Can DNA Methylation Profiling Classify Histologic Subtypes and Grades in Soft Tissue Sarcoma?

BACKGROUND: A clear classification of the subtype and grade of soft tissue sarcoma is important for predicting prognosis and establishing treatment strategies. However, the rarity and heterogeneity of these tumors often make diagnosis difficult. In addition, it remains challenging to predict the response to chemotherapy and prognosis. Thus, we need a new method to help diagnose soft tissue sarcomas and determine treatment strategies in conjunction with traditional methods. Genetic alterations can be found in some subtypes of soft tissue sarcoma, but many other types show dysregulated gene expression attributed to epigenetic changes, such as DNA methylation status. However, research on DNA methylation profiles in soft tissue sarcoma is still insufficient to provide information to assist in diagnosis and therapeutic decisions. QUESTIONS/PURPOSES: (1) Do DNA methylation profiles differ between normal tissue and soft tissue sarcoma? (2) Do DNA methylation profiles vary between different histologic subtypes of soft tissue sarcoma? (3) Do DNA methylation profiles differ based on tumor grade? METHODS: Between January 2019 and December 2022, we treated 85 patients for soft tissue sarcomas. We considered patients whose specimens were approved for pilot research by the Human Biobank of St. Vincent's Hospital, The Catholic University of Korea, as potentially eligible. Based on this, 41% (35 patients) were eligible; 1% (one patient) was excluded because of gender mismatch between clinical and genetic data after controlling for data quality. Finally, 39 specimens (34 soft tissue sarcomas and five normal samples) were included from 34 patients who had clinical data. All tissue samples were collected intraoperatively. The five normal tissue samples were from muscle tissues. There were 20 female patients and 14 male patients, with a median age of 58 years (range 19 to 82 years). Genomic DNA was extracted from frozen tissue, and DNA methylation profiles were obtained. Genomic annotation of DNA methylation sites and hierarchical cluster analysis were performed to interpret results from DNA methylation profiling. A t-test was used to analyze different methylation probes. Benjamini-Hochberg-adjusted p value calculations were used to account for bias resulting from evaluating thousands of methylation sites. RESULTS: The most common histologic subtypes were liposarcoma (n = 10) and leiomyosarcoma (n = 9). The tumor grade was Fédération Nationale des Centres de Lutte Contre Le Cancer Grades 1, 2, and 3 in 3, 15, and 16 patients, respectively. DNA methylation profiling demonstrated differences between soft tissue sarcoma and normal tissue as 21,188 cytosine-phosphate-guanine sites. Despite the small number of samples, 72 of these sites showed an adjusted p value of < 0.000001, suggesting a low probability of statistical errors. Among the 72 sites, 70 exhibited a hypermethylation pattern in soft tissue sarcoma, with only two sites showing a hypomethylation pattern. Thirty of 34 soft tissue sarcomas were distinguished from normal samples using hierarchical cluster analysis. There was a different methylation pattern between leiomyosarcoma and liposarcoma at 7445 sites. Using the data, hierarchical clustering analysis showed that liposarcoma was distinguished from leiomyosarcoma. When we used the same approach and included other subtypes with three or more samples, only leiomyosarcoma and myxofibrosarcoma were separated from the other subtypes, while liposarcoma and alveolar soft-part sarcoma were mixed with the others. When comparing DNA methylation profiles between low-grade (Grade 1) and high-grade (Grades 2 and 3) soft tissue sarcomas, a difference in methylation pattern was observed at 144 cytosine-phosphate-guanine sites. Among these, 132 cytosine-phosphate-guanine sites exhibited hypermethylation in the high-grade group compared with the low-grade group. Hierarchical clustering analysis showed a division into two groups, with most high-grade sarcomas (28 of 31) separated from the low-grade group and few (3 out of 31) clustered together with the low-grade group. However, three high-grade soft tissue sarcomas were grouped with the Grade 1 cluster, and all of these sarcomas were Grade 2. When comparing Grades 1 and 2 to Grade 3, Grade 3 tumors were separated from Grades 1 and 2. CONCLUSION: We observed a different DNA methylation pattern between soft tissue sarcomas and normal tissues. Liposarcoma was distinguished from leiomyosarcoma using methylation profiling. High-grade soft tissue sarcoma samples showed a hypermethylation pattern compared with low-grade ones. Our findings indicate the need for research using methylation profiling to better understand the diverse biological characteristics of soft tissue sarcoma. Such research should include studies with sufficient samples and a variety of subtypes, as well as analyses of the expression and function of related genes. Additionally, efforts to link this research with clinical data related to treatment and prognosis are necessary. LEVEL OF EVIDENCE: Level III, diagnostic study.

