Purpose The locally advanced unresectable intrahepatic cholangiocarcinoma (ICC) has detrimental oncological outcomes. In this study, we aimed to investigate the efficacy of radiotherapy in patients with locally advanced unresectable ICC.
Materials and Methods Between 2001 and 2021, 116 patients were identified through medical record who underwent radiotherapy for locally advanced unresectable ICC. The resectability of ICC is determined by the multidisciplinary team at each institution. Overall survival (OS) were analyzed using the Kaplan-Meier method, and prognostic factors were analyzed using the Cox proportional hazards model.
Results The median equivalent radiotherapy dose in 2 Gy fractions (EQD2) was 52 Gy (range, 30 to 110 Gy). Forty-seven patients (40.5%) received sequential gemcitabine-cisplatin based chemotherapy (GEM-CIS CTx). Multivariate analysis identified two risk factors, EQD2 of ≥ 60 Gy and application of sequential GEM-CIS CTx for OS. Patients were grouped by these two risk factors: group 1, EQD2 ≥ 60 Gy with sequential GEM-CIS CTx (n=25); group 2, EQD2 < 60 Gy with sequential GEM-CIS CTx or fluoropyrimidine-based concurrent chemoradiotherapy (n=70); and group 3, radiotherapy alone (n=21). Curative resection was more frequently undergone in group 1 than in groups 2 or 3 (28% vs. 8.6% vs. 0%, respectively). Consequently, OS was significantly better in group 1 than in groups 2 and 3 (p < 0.05).
Conclusion Combined high-dose radiotherapy with sequential GEM-CIS CTx improved oncologic outcomes in patients with locally advanced unresectable ICC. Further prospective studies are required to validate these findings.
Younghee Park, Tae Hyun Kim, Kyubo Kim, Jeong Il Yu, Wonguen Jung, Jinsil Seong, Woo Chul Kim, Jin Hwa Choi, Ah Ram Chang, Bae Kwon Jeong, Byoung Hyuck Kim, Tae Gyu Kim, Jin Hee Kim, Hae Jin Park, Hyun Soo Shin, Jung Ho Im, Eui Kyu Chie
Cancer Res Treat. 2024;56(1):272-279. Published online July 31, 2023
Purpose Risk factors predicting distant metastasis (DM) in extrahepatic bile duct cancer (EHBDC) patients treated with curative resection were investigated.
Materials and Methods Medical records of 1,418 EHBDC patients undergoing curative resection between Jan 2000 and Dec 2015 from 14 institutions were reviewed. After resection, 924 patients (67.6%) were surveilled without adjuvant therapy, 297 (21.7%) were treated with concurrent chemoradiotherapy (CCRT) and 148 (10.8%) with CCRT followed by chemotherapy. To exclude the treatment effect from innate confounders, patients not treated with adjuvant therapy were evaluated.
Results After a median follow-up of 36.7 months (range, 2.7 to 213.2 months), the 5-year distant metastasis-free survival (DMFS) rate was 57.7%. On multivariate analysis, perihilar or diffuse tumor (hazard ratio [HR], 1.391; p=0.004), poorly differentiated histology (HR, 2.014; p < 0.001), presence of perineural invasion (HR, 1.768; p < 0.001), positive nodal metastasis (HR, 2.670; p < 0.001) and preoperative carbohydrate antigen (CA) 19-9 ≥ 37 U/mL (HR, 1.353; p < 0.001) were significantly associated with inferior DMFS. The DMFS rates significantly differed according to the number of these risk factors. For validation, patients who underwent adjuvant therapy were evaluated. In patients with ≥ 3 factors, additional chemotherapy after CCRT resulted in a superior DMFS compared with CCRT alone (5-year rate, 47.6% vs. 27.7%; p=0.001), but the benefit of additional chemotherapy was not observed in patients with 0-2 risk factors.
