Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 117
Filter
1.
Article in English | WPRIM | ID: wpr-913826

ABSTRACT

Purpose@#Metachronous brain-only oligorecurrence in patients with non–small cell lung cancer (NSCLC) is a rare event with favorable prognosis, but the clinical outcome has not been fully determined. We retrospectively analyzed clinical outcomes and prognostic factors in metachronous brain-only oligorecurrence in patients with NSCLC who underwent definitive treatment. @*Materials and Methods@#We reviewed 4,437 NSCLC patients without oncogenic driver mutations who underwent definitive treatment between 2008 and 2018. Among them, we identified 327 patients who developed 1 to 5 brain metastases with or without systemic metastasis. Of the 327 patients, 71 had metachronous brain-only oligorecurrence without extracranial progression and were treated with local therapy to the brain. Overall survival (OS), progression-free survival (PFS), and prognostic factors affecting OS were analyzed. @*Results@#The median OS was 38.9 months (95% confidence interval [CI], 21.8 to 56.1 months) in 71 patients. The 2-year OS rate was 67.8% and the 5-year OS rate was 33.1%. The median PFS was 25.5 months (95% CI, 12.2 to 14.4 months). The longest surviving patient had a survival period of 115 months. Through multivariate analysis, Eastern Cooperative Oncology Group ≥ 1 (hazard ratio, 5.33; p=0.005) was associated with poor survival. There was no significant difference in OS between patients with local therapy and those with local plus systemic therapy (18.5 months vs. 34.7 months, p=0.815). @*Conclusion@#Metachronous brain-only oligorecurrence NSCLC patients who underwent definitive treatment experienced long-term survival with local therapy, highlighting the unique patient population. The role of systemic chemotherapy in this patient population requires further investigation.

2.
Article in English | WPRIM | ID: wpr-874818

ABSTRACT

: Immune checkpoint inhibitors (ICIs) are approved for treating non-small-cell lung cancer (NSCLC); however, the safety and efficacy of combined ICI and Gamma Knife radiosurgery (GKS) treatment remain undefined. In this study, we retrospectively analyzed patients treated with ICIs with or without GKS at our institute to manage patients with brain metastases from NSCLC. Methods : We retrospectively reviewed medical records of patients with brain metastases from NSCLC treated with ICIs between January 2015 and December 2017. Of 134 patients, 77 were assessable for brain responses and categorized into three groups as follows : group A, ICI alone (n=26); group B, ICI with concurrent GKS within 14 days (n=24); and group C, ICI with non-concurrent GKS (n=27). Results : The median follow-up duration after brain metastasis diagnosis was 19.1 months (range, 1–77). At the last follow-up, 53 patients (68.8%) died, 20 were alive, and four were lost to follow-up. The estimated median overall survival (OS) of all patients from the date of brain metastasis diagnosis was 20.0 months (95% confidence interval, 12.5–27.7) (10.0, 22.5, and 42.1 months in groups A, B, and C, respectively). The OS was shorter in group A than in group C (p=0.001). The intracranial disease progression-free survival (p=0.569), local progression-free survival (p=0.457), and complication rates did not significantly differ among the groups. Twelve patients showed leptomeningeal seeding (LMS) during follow-up. The 1-year LMS-free rate in treated with ICI alone group (69.1%) was significantly lower than that in treated with GKS before ICI treatment or within 14 days group (93.2%) (p=0.004). Conclusion : GKS with ICI showed no favorable OS outcome in treating brain metastasis from NSCLC. However, GKS with ICI did not increase the risk of complications. Furthermore, compared with ICI alone, GKS with ICI may be associated with a reduced incidence of LMS. Further understanding of the mechanism, which remains unknown, may help improve the quality of life of patients with brain metastasis.

