Candidate tumor-specific CD8+ T cell subsets identified in the malignant pleural effusion of advanced lung cancer patients by single-cell analysis.

Isolation of tumor-specific T cells and their antigen receptors (TCRs) from malignant pleural effusions (MPE) may facilitate the development of TCR-transduced adoptive cellular immunotherapy products for advanced lung cancer patients. However, the characteristics and markers of tumor-specific T-cells in MPE are largely undefined. To this end, to establish the phenotypes and antigen specificities of CD8+ T cells, we performed single-cell RNA and TCR sequencing of samples from three advanced lung cancer patients. Dimensionality reduction on a total of 4,983 CD8+ T cells revealed 10 clusters including naïve, memory, and exhausted phenotypes. We focused particularly on exhausted T cell clusters and tested their TCR reactivity against neoantigens predicted from autologous cancer cell lines. Four different TCRs specific for the same neoantigen and one orphan TCR specific for the autologous cell line were identified from one of the patients. Differential gene expression analysis in tumor-specific T cells relative to the other T cells identified CXCL13, as a candidate gene expressed by tumor-specific T cells. In addition to expressing CXCL13, tumor-specific T cells were present in a higher proportion of T cells co-expressing PDCD1(PD-1)/TNFRSF9(4-1BB). Furthermore, flow cytometric analyses in advanced lung cancer patients with MPE documented that those with high PD-1/4-1BB expression have a better prognosis in the subset of 57 adenocarcinoma patients (p = .039). These data suggest that PD-1/4-1BB co-expression might identify tumor-specific CD8+ T cells in MPE, which are associated with patients' prognosis. (233 words).

Novel gene fusions in human oropharyngeal carcinoma.

Few reports have analyzed the fusion genes involved in carcinogenesis in the oropharynx, where the incidence of human papillomavirus-associated tumors is relatively low. The aim of this study was to identify novel driver fusion genes in patients with oropharyngeal cancer. The study enrolled fifty-seven patients who were diagnosed with oropharyngeal carcinoma. RNA sequencing data from fresh-frozen specimens were used to identify candidate fusion genes via the JAFFA, arriba, and STAR-Fusion pipelines. Candidate fusion genes were confirmed by direct sequencing. The expression level of a candidate fusion gene was compared to that of tumors without fusion genes. Finally, filtering was performed for driver genes using the annoFuse pipeline. In addition, the VIRTUS pipeline was used to analyze the presence of human papillomavirus in the tumors. We identified 5 (8.8 %) novel potential driver in-frame fusion genes, MKNK2::MOB3A, ICMT::RPS6KA3, ATP1B3::GRK7, CSNK2A1::KIF16B, and FGFR3::MAEA, and 1 (1.8 %) known in-frame fusion gene, FGFR3::TACC3, in 57 patients with pharyngeal carcinoma. Our results suggest that sporadic fusion genes may contribute to tumorigenesis in oropharyngeal carcinomas.

The incidence of drug-induced interstitial lung disease caused by epidermal growth factor receptor tyrosine kinase inhibitors or immune checkpoint inhibitors in patients with non-small cell lung cancer in presence and absence of vascular endothelial growth factor inhibitors: a systematic review.

