Mechanism of ERBB2 gene overexpression by the formation of super-enhancer with genomic structural abnormalities in lung adenocarcinoma without clinically actionable genetic alterations.

BACKGROUND: In an extensive genomic analysis of lung adenocarcinomas (LUADs), driver mutations have been recognized as potential targets for molecular therapy. However, there remain cases where target genes are not identified. Super-enhancers and structural variants are frequently identified in several hundred loci per case. Despite this, most cancer research has approached the analysis of these data sets separately, without merging and comparing the data, and there are no examples of integrated analysis in LUAD. METHODS: We performed an integrated analysis of super-enhancers and structural variants in a cohort of 174 LUAD cases that lacked clinically actionable genetic alterations. To achieve this, we conducted both WGS and H3K27Ac ChIP-seq analyses using samples with driver gene mutations and those without, allowing for a comprehensive investigation of the potential roles of super-enhancer in LUAD cases. RESULTS: We demonstrate that most genes situated in these overlapped regions were associated with known and previously unknown driver genes and aberrant expression resulting from the formation of super-enhancers accompanied by genomic structural abnormalities. Hi-C and long-read sequencing data further corroborated this insight. When we employed CRISPR-Cas9 to induce structural abnormalities that mimicked cases with outlier ERBB2 gene expression, we observed an elevation in ERBB2 expression. These abnormalities are associated with a higher risk of recurrence after surgery, irrespective of the presence or absence of driver mutations. CONCLUSIONS: Our findings suggest that aberrant gene expression linked to structural polymorphisms can significantly impact personalized cancer treatment by facilitating the identification of driver mutations and prognostic factors, contributing to a more comprehensive understanding of LUAD pathogenesis.

Advances in cancer DNA methylation analysis with methPLIER: use of non-negative matrix factorization and knowledge-based constraints to enhance biological interpretability.

DNA methylation is an epigenetic modification that results in dynamic changes during ontogenesis and cell differentiation. DNA methylation patterns regulate gene expression and have been widely researched. While tools for DNA methylation analysis have been developed, most of them have focused on intergroup comparative analysis within a dataset; therefore, it is difficult to conduct cross-dataset studies, such as rare disease studies or cross-institutional studies. This study describes a novel method for DNA methylation analysis, namely, methPLIER, which enables interdataset comparative analyses. methPLIER combines Pathway Level Information Extractor (PLIER), which is a non-negative matrix factorization (NMF) method, with regularization by a knowledge matrix and transfer learning. methPLIER can be used to perform intersample and interdataset comparative analysis based on latent feature matrices, which are obtained via matrix factorization of large-scale data, and factor-loading matrices, which are obtained through matrix factorization of the data to be analyzed. We used methPLIER to analyze a lung cancer dataset and confirmed that the data decomposition reflected sample characteristics for recurrence-free survival. Moreover, methPLIER can analyze data obtained via different preprocessing methods, thereby reducing distributional bias among datasets due to preprocessing. Furthermore, methPLIER can be employed for comparative analyses of methylation data obtained from different platforms, thereby reducing bias in data distribution due to platform differences. methPLIER is expected to facilitate cross-sectional DNA methylation data analysis and enhance DNA methylation data resources.

BRCA1/2 reversion mutations in a pan-cancer cohort.