MRI-based volumetric tumor parameters before and during chemoradiation predict tumor recurrence and patient survival in locally advanced cervical cancer: a subgroup analysis of a phase II prospective trial.

BACKGROUND: This subgroup analysis of a prospective phase II trial aimed to identify valuable and accessible prognostic factors for overall survival (OS) and progression-free survival (PFS) of patients with locally advanced cervical cancer (LACC). METHODS: Patients with FIGO II to IVA cervical cancer were assessed in this study. All patients underwent concurrent chemoradiotherapy (CCRT) followed by brachytherapy. Tumor parameters based on MRI scans before and during CCRT were evaluated for Overall survival (OS) and Progression-free survival (PFS). RESULTS: A total of 86 patients were included in this analysis with a median follow-up period of 31.7 months. Three-year OS and PFS rates for all patients were 87.1% and 76.5%, respectively. Univariate Cox regression analysis showed that restaging tumor size (rTS) over 2.55 cm (p < 0.001), initial tumor volume (iTV) over 55.99 cc (p < 0.001), downstaging (p = 0.042), and restaging tumor volume (rTV) over 6.25 cc (p = 0.006) were significantly associated with OS. rTS (p < 0.001), iTV (p < 0.001), downstaging (p = 0.027), and rTV (p < 0.001) were identified as significant prognostic factors for PFS. In the stepwise multivariable analysis, only rTS > 2.55 cm showed statistically significant with OS (HR: 5.47, 95% CI 1.80-9.58, p = 0.035) and PFS (HR: 3.83, 95% CI 1.50-11.45; p = 0.025). CONCLUSIONS: Initial tumor size and restaging tumor volume that are easily accessible during radiotherapy provide valuable prognostic information for cervical cancer. MRI-based measurable volumetric scoring system can be readily applied in real-world practice of cervical cancer. CLINICAL TRIAL INFORMATION: This study is a subgroup analysis of prospective trial registered at ClinicalTrials.gov Identifier: NCT02993653.

Two-Day Fraction Gamma Knife Radiosurgery for Large Brain Metastasis.

Objective: We investigated how treating large brain metastasis (LBM) using two-day fraction gamma knife radiosurgery (GKRS) affects tumor control and patient survival. A prescription dose of 10.3 Gy was applied for two consecutive days, with a biologically effective dose (BED) equivalent to a tumor single-fraction dose of 16.05 Gy and a brain single-fraction dose of 15.12 Gy. Methods: Between November 2017 and December 2021, 42 patients (mean age: 68.3 years, range: 50-84 years, male: 29 [69.1%], female: 13 [30.9%]) with 44 tumors underwent two-day fraction GKRS to treat large volume brain metastasis. The main cancer types were non-small cell lung cancer (NSCLC, N=16), small cell lung cancer (SCLC, N=7), colorectal cancer (N=7), breast cancer (N=3), gastric cancer (N=2), and other cancers (N=7). Twenty-one (50.0%) patients had a single LBM, nineteen (46.3%) had a single LBM and other metastasi(e)s, and two had two (4.7%) large brain metastases. At the time of the two-day fraction GKRS, the tumors had a mean volume of 23.1 cc (range: 12.5-67.4). on each day, radiation was administered at a dose of 10.3 Gy, mainly using a 50% isodose-line. Results: We obtained clinical and magnetic resonance imaging (MRI) follow-up data for 34 patients (81%) with 35 tumors, who had undergone two-day fraction GKRS. These patients did not experience acute or late radiation-induced complications during follow-up. The median and mean progression-free survival (PFS) periods were 188 and 194 days, respectively. The local control rates at 6, 9, and 12 months were 77%, 40%, and 34%, respectively. The prognostic factors related to PFS were prior radiotherapy (P = 0.019) and lung cancer origin (P = 0.041). Other factors such as tumor volumes, each isodose volumes, and peri-GKRS systemic treatment were not significantly related to PFS. The overall survival period of the 44 patients following repeat SRS ranged from 15-878 days (median: 263±38 days, mean: 174±43) after the two-day fraction GKRS. Eight patients (18.2%) were still alive. Conclusion: Considering the unsatisfactory tumor control, a higher prescription dose should be needed in this procedure as a salvage management. Moreover, in the treatment for LBM with fractionated SRS, using different isodoses and prescription doses at the treatment planning for LBMs should be important. However, this report might be a basic reference with the same fraction number and prescription dose in the treatment for LBMs with frame-based SRS.

High-dose (60 Gy) intensity-modulated radiotherapy with concurrent weekly cisplatin followed by intracavitary radiation in locally advanced cervical cancer: A phase II prospective clinical trial.

