99mTc-DMSA and 99mTc-DTPA identified renal dysfunction due to microplastic polyethylene in murine model.

In the previous study (Im et al., 2022), we revealed microplastic (MP) was accumulated and cleared through the kidneys via PET imaging. Here, we aimed to identify the renal dysfunction due to polyethylene (PE) MP in the kidney tissue. Mice were exposed to 100 ppm (∼equivalent to 0.1 mg/mL)/100 µL of PE for 12 weeks (n = 10). PE uptake in the kidney tissues was confirmed using confocal microscopy. QuantSeq analysis was performed to determine gene expression. Renal function assessment was performed using 99mTc-Diethylene triamine penta acetic acid or 99mTc-Dimercaptosuccinic acid. Measurement of creatinine, BUN, and albumin levels in serum and urine samples was also estimated. [18F]-FDG was also acquired. PE increased expression of Myc, CD44, Programmed Death-Ligand 1 (PD-L1), and Hypoxia-Inducible Factor (HIF)-1α, which indicates a potential link to an increased risk of early-onset cancer. An increase in glucose metabolism of [18F]-FDG were observed. We assessed renal failure using 99mTc-Diethylene triamine penta acetic acid and 99mTc-Dimercaptosuccinic acid scintigraphy to determine the renal function. Renal failure was confirmed using serum and urine creatinine, serum blood urea nitrogen levels, serum albumin levels, and urine albumin levels in PE exposed mice, relative to the control. In sum, PE exposure induced renal dysfunction in a murine model.

A Phase II Study of 131I-rituximab for Patients With Relapsed or Refractory Marginal Zone Lymphoma.

Background: Radioimmunotherapy (RIT) is a rare treatment option for relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). We investigated the safety and efficacy of 131I-rituximab in patients with relapsed or refractory marginal zone lymphomas. Methods: Patients with pathologically confirmed marginal zone lymphoma who relapsed or were resistant to prior therapy were enrolled. The patients received 250 mg/m2 of unlabeled rituximab immediately before receiving a therapeutic 131I-rituximab dose. The primary endpoint was the objective response rate (ORR), and the secondary endpoints were toxicity assessment, progression-free survival (PFS), and overall survival (OS). Results: Ten patients (median age = 57.5 years; range = 32-71) were included. Owing to poor enrollment, only 10 of the initially intended 25 patients were included in the study, rendering it unfeasible to perform the primary endpoint analysis. Before RIT, patients received chemotherapy, with 40% (n = 4) receiving rituximab therapy. Median PFS and OS were 18.9 months (95% confidence interval [CI]: 0.0-38.9) and 100.0 months (95% CI: 39.8-160.1), respectively. The ORR was 90%, and the duration of response was 29.7 months (95% CI: 0.0-61.3). Considering a median follow-up of 78.5 months (95% CI: 42.7-114.3), 4 patients (40%) were diagnosed with secondary malignancy. Hematological toxicities were common treatment-related adverse events, and 60% and 50% of the patients experienced grade 3 to 4 thrombocytopenia and neutropenia, respectively. Conclusions: 131I-rituximab showed marked efficacy in patients with relapsed or refractory marginal zone lymphoma, with a considerable risk of secondary malignancies during long-term follow-up. Radioimmunotherapy is not a recommended treatment option for relapsed or refractory marginal zone lymphoma but may be considered when other treatment options are not feasible.

A stepwise approach to fine needle aspiration cytology of lymph nodes.

The cytological diagnosis of lymph node lesions is extremely challenging because of the diverse diseases that cause lymph node enlargement, including both benign and malignant or metastatic lymphoid lesions. Furthermore, the cytological findings of different lesions often resemble one another. A stepwise diagnostic approach is essential for a comprehensive diagnosis that combines: clinical findings, including age, sex, site, multiplicity, and ultrasonography findings; low-power reactive, metastatic, and lymphoma patterns; high-power population patterns, including two populations of continuous range, small monotonous pattern and large monotonous pattern; and disease-specific diagnostic clues including granulomas and lymphoglandular granules. It is also important to remember the histological features of each diagnostic category that are common in lymph node cytology and to compare them with cytological findings. It is also essential to identify a few categories of diagnostic pitfalls that often resemble lymphomas and easily lead to misdiagnosis, particularly in malignant small round cell tumors, poorly differentiated squamous cell carcinomas, and nasopharyngeal undifferentiated carcinoma. Herein, we review a stepwise approach for fine needle aspiration cytology of lymphoid diseases and suggest a diagnostic algorithm that uses this approach and the Sydney classification system.

