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Triple-negative breast cancer (TNBC) accounts for approximately 15–20% of all breast cancer types, indicating a poor survival prognosis with a more aggressive biology of metastasis to the lung and a short response duration to available therapies. Ibulocydine (IB) is a novel (cyclin-dependent kinase) CDK7/9 inhibitor prodrug displaying potent anti-cancer effects against various cancer cell types. We performed in vitro and in vivo experiments to determine whether IB inhibits metastasis and eventually overcomes the poor drug response in TNBC. The result showed that IB inhibited the growth of TNBC cells by inducing caspase-mediated apoptosis and blocking metastasis by reducing MMP-9 expression in vitro. Concurrently, in vivo experiments using the metastasis model showed that IB inhibited metastasis of MDA-MB-231-Luc cells to the lung. Collectively, these results demonstrate that IB inhibited the growth of TNBC cells and blocked metastasis by regulating MMP-9 expression, suggesting a novel therapeutic agent for metastatic TNBC.

Purpose: To identify changes in prostate cancer (PCa) risk-stratification during the last two decades in Korea, where the social perception of PCa was limited due to a relatively low incidence but has recently been triggered by the rapidly increasing incidence of benign prostate hyperplasia. Materials and Methods: Retrospective data of patients who had received a diagnosis of PCa in a single Korean province (Daegu-Gyeongsangbuk) at all seven training hospitals in the years 2003, 2007, 2011, 2015, 2019, and 2021 were subjected to analysis. Changes in PCa risk-stratification were investigated with respect to serum prostate-specific antigen (PSA), Gleason score (GS), and clinical stage. Results: Of the 3,393 study subjects that received a diagnosis of PCa, 64.1% had high-risk disease, 23.0% intermediate, and 12.9% low-risk disease. The proportion diagnosed with high-risk disease was 54.8% in 2003, 30.6% in 2019, but then increased to 35.1% in 2021. The proportion of patients with high PSA (>20 ng/mL) steadily decreased from 59.4% in 2003 to 29.6% in 2021, whereas the proportion with a high GS (>8) increased from 32.8% in 2011 to 34.0% in 2021, and the proportion with advanced stage disease (over cT2c) increased from 26.5% in 2011 to 37.1% in 2021. Conclusions: In this retrospective study, conducted in a single Korean province, high-risk PCa accounted for the largest proportion of newly registered Korean PCa patients during the last two decades and increased in the early 2020s. This outcome supports the adoption of nationwide PSA screening, regardless of current Western guidelines.

Abstract Background The Korean Radiation Oncology Group (KROG) 19 − 09 prospective cohort study aims to determine the effect of regional nodal irradiation on regional recurrence rates in ypN0 breast cancer patients. Dosimetric variations between radiotherapy (RT) plans of participating institutions may affect the clinical outcome of the study. We performed this study to assess inter-institutional dosimetric variations by dummy run. Methods Twelve participating institutions created RT plans for four clinical scenarios using computed tomography images of two dummy cases. Based on a reference structure set, we analyzed dose-volume histograms after collecting the RT plans. Results We found variations in dose distribution between institutions, especially in the regional nodal areas. Whole breast and regional nodal irradiation (WBI + RNI) plans had lower inter-institutional agreement and similarity for 95% isodose lines than WBI plans. Fleiss’s kappa values, which were used to measure inter-institutional agreement for the 95% isodose lines, were 0.830 and 0.767 for the large and medium breast WBI plans, respectively, and 0.731 and 0.679 for the large and medium breast WBI + RNI plans, respectively. There were outliers in minimum dose delivered to 95% of the structure (D95%) of axillary level 1 among WBI plans and in D95% of the interpectoral region and axillary level 4 among WBI + RNI plans. Conclusion We found inter-institutional and inter-case variations in radiation dose delivered to target volumes and organs at risk. As KROG 19 − 09 is a prospective cohort study, we accepted the dosimetric variation among the different institutions. Actual patient RT plan data should be collected to achieve reliable KROG 19 − 09 study results.

