Purpose: Programmed death-1 blockade with pembrolizumab has shown promising activity in relapsed/refractory (R/R) extranodal natural killer/T-cell lymphoma (NKTCL), but studies are limited, with small patient numbers. Materials and Methods: Thirteen institutes involved with the Consortium for Improving Survival of Lymphoma, a Korean lymphoma study group, collected the clinical data of 59 patients treated with pembrolizumab as salvage therapy between 2016 and 2022. Results: The median age of the patients was 60 years (range, 22 to 87 years), and 76.3% had advanced Ann Abor stage disease. Pembrolizumab was given to 35.6%, 40.7%, and 23.7% of the patients as second-, third-, and fourth- or higher-line chemotherapy, respectively. The overall response rate was 40.7%, with 28.8% having complete response. The estimated 2-year progression-free survival (PFS) and overall survival rates for all patients were 21.5% and 28.7%, respectively; for responders, the rates were 53.0% and 60.7%, respectively. Although not statistically significant, Eastern Cooperative Oncology Group performance status ≥ 2 (hazard ratio [HR], 1.91; 95% confidence interval [95% CI], 0.93 to 3.94; p=0.078) and stage III or IV disease (HR, 2.59; 95% CI, 0.96 to 6.96; p=0.060) were associated with a trend toward shorter PFS in multivariate analysis. Grade 3 or 4 adverse events (AEs) were noted in 12 patients (20.3%); neutropenia (10.2%), fatigue (6.8%), and pneumonitis (5.1%) were most common AEs. Conclusion In conclusion, while pembrolizumab had a modest effect on patients with R/R NKTCL, it may be a useful salvage therapy for patients with localized disease and good performance status.

Background/Aims: Daratumumab has shown an encouraging antitumor effect in patients with multiple myeloma (MM), and was known to alter the immune properties by off-targeting immunosuppressive cells. Here, we aimed to evaluate the change in absolute lymphocyte count (ALC) as a surrogate marker for predicting survival outcomes of patients treated with daratumumab. Methods: Between 2018 and 2021, the medical records of patients with relapsed/refractory MM (RRMM) treated with daratumumab monotherapy at 10 centers in South Korea were reviewed. We collected the ALC data at pre-infusion (D0), day 2 after the first infusion (D2), and prior to the third cycle of daratumumab therapy (D56). Results: Fifty patients who were administered at least two cycles of daratumumab were included. Overall response rate was 54.0% after two cycles of daratumumab treatment. On D2, almost all patients experienced a marked reduction in ALC. However, an increase in ALC on D56 (ALCD56) was observed in patients with non-progressive disease, whereas failure of ALC recovery was noted in those with progressive disease. Patients with ALCD56 > 700/μL (n = 39, 78.0%) had prolonged progression- free survival (PFS) and overall survival (OS) than those with ALCD56 ≤ 700/μL (median PFS: 5.8 months vs. 2.6 months, p = 0.025; median OS: 24.1 months vs. 6.1 months, p = 0.004). In addition, ALCD56 >700/μL was a significant favorable prognostic factor for PFS (hazard ratio [HR], 0.22; p = 0.003) and OS (HR, 0.23; p = 0.012). Conclusions Increase in ALC during daratumumab treatment was significantly associated with prolonged survival outcomes in patients with RRMM. The ALC value can predict clinical outcomes in patients treated with daratumumab.

Background: Hodgkin's lymphoma (HL) constitutes 10%–20% of all malignant lymphomas and has a high cure rate (5-year survival, around 90%). Recently, interest has increased concerning preventing secondary complications (secondary cancer, endocrine disorders) in long-term survivors. We aimed to study the epidemiologic features and therapeutic outcomes of HL in children, adolescents, and young adults in Korea. Methods: We performed a multicenter, retrospective study of 224 patients aged < 25 years diagnosed with HL at 22 participating institutes in Korea from January 2007 to August 2016. Results: A higher percentage of males was diagnosed at a younger age. Nodular sclerosis histopathological HL subtype was most common, followed by mixed cellularity subtype.Eighty-one (36.2%), 101 (45.1%), and 42 (18.8%) patients were classified into low, intermediate, and high-risk groups, respectively. Doxorubicin, bleomycin, vinblastine, dacarbazine was the most common protocol (n = 102, 45.5%). Event-free survival rate was 86.0% ± 2.4%, while five-year overall survival (OS) rate was 96.1% ± 1.4%: 98.7% ± 1.3%, 97.7% ± 1.6%, and 86.5% ± 5.6% in the low, intermediate, and high-risk groups, respectively (P = 0.021). Five-year OS was worse in patients with B-symptoms, stage IV disease, highrisk, splenic involvement, extra-nodal lymphoma, and elevated lactate dehydrogenase level.In multivariate analysis, B-symptoms and extra-nodal involvement were prognostic factors for poor OS. Late complications of endocrine disorders and secondary malignancy were observed in 17 and 6 patients, respectively. Conclusion This is the first study on the epidemiology and treatment outcomes of HL in children, adolescents, and young adults in Korea. Future prospective studies are indicated to develop therapies that minimize treatment toxicity while maximizing cure rates in children, adolescents, and young adults with HL.

