Atypical Skin Manifestations During Immune Checkpoint Blockage in Coronavirus Disease 2019–Infected Patients With Lung Cancer

A new coronavirus, named severe acute respiratory syndrome–coronavirus-2 by the WHO, has rapidly spread around the world since its first reported case in late December of 2019 from Wuhan, the People’s Republic of China. As of mid-April 2020, this virus has affected more than 180 countries and territories, infecting more than 1,650,000 individuals and causing over 100,000 deaths. With approximately 20 million new cases globally per year, cancer affects a substantial portion of the population. Individuals affected by cancer are more susceptible to infections owing to coexisting chronic diseases (cardiovascular, pulmonary, and diabetes), overall poor health status, and systemic immunosuppressive states caused by both cancer and the anticancer treatment. As a consequence, patients with malignancies, especially those with lung cancer who develop coronavirus disease 2019, experience more difficult outcomes. A recent multicenter study carried out by the Hubei Anti-Cancer Association has also documented that patients with lung cancer had an increased risk of death, intensive care unit requirement, risk of presenting severe or critical symptoms, and use of invasive mechanical ventilation. Here, we present two representative cases of patients with lung cancer and coronavirus disease 2019 without respiratory compromise and with atypical and severe skin manifestations—findings that could be influenced by the long-term use of anti–programmed cell death protein 1 antibody.     

Lung Cancer and Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Identifying Important Knowledge Gaps for Investigation

Patients with lung cancer are especially vulnerable to coronavirus disease 2019 (COVID-19) with a greater than sevenfold higher rate of becoming infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19, a greater than threefold higher hospitalization rate with high complication rates, and an estimated case fatality rate of more than 30%. The reasons for the increased vulnerability are not known. In addition, beyond the direct impact of the pandemic on morbidity and mortality among patients with lung cancer, COVID-19, with its disruption of patient care, has also resulted in substantial impact on lung cancer screening and treatment/management.COVID-19 vaccines are safe and effective in people with lung cancer. On the basis of the available data, patients with lung cancer should continue their course of cancer treatment and get vaccinated against the SARS-CoV-2 virus. For unknown reasons, some patients with lung cancer mount poor antibody responses to vaccination. Thus, boosting vaccination seems urgently indicated in this subgroup of vulnerable patients with lung cancer. Nevertheless, many unanswered questions regarding vaccination in this population remain, including the magnitude, quality, and duration of antibody response and the role of innate and acquired cellular immunities for clinical protection. Additional important knowledge gaps also remain, including the following: how can we best protect patients with lung cancer from developing COVID-19, including managing care in patient with lung cancer and the home environment of patients with lung cancer; are there clinical/treatment demographics and tumor molecular demographics that affect severity of COVID-19 disease in patients with lung cancer; does anticancer treatment affect antibody production and protection; does SARS-CoV-2 infection affect the development/progression of lung cancer; and are special measures and vaccine strategies needed for patients with lung cancer as viral variants of concern emerge.     

Cancer and COVID-19: Unmasking their ties

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) and its clinical manifestation, the coronavirus disease 2019 (COVID19) have rapidly spread across the globe, leading to the declaration of a pandemic. While most present mild symptoms, it appears as though nearly 20% of confirmed patients develop significant complications. These include acute respiratory distress syndrome, septic shock and multi-organ failure, with a 3–6% mortality. A plethora of treatments has been or is being assessed, but to date, none has been proven effective. Management is mainly symptomatic, with organ support for the critically ill. Several reports, mainly case series, from across the world have concluded that patients with malignancy appear more susceptible to severe infection and mortality from COVID-19. This could be attributed to immunosuppression, co-existing medical conditions and underlying pulmonary compromise which is often the case in lung malignancy. Patients with haematological cancer and those who are receiving active chemotherapy treatment may be at greatest risk due to increased immunosuppression. This pandemic tested the resilience of worldwide health-care systems in an unprecedented manner. It has forced oncologists to rethink the entire diagnostic and therapeutic process, based on the local prevalence and impact of COVID-19. In this review we will discuss the impact of COVID-19 on patients affected by cancer, their diagnosis and management, as well as the pathophysiology of COVID-19 induced acute respiratory distress symptoms and currently investigated treatment approaches.     

