Study Group. The topics covered included: pulmonary toxicity, cardiac toxicity, radiotherapy dose, fractionation and volumes, unfit/elderly patients, multidisciplinary management. EXPERT OPINION: The debate was focused on the unmet needs triggered by case reports, personal experiences and questions; the answers were often not univocal; however, the exchange of opinion and the contribution of different centers confirmed the role of multidisciplinary management and the necessity that the most critical issues should be investigated in clinical trials.

A Definitive Prognostication System for Patients With Thoracic Malignancies Diagnosed With Coronavirus Disease 2019: An Update From the TERAVOLT Registry.

INTRODUCTION: Patients with thoracic malignancies are at increased risk for mortality from coronavirus disease 2019 (COVID-19), and a large number of intertwined prognostic variables have been identified so far. METHODS: Capitalizing data from the Thoracic Cancers International COVID-19 Collaboration (TERAVOLT) registry, a global study created with the aim of describing the impact of COVID-19 in patients with thoracic malignancies, we used a clustering approach, a fast-backward step-down selection procedure, and a tree-based model to screen and optimize a broad panel of demographics and clinical COVID-19 and cancer characteristics. RESULTS: As of April 15, 2021, a total of 1491 consecutive eligible patients from 18 countries were included in the analysis. With a mean observation period of 42 days, 361 events were reported with an all-cause case fatality rate of 24.2%. The clustering procedure screened 73 covariates in 13 clusters. A further multivariable logistic regression for the association between clusters and death was performed, resulting in five clusters significantly associated with the outcome. The fast-backward step-down selection procedure then identified the following seven major determinants of death: Eastern Cooperative Oncology Group-performance status (ECOG-PS) (OR = 2.47, 1.87-3.26), neutrophil count (OR = 2.46, 1.76-3.44), serum procalcitonin (OR = 2.37, 1.64-3.43), development of pneumonia (OR = 1.95, 1.48-2.58), C-reactive protein (OR = 1.90, 1.43-2.51), tumor stage at COVID-19 diagnosis (OR = 1.97, 1.46-2.66), and age (OR = 1.71, 1.29-2.26). The receiver operating characteristic analysis for death of the selected model confirmed its diagnostic ability (area under the receiver operating curve = 0.78, 95% confidence interval: 0.75-0.81). The nomogram was able to classify the COVID-19 mortality in an interval ranging from 8% to 90%, and the tree-based model recognized ECOG-PS, neutrophil count, and c-reactive protein as the major determinants of prognosis. CONCLUSIONS: From 73 variables analyzed, seven major determinants of death have been identified. Poor ECOG-PS was found to have the strongest association with poor outcome from COVID-19. With our analysis, we provide clinicians with a definitive prognostication system to help determine the risk of mortality for patients with thoracic malignancies and COVID-19.

Rapid Improvement Following Receipt of Infliximab in Steroid-refractory Durvalumab-Associated Grade 3 Pneumonitis.

Immune checkpoint inhibitors (ICIs) are important novel agents used in advanced non-small cell lung cancer (NSCLC) standard regimens; however, their use increases the risk of immune-related adverse effects (IRAEs). The incidence of IRAE pneumonitis is well documented in ICI use. Corticosteroids continue to be the mainstay of treatment for IRAEs. Here we report one of the first cases of using infliximab to treat durvalumab-associated pneumonitis.

A narrative review on the implementation of liquid biopsy as a diagnostic tool in thoracic tumors during the COVID-19 pandemic.