Conclusion Tumor location, histologic differentiation, perineural invasion, lymph node metastasis, and preoperative CA 19-9 level predicted DM risk in resected EHBDC. These risk factors might help identifying a subset of patients who could benefit from additional chemotherapy after resection.
Hyunji Jo, Seung Tae Kim, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Jeong Il Yu, Hee Chul Park, Doo Ho Choi, Yoonah Park, Yong Beom Cho, Jung Wook Huh, Seong Hyeon Yun, Hee Cheol Kim, Woo Yong Lee, Won Ki Kang
Cancer Res Treat. 2023;55(1):189-195. Published online June 8, 2022
Purpose The purpose of this phase II trial was to evaluate whether the addition of simvastatin, a synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, to preoperative chemoradiotherapy (CRT) with capecitabine confers a clinical benefit to patients with locally advanced rectal cancer (LARC).
Materials and Methods Patients with LARC (defined by clinical stage T3/4 and/or lymph node positivity) received preoperative radiation (45-50.4 Gy in 25-28 daily fractions) with concomitant capecitabine (825 mg/m2 twice per day) and simvastatin (80 mg, daily). Curative surgery was planned 4-8 weeks after completion of the CRT regimen. The primary endpoint was pathologic complete response (pCR). The secondary endpoints included sphincter-sparing surgery, R0 resection, disease-free survival, overall survival, the pattern of failure, and toxicity.
Results Between October 2014 and July 2017, 61 patients were enrolled; 53 patients completed CRT regimen and underwent total mesorectal excision. The pCR rate was 18.9% (n=10) by per-protocol analysis. Sphincter-sparing surgery was performed in 51 patients (96.2%). R0 resection was achieved in 51 patients (96.2%). One patient experienced grade 3 liver enzyme elevation. No patient experienced additional toxicity caused by simvastatin.
Conclusion The combination of 80 mg simvastatin with CRT and capecitabine did not improve pCR in patients with LARC, although it did not increase toxicity.
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Effects of Hyperlipidemia on Osseointegration of Dental Implants and Its Strategies Haiyang Sun, Shuhuai Meng, Junyu Chen, Qianbing Wan Journal of Functional Biomaterials.2023; 14(4): 194. CrossRef
Purpose
This study aimed to compare the early hematological dynamics and acute toxicities between proton beam craniospinal irradiation (PrCSI) and photon beam craniospinal irradiation (PhCSI) for pediatric brain tumors.
Materials and Methods
We retrospectively reviewed patients with pediatric brain tumors who received craniospinal irradiation (CSI). The average change in hemoglobin levels (ΔHbavg), absolute lymphocyte counts (ΔALCavg), and platelet counts (ΔPLTavg) from baseline values was evaluated and compared between the PrCSI and PhCSI groups at 1 and 2 weeks after the initiation of CSI, 1 week before and at the end of radiotherapy, and 3-4 weeks after the completion of radiotherapy using t test and mixed-model analysis.
Results
The PrCSI and PhCSI groups consisted of 36 and 30 patients, respectively. There were no significant differences in ΔHbavg between the two groups at any timepoint. However, ΔALCavg and ΔPLTavg were significantly lower in the PhCSI group than in PrCSI group at every timepoint, demonstrating that PrCSI resulted in a significantly lower rate of decline and better recovery of absolute lymphocyte and platelet counts. The rate of grade 3 acute anemia was significantly lower in the PrCSI group than in in the PhCSI group.
Conclusion
PrCSI showed a lower rate of decline and better recovery of absolute lymphocyte and platelet counts than PhCSI in the CSI for pediatric brain tumors. Grade 3 acute anemia was significantly less frequent in the PrCSI group than in the PhCSI group. Further large-scale studies are warranted to confirm these results.
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Cancer Res Treat. 2020;52(2):446-454. Published online September 25, 2019
Purpose
The purpose of this study was to investigate the role of carcinoembryonic antigen (CEA) levels in improving the performance of magnetic resonance imaging (MRI) for the prediction of pathologic response after the neoadjuvant chemoradiation (NCRT) for patients with rectal
cancer.
