1.Sites of Metastasis and Survival in Metastatic Renal Cell Carcinoma:Results From the Korean Renal Cancer Study Group Database
Chan Ho LEE ; Minyong KANG ; Cheol KWAK ; Young Hwii KO ; Jung Kwon KIM ; Jae Young PARK ; Seokhwan BANG ; Seong Il SEO ; Jungyo SUH ; Wan SONG ; Cheryn SONG ; Hyung Ho LEE ; Jinsoo CHUNG ; Chang Wook JEONG ; Jung Ki JO ; Seock Hwan CHOI ; Joongwon CHOI ; Changil CHOI ; Seol Ho CHOO ; Jang Hee HAN ; Sung-Hoo HONG ; Eu Chang HWANG
Journal of Korean Medical Science 2024;39(45):e293-
Background:
In patients with metastatic renal cell carcinoma (mRCC), sites of metastatic involvement have been reported to be associated with a difference in survival. However, the frequency and survival according to different sites of metastases in Korean patients with mRCC remain unclear. Therefore, this study aimed to assess the frequency of metastatic site involvement and the association between sites of metastatic involvement and survival in Korean patients with mRCC.
Methods:
This retrospective study used the multicenter cohort of the Korean Renal Cancer Study Group mRCC database to identify patients who started targeted therapy between December 2005 and March 2018. Data on the frequency of metastatic organ involvement at the time of mRCC diagnosis and oncologic outcomes according to different sites of metastasis were analyzed.
Results:
A total of 1,761 patients were eligible for analysis. Of the 1,761 patients, 1,564 (88.8%) had clear cell RCC, and 1,040 (59.1%) had synchronous metastasis. The median number of metastasis sites was 2 (interquartile range [IQR], 1–6). The median age at the initiation of systemic therapy was 60 years (IQR, 29–88), 1,380 (78.4%) were men, and 1,341 (76.1%) underwent nephrectomy. Based on the International Metastatic Renal Cell Carcinoma Database Consortium model, patients were stratified into favorable-, intermediate-, and poor-risk groups with 359 (20.4%), 1,092 (62.0%), and 310 (17.6%) patients, respectively. The lung (70.9%), lymph nodes (37.9%), bone (30.7%), liver (12.7%), adrenal gland (9.8%), and brain (8.2%) were the most common sites of metastasis, followed by the pancreas, pleura, peritoneum, spleen, thyroid, and bowel. Among the most common sites of metastasis (> 5%), the median cancer-specific survival (CSS) ranged from 13.9 (liver) to 29.1 months (lung). An association was observed between liver, bone, and pleural metastases and the shortest median CSS (< 19 months).
Conclusion
In Korean patients with mRCC, metastases to the lung, lymph nodes, bone, liver, adrenal gland, and brain were more frequent than those to other organs. Metastases to the liver, bone, and pleura were associated with poor CSS. The findings of this study may be valuable for patient counseling and guiding future study designs.
2.Sites of Metastasis and Survival in Metastatic Renal Cell Carcinoma:Results From the Korean Renal Cancer Study Group Database
Chan Ho LEE ; Minyong KANG ; Cheol KWAK ; Young Hwii KO ; Jung Kwon KIM ; Jae Young PARK ; Seokhwan BANG ; Seong Il SEO ; Jungyo SUH ; Wan SONG ; Cheryn SONG ; Hyung Ho LEE ; Jinsoo CHUNG ; Chang Wook JEONG ; Jung Ki JO ; Seock Hwan CHOI ; Joongwon CHOI ; Changil CHOI ; Seol Ho CHOO ; Jang Hee HAN ; Sung-Hoo HONG ; Eu Chang HWANG
Journal of Korean Medical Science 2024;39(45):e293-
Background:
In patients with metastatic renal cell carcinoma (mRCC), sites of metastatic involvement have been reported to be associated with a difference in survival. However, the frequency and survival according to different sites of metastases in Korean patients with mRCC remain unclear. Therefore, this study aimed to assess the frequency of metastatic site involvement and the association between sites of metastatic involvement and survival in Korean patients with mRCC.
Methods:
This retrospective study used the multicenter cohort of the Korean Renal Cancer Study Group mRCC database to identify patients who started targeted therapy between December 2005 and March 2018. Data on the frequency of metastatic organ involvement at the time of mRCC diagnosis and oncologic outcomes according to different sites of metastasis were analyzed.
