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Purpose@#Long-course chemoradiotherapy (LCRT) has been widely recommended in a majority of rectal cancer patients. Recently, encouraging data on short-course radiotherapy (SCRT) for rectal cancer has emerged. In this study, we aimed to compare these two methods in terms of short-term outcomes and cost analysis under the Korean medical insurance system. @*Materials and Methods@#Sixty-two patients with high-risk rectal cancer, who underwent either SCRT or LCRT followed by total mesorectal excision (TME), were classified into two groups. Twenty-seven patients received 5 Gy×5 with two cycles of XELOX (capecitabine 1000 mg/m 2 and oxaliplatin 130 mg/m 2 every 3 weeks) followed by TME (SCRT group). Thirty-five patients received capecitabine-based LCRT followed by TME (LCRT group). Short-term outcomes and cost estimation were assessed between the two groups. @*Results@#Pathological complete response was achieved in 18.5% and 5.7% of patients in the SCRT and LCRT groups, respectively (p=0.223). The 2-year recurrence-free survival rate did not show significant difference between the two groups (SCRT vs. LCRT:91.9% vs. 76.2%, p=0.394). The average total cost per patient for SCRT was 18% lower for inpatient treatment (SCRT vs. LCRT: $18787 vs. $22203, p<0.001) and 40% lower for outpatient treatment (SCRT vs. LCRT: $11955 vs. $19641, p<0.001) compared to LCRT. SCRT was shown to be the dominant treatment option with fewer recurrences and fewer complications at a lower cost. @*Conclusion@#SCRT was well-tolerated and achieved favorable short-term outcomes. In addition, SCRT showed significant reduction in the total cost of care and distinguished cost-effectiveness compared to LCRT.
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Purpose@#This post-marketing surveillance (PMS) study was conducted to monitor the usage of axitinib (Inlyta) in clinical practice of Korean patients with advanced renal cell carcinoma (RCC) with disease progression during or after a prior systemic therapy in real world. @*Materials and Methods@#In this multicenter, observational study, patients indicated for oral axitinib 5 mg twice daily as second-line therapy for advanced RCC were followed up under routine clinical practices, and their safety and effectiveness outcomes were collected. @*Results@#Between 2012 and 2021, 125 patients were enrolled, and data from 111 patients were analyzed. Median age was 65 years (range, 30 to 84 years), 81% was male, and 110 (99%) had clear cell RCC. The median daily dose of axitinib was 10 mg (range, 4.36 to 15.95 mg) with a median administration period of 5.6 months (range, 15 to 750 days). Eighty-three percentage of patients experienced any grade of adverse events, 71% of which were related to study treatment, including diarrhea (36%), hypertension (21%), stomatitis (17%), decreased appetite (14%), palmar-plantar erythrodysesthesia syndrome (12%), and asthenia (11%). Most adverse events were generally well tolerated and manageable, with 13% of grade ≥ 3. Axitinib dose reduction was required in 20% of the adverse events and discontinuation in 8%. Median progression-free survival was 12.4 months (95% confidence interval [CI], 9.6 to 18.9). Objective responses were observed in 30% of patients (95% CI, 21 to 39) with 4% of complete response and 26% of partial response. @*Conclusion@#No new safety signal was found in the present PMS study of Korean RCC patients. Axitinib showed consistent outcomes in terms of effectiveness and safety confirming that the drug is a valid option for second-line therapy in patients with advanced RCC in a real-world setting.
