Favorable clinical efficacy of cytotoxic chemotherapy in patients with progressive desmoid tumors: a retrospective real-world study.

BACKGROUND: The real-world evidence about the efficacy of cytotoxic chemotherapy in desmoid tumors is still limited. We investigated the efficacy of chemotherapy in the treatment of recurrent or progressive desmoid tumors. METHODS: The patients with desmoid tumors who had received cytotoxic chemotherapy between November 2007 and June 2020 in two tertiary hospitals in Korea were reviewed. RESULTS: A total of 25 patients were included in the analysis. The most common primary tumor site was the intra-abdominal or pelvic cavity (56%), followed by the trunk and abdominal wall (24%), extremities (16%), and head and neck (4%). Sixty percent of the patients had familial adenomatous polyposis and 76% received doxorubicin plus dacarbazine. The objective response rate and disease control rate was 64% (95% confidence interval [CI]: 40.7-82.8) and 96% (95% CI: 77.2-99.9), respectively. With the median follow-up time of 55 months (95% CI: 41.0-68.2), the 3-year PFS rate was 65% (95% CI: 41.1-80.5), and the 3-year OS rate was 89% (95% CI: 63.8-97.3). Grade 3 or 4 hematologic adverse events were reported in 14 patients, all of which were manageable. CONCLUSION: Our real-world evidence suggests that doxorubicin-based cytotoxic chemotherapy can be an effective treatment option for recurrent and progressive desmoid tumors with respect to favorable clinical outcomes.

Changes in Metabolic Syndrome Status are Associated With Altered Risk of Pancreatic Cancer: A Nationwide Cohort Study.

BACKGROUND AND AIMS: Metabolic syndrome (MetS) is reversible; however, the effect of changes in MetS status on pancreatic cancer risk is unknown. We aimed to investigate the effects of changes and persistence in MetS status on pancreatic cancer risk. METHODS: This nationwide cohort study included 8,203,492 adults without cancer who underwent 2 consecutive biennial health screenings provided by the Korean National Health Insurance System between 2009 and 2012 and were followed up until 2017. MetS was defined as the presence of 3 of its 5 components, which were evaluated at 2 consecutive biennial health screenings. Participants were categorized into the MetS-free, MetS-recovered, MetS-developed, or MetS-persistent group. Multivariable Cox proportional hazards regression models were used. RESULTS: During the 40,464,586 person-years of follow-up (median, 5.1 years), 8010 individuals developed pancreatic cancer. Compared with the MetS-free group, the MetS-persistent group had the highest risk of pancreatic cancer (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.23-1.37), followed by the MetS-developed group (HR, 1.17; 95% CI, 1.09-1.25) and the MetS-recovered group (HR, 1.12; 95% CI, 1.04-1.21) after adjusting for potential confounders (P for trend <.001). The MetS-recovered group was associated with a lower risk of pancreatic cancer than that in the MetS-persistent group (P < .001). The association between changes in MetS status and pancreatic cancer risk did not differ according to sex or obesity (all P for interactions >.05). CONCLUSIONS: In this study, recovering from MetS was associated with a reduced risk of pancreatic cancer compared with persistent MetS, suggesting that pancreatic cancer risk can be altered by changes in MetS.

Smoking Cessation and Pancreatic Cancer Risk in Individuals With Prediabetes and Diabetes: A Nationwide Cohort Study.

