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Purpose@#In patients with epidermal growth factor receptor (EGFR)-mutant non–small cell lung cancer (NSCLC), EGFR tyrosine kinase inhibitors (TKIs) improve response rate and survival. However, most patients eventually develop resistance. This study aimed to identify the role of CD73 in EGFR-mutant NSCLC and explore whether CD73 inhibition may serve as a therapeutic strategy in NSCLC patients with acquired resistance to EGFR-TKIs. @*Materials and Methods@#We evaluated the prognostic role of CD73 expression in EGFR-mutant NSCLC using tumor samples from a single institution. We silenced CD73 in EGFR-TKI–resistant cell lines using short hairpin RNA (shRNA) targeting CD73 and also transfected a vector alone as a negative control. Using these cell lines, cell proliferation and viability assays, immunoblot assays, cell cycle analysis, colony-forming assays, flow cytometry, and apoptosis analysis were performed. @*Results@#High expression of CD73 was associated with shorter survival in patients with metastatic EGFR-mutant NSCLC treated with first-generation EGFR-TKI. CD73 inhibition synergistically inhibited cell viability with first-generation EGFR-TKI treatment compared with the negative control. When CD73 inhibition and EGFR-TKI treatment were combined, G0/G1 cell cycle arrest was induced through the regulation of p21 and cyclin D1. In addition, the apoptosis rate was increased in CD73 shRNA-transfected cells treated with EGFR-TKI. @*Conclusion@#High expression of CD73 adversely affects the survival of patients with EGFR-mutant NSCLC. The study demonstrated that inhibiting CD73 in EGFR-TKI–resistant cell lines resulted in increased apoptosis and cell cycle arrest, which overcame the acquired resistance to first-generation EGFR-TKIs. Further research is needed to determine whether blocking CD73 plays a therapeutic role in EGFR-TKI–resistant patients with EGFR-mutant NSCLC.
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Background@#Given that the role of serum testosterone on incident cardiovascular disease has been uncertain, it is necessary to find out the relationship between serum testosterone and carotid atherosclerosis. @*Methods@#The study participants included 1,302 Korean adults (873 men and 429 postmenopausal women) who participated in the Healthy Twin Study and were not receiving androgen deprivation therapy. The participants were classified into three groups: men aged <40 and ≥40 years and postmenopausal women. Total testosterone (TT) and sex hormone-binding globulin (SHBG) concentrations were measured using electrochemiluminescence immunoassays, and free testosterone (cFT) levels were calculated using Vermeulen’s method. Carotid intima-media thickness (IMT) was measured at three levels using a high-resolution B-mode ultrasound equipped with a 7-MHz linear transducer. The associations between sex hormone concentrations and carotid IMT were evaluated using a mixed linear regression analysis. @*Results@#After adjusting for cardiovascular risk factors, TT was found to be inversely associated with common carotid IMT in men aged ≥40 years, with a 4.5% decrease in common carotid IMT for every one-standard deviation increase in TT concentration (P=0.0063). In contrast, TT was not significantly associated with carotid IMT in all segments in men aged <40 years and postmenopausal women. Additionally, SHBG and cFT were not associated with carotid IMT in any segment. @*Conclusion@#The significant association between TT level and common carotid IMT in men aged ≥40 years suggests that decreased testosterone levels are involved in the development of atherosclerosis in men.
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Purpose@#We aimed to assess the real-world efficacy of nab-paclitaxel in metastatic breast cancer patients. @*Materials and Methods@#This is a retrospective study performed in two tertiary referral hospitals in Korea. Patients with metastatic breast cancer treated with nab-paclitaxel (Abraxane®) between March 2016 and March 2020 were enrolled. @*Results@#A total of 102 patients with metastatic breast cancer were included. Patients were heavily pre-treated with a median of four prior lines of chemotherapy (5 lines when including endocrine therapy in hormone-receptor-positive patients), and 66 patients (64.7%) were exposed to taxanes in the metastatic setting. According to St. Gallen molecular subtypes, 36 patients (35.3%) were luminal A, 28 (27.5%) were luminal B, 18 (17.7%) were human epidermal growth factor receptor 2–positive and 20 (19.6%) had triple-negative disease. Fifty patients (49.0%) were treated with a 3-weekly regimen (260 mg/m2 on day 1 every 3 weeks), and 52 (51.0%) were treated with a weekly regimen (100 mg/m2 every week). Objective response rate was 22.9%. After a median follow-up of 22.0 months, median progression-free survival (PFS) was 4.0 months (95% confidence interval [CI], 2.6 to 4.8) and median overall survival was 8.7 months (95% CI, 7.5 to 11.2). Patients treated with weekly regimen had longer PFS compared to 3-weekly regimen (5.5 vs. 2.3 months, p < 0.001). Multivariate analysis revealed the treatment regimen as an independent prognostic factor for PFS. There was no grade 3 or 4 hypersensitivity reaction. @*Conclusion@#This real-world data shows that nab-paclitaxel is a reasonable treatment option in heavily pre-treated and/or taxane-exposed metastatic breast cancer patients.