BackgroundOver 90% of patients with cancer experience 1 or more symptoms caused directly by cancer or its treatment. These symptoms negatively impact on the completion of planned treatment as well as patients’ health-related quality of life (HRQoL). It often results in serious complications and even life-threatening outcomes. Thus, it has been recommended that surveillance of symptom burden should be performed and managed during cancer treatment. However, differences in symptom profiles in various patients with cancer have not been fully elucidated for use in performing surveillance in the real world. ObjectiveThis study aims to evaluate the burden of symptoms in patients with various types of cancers during chemotherapy or radiation therapy using the PRO-CTCAE (Patient-Reported Outcome Version of the Common Terminology Criteria for Adverse Events) and its impact on quality of life. MethodsWe performed a cross-sectional study of patients undergoing outpatient-based chemotherapy, radiation therapy, or both at the National Cancer Center at Goyang or at the Samsung Medical Center in Seoul, Korea between December 2017 and January 2018. To evaluate cancer-specific symptom burden, we developed 10 subsets for using the PRO-CTCAE-Korean. To measure HRQoL, we used the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Participants answered questions prior to their clinic appointments on tablets. Multivariable linear regression was used to analyze symptoms based on cancer type and to evaluate the association between the PRO-CTCAE items and the EORTC QLQ-C30 summary score. ResultsThe mean age (SD) of the patients was 55.0 (11.9) years, and 39.94% (540/1352) were male. Overall, symptoms in the gastrointestinal category were the most dominant in all cancers. Fatigue (1034/1352, 76.48%), decreased appetite (884/1352, 65.38%), and numbness and tingling (778/1352, 57.54%) were the most frequently reported. Patients reported more local symptoms caused by a specific cancer. In terms of nonsite-specific symptoms, patients commonly reported concentration (587/1352, 43.42%), anxiety (647/1352, 47.86%), and general pain (605/1352, 44.75%). More than 50% of patients with colorectal (69/127, 54.3%), gynecologic (63/112, 56.3%), breast (252/411, 61.3%), and lung cancers (121/234, 51.7%) experienced decreased libido, whereas 67/112 (59.8%) patients with gynecologic cancer and lymphoma/myeloma reported pain during sexual intercourse. Patients with breast, gastric, and liver cancers were more likely to have the hand-foot syndrome. Worsening PRO-CTCAE scores were associated with poor HRQoL (eg, fatigue: coefficient –8.15; 95% CI –9.32 to –6.97), difficulty in achieving and maintaining erection (coefficient –8.07; 95% CI –14.52 to –1.61), poor concentration (coefficient –7.54; 95% CI –9.06 to –6.01), and dizziness (coefficient –7.24; 95% CI –8.92 to –5.55). ConclusionsThe frequency and severity of symptoms differed by cancer types. Higher symptom burden was associated with poor HRQoL, which suggests the importance of appropriate surveillance of PRO symptoms during cancer treatment. Considering patients had comprehensive symptoms, it is necessary to include a holistic approach in the symptom monitoring and management strategies based on comprehensive patient-reported outcome measurements.

BackgroundFew studies of proton beam therapy (PBT) for patients with liver metastasis from breast cancer (LMBC) are available to date. The aim of the present study was to evaluate the clinical effectiveness of PBT for patients with LMBC.Material and MethodsSeventeen patients with LMBC treated with PBT were included in this study. The median prescribed dose of PBT was 66 GyE (range, 60–80) in 10 fractions, 5 times a week. In patients with LMBC receiving PBT, freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) rates were assessed.ResultsThe median follow-up time was 34.2 months (range, 11.5–56.1). The median FFLP time was not yet reached, and the 3-year FFLP rates were 94.1% (95% confidence interval [CI], 82.9–105.3). The median times of PFS and OS were 7.9 months (95% CI, 5.3–10.5) and 39.3 months (95% CI, 33.2–51.9), respectively, and the 3-year PFS and OS rates were 19.6% (95% CI, -1.8–41.0) and 71.7% (95% CI, 46.8–96.6), respectively. Grade 3 or higher adverse events were not observed.ConclusionPBT for patients with LMBC showed promising FFLP and OS with safe toxicity profiles. These findings suggest that PBT can be considered a local treatment option in patients with LMBC.

Abstract Background We performed a prospective phase II study to compare acute toxicity among five different hypofractionated schedules using proton therapy. This study was an exploratory analysis to investigate the secondary end-point of biochemical failure-free survival (BCFFS) of patients with long-term follow-up. Methods Eighty-two patients with T1-3bN0M0 prostate cancer who had not received androgen-deprivation therapy were randomized to one of five arms: Arm 1, 60 cobalt gray equivalent (CGE)/20 fractions/5 weeks; Arm 2, 54 CGE/15 fractions/5 weeks; Arm 3, 47 CGE/10 fractions/5 weeks; Arm 4, 35 CGE/5 fractions/2.5 weeks; and Arm 5, 35 CGE/5 fractions/4 weeks. In the current exploratory analysis, these ardms were categorized into the moderate hypofractionated (MHF) group (52 patients in Arms 1–3) and the extreme hypofractionated (EHF) group (30 patients in Arms 4–5). Results At a median follow-up of 7.5 years (range, 1.3–9.6 years), 7-year BCFFS was 76.2% for the MHF group and 46.2% for the EHF group (p = 0.005). The 7-year BCFFS of the MHF and EHF groups were 90.5 and 57.1% in the low-risk group (p = 0.154); 83.5 and 42.9% in the intermediate risk group (p = 0.018); and 41.7 and 40.0% in the high risk group (p = 0.786), respectively. Biochemical failure tended to be a late event with a median time to occurrence of 5 years. Acute GU toxicities were more common in the MHF than the EHF group (85 vs. 57%, p = 0.009), but late GI and GU toxicities did not differ between groups. Conclusions Our results suggest that the efficacy of EHF is potentially inferior to that of MHF and that further studies are warranted, therefore, to confirm these findings. Trial registration This study is registered at ClinicalTrials.gov, no. NCT01709253; registered October 18, 2012; retrospectively registered).