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Purpose@#We aimed to assess the humoral response to and reactogenicity of coronavirus disease 2019 (COVID-19) vaccination according to the vaccine type and to analyze factors associated with immunogenicity in actively treated solid cancer patients (CPs). @*Materials and Methods@#Prospective cohorts of CPs, undergoing anticancer treatment, and healthcare workers (HCWs) were established. The participants had no history of previous COVID-19 and received either mRNA-based or adenovirus vector–based (AdV) vaccines as the primary series. Blood samples were collected before the first vaccination and after 2 weeks for each dose vaccination. Spike-specific binding antibodies (bAbs) in all participants and neutralizing antibodies (nAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wild-type, Delta, and Omicron variants in CPs were analyzed and presented as the geometric mean titer. @*Results@#Age-matched 20 HCWs and 118 CPs were included in the analysis. The bAb seroconversion rate and antibody concentrations after the first vaccination were significantly lower in CPs than in HCWs. After the third vaccination, antibody levels in CPs with a primary series of AdV were comparable to those in HCWs, but nAb titers against the Omicron variant did not quantitatively increase in CPs with AdV vaccine as the primary series. The incidence and severity of adverse reactions post-vaccination were similar between CPs and HCWs. @*Conclusion@#CPs displayed delayed humoral immune response after SARS-CoV-2 vaccination. The booster dose elicited comparable bAb concentrations between CPs and HCWs, regardless of the primary vaccine type. Neutralization against the Omicron variant was not robustly elicited following the booster dose in some CPs, implying the need for additional interventions to protect them from COVID-19.
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Purpose@#Advanced stage clear cell renal cell carcinoma (ccRCC) involves a poor prognosis. Several studies have reported that dysfunctions in iron metabolism‒related proteins may cause tumor progression and metastasis of this carcinoma. In this study, we investigated the impact of the expression of iron metabolism‒related proteins on patient prognoses in advanced stage ccRCCs. @*Materials and Methods@#All of 143 advanced stage ccRCC specimens were selected following validation with double blind reviews. Several clinicopathological parameters including nuclear grade, perirenal fat invasion, renal sinus fat invasion, vascular invasion, necrosis, and sarcomatoid/rhabdoid differentiation were compared with the expression of ferroportin (FPN), and F-Box and leucine rich repeat protein 5 (FBXL5), by immunohistochemistry. FPN and FBXL5 mRNA level of ccRCC from The Cancer Genome Atlas database were also analyzed for validation. @*Results@#FPN and FBXL5 immunohistochemistry showed membrane and cytoplasmic expression, respectively. Based on the H-score, cases were classified as low or high expression with a cutoff value of 20 for FPN and 15 for FBXL5, respectively. Low expression of FPN and FBXL5 were significantly associated with patient death (p=0.022 and p=0.005, respectively). In survival analyses, low expression of FPN and FBXL5 were significantly associated with shorter overall survival (p=0.003 and p=0.004, respectively). On multivariate analysis, low expression of FBXL5 (hazard ratio, 2.001; p=0.034) was significantly associated with shorter overall survival. @*Conclusion@#FPN and FBXL5 can be used as potential prognostic markers and therapeutic targets for advanced stage ccRCC.
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Purpose@#Adjuvant radiotherapy (RT) has been performed to reduce locoregional failure (LRF) following radical cystectomy for locally advanced bladder cancer; however, its efficacy has not been well established. We analyzed the locoregional recurrence patterns of post-radical cystectomy to identify patients who could benefit from adjuvant RT and determine the optimal target volume. @*Materials and Methods@#We retrospectively reviewed 160 patients with stage ≥ pT3 bladder cancer who were treated with radical cystectomy between January 2006 and December 2015. The impact of pathologic findings, including the stage, lympho-vascular invasion, perineural invasion, margin status, nodal involvement, and the number of nodes removed on failure patterns, was assessed. @*Results@#Median follow-up period was 27.7 months. LRF was observed in 55 patients (34.3%), 12 of whom presented with synchronous local and regional failures as the first failure. The most common failure pattern was distant metastasis (40%). Among LRFs, the most common recurrence site was the cystectomy bed (15.6%). Patients with positive resection margins had a significantly higher recurrence rate compared to those without (28% vs. 10%, p=0.004). The pelvic nodal recurrence rate was < 5% in pN0 patients; the rate of recurrence in the external and common iliac nodes was 12.5% in pN+ patients. The rate of recurrence in the common iliac nodes was significantly higher in pN2–3 patients than in pN0–1 patients (15.2% vs. 4.4%, p=0.04). @*Conclusion@#Pelvic RT could be beneficial especially for those with positive resection margins or nodal involvement after radical cystectomy. Radiation fields should be optimized based on the patient-specific risk factors.
