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Purpose This study aimed to compare treatment outcomes and toxicity profile between imaged-guided brachytherapy (IGBT) versus conventional brachytherapy (CBT) performed by the same practitioner during the same time period.Materials and Methods Medical records of 104 eligible patients who underwent brachytherapy for locally advanced cervical cancer were retrospectively reviewed. Fifty patients (48.1%) underwent IGBT, and 54 (51.9%) patients underwent CBT. All patients underwent concurrent chemoradiation with cisplatin. High-dose-rate intracavitary brachytherapy with dose prescription of 25-30 Gy in 4-6 fractions was performed for all patients. Late lower gastrointestinal (GI) and urinary toxicities occurred more than 3 months after the end of brachytherapy were included for comparative and dosimetric analyses.Results The median follow-up period was 18.33 months (range, 3.25 to 38.43 months). There were no differences in oncologic outcomes between the two groups. The IGBT group had lower rate of actuarial grade ≥ 3 toxicity than the CBT group (2-year, 4.5% vs. 25.7%; p=0.030). Cumulative equieffective D2cc of sigmoid colon was significantly correlated with grade ≥ 2 lower GI toxicity (p=0.033), while equieffective D2cc of rectum (p=0.055) and bladder (p=0.069) showed marginal significance with corresponding grade ≥ 2 toxicities in the IGBT group. Half of grade ≥ 3 lower GI toxicities impacted GI tract above the rectum. Optimal thresholds of cumulative D2cc of sigmoid colon and rectum were 69.7 Gy and 70.8 Gy, respectively, for grade ≥ 2 lower GI toxicity.Conclusion IGBT showed superior toxicity profile to CBT. Evaluating the dose to the GI tract above rectum by IGBT might prevent some toxicities.

PurposeIn the present study, we aimed to establish a liquid biopsy-based monitoring method using peripheral blood cell-free DNA (cfDNA) for patients with cervical cancer who underwent radical radiotherapy (RT).Materials and MethodsTwenty-five patients with cervical cancer were prospectively recruited and treated with external beam RT and brachytherapy. In all patients, except one, chemotherapy was administered concurrently during RT. Whole peripheral blood samples were obtained at least twice from each patient. We performed next-generation sequencing (NGS) for the target-captured libraries (67 oncogenes and human papillomavirus [HPV] type 16/18) using 64 plasma cfDNA samples from the 25 participants. The ratio of HPV cfDNA and the variant allele frequency (VAF) in cfDNA was calculated, and their dynamic changes were monitored. The median follow-up duration was 25.4 months.ResultsIn total, we identified 21,866 cfDNA variants. ARID1A and frameshift variants occupied the largest portion of altered genes and HIGH-grade variant types, respectively. In most cases, tumor shrinkage was followed by a decrease in the HPV ratio; however, an increase in HPV ratio indicated distant metastasis, despite the reduced tumor size. The initial HPV ratio reflecting the tumor burden was likely associated with treatment outcomes (p = 0.16). We did not determine a role for serial changes in the VAF in cfDNA.ConclusionOur findings suggest that the HPV cfDNA ratio, calculated after targeted NGS, may be valuable for monitoring and predicting treatment responses. Accordingly, further validation of these findings is warranted.

Despite the standard interval of 6-8 weeks between neoadjuvant chemoradiotherapy (nCRT) and surgery, it is debated whether an interval of8 weeks increases the pathologic complete response (pCR) rate. We investigated the interval between nCRT and surgery, and its impact on oncological outcomes and postoperative complications in patients with locally advanced rectal cancer.We retrospectively reviewed patients with rectal cancer who underwent total mesorectal excision after long-course nCRT between 2000 and 2020. They were divided into two groups-those who underwent surgery at 6-8 and8 weeks after nCRT. Surgical outcomes (stoma rate and postoperative complications), pCR, tumor regression grade (TRG), recurrence-free survival (RFS), and overall survival (OS) were compared.We selected 770/1153 patients with rectal cancer, including 502 and 268 patients surgically treated at 6-8 and8 weeks after nCRT, respectively. The pCR rates were similar between the two groups (14.7% vs. 15.3%, p = 0.836), while the TRG was significantly better in the8 weeks group (p = 0.267). Additionally, the postoperative complications, recurrence, 5-year RFS, and OS rates were not significantly different between the two groups.Although tumor regression increased in the8 weeks group, the oncological benefits of surgery8 weeks after nCRT remain uncertain.