Results:
A total of 1,761 patients were eligible for analysis. Of the 1,761 patients, 1,564 (88.8%) had clear cell RCC, and 1,040 (59.1%) had synchronous metastasis. The median number of metastasis sites was 2 (interquartile range [IQR], 1–6). The median age at the initiation of systemic therapy was 60 years (IQR, 29–88), 1,380 (78.4%) were men, and 1,341 (76.1%) underwent nephrectomy. Based on the International Metastatic Renal Cell Carcinoma Database Consortium model, patients were stratified into favorable-, intermediate-, and poor-risk groups with 359 (20.4%), 1,092 (62.0%), and 310 (17.6%) patients, respectively. The lung (70.9%), lymph nodes (37.9%), bone (30.7%), liver (12.7%), adrenal gland (9.8%), and brain (8.2%) were the most common sites of metastasis, followed by the pancreas, pleura, peritoneum, spleen, thyroid, and bowel. Among the most common sites of metastasis (> 5%), the median cancer-specific survival (CSS) ranged from 13.9 (liver) to 29.1 months (lung). An association was observed between liver, bone, and pleural metastases and the shortest median CSS (< 19 months).
Conclusion
In Korean patients with mRCC, metastases to the lung, lymph nodes, bone, liver, adrenal gland, and brain were more frequent than those to other organs. Metastases to the liver, bone, and pleura were associated with poor CSS. The findings of this study may be valuable for patient counseling and guiding future study designs.
3.Sites of Metastasis and Survival in Metastatic Renal Cell Carcinoma:Results From the Korean Renal Cancer Study Group Database
Chan Ho LEE ; Minyong KANG ; Cheol KWAK ; Young Hwii KO ; Jung Kwon KIM ; Jae Young PARK ; Seokhwan BANG ; Seong Il SEO ; Jungyo SUH ; Wan SONG ; Cheryn SONG ; Hyung Ho LEE ; Jinsoo CHUNG ; Chang Wook JEONG ; Jung Ki JO ; Seock Hwan CHOI ; Joongwon CHOI ; Changil CHOI ; Seol Ho CHOO ; Jang Hee HAN ; Sung-Hoo HONG ; Eu Chang HWANG
Journal of Korean Medical Science 2024;39(45):e293-
Background:
In patients with metastatic renal cell carcinoma (mRCC), sites of metastatic involvement have been reported to be associated with a difference in survival. However, the frequency and survival according to different sites of metastases in Korean patients with mRCC remain unclear. Therefore, this study aimed to assess the frequency of metastatic site involvement and the association between sites of metastatic involvement and survival in Korean patients with mRCC.
Methods:
This retrospective study used the multicenter cohort of the Korean Renal Cancer Study Group mRCC database to identify patients who started targeted therapy between December 2005 and March 2018. Data on the frequency of metastatic organ involvement at the time of mRCC diagnosis and oncologic outcomes according to different sites of metastasis were analyzed.
Results:
A total of 1,761 patients were eligible for analysis. Of the 1,761 patients, 1,564 (88.8%) had clear cell RCC, and 1,040 (59.1%) had synchronous metastasis. The median number of metastasis sites was 2 (interquartile range [IQR], 1–6). The median age at the initiation of systemic therapy was 60 years (IQR, 29–88), 1,380 (78.4%) were men, and 1,341 (76.1%) underwent nephrectomy. Based on the International Metastatic Renal Cell Carcinoma Database Consortium model, patients were stratified into favorable-, intermediate-, and poor-risk groups with 359 (20.4%), 1,092 (62.0%), and 310 (17.6%) patients, respectively. The lung (70.9%), lymph nodes (37.9%), bone (30.7%), liver (12.7%), adrenal gland (9.8%), and brain (8.2%) were the most common sites of metastasis, followed by the pancreas, pleura, peritoneum, spleen, thyroid, and bowel. Among the most common sites of metastasis (> 5%), the median cancer-specific survival (CSS) ranged from 13.9 (liver) to 29.1 months (lung). An association was observed between liver, bone, and pleural metastases and the shortest median CSS (< 19 months).
