[en] This study aimed to develop a deep learning architecture combining two task models to generate synthetic computed tomography (sCT) images from low-tesla magnetic resonance (MR) images to improve metallic marker visibility. Twenty-three patients with cervical cancer treated with intracavitary radiotherapy (ICR) were retrospectively enrolled, and images were acquired using both a computed tomography (CT) scanner and a low-tesla MR machine. The CT images were aligned to the corresponding MR images using a deformable registration, and the metallic dummy source markers were delineated using threshold-based segmentation followed by manual modification. The deformed CT(dCT), MR, and segmentation mask pairs were used for training and testing. The sCT generation model has a cascaded three-dimensional (3D) U-Net-based architecture that converts MR images to CT images and segments the metallic marker. The performance of the model was evaluated with intensity-based comparison metrics. The proposed model with segmentation loss outperformed the 3D U-Net in terms of errors between the sCT and dCT. The structural similarity score difference was not significant. Our study shows the two-task-based deep learning models for generating the sCT images using low-tesla MR images for 3D ICR. This approach will be useful to the MR-only workflow in high-dose-rate brachytherapy

[en] Online magnetic resonance-guided adaptive radiotherapy (MRgART), an emerging technique, is used to address the change in anatomical structures, such as treatment target region, during the treatment period. However, the electron density map used for dose calculation differs from that for daily treatment, owing to the variation in organ location and, notably, air pockets. In this study, we evaluate the dosimetric effect of electron density override on air pockets during online ART for pancreatic cancer cases. Five pancreatic cancer patients, who were treated with MRgART at the Seoul National University Hospital, were enrolled in the study. Intensity modulated radiation therapy plans were generated for each patient with ⁶⁰Co beams on a viewrayTM system, with a 45 Gy prescription dose for stereotactic body radiation therapy. During the treatment, the electron density map was modified based on the daily MR image. We recalculated the dose distribution on the plan, and the dosimetric parameters were obtained from the dose volume histograms of the planning target volume (PTV) and organs at risk. The average dose difference in the PTV was 0.86Gy, and the observed difference at the maximum dose was up to 2.07 Gy. The variation in air pockets during treatment resulted in an under- or overdose in the PTV. We recommend the re-contouring of the air pockets to deliver an accurate radiation dose to the target in MRgART, even though it is a time-consuming method

[en] To determine whether the maximum standardized uptake value (SUV) of [18F] fluorodeoxyglucose uptake by positron emission tomography (FDG PET) ratio of lymph node to primary tumor (mSUVR) could be a prognostic factor for node positive non-small cell lung cancer (NSCLC) patients treated with definitive radiotherapy (RT). A total of 68 NSCLC T1-4, N1-3, M0 patients underwent FDG PET before RT. Optimal cutoff values of mSUVR were chosen based on overall survival (OS). Independent prognosticators were identified by Cox regression analysis. The most significant cutoff value for mSUVR was 0.9 with respect to OS. Two-year OS was 17% for patients with mSUVR > 0.9 and 49% for those with mSUVR ≤ 0.9 (p = 0.01). In a multivariate analysis, including age, performance status, stage, use of chemotherapy, and mSUVR, only performance status (p = 0.05) and mSUVR > 0.9 (p = 0.05) were significant predictors of OS. Two-year OS for patients with both good performance (Eastern Cooperative Oncology Group [ECOG] ≤ 1) and mSUVR ≤ 0.9 was significantly better than that for patients with either poor performance (ECOG > 1) or mSUVR > 0.9, 23% (71% vs. 23%, p = 0.04). Our results suggested that the mSUVR was a strong prognostic factor among patients with lymph node positive NSCLC following RT. Addition of mSUVR to performance status identifies a subgroup at highest risk for death after RT.

[en] Background and purpose: To identify the impact of 3D CT-based high-dose-rate intracavitary radiotherapy (ICR) on late rectal bleeding (LRB) and local control (LC) in patients with cervical cancer. Material and methods: The outcomes of 97 consecutive patients treated with 3D CT-based ICR (3D-ICR) were compared with those of 133 consecutive historical patients with conventional 2D brachytherapy planning (2D-ICR). The median follow-up periods were 41 and 56 months for the 3D and 2D groups, respectively. Results: The overall rectal bleeding rate was similar between the groups (42% for 3D-ICR vs. 44% for 2D-ICR); however, the incidence of severe LRB was higher in the 2D-ICR group than in the 3D-ICR group (13% vs. 2%, respectively; p = 0.02). In multivariate analysis, the factors associated with severe LRB were tumor >4 cm (12% vs. 3%) and 2D-ICR (10% vs. 2%). The LC rates were 97% and 91% for 3D-ICR and 2D-ICR, respectively (p = 0.14); the progression-free survival rate was 80% for both groups. A significant difference in the LC rates between the two groups was observed in patients with larger tumor sizes with the tumor diameter of over 4 cm (98% vs. 81% by 3D-ICR vs. 2D-ICR, respectively; p = 0.02). Conclusions: The implementation of 3D-ICR in radiotherapy for cervical cancer can reduce the incidence of severe LRB and may improve the LC rate.