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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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Purpose@#Adjuvant radiotherapy (RT) has been performed to reduce locoregional failure (LRF) following radical cystectomy for locally advanced bladder cancer; however, its efficacy has not been well established. We analyzed the locoregional recurrence patterns of post-radical cystectomy to identify patients who could benefit from adjuvant RT and determine the optimal target volume. @*Materials and Methods@#We retrospectively reviewed 160 patients with stage ≥ pT3 bladder cancer who were treated with radical cystectomy between January 2006 and December 2015. The impact of pathologic findings, including the stage, lympho-vascular invasion, perineural invasion, margin status, nodal involvement, and the number of nodes removed on failure patterns, was assessed. @*Results@#Median follow-up period was 27.7 months. LRF was observed in 55 patients (34.3%), 12 of whom presented with synchronous local and regional failures as the first failure. The most common failure pattern was distant metastasis (40%). Among LRFs, the most common recurrence site was the cystectomy bed (15.6%). Patients with positive resection margins had a significantly higher recurrence rate compared to those without (28% vs. 10%, p=0.004). The pelvic nodal recurrence rate was < 5% in pN0 patients; the rate of recurrence in the external and common iliac nodes was 12.5% in pN+ patients. The rate of recurrence in the common iliac nodes was significantly higher in pN2–3 patients than in pN0–1 patients (15.2% vs. 4.4%, p=0.04). @*Conclusion@#Pelvic RT could be beneficial especially for those with positive resection margins or nodal involvement after radical cystectomy. Radiation fields should be optimized based on the patient-specific risk factors.
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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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Purpose@#We investigated the clinical efficacy of immune checkpoint blocker (ICB) therapy for metastatic or advanced melanoma in Korean patients. As well, we assessed whether the effects of ICBs can be enhanced by combination therapy with palliative radiotherapy (RT). @*Materials and Methods@#We retrospectively reviewed the records of 127 patients with metastatic melanoma who received ICB with or without palliative RT between 2014 and 2018. The melanoma subtypes were classified as follows: chronic sun-damaged (CSD), acral, mucosal, and uveal. The primary endpoint was the objective response rate (ORR). @*Results@#The overall ORR was 15%, with 11 complete and eight partial responses. ORRs for CSD, acral/mucosal, and uveal melanomas were 50%, 16.5%, and 0%, respectively (p=0.009). In addition to the subtype, stage at treatment, total tumor burden at treatment, and ICB type were significantly associated with ORR (all p < 0.05). Palliative RT was administered in 44% of patients during the treatment, and it did not affect ORR. Clinical responders to ICB therapy exhibited significantly higher 1-year progression-free and overall survival rates than nonresponders. @*Conclusion@#ORR for ICB monotherapy in Korean patients with melanoma is relatively modest compared with that in Western patients because the non-CSD subtypes are predominant in the Korean population. Our findings regarding combination therapy with ICB provided a rationale for the initiation of our phase II study (NCT04017897).
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Purpose@#Melanoma is a potentially fatal cutaneous malignancy and regional lymph node (LN) metastases are the most important predictors of mortality. This study aimed to analyze clinical features and risk factors of complications associated with inguinal LN dissection (LND) to establish treatment protocols. @*Methods@#This single-center retrospective study (2000 to 2018) consisted of patients who underwent inguinal area sentinel LN biopsy (SLNB) or LND due to malignant melanoma. Risk factors and outcomes were analyzed. @*Results@#One hundred patients underwent SLNB alone (n=67; patients with negative SLNB), complete LND (CLND) after positive SLNB (n=19), or radical LND without SLNB (n=14). Five-year overall survival and disease-free survival rates among these groups were 87.3%, 57.4%, and 61.9%, and 59.0%, 22.7%, and 28.1%, respectively. The complication rate in the SLNB alone group was lower than the other groups (22.4% vs. 47.4% and 35.7%, respectively; P=0.048). Seroma was the most common complication in the SLNB alone group (15.0%); lymphedema was most common in the CLND after SLNB group (21.1%). Multivariate analysis of risk factors for postoperative complications found the hazard ratio for body mass index >28 kg/m2 was 4.376 (95% confidence interval [CI], 1.243–15.401; P=0.022). The hazard ratio for LND (including CLND after SLNB and radical LND without SLNB) was 3.263 (95% CI, 1.248–8.529; P=0.016). @*Conclusion@#Inguinal LND is a higher risk procedure compared to SLNB and other sites for postoperative complications, irrespective of meticulous surgical techniques. More studies are needed to establish treatment protocols (e.g., observation vs. CLND after a positive SLNB result) and the risks and benefits in Asian populations.