Materials and Methods
We retrospectively reviewed the medical records of 524 rectal cancer patients who underwent NCRT and total mesorectal excision between January 2009 and December 2014. The performances of MRI with or without CEA parameters (initial CEA and CEA dynamics) for prediction of pathologic tumor response grade (pTRG) were compared by receiver-operating characteristic analysis with DeLong’s method. Cox regression was used to identify the independent factors associated to pTRG and disease-free survival (DFS) after NCRT.
Results
The median follow-up was 64.0 months (range, 3.0 to 113.0 months). On multivariate analysis, poor tumor regression grade on MRI (mrTRG; p < 0.001), initial CEA (p < 0.001) and the mesorectal fascia involvement on MRI before NCRT (mrMFI; p=0.054) showed association with poor pTRG. The mrTRG plus CEA parameters showed significantly improved performances in the prediction of pTRG than mrTRG alone. All of mrTRG, mrMFI, and initial CEA were also identified as independent factors associated with DFS. The initial CEA further discriminated DFS in the subgroups with good mrTRG or that without mrMFI.
Conclusion
The CEA parameters significantly improved the performance of MRI in the prediction of pTRG after NCRT for patients with rectal cancer. The DFS was further discriminated by initial CEA level in the groups with favorable MRI parameters.
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Purpose
This first Korean prospective study is to evaluate the feasibility of prone breast radiotherapy after breast conserving surgery for left breast cancer patients who have relatively small breast size and we present dosimetric comparison between prone and supine positions.
Materials and Methods
Fifty patients underwent two computed tomography (CT) simulations in supine and prone positions. Whole breast, ipsilateral lung, heart, and left-anterior-descending coronary artery were contoured on each simulation CT images. Tangential-fields treatment plan in each position was designed with total 50 Gy in 2-Gy fractions, and then one of the positions was designated for the treatment by comparing target coverage and dose to normal organs. Also, interfractional and intrafractional motion was evaluated using portal images.
Results
In total 50 patients, 32 cases were decided as prone-position–beneficial group and 18 cases as supine-position–beneficial group based on dosimetric advantage. Target dose homogeneity was comparable, but target conformity in prone position was closer to optimal than in supine position. For both group, prone position significantly increased lung volume. However, heart volumewas decreased by prone position for prone-position–beneficial group but was comparable between two positions for supine-position–beneficial group. Lung and heart doses were significantly decreased by prone position for prone-position–beneficial group. However, prone position for supine-position–beneficial group increased heart dose while decreasing lung dose. Prone position showed larger interfractional motion but smaller intra-fractional motion than supine position.
Conclusion
Prone breast radiotherapy could be beneficial to a subset of small breast patients since it substantially spared normal organs while achieving adequate target coverage.
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Cancer Res Treat. 2019;51(3):1041-1051. Published online November 1, 2018
Purpose
We compared the oncologic outcomes of breast-conserving surgery plus radiation therapy (BCS+RT) and modified radical mastectomy (MRM) under anthracycline plus taxane-based (AT) regimens and investigated the role of adjuvant radiation therapy (RT) in patients with pathologic N1 (pN1) breast cancer treated by mastectomy.
Materials and Methods
We retrospectively reviewed the medical records of 2,011 patients with pN1 breast cancer who underwent BCS+RT or MRM alone at 12 institutions between January 2006 and December 2010. Two-to-one propensity score matching was performed for balances in variables between the groups.