Conclusion
In Korean patients with mRCC, metastases to the lung, lymph nodes, bone, liver, adrenal gland, and brain were more frequent than those to other organs. Metastases to the liver, bone, and pleura were associated with poor CSS. The findings of this study may be valuable for patient counseling and guiding future study designs.
4.Sites of Metastasis and Survival in Metastatic Renal Cell Carcinoma:Results From the Korean Renal Cancer Study Group Database
Chan Ho LEE ; Minyong KANG ; Cheol KWAK ; Young Hwii KO ; Jung Kwon KIM ; Jae Young PARK ; Seokhwan BANG ; Seong Il SEO ; Jungyo SUH ; Wan SONG ; Cheryn SONG ; Hyung Ho LEE ; Jinsoo CHUNG ; Chang Wook JEONG ; Jung Ki JO ; Seock Hwan CHOI ; Joongwon CHOI ; Changil CHOI ; Seol Ho CHOO ; Jang Hee HAN ; Sung-Hoo HONG ; Eu Chang HWANG
Journal of Korean Medical Science 2024;39(45):e293-
Background:
In patients with metastatic renal cell carcinoma (mRCC), sites of metastatic involvement have been reported to be associated with a difference in survival. However, the frequency and survival according to different sites of metastases in Korean patients with mRCC remain unclear. Therefore, this study aimed to assess the frequency of metastatic site involvement and the association between sites of metastatic involvement and survival in Korean patients with mRCC.
Methods:
This retrospective study used the multicenter cohort of the Korean Renal Cancer Study Group mRCC database to identify patients who started targeted therapy between December 2005 and March 2018. Data on the frequency of metastatic organ involvement at the time of mRCC diagnosis and oncologic outcomes according to different sites of metastasis were analyzed.
Results:
A total of 1,761 patients were eligible for analysis. Of the 1,761 patients, 1,564 (88.8%) had clear cell RCC, and 1,040 (59.1%) had synchronous metastasis. The median number of metastasis sites was 2 (interquartile range [IQR], 1–6). The median age at the initiation of systemic therapy was 60 years (IQR, 29–88), 1,380 (78.4%) were men, and 1,341 (76.1%) underwent nephrectomy. Based on the International Metastatic Renal Cell Carcinoma Database Consortium model, patients were stratified into favorable-, intermediate-, and poor-risk groups with 359 (20.4%), 1,092 (62.0%), and 310 (17.6%) patients, respectively. The lung (70.9%), lymph nodes (37.9%), bone (30.7%), liver (12.7%), adrenal gland (9.8%), and brain (8.2%) were the most common sites of metastasis, followed by the pancreas, pleura, peritoneum, spleen, thyroid, and bowel. Among the most common sites of metastasis (> 5%), the median cancer-specific survival (CSS) ranged from 13.9 (liver) to 29.1 months (lung). An association was observed between liver, bone, and pleural metastases and the shortest median CSS (< 19 months).
Conclusion
In Korean patients with mRCC, metastases to the lung, lymph nodes, bone, liver, adrenal gland, and brain were more frequent than those to other organs. Metastases to the liver, bone, and pleura were associated with poor CSS. The findings of this study may be valuable for patient counseling and guiding future study designs.
5.2021 Consensus Statements on the Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma From the Korean Renal Cancer Study Group (KRoCS)
Chan Ho LEE ; Minyong KANG ; Cheol KWAK ; Sung Han KIM ; Jung Kwon KIM ; Jae Young PARK ; Seong Il SEO ; Ill Young SEO ; Jungyo SUH ; Wan SONG ; Cheryn SONG ; Hyeong Dong YUK ; Sangchul LEE ; Hyung Ho LEE ; Jinsoo CHUNG ; Chang Wook JEONG ; Jung Ki JO ; Chang Il CHOI ; Seol Ho CHOO ; Jun Hyun HAN ; Eu Chang HWANG ; Miso KIM ; Chan KIM ; Seock Hwan CHOI ; Sung-Hoo HONG
Korean Journal of Urological Oncology 2022;20(3):151-162
Purpose:
The Korean Renal Cancer Study Group (KRoCS) provides consensus recommendations on the role of cytoreductive nephrectomy (CRN) in patients with metastatic renal cell carcinoma (mRCC).
Materials and Methods:
A group of mRCC experts from the Korean Urological Oncology Society convened at the 2021 KRoCS meeting on CRN for mRCC.