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Purpose@#Melanoma is a potentially fatal cutaneous malignancy and regional lymph node (LN) metastases are the most important predictors of mortality. This study aimed to analyze clinical features and risk factors of complications associated with inguinal LN dissection (LND) to establish treatment protocols. @*Methods@#This single-center retrospective study (2000 to 2018) consisted of patients who underwent inguinal area sentinel LN biopsy (SLNB) or LND due to malignant melanoma. Risk factors and outcomes were analyzed. @*Results@#One hundred patients underwent SLNB alone (n=67; patients with negative SLNB), complete LND (CLND) after positive SLNB (n=19), or radical LND without SLNB (n=14). Five-year overall survival and disease-free survival rates among these groups were 87.3%, 57.4%, and 61.9%, and 59.0%, 22.7%, and 28.1%, respectively. The complication rate in the SLNB alone group was lower than the other groups (22.4% vs. 47.4% and 35.7%, respectively; P=0.048). Seroma was the most common complication in the SLNB alone group (15.0%); lymphedema was most common in the CLND after SLNB group (21.1%). Multivariate analysis of risk factors for postoperative complications found the hazard ratio for body mass index >28 kg/m2 was 4.376 (95% confidence interval [CI], 1.243–15.401; P=0.022). The hazard ratio for LND (including CLND after SLNB and radical LND without SLNB) was 3.263 (95% CI, 1.248–8.529; P=0.016). @*Conclusion@#Inguinal LND is a higher risk procedure compared to SLNB and other sites for postoperative complications, irrespective of meticulous surgical techniques. More studies are needed to establish treatment protocols (e.g., observation vs. CLND after a positive SLNB result) and the risks and benefits in Asian populations.
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PURPOSE: This study was conducted to identify the level of oxaliplatin-induced peripheral neuropathy (OIPN), symptoms, distress, and quality of life (QoL) in gastrointestinal (GI) cancer patients and to identify the factors influencing QoL.METHODS: A total of 123 patients were recruited for this cross-sectional study. Surveys used were the Therapy-Induced Neuropathy Assessment Scale (TNAS) for OIPN, the MD Anderson Symptom Inventory (MDASI-GI) for general symptoms associated with gastrointestinal cancer and its treatment, a distress thermometer, and the Euro Quality of Life Questionnaire 5-Dimensional Classification (EQ-5D) for QoL.RESULTS: The patients were classified into three groups based on their treatment completion time (current, completed less than one year ago, completed more than one year ago). The scores of MDASI-GI and distress were significantly lower in patients who had completed chemotherapy compared to those who were undergoing treatment (p=.04 and .02 respectively). However, TNAS score was significantly higher in patients who completed chemotherapy less than one year ago than the other two groups (p=.001). In multivariate regression models, the OIPN and distress or general symptoms were identified as factors associated with QoL.CONCLUSION: In this study, we identified the symptoms that are factors related to the QoL in patients with GI cancer. In particular, the symptoms of OIPN are reported at significantly increased levels for patients who have finished chemotherapy less than one year ago, so efforts to prevent and manage the symptoms of OIPN are needed in this timeframe. To improve QoL of patients with GI cancer, continuous attention and care are required not only during the treatment of cancer but also after the completion of treatment.
