Thoracic Oncology Research Articles

P09.35 COVID-19 in Patients with Lung Cancer – Experience from a Thoracic Oncology Center

Cancer patients appear to be at higher risk of complications from sars-cov-2 infection. Specific data regarding lung cancer patients, on active treatment and/or recent diagnosis is limited. Recent data suggests that a bad prognosis is associated with older age (>65 years-old), comorbidities, ECOG2, steroids (>10mg prednisolone), anticoagulants, chemotherapy and chemotherapy-immunotherapy. With this study we aim to investigate the clinical presentation, baseline characteristics and outcomes of patients with lung cancer and Covid-19.

Prognostic Impact of KRAS G12C Mutation in Patients With NSCLC: Results From the European Thoracic Oncology Platform Lungscape Project

IntroductionKRAS mutations, the most frequent gain-of-function alterations in NSCLC, are currently emerging as potential predictive therapeutic targets. The role of KRAS-G12C (Kr_G12C) is of special interest after the recent discovery and preclinical analyses of two different Kr_G12C covalent inhibitors (AMG-510, MRTX849). MethodsKRAS mutations were evaluated in formalin-fixed, paraffin-embedded tissue sections by a microfluidic-based multiplex polymerase chain reaction platform as a component of the previously published European Thoracic Oncology Platform Lungscape 003 Multiplex Mutation study, of clinically annotated, resected, stage I to III NSCLC. In this study, -Kr_G12C mutation prevalence and its association with clinicopathologic characteristics, molecular profiles, and postoperative patient outcome (overall survival, relapse-free survival, time-to-relapse) were explored. ResultsKRAS gene was tested in 2055 Lungscape cases (adenocarcinomas: 1014 [49%]) with I or II or III stage respective distribution of 53% or 24% or 22% and median follow-up of 57 months. KRAS mutation prevalence in the adenocarcinoma cohort was 38.0% (95% confidence interval (CI): 35.0% to 41.0%), with Kr_G12C mutation representing 17.0% (95% CI: 14.7% to 19.4%). In the "histologic-subtype" cohort, Kr_G12C prevalence was 10.5% (95% CI: 9.2% to 11.9%). When adjusting for clinicopathologic characteristics, a significant negative prognostic effect of Kr_G12C presence versus other KRAS mutations or nonexistence of KRAS mutation was identified in the adenocarcinoma cohort alone and in the "histologic-subtype" cohort. For overall survival in adenocarcinomas, hazard ratio (HR)G12C versus other KRAS is equal to 1.39 (95% CI: 1.03 to 1.89, p = 0.031) and HRG12C versus no KRAS is equal to 1.32 (95% CI: 1.03 to 1.69, p = 0.028) (both also significant in the "histologic-subtype" cohort). For time-to-relapse, HRG12C versus other KRAS is equal to 1.41 (95% CI: 1.03 to 1.92, p = 0.030). In addition, among all patients, for relapse-free survival, HRG12C versus no KRAS is equal to 1.27 (95% CI: 1.04 to 1.54, p = 0.017). ConclusionsIn this large, clinically annotated stage I to III NSCLC cohort, the specific Kr_G12C mutation is significantly associated with poorer prognosis (adjusting for clinicopathologic characteristics) among adenocarcinomas and in unselected NSCLCs.

Targeting rare and non-canonical driver variants in NSCLC – An uncharted clinical field