OBJECTIVE: Radiotherapy dose-escalation using intensity-modulated radiotherapy (IMRT) has been necessary to improve treatment results in cervical cancer. METHODS: This was a phase II prospective clinical trial. 88 patients with FIGO II-IVa cervical cancer were enrolled in a single center. They received high-dose (60 Gy) IMRT with weekly cisplatin to the primary tumor and clinically positive nodes followed by intracavitary radiation. The primary endpoint was 30-month PFS rate (Target; 82%, an increase of 20% compared to GOG 120 trial using standard-dose radiotherapy). Secondary endpoints were tumor response, toxicity, recurrence, distant metastasis, and overall survival. RESULTS: Progression-free survival rate at 30 months was 82.8%. Overall survival, locoregional recurrence, distant metastasis, and para-aortic recurrence rates at 30 months were 93.6%, 8.2%, 9.2%, and 2.4%, respectively. Forty-five (51.1%) of 88 patients achieved downstaging on MRI during radiotherapy and 80 (90.9%) patients had clinically complete response at three months after high-dose IMRT and intracavitary radiotherapy. The 30-month recurrence-free survival (92.9% vs. 73.1%, P = 0.009) and overall survival (100% vs. 87.0%, P = 0.006) were significantly higher in the downstaged group than in the non-downstaged group during radiotherapy. Grade 3 or higher hematologic toxicity was found in 11 (12.5%) patients and grade 3 or higher non-hematologic toxicity was found in 3 (3.4%) patients. Fourteen had chronic urinary (8.0%), intestinal (5.7%) toxicity, pelvic insufficiency fracture (2.3%) or vesicovaginal fistula (2.3%). CONCLUSION: High-dose (60 Gy) IMRT with concurrent weekly cisplatin in locally advanced cervical cancer yielded favorable progression-free survival outcome. Tumor response during radiotherapy can be a significant prognostic factor for PFS. CLINICAL TRIAL INFORMATION: This prospective trial is registered at ClinicalTrials.gov Identifier: NCT02993653.

Effect of Various LED Light Qualities, Including Wide Red Spectrum-LED, on the Growth and Quality of Mini Red Romaine Lettuce (cv. Breen).

Recently, LEDs with various light qualities have been used in closed plant factories, and they are known to have different effects on the growth and quality of crops. Therefore, this study was conducted to investigate the change in growth and quality in mini red romaine lettuce using LEDs with various light qualities. Wide red spectrum (WRS)-LEDs, blue (B)-LEDs, blue + red (BR)-LEDs, red (R)-LEDs, and white (W)-LEDs were used as the artificial light sources. Regarding growth, the R-LED treatment showed the most positive effect, but the leaf shape was not normal and the Hunter b* value was not suitable because it was higher than that of the other treatments. The Hunter a*, SPAD, and NDVI values of the B- and BR-LED treatments were effective, but this was not the case for those of the R- and W-LED treatments. The anthocyanin reflectance index 1 (ARI1) was 20 times higher in the B-LED treatment than in the R-LED treatment, and the ascorbic acid content was the highest in the WRS-LED treatment. In the sensory evaluation, bitterness and sweetness showed opposite tendencies. Regarding the overall preference, the BR-LED treatment received the highest score. Correlation analysis showed that the bitterness was closely correlated with the anthocyanin content and leaf color. Taken together, BR-LEDs provided a good top fresh weight, dark red leaves, and high anthocyanin and ascorbic acid contents, with the highest overall preference; therefore, BR-LEDs were the most suitable for the cultivation of mini red romaine lettuce.

Effect of Supplemental Inter-Lighting on Paprika Cultivated in an Unheated Greenhouse in Summer Using Various Light-Emitting Diodes.

This study investigated the effects of supplemental inter-lighting on paprika (cv. Nagano RZ) in South Korea in summer using various LED light sources. The following LED inter-lighting treatments were used: QD-IL (blue + wide-red + far-red inter-lighting), CW-IL (cool-white inter-lighting), and B+R-IL (blue + red (1:2) inter-lighting). To investigate the effect of supplemental lighting on each canopy, top-lighting (CW-TL) was also used. Additionally, a control without supplemental lighting was included for comparison. Significant variations were observed in the plant growth indexes 42 days after treatment. The SPAD values and total chlorophyll content in the last period of cultivation were significantly higher than those of the control. In November, the marketable fruit yield was significantly higher than that of the control. QD-IL, CW-IL, and CW-TL resulted in significantly higher values of total soluble solids than the control, and CW-IL resulted in higher values of ascorbic acid content than the control. Regarding the economic analysis, CW-IL resulted in the highest net income rate (12.70%) compared with the control. Therefore, the light sources of CW-IL were assessed as suitable for supplemental lighting due to the highest total soluble solids, ascorbic acid content, and net income rate obtained.

Effect of Pre-Storage CO2 Treatment and Modified Atmosphere Packaging on Sweet Pepper Chilling Injury.

