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Purpose@#Plasma circulating tumor DNA (ctDNA) could reflect the genetic alterations present in tumor tissues. However, there is little information about the clinical relevance of cell-free DNA genotyping in peripheral T-cell lymphoma (PTCL). @*Materials and Methods@#After targeted sequencing plasma cell-free DNA of patients with various subtypes of PTCL (n=94), we analyzed the mutation profiles of plasma ctDNA samples and their predictive value of dynamic ctDNA monitoring for treatment outcomes. @*Results@#Plasma ctDNA mutations were detected in 53 patients (56%, 53/94), and the detection rate of somatic mutations was highest in angioimmunoblastic T-cell lymphoma (24/31, 77%) and PTCL, not otherwise specified (18/29, 62.1%). Somatic mutations were detected in 51 of 66 genes that were sequenced, including the following top 10 ranked genes: RHOA, CREBBP, KMT2D, TP53, IDH2, ALK, MEF2B, SOCS1, CARD11, and KRAS. In the longitudinal assessment of ctDNA mutation, the difference in ctDNA mutation volume after treatment showed a significant correlation with disease relapse or progression. Thus, a ≥ 1.5-log decrease in genome equivalent (GE) between baseline and the end of treatment showed a significant association with better survival outcomes than a < 1.5-log decrease in GE. @*Conclusion@#Our results suggest the clinical relevance of plasma ctDNA analysis in patients with PTCL. However, our findings should be validated by a subsequent study with a larger study population and using a broader gene panel.
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Purpose@#Prognostic Index for Natural Killer Lymphoma (PINK) is the most widely accepted prognostic model for patients withextranodal natural killer/T-cell lymphoma (ENKTL) treated with non-anthracycline–based therapy. We aimed to evaluate the prognostic implications of serum β-2 microglobulin (β2M) in the context of PINK and proposed a new prognostic model. @*Materials and Methods@#A total of 138 patients who were newly diagnosed with ENKTL and treated with non-anthracycline-based chemotherapy were identified. The cut-off value of high serum β2M was calculated by maximal-chi square methods (4.1 mg/L). A new prognostic model incorporating serum β2M into PINK was proposed and validated in an independent validation cohort (n=88). @*Results@#The patients’ median age was 53.5 years (range, 19 to 80 years). Patients with high serum β2M levels had significantly worse overall survival (OS) and progression-free survival (PFS). In multivariate analysis, high serum β2M was an independent adverse prognostic factor for OS. A new PINK-B (Prognostic Index for Natural Killer Lymphoma-serum β-2 microglobulin) model stratifiedpatients into three groups with distinct OS and PFS in the training cohort (3-year OS, 84.1% [95% confidence interval, 75.1 to 94.2], 46.8% [36.1 to 60.8] and 17.6% [6.3 to 49.2] for the low-, intermediate, and high-risk groups, respectively; 3-year PFS, 70.6% [59.4 to 83.8], 35.9% [25.9 to 49.8], and 7.35% [1.1 to 46.7] for the low-, intermediate-, and high-risk groups, respectively). The PINK-B model was further validated in an independent cohort. @*Conclusion@#Serum β2M is an independent prognostic factor for ENKTL patients. The new serum β2M-based prognostic model may be useful for identifying ultra-high-risk patients, and it can easily be adopted into daily clinical practice.
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Erdheim-Chester disease (ECD), also known as non-Langerhans cell histiocytosis, is a multi-systemic disease with unclear pathogenesis. Based on a small number of case studies, pegylated interferon-α (PEG-IFN-α) has been used as the front-line treatment option. However, there are limited data regarding administration of ropegylated-interferon α-2b (ROPEG-IFN-α 2b) for ECD patients. Herein, we report two cases of severe ECD treated with two types of PEG-IFN-α. One patient with heart and skeleton involvement and BRAF V600E mutation was treated with weekly PEG-IFN-α 2a. Another patient with bone involvement and no BRAF V600E mutation was administered monthly ROPEG-IFN-α 2b. The two types of PEG-IFN-α showed excellent disease control, excellent survival outcomes, and manageable toxicities in ECD patients. These results suggest that ROPEG-IFN-α 2b could be used equivalently to PEG-IFN-α 2a for management of advanced ECD.