ObjectivesImplementation of tyrosine kinase inhibitors (TKI) and other targeted therapies was a main advance in thoracic oncology with survival gains ranging from several months to years for non-small-cell lung cancer (NSCLC) patients. High-throughput comprehensive molecular profiling is of key importance to identify patients that can potentially benefit from these novel treatments. Material and MethodsNext-generation sequencing (NGS) was performed on 4500 consecutive formalin-fixed, paraffin-embedded specimens of advanced NSCLC (n = 4172 patients) after automated extraction of DNA and RNA for parallel detection of mutations and gene fusions, respectively. Results and ConclusionBesides the 24.9 % (n = 1040) of cases eligible for approved targeted therapies based on the presence of canonical alterations in EGFR exons 18–21, BRAF, ROS1, ALK, NTRK, and RET, an additional n = 1260 patients (30.2 %) displayed rare or non-canonical mutations in EGFR (n = 748), BRAF (n = 135), ERBB2 (n = 30), KIT (n = 32), PIK3CA (n = 221), and CTNNB1 (n = 94), for which targeted therapies could also be potentially effective. A systematic literature search in conjunction with in silico evaluation identified n = 232 (5.5 %) patients, for which a trial of targeted treatment would be warranted according to available evidence (NCT level 1, i.e. published data showing efficacy in the same tumor entity).In conclusion, a sizeable fraction of NSCLC patients harbors rare or non-canonical alterations that may be associated with clinical benefit from currently available targeted drugs. Systematic identification and individualized management of these cases can expand applicability of precision oncology in NSCLC and extend clinical gain from established molecular targets. These results can also inform clinical trials.

Gene polymorphisms role of blood coagulation in myocardial infarction development in patients with malignant tumors of thoracoabdominal localization

Aim. To evaluate the role of polymorphic variants of blood coagulation genes (F2, F5, F7, F13, FGB, ITGA2, ITGB3, PAI-1) in the development of myocardial infarction in patients with malignant tumors of thoracoabdominal localization.
 Materials and methods. The study included 143 patients with thoracoabdominal tumors operated in the oncological Department of surgical methods of treatment No.11 (thoracic Oncology) of the thoracoabdominal Department of the Blokhin National Medical Research Center of Oncology in 20182019. The study group (n=62) consisted of patients with a history of myocardial infarction or in the perioperative period. The control group (n=81) included patients who did not have severe concomitant cardiovascular diseases, including a family history. Molecular genetic study to determine the gene polymorphisms of blood coagulation were performed in the laboratory of clinical oncogenetic of the Blokhin National Medical Research Center of Oncology with use of reagents Cardiogenetic Thrombophilia (LLC DNA-Technology, Russia, RU No. FSR 2010/08414 from 22.11.2016).
 Results. In the study group, 90.3% (n=56) of cases showed polymorphism -675 5G4G of the PAI-1 gene (SERPINE1, a plasminogen activator inhibitor) associated with a decrease in the activity of the fibrinolytic system and an increased risk of thrombosis. In the control group, this mutation was observed significantly less frequently in 67.9% (n=55) of cases (p0.001). In the group of patients with myocardial infarction, polymorphism 807 CT of the ITGA2 (integrin a2) gene responsible for platelet aggregation was detected in 66.1% (n=41) compared to 19.8% (n=16) in the control group (p0.0001). Polymorphism 1565 TC of the ITGB3 gene (platelet-derived fibrinogen receptor) responsible for fibrinogen-induced platelet aggregation was observed in 25.8% (n=16) of cases in the group of patients with myocardial infarction and in 12.4% (n=10) of cases in the group of patients without concomitant severe cardiovascular pathology (p0.05). In 48.4% (n=30) of patients of the study group, genetic disorders of the FGB gene (fibrinogen, missense mutation -455GA) were also registered, which resulted in the development of dysfibrinogenemia, leading to increased blood thrombogenicity; in the control group, this mutation was 2 times less common 25.9% (n=21) of cases (p0.01). Polymorphism 1691 GA of the F5 gene (coagulation factor V, Leiden factor), which is considered one of the most significant genetic risk factors for thrombosis in Caucasians, was detected in 4.8% (n=3) of cases in the study group, while this mutation was not found in the control group. Polymorphism 20210 GA of the F2 gene (coagulation factor II prothrombin), which is a key protein of the coagulation cascade associated with increased blood levels of prothrombin, was observed in 3.2% (n=2) of patients after myocardial infarction; in the control group, the carrier of this polymorphism was not found in any case. Disorders in the genes that promote hypocoagulation were also noted. Among patients who had a myocardial infarction, polymorphism 10976 GA of the F7 gene (coagulation factor VII) was detected in 17.7% (n=11) of cases, polymorphism 103 GT of the F13 gene (coagulation factor XIII) in 41.9% (n=26) of cases. In patients of the control group, these genetic aberrations were found: in 18.5% (n=15) of cases a mutation in the F7 gene (p0.05) and in 45.7% (n=37) in the F13 gene (p0.05), respectively.
 Conclusion. Based on the results of a molecular genetic study of factors associated with thrombogenic risk, a statistically significant difference in the frequency of occurrence of polymorphisms of genes involved in the process of thrombosis (polymorphisms: -455 GA of the FGB gene, 807 CT of the ITGA2 gene, 1565 TC of the ITGB3 gene, -675 5G4G of the PAI-1 gene) in patients who had a myocardial infarction, compared with patients without severe concomitant cardiovascular diseases. The frequency of 1691 GA polymorphism of the F5 gene, one of the most significant genetic risk factors for thrombosis, reached 4.8%. The obtained data on the use of molecular genetic markers of thrombophilia in patients with malignant tumors of thoracoabdominal localization allow us to identify a group of patients with a high risk of developing perioperative myocardial infarction and take additional measures for the prevention and treatment of thrombotic complications.