Tumor sensitivity to platinum (Pt)-based chemotherapy and poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors is increased by homologous recombination deficiency-causing mutations; in particular, reversion mutations cause drug resistance by restoring protein function. Treatment response is predicted by breast cancer susceptibility gene 1/2 (BRCA1/2) mutations; however, BRCA1/2 reversion mutations have not been comprehensively studied in pan-cancer cohorts. We aimed to characterize BRCA1/2 reversion mutations in a large pan-cancer cohort of Japanese patients by retrospectively analyzing sequencing data for BRCA1/2 pathogenic/likely pathogenic mutations in 3738 patients with 32 cancer types. We identified somatic mutations in tumors or circulating cell-free DNA that could restore the ORF of adverse alleles, including reversion mutations. We identified 12 (0.32%) patients with somatic BRCA1 (n = 3) and BRCA2 (n = 9) reversion mutations in breast (n = 4), ovarian/fallopian tube/peritoneal (n = 4), pancreatic (n = 2), prostate (n = 1), and gallbladder (n = 1) cancers. We identified 21 reversion events-BRCA1 (n = 3), BRCA2 (n = 18)-including eight pure deletions, one single-nucleotide variant, six multinucleotide variants, and six deletion-insertions. Seven (33.3%) reversion deletions showed a microhomology length greater than 1 bp, suggesting microhomology-mediated end-join repair. Disease course data were obtained for all patients with reversion events: four patients acquired mutations after PARP-inhibitor treatment failure, two showed somatic reversion mutations after disease progression, following Pt-based treatment, five showed mutations after both treatments, one patient with pancreatic cancer and BRCA1 reversion mutations had no history of either treatment. Although reversion mutations commonly occur in BRCA-associated cancers, our findings suggest that reversion mutations due to Pt-chemotherapy might be correlated with BRCA1/2-mediated tumorigenesis even in non-BRCA-associated histologies.

Sketch-based semantic retrieval of medical images.

The volume of medical images stored in hospitals is rapidly increasing; however, the utilization of these accumulated medical images remains limited. Existing content-based medical image retrieval (CBMIR) systems typically require example images, leading to practical limitations, such as the lack of customizable, fine-grained image retrieval, the inability to search without example images, and difficulty in retrieving rare cases. In this paper, we introduce a sketch-based medical image retrieval (SBMIR) system that enables users to find images of interest without the need for example images. The key concept is feature decomposition of medical images, which allows the entire feature of a medical image to be decomposed into and reconstructed from normal and abnormal features. Building on this concept, our SBMIR system provides an easy-to-use two-step graphical user interface: users first select a template image to specify a normal feature and then draw a semantic sketch of the disease on the template image to represent an abnormal feature. The system integrates both types of input to construct a query vector and retrieves reference images. For evaluation, ten healthcare professionals participated in a user test using two datasets. Consequently, our SBMIR system enabled users to overcome previous challenges, including image retrieval based on fine-grained image characteristics, image retrieval without example images, and image retrieval for rare cases. Our SBMIR system provides on-demand, customizable medical image retrieval, thereby expanding the utility of medical image databases.

Pathogenic Germline Variants in BRCA1/2 and p53 Identified by Real-world Comprehensive Cancer Genome Profiling Tests in Asian Patients.

Cancer genome profiling (CGP) occasionally identifies pathogenic germline variants (PGV) in cancer susceptibility genes (CSG) as secondary findings. Here, we analyzed the prevalence and clinical characteristics of PGVs based on nationwide real-world data from CGP tests in Japan. We analyzed the genomic information and clinical characteristics of 23,928 patients with solid cancers who underwent either tumor-only (n = 20,189) or paired tumor-normal (n = 3,739) sequencing CGP tests between June 2019 and December 2021 using the comprehensive national database. We assigned clinical significance for all variants and highlighted the prevalence and characteristics of PGVs. Our primary analysis of the tumor-normal sequencing cohort revealed that 152 patients (4.1%) harbored PGVs in 15 CSGs. Among 783 germline variants, 113 were annotated as PGVs, 70 as benign variants, and 600 as variants of uncertain significance. The number of PGVs identified was highest in BRCA1/2, with 56, followed by TP53, with 18. PGVs were the most prevalent in ovarian and peritoneal cancers, including among cancer types common in Asia. In the tumor-only sequencing cohort, of the 5,184 pathogenic somatic variants across 26 CSGs, 784 (15.1%) were extracted according to the European Society for Medical Oncology recommendations for germline-focused tumor analysis. The prevalence of PGVs was similar to that previously reported in Europe and the United States. This is the largest analysis based on real-world tumor-normal sequencing tests in Asia. The more widespread use of the tumor-normal sequencing CGP test could be reasonable for evaluating PGVs. SIGNIFICANCE: We analyzed real-world data from over 23,000 patients in Japan, revealing 4.1% harbored PGVs, particularly in BRCA1/2 and TP53, in CSGs. It highlights the prevalence of PGVs in Asian populations and supports the broader adoption of tumor-normal sequencing CGP tests for PGV evaluation.