Purpose: To evaluate the efficacy and toxicities of skin-directed radiotherapy (RT) in primary cutaneous T-cell lymphoma (CTCL). Materials and Methods: We retrospectively analyzed 57 CTCL lesions treated with skin-directed RT between January 2000 and December 2022. Lesions were categorized into three distinct groups: early- stage disease treated with local RT, advanced-stage disease treated with local RT, and advanced- stage disease treated with total skin electron beam therapy (TSEBT). Treatment outcomes, including response rates, recurrence patterns, and local progression probability, were assessed for each group. Results: Mycosis fungoides (MF) constituted 90.9% of the advanced-stage pathologies, while CD4+ primary cutaneous small/medium T-cell lymphoproliferative disorder was common in the early stage lesions (55%). Median RT doses were 30.6 Gy, 27 Gy, and 32 Gy for the local RT with early stage, the local RT with advanced stage, and TSEBT with advanced stage, respectively. The complete response rates were high across the groups: 95.5%, 70.8%, and 90.9%, respectively. Seven local recurrences (29.2%) occurred in the local RT group with advanced stage, while seven patients (63.6%) in the TSEBT group experienced local failure. All recurrences were observed in lesions and patients with MF. Acute toxicities were mainly grade 1 or 2, with no grade 3 or higher events. No significant association between RT dose and local progression rates in MF lesions was found. Conclusion: Skin-directed RT in CTCL is effective for local control and well-tolerated with less toxicity. [ABSTRACT FROM AUTHOR]

Hypofractionated radiotherapy (RT) has become a trend in the modern era, as advances in RT techniques, including intensity-modulated RT and image-guided RT, enable the precise and safe delivery of high-dose radiation. Hypofractionated RT offers convenience and can reduce the financial burden on patients by decreasing the number of fractions. Furthermore, hypofractionated RT is potentially more beneficial for tumors with a low α/β ratio compared with conventional fractionation RT. Therefore, hypofractionated RT has been investigated for various primary cancers and has gained status as a standard treatment recommended in the guidelines. In genitourinary (GU) cancer, especially prostate cancer, the efficacy, and safety of various hypofractionated dose schemes have been evaluated in numerous prospective clinical studies, establishing the standard hypofractionated RT regimen. Hypofractionated RT has also been explored for gynecological (GY) cancer, yielding relevant evidence in recent years. In this review, we aimed to summarize the representative evidence and current trends in clinical studies on hypofractionated RT for GU and GY cancers addressing several key questions. In addition, the objective is to offer suggestions for the available dose regimens for hypofractionated RT by reviewing protocols from previous clinical studies. [ABSTRACT FROM AUTHOR]

Several recent studies have investigated the use of hypofractionated radiotherapy (HFRT) for various cancers. However, HFRT for non-small cell lung cancer (NSCLC) with or without concurrent chemotherapy is not yet widely used because of concerns about serious side effects and the lack of evidence for improved treatment results. Investigations of HFRT with concurrent chemotherapy in NSCLC have usually been performed in single-arm studies and with a small number of patients, so there are not yet sufficient data. Therefore, the Korean Society for Radiation Oncology Practice Guidelines Committee planned this review article to summarize the evidence on HFRT so far and provide it to radiation oncology clinicians. In summary, HFRT has demonstrated promising results, and the reviewed data support its feasibility and comparable efficacy for the treatment of locally advanced NSCLC. The incidence and severity of esophageal toxicity have been identified as major concerns, particularly when treating large fraction sizes. Strategies, such as esophagus-sparing techniques, image guidance, and dose constraints, may help mitigate this problem and improve treatment tolerability. Continued research and clinical trials are essential to refine treatment strategies, identify optimal patient selection criteria, and enhance therapeutic outcomes. [ABSTRACT FROM AUTHOR]