BACKGROUND: Individuals with diabetes and prediabetes are at increased risk of pancreatic cancer. However, little is known about the effects of smoking or smoking cessation on pancreatic cancer risk in individuals with diabetes and prediabetes. We investigated the association between smoking status (particularly smoking cessation) and pancreatic cancer risk according to glycemic status. PATIENTS AND METHODS: This nationwide cohort study included 9,520,629 adults without cancer who underwent the Korean National Health Screening in 2009 and were followed until 2018. Hazard ratios and 95% confidence intervals for pancreatic cancer were estimated after adjusting for potential confounders. RESULTS: During the 78.4 million person-years of follow-up, 15,245 patients were newly diagnosed with pancreatic cancer. Among individuals with diabetes and prediabetes, current smoking synergistically increased pancreatic cancer risk (all P<.01). However, quitters with diabetes and prediabetes had a pancreatic cancer risk comparable to that of never-smokers (all P>.05). For pancreatic cancer in current smokers, quitters, and never-smokers, respectively, the hazard ratios were 1.48 (95% CI, 1.40-1.58), 1.11 (95% CI, 1.03-1.19), and 1.00 (reference) among individuals with normoglycemia; 1.83 (95% CI, 1.70-1.97), 1.28 (95% CI, 1.18-1.39), and 1.20 (95% CI, 1.14-1.26) among individuals with prediabetes; and 2.72 (95% CI, 2.52-2.94), 1.78 (95% CI, 1.63-1.95), and 1.63 (95% CI, 1.54-1.72) among individuals with diabetes. There were no differences in risk between quitters with a <20 pack-year smoking history and never-smokers in all glycemic status groups. CONCLUSIONS: Pancreatic cancer risk synergistically increased in current smokers with diabetes and prediabetes. However, smoking cessation reduced the synergistically increased risk of pancreatic cancer to the level of never-smokers, especially when smoking history was <20 pack-years. More individualized and intensive cancer prevention education should be underscored for individuals at an increased risk of pancreatic cancer beyond the one-size-fits-all approach.

Determining Which Patients Require Preoperative Pelvic Radiotherapy Before Curative-Intent Surgery and/or Ablation for Metastatic Rectal Cancer.

BACKGROUND: The aim of this study is to determine the optimal indications for preoperative pelvic radiotherapy (RT) in patients with metastatic rectal cancer who underwent curative-intent surgical resection and/or ablation. METHODS: Between January 2000 and October 2019, 246 patients who met our inclusion criteria were enrolled. Preoperative RT was performed in 22 patients (8.9%). Lower margin below the peritoneal reflection (p < 0.001), mesorectal fascia (MRF) invasion (p = 0.02), and lateral pelvic lymph node (LPLN) involvement (p = 0.005) were more frequent in the preoperative RT group. RESULTS: During the median follow-up period of 13.3 months (interquartile range [IQR]: 6.0-36.3 months), local recurrence (LR) was identified in 60 patients (24.4%). It was the first site of recurrence in 45 of them (18.3%). Among them, three patients were in the preoperative RT group. On multivariable analysis, lower margin below the peritoneal reflection, MRF invasion, LPLN involvement, carcinoembryonic antigen (CEA) level ≥ 10 ng/mL before treatment, and preoperative RT were significant prognostic factors for LR-free survival (LRFS). In the patient group without any risk factors, the 2-year LRFS rate was 94.9% without preoperative RT. In the patient group with one or more risk factors, the 2-year LRFS was 64.4% without and 95.2% with preoperative RT. CONCLUSION: LR developed in about 25% of patients within 2 years. Preoperative RT should be considered, especially in patients with a risk factor for LR, including lower margin below the peritoneal reflection, MRF invasion, LPLN involvement, or CEA ≥ 10 ng/mL before treatment.

Efficacy and safety of atezolizumab plus bevacizumab in Korean patients with advanced hepatocellular carcinoma.

BACKGROUND & AIMS: Atezolizumab plus bevacizumab (Ate/Bev) has demonstrated efficacy and safety in patients with advanced hepatocellular carcinoma (HCC) in the phase III trial. Further evaluation is necessary to investigate the safety and efficacy of Ate/Bev in real settings. METHODS: This was a multicentre retrospective analysis. Between May 2020 and February 2021, 138 patients received Ate/Bev as first-line treatment for advanced HCC from 11 institutions. We excluded patients with Child-Pugh B or C and BCLC D stage, and the remaining 121 patients were included in this analysis. RESULTS: According to RECIST 1.1, the objective response and disease control rates were 24.0% and 76.0%. The median follow-up duration was 5.9 months (95% confidence interval [CI], 5.4-6.4), the median progression-free survival (PFS) was 6.5 months (95% CI, 4.1-9.0), and median overall survival (OS) was not reached (95% CI, not available). The most frequent grade 3-4 adverse event was aspartate aminotransferase elevation (10.7%). In the multivariate analyses, AFP increase (P = .037), baseline neutrophil-to-lymphocyte ratio (NLR) ≥ 5 (P = .023), and best response to stable disease or progressive disease (P = .019) were significantly associated with worse PFS. Macrovascular invasion (P = .048) and baseline NLR ≥5 (P < .001) were significantly associated with worse OS. CONCLUSIONS: Ate/Bev showed real-life efficacy and safety in Korean patients with advanced HCC, in line with results from phase III trial. Considering unfavourable survival outcomes of Ate/Bev in patients with elevated NLR, careful assessment of treatment response needs to be performed in this group.