Ocular toxicity of investigational anti-cancer drugs in early phase clinical trials.

Ocular toxicities arising from anti-cancer drugs occur sporadically and are sometimes underestimated because they are not life-threatening. Reports focusing on ocular toxicities from cancer therapy are limited. We investigated the detailed progress of ocular toxicities of anti-cancer drugs including first-in-class ones. A retrospective review of medical records was conducted for patients who were involved in early phase clinical trials with scheduled ophthalmologic examinations according to their protocols between January 2014 and August 2021. Patients with ocular toxicity suspected to be related to the investigational drugs in the ophthalmic examination were investigated in detail. In total, 37 ocular toxicities related to investigational drugs occurred in 7.6% of patients (33/434). The median age of the 33 patients was 61 years (range, 33-76 years), and 20 were male. Causal drugs with a high incidence of ocular toxicities were HSP90 inhibitors and FGFR inhibitors. Retinopathy was most frequent, while conjunctivitis, dry eye, keratitis, keratopathy, and uveitis were also observed. Dim vision as a subjective finding was a unique adverse event. Most patients developed ocular toxicities even though their dose was below the drug's maximum tolerated dose. Except for one case, all ocular toxicities occurred bilaterally. About 60% (22/37) of ocular toxicity cases needed a temporary hold of the drug. All except for three cases fully recovered. This study reported the risks and timing of the onset of a variety of ocular toxicities of anti-cancer drugs, which were fundamentally controllable. (Trial registration number. Retrospectively registered).

Clinical utility of comprehensive genomic profiling tests for advanced or metastatic solid tumor in clinical practice.

Previous clinical trials indicate that 10%-25% of patients received genomically matched therapy after comprehensive genomic profiling (CGP) tests. However, the clinical utility of CGP tests has not been assessed in clinical practice. We assessed the clinical utility of CGP tests for advanced or metastatic solid tumor and determined the proportion of patients receiving genomically matched therapy among those with common and non-common cancers. From August 2019 to July 2020, a total of 418 patients had undergone CGP tests, and the results were discussed through the molecular tumor board at our site. The median age of patients was 57 (range: 3-86) years. Colorectal cancer was the most common, with 47 (11%) patients. Actionable genomic alterations (median 3, range: 1-17) were identified in 368 (88.0%) of 418 patients. Druggable genomic alterations were determined in 196 (46.9%) of 418 patients through the molecular tumor board. Genomically matched therapy was administered as the subsequent line of therapy in 51 (12.2%) patients, which is comparable to the proportion we previously reported in a clinical trial (13.4%) (p = 0.6919). The proportion of patients receiving genomically matched therapy was significantly higher among those with common cancers (16.2%) than non-common cancers (9.4%) (p = 0.0365). Genomically matched therapy after the CGP tests was administered to 12.2% of patients, which is similar to the proportion reported in the previous clinical trials. The clinical utility of CGP tests in patients with common cancers greatly exceeded that in patients with non-common cancers.

Emerging PD-1/PD-L1 targeting immunotherapy in non-small cell lung cancer: Current status and future perspective in Japan, US, EU, and China.

