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Background: Polo-like kinase 4 (PLK4) is a serine/threonine protein kinase located in the centriole of the chromosome during the cell cycle. PLK4 overexpression has been described in a variety of many common human epithelial tumors. Conversely, PLK4 acts as a haploinsufficient tumor suppressor in some situations, highlighting the importance of strict regulation of PLK4 expression, activity, and function. Meanwhile, the importance of chemoradiation resistance in rectal cancer is being emphasized more than ever. We aimed to analyze PLK4 expression and the tumor regression grade (TRG) in patients with rectal cancer, treated with chemoradiotherapy (CRT).Methods: A retrospective study was conducted on 102 patients with rectal cancer who received preoperative CRT. Immunohistochemistry for PLK4 in paraffin-embedded tissue was performed from the biopsy and surgical specimens. Results: We found significant association between high expression of PLK4 and poor response to neoadjuvant CRT (according to both Mandard and The Korean Society of Pathologists TRG systems) in the pre-CRT specimens. Other clinicopathologic parameters did not reveal any correlation with PLK4 expression. Conclusions: This study revealed an association between high expression of PLK4 in the pre-CRT specimens and TRG. Our results indicated that PLK4 could potentially be a new predictor for CRT effect in patients with rectal cancer.

Background: Concurrent chemoradiation therapy is standard treatment in locally advanced rectal cancer. 5-FU is a commonly used chemotherapeutic agent, and radiotherapy is delivered with conventional or short-course fractionations. Immunotherapy is a new strategy with systemic effect, and several combinations with other treatments including surgery, chemotherapy, or radiotherapy in various sequences are evaluated. After irradiation, there is immunogenic changes in the tumor microenvironment, which is expected to improve the response of the added immunotherapy. The purpose of this study is to investigate the difference in immune response according to the radiation fractionation schedules after irradiation in various colon cancer cell lines. Materials and Methods: The human colorectal cancer cell lines, DLD-1 and HCT116, were cultured and irradiated with total 1.8 Gy of X-rays in 10 fractions and 5 Gy of X-rays in 3 fractions using linear accelerator for 10 and 3 consecutive days. The mRNA expression levels of immune related genes including CD274, TREX1, CD74, IFNG, CALR, HMGB1, TGFB1 were evaluated using real-time PCR in 0, 3, and 7 days after irradiation. Result: The mRNA expression levels of CD74, HMGB1 and CD274 were increased in both DLD-1 and HCT116 cell lines, and IFNG increased only in DLD-1. However, there was a difference in the increasing patterns over time between the two radiation fractionations. According to the radiation fractionation, increasement of the mRNA expression levels was more prominent in 1.8 Gy in 10 fractions than 5 Gy in 3 fractions. In addition, the radiation-resistant DLD-1 cell line showed a more marked increase in the levels of CD274 mRNA as well as other genes associated with CD274 than the radiation-sensitive HCT116 cells. Moreover, DLD-1 cell line, which is more resistant to radiation, showed more prominent elevation in CD274 mRNA level than HCT-116. Conclusions: We could find that more fractionated irradiation schedule with smaller dose per fraction further increases the immune response. Even in radio-resistant tumor cells, better immune response could be expected after irradiation than radio-sensitive cells. It would be needed to verify the results in real tumor conditions, such as the tumor microenvironment containing immune cells and cancer-associate fibroblasts. It is also thought that studies on the appropriate time to use immunotherapeutic agent are needed. Citation Format: Sang Jun Byun, Shin Kim, Incheol Seo, Hye Won Lee, Sung Uk Bae, Seong Kyu Baek, Woon Kyung Jeong, Seung Gyu Park, Euncheol Choi. Enhanced immune response according to different radiation fractionations in colorectal cancer cell lines. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4163.

This study evaluated the correlation between tumor-associated macrophages (TAMs) and long-term oncologic outcomes in colorectal cancer (CRC). We evaluated TAMs based on the expression of CD68, CD11c, and CD163 as optimal markers via immunohistochemistry in 148 patients with CRC who underwent surgical resection between September 1999 and August 2004. A high proportion of CD68-positive macrophages were associated with the occurrence of distant metastasis. A low proportion of CD11c-positive macrophages were associated with unfavorable overall survival (OS) and disease-free survival. CD11c-positive macrophages were found to act as independent prognostic factors for OS. An analysis of our long-term data indicated that TAMs are significantly associated with OS and prognosis in CRC.