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Purpose@#Epidermal growth factor receptor kinase domain duplication (EGFR-KDD) is a rare and poorly understood oncogenic mutation in non–small cell lung cancer (NSCLC). We aimed to investigate the acquired resistance mechanism of EGFR-KDD against EGFR-TKIs. @*Materials and Methods@#We identified EGFR-KDD in tumor tissue obtained from a patient with stage IV lung adenocarcinoma and established the patient-derived cell line SNU-4784. We also established several EGFR-KDD Ba/F3 cell lines: EGFR-KDD wild type (EGFR-KDDWT), EGFR-KDD domain 1 T790M (EGFR-KDDD1T), EGFR-KDD domain 2 T790M (EGFR-KDDD2T), and EGFR-KDD both domain T790M (EGFR-KDDBDT). We treated the cells with EGFR tyrosine kinase inhibitors (TKIs) and performed cell viability assays, immunoblot assays, and ENU (N-ethyl-N-nitrosourea) mutagenesis screening. @*Results@#In cell viability assays, SNU-4784 cells and EGFR-KDDWT Ba/F3 cells were sensitive to 2nd generation and 3rd generation EGFR TKIs. In contrast, the T790M-positive EGFR-KDD Ba/F3 cell lines (EGFR-KDDT790M) were only sensitive to 3rd generation EGFR TKIs. In ENU mutagenesis screening, we identified the C797S mutation in kinase domain 2 of EGFR-KDDBDT Ba/F3 cells. Based on this finding, we established an EGFR-KDD domain 1 T790M/domain 2 cis-T790M+C797S (EGFR-KDDT/T+C) Ba/F3 model, which was resistant to EGFR TKIs and anti-EGFR monoclonal antibody combined with EGFR TKIs. @*Conclusion@#Our study reveals that the T790M mutation in EGFR-KDD confers resistance to 1st and 2nd generation EGFR TKIs, but is sensitive to 3rd generation EGFR TKIs. In addition, we identified that the C797S mutation in kinase domain 2 of EGFR-KDDT790M mediates a resistance mechanism against 3rd generation EGFR TKIs.
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Next-generation sequencing (NGS) is becoming essential in the fields of precision oncology. With implementation of NGS in daily clinic, the needs for continued education, facilitated interpretation of NGS results and optimal treatment delivery based on NGS results have been addressed. Molecular tumor board (MTB) is multidisciplinary approach to keep pace with the growing knowledge of complex molecular alterations in patients with advanced solid cancer. Although guidelines for NGS use and MTB have been developed in western countries, there is limitation for reflection of Korea’s public health environment and daily clinical practice. These recommendations provide a critical guidance from NGS panel testing to final treatment decision based on MTB discussion.
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In 2017, Korean Society of Medical Oncology (KSMO) published the Korean management guideline of metastatic prostate cancer. This paper is the 2nd edition of the Korean management guideline of metastatic prostate cancer. We updated recent many changes of management in metastatic prostate cancer in this 2nd edition guideline. The present guideline consists of the three categories: management of metastatic hormone sensitive prostate cancer; management of metastatic castration resistant prostate cancer; and clinical consideration for treating patients with metastatic prostate cancer. In category 1 and 2, levels of evidence (LEs) have been mentioned according to the general principles of evidence-based medicine. And grades of recommendation (GR) was taken into account the quality of evidence, the balance between desirable and undesirable effects, the values and preferences, and the use of resources and GR were divided into strong recommendations (SR) and weak recommendations (WR). A total of 16 key questions are selected. And we proposed recommendations and described key evidence for each recommendation. The treatment landscape of metastatic prostate cancer is changing very rapid and many trials are ongoing. To verify the results of the future trials is necessary and should be applied to the treatment for metastatic prostate cancer patients in the clinical practice. Especially, many prostate cancer patients are old age, have multiple underlying medical comorbidities, clinicians should be aware of the significance of medical management as well as clinical efficacy of systemic treatment.