Non-small cell lung cancer (NSCLC), one of the deadliest types of cancers worldwide, has been the target of immunotherapy due to its high immune antigenicity. With the addition of immune-checkpoint inhibitors (ICIs), including anti-PD-1/PD-L1 antibodies, as an indispensable and powerful regimen for the treatment of this lethal disease, the median survival time for patients with stage IV NSCLC is approximately 2 years. In contrast, the response rate to ICIs remains less than 50%, even if the patients are selected using biomarkers such as PD-L1. Pharmaceutical companies have begun to develop additional anti-PD-1/PD-L1 antibodies to overcome resistance and are devising further immunotherapy combinations. More than 20 anti-PD-1/PD-L1antibodies have been approved or are currently in development. Numerous combination therapies are under development, and several combination therapies have provided positive results in randomized controlled trials. This review aimed to examine the current status of approved and investigational anti-PD-1/PD-L1antibodies for NSCLC in Japan, the United States, the European Union, and China. Further, this review discusses the challenges and future perspectives for developing new ICIs in alignment with the global developments in Japan.

Rapidly progressing metastatic malignant melanoma mimicking primary pleural tumor: A case report.

Malignant melanoma is the most aggressive skin cancer that originates from melanocytes. Primary or metastatic pleural melanoma shares clinical and imaging characteristics with primary pleural tumors, such as pleural mesothelioma. Identification of the primary site can be challenging to distinguish between primary and secondary melanomas. We report a case of a 46-year-old woman with metastatic, rapidly progressing pleural melanoma mimicking primary pleural tumor. The metastatic pleural tumor from a primary cutaneous melanoma was diagnosed by reevaluating a previous surgical specimen. When evaluating patients with pleural melanoma, the primary site should be reevaluated to distinguish between primary and secondary melanomas.

Smoking History Predicts High Presence of TILs and Efficacy of PD-1 Blockade in PD-L1 Expression-negative Non-small Cell Lung Cancer Patients.

BACKGROUND/AIM: Programmed death-ligand 1 (PD-L1) expression on tumor cells is a predictive biomarker of programmed cell death 1 (PD-1) blockade therapy. This study sought to clarify predictors of the efficacy of nivolumab in non-small cell lung cancer (NSCLC) patients with PD-L1 expression-negative tumors. PATIENTS AND METHODS: We retrospectively reviewed the records of advanced NSCLC patients between January 2016 and April 2019, and investigated the predictive marker of nivolumab including the status of CD8+ tumor infiltrating lymphocytes (TILs). RESULTS: A total of 70 NSCLC patients were included. Overall response rate (ORR) and progression-free survival (PFS) were better in patients with a heavy smoking history (smoking index: SI≥600) than in those without (SI<600) [ORR: 20.6% vs. 2.8%, (p=0.02), and PFS: 2.4 months vs. 1.8 months, (p=0.04)]. A high density of CD8+ TILs was significantly associated with a heavy smoking history (p=0.04). Conlusion: Heavy smoking history (SI≥600), which was correlated with a large number of CD8+ TILs, could be a predictor of the efficacy of nivolumab in NSCLC patients with PD-L1 expression-negative tumors.

Study protocol for NCCH1908 (UPFRONT-trial): a prospective clinical trial to evaluate the feasibility and utility of comprehensive genomic profiling prior to the initial systemic treatment in advanced solid tumour patients.

Comprehensive genomic profiling has been approved for use in patients with advanced solid tumours; however, it is only indicated in advanced solid tumour patients without available standard chemotherapeutic treatment or those who have completed standard treatments in Japan, and there are no available data on the clinical feasibility and utility of comprehensive genomic profiling in treatment-naive patients. This multicentre, single-arm, prospective study aims to evaluate the feasibility and utility of the OncoGuide NCC Oncopanel System in treatment-naive patients with six advanced major malignancies: non-small cell lung cancer, breast cancer, gastric cancer, colon cancer, pancreatic cancer and biliary tract cancer (NCCH1908). This study (study cohort) will be compared with the other prospective observational study (control cohort), which enrols patients not receiving comprehensive genomic profiling prior to initial systemic treatment. A total of 200 patients will be enrolled in the study over 21 months. This study has been registered in the UMIN Clinical Trials Registry (www.umin.ac.jp/ctr/) (UMIN000040743). CLINICAL TRIAL REGISTRATION: This study, initiated in June 2020, has been registered in the UMIN Clinical Trials Registry (www.umin.ac.jp/ctr/) (registration number: UMIN000040743). We plan to enrol a total of 200 patients over a period of 21 months.