The effect of 10% CO2 pre-storage treatment for 12, 24, and 48 h alongside modified atmosphere packaging (MAP) on chilling injury was determined in this study. This study found significant interactions between chilling injuries and cell membrane damage indicators. The results show that chilling injuries can be somewhat reduced by the use of CO2 treatment for sweet peppers. It was noticed that the fruit's respiration rate increased as the treatment duration increased immediately after the treatments, while the resultant did not affect the ethylene production rate, electrolyte leakage, or malondialdehyde. Similarly, after cold storage and on the final day, no really significant differences were shown in all those parameters except for the weight loss rate, chilling injury, calyx browning, and firmness, which were at the poorest state in the control group. Of all the treatments in this study, MAP appeared to be the best treatment, and preference may be given to the 24 h treatment of pretreated fruits. Weight loss, firmness, calyx browning, and chilling injury were maintained best in MAP due to the presence of CO2 and high humidity.

Spontaneous regression of colloid cyst on the third ventricle: a case report with the review of the literature.

BACKGROUND: Colloid cyst (CC) is a rare and benign cyst found in the third ventricle near the foramen of Monro. Although the role of surgical resection is well established in symptomatic large-sized CC, it remains debatable whether surgical removal of CC with no symptoms or minimal symptoms is necessary. CASE PRESENTATION: A 49-year-old male patient visited our institute for incidentally detected intracranial mass. MRI demonstrated typical, 12 mm-sized CC located in the third ventricle. It was noticed that the cyst spontaneously decreased in size from 12 mm to 4 mm on MRI at 18 months after the first visit. CONCLUSION: Although spontaneous regression is a very rare phenomenon in CC, regular imaging study and frequent neurologic examination can be an alternative option for well-selected, asymptomatic cases.

Postoperative radiotherapy with intensity-modulated radiation therapy versus 3-dimensional conformal radiotherapy in early breast cancer: A randomized clinical trial of KROG 15-03.

PURPOSE: To investigate the safety and efficacy of intensity-modulated radiation therapy (IMRT) for early breast cancer compared with 3-dimensional conformal radiotherapy (3D-CRT) in a prospective and randomized trial. METHODS AND MATERIALS: From March 2015 to February 2018, 693 patients with pT1-2N0M0 early breast cancer who underwent breast-conserving surgery were enrolled and randomly assigned into IMRT and 3D-CRT. The primary endpoint was 3-year locoregional recurrence-free survival (LRRFS). The secondary endpoints were recurrence-free survival, overall survival, acute toxicity, target coverage index, irradiation dose to organs at risk, and fatigue inventory. The radiation dose for the 3D-CRT arm was 59.4 Gy in 33 fractions for 6.5 weeks. It was 57.4 Gy in 28 fractions with simultaneous integrated boost for 5.5 weeks for the IMRT arm. RESULTS: Of 693 patients, 349 and 344 patients received 3D-CRT and IMRT, respectively. There was no significant difference in LRRFS between the two arms. Conformity index of planning target volume was significantly superior in the IMRT arm than the 3D-CRT arm (p < 0.001). The mean lung dose and V5-V50 for the ipsilateral lung were significantly lower in the IMRT arm than the 3D-CRT arm (all p < 0.05). The incidence of grade 2 or higher dermatitis was significantly lower in the IMRT arm (p = 0.009). CONCLUSION: Compared to 3D-CRT, IMRT showed similar results in locoregional tumor control but superior results in planning target volume coverage. When IMRT is used in breast cancer, the irradiation dose to an ipsilateral lung and skin toxicity can be reduced.

Pathologic Staging Inconsistency Between ypT4N0 (stage II) and ypT1-2N1 (stage III) After Preoperative Chemoradiotherapy and Total Mesorectal Excision in Rectal Cancer: A Multi-Institutional Study.

BACKGROUND: In the Surveillance, Epidemiology, and End Results population-based data, the survival curves reversed between T4N0 (stages IIB or IIC) and T1-2N1 (stage IIIA) in rectal cancer. However, T4N0 had a higher stage than T1-2N1 in the current colorectal staging system. PATIENTS AND METHODS: We analyzed 1804 patients with rectal cancer who were treated with preoperative chemoradiotherapy and curative surgery. We grouped patients by pathologic stage, and recurrence-free survival (RFS) and overall survival rates were calculated and compared for each stage. We evaluated prognostic factors that influenced recurrence and survival. RESULTS: In the recurrence and survival analysis, 3-year RFS rates were 95.9% for ypStage 0, 94.0% for ypStage I, 78.9% for ypStage IIA, 55.8% for ypStage IIB/C, 80.2% for ypStage IIIA, 64.6% for ypStage IIIB, and 44.9% for ypStage IIIC. Patients with ypStage IIB/C showed significantly worse RFS (P = .004) than did those with ypStage IIIA. The ypStage IIB/C group showed significantly higher rates of both locoregional recurrence (24.3% vs. 5.5%; P = .02) and distant metastasis (31.6% vs. 17.1%; P = .048) than did the ypStage IIIA group. Compared with ypStage IIIA, ypStage IIB/C showed significantly higher pre-chemoradiotherapy carcinoembryonic antigen (P = .004), circumferential radial margin involvement (P = .001), and positive perineural invasion (P = .014). CONCLUSION: Patients with rectal cancer staged ypT4N0 were associated with higher locoregional recurrence and distant metastasis rates than those staged ypT1-2N1 in the current staging system.