3.
Article in English | WPRIM | ID: wpr-897407

ABSTRACT

Background@#There have been no guidelines for the management of adult patients with diffuse midline glioma (DMG), H3K27M-mutant in Korea since the 2016 revised WHO classification newly defined this disease entity. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, had begun preparing guidelines for DMG since 2019. @*Methods@#The Working Group was composed of 27 multidisciplinary medical experts in Korea.References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of keywords. As ‘diffuse midline glioma’ was recently defined, and there was no international guideline, trials and guidelines of ‘diffuse intrinsic pontine glioma’ or ‘brain stem glioma’ were thoroughly reviewed first. @*Results@#The core contents are as follows. The DMG can be diagnosed when all of the following three criteria are satisfied: the presence of the H3K27M mutation, midline location, and infiltrating feature. Without identification of H3K27M mutation by diagnostic biopsy, DMG cannot be diagnosed. For the primary treatment, maximal safe resection should be considered for tumors when feasible. Radiotherapy is the primary option for tumors in case the total resection is not possible. A total dose of 54 Gy to 60 Gy with conventional fractionation prescribed at 1-2 cm plus gross tumor volume is recommended. Although no chemotherapy has proven to be effective in DMG, concurrent chemoradiotherapy (± maintenance chemotherapy) with temozolomide following WHO grade IV glioblastoma’s protocol is recommended. @*Conclusion@#The detection of H3K27M mutation is the most important diagnostic criteria for DMG. Combination of surgery (if amenable to surgery), radiotherapy, and chemotherapy based on comprehensive multidisciplinary discussion can be considered as the treatment options for DMG.

4.
Article in English | WPRIM | ID: wpr-897406

ABSTRACT

Background@#To date, there has been no practical guidelines for the prescription of antiepileptic drugs (AEDs) in brain tumor patients in Korea. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, had begun preparing guidelines for AED usage in brain tumors since 2019. @*Methods@#The Working Group was composed of 27 multidisciplinary medical experts in Korea.References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of the keywords. @*Results@#The core contents are as follows. Prophylactic AED administration is not recommended in newly diagnosed brain tumor patients without previous seizure history. When AEDs are administered during peri/postoperative period, it may be tapered off according to the following recommendations. In seizure-naïve patients with no postoperative seizure, it is recommended to stop or reduce AED 1 week after surgery. In seizure-naïve patients with one early postoperative seizure (<1 week after surgery), it is advisable to maintain AED for at least 3 months before tapering. In seizure-naïve patients with ≥2 postoperative seizures or in patients with preoperative seizure history, it is recommended to maintain AEDs for more than 1 year. The possibility of drug interactions should be considered when selecting AEDs in brain tumor patients. Driving can be allowed in brain tumor patients when proven to be seizure-free for more than 1 year. @*Conclusion@#The KSNO suggests prescribing AEDs in patients with brain tumor based on the current guideline. This guideline will contribute to spreading evidence-based prescription of AEDs in brain tumor patients in Korea.

5.
Article in English | WPRIM | ID: wpr-889703

ABSTRACT

Background@#There have been no guidelines for the management of adult patients with diffuse midline glioma (DMG), H3K27M-mutant in Korea since the 2016 revised WHO classification newly defined this disease entity. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, had begun preparing guidelines for DMG since 2019. @*Methods@#The Working Group was composed of 27 multidisciplinary medical experts in Korea.References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of keywords. As ‘diffuse midline glioma’ was recently defined, and there was no international guideline, trials and guidelines of ‘diffuse intrinsic pontine glioma’ or ‘brain stem glioma’ were thoroughly reviewed first. @*Results@#The core contents are as follows. The DMG can be diagnosed when all of the following three criteria are satisfied: the presence of the H3K27M mutation, midline location, and infiltrating feature. Without identification of H3K27M mutation by diagnostic biopsy, DMG cannot be diagnosed. For the primary treatment, maximal safe resection should be considered for tumors when feasible. Radiotherapy is the primary option for tumors in case the total resection is not possible. A total dose of 54 Gy to 60 Gy with conventional fractionation prescribed at 1-2 cm plus gross tumor volume is recommended. Although no chemotherapy has proven to be effective in DMG, concurrent chemoradiotherapy (± maintenance chemotherapy) with temozolomide following WHO grade IV glioblastoma’s protocol is recommended. @*Conclusion@#The detection of H3K27M mutation is the most important diagnostic criteria for DMG. Combination of surgery (if amenable to surgery), radiotherapy, and chemotherapy based on comprehensive multidisciplinary discussion can be considered as the treatment options for DMG.