Neoadjuvant chemotherapy promotes the expression of HER3 in patients with ovarian cancer.

HER3 (erbB3) signaling serves an important role in the development and chemoresistance of ovarian cancer, and is activated by chemotherapy. To evaluate the influence of neoadjuvant chemotherapy and other clinical factors on the expression of HER3, as well as to examine its role as a prognostic marker, the present study evaluated archived tissues from patients who underwent surgery for ovarian cancer between 2011 and 2018 at our hospital. Immunohistochemical staining for HER3 was performed using formalin-fixed paraffin-embedded surgical specimens and biopsy samples. In total, data from 111 patients with sufficient surgically resected tumor samples were extracted. A total of 28 patients with histology type high-grade serous carcinoma (HGSC) had specimens available from both pre-chemotherapy biopsies and post-chemotherapy surgery. High HER3 expression (HER3-high) was observed in 64 patients (58%), whereas low HER3 expression (HER3-low) was observed in 47 patients (42%). Multivariate logistic regression analysis identified neoadjuvant chemotherapy [odds ratio (OR), 7.49; 95% confidence interval (CI), 2.48-22.64; P<0.001) and non-HGSC histology (OR, 5.42; 95% CI, 1.99-14.78; P<0.001) as significant predictive factors for HER3-high. In pre-chemotherapy biopsy specimens, 15 patients were HER3-high and 13 were HER3-low. After chemotherapy, eight of 13 patients with HER3-low exhibited a change in status to HER3-high, with a trend toward poorer progression-free survival compared to that of patients whose status remained HER3-low. In conclusion, HER3 overexpression was revealed to be common among patients with ovarian cancer, especially in those with non-HGSC histology. In addition, HER3 expression may be promoted by chemotherapy. These findings suggested that patients with ovarian cancer are good candidates for emerging HER3-targeting therapies.

HER3 protein expression as a risk factor for post-operative recurrence in patients with early-stage adenocarcinoma and adenosquamous carcinoma of the cervix.

Patients with cervical adenocarcinoma (AC) and adenosquamous carcinoma (ASC) have a poorer prognosis than those with squamous cell carcinoma (SCC). Erb-b2 receptor tyrosine kinase 3 (HER3) is a member of the epidermal growth factor receptor family and its expression is associated with unfavorable prognosis in several cancer types, including SCC of the cervix. As there is limited information on the prognostic value of HER3 for AC and ASC of the cervix, the present study aimed to evaluate the expression of HER3 and its impact on post-operative recurrence in patients with AC and ASC of the cervix. This retrospective study included 39 patients with early-stage AC and ASC who underwent primary surgery between January 1997 and December 2017. Immunohistochemical staining for HER3 was performed on formalin-fixed paraffin-embedded surgical specimens. The possible influence of HER3 expression on disease-free survival (DFS) was studied by using multivariate Cox regression with adjustment for established risk factors of post-operative recurrence. High expression of HER3 (HER3-high) was detected in 85.1% of cases of AC (23/27) and in 58.3% of cases of ASC (7/12). The median follow-up duration was 63.1 months and Kaplan-Meier analysis indicated that the 5-year DFS rates of patients with AC and ASC of the cervix were 56.7% in patients with HER3-high and 77.8% in patients with HER3-low (log rank, P=0.20). On multivariate analysis, HER3-high [hazard ratio (HR)=6.32, 95% CI: 1.10-36.26, P=0.039), pelvic lymph node metastasis (HR=7.61, 95% CI: 2.07-28.00, P=0.002) and vascular invasion (HR=4.28, 95% CI: 1.12-16.31, P=0.033) were indicated to be independent predictors of DFS. To date, the present study is the most comprehensive analysis to evaluate the expression of HER3 in patients with early-stage AC and ASC of the cervix. The results suggested that HER3 overexpression may be an independent risk factor for post-operative recurrence. However, these results and the prognostic value of HER3 should be confirmed in a larger sample.

