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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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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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Purpose@#This study aimed to confirm the decision-making patterns for life-sustaining treatment (LST) and analyze medical service utilization changes after enforcement of the Life-Sustaining Treatment Decision-Making Act. @*Materials and Methods@#Of 1,237 patients who completed legal forms for life-sustaining treatment (hereafter called the LST form) at three academic hospitals and died at the same institutions, 1,018 cancer patients were included. Medical service utilization and costs were analyzed using claims data. @*Results@#The median time to death from completion of the LST form was three days (range, 0 to 248 days). Of these, 517 people died within two days of completing the document, and 36.1% of all patients prepared the LST form themselves. The frequency of use of the intensive care unit, continuous renal replacement therapy, and mechanical ventilation was significantly higher when the families filled out the form without knowing the patient’s intention. In the top 10% of the medical expense groups, the decision-makers for LST were family members rather than patients (28% patients vs. 32% family members who knew and 40% family members who did not know the patient’s intention). @*Conclusion@#The cancer patient’s own decision-making rather than the family’s decision was associated with earlier decision-making, less use of some critical treatments (except chemotherapy) and expensive evaluations, and a trend toward lower medical costs.
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Advances in medical technology have increased people’s lifespans, and evidence-based medicine that utilizes health technology assessments has contributed significantly to medical development. Owing to the ever-increasing costs of medical services, cost-effectiveness analysis has been adopted to ensure the efficient use of limited healthcare resources.However, problems that cannot be solved through medical technology alone have emerged because of the aging of the global population. When faced with a choice providing lifesustaining treatment to a terminally ill patient or offering them comfortable end-of-life care in a hospice, value-based choice takes precedence over technical judgment.In addition to cost, various values must be considered when making medical decisions. The World Health Organization (WHO) and the Organization for Economic Cooperation and Development (OECD) expect “value-based healthcare” (VBHC) to play a major role in solving these problems. 1 However, the concept itself remains vague and has not attracted significant attention in the field of medicine.
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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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Background/Aims@#Adenoid cystic carcinoma (ACC) is a rare salivary gland tumor characterized by indolence, with a high rate of local recurrence and distant metastasis. This study aimed to investigate the effect of concurrent chemoradiation (CCRT) on locally advanced unresectable ACC. @*Methods@#We retrospectively analyzed clinical data from 10 patients with pathologically confirmed ACC of the head and neck who received CCRT with cisplatin in Seoul National University Hospital between 2013 and 2018. @*Results@#Ten patients with unresectable disease at the time of diagnosis or with positive margins after surgical resection received CCRT with weekly cisplatin. Eight patients (80%) achieved complete remission, of which three later developed distant metastases without local relapse; one patient developed distant metastasis and local relapse. Two patient achieved partial remission without progression. Patients experienced several toxicities, including dry mouth, radiation dermatitis, nausea, and salivary gland inflammation of mostly grade 1 to 2. Only one patient showed grade 3 oral mucositis. Median relapse-free survival was 34.5 months (95% confidence interval, 22.8 months to not reached). @*Conclusions@#CCRT with cisplatin is effective for local control of ACC with manageable toxicity and may be an effective treatment option for locally advanced unresectable ACC.
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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@#This study aimed to investigate difficulties doctors experience during life-sustaining treatment (LST) discussion with seriously ill patients and their families after enactment of the LST Decisions Act in February 2018. @*Materials and Methods@#A cross-sectional survey was conducted in a tertiary hospital in the Republic of Korea in August 2019. Six hundred eighty-six doctors who care for seriously ill patients were given a structured questionnaire, and difficulties during the discussion were examined. @*Results@#One hundred thirty-two doctors completed the questionnaire. Eighty-five percent answered they treat cancer patients. Most (86.4%) experienced considerable difficulties during LST discussions (mean score, 7.4±1.6/10). The two most common difficulties were communication with patients and family and determining when to discuss LST. Two-thirds of doctors found direct discussions with the patient difficult and said they would initiate LST discussions only with family. LST discussions were actually initiated later than considered appropriate. When medically assessing whether the patient is imminently dying, 56% of doctors experienced disagreements with other doctors, which could affect their decisions. @*Conclusion@#This study found that most doctors experienced serious difficulties regarding communication with patients and family and medical assessment of dying process during LST discussions. To alleviate these difficulties, further institutional support is needed to improve the LST discussion between doctors, patients, and family.