Purpose: Neoadjuvant chemoradiation therapy (CRT) is a widely and effectively used preoperative treatment strategy in locally advanced rectal cancers. Tumors demonstrating microsatellite instability (MSI) are known to be infiltrated by higher numbers of lymphocytes and to be characterized by a more favorable prognosis as compared with tumors with intact repair systems, and MSI is the only potential biomarker to predict the outcome of immune checkpoint inhibitors. However, the relationship between MSI and response to neoadjuvant CRT and changes in MSI status after CRT in rectal cancer are not well understood. The aim of the present study was to investigate the MSI status before and after CRT and its association with CRT response in rectal cancer. Materials and methods: Formalin-fixed paraffin-embedded tissue specimens from pre-operative biopsy via sigmoidoscopy and surgical resection of the primary tumor were obtained from 84 rectal adenocarcinoma patients who underwent neoadjuvant CRT between March 2010 and May 2018. MSI assays were performed on DNA extracted from FFPE and matched normal tissues the extracted DNA was amplified by PCR with fluorescent dye-labeled primers targeting five microsatellite loci: BAT25, BAT26, D5S346, D2S123 and D17S250. Three immune biomarker scores were calculated from the 19 patients who were able to perform RNA sequencing analysis to compare the immune activities of the specimens between responder (n = 8) and non-responder (n = 11). The gene lists included in each score calculation were as follows: CXCL9, CXCL10, IDO1, IFNG, HLA-DRA, and STAT1; GZMA and PRF1; and CD247, CD2, CD3E, GZMH, NKG7, PRF1 and GZMK for the interferon-γ (IFN-γ) signature,1 the cytolytic activity2 and the immune signature,3 respectively. Results: Patients were classified, according to Mandard tumor regression grade (TRG), as responders (grade 1 or 2; 25 patients, 29.8%) and non-responders (grade 3, 4 or 5; 59 patients, 70.2%). The TRG of 84 patients was significantly different according to the pre-CRT MSI status (P = 0.024), but was not different according to the post-CRT MSI status among 60 patients who were eligible for the paired MSI test (P = 0.788). Changes in MSI status were observed in 11 of the 60 patients; MSS to MSI-low in 9 patients, MSS to MSI-high in 1 patient, and MSI-low to MSS in 1 patient. All three immune biomarker scores (the IFN-γ signature, the cytolytic activity and the immune signature) were higher in the responder group without significant difference (p = 0.536, p = 0.152, and p = 0.272, respectively). Conclusion: Our findings demonstrated that neoadjuvant CRT modulated the MSI status of rectal cancer and pre-CRT MSI status was significantly associated with response of CRT. Future studies on various immuno-profiles that can influence the CRT response using more samples are needed. Citation Format: Sung Uk Bae, Shin Kim, Sang Jun Byun, Hye Won Lee. Impact of microsatellite instability status and immune scores on tumor after neoadjuvant chemoradiation therapy in locally advanced rectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1017.

BackgroundNeoadjuvant chemoradiation therapy (CRT) is a widely used preoperative treatment strategy for locally advanced rectal cancer (LARC). However, a few studies have evaluated the molecular changes caused by neoadjuvant CRT in these cancer tissues. Here, we aimed to investigate changes in immunotherapy-related immunogenic effects in response to preoperative CRT in LARC.MethodsWe analyzed 60 pairs of human LARC tissues before and after irradiation from three independent LARC cohorts, including a LARC patient RNA sequencing (RNA-seq) dataset from our cohort and GSE15781 and GSE94104 datasets.ResultsGene ontology analysis showed that preoperative CRT significantly enriched the immune response in LARC tissues. Moreover, gene set enrichment analysis revealed six significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways associated with downregulated genes, including mismatch repair (MMR) genes, in LARC tissues after CRT in all three cohorts. Radiation also induced apoptosis and downregulated various MMR system-related genes in three colorectal cancer cells. One patient with LARC showed a change in microsatellite instability (MSI) status after CRT, as demonstrated by the loss of MMR protein and PCR for MSI. Moreover, CRT significantly increased tumor mutational burden in LARC tissues. CIBERSORT analysis revealed that the proportions of M2 macrophages and CD8 T cells were significantly increased after CRT in both the RNA-seq dataset and GSE94104. Notably, preoperative CRT increased various immune biomarker scores, such as the interferon-γ signature, the cytolytic activity and the immune signature.ConclusionsTaken together, our findings demonstrated that neoadjuvant CRT modulated the immune-related characteristics of LARC, suggesting that neoadjuvant CRT may enhance the responsiveness of LARC to immunotherapy.