A Novel Mouse Model of Radiation-Induced Cardiac Injury Reveals Biological and Radiological Biomarkers of Cardiac Dysfunction with Potential Clinical Relevance.

Radiation-induced cardiotoxicity is a significant concern in thoracic oncology patients. However, the basis for this disease pathology is not well characterized. We developed a novel mouse model of radiation-induced cardiotoxicity to investigate pathophysiologic mechanisms and identify clinically targetable biomarkers of cardiac injury. Single radiation doses of 20, 40, or 60 Gy were delivered to the cardiac apex of female C57BL/6 mice ages 9-11 weeks, with or without adjacent lung tissue, using conformal radiotherapy. Cardiac tissue was harvested up to 24 weeks post-radiotherapy for histologic analysis. Echocardiography and Technetium-99m sestamibi single photon emission computed tomography (SPECT) at 8 and 16 weeks post-radiotherapy were implemented to evaluate myocardial function and perfusion. Mouse cardiac tissue and mouse and human plasma were harvested for biochemical studies. Histopathologically, radiotherapy resulted in perivascular fibrosis 8 and 24 (P < 0.05) weeks post-radiotherapy. Apical perfusion deficits on SPECT and systolic and diastolic dysfunction on echocardiography 8 and 16 weeks post-radiotherapy were also observed (P < 0.05). Irradiated cardiac tissue and plasma showed significant increases in placental growth factor (PlGF), IL6, and TNFα compared with nonradiated matched controls, with greater increases in cardiac cytokine levels when radiotherapy involved lung. Human plasma showed increased PlGF (P = 0.021) and TNFα (P = 0.036) levels after thoracic radiotherapy. PlGF levels demonstrated a strong correlation (r = 0.89, P = 0.0001) with mean heart dose. We developed and characterized a pathophysiologically relevant mouse model of radiation-induced cardiotoxicity involving in situ irradiation of the cardiac apex. The model can be used to integrate radiomic and biochemical markers of cardiotoxicity to inform early therapeutic intervention and human translational studies.

Historical Observations on Clamshell Thoracotomy.

Bilateral transverse thoracosternotomy, known colloquially as "clamshell thoracotomy," provides quick and extensive exposure to the thoracic organs. The origins of the radical incision are unclear, and its influence on historical developments in surgery has not been elaborated. Transsternal extension to bilateral thoracotomy likely occurred during World War I and was designated as Tuffier's method by 1922. Théodore Tuffier had already solidified his reputation as a trailblazing thoracic surgeon in Paris when the French army summoned him to design triage systems for trauma patients during the Great War. Following World War II, cardiac surgery grew tremendously during the 1950s, and many pioneering open-heart procedures utilized the bilateral incision for safe exposures with satisfactory results. Median sternotomy became the incision of choice for open-heart surgery by the early 1960s; however, thoracotomy remained important to the trauma surgeon's repertoire. Transsternal conversion was only briefly mentioned in trauma literature through the 1980s, although up to one-half of reported emergency thoracotomies at busy trauma centers were clamshells. The moniker clamshell thoracotomy came in 1994 when thoracic surgical oncology and lung transplantation flourished with complex operations requiring larger incisions. The twenty-first century has brought two iterations of evidence-based guidelines for emergency thoracotomy, but incision choice has not been formally discussed. Renewed conversation in recent years has advocated for the clamshell as arguably the best approach for patients in extremis. Given these trends, the tortuous history of this controversial incision deserves attention.