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Background/Aims@#Programmed death-ligand 1 (PD-L1) expression, a validated predictive biomarker for anti-PD-1/PD-L1 inhibitors, is reported to change over time. This poses challenges during clinical application in non-small cell lung cancer. @*Methods@#This study included patients with non-small cell lung cancer who underwent surgery or biopsy and evaluation of PD-L1 expression in tumor cells via immunohistochemistry more than twice. We set the threshold of PD-L1 positivity to 10% and categorized patients into four groups according to changes in PD-L1 expression. Clinicopathologic information was collected from medical records. Statistical analyses, including Fisher’s exact test and log-rank test, were performed. @*Results@#Of 109 patients, 38 (34.9%) and 45 (41.3%) had PD-L1 positivity in archival and recent samples, respectively. PD-L1 status was maintained in 78 (71.6%) patients, but changed in 31 (28.4%), with 19 (17.4%) from negative to positive. There were no significant differences in characteristics between patients who maintained PD-L1 negativity and whose PD-L1 status changed from negative to positive. Patients harboring PD-L1 positivity in either archival or recent samples achieved better responses (p = 0.129) and showed longer overall survival than those who maintained PD-L1 negativity when they received immune checkpoint inhibitors after platinum failure (median overall survival 14.4 months vs. 4.93 months; hazard ratio, 0.43; 95% confidence interval, 0.20 to 0.93). @*Conclusions@#PD-L1 status changed in about one-fourth of patients. PD-L1 positivity in either archival or recent samples was predictive of better responses to immune checkpoint inhibitors. Therefore, archival samples could be used for assessment of PD-L1 status. The need for new biopsies should be decided individually.
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Purpose@#Angiosarcoma is a highly aggressive mesenchymal tumor. Although systemic chemotherapy is often considered for the inoperable or metastatic angiosarcoma, the outcome of such treatment is unsatisfactory and poorly delineated. @*Materials and Methods@#We reviewed electronic medical records of 75 patients with angiosarcoma who were treated with systemic chemotherapy for inoperable or metastatic disease. Patients were classified as having liver involvement if they had either primary or metastatic hepatic lesions. @*Results@#Among the patients evaluated, 51 patients were male (68%) and 24 patients (32%) had primary cutaneous angiosarcoma. Liver involvement was present in 28 patients (37.3%). A total of 59 patients received first-line weekly paclitaxel (wPac) and showed an objective response rate (ORR) of 23.7% (n=14), a median progression free survival (mPFS) of 4.0 months (95% confidence interval [CI] 3.0–6.1), and a median overall survival (mOS) of 10.2 months (95% CI 7.0–14.6). Among patients without liver involvement, patients receiving wPac (n=35) had significantly prolonged mPFS (5.8 vs. 3.2 months, respectively, p=0.014) with a tendency for prolonged mOS (13.8 vs. 11.6 months, respectively, p=0.13) than those receiving other regimens (n=12). A total of 24 patients received second- or later-line pazopanib monotherapy and showed an ORR of 16.7% (n=4), a mPFS of 2.4 months (95% CI 1.8–4.3) and a mOS of 5.4 months (95% CI 3.5–NA). @*Conclusion@#Treatment with first-line wPac and later-line pazopanib seems to provide survival benefit, especially for patients with advanced angiosarcoma without liver involvement.