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Humanos , Classificação , Estudos Transversais , Tratamento Farmacológico , Neoplasias Gastrointestinais , Doenças do Sistema Nervoso Periférico , Qualidade de Vida , TermômetrosRESUMO
BACKGROUND: The National Lung Screening Trial (NLST) and NELSON trial showed that low-dose chest computed tomography (LDCT) screening significantly reduced the mortality form lung cancer. Although cancer survivors are known to have high risk for second malignant neoplasm (SMN), the usefulness of LDCT screening for lung cancer in cancer survivors is not clear. METHODS: Between August 2016 and August 2017, 633 long-term colorectal cancer (CRC) survivors visited the survivorship clinic in Cancer Prevention Center, Yonsei Cancer Center, Seoul, Republic of Korea. We surveyed the smoking status and recommended LDCT screening to ever-smoking CRC survivors aged 55–80 years. The participants were classified into three risk groups: risk group 1 (RG1) who met the NLST criteria (Age 55–74 years, ≥ 30 pack-years of smoking, smoking cessation < 15 years); risk group 2 (RG2) who would not meet the NLST criteria but were at increased 6-year risk of lung cancer (PLCOM2012 ≥ 0.0151); risk group 3 (RG3) who did not meet any of the criteria above. RESULTS: Among 176 ever-smoking CRC survivors, 173 (98.3%) were male, 32 (18.2%) were current-smoker, and median age was 66 years (range, 55–79 years). We found 38 positive findings (non-calcified nodule ≥ 4 mm), 8 clinically significant findings, 66 minor abnormalities, and 64 negative findings on LDCT. Positive findings were identified in 15 of 79 (19.0%) of RG1, in 9 of 36 (25%) of RG2, and in 14 of 61 (23.0%) of RG3. Second primary lung cancers were found in 2 patients of RG2, and in 1 patient of RG3. SMN was most frequently found in RG2 (11 of 36 patients, 30.6%), compared with RG1 (12.7%) or RG3 (9.8%) (P = 0.016). CONCLUSIONS: LDCT screening for lung cancer in Korean CRC survivors is feasible. Well-designed clinical trial for defining high risk patients for lung cancer among CRC survivors is needed.
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Humanos , Masculino , Neoplasias Colorretais , Detecção Precoce de Câncer , Neoplasias Pulmonares , Pulmão , Programas de Rastreamento , Mortalidade , Segunda Neoplasia Primária , República da Coreia , Seul , Fumaça , Fumar , Abandono do Hábito de Fumar , Taxa de Sobrevida , Sobreviventes , TóraxRESUMO
PURPOSE: Dysregulation of the Wnt pathway is a crucial step in the tumorigenesis of colorectal cancer (CRC). This study aimed to determine whether DNA methylation of Wnt pathway genes helps predict treatment response and survival in patients with metastatic or recurrent CRC. MATERIALS AND METHODS: We retrospectively collected primary tumor tissues from 194 patients with metastatic or recurrent CRC. Pyrosequencing was used to examine the methylation of 10 CpG island loci in DNA extracted from formalin-fixed paraffin-embedded specimens. To elucidate the predictive role of DNA methylation markers, Kaplan-Meier survival estimation and Cox regression were performed for progression-free survival and overall survival (OS). RESULTS: The methylation frequencies of the 10 genes analyzed (p16, p14, MINT1, MINT2, MINT31, hMLH1, DKK3, WNT5A, AXIN2, and TFAP2E) were 47.9%, 10.8%, 21.1%, 16.0%, 20.6%, 0.5%, 53.1%, 32.0%, 2.6%, and 2.1%, respectively. We divided patients into three groups based on the number of methylated genes (group 1, no methylation n=38; group 2, 1–2 methylations n=92; group 3, 3 or more methylations n=64). Among patients treated with palliative chemotherapy (n=167), median OSs of groups 1, 2, and 3 were 39.1, 39.7, and 29.1 months, respectively (log rank p=0.013). After adjustment, number of methylations was identified as an independent poor prognostic factor (0–2 methylated vs. ≥3 methylated: hazard ratio, 1.72; 95% confidence interval, 1.16–2.56, p=0.007). CONCLUSION: This study suggests that methylation of Wnt pathway genes, in addition to known CpG island methylator phenotype markers, may help predict treatment outcome and survival in patients with CRC.