Adjuvant Chemotherapy in Rectal Cancer Patients Treated With Preoperative Chemoradiation and Total Mesorectal Excision: A Multicenter and Retrospective Propensity-Score Matching Study.

PURPOSE: The role of adjuvant chemotherapy after preoperative chemoradiation therapy (CRT) and curative surgery in rectal cancer has yet to be definitely determined. We performed a retrospective and multicenter study to evaluate whether adjuvant chemotherapy (AC) could reduce recurrence and improve survival in locally advanced rectal cancer. METHODS AND MATERIALS: We analyzed data from 8 tertiary institutions for 1442 patients with rectal cancer who underwent preoperative CRT and total mesorectal excision. Patients were classified into 2 groups: the AC group (patients who received chemotherapy after surgery) and the observation group (those who did not receive chemotherapy after surgery). Propensity-score matching was used to assess the exact role of AC. The AC group was then subdivided to investigate the impact of adding oxaliplatin to 5-fluorouracil (5-FU). Group 1 was treated with 5-FU/folinic acid or capecitabine without oxaliplatin, and group 2 received 5-FU/folinic acid or capecitabine with oxaliplatin. RESULTS: The 3-year relapse-free survival rates in the AC and observation groups were 85.9% and 84.3%, respectively (P = .532). The 3-year overall survival rates in the AC and observation groups were 94.9% and 89.9%, respectively (P = .123). The rates of locoregional recurrence (2.2% vs 3.2%, P = .294) and distant metastasis (12.4% vs 12.9%, P = .927) at 3 years were not significantly different between the two groups. The 3-year relapse-free survival rates of group 1 and group 2 were 71.5% and 74.8%, respectively (P = .426). The 3-year overall survival rates of group 1 and group 2 were 89.9% and 96.5%, respectively (P = .102). CONCLUSIONS: This multicenter study found insufficient evidence to support the use of 5-FU-based AC after preoperative CRT and curative surgery in rectal cancer.

Nadir/pre-chemoradiotherapy ratio of white blood-cell count can predict tumor response and recurrence-free survival in locally advanced rectal cancer: a multi-institutional analysis.

PURPOSE: The objective of this study was to evaluate whether change of white blood-cell (WBC) count before and during chemoradiotherapy (CRT) might be associated with susceptibility to radiation and tumor response. METHODS: Medical records of 641 patients with rectal cancer who received preoperative CRT followed by curative surgery were retrospectively reviewed in five tertiary centers. Complete blood cell with differential count was measured weekly during the period of CRT. We assessed nadir/pre-CRT ratio of WBC count as a predictor for tumor response to CRT and a prognostic factor for recurrence-free survival. RESULTS: Enrolled patients were divided into low WBC ratio (LWR) and high WBC ratio (HWR) arms with cut-off value of 0.49 calculated by receiver operating characteristic curve. Of 641 patients, 490 (76.4%) and 151 (23.6%) were categorized into HWR (> 0.49) arm and LWR (≤ 0.49) arms, respectively. Complete pathologic response rate after CRT was significantly higher in LWR arm than that in HWR arm (23.8% vs. 12.2%, p = 0.001). In logistic regression analysis, carcinoembryonic antigen (CEA) level over 5 ng/ml [adjusted odds ratio (OR) 0.566, 95% confidence interval (CI) 0.351-0.912; p = 0.019) and HWR (adjusted OR 0.412, 95% CI 0.256-0.663; p = 0.001) were significantly negative factors of pathologic complete response. The 5-year recurrence-free survival rate was significantly higher in the LWR group than that in the HWR group (83.3% vs. 67.6%, p = 0.001). CONCLUSION: Low nadir/pre-chemoradiotherapy ratio during preoperative CRT can predict good tumor response. It is significantly associated with improved recurrence-free survival in rectal cancer.

Retrospective analysis of intensity-modulated radiotherapy and three-dimensional conformal radiotherapy of postoperative treatment for biliary tract cancer.