Advances in radiotherapy (RT) techniques, including intensity-modulated RT and image-guided RT, have allowed hypofractionation, increasing the fraction size over the conventional dose of 1.8-2.0 Gy. Hypofractionation offers advantages such as shorter treatment times, improved compliance, and under specific conditions, particularly in tumors with a low a/ß ratio, higher efficacy. It was initially explored for use in RT for prostate cancer and adjuvant RT for breast cancer, and its application has been extended to various other malignancies. Hypofractionated RT (HFRT) may also be effective in patients who are unable to undergo conventional treatment owing to poor performance status, comorbidities, or old age. The treatment of brain tumors with HFRT is relatively common because brain stereotactic radiosurgery has been performed for over two decades. However, re-irradiation of recurrent lesions and treatment of elderly or frail patients are areas under investigation. HFRT for head and neck cancer has not been widely used because of concerns regarding late toxicity. Thus, we aimed to provide a comprehensive summary of the current evidence for HFRT for brain tumors and head and neck cancer and to offer practical recommendations to clinicians faced with the challenge of choosing new treatment options. [ABSTRACT FROM AUTHOR]

Background: Intensive multimodal treatment can improve survival in patients with high-risk neuroblastoma, and consolidative radiation therapy has contributed to local control. We examined the clinical outcomes of patients who underwent consolidative radiation therapy at our institution. Methods: We retrospectively reviewed the records of patients with high-risk neuroblastoma who underwent consolidative radiation therapy from March 2001 to March 2021 at Asan Medical Center. Patients underwent multimodal treatment including high-dose chemotherapy, surgery, stem cell transplantation, and maintenance therapy. Radiation (median, 21.0 Gy; range, 14-36) was administered to the primary site and surrounding lymph nodes. Results: This study included 37 patients, and the median age at diagnosis was 2.8 years (range, 1.3-10.0). Four patients exhibited local failure, and 5-year free-from locoregional failure rate was 88.7%, with a median followup period of 5.7 years. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 59.1% and 83.6%, respectively. Univariate analysis revealed that patients with neuron-specific enolase levels >100 ng/mL had significantly worse DFS and OS (P = 0.036, 0.048), and patients with no residual disease before radiation therapy showed superior OS (P = 0.029). Furthermore, patients with 11q deletion or 17q gain exhibited poor DFS and OS, respectively (P = 0.021, 0.011). Six patients experienced grade 1 acute toxicity. Late toxicity was confirmed in children with long-term survival, predominantly hypothyroidism and hypogonadism, typically < grade 3, possibly attributed to combination treatment. Four patients experienced late toxicity = grade 3 with chronic kidney disease, growth hormone abnormality, ileus, premature epiphyseal closure, and secondary tumor, and recovered by hospitalization or surgical treatment. Conclusions. In patients with high-risk neuroblastoma, consolidative radiotherapy to the primary tumor site resulted in excellent local control and a tolerable safety profile. [ABSTRACT FROM AUTHOR]

Purpose: Surface-guided radiation therapy is an image-guided method using optical surface imaging that has recently been adopted for patient setup and motion monitoring during treatment. We aimed to determine whether the surface guide setup is accurate and efficient compared to the skin-marking guide in prostate cancer treatment. Materials and Methods: The skin-marking setup was performed, and vertical, longitudinal, and lateral couch values (labeled as "M") were recorded. Subsequently, the surface-guided setup was conducted, and couch values (labeled as "S") were recorded. After performing cone-beam computed tomography (CBCT), the final couch values was recorded (labeled as "C"), and the shift value was calculated (labeled as "Gap (M-S)," "Gap (M-C)," "Gap (S-C)") and then compared. Additionally, the setup times for the skin marking and surface guides were also compared. Results: One hundred and twenty-five patients were analyzed, totaling 2,735 treatment fractions. Gap (M-S) showed minimal differences in the vertical, longitudinal, and lateral averages (-0.03 cm, 0.07 cm, and 0.06 cm, respectively). Gap (M-C) and Gap (S-C) exhibited a mean difference of 0.04 cm (p = 0.03) in the vertical direction, a mean difference of 0.35 cm (p = 0.52) in the longitudinal direction, and a mean difference of 0.11 cm (p = 0.91) in the lateral direction. There was no correlation between shift values and patient characteristics. The average setup time of the skin-marking guide was 6.72 minutes, and 7.53 minutes for the surface guide. Conclusion: There was no statistically significant difference between the surface and skin-marking guides regarding final CBCT shift values and no correlation between translational shift values and patient characteristics. We also observed minimal difference in setup time between the two methods. Therefore, the surface guide can be considered an accurate and time-efficient alternative to skin-marking guides. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the current status of postoperative management of uterine endometrial cancer (EC) in Korea. Methods: A mail survey was administered to members of the Korean Gynecologic Oncology Group and Korean Radiation Oncology Group. A total of 38 gynecologic cancer surgeons (GYNs) and 31 radiation oncologists (RO) in 43 institutions was responded. The questionnaire consisted of general questions for clinical decision and clinical case questions. The GYN and RO responses were compared using chi-square statistics. Results: The 2 expert groups had similar responses for clinical decision based on the results of the Gynecologic Oncology Group (GOG)-249 and Postoperative Radiation Therapy for Endometrial Carcinoma-III trials in the early-stage EC. In contrast, the responses based on GOG-258 results differed, as GYNs most frequently opted for sequential chemotherapy (CTx) and radiotherapy (RT), while ROs preferred concurrent chemoradiotherapy in locally advanced stage (p<0.05). Based on the GOG-258, GYNs preferred CTx alone for adjuvant treatment of serous or clear cell adenocarcinoma histology, whereas ROs advocated for combined CTx and RT (sequential or concurrent). Among the clinical case questions, GYNs were more likely than ROs to choose CTx alone rather than the combination of CTx and RT (sequential or concurrent) as the answers to case questions representing patients with locally advanced stage or unfavorable histology (all p<0.05). Conclusion: The present study showed several different opinions of GYNs and ROs regarding adjuvant treatment for EC, particularly for adjuvant RT in advanced stage or unfavorable histology. [ABSTRACT FROM AUTHOR]