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Purpose@#This study investigated the association of insulin, metformin, and statin use with survival and whether the association was modified by the hormone receptor status of the tumor in patients with breast cancer. @*Materials and Methods@#We studied 7,452 patients who had undergone surgery for breast cancer at Seoul National University Hospital from 2008 to 2015 using the nationwide claims database. Exposure was defined as a recorded prescription of each drug within 12 months before the diagnosis of breast cancer. @*Results@#Patients with prior insulin or statin use were more likely to be older than 50 years at diagnosis and had a higher comorbidity index than those without it (p < 0.01 for both). The hazard ratio (HR) for death with insulin use was 5.7 (p < 0.01), and the effect was attenuated with both insulin and metformin exposure with an HR of 1.2 (p=0.60). In the subgroup analyses, a heightened risk of death with insulin was further prominent with an HR of 17.9 (p < 0.01) and was offset by co-administration of metformin with an HR of 1.3 (p=0.67) in patients with estrogen receptor (ER)–negative breast cancer. Statin use was associated with increased overall mortality only in patients with ER-positive breast cancer with HR for death of 1.5 (p=0.05). @*Conclusion@#Insulin or statin use before the diagnosis of breast cancer was associated with an increase in all-cause mortality. Subsequent analyses suggested that metformin or statin use may have been protective in patients with ER-negative disease, which warrants further studies.
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Background@#Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant cancer predisposition syndrome. HLRCC is characterized by the development of cutaneous leiomyomas, early-onset uterine leiomyomas, and HLRCC-associated renal cell cancer (RCC) and caused by germline fumarate hydratase (FH) deficiency. We investigated the genotypic and phenotypic characteristics of Korean patients with HLRCC. @*Methods@#We performed direct sequencing analysis of FH in 13 patients with suspected HLRCC and their family members. A chromosomal microarray test was performed in female patients with negative sequencing results but highly suspected HLRCC. In addition, we analyzed the clinical characteristics and evaluated the genotype–phenotype correlations in Korean patients with HLRCC. @*Results@#We identified six different pathogenic or likely pathogenic FH variants in six of the 13 patients (46.2%). The variants included two nonsense variants, two splicing variants, one frameshift variant, and one missense variant. Of the six variants, two (33.3%) were novel (c.132+1G > C, and c.243dup). RCC and early-onset uterine leiomyoma were frequently observed in families with HLRCC, while cutaneous leiomyoma was less common. No significant genotype–phenotype correlation was observed. @*Conclusions@#We describe the genotypic and phenotypic spectrum in a small series of Korean patients with HLRCC. Our data reveal the unique characteristics of Korean patients with HLRCC and suggest a need for establishing an optimal diagnostic approach for them.
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Background and Objectives@#The relationship between metabolic stress, inflammation, and cardiovascular disease is being studied steadily. The aim of this study was to evaluate the effect of palmitate (PA) and minimally modified low-density lipoprotein (mmLDL) on macrophages and to identify the associated pathways. @*Methods@#J774 macrophages were incubated with PA or mmLDL and lipopolysaccharide (LPS). Secretion of inflammatory chemokines and the expression of corresponding genes were determined. The phosphorylation of extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase was also assessed. RNA sequencing of macrophages was performed to identify the genes regulated by PA or mmLDL. Some of the genes regulated by the 2 agents were validated by knocking down the cells using small interfering RNA. @*Results@#PA or mmLDL promoted the secretion of interleukin (IL)-6 and IL-1β in LPSstimulated macrophages, and this was accompanied by higher phosphorylation of ERK. RNA sequencing revealed dozens of genes that were regulated in this process, such as Csf3 and Edn1, which were affected by PA and mmLDL, respectively. These agents also increased Nlrp3 expression. The effect of Csf3 or Edn1 silencing on inflammation was modest, whereas toll-like receptor (TLR) 4 inhibition reduced a large proportion of macrophage activation. @*Conclusions@#We demonstrated that the proinflammatory milieu with high levels of PA or mmLDL promoted macrophage activation and the expression of associated genes such as Nlrp3, Csf3, and Edn1. Although the TLR4 pathway appeared to be most relevant, additional role of other genes in this process provided insights regarding the potential targets for intervention.
ABSTRACT
In 2017, Korean Society of Medical Oncology (KSMO) published the Korean management guideline of metastatic prostate cancer. This paper is the 2nd edition of the Korean management guideline of metastatic prostate cancer. We updated recent many changes of management in metastatic prostate cancer in this 2nd edition guideline. The present guideline consists of the three categories: management of metastatic hormone sensitive prostate cancer; management of metastatic castration resistant prostate cancer; and clinical consideration for treating patients with metastatic prostate cancer. In category 1 and 2, levels of evidence (LEs) have been mentioned according to the general principles of evidence-based medicine. And grades of recommendation (GR) was taken into account the quality of evidence, the balance between desirable and undesirable effects, the values and preferences, and the use of resources and GR were divided into strong recommendations (SR) and weak recommendations (WR). A total of 16 key questions are selected. And we proposed recommendations and described key evidence for each recommendation. The treatment landscape of metastatic prostate cancer is changing very rapid and many trials are ongoing. To verify the results of the future trials is necessary and should be applied to the treatment for metastatic prostate cancer patients in the clinical practice. Especially, many prostate cancer patients are old age, have multiple underlying medical comorbidities, clinicians should be aware of the significance of medical management as well as clinical efficacy of systemic treatment.