Prediction of epithelial-to-mesenchymal transition molecular subtype using CT in gastric cancer.

OBJECTIVES: To develop a prediction model with computed tomography (CT) images and to build a nomogram incorporating known clinicopathologic variables for individualized estimation of epithelial-to-mesenchymal transition (EMT) subtype gastric cancer. METHODS: Patients who underwent primary resection of gastric cancer (GC) and molecular subgroup analysis (n = 451) were reviewed. Multivariable analysis using a stepwise variable selection method was performed to build a predictive model for EMT subtype GC. A nomogram using the results of the multivariable analysis was constructed. An optimal cutoff value of total prognostic points of the nomogram for the prediction of EMT subtype was determined. The predictive model for the EMT subtype was internally validated by bootstrap resampling method. RESULTS: There were 88 patients with EMT subtype and 363 patients with non-EMT subtype based on transcriptome analysis. The patient's age, Lauren classification, and mural stratification on CT were variables selected for the predictive model. The area under the curve (AUC) of the model was 0.865, and the validated AUC of the bootstrap sample was 0.860. The optimal cutoff value of total prognostic points for the prediction of EMT subtype was 94.622, with 90.9% sensitivity, 67.2% specificity, and 71.8% accuracy. CONCLUSION: A predictive model using patient's age, Lauren classification, and mural stratification on CT for EMT molecular subtype GC was made. A nomogram was built which would serve as a useful screening tool for an individualized estimate of EMT subtype. KEY POINTS: • A predictive model for epithelial-to-mesenchymal transition (EMT) subtype incorporating patient's age, Lauren classification, and mural stratification on CT was built. • The predictive model had high diagnostic accuracy (area under the curve (AUC) = 0.865) and was validated (bootstrap AUC = 0.860). • Adding CT findings to clinicopathologic variables increases the accuracy of the predictive model than using only.

Incorporating sarcopenia and inflammation with radiation therapy in patients with hepatocellular carcinoma treated with nivolumab.

BACKGROUND: We investigated the combined effects of sarcopenia and inflammation on outcomes in patients with HCC treated with nivolumab. MATERIALS AND METHODS: We reviewed 102 patients treated with nivolumab between 2017 and 2018. Sarcopenia was diagnosed when the L3 skeletal muscle indices were < 42 cm2/m2 and < 38 cm2/m2 in men and women, respectively. Baseline neutrophil-to-lymphocyte ratio (NLR) and absolute lymphocyte count were used as surrogate markers of inflammation and immune cell reservoir. High NLR (hNLR) was defined as NLR ≥ 3, and severe lymphopenia (sLP) was defined as lymphocyte < 800/µL. The overall survival (OS) and progression-free survival (PFS) were analyzed. RESULTS: With a median follow-up of 21.9 (interquartile range, 8.3-58.3) months, patients with sarcopenia showed shorter OS than those without sarcopenia (median, 2.9 vs. 7.5 months, respectively). Patients with either hNLR or sLP exhibited inferior survival than those without risk factor (median OS, 2.8 vs. 14.5 months; median PFS, 1.3 vs. 3.7 months, respectively). Among 70 patients treated with RT, benefit of RT was observed in patients with sarcopenia or those without hNLR/sLP (all p < 0.05). After multivariable analysis, RT, hNLR/sLP, albumin-bilirubin (ALBI) grade, and alpha-fetoprotein were significantly associated with OS (all p < 0.05), and hNLR/sLP was also associated with decreased PFS together with ALBI grade, alpha-fetoprotein, and RT (all p < 0.05). CONCLUSION: The current study hypothetically demonstrated that the risk group stratified by hNLR/sLP outweighs the significance of sarcopenia in predicting outcomes after nivolumab. Furthermore, patients with sarcopenia might benefit from RT, especially those without risk factors of hNLR/sLP.

Programmed Death Ligand 1 Expression as a Prognostic Marker in Patients with Advanced Biliary Tract Cancer.