6.
Article in English | WPRIM | ID: wpr-889702

ABSTRACT

Background@#To date, there has been no practical guidelines for the prescription of antiepileptic drugs (AEDs) in brain tumor patients in Korea. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, had begun preparing guidelines for AED usage in brain tumors since 2019. @*Methods@#The Working Group was composed of 27 multidisciplinary medical experts in Korea.References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of the keywords. @*Results@#The core contents are as follows. Prophylactic AED administration is not recommended in newly diagnosed brain tumor patients without previous seizure history. When AEDs are administered during peri/postoperative period, it may be tapered off according to the following recommendations. In seizure-naïve patients with no postoperative seizure, it is recommended to stop or reduce AED 1 week after surgery. In seizure-naïve patients with one early postoperative seizure (<1 week after surgery), it is advisable to maintain AED for at least 3 months before tapering. In seizure-naïve patients with ≥2 postoperative seizures or in patients with preoperative seizure history, it is recommended to maintain AEDs for more than 1 year. The possibility of drug interactions should be considered when selecting AEDs in brain tumor patients. Driving can be allowed in brain tumor patients when proven to be seizure-free for more than 1 year. @*Conclusion@#The KSNO suggests prescribing AEDs in patients with brain tumor based on the current guideline. This guideline will contribute to spreading evidence-based prescription of AEDs in brain tumor patients in Korea.

7.
Immune Network ; : e48-2020.
Article in English | WPRIM | ID: wpr-898548

ABSTRACT

Hyperprogressive disease (HPD) is a distinct pattern of progression characterized by acceleration of tumor growth after treatment with anti-PD-1/PD-L1 Abs. However, the immunological characteristics have not been fully elucidated in patients with HPD. We prospectively recruited patients with metastatic non-small cell lung cancer treated with anti-PD-1/PD-L1 Abs between April 2015 and April 2018, and collected peripheral blood before treatment and 7-days post-treatment. HPD was defined as ≥2-fold increase in both tumor growth kinetics and tumor growth rate between pre-treatment and post-treatment.Peripheral blood mononuclear cells were analyzed by multi-color flow cytometry to phenotype the immune cells. Of 115 patients, 19 (16.5%) developed HPD, 52 experienced durable clinical benefit (DCB; partial response or stable disease ≥6 months), and 44 experienced non-hyperprogressive progression (NHPD). Patients with HPD had significantly lower progression-free survival (p<0.001) and overall survival (p<0.001). When peripheral blood immune cells were examined, the pre-treatment frequency of CD39+ cells among CD8+T cells was significantly higher in patients with HPD compared to those with NHPD, although it showed borderline significance to predict HPD. Other parameters regarding regulatory T cells or myeloid derived suppressor cells did not significantly differ among patient groups. Our findings suggest high pre-treatment frequency of CD39+ CD8+ T cells might be a characteristic of HPD. Further investigations in a larger cohort are needed to confirm our results and better delineate the immune landscape of HPD.

8.
Immune Network ; : e48-2020.
Article in English | WPRIM | ID: wpr-890844

ABSTRACT

Hyperprogressive disease (HPD) is a distinct pattern of progression characterized by acceleration of tumor growth after treatment with anti-PD-1/PD-L1 Abs. However, the immunological characteristics have not been fully elucidated in patients with HPD. We prospectively recruited patients with metastatic non-small cell lung cancer treated with anti-PD-1/PD-L1 Abs between April 2015 and April 2018, and collected peripheral blood before treatment and 7-days post-treatment. HPD was defined as ≥2-fold increase in both tumor growth kinetics and tumor growth rate between pre-treatment and post-treatment.Peripheral blood mononuclear cells were analyzed by multi-color flow cytometry to phenotype the immune cells. Of 115 patients, 19 (16.5%) developed HPD, 52 experienced durable clinical benefit (DCB; partial response or stable disease ≥6 months), and 44 experienced non-hyperprogressive progression (NHPD). Patients with HPD had significantly lower progression-free survival (p<0.001) and overall survival (p<0.001). When peripheral blood immune cells were examined, the pre-treatment frequency of CD39+ cells among CD8+T cells was significantly higher in patients with HPD compared to those with NHPD, although it showed borderline significance to predict HPD. Other parameters regarding regulatory T cells or myeloid derived suppressor cells did not significantly differ among patient groups. Our findings suggest high pre-treatment frequency of CD39+ CD8+ T cells might be a characteristic of HPD. Further investigations in a larger cohort are needed to confirm our results and better delineate the immune landscape of HPD.

