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.     

Acute Immune Signatures and Their Legacies in Severe Acute Respiratory Syndrome Coronavirus-2 Infected Cancer Patients

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Efficacy of Severe Acute Respiratory Syndrome Coronavirus-2 Vaccine in Patients With Thoracic Cancer: A Prospective Study Supporting a Third Dose in Patients With Minimal Serologic Response After Two Vaccine Doses

IntroductionCoronavirus disease 2019 resulted in a 30% mortality rate in patients with thoracic cancer. Given that patients with cancer were excluded from serum antisevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine registration trials, it is still unknown whether they would develop a protective antispike antibody response after vaccination. This prospective vaccine monitoring study primarily aimed to assess humoral responses to the SARS-CoV-2 vaccine in patients with thoracic cancer.MethodsSARS-CoV-2–spike antibodies were measured using the Abbot Architect SARS-CoV-2 immunoglobulin G immunoassay before the first injection of BNT162b2 mRNA vaccine, at week 4, and 2 to 16 weeks after the second vaccine dose administration. The factors associated with antibody response were analyzed.ResultsOverall, 306 patients, with a median age of 67.0 years (interquartile range: 58–74), were vaccinated. Of these, 283 patients received two vaccine doses at 28-day intervals. After a 6.7-month median follow-up, eight patients (2.6%) contracted proven symptomatic SARS-CoV-2 infection, with rapid favorable evolution. Of the 269 serologic results available beyond day 14 after the second vaccine dose administration, 17 patients (6.3%) were still negative (<50 arbitrary units/mL, whereas 34 (11%) were less than 300 arbitrary units/mL (12.5th percentile). In multivariate analysis, only age (p < 0.01) and long-term corticosteroid treatment (p = 0.01) were significantly associated with a lack of immunization. A total of 30 patients received a third vaccine dose, with only three patients showing persistently negative serology thereafter, whereas the others exhibited clear seroconversion.ConclusionsSARS-CoV2 vaccines were found to be efficient in patients with thoracic cancer, most of them being immunized after two doses. A third shot given to 1% of patients with persistent low antibody titers resulted in an 88% immunization rate.     

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.     

The Current Lung Cancer Neoantigen Landscape and Implications for Therapy

All tumors harbor unique mutant peptides, some of which are able to elicit T-cell–mediated immune responses. These are known as neoantigens. Lung cancers bear a heavy mutational burden and hence many potential neoantigens. Neoantigens are increasingly recognized as key mediators of tumor-specific immune activation and have been identified as potential targets for personalized cancer therapies. In this review, we discuss the current data on neoantigens in lung cancer and provide an overview of the recent advances in neoantigen-based immunotherapy. Furthermore, we look ahead to highlight the major opportunities and challenges for the clinical application of neoantigen-based treatment strategies for thoracic and other malignancies.     

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.     

The Short-Term Impact Of COVID-19 Pandemic on Cervical Cancer Screening: A Systematic Review and Meta-Analysis

Objective: A systematic review and meta-analysis were carried out to assess the pooled proportion of women screened for cervical cancer before and during the COVID-19 pandemic. Methods: After ruling out registered or ongoing systematic reviews in the PROSPERO database regarding the impact of the COVID-19 pandemic in cervical cancer screening, the protocol of our systematic review and meta-analysis was registered in PROSPERO (CRD42021279305). The electronic databases were searched for articles published in English between January 2020 and October 2021and the study was designed based on PRISMA guidelines updated in 2020. Meta-analysis was accomplished in STATA version 13.0 (College Station, Texas 77,845 USA). The pooled proportion of women who had undergone cervical cancer screening was reported with 95% CI. In order to quantify the heterogeneity, Chi2 statistic (Q statistic) and I2 index were used. Results: The meta-analysis included seven studies from Slovenia, Italy, Ontario (Canada), Scotland, Belgium, and the USA, comprising 403,986 women and 199,165 women who were screened for cervical cancer before the COVID-19 pandemic in 2019 and during the pandemic in 2020, respectively. The pooled proportion of women screened for cervical cancer in 2019 was 9.79% (95% CI 6.00%-13.59%, 95% prediction interval 0.42%-23.81%). During the pandemic, the pooled proportion of screened women declined to 4.24% (95% CI 2.77%-5.71%, 95% prediction interval 0.9%-17.49%). Conclusion: There was a substantial drop in the cervical cancer screening rate due to lockdowns and travel restrictions to curb the COVID-19 pandemic. Scaling up cervical cancer screening strategies is essential to prevent the long-term impact of cervical cancer burden.     

