Safety and efficacy of new staple-line reinforcement in lung resection: a prospective study of 48 patients.

PURPOSE: To evaluate the safety and efficacy of new staple-line reinforcement (SLR) in pulmonary resection through a prospective study and to compare the results of this study with historical control data in an exploratory study. METHODS: The subjects of this study were 48 patients who underwent thoracoscopic lobectomy. The primary endpoint was air leakage from the staple line. The secondary endpoints were the location of air leakage, duration of air leakage, and postoperative pulmonary complications. RESULTS: The incidence of intraoperative air leakage from the staple line was 6.3%. Three patients had prolonged air leakage as a postoperative pulmonary complication. No malfunction was found in patients who underwent SLR with the stapling device. When compared with the historical group, the SLR group had a significantly lower incidence of air leakage from the staple line (6.3% vs. 28.5%, P < 0.001) and significantly shorter indwelling chest drainage time (P = 0.049) and length of hospital stay (P < 0.001). CONCLUSIONS: The use of SLR in pulmonary resection was safe and effective. When compared with conventional products, SLR could control intraoperative air leakage from the staple line and shorten time needed for indwelling chest drainage and the length of hospital stay.

Factors affecting the short-term outcomes of robotic-assisted thoracoscopic surgery for lung cancer.

PURPOSE: Robotic-assisted thoracoscopic surgery (RATS) is a relatively new approach to lung cancer surgery. To promote the development of RATS procedures, we investigated the factors related to short-term postoperative outcomes. METHODS: We analyzed the records of patients who underwent RATS lobectomy for primary lung cancer at our institution between June, 2018 and January, 2023. The primary outcome was operative time, and the estimated value of surgery-related factors was calculated by linear regression analysis. The secondary outcome was surgical morbidity and the risk was assessed by logistic regression analysis. RESULTS: The study cohort comprised 238 patients. Left upper lobectomy had the longest mean operative time, followed by right upper lobectomy. Postoperative complications occurred in 13.0% of the patients. Multivariate analysis revealed that upper lobectomy, the number of staples used for interlobular fissures, and the number of cases experienced by the surgeon were significantly associated with a longer operative time. The only significant risk factor for postoperative complications was heavy smoking. CONCLUSION: Patients with well-lobulated middle or lower lobe lung cancer who are not heavy smokers are recommended for the introductory period of RATS lobectomy. Improving the procedures for upper lobectomy and dividing incomplete interlobular fissures will promote the further development of RATS.

Implication of cytoplasmic p53 expression in pulmonary neuroendocrine carcinoma using next-generation sequencing analysis.

AIMS: Cytoplasmic p53 expression indicates a high frequency of TP53 abnormalities in gynaecological carcinoma. However, the implication of this expression in pulmonary neuroendocrine carcinoma (NEC) remains unclear. Thus, our study aimed to fill this research gap. METHODS AND RESULTS: Immunohistochemistry (IHC) of p53 was performed on 146 cases of resected small-cell lung carcinoma and large-cell NEC, and next-generation sequencing was conducted on cases showing cytoplasmic and wild-type p53 expression. IHC revealed overexpression in 57% of the cases (n = 83), complete absence in 31% (n = 45), cytoplasmic expression in 8% (n = 12) and wild-type expression in 4% (n = 6) of the cases. TP53 mutations were identified in nine of the 13 cases with available genetic analysis. The TP53 mutation rates in cases with cytoplasmic and wild-type p53 expression were 88% (seven of eight) and 40% (two of five), respectively. All seven cases showing cytoplasmic expression with TP53 mutations harboured loss-of-function type mutations: four had mutations in the DNA-binding domain, two in the nuclear localisation domain and one in the tetramerisation domain. Clinically, cases with cytoplasmic p53 expression had a poor prognosis similar to that in cases with p53 overexpression or complete absence. CONCLUSIONS: Cytoplasmic p53 expression in patients with pulmonary NEC suggests a high TP53 mutation rate, which is associated with a poor prognosis similar to that in patients with p53 overexpression or complete absence. This cytoplasmic expression should not be misidentified as a wild-type expression. This is the first report, to our knowledge, that demonstrates the implication of cytoplasmic p53 expression in pulmonary NEC.

POU2F3-Expressing Small Cell Lung Carcinoma and Large Cell Neuroendocrine Carcinoma Show Morphologic and Phenotypic Overlap.

