Myeloproliferative neoplasms (MPNs) are classified as chronic myeloid leukemia (CML) and Philadelphia chromosome-negative MPN. In MPN cases, the presence of a BCR-ABL1 translocation with a coexisting mutation is exceptionally rare. Herein, we report the first documented patient with CML harboring CALR mutation in Korea. A 33-year-old woman was referred to our hospital in February 2015 with splenomegaly, leukocytosis, and thrombocytosis. She was diagnosed with CML and started receiving nilotinib. In October 2015, a major molecular response was observed, but thrombocytosis persisted. A repeat bone marrow (BM) examination revealed no specific findings. However, as thrombocytosis worsened, we changed nilotinib to dasatinib. In May 2019, owing to persistent thrombocytosis, we repeated the BM examination and found CALR mutation (15.97%) on the MPN–next generation sequencing (NGS) test. We then retrospectively performed repeat MPN-NGS testing using the BM aspirate sample obtained in 2015 and found CALR mutation (10.64%).
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Hee Yeon Lee, Ji Hyung Hong, Jae Ho Byun, Hee-Jun Kim, Sun Kyung Baek, Jin Young Kim, Ki Hyang Kim, Jina Yun, Jung A Kim, Kwonoh Park, Hyo Jin Lee, Jung Lim Lee, Young-Woong Won, Il Hwan Kim, Woo Kyun Bae, Kyong Hwa Park, Der-Sheng Sun, Suee Lee, Min-Young Lee, Guk Jin Lee, Sook Hee Hong, Yun Hwa Jung, Ho Jung An
Cancer Res Treat. 2020;52(1):277-283. Published online July 12, 2019
Purpose
The purpose of this study was to evaluate clinical characteristics and treatment pattern of ovarian clear cell carcinoma (OCCC) in Korea and the role of adjuvant chemotherapy in early
stage.
Materials and Methods
Medical records of 308 cases of from 21 institutions were reviewed and data including age, performance status, endometriosis, thromboembolism, stage, cancer antigen 125, treatment, recurrence, and death were collected.
Results
Regarding stage of OCCC, it was stage I in 194 (63.6%), stage II in 34 (11.1%), stage III in 66 (21.6%), and stage IV in 11 (3.6%) patients. All patients underwent surgery. Optimal surgery (residual disease ≤ 1 cm) was achieved in 89.3%. Majority of patients (80.5%) received postoperative chemotherapy. The most common regimen was taxane-platinum combination (96%). Median relapse-free survival (RFS) was 138.5 months for stage I, 33.4 for stage II, 19.3 for stage III, and 9.7 for stage IV. Median overall survival (OS) were not reached, 112.4, 48.7, and 18.3 months for stage I, II, III, and IV, respectively. Early-stage (stage I), endometriosis, and optimal debulking were identified as favorable prognostic factors for RFS. Early-stage and optimal debulking were also favorable prognostic factors for OS. Majority of patients with early-stage received adjuvant chemotherapy. However, additional survival benefit was not found in terms of recurrence.
Conclusion
Majority of patients had early-stage and received postoperative chemotherapy regardless of stage. Early-stage and optimal debulking were identified as favorable prognostic factors. In stage IA or IB, adding adjuvant chemotherapy did not show difference in survival. Further study focusing on OCCC is required.
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Cancer Res Treat. 2017;49(4):906-914. Published online December 26, 2016
Purpose Papillary thyroid carcinomas (PTCs) frequently involve genetic alterations. The objective of this study was to investigate genetic alterations and further explore the relationships between these genetic alterations and clinicopathological characteristics in a high-recurrence risk (node positive, N1) PTC group.
Materials and Methods Tumor tissue blocks were obtained from 240 surgically resected patients with histologically confirmed stage III/IV (pT3/4 or N1) PTCs. We screened gene fusions using NanoString’s nCountertechnology and mutational analysiswas performed by directDNA sequencing.Data describing the clinicopathological characteristics and clinical courses were retrospectively collected.
Results Of the 240 PTC patients, 207 (86.3%) had at least one genetic alteration, including BRAF mutation in 190 patients (79.2%), PIK3CA mutation in 25 patients (10.4%), NTRK1/3 fusion in six patients (2.5%), and RET fusion in 24 patients (10.0%). Concomitant presence of more than two genetic alterations was seen in 36 patients (15%). PTCs harboring BRAF mutation were associated with RET wild-type expression (p=0.001). RET fusion genes have been found to occur with significantly higher frequency in N1b stage patients (p=0.003) or groups of patients aged 45 years or older (p=0.031); however, no significant correlation was found between other genetic alterations. There was no trend toward favorable recurrence-free survival or overall survival among patients lacking genetic alterations.
Conclusion
In the selected high-recurrence risk PTC group, most patients had more than one genetic alteration. However, these known alterations could not entirely account for clinicopathological features of high-recurrence risk PTC.
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Cancer Res Treat. 2016;48(2):527-536. Published online September 15, 2015
Purpose
Oropharyngeal squamous cell carcinoma (OSCC) has been recognized as an immunosuppressive disease. Various mechanisms have been proposed for immune escape, including dysregulation of immune checkpoints such as the PD-1:PD-L1 pathway. We investigated the expression of programmed cell death-ligand 1 (PD-L1) in HPV-negative and HPV-positive OSCC to determine its prevalence and prognostic relevance.