The 3 Bs of cancer care amid the COVID-19 pandemic crisis: “Be safe,be smart,be kind”—A multidisciplinary approach increasing the use of radiation and embracing telemedicine for head and neck cancer

Because of the national emergency triggered by the coronavirus disease 2019 (COVID-19) pandemic, government-mandated public health directives have drastically changed not only social norms but also the practice of oncologic medicine. Timely head and neck cancer (HNC) treatment must be prioritized, even during emergencies. Because severe acute respiratory syndrome coronavirus 2 predominantly resides in the sinonasal/oral/oropharyngeal tracts, nonessential mucosal procedures are restricted, and HNCs are being triaged toward nonsurgical treatments when cures are comparable. Consequently, radiation utilization will likely increase during this pandemic. Even in radiation oncology, standard in-person and endoscopic evaluations are being restrained to limit exposure risks and preserve personal protective equipment for other frontline workers. The authors have implemented telemedicine and multidisciplinary conferences to continue to offer standard-of-care HNC treatments during this uniquely challenging time. Because of the lack of feasibility data on telemedicine for HNC, they report their early experience at a high-volume cancer center at the domestic epicenter of the COVID-19 crisis.     

Safety and Immunogenicity of mRNA Vaccines Against Severe Acute Respiratory Syndrome Coronavirus 2 in Patients With Lung Cancer Receiving Immune Checkpoint Inhibitors: A Multicenter Observational Study in Japan

IntroductionPatients with cancer have been prioritized for vaccination against severe acute respiratory syndrome coronavirus 2. Nevertheless, there are limited data regarding the safety, efficacy, and risk of developing immune-related adverse events (irAEs) associated with mRNA vaccines in patients with lung cancer, especially those being actively treated with immune checkpoint inhibitors.MethodsThis multicenter observational study was conducted at nine hospitals in Japan. Patients with lung cancer (≥20 y) actively treated with immune checkpoint inhibitors between 4 weeks prefirst vaccination and 4 weeks postsecond vaccination were enrolled. The primary end point was the incidence of irAEs of any grade on the basis of an assumed incidence without vaccination rate of 35%. Immunogenicity was assessed by measuring anti–spike (S)-IgG antibody levels against severe acute respiratory syndrome coronavirus 2.ResultsA total of 126 patients with lung cancer (median age, 71 y; interquartile range, 65–74) were enrolled from May to November 2021 and followed up until December 2021. There were 26 patients (20.6%, 95% confidence interval: 13.9%–28.8%) and seven patients (5.6%, 95% confidence interval: 2.3%–11.1%) who developed irAEs of any grade pre- and postvaccination, respectively, which was lower than the predicted incidence without vaccination. None of the patients experienced exacerbation of preexisting irAE postvaccination. S-IgG antibodies were seroconverted in 96.7% and 100% of the patients with lung cancer and controls, respectively, but antibody levels were significantly lower in patients with lung cancer (p < 0.001).ConclusionsPatients with lung cancer who were actively treated with ICIs were safely vaccinated without an increased incidence of irAEs; however, their vaccine immunogenicity was lower. This requires further evaluation.     

