PURPOSE: To evaluate the impact of postoperative radiotherapy (PORT) on patterns of failure and survivals in uterine carcinosarcoma patients treated with radical surgery. MATERIALS AND METHODS: Between October 1998 and August 2010, 19 patients with stage I-III uterine carcinosarcoma received curative hysterectomy and bilateral salpingo-oophorectomy with or without PORT at Seoul National University Hospital. Their hospital medical records were retrospectively reviewed. PORT and non-PORT groups included 11 and 8 patients, respectively. They were followed for a mean of 22.7 months (range, 7.8 to 126.6 months). RESULTS: At 5 years, the overall survival rates were 51.9% for entire, 61.4% for PORT, and 41.7% for non-PORT groups, respectively. There was no statistical difference between PORT and non-PORT groups with regard to overall survival (p = 0.682). Seven out of 19 (36.8%) patients showed treatment failures, which all happened within 12 months. Although the predominant failures were distant metastasis in PORT group and loco-regional recurrence in non-PORT group, there was no statistically significant difference in loco-regional recurrence-free survival (LRRFS) (p = 0.362) or distant metastasis-free survival (DMFS) (p = 0.548). Lymph node metastasis was found to be a significant prognostic factor in predicting poor LRRFS (p = 0.013) and DMFS (p = 0.021), while the International Federation Gynecology and Obstetrics (FIGO) stage (p = 0.043) was associated with LRRFS. CONCLUSION: Considering that adjuvant radiotherapy after surgical resection was effective to decrease loco-regional recurrence and most treatment failures were distant metastasis, multimodal therapy including surgery, radiotherapy, and chemotherapy might be an optimal treatment for uterine carcinosarcoma patients.
Carcinosarcoma ; Gynecology ; Humans ; Hysterectomy ; Lymph Nodes ; Medical Records ; Neoplasm Metastasis ; Obstetrics ; Radiotherapy, Adjuvant ; Recurrence ; Retrospective Studies ; Survival Rate ; Treatment Failure ; Uterus

Idiopathic hypertrophic spinal pachymeningitis (IHSP) is a rare, diffuse inflammatory fibrosis of the dura mater that can lead to spinal cord compression. Though the optimal treatment is controversial, some reports recommend decompressive surgery and postoperative steroid therapy. However, we encountered a case of pachymeningitis that worsened after decompressive surgery. A 79-year-old woman presented with gait disturbance and bilateral lower extremity weakness that began 6 months prior. She had radiating pain on the C5 and T1 dermatomes and clumsiness in both hands. Magnetic resonance imaging (MRI) revealed diffuse thickening of the posterior longitudinal ligament of C6 to T4/5 and ligamentum flavum of C3/4 to T4/5, causing central canal stenosis and compressive myelopathy. She underwent posterior decompressive laminectomy from C4 to T1 total (T2 subtotal) and cervicothoracic screw fixation. During surgery, we found severe adhesion of the posterior longitudinal ligament and ligamentum flavum to the dura mater. Chronic inflammation with fibrosis and lymphoplasmacytic infiltration were present. After surgery, the patient's motor weakness worsened. Despite steroid treatment, her symptom severity fluctuated. Follow-up MRI obtained 3 months postoperation revealed high signal intensity from C5 to T2, possibly indicating aggravated compressive myelopathy. Thus, in this case, decompressive surgery and steroid therapy were detrimental.

PURPOSE: A new fiduciary plate and orientation marker have been devised to assist the quality assurance (QA) procedures for port films in radiation therapy department. The plate is used in conjunction with the film/cassette combination during weekly QA procedures, at Seoul National University Hospital (SNUH), in order to verify treatment fields in high energy radiation therapy. MATERIALS AND METHODS: A new fiduciary plate was fabricated using an acrylic plate, cerrobend, standard blocking tray and mercury. The acrylic plate had the dimension of 1x25x25 cm, with two fiduciary markers. The plate was rigidly attached onto the standard blocking tray, thus making it easier to set the fiduciary plate to the center of the radiation field of the linear accelerator. The plate had two 2-mm vertical and horizontal lines, with the minor scales in 2-cm steps. The orientation marker was a small mercury filled disk, which was inserted into the plate. RESULTS: The geometrical structure of the lines in the plate makes it easier to correlate two different images between the simulation and port films. The marker clearly indicated the orientation of the film, for example, the anterior, posterior, left, right and various oblique orientations, without the placement of a conventional orientation marker. Also, the new orientation marker could easily be applied to the simulator by placing the small orientation marker onto the image intensifier or in front of the film/cassette holder. CONCLUSIONSs: The new fiduciary plate appears to be useful in verifying the treatment fields, and the new orientation marker makes the film orientation simple, which is expected to lower the block fabrication errors.
Particle Accelerators ; Seoul ; Weights and Measures