This study evaluates the oncogenic role of PIBF1 in triple-negative breast cancer (TNBC). TNBC is considered to have a poorer prognosis than other types of breast cancer and is associated with high risk of recurrence and distant metastasis. Currently, there are no effective therapies for the TNBC patients with distant metastasis due to the lack of targeted therapeutic options. The effects of PIBF1 knockdown on the cell viability and motility of TNBC cell lines were investigated. Effects of PIBF1 overexpression on tumorigenicity and cell motility were confirmed using Ba/F3 cell line and xenograft study on BALB/c nude mice. In TNBC cell lines that highly express PIBF1, knockdown of PIBF1 induces apoptosis and suppresses cell viability and motility with activation of the ATR/CHK1 signaling pathway. Moreover, the oncogenic function of PIBF1 was confirmed using the Ba/F3 cell line. For the first time, these findings clarify the role of PIBF1 in regulating ATR/CHK1 signaling pathway and inhibiting the proliferation and migration of TNBC cell lines. These results demonstrate the oncogenic roles of PIBF1 and provide new insights into the function and the molecular mechanism of PIBF1 in malignant TNBC.

Purpose We compared how doses delivered via two-dimensional (2D) intracavitary brachytherapy (ICBT) and three-dimensional (3D) ICBT varied anatomically. Materials and Methods A total of 50 patients who received 30 Gy of 3D ICBT after external radiotherapy (RT) were enrolled. We compared the doses of the actual 3D and 2D ICBT plans among patients grouped according to six anatomical variations: differences in a small-bowel V2Gy, small bowel circumference, the direction of bladder distension, bladder volume, sigmoid V3.5Gy, and sigmoid circumference. Seven dose parameters were measured in line with the EMBRACE recommendations. Results In terms of bladder volume, the bladder and small-bowel D2cc values were lower in the 150–250 mL bladder volume subgroup; and the rectum, sigmoid, and bladder D2mL values were all lower in the >250 mL subgroup, for 3D vs. 2D ICBT. In the sigmoid V3.5Gy >2 mL subgroup, the sigmoid and bladder D2mL values were significantly lower for 3D than 2D ICBT. The bladder D2mL value was also significantly lower for 3D ICBT, as reflected by the sigmoid circumference. In patients with a small bowel V2.0Gy >10 mL or small bowel circumference >15%, most dose parameters were significantly lower for 3D than 2D ICBT. The bladder distension direction did not significantly affect the doses. Conclusion Compared to 2D ICBT, a greater bladder volume can reduce the internal 3D ICBT organ dose without affecting the target dose.

Purpose To investigate the outcomes of postoperative radiotherapy (RT), in patients with extrahepatic bile duct (EHBD) cancer by comparing the survival rate between patients undergoing surgery alone or surgery plus postoperative RT, and to identify the prognostic factors affecting survival. Materials and methods Between 2000 and 2013, 52 patients with EHBD cancer underwent surgical resection. Of these, 33 patients did not receive postoperative RT (group I), and 19 patients did (group II). R1 resection was significantly more frequent in group II. The median radiation dose was 5,040 cGy. Results The 3-year overall survival (OS) rate for group I and group II was 38% and 56%, respectively (p = 0.274). The 3-year disease free survival (DFS) rate for group I and group II was 20% and 31%, respectively (p = 0.049), and the 3-year loco-regional recurrence free survival (LRFS) rates were 19% and 58%, respectively (p = 0.002). Multivariate analyses showed that postoperative RT and lymphovascular invasion were independent prognostic factors for DFS and LRFS. Overall, 42 patients (80%) experienced treatment failure. Distant metastasis was the predominant pattern of failure in group II. Conclusion Postoperative RT after surgical resection appeared to improve the loco-regional control and DFS rate. More effort is needed to reduce distant metastasis, the major pattern of failure, in patients who receive postoperative RT.

Purpose: Neoadjuvant chemoradiation therapy (CRT) is a widely and effectively used preoperative treatment strategy in locally advanced rectal cancers. However, little research has been done to characterize the molecular changes caused by neoadjuvant CRT in these cancer tissues. The purpose of this study was to investigate the effects of preoperative CRT on tumor gene expression in Korean patients with colorectal cancer (CRC). Materials and methods: We included 11 paired human rectal cancer tissues before and after irradiation between August 2016 and December 2017, and performed RNA sequencing analysis. Principal component analysis of CRC demonstrated strong similarity in respective groups of CRC tissues before and after CRT from CRC patients at the transcriptome level. Results: Volcano plot filtering identified 3325 differentially expressed genes (DEGs) in CRC tissues after CRT, compared to CRC tissues before CRT. Gene set enrichment analysis with DEGs revealed 45 signaling pathways associated with down-regulated target genes, significantly including the mismatch repair signaling pathway. CRT significantly increased tumor mutation burden (TMB) in CRC tissues. Notably, preoperative CRT increased immune signature scores including interferon-gamma, immune cytolytic score, and immune signature. Conclusion: Neoadjuvant CRT modulates immune-related characteristics of CRC, including increasing TMB and various immune signature scores, suggesting that neoadjuvant CRT has potential to improve responsiveness to immunotherapy. Citation Format: SungUk Bae, Shin Kim, Hye Won Lee, Sang Jun Byun, Jee Young Park, Hyeonji Min. Preoperativechemoradiation increases levels of immune system modulators in tumor tissue in locally advanced rectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 475.