Results
The median follow-up duration for the total cohort was 69 months (range, 1 to 114 months). After propensity score matching, 1,074 patients (676 in the BCS+RT group and 398 in the MRM-alone group) were analyzed finally. The overall survival, disease-free survival, locoregional failure-free survival, and regional failure-free survival (RFFS) curves of the BCS+RT group vs. MRM-alone group were not significantly different. The subgroup analysis revealed that in the group with both lymphovascular invasion (LVI) and histologic grade (HG) III, the BCS+RT showed significantly superior RFFS (p=0.008). Lymphedema (p=0.007) and radiation pneumonitis (p=0.031) occurred more frequently in the BCS+RT group than in the MRM-alone group, significantly.
Conclusion
There are no differences in oncologic outcomes between BCS+RT and MRM-alone groups under the AT chemotherapy regimens for pN1 breast cancer. However, BCS+RT group showed superior RFFS to MRM-alone group in the patients with LVI and HG III. Adjuvant RT might be considerable for pN1 breast cancer patients with LVI and HG III.
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Cancer Res Treat. 2019;51(3):876-885. Published online October 1, 2018
Purpose
The purpose of this study was to compare prognostic differentiation performances of the 7th and the 8th edition of American Joint Commission on Cancer (AJCC) staging system for gastric cancer (GC) patients.
Materials and Methods
A total of 1,633 GC patients who underwent curative D2 resection followed by adjuvant chemotherapy alone (CA) or concurrent chemo-radiotherapy (CCRT) from 2004 to 2013 were included. Concordance index (c-index) was applied to compare the discriminatory ability.
Results
In the 8th edition, migration of stage was detected in 248 patients (15.2%). Among them, 121 patients were up-staged while 127 patients were down-staged. Overall, there was no statistically significant difference in the discriminatory ability between the 7th and 8th editions. The new edition of staging system, however, showed a trend of better prognostic performance not only in recurrence-free survival (c-index=0.734; 95% confidence interval [CI], 0.706 to 0.762 in the 7th edition vs. c-index=0.740; 95% CI, 0.712 to 0.768 in the 8th edition; p=0.14), but also in overall survival (c-index=0.717; 95% CI, 0.688 to 0.745 in the 7th edition vs. c-index=0.722; 95% CI, 0.694 to 0.751 in the 8th edition; p=0.19), especially in stage III. This finding was repeated in the subgroup analysis regardless of adjuvant CA or CCRT.
Conclusion
Generally, the 8th edition of AJCC staging system had failed to show a superior discriminatory ability for curatively D2 resected GC patients than the 7th edition, although there was a trend of better prognostic performance of the new edition, regardless of adjuvant treatment method.
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Cancer Res Treat. 2017;49(4):970-980. Published online January 4, 2017
Purpose
This study was conducted to evaluate the impact of supraclavicular lymph node radiotherapy (SCNRT) on N1 breast cancer patients receiving post-lumpectomy whole-breast irradiation (WBI) and anthracycline plus taxane-based (AT) chemotherapy.
Materials and Methods
We performed a case-control analysis to compare the outcomes of WBI and WBI plus SCNRT (WBI+SCNRT). Among 1,147 patients with N1 breast cancer who received post-lumpectomy radiotherapy and AT-based chemotherapy in 12 hospitals, 542 were selected after propensity score matching. Patterns of failure, disease-free survival (DFS), distant metastasis-free survival (DMFS), and treatment-related toxicity were compared between groups.
Results
A total of 41 patients (7.6%) were found to have recurrence. Supraclavicular lymph node (SCN) failure was detected in three patients, two in WBI and one in WBI+SCNRT. All SCN failures were found simultaneously with distant metastasis. There was no significant difference in patterns of failure or survival between groups. The 5-year DFS and DMFS for patients with WBI and WBI+SCNRT were 94.4% versus 92.6% (p=0.50) and 95.1% versus 94.5% (p=0.99), respectively. The rates of lymphedema and radiation pneumonitis were significantly higher in the WBI+SCNRT than in the WBI.
Conclusion
We did not find a benefit of SCNRT for N1 breast cancer patients receiving AT-based chemotherapy.