Background: Psammaplin A (PsA) is a radiosensitizer whereas its clinical application is hampered by poor bioavailability. This study aimed to synthesize novel radiosensitizers using PsA as the lead compound. Materials and Methods: Eight homodimeric disulfides were synthesized from corresponding acid and cystamine dihydrochloride in N-hydroxysuccinimide and dicyclohexylcarbodiimide coupling conditions. One monomeric thiol analog was obtained by reduction of homodimeric disulfide with dithiothreitol. Clonogenic assay was used to measure cell survival after irradiation and drug treatment in human lung cancer (A549) and glioblastoma (U373MG) cells. Results and Discussion: Using the PsA backbone, nine compounds were synthesized. Eight compounds showed variable cytotoxicity with 50% inhibitory concentrations ranging 16.14 μM to 150.10 μM (A549), and 13.25 μM to 50.15 μM (U373MG). Four and six compounds radiosensitized A549 and U373MG cells, respectively. Two compounds that radiosensitized both cell lines were tested for its inhibitory effects on DNMT1. One of them was shown to significantly inhibit DNMT1 activity. Conclusion: Novel compounds with radiosensitizing activity were synthesized. These compounds have a great potential to serve as a basis for the development of future radiosensitizers. Further investigation is warranted for their clinical application.

To determine the impact of dedicated subspecialized radiologists in multidisciplinary team (MDT) discussions on the management of lower gastrointestinal (GI) tract malignancies.We retrospectively analyzed the data of 244 patients (mean age ± standard deviation, 61.7 ± 11.9 years) referred to MDT discussions 249 times (i.e., 249 cases, as five patients were discussed twice for different issues) for lower GI tract malignancy including colorectal cancer, small bowel cancer, GI stromal tumor, and GI neuroendocrine tumor between April 2018 and June 2021 in a prospective database. Before the MDT discussions, dedicated GI radiologists reviewed all imaging studies again besides routine clinical reading. The referring clinician's initial diagnosis, initial treatment plan, change in radiologic interpretation compared with the initial radiology report, and the MDT's consensus recommendations for treatment were collected and compared. Factors associated with changes in treatment plans and the implementation of MDT decisions were analyzed.Of the 249 cases, radiologic interpretation was changed in 73 cases (29.3%) after a review by dedicated GI radiologists, with 78.1% (57/73) resulting in changes in the treatment plan. The treatment plan was changed in 92 cases (36.9%), and the rate of change in the treatment plan was significantly higher in cases with changes in radiologic interpretation than in those without (78.1% [57/73] vs. 19.9% [35/176],MDT discussion involving additional review of radiology examinations by dedicated GI radiologists resulted in a change in the treatment plan in 36.9% of cases. Changes in treatment plans were significantly associated with changes in radiologic interpretation.

The purpose of this study was to investigate the impact of sarcopenia and body composition change during primary treatment on survival outcomes in patients with early cervical cancer. We retrospectively identified patients diagnosed with 2009 International Federation of Gynecology and Obstetrics stage IB1-IIA2 cervical cancer who underwent primary radical hysterectomy between 2007 and 2019. From pre-treatment CT scans (n = 306), the skeletal muscle area at the third lumbar vertebra (L3) and the waist skeletal muscle volume were measured using an artificial intelligence-based tool. These values were converted to the L3 and volumetric skeletal muscle indices by normalization. We defined L3 and volumetric sarcopenia using 39.0 cm2/m2 and the first quartile (Q1) value, respectively. From pre- and post-treatment CT scan images (n = 192), changes (%) in waist skeletal muscle and fat volumes were assessed. With the use of Cox regression models, factors associated with progression-free survival (PFS) and overall survival (OS) were analyzed. Between the L3 sarcopenia and non-sarcopenia groups, no differences in PFS and OS were observed. In contrast, volumetric sarcopenia was identified as a poor prognostic factor for PFS (adjusted hazard ratio [aHR], 1.874; 95% confidence interval [CI], 1.028–3.416; p = 0.040) and OS (aHR, 3.001; 95% CI, 1.016–8.869; p = 0.047). During primary treatment, significant decreases in waist skeletal muscle (median, −3.9%; p < 0.001) and total fat (median, −5.3%; p < 0.001) were observed. Of the two components, multivariate analysis revealed that the waist fat gain was associated with worse PFS (aHR, 2.007; 95% CI, 1.009–3.993; p = 0.047). The coexistence of baseline volumetric sarcopenia and waist fat gain further deteriorated PFS (aHR, 2.853; 95% CI, 1.257–6.474; p = 0.012). In conclusion, baseline volumetric sarcopenia might be associated with poor survival outcomes in patients with early cervical cancer undergoing primary RH. Furthermore, sarcopenia patients who gained waist fat during primary treatment were at a high risk of disease recurrence.