[en] To investigate the role of radiotherapy for squamous cell carcinomas of the external auditory canal and middle ear. A series of 35 patients who were treated at a single institution from 1981 through 2007 were retrospectively analyzed. Thirteen patients were treated by radiotherapy alone; four by surgery only and 18 by a combination of surgery and radiotherapy. The total radiation dose ranged from 39∼70 Gy (median, 66 Gy) in 13∼35 fractions for radiotherapy alone and 44∼70 Gy (median, 61.2 Gy) in 22∼37 fractions for the combined therapy. Clinical end-points were the cause of specific survival (CSS) and local relapse-free survival (LRFS). The median follow-up time was 2.8 years (range, 0.2∼14.6 years). The 3-year CSS and LRFS rate was 80% and 63%, respectively. Based on a univariate analysis, performance status and residual disease after treatment had a significant impact on CSS; performance status and histologic grade for LRFS. Patients treated by radiotherapy alone had more residual disease following the course of treatment compared to patients treated with the combined therapy; 69% vs. 28%, respectively. Our results suggest that radiation alone was not an inferior treatment modality for CSS compared to the combined therapy for squamous cell carcinoma of the external auditory canal and middle ear. However, local failure after radiotherapy is the main issue that will require further improvement to gain optimal local control

[en] To examine the effect of suboptimal chemotherapy in patients undergoing preoperative chemoradiotherapy for the treatment of rectal cancer. The medical records of 43 patients who received preoperative concurrent chemoradiotherapy, followed by radical surgery for the treatment of pathologically proven adenocarcinoma of the rectum from April 2003 to April 2006 were retrospectively reviewed. The delivered radiation dose ranged from 41.4 to 50.4 Gy. The standard group consisted of patients receiving two cycles of a 5-FU bolus injection for three days on the first and fifth week of radiotherapy or twice daily with capecitabine. The standard group included six patients for each regimen. The non-standard group consisted of patients receiving one cycle of 5-FU bolus injection for three days on the first week of radiotherapy. The non-standard group included 31 patients. Radical surgery was performed at a median of 58 days after the end of radiotherapy. A low anterior resection was performed in 36 patients, whereas an abdominoperineal resection was performed in 7 patients. No significant difference was observed between the groups with respect to pathologic responses ranging from grades 3 to 5 (83.3% vs. 67.7%, p=0.456), downstaging (75.0% vs. 67.7%, p=0.727), and a radial resection margin greater than 2 mm (66.7% vs. 83.9%, p=0.237). The sphincter-saving surgery rate in low-lying rectal cancers was lower in the non-standard group (100% vs. 75%, p=0.068). There was no grade 3 or higher toxicity observed in all patients. Considering that the sphincter-saving surgery rate in low-lying rectal cancer was marginally lower for patients treated with non-standard, suboptimal chemotherapy, and that toxicity higher than grade 2 was not observed in the both groups, suboptimal chemotherapy should be avoided in this setting

[en] 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.

[en] 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. Total 19 patients confirmed with MF between 1999–2015 were retrospectively reviewed. Clinical and treatment characteristics, clinical outcomes, and and toxicities were analyzed. 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. 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

[en] 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. 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. 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. 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

[en] This study was designed to evaluate the efficacy and safety of topically applied recombinant human epidermal growth factor (rhEGF) for the prevention of radiation-induced dermatitis in cancer patients. From December 2010 to April 2012, a total of 1,172 cancer patients who received radiotherapy (RT) of more than 50 Gy were prospectively enrolled and treated with EGF-based cream. An acute skin reaction classified according to the Radiation Therapy Oncology Group 6-point rating scale was the primary end point and we also assessed the occurrence of edema, dry skin, or pruritus. The percentage of radiation dermatitis with maximum grade 0 and grade 1 was 19% and 58% at the time of 50 Gy, and it became 29% and 47% after completion of planned RT. This increment was observed only in breast cancer patients (from 18%/62% to 32%/49%). Adverse events related to the EGF-based cream developed in 49 patients (4%) with mild erythema the most common. Skin toxicity grade >2 was observed in 5% of the patients. Edema, dry skin, and pruritus grade > or =3 developed in 9%, 9%, and 1% of the patients, respectively. Prophylactic use of an EGF-based cream is effective in preventing radiation dermatitis with tolerable toxicity. Further studies comparing EGF cream with other topical agents may be necessary.