Interstitial lung disease (ILD) or pneumonitis caused by epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) or immune checkpoint inhibitors (ICI) is a major concern in the treatment of non-small cell lung cancer (NSCLC). Whether the addition of vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors can reduce the incidence of drug-induced ILD remains unclear. We conducted a systematic review to assess the incidence of ILD induced by EGFR-TKIs or ICIs in the presence or absence of VEGF/VEGFR inhibitors in relevant randomized trials between January 2009 and October 2023. The primary outcome was the odds ratio for the incidence of ILD in all patients worldwide and Asians. Secondary outcomes were the odds ratios (ORs) of the incidence at grade-3 or higher ILD in all patients worldwide and Asians. We identified 13 randomized studies, one sub-analysis in the EGFR-TKI group, and three randomized studies in the ICI group. In the EGFR-TKI group, the OR of ILD incidence at any grade with VEGF/VEGFR inhibitors was 0.54 (95% CI, 0.32-0.90; p = 0.02), which represented a significantly lower incidence than that without VEGF/VEGFR inhibitors. Contrarily, the OR of ILD incidence at grade ≥ 3 with VEGF/VEGFR inhibitors was 1.00 (95% CI, 0.43-2.36; p = 0.99). In all subjects in the ICI group, the OR of ILD incidence at any grade with VEGF/VEGFR inhibitors was 0.78 (95% CI, 0.51-1.21; p = 0.27). The systematic review demonstrated that the addition of VEGF/VEGFR inhibitors could reduce the incidence of drug-induced ILD at any grade caused by EGFR-TKI in patients with NSCLC but could not reduce that at grade ≥ 3. The ILD induced by ICIs remains undetermined owing to the limited number of randomized trials for which ILD data are available. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=409534, identifier CRD42023409534.

Atezolizumab and nintedanib in patients with non-small cell lung cancer and interstitial lung disease.

In patients with non-small cell lung cancer (NSCLC), pre-existing interstitial lung disease (ILD) is a risk factor for the development of pneumonitis induced by immune checkpoint inhibitors (ICIs). Anti-fibrotic agents, including nintedanib, reduce the potential for acute exacerbation of idiopathic pulmonary fibrosis (IPF). However, whether nintedanib can reduce the potential for ICI-induced pneumonitis is unknown. From among 140 patients with NSCLC treated with atezolizumab monotherapy at our institution, we retrospectively investigated 4 patients with pre-existing ILD treated concurrently with nintedanib. On computed tomography (CT), a usual interstitial pneumonia (UIP) pattern was present in one patient, probable UIP pattern in one patient, and indeterminate for UIP pattern in two patients. Of those four patients with pre-existing ILD, two achieved a partial response to ICI treatment, with response durations of 8.1 and 7.6 months. The other two patients experienced progressive disease. Notable adverse events included the development of non-symptomatic grade 1 pneumonitis in the patient with a probable UIP pattern and grade 3 lower gastrointestinal hemorrhage in another patient. None of the patients experienced a worsening of respiratory symptoms. In patients with NSCLC and pre-existing ILD, nintedanib might reduce the potential for ICI-induced pneumonitis and enhance the antitumor effect.

Unrealistic expectations and disclosure of incurability in patients with non-small cell lung cancer.

PURPOSE: Determining whether patients' unrealistic expectations of chemotherapy as a cure were associated with their perception of the disclosure of incurability. METHODS: This prospective study included consecutive patients with pretreated non-small cell lung cancer from four study sites. Patients and their oncologists were asked whether they perceived the disclosure of cancer incurability. Patients were also asked if they thought that chemotherapy was curative. We followed up on whether the deceased patients received specialized palliative care 14 months after their last enrollment. Multiple regression analyses were conducted to examine the association between the expectation of chemotherapy as a cure and patient/oncologist-reported perceptions of the disclosure of incurability. RESULTS: We analyzed 200 patients, 77 (38.5%) of whom had unrealistic expectations of a cure. Based on patients' perceptions, incurability was disclosed to 138 (69.0%) patients, and based on their oncologists' perceptions, incurability was disclosed to 185 (92.5%) patients (patient/oncologist agreements, κ = 0.19). Patients without a perception of the oncologist's disclosure of incurability-regardless of their oncologist's perception-were more likely to have unrealistic expectations of a cure than patients for whom both patient and oncologist perceptions were present. Patients who had unrealistic expectations of chemotherapy as a cure were shown to be significantly less likely to have received specialized palliative care, after adjusting for covariates (adjusted OR, 0.45; 95% CI, 0.23-0.91; p = .027). CONCLUSION: Oncologists' disclosure of incurability was not fully recognized by patients, and expectations of chemotherapy as a cure were associated with patients' perception of the disclosure of incurability.

Genomic landscape of glioblastoma without IDH somatic mutation in 42 cases: a comprehensive analysis using RNA sequencing data.