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Purpose@#This study aimed to investigate difficulties doctors experience during life-sustaining treatment (LST) discussion with seriously ill patients and their families after enactment of the LST Decisions Act in February 2018. @*Materials and Methods@#A cross-sectional survey was conducted in a tertiary hospital in the Republic of Korea in August 2019. Six hundred eighty-six doctors who care for seriously ill patients were given a structured questionnaire, and difficulties during the discussion were examined. @*Results@#One hundred thirty-two doctors completed the questionnaire. Eighty-five percent answered they treat cancer patients. Most (86.4%) experienced considerable difficulties during LST discussions (mean score, 7.4±1.6/10). The two most common difficulties were communication with patients and family and determining when to discuss LST. Two-thirds of doctors found direct discussions with the patient difficult and said they would initiate LST discussions only with family. LST discussions were actually initiated later than considered appropriate. When medically assessing whether the patient is imminently dying, 56% of doctors experienced disagreements with other doctors, which could affect their decisions. @*Conclusion@#This study found that most doctors experienced serious difficulties regarding communication with patients and family and medical assessment of dying process during LST discussions. To alleviate these difficulties, further institutional support is needed to improve the LST discussion between doctors, patients, and family.
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Purpose@#We aimed to refine the radiotherapy (RT) volume and dose for intracranial germinoma considering recurrences and long-term toxicities. @*Materials and Methods@#Total 189 patients with intracranial germinoma were treated with RT alone (n=50) and RT with upfront chemotherapy (CRT) (n=139). All cases were confirmed histologically. RT fields comprised the extended-field and involved-field only for primary site. The extended-field, including craniospinal, whole brain (WB), and whole ventricle (WV) for cranial field, is followed by involved-field boost. The median follow-up duration was 115 months. @*Results@#The relapses developed in 13 patients (6.9%). For the extended-field, cranial RT dose down to 18 Gy exhibited no cranial recurrence in 34 patients. In CRT, 74 patients (56.5%) showed complete response to chemotherapy and no involved-field recurrence with low-dose RT of 30 Gy. WV RT with chemotherapy for the basal ganglia or thalamus germinoma showed no recurrence. Secondary malignancy developed in 10 patients (5.3%) with a latency of 20 years (range, 4 to 26 years) and caused mortalities in six. WB or craniospinal field rather than WV or involved-field significantly increased the rate of hormone deficiencies, and secondary malignancy. RT dose for extended-field correlated significantly with the rate of hormone deficiencies, secondary malignancy, and neurocognitive dysfunction. @*Conclusion@#De-intensifying extended-field rather than involved-field or total scheme of RT will be critical to decrease the late toxicities. Upfront chemotherapy could be beneficial for the patients with complete response to minimize the RT dose down to 30 Gy. Prospective trials focused on de-intensification of the extended-field RT are warranted.
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Purpose@#This study was aim to evaluate the patterns of failure according to radiotherapy (RT) target volume for cervical lymph nodes in metastases of unknown primary origin in head and neck region (HNMUO). @*Materials and Methods@#Sixty-two patients with HNMUO between 1998 and 2016 were retrospectively reviewed. We analyzed the clinical outcomes and primary site failure depending on the radiation target volume. The target volume was classified according to whether the potential head and neck mucosal sites were included and whether the neck node was treated involved side only or bilaterally. @*Results@#Potential mucosal site RT (mucosal RT) was done to 23 patients and 39 patients did not receive mucosal RT. Mucosal RT showed no significant effect on overall survival (OS) and locoregional recurrence (LRR). The location of primary site failure encountered during follow-up period was found to be unpredictable and 75% of patients with recurrence received successful salvage therapies. No significant differences in OS and LRR were found between patients treated to unilateral (n = 35) and bilateral neck irradiation (n = 21). Treatment of both necks resulted in significantly higher mucositis. @*Conclusions@#We found no advantages in OS and LRR of patients with HNMUO when mucosal sites and bilateral neck node were included in the radiation target volume.