Considering the differences in protein expression in small cell lung carcinoma (SCLC) by molecular classification, it is likely that there are differences in morphology, but the relationship between molecular classification and morphology has not been examined. Furthermore, there are limited reports concerning this molecular classification for large cell neuroendocrine carcinoma (LCNEC) and SCLC simultaneously. Therefore, we investigated the relationship between immunohistochemistry-based molecular classification and morphology, protein expression, and clinical features of 146 consecutive resection specimens of pulmonary neuroendocrine carcinoma (NEC), focusing mainly on POU2F3, the master transcription factor involved in tuft cell generation. POU2F3-dominant SCLC (n=24) and LCNEC (n=14) showed overlap in cytomorphology, while non-POU2F3-dominant SCLC (n=71) and LCNEC (n=37) showed distinct differences in cytomorphology. In addition, POU2F3-dominant NEC exhibited significantly more abundant tumor stroma, more prominent nest formation, more frequent bronchial intraepithelial involvement, and less frequent background fibrosis than non-POU2F3-dominant NEC. Immunohistochemically, POU2F3-dominant SCLC and LCNEC were characterized by lower expression of TTF-1, CEA, and neuroendocrine markers and higher expression of bcl-2, c-Myc, and c-kit. Clinically, POU2F3-dominant NEC had a significantly better prognosis than non-POU2F3-dominant NEC for recurrence-free survival. POU2F3-dominant NEC had a higher smoking index than non-POU2F3-dominant NEC. POU2F3-dominant NEC forms a unique population, exhibiting intermediate morphologic features between SCLC and LCNEC, with distinct protein expression as tuft cell-like carcinoma. Recognition of this unique subtype may provide clues for solving the long-standing issues of NEC and appropriate therapeutic stratification. It is important to accurately identify POU2F3-expressing carcinomas by immunohistochemistry and to analyze their clinicopathological features.

Sarcomatoid mesothelioma diagnosed in a patient with mesothelioma in situ: a case report on morphologic differences after 9-month interval with details analysis of cytology in early-stage mesothelioma.

BACKGROUND: Overlapping morphological features of mesothelial cells have been rendered it difficult to distinguish between reactive and malignant conditions. The development of methods based on detecting genomic abnormalities using immunohistochemistry and fluorescence in situ hybridization have contributed markedly to solving this problem. It is important to identify bland mesothelioma cells on cytological screening, perform efficient genomic-based testing, and diagnose mesothelioma, because the first clinical manifestation of pleural mesothelioma is pleural effusion, which is the first sample available for pathological diagnosis. However, certain diagnostic aspects remain challenging even for experts. CASE PRESENTATION: This report describes a case of a 72-year-old man with a history of asbestos exposure who presented with pleural effusion as the first symptom and was eventually diagnosed as mesothelioma. Mesothelioma was suspected owing to prominent cell-in-cell engulfment in mesothelial cells on the first cytological sample, and the diagnosis of mesothelioma in situ was confirmed by histology. Unexpectedly, sarcomatoid morphology of mesothelioma was found in the second pathology samples 9 months after the first pathological examination. Both the mesothelioma in situ and invasive lesion showed immunohistochemical loss of methylthioadenosine phosphorylase (MTAP) and homozygous deletion of cyclin dependent kinase inhibitor 2A (CDKN2A) on fluorescence in situ hybridization. The patient received medication therapy but died of disease progression 12 months after the diagnosis of the sarcomatoid morphology of mesothelioma. CONCLUSION: Our case suggests that cell-in-cell engulfment can be conspicuous in early-stage mesothelioma with inconspicuous nuclear atypia and few multinucleated cells. In addition, the presence of MTAP loss and CDKN2A homozygous deletion are suspected to be involved in early formation to invasive lesions and/or sarcomatoid morphology. We believe that it is important to consider genetic abnormalities when deciding on individual patient management. Furthermore, cases of mesothelioma, even those of an in situ lesion, with MTAP loss and/or CDKN2A deletion should be carefully followed up or subjected to early treatment.

Autocrine TGF-ß-positive feedback in profibrotic AT2-lineage cells plays a crucial role in non-inflammatory lung fibrogenesis.