International Association for the Study of Lung Cancer Study of the Impact of Coronavirus Disease 2019 on International Lung Cancer Clinical Trials

IntroductionTo evaluate the effects of the global coronavirus disease 2019 (COVID-19) pandemic on lung cancer trials, we surveyed investigators and collected aggregate enrollment data for lung cancer trials across the world before and during the pandemic.MethodsA Data Collection Survey collected aggregate monthly enrollment numbers from 294 global lung cancer trials for 2019 to 2020. A 64-question Action Survey evaluated the impact of COVID-19 on clinical trials and identified mitigation strategies implemented.ResultsClinical trial enrollment declined from 2019 to 2020 by 14% globally. Most reductions in enrollment occurred in April to June where we found significant decreases in individual site enrollment (p = 0.0309). Enrollment was not significantly different in October 2019 to December of 2019 versus 2020 (p = 0.25). The most frequent challenges identified by the Action Survey (N = 172) were fewer eligible patients (63%), decrease in protocol compliance (56%), and suspension of trials (54%). Patient-specific challenges included access to trial site (49%), ability to travel (54%), and willingness to visit the site (59%). The most frequent mitigation strategies included modified monitoring requirements (47%), telehealth visits (45%), modified required visits (25%), mail-order medications (25%), and laboratory (27%) and radiology (21%) tests at nonstudy facilities. Sites that felt the most effective mitigation strategies were telehealth visits (85%), remote patient-reported symptom collection (85%), off-site procedures (85%), and remote consenting (89%).ConclusionsThe COVID-19 pandemic created many challenges for lung cancer clinical trials conduct and enrollment. Mitigation strategies were used and, although the pandemic worsened, trial enrollment improved. A more flexible approach may improve enrollment and access to clinical trials, even beyond the pandemic.     

新型冠状病毒感染对肿瘤治疗的影响

2019年12月新型冠状病毒（severe acute respiratory syndrome coronavirus 2，SARS-CoV-2）在全球蔓延，促使世界卫生组织宣布2019冠状病毒病（COVID-19）流行为国际性突发公共卫生事件。人群普遍易感SARS-CoV-2，而肿瘤患者由于肿瘤生长和抗癌治疗抑制全身免疫系统，成为更易感染并发展为重症SARS-CoV-2症状的脆弱人群。SARS-CoV-2感染后的炎症因子风暴与免疫抑制在SARS-CoV-2感染的肿瘤患者体内产生矛盾，其表现和预后及治疗结果仍未明确。本文基于现有研究文献综述，旨在了解SARS-CoV-2感染对肿瘤患者的生物学及生存预后的影响，以期为疫情期间肿瘤患者的临床治疗提供参考。      

Pulmonary Pathology of Early-Phase 2019 Novel Coronavirus (COVID-19) Pneumonia in Two Patients With Lung Cancer

There is currently a lack of pathologic data on the novel coronavirus (severe acute respiratory syndrome coronavirus 2) pneumonia, or coronavirus disease 2019 (COVID-19), from autopsy or biopsy. Two patients who recently underwent lung lobectomies for adenocarcinoma were retrospectively found to have had COVID-19 at the time of the operation. These two cases thus provide important first opportunities to study the pathology of COVID-19. Pathologic examinations revealed that apart from the tumors, the lungs of both patients exhibited edema, proteinaceous exudate, focal reactive hyperplasia of pneumocytes with patchy inflammatory cellular infiltration, and multinucleated giant cells. Hyaline membranes were not prominent. Because both patients did not exhibit symptoms of pneumonia at the time of operation, these changes likely represent an early phase of the lung pathology of COVID-19 pneumonia.     

Screening for Lung Cancer in Individuals Who Never Smoked: An International Association for the Study of Lung Cancer Early Detection and Screening Committee Report