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Humanos , Carcinogênese , Neoplasias Colorretais , Ilhas de CpG , Intervalo Livre de Doença , DNA , Metilação de DNA , Tratamento Farmacológico , Metilação , Fenótipo , Estudos Retrospectivos , Resultado do Tratamento , Via de Sinalização WntRESUMO
PURPOSE: Uveal melanoma has a very poor prognosis despite successful local primary tumor treatment. In this study, we investigated prognostic factors that more accurately reflected the likelihood of recurrence and survival and delineated a prognostic model that could effectively identify different risk groups based on initial clinical parameters. MATERIALS AND METHODS: Prognostic factors associated with distant recurrence, recurrence-free survival (RFS), progression-free survival, and overall survival from distant recurrence to death (OS2) were analyzed in 226 patients with stage I-III uveal melanoma who underwent primary local therapy. RESULTS: Forty-nine patients (21.7%) had distant recurrences, which occurred most frequently in the liver (87.7%). In a multivariate analysis, local radiotherapy improved RFS among patients with multiple recurrence risk factors relative to excision (not reached vs. 19.0 months, p=0.004). Patients with BRCA1-associated protein-1 (BAP1)–negative primary tumors showed a longer RFS duration after primary treatments, while those with BAP1-negative metastatic tissues had a shorter OS2 compared to those with BAP1-positive tumors, both not statistically insignificance (RFS: not reached vs. 82.0 months, p=0.258; OS2: 15.7 vs. 24.4 months, p=0.216). Male sex (hazard ratio [HR], 3.79; p=0.012), a short RFS (HR, 4.89; p=0.014), and a largest metastatic tumor linear diameter ≥ 45 mm (HR, 5.48; p=0.017) were found to correlate with worse post-recurrence survival. CONCLUSION: Risk factors could be used to classify uveal melanoma cases and subsequently direct individual treatment strategies. Furthermore, metastasectomy appears to contribute to improved survival outcomes.
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Humanos , Masculino , Intervalo Livre de Doença , Fígado , Melanoma , Metastasectomia , Análise Multivariada , Prognóstico , Radioterapia , Recidiva , Fatores de Risco , Neoplasias UveaisRESUMO
PURPOSE: Melanoma is a highly heterogeneous neoplasm, composed of subpopulations of tumor cells with distinct molecular and biological phenotypes and genotypes. In this study, to determine the genetic heterogeneity between primary and metastatic melanoma in Korean melanoma patients, we evaluated several well-known genetic alterations of melanoma. In addition, to elucidate the clinical relevance of each genetic alteration and heterogeneity between primary and metastatic lesions, clinical features and patient outcome were collected. MATERIALS AND METHODS: In addition to clinical data, BRAF, NRAS, GNAQ/11 mutation and KIT amplification data was acquired from an archived primary Korean melanoma cohort (KMC) of 188 patients. Among these patients, 43 patients were included for investigation of tumor heterogeneity between primary melanoma and its corresponding metastatic lesions. RESULTS: Overall incidence of genetic aberrations of the primary melanomas in KMC was 17.6% of BRAF V600, 12.6% of NRAS mutation, and 28.6% of KIT amplification. GNAQ/11 mutation was seen in 66.6% of the uveal melanoma patients. Patients with BRAF mutation were associated with advanced stage and correlated to poor prognosis (p < 0.01). Among 43 patients, 55.8% showed heterogeneity between primary and metastatic lesion. The frequency of BRAF mutation and KIT amplification significantly increased in the metastatic lesions compared to primary melanomas. GNAQ/11 mutation showed 100% homogeneity in uveal melanoma patients. CONCLUSION: Our data demonstrated heterogeneity between primary melanomas and corresponding metastatic lesions for BRAF, NRAS mutation and KIT amplification. However, GNAQ/11 mutation was genetically homogeneous between primary and metastatic melanoma lesions in uveal melanoma.