PURPOSE: Glioblastoma is a malignant brain tumor with a poor prognosis. Genetic mutations associated with this disease are complex are not fully understood and require further elucidation for the development of new treatments. The purpose of this study was to comprehensively analyze genetic mutations in glioblastomas and evaluate the usefulness of RNA sequencing. PATIENTS AND METHODS: We analyzed 42 glioblastoma specimens that were resected in routine clinical practice and found wild-type variants of the IDH1 and IDH2 genes. RNA was extracted from frozen specimens and sequenced, and genetic analyses were performed using the CLC Genomics Workbench. RESULTS: The most common genetic alterations in the 42 glioblastoma specimens were TP53 mutation (28.6%), EGFR splicing variant (16.7%), EGFR mutation (9.5%), and FGFR3 fusion (9.5%). Novel genetic mutations were detected in 8 patients (19%). In 12 cases (28.6%), driver gene mutations were not detected, suggesting an association with PPP1R14A overexpression. Our findings suggest the transcription factors SOX10 and NKX6-2 are potential markers in glioblastoma. CONCLUSION: RNA sequencing is a promising approach for genotyping glioblastomas because it provides comprehensive information on gene expression and is relatively cost-effective.

Elements of End-of-Life Discussions Associated With Patients' Reported Outcomes and Actual End-of-Life Care in Patients With Pretreated Lung Cancer.

BACKGROUND: End-of-life discussions for patients with advanced cancer are internationally recommended to ensure consistency of end-of-life care with patients' values. This study examined the elements of end-of-life discussions associated with end-of-life care. MATERIALS AND METHODS: We performed a prospective observational study among consecutive patients with pretreated non-small cell lung cancer after the failure of first-line chemotherapy. We asked oncologists whether they had ever discussed "prognosis," "do not attempt resuscitation," "hospice," and "preferred place of death" with a patient at baseline. The quality of life (QOL) and depressive symptoms of patients were assessed using validated questionnaires at baseline and 3 months later. The end-of-life care that patients received was investigated using medical records. Oncologists' compassion and caregivers' preferences for hospice care were also assessed using questionnaires. Multiple regression analyses were conducted to examine the association between elements of end-of-life discussions and patient-reported outcomes as well as actual end-of-life care. RESULTS: We obtained 200 valid responses at baseline, 147 valid responses 3 months later, and 145 data points for medical care at the end-of-life stage. No element of the end-of-life discussion between the patient and their oncologist was significantly associated with patients' reported outcomes or actual end-of-life care. In addition, oncologists' compassion was significantly associated with improvement in both comprehensive QOL and depressive symptoms, and caregivers' preferences for hospice care and high educational level were significantly associated with hospice death. CONCLUSION: Oncologist-patient alliances and caregivers' involvement in end-of-life discussions may be influential in achieving optimal end-of-life care.

Current diagnosis and treatment of salivary gland-type tumors of the lung.

Salivary gland-type tumors of the lung are thought to originate from the submucosal exocrine glands of the large airways. Due to their rare occurrence, reports of their study are limited to small-scale or case reports. Therefore, daily clinical practices often require a search for previous reports. In the last 20 years, several genetic rearrangements have been identified, such as MYB::NF1B rearrangements in adenoid cystic carcinoma, CRTC1::MAML2 rearrangements in mucoepidermoid carcinoma, EWSR1::ATF1 rearrangements in hyalinizing clear cell carcinoma and rearrangements of the EWSR1 locus or FUS (TLS) locus in myoepithelioma and myoepithelial carcinoma. These molecular alterations have been useful in diagnosing these tumors, although they have not yet been linked to molecularly targeted therapies. The morphologic, immunophenotypic, and molecular characteristics of these tumors are similar to those of their counterparts of extrapulmonary origin, so clinical and radiologic differential diagnosis is required to distinguish between primary and metastatic disease of other primary sites. However, these molecular alterations can be useful in differentiating them from other primary lung cancer histologic types. The management of these tumors requires broad knowledge of the latest diagnostics, surgery, radiotherapy, bronchoscopic interventions, chemotherapy, immunotherapy as well as therapeutic agents in development, including molecularly targeted agents. This review provides a comprehensive overview of the current diagnosis and treatment of pulmonary salivary gland tumors, with a focus on adenoid cystic carcinoma and mucoepidermoid carcinoma, which are the two most common subtypes.