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Purpose@#Life-sustaining treatment (LST) decisions for patients and caregivers at the end-of-life (EOL) process are supported by the “Act on Hospice and Palliative Care and Decisions on LST for Patients at the EOL,” enforced in February 2018. Itremains unclearwhetherthe act changes EOL decisions and LST implementation in clinical practice. For this study, we investigated patients’ decision-making regarding LSTs during the EOL process since the act’s enforcement. @*Materials and Methods@#Retrospective reviews were conducted on adult patients who were able to decide to terminate LST and died at Seoul National University Hospital between February 5, 2018, and February 5, 2019. We examined demographics, who made the decisions, the type and date of documentation confirming patient's LST, and whether the LST was withheld or withdrawn. @*Results@#Of 809 patients who were enrolled, 29% (n=231) completed forms regarding LST themselves, and 71% (n=578) needed family members to decide. The median time from confirmation of the EOL process to death and from the Advance Statement to death were 2 and 5 days, respectively (both ranges, 0 to 244). In total, 90% (n=727) of patients withheld treatment, and 10% (n=82)withdrewit. We found a higherwithdrawalratewhen family members made the decisions (13.3% vs. 1.7%, p < 0.001). @*Conclusion@#After the act’s enforcement, withdrawing LSTs became lawful and self-determination rates increased. Family members still make 71% of decisions regarding LSTs, but these are often inconsistent with the patients’ wishes; thus, further efforts are needed to integrate the new act into clinical practice.
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PURPOSE: The purpose of this study was to evaluate the relationships between the resistance of anaplastic lymphoma kinase (ALK)‒positive non-small cell lung cancer (NSCLC) to ALK inhibitors and the programmed cell death-1/programmed cell death–ligand 1 (PD-L1) pathway, we evaluated alterations in PD-L1 following acquisition of resistance to ALK inhibitors in ALK-positive lung cancer. MATERIALS AND METHODS: We established ALK inhibitor-resistant cell lines (H3122CR1, LR1, and CH1) by exposing the parental H3122 ALK-translocated NSCLC cell line to ALK inhibitors. Then, the double-resistant cell lines H3122CR1LR1 and CR1CH1 were developed by exposing the H3122CR1 to other ALK inhibitors. We compared the alterations in PD-L1 expression levels using western blotting, flow cytometry, and quantitative polymerase chain reaction. We also investigated gene expression using RNA sequencing. The expression of PD-L1 in the tumors from 26 ALK-positive metastatic NSCLC patients (11 ALK inhibitor-naïve and 15 ALK inhibitor-resistant patients) was assessed by immunohistochemistry and analyzed. RESULTS: PD-L1 was expressed at higher levels in ALK inhibitor-resistant cell lines than in the ALK inhibitor-naïve parental cell line at the total protein, surface protein, and mRNA levels. Furthermore, PD-L1 expression in the double-resistant cell lines was much higher than that in the single resistant cell lines. RNA sequencing demonstrated that expression of immune-related genes were largely involved in ALK inhibitor resistance. The mean value of the PD-L1 H-score was 6.5 pre-treatment and 35.0 post-treatment, and the fold difference was 5.42 (p=0.163). CONCLUSION: PD-L1 expression increased following acquisition of ALK inhibitor resistance in ALK-positive NSCLC cell lines and tumors.