BACKGROUND: Biliary tract cancer (BTC) is associated with poor prognosis because of its aggressive and heterogeneous nature. Programmed death ligand 1 (PD-L1) has been considered a novel biomarker for prognosis and response of immune checkpoint inhibitors in various tumors. However, there are limited data reporting on the role of PD-L1 in advanced BTC patients. PATIENTS AND METHODS: We analyzed 186 patients with advanced BTC who received palliative gemcitabine and platinum between May 2010 and December 2019. All patients were evaluated for PD-L1 expression by combined positive score positivity. RESULTS: Of the 186 patients, the primary tumor location was intrahepatic cholangiocarcinoma (IHCC) in 72 (38.7%), extrahepatic cholangiocarcinoma (EHCC) in 90 (48.4%), and gallbladder (GB) cancer in 24 (12.9%). Among all the patients, 53 (28.5%) had PD-L1 positivity. The median overall survival (OS) of patients with PD-L1 positivity or negativity was 12.1 and 15.4 months, respectively. The median progression-free survival (PFS) in patients with PD-L1 positivity or negativity was 5.7 and 7.1 months, respectively. OS and PFS were not statistically different between groups. In subgroup analysis, EHCC patients with PD-L1 negativity had more favorable OS (17.2 vs. 11.6 months, p = 0.002) and PFS (7.8 vs. 5.4 months, p = 0.005) than those who were PD-L1-positive. However, this finding was not reproduced in patients with IHCC or GB cancer. CONCLUSION: This study demonstrated that PD-L1 expression might be a novel prognostic biomarker in patients with EHCC but not in patients with IHCC or GB cancer.

Prognostic significance of sarcopenia in microsatellite-stable gastric cancer patients treated with programmed death-1 inhibitors.

BACKGROUND: Sarcopenia has been underscored as a significant predictor of poor prognosis in cancer patients undergoing immunotherapy with programmed death-1 (PD-1) inhibitors. We aimed to investigate the prognostic significance of computed tomography (CT)-determined sarcopenia in patients with microsatellite-stable (MSS) gastric cancer (GC) treated with PD-1 inhibitors. METHODS: We retrospectively assessed patients with MSS GC who had been treated with PD-1 inhibitors from March 2016 to June 2019. Pre-treatment sarcopenic status was determined by analyzing L3 skeletal muscle index with abdominal CT. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and the differences in survival probability according to sarcopenic status were compared using the log-rank test. Cox proportional hazards regression analyses were performed to identify predictors of PFS and OS. RESULTS: Of 149 patients with MSS GC (mean age, 57.0 ± 12.3 years; 93 men), 79 (53.0%) had sarcopenia. Patients with sarcopenia had significantly shorter PFS than patients without sarcopenia (median, 1.4 months vs. 2.6 months; P = 0.026). Sarcopenia was independently associated with shorter PFS (adjusted hazard ratio [HR], 1.79; 95% confidence interval [CI], 1.10-2.93; P = 0.020). Patients with sarcopenia had shorter OS than patients without sarcopenia (median, 3.6 months vs. 4.9 months; P = 0.052), but sarcopenia itself was not a significant prognostic factor for OS (adjusted HR, 1.01; 95% CI, 0.58-1.75; P = 0.974). CONCLUSIONS: CT-determined sarcopenia is an independent prognostic factor for PFS in patients with MSS GC treated with PD-1 inhibitors.

Regional Lymph Node Metastasis of Scalp Angiosarcoma: A Detailed Clinical Observation Study of 40 Cases.

BACKGROUND: The incidence of lymph node metastasis (LNM) of angiosarcomas is reported to be less than 15%, and elective neck management has not been indicated. This study evaluated the incidence and pattern of regional LNM in patients with scalp angiosarcomas using the clinical data of its full course to understand time-event sequences of scalp angiosarcomas. METHODS: This retrospective study included all consecutive cases of pathology-confirmed angiosarcomas and analyzed 40 cases of scalp angiosarcomas. The survival plots were estimated using the Kaplan-Meier method, and the results are presented mainly in a descriptive manner. RESULTS: The overall survival rate for the patients was 35.8% at 2 years. In contrast to previous reports, regional LNM was observed in more than half of the patients (52.5%) with scalp angiosarcoma. Meanwhile, a direct spread to distant organs occurred in only 27.5% of the patients. Regional LNM could predict clinical manifestation of systemic disease within 3 to 6 months. No differences in survival rates between patients with and without LNM were observed in this series. Occurrence of LNM seemed to be correlated with a high mitotic rate of primary tumors, but not with tumor grade or tumor dimension. The first-echelon lymph nodes from scalp angiosarcoma were peri-parotid, post-auricular, and level 2 lymph nodes. CONCLUSIONS: For a localized scalp angiosarcoma, it seems reasonable for initial curative surgery to include prophylactic evaluation of regional lymph nodes for pathologic nodal staging, prognosis estimation, and the decision for systemic treatments.

