Hye Won Lee, Eui Hyun Jung, Kyung Hwan Kim, Hong Koo Ha, Jong Jin Oh, Seok Ho Kang, Seung-hwan Jeong, Hyeong Dong Yuk, Ji Eun Heo, Won Sik Ham, Eu Chang Hwang, Seung Il Jung, Wan Song, Bumjin Lim, Bumsik Hong, Byung Chang Jeong, Ho Kyung Seo
Received January 23, 2025 Accepted May 11, 2025 Published online May 12, 2025
Purpose
This study aimed to report the real-world outcomes of intravesical gemcitabine for bacillus Calmette–Guérin (BCG)–unresponsive, high-risk, non–muscle-invasive bladder cancer (HR-NMIBC) in Korean patients who were unable or unwilling to undergo radical cystectomy (RC).
Materials and Methods
This retrospective study included 131 patients (median age, 69 years; 88.5% men) treated with intravesical gemcitabine for BCG-unresponsive HR-NMIBC at nine centers between May 2019 and April 2022. The primary endpoint was 1-year recurrence-free survival (RFS). The secondary endpoints included factors influencing RFS, progression-free survival (PFS), cystectomy- free survival, cancer-specific survival (CSS), overall survival (OS), and safety. Survival analysis was performed using the Kaplan-Meier method, and risk factors for recurrence were assessed using Cox regression models.
Results
Patients were followed up for a median duration of 25 months, with carcinoma in situ (CIS) in 41.9% of the patients. The 1-year and 2-year RFS rates were 68% and 42%, while the 1-year and 2-year PFS rates were 87% and 77%, respectively. No significant factors influencing RFS were identified. Seventeen patients underwent RC during a median follow-up of 16 months, with the condition in three patients progressing to muscle-invasive disease on final pathological analysis. The 2-year CSS and OS rates were 98% and 97%, respectively. Intravesical gemcitabine was well-tolerated, with only seven patients (5.3%) unable to complete the full induction course.
Conclusion
Our research highlights the potential of intravesical gemcitabine as a viable bladder-sparing treatment option for BCG-unresponsive HR-NMIBC, providing real-world evidence on its safety, efficacy, and tolerability.
Purpose
The aim of this study is to summarize cancer risk among patients with clinical indications of immunosuppressive and antineoplastic drugs in Korea, which are pharmaceuticals defined as group 1 by International Agency for Research on Cancer.
Materials and Methods
We conducted a nationwide population-based retrospective cohort study using the Korean National Health Insurance Service claims data from 2002 to 2018. Patients with clinical indications for group 1 pharmaceuticals from 2002 to 2017 were selected as baseline population, and followed up until 2018. Cox proportional hazards regression model was used to analyze the risk of cancer and dose-response relationship between group 1 pharmaceuticals and cancer.
Results
Azathioprine use increased the risk of skin and hematologic cancer (hazard ratio [HR], 4.63; 95% confidence interval [CI], 2.91 to 7.39 and HR, 3.15; 95% CI, 2.41 to 4.13). Cyclosporine use increased the risk of skin and hematologic cancer (HR, 2.30; 95% CI, 1.79 to 2.95 and HR, 2.96; 95% CI, 2.59 to 3.40). Cyclophosphamide use increased the risk of bladder and hematologic cancer (HR, 2.69; 95% CI, 1.92 to 3.78 and HR, 3.83; 95% CI, 3.20 to 4.59). Chlorambucil use increased the risk of hematologic cancer (HR, 3.51; 95% CI, 2.53 to 4.87) and melphalan use increased the risk of hematologic cancer (HR, 16.31; 95% CI, 13.41 to 19.85). Methoxsalen use increased the risk of skin cancer (HR, 2.32; 95% CI, 1.36 to 3.95).
Conclusion
Group 1 pharmaceuticals were associated with increased risk of cancer. The results are expected to help establish alternative clinical strategies and policies for patients with clinical indications of group 1 pharmaceuticals, by continuous risk analysis and discussions on the surveillance systems.
Purpose
Sentinel lymph node biopsy (SLNB) using dye and isotope (DUAL) is recommended over the dye-only (DYE) method after neoadjuvant chemotherapy (NCT) due to potentially lower false-negative rates. However, the long-term outcome of either method is unclear. We aimed to compare the long-term oncological outcomes of DYE versus DUAL SLNB methods in patients who received NCT.
Materials and Methods
In this retrospective cohort study, 893 patients who underwent SLNB following NCT and had pathologically negative lymph nodes were included. After propensity score matching for cT, cN, and pT categories, 280 patients were in the DYE group and 560 in the DUAL group. Indigo carmine was used for dye and Tc-99m antimony trisulfate for isotope mapping.