Screening with low-dose computed tomography of high-risk individuals with a smoking history reduces lung cancer mortality. Current screening guidelines and eligibility criteria can miss more than 50% of lung cancers, and in some geographic areas, such as East Asia, a large proportion of the missed lung cancers are in never-smokers. Although randomized trials revealed the benefits of screening for people who smoke, these trials generally excluded never-smokers. Thus, the feasibility and effectiveness of lung cancer screening of individuals who never smoked are uncertain. Several known and suspected risk factors for lung cancers in never-smokers such as exposure to secondhand smoke, occupational carcinogens, radon, air pollution, and pulmonary diseases, such as chronic obstructive pulmonary disease and interstitial lung diseases, and intrinsic factors, such as age, are well noted. In this regard, knowledge of risk factors may make possible quantification and prediction of lung cancer risk in never smokers. It is worth considering if and how never smokers could be included in population-based screening programs. As the implementation of these programs is challenging in many countries owing to multiple factors and the epidemiologic differences by global regions, these issues will need to be evaluated in each country taking into account various factors, including accuracy of risk assessment and cost-effectiveness of screening in never smokers. This report aims to outline current knowledge on risk factors for lung cancer in never smokers to propose research strategies for this topic and initiate a broader discussion on lung cancer screening of never smokers. Similar considerations can be made in current and ex-smokers, which do not fulfill the current screening inclusion criteria, but otherwise are at increased risk. Although screening of never smokers may in the future be effectively conducted, current evidence to support widespread implementation of this practice is lacking.     

Reduced Fractionation in Lung Cancer Patients Treated with Curative-intent Radiotherapy during the COVID-19 Pandemic

Patients treated with curative-intent lung radiotherapy are in the group at highest risk of severe complications and death from COVID-19. There is therefore an urgent need to reduce the risks associated with multiple hospital visits and their anti-cancer treatment. One recommendation is to consider alternative dose-fractionation schedules or radiotherapy techniques. This would also increase radiotherapy service capacity for operable patients with stage I-III lung cancer, who might be unable to have surgery during the pandemic.Here we identify reduced-fractionation for curative-intent radiotherapy regimes in lung cancer, from a literature search carried out between 20/03/2020 and 30/03/2020 as well as published and unpublished audits of hypofractionated regimes from UK centres. Evidence, practical considerations and limitations are discussed for early-stage NSCLC, stage III NSCLC, early-stage and locally advanced SCLC. We recommend discussion of this guidance document with other specialist lung MDT members to disseminate the potential changes to radiotherapy practices that could be made to reduce pressure on other departments such as thoracic surgery. It is also a crucial part of the consent process to ensure that the risks and benefits of undergoing cancer treatment during the COVID-19 pandemic and the uncertainties surrounding toxicity from reduced fractionation have been adequately discussed with patients. Furthermore, centres should document all deviations from standard protocols, and we urge all colleagues, where possible, to join national/international data collection initiatives (such as COVID-RT Lung) aimed at recording the impact of the COVID-19 pandemic on lung cancer treatment and outcomes.     

The Prefectural Participation Rates of Lung Cancer Screening Had a Negative Correlation with the Lung Cancer Mortality Rates

Background: The participation rate is one of the most important indexes in the cancer screening. Historicallyin Japan, each local government has developed their own equations to calculate the subjects for population-basedscreening, which were different from each other, and therefore the participation rates of screening were not comparable.Recently, local governments were ordered to use the standardized equation in reporting data, which made it possibleto compare the participation rates of cancer screening nationwide for the first time. We therefore investigated thecorrelation between the prefectural lung cancer mortality and several indicators of lung cancer screening. Methods:The prefectural participation rates of lung, gastric and colonic cancer screening, test positive rates, attendance ratesfor further examination, lung cancer detection rates and positive predictive values of lung cancer screening werecollected from “Cancer Registration and Statistics” of the National Cancer Research Center website. The age-adjustedlung, gastric and colonic cancer mortality rates, smoking rates were also collected. The EZR software program wasused for statistical analyses. Results: The participation rates of lung cancer screening had a strong positive correlationwith the participation rates of gastric/colonic cancer screening (P<0.001). The prefectural lung cancer mortality rateshad a moderate to weak negative correlation with the participation rates of lung cancer screening (P=0.009). A littlecorrelation was noted between other quality assurance indicators of lung cancer screening and lung cancer mortalityrates. Conclusion: These results suggested that participating in lung cancer screening might help reduce lung cancermortality rates in some extent.     