Adjustment of creatinine clearance for carboplatin dosing in Calvert's formula and clinical efficacy for lung cancer.

BACKGROUND: The Cockcroft-Gault formula is commonly used as a substitute for glomerular filtration rate (GFR) in Calvert's formula for carboplatin dosing, where adjusting serum creatinine measured using the enzymatic method with 0.2 mg/dL has been suggested in Japan. However, the effects of these adjustments on efficacy in patients with non-small-cell lung cancer remain unknown. METHODS: We conducted a post hoc analysis of the PREDICT1 study (CJLSG1201), a multicenter prospective observational trial of carboplatin-pemetrexed. Glomerular filtration rate values in Calvert's formula were back-calculated from the administered dosages of carboplatin and the reported value of the target area under the curve. We estimated the serum creatinine adjustments and divided the patients into crude and adjusted groups. RESULTS: Patients in the crude group (N = 169) demonstrated similar efficacy to those in the adjusted group (N = 104) in progression-free survival (PFS) and overall survival (OS) (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.76-1.35; p = 0.916 vs. HR, 0.87; 95% CI, 0.65-1.17; p = 0.363), with higher grade 3-4 hematologic toxicity. Among patients aged ≥75 years, the crude group (N = 47) showed superior efficacy compared with the adjusted group (N = 17) in PFS and OS (HR, 0.37; 95% CI, 0.20-0.69; p = 0.002 vs. HR, 0.43; 95% CI, 0.23-0.82; p = 0.010). CONCLUSIONS: Serum creatinine adjustment may be associated with similar efficacy compared to the crude serum creatinine value. In older patients, the adjustment should be cautiously applied owing to the potential for reduced efficacy.

Prognostic Awareness and Discussions of Incurability in Patients with Pretreated Non-Small Cell Lung Cancer and Caregivers: A Prospective Cohort Study.

BACKGROUND: Although patients with advanced cancer often have poor prognostic awareness, the most effective communication approach for improving prognostic awareness is unclear. In addition, the association between prognostic awareness and preferences for future medical treatment remains unexplored. MATERIALS AND METHODS: We performed a prospective observational study of consecutive patients with advanced or post-operative recurrent non-small cell lung cancer whose disease had progressed after first-line chemotherapy, and their caregivers. We evaluated patterns of clinical discussions about incurability, prognostic awareness, and preference for future medical treatment at baseline and 3 months later. RESULTS: We obtained 200 valid responses to the questionnaires at baseline and 147 valid responses 3 months later. In addition, 180 caregivers returned valid responses. A total of 54% of patients and 51% of caregivers had accurate awareness at baseline, and 52% of patients had accurate awareness 3 months later. Multiple logistic regression analysis revealed that patients who were informed about incurability in recent and past discussions were significantly more likely to have accurate awareness 3 months later, compared with those who were only informed recently (adjusted odds ratio 5.08; 95% CI, 1.31-19.78; P = .019). Accurate awareness at 3 months was significantly negatively associated with preference for life-prolonging treatment at 3 months after adjusting for covariates (adjusted odds ratio 0.39; 95% CI, 0.17-0.90; P = .028). CONCLUSION: Patients with advanced cancer who had both recent and past discussions about incurability with their oncologists have more accurate prognostic awareness. Improving prognostic awareness could reduce the preference for life-prolonging treatment.

Sensitivity to dabrafenib and trametinib treatments in patients with non-small-cell cancer harboring BRAF compound mutations: A pooled analysis of BRAF p.V600E-positive advanced non-small-cell lung cancer.