Validation of a Machine Learning Expert Supporting System, ImmunoGenius, Using Immunohistochemistry Results of 3000 Patients with Lymphoid Neoplasms.

(1) Background: Differential diagnosis using immunohistochemistry (IHC) panels is a crucial step in the pathological diagnosis of hematolymphoid neoplasms. In this study, we evaluated the prediction accuracy of the ImmunoGenius software using nationwide data to validate its clinical utility. (2) Methods: We collected pathologically confirmed lymphoid neoplasms and their corresponding IHC results from 25 major university hospitals in Korea between 2015 and 2016. We tested ImmunoGenius using these real IHC panel data and compared the precision hit rate with previously reported diagnoses. (3) Results: We enrolled 3052 cases of lymphoid neoplasms with an average of 8.3 IHC results. The precision hit rate was 84.5% for these cases, whereas it was 95.0% for 984 in-house cases. (4) Discussion: ImmunoGenius showed excellent results in most B-cell lymphomas and generally showed equivalent performance in T-cell lymphomas. The primary reasons for inaccurate precision were atypical IHC profiles of certain cases, lack of disease-specific markers, and overlapping IHC profiles of similar diseases. We verified that the machine-learning algorithm could be applied for diagnosis precision with a generally acceptable hit rate in a nationwide dataset. Clinical and histological features should also be taken into account for the proper use of this system in the decision-making process.

Radioimmunotherapy with 131 I-rituximab for patients with relapsed or refractory follicular or mantle cell lymphoma.

AIM: This study aimed to evaluate the safety and efficacy of 131 I-rituximab in patients with relapsed or refractory follicular or mantle cell lymphoma. METHODS: Twenty-four patients with relapsed or refractory follicular or mantle cell lymphoma were administered unlabeled rituximab (70 mg) immediately before receiving a therapeutic dose of 131 I-rituximab. Contrast-enhanced 18F-fluorodeoxyglucose positron emission tomography/computed tomography was used a month later to assess tumor response. RESULTS: This study enrolled 24 patients between June 2012 and 2022. Depending on how they responded to radioimmunotherapy (RIT), 131 I-rituximab was administered one to five times. Of the 24 patients, 9 achieved complete response after RIT and 8 achieved partial response. The median progression-free and overall survival was 5.9 and 37.9 months, respectively. During the follow-up period of 64.2 months, three patients were diagnosed with a secondary malignancy. Among treatment-related adverse events, hematologic toxicities were common, and grade 3-4 thrombocytopenia and neutropenia were reported in 66.6% of cases. CONCLUSION: 131 I-rituximab has an effective and favorable safety profile in patients with relapsed or refractory follicular lymphoma and mantle cell lymphoma. This suggests that RIT may also be considered a treatment option for patients with relapsed or refractory follicular lymphoma and mantle cell lymphoma.

Utility and Limitations of Fine-Needle Aspiration Cytology in the Diagnosis of Lymphadenopathy.