Results:
The consensus document was developed to address 4 questions related that were judged to be the most relevant to patient care: (1) Is there a role for CRN in patients planning targeted therapy? (2) Is there a role for CRN in patients planning immuno-oncology agents? (3) When is the optimal time of CRN in patients planning systemic treatment? (4) What is the ideal patient selection for CRN? The panelists have come up with following consensus. For mRCC patients, CRN should be considered only in those with IMDC (International Metastatic Renal Cell Carcinoma Database Consortium) favorable and intermediate risk disease, regardless of the systemic treatment plans. Timing of CRN should consider the risk group as well as the number of risk factors, but is generally recommended for after assessing the degree of response to initial systemic treatment. Patients with good performance status, limited metastatic burden on top of resectable primary tumor are candidates recommended for CRN with or without metastasectomy with priority.
Conclusions
In conclusion, there is still a role for CRN in the multimodality treatment of mRCC. Careful patient selection is of paramount importance. As the treatment landscape of mRCC continues to change, the role of CRN in the current immuno-oncology era will require more exploration.
6.A Real-world Efficacy of Nab-paclitaxel Monotherapy in Metastatic Breast Cancer
Jung Sun KIM ; Koung Jin SUH ; Dae-Won LEE ; Go-un WOO ; Miso KIM ; Se Hyun KIM ; Han Suk RYU ; Kyung-Hun LEE ; Tae-Yong KIM ; Sae-Won HAN ; So Yeon PARK ; In Ae PARK ; Jee Hyun KIM ; Seock-Ah IM
Cancer Research and Treatment 2022;54(2):488-496
Purpose:
We aimed to assess the real-world efficacy of nab-paclitaxel in metastatic breast cancer patients.
Materials and Methods:
This is a retrospective study performed in two tertiary referral hospitals in Korea. Patients with metastatic breast cancer treated with nab-paclitaxel (Abraxane®) between March 2016 and March 2020 were enrolled.
Results:
A total of 102 patients with metastatic breast cancer were included. Patients were heavily pre-treated with a median of four prior lines of chemotherapy (5 lines when including endocrine therapy in hormone-receptor-positive patients), and 66 patients (64.7%) were exposed to taxanes in the metastatic setting. According to St. Gallen molecular subtypes, 36 patients (35.3%) were luminal A, 28 (27.5%) were luminal B, 18 (17.7%) were human epidermal growth factor receptor 2–positive and 20 (19.6%) had triple-negative disease. Fifty patients (49.0%) were treated with a 3-weekly regimen (260 mg/m2 on day 1 every 3 weeks), and 52 (51.0%) were treated with a weekly regimen (100 mg/m2 every week). Objective response rate was 22.9%. After a median follow-up of 22.0 months, median progression-free survival (PFS) was 4.0 months (95% confidence interval [CI], 2.6 to 4.8) and median overall survival was 8.7 months (95% CI, 7.5 to 11.2). Patients treated with weekly regimen had longer PFS compared to 3-weekly regimen (5.5 vs. 2.3 months, p < 0.001). Multivariate analysis revealed the treatment regimen as an independent prognostic factor for PFS. There was no grade 3 or 4 hypersensitivity reaction.
Conclusion
This real-world data shows that nab-paclitaxel is a reasonable treatment option in heavily pre-treated and/or taxane-exposed metastatic breast cancer patients.
7.Prognostic Role of Androgen Receptor Expression in Surgically Resected Early Breast Cancer Patients
Yaewon YANG ; Ahrum MIN ; Kyung-Hun LEE ; Han Suk RYU ; Tae-Yong KIM ; Go-un WOO ; Koung Jin SUH ; Dae-Won LEE ; Han-Byoel LEE ; Hyeong-Gon MOON ; Wonshik HAN ; In Ae PARK ; Dong-Young NOH ; Seock-Ah IM
Journal of Breast Cancer 2020;23(2):182-193
Purpose:
Endocrine therapy is a standard treatment for hormone receptor-positive breast cancer, which accounts for 60%–75% of all breast cancer. Hormone receptor positivity is a prognostic and predictive biomarker in breast cancer. Approximately 50%–80% of breast cancer is also positive for androgen receptor (AR), but the prognostic and predictive value of AR expression in breast cancer is controversial. Here, we investigated AR expression and its prognostic value in patients with surgically resected breast cancer in Korea.