Purpose This study aimed to investigate the impact of postoperative radiotherapy (PORT) in de novo metastatic breast cancer (dnMBC) patients undergoing planned primary tumor resection (PTR) and to identify the subgroup of patients who would most benefit from PORT. Materials and Methods This study enrolled 426 patients with dnMBC administered PTR alone or with PORT. The primary and secondary outcomes were overall and progression-free survival (OS and PFS), respectively. Results The median follow-up time was 53.7 months (range, 3.1 to 194.4). The 5-year OS and PFS rates were 73.2% and 32.0%, respectively. For OS, clinical T3/4 category, triple-negative breast cancer (TNBC), postoperative chemotherapy alone were significantly poor prognostic factors, and administration of PORT failed to show its significance. Regarding PFS, PORT was a favorable prognostic factor (hazard ratio, 0.64; 95% confidence interval, 0.50 to 0.82; p < 0.001), in addition to T1/2 category, ≤ 5 metastases, and non-TNBC. According to the multivariate analyses of OS in the PORT group, we divided the patients into three groups (group 1, T1/2 and non-TNBC [n=193]; group 2, T3/4 and non-TNBC [n=171]; and group 3, TNBC [n=49]), and evaluated the effect of PORT. Although PORT had no significance for OS in all subgroups, it was a significant factor for good prognosis regarding PFS in groups 1 and 2, not in group 3. Conclusion PORT was associated with a significantly better PFS in patients with dnMBC who underwent PTR. Patients with clinical T1/2 category and non-TNBC benefited most from PORT, while those with TNBC showed little benefit. [ABSTRACT FROM AUTHOR]

Purpose This study was to evaluate anti-tumor efficacy of osimertinib in patients positive for acquired epidermal growth factor receptor (EGFR) T790M mutation in liquid biopsy using plasma, bronchoalveolar lavage fluid (BALF) or bronchial washing fluid (BWF), and pleural effusion. Materials and Methods Among patients benefited from previous EGFR-tyrosine kinase inhibitor (TKI) treatment followed by treatment failure, patients in whom T790M mutations are detected in at least one of the samples including tumor tissues, BALF/BWF, plasma, and pleural effusion were enrolled. T790M mutation was detected by extracting cell free DNA from liquid biopsy samples, using PANA Mutyper. Objective response rate (ORR) and progression-free survival (PFS) with osimertinib treatment were evaluated. Results Between January 2018 and December 2019, 63 patients were enrolled and received osimertinib. Mean age was 63 years, and 38 (60.3%) were female. Twenty-six patients had T790M mutation in both liquid and tissue samples (group A), 19 patients had only in tissue biopsy samples (group B), and 18 patients had T790M mutation only in liquid biopsy samples (group C). ORR in overall population was 63.5%, and was 61.5% in group A, 68.4% in group B, and 61.1% in group C, respectively. Median PFS in overall patients was 15.6 months (95% confidence interval, 10.7 to 24.2). There was no significant difference in ORR or PFS between groups. Conclusion Osimertinib showed favorable efficacy in lung cancer patients with acquired resistance to prior EGFR-TKI therapies, who screened positive for harboring T790M mutation detected from cell free DNA extracted from plasma, BALF/BWF, and pleural effusion. [ABSTRACT FROM AUTHOR]