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Purpose@#We intend to evaluate the efficacy of salvage treatments for relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) through meta-analysis. @*Materials and Methods@#R/R DLBCL trials were divided into two groups based on eligibility for autologous stem-cell transplantation (ASCT), and meta-analysis of each group was performed. Random effects models were used to estimate the 1-year progression-free survival (PFS) rate, and chimeric antigen receptor (CAR) T-cell therapy was used as reference treatment. @*Results@#Twenty-six ASCT-eligible cohorts from 17 studies comprising 2,924 patients and 59 ASCT-ineligible cohorts from 53 studies comprising 3,617 patients were included in the pooled analysis. In the ASCT-eligible group, the pooled 1-year PFS rate was 0.40 (95% confidence interval [CI], 0.15 to 0.65) for the CAR T-cell group and 0.34 (95% CI, 0.30 to 0.37) for the group with chemotherapy followed by ASCT intention. The two treatments were not significantly different in meta-regression analysis. In the ASCT-ineligible group, the pooled 1-year PFS was 0.40 (95% CI, 0.35 to 0.46) for CAR T-cell, and the highest primary outcome was 0.47 (95% CI, 0.37 to 0.57) for the tafasitamab group. CAR T-cell therapy showed significantly better outcomes than chemotherapy and therapies based on ibrutinib, lenalidomide, and selinexor. However, loncastuximab, polatuzumab plus bendamustine and rituximab, and the tafasitamab group showed no different efficacy than CAR T-cell therapy after adjusting for median number of previous lines of treatment. @*Conclusion@#Although several regimens were crudely grouped for classification, CAR T-cell therapy did not outperform chemotherapy followed by ASCT in the second-line setting or several recently developed agents in the ASCT-ineligible setting.
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Purpose@#Analysis of circulating tumor DNA (ctDNA) in blood could allow noninvasive genetic analysis of primary tumors. Although there have been unmet needs for noninvasive methods in patients with primary central nervous system lymphoma (PCNSL), it is still not determined whether plasma ctDNA analysis could be useful for patients with PCNSL. @*Materials and Methods@#Targeted deep sequencing of 54 genes was performed in cell-free DNA isolated from plasma samples collected pretreatment, during treatment, and at the end of treatment in 42 consecutively diagnosed PCNSL patients between January 2017 and December 2018. @*Results@#Targeted sequencing of plasma cell-free DNA detected somatic mutations representing ctDNA in 11 cases (11/41, 27%). The detection of ctDNA was not related to the concentration of cell-free DNA or tumor volume. The mutation profiles of these 11 cases varied between patients. The most frequently mutated gene was PIM1 (4/11, 36.4%), whereas KMT2D, PIK3CA, and MYD88 were each observed in three patients (3/11, 27%). The mutations of 13 genes were concordantly found in primary tumor tissue and plasma ctDNA, giving a detection sensitivity of 45%. During the serial tracking of seven patients with complete response, the disappearance of ctDNA mutations was found in four patients, whereas three patients had detected ctDNA mutation at the end of treatment. @*Conclusion@#The plasma ctDNA mutation analysis still has limited value for surveillance and predicting treatment outcomes of PCNSL because the detection efficiency was lower than other systemic lymphomas. Thus, analytical platforms should be improved to overcome anatomical hurdles associated with PCNSL.
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Objectives@#This study examined the current status of depression and related factors among children using community child center. @*Methods@#A cross-sectional study selected children in grades 4-6 who used the Gwangju and Jeollanamdo community child center (n=224) using a convenience sampling method. General characteristics, family characteristics, children's emotional characteristics, children's school life environment and depression status were assessed using a self-reported questionnaire. @*Results@#The average score of depression among children using community child center was 15.31±7.70 out of a total of 27. Fifty-eight (25.9%) children had depression above 22 points. Variables related to children's depression were shown as grade, subjective economic level awareness, after-school activities excluding local children's centers, presence of family members after school, and family structure. @*Conclusions@#The depression prevalence of children using community child center was higher. Policy support such as children's psychological support programs would be needed to reduce children's depression, and community child centers are expected to be effective in reducing children's depression if continuous child psychological support services are developed for children's mental health.
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Background@#Treatment protocols for light chain (AL) amyloidosis have been derived from myeloma treatment. Bortezomib is a key drug used for the treatment of myeloma and AL amyloidosis. We retrospectively investigated the efficacy and toxicity of bortezomib-based chemotherapy in patients with newly diagnosed AL amyloidosis. @*Methods@#We reviewed the outcomes of newly diagnosed autologous stem cell transplantation (auto-SCT)-ineligible AL amyloidosis patients who received bortezomib-based chemotherapy at a referral center between 2011 and 2017. @*Results@#Of 63 patients who received bortezomib-based chemotherapy, 32 were male, and the median age was 66 years (range, 42‒82 yr). The hematologic overall response rate (ORR) was 65.1%, and the chemotherapy regimen with the best hematologic response was VMP (75.7%, 28/37). Sixty patients had significant organ (heart or kidney) involvement; 28.3% of patients (N=17) had major organ responses after chemotherapy. With a median follow-up of 34 months, there was no significant difference in progression-free survival (P =0.49) or overall survival (P =0.67) according to regimen. Most hematologic and non-hematologic problems were manageable. @*Conclusion@#Various chemotherapy combinations based on bortezomib are currently employed in the clinical setting, but no difference was found in terms of efficacy or toxicity.