Therapeutic Sequencing in ALK+ NSCLC.

Anaplastic lymphoma kinase-rearranged non-small-cell lung cancer (ALK+ NSCLC) is a model disease for the use of targeted pharmaceuticals in thoracic oncology. Due to higher systemic and intracranial efficacy, the second-generation ALK tyrosine kinase inhibitors (TKI) alectinib and brigatinib have irrevocably displaced crizotinib as standard first-line treatment, based on the results of the ALEX and ALTA-1L trials. Besides, lorlatinib and brigatinib are the preferred second-line therapies for progression under second-generation TKI and crizotinib, respectively, based on the results of several phase II studies. Tissue or liquid rebiopsies at the time of disease progression, even though not mandated by the approval status of any ALK inhibitor, are gaining importance for individualization and optimization of patient management. Of particular interest are cases with off-target resistance, for example MET, HER2 or KRAS alterations, which require special therapeutic maneuvers, e.g., inclusion in early clinical trials or off-label administration of respectively targeted drugs. On the other hand, up to approximately half of the patients failing TKI, develop anatomically restricted progression, which can be initially tackled with local ablative measures without switch of systemic therapy. Among the overall biologically favorable ALK+ tumors, with a mean tumor mutational burden uniquely below 3 mutations per Mb and the longest survival among NSCLC currently, presence of the EML4-ALK fusion variant 3 and/or TP53 mutations identify high-risk cases with earlier treatment failure and a need for more aggressive surveillance and treatment strategies. The potential clinical utility of longitudinal ctDNA assays for earlier detection of disease progression and improved guidance of therapy in these patients is a currently a matter of intense investigation. Major pharmaceutical challenges for the field are the development of more potent, fourth-generation TKI and effective immuno-oncological interventions, especially ALK-directed cell therapies, which will be essential for further improving survival and achieving cure of ALK+ tumors.

Practical Considerations Relating to Routine Clinical Biomarker Testing for Non-small Cell Lung Cancer: Focus on Testing for RET Fusions.

For patients with advanced non–small cell lung cancer, genomic profiling of tumors to identify potentially targetable alterations and thereby inform treatment selection is now part of standard care. While molecular analyses are primarily focused on actionable biomarkers associated with regulatory agency-approved therapies, there are a number of emerging biomarkers linked to investigational agents in advanced stages of clinical development will become approved agents. A particularly timely example is the reported data and US Food and Drug Administration approval of highly specific small molecule inhibitors of the proto-oncogene tyrosine-protein kinase receptor RET indicate that testing for tumor RET gene fusions in patients with NSCLC has become clinically important. As the number of biomarkers to be tested in NSCLC grows, it becomes increasingly important to optimize and prioritize the use of biopsy tissue, in order to both continue to allow accurate histopathological diagnosis and also to support concurrent genomic profiling to identify perhaps relatively uncommon genetic events. In order to provide practical expert consensus guidance to optimize processes facilitating genomic testing in NSCLC and to overcome barriers to access and implementation, a multidisciplinary advisory board was held in New York, on January 30, 2019. The panel comprised physicians involved in sample procurement (interventional radiologists and a thoracic surgeon), surgical pathologists specializing in the lung, molecular pathologists, and thoracic oncologists. Particular consideration was given to the key barriers faced by these experts in establishing institutional genomic screening programs for NSCLC. Potential solutions have been devised in the form of consensus opinions that might be used to help resolve such issues.

ESMO20 YO for YO: highlights on metastatic NSCLC-Keynote 024 update

In this podcast, Dr Elene Mariamidze (a member of the ESMO Young Oncologists Committee and the Georgian Group of Young Oncologists) interviews Dr Laura Mezquita (Thoracic Oncology Group) regarding novelties presented in ESMO 2020 in the field of metastatic non-small-cell lung cancer (NSCLC).