Objective: External beam radiation therapy (EBRT) with concurrent chemotherapy followed by intracavitary brachytherapy is the standard treatment in locally advanced cervical cancer. This study examined the brachytherapy utilization rate and evaluated the effect of brachytherapy on survival in cervical cancer patients in Korea. Methods: In this study, data from the Korea Central Cancer Registry and Korean National Health Insurance Service and data on mortality from Statistics Korea were linked and used. Patients with other cancers, distant metastasis at diagnosis, or unknown stage or who underwent hysterectomy were excluded. A total of 12,721 cervical cancer patients were analyzed in this study. Results: The brachytherapy utilization rate (%) was calculated as the proportion of patients who received brachytherapy among those who received curative EBRT. The brachytherapy utilization rate decreased from 84% in 2005 to 78% in 2013 (p<0.001). Brachytherapy utilization rates varied by region, ranging from 72% to 100% except for in Jeju Island, where the rate was 56%. The brachytherapy utilization rate was lower in patients older than 80 years; patients with localized disease, non-squamous cell carcinoma, or Charlson comorbidity index 3 or more; patients diagnosed after 2010; patients from certain regions; patients receiving medical aid; and patients who underwent gynecologic procedures. Multivariable Cox regression analysis showed that brachytherapy when added to curative EBRT was independently associated with better cancer-specific survival (CSS) and overall survival (OS) than curative EBRT only. Conclusion: The brachytherapy utilization rate decreased from 2005 to 2013 and varied by region in Korea. Brachytherapy use is independently associated with significantly higher CSS and OS in cervical cancer. [ABSTRACT FROM AUTHOR]

Melanoma dedifferentiation has been reported to be a state of cellular resistance to targeted therapies and immunotherapies as cancer cells revert to a more primitive cellular phenotype. Here, we show that, counterintuitively, the biopsies of patient tumors that responded to anti-programmed cell death 1 (anti-PD-1) therapy had decreased expression of melanocytic markers and increased neural crest markers, suggesting treatment-induced dedifferentiation. When modeling the effects in vitro, we documented that melanoma cell lines that were originally differentiated underwent a process of neural crest dedifferentiation when continuously exposed to IFN-γ, through global chromatin landscape changes that led to enrichment in specific hyperaccessible chromatin regions. The IFN-γ-induced dedifferentiation signature corresponded with improved outcomes in patients with melanoma, challenging the notion that neural crest dedifferentiation is entirely an adverse phenotype. [ABSTRACT FROM AUTHOR]

Background/Aim: To compare absolute volume (AV) assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) for the response evaluation of desmoid tumors (DTs) treated with radiotherapy. Patients and Methods: Eighteen patients with DTs ≥3 cm in size were included. Results: The median follow-up duration was 78.0 months. Five patients achieved a complete response according to RECIST, seven reached a partial response (PR), and one eventually exhibited progression. The overall response rate was 61%, the median time to PR was 8.0 months. Six patients achieved stable disease, although three developed progressions. Of the six patients with a PR, the median change in maximum diameter was -46%, and the median change in maximum volume was -84%. Three patients could have been diagnosed with progression at least 6 months earlier if the AV increment was considered. Conclusion: An AV assessment is essential for an accurate response assessment of DTs and radiotherapy seems feasible as a first-line treatment for DTs. [ABSTRACT FROM AUTHOR]