Number of metastatic organs negatively affects the treatment sequence in patients with EGFR-TKI failure.

BACKGROUND: Several studies have previously demonstrated the survival benefit of both EGFR-TKI treatment and chemotherapy in patients with non-small cell lung cancer (NSCLC) harboring EGFR mutations. The aim of the present study was to clarify the factors influencing the treatment sequence after failure of EGFR-TKI therapy, focusing on the number of organs with metastasis (hereafter, metastatic organs). METHODS: Between January 2010 and December 2016, consecutive patients with EGFR-mutated NSCLC who were started on first-line EGFR-TKI were reviewed. The factors influencing withholding systemic chemotherapy and the post-progression survival (PPS) after failure of EGFR-TKI were investigated. RESULTS: A total of 393 patients were started on first-line EGFR-TKI during the study period. After excluding patients maintained on EGFR-TKI or who received osimertinib targeting secondary EGFR T790M, 297 patients were included in the analysis. Among these, 180 (60.6%) received chemotherapy after failure of EGFR-TKI (TKI-Ct group), while the remaining 117 (39.4%) received no chemotherapy (TKI-only group). Multivariate analysis identified older age (≥75 years: odds ratio [OR] = 0.25, 95% confidence interval [CI]: 0.11-0.43, P < 0.001), poor performance status (PS) (≥2: OR = 0.06, 95% CI: 0.03-0.15, P < 0.001), and three or more metastatic organs (OR = 0.42, 95% CI: 0.22-0.80, P = 0.008) as being significantly associated with withholding of chemotherapy after failure of EGFR-TKI. CONCLUSION: A relatively large number of metastatic organs and a poor PS were associated with the withholding of subsequent chemotherapy after failure of EGFR-TKI in EGFR-mutated NSCLC patients. Further research for patients with such a poor prognosis should be investigated in the future.

Efficacy and safety of crizotinib in patients with ROS1 rearranged non-small cell lung cancer: a retrospective analysis.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) are remarkably effective in patients with non-small cell lung carcinoma (NSCLC) harboring driver gene mutations and rearrangements. Crizotinib, a small-molecule TKI, has been demonstrated to be an efficacious drug against c-ros oncogene 1-rearranged NSCLC (ROS1-NSCLC) in clinical trials. However, information regarding the use of crizotinib in clinical practice in Japan is limited. METHODS: Subjects with a definite diagnosis of advanced/relapsed ROS1-NSCLC were selected from consecutive NSCLC patients treated at the National Cancer Center Hospital between December 2014 and May 2018. We retrospectively assessed the efficacy and safety of crizotinib in clinical practice. RESULTS: Among 24 patients with ROS1-NSCLC, the ROS1 rearrangement status was assessed using reverse transcription polymerase chain reaction (RT-PCR) (n=17), fluorescence in situ hybridization (FISH) (n=8), or next-generation sequencing (n=5) (some overlap occurred). Thirteen patients were treated with crizotinib in clinical practice. Among the 10 patients in whom clinical efficacy could be evaluated, the objective response rate (ORR) was 80.0% [95% confidence interval (CI), 49.0 to 94.3]. The median follow-up time was 35.5 months (95% CI, 8.9 to 44.6), the median progression-free survival (PFS) time was 10.0 months (95% CI, 5.1 to 27.0), and the median overall survival (OS) time was 28.7 months (95% CI, 6.7 to not reached). The most common adverse events were an aspartate/alanine aminotransferase (AST/ALT) increased and vision disorder. No severe adverse events related to crizotinib occurred. CONCLUSIONS: The use of crizotinib in patients with ROS1-NSCLC was effective and well tolerated in clinical practice in Japan without severe adverse events.

Comparison between stereotactic radiosurgery and whole-brain radiotherapy for 10-20 brain metastases from non-small cell lung cancer.