Evaluation of Serologic Changes of IgG and IgM Antibodies Associated with SARS-COV-2 in Cancer Patients: A Cohort Seroprevalence Study

Background: While the coronavirus disease 2019 (COVID-19) pandemic spreads, there is increasing evidence to suggest the elevated risk of SARS-CoV-2 infection and following morbidity and mortality in cancer patients. Serology testing using ELISA proposes major advantages as a diagnostic and preventive tool to control the present SARS-CoV-2 outbreak. This cohort study was to determine the SARS-CoV-2 seroconversion in asymptomatic cancer patients. Methods: Patients in all age groups and with any type of cancer who have been in remission or have stable disease and received their latest anticancer therapy over 2 months ago included in the study. All patients were evaluated for COVID-19 symptoms and only asymptomatic patients were enrolled for serologic screening for SARS-CoV-2. Serum samples evaluated serologically for SARS-CoV-2 antibodies by enzyme-linked immunosorbent assay. Results: A total of 168 asymptomatic cancer patients were included in the study. Of the 168 cases with a history of cancer who were asymptomatic for Covid-19, 29 cases (17.26%) had a positive serological test. Conclusion: In conclusion, in the present study asymptomatic cancer patients revealed 17% seropositivity, approximately equal to the general population of the same age, sex, geographic region, and epidemic status. Asymptomatic infections should further be investigated and considered as playing an important role in the COVID-19 transmission chain.     

Coronavirus 2019 Infectious Disease Epidemic: Where We Are,What Can Be Done and Hope For

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads mainly by means of aerosols (microdroplets) in enclosed environments, especially those in which temperature and humidity are regulated by means of air-conditioning. About 30% of individuals infected with SARS-CoV-2 develop coronavirus disease 2019 (COVID-19) disease. Among them, approximately 25% require hospitalization. In medicine, cases are identified as those who become ill. During this pandemic, cases have been identified as those with a positive SARS-CoV-2 polymerase chain reaction test, including approximately 70% who were asymptomatic—this has caused unnecessary anxiety. Individuals more than 65 years old, those affected by obesity, diabetes, asthma, or are immune-depressed owing to cancer and other conditions, are at a higher risk of hospitalization and of dying of COVID-19. Healthy individuals younger than 40 years very rarely die of COVID-19. Estimates of the COVID-19 mortality rate vary because the definition of COVID-19–related deaths varies. Belgium has the highest death rate at 154.9 per 100,000 persons, because it includes anyone who died with symptoms compatible with COVID-19, even those never tested for SARS-CoV-2. The United States includes all patients who died with a positive test, whether they died because of, or with, SARS-CoV-2. Countries that include only patients in which COVID-19 was the main cause of death, rather than a cofactor, have lower death rates. Numerous therapies are being developed, and rapid improvements are anticipated. Because of disinformation, only approximately 50% of the U.S. population plans to receive a COVID-19 vaccine. By sharing accurate information, physicians, health professionals, and scientists play a key role in addressing myths and anxiety, help public health officials enact measures to decrease infections, and provide the best care for those who become sick. In this article, we discuss these issues.     

骨膦与化疗和放疗联合治疗肺癌骨转移的临床研究

本文依据５９例肺癌骨转移患者的临床资料，总结分析了肺癌骨转移的特点，着重探讨了骨膦与化疗和放疗联合治疗肺癌骨转移的疗效。结果示：骨膦治疗组３９例止痛总有效率为８７．２％，非骨膦治疗组２０例止痛总有效率为６０％，两者有显著差异（Ｐ〈０．０５）；骨膦治疗组的平均生存期（８．５个月）较非骨膦治疗组（５个月）明显延长（Ｐ〈０．０５）；骨膦治疗组较非骨膦治疗组无明显的毒性反应。另外骨膦用药的时间和疗程对疗效都有一定影响。     

小细胞肺癌目前治疗的策略与未来方向

小细胞肺癌是一种致死率较高的恶性肿瘤,现阶段的治疗方式有手术,化疗和放疗,但预后极差.近些年来涌现的靶向治疗和免疫治疗也都在进行着大量的临床试验,本文将对小细胞肺癌目前的治疗策略以及未来研究的方向进行综述.     

Cancer,Mortality, and Acute Kidney Injury among Hospitalized Patients with SARS-CoV-2 Infection

Background: To evaluate Coronavirus Disease 2019-(COVID19) patients treated within our academic medical system to determine if history of malignancy, both in general and specifically in genitourinary oncology patients, is associated with adverse clinical outcomes, including acute kidney injury (AKI) and mortality. Methods: We conducted a retrospective cohort study among patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a multi-hospital, academic medical institution in New York City. Outcomes included mortality, intensive care unit (ICU) admission and AKI among hospitalized patients. We also evaluated risk of hospitalization among all patients with SARS-CoV-2 infection. Multilevel logistic regression models were used for analysis. Results: We identified 6,893 patients who met inclusion criteria, of which 4,018 were hospitalized. Among hospitalized patients 374 (9%) had a history of cancer, 281 (7%) experienced AKI, and 1,045 (26%) died. In adjusted analyses, patients with a history of cancer had 1.33 (95% CI = 1.05, 1.69) times the odds of death compared to those without cancer and this appeared to be driven by lung cancer (odds ratio (OR) = 2.44, 95% CI= 1.05, 4.39). Patients with a history of genitourinary cancer were not at higher risk of mortality compared to those without cancer (OR=0.99, 95% CI= 0.61, 1.62). History of cancer was not associated with ICU admission or AKI in overall and subgroup analyses. Conclusions: Patients with a history of cancer who are hospitalized with SARS-CoV-2 infection are not at greater risk for AKI, though they are at higher risk for mortality as compared to patients without a history of cancer. The increased risk in mortality appears driven by patients with pulmonary neoplasms. Patients with a history of genitourinary malignancies do not appear to be at higher risk for AKI or for mortality compared to the general population.     