Special considerations should be made when selecting medications for the treatment of lower urinary tract symptoms (LUTS) in older patients especially those over 65 years old. This review summarizes the relationship between current treatments for LUTS and cognitive impairment. Although the recently reported association between dementia and tamsulosin is debatable, the effects of a-blockers and pharmacokinetics are not reported in this context. Five-alpha reductase inhibitors appear to affect mood. However, the association between the development of dementia and cognitive impairment is unlikely. Anticholinergic agents, other than trospium, fesoterodine, and imdafenacin have a relatively high distribution in the central nervous system. In particular, oxybutynin is reported to cause cognitive impairment. Several animal studies on the blood-brain barrier permeability of oxybutynin support this. Therefore, care must be taken when they are used in older patients (65 years and older). Beta-3 agonists are an alternative to, or may be used in combination with, anticholinergic drugs for patients with an overactive bladder (OAB). Several phase 2 and 3 clinical studies report high tolerability and efficacy, making them relatively safe for OAB treatment. However, there is a possibility that cognitive function may be affected; thus, long-term study data are required. We have reviewed studies investigating the correlation of urologic medications with cognitive dysfunction and have provided an overview of drug selection, as well as other considerations in older patients (65 years and older) with LUTS. This narrative review has focused primarily on articles indexed in PubMed, Google Scholar, Scopus, and Embase databases. No formal search strategy was used, and no meta-analysis of data was performed. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to compare the clinical outcomes of chemoradiotherapy with or without bevacizumab in patients with newly diagnosed International Federation of Gynecology and Obstetrics (FIGO) stage IVB cervical cancer. Methods 41 patients with stage IVB cervical cancer who underwent chemoradiotherapy between August 2015 and December 2017 were retrospectively analyzed. This study included 11 patients who received bevacizumab before or after radiotherapy (group A) and 30 patients who received conventional chemoradiotherapy without bevacizumab (group B). We excluded the following patients: those with dual primary cancers; those whose pathologic diagnosis was neither squamous cell carcinoma nor adenocarcinoma; those who did not undergo radiotherapy; or those from whom follow-up data could not be collected. We analyzed the treatment responses, toxicities, progression-free survival, and overall survival rates. results A total of 41 patients were included in the analysis. The median follow-up was 19 months (range 3-108). The response rates at 3 months after treatment were 90.9% in group A and 83.3% in group B (p=0.54). After completing all treatments, the complete response rates were 81.8% in group A and 47% in group B (p=0.04). Grade ≥3 gastrointestinal toxicities, including bleeding, fistula, perforation, and obstruction, were more frequent in group A (54.5%) than in group B (6.7%) (p=0.003). The 12 month progression-free survival and overall survival rates were similar in both arms (12 month progression-free survival: 45.5% vs 46.7%, respectively, p=0.22; 12 month overall survival: 81.8% vs 72.9%, respectively, p=0.57). Patients with node-only metastasis had better 12 month progression-free survival in group B than in group A (59.1% vs 42.9%, respectively, p=0.04). However, the responses to both treatments did not differ in patients with organ metastasis. Conclusions Bevacizumab for stage IVB cervical cancer is associated with higher complete response rates. However, patients treated with bevacizumab experienced more bowel toxicities. Bevacizumab did not improve progression-free survival among patients with node-only metastasis. [ABSTRACT FROM AUTHOR]

Objectives: There is no consensus on whether giving adjuvant concurrent chemoradiotherapy (CCRT) is more effective than adjuvant radiotherapy (RT) alone in patients with early stage cervical cancer and intermediate-risk factor(s). The purpose of this study was to evaluate survival difference according to adjuvant treatment in the intermediate-risk group. Methods: From 2000 to 2014, the medical records of patients with stage IB-IIA cervical cancer and a history of radical hysterectomy with pelvic lymph node dissection, followed by pelvic RT at a dose =40 Gy were retrospectively reviewed. Among these, 316 patients with one or more intermediate-risk factor(s) and no high-risk factors were included. The criteria defined the intermediate-risk group as those patients with any of the following intermediate-risk factors: lymphovascular space involvement, over one-half stromal invasion, or tumor size =4 cm. Results: The median follow-up duration was 70 months (range: 3-203 months). According to adjuvant treatment (adjuvant RT alone vs. adjuvant CCRT), the 5-year recurrence-free survival rates (90.8% vs. 88.9%, p=0.631) and 5-year overall survival rates (95.9% vs. 91.0%, p=0.287) did not show a significant difference in patients with any of the intermediate-risk factors. In multivariate analysis, a distinct survival difference according to adjuvant treatment was not found regardless of the number of risk factors. Conclusion: The present study showed that giving RT together with chemotherapy is not more effective than RT alone for stage IB-IIA cervical cancer patients with intermediate-risk factor(s). [ABSTRACT FROM AUTHOR]

Objectives: To perform a systematic review and meta-analysis of the prognostic value of posttreatment 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in uterine cervical cancer patients treated with radiotherapy (RT) with or without chemotherapy. Methods: PubMed and Embase databases were searched up to July 22, 2018, for studies which evaluated the response outcomes of 18F-FDG PET following RT, and their prognostic significance in uterine cervical cancer was assessed with overall survival (OS) or progressionfree survival (PFS) as endpoints. Hazard ratios (HRs) were meta-analytically pooled using the random-effects model. Results: Eleven studies with 12 patient cohorts including 1,104 patients were included. For a quantitative synthesis of OS, 7 cohorts were included. Two cohorts which reported disease-specific survival instead of OS were also included with flexibility. Pooled HR of complete metabolic response (CMR) compared to partial metabolic response (PMR) was 0.19 (95% confidence interval [CI]=0.11-0.31). Pooled HR of CMR compared to progressive metabolic disease (PMD) was more evident at 0.07 (95% CI=0.04-0.12), and that of CMR compared to both PMR and PMD was 0.20 (95% CI=0.12-0.34). Quantitative synthesis for PFS was performed with a total of 8 cohorts. Pooled HR of CMR was 0.17 (95% CI=0.10-0.29) compared to PMR, 0.02 (95% CI=0.01-0.06) compared to PMD and 0.12 (95% CI=0.07-0.19) compared to both PMR and PMD. Conclusion: Response results of post-RT 18F-FDG PET were significant prognostic factors in patients with uterine cervical cancer, and 18F-FDG PET could be a reasonable follow-up imaging modality. [ABSTRACT FROM AUTHOR]