PURPOSE: microRNAs (miRNAs) are non-coding RNAs composed of 20 to 22 nucleotides that regulate development and differentiation in various organs by silencing specific RNAs and regulating gene expression. In the present study, we show that the microRNA (miR)-183 cluster is upregulated during hair cell regeneration and that its inhibition reduces hair cell regeneration following neomycin-induced ototoxicity in zebrafish. MATERIALS AND METHODS: miRNA expression patterns after neomycin exposure were analyzed using microarray chips. Quantitative polymerase chain reaction was performed to validate miR-183 cluster expression patterns following neomycin exposure (500 µM for 2 h). After injection of an antisense morpholino (MO) to miR-183 (MO-183) immediately after fertilization, hair cell regeneration after neomycin exposure in neuromast cells was evaluated by fluorescent staining (YO-PRO1). The MO-183 effect also was assessed in transgenic zebrafish larvae expressing green fluorescent protein (GFP) in inner ear hair cells. RESULTS: Microarray analysis clearly showed that the miR-183 cluster (miR-96, miR-182, and miR-183) was upregulated after neomycin treatment. We also confirmed upregulated expression of the miR-183 cluster during hair cell regeneration after neomycin-induced ototoxicity. miR-183 inhibition using MO-183 reduced hair cell regeneration in both wild-type and GFP transgenic zebrafish larvae. CONCLUSION: Our work demonstrates that the miR-183 cluster is essential for the regeneration of hair cells following ototoxic injury in zebrafish larvae. Therefore, regulation of the miR-183 cluster can be a novel target for stimulation of hair cell regeneration.
Animals ; Animals, Genetically Modified ; Cell Count ; Gene Expression Profiling ; Gene Expression Regulation/drug effects ; Gene Knockdown Techniques ; Green Fluorescent Proteins/metabolism ; Hair Cells, Auditory/drug effects ; Hair Cells, Auditory/physiology ; Larva/drug effects ; Larva/genetics ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Morpholinos/pharmacology ; Neomycin/toxicity ; Regeneration/drug effects ; Regeneration/genetics ; Zebrafish/genetics

PURPOSE: The purpose of this study was to assess the clinical outcomes of hypofractionated radiotherapy (HFRT) with three-dimensional conformal technique for medically inoperable patients with early stage non-small-cell lung cancer (NSCLC) and to evaluate prognostic factors. MATERIALS AND METHODS: We performed a retrospective review of 26 patients who underwent HFRT for early stage NSCLC between September 2005 and August 2011. Only clinical stage T1-3N0 was included. The median RT dose was 70 Gy (range, 60 to 72 Gy) and the median biologically equivalent dose (BED) was 94.5 Gy (range, 78.0 to 100.8 Gy). In 84.6% of patients, 4 Gy per fraction was used. Neoadjuvant chemotherapy with paclitaxel and cisplatin was given to 2 of 26 patients. RESULTS: The median follow-up time for surviving patients was 21 months (range, 13 to 49 months). The overall response rate was 53.9%, and the initial local control rate was 100%. The median survival duration was 27.8 months. Rates of 2-year overall survival, progression-free survival (PFS), local control (LC), and locoregional-free survival (LRFS) were 54.3%, 61.1%, 74.6%, and 61.9%, respectively. Multivariate analysis showed that BED (>90 vs. < or =90 Gy) was an independent prognostic factor influencing PFS, LC, and LRFS. Severe toxicities over grade 3 were not observed. CONCLUSION: Radical HFRT can yield satisfactory disease control with acceptable rates of toxicities in medically inoperable patients with early stage NSCLC. HFRT is a viable alternative for clinics and patients ineligible for stereotactic ablative radiotherapy. BED over 90 Gy and 4 Gy per fraction might be appropriate for HFRT.
Cisplatin ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Lung ; Lung Neoplasms ; Multivariate Analysis ; Paclitaxel ; Radiotherapy, Conformal ; Retrospective Studies

