Comprehensive Molecular Characterization of Soft Tissue Sarcoma for Prediction of Pazopanib-Based Treatment Response

홍정용,조희진,윤금희,이영한,김승현,백우열,김상겸,이유리미,최윤라,권민석,김효송,이지윤 대한암학회 2023 Cancer Research and Treatment Vol.55 No.2

Purpose Even though pazopanib, a multitargeted tyrosine kinase inhibitor, has been approved for refractory soft tissue sarcoma (STS), little is known about the molecular determinants of the response to pazopanib. We performed integrative molecular characterization to identify potential predictors of pazopanib efficacy. Materials and Methods We obtained fresh pre-treatment tumor tissue from 35 patients with advanced STS receiving pazopanib-based treatment. Among those, 18 (51.4%) received pazopanib monotherapy, and the remaining 17 (48.6%) received pazopanib in combination with durvalumab, programmed death-ligand 1 blockade. Whole-exome and transcriptome sequencing were performed for each tumor and patient germline DNA. Results Of the 35 patients receiving pazopanib-based treatment, nine achieved a partial response (PR), resulting in an objective response rate (ORR) of 27.3%, and the median progression-free survival (PFS) was 6.0 months. Patients with CDK4 amplification (copy ratio tumor to normal > 2) exhibited shorter PFS (3.7 vs. 7.9 months, p=2.09×10–4) and a poorer response (ORR; 0% vs. 33.3%) compared to those without a gene amplification (copy ratio ≤ 2). Moreover, non-responders demonstrated transcriptional activation of CDK4 via DNA amplification, resulting in cell cycle activation. In the durvalumab combination cohort, seven of the 17 patients (41.2%) achieved a PR, and gene expression analysis revealed that durvalumab responders exhibited high immune/stromal cell infiltration, mainly comprising natural killer cells, compared to non-responders as well as increased expression of CD19, a B-cell marker. Conclusion Despite the limitation of heterogeneity in the study population and treatment, we identified possible molecular predictors of pazopanib efficacy that can be employed in future clinical trials aimed at evaluating therapeutic strategies.

양전자방출단층촬영술에서 미만성 폐섭취를 보인 재발성 혈관내 B 대세포 림프종

홍정용,최문기,김경희,주은정,장준호,이경수,고영혜,김원석 대한혈액학회 2008 Blood Research Vol.43 No.2

Intravascular lymphoma (IVL) is a rare form of non-Hodgkin's lymphoma that is characterized by the preferential growth of malignant lymphocytes within blood vessels. Pulmonary presentation of IVL is uncommon, and only a few cases have been reported in Korea. Here, we report on a 59-year-old woman with relapsed intravascular large B-cell lymphoma in the lungs. She had been treated with 6 cycles of rituximab, cyclophosphamide, adriamycin, vincristine, and prednisolone (R-CHOP) combination chemotherapy for intravascular large B-cell lymphoma in the nasal cavity, and was followed up regularly with no evidence of disease recurrence. About 1 year later, her chest computed tomography showed extensive ground-glass opacity, suggesting interstitial lung disease and, interestingly, diffuse pulmonary fluorodeoxyglucose (FDG) uptake was observed in positron emission tomography (PET). We performed bronchoscopy, bronchoalveolar lavage, and transbronchial lung biopsy. Pathology revealed relapsed intravascular large B-cell lymphoma in the lungs, and she commenced ifosfamide, methotrexate, etoposide, prednisolone (IMVP-16/PD) salvage chemotherapy. After 3 cycles of chemotherapy, PET showed no abnormal FDG uptake. We suggest that a primary or relapsed pulmonary IVL should be considered in the differential diagnosis of unexplained interstitial lung disease and that PET appears be useful in evaluating pulmonary IVL.