A phase II study of etoposide, methylprednisolone, high-dose cytarabine, and oxaliplatin (ESHAOx) for patients with refractory or relapsed Hodgkin's lymphoma.

We assessed the efficacy and toxicity of etoposide, methylprednisolone, high-dose cytarabine, and oxaliplatin (ESHAOx) combination chemotherapy in patients with refractory or relapsed Hodgkin's lymphoma (HL). This was an open-label, non-randomized, multi-center phase II study. The ESHAOx regimen consisted of intravenous (i.v.) etoposide 40 mg/m2 on days 1 to 4, i.v. methylprednisolone 500 mg on days 1 to 5, i.v. cytarabine 2 g/m2 on day 5, and i.v. oxaliplatin 130 mg/m2 on day 1. Cycles (up to six) were repeated every 3 weeks. In an effort to identify prognostic markers, the serum levels of cytokines including tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and vascular endothelial growth factor (VEGF) were measured at the time of study entry. A total of 37 patients were enrolled, and 36 were available for evaluation of tumor response. The overall response rate was 72.2% (26/36) (complete response, 33.3% [12/36]; partial response, 38.9% [14/36]). The median time to progression was 34.9 months (95% confidence interval, 23.1-46.7 months). The most common grade 3 or 4 hematological adverse events were neutropenia (16/37, 43.2%), followed by thrombocytopenia (10/37, 27.0%). Grade 3 or 4 non-hematological adverse events were nausea (3/37, 8.1%), anorexia (2/37, 5.4%), mucositis (1/37, 2.7%), and skin rash (1/37, 2.7%). There were no treatment-related deaths. High levels of TNF-α and CRP were significantly associated with poorer overall survival (p = 0.00005 for TNF-α, p = 0.0004 for CRP, respectively). The ESHAOx regimen exhibited antitumor activity and an acceptable safety profile in patients with refractory or relapsed HL. Trial Registration: ClinicalTrials.gov. Registered February 21, 2011, https://clinicaltrials.gov/ct2/show/NCT01300156.

Regorafenib in patients with advanced Child-Pugh B hepatocellular carcinoma: A multicentre retrospective study.

INTRODUCTION: Regorafenib is an approved agent in patients with advanced hepatocellular carcinoma (HCC) who progressed on sorafenib, but little is known about its clinical outcomes in Child-Pugh B patients. We aimed to investigate the safety and effectiveness of regorafenib in Child-Pugh B HCC patients. METHODS: This multicentre retrospective study included 59 patients with Child-Pugh B HCC who received regorafenib. Comparative analyses were performed with an independent cohort of Child-Pugh class A patients from the same registry (n = 440). RESULTS: The median age was 58 years (range, 19-83). All patients had progression on prior sorafenib. Regorafenib was given as 2nd line, and 3rd-4th line systemic therapy in 37 (62.7%) and 22 (37.3%) patients respectively. Compared to Child-Pugh A cohort, grade 3-4 AEs were more common in the Child-Pugh B cohort (27.1% vs 14.1%, P = .017). The median progression-free survival (PFS) and overall survival (OS) were 1.8 and 4.6 months, respectively, and these were significantly poorer than the Child-Pugh A cohort (P = .008 and P < .001 respectively). Child-Pugh B patients with albumin-bilirubin (ALBI) grade 3 had a significantly higher frequency of increased bilirubin (P = .01 for any grade and P = .01 for grade 3-4) and showed significantly poorer OS (P = .021), compared to those with ALBI grade 1 or 2. CONCLUSION: Regorafenib's poor clinical outcomes and increased frequency of severe adverse events lead us to discourage its use in the Child-Pugh B population. In particular, regorafenib should not be used in Child-Pugh B patients with ALBI grade 3.

How Cancer Patients Perceive Clinical Trials (CTs) in the Era of CTs: Current Perception and Its Differences Between Common and Rare Cancers.