BACKGROUND: Fine needle aspiration cytology (FNAC) is a valuable tool for evaluating lymphadenopathy. The purpose of this study was to assess the reliability and effectiveness of FNAC in the diagnosis of lymphadenopathy. METHODS: Cytological characteristics were evaluated in 432 patients who underwent lymph node FNAC and follow-up biopsy at the Korea Cancer Center Hospital from January 2015 to December 2019. RESULTS: Fifteen (3.5%) of the four hundred and thirty-two patients were diagnosed as inadequate by FNAC, with five (33.3%) of these diagnosed as metastatic carcinoma on histological examination. Of the 432 patients, 155 (35.9%) were diagnosed as benign by FNAC, with seven (4.5%) of these diagnosed histologically as metastatic carcinoma. A review of the FNAC slides, however, showed no evidence of cancer cells, suggesting that the negative results may have been due to FNAC sampling errors. An additional five samples regarded as benign on FNAC were diagnosed as non-Hodgkin lymphoma (NHL) by histological examination. Of the 432 patients, 223 (51.6%) were cytologically diagnosed as malignant, with 20 (9.0%) of these diagnosed as tissue insufficient for diagnosis (TIFD) or benign on histological examination. A review of the FNAC slides of these 20 patients, however, showed that 17 (85.0%) were positive for malignant cells. The sensitivity, specificity, positive predictive value (PPV), negative predictive values (NPV), and accuracy of FNAC were 97.8%, 97.5%, 98.7%, 96.0%, and 97.7%, respectively. CONCLUSIONS: Preoperative FNAC was safe, practical, and effective in the early diagnosis of lymphadenopathy. This method, however, had limitations in some diagnoses, suggesting that additional attempts may be required according to the clinical situation.

PINX1 promotes malignant transformation of thyroid cancer through the activation of the AKT/MAPK/ß-catenin signaling pathway.

Although thyroid cancer is the most prevalent endocrine malignancy, overall patients with thyroid cancer have a good long-term survival. However, a small percentage of patients with progressive thyroid cancer have poor outcomes, and the genetic drivers playing a key role thyroid cancer progression are mostly unknown. Here, we investigated the role of the PINX1 in thyroid cancer progression. Interestingly, PINX1 expression was significantly higher in ATC than in PTC in both patients and cell lines. When PINX1 was knockdown in ATC cells, cell proliferation rates, colony formation capacity, and cell cycle progression were significantly reduced. Furthermore, cell motility and the expression of EMT drivers were reduced by PINX1 downregulation. In contrast, the overexpression of PINX1 in PTC cells significantly increased those phenotypes of tumor progression, which demonstrates that PINX1 could promote tumor proliferation and malignant transformation in both PTC and ATC cells. To further understand whether PINX1 is also involved in the progression of PTC to ATC, we examined PI3K/AKT, MAPK, and ß-catenin signaling activation after PINX1 modulation. Decreased PINX1 expression reduced the levels of p-AKT, p-ERK, p-p38, and ß-catenin in ATC cells, but the increase of PINX1 expression upregulated the phosphorylation of AKT, ERK, and p38 and the levels of ß-catenin in PTC cells. These results were all confirmed in xenograft mouse tumors. Our findings suggest that PINX1 regulates thyroid cancer progression by promoting cell proliferation, EMT, and signaling activation, and support the hypothesis that PINX1 could be a prognostic marker and a therapeutic target of thyroid cancer.

Expansion of monocytic myeloid-derived suppressor cells ameliorated intestinal inflammatory response by radiation through SOCS3 expression.

Radiation-induced colitis is a common clinical problem after radiation therapy and accidental radiation exposure. Myeloid-derived suppressor cells (MDSCs) have immunosuppressive functions that use a variety of mechanisms to alter both the innate and the adaptive immune systems. Here, we demonstrated that radiation exposure in mice promoted the expansion of splenic and intestinal MDSCs and caused intestinal inflammation due to the increased secretion of cytokines. Depletion of monocytic MDSCs using anti-Ly6C exacerbated radiation-induced colitis and altered the expression of inflammatory cytokine IL10. Adoptive transfers of 0.5 Gy-derived MDSCs ameliorated this radiation-induced colitis through the production IL10 and activation of both STAT3 and SOCS3 signaling. Intestinal-inflammation recovery using 0.5 Gy-induced MDSCs was assessed using histological grading of colitis, colon length, body weight, and survival rate. Using in vitro co-cultures, we found that 0.5 Gy-induced MDSCs had higher expression levels of IL10 and SOCS3 compared with 5 Gy-induced MDSCs. In addition, IL10 expression was not enhanced in SOCS3-depleted cells, even in the presence of 0.5 Gy-induced monocytic MDSCs. Collectively, the results indicate that 0.5 Gy-induced MDSCs play an important immunoregulatory role in this radiation-induced colitis mouse model by releasing anti-inflammatory cytokines and suggest that IL10-overexpressing mMDSCs may be potential immune-therapy targets for treating colitis.