脊椎結核에 관한 硏究 : 脊椎結核 前方癒合術에 관한 臨床的 考察 Anterior Fusion for the Tuberculosis of the Spine

洪正龍 최신의학사 1977 最新醫學 Vol.20 No.12

The anterior interbody fusion for the 445 patients of tuberculosis of the spine was, experienced at our department, and we agree this opinion that the anterior spinal fusion was the most favorable method to the spinal tuberculosis, published by many other authors. Following results were obtained from the 445 cases, treated during the period of 1957 to 1977, 6. 1. Spine was the most common site in bone and joint tuberculosis (60.4%), and was followed by hip, knee, ankle, in orders. 2. The highest age incidence was 1st decade (39.1%) 3. Average period of disease preoperatively was 27 months. 4. The relative frequency with the level of lesion were thoracic (34.8%), lumbar (33.0%), thoracolumbar (18.9%), in orders. 5: The average number of vertebrae involved was 2.4 segments. 6. 152 patients (34%) had other active tuberculous foci in the body, and 80 patients (18.0%) had paraplegia of paraparesis, at that time of admission. Reoperation was done in 23 cases, but we have included the 5 cases treated for the correction of kyphotic deformity. 8. The combined procedure of anterior fusion with posterior fusion is the preferable treatment for immature spines with this disease.

폐암에서 유래된 종골의 전이성 골종양

정필현,강석,채동주,조윤철,김태영,홍정용 東國大學校醫學硏究所 1997 東國醫學 Vol.4 No.-

전이성 골종양은 악성 골종양중 발생빈도가 가장 흔한 것으로 알려져 있으며 다발성 전이가 빈번하고 심한 통증 및 병적골절을 유발하게 된다. 골격으로 전이되는 암의 원발병소로는 유방암, 전립선암, 폐암, 갑상선암, 신장암이 전체의 80%이상을 차지하며 전이부위는 적색골수가 존재하는 곳에 호발하는데 주로 척추, 늑골, 골반골, 장광골의 근위 말단부, 흉골, 두개골의 순서로 빈도가 증가한다고 한다. 전이성 골종양은 대부분 구간골격에서 발견되며 사지골격으로의 전이는 흔치 않은 것으로 알려져 있으며, 특히 수부, 족부로의 전이는 매우 드문 것으로 보고되어 있다. 본 정형외과학 교실에서는 편평 상피세포암종을 가진 환자에서 발견된 좌측 종골의 전이성 골종양 1례를 경험하였기에 문헌고찰과 함께 보고하는 바이다. Metastatic lesions of bone are more common than primary malignant tumors, are usually multiple, and compromise the patient's health by causing intense pain, interfering with surrounding neural or muscular structures, causing pathological fractures. More than 80% of cancers that spread to bone are those of the breast, protate, lung, thyroid gland and kidney. The sites of metastasis are predominantly in red bone marrow. The metastatic foci are commomly centally distributed. The spine is most commonly involved, followed by the rib, pelvis, proximal ends of long bones, sternum and skull. The peripheral bone involvement is rare. Particularly, metastases to the bones of the hand and feet are extremely rare. The authors present a case of metastatic bone tumor of the calcaneus from squamous cell carcinoma of the lung with clinical details.

TTP-HUS Associated with Sunitinib

최문기,홍정용,장준호,임호영 대한암학회 2008 Cancer Research and Treatment Vol.40 No.4

Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is a rare condition that is severe and may be fatal. Adverse reactions to drugs increasingly are reported as probable causes of TTP-HUS. Many chemotherapeutic agents have also been implicated in causing TTP-HUS. We reported a woman with metastatic renal cell carcinoma who presented with TTPHUS associated with sunitinib. She had gross hematuria and generalized edema. The hemoglobin concentration was 8.9 g/dl and the platelet count was 46,000/mm³. Her reticulocyte count was increased to 4.1% and the peripheral blood smear revealed red blood cell fragmentation and spherocytes. The patient completely recovered after discontinuing the use of sunitinib and undergoing plasmapheresis. Because of the increasing use of sunitinib in the treatment of cancer patients, oncologists should be aware of the possibility of TTP-HUS related to sunitinib, as early recognition and prompt therapeutic intervention can be beneficial.