BACKGROUND: Growing evidence suggests that metastasis-directed therapy and/or prostate-directed therapy may benefit patients with oligometastatic prostate cancer (OMPC). Stereotactic body radiotherapy (SBRT) is increasingly used to treat oligometastases in various cancers. The purpose of this study was to investigate the current patterns of curative-intent SBRT for OMPC in Korea. METHODS: A 20-item questionnaire was sent to 326 radiation oncologists in 93 institutions in Korea. Only 1 physician per institution was required to complete the survey. Subsequently, the second survey consisting of 3 clinical scenarios was sent to 64 physicians with clinical experience in SBRT: case 1, cT4N0M1 (direct invasion to two pelvic bones); case 2, cT2N0M1 (three bone metastases); and case 3, solitary spine metastasis after radical prostatectomy. RESULTS: Seventy-six physicians from 93 institutions (82%) answered the first survey. The multidisciplinary team approach was practiced in 16 institutions (21%). Most physicians (75%) agreed on the definition of oligometastases as limited lesions and/or organs ≤5: 25% agreed with low-volume disease according to CHAARTED trial. During the last year, 49 physicians (64%) treated OMPC patients with curative intent. Sixty four physicians (84%) had a clinical experience with SBRT: 48 (75%) stated that both dose and fraction number should be considered when defining SBRT, whereas others (25%) stated that only fraction size should be considered. Fifty-five faculties (86%) answered the second survey. Physicians agreed with oligometastases in 89% for case 1, in 80% for case 2, and in 100% for case 3. The rate of SBRT application was the highest in case 3 (70%). CONCLUSIONS: There was diversity in the patterns of SBRT for OMPC in Korea. Additional prospective studies are necessary to strengthen evidence regarding role of SBRT in OMPC.

Purpose: Several cell-free DNA (cf-DNA) features, such as genome-wide coverage, fragment size, and fragment end motif frequency, have shown their potentials for cancer detection. In this study, we developed two independent models, GC (gross chromatin), and FEMS (fragment end motif frequency and size). Each model uses images generated from genome-wide normalized sequencing coverage and cf-DNA fragment end motif frequencies according to the different cf-DNA size profiles. Then we integrated them into a single ensemble model to improve cancer detection and multi-cancer type classification accuracy. Methods: Low depth cf-WGS data was generated from 1,396 patients (stage I: 14.9%, stage II: 35.6%, stage III: 24.9%, stage IV: 24.2%, unknown: 0.4%) with breast (n=702), liver (n=213), esophageal (n=155), ovarian (n=151), pancreatic (n=85), lung (n=53), head and neck (n=16), biliary tract (n=15), and colon cancer (n=6) and 417 healthy individuals. Samples were randomly split into training, validation, and test set stratifying cancer type and stages. Cancer types with a small number of samples ( Results: For cancer detection, the ensemble model achieved sensitivities of 85.2% [95% confidence interval (CI): 71.8% to 94.5%], 74.9% (CI: 68.0% to 88.0%), 73.2% (CI: 66.7% to 85.9%) at a specificity of 95%, 98% and 99% and the AUC value of 0.97(CI: 0.95-0.99) in the test dataset. By the cancer stages, sensitivity was 62.8% (CI: 48.8% to 83.7%) in stage I, 66.3% (CI: 57.7% to 82.7%) in stage II, 85.9% (CI: 77.5% to 94.4%) in stage III, and 76.1% (CI: 63.4% to 87.3%) in stage IV at 99% specificity. For multi-cancer classification, the overall accuracy of 85.1% (CI: 80.4% to 89.3%) was achieved including 6 cancer types. Conclusions: Highly sensitive and accurate deep learning model for cancer detection and multi-cancer classification was generated by combining different types of cf-DNA features. This result provides the opportunity for general population multi-cancer screening using various cf-DNA features. Citation Format: Tae-Rim Lee, Jin Mo Ahn, Joo Hyuk Sohn, Sook Ryun Park, Min Hwan Kim, Gun Min Kim, Ki-Byung Song, Eunsung Jun, Dongryul Oh, Jeong-Won Lee, Joseph J Noh, Young Sik Park, Sun-Young Kong, Sang Myung Woo, Bo Hyun Kim, Eui Kyu Chie, Hyun-Cheol Kang, Youn Jin Choi, Ki-Won Song, Jeong-Sik Byeon, Junnam Lee, Dasom Kim, Chang-Seok Ki, Eunhae Cho. Deep learning algorithm for multi-cancer detection and classification using cf-WGS [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 6371.

BACKGROUND/AIM Improvement of the efficacy of radiotherapy for lung cancer and glioblastoma is urgently needed. MATERIALS AND METHODS We synthesized several novel DNA methyltransferase inhibitors and evaluated their potentials as possible radiosensitizers. Eleven non-nucleoside compounds were synthesized and evaluated along with one known compound using human lung cancer (A549) and glioblastoma (U373MG) cells. Cytotoxicity and radiosensitizing effects were evaluated using clonogenic assay. Sensitizer enhancement ratios at a survival fraction of 0.5 were calculated, and statistical analysis was performed using the ratio paired t-test. The inhibitory effects of three selected compounds on the activity of DNA methyltransferase 1 (DNMT1) and the pharmacokinetic profiles were analyzed. RESULTS All twelve compounds demonstrated various levels of cytotoxicity. Of the twelve compounds, eleven and eight compounds radiosensitized A549 and U373MG cells, respectively, with at least marginal significance (p