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Yeon-Joo Kim, Won Park, Boram Ha, Boram Park, Jungnam Joo, Tae Hyun Kim, In Hae Park, Keun Seok Lee, Eun Sook Lee, Kyung Hwan Shin, Haeyoung Kim, Jeong Il Yu, Doo Ho Choi, Seung Jae Huh, Chan Woo Wee, Kyubo Kim, Kyung Ran Park, Yong Bae Kim, Sung Ja Ahn, Jong Hoon Lee, Jin Hee Kim, Mison Chun, Hyung-Sik Lee, Jung Soo Kim, Jihye Cha
Cancer Res Treat. 2017;49(4):927-936. Published online December 26, 2016
Purpose
The purpose of this study was to evaluate the impact of postmastectomy radiotherapy (PMRT) on loco-regional recurrence-free survival (LRRFS), disease-free survival (DFS), and overall survival (OS) in pT1-2N1 patients treated with taxane-based chemotherapy.
Materials and Methods
We retrospectively reviewed the medical data of pathological N1 patients who were treated with modified radical mastectomy and adjuvant taxane-based chemotherapy in 12 hospitals between January 2006 and December 2010.
Results
We identified 714 consecutive patients. The median follow-up duration was 69 months (range, 1 to 114 months) and the 5-year LRRFS, DFS, and OS rates were 97%, 94%, and 98%, respectively, in patients who received PMRT (PMRT [+]). The corresponding figures were 96%, 90%, and 96%, respectively, in patients who did not receive PMRT (PMRT [–]). PMRT had no significant impact on survival. Upon multivariable analysis, only the histological grade (HG) was statistically significant as a prognostic factor for LRRFS and DFS. In a subgroup analysis of HG 3 patients, PMRT (+) showed better DFS (p=0.081).
Conclusion
PMRT had no significant impact on LRRFS, DFS, or OS in pT1-2N1 patients treated with taxane-based chemotherapy. PMRT showed a marginal benefit for DFS in HG 3 patients. Randomized studies are needed to confirm the benefit of PMRT in high risk patients, such as those with HG 3.
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Cancer Res Treat. 2017;49(1):61-69. Published online June 13, 2016
Purpose The aim of this study was to examine patterns of radiotherapy (RT) in Korean patients with hepatocellular carcinoma (HCC) according to the evolving guideline for HCC established by the Korean Liver Cancer Study Group-National Cancer Center (KLCSG-NCC).
Materials and Methods We reviewed 765 patients with HCC who were treated with RT between January 2011 and December 2012 in 12 institutions.
Results The median follow-up period was 13.3 months (range, 0.2 to 51.7 months). Compared with previous data between 2004 and 2005, the use of RT as a first treatment has increased (9.0% vs. 40.8%). Increased application of intensity-modulated RT resulted in an increase in radiation dose (fractional dose, 1.8 Gy vs. 2.5 Gy; biologically effective dose, 53.1 Gy10 vs. 56.3 Gy10). Median overall survival was 16.2 months, which is longer than that reported in previous data (12 months). In subgroup analysis, treatments were significantly different according to stage (p < 0.001). Stereotactic body RT was used in patients with early HCC, and most patients with advanced stage were treated with three-dimensional conformal RT.
Conclusion Based on the evolving KLCSG-NCC practice guideline for HCC, clinical practice patterns of RT have changed. Although RT is still used mainly in advanced HCC, the number of patients with good performance status who were treated with RT as a first treatment has increased. This change in practice patterns could result in improvement in overall survival.
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Purpose
The Korean Society of Radiation Oncologists (KOSRO) conducted the Patterns of Care Study (PCS) of radiotherapy (RT) for spine metastases in 2009. The current study was conducted to investigate current practice patterns and compare them with the results of the PCS.
Materials and Methods
The survey questionnaire was composed of 10 questions regarding general information and seven questions for each of two clinical scenarios.