9.
Cancer Research and Treatment ; : 1288-1290, 2020.
Article | WPRIM | ID: wpr-831136

ABSTRACT

The non-small cell lung cancer with activating epidermal growth factor receptor (EGFR) mutation eventually acquires resistant to either first or second-generation EGFR tyrosine kinase inhibitor (TKI). As the following option, targeting EGFR T790M with third-generation EGFR TKI is now established as a standard treatment option. In this study, we are reporting the first case of resistance mechanism to the novel third-generation EGFR TKI, lazertinib, which showed promising clinical efficacy in phase 1-2 study. The patients showed resistance to the treatment by acquiring the additional EGFR C797S mutation in cis which is also confirmed from the patient-derived cell lines.

10.
Article | WPRIM | ID: wpr-831068

ABSTRACT

Purpose@#Human epidermal growth factor receptor 2 (HER2) alterations are found in approximately 1%-3% of non-small cell lung cancers (NSCLCs). We evaluated the clinical features and outcomes of NSCLC harboring HER2 alteration detected by next-generation sequencing (NGS) in Korea. @*Materials and Methods@#A total of 1,108 patients who were diagnosed with NSCLC between December 2015 and December 2017 were screened and analyzed by NGS. Medical records were reviewed retrospectively to analyze the clinical characteristics and outcomes from various treatments. @*Results@#HER2 alterations were identified in 36 NSCLC patients. Of the patients, 22 (61.1%) had an exon 20 in-frame insertion mutation, 15 (41.7%) had HER2 amplification, and one had both. The median patient age was 58 years, 55.6% were male, and 50.0% were never-smokers. Adenocarcinoma was predominant (88.9%). The most common metastatic site was bone (58.3%), and 66.7% of patients were stage IV at initial diagnosis. Six patients (16.7%) had a coexistent sensitizing epidermal growth factor receptor (EGFR) mutation, and two patients (5.6%) had anaplastic lymphoma kinase (ALK) rearrangement. With a median 14 months of follow-up, the median progression-free survival of first-line treatment was 6 months (95% confidence interval, 4.172 to 7.828), and median overall survival was not reached. The proportions of adenocarcinoma, never-smokers, and metastasis to the liver were higher in the exon 20 in-frame insertion mutation group, whereas coexistence of EGFR mutation was more frequently found in the HER2 amplification group. @*Conclusion@#HER2-altered NSCLC showed distinct clinical features. Moreover, different characteristics were identified between the HER2 in-frame insertion mutation group and the HER2 amplification group.