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Humanos , Antígeno B7-H1 , Western Blotting , Carcinoma de Pulmón de Células no Pequeñas , Línea Celular , Resistencia a Medicamentos , Citometría de Flujo , Expresión Génica , Inmunohistoquímica , Neoplasias Pulmonares , Pulmón , Linfoma , Padres , Fosfotransferasas , Reacción en Cadena de la Polimerasa , ARN Mensajero , Análisis de Secuencia de ARNRESUMEN
PURPOSE: Amplified mesenchymal-epithelial transition factor, MET, is a receptor tyrosine kinase (RTK) that has been considered a druggable target in non-small cell lung cancer (NSCLC). Although multiple MET tyrosine kinase inhibitors (TKIs) are being actively developed for MET-driven NSCLC, the mechanisms of acquired resistance to MET-TKIs have not been well elucidated. To understand the mechanisms of resistance and establish therapeutic strategies, we developed an in vitro model using the MET-amplified NSCLC cell line EBC-1. MATERIALS AND METHODS: We established capmatinib-resistant NSCLC cell lines and identified alternative signaling pathways using 3′ mRNA sequencing and human phospho-RTK arrays. Copy number alterations were evaluated by quantitative polymerase chain reaction and cell proliferation assay; activation of RTKs and downstream effectors were compared between the parental cell line EBC-1 and the resistant cell lines. RESULTS: We found that EBC-CR1 showed an epidermal growth factor receptor (EGFR)‒dependent growth and sensitivity to afatinib, an irreversible EGFR TKI. EBC-CR2 cells that had overexpression of EGFR-MET heterodimer dramatically responded to combined capmatinib with afatinib. In addition, EBC-CR3 cells derived from EBC-CR1 cells that activated EGFR with amplified phosphoinositide-3 kinase catalytic subunit α (PIK3CA) were sensitive to combined afatinib with BYL719, a phosphoinositide 3-kinase α (PI3Kα) inhibitor. CONCLUSION: Our in vitro studies suggested that activation of EGFR signaling and/or genetic alteration of downstream effectors like PIK3CA were alternative resistance mechanisms used by capmatinib-resistant NSCLC cell lines. In addition, combined treatments with MET, EGFR, and PI3Kα inhibitors may be effective therapeutic strategies in capmatinib-resistant NSCLC patients.
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Humanos , Carcinoma de Pulmón de Células no Pequeñas , Dominio Catalítico , Línea Celular , Proliferación Celular , Técnicas In Vitro , Padres , Fosfotransferasas , Reacción en Cadena de la Polimerasa , Proteínas Tirosina Quinasas , Receptores ErbB , ARN MensajeroRESUMEN
PURPOSE: We first analyzed the prognostic power of albumin-to-alkaline phosphatase ratio (AAPR) before radical radiotherapy (RT) in non-metastatic nasopharyngeal carcinoma (NPC) patients. MATERIALS AND METHODS: The records of 170 patients with biopsy-proven, non-metastatic NPC treated by radical RT between 1998 and 2016 at our institution were retrospectively reviewed. Median follow-up duration was 50.6 months. All patients received intensity-modulated RT and cisplatin based chemotherapy before, during, or after RT. The major treatment of patients was based on concurrent chemoradiotherapy (92.4%). The AAPR was calculated by the last value of both albumin and alkaline phosphatase within 1 month immediately preceding RT. The optimal cut-off level of AAPR was determined by using Cutoff Finder, a web-based system. Propensity score matching (PSM) analysis was performed. RESULTS: The optimal cut-off level of AAPR was 0.4876. After PSM analysis of whole cohort, an AAPR was not related to survival outcomes. In PSM analysis for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC), an AAPR ≥ 0.4876 was related to better overall survival (OS), progression-free survival (PFS), and locoregional relapse–free survival (LRRFS) (OS: hazard ratio [HR], 0.341; 95% confidence interval [CI], 0.144 to 0.805; p=0.014; PFS: HR, 0.416; 95% CI, 0.189 to 0.914; p=0.029; and LRRFS: HR, 0.243; 95% CI, 0.077 to 0.769; p=0.016, respectively). CONCLUSION: The AAPR, inexpensive and readily derived from a routine blood test, could be an independent prognostic factor for patients with LA-NPC. And it might help physicians determine treatment plans by identifying the patient's current status. Future prospective clinical trials to validate its prognostic value are needed.