Despite frequent use in the clinical setting, especially for patients with high-risk factors for relapse, the role of adjuvant treatment has not been clarified in nonhilar extrahepatic bile duct cancer (NH-EHBDC). The goal of this study is to identify the role of adjuvant chemoradiotherapy (CRT) in NH-EHBDC patients after radical surgery.Patients with NH-EHBDC who underwent radical surgery from July 2007 to December 2018 were reviewed retrospectively. Univariate and multivariate analyses were conducted to identify prognostic factors for locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS). Subgroup analyses were performed to further identify the role of adjuvant CRT.Three hundred twenty-eight patients were accrued. At a median follow-up of 37.1 months (range, 1.0-144.2 months), the 3-year LRRFS, DMFS, DFS, and OS were 63.4%, 59.0%, 53.2%, and 67.5%, respectively. In multivariate analysis, adjuvant CRT was an independent prognostic factor for LRRFS, DMFS, DFS, and OS (P.05). For patients with nodal involvement, pT3 stage, tumor size ≥ 5 cm, poorly differentiated tumor, and R1 resection, adjuvant CRT significantly improved DFS (P.05).In patients with NH-EHBDC, adjuvant CRT significantly improved LRRFS and DFS. For patients with risk factors such as nodal involvement, pT3 stage, poorly differentiated tumor, tumor size ≥ 5 cm, or R1 resection, adjuvant CRT might contribute to improve treatment outcomes.

To perform a systematic review and meta-analysis of the impact of brachytherapy (BT) technique (two-dimensional [2D] or three-dimensional image-guided [3D]) on outcomes of cervical cancer patients. PubMed and EMBASE databases were searched up to April 16, 2019, for studies which evaluated the effect of 3D-BT compared to 2D-BT in cervical cancer. Endpoints included cumulative incidence of severe toxicity, locoregional recurrence-free survival (LRRFS), progression-free survival (PFS), and overall survival (OS). Hazard ratios (HRs) were pooled in the meta-analysis using the random-effects model. Six studies of eight cohorts were included in the quantitative synthesis. The pooled HR regarding toxicity was evaluated in five cohorts in three studies, and the HR of 3D-BT compared to 2D-BT was 0.54 (95% confidence interval [CI] 0.37–0.77). All six studies were included for the synthesis for LRRFS, and the pooled HR favors 3D-BT (0.61 [95% CI 0.40–0.93]). For PFS, three studies were included for analysis and 3D-BT was superior to 2D-BT (HR = 0.75 [95% CI 0.59–0.96]). Five studies were included for the pooled HR regarding OS, and pooled HR of 3D-BT compared to 2D-BT was 0.65 (95% CI 0.40–1.06). 3D-BT might reduce severe toxicity and improve LRRFS and PFS in patients with cervical cancer. 3D-BT should be considered for standard management of cervical cancer, and efforts for adopting this procedure in Korea should be pursued.

Background: To perform a systematic review and meta-analysis of the impact of brachytherapy (BT) technique (two-dimensional [2D] or three-dimensional image-guided [3D]) on outcomes of cervical cancer patients.Methods: PubMed and Embase databases were searched up to April 16, 2019, for studies which evaluated the effect of 3D-BT compared to 2D-BT in cervical cancer, and endpoints included cumulative incidence of severe toxicity, locoregional recurrence-free survival (LRRFS), progression-free survival (PFS), and overall survival (OS). Hazard ratios (HRs) were pooled in the meta-analysis using the random-effects model.Results: Six studies of 8 cohorts were included in the quantitative synthesis. The pooled hazard ratio (HR) regarding toxicity was evaluated in 5 cohorts in 3 studies, and the HR of 3D-BT compared to 2D-BT was 0.54 (95% confidence interval [CI], 0.37-0.77). All 6 studies were included for the synthesis for LRRFS, and the pooled HR favors 3D-BT (0.61 [95% CI, 0.40-0.93]). For PFS, 3 studies were included for analysis and 3D-BT was superior to 2D-BT (HR = 0.75 [95% CI, 0.0.59–0.96]). Five studies were included for the pooled HR regarding OS, and pooled HR of 3D-BT compared to 2D-BT was 0.65 (95% CI, 0.40–1.06).Conclusions: 3D-BT might reduce severe toxicity and improve LRRFS, and PFS in patients with cervical cancer. 3D-BT should be considered for standard management of cervical cancer, and efforts for adopting this procedure in Korea should be pursued.