PURPOSE: The present study clarified the sensitivity of the BRAF tyrosine kinase inhibitor mechanism in patients with BRAF compound mutation and predicted the sensitivity using molecular dynamics simulation. METHODS: We examined 16 BRAF tumors with p.V600E-positive non-small-cell lung cancer. RESULTS: One patient (6.2%) had a BRAF p.V600E and p.K601_W604 compound mutation with a good clinical response to dabrafenib and trametinib. Molecular dynamics simulation also complemented the effect. CONCLUSIONS: The combination of a genetic analysis and computational simulation model may help predict the sensitivity for dabrafenib in cases with a rare BRAF compound mutation. The construction of a genomic and simulation fused database is important for the development of personalized medicine in this field.

Successful IMRT and concurrent chemotherapy for a patient with intrathoracic extensive-stage small cell lung cancer.

Treatment of extensive-stage (ES) small cell lung cancer (SCLC) is a challenge with poor local control and dismal overall survival. Although single extrathoracic metastasis was defined as M1b according to the eighth edition of the tumour-node-metastasis (TNM) classification of lung cancer, M1b includes involvement of a single intrathoracic nonregional lymph node (LN) such as pericardial, internal mammary or paravertebral LNs. Here, we report a successful treated case of a 50-year-old female with ES-SCLC with right pericardial LN involvement, cT1cN3M1b (LYM). She initially received two cycles of induction chemotherapy consisting of cis-Diamminedichloroplatinum/cisplatin (CDDP) and etoposide and achieved a very good partial response. She then received curative chemoradiotherapy with intensity-modulated techniques (45 Gy in 30 fractions BID), followed by an additional cycle of chemotherapy. She is free of recurrence for more than 2.5 years.

Risk factors for pneumonitis in patients with non-small cell lung cancer treated with immune checkpoint inhibitors plus chemotherapy: A retrospective analysis.

BACKGROUND: Immune checkpoint inhibitor (ICI) therapy plus chemotherapy has become a standard of care for patients with advanced non-small cell lung cancer (NSCLC). Pre-existing interstitial lung disease (ILD) is a risk factor for drug-induced pneumonitis caused by chemotherapy or ICI monotherapy. However, clinical data in patients with pre-existing ILD who received ICI therapy plus chemotherapy are limited. This study aimed to identify the risk factors for drug-induced pneumonitis in patients with NSCLC treated with ICIs plus chemotherapy. METHODS: We retrospectively reviewed the medical records of 160 consecutive patients who were diagnosed with NSCLC and treated with ICIs plus chemotherapy at Aichi Cancer Center Hospital between December 2018 and November 2020. Patients with a prior history of ICI treatment or thoracic radiotherapy were excluded from the analysis. RESULTS: Among 125 patients, pre-existing ILD was observed in 20 patients (16.0%). Drug-induced pneumonitis developed in 17 patients (13.6%), with a median time to onset of 19.3 weeks (range, 1.6-108.9 weeks). In multivariate logistic analysis, pre-existing ILD (odds ratio = 19.07, p = 0.0001) and PEM exposure (odds ratio = 5.67, p = 0.022) were identified as risk factors for the development of drug-induced pneumonitis. CONCLUSIONS: Pre-existing ILD and pemetrexed exposure are risk factors for drug-induced pneumonitis in patients with NSCLC.

Emerging therapies for non-small cell lung cancer harboring EGFR exon 20 insertion mutations: narrative review.