Materials and Methods
Using immunohistochemistry, 133 cases of OSCC were evaluated for expression of PD-L1. Formalin-fixed paraffin-embedded tumor samples were stained with monoclonal antibody (clone 5H1) to PD-L1. PD-L1 positivity was defined as membrane staining in ≥20% of tumor cells. Correlations between PD-L1 expression and HPV status and survival parameters were analyzed.
Results
Of the 133 patients, 68% showed PD-L1 expression, and 67% of patients were positive for p16 expression by immunohistochemistry. No significant difference in PD-L1 expression was observed between HPV(-) and HPV(+) tumors (61% vs. 71%, p=0.274). No significant difference in age, gender, smoking history, location of tumor origin, or stage was observed according to PD-L1 status. With a median follow-up period of 44 months, older age (≥65) (p=0.017) and T3-4 stage (p<0.001) were associated with poor overall survival (OS), whereas PD-L1 expression did not affect OS in univariate and multivariate analysis.
Conclusion
PD-L1 expression was observed in the majority of OSCC patients regardless of HPV status. Further large prospective studies are required to determine the role of PD-L1 expression as a prognostic or predictive biomarker, and clinical studies of immune checkpoint inhibitors in OCSS are warranted regardless of HPV status.
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Ji Yun Lee, Sung Hee Lim, Min-Young Lee, Haesu Kim, Moonjin Kim, Sungmin Kim, Hyun Ae Jung, Insuk Sohn, Won Ho Gil, Jeong Eon Lee, Seok Won Kim, Seok Jin Nam, Jin Seok Ahn, Young-Hyuck Im, Yeon Hee Park
Cancer Res Treat. 2015;47(4):765-773. Published online January 13, 2015
Purpose The purpose of this study is to evaluate the role of regular postoperative surveillance to improve the prognosis of patients with breast cancer after curative surgery. Materials and Methods We retrospectively analyzed the medical records of 4,119 patients who received curative surgery for breast cancer at Samsung Medical Center between January 2000 and September 2008. Patients were divided into two groups (group I, regular postoperative surveillance; group II, control group) according to their post-therapy follow-up status for the first 5 years after surgery. Results Among the 3,770 patients selected for inclusion, groups I and II contained 3,300 (87%) and 470 (13%) patients, respectively. The recurrence rates at 5 years for groups I and II were 10.6% and 16.4%, respectively (hazard ratio, 0.85; 95% confidence interval [CI], 0.67 to 1.09; p=0.197). The 10-year mortality cumulative rates were 8.8% for group I and 25.4% for group II (hazard ratio, 0.28; 95% CI, 0.22 to 0.35; p < 0.001). In multivariate analysis for recurrence-free survival (RFS), age over 40 years (p < 0.001), histologic grade 1 (p < 0.001), and pathologic stage I (p < 0.001) were associated with longer RFS but not with follow- up status. Multivariate analysis for overall survival (OS) revealed that patients in group I showed significantly improved OS (hazard ratio, 0.29; 95% CI, 0.23 to 0.37; p < 0.001). Additionally, age over 40 years, histologic grade I, and pathologic stage I were independent prognostic factors for OS. Conclusion Regular follow-up for patients with breast cancer after primary surgery resulted in clinically significant improvements in patient OS.
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Purpose
Regorafenib, an oral multi-targeted tyrosine kinase inhibitor, is considered the new standard
of care in patients with chemotherapy-refractory colorectal cancers (CRCs). However, there are no data on this drug in Korean patients.
Materials and Methods
We evaluated patients who received oral regorafenib 160 mg once daily during the first 3
weeks of each 4-week cycle between August 2013 and September 2013. All patients had
previously progressed fluorouracil, irinotecan, and oxaliplatin with or without biologic agents
such as cetuximab or bevacizumab.
Results
Thirty-two patients were enrolled (median age, 57 years; male:female ratio, 20:12; Eastern
Cooperative Oncology Group performance status [0-1:2], 31:1; colon:rectum, 21:11). The
overall response rate was 3.1% and the disease control rate was 50.0% (95% confidence
interval [CI]) with one partial response and 15 patients with stable disease. The median
progression-free survival was 4.2 months (95% CI, 3.1 to 5.2 months) and the median
overall survival has not yet been reached. The most common adverse events of grade two
or higher related to regorafenib were hand-foot skin reaction (25%), mucositis (19%),
abdominal pain (9%), and liver function test (LFT) abnormalities (9%). Grade 3 or 4 toxicities included LFT abnormalities (9%), abdominal pain (9%), rash (6%), anemia (3%), leukopenia (3%), neutropenic fever (3%), and fatigue (3%). There was no treatment-related death.
Conclusion
Regorafenib appears to have promising activity and tolerable toxicity profiles in Korean
patients with refractory CRC, consistent with the CORRECT trial findings.
Citations
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The real-world use of regorafenib for metastatic colorectal cancer: multicentre analysis of treatment pattern and outcomes in Hong Kong Ka-On Lam, Kin-Chung Lee, Joanne Chiu, Victor Ho-Fun Lee, Roland Leung, T S Choy, Thomas Yau Postgraduate Medical Journal.2017; 93(1101): 395. CrossRef
Pseudocirrhosis caused by regorafenib in an advanced rectal cancer patient with multiple liver metastases Kensuke Kumamoto, Shungo Endo, Noriyuki Isohata, Azuma Nirei, Daiki Nemoto, Kenichi Utano, Takuro Saito, Kazutomo Togashi Molecular and Clinical Oncology.2017; 6(1): 63. CrossRef
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