Results
Median follow-up was 75.6 months in the DYE group and 83.0 months in the DUAL group. Mean (±standard deviation) number of harvested sentinel nodes was 6.7 (±3.9) and 6.7 (±3.3) in the DYE and DUAL groups (p=0.875). Five-year distant metastasisfree survival was 95.2% in DYE group and 93.3% in DUAL group (hazard ratio [HR], 1.45; 95% confidence interval [CI], 0.82 to 2.57; p=0.192). Disease-free survival (HR, 0.97; 95% CI, 0.69 to 1.50; p=0.914) and overall survival (HR, 0.98; 95% CI, 0.56 to 1.69; p=0.954) were not significantly different. Axillary recurrence rate was 1.8% and 2.5% in DYE and DUAL groups (p=0.647).
Conclusion
Long-term oncological outcomes did not significantly differ between DYE and DUAL SLNB methods. The dye-only method can be safely recommended for breast cancer patients who received NCT.
Youjin Hong, Soseul Sung, Woojin Lim, Sungji Moon, Kwang-Pil Ko, Jung Eun Lee, Inah Kim, Sun Ha Jee, Sun-Seog Kweon, Min-Ho Shin, Sangmin Park, Seung-Ho Ryu, Sun Young Yang, Jeongseon Kim, Sang-Wook Yi, Yoon-Jung Choi, Jeong-Soo Im, Hong Gwan Seo, Sue K. Park
Cancer Res Treat. 2025;57(3):649-658. Published online November 19, 2024
Purpose Population attributable fractions (PAFs) for hormone and reproductive factors have been estimated in several countries. International Agency for Research on Cancer (IARC) designated as group 1 and group 2A carcinogen for hormone factors in breast, ovarian, endometrial and uterine cervix cancer. This study aimed to estimate the PAFs of hormone/reproductive factor attributed to cancer incidence and deaths in Korean women and projected trends from 2015 to 2030.
Materials and Methods The PAF was estimated with using the 2005 standardized prevalence rates and 2020 incidence and deaths with a 15-year latency. Based on the Levin’s formula, prevalence rates were calculated using the Korea National Health and Nutrition Examination Survey (KNHANES) and the relative risks, which were the risk of selected female cancer associated with oral contraceptive, hormone replacement therapy and duration of breastfeeding, were estimated from the meta-analysis of studies performed in Korean women population. Studies based on the Asian and Global populations were calculated as a sensitivity analysis.
Results The estimation PAFs for hormone was 1.02% with 1,192 cases and reproductive was 2.67% with 3,112 cases. Moreover, 0.40% (125 deaths) and 1.09% (342 deaths) in female-related cancer deaths in order. Estrogen-progesterone combined hormone replacement therapy (HRT) accounted the most proportion in hormone factors and breastfeeding in reproductive factors. Also, the breast cancer had the highest percent in both hormone and reproductive factors.
Conclusion Through this study, 1.02% and 2.67% of female-related cancer incidence will be reduced by encouraging avoiding the use of oral contraceptives and HRT and breastfeeding for more than 6 months in reproductive factors. Additionally, among four selected female cancers in this study, breast cancer was observed to be a significant level of prevention.
Purpose This study aims to estimate and project the population attributable fraction (PAF) of cancer incidence and death due to carcinogenic drug use in Korea from 2015 to 2030, to estimate the degree of cancer prevention from exposure to carcinogenic drugs in Korea. Selected carcinogenic drugs were immunosuppressive and antineoplastic drugs classified as group I by the International Agency for Research on Cancer.
Materials and Methods Systematic review and meta-analyses were conducted to estimate the relative risk of cancer associated with carcinogenic drug use. Age was standardized using the annual prevalence rate of the National Health Insurance Service sample cohort (NHIS-NSC) from 2002 to 2013 to calculate the standardized prevalence rate of carcinogenic drug use each year. The PAF of specific cancer incidence and death were calculated using Levin’s formula and Monte Carlo methods. The prevalence rates were extrapolated to estimate the trend of PAF from 2015 to 2030.
Results In 2015, carcinogenic drugs attributed to 0.003% and 0.002% among the causes of cancer incidence and death in Korea. However, carcinogenic drugs attributed to 1.1% among the causes of both cancer incidence and death in patients with clinical indications of carcinogenic drugs.