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Background/Aims@#Waldenström macroglobulinemia (WM) is a rare lymphoproliferative disorder that usually follows an indolent clinical course. However, some patients show an aggressive clinical course leading to death. We explored the risk factors predicting poor prognosis in WM patients. @*Methods@#We retrospectively analyzed 47 patients diagnosed with WM between 2000 and 2018 to explore risk factors predicting poor prognosis using various clinical and laboratory parameters and risk models including the International Prognostic Staging System for WM (IPSS-WM). @*Results@#Over a median follow-up duration of 80.4 months, 29 patients died. The main causes of death were disease progression, organ failure related to amyloidosis, and infection. The median overall survival (OS) was 55.1 months, and 14 patients, including three with amyloidosis, died within 2 years. Serum β2-microglobulin level higher than 4 mg/dL was significantly associated with poor OS. Accordingly, the IPSS-WM showed a significant association with poor prognosis compared with other risk models, and the low-risk group had better OS than intermediate- and high-risk groups. In the retrospective analysis using the results of targeted sequencing in two cases representing good and bad prognosis, different patterns of mutation profiles were observed, including mutations of MYD88, TP53, ARID1A, and JAK2 in a refractory case. @*Conclusions@#Serum β2-microglobulin could be a single biomarker strongly predictive of poor survival of WM patients, and the low-risk group of the IPSS-WM risk model including serum β2-microglobulin has better prognostic value than other risk models. Mutation analysis also might provide additional information to predict high-risk patients.
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Background/Aims@#Waldenström macroglobulinemia (WM) is a rare lymphoproliferative disorder that usually follows an indolent clinical course. However, some patients show an aggressive clinical course leading to death. We explored the risk factors predicting poor prognosis in WM patients. @*Methods@#We retrospectively analyzed 47 patients diagnosed with WM between 2000 and 2018 to explore risk factors predicting poor prognosis using various clinical and laboratory parameters and risk models including the International Prognostic Staging System for WM (IPSS-WM). @*Results@#Over a median follow-up duration of 80.4 months, 29 patients died. The main causes of death were disease progression, organ failure related to amyloidosis, and infection. The median overall survival (OS) was 55.1 months, and 14 patients, including three with amyloidosis, died within 2 years. Serum β2-microglobulin level higher than 4 mg/dL was significantly associated with poor OS. Accordingly, the IPSS-WM showed a significant association with poor prognosis compared with other risk models, and the low-risk group had better OS than intermediate- and high-risk groups. In the retrospective analysis using the results of targeted sequencing in two cases representing good and bad prognosis, different patterns of mutation profiles were observed, including mutations of MYD88, TP53, ARID1A, and JAK2 in a refractory case. @*Conclusions@#Serum β2-microglobulin could be a single biomarker strongly predictive of poor survival of WM patients, and the low-risk group of the IPSS-WM risk model including serum β2-microglobulin has better prognostic value than other risk models. Mutation analysis also might provide additional information to predict high-risk patients.
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Purpose@#The study aimed to investigate the role of Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) in predicting incidental prostate cancer (PCa) or urothelial carcinoma (UCa) extension in urinary bladder (UB) cancer patients. @*Materials and Methods@#A total of 72 UB cancer patients who underwent radical cystoprostatectomy and 3 Tesla multiparametric MRI before surgery were enrolled. PI-RADS v2 ratings were assigned by two independent radiologists. All prostate specimens were examined by a single pathologist. We compared the multiparametric MRI findings rated using PI-RADS v2 with the pathologic data. @*Results@#Of the 72 UB cancer patients, 29 had incidental PCa (40.3%) and 20 showed UCa extension (27.8%), with an overlap for 3 patients. With a score of 4 as the cut-off value for predicting incidental PCa, the diagnostic accuracy was 65.3%, specificity was 90.7%, and positive predictive value (PPV) was 66.7%. The diagnostic accuracy for incidental UCa extension was 47.2%, specificity was 92.3%, and PPV was 83.3%. @*Conclusion@#Despite the low diagnostic accuracy, the PPV and specificity were relatively high. Therefore, PI-RADS v2 scores of 1, 2, or 3 may help exclude the probability of incidental PCa or UCa extension.