Objective Avoidance of organs at risk has become possible with advances in image-guided volumetric-modulated arc therapy (VMAT) techniques. This study was designed to evaluate the safety and feasibility of stereotactic ablative radiotherapy (SABR) for early stage glottic cancer. This report presents the preliminary result of the first and second dose level. Methods Fraction size was increased from 3.5 gray (Gy) (total dose 59.5 Gy) to 9 Gy (total dose 45 Gy). Dose-limiting toxicities were defined as grade 3 or higher treatment-related toxicities. Voice outcome was assessed with electroglottography, and quality of life (QoL) was measured with the Head and Neck Cancer Inventory (HNCI). Results Seven patients received 59.5 Gy at 3.5 Gy per fraction as the first dose level, and five patients received 55 Gy at 5 Gy per fraction as the second dose level. None of the patients developed grade 3+ toxicity throughout a median follow-up of 17.5 months (range, 1.7-30.6 months). One patient in the second dose level recurred in the primary site at 4 months after radiotherapy (RT) and received total laryngectomy. The rest of participants were disease-free at locoregional and distant sites. Jitter, shimmer, mean phonation time, and noise-to-harmony ratio did not change significantly at 6 months after RT. HNCI scores between pretreatment and posttreatment were not significantly different (P = 0.221). Conclusion This study revealed acceptable toxicity, voice outcome, and QoL in patients treated with hypofractionated VMAT of 3.5 Gy and 5 Gy per fraction. This phase I study is currently ongoing with a dose of 55 Gy in 11 fractions and 45 Gy in five fractions. Level of evidence 2b. Laryngoscope, 2560-2565, 2018.

Background To compare the acute gastrointestinal (GI) and genitourinary (GU) toxicity profiles between intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT) in rectal cancer patients treated with neoadjuvant chemoradiation (NCRT) using meta-analysis and pooled-analysis from published articles. Methods Literature search was performed in PubMed and EMBASE from inception to March 2017. The odd ratios (ORs) were calculated and random effects model was used for meta-analysis. Chi-square or Fisher's exact test was performed for the pooled-analysis. Results Six studies including a total of 859 patients met the inclusion criteria. Most patients (98.7%) received NCRT. In the meta-analysis, IMRT reduced grade ≥ 2 acute overall GI toxicity, diarrhea and proctitis with ORs of 0.38, 0.32 and 0.60, respectively (all P < 0.05), compared to 3DCRT. IMRT also reduced acute grade ≥ 3 proctitis compared to 3D-CRT (OR, 0.24; P = 0.03). No significant heterogeneity or publication bias was detected. In the pooled-analysis, IMRT reduced the incidence of grade ≥ 2 acute overall GI toxicity, diarrhea, proctitis and GU toxicity (all P < 0.05). Moreover, lower incidence of grade ≥ 3 acute overall GI toxicity, diarrhea and proctitis were observed in the patients treated with IMRT (all P < 0.05). Conclusions IMRT significantly reduced acute toxicity in locally advanced rectal cancer patients treated with NCRT compared to 3DCRT.

PURPOSE/OBJECTIVE(S) Consolidation immunotherapy becomes a new standard treatment after definitive chemoradiotherapy (CRT) in locally advanced non-small cell lung cancer (NSCLC). However, the efficacy of immunotherapy can be compromised by treatment-related immune suppression status. We aimed to evaluate clinical and dose-volumetric predictors of delayed lymphopenia at the time of consolidation immunotherapy after CRT in locally advanced NSCLC. MATERIALS/METHODS We retrospectively reviewed 318 patients with locally advanced non-small cell lung cancer who received definitive CRT from January 2012 to December 2020. Patients diagnosed between 2012 and 2018 were assigned as training set (n = 244), and rest were selected as validation set (n = 74). Absolute lymphocyte count (ALC) was recorded at baseline, during CRT, and 4 to 12 weeks after CRT. Dose-volume histogram parameters for planned target volume, whole body, heart, lung, great vessels, spleen, esophagus and thoracic vertebral bodies were evaluated. Dose-volume histogram parameters reported as mean, maximum and minimum dose with volume receiving 5 Gy (V5), 10 Gy (V10), 20 Gy (V20), 30 Gy (V30), 40 Gy (V40), 50 Gy (V50), and 60 Gy (V60). Overall survival (OS) was analyzed using Kaplan-Meier survival analysis, log-rank test, and Cox regression model. Area under the receiver operating characteristic curve (ROC) analysis and multivariate logistic regression were used to determine the predictors of severe lymphopenia. RESULTS Grade 3 lymphopenia (ALC nadir < 500/mm3) were 81.1%, 48.1%, and 11.4% cases during CRT, 0 to 4 weeks, and 4 to 12 weeks after CRT, respectively. Kaplan-Meier survival curves and multivariate cox regression analysis revealed that patients with delayed lymphopenia (grade 3 lymphopenia during 4 to 12 weeks after CRT) was associated with inferior overall survival (P < 0.0001). On multivariable logistic regression models, age (OR = 1.116; P = 0.018), baseline ALC (OR = 0.998; P = 0.010), albumin nadir during CRT (OR = 0.111, P = 0.001), and lung V5 (OR = 1.089, P < 0.001) were significant predictors for delayed lymphopenia. The prediction nomogram was developed according to the above four independent variables. The AUC value of the nomogram model was 0.928. In the validation set (n = 74) the performance was 0.859. CONCLUSION Delayed lymphopenia is an independent predictor of poor overall survival. Age, baseline ALC, albumin nadir during CRT, and lung V5 revealed as the dominant contributor to delayed lymphopenia at the time of consolidation immunotherapy after definitive chemoradiotherapy.