The molecular etiology of idiopathic pulmonary fibrosis (IPF) has been extensively investigated to identify new therapeutic targets. Although anti-inflammatory treatments are not effective for patients with IPF, damaged alveolar epithelial cells play a critical role in lung fibrogenesis. Here, we establish an organoid-based lung fibrosis model using mouse and human lung tissues to assess the direct communication between damaged alveolar type II (AT2)-lineage cells and lung fibroblasts by excluding immune cells. Using this in vitro model and mouse genetics, we demonstrate that bleomycin causes DNA damage and activates p53 signaling in AT2-lineage cells, leading to AT2-to-AT1 transition-like state with a senescence-associated secretory phenotype (SASP). Among SASP-related factors, TGF-ß plays an exclusive role in promoting lung fibroblast-to-myofibroblast differentiation. Moreover, the autocrine TGF-ß-positive feedback loop in AT2-lineage cells is a critical cellular system in non-inflammatory lung fibrogenesis. These findings provide insights into the mechanism of IPF and potential therapeutic targets.

Console and bedside surgeon fused robot-assisted thoracic surgery.

In the last decade, even thoracic surgery has seen an increase in the use of robotic surgical systems, and robot-assisted thoracic surgery (RATS) is considered one of the main issues. While RATS is associated with solo manipulative freedom and high-definition optical systems, several disadvantages, such as the lack of tactile sensation and difficult learning curves for the whole team, have been raised. Therefore, to overcome these issues, we developed a 'fusion surgery' approach combining a robotic procedure with manual maneuvers, where the table surgeon retracts the lung and staples the pulmonary vasculature and bronchus. Herein, we introduce our 'fusion surgery' procedure and elaborate on its advantage from technical and educational perspectives.

Programmed death ligand-1 expression and occult lymph node metastasis in non-small cell lung cancer.

BACKGROUND: Identifying the preoperative risk factors for lymph node upstaging could contribute to the development of individualized perioperative treatment for patients with non-small cell lung cancer (NSCLC). The current study aimed to evaluate the risk factors for lymph node upstaging, including gene mutation and programmed death ligand-1 expression in patients with resectable NSCLC. METHODS: Data on the clinicopathological characteristics of patients who underwent lobectomy for clinical N0 NSCLC at our institution were collected. The clinicopathological findings of the pathological N0 and lymph node upstaging groups were then analyzed. Univariate and multivariate analyses were performed to examine the predictive factors for nodal upstaging. RESULTS: Of 291 patients, 40 had postoperative nodal upstaging (n = 25, N1; n = 15, N2). Large tumor size and high maximum standardized uptake value were significantly associated with nodal upstaging. The nodal upstaging group had a higher proportion of patients with solid adenocarcinoma and lymphatic, vascular, and pleural invasion than the pathological N0 group. Further, the nodal upstaging group had a higher proportion of patients with positive programmed death ligand-1 expression than the pathological N0 group. Univariate and multivariate analyses showed that tumor size and positive programmed death ligand-1 expression were associated with nodal upstaging. CONCLUSION: The appropriate therapeutic strategy including preoperative treatment and resection should be cautiously considered preoperatively in patients with clinical N0 NSCLC who have large tumors and positive programmed death ligand-1 expression.

Electrogenetic control of gene expression in Shewanella oneidensis MR-1 using Arc-dependent transcriptional promoters.

Electrochemically active bacteria (EAB) are capable of electrically interacting with electrodes, enabling their application in bioelectrochemical systems (BESs). As the performance of BES is related to the metabolic activities of EAB, the development of methods to control their metabolic activities is important to facilitate BES applications. A recent study found that the EAB Shewanella oneidensis MR-1 uses the Arc system to regulate the expression of catabolic genes in response to electrode potentials, suggesting that a methodology for electrical control of gene expression in EAB, referred to as electrogenetics, can be developed by using electrode potential-responsive, Arc-dependent transcriptional promoters. Here, we explored Arc-dependent promoters in the genomes of S. oneidensis MR-1 and Escherichia coli to identify electrode potential-responsive promoters that are differentially activated in MR-1 cells exposed to high- and low-potential electrodes. LacZ reporter assays using electrode-associated cells of MR-1 derivatives revealed that the activities of promoters located upstream of the E. coli feo gene (Pfeo) and the MR-1 nqrA2 (SO_0902) gene (Pnqr2) were significantly increased when S. oneidensis cells were exposed to electrodes poised at +0.7 V and -0.4 V (versus the standard hydrogen electrode), respectively. Additionally, we developed a microscopic system for in situ monitoring of promoter activity in electrode-associated cells and found that Pnqr2 activity was persistently induced in MR-1 cells associated with an electrode poised at -0.4 V. Our results indicate that these electrode potential-responsive promoters enable efficient regulation of gene expression in EAB, providing a molecular basis for the development of electrogenetics.