PurposeTo investigate whether whole pelvic radiotherapy (WPRT) improves biochemical relapse-free survival (bRFS) vs. prostate bed radiotherapy (PBRT) in prostate cancer patients receiving salvage radiotherapy (SRT) after radical prostatectomy.MethodsData from patients with prostate cancer who underwent SRT for biochemical recurrence between 2005 and 2012 in two academic institutions were retrospectively reviewed. Patients treated with WPRT in one hospital were compared with patients treated with PBRT in the other. Propensity scoring was performed to balance the characteristics of the different treatment groups, and bRFS was compared.ResultsData from a total of 191 patients were included in the analysis (WPRT, n = 108; PBRT, n = 83). The median follow-up period was 66 months. Prior to matching, patients who received WPRT had higher pathologic Gleason scores as well as a higher incidence of pre-SRT PSA levels >0.5 ng/mL and lower rates of concurrent androgen-deprivation therapy. Propensity score matching balanced these characteristics and generated a cohort comprising 56 patients from each group. In the matched cohort, the 5 year bRFS of the WPRT group was significantly higher than that of the PBRT group (65.9 vs. 42.2%, p = 0.017). Multivariate analysis revealed that WPRT was an independent prognostic factor for bRFS (hazard ratio: 0.45, 95% confidence interval: 0.26-0.75, p = 0.002). This benefit of WPRT on bRFS was maintained in subgroup analyses, especially in patients with preoperative PSA level ≤20 ng/mL or pre-SRT PSA level ≥0.4 ng/mL.ConclusionsThese data suggest that, following radical prostatectomy, elective WPRT during SRT may improve bRFS compared with PBRT in selected patients. Patients with preoperative PSA level ≤20 ng/mL or pre-SRT PSA level ≥0.4 ng/mL represent a potential subgroup who benefit most from receiving WPRT. Results of prospective randomized trials are awaited to confirm this finding.

Background The optimal field size of salvage radiotherapy (SRT) for biochemical recurrence, particularly for patients with high-risk prostate cancer, remains undefined. This retrospective analysis was performed to investigate oncological outcomes as well as treatment-related toxicity following salvage intensity-modulated radiotherapy (IMRT) to the whole pelvis and to compare the results with other studies implementing a small field size of the prostate bed. Methods The medical records of 170 patients with high-risk prostate cancer who received SRT for biochemical recurrence following prostatectomy were reviewed. Whole-pelvic IMRT was administered with a median dose of 66 Gy in 30 fractions. To improve treatment accuracy, an endorectal balloon device and daily cone-beam computed tomography were utilized. Androgen-deprivation therapy combined with SRT was administered to 97 (57.1%) patients. Results Eventually, 68 (40.0%) patients showed biochemical progression (BCP) after SRT. With a median follow-up period of 56 months, the 5-year BCP-free survival was 38.6%. The overall and cause-specific survival rates were 90.9% and 96.7%, respectively. Regarding BCP-free survival analysis, pathological T stage, persistent prostate-specific antigen (PSA) elevation after prostatectomy, and preSRT PSA level were significant prognostic factors on univariate analysis. On multivariate analysis, pathological T stage and preSRT PSA value retained their significance. Acute and late grade-3 genitourinary toxicities were observed in one (0.6%) and five (2.9%) patients, respectively. One patient each developed acute and late grade-3 gastrointestinal toxicity. Conclusion SRT to whole pelvis using IMRT and image guidance is as safe as SRT to the prostate bed, but its efficacy should be confirmed in ongoing randomized trials. PreSRT PSA was the only controllable prognostic factor, suggesting the benefit of early SRT.