肺癌筛查方法现状

肺癌是目前恶性肿瘤死亡的首要原因,早期诊断对肺癌的预后至关重要。研究显示低剂量计算机断层扫描（computed tomography, CT）筛查可以使肺癌的死亡率下降。但其存在的问题不可忽视,如过高的假阳性率、过度诊断、辐射效应等。作为一种肿瘤无创筛查方法,血液相关肿瘤标志物的检测,在肺癌早期诊断中显示出良好的敏感性和特异性。如何利用现有的筛查手段,建立肺癌筛查综合模式,需要更多大规模的临床研究。     

Evaluating the burden of the COVID-19 pandemic on patients with colorectal cancer

After the emergence of the coronavirus disease 2019 (COVID-19) pandemic, individuals needing medical help preferred to not go to the hospital to avoid the risk of severe acute respiratory syndrome coronavirus 2 infection. The present study investigated the influence of the COVID-19 pandemic on patients with colorectal cancer. Patients with colorectal cancer treated between January and December 2019 were classified as the pre-pandemic group (pre-group) and those treated between April 2020 and March 2021 as the post-pandemic group (pandemic group). The clinicopathologic features of patients who underwent surgery for colorectal cancer in the two groups were retrospectively compared. A total of 161 patients were enrolled: 79 In the pre-group and 82 in the pandemic group. Although no significant differences were observed in tumor location and surgical procedure between the two groups, circumferential lesions (P<0.001), colorectal stenting (P=0.016) and Stage IV classification (P=0.019) had a higher frequency in the pandemic group compared with the pre-group; additionally, surgical curability was significantly lower (P=0.036) in the pandemic group. The spread of COVID-19 has increased the incidence of patients with advanced colorectal cancer. To reduce this incidence, healthcare professionals should inform the general public not only about the risk of COVID-19, but also about the increased incidence of advanced colorectal cancer after the pandemic.     

Severe Acute Respiratory Syndrome–Coronavirus-2 Infection and Patients With Lung Cancer: The Potential Role of Interleukin-17 Target Therapy

The coronavirus disease 2019 outbreak is evolving rapidly worldwide. The lungs are the target of the primary infection and patients with lung cancer seem to have a poor prognosis. To our knowledge, this is the first reported investigation of a possible role of interleukin-17 target therapy in patients with lung cancer and concomitant severe acute respiratory syndrome–coronavirus-2 infection.     

Feasibility and Predictive Performance of a Triage System for Patients with Cancer During the COVID-19 Pandemic

BackgroundTriage procedures have been implemented to limit hospital access and minimize infection risk among patients with cancer during the coronavirus disease (COVID‐19) outbreak. In the absence of prospective evidence, we aimed to evaluate the predictive performance of a triage system in the oncological setting.Materials and MethodsThis retrospective cohort study analyzes hospital admissions to the oncology and hematology department of Udine, Italy, during the COVID‐19 pandemic (March 30 to April 30, 2020). A total of 3,923 triage procedures were performed, and data of 1,363 individual patients were reviewed.ResultsA self‐report triage questionnaire identified 6% of triage‐positive procedures, with a sensitivity of 66.7% (95% confidence interval [CI], 43.0%–85.4%), a specificity of 94.3% (95% CI, 93.5%–95.0%), and a positive predictive value of 5.9% (95% CI, 4.3%–8.0%) for the identification of patients who were not admitted to the hospital after medical review. Patients with thoracic cancer (odds ratio [OR], 1.69; 95% CI, 1.13–2.53, p = .01), younger age (OR, 1.52; 95% CI, 1.15–2.01, p < .01), and body temperature at admission ≥37°C (OR, 9.52; 95% CI, 5.44–16.6, p < .0001) had increased risk of positive triage. Direct hospital access was warranted to 93.5% of cases, a further 6% was accepted after medical evaluation, whereas 0.5% was refused at admission.ConclusionA self‐report questionnaire has a low positive predictive value to triage patients with cancer and suspected severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) symptoms. Differential diagnosis with tumor‐ or treatment‐related symptoms is always required to avoid unnecessary treatment delays. Body temperature measurement improves the triage process''s overall sensitivity, and widespread SARS‐CoV‐2 testing should be implemented to identify asymptomatic carriers.Implications for PracticeThis is the first study to provide data on the predictive performance of a triage system in the oncological setting during the coronavirus disease outbreak. A questionnaire‐based triage has a low positive predictive value to triage patients with cancer and suspected severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) symptoms, and a differential diagnosis with tumor‐ or treatment‐related symptoms is mandatory to avoid unnecessary treatment delays. Consequently, adequate recourses should be reallocated for a triage implementation in the oncological setting. Of note, body temperature measurement improves the overall sensitivity of the triage process, and widespread testing for SARS‐CoV‐2 infection should be implemented to identify asymptomatic carriers.     