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Humanos , Estudos de Coortes , Heterogeneidade Genética , Genótipo , Incidência , Melanoma , Fenótipo , Características da População , PrognósticoRESUMO
PURPOSE: Ipilimumab improves survival in advanced melanoma patients. However, the efficacy and safety of ipilimumab has not been evaluated in Asian melanoma patients with a high frequency of mucosal and acral melanoma subtypes. MATERIALS AND METHODS: Advanced melanoma patients treated with 3 mg/kg ipilimumab in a Korean multicenter named-patient program (NPP) were evaluated between September 2014 and July 2015. Baseline characteristics and blood parameters including neutrophil to lymphocyte ratio (NLR) were assessed, and outcome and adverse events were evaluated according to subtypes. RESULTS: A total of 104 advanced melanoma patients were treated. The primary sites were acral (31.7%), mucosal (26%), cutaneous (26%), uveal (9.6%), and unknown (6.7%). Sixty-eight patients (65.4%) experienced adverse events, and the most common toxicity was skin rash (22.1%), 10 patients (9.6%) experienced adverse events of grade 3 or higher. The median progression-free survival (PFS) was 2.73 months (95% confidence interval, 2.67 to 2.85), and there was no difference in PFS according to subtypes. Poor performance status, liver metastasis, and NLR (≥ 5) were independent poor prognostic factors by multivariate analysis. CONCLUSION: In the Korean NPP cohort, ipilimumab showed similar efficacy and tolerability compared to Western patients, regardless of subtypes. All subtypes should benefit from ipilimumab with consideration of performance status, liver metastasis, and NLR.
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Humanos , Povo Asiático , Biomarcadores , Estudos de Coortes , Intervalo Livre de Doença , Exantema , Imunoterapia , Fígado , Linfócitos , Melanoma , Análise Multivariada , Metástase Neoplásica , NeutrófilosRESUMO
PURPOSE: Hypermethylation of the CpG island of p16(INK4a) occurs in a significant proportion of colorectal cancer (CRC). We aimed to investigate its predictive role in CRC patients treated with 5-fluorouracil, leucovorin, irinotecan (FOLFIRI), and cetuximab. MATERIALS AND METHODS: Pyrosequencing was used to identify KRAS mutation and hypermethylation of 6 CpG island loci (p16, p14, MINT1, MINT2, MINT31, and hMLH1) in DNA extracted from formalin-fixed paraffin-embedded specimens. Logistic regression and Cox regression were performed for analysis of the relation between methylation status of CpG island methylator phenotype (CIMP) markers including p16 and clinical outcome. RESULTS: Hypermethylation of the p16 gene was detected in 14 of 49 patients (28.6%) and showed significant association with KRAS mutation (Fisher exact, p=0.01) and CIMP positivity (Fisher exact, p=0.002). Patients with p16-unmethylated tumors had significantly longer time to progression (TTP; median, 9.0 months vs. 3.5 months; log-rank, p=0.001) and overall survival (median, 44.9 months vs. 16.4 months; log-rank, p=0.008) than those with p16-methylated tumors. Patients with both KRAS and p16 aberrancy (n=6) had markedly shortened TTP (median, 2.8 months) compared to those with either KRAS or p16 aberrancy (n=11; median, 8.6 months; p=0.021) or those with neither (n=32; median, 9.0 months; p < 0.0001). In multivariate analysis, KRAS mutation and p16 methylation showed independent association with shorter TTP (KRAS mutation: hazard ratio [HR], 3.21; p=0.017; p16 methylation: HR, 2.97; p=0.027). CONCLUSION: Hypermethylation of p16 was predictive of clinical outcome in metastatic CRC patients treated with cetuximab and FOLFIRI, irrespective of KRAS mutation.