SARS-CoV-2流行期间癌症患者治疗选择的临时指南

In the current pandemic of SARS-Cov-2 (formally known as novel coronavirus disease 2019, COVID-19), the cancer treatment is particularly a challenge that must be overcome as soon as possible. Currently, the clinical data on the prevalence of SARS-Cov-2 in cancer patients is very limited, alone with constant evolving situations. To obtain existing evidence, we reviewed a wide range of medical literature and relevant websites including the National Health Commission of China. With the actual situation of Hubei Cancer Hospital, we formulated the interim guideline which was developed by all contributors from different disciplines after fully discussion, to provide the reference for treatment options on cancer patients, especially the cancer patients recovered from COVID-19 infection. This guideline highlighted the multidisciplinary team (MDT) diagnostic model, the assessment between risks and benefits prior to treatment, individualized service for patients’ medical needs, and the acceptability in ethics and patients’ socio-economic conditions. © 2020, CHINA RESEARCH ON PREVENTION AND TREATMENT. All rights reserved.     

洛铂、顺铂联合药物治疗晚期肺癌的疗效对比研究

目的探讨洛铂顺铂联合药物治疗晚期肺癌的疗效对比。方法随机选取肺癌患者120例,分成6组:A1组患者20例,洛铂联合多西他赛方案化疗;A2组患者20例,顺铂联合多西他赛方案化疗;B1组患者20例,洛铂联合吉西他滨方案化疗;B2组患者20例,顺铂联合吉西他滨方案化疗;C1组患者20例,洛铂联合依托泊苷方案化疗;C2组患者20例,顺铂联合吉西他滨方案化疗,至少完成2个周期以上的治疗。化疗过程中,进行抗过敏预防和保肝护胃处理,记录化疗前、中、后骨髓抑制情况。结果 A1组、B1组、C1组患者有效率分别为35.0%、30.0%、50.0%,疾病控制率分别为52.0%、75.0%、85.0%;A2组、B2组、C2组有效率分别为40.0%、45.0%、60.0%,疾病控制率分别为75.0%、80.0%、90.0%。A1、B1、C1组的近期疗效与A2、B2、C2组无统计学差异(P>0.05)。A1组、B1组、C1组中重度白细胞、血小板降低的发生率比A2、B2、C2组高,但胃肠消化系统反应发生率要低,差异具有统计学意义(P<0.05)。结论洛铂和顺铂联合药物治疗肺癌时,近期临床效果相似;但是洛铂对患者造成的毒副作用要比顺铂小。     

Human Endogenous Retrovirus-H Long Terminal Repeat- Associating Protein 2 (HHLA2) is a Novel Immune Checkpoint Protein in Lung Cancer which Predicts Survival

ackground: Lung cancer is one of the most frequently diagnosed malignancies. Human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) is a recently discovered ligand of the B7 family. Blocking this immune checkpoint has become an important treatment option for lung cancer. Methods: The study includes 62 biopsy specimens either bronchoscopic or CT-guided biopsies diagnosed as lung cancer in Hospitals of Faculty of Medicine, Mansoura University, Egypt during the period from 2016 to 2020. Immunohistochemical Staining for HHLA2 and EGFR was performed. HHLA2 expression was assessed in different pathological types of lung Cancer, and it was correlated with other clinicopathologic parameters and patient prognosis. Results: We found a significant association between HHLA2 expression and metastasis. About 83% of patients presented with metastasis showed positive expression of HHLA2 compared to 44.4% in patients with no metastasis (p=0.02). Also, results show significant mild positive correlation between expression of HHLA2 and EGFR markers (p=0.045). The mean OS time in cases with positive HHLA2 expression was nearly half that of patients with negative expression of the markers. However, this difference was not statistically significant. But, PFS of patients was significantly lower among the group with positive expression of HHLA2 compared to the group with negative expression of HHLA2 (p= 0.01). Conclusions: This study reports that recently discovered, HHLA2 is over expressed in lung cancer associating with higher stage. It is also correlated with EGFR overexpression. HHLA2 could serve as a predictor of progression and distant metastasis. Also, it has potential to be effective immune target in lung cancer immunotherapy such as checkpoint blockade and antibody-drug conjugate treatment.