ABSTRACT
Background/Aims@#Programmed death-ligand 1 (PD-L1) expression, a validated predictive biomarker for anti-PD-1/PD-L1 inhibitors, is reported to change over time. This poses challenges during clinical application in non-small cell lung cancer. @*Methods@#This study included patients with non-small cell lung cancer who underwent surgery or biopsy and evaluation of PD-L1 expression in tumor cells via immunohistochemistry more than twice. We set the threshold of PD-L1 positivity to 10% and categorized patients into four groups according to changes in PD-L1 expression. Clinicopathologic information was collected from medical records. Statistical analyses, including Fisher’s exact test and log-rank test, were performed. @*Results@#Of 109 patients, 38 (34.9%) and 45 (41.3%) had PD-L1 positivity in archival and recent samples, respectively. PD-L1 status was maintained in 78 (71.6%) patients, but changed in 31 (28.4%), with 19 (17.4%) from negative to positive. There were no significant differences in characteristics between patients who maintained PD-L1 negativity and whose PD-L1 status changed from negative to positive. Patients harboring PD-L1 positivity in either archival or recent samples achieved better responses (p = 0.129) and showed longer overall survival than those who maintained PD-L1 negativity when they received immune checkpoint inhibitors after platinum failure (median overall survival 14.4 months vs. 4.93 months; hazard ratio, 0.43; 95% confidence interval, 0.20 to 0.93). @*Conclusions@#PD-L1 status changed in about one-fourth of patients. PD-L1 positivity in either archival or recent samples was predictive of better responses to immune checkpoint inhibitors. Therefore, archival samples could be used for assessment of PD-L1 status. The need for new biopsies should be decided individually.
ABSTRACT
Background and Objectives@#The relationship between metabolic stress, inflammation, and cardiovascular disease is being studied steadily. The aim of this study was to evaluate the effect of palmitate (PA) and minimally modified low-density lipoprotein (mmLDL) on macrophages and to identify the associated pathways. @*Methods@#J774 macrophages were incubated with PA or mmLDL and lipopolysaccharide (LPS). Secretion of inflammatory chemokines and the expression of corresponding genes were determined. The phosphorylation of extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase was also assessed. RNA sequencing of macrophages was performed to identify the genes regulated by PA or mmLDL. Some of the genes regulated by the 2 agents were validated by knocking down the cells using small interfering RNA. @*Results@#PA or mmLDL promoted the secretion of interleukin (IL)-6 and IL-1β in LPSstimulated macrophages, and this was accompanied by higher phosphorylation of ERK. RNA sequencing revealed dozens of genes that were regulated in this process, such as Csf3 and Edn1, which were affected by PA and mmLDL, respectively. These agents also increased Nlrp3 expression. The effect of Csf3 or Edn1 silencing on inflammation was modest, whereas toll-like receptor (TLR) 4 inhibition reduced a large proportion of macrophage activation. @*Conclusions@#We demonstrated that the proinflammatory milieu with high levels of PA or mmLDL promoted macrophage activation and the expression of associated genes such as Nlrp3, Csf3, and Edn1. Although the TLR4 pathway appeared to be most relevant, additional role of other genes in this process provided insights regarding the potential targets for intervention.