Methods:
We retrospectively reviewed the medical records of patients who had surgically resected breast cancer to collect AR expression data and other clinicopathological data. The optimal cut-off for AR positivity was determined using a receiver operating characteristic curve analysis.
Results:
We reviewed 957 patients with surgically resected breast cancer from June 2012 to April 2013. The median follow-up was 62 months, and relapse events occurred in 101 (10.6%) patients. Unlike the cut-off value of 1% or 10% in previous reports, 35% was determined to be best for predicting relapse-free survival (RFS) in this study. At the cut-off value of 35%, 654 (68.4%) patients were AR-positive. AR expression was more prevalent in luminal A (87.6%) and luminal B (73.1%) types than in human epidermal growth factor receptor 2-positive (56.2%) or triple-negative (20.6%) types. AR expression of ≥ 35% was significantly related to longer RFS in a multivariate analysis (hazard ratio, 0.430; 95% confidence interval, 0.260–0.709; p = 0.001).
Conclusion
We propose a cut-off value of 35% to best predict RFS in patients with surgically resected breast cancer. AR expression was positive in 68.4% of patients, and AR positivity was found to be an independent prognostic factor for longer RFS.
8.Real-world Treatment Pattern and Outcomes of Hypercalcemia among Solid Tumor Patients
Da Eun SHIN ; Seol Hee PARK ; Sung Hwan KIM ; Sung Yun SUH ; Yun Hee JO ; Yoon Sook CHO ; Seock Ah IM ; Ju Yeun LEE
Korean Journal of Clinical Pharmacy 2019;29(3):166-172
BACKGROUND: Hypercalcemia is an important metabolic emergency condition in cancer patients. Bisphosphonate is the treatment of choice for hypercalcemia, whereas calcitonin and hydration with furosemide are recommended for acute supportive therapy. However, data regarding real-world treatment patterns and outcomes of pharmacological treatments are limited. Therefore, we aimed to investigate the treatment patterns and clinical outcomes of hypercalcemia treatment in solid tumor patients. METHODS: Electronic medical records of 123 adults with solid cancers and albumin-corrected calcium levels >10.5 mg/dL or ionized calcium levels >1.35 mmol/L were reviewed. We retrospectively analyzed the pharmacological treatment and recovery rate according to the severity of hypercalcemia. RESULTS: A total of 177 cases were identified, of which 49 were not treated and 30 were treated with hydration only. In moderate-to-severe cases, 86.5% received pharmacological treatment. Thirty-four cases (19.2%) were treated with bisphosphonate alone and 58 cases (32.8%) were treated with bisphosphonate and calcitonin. In mild hypercalcemia cases, the recovery rate was higher for those receiving hydration only or pharmacological treatment (79.7%) than for those receiving no treatment (61.4%, p = 0.041). Most moderate-to-severe cases were treated with medication and of those treated, 56.3% recovered. The recovery rate was lower in those treated with bisphosphonate alone (38.2%) than in those who underwent calcitonin combination treatment (73.7%, p = 0.001). CONCLUSIONS: Bisphosphonate combined with calcitonin was found to be more effective than bisphosphonate alone for the treatment of moderate-to-severe hypercalcemia. Considering the current shortage of calcitonin, further efforts are required to ensure its stable supply.