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Humanos , Neoplasias Colorretais , Ilhas de CpG , Inibidor p16 de Quinase Dependente de Ciclina , DNA , Tratamento Farmacológico , Fluoruracila , Genes p16 , Leucovorina , Modelos Logísticos , Metilação , Análise Multivariada , FenótipoRESUMO
PURPOSE: The purpose of this study is to investigate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and plasma cytokines and angiogenic factors (CAFs) as pharmacodynamic and prognostic biomarkers of bevacizumab monotherapy in colorectal cancer with liver metastasis (CRCLM). MATERIALS AND METHODS: From July 2011 to March 2012, 28 patients with histologically confirmed CRCLM received bevacizumab monotherapy followed by combined FOLFOX therapy. The mean age of the patients was 57 years (range, 30 to 77 years). DCE-MRI (K(trans) and IAUC₆₀) was performed at baseline, first follow-up (3 days after bevacizumab monotherapy), and second follow-up (3 days after combined therapy). CAF levels (vascular endothelial growth factor [VEGF], placental growth factor [PlGF], and interleukin-8) were assessed on the same days. Progression-free survival (PFS) time distributions were summarized using the Kaplan-Meier method and compared using log-rank tests. RESULTS: The median PFS period was 11.2 months. K(trans), IAUC₆₀, VEGF, and PlGF values on the first follow-up day were significantly different compared with baseline values. No differences were observed on the second follow-up day. A > 40% decrease in K(trans) from baseline to first follow-up was associated with a longer PFS (hazard ratio, 0.349; 95% confidence interval, 0.133 to 0.912; p=0.032). Changes in CAFs did not show correlation with PFS time. CONCLUSION: DCE-MRI parameters and CAFs are pharmacodynamic biomarkers of bevacizumab for CRCLM. In our study, change in K(trans) at 3 days after bevacizumab monotherapy was a favorable prognostic factor; however, the value of CAFs as a prognostic biomarker was not found.
Assuntos
Humanos , Indutores da Angiogênese , Bevacizumab , Biomarcadores , Neoplasias Colorretais , Citocinas , Intervalo Livre de Doença , Fatores de Crescimento Endotelial , Seguimentos , Fígado , Imageamento por Ressonância Magnética , Métodos , Metástase Neoplásica , Plasma , Fator A de Crescimento do Endotélio VascularRESUMO
PURPOSE: Pediatric-type sarcomas such as rhabdomyosarcoma (RMS), Ewing sarcoma (EWS), primitive neuroectodermal tumor (PNET), and desmoplastic small round-cell tumor (DSRCT) are rare in adults, with limited studies on their prognosis and optimal treatment strategies. We aimed to examine the outcome of children and adult patients with RMS, EWS, PNET, and DSRCT and relevant prognostic factors. MATERIALS AND METHODS: We retrospectively reviewed 220 pediatric-type sarcoma patients at a single institution between 1985 and 2011. Comparisons were made in order to examine differences in demographics, disease characteristics, and survival. Survival analyses were performed using the Kaplan-Meier method with log-rank tests and Cox proportional hazards models. RESULTS: A total of 220 consecutive patients were identified at our institute. Median age was 15.6 years (range, 0 to 81 years) and there were 108 children (49%) and 112 adult patients (51%). According to histological classification, 106 patients (48.2%) had RMS, 60 (27.3%) had EWS, 50 (22.7%) had PNET, and 4 (1.8%) had DSRCT. With a median follow-up period of 6.6 years, the estimated median overall survival (OS) of all patients was 75 months (95% confidence interval [CI], 27.2 to 122.8 months) and median event-free survival (EFS) for all patients was 11 months (95% CI, 8.8 to 13.2 months). No significant difference in OS and EFS was observed between adults and children. In multivariate analysis, distant metastasis (hazard ratio [HR], 1.617; 95% CI, 1.022 to 2.557; p=0.040) and no debulking surgery (HR, 1.443; 95% CI, 1.104 to 1.812; p=0.012) showed independent association with worse OS. CONCLUSION: Metastatic disease and no surgical treatment are poor prognostic factors for OS among pediatric-type sarcomas for both adults and children.