Intentions to Undergo Lung Cancer Screening among Korean Men

Opportunistic screening for lung cancer is commonly conducted in Korea in accordance with physicianrecommendations and screenee’s preferences. However, studies have yet to thoroughly examine the public’sunderstanding of the risks posed by lung cancer screening. This study was conducted to assess changes inintentions to undergo lung cancer screening in response to being informed about exposure to radiation duringlow-dose computed tomography (LDCT) tests and to identify factors with the greatest influence thereonamong Korean men. We conducted sub-group interviews among men chosen from the 2013 Korea NationalCancer Screening Survey (KNCSS), a nationwide, population-based, cross-sectional survey of men aged 40 to74 years and women aged 30 to 74 years. From 4100 participants in the KNCSS, 414 men who underwent anycancer screening test within the last 2 years were randomly selected for inclusion in this study. Via face-to-faceinterviews, their intentions to undergo lung cancer screening were assessed before and after being informedabout exposure to radiation during LDCT testing. Of the 414 participants, 50% were current smokers. Afterreceiving information on the benefits of the test, 95.1% stated an intention to undergo screening; this decreasedto 81.6% after they received information on the harms of the test. The average decrease in intention rate was35.3%. Smoking status, household income, and education level were not associated with lowered intentions toundergo lung cancer screening. Participants who were older than 60 years old (OR=0.56; 95% CI= 0.33-0.96)and those with less concern for radiation exposure (OR=0.56; 95% CI=0.36-0.89) were less likely to lower theirscreening intentions. The results of this study suggest that there is a need to educate both non-smokers andformer smokers on the harms of lung cancer screening.     

How to Guarantee the Best of Care to Patients with Cancer During the COVID-19 Epidemic: The Italian Experience

Italy and the rest of the world are experiencing an outbreak of a novel beta-coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this context, in Italy, we reorganized the National Health System and prioritized the clinical cancer care scenario, balancing risk of SARS-CoV-2 transmission versus the magnitude of clinical benefit deriving from a specific therapeutic approach. As initial actions, we recommended that routine screening be suspended and that patients with early and advanced cancer be treated as outpatients as much as possible and at the nearest medical center. Patients who need to be hospitalized for cancer treatment were protected from potential SARS-CoV-2 infection by creating a dedicated diagnostic and therapeutic internal pathway for cancer treatment. We implemented reorganization of the hospital networks, based on a hub-and-spoke design. Stronger personal protection was made available for patients with cancer. Because of the extreme burden created by COVID-19, antitumor treatment was initiated only after considering patient performance status, comorbidities, biology of disease, and the likely impact of treatment on outcome. Treatment strategies were discussed in the context of a multidisciplinary tumor board. Treatment decision making balanced risk and benefits of treatment in the context of the specific pandemic level, on a case-by-case basis.