Perception has recently been highlighted as a critical determinant for participation in clinical trials (CTs) among cancer patients. We evaluated cancer patients' current perceptions of CTs using the PARTAKE questionnaires, focusing on differences between patients with common and rare cancers. From November 2015 to May 2017, we prospectively surveyed patients who had received anti-cancer treatment at Asan Medical Center. Among 333 respondents, 70.9% had common and 29.1% had rare cancers. In the cohort, 87.7% of patients with common cancers and 75.3% of patients with rare cancers answered that they heard of and knew about CTs. However, willingness to participate in CTs was expressed only in approximately 56% of patients, although it was significantly associated with awareness and perception. Surprisingly, patients with rare cancers when compared with patients with common cancers showed significantly lower levels of awareness and perception (64.2% vs 79.9%, p = 0.003 and 77.3% vs 91.9%, p < 0.001), and consequently less willingness to participate in CTs (47.4% vs 58.9%, p = 0.06). In addition, cancer patients still harbored fear and concerns about safety and reward of CTs, and demonstrated substantial lack of knowledge about the voluntary nature of CTs, which was more obvious in patients with rare cancers. We identified relatively modest willingness of cancer patients to participate in CTs regardless of generally favorable perception. These findings are highlighted by the more negative perception of CTs among patients with rare cancers relative to those with common cancers. Further education and encouragement by research and public entities seem essential to improve motivation of CTs in cancer patients beyond good perception, especially for patients with rare cancers.

Ruxolitinib shows activity against Hodgkin lymphoma but not primary mediastinal large B-cell lymphoma.

BACKGROUND: The upregulated expression of the JAK/STAT pathway promotes tumor growth in Hodgkin lymphoma (HL) and primary mediastinal large B-cell lymphoma (PMBCL). Based on the hypothesis that JAK2 is a therapeutic target, we performed a prospective pilot study using ruxolitinib. METHODS: Relapsed or refractory patients with HL or PMBCL were eligible for this study, and JAK2 amplification was assessed by fluorescence in situ hybridization. Ruxolitinib was administered orally at a dose of 20 mg twice daily for a 28-day cycle. Treatment was continued for up to 16 cycles or until progressive disease or intolerability. The primary objective was to assess the overall disease control rate comprising complete response (CR), partial response (PR), or stable disease (SD). RESULTS: We analyzed 13 HL patients and six PMBCL patients. All responders (one CR, five PR, and one SD) had HL whereas all cases of PMBCL progressed after first or second cycle. The disease control rate for HL was 54% (7/13) with median response duration of 5.6 months. JAK2 amplification was present in six of nine patients tested (four HL, two PMBCL), and three of these HL patients showed PR (n = 2) or SD (n = 1). None of the three HL patients shown to not have JAK2 amplification responded to ruxolitinib. Most treatment-related adverse events were grade 1 or 2 and manageable. CONCLUSIONS: Ruxolitinib has single-agent activity against HL but does not act against PMBCL with or without JAK2 amplification. TRIAL REGISTRATION: The study population was patients who had relapsed or refractory HL or PMBCL, and patients were registered for our pilot study after providing written informed consent between November 2013 and November 2015 (CilinicalTrials.gov: NCT01965119).

Pharmacokinetic and pharmacodynamic study of lenograstim for hematopoietic stem cell mobilization: a prospective randomized study for optimal apheresis.

BACKGROUND: This study evaluated the correlation between the pharmacokinetics and pharmacodynamics of granulocyte colony-stimulating factor (lenograstim) and the impact of initiation time of apheresis on stem cell mobilization in patients with multiple myeloma. STUDY DESIGN AND METHODS: Twenty-four patients with multiple myeloma were randomized into one of the two groups (early vs. late). Lenograstim at 10 µg/kg/day once daily was injected for at least 4 consecutive days. Apheresis was initiated 2 hours after the fourth dose of lenograstim in the early collection group and 16 hours after the fourth dose of lenograstim in the late collection group. Blood sampling for pharmacokinetics was performed within 30 minutes before, and 1, 2, 6, and 24 hours after the fourth dose of lenograstim. RESULTS: Overall, the two groups (early vs. late, n = 10 vs. 14) exhibited similar baseline characteristics including age, sex, subtype of myeloma, stage distribution, and myeloma-associated symptoms. No correlation was found between plasma lenograstim concentration and peripheral blood (PB) CD34+ cell counts or hematopoietic progenitor cells. In the late collection group, the median number of apheresis procedures for minimal collection was significantly lower (early vs. late: 2 vs. 1; p = 0.04) and there was a higher number of total collected PB CD34+ cells in a single session of apheresis (1.4 vs. 3.1; p = 0.06). There were no differences in median overall PB stem cell collection efficiency. CONCLUSION: Late collection positively impacted the number of apheresis procedures for minimal collection, with numerically improved PB stem cell collection efficiency at first apheresis in patients with multiple myeloma.