Editorial introductions.

Editorial introductions.

Double Blind Pilot Randomized Trial Comparing Extended Anticoagulation to Placebo Following Major Lung Resection for Cancer

Venous thromboembolism (VTE), which comprises pulmonary embolus (PE) and deep vein thrombosis (DVT), is a significant cause of postoperative morbidity and mortality. This pilot randomized control trial (RCT) evaluated the feasibility of a full-scale RCT investigating extended thromboprophylaxis in patients undergoing oncological lung resections. Patients undergoing oncological lung resections in 2 tertiary centers received in-hospital, thromboprophylaxis and were randomized to receive post-discharge low-molecular-weight heparin (LMWH) or placebo injections once-daily for 30 days. At 30 days postoperatively, all patients underwent chest computed tomography with PE protocol and bilateral leg venous ultrasound. Primary outcomes included feasibility and safety; VTE incidence and 90-day survival were secondary outcomes. Between December 2015 and June 2018, 619 patients were screened, of whom 62.7% (165/263) of eligible patients consented to participate, and 133 (81%) were randomized. One-hundred and 3 patients, (77.4%), completed the 90-day study follow-up. Reasons for non-participation pre-randomization included patient discomfort and LMWH/placebo administration challenges. Post-randomization withdrawals were due to patient preference, surgeon preference and minor adverse events. Six asymptomatic VTE events (5 PE and 1 DVT) were detected within 30 days (3 in each group), for an overall incidence of 7%. There were 3 minor and no major adverse events. This study is the first to demonstrate the feasibility and safety of a full-scale extended thromboprophylaxis RCT in thoracic surgical oncology. Our results demonstrate that, while recruitment and retention rates were modest, the study design is feasible and with minimal adverse events and no intervention-related mortality.

Implementation of an Early Palliative Care Referral Program in Lung Cancer: A Quality Improvement Project at the Tata Memorial Hospital, Mumbai, India.

Objectives:Access to early palliative care (EPC) for all patients with metastatic lung cancer is yet to be achieved in spite of recommendations. This quality improvement (QI) project was initialized to improve the rates of such referrals from the thoracic oncology clinic for all new outpatients in a premier cancer center in India.Materials and Methods:Change in the proportion of patients receiving referrals for EPC during and after intervention (April–May 2018), compared to baseline (January–March 2018) were explored. Interventions included understanding of the process flow, identification of key drivers, and root cause analysis which identified the gaps as lack of documentation for EPC. Teaching and encouraging staff at the clinic to incorporate referrals into all initial visits for patients with metastatic lung cancer were incorporated.Results:The bundle of QI interventions increased referrals from an average of 50% to 75%, mean difference = 12.64 (standard deviation = 10.13) (95% confidence interval = 22.01–3.29), P = 0.016 (two-tailed) on paired sample test.Conclusion:Improved referral rates for EPC in a multidisciplinary cancer clinic is possible with a QI project. This project also identifies the importance of data documentation and patient information processes that can be targeted for improvement.

Targeted Next-Generation Sequencing Reveals Exceptionally High Rates of Molecular Driver Mutations in Never-Smokers with Lung Adenocarcinoma