Conclusion The PAF in patients with clinical indications of carcinogenic drugs were significantly high and expected to increase rapidly over time. Since these drugs are listed as essential by the World Health Organization, and may be difficult to replace, a surveillance system on susceptible populations using group I carcinogenic drugs must be discussed and implemented.
Purpose This study evaluated whether an addition of simvastatin to chemotherapy improves survival in ever-smokers with extensive disease (ED)–small cell lung cancer (SCLC).
Materials and Methods This is an open-label randomized phase II study conducted in National Cancer Center (Goyang, Korea). Chemonaive patients with ED-SCLC, smoking history (≥ 100 cigarettes lifetime), and Eastern Cooperative Oncology Group performance status of ≤ 2 were eligible. Patients were randomized to receive irinotecan plus cisplatin alone or with simvastatin (40 mg once daily orally) for a maximum of six cycles. Primary endpoint was the the 1-year survival rate.
Results Between September 16, 2011, and September 9, 2021, 125 patients were randomly assigned to the simvastatin (n=62) or control (n=63) groups. The median smoking pack year was 40 years. There was no significant difference in the 1-year survival rate between the simvastatin and control groups (53.2% vs. 58.7%, p=0.535). The median progression-free survival and overall survival between the simvastatin arm vs. the control groups were 6.3 months vs. 6.4 months (p=0.686), and 14.4 months vs. 15.2 months, respectively (p=0.749). The incidence of grade 3-4 adverse events was 62.9% in the simvastatin group and 61.9% in the control group. In the exploratory analysis of lipid profiles, patients with hypertriglyceridemia had significantly higher 1-year survival rates than those with normal triglyceride levels (80.0% vs. 52.7%, p=0.046).
Conclusion Addition of simvastatin to chemotherapy provided no survival benefit in ever-smokers with ED-SCLC. Hypertriglyceridemia may be associated with better prognosis in these patient population.
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Erdheim-Chester disease (ECD), also known as non-Langerhans cell histiocytosis, is a multi-systemic disease with unclear pathogenesis. Based on a small number of case studies, pegylated interferon-α (PEG-IFN-α) has been used as the front-line treatment option. However, there are limited data regarding administration of ropegylated-interferon α-2b (ROPEG-IFN-α 2b) for ECD patients. Herein, we report two cases of severe ECD treated with two types of PEG-IFN-α. One patient with heart and skeleton involvement and BRAF V600E mutation was treated with weekly PEG-IFN-α 2a. Another patient with bone involvement and no BRAF V600E mutation was administered monthly ROPEG-IFN-α 2b. The two types of PEG-IFN-α showed excellent disease control, excellent survival outcomes, and manageable toxicities in ECD patients. These results suggest that ROPEG-IFN-α 2b could be used equivalently to PEG-IFN-α 2a for management of advanced ECD.
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Purpose In sentinel lymph node (SLN) biopsy (SLNB) during breast cancer surgery, SLN mapping using dye and isotope (DUAL) may have lower false-negative rates than the dye-only (DYE) method. However, the long-term outcomes of either method are unclear. We aimed to compare long-term oncological outcomes of DYE and DUAL for SLNB in early breast cancer.
Materials and Methods This retrospective single-institution cohort study included 5,795 patients (DYE, 2,323; DUAL, 3,472) with clinically node-negative breast cancer who underwent SLNB and no neoadjuvant therapy. Indigo carmine was used for the dye method and Tc99m-antimony trisulfate for the isotope. To compare long-term outcomes, pathologic N0 patients were selected from both groups, and propensity score matching (PSM), considering age, pT category, breast surgery, and adjuvant treatment, was performed (1,441 patients in each group).
Results The median follow-up duration was 8.7 years. The median number of harvested sentinel nodes was 3.21 and 3.12 in the DYE and DUAL groups, respectively (p=0.112). The lymph node–positive rate was not significantly different between the two groups in subgroups of similar tumor sizes (p > 0.05). Multivariate logistic regression revealed that the mapping method was not significantly associated with the lymph node–positive rate (p=0.758). After PSM, the 5-year axillary recurrence rate (DYE 0.8% vs. DUAL 0.6%, p=0.096), and 5-year disease-free survival (DYE 93.9% vs. DUAL 93.7%, p=0.402) were similar between the two groups.
Conclusion Dye alone for SLNB was not inferior to dual mapping regarding long-term oncological outcomes in early breast cancer.