11.
Article | WPRIM | ID: wpr-831026

ABSTRACT

Background@#: The Guideline Working Group of the Korean Society for Neuro-Oncology (KSNO)conducted a nationwide questionnaire survey for diverse queries faced in the treatment of brain tumors.As part I of the survey, the aim of this study is to evaluate national patterns of clinical practiceabout antiepileptic drug (AED) and steroid usage for management of brain tumors. @*Methods@#: A web-based survey was sent to all members of the KSNO by email. The survey included9 questions of AED usage and 5 questions of steroid usage for brain tumor patients. All questionswere developed by consensus of the Guideline Working Group. @*Results@#: The overall response rate was 12.8% (54/423). Regarding AED usage, the majority ofrespondents (95.2%) routinely prescribed prophylactic AEDs for patients with seizure at the peri/postoperativeperiod. However, as many as 72.8% of respondents prescribed AED routinely for seizure-naïvepatients, and others prescribed AED as the case may be. The duration of AED prophylaxis showedwide variance according to the epilepsy status and the location of tumor. Levetiracetam (82.9%) wasthe most preferred AED for epilepsy prophylaxis. Regarding steroid usage, 90.5% of respondents usesteroids in perioperative period, including 34.2% of them as a routine manner. Presence of peritumoraledema (90.9%) was considered as the most important factor determining steroid usage followed bydegree of clinical symptoms (60.6%). More than half of respondents (51.2%) replied to discontinue thesteroids within a week after surgery if there are no specific medical conditions, while 7.3% preferredslow tapering up to a month after surgery. @*Conclusion@#: The survey demonstrated the prevailing practice patterns on AED and steroid usagein neuro-oncologic field among members of the KSNO. This information provides a point of referencefor establishing a practical guideline in the management of brain tumor patients.

12.
Article | WPRIM | ID: wpr-831025

ABSTRACT

Background@#: The Guideline Working Group of the Korean Society for Neuro-Oncology (KSNO)conducted a nationwide questionnaire survey for diverse queries faced in the treatment of brain tumors.As part II of the survey, the aim of this study is to evaluate the national patterns of clinical practicefor patients with diffuse midline glioma and meningioma. @*Methods@#: A web-based survey was sent to all members of the KSNO by email. The survey included4 questions of diffuse midline glioma and 6 questions of meningioma (including 2 case scenarios).All questions were developed by consensus of the Guideline Working Group. @*Results@#: In the survey about diffuse midline glioma, 76% respondents performed histologicconfirmation to identify H3K27M mutation on immunohistochemical staining or sequencing methods.For treatment of diffuse midline glioma, respondents preferred concurrent chemoradiotherapy withtemozolomide (TMZ) and adjuvant TMZ (63.8%) than radiotherapy alone (34.0%). In the surveyabout meningioma, respondents prefer wait-and-see policy for the asymptomatic small meningiomawithout peritumoral edema. However, a greater number of respondents had chosen surgical resectionas the first choice for all large size meningiomas without exception, and small size meningiomaswith either peritumoral edema or eloquent location. There was no single opinion with major consensuson long-term follow-up plans for asymptomatic meningioma with observation policy. As many as68.1% of respondents answered that they would not add any adjuvant therapies for World Health Organizationgrade II meningiomas if the tumor was totally resected including dura. @*Conclusion@#: The survey demonstrates the prevailing clinical practice patterns for patients with diffusemidline glioma and meningioma among members of the KSNO. This information provides a pointof reference for establishing a practical guideline in the management of diffuse midline glioma andmeningioma.

13.
Article | WPRIM | ID: wpr-831024

ABSTRACT

Background@#: The Guideline Working Group of the Korean Society for Neuro-Oncology (KSNO)conducted the nationwide questionnaire survey for diverse queries facing to treat patients with braintumor. As part III of the survey, the aim of this study is to evaluate the national patterns of clinical practicefor patients with brain metastasis and primary central nervous system lymphoma (PCNSL). @*Methods@#: A web-based survey was sent to all members of the KSNO by email. The survey included7 questions of brain metastasis and 5 questions of PCNSL, focused on the management strategiesin specific situations. All questions were developed by consensus of the Guideline WorkingGroup. @*Results@#" In the survey about brain metastasis, respondents preferred surgical resection withadjuvant treatment for patients with a surgically accessible single brain metastatic lesion less than 3cm in size without extracranial systemic lesions. However, most respondents considered radiosurgeryfor surgically inaccessible lesions. As the preferred treatment of multiple brain metastases according tothe number of brain lesions, respondents tended to choose radiotherapy with increasing number of lesions.Radiosurgery was mostly chosen for the brain metastases of less than or equal to 4. In the surveyabout PCNSL, a half of respondents choose high-dose methotrexate-based polychemotherapy asthe first-line induction therapy for PCNSL. The consolidation and salvage therapy showed a little variationamong respondents. For PCNSL patients with cerebrospinal fluid dissemination, intrathecal chemotherapywas most preferred. @*Conclusion@#: The survey demonstrates the prevailing clinical practice patterns for patients withbrain metastasis and PCNSL among members of the KSNO. This information provides a point of referencefor establishing a practical guideline in the management of brain metastasis and PCNSL.