Genomic Sequencing for Bladder Urothelial Carcinoma and Its Clinical Implications for Immunotherapy

김률,홍정용,이지연,권기영,정병창,박세훈 대한암학회 2022 Cancer Research and Treatment Vol.54 No.3

Purpose This study aimed to explore the genomic and transcriptomic landscape of bladder cancer (BC) and its implication for treatment with an immune checkpoint inhibitor (ICI).Materials and Methods We analyzed whole-exome and -transcriptome sequences of tumor samples from 64 BC patients who underwent surgical resection with either transurethral resection or radical cystectomy. For exploratory purposes, programmed death-ligand 1 (PD-L1) expression was evaluated in a subset of patients (n=57) including those treated with ICI (n=8).Results We identified frequent molecular dysregulations in chromatin regulatory genes (<i>KDM6A, ARID1A, MLL2,</i> and <i>STAG2</i>) and recurrent copy number alterations. Thirty-five samples (54.7%) were PD-L1–positive (PD-L1 combined positive score ≥ 1) with a significantly higher exonic tumor mutational burden (TMB) compared to PD-L1–negative BC samples (p=0.010). We observed that various immune-responsive pathways, including the PD-L1 signaling pathway, were enriched significantly in PD-L1–positive BCs. Interestingly, genes in the CTLA4 pathway were enriched significantly in PD-L1–positive BC as well. Among eight patients who received ICI, progressive disease was confirmed in one patient, whose tumor had low exonic TMB, negative PD-L1 status, and a relatively colder microenvironment.Conclusion Gaining new insights into the molecular landscape of BC will improve treatment strategies. Our analysis suggests a rationale for studying dual checkpoint inhibition against BC.

Treatment outcomes of dose-attenuated CHOP chemotherapy in elderly patients with peripheral T cell lymphoma

최은지,홍정용,윤덕현,강지훈,박찬식,허주령,채은진,이윤세,류진숙,서철원 대한혈액학회 2017 Blood Research Vol.52 No.4

Background: While cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) is the most commonly used chemotherapeutic regimen for patients with peripheral T-cell lym-phomas (PTCLs), elderly patients are more vulnerable to associated toxicities. We eval-uated the efficacy and safety of dose-attenuated CHOP in elderly patients with PTCL. Methods: Patients with PTCL aged >70 years or 65‒70-years with comorbidities were treated with dose-attenuated CHOP (cyclophosphamide: 562.5 mg/m2, doxorubicin: 37.5 mg/m2, vin-cristine: 1.4 mg/m2, and prednisolone: 100 mg for five days; 25% reduced dose of cyclo-phosphamide and doxorubicin vs. full-dose CHOP) as first-line therapy were included. Results: Forty-four patients (median age, 74 yr) were analyzed. The majority (N=42, 95.5%) had advanced stage disease and 36 (81.8%) were classified as high/high-intermediate risk by the international prognostic index. The overall response rate was 61.4%, and 21 patients achieved complete response (47.7%). With median follow-up period of 28.8 months, the estimated two-year progression-free and overall survival rates were 36.7% and 46.6%, respectively. Grade 3/4 neutropenia and thrombocytopenia occurred in 26.9% and 7.4% of 204 total cycles, which affected 76.7% and 25.6% of the patients, respectively. Nineteen patients (44.2%) experienced febrile neutropenia, and six died due to treatment-related toxicities. High lactate dehydrogenase levels and an involvement of >1 extranodal sites were prognostic indicators of poor survival. Conclusion: Dose-attenuated CHOP does not compromise treatment efficacy but retains significant toxicity. Our results suggest that some patients can be effectively treated with dose-atte-nuated CHOP, however a novel therapy for elderly patients with PTCL is required.