PURPOSE: In order to avoid functional disability that may be caused by radical excision or amputation in extremity soft tissue sarcomas, authors employed limb-conserving surgery together with extemal radiation therapy plus interstitial brachytherapy. MATERIALS AND METHODS: From June 1995 to Febrary 1997, 10 extremity soft tissue sarcoma patients were treated with limb-conserving surgery and external radiation therapy plus interstitial brachytherapy. In six patients, whose histologic diagnoses were made at the time of surgery, wide or marginal excision and interstitial brachytherapy was done 4 weeks before postoperative external radiation therapy. In four patients whose histologic confinnations were done before definitive treatment, preoperative external radiation therapy was given 4 weeks before surgery and interstitial brachytherapy. The types of surgery were wide excision in five patients, and marginal excision in five patients. Gross or microscopic residual was left at the surgical resection margins in four patients. The brachytherapy dose ranged from 17.5 Gy to 24 Gy and external beam radiation did from 40 Gy to 45 Gy. RESULTS: With the median follow-up duration of 21.5 months(range: 13 to 29 months); one local recurrence, and three new distant metastases were observed. There were three patients with wound complications attributable to the current treatment regimen. CONCLUSION: Satisfactory local tumor control may be achievable with limb-conserving surgery and external radiation therapy plus brachytherapy in patients with extremity soft tissue sarcomas, while more caution should be used to avoid wound problems.
Amputation ; Brachytherapy* ; Diagnosis ; Extremities* ; Follow-Up Studies ; Humans ; Neoplasm Metastasis ; Recurrence ; Sarcoma* ; Wounds and Injuries

Racial and regional differences exist in morbidity, histology, drug response, toxicity, and prognosis of gynecologic cancer. However, most large-scale phase III studies have been conducted in Western countries, and these data on Asians, who account for more than half of the world’s population, are limited. To build a global clinical trial network in Asia, four clinical trial groups with high expertise and international competitiveness in East Asia, namely the Japanese Gynecologic Oncology Group in Japan, the Korean Gynecologic Oncology Group in Korea, the Taiwanese Gynecologic Oncology Group in Taiwan, and the Chinese Gynecologic Cancer Society in the People’s Republic of China, established a new group called the East Asia Gynecologic Oncology Trial Group (EAGOT) on November 19, 2021. It includes four committees: the Cervical Cancer Committee, Uterine Corpus Cancer Committee, Ovarian Cancer Committee, and Translational Research Committee. The purpose of EAGOT is to conduct international clinical trials in an effort to provide the best treatments for Asian women affected by gynecologic cancer. Discussions on new collaborative clinical trials have already begun. The first Annual EAGOT Meeting was held on May 25-27, 2023 in Niigata, Japan. EAGOT, the largest healthcare/investigational innovation network in Asia in the area of gynecologic cancers, will become a platform for establishing standards of care and lead to guidelines for Asian women suffering from gynecologic cancer. The harmonization of regulatory/investigator-initiated clinical trials, simultaneous approval of unapproved drugs in the four countries under a common protocol, and expansion of indications will improve the prognosis of gynecologic cancers in Asia in the near future.

Purpose: Exogenous epidermal growth factor (EGF) causes apoptosis in EGF receptor (EGFR)–overexpressing cell lines. The apoptosis-inducing factors could be a therapeutic target. We aimed to determine the mechanism of EGF-induced apoptosis using a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)-based knockout screen. Materials and Methods: Two-vector system of the human genome-scale CRISPR knockout library v2 was used to target 19,050 genes using 123,411 single guide RNAs (sgRNAs). Recombinant human EGF (100 nM) or distilled water four times was administered to the experimental and control groups, respectively. The read counts of each sgRNA obtained from next-generation sequencing were analyzed using the edgeR algorithm. We used another EGFR-overexpressing cell line (A549) and short hairpin RNAs (shRNAs) targeting five EGF-resistance genes for validation. DUSP1 expression in A431, A549, and HEK293FT cells was calculated using reverse transcription–quantitative polymerase chain reaction. Results: We found 77 enriched and 189 depleted genes in the experimental group using the CRISPR-based knockout screen and identified the top five EGF-resistance genes: DDX20, LHFP, REPS1, DUSP1,<.i> and KRTAP10-12. Transfecting shRNAs targeting these genes into A549 cells significantly increased the surviving fractions after EGF treatment, compared with those observed in the control shRNA-transfected cells. The expression ratio of DUSP1 (inhibits ERK signaling) increased in A431 and A549 cells after EGF treatment. However, DUSP1 expression remained unchanged in HEK293FT cells after EGF treatment. Conclusion The CRISPR-based knockout screen revealed 266 genes possibly responsible for EGF-induced apoptosis. DUSP1 might be a critical component of EGF-induced apoptosis and a novel target for EGFR-overexpressing cancers.