PURPOSE: This study was conducted to compare the outcome of three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) for the postoperative treatment of biliary tract cancer. MATERIALS AND METHODS: From February 2008 to June 2016, 57 patients of biliary tract cancer treated with curative surgery followed by postoperative 3D-CRT (n = 27) or IMRT (n = 30) were retrospectively enrolled. RESULTS: Median follow-up time was 23.6 months (range, 5.2 to 97.6 months) for all patients and 38.4 months (range, 27.0 to 89.2 months) for survivors. Two-year recurrence-free survival is higher in IMRT arm than 3D-CRT arm with a marginal significance (25.9% vs. 47.4%; p = 0.088). Locoregional recurrence-free survival (64.3% vs. 81.7%; p = 0.122) and distant metastasis-free survival (40.3% vs. 55.8%; p = 0.234) at two years did not show any statistical difference between two radiation modalities. In the multivariate analysis, extrahepatic cholangiocarcinoma, poorly-differentiated histologic grade, and higher stage were significant poor prognostic factors for survival. Severe treatment-related toxicity was not significantly different between two arms. CONCLUSION: IMRT showed comparable results with 3D-CRT in terms of recurrence, and survival, and radiotherapy toxicity for the postoperative treatment of biliary tract cancer.

Evaluation of tissue computed tomography number changes and dosimetric shifts after conventional whole-breast irradiation in patients undergoing breast-conserving surgery.

The aim of this study was to assess tissue computed tomography (CT) number changes and corresponding dosimetric shifts in repeatedly performed simulation CT (re-sim CT) scans after conventionally fractionated irradiation in breast cancer patients. A total of 28 breast cancer patients who underwent breast-conserving surgery were enrolled in this study. All the patients had received 50.4 Gy of conventional whole-breast irradiation (WBI) and underwent re-sim CT scans for tumor bed boost. For evaluation of dosimetric shifts between initial and re-sim CT scans, electron boost plans in the same field size with the same monitor unit with source-to-skin distance of 100 cm were conducted. Dosimetric parameters (V105%, V103%, V100%, V98%, V95%, V90%: Vx% indicates volumes which receive X% of prescribed doses) between initial and re-sim CT scans were compared. The CT number data (CTmean, CTmax, CTmin) of the original and irradiated CT (re-sim CT) scans from each representative structure (lung, rib bone, soft tissue, muscle, etc.) were examined and recruited. CT numbers showed highly variable changes. Soft tissue CTmean and muscle CTmax/CTmin showed statistically and significantly increased values in the CT (re-sim CT) compared to the original CT scans. Rib bone CTmean/CTmin showed statistically and significantly decreased values in the re-sim CT compared to the original CT scans. Other CT number values showed no statistically significant changes. Among the dosimetric parameters, only V105% (p = 0.015, mean = 3.07 cc versus 1.63 cc) and V103% (p = 0.017, mean = 13.8 cc versus 11.9 cc) exhibited statistically increased values in the re-sim CT compared to the original CT scans. CT number changes after conventional WBI were different according to tissue component. For electron boost plans, the implementation of a re-sim CT might be helpfully considered because significant dosimetric factor changes were observed especially in the high-dose areas (hot spots: V105% and V103%).

Treatment outcome of diffuse large B-cell lymphoma involving the head and neck: Two-institutional study for the significance of radiotherapy after R-CHOP chemotherapy.

This study was performed to analyze the treatment outcome for diffuse large B-cell lymphoma (DLBCL) involving the head and neck and to evaluate the role of radiotherapy in the rituximab era. Fifty-six patients diagnosed with DLBCL involving the head and neck were assessed. All patients were treated with 6 cycles of rituximab, cyclophosphamide, adriamycin, vincristine, and prednisolone (R-CHOP). After chemotherapy, radiation was delivered to the head and neck area in a median dose of 36 Gy. Radiation was delivered using 3-dimensional radiotherapy (n  =  25) or intensity-modulated radiotherapy (n  =  31). Primary endpoints were relapse-free survival (RFS), overall survival (OS), and local control rate. After median follow-up time of 45 months, the 5-year RFS and OS rates were 72% and 61%, respectively. Fourteen (25%) of 56 patients relapsed; 1 had a local relapse, 11 had distant relapses, and 2 had both local and distant relapses. The final local control rate after radiotherapy was 94%. Age, performance status, international prognostic index score, and radiotherapy response were significant prognostic factors for both RFS and OS in the multivariate analysis. Incidence of acute grade 3 and 4 hematologic toxicity was 9% and 4%, respectively. Grade 3 nonhematologic toxicity occurred in 2 (4%) patients, and there was no grade 4 nonhematologic toxicity for the irradiated patients. Excellent local control and survival rates can be achieved with R-CHOP followed by radiotherapy in patients with DLBCL involving the head and neck. Treatment-related toxicity after the introduction of modern radiotherapy was acceptable and limited.

