Purpose The optimal short-course chemotherapeutic regimen for rectal cancer has not been clearly defined until now. KROG 10-01 and KROG 11-02 prospective trials investigated the efficacy and safety of 1- and 2-week chemoradiotherapy (CRT), respectively.
Materials and Methods Patients eligible for KROG 10-01 and KROG 11-02 involved those with clinical T3-4N0-2M0 rectal cancers. They received preoperative CRT and total mesorectal excision. Patients in KROG 10-01 received radiation of 25 Gy in 5 fractions during 1 week with 5-fluorouracil/leucovorin. Patients in KROG 11-02 received radiation of 33 Gy in 10 fractions for 2 weeks with oral capecitabine.
Results A total of 150 patients consisting of 70 patients from KROG 10-01 and 80 patients from KROG 11-02 were collectively analyzed. With a median follow-up time of 89.2 months, the 5-year overall survival rate was 86.5% in 1-week CRT and 85.3% in 2-week CRT (p=0.841). The 5-year recurrence-free survival rate was 83.5% in 1-week CRT and 77.1% in 2-week CRT (p=0.448). One patient (1.4%) in 1-week CRT and 11 patients (13.8%) in 2-week CRT exhibited pathologic complete regression (ypT0N0M0) after radiotherapy (p=0.006). One-week CRT had significantly higher acute hematologic (12.8% vs. 3.8%, p=0.040) and nonhematologic (38.6% vs. 16.3%, p=0.002) toxicity than 2-week CRT.
Conclusion Both 1- and 2-week schedules of CRT showed favorable survival outcomes after 7 years of follow-up. But, 2-week course achieved more increased tumor response and decreased acute toxicity than 1-week course.
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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Gyu Sang Yoo, Hee Chul Park, Jeong Il Yu, Doo Ho Choi, Won Kyung Cho, Young Suk Park, Joon Oh Park, Ho Yeong Lim, Won Ki Kang, Woo Yong Lee, Hee Cheol Kim, Seong Hyeon Yun, Yong Beom Cho, Yoon Ah Park, Kyoung Doo Song, Seok-Hyung Kim, Sang Yun Ha
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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Cancer Res Treat. 2019;51(4):1589-1599. Published online April 10, 2019
Purpose
There is limited data on radiotherapy (RT) for hepatocellular carcinoma (HCC) in patients with Child-Pugh classification B (CP-B). This study aimed to evaluate the treatment outcomes of fractionated conformal RT in HCC patients with CP-B.
Materials and Methods
We retrospectively reviewed the data of HCC patients with CP-B treated with RT between 2009 and 2014 at 13 institutions in Korea. HCC was diagnosed by the Korea guideline of 2009, and modern RT techniques were applied. Fraction size was ≤ 5 Gy and the biologically effective dose (BED) ≥ 40 Gy10 (α/β = 10 Gy). A total of 184 patients were included in this study.
Results
Initial CP score was seven in 62.0% of patients, eight in 31.0%, and nine in 7.0%. Portal vein tumor thrombosis was present in 66.3% of patients. The BED ranged from 40.4 to 89.6 Gy10 (median, 56.0 Gy10). After RT completion, 48.4% of patients underwent additional treatment. The median overall survival (OS) was 9.4 months. The local progression-free survival and OS rates at 1 year were 58.9% and 39.8%, respectively. In the multivariate analysis, non-classic radiation-induced liver disease (RILD) (p < 0.001) and additional treatment (p < 0.001) were the most significant prognostic factors of OS. Among 132 evaluable patients without progressive disease, 19.7% experienced non-classic RILD. Normal liver volume was the most predictive dosimetric parameter of non-classic RILD.
Conclusion
Fractionated conformal RT showed favorable OS with a moderate risk non-classic RILD. The individual radiotherapy for CP-B could be cautiously applied weighing the survival benefits and the RILD risks.
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Cancer Res Treat. 2018;50(3):1039-1050. Published online November 21, 2017
Purpose
A pooled analysis of multi-institutional trials was performed to analyze the effect of surgical timing on tumor response by comparing short course concurrent chemoradiotherapy (CCRT) with long course CCRT followed by delayed surgery in locally advanced rectal cancer.