Radiation-Induced Overexpression of TGFß and PODXL Contributes to Colorectal Cancer Cell Radioresistance through Enhanced Motility.

The primary cause of colorectal cancer (CRC) recurrence is increased distant metastasis after radiotherapy, so there is a need for targeted therapeutic approaches to reduce the metastatic-relapse risk. Dysregulation of the cell-surface glycoprotein podocalyxin-like protein (PODXL) plays an important role in promoting cancer-cell motility and is associated with poor prognoses for many malignancy types. We found that CRC cells exposed to radiation demonstrated increased TGFß and PODXL expressions, resulting in increased migration and invasiveness due to increased extracellular matrix deposition. In addition, both TGFß and PODXL were highly expressed in tissue samples from radiotherapy-treated CRC patients compared to those from patients without this treatment. However, it is unclear whether TGFß and PODXL interactions are involved in cancer-progression resistance after radiation exposure in CRC. Here, using CRC cells, we showed that silencing PODXL blocked radiation-induced cell migration and invasiveness. Cell treatment with galunisertib (a TGFß-pathway inhibitor) also led to reduced viability and migration, suggesting that its clinical use may enhance the cytotoxic effects of radiation and lead to the effective inhibition of CRC progression. Overall, the results demonstrate that downregulation of TGFß and its-mediated PODXL may provide potential therapeutic targets for patients with radiotherapy-resistant CRC.

Overexpression of dopamine receptor D2 promotes colorectal cancer progression by activating the ß-catenin/ZEB1 axis.

Colorectal cancer (CRC) is a recurring cancer that is often resistant to conventional therapies and therefore requires the development of molecular-based therapeutic approaches. Dopamine receptor D2 (DRD2) is associated with the growth of many types of tumors, but its oncogenic role in CRC is unclear. Here, we observed that elevated DRD2 expression was associated with a poor survival rate among patients with CRC. Depletion of DRD2 suppressed CRC cell growth and motility by downregulating ß-catenin/ZEB signaling in vitro and in vivo, whereas overexpression of DRD2 promoted CRC cell progression. Inhibition of DRD2 by the antagonist pimozide inhibited tumor growth and lymph node metastasis in vivo and enhanced the cytotoxic effects of conventional agents in vitro. Taken together, our findings indicate that targeting the DRD2/ß-catenin/ZEB1 signaling axis is a potentially promising therapeutic strategy for patients with CRC.

Early prediction of neoadjuvant chemotherapy response for advanced breast cancer using PET/MRI image deep learning.

This study aimed to investigate the predictive efficacy of positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) for the pathological response of advanced breast cancer to neoadjuvant chemotherapy (NAC). The breast PET/MRI image deep learning model was introduced and compared with the conventional methods. PET/CT and MRI parameters were evaluated before and after the first NAC cycle in patients with advanced breast cancer [n = 56; all women; median age, 49 (range 26-66) years]. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were obtained with the corresponding baseline values (SUV0, MTV0, and TLG0, respectively) and interim PET images (SUV1, MTV1, and TLG1, respectively). Mean apparent diffusion coefficients were obtained from baseline and interim diffusion MR images (ADC0 and ADC1, respectively). The differences between the baseline and interim parameters were measured (ΔSUV, ΔMTV, ΔTLG, and ΔADC). Subgroup analysis was performed for the HER2-negative and triple-negative groups. Datasets for convolutional neural network (CNN), assigned as training (80%) and test datasets (20%), were cropped from the baseline (PET0, MRI0) and interim (PET1, MRI1) images. Histopathologic responses were assessed using the Miller and Payne system, after three cycles of chemotherapy. Receiver operating characteristic curve analysis was used to assess the performance of the differentiating responders and non-responders. There were six responders (11%) and 50 non-responders (89%). The area under the curve (AUC) was the highest for ΔSUV at 0.805 (95% CI 0.677-0.899). The AUC was the highest for ΔSUV at 0.879 (95% CI 0.722-0.965) for the HER2-negative subtype. AUC improved following CNN application (SUV0:PET0 = 0.652:0.886, SUV1:PET1 = 0.687:0.980, and ADC1:MRI1 = 0.537:0.701), except for ADC0 (ADC0:MRI0 = 0.703:0.602). PET/MRI image deep learning model can predict pathological responses to NAC in patients with advanced breast cancer.