Background: Historically, high rates of actionable driver mutations have been reported in never-smokers with lung adenocarcinoma (LUAD); however, in the era of modern, comprehensive cancer mutation sequencing, this relationship necessitates a more detailed analysis. Methods: All Mount Sinai patients between 01/01/2015 and 6/01/2020 with a diagnosis of LUAD of any stage with known smoking status who received genomic testing were included. Most patients were analyzed using the Sema4 hotspot panel or the OCAv3 NGS panel conducted at Sema4. Patients were considered fully genotyped if they were comprehensively analyzed for alterations in EGFR, KRAS, MET, ALK, RET, ROS1, BRAF, NTRK1-3, and ERBB2, otherwise they were considered partially genotyped.Findings236 never-smokers and 671 smokers met the above criteria. Of the never-smokers, 201 (85%) had a driver mutation with 175 (74%) considered actionable. Among smokers, 436 (65%) had an identified driver mutation with 268 (40%) actionable (p<0.0001). When comprehensively sequenced, 95% (70/74) of never-smokers had a driver mutation with 80% (59/74) actionable; whereas, for smokers, 73% (131/180) had a driver with only 44% (79/180) actionable (p<0.0001). Within mutations groups, EGFR G719X and KRAS G12Cs were more common to smokers. For stage IV patients harboring EGFR-mutant tumors treated with EGFR-directed therapies, never-smokers had significantly improved overall survival compared to smokers (HR=3.50; p=0.0066). In multivariable analysis, Asian ancestry and female gender remained significant predictors of 1) overall survival i n stage IV patients and 2) likelihood of harboring an actionable driver mutation. Interpretation: Comprehensive NGS revealed driver alterations in 95% of never-smokers, with the majority having an associated therapy available. All efforts should be exhausted to identify or rule out the presence of an actionable driver mutation in LUAD patients requiring systemic treatment. Funding: Center for Thoracic Oncology Seed funding Declaration of Interests: MIK, KLA, XZ, SG, MF, MR, HA, FMH, WKO, SN, EES, RC are employed by Sema4 and some declare ownership of stock options of Sema4. No other competing interests to declare. PCM has received honoraria from Guardant Health and Amgen. FRH served on advisory boards for Bristol-Myers Squibb, Merck, Novartis, Genentech, AstraZeneca/Daiichi, Sanofi/Regeneron, OncoCyte, Amgen. Patent: “EGFR copy number and Protein Expression as Predictive Biomarker for EGFR directed Therapy” Co-inventor. Patent through University of Colorado. (no royalties) Ethics Approval Statement: Study permission was granted by the Mount Sinai IRB. The procedures followed in this study were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration.

Management guidelines for stage III non-small cell lung cancer.

Management of stage III non- small cell lung cancer (NSCLC) is very challenging due to being a group of widely heterogeneous diseases that require multidisciplinary approaches with timely and coordinated care. The standards of care had significant changes over the last couple of years because of the introduction of consolidation therapy with checkpoint inhibitor following concurrent chemo-radiotherapy and the evolving new role of tyrosine kinase inhibitors in the adjuvant setting. The manuscript presents evidence-based recommendations for the workup, staging, treatment and follow up of the various subtypes of stage III NSCLC. The guidelines were developed by experts in various fields of thoracic oncology and guidelines development. The guidelines consider the sequence of interventions and the role of each discipline in the management of the disease taking into account the recent development and included required resources to help physicians provide better care.

Analysis of the feasibility and prognostic value of circulating tumor DNA in detecting gene mutations in small cell lung cancer

Objective: To investigate the feasibility of circulating tumor DNA (ctDNA) in detecting small cell lung cancer (SCLC) gene mutations and its prognostic value in chemotherapy and/or radiotherapy for SCLC patients. Methods: A total of 77 SCLC patients who were admitted to the Department of Thoracic Medical Oncology and the Department of Thoracic Radiation Oncology of Zhejiang Cancer Hospital from July 2016 to November 2019 were included. There were 66 males and 11 females, with a median age of 60 years. Among them, 42 cases were in limited stage (LS) and 35 cases were in extensive stage (ES). Next-generation sequencing (NGS) of patients' plasma ctDNA was performed before treatment. The differences of mutated genes and signaling pathways between LS and ES patients were analyzed and compared. Blood-based tumor mutation burden (bTMB) was calculated according to detected somatic cell mutations. Patients were divided into the high bTMB and the low bTMB groups according to the optimal threshold calculated by R software. Log-rank tests were used to compare progression-free survival (PFS) between the high bTMB and the low bTMB groups. Results: Among the 77 patients, 76 patients had gene mutations detected in their plasma, and the positive rate of ctDNA test was 98%. Among the 76 patients, the genes with the highest mutation frequency were TP53 (89%), RB1 (70%), LRP1B (34%), CREBBP (21%), MLL3 (21%), MLL2 (16%), NOTCH1 (13%), ROS1 (13%), BRCA2 (12%), and PTPRD (12%). The most common mutated genes in LS patients were TP53 (90%), RB1 (68%), LRP1B (24%), MLL2 (22%), and BRCA2 (17%); the most common mutated genes in ES patients were TP53 (89%), RB1 (71%), LRP1B (46%), CREBBP (31%), and MLL3 (29%). The mutation rates of NOTCH1 and CREBBP genes were significantly higher in ES patients (31.4% and 22.9%) than those in LS patients (11.9% and 4.8%) (both P<0.05). Signaling pathway analysis showed that there were more NOTCH pathway gene variations in ES patients. Among LS patients, patients in the high bTMB group (≥ 6.96 mutations/Mb) had a longer PFS than that in the low bTMB group (<6.96 mutations/Mb) (P=0.033); but no such difference was noted in ES patients. Conclusion: Plasma ctDNA sequencing detected SCLC gene mutation profiles similar to those reported in previous literature, thus ctDNA could be used as a tool to study SCLC genomics; the mutation spectra of ES-SCLC and LS-SCLC were different. bTMB has potential prognostic value in LS-SCLCs treated with chemoradiotherapy.