The efficacy of thoracoscopic surgery for descending necrotizing mediastinitis.

OBJECTIVES: Thoracotomy is a reliable approach for descending necrotizing mediastinitis (DNM), and the use of video-assisted thoracic surgery (VATS), a minimally invasive procedure, has been increasing. However, which approach is more effective for DNM treatment is controversial. METHODS: We analysed patients who underwent mediastinal drainage via VATS or thoracotomy, using a database with DNM from 2012 to 2016 in Japan, which was constructed by the Japanese Association for Chest Surgery and the Japan Broncho-esophagological Society. The primary outcome was 90-day mortality, and the adjusted risk difference between the VATS and thoracotomy groups using a regression model, which incorporated the propensity score, was estimated. RESULTS: VATS was performed on 83 patients and thoracotomy on 58 patients. Patients with a poor performance status commonly underwent VATS. Meanwhile, patients with infection extending to both the anterior and posterior lower mediastinum frequently underwent thoracotomy. Although the postoperative 90-day mortality was different between the VATS and thoracotomy groups (4.8% vs 8.6%), the adjusted risk difference was almost the same, -0.0077 with 95% confidence interval of -0.0959 to 0.0805 (P = 0.8649). Moreover, we could not find any clinical and statistical differences between the 2 groups in terms of postoperative 30-day and 1-year mortality. Although patients who underwent VATS had higher postoperative complication (53.0% vs 24.1%) and reoperation (37.9% vs 15.5%) rates than those who underwent thoracotomy, the complications were not serious and most could be treated with reoperation and intensive care. CONCLUSIONS: The outcome of DNM treatment does not depend on thoracotomy or VATS.

Uniportal left S1 + 2 segmentectomy.

The left upper lobe is one of the largest lobes of the lung; left upper segmentectomy is well established among thoracic surgeons. In uniportal left S1 + 2 segmentectomy, dissection of the vasculature, bronchus, and intersegmental plane can be performed anteriorly. Given that the fissureless technique is commonly used in uniportal video-assisted thoracoscopic surgery, S1 + 2 segmentectomy exhibits high affinity with the unidirectional approach. We have frequently performed left S1 + 2 segmentectomy for early non-small cell lung cancer located in the apical segment, since this procedure has the potential to preserve pulmonary function over tri-segmentectomy. Herein, we introduce our approach to uniportal left S1 + 2 segmentectomy as a minimally invasive alternative for preserving lung function.

Comparable efficacy and safety of COVID-19 vaccines for patients receiving tegafur-uracil as postoperative adjuvant chemotherapy.

PURPOSE: Many effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed, but a weaker response in individuals undergoing anticancer treatment has been reported. This study evaluates the immunogenic status and safety of SARS-CoV-2 vaccines for patients with non-small-cell lung cancer (NSCLC), receiving tegafur-uracil (UFT) as postoperative adjuvant chemotherapy. METHODS: The subjects of this prospective study were 40 patients who underwent surgery for NSCLC and received SARS-CoV-2 vaccines postoperatively. We compared the antibody titers of SARS-CoV-2 vaccines and the adverse events between patients who received adjuvant UFT and patients who did not. RESULTS: The mean anti-S1 IgG titers were not significantly different between the UFT and without-UFT groups (mean optimal density, 0.194 vs. 0.205; P = 0.76). Multivariate analysis identified the period after the second vaccination as an independent predictor of anti-S1 IgG titer (P = 0.049), but not the UFT status (with or without-UFT treatment; P = 0.47). The prevalence of adverse events did not differ significantly between the groups, and no severe adverse events occurred. CONCLUSIONS: The efficacy and safety of the SARS-CoV-2 vaccines for NSCLC patients who received postoperative adjuvant UFT chemotherapy were comparable to those for NSCLC patients who did not receive postoperative adjuvant UFT chemotherapy. CLINICAL TRIAL REGISTRATION: This study was registered with the University Hospital Medical Information Network (UMIN) in Japan (UMIN000047380).

Intraoperative rapid immunohistochemistry with noncontact antibody mixing for undiagnosed pulmonary tumors.