Materials and Methods
Three hundred patients with cT3-4N0-2 rectal adenocarcinoma were included. Long course patients from KROG 14-12 (n=150) were matched 1:1 to 150 short course patients from KROG 10-01 (NCT01129700) and KROG 11-02 (NCT01431599) according to stage, age, and other risk factors. The primary endpoint was to determine the interval between surgery and the last day of neoadjuvant CCRT which yields the best tumor response after the short course and long course CCRT. Downstaging was defined as ypT0-2N0M0 and pathologic complete response (ypCR) was defined as ypT0N0M0, respectively.
Results
Both the long and short course groups achieved lowest downstaging rates at < 6 weeks (long 20% vs. short 8%) and highest downstaging rates at 6-7 weeks (long 44% vs. short 40%). The ypCR rates were lowest at < 6 weeks (both long and short 0%) and highest at 6-7 weeks (long 21% vs. short 11%) in both the short and long course arms. The downstaging and ypCR rates of long course group gradually declined after the peak at 6-7 weeks and those of the short course group trend to constantly increase afterwards.
Conclusion
It is optimal to perform surgery at least 6 weeks after both the short course and long course CCRT to obtain maximal tumor regression in locally advanced rectal adenocarcinoma.
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Purpose This study was conducted to validate the prognostic influence of treatment response among patients with positive circumferential resection margin for locally advanced rectal cancer.
Materials and Methods Clinical data of 197 patientswith positive circumferentialresection margin defined as ≤ 2 mm after preoperative chemoradiotherapy followed by total mesorectal excision between 2004 and 2009were collected forthis multicenter validation study. All patients underwent median 50.4Gy radiationwith concurrentfluoropyrimidine based chemotherapy. Treatmentresponse was dichotomized to good response, including treatmentresponse of grade 2 or 3, and poor response, including grade 0 or 1.
Results After 52 months median follow-up, 5-year overall survival (OS) for good responders and poor responders was 79.1% and 48.4%, respectively (p < 0.001). In multivariate analysis, circumferential resection margin involvement and treatment response were a prognosticator for OS and locoregional recurrence-free survival. In subgroup analysis, good responders with close margin showed significantly better survival outcomes for survival. Good responders with involved margin and poor responders with close margin shared similar results, whereas poorresponderswith involved margin hadworst survival (5-year OS, 81.2%, 57.0%, 50.0%, and 32.4%, respectively; p < 0.001).
Conclusion Among patients with positive circumferential resection margin after preoperative chemoradiotherapy, survival of the good responders was significantly better than poor responders. Subgroup analysis revealed that definition of positive circumferential resection margin may be individualized as involvement for good responders, whereas ≤ 2 mm for poor responders.
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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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Purpose The purpose of this study is to investigate the dosimetric and clinical influence of computed tomography–based (3-dimensional [3D]) simulation versus conventional 2-dimensional (2D)–based simulation in postoperative chemoradiotherapy (CRT) for patients with advanced gastric cancer in terms of parallel opposed anteroposterior-posteroanterior field arrangement. Materials and Methods A retrospective stage-matched cohort study was conducted in 158 patients treated with adjuvant CRT following curative surgery and D2 dissection from 2006 to 2008 at Samsung Medical Center: 98 patients in the 3D group; and 60 patients in the 2D group. For comparison of the dosimetric parameters between 3D plan and 2D plan, second sets of radiation treatment plans were generated according to the same target delineation method used in the 2D group for each patient in the 3D group (V2D). Acute toxicity, recurrence, and survival were analyzed. The median follow-up period was 28 months (range, 5 to 51 months). Results The 3D group showed better dose-volume histogram (DVH) profiles than the V2D group for all dosimetric parameters, including the kidneys, liver, spinal cord, duodenum, pancreas, and bowel. However, no difference in acute gastrointestinal toxicity and survival outcomes was observed between the 3D group and the 2D group. Conclusion The 3D plan enabled precise delineation of the target volume and organs at risk by visualization of geometric changes in the internal organs after surgery. The DVH of normal tissues in the 3D plan was superior to that of the V2D plan, but similar clinical features were observed between the 3D group and the 2D group.