Background and Objective: Epidermal growth factor receptor (EGFR) exon 20 insertion mutations (ex20ins) are uncommon in non-small cell lung cancer (NSCLC). These mutations are generally resistant to first-generation EGFR tyrosine kinase inhibitors, unlike common EGFR mutations, including exon 19 deletions or exon 21 L858R point mutation. The development of effective targeted therapies for NSCLC harboring EGFR ex20ins has been eagerly anticipated over the years. Recently, the therapeutic landscape of this subgroup of EGFR-mutant NSCLC patients has rapidly evolved due to the emergence of new drugs. In 2021, several novel agents, such as amivantamab and mobocertinib, have been approved by the US Food and Drug Administration for patients with advanced platinum-resistant NSCLC harboring EGFR ex20ins. In this review, we mainly focus on emerging therapies targeting NSCLC with EGFR ex20ins, as well as important ongoing clinical trials. Methods: Searches were conducted in PubMed and supplemented with recent conference proceedings in November 30th, 2021. Key Content and Findings: Several novel emerging therapies showed favorable safety profile and promising anti-tumor activity in NSCLC patients with EGFR ex20ins in recent several clinical trials. Conclusions: There is still room for improvement in the treatment results of NSCLC harboring EGFR ex20ins. Future research should focus on the molecular heterogeneity in the size and location of distinct EGFR ex20ins, the mechanisms of acquired resistance to novel EGFR inhibitors, effective treatment that have good central nervous system penetrance, and the potential role of combination strategy.

Pre-existing interstitial lung disease is associated with onset of nivolumab-induced pneumonitis in patients with solid tumors: a retrospective analysis.

BACKGROUND: Nivolumab, an anti-programmed death 1 (PD-1) monoclonal antibody, has shown survival benefit in clinical trials of various malignant tumors. Nivolumab-induced pneumonitis is major immune-related adverse event (irAE) that is occasionally serious and life-threatening. The aim of this study was to examine the association between pre-existing interstitial lung disease (ILD) on chest computed tomography (CT) and nivolumab-induced pneumonitis among different types of solid tumors. METHODS: We retrospectively collected the clinical data of 311 patients who were diagnosed with non-small cell lung cancer (NSCLC), head and neck cancer (HNC), or gastric cancer (GC), and treated with nivolumab monotherapy. Patients who underwent chest CT immediately before starting nivolumab without previous thoracic radiotherapy or other immune checkpoint inhibitors were eligible. We collected baseline patient characteristics and assessed pre-existing ILD on baseline chest CT. RESULTS: Finally, 188 patients were included in the analysis: 96 patients with NSCLC, 43 patients with HNC, and 49 patients with GC. NSCLC patients had a significantly higher rate of pre-existing ILD compared with HNC/GC patients (P = 0.047). Nivolumab-induced pneumonitis occurred in 11.7% (22 of 188), including 14.6% (14 of 96) of NSCLC, and 8.7% (8 of 92) of HNC/GC. Univariate and multivariate logistic regression analyses revealed that pre-existing ILD (odds ratio, 5.92; 95% confidence interval (CI), 2.07-18.54, P = 0.0008) and male sex (odds ratio, 5.58; 95% CI, 1.01-104.40, P = 0.049) significantly increased the risk of nivolumab-induced pneumonitis. CONCLUSION: Our results indicated that pre-existing ILD and male sex are risk factors for nivolumab-induced pneumonitis in solid tumors.

Drug-Induced Liver Injury in a Patient with Nonsmall Cell Lung Cancer after the Self-Administration of Fenbendazole Based on Social Media Information.

Fenbendazole is a benzimidazole anthelmintic agent, with a broad antiparasitic range in animals such as dogs and pigs. The agent is also reported to exert antitumor effects and inhibit microtubule-associated tubulin polymerization, but its safety and tolerability profile in humans remains unclear. An 80-year-old female patient with advanced nonsmall cell lung cancer (NSCLC) was started on pembrolizumab monotherapy. The patient experienced severe liver injury 9 months later. An interview with her and her family revealed that she had been taking fenbendazole for a month, solely based on social media reports suggesting its effectiveness against cancer. After discontinuation of the self-administration of fenbendazole, the patient's liver dysfunction spontaneously resolved. The antitumor inhibitory effects of fenbendazole have been reported; however, she did not experience tumor shrinkage. This is the first case report of a patient with advanced NSCLC who self-administered the anthelmintic, fenbendazole. Twitter and Facebook are online social media platforms which have been constructively used to exchange information among cancer patients. However, sources of medical information on these platforms are often unproven, and it is difficult for nonmedical professionals to accurately select and filter complex medical information. Physicians should enquire patients about self-administration of orally ingested products, including dietary supplements, herbs, or bioactive compounds, in cases of unexpected adverse reactions.