Knowledge of the histologic type and primary origin of pulmonary tumors is essential when preparing a surgical strategy. Intraoperative diagnosis of hematoxylin and eosin (H&E)-stained frozen sections is the gold standard, but reliable pathology requires time-consuming immunohistochemistry (IHC) to distinguish among histological types/organ origins and to analyze molecular status. The aim of this study was to evaluate the clinical reliability of a new rapid-IHC technique for intraoperative diagnosis of pulmonary tumors. In total, 169 patients with undiagnosed pulmonary tumors were enrolled in a multicenter prospective observational study. At three institutes, pulmonary tumor samples were collected through core needle biopsy and/or surgery to determine surgical strategies. Using a new device for rapid IHC, we applied a high-voltage, low-frequency alternating current (AC) field, which mixes the available antibody as the voltage is switched on/off. Rapid IHC can provide tumor histologic type/origin diagnoses within 20 min, as opposed to the 3-6 h required for conventional IHC. No false diagnoses of malignancy were rendered in any of the cases when using simple H&E staining. With H&E staining alone, the overall definitive diagnosis rate, the rate of defined tumor origin, and the rate of determined histological type were 76.92%, 85.80%, and 90.53%, respectively. When rapid IHC was added, those rates were significantly improved to 88.76%, 94.67%, and 91.72%, respectively. By providing prompt and accurate intraoperative histological/molecular analysis, rapid IHC driven by AC mixing could serve as an effective clinical tool guiding the surgical strategy for undiagnosed pulmonary tumors.

Effect of myasthenia gravis on the surgical outcomes of patients with thymoma.

BACKGROUND: Myasthenia gravis (MG) is the most common paraneoplastic syndrome in thymoma. However, the association between MG and postoperative outcomes is controversial. Therefore, we examined the effect of MG on the surgical outcomes of patients with thymoma. METHODS: This study enrolled 145 consecutive patients with thymoma who underwent surgical resection at our institution between January 2000 and December 2020. The patients were classified into thymoma with MG (MG group) and without MG (non-MG group). Data about characteristics of patients, surgical outcomes, and prognostic factors were compared between the two groups. RESULTS: Of 145 patients, 47 (32%) presented with MG and 98 (68%) did not. There was no significant difference in terms of the incidence of postoperative complications, overall survival (OS), and recurrence-free survival (RFS) between the two groups. The deaths were not caused by thymoma. Among the patients aged >60 years, the MG group had a lower survival rate than the non-MG group. In the univariate analysis, age ≥60 years was a poor prognostic factor for OS, whereas in the multivariate analysis, Masaoka stage III and IV classifications were poor prognostic factors for RFS. CONCLUSION: The incidence of postoperative complications did not differ between patients with thymoma and without MG. In the MG group, age ≥60 years was a poor prognostic factor for OS. The postoperative follow-up of patients aged ≥60 years with thymoma with MG should focus on not only recurrence but also progression of diseases other than thymoma.

ROS1-Rearranged Lung Cancer Successfully Resected after Response to Crizotinib: A Case Report.

The usefulness of molecularly targeted therapy as a preoperative therapy for the c-ros oncogene 1 receptor tyrosine kinase (ROS1)-rearranged lung cancer has not been established. We present the case of ROS1- rearranged lung cancer successfully resected after response to crizotinib. The patient was a 71-year-old woman with prolonged cough. She was diagnosed with ROS1-rearranged lung adenocarcinoma (cT4N2M0, stage IIIB). After eight weeks of crizotinib treatment, right upper lobectomy with chest wall resection, angioplasty, and bronchoplasty were performed. The postoperative course was good, and the patient survived for 41 months after the surgery without recurrence. Surgical resection after molecularly targeted therapy for ROS1-positive lung cancer may lead to good local control.

Prognostic value of preoperative plasma fibrinogen levels in resected stage I non-small cell lung cancer.

BACKGROUND: The number of surgical procedures has increased among patients with early-stage lung cancer. If the poor prognostic factors for stage I non-small cell lung cancer (NSCLC) can be simply validated preoperatively, appropriate treatment will be provided. The current study aimed to evaluate the prognostic value of preoperative plasma fibrinogen levels in patients with resected stage I NSCLC. METHODS: We retrospectively analyzed the clinicopathological information of patients (n = 149) who underwent lobectomy for stage I NSCLC between May 2014 and July 2016. Data about peripheral blood analysis, histopathological finding, and follow-up assessment results were collected from the databases. Patients were divided into the low and high fibrinogen groups. Univariate and multivariate analyses were performed to evaluate the predictors of recurrence and survival. RESULTS: Compared with the low fibrinogen group (<377 mg/dl), the high fibrinogen group (≥377 mg/dl) had a significantly greater number of male participants (p = 0.04), smokers (p < 0.001), and those with elevated cytokeratin antigen levels (p = 0.04), lymphatic invasion (p = 0.007), and squamous cell carcinoma (p < 0.001). Plasma fibrinogen level was considered a significant independent factor for recurrence and overall survival on both the univariate and multivariate analyses (p < 0.001 and p = 0.010) and the multivariate analysis alone (p = 0.020 and p < 0.012). CONCLUSION: Preoperative plasma fibrinogen level might be a useful predictor of recurrence and survival in patients with stage I NSCLC. The treatment strategy for patients with high fibrinogen levels could be cautiously considered preoperatively.