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Purpose
In this study, we retrospectively investigated the prevalence of arterioportal (AP) shunts in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) and evaluated the changes in AP shunts after chemoembolization followed by external beam radiation therapy (EBRT).
Materials and Methods
We analyzed 54 HCC patients with PVTT who were treated with chemoembolization followed by EBRT. EBRT was uniformly delivered at a total dose of 30 to 45 Gy (median, 35 Gy), with a daily dose of 2 to 4.5 Gy. Angiographic images of chemoembolization before and after radiation therapy (RT) were reviewed to investigate the AP shunt.
Results
During the initial session of chemoembolization, 33 of 54 patients (61%) had an AP shunt. After EBRT, 32 out of 33 patients had an additional session of chemoembolization and were evaluated for a change in the AP shunt. The AP shunt decreased in 20 of 32 patients (63%) after chemoembolization followed by EBRT. The 1-year calculated overall survival (OS) rate for all patients was 52.6% and the 2-year OS was 36.4%. The median OS in all patients was 13 months. Patients with AP shunt showed poorer median OS than those without AP shunt, but there was no statistically significant difference (median, 12 months vs. 17 months).
Conclusion
The AP shunt frequently occurs in HCC patients with PVTT. This study suggests that a poor prognosis is associated with an AP shunt. Chemoembolization followed by RT may produce a decrease in AP shunts.
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Clinical impact of combined transarterial chemoembolization and radiotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis: An external validation study Jeong Il Yu, Jae Won Park, Hee Chul Park, Sang Min Yoon, Do Hoon Lim, Joon Hyeok Lee, Han Chu Lee, Seon Woo Kim, Jong Hoon Kim Radiotherapy and Oncology.2016; 118(2): 408. CrossRef
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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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PURPOSE Transcatheter arterial chemoembolization (TACE) has been actively performed for the treatment of unresectable or inoperable hepatocellular carcinoma. However, for the patients with treatment failure after TACE, few options are available for salvage.
The purpose of this study was to investigate the efficacy of local radiotherapy as a salvage moda- lity for treatment failure after TACE. MATERIALS AND METHODS From January 1993 to December 1997, 27 patients were included in this study. Exclusion criteria included the presence of extrahepatic metastasis, liver cirrhosis of Childs class C, tumors occupying more than two thirds of the entire liver, and performance status on the ECOG scale of more than 3. Mean tumor size was 7.2+/- 2.9 cm.
Liver cirrhosis was associated in 10 patients. Portal vein thrombosis was presented in 5 patients. Serum alpha-fetoprotein was positive in 8 patients.
According to VICC staging, the number of patients in III and IVA were 17 and 10, respectively. Treatment failure to TACE was evaluated by CT scan and angiography. Radiotherapy was given to the field including tumor with generous margin using 10-MV X-ray. Mean tumor dose was 51.8+-7.9 Gy in daily 1.8 Gy fractions. Tumor response was based on CT scans 4~6 weeks following completion of treatment. RESULTS An objective response was observed in 16 of 24 patients who were possible to be evaluated, giving a response rate of 66.7%.
Survival rates after salvage radiotherapy at 1, 2, 3 years were 55.9%, 35.7%, and 21.4%, respectively. The median survival was 14 months. Six patients among responders are surviving at present. Acute toxicity included G1 elevation of AST/ALT in 4 patients, G2 thrombocytopenia in 2, G2 hyperbilirubinemia in 5, and G2 hypoalbuminemia in 3. During follow-up, 4 patients developed ascites. At 6 months after treatment, gastric ulcers and duodenal ulcer were developed in 2 and 1 patient, respectively. CONCLUSION Local radiotherapy for treatment failure after TACE in hepatocellular carci- noma appears to be a feasible and effective salvage modality. It gives a 66.7% response rate with a median survival of 14 months. Acute toxicity was self-limiting and manageable. Gastric and duodenal ulcer were significant toxicities after treatment. Further studies are required to find optimal methods of radiotherapy to minimize toxicity.