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Humanos , Fosfatasa Alcalina , Quimioradioterapia , Cisplatino , Estudios de Cohortes , Supervivencia sin Enfermedad , Quimioterapia , Estudios de Seguimiento , Pruebas Hematológicas , Pronóstico , Puntaje de Propensión , Estudios Prospectivos , Radioterapia , Estudios RetrospectivosRESUMEN
PURPOSE: Physician competency in end-of-life (EOL) care is becoming increasingly important. This study investigated the EOL care curricula in Korean medical schools.METHODS: Questionnaires were issued to the faculty members responsible for the EOL care curricula at each of the medical schools. These included questions on the structure and content of the curricula, teaching methods, and faculty members' attitudes to the curricula.RESULTS: Characteristics of the EOL care curricula were compiled from 27 (66%) of the 41 medical schools. All of the medical schools taught essential aspects of the EOL care curriculum either as a separate course or embedded within other medical education courses. The mean time spent on EOL care teaching was 10 hrs (range, 2~32 hrs). The most frequently taught topics were delivering bad news (100%) and symptom management (74%). When the palliative care education assessment tool (PEAT) was used to evaluate the curricula, a median of 11 PEAT objectives was met (range, 2~26; maximum, 83). More than two teaching methods were used in most of the curricula. However, lectures were the only teaching method used by three medical schools. 78% of faculty members who were responsible for curriculum reported dissatisfaction with it, whereas 18% believed that the time allotted to it was adequate. Only 7% of these faculty members believed that their students were adequately prepared to practice EOL care.CONCLUSION: There is a need to improve EOL care education in basic medical curricula and to take a more systematic approach to achieving learning outcomes.
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Humanos , Curriculum , Educación , Educación Médica , Cuidados Paliativos al Final de la Vida , Aprendizaje , Clase , Cuidados Paliativos , Facultades de Medicina , Suelo , Enseñanza , Cuidado TerminalRESUMEN
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.
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Humanos , Carcinoma de Pulmón de Células no Pequeñas , Quimioterapia , Clorhidrato de Erlotinib , Herpes Zóster , Incidencia , Métodos , Proteínas Tirosina Quinasas , Receptores ErbB , Seúl , TirosinaRESUMEN
PURPOSE: This randomized phase III study was designed to compare the efficacy and safety of irinotecan plus cisplatin (IP) over etoposide plus cisplatin (EP) in Korean patients with extensive-disease small-cell lung cancer (SCLC). MATERIALS AND METHODS: Patients were randomly assigned to receive IP, composed of irinotecan 65 mg/m2 intravenously on days 1 and 8+cisplatin 70 mg/m2 intravenously on day 1 every 3 weeks, or EP, composed of etoposide 100 mg/m2 intravenously on days 1, 2, 3+cisplatin 70 mg/m2 intravenously on day 1, every 3 weeks for a maximum of six cycles, until disease progression, or until unacceptable toxicity occurred. The primary endpoint was overall survival. RESULTS: A total of 362 patients were randomized to IP (n=173) and EP (n=189) arms. There were no significant differences between IP and EP arms for the median overall survival (10.9 months vs. 10.3 months, p=0.120) and the median progression-free survival (6.5 months vs. 5.8 months, p=0.115). However, there was a significant difference in response rate (62.4% vs. 48.2%, p=0.006). The pre-planned subgroup analyses showed that IP was associated with longer overall survival in male (11.3 months vs. 10.1 months, p=0.036), < 65 years old (12.7 months vs. 11.3 months, p=0.024), and Eastern Cooperative Oncology Group performance status 0/1 (12.4 months vs. 10.9 months, p=0.040) patient groups. The severity of treatment-related adverse events such as grade 3/4 anemia, nausea and diarrhea was more frequent in patients treated with IP. CONCLUSION: The IP chemotherapy did not significantly improve the survival compared with EP chemotherapy in Korean patients with extensive-disease SCLC.
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Humanos , Masculino , Anemia , Brazo , Cisplatino , Diarrea , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Quimioterapia , Etopósido , Neoplasias Pulmonares , Náusea , Carcinoma Pulmonar de Células PequeñasRESUMEN
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.