Pretransplant alpha-fetoprotein (AFP) is a useful tumor marker predicting recurrence of hepatocellular carcinoma (HCC). Little is known, however, about the relationship between changes in AFP concentration and prognosis. This study investigated the clinical significance of change in peri-transplant AFP level as a predictor of HCC recurrence. Data from 125 HCC patients with elevated pretransplant AFP level who underwent liver transplantation (LT) between February 2000 and December 2010 were retrospectively reviewed. Patients with AFP normalization within 1 month after LT were classified into the rapid normalization group (n = 97), with all other patients classified into the non-rapid normalization group (n = 28). Tumor recurrence was observed in 17 of the 97 patients (17.5%) with rapid normalization; of these, 11 patients had high AFP levels and six had normal levels at recurrence. In contrast, tumor recurrence was observed in 24 of the 28 patients (85.7%) without rapid normalization, with all 24 having high AFP levels at recurrence. Multivariate analysis showed that non-rapid normalization (harzard ratio [HR], 4.41, P < 0.001), sex (HR, 3.26, P = 0.03), tumor size (HR, 1.15, P = 0.001), and microvascular invasion (HR, 2.65, P = 0.005) were independent risk factors for recurrence. In conclusion, rapid normalization of post-LT AFP level at 1 month is a useful clinical marker for HCC recurrence. Therefore, an adjuvant strategy and/or intensive screening are needed for patients who do not show rapid normalization.
Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Carcinoma, Hepatocellular/blood/mortality/*pathology/therapy ; Female ; Humans ; Kaplan-Meier Estimate ; Liver Neoplasms/blood/mortality/*pathology/therapy ; *Liver Transplantation ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Recurrence, Local ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; alpha-Fetoproteins/analysis

BACKGROUND/AIMS: The most commonly used immunosuppressant therapy after liver transplantation (LT) is a combination of tacrolimus and steroid. Basiliximab induction has recently been introduced; however, the most appropriate immunosuppression for hepatocellular carcinoma (HCC) patients after LT is still debated. METHODS: Ninety-three LT recipients with HCC who took tacrolimus and steroids as major immunosuppressants were included. Induction with basiliximab was implemented in 43 patients (46.2%). Mycophenolate mofetil (MMF) was added to reduce the tacrolimus dosage (n=28, 30.1%). The 1-year tacrolimus exposure level was 7.2 +/- 1.3 ng/mL (mean +/- SD). RESULTS: The 1- and 3-year recurrence rates of HCC were 12.9% and 19.4%, respectively. Tacrolimus exposure, cumulative steroid dosages, and MMF dosages had no impact on HCC recurrence. Induction therapy with basiliximab, high alpha fetoprotein (AFP; >400 ng/mL) and protein induced by vitamin K absence/antagonist-II (PIVKA-II; >100 mAU/mL) levels, and microvascular invasion were significant risk factors for 1-year recurrence (P<0.05). High AFP and PIVKA-II levels, and positive 18fluoro-2-deoxy-d-glucose positron-emission tomography findings were significantly associated with 3-year recurrence (P<0.05). CONCLUSIONS: Induction therapy with basiliximab, a strong immunosuppressant, may have a negative impact with respect to early HCC recurrence (i.e., within 1 year) in high-risk patients.
Adult ; Aged ; Biological Markers/analysis ; Carcinoma, Hepatocellular/mortality/pathology/*therapy ; Female ; Humans ; Immunosuppressive Agents/*therapeutic use ; Liver Neoplasms/mortality/pathology/*therapy ; *Liver Transplantation ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Positron-Emission Tomography ; Protein Precursors/analysis ; Prothrombin/analysis ; Regression Analysis ; Risk Factors ; Severity of Illness Index ; Survival Rate ; alpha-Fetoproteins/analysis