Purpose This study evaluated the efficacy of extended field irradiation (EFI) in patients with locally advanced cervical cancer without para-aortic nodal involvement. Materials and Methods A total of 203 patients with locally advanced cervical cancer (International Federation of Gynecology and Obstetrics [FIGO] stage, IB2-IIIB) treated with radiotherapy at Keimyung University Dongsan Medical Center from 1996 to 2010 were retrospectively analyzed. The median patient age was 59 years (range, 29 to 83 years). None of the patients had para-aortic node metastases. Of the 203 patients, 88 underwent EFI and 115 underwent irradiation of the pelvis only. Concurrent chemoradiotherapy (CCRT) was administered to 133 patients. EFI field was used for treatment of 26 patients who received radiotherapy alone and 62 who received CCRT. Results The median follow-up period was 60 months. The 2- and 5-year overall survival (OS) rates were 87.8% and 73.5%, respectively, and the 2- and 5-year disease-free survival rates were 81.7% and 75.0%, respectively, however, no survival differences were observed between the two treatment field groups. EFI tended to increase OS in the radiotherapy alone group, but not in the CCRT group. Conclusion These findings suggest that EFI does not have a significant effect in patients with locally advanced cervical cancer, especially in patients receiving CCRT. Conduct of additional studies will be required in order to confirm these findings.

Purpose: We designed this study to evaluate relations between microsatellite instability (MSI) status and programmed death-ligand 1 (PD-L1) and tumor response following neoadjuvant concurrent chemoradiation therapy (CCRT) in locally advanced rectal cancer. Materials and methods: In the prospective study, we collected 54 rectal adenocarcinoma patients who underwent neoadjuvant concurrent chemoradiation therapy between August 2016 and December 2017. With exclusion criteria, we finally included 24 patients and evaluated the PD-L1 expression using immunohistochemistry (IHC) and tested the MSI status with pre- and post- CCRT samples. Human colorectal cell lines DLD 1, HT-29 and HCT116 were obtained and cell morphology, cell viability, and PD-L1 expressions were evaluated using flow cytometry 24, 48 and 72 hours after irradiation. Using 4-fields box technique, 50.4 to 54 Gy in daily 1.8Gy fractions of radiation was delivered to pelvis including rectal mass and surgery was performed 6 to 8 weeks after completion of neoadjuvant CCRT. Tumor response was estimated by using Mandard grading system. Results: According to the tumor regression grade, patients were classified into two groups; responder (grade 0, 1 or 2; 9 patients, 37.5%) and non-responder (grade 3 or 4; 15 patients, 62.5%). Between the two groups, there was no statistically significant differences in several tumor characteristics including histologic type, lymphocytic response, tumor budding, BRAF or K-ras mutations except tumor stage; more patients with advanced T stage in non-responder (p = 0.019). MSI-high status was reported in two responders (25%), but no one with pre-CCRT MSI-high status in non-responder group (relative risk = 3.143, 95% CI = 1.705 - 5.794). High PD-L1 expression on tumor marginally significantly increased from 16.7% before CCRT to 45.0% after CCRT by IHC (P = 0.053), especially in non-responder group. PD-L1 gene expression by irradiation in three human cell lines using flow cytometry analysis was increased, mostly in radio-resistant cell line, DLD 1. Conclusion: This prospective study verified the chemoradiation-induced immune-oncologic shift toward increases in PD-L1 expression that may be associated with radio-resistance. MSI status was associated with tumor response after chemoradiotherapy for locally advanced rectal cancer. Key words: Locally advanced rectal cancer, neoadjuvant concurrent chemoradiation therapy, tumor regression, microsatellite instability, programmed death-ligand Note: This abstract was not presented at the meeting. Citation Format: SungUk Bae, Hye Won Lee, Sang Jun Byun, Woon Kyung Jeong, Seong Kyu Baek. Immune-oncologic shift in programmed death-ligand 1 expression and microsatellite instability after neoadjuvant chemoradiation therapy in locally advanced rectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 525.

Objective To investigate the disease course and identify prognostic factors for survival in patients with residual disease according to post-treatment magnetic resonance imaging (MRI) following definitive concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer. Methods We reviewed clinical data from the medical records of 545 consecutive women with biopsy-proven, International Federation of Gynecology and Obstetrics stage IB2–IVA uterine cervical cancer treated with CCRT. Post-treatment MRI was checked in all patients 3months after CCRT completion. Out of the 545 patients, 53 with residual cervical cancer based on MRI following definitive CCRT were included in this analysis. Results Thirty-two patients were disease-free at the last follow-up. Of them, 31 had a residual tumor size of ≤2cm. Of these 32 women, 30 showed spontaneous regression of residual tumor during follow-up without salvage treatments, whereas the remaining two were alive with no evidence of disease after salvage surgery and chemotherapy. Disease progression was observed in 21 patients, including 7 local, 8 distant and 6 local and distant failures. Of these 21 women, 13 died of disease, 6 were alive with disease, and 2 remained disease-free after salvage treatments. Initial and residual tumor sizes were significant prognostic factors for overall survival; only residual tumor size was significant for local progression-free survival. Conclusions About 60% of patients with residual disease detected on post-treatment MRI remained disease-free without further disease progression. Careful observation without immediate salvage treatments might be feasible in selected patients with a residual tumor size ≤2cm.