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Purpose Decision-making for treatment of newly diagnosed prostate cancer (PCa) is complex due to the multiple initial treatment modalities available. We aimed to externally validate the SCaP (Severance Study Group of Prostate Cancer) Survival Calculator that incorporates a long short-term memory artificial neural network (ANN) model to estimate survival outcomes of PCa according to initial treatment modality. Materials and Methods The validation cohort consisted of clinicopathological data of 4,415 patients diagnosed with biopsy-proven PCa between April 2005 and November 2018 at three institutions. Area under the curves (AUCs) and time-to-event calibration plots were utilized to determine the predictive accuracies of the SCaP Survival Calculator in terms of progression to castration-resistant PCa (CRPC)–free survival, cancer-specific survival (CSS), and overall survival (OS). Results Excellent discrimination was observed for CRPC-free survival, CSS, and OS outcomes, with AUCs of 0.962, 0.944, and 0.884 for 5-year outcomes and 0.959, 0.928, and 0.854 for 10-year outcomes, respectively. The AUC values were higher for all survival endpoints compared to those of the development cohort. Calibration plots showed that predicted probabilities of 5-year survival endpoints had concordance comparable to those of the observed frequencies. However, calibration performances declined for 10-year predictions with an overall underestimation. Conclusion The SCaP Survival Calculator is a reliable and useful tool for determining the optimal initial treatment modality and for guiding survival predictions for patients with newly diagnosed PCa. Further modifications in the ANN model incorporating cases with more extended follow-up periods are warranted to improve the ANN model for long-term predictions.
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Cancer Res Treat. 2018;50(4):1186-1193. Published online December 14, 2017
Purpose
Patients treated with anticancer agents often experience a variety of treatment-related skin problems, which can impair their quality of life.
Materials and Methods
In this cross-sectional study, Dermatology Life Quality Index (DLQI) and clinical information were evaluated in patients under active anticancer treatment using a questionnaire survey and their medical records review.
Results
Of 375 evaluated subjects with anticancer therapy, 136 (36.27%) and 114 (30.40%) were treated for breast cancer and colorectal cancer, respectively. We found that women, breast cancer, targeted agent use, and longer duration of anticancer therapy were associated with higher dermatology-specific quality of life distraction. In addition, itching, dry skin, easy bruising, pigmentation, papulopustules on face, periungual inflammation, nail changes, and palmoplantar lesions were associated with significantly higher DLQI scores. Periungual inflammation and palmoplantar lesions scored the highest DLQI.
Conclusion
We believe our findings can be helpful to clinicians in counseling and managing the patients undergoing anticancer therapy.
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Cancer Res Treat. 2018;50(4):1140-1148. Published online December 7, 2017
Purpose
This study aimed to identify predictors for distant metastatic behavior and build a related prognostic nomogram in breast cancer.
Materials and Methods
A total of 1,181 patients with non-metastatic breast cancer between 2003 and 2011 were analyzed. To predict the probability of distant metastasis, a nomogram was constructed based on prognostic factors identified using a Cox proportional hazards model.
Results
The 7-year overall survival and 5-year post-progression survival of locoregional versus distant recurrence groups were 67.6% versus 39.1% (p=0.027) and 54.2% versus 33.5% (p=0.043), respectively. Patients who developed distant metastasis showed early and late mortality risk peaks within 3 and after 5 years of follow-up, respectively, but a broad and low risk increment was observed in other patients with locoregional relapse. In multivariate analysis of distant metastasis-free interval, age (≥ 45 years vs. < 45 years), molecular subtypes (luminal A vs. luminal B, human epidermal growth receptor 2, and triple negative), T category (T1 vs. T2-3 and T4), and N category (N0 vs. N1 and N2-3) were independently associated (p < 0.05 for all). Regarding the significant factors, a well-validated nomogram was established (concordance index, 0.812). The risk score level of patients with initial brain failure was higher than those of non-brain sites (p=0.029).
Conclusion
The nomogram could be useful for predicting the individual probability of distant recurrence in breast cancer. In high-risk patients based on the risk scores, more aggressive systemic therapy and closer surveillance for metastatic failure should be considered.
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Erdheim-Chester disease is a rare non-Langerhans–cell histiocytosis with bone and organ involvement. A 76-year-old man presented with low back pain and a history of visits for exertional dyspnea. We diagnosed him with anemia of chronic disease, cytopenia related to chronic illness, chronic renal failure due to hypertension, and hypothyroidism. However, we could not determine a definite cause or explanation for the cytopenia. Multiple osteosclerotic axial skeleton lesions and axillary lymph node enlargement were detected by computed tomography. Bone marrow biopsy revealed histiocytic infiltration, which was CD68-positive and CD1a-negative. This report describes an unusual presentation of Erdheim-Chester disease involving the bone marrow, axial skeleton, and lymph nodes.