Results
Fifty-four members of the KOSRO answered at least one question on the web-based questionnaire. The yearly number of patients treated who underwent palliative spine RT was greater than 200 in 14 (25.9%), 51 to 100 in 13 (24.1%), and 31 to 50 in 11 respondents (20.4%). Scenario 1 described a patient presenting with cord compressive spine metastasis in multiple bones and liver metastasis from non-small cell lung cancer. Thirty gray (Gy) in 10 fractions was chosen by 35 respondents (64.8%). Scenario 2 described a case of a single spine metastasis without progression after targeted therapy. Thirty Gy in 10 fractions was chosen by 19 respondents (35.2%), and a single fraction or less than four fractions of stereotactic ablative radiotherapy (SABR) were selected by 18 respondents (33.3%). When compared with the 2009 PCS, practice patterns of Korean radiation oncologists had not changed significantly over 5 years, except that SABR emerged as a new treatment modality in the selected population.
Conclusion
The 2014 PCS demonstrated that multiple fraction RT is still preferred in a considerable proportion of Korean radiation oncologists.
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Purpose The purpose of this study is to evaluate the efficacy of hypofractionated radiation therapy (RT) in the treatment of unresectable hepatocellular carcinoma (HCC) after failure of transarterial chemoembolization (TACE) or in cases of refractory HCC, and to investigate biliary complications after hypofractionated RT. Materials and Methods We retrospectively enrolled patients with unresectable, TACE-unresponsive, or refractory HCC treated with hypofractionated RT between July 2006 and December 2012. The perihilar region was defined as the 1-cm area surrounding the right, left, and the common hepatic duct, including the gallbladder and the cystic duct. Significant elevation of total bilirubin was defined as an increase of more than 3.0 mg/dL, and more than two times that of the previous level after completion of RT.
Results Fifty patients received hypofractionated RT and 27 (54%) had a tumor located within the perihilar region. The median follow-up period was 24.7 months (range, 4.3 to 95.5 months). None of the patients developed classic radiation disease symptoms, but four patients (8%) showed significant elevation of total bilirubin within 1 year after RT. During follow-up, 12 patients (24%) developed radiologic biliary abnormalities, but only two patients had toxicities requiring intervention. Estimated local progression-free survival, progression-free survival, and overall survival of the patients at 3-year post-hypofractionated RT were 89.7%, 11.2%, and 57.4%, respectively. Conclusion Biliary complications associated with a higher dose exposure of hypofractionated RT were minimal, even in the perihilar region. Hypofractionated RT provided excellent local control and may be a valuable option for treatment of unresectable cases of TACE-unresponsive or refractory HCC.
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Cancer Res Treat. 2014;46(4):348-357. Published online July 16, 2014
Purpose We previously reported on a staging system and prognostic index (PITH) for portal vein tumor thrombosis (PVTT) in hepatocellular carcinoma (HCC) patients treated with radiotherapy (RT) at a single institution. The aim of this study is to validate the PITH staging system using data from patients at other institutions and to compare it with other published staging systems. Materials and Methods A total of 994 HCC patients with PVTT who were treated with RT between 1998 and 2011 by the Korean Radiation Oncology Group were analyzed retrospectively. All patients were staged using the Cancer of the Liver Italian Program (CLIP), Japanese Integrated Staging (JIS), Okuda, and PITH staging systems, and survival data were analyzed. The likelihood ratio, Akaike information criteria (AIC), time-dependent receiver operating characteristics, and prediction error curve analysis were used to determine discriminatory ability for comparison of staging systems. Results The median survival was 9.2 months. Compared with the other staging systems, the PITH score gave the highest values for likelihood ratio and lowest AIC values, demonstrating that PITH may be a better prognostic model. Although the values were not significant and differences were not exceptional, the PITH score showed slightly better performance with respect to time-dependent area under curve and integrated Brier score of prediction error curve. Conclusion The PITH staging system was validated in this multicenter retrospective study and showed better stratification ability in HCC patients with PVTT than other systems.
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