Continuous Effect of Radial Resection Margin on Recurrence and Survival in Rectal Cancer Patients Who Receive Preoperative Chemoradiation and Curative Surgery: A Multicenter Retrospective Analysis.

PURPOSE: To elucidate the proper length and prognostic value of resection margins in rectal cancer patients who received preoperative chemoradiotherapy (CRT) followed by curative total mesorectal excision (TME). METHODS AND MATERIALS: A total of 1476 rectal cancer patients staging cT3-4N0-2M0 were analyzed. All patients received radiation dose of 50.4 Gy in 28 fractions with concurrent 5-fluorouracil or capecitabine. Total mesorectal excision was performed 4 to 8 weeks after radiation therapy. RESULTS: The recurrence-free survival (RFS) at 5 years showed a significant difference between 3 groups: patients with circumferential resection margin (CRM) ≤1 mm, CRM 1.1 to 5 mm, and CRM >5 mm (46.2% vs 68.6% vs 77.5%, P<.001). Patients with CRM ≤1 mm showed a significantly higher cumulative incidence of locoregional recurrence (P<.001) and distant metastasis (P<.001) at 5 years compared with the other 2 groups. Patients with CRM 1.1 to 5 mm showed a significantly higher cumulative incidence of distant metastasis (P<.001), but not locoregional recurrence (P=.192), compared with those with CRM >5 mm. Distal resection margin (≤5 vs >5 mm) did not show any significant difference in cumulative incidence of locoregional recurrence (P=.310) and distant metastasis (P=.926). CONCLUSION: Rectal cancer patients with CRM ≤1 mm are a high-risk group, with the lowest RFS. Patients with CRM 1.1 to 5 mm may be at intermediate risk, with moderately increased distant recurrence. Distal resection margin was not significantly associated with RFS in rectal cancer after neoadjuvant CRT and total mesorectal excision.

Displacement of Surgical Clips during Postoperative Radiotherapy in Breast Cancer Patients Who Received Breast-Conserving Surgery.

PURPOSE: Surgical clips are used as a target for postoperative breast radiotherapy, and displacement of surgical clips would result in inaccurate delivery of radiation. We investigated the displacement range of surgical clips in the breast during postoperative radiotherapy following breast-conserving surgery. METHODS: A total of 178 patients who received breast-conserving surgery and postoperative radiation of 59.4 Gy in 33 fractions to the involved breast for 6.5 weeks were included. Surgical clips were used to mark the lumpectomy cavity during breast-conserving surgery. Patients undertook planning computed tomography (CT) scan for whole breast irradiation. Five weeks after beginning radiation, when the irradiation dose was 45 Gy, planning CT scan was performed again for a boost radiotherapy plan in all patients. The surgical clips were defined in both CT images and compared in lateromedial (X), anteroposterior (Y), superoinferior (Z), and three-dimensional directions. RESULTS: The 90th percentile of displacement of surgical clips was 5.31 mm (range, 0.0-22.2 mm) in the lateromedial direction, 7.1 mm (range, 0.0-14.2 mm) in the anteroposterior direction, and 6.0 mm (range, 0.0-10.0 mm) in the superoinferior direction. The 90th percentile of three-dimensional displacement distance was 9.8 mm (range, 0.0-28.2 mm). On the multivariate analysis, seroma ≥15 mL was the only independent factor associated with the displacement of surgical clips. In patients with seroma ≥15 mL, the 90th percentile of displacement of surgical clips was 15.1 mm in the lateromedial direction, 12.7 mm in the anteroposterior direction, 10.0 mm in the superoinferior direction, and 21.8 mm in the three-dimensional distance. CONCLUSION: A target volume expansion of 10 mm from surgical clips may be sufficient to compensate for the displacement of clips during postoperative radiotherapy after breast-conserving surgery. For patients who had a seroma, a replanning CT scan for a boost radiation should be considered to ensure exact postoperative radiotherapy in breast cancer.

Nanoparticulated docetaxel exerts enhanced anticancer efficacy and overcomes existing limitations of traditional drugs.