Purpose: Hepatocellular carcinoma (HCC) involving the inferior vena cava (IVC) and/or right atrium (RA) can affect systemic circulation, causing fatal complications. Standard treatment is yet to be...

BACKGROUND/AIM Strategies to enhance the therapeutic ratio of radiotherapy in glioblastoma are warranted. Our aim was to report a novel DNA methyltransferase inhibitor as a potential radiosensitizing agent in glioblastoma. MATERIALS AND METHODS Four glioblastoma cell lines and one normal astrocyte cell line were incubated with a newly-synthetized phthalimido-alkanamide derivative, MA17, and its radiosensitizing effects were assessed. We performed a tumor growth delay assay in two glioblastoma lines: U87MG and U138MG. We evaluated DNA methyltransferase (DNMT) inhibition, apoptosis, autophagy, DNA damage repair, and FANCA expression. RESULTS MA17 radiosensitized all glioblastoma cells (all p

Although some existing evidence supports the addition of chemotherapy (CT) to radiation therapy (RT) for anaplastic oligodendroglioma treatment, controversy about both the criteria for suitable candidates and the optimal treatment schedule remains. We reviewed data from 376 newly diagnosed anaplastic oliogodendroglial tumor patients from nine Korean institutes were reviewed from 2000 to 2010. Total tumor removal was performed in 146 patients. More than 85% of the entire patients received postoperative RT, and 59% received CT. Approximately 50% (n = 189) received CT in addition to RT and 9% (n = 32) received CT only. A multivariate analysis revealed that younger age, frontal lobe location of the tumor, gross total removal, 1p/19q codeletion, and initial RT were associated with longer progression-free and overall survival rates. No difference was observed in outcomes from the treatment that included either temozolomide or PCV (procarbazine, lomustine, and vincristine) in addition to RT regardless of the 1p/19q deletion status. A clear improvement in progression-free and overall survival was observed for RT and combined CT/RT in compared with CT only. Postoperative RT appears to improve survival for entire group thus total removal and 1p/19q codeletion may not be sufficient criteria to omit RT as a treatment option. These results suggest that RT should continue to be offered as the standard treatment option for patients with anaplastic oligodendroglial tumors.

To compare the impact of elective whole pelvic radiotherapy (WPRT) versus prostate bed-only radiotherapy (PBRT) on biochemical relapse-free survival (bRFS) in prostate cancer patients treated with salvage radiotherapy following radical prostatectomy (RP).In our database, 163 lymph node-negative prostate cancer patients who had undergone salvage radiotherapy (SRT) for biochemical relapse after RP between September 2004 and April 2012 were identified. PBRT was administered to 134 patients (the PBRT group), while the remaining 29 patients (the WPRT group) received WPRT.Median follow-up was 57 months (range 18-122 months). In the propensity score-matched cohort, the 4-year bRFS of the WPRT group was significantly higher compared to the PBRT group (63.1 vs. 43.4%, p = 0.034). Subgroup analysis showed that the bRFS of patients who had two or more risk factors (seminal vesicle invasion, Roach score for lymph node invasion ≥ 45%, and number of harvested lymph nodes ≤ 5) and were treated with WPRT was significantly improved compared to those who received PBRT (hazard ratio, HR 0.33; 95% confidence interval, CI 0.13-0.83; p = 0.018).Elective WPRT for SRT may improve bRFS in patients with unfavorable risk factors. These results need to be confirmed by a prospective randomized trial.