// Yeon Joo Kim 1 , Sang Jun Byun 1 , Hanjong Ahn 2 , Choung-Soo Kim 2 , Beom-Sik Hong 2 , Sangjun Yoo 2 , Jae-Lyun Lee 3 and Young Seok Kim 1 1 Department of Radiation Oncology, Asan Medical Center, University of Ulsan, College of Medicine, Songpa-Gu, Seoul, Republic of Korea 2 Urology, Asan Medical Center, University of Ulsan, College of Medicine, Songpa-Gu, Seoul, Republic of Korea 3 Oncology, Asan Medical Center, University of Ulsan, College of Medicine, Songpa-Gu, Seoul, Republic of Korea Correspondence to: Young Seok Kim, email: // Keywords : muscle-invasive bladder cancer, radical cystectomy, trimodal therapy, radiotherapy, chemotherapy Received : July 14, 2016 Accepted : March 15, 2017 Published : March 25, 2017 Abstract Although radical cystectomy (RC) is considered as the standard therapy for muscle-invasive bladder cancer (MIBC), trimodal therapy (TMT) combining transurethral resection of the tumor with radiotherapy and chemotherapy is increasingly recommended as an alternative approach for bladder preservation. In the absence of randomized trials, we compared the clinical outcomes between RC and TMT using propensity score matching with 50 patients in the RC arm and 29 patients in the TMT arm. With respective median follow-up periods of 23 and 32 months for the RC and TMT groups, 5-year distant metastasis-free survival (58% vs. 67%), overall survival (56% vs. 57%), and cancer-specific survival (69% vs . 63%) rates between the RC and TMT groups, respectively, were similar. However, the 5-year local recurrence-free survival was significantly better in the RC group than in the TMT group (74% vs . 35%). Following TMT, acute grade 3 hematological ( n = 2) and late grade 3 genitourinary ( n = 1) toxicities were reported. These findings demonstrated that oncological outcomes of TMT were comparable with those of RC, except for poorer local control. Large-scale, randomized trials are warranted to confirm the findings of the present retrospective comparison and to guide toward best treatment options.

Purpose The purpose of this study is to evaluate survival and prognostic factors for rectal cancer, including interval between surgery and radiation therapy after surgery, radiation therapy, and chemotherapy. Materials and Methods We conducted a retrospective study of 153 patients with rectal cancer who were treated with surgery, radiotherapy with/without chemotherapy at Keimyung University Dongsan Medical Center from January, 1988 to December, 2005. The study included 89 males and 64 females, with a median age of 56 years (range, 23 to 81 years). Tumor, node and metastasis (TNM) was I in 23 patients, II in 39, and III in 91. Radiation therapy was performed on pelvic fields using a median dose of 54 Gy five days per week, 1.8 Gy once per day. Ninety two patients were treated with radiotherapy, 43 with concurrent chemo-radiation therapy and 18 with sequential therapy after surgery. The median follow-up period was 52 months (range, 4 to 272 months). The interval between surgery and radiation was 1-25 weeks (median, 5 weeks). Results Two-year and five-year overall survival rate was 64.7% and 46.4%, respectively. Two-year and five-year disease-free-survival (DFS) rate was 58.6% and 43.1%, respectively. Median DFS was 39 months. Loco-regional failure was evident in 10.5% of patients, 8.4% had distant metastasis, and 9.2% had both. In multivariate analysis, TNM stage and interval between surgery and radiation therapy (≤5 weeks vs. >5 weeks; 95% confidence interval, 1.276 to 2.877; hazard ratio, 1.916; p=0.002) were significant prognostic factors of DFS. Conclusion Survival rates for rectal cancer after surgery, chemotherapy, and radiation therapy were similar to those reported in previous studies. Starting radiation therapy as soon as possible after surgery, especially within the first five weeks after surgery, is suggested.