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BACKGROUND AND OBJECTIVES: Recent studies have examined the structure-function relationship of high-density lipoprotein (HDL). This study aimed to identify and rank HDL-associated proteins involved in several biological function of HDL.METHODS: HDLs isolated from 48 participants were analyzed. Cholesterol efflux capacity, effect of HDL on nitric oxide production, and vascular cell adhesion molecule-1 expression were assessed. The relative abundance of identified proteins in the highest vs. lowest quartile was expressed using the normalized spectral abundance factor ratio.RESULTS: After adjustment by multiple testing, six proteins, thyroxine-binding globulin, alpha-1B-glycoprotein, plasma serine protease inhibitor, vitronectin, angiotensinogen, and serum amyloid A-4, were more abundant (relative abundance ratio ≥2) in HDLs with the highest cholesterol efflux capacity. In contrast, three proteins, complement C4-A, alpha-2-macroglobulin, and immunoglobulin mu chain C region, were less abundant (relative abundance ratio <0.5). In terms of nitric oxide production and vascular cell adhesion molecule-1 expression, no proteins showed abundance ratios ≥2 or <0.5 after adjustment. Proteins correlated with the functional parameters of HDL belonged to diverse biological categories.CONCLUSIONS: In summary, this study ranked proteins showing higher or lower abundance in HDLs with high functional capacities and newly identified multiple proteins linked to cholesterol efflux capacity.
Subject(s)
Amyloid , Angiotensinogen , Atherosclerosis , Cardiovascular Diseases , Cholesterol , Complement System Proteins , Immunoglobulin mu-Chains , Lipoproteins , Nitric Oxide , Plasma , Proteomics , Serine Proteases , Thyroxine-Binding Globulin , Vascular Cell Adhesion Molecule-1 , VitronectinABSTRACT
BACKGROUND AND OBJECTIVES@#Recent studies have examined the structure-function relationship of high-density lipoprotein (HDL). This study aimed to identify and rank HDL-associated proteins involved in several biological function of HDL.@*METHODS@#HDLs isolated from 48 participants were analyzed. Cholesterol efflux capacity, effect of HDL on nitric oxide production, and vascular cell adhesion molecule-1 expression were assessed. The relative abundance of identified proteins in the highest vs. lowest quartile was expressed using the normalized spectral abundance factor ratio.@*RESULTS@#After adjustment by multiple testing, six proteins, thyroxine-binding globulin, alpha-1B-glycoprotein, plasma serine protease inhibitor, vitronectin, angiotensinogen, and serum amyloid A-4, were more abundant (relative abundance ratio ≥2) in HDLs with the highest cholesterol efflux capacity. In contrast, three proteins, complement C4-A, alpha-2-macroglobulin, and immunoglobulin mu chain C region, were less abundant (relative abundance ratio <0.5). In terms of nitric oxide production and vascular cell adhesion molecule-1 expression, no proteins showed abundance ratios ≥2 or <0.5 after adjustment. Proteins correlated with the functional parameters of HDL belonged to diverse biological categories.@*CONCLUSIONS@#In summary, this study ranked proteins showing higher or lower abundance in HDLs with high functional capacities and newly identified multiple proteins linked to cholesterol efflux capacity.
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BACKGROUND/AIMS@#Although crizotinib is standard chemotherapy for advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), clinical factors affecting progression-free survival (PFS) have not been reported. The purpose of this study was to identify clinical factors affecting PFS of crizotinib and develop a prognostic model for advanced ALK-positive NSCLC.@*METHODS@#Clinicopathologic features of patients enrolled in PROFILE 1001, 1005, 1007, and 1014 (training cohort) were reviewed. We conducted multivariate Cox analysis for PFS and overall survival (OS) in the training cohort (n = 159) and generated a proportional hazards model based on significant clinicopathologic factors, and then validated the model in an independent validation cohort (n = 40).@*RESULTS@#In the training cohort, the objective response rate was 81.5%. Median PFS and OS from the start of crizotinib were 12.4 and 31.3 months, respectively. Multivariate Cox analysis showed poor performance status, number of metastatic organs (≥ 3), and no response to crizotinib independently associated shorter PFS. Based on a score derived from these three factors, median PFS and OS of patients with one or two factors were significantly shorter compared to those without these factors (median PFS, 22.4 months vs. 10.5 months vs. 6.5 months; median OS, not reached vs. 29.1 months vs. 11.8 months, respectively; p < 0.001 for each group). This model also had validated in an independent validation cohort.@*CONCLUSIONS@#Performance status, number of metastatic organs, and response to crizotinib affected PFS of crizotinib in ALK-positive NSCLC. Based on these factors, we developed a simple and useful prediction model for PFS.