14.
Article | WPRIM | ID: wpr-832731

ABSTRACT

Background@#The use of makeup is popular among Korean adolescents. With the increased use of color cosmetics, there are concerns that heavy application may cause skin problems or aggravate acne, a condition highly prevalent in this age group. Other than makeup, cosmetic products targeting acne are also easily accessible and often used. Currently, little is known about the use of these products in Korean middle school students and their understanding of its effect on the skin. @*Objective@#This study investigated the prevalence of “color cosmetics” and cosmetics targeting acne” among Korean students and their awareness of the effects of these products on their skin.Method: A questionnaire survey was conducted of 192 students from Dawon Middle School in Hwasung. The questionnaire consisted of detailed inquiries regarding the use of color cosmetics and cosmetics targeting acne and their effect on the skin. @*Results@#A total of 192 responses were analyzed. Sixty-three (32.8%) students reported experience with putting on makeup. Among these 63 students, 35 (55.5%) responded that their skin condition had worsened after applying makeup, which was associated with the frequency and extent of color cosmetic use (p<0.05). Among the 106 (52.2%) students with acne, 63% reported having tried acne-targeting cosmetics. Approximately 14.3% of this population reported feeling very satisfied with the effect of these cosmetics on acne. @*Conclusion@#The results of our study indicated that a significant percentage of middle school adolescents are using makeup. As skin troubles may arise with the use of color cosmetics, an educational guide on minimizing application and properly removing the products should be provided to this population. Acne is highly prevalent in adolescents and cosmetics targeting acne are easily accessible. The belief that acne-targeting cosmetics can replace hospital treatment can be risky and should be thoroughly explained by dermatologists.

15.
Article in English | WPRIM | ID: wpr-763145

ABSTRACT

PURPOSE: This study was conducted to evaluate the relationship between epidermal growth factor receptor (EGFR) mutation and clinical outcomes in patients with stage III non-squamous cell lung cancer treated with definitive concurrent chemoradiotherapy (CCRT). MATERIALS AND METHODS: From January 2008 to December 2013, the medical records of 197 patients with stage III non- squamous non-small cell lung cancer treated with definitive CCRT were analyzed to determine progression-free survival (PFS) and overall survival (OS) according to EGFR mutation status. RESULTS: Among 197 eligible patients, 81 patients were EGFR wild type, 36 patients had an EGFR mutation (exon 19 Del, n=18; L858R, n=9, uncommon [G719X, L868, T790M], n=9), and 80 patients had unknown EGFR status. The median age was 59 years (range, 28 to 80 years) and 136 patients (69.0%) were male. The median follow-up duration was 66.5 months (range, 1.9 to 114.5 months). One hundred sixty-four patients (83.2%) experienced disease progression. Median PFS was 8.9 months for the EGFR mutation group, 11.8 months for EGFR wild type, and 10.5 months for the unknown EGFR group (p=0.013 and p=0.042, respectively). The most common site of metastasis in the EGFR mutant group was the brain. However, there was no significant difference in OS among the three groups (34.6 months for EGFR mutant group vs. 31.9 months for EGFR wild type vs. 22.6 months for EGFR unknown group; p=0.792 and p=0.284). A total of 29 patients (80.6%) with EGFR mutation were treated with EGFR tyrosine kinase inhibitor (gefitinib, n=24; erlotinib, n=3; afatinib, n=2) upon progression. CONCLUSION: EGFR mutation is associatedwith short PFS and the brain is the most common site of distant metastasis in patients with stage III non- squamous cell lung cancer treated with CCRT.