Thiotepa, busulfan, and cyclophosphamide or busulfan, cyclophosphamide, and etoposide high-dose chemotherapy followed by autologous stem cell transplantation for consolidation of primary central nervous system lymphoma.

Primary central nervous system lymphoma (PCNSL) is a rare extranodal non-Hodgkin lymphoma for which standard treatment has yet to be established. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a suitable consolidation strategy for patients who respond to induction chemotherapy. The purpose of this study was to compare the outcome and toxicity profile of the combination of busulfan, cyclophosphamide, and etoposide (BuCyE) with that of the combination of thiotepa, busulfan, and cyclophosphamide (TBC) as conditioning regimens of upfront ASCT for consolidation therapy in PCNSL. The PCNSL registry data set, prospectively collected from March 1993 to May 2017 at Asan Medical Center, was reviewed retrospectively. Patients with objective response to induction chemotherapy who received BuCyE or TBC as conditioning regimen for ASCT were included in the analysis. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Among 241 patients with a diagnosis of PCNSL, 53 received ASCT as upfront consolidation therapy with TBC (28 patients) or BuCyE (25 patients) as conditioning regimen. No median OS or PFS was reached in the TBC group, while the BuCyE group reached a median OS of 4.9 years (p = 0.02) and median PFS of 1.1 years (p = 0.007). The incidence of oral mucositis, nausea, and vomiting was higher with TBC than BuCyE. The median admission duration and days to engraftment were similar between the two groups. Despite the greater incidence of adverse events, TBC showed better outcomes than BuCyE in terms of survival.

Multicenter retrospective analysis of the clinicopathologic features of monomorphic epitheliotropic intestinal T-cell lymphoma.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a provisional entity in the 2017 World Health Organization classifications. To further elucidate the clinicopathologic features of this new disease, we carried out a retrospective, multicenter analysis of 42 patients with MEITL. The median age of the patients was 59 years (range, 20-84 years), and 27 patients (64 %) were male. Thirty-two patients (76 %) were Ann-Arbor stages I-II and 28 (67 %) were Lugano stages I-II1&2. The most frequent site of involvement was the jejunum (N = 21). Most cases expressed CD8 (79 %) and CD56 (95 %) and did not express CD30 (5 %) or EBER (0 %). The median progression-free survival was 6.9 months (95 % CI 4.3-9.6); the median OS was 14.8 months (2.4-27.2). Thirty-two patients (76 %) underwent surgery and 37 (88 %) received chemotherapy. A complete response (CR) rate was 38 %. Sixteen patients had undergone autologous stem cell transplantation (ASCT). Relapse or progression was documented in 24 cases, most frequently in the primary site (N = 23). Four cases showed central nervous system relapse. Age over 55 years, poor performance scale, advanced Lugano stage (IIE-IV), not achieving CR, and not receiving ASCT were associated with inferior OS. While the optimal management of MEITL remains undetermined, achieving CR and consolidative ASCT seem essential. As CHOP might be insufficient for achieving CR, more efficient combinations should be investigated. Additionally, considering the frequent local failure and CNS relapse, novel therapeutic approaches are required to improve survival.

Phase I study of CKD-581, a pan-histone deacetylase inhibitor, in patients with lymphoma or multiple myeloma refractory to standard therapy.