Inhibition of EphA2 by Dasatinib Suppresses Radiation-Induced Intestinal Injury.

Radiation-induced multiorgan dysfunction is thought to result primarily from damage to the endothelial system, leading to a systemic inflammatory response that is mediated by the recruitment of leukocytes. The Eph-ephrin signaling pathway in the vascular system participates in various disease developmental processes, including cancer and inflammation. In this study, we demonstrate that radiation exposure increased intestinal inflammation via endothelial dysfunction, caused by the radiation-induced activation of EphA2, an Eph receptor tyrosine kinase, and its ligand ephrinA1. Barrier dysfunction in endothelial and epithelial cells was aggravated by vascular endothelial-cadherin disruption and leukocyte adhesion in radiation-induced inflammation both in vitro and in vivo. Among all Eph receptors and their ligands, EphA2 and ephrinA1 were required for barrier destabilization and leukocyte adhesion. Knockdown of EphA2 in endothelial cells reduced radiation-induced endothelial dysfunction. Furthermore, pharmacological inhibition of EphA2-ephrinA1 by the tyrosine kinase inhibitor dasatinib attenuated the loss of vascular integrity and leukocyte adhesion in vitro. Mice administered dasatinib exhibited resistance to radiation injury characterized by reduced barrier leakage and decreased leukocyte infiltration into the intestine. Taken together, these data suggest that dasatinib therapy represents a potential approach for the protection of radiation-mediated intestinal damage by targeting the EphA2-ephrinA1 complex.

Major Clues and Pitfalls in the Differential Diagnosis of Parathyroid and Thyroid Lesions Using Fine Needle Aspiration Cytology.

BACKGROUND: It is difficult to distinguish parathyroid lesions (PLs) from thyroid lesions using fine needle aspiration cytology (FNAC) because of their proximity and their similar cytomorphological features. METHODS: FNAC smears of 46 patients with pathologically proven PLs that were histologically diagnosed as parathyroid adenoma (PA, n = 35), parathyroid hyperplasia (PH, n = 3), atypical parathyroid adenoma (APA, n = 1), and parathyroid carcinoma (PC, n = 7) were retrospectively reviewed and analyzed. RESULTS: Our initial cytological diagnoses indicated correct diagnoses in 31 of 46 PL patients (67%). The 15 erroneous diagnoses were 5 patients with non-specific benign disease (11%), 4 with nodular hyperplasia of the thyroid (9%), 5 with atypical cells (11%), and 1 with a metastatic papillary thyroid carcinoma (2%). Follicular pattern, papillary structures, colloid-like material, and macrophages, which often suggest thyroid lesions, were also present in some PLs. We found that branching capillaries along the papillary structures, stippled nuclear chromatin, and frequent occurrence of naked nuclei were useful for determining a parathyroid origin. CONCLUSIONS: It is important to be aware that PLs are frequently mistaken for thyroid lesions based on FNAC. The specific and unique characteristics of PLs identified here may be helpful in diagnosis.

Inhibition of HIF-1α by Atorvastatin During 131I-RTX Therapy in Burkitt's Lymphoma Model.