The efficacy and safety of stereotactic radiosurgery (SRS) in comparison with whole brain radiotherapy (WBRT) for brain metastases (BMs) remains unclear. The present study retrospectively reviewed 44 patients who received SRS or WBRT as an initial treatment for 10-20 BMs from non-small cell lung cancer between 2009 and 2016. Of the patients, 24 (54.5%) were treated with SRS and 20 (45.5%) were treated with WBRT. Overall survival (OS), time to intracranial progression (TTIP), neurological survival (NS), and prognostic factors were examined. OS did not significantly differ between the two groups: 7.3 months in the SRS group vs. 7.2 months in the WBRT group (P=0.502). Median TTIP was significantly shorter in the SRS group than in the WBRT group (7.1 vs. 19.1 months, P=0.009). In contrast, there were no significant differences in NS between the two groups (14.5 months in the SRS group vs. 12.9 months in the WBRT group, P=0.346). Univariate and multivariate analysis revealed that the type of initial treatment for BMs (WBRT or SRS) was not a significant prognostic factor (hazard ratio=0.80, 95% confidence interval: 0.42-1.52, P=0.502). However, histology, performance status, subsequent molecular targeted drugs, subsequent chemotherapy and salvage treatment were independent prognostic factors. There were no significant differences in OS and NS between treatment with SRS and treatment with WBRT in patients with 10-20 BMs, although TTIP was improved with WBRT. As an upfront treatment for 10-20 BMs, SRS may delay WBRT and the adverse events associated with WBRT.

A propensity score-matched comparison of the efficacies of OK-432 and talc slurry for pleurodesis for malignant pleural effusion induced by lung adenocarcinoma.

BACKGROUND: The choice of an optimal sclerosant for pleurodesis for malignant pleural effusion remains controversial. This retrospective clinical study compared the efficacy and safety of two sclerosants; talc slurry (talc-s) and OK-432. METHODS: We compared the characteristics, 30/90-day success rates, and adverse events in patients with lung adenocarcinoma who underwent pleurodesis by using either OK-432 or talc-s. Propensity score matching was used to compare the two scelrosants. RESULTS: Ninety-four patients (mean age=71.6±9.6 years) were included in this retrospective study, of whom 64 received OK-432 and 30 received talc-s. Seventy-three patients (77.6%) were initially diagnosed with clinical stage IV lung cancer, with a 28.7% epidermal growth factor receptor mutation frequency. The propensity score-matched cohort included 26 patients from each group. The 30-day success rates for OK-432 and talc-s were 80.7% and 76.9%, respectively (odds ratio: 1.26, 95% confidence interval: 0.33-4.77, p=0.73). Neither the overall incidence of adverse events nor the 90-day success rates differed significantly. Multivariate logistic regression revealed that the predictors of 30-day success were lower drainage volume on the previous day, particularly <250mL/day, the presence of full lung expansion, and pre-therapy with an epidermal growth factor receptor-tyrosine kinase inhibitor. The median post-pleurodesis survival time was 6.9 months, which was not significantly different between the study groups. CONCLUSIONS: Propensity score-matched analyses showed that pleurodesis using OK-432 and talc-s demonstrated comparable efficacy and safety profiles in patients with lung adenocarcinoma. This indicated that OK-432 could be a viable alternative to talc-s in this procedure.

[A Case of Acute Arterial Occlusion of the Lower Limb during Chemotherapy for Lung Cancer].

A 69-year-old man visited a clinic for left leg weakness. With suspicions of lung cancer and a metastatic brain tumor, he was referred to our hospital and was diagnosed with large cell neuroendocrine carcinoma, cT1bN0M1b (BRA), stage IV. After stereotactic radiosurgery for his brain metastasis, he was treated with chemotherapy containing cisplatin and irinotecan. A week after initiating chemotherapy, he suddenly developed severe right leg pain and adynamia. A computed tomography angiogram revealed occlusion of the right common femoral artery, and percutaneous thrombectomy was performed. The symptoms resolved completely, and he was discharged without any sequelae or recurrence. Acute arterial occlusion of the limbs during chemotherapy is uncommon and requires prompt diagnosis and treatment; hence, caution should be paid when it is clinically suspected.