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.

Thoracic Surgery during Coronavirus Disease 2019 (COVID-19): The Experience of a Level 1 Trauma Center.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus primarily affecting the respiratory system, was initially diagnosed in Wuhan, China, in late 2019. Identified as coronavirus disease 2019 (COVID-19) by the World Health Organization, the virus rapidly became a global pandemic. The effects on health care worldwide were unprecedented as countries adapted services to treat masses of critically ill patients.The aim of this study is to analyze the effect that the COVID-19 pandemic had on thoracic surgery at a major trauma center during peak prevalence. Prospective unit data were collected for all patients who underwent thoracic surgery during March 2020 until May 2020 inclusive. Retrospective data were collected from an earlier comparable time period as a comparison. In the aforementioned time frame, 117 thoracic surgical operations were performed under the care of four thoracic surgeons. Six operations were performed on three patients who were being treated for SARS-CoV-2. One operation was performed on a patient who had recovered from SARS-CoV-2. There were no deaths due to SARS-CoV-2 in any patient undergoing thoracic surgery. This study demonstrates that during the first surge of SARS-CoV-2, it was possible to adapt a thoracic oncology and trauma service without increase in mortality due to COVID-19. This was only possible due to a significant reduction in trauma referrals, cessation of benign and elective work, and the more stringent reprioritization of cancer surgery. This information is vital to learn from our experience and prepare for the predicted second surge and any similar future pandemics we might face.

Impact of PET/CT for Assessing Response to Immunotherapy-A Clinical Perspective.

Cancer immunotherapy using immune-checkpoint inhibitors (ICI) has revolutionized the therapeutic landscape of various malignancies like non-small-cell lung cancer or melanoma. Pre-therapy response prediction and assessment during ICI treatment is challenging due to the lack of reliable biomarkers and the possibility of atypical radiological response patterns. Positron emission tomography/computed tomography (PET/CT) enables the visualization and quantification of metabolic lesion activity additional to conventional CT imaging. Various biomarkers derived from PET/CT have been reported as predictors for response to ICI and may aid to overcome the challenges clinicians currently face in the management of ICI-treated patients. In this narrative review, experts in nuclear medicine, thoracic oncology, dermatooncology, hemato- and internal oncology, urological and head/neck tumors performed literature reviews in their respective field and a joint discussion on the use of PET/CT in the context of ICI treatment. The aims were to give a clinical overview on present standards and evidence, to identify current challenges and fields of research and to enable an outlook to future developments and their possible implications. Multiple promising studies concerning ICI response assessment or prediction using biomarkers derived from PET/CT alone or as composite biomarkers have been identified for various malignancies and disease stages. Of interest, additional major incentives in the field may evolve from novel tracers specifically targeting immune-checkpoint molecules which could allow not only response assessment and prognosis, but also visualization of histological tumor cell properties like programmed death-ligand (PD-L1) expression in vivo. Despite the broad range of existing literature on PET/CT-derived biomarkers in ICI therapy, implications for daily clinical practice remain elusive. High-quality prospective data are urgently warranted to determine whether patients benefit from the application of PET/CT in terms of prognosis. At the moment, the lack of such evidence as well as the absence of standardized imaging methods and biomarkers still precludes PET/CT imaging to be included in the relevant clinical practice guidelines.