Successful bronchial arterial infusion chemotherapy combined with radiotherapy for an endobronchial metastasis after resection of small cell lung cancer.

Bronchial arterial infusion (BAI) chemotherapy has been reported to be an effective treatment option for centrally located early-stage squamous cell lung cancer (SCC) and has a favourable response rates for patients with stage III or IV or recurrent non-small cell lung cancer (NSCLC) without distant metastases who cannot tolerate standard chemotherapy. Here, we report a case of an 83-year-old male with a solitary polypoid endobronchial metastatic tumour in the left main bronchus one year and 10 months after video-assisted thoracoscopic surgery (VATS) combined segmentectomy (left S6 + S8a) for small cell lung cancer (SCLC), pT1bN0. He was treated with BAI of 100 mg of cis-Diamminedichloroplatinum/cisplatin (CDDP), followed by thoracic radiotherapy (56 Gy in 28 fractions). There was no recurrence for 2.5 years. BAI chemotherapy combined with radiotherapy seemed to be an effective salvage option for the treatment of solitary endobronchial metastases of SCLC in patients unfit for standard chemoradiotherapy.

Weak-evidence Fusion Candidates Detected by a FusionPlex Assay Using the Ion Torrent System.

BACKGROUND/AIM: The Archer FusionPlex platform is widely used for comprehensive fusion-gene detection in cancer tissues. This platform separately displays results for strong-evidence and weak-evidence fusion candidates (WEFCs). Distinctive fusion patterns are frequently found in the weak-evidence category and information about the patterns is clinically essential. PATIENTS AND METHODS: We describe the type and frequency of WEFCs observed using the FusionPlex Sarcoma Panel (S Panel) and the FusionPlex ALK, RET, and ROS1 ver2 Panel (ARR Panel). RESULTS: A total of 97 specimens were examined and 620 candidates were detected and categorized as WEFCs. A median of five WEFCs were detected per sample. In the S Panel group, there were 13 WEFCs with a frequency of more than 1%. In the ARR Panel group, a total of 16 WEFCs were detected with a frequency of more than 1%. CONCLUSION: Specific WEFCs were detected according to the panel selected.

Life-threatening massive bleeding in the pulmonary trunk adjacent to the right ventricular outflow tract during the resection of a large mediastinal germ cell tumor: proposed safety measures in the absence of cardiovascular surgeons: a case report.

This report presents an unusual case of life-threatening massive bleeding in the pulmonary trunk adjacent to the right ventricular outflow tract during resection of a large primary mediastinal nonseminomatous germ cell tumor (PMNSGCT) in the absence of cardiovascular surgeons. The patient was a 21-year-old male whose large mediastinal tumor was diagnosed as an extragonadal PMNSGCT, which was a mixture of a yolk sac tumor and an immature teratoma. Generally, chemotherapy causes extensive peripheral tumor necrosis of PMNSGCTs, thus enabling their complete resection. In this case, surgeons considered the resection as possible by dissecting the peripheral necrotic tissue, and cardiovascular surgeons were thus not consulted. Enlarged modified left hemi-clamshell thoracotomy (HCST) was applied. While dissecting around the pulmonary trunk, the assistant-held forceps accidentally touched the tensed pulmonary trunk, which caused bleeding. We immediately contacted the collaborating cardiac surgery department at another hospital for assistance. Meanwhile, massive bleeding occurred, leading to hemorrhagic shock, and thus direct cardiac massage was required. Our team managed to establish a venoarterial (VA) extracorporeal membrane oxygenation (ECMO). After the arrival of cardiac surgeons, a suction circuit was added, and bleeding was stopped using sutures. Finally, complete resection of the tumor was achieved, and the patient awoke the following day without any brain dysfunction. After discussions with all the members involved in the surgery, we developed an in-hospital consensus on how to perform surgeries for large thoracic tumors safely at our cancer center without the cardiovascular surgery department. We herein present the case and consensus and discuss the relevant issues.