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Background/Aims@#There are limited data about the influence of the central nervous system (CNS) involvement on the prognosis for patients with the Asian variant of intravascular large B-cell lymphoma (IVLBCL). @*Methods@#We analyzed 46 patients who were diagnosed with IVLBCL between 2001 and 2018. All patients were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). @*Results@#CNS involvement was diagnosed by cerebrospinal fluid analysis (n = 6) and brain imaging (n = 5) in 11 patients at diagnosis, and four cases with CNS relapse were found. Thus, 15 patients had CNS involvement (15/46, 33%). The clinical characteristics were not different between patients with and without CNS involvement, but all patients with CNS involvement belonged to the high-risk group of CNS-International Prognostic Index (IPI). Thirty-one patients achieved a complete response (67%, 31/46) whereas eight patients showed disease progression and six patients died after the first or second cycle of R-CHOP. CNS-directed therapy such as high-dose methotrexate was combined with R-CHOP for patients with CNS involvement, and five patients were alive without relapse. The median overall survival of all patients was 45.0 months, and overall survival was not different according to the involvement of CNS. @*Conclusions@#The treatment outcome of patients with the Asian variant of IVLBCL is still not satisfactory. The prediction of CNS involvement based on the clinical features including CNS-IPI score might not serve to identify patients at high risk of CNS involvement, either. Thus, more effective strategies for diagnosis and treatment should be developed.
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Background@#Immune checkpoint inhibitors have demonstrated efficacy in the treatment of classical Hodgkin’s lymphoma (cHL). We analyzed the efficacy and safety of pembrolizumab or nivolumab in patients with pretreated cHL. @*Methods@#Clinical data from the cancer chemotherapy registry of Samsung Medical Center were retrospectively analyzed to study patients with cHL treated with pembrolizumab or nivolumab between Oct 2015 and Dec 2018. @*Results@#Of the 20 patients, seven (35%) were enrolled in the study after a relapse following autologous hematopoietic stem cell transplantation (ASCT) and 12 (60%) after a relapse following receipt of brentuximab vedotin (BV). Sixteen (80%) patients received pembrolizumab, and four (20%) patients received nivolumab. The complete remission rate was 45% (9/20), and 30% (6/20) of patients achieved partial remission, for an overall response rate (RR) of 75% [15/20; 95% confidence interval (CI), 34.7‒93.3]. With a median follow-up duration of 14 months, the median PFS was 18 months (95% CI, 2.4‒33.5 mo), and the median OS was 36 months [95% CI, 36-not applicable (NA) mo]. Pembrolizumab and nivolumab were generally well tolerated. @*Conclusion@#In this study, pembrolizumab and nivolumab both demonstrated clinical efficacy and tolerability in patients with cHL who failed previous chemotherapy or ASCT.
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Purpose@#To evaluate the safety and efficacy of the percutaneous manual aspiration thrombectomy technique to treat thrombotic occlusion of native arteriovenous fistulas. @*Materials and Methods@#A retrospective review of 20 patients who underwent percutaneous manual aspiration thrombectomy for native thrombotic arteriovenous fistula occlusion from March 2012 to December 2017 was performed. We evaluated technical and clinical success rates and complications. The primary and secondary patency rates were calculated using the Kaplan-Meier analysis. @*Results@#Percutaneous manual aspiration thrombectomy was performed in 20 patients (n = 20) with concomitant balloon angioplasty. The overall technical and clinical success rates were both 85% (n = 17). The native arteriovenous fistulas, based on their site, were the left radiocephalic (n = 13), left brachiocephalic (n = 4), and right radiocephalic (n = 3) fistulas. An underlying stenosis was detected in the juxta-anastomotic venous site (n = 16), outflow draining vein (n = 12), and central vein (n = 4). The primary and secondary patency rates at 1, 3, 6, and 12 months were 100%, 70.6%, 70.6%, and 56.5% and 100%, 94.1%, 94.1%, and 86.9%, respectively. There were no complications associated with procedure. @*Conclusion@#Percutaneous manual aspiration thrombectomy is a safe and effective method to treat thrombotic native arteriovenous fistula occlusion.