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Purpose This study evaluates the long-term results of definitive radiotherapy (RT) for early glottic cancer. Clinical and treatment factors related to local control and patterns of failure are analyzed. Materials and Methods We retrospectively reviewed 222 patients with T1-2N0 squamous cell carcinoma of the glottic larynx treated with definitive RT from 1981 to 2010. None of the patients received elective nodal RT or combined chemotherapy. The median total RT dose was 66 Gy. The daily fraction size was < 2.5 Gy in 69% and 2.5 Gy in 31% of patients. The RT field extended from the hyoid bone to the cricoid cartilage.
Results The median age was 60 years, and 155 patients (70%) had T1 disease. The 5-year rates of local recurrence-free survival (LRFS) and ultimate LRFS with voice preservation were 87.8% and 90.3%, respectively. T2 (hazard ratio [HR], 2.30; 95% confidence interval [CI], 1.08 to 4.94) and anterior commissural involvement (HR, 3.37; 95% CI, 1.62 to 7.02) were significant prognostic factors for LRFS. In 34 patients with local recurrence, tumors recurred in the ipsilateral vocal cord in 28 patients. There were no contralateral vocal cord recurrences. Most acute complications included grade 1-2 dysphagia and/or hoarseness. There was no grade 3 or greater chronic toxicity.
Conclusion Definitive RT achieved a high cure rate, voice preservation, and tolerable toxicity in early glottic cancer. T2 stage and anterior commissural involvement were prognostic factors for local control. Further optimization of the RT method is needed to reduce the risk of ipsilateral tumor recurrence.
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Purpose
The purpose of this study was to evaluate whether an exogenous epidermal growth factor (EGF) could induce anti-tumor and radiosensitizing effects in vivo.
Materials and Methods
BALB/c-nu mice that were inoculated with A431 (human squamous cell carcinoma) cells in the right hind legs were divided into five groups: I (no treatment), II (EGF for 6 days), III (EGF for 20 days), IV (radiotherapy [RT]), and V (RT plus concomitant EGF). EGF was administered intraperitoneally (5 mg/kg) once a day and the RT dose was 30 Gy in six fractions. Hematoxylin and eosin (H&E) stained sections of tumor, liver, lung, and kidney tissues were investigated. Additionally, tumors were subjected to immunohistochemistry staining with caspase-3.
Results
EGF for 6 days decreased tumor volume, but it approached the level of the control group at the end of follow-up (p=0.550). The duration of tumor shrinkage was prolonged in group V while the slope of tumor re-growth phase was steeper in group IV (p=0.034). EGF for 20 days decreased tumor volume until the end of the observation period (p < 0.001). Immunohistochemistry revealed that mice in group V showed stronger intensity than those in group IV. There were no abnormal histological findings upon H&E staining of the normal organs.
Conclusion
EGF-induced anti-tumor effect was ascertained in the xenograft mouse models with A431 cells. Concomitant use of EGF has the potential role as a radiosensitizer in the design of fractionated irradiation.
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We evaluated 53 patients who underwent Whipple operation at surgical department, Dong San Medical Center, Keimyung University during 5 years from Jan. 1989 to Dec, 1993. The results were as follows: The most prevalent age group was 50(20 cases) and male to female ratio was 2:l. Among 53 cases, 16 were ampulla of Vater cancers, followed by distal CBD cancer (12 cases), pancreatic head cancer(l 1 cases), duodenal cancer (7 cases), and others (7 cases). Fre- quent symptoms and physical findings were jaundice(66%), RUQ abdominal pain(64%), weight loss(50%), general weakness, fever, chill and indigestion. Abnormal laboratory findings were shown in bilirubin (36 cases), alkaline phosphatase (35 cases), CA 19-9 (21 cases), and CEA(12 cases), ERCP was superior than any other radiologic diagnostic tools such as C-T, U-S, PTC and UGI. Frequent postoperative complications were wound infection(8 cases), intraabdominal abscess (5 cases), anastomotic site leakage(4 cases), pleural e#ffusion, pneumonia (4 cases) and others. There was one case of postoperative mortality due to respiratory failure caused by massive transfusion for control of postoperative bleeding. Histologically pathologic invasion from distal CBD to pancreas occured in 9 cases, from ampulla of Vater to distal CBD in 5 cases, from pancreatic head to distal CBD in 3 cases. Survival was much higher in ampulla of Vater cancer (1 year survival 100%, 3 year survival 88%) than that of any other cancers of pancreaticoduodenal region.