Purpose: This study aimed to compare the failure patterns before and after the introduction of immunotherapy and to determine the role of thoracic radiotherapy (TRT) in extensive-stage small-cell lung cancer (ES-SCLC) treatment. Materials and Methods: We retrospectively reviewed 294 patients with ES-SCLC, of which 62.2% underwent chemotherapy alone, 13.3% underwent chemotherapy followed by consolidative TRT (TRT group), and 24.5% underwent chemotherapy with immune checkpoint inhibitor (ICI group). We performed propensity-score matching (PSM) to compare each treatment group. Results: The median follow-up duration was 10.4 months. At the first relapse, in the cohort showing objective response, the proportion of cases showing intrathoracic progression was significantly lower in the TRT group (37.8%) than in the chemotherapy-alone (77.2%, p < 0.001) and the ICI (60.3%, p=0.03) groups. Furthermore, in the subgroup analysis, TRT showed benefits related to intrathoracic progression-free survival (PFS) in comparison with ICI in patients with less than two involved extrathoracic sites (p=0.008) or without liver metastasis (p=0.02) or pleural metastasis (p=0.005) at diagnosis. After PSM, the TRT group showed significantly better intrathoracic PFS than both chemotherapy-alone and ICI groups (p < 0.001 and p=0.04, respectively), but showed no significant benefit in terms of PFS and overall survival in comparison with the ICI group (p=0.17 and p=0.31, respectively). Conclusion In ES-SCLC, intrathoracic progression was the most dominant failure pattern after immunotherapy. In the era of chemoimmunotherapy, consolidative TRT can still be considered a useful treatment strategy for locoregional control.

PURPOSE: To analyze the prognostic factors for survivals and to evaluate the impact of postoperative whole pelvic radiotherapy (WPRT) on pelvic failure in patients with uterine sarcoma treated with radical surgery. MATERIALS AND METHODS: We retrospectively analyzed 75 patients with uterine sarcoma who underwent radical surgery with (n = 22) or without (n = 53) radiotherapy between 1990 and 2010. There were 23 and 52 patients with carcinosarcoma and non-carcinosarcoma (leiomyosarcoma, 22; endometrial stromal sarcoma, 25; others, 5), respectively. The median follow-up period was 64 months (range, 17 to 269 months). RESULTS: The 5-year overall survival (OS) and pelvic failure-free survival (PFFS) of total patients was 64.2% and 83.4%, respectively. Multivariate analysis revealed that mitotic count (p = 0.006) was a significant predictor of OS. However, factors were not found to be associated with PFFS. On analyzing each of the histologic subtypes separately, postoperative WPRT significantly reduced pelvic failure in patients with carcinosarcoma (10.0% vs. 53.7%; p = 0.046), but not in patients with non-carcinosarcoma (12.5% vs. 9.9%; p = 0.866). Among the patients with carcinosarcoma, 4 patients (17%) had recurrence within the pelvis and 3 patients (13%) had recurrence in other sites as an initial failure, whereas among the patients with non-carcinosarcoma, 3 patients (6%) experienced pelvic failure and 13 patients (25%) experienced distant failure. CONCLUSION: The most significant predictor of OS was mitotic count. Based on the improved PFFS after postoperative WPRT only in patients with carcinosarcoma and the difference in patterns of failure between histologic subtypes, optimal adjuvant treatment options should be offered to patients based on the risk of recurrence patterns.
Carcinosarcoma ; Follow-Up Studies ; Humans ; Multivariate Analysis ; Pelvis ; Radiotherapy ; Radiotherapy, Adjuvant ; Recurrence ; Retrospective Studies ; Sarcoma* ; Sarcoma, Endometrial Stromal ; Uterus