Purpose To evaluate survival rates and prognostic factors related to treatment outcomes after bladder preserving therapy including transurethral resection of bladder tumor, radiotherapy (RT) with or without concurrent chemotherapy in bladder cancer with a curative intent. Materials and methods We retrospectively studied 50 bladder cancer patients treated with bladder-preserving therapy at Keimyung University Dongsan Medical Center from January 1999 to December 2010. Age ranged from 46 to 89 years (median, 71.5 years). Bladder cancer was the American Joint Committee on Cancer (AJCC) stage II, III, and IV in 9, 27, and 14 patients, respectively. Thirty patients were treated with concurrent chemoradiotherapy (CCRT) and 20 patients with RT alone. Nine patients received chemotherapy prior to CCRT or RT alone. Radiation was delivered with a four-field box technique (median, 63 Gy; range, 48.6 to 70.2 Gy). The follow-up periods ranged from 2 to 169 months (median, 34 months). Results Thirty patients (60%) showed complete response and 13 (26%) a partial response. All patients could have their own bladder preserved. Five-year overall survival (OS) rate was 37.2%, and the 5-year disease-free survival (DFS) rate was 30.2%. In multivariate analysis, tumor grade and CCRT were statistically significant in OS. Conclusion Tumor grade was a significant prognostic factor related to OS. CCRT is also considered to improve survival outcomes. Further multi-institutional studies are needed to elucidate the impact of RT in bladder cancer.

Purpose To investigate the prognostic factors and effectiveness of postoperative radiotherapy alone for endometrial carcinoma. Materials and Methods Sixty four patients with stage I-III endometrial cancer (EC) treated with postoperative radiotherapy alone between January 1989 and December 2008 at the Keimyung University Dongsan Medical Center were chosen for the present study. Typically, total hysterectomy, salpingo-oophorectomy and lymphadenectomy were performed on the patient's pelvis. Total dose from 50.4 Gy to 63 Gy was irradiated at pelvis or extended field. Thirteen patients were treated with Co-60 or Ir-192 intracavitary radiotherapy. Follow-up periods were from 7 to 270 months, with a median of 56 months. Results Five year overall survival (OS) rate was 58.7%, respectively. Five year disease-free survival (DFS) rate was 59.2%, respectively. In univariate analysis for OS and DFS, stage, menopausal age, type of operation, serosal invasion, and lymph node involvement were found to be statistically significant. Histologic type was marginally significant. In multivariate analysis for OS and DFS, stage, types of operation, histologic type were also found to be statistically significant. Treatment failure occurred in 14 patients. The main pattern of failure was found to be distant metastasis. Time to distant metastasis was from 3 to 86 months (median, 12 months). There were no grade 3 or 4 complications. Conclusion Stage, types of operation, and histologic type could be the predictive prognostic factors in patients. We contemplated postoperative radiation as effective and safe treatment method for EC. Additional treatment would be needed to reduce distant metastasis.

목 적: 간문맥종양혈전증을 동반한 간세포암에서 방사선 치료의 효과와 이에 영향을 미치는 인자들에 대해 알아보기 위하여 연구를 계획하였다 대상 및 방법: 2004년 12월부터 2009년 4월까지 계명대학교 동산의료원 방사선종양학과에서 간세포종양에 의한 간문맥 혈전부위에 방사선 치료를 받은 환자는 70명이었고 그 중 30 Gy 미만의 방사선 조사를 받은 19명의 환자와 간이식을 시행한 1명의 환자를 제외한 50명의 환자를 대상으로 하였다. 성별 구성은 남성이 45명, 여성이 5명이었고, 연령분포는 32세에서 79세(중앙값, 55세)이었다. 39명의 환자가 방사선 치료 전 간동맥 화학 색전술, 경피적 에탄올 주입술 등의 시술을 받았다. TNM 병기에 따른 분류는 III기 27명(54.0%), IV기 23명(46.0%)이었다. 방사선 치료는 총 조사선량 30~54 Gy(중앙값, 45)의 외부방사선을 조사하였으며, 이 중 동시항암화학방사선 치료를 받은 환자는 30명 (60.0%)이었다. 추적관찰기간은 3개월에서 70개월(중앙값, 13.5)이었다. 곁 과: 방사선치료 시작부터 전체 환자의 중앙생존기간은 9개월이었고, 1년 생존률은 24.9%, 2년 생존률은 11.2%이었다. 현재 무병생존은 3명(6.0%), 유병생존은 7명(14.0%), 질병악화로 인한 사망은 40명(80.0%)이었다. 생존율에 영향을 미치는 인자에 대한 단변량분석 상, 동시항암화학방사선 치료는 방사선치료 단독치료보다 낮은 생존율을 보였다(p=0.034). 방사선치료에 대한 종양의 반응(p=0.037), CLIP 병기(p=0.017), TNM 병기(p=0.041)가 통계적으로 유의한 결과를 보였다. 방사선에 의한 간독성은 관찰되지 않았다. 결론: 간문맥종양혈전을 동반한 간세포암에서 방사선치료는 안전하게 생존율의 향상을 얻을 수 있는 방법으로 생각된다. 향후 간문맥종양혈전을 동반한 간세포암에서 방사선치료의 역할을 알아보기 위한 무작위 전향적 임상연구가 필요하리라 생각된다. 【Purpose: To evaluate the effectiveness of radiation therapy (RT) for hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) and to analyze the prognostic factors. Materials and Methods: From December 2004 to April 2009, 70 patients who had HCC with PVTT were treated with RT at Keimyung University Dongsan Medical Center. Nineteen patients whose total dose was below 30 Gy and one patient who underwent liver transplantation were excluded. The remaining 50 patients (45 males, 5 females; median age 55 years) were analyzed. According to the LCSGJ TNM stage, there were 27 patients (54.0%) with stage III and 23 (46.0%) with stage IV. Total dose of 30~54 Gy was administered (median 45). Thirty patients (60.0%) were treated with concurrent chemoradiation therapy (CCRT). The median follow-up duration was from 13.5 months (range, 3 to 70 months). Results: The median survival time from the start of RT was 9 months. One-year and 2-year overall survival rates were 24.9% and 11.2%, respectively. At the follow-up time, three patients (6.0%) displayed no evidence of disease. Seven patients (14.0%) were alive with disease, and 40 (80.0%) patients had expired due to disease progression. CCRT was associated with worse survival than RT alone (p=0.034), Response to RT (p=0.037), CLIP stage (p=0.017), and TNM stage (p=0.041) were statistically significant prognostic factors. There was no radiation-induced liver disease. Conclusion: RT is an effective and safe modality for HCC with PVTT. Further studies such as prospective randomized trials are needed to confirm the role of RT for HCC with PVTT.】