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Purpose@#To evaluate the safety and efficacy of the percutaneous manual aspiration thrombectomy technique to treat thrombotic occlusion of native arteriovenous fistulas. @*Materials and Methods@#A retrospective review of 20 patients who underwent percutaneous manual aspiration thrombectomy for native thrombotic arteriovenous fistula occlusion from March 2012 to December 2017 was performed. We evaluated technical and clinical success rates and complications. The primary and secondary patency rates were calculated using the Kaplan-Meier analysis. @*Results@#Percutaneous manual aspiration thrombectomy was performed in 20 patients (n = 20) with concomitant balloon angioplasty. The overall technical and clinical success rates were both 85% (n = 17). The native arteriovenous fistulas, based on their site, were the left radiocephalic (n = 13), left brachiocephalic (n = 4), and right radiocephalic (n = 3) fistulas. An underlying stenosis was detected in the juxta-anastomotic venous site (n = 16), outflow draining vein (n = 12), and central vein (n = 4). The primary and secondary patency rates at 1, 3, 6, and 12 months were 100%, 70.6%, 70.6%, and 56.5% and 100%, 94.1%, 94.1%, and 86.9%, respectively. There were no complications associated with procedure. @*Conclusion@#Percutaneous manual aspiration thrombectomy is a safe and effective method to treat thrombotic native arteriovenous fistula occlusion.
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PURPOSE: End-of-life (EoL) decisions are challenging and multifaceted for patients and physicians. This study was aimed to explore how EoL care is practiced for patients with a do-not-resuscitate (DNR) order. METHODS: We retrospectively analyzed medical records of patients who died after agreeing to a DNR order in 2016 at a university hospital. Characteristics including cause of death, intensity of EoL care, and other factors were reviewed and statistically analyzed. RESULTS: Of total 375 patients, 170 patients (45.3%) died with malignancies, and 205 patients (54.6%) with other causes involving the central nervous system (19.2%), pulmonary (14.7%), cardiologic (6.7%) and infectious (6.4%) conditions. Both the cancer and non-cancer patient groups showed a short duration from DNR to death (median 3 days vs 2 days, P=0.629). An intensive care group comprising patients who received one or more intensive treatments such as ventilator (n=205) showed a higher number of non-cancer patients and a shorter duration from DNR to death than a group that withheld treatment before DNR (P < 0.05). CONCLUSION: EoL decisions were made very late by both cancer and non-cancer patients. About half of the patients did not have cancer, and two-thirds of them decided DNR during intensive treatment. To make a good EoL decision, a shared decision making with patients should be done at an earlier stage.
Subject(s)
Humans , Advance Care Planning , Cause of Death , Central Nervous System , Critical Care , Decision Making , Medical Records , Resuscitation Orders , Retrospective Studies , Terminal Care , Ventilators, MechanicalABSTRACT
Pancreatic cancer tends to be delayed in diagnosis because of the lack of early symptom and less than 20% of patients present with resectable masses. A 95-year-old male visited due to recurrent abdominal pain and vomiting. About 2 years ago, a polypoid lesion was detected at the post-bulbar area on esophagogastroduodenoscopy for medical check-up. Endoscopic biopsy noted chronic inflammation with glandular atypia. On the CT scan, there was an intraluminal polypoid mass lesion with mixed hypodensity at the duodenal second portion. Ultrasound guided biopsy targeting the hypodense lesion was performed and revealed chronic pancreatitis. The vomiting persisted and the patient received a palliative gastrojejunostomy. Twenty-five days after gastrojejunostomy, jaundice occurred and an ill-defined mass at the pancreas head was noted on the CT. Pylorus preserving pancreatoduodenectomy was performed and a 3.5 cm sized, moderate to poorly differentiated ductal adenocarcinoma of pancreas head was diagnosed. Nineteen days after operation, the patient was discharged in good condition.
Subject(s)
Humans , Male , Abdominal Pain , Adenocarcinoma , Biopsy , Diagnosis , Duodenal Obstruction , Endoscopy, Digestive System , Gastric Bypass , Head , Inflammation , Jaundice , Pancreas , Pancreatic Neoplasms , Pancreaticoduodenectomy , Pancreatitis , Pancreatitis, Chronic , Pylorus , Tomography, X-Ray Computed , Ultrasonography , VomitingABSTRACT
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions to drugs, which carry significant morbidities and mortalities. Although SJS and TEN can be treated by corticosteroids or intravenous immunoglobulin, they may be induced by steroids. We experienced a 36-year-old man who developed whole body erythromatous maculopapular rashes and multiple bullae after ingestion of deflazacort. After avoidance of deflazacort and use of dexamethasone, skin lesions resorbed. We reported a case of TEN diagnosed by characteristic clinical findings with a brief review of the literature.