Subject(s)
Brain , Carcinoma, Non-Small-Cell Lung , Chemoradiotherapy , Disease Progression , Disease-Free Survival , Epithelial Cells , Erlotinib Hydrochloride , Follow-Up Studies , Humans , Lung Neoplasms , Lung , Male , Medical Records , Neoplasm Metastasis , Protein-Tyrosine Kinases , ErbB Receptors
16.
Article in English | WPRIM | ID: wpr-763144

ABSTRACT

PURPOSE: We tried to evaluate whether there are any specific features in treatment outcomes of firstline afatinib in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC), compared with gefitinib or erlotinib. MATERIALS AND METHODS: We analyzed patients treated with first-line afatinib, gefitinib, or erlotinib for advanced EGFR-mutant NSCLC at Samsung Medical Center between 2014 and 2016. RESULTS: In total, 467 patients received first-line afatinib (n=165), gefitinib (n=230), or erlotinib (n=72). Afatinib was used more often in patients with tumors harboring deletion in exon 19 (Del19), whereas the gefitinib group had more elderly, females, and never smokers. The median progression-free survival (PFS) time for afatinib, gefitinib, and erlotinib was 19.1 months, 13.7 months, and 14.0 months, respectively (p=0.001). The superior PFS of afatinib was more remarkable in subgroups of Del19 or uncommon EGFR mutations. Overall toxicity profiles of the three drugs were comparable, though more grade 3 or 4 toxicities were detected in afatinib (7.3%) compared with gefitinib (2.6%) or erlotinib (1.8%). The common grade 3 or 4 toxicities of afatinib included diarrhea (3.0%), paronychia (2.4%), and skin rash (1.8%). Dose modification was more frequently required in patients treated with afatinib (112/165, 68%), compared with gefitinib (5/230, 2%) and erlotinib (4/72, 6%). Interestingly, however, dose reduction in the afatinib group did not impair its efficacy in terms of PFS (dose reduction vs. no reduction group, 23.5 months vs. 12.4 months). CONCLUSION: First-line afatinib showed satisfactory efficacy data and manageable toxicity profiles.


Subject(s)
Aged , Carcinoma, Non-Small-Cell Lung , Diarrhea , Disease-Free Survival , Erlotinib Hydrochloride , Exanthema , Exons , Female , Humans , Paronychia , ErbB Receptors
17.
Article in English | WPRIM | ID: wpr-763132

ABSTRACT

PURPOSE: Epidermal growth factor receptor (EGFR) exon 20 insertion mutations account for approximately 4% of all EGFR mutations. Given the rarity of this mutation, its clinical outcomes are not fully established. MATERIALS AND METHODS: Between 2009 and 2017, non-small cell lung cancer (NSCLC) patients who showed an exon 20 insertion were retrospectively reviewed for clinical characteristics and outcomes, including responses to chemotherapy (CTx) or targeted therapy. RESULTS: Of 3,539 NSCLC patients who harbored an activating EGFR mutation, 56 (1.6%) had an exon 20 insertion. Of the advanced NSCLC patients, 27 of 1,479 (1.8%) had an exon 20 insertion. The median overall survival was 29.4 months (95% confidence interval 9.3 to 49.6) for 27 advancedNSCLC patients. The 22 patientswho received systemic CTx achieved a 50.0% response rate and a 77.2% disease control rate, with 4.2 months of progression-free survival. Six patients received EGFR tyrosine kinase inhibitors (TKIs). Three of the four patients that had only an exon 20 insertion showed progressive disease, while one showed stable disease. The othertwo patients had an exon 20 insertion and another EGFR mutation and achieved a partial response. CONCLUSION: The incidence of an exon 20 insertion mutation is rare in Korea and occasionally accompanied by other common EGFR mutations. Although the response to systemic CTx. in these patients is comparable to that of patients with other mutations, the response rate to first- or second-generation EGFR TKIs is quite low. Therefore, the development of a more efficient agent is urgently needed.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Disease-Free Survival , Drug Therapy , Exons , Humans , Incidence , Korea , Mutagenesis, Insertional , Protein-Tyrosine Kinases , ErbB Receptors , Retrospective Studies
18.
Article in English | WPRIM | ID: wpr-763124