Optimal Management of Radiation Pneumonitis: Preliminary Findings of an International Delphi Consensus Study

Radiation pneumonitis (RP) is a dose-limiting toxicity for patients undergoing radiotherapy (RT) and systemic therapy for lung cancer; however, the optimal practice for diagnosis, management and follow-up remains unclear. We sought to establish expert consensus recommendations for RP management. Following literature review on RP, 9 open-ended questions related to knowledge, risk-reduction, diagnosis and treatment were generated for this first round of a consensus-building Delphi process. International leaders in multidisciplinary thoracic oncology were invited to participate (n = 31). Key statements regarding RP diagnosis and management were generated from responses to produce statements for Round 2. Participants will be solicited regarding agreement/disagreement with statements using a 5-point Likert scale. Subsequent rounds will seek consensus in areas that remain unresolved. For Round 1, a 74% response rate (n = 23; 12 radiation oncologists, 5 clinical oncologists, 6 respirologists) was achieved. Eighty-three percent of respondents were not aware of any guidelines for management of RP and 17% used local guidelines or expert review articles. Clinical history, exam and lab criteria (13 respondents) and imaging (15 respondents) were cited as used for diagnosis, and RTOG (9 respondents) and CTCAE grading (14 respondents) for assessment. Radiation-specific factors predictive of RP included irradiated lung volume (especially V20), dose, RT technique and location. The majority of clinical and radiation oncologists used motion management, image guidance and IMRT planning to achieve dosimetric constraints and minimize normal lung dose. Systemic therapy-related RP predictive factors included adjuvant or concurrent chemotherapy, immunotherapy (IO), and use of other pulmonotoxic medications. Patient-related predictive factors included lung function, autoimmune disease, age, performance status and smoking status. Majority of clinicians use risk stratification of patients in order to mitigate RP. Respondents uniformly agreed that steroid therapy is the mainstay of treatment for moderate to severe RP, with variability in the dosing and tapers used. A multidisciplinary management approach was favored by all, including radiation and medical oncologists, respirologists, thoracic radiologists and/or infectious disease or rheumatology specialists if indicated. The majority believe that IO will add complexity in identifying RP. Regarding additional measures to prevent RP in IO patients, respondents were split, with 50% taking additional measures and 50% not, though majority favored monitoring by oncologists during IO cycles and counseling patients on increased RP risk. Responses from international thoracic oncology experts highlight areas lacking consensus in the diagnosis and management of RP. These data will inform the next round of Delphi questions, with an aim of reaching consensus on this common issue.

Chinses expert consensus on the multidisciplinary team diagnosis and treatment of lung cancer

Lung cancer is by far the most common cancer and the leading cause of cancer death in China. Through multidimensional discussion and analysis of disease, the multidisciplinary team (MDT) diagnosis and treatment brings lots of benefits for cancer patients, including increasing patient satisfaction, reducing hospitalization expense, shortening treatment waiting time, providing more reasonable diagnosis and treatment pathways and strategies, relieving medical disputes, increasing enrollment opportunities for patients in high-quality clinical trials, patients'prognosis and life quality and so on. Presently, lung cancer MDT in China needs to be improved, including guideline following, democratic decision, landing performance and feedback, meeting records, patient follow-up and so on. So this consensus combines lung cancer MDT experience of China with leading-edge global oncology MDT experience to construct patient-centered lung cancer MDT diagnosis and treatment model, including MDT responsibility and obligations, organizational framework, working modality, standard procedures, assessment methods, and encouragement mechanisms and so on. Chinese Thoracic Oncology Group; Chinese Society of Lung Cancer; Lung Cancer Group of Oncology Branch, Chinese Medical Association; Multidisciplinary Team Diagnosis and Treatment Committee, Chinses Medical Doctor Association jointly publish this consensus. The purpose of this consensus is to provide procedures and criteria for lung cancer MDT of China.