†Purpose: This study was designed to evaluate the results of local control, survival rate, prognostic factors, and failure pattern in locally advanced esophageal cancer. Materials and Methods: We retrospectively studied 50 patients with locally advanced esophageal cancer treated with concurrent chemoradiotherapy at Keimyung University Dongsan Medical Center from June of 1999 to August of 2008. Seven patients with inappropriate data were excluded, and 43 patients were analyzed. There were 39 males and four female patients ranging in age from 43 to 78 years (median, 63 years). There were seven patients with stage IIA and 36 with stage III. Irradiation from 46 Gy to 63 Gy (median, 54 Gy) was carried out 5 days per week, 1.8 Gy once a day. There were eight patients with neo-adjuvant chemotherapy, and we mostly used 5-fluorouracil, cisplatin with 3 cycles for concurrent che motherapy. The range of follow up periods was from 2 to 82 months (median, 15.5). Results: There were nine patients that exhibited a complete response, 23 that exhibited a partial response, 9 that exhibited no response, and 2 that exhibited disease progression. The median survival time was 15 months. Two-year and 5-year survival rates were 36.5% and 17.3%, respectively. Two-year and 5-year disease-free survival rates were 32.4% and 16%, respectively. Treatment failure occurred in 22 patients (51.2%). Patterns of failure were categorized as local failure in 18 patients and distant metastasis in four patients. In a univariate analysis for prognostic factors related to overall survival and disease-free survival, the hemoglobin levels during chemoradiotherapy (≥ 12 vs.

Purpose: To evaluate the long-term results after breast-conserving surgery and radiation therapy in early breast cancer in terms of failure, survival, and cosmesis. Materials and Methods : One hundred fifty-four patients with stage I and II breast cancer were treated with conservative surgery plus radiotherapy between January 1992 and December 2002 at the Keimyung University Dongsan Medical Center. According to TNM stage, 93 patients were stage I, 50 were IIa, and 11 were IIb. The affected breasts were irradiated with 6 MV photons to 50.4 Gy i n 28 fractions over 5.5 weeks with a boost irradiation dose of 10∼16 Gy to the excision site. Chemotherapy was administered in 75 patients and hormonal therapy in 92 patients with tamoxifen. Follow-up periods were 13∼179 months, with a median of 92.5 months. Results : The 5- and 10-year overall survival rates were 97.3% and 94.5%, respectively. The 5- and 10-year disease-free survival (5YDFS and 10YDFS, respectively) rates were 92.5% and 88.9%, respectively; the ultimate 5YDFS and 10YDFS rates after salvage treatment were 93.9% and 90.2%, respectively. Based on multivariate analysis, only the interval between surgery and radiation therapy (≤6 weeks vs. ＞6 weeks, p=0.017) was a statistically significant prognostic factor for DFS. The major type of treatment failure was distant failure (78.5%) and the most common distant metastatic site was the lungs. The cosmetic results were good-to-excellent in 96 patients (80.7%). Conclusion : Conservative surgery and radiation for early stage invasive breast cancer yielded excellent survival and cosmetic results. Radiation therapy should be started as soon as possible after breast-conserving surgery in patients with early breast cancer, ideally within 6 weeks.