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BACKGROUND/AIMS@#This study was to evaluate the clinical significance of infusion-related reaction (IRR) of rituximab in diffuse large B-cell lymphoma (DLBCL) patients who received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) as a first-line chemotherapy.@*METHODS@#The medical records of 326 patients diagnosed with DLBCL were re trospectively analyzed. Both doctor's progress records and nursing records were reviewed. IRR was graded according to the National Cancer Institute Common Terminology Criteria.@*RESULTS@#IRR was not associated with overall survival (OS) or progression-free survival (PFS) of DLBCL patients as compared to those who did not have IRR (OS: median 78.0 months vs. 69.0 months, p = 0.700; PFS: median 65.4 months vs. 64.0 months, p = 0.901). IRR grade did not affect OS or PFS. B symptoms was independently associated with IRR (hazard ratio [HR], 1.850; 95% confidence interval [CI], 1.041 to 3.290; p = 0.036). Further, bone marrow involvement was independently associated with re-IRR (HR, 4.904; 95% CI, 0.767 to 3.118; p = 0.029).@*CONCLUSIONS@#Our study shows that IRR of rituximab is not associated with OS or PFS of DLBCL patients who received R-CHOP. Furthermore, our study suggests a need for more careful observation for IRR in patients with B symptoms or bone marrow involvement.
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BACKGROUND/AIMS@#The role of [18F]-f luorodeoxyglucose positron emission tomography-computed tomography (PET/CT) in patients with diffuse large B-cell lymphoma (DLBCL) in first remission is unclear.@*METHODS@#Medical costs within the first 3 years of treatment completion and clinical outcomes of 118 patients with DLBCL in first remission with and without surveillance PET/CT (PET/CT [+] group [n = 76] and PET/CT [−] group [n = 42], respectively) were retrospectively analyzed.@*RESULTS@#In a propensity matched cohort with adjustment for International Prognostic Index risk and relapse, the PET/CT (+) group was shown to have similar medical costs as the PET/CT (−) group. Relapse-free survival (RFS) and overall survival (OS) were comparable between the two groups (median RFS not reached [NR] for both groups, p = 0.133; median OS NR, p = 0.542). Among 76 patients with surveillance PET/CT, 31 (40.8%) had findings suggestive of recurrence and 16 of these (51.6%) were later confirmed to have recurrent disease. Fifteen patients (48.4%) were confirmed to not have recurrence after follow-up CT or PET/CT evaluation (n = 10) and biopsy (n = 4). None of the patients with negative PET/CT findings had disease recurrence. Sensitivity, specificity, positive predictive value, and negative predictive value of PET/CT for detection of recurrence were 1, 0.75, 0.52, and 1, respectively.@*CONCLUSIONS@#Surveillance PET/CT resulted in similar clinical outcomes and medical costs compared to no surveillance PET/CT. Approximately half of patients with PET/CT findings of recurrence had no recurrence after follow-up imaging and biopsy, which would not have been carried out if PET/CT had not been performed in the first place.
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PURPOSE: Despite the successful use of tyrosine kinase inhibitors (TKIs) in cancer patients, their effect on herpes zoster development has not been studied. The aim of this study was to evaluate and compare the effects of epidermal growth factor receptor (EGFR) TKI and cytotoxic chemotherapy on the risk of herpes zoster development in non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: We conducted a medical review of all eligible NSCLC patients in Seoul National University hospital between 2002 and 2015. We classified patients based on whether they previously underwent EGFR TKI therapy into either the TKI group or the cytotoxic group. We compared the incidence rates of herpes zoster during TKI therapy and cytotoxic chemotherapy. Additionally, the longitudinal risk of herpes zoster from TKIs was analyzed using the incidence rate ratio (IRR) of the TKI group to the cytotoxic group and the log-rank test of the Kaplan-Meier method. RESULTS: Of the 2,981 NSCLC patients, 54 patients (1.54%) developed herpes zoster. In the TKI group (2,002 patients), the IRR of herpes zoster during TKI therapy compared to that during cytotoxic chemotherapy was 1.05 (95% confidence interval [CI], 0.53 to 2.09). The IRR of the TKI group compared to the cytotoxic group was 1.33 (95% CI, 0.64 to 2.76). The Kaplan-Meier cumulative risk of both groups was not significantly different. CONCLUSION: Our results show that the incidence rate of herpes zoster in the TKI group was not statistically different from the incidence in the cytotoxic group during and after chemotherapy in NSCLC patients.