BACKGROUNDS: Radioimmunotherapy (RIT) serves as a targeted therapy for non-Hodgkin lymphomas (NHL). Although HIF(Hypoxia-inducible factors)-1α is an important biomarker during radiation therapy, its role in NHL is unclear. Atorvastatin (ATV) is used as a combination drug for chemotherapy. METHODS: We investigated whether ATV downregulated tumor radio-resistance and enhanced the anticancer effect of 131I-RTX (rituximab) in Raji xenograft mouse models. First, the increased uptake and enhanced therapeutic effect of 131I-RTX by ATV was confirmed using molecular imaging in Raji xenograft subcutaneous model and orthotropic model with SPECT and IVIS images. Second, we examined the profile of differentially expressed miRNAs using miRNA array. RESULTS: We found that miR-346 inhibited HIF-1α/VEGF (Vascular endothelial growth factor) during ATV combination therapy with 131I-RTX. The underlying mechanism of ATV involved induction of anti-angiogenesis and radiosensitivity by downregulating HIF-1α in Raji cells. CONCLUSION: Our findings suggested that combination therapy with ATV and 131I-RTX is a promising strategy for enhancing the potency of 131I-RTX therapy in poorly responding patients and those with radio-resistance.

Efficacy of Brentuximab Vedotin in Relapsed or Refractory High-CD30-Expressing Non-Hodgkin Lymphomas: Results of a Multicenter, Open-Labeled Phase II Trial.

PURPOSE: The treatment outcome of brentuximab vedotin (BV) has not been related with CD30 expression in previous studies enrolling patients with a wide range of CD30 expression level. Thus, this study explored the efficacy of BV in high-CD30-expressing non-Hodgkin lymphoma (NHL) patients most likely to benefit. MATERIALS AND METHODS: This phase II study (Clinicaltrials.gov: NCT02280785) enrolled relapsed or refractory high-CD30-expressing NHL, with BV administered intravenously at 1.8 mg/kg every 3 weeks. The primary endpoint was > 40% disease control rate, consisting of complete response (CR), partial response (PR), or stable disease. We defined high CD30 expression as ≥ 30% tumor cells positive for CD30 by immunohistochemistry. RESULTS: High-CD30-expressing NHL patients (n=33) were enrolled except anaplastic large cell lymphoma. The disease control rate was 48.5% (16/33) including six CR and six PR; six patients (4CR, 2PR) maintained their response over 16 completed cycles. Response to BV and survival were not associated with CD30 expression levels. Over a median of 29.2 months of follow-up, the median progression-free and overall survival rates were 1.9 months and 6.1 months, respectively. The most common adverse events were fever (39%), neutropenia (30%), fatigue (24%), and peripheral sensory neuropathy (27%). In a post-hoc analysis for the association of multiple myeloma oncogene 1 (MUM1) on treatment outcome, MUM1- negative patients showed a higher response (55.6%, 5/9) than MUM1-positive patients (13.3%, 2/15). CONCLUSION: BV performance as a single agent was acceptable in terms of disease control rates and toxicity profiles, especially MUM1-negative patients.

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).

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.

A phase II trial of bendamustine, carboplatin, and dexamethasone for refractory or relapsed peripheral T-cell lymphoma (BENCART trial).

This trial was designed to investigate the efficacy and toxicity of bendamustine, carboplatin, and dexamethasone (BCD) for relapsed or refractory peripheral T-cell lymphomas (PTCLs), which would be expected to exhibit more promising clinical outcomes compared with bendamustine therapy alone. After treatments with BCD, eight patients exhibited a complete response (CR; 29%) and seven exhibited a partial response (PR; 25%). The overall response rate (ORR) was 54%. Five patients proceeded to ASCT and three patients finally achieved CR. The median progression-free survival (PFS) was 4.4 months (2.8-6.0, 95% CI). For a total of 85 cycles of BCD, grade 3 or 4 neutropenia, thrombocytopenia, and anemia occurred in 17.6, 38.8, and 16.5% of cycles, respectively. Only one patient experienced febrile neutropenia. BCD was a considerable salvage regimen for relapsed or refractory PTCLs with acceptable toxicity; AITL or ASCT eligible patients were more effective to BCD.ClinicalTrials.gov Identifier:NCT02424045.