Annexin A10 Expression as a Novel Prognostic Marker in Lung Adenocarcinoma.

BACKGROUND/AIM: Annexin A10 (ANXA10) is a member of the annexin family and a calcium-dependent phospholipid-binding protein. The aim of this study was to clarify the clinical significance of ANXA10 expression in lung adenocarcinoma. MATERIALS AND METHODS: ANXA10 expression was immunohistochemically examined in surgical specimens of lung adenocarcinoma obtained from 74 consecutive patients who underwent complete resection from January 2014 to December 2014. Expression of ANXA10 was down-regulated in A549 cells via siRNA transfection and the effect of ANXA10 on cell migration was assessed by the wound healing assay. Expression of ANXA10 was examined by immunocytochemistry and polymerase chain reaction. RESULTS: High ANXA10 expression was significantly correlated with poor overall survival (p=0.00705). Multivariate analysis with the Cox proportional hazard model demonstrated that ANXA10 expression was an independent prognostic factor. Cell migration was suppressed in ANXA10-down-regulated A549 cell lines. CONCLUSION: ANXA10 has a role in cancer cell migration and high ANXA10 expression is a novel prognostic marker in lung adenocarcinoma.

The Gut Microbiome as a Biomarker of Cancer Progression Among Female Never-smokers With Lung Adenocarcinoma.

BACKGROUND/AIM: The gut microbiome plays an important role in the immune system and has attracted attention as a biomarker of several diseases, including cancer. In this study, we examined the relationship between the gut microbiome and lung cancer progression. PATIENTS AND METHODS: Female never-smokers diagnosed with lung adenocarcinoma were consecutively enrolled between May 2018 and August 2019, and fecal samples were collected. Principal coordinate analyses were performed using Bray-Curtis distance matrices to investigate the effects of clinical variables (age, body mass index, Tumor-Node-Metastasis stage, T category, N category, M category, primary tumor size, performance status, and EGFR mutation status) on the gut microbial community. RESULTS: A total of 37 patients were enrolled. T category and primary tumor size were significantly correlated with the gut microbial community (p=0.018 and 0.041, respectively). CONCLUSION: This study identified the gut microbiome as a promising biomarker of lung cancer progression.

Safety and immunogenicity of the COVID-19 vaccine BNT162b2 in patients undergoing chemotherapy for solid cancer.

BACKGROUND: Although COVID-19 severity in cancer patients is high, the safety and immunogenicity of the BNT162b2 mRNA COVID-19 vaccine in patients undergoing chemotherapy for solid cancers in Japan have not been reported. METHODS: We investigated the safety and immunogenicity of BNT162b2 in 41 patients undergoing chemotherapy for solid cancers and in healthy volunteers who received 2 doses of BNT162b2. We evaluated serum IgG antibody titers for S1 protein by ELISA at pre-vaccination, prior to the second dose and 14 days after the second vaccination in 24 cancer patients undergoing cytotoxic chemotherapy (CC group), 17 cancer patients undergoing immune checkpoint inhibitor therapy (ICI group) and 12 age-matched healthy volunteers (HV group). Additionally, inflammatory cytokine levels were compared between the HV and ICI groups at pre and the next day of each vaccination. RESULTS: Anti-S1 antibody levels were significantly lower in the ICI and CC groups than in the HV group after the second dose (median optimal density: 0.241 [0.063-1.205] and 0.161 [0.07-0.857] vs 0.644 [0.259-1.498], p = 0.0024 and p < 0.0001, respectively). Adverse effect profile did not differ among the three groups, and no serious adverse event occurred. There were no differences in vaccine-induced inflammatory cytokines between the HV and ICI groups. CONCLUSION: Although there were no significant differences in adverse events in three groups, antibody titers were significantly lower in the ICI and CC groups than in the HV group. Further protection strategies should be considered in cancer patients undergoing CC or ICI.