Adult
;
Calcitonin
;
Calcium
;
Electronic Health Records
;
Emergencies
;
Furosemide
;
Humans
;
Hypercalcemia
;
Retrospective Studies
9.Predictors of Severe or Moderate Coronary Artery Disease in Asymptomatic Individuals with Extremely Low Coronary Calcium Scores
Hyung Bok PARK ; Hyeonju JEONG ; Ji Hyun LEE ; Yongsung SUH ; Eui Seock HWANG ; Yun Hyeong CHO ; Deok Kyu CHO
Yonsei Medical Journal 2019;60(7):619-625
PURPOSE: To evaluate predictors of severe or moderate coronary artery disease (CAD) in individuals with zero or very low (<10) coronary artery calcium (CAC) scores. MATERIALS AND METHODS: The 1175 asymptomatic persons with zero or very low (<10) CAC scores were analyzed for CAD stenosis using coronary computed tomography angiography. Moderate and severe CADs were defined as having more than 50% and more than 70% stenosis in any of the major coronary arteries, respectively. Age, gender, body mass index, hypertension, type II diabetes, dyslipidemia, lipid profile, creatinine, and smoking status were evaluated as predictors for moderate and severe CAD. RESULTS: In the study population, moderate and severe CADs were found in 7.5% and 3.3%, respectively. Among evaluated risk factors, age [odds ratio (OR) 1.04, 95% confidence interval (CI) 1.02−1.07, p<0.001], current smoking status (OR 3.12, 95% CI 1.82−5.34, p<0.001), and CAC 1−9 (OR 1.80, 95% CI 1.08−3.00, p=0.024) were significantly associated with moderate CAD. Meanwhile, age (OR 1.05, 95% CI 1.02−1.08, p=0.003), low high density lipoprotein (HDL) (OR 0.96, 95% CI 0.93−0.99, p=0.003), and current smoking status (OR 2.34, 95% CI 1.14−5.30, p=0.022) were found to be significantly associated with severe CAD. Improvement of discrimination power for predicting severe CAD was observed when smoking and HDL cholesterol were serially added into the age model. CONCLUSION: Smoking showed significant correlations with moderate or severe CAD, and low HDL cholesterol also proved to be a predictor of severe CAD in asymptomatic individuals with extremely low CAC scores.
Angiography
;
Asymptomatic Diseases
;
Body Mass Index
;
Calcium
;
Cholesterol, HDL
;
Constriction, Pathologic
;
Coronary Artery Disease
;
Coronary Vessels
;
Creatinine
;
Discrimination (Psychology)
;
Dyslipidemias
;
Humans
;
Hypertension
;
Lipoproteins
;
Risk Factors
;
Smoke
;
Smoking
10.Pan-Pim Kinase Inhibitor AZD1208 Suppresses Tumor Growth and Synergistically Interacts with Akt Inhibition in Gastric Cancer Cells
Miso LEE ; Kyung Hun LEE ; Ahrum MIN ; Jeongeun KIM ; Seongyeong KIM ; Hyemin JANG ; Jee Min LIM ; So Hyeon KIM ; Dong Hyeon HA ; Won Jae JEONG ; Koung Jin SUH ; Yae Won YANG ; Tae Yong KIM ; Do Youn OH ; Yung Jue BANG ; Seock Ah IM
Cancer Research and Treatment 2019;51(2):451-463
PURPOSE: Pim kinases are highly conserved serine/threonine kinases, and different expression patterns of each isoform (Pim-1, Pim-2, and Pim-3) have been observed in various types of human cancers, including gastric cancer. AZD1208 is a potent and selective inhibitor that affects all three isoforms of Pim. We investigated the effects of AZD1208 as a single agent and in combination with an Akt inhibitor in gastric cancer cells. MATERIALS AND METHODS: The antitumor activity of AZD1208 with/without an Akt inhibitor was evaluated in a large panel of gastric cancer cell lines through growth inhibition assays. The underlying mechanism was also examined by western blotting, immunofluorescence assay, and cell cycle analysis. RESULTS: AZD1208 treatment decreased gastric cancer cell proliferation rates and induced autophagy only in long-term culture systems. Light chain 3B (LC3B), a marker of autophagy, was increased in sensitive cells in a dose-dependent manner with AZD1208 treatment, which suggested that the growth inhibition effect of AZD1208 was achieved through autophagy, not apoptosis. Moreover, we found that cells damaged by Pim inhibition were repaired by activation of the DNA damage repair pathway, which promoted cell survival and led the cells to become resistant to AZD1208. We also confirmed that the combination of an Akt inhibitor with AZD1208 produced a highly synergistic effect in gastric cancer cell lines. CONCLUSION: Treatment with AZD1208 alone induced considerable cell death through autophagy in gastric cancer cells. Moreover, the combination of AZD1208 with an Akt inhibitor showed synergistic antitumor effects through regulation of the DNA damage repair pathway.
Apoptosis
;
Autophagy
;
Blotting, Western
;
Cell Cycle
;
Cell Death
;
Cell Line
;
Cell Proliferation
;
Cell Survival
;
DNA Damage
;
Fluorescent Antibody Technique
;
Humans
;
Phosphotransferases
;
Protein Isoforms
;
Stomach Neoplasms

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