We aimed to identify natural course and optimal management of spontaneous isolated celiac artery dissection (SICAD) according to morphologic classification determined on computed tomography angiography (CTA), and to investigate the association between symptoms and morphological classification of SICAD. This retrospective observational study included 21 consecutive patients with SICAD from January 2012 to April 2017. Demographic data, clinical features, treatment modalities, follow-up results, and CTA findings including morphologic classification, dissection length, and relative diameter of the true lumen (TLRD) were reviewed. Changes in follow-up CTA were recorded and compared to prior studies to reveal natural course of the disease. The serial changes of SICAD on follow-up CTA according to morphologic classifications were as follows; type I (5/5, no interval change), type IIa (1/1, no interval change), type IIb (1/1, partial remodeling), type IIIa (1/4, complete remodeling; 1/4, partial remodeling; 1/4, no interval change; 1/4, deterioration), type IIIb (4/6, no interval change; 2/6, partial remodeling), and type IV (2/2, no interval change). Thirteen (61.9%) symptomatic and 8 (38.1%) asymptomatic patients were all treated with conservative management with or without antiplatelet and/or anticoagulation therapies. Symptomatic group (SG) more commonly had type IIb, IIIa, IIIb, and IV than asymptomatic group (AG) (SG; 11 patients, AG; 1 patient, P = .002). TLRD in AG was larger than that in SG (SG: 40.5 ± 24.1%, AG: 61.7 ± 7.0%, P = .045). SICAD might be treated by conservative management in stable patients irrespective of the morphologic classification except for with type IV (dissecting aneurysm) and extension of celiac branch who may need an early intervention. Types IIb, IIIa, IIIb, and IV are TLRD are associated with patients’ symptoms. Further studies on extended natural course of SICAD with a larger number of subjects are needed to draw a strong conclusion.

Purpose We aimed to evaluate clinical outcomes including progression-free survival (PFS), overall survival (OS), partial response, and complete response in patients who underwent radiation therapy (RT) for mycosis fungoides (MF). Also, we sought to find prognostic factors for clinical outcomes. Materials and. Methods Total 19 patients confirmed with MF between 1999-2015 were retrospectively reviewed. Clinical and treatment characteristics, clinical outcomes, and and toxicities were analyzed. Results Eleven patients were treated with total skin electron beam radiotherapy (TSEBT) and 8 patients with involved field radiation therapy (IFRT) with median dose of 30 Gy, respectively. The median time interval from diagnosis to RT was 2.6 months (range, 0.4 to 87.3 months). The overall response rate was 100%; 11 patients (57.9%) had a complete response and 8 patients (42.1%) a partial response. The presence of positive lymph node at the time of consultation of RT was associated with lower OS (p = 0.043). In multivariate analysis, PFS was significantly lower for patients with increased previous therapies experienced following RT (p = 0.019) and for patients showing PR during RT (p = 0.044). There were no reported grade 3 or more skin toxicities related with RT. Conclusion Both IFRT and TSEBT are effective treatment for MF patients. Patients with short disease course before RT or complete response during RT are expected to have longer PFS. Positive lymph node status at the initiation of RT was associated woth poor OS, suggesting other treatment modalities such as low-dose RT for patients with low life-expectancy.

Background Fluid collection (FC) of lymph or blood may accumulate at the site of excision after surgery for soft tissue sarcoma, with reported incidence rates from 10% to 36%. The purpose of this study is to analyze the impact of FC on local recurrence (LR) and wound complication rates after adjuvant postoperative radiotherapy (PORT) in lower extremity soft tissue sarcoma (LE-STS). Methods Eighty-eight patients diagnosed with LE-STS were curatively treated with wide excision and PORT. FC developed in 51.1% of patients. Full FC volumes were included in the irradiation field throughout the full course of PORT for 36 patients (80.0%). A median of 61.2 and 63 Gy was prescribed for patients with and without FC, respectively. Results After a median follow-up of 4.3 years, patients with and without FC had 5-year local control rates of 77.7% and 90.8% (P = 0.105). Eight patients with FC had LR, of which six patients had recurrent tumors at or within 4 cm of the FC wall and three of these patients had out-of-field LR. Wound complication occurred after RT in 3 (6.7%) of 45 patients with FC and 1 (2.3%) of 43 patients without FC. Conclusions FC presents a potential risk for increased LR, particularly near the FC wall. Based on reasonable wound complication rates, we suggest the need and feasibility of fully including FC volumes in the irradiation field.

Purpose To investigate the plan quality of tri-Co-60 intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) for cervical cancer. Methods A total of 20 patients who received postoperative radiotherapy for cervical cancer were selected. For each patient, a tri-Co-60 IMRT plan for which the target volume was the planning target volume (PTV) generated by adding 1 mm isotropic margins from the clinical target volume (CTV) and a VMAT plan for which the target volume was the PTV generated by adding 7 mm and 10 mm margins from the CTV were generated. The tri-Co-60 IMRT plans were generated with the ViewRay™ system while the VMAT plans were generated with 15-MV photon beams from a linear accelerator (prescription dose = 50.4 Gy in 28 fractions). Results The average volumes of the PTVs and CTVs were 704.9 cc ± 87.8 cc and 271.6 cc ± 51.6 cc, respectively. No noticeable differences in the dose-volumetric parameters for the target volumes were observed between the tri-Co-60 IMRT and VMAT plans. The values of V 40Gy for the small bowel and rectal wall, V 45Gy of the bladder, and V 35Gy of the femoral heads for the VMAT plans were 14.6% ± 7.8%, 54.4% ± 4.2%, 30.0% ± 4.7%, and 8.9% ± 3.3%, respectively. Those of the tri-Co-60 IMRT plans were 2.8% ± 2.1%, 23.0% ± 8.9%, 17.1% ± 6.1%, and 0.3% ± 0.4%, respectively. Conclusions Owing to the target margin reduction capability, the tri-Co-60 IMRT plans were more favorable than the VMAT plans for cervical cancer.