Background The objective of this study was to assess the safety, dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), pharmacokinetics, and anti-tumor efficacy of CKD-581, a novel pan-histone deacetylase inhibitor, in patients with lymphoma or multiple myeloma (MM) refractory to standard therapy. Methods In this phase I study, CKD-581 was intravenously administered on days 1, 8, and 15 of a 28-day cycle. A standard 3 + 3 cohort design was used to determine the MTD. Acetylated histones H3 and H4 in peripheral blood mononuclear cells were measured for pharmacodynamic assessment in a subpopulation of patients. Results Thirty-nine patients were treated with CKD-581 at 9 dose levels from 10 mg/m2 to 210 mg/m2. The DLTs were grade 3 neutropenia that delayed the treatment for >2 weeks (one patient at a dose of 50 mg/m2) and grade 4 thrombocytopenia (two patients at a dose of 210 mg/m2). The MTD of CKD-581 was 160 mg/m2. The most common grade 3/4 treatment-related adverse events were thrombocytopenia (n = 5, 12.8%) and neutropenia (n = 2, 5.1%). The peak concentration and area under the curve values for CKD-581 increased in proportion to the dose, indicating linear pharmacokinetics. A partial response was observed in 2 patients (5.6%), and stable disease was observed in 16 (44.4%) patients. In the pharmacodynamic evaluation, acetylation of H3 and H4 was observed at all doses of ≥50 mg/m2. Conclusion CKD-581 was well tolerated by the patients with lymphoma or MM refractory to standard therapy. It exhibited dose-proportional pharmacokinetics and modest anti-tumor efficacy.

The cell-of-origin classification of diffuse large B cell lymphoma in a Korean population by the Lymph2Cx assay and its correlation with immunohistochemical algorithms.

Cell-of-origin (COO) classification of diffuse large B cell lymphoma (DLBCL) is increasingly important due to its prognostic significance and the development of subtype-specific therapeutics. We compared the clinical utility of the Lymph2Cx assay against four widely used immunohistochemical algorithms in 150 R-CHOP-treated DLBCL patients using archival tissue. In contrast to the predominance of germinal center B cell-like (GCB) subtype in Western populations, Lymph2Cx assay classified more than half of the Korean cases as the activated B cell-like (ABC) subtype (ABC, 83/150 [55.3%]; GCB, 51/150 [34.0%]; unclassifiable, 16/150 [10.7%]). Predominance of ABC subtype tended to be more pronounced in the nodal lymphomas than in the extranodal lymphomas. However, among the primary extranodal sites, ABC subgroups predominated in primary testicular, breast, and adrenal gland lymphomas. The classification of COO by Lymph2Cx assay did not show any significant association with clinical parameters. The overall concordance rates of the immunohistochemical algorithms with the Lymph2Cx ranged from 78.0 to 84.3%. However, 47.1-66.7% of the cases of the Lymph2Cx-defined GCB subgroup were misclassified as the non-GCB class by the IHC algorithms. The survival of Lymph2Cx-classified COO subtypes was not significantly different in the present cohort. In conclusion, ABC subtype predominated over GCB in Korean patients. There are significant discrepancies between the immunohistochemistry and Lymph2Cx classifications, especially in GCB subtype.

Treating synchronous bilateral ocular adnexal marginal zone lymphoma: the consortium for improving survival of lymphoma study.

Both-side synchronous involvement has been reported to account for 7-24% of ocular adnexal marginal zone lymphoma (OAML). We conducted a retrospective analysis to identify the clinical features and treatment outcomes of synchronous bilateral OAML (SB-OAML) by treatment modality. We analyzed patients with a histologic diagnosis of SB-OAML, excluding metachronous bilateral involved OAML. We enrolled a total of 95 patients for this analysis, 36 males and 59 females; the median patient age was 42 years (range 16-77 years). Eleven (11.6%) patients had been treated with chemotherapy or chemo-immunotherapy (eight R-CVP, two CVP, and one R-CHOP). The median number of treatments was 6 (range 6-8); there were 9 complete responses (CRs; 81.8%) and 2 partial responses (PRs; 18.2%). Nearly all patients (88.4%) received radiotherapy in both eyes, and the median radiation dose was 27 Gy (range 20-40 Gy) to each eye; 68 CRs (80.9%) and 14 PRs (16.7%) were achieved. Ten-year progression-free survival (PFS) and overall survival (OS) rates were 79.8 and 91.1%, respectively. Radiotherapy continued to be an independent prognostic marker, with the hazard of progression (P = 0.036). Eleven patients (13.1%) had surgery for cataract treatment during follow-up, and patients who received low-dose radiation (< 30.3 Gy) experienced fewer cataract operations. SB-OAML was predominantly observed in young females, and they had good response and prognosis regardless of treatment modalities. Low-dose radiotherapy to both eyes showed a tendency of longer PFS than did chemotherapy and could decrease cataract operations.