Nanoparticulation of insoluble drugs improves dissolution rate, resulting in increased bioavailability that leads to increased stability, better efficacy, and reduced toxicity of drugs. Docetaxel (DTX), under the trade name Taxotere™, is one of the representative anticancer chemotherapeutic agents of this era. However, this highly lipophilic and insoluble drug has many adverse effects. Our novel and widely applicable nanoparticulation using fat and supercritical fluid (NUFS™) technology enabled successful nanoscale particulation of DTX (Nufs-DTX). Nufs-DTX showed enhanced dissolution rate and increased aqueous stability in water. After confirming the preserved mechanism of action of DTX, which targets microtubules, we showed that Nufs-DTX exhibited similar effects in proliferation and clonogenic assays using A549 cells. Interestingly, we observed that Nufs-DTX had a greater in vivo tumor growth delay effect on an A549 xenograft model than Taxotere™, which was in agreement with the improved drug accumulation in tumors according to the biodistribution result, and was caused by the enhanced permeability and retention (EPR) effect. Although both Nufs-DTX and Taxotere™ showed negative results for our administration dose in the hematologic toxicity test, Nufs-DTX showed much less toxicity than Taxotere™ in edema, paralysis, and paw-withdrawal latency on a hot plate analysis that are regarded as indicators of fluid retention, peripheral neuropathy, and thermal threshold, respectively, for toxicological tests. In summary, compared with Taxotere™, Nufs-DTX, which was generated by our new platform technology using lipid, supercritical fluid, and carbon dioxide (CO2), maintained its biochemical properties as a cytotoxic agent and had better tumor targeting ability, better in vivo therapeutic effect, and less toxicity, thereby overcoming the current hurdles of traditional drugs.

Perforation of Surgical Gloves during Lower Extremity Fracture Surgery and Hip Joint Replacement Surgery.

PURPOSE: To assess the frequencies and sites of surgical glove perforations in lower extremity fracture surgery and hip joint replacement (HJR) surgery. Additionally, we also studied the usefulness of an indicator system glove. MATERIALS AND METHODS: We assessed surgical glove perforations in 30 cases of lower extremity fracture surgery and 18 cases of HJR surgery conducted by one right handed 1st operator from April 2013 to July 2013. We assessed frequencies and sites of perforation in 152 gloves; 95 used in lower extremity fracture surgery and 57 used in HJR surgery. We studied the perforation rates and sites according to participants and operation types. Using the Biogel indicator system glove, which is well known as a fast indicator of glove perforation, we were also able to assess the time difference between operative participant detection of perforation and inspector nurse detection while observing in the operative field. RESULTS: There were 18 of 30 cases in lower extremity fracture surgeries and 12 of 18 cases in HJR surgeries which had more than one surgical glove perforation event. Of all 152 gloves used, perforation occurred in 15 of 57 gloves (26.3%) in HJR surgery and 23 of 95 gloves (24.2%) in lower extremity fracture surgery. Perforation occurred more frequently in operators than assistant doctors or scrub nurses. The most frequent perforation site was the second digit of the left hand. On average, the time difference between operative participant notice of perforation and inspector nurse notice of perforation was 20.6 seconds. CONCLUSION: The perforation of surgical gloves happened in approximately one out of every four persons. Importantly, we noted a 37.0% prevalence of glove perforation in 1st operators. Considering that glove perforation is a critical factor responsible for intra-operative infection, surgeons must be conscious of the risk of surgical glove perforation and use double gloving regularly. Furthermore, indicator double gloving is recommended for fast detection of outer glove perforation.

High-dose-rate brachytherapy for the treatment of vaginal intraepithelial neoplasia.

PURPOSE: Vaginal intraepithelial neoplasia (VAIN), a rare premalignant condition, is difficult to eradicate. We assess the effectiveness of high-dose rate intracavitary brachytherapy (HDR-ICR) in patients with VAIN or carcinoma in situ (CIS) of the vagina after hysterectomy. MATERIALS AND METHODS: We reviewed 34 patients treated for posthysterectomy VAIN or CIS of the vagina by brachytherapy as the sole treatment. All patients underwent a coloposcopic-directed punch biopsy or had abnormal cytology, at least 3 consecutive times. All patients were treated with a vaginal cylinder applicator. The total radiation dose was mainly 40 Gy in 8 fractions during the periods of 4 weeks at a prescription point of the median 0.2 cm (range, 0 to 0.5 cm) depth from the surface of the vaginal mucosa. RESULTS: Acute toxicity was minimal. Seven patients had grade 1/2 acute urinary and rectal complications. There were 15 cases of late toxicity, predominantly vaginal mucosal reaction in 12 patients. Of these patients, two patients suffered from grade 3 vaginal stricture and dyspareunia continuously. After a median follow-up time of 48 months (range, 4 to 122 months), there were 2 recurrences and 2 persistent diseases, in which a second-line therapy was needed. The success rate was 88.2%. The average prescription point in failure patients was 1.1 mm from the surface of the vagina compared to an average of 2.6 mm in non-recurrent patients (p=0.097). CONCLUSION: HDR-ICR is an effective treatment method in VAIN patients. In spite of high cure rates, we should consider issues regarding vaginal toxicity and radiation techniques to reduce the occurrence of failure and toxicity.