Purpose The aim of this study is to develop a visual guidance patient-controlled (VG-PC) respiratory gating system for respiratory-gated magnetic-resonance image-guided radiation therapy (MR-IGRT) and to evaluate the performance of the developed system. Methods The near-real-time cine planar MR image of a patient acquired during treatment was transmitted to a beam projector in the treatment room through an optical fiber cable. The beam projector projected the cine MR images inside the bore of the ViewRay system in order to be visible to a patient during treatment. With this visual information, patients voluntarily controlled their respiration to put the target volume into the gating boundary (gating window). The effect of the presence of the beam projector in the treatment room on the image quality of the MRI was investigated by evaluating the signal-to-noise ratio (SNR), uniformity, low-contrast detectability, high-contrast spatial resolution, and spatial integrity with the VG-PC gating system. To evaluate the performance of the developed system, we applied the VG-PC gating system to a total of seven patients; six patients received stereotactic ablative radiotherapy (SABR) and one patient received conventional fractionated radiation therapy. Results The projected cine MR images were visible even when the room light was on. No image data loss or additional time delay during delivery of image data were observed. Every indicator representing MRI quality, including SNR, uniformity, low-contrast detectability, high-contrast spatial resolution, and spatial integrity exhibited values higher than the tolerance levels of the manufacturer with the VG-PC gating system; therefore, the presence of the VG-PC gating system in the treatment room did not degrade the MR image quality. The average beam-off times due to respiratory gating with and without the VG-PC gating system were 830.3 ± 278.2 s and 1264.2 ± 302.1 s, respectively (p = 0.005). Consequently, the total treatment times excluding the time for patient setup with and without the VG-PC gating system were 1453.3 ± 297.3 s and 1887.2 ± 469.6 s, respectively, on average (p = 0.005). The average number of beam-off events during whole treatment session was reduced from 457 ± 154 times to 195 ± 90 times by using the VG-PC gating system (p < 0.001). Conclusions The developed system could improve treatment efficiency when performing respiratory-gated MR-IGRT. The VG-PC gating system could be applied to any kind of bore-type radiotherapy machine. This article is protected by copyright. All rights reserved.

This study was done to evaluate the association of cyclooxygenase 2 (COX-2) and brain fatty acid binding protein (BFABP) with tumor grade and outcome of grades I-II meningiomas treated with radiotherapy. From 1996 to 2008, 40 patients with intracranial grades I-II meningiomas were treated with radiotherapy. Immunohistochemical staining for COX-2 and BFABP were performed on formalin-fixed paraffin-embedded tissues. COX-2 expression was significantly associated with BFABP status and both COX-2 (P < 0.01) and BFABP (P = 0.01) expression were stronger in the grade II meningiomas than in grade I tumors. Among the clinicopathologic factors, age and COX-2 status were prognostic in progression-free survival. Patients with moderate or strong COX-2 expression had worse outcome than those with negative or weak COX-2 expression (P = 0.03) after controlling for potential confounders. Our results suggest that the molecular biomarker COX-2 has prognostic significance in intracranial grades I-II meningiomas following radiotherapy.

The goal of this study is to compare the risk of lower extremity lymphedema (LEL) between pelvic external beam radiation therapy (EBRT) and vaginal brachytherapy, and to identify risk factors for LEL in gynecologic cancer patients treated with adjuvant radiation therapy (RT) after radical surgery. A total of 263 stage I&ndash, III gynecologic cancer patients who underwent adjuvant RT were retrospectively reviewed. One-to-one case-matched analysis was conducted with propensity scores generated from patient, tumor, and treatment characteristics. Using the risk factors found in this study, high- and low-risk groups were identified. With a median follow-up of 36.0 months, 35 of 263 (13.3%) patients developed LEL. In multivariate analysis, laparoscopic surgery (HR 2.548, p = 0.024), harvesting more than 30 pelvic lymph nodes (HR 2.246, p = 0.028), and para-aortic lymph node dissection (PALND, HR 2.305, p = 0.014) were identified as independent risk factors for LEL. After propensity score matching, the LEL incidence of the brachytherapy group was significantly lower than the EBRT group (p = 0.025). In conclusion, high-risk patients with risk factors such as laparoscopic surgery, harvesting more than 30 pelvic lymph nodes, PALND, and adjuvant pelvic EBRT require closer observation for LEL.