Clinical features and survival outcomes of patients with lymphoplasmacytic lymphoma, including non-IgM type, in Korea: a single-center experience

강지훈,홍정용,서철원 대한혈액학회 2018 Blood Research Vol.53 No.3

Background The incidence of lymphoplasmacytic lymphoma (LPL) is lower in Asian than in Western populations. Few studies have described the clinical features and treatment outcomes of patients with LPL, including non-IgM LPL, in East Asia. Methods We retrospectively analyzed patients diagnosed with LPL at Asan Medical Center between January 2001 and March 2016. We evaluated the clinical features and survival outcomes of patients with LPL and non-IgM LPL and compared these data with those of patients with LPL/Waldenström’s macroglobulinemia (WM). Results The median age at diagnosis of patients with LPL was 61.5 years (range, 34‒77 yr); most patients were male (91%). Approximately three-quarters of the 22 patients with LPL were in the low or intermediate risk groups according to the International Prognostic Scoring System for Waldenström’s Macroglobulinemia classification. The median follow-up du-ration was 75 months [95% confidence interval (CI), 48‒102 mo], and the median overall survival (OS) was 81 months (95% CI, 0‒167 mo). The number of patients in the non-IgM LPL group who exhibited extramedullary involvement was higher than in the LPL/WM group. OS of the LPL/WM group was improved compared with that of the non-IgM LPL group [median not reached vs. 10.0 mo (95% CI, 0‒36.7); P=0.05]. Conclusion We present a single-center experience of 22 patients with LPL, including a non-IgM co-hort, in Korea. The treatment of non-IgM LPL was heterogeneous, and patients with non-IgM LPL showed a higher 5-year mortality rate and more adverse prognostic factors than those with LPL/WM.

원발 중추신경계림프종의 단일 기관 현실 세계 21세기 경험

조형우,홍정용,이대호,김신,이경민,강은희,이순종,박정선,김정훈,류진숙,허주령,서철원 대한내과학회 2024 대한내과학회지 Vol.99 No.1

Background/Aims: In Korea, the incidence of primary diffuse large B-cell lymphoma of the central nervous system (PCNSL) is increasing and autologous stem cell transplantation (ASCT) has improved the survival of younger patients. We explored our real-world experience with PCNSL at Asan Medical Center (AMC). Methods: We used the AMC lymphoma registry to collect patient data prospectively. We analyzed 279 patients diagnosed from 2002 until August 2019. Results: The PCNSL incidence at AMC increased progressively and comprised 7.4-8.9% of new non-Hodgkin lymphoma patients annually during the most recent 4 years. The median age was 60 years (range, 17-85) and males comprised 55%. Patients under 65 years of age (n = 183) had no significant differences in characteristics compared to those aged 65 years or over, with the exception of less occipital lobe involvement and lower beta-2 microglobulin levels. Rituximab, methotrexate, procarbazine, and vincristine (R-MPV) combination induction had the best overall response, of 95%. The median overall survival was 3.8 years with 5- and 10-year survival rates of 41.5% and 30.2%, respectively. Survival was better in younger patients and those treated with ASCT. Thiotepa, busulfan, and cytoxan (TBC) conditioning chemotherapy had better survival than other combinations. The International Extranodal Lymphoma Study Group and Memorial Sloan Kettering Cancer Center prognostic score systems were valid in this cohort. Age and performance status were independent prognostic factors. Exclusive extra-central nervous system failure occurred in six patients (5.6%) among 107 failures. Conclusions: The incidence of PCNSL is rising. R-MPV induction therapy followed by ASCT with TBC has improved the survival of young, fit PCNSL patients.

NAFLD and pancreatic cancer risk

최대호,홍정용,박주현,한경도,한인웅,강원석,박주경 대한내과학회 2021 대한내과학회 추계학술대회 Vol.2021 No.1