ABSTRACT

PURPOSE: The optimal cytotoxic regimens have not been established for patients with non-small cell lung cancer (NSCLC) who develop disease progression on first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). MATERIALS AND METHODS: We conducted a multi-center randomized phase II trial to compare the clinical outcomes between pemetrexed plus cisplatin combination therapy followed by maintenance pemetrexed (PC) and pemetrexed monotherapy (P) after failure of first-line EGFR-TKI. The primary objective was progression-free survival (PFS), and secondary objectives included overall response rate (ORR), overall survival (OS), health-related quality of life (HRQOL), and safety and toxicity profiles. RESULTS: A total of 96 patientswere randomized, and 91 patientswere treated at 14 centers in Korea. The ORR was 34.8% (16/46) for the PC arm and 17.8% (8/45) for the P arm (p=0.066). With 23.4 months of follow-up, the median PFS was 5.4 months in the PC arm and 6.4 months in the P arm (p=0.114). The median OS was 17.9 months and 15.7 months in PC and P arms, respectively (p=0.787). Adverse events ≥ grade 3 were reported in 12 patients (26.1%) in the PC arm and nine patients (20.0%) in the P arm (p=0.491). The overall time trends of HRQOL were not significantly different between the two arms. CONCLUSION: The outcomes of pemetrexed therapy in NSCLC patients with disease progression after firstline EGFR-TKI might not be improved by adding cisplatin.


Subject(s)
Arm , Carcinoma, Non-Small-Cell Lung , Cisplatin , Disease Progression , Disease-Free Survival , Epidermal Growth Factor , Follow-Up Studies , Humans , Korea , Lung Neoplasms , Lung , Pemetrexed , Protein-Tyrosine Kinases , Quality of Life , ErbB Receptors , Tyrosine
19.
Safety and Health at Work ; : 103-108, 2019.
Article in English | WPRIM | ID: wpr-761330

ABSTRACT

BACKGROUND: This study was designed to provide logical backgrounds for the revision of biological exposure indices (BEIs) for styrene exposure in Korea. In order to investigate the correlation between airborne styrene and biological exposure indices, we measured urinary mandelic acid (MA) and phenylglyoxylic acid (PGA) in workers exposed to styrene occupationally, as well as airborne styrene at workplaces. METHODS: Surveys were conducted for 56 subjects. The concentrations of airborne styrene and urinary metabolites of styrene were measured in 36 workers who were occupationally exposed to styrene, and in 20 controls. Air samples were collected using personal air samplers and analyzed by gas chromatography. Urine samples were collected at the end of the shift and analyzed by high performance liquid chromatography. RESULTS: The geometric mean concentration of airborne styrene was 9.6 ppm. The concentrations of urinary MA, PGA, and MA+PGA in the exposure group were 267.7, 143.3, and 416.8 mg/g creatinine, respectively. The correlation coefficients for correlation between airborne styrene and MA, PGA, and MA+PGA were 0.714, 0.604, and 0.769, respectively. The sum of urinary MA and PGA corresponding to an exposure of 20 ppm styrene was 603 mg/g creatinine. CONCLUSION: The correlation of the sum of urinary MA and PGA with airborne styrene was better than the correlation of each individual urinary determinant. It is considered appropriate to amend the concentration of urinary MA+PGA to 600 mg/g creatinine as a BEI, which corresponds to an airborne styrene concentration of 20 ppm in Korea.


Subject(s)
Chromatography, Gas , Chromatography, Liquid , Creatinine , Humans , Korea , Logic , Occupations , Styrene
20.
Article in English | WPRIM | ID: wpr-719428

ABSTRACT

PURPOSE: With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data. MATERIALS AND METHODS: To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared. RESULTS: We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration. CONCLUSION: In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.


Subject(s)
Academies and Institutes , Asian Continental Ancestry Group , DNA , Humans , Korea , Methods , Paraffin , Point Mutation , Precision Medicine , Prevalence
SELECTION OF CITATIONS
SEARCH DETAIL