OBJECTIVE: In this review, we evaluate the role of liquid biopsy in managing lung cancer patients during the still ongoing coronavirus disease 2019 (COVID-19) healthcare emergency. BACKGROUND: The novel influenza coronavirus (severe acute respiratory syndrome coronavirus or SARS-CoV-2) has upended several aspects of our lives, including medical activities. In this setting, many routine cancer diagnostic and therapeutic procedures have been suspended, leading to delays in diagnosis, treatments, and, ultimately, increases in cancer mortality rates. Equally drastic has been the impact of COVID-19 on clinical trials, many of which have been stalled or have never begun. This has left many patients who were hoping to receive innovative treatments in a limbo. Although, as of today, the introduction of drastic security measures has been crucially important to contain the pandemic, one cannot ignore the need to continue providing chronically ill patients all the health care they need, in terms of detection, prevention, and treatment. In these unprecedented times, liquid biopsy, more than ever before, may play a relevant role in the adequate management of these frail patients. METHODS: we performed a deep analysis of the recent international literature published in English on PUBMED in the last six months focused on the impact of SARS-CoV-2 on the management of lung cancer patients, focusing the attention on the role of liquid biopsy. CONCLUSIONS: COVID-19 pandemic has significantly modified our lives and overall medical practice. In these unprecedented times, liquid biopsy may represent a valid and less time-consuming diagnostic approach than conventional tissue and cytological specimens.

Systematic Review of Single-Fraction Stereotactic Body Radiation Therapy for Early Stage Non-Small-Cell Lung Cancer and Lung Oligometastases: How to Stop Worrying and Love One and Done.

Adoption of single-fraction lung stereotactic body radiation therapy (SBRT) for patients with medically inoperable early stage non-small-cell lung cancer (NSCLC) or oligometastatic lung disease, even during the coronavirus disease 2019 (COVID-19) pandemic, was limited despite encouraging phase II trial results. Barriers to using single-fraction SBRT may include lack of familiarity with the regimen and lack of clarity about the expected toxicity. To address these concerns, we performed a systematic review of prospective literature on single-fraction SBRT for definitive treatment of early stage and oligometastatic lung cancer. A PubMed search of prospective studies in English on single-fraction lung SBRT was conducted. A systematic review was performed of the studies that reported clinical outcomes of single-fraction SBRT in the treatment of early stage non-small-cell lung cancer and lung oligometastases. The current prospective literature including nine trials supports the use of single-fraction SBRT in the definitive treatment of early stage peripheral NSCLC and lung oligometastases. Most studies cite local control rates of >90%, mild toxicity profiles, and favorable survival outcomes. Most toxicities reported were grade 1-2, with grade ≥3 toxicity in 0-17% of patients. Prospective trial results suggest potential consideration of utilizing single-fraction SBRT beyond the COVID-19 pandemic.

Case Report: Clinical Management of a Patient With Metastatic Non-Small Cell Lung Cancer Newly Receiving Immune Checkpoint Inhibition During Symptomatic COVID-19.

Effects of initiation of programmed-death-protein 1 (PD1) blockade during active SARS-CoV-2 infection on antiviral immunity, COVID-19 course, and underlying malignancy are unclear. We report on the management of a male in his early 40s presenting with highly symptomatic metastatic lung cancer and active COVID-19 pneumonia. After treatment initiation with pembrolizumab, carboplatin, and pemetrexed, the respiratory situation initially worsened and high-dose corticosteroids were initiated due to suspected pneumonitis. After improvement and SARS-CoV-2 clearance, anti-cancer treatment was resumed without pembrolizumab. Immunological analyses with comparison to otherwise healthy SARS-CoV-2-infected ambulatory patients revealed a strong humoral immune response with higher levels of SARS-CoV-2-reactive IgG and neutralizing serum activity. Additionally, sustained increase of Tfh as well as activated CD4+ and CD8+ T cells was observed. Sequential CT scans showed regression of tumor lesions and marked improvement of the pulmonary situation, with no signs of pneumonitis after pembrolizumab re-challenge as maintenance. At the latest follow-up, the patient is ambulatory and in ongoing partial remission on pembrolizumab. In conclusion, anti-PD1 initiation during active COVID-19 pneumonia was feasible and cellular and humoral immune responses to SARS-CoV-2 appeared enhanced in our hospitalized patient. However, distinguishing COVID-19-associated changes from anti-PD1-associated immune-related pneumonitis posed a considerable clinical, radiographic, and immunologic challenge.