The indication for hepatocellular carcinoma (HCC) is expanding in living donor liver transplantation (LDLT). Early detection and effective management of recurrence has become an important issue in LDLT for HCC. This study aimed to find an optimal screening protocol in terms of screening interval and screening tools by analyzing recurrence pattern after LDLT for HCC. A total of 205 LDLT patients in two centers from February 1999 to October 2010 was reviewed. Recurrence appeared in 55 cases. Six risk factors for recurrence were identified: preoperative alpha-fetoprotein >400, Edmonson grade 3 or 4, tumor size >7 cm, tumor number > or =7, minimal tumor necrosis in the transarterial chemoembolization group and positive micro-vascular invasion. Four groups with different ranges of index scores showed different recurrence-free survival and median time to recurrence. Group I showed low and late recurrence. Groups II and III showed linearly increased rate of recurrence until 18 months. Group IV showed very early recurrence within 6 months. Across the groups, extra-hepatic recurrence developed in more than 40% of cases and multi-organ recurrence rate was 20%. The screening interval should be different based on the risk of recurrence. Screening should include work-up for extra-hepatic recurrence as well as intra-hepatic recurrence.
Carcinoma, Hepatocellular/pathology/*surgery ; Chemoembolization, Therapeutic/adverse effects ; Disease-Free Survival ; Female ; Humans ; Liver Neoplasms/pathology/*surgery ; *Liver Transplantation ; Living Donors ; Male ; Middle Aged ; Neoplasm Recurrence, Local/*pathology ; Risk Factors ; Treatment Outcome

BACKGROUND AND OBJECTIVES: We evaluated the two-year clinical outcomes in patients with angiographically intermediate lesions according to the plaque burden and treatment strategy. SUBJECTS AND METHODS: We prospectively enrolled patients with angiographically intermediate lesions (diameter stenosis 30-70%) with an intravascular ultrasound (IVUS) minimum lumen area (MLA) <4 mm2 with 50-70% plaque burden of 16 Korean percutaneous coronary intervention centers. Patients were divided into medical therapy group (n=85) and zotarolimus-eluting stent group (ZES; Resolute) group (n=74). We evaluated the incidences of two-year major adverse cardiovascular events (MACE). RESULTS: A two-year clinical follow-up was completed in 143 patients and MACE occurred in 12 patients. There were no significant differences in the incidences of death (1.3% vs. 3.0%, p=0.471), target vessel-related non-fatal myocardial infarction (0.0% vs. 0.0%, p=1.000) and target vessel revascularizations (7.8% vs. 4.5%, p=0.425) between medical and ZES groups. Independent predictors of two-year MACE included acute myocardial infarction {odds ratio (OR)=2.87; 95% confidence interval (CI) 1.43-6.12, p=0.014}, diabetes mellitus (OR=2.46; 95% CI 1.24-5.56, p=0.028) and non-statin therapy (OR=2.32; 95% CI 1.18-5.24, p=0.034). CONCLUSION: Medical therapy shows comparable results with ZES, and myocardial infarction, diabetes mellitus and non-statin therapy were associated with the occurrence of two-year MACE in patients with intermediate lesion with IVUS MLA <4 mm2 with 50-70% of plaque burden.
Constriction, Pathologic ; Coronary Artery Disease ; Coronary Stenosis* ; Diabetes Mellitus ; Follow-Up Studies ; Humans ; Incidence ; Myocardial Infarction ; Percutaneous Coronary Intervention ; Plaque, Atherosclerotic ; Prospective Studies ; Research Personnel* ; Stents ; Ultrasonography ; Ultrasonography, Interventional

PURPOSE: Hepatic resection is a standard method of treatment for colorectal liver metastases (CRLM). However, the pathologic factors of metastatic lesions that affect tumor recurrence are less well defined in CRLM. The aim of this study was to evaluate the risk factors for recurrence of CRLM, focusing on histopathologic factors of metastatic lesions of the liver. METHODS: From January 2003 to December 2008, 117 patients underwent curative hepatic resection for CRLM were reviewed. Tumor size and number, differentiation, tumor budding, angio-invasion, dedifferentiation and tumor infiltrating inflammation of metastatic lesions were investigated. RESULTS: The mean number of hepatic tumors was 2 (range, 1-8). The mean size of the largest tumor was 2.9 cm (range, 0.3-18.5 cm) in diameter. The moderate differentiation of the hepatic tumor was the most common in 86.3% of the patients. Tumor budding, angio-invasion, and dedifferentiation were observed in 81%, 34%, and 12.8% of patients. Inflammation infiltrating tumor was detected in 6.8% of patients. Recurrence after hepatic resection appeared in 69 out of 117 cases (58.9%). Recurrence-free survival at 1, 2 and 5 years were 62.4%, 43.6%, and 34.3%. The multivariate analysis showed the number of metastases > or =3 (P = 0.007), the tumor infiltrating inflammation (P = 0.047), and presence of dedifferentiation (P = 0.020) to be independent risk factors for tumor recurrence. CONCLUSION: Histopathological factors, i.e., dedifferentiation and tumor infiltrating inflammation of the metastatic lesion, could be one of the risk factors of aggressive behavior as well as the number of metastases even after curative resection for CRLM.
Colorectal Neoplasms ; Humans ; Inflammation ; Liver* ; Multivariate Analysis ; Neoplasm Metastasis* ; Recurrence* ; Risk Factors