Purpose We compared the oncologic outcomes of breast-conserving surgery plus radiation therapy (BCS+RT) and modified radical mastectomy (MRM) under anthracycline plus taxane-based (AT) regimens and investigated the role of adjuvant radiation therapy (RT) in patients with pathologic N1 (pN1) breast cancer treated by mastectomy. Materials and Methods We retrospectively reviewed the medical records of 2,011 patients with pN1 breast cancer who underwent BCS+RT or MRM alone at 12 institutions between January 2006 and December 2010. Two-to-one propensity score matching was performed for balances in variables between the groups. Results The median follow-up duration for the total cohort was 69 months (range, 1 to 114 months). After propensity score matching, 1,074 patients (676 in the BCS+RT group and 398 in the MRM-alone group) were analyzed finally. The overall survival, disease-free survival, locoregional failure-free survival, and regional failure-free survival (RFFS) curves of the BCS+RT group vs. MRM-alone group were not significantly different. The subgroup analysis revealed that in the group with both lymphovascular invasion (LVI) and histologic grade (HG) III, the BCS+RT showed significantly superior RFFS (p=0.008). Lymphedema (p=0.007) and radiation pneumonitis (p=0.031) occurred more frequently in the BCS+RT group than in the MRM-alone group, significantly. Conclusion There are no differences in oncologic outcomes between BCS+RT and MRM-alone groups under the AT chemotherapy regimens for pN1 breast cancer. However, BCS+RT group showed superior RFFS to MRM-alone group in the patients with LVI and HG III. Adjuvant RT might be considerable for pN1 breast cancer patients with LVI and HG III. [ABSTRACT FROM AUTHOR]

Background: The aim of the present study was to verify the dosimetric accuracy of two-dimensional (2D) in vivo rectal dosimetry using an endorectal balloon (ERB) with unfoldable EBT3 films for high-dose- rate (HDR) brachytherapy for cervical cancer. The clinical applicability of the technique was discussed. Material and methods: ERB inflation makes the EBT3 films unrolled, whereas its deflation makes them rolled. Patient-specific quality assurance (pQA) tests were performed in 20 patient plans using an Ir-192 remote afterloading system and a water-filled cervical phantom with the ERB. The dose distributions measured in ERBs were compared with those of the treatment plans. Results: The absolute dose profiles measured by the ERBs were in good agreement with those of treatment plans. The global gamma passing rates were 96-100% and 91-100% over 20 pQAs under the criteria of 3%/3mm and 3%/2mm, respectively, with a 30% low-dose threshold. Dose-volume histograms of the rectal wall were obtained from the measured dose distributions and showed small volume differences less than 2% on average from the patients' plans over the entire dose interval. The positioning error of the applicator set was detectable with high sensitivity of 12% dose area variation per mm. Additionally, the clinical applicability of the ERB was evaluated in volunteers, and none of them felt any pain when the ERB was inserted or removed. Conclusions: The 2D in vivo rectal dosimetry using the ERB with EBT3 films was effective and might be clinically applicable for HDR brachytherapy for cervical and prostate cancers to monitor treatment accuracy and consistency as well as to predict rectal toxicity. [ABSTRACT FROM AUTHOR]

Background: Combination therapy using external-beam radiotherapy (EBRT) with a brachytherapy boost has demonstrated superior biochemical control than dose-escalated EBRT alone. Whereas brachytherapy is disadvantageous because it is an invasive procedure, stereotactic body-radiotherapy (SBRT) using CyberKnife could emulate the dose distribution of brachytherapy and is a non-invasive and safe modality to control intra-fractional movement. We therefore adopted SBRT using CyberKnife as a boost therapy after whole-pelvic radiotherapy (WPRT).Methods/design: In this prospective, randomized, single-center, pilot study for intermediate- and high-risk prostate cancer without nodal or distant metastasis, after androgen-deprivation therapy and WPRT, patients will be randomized to one of two SBRT boost regimens, i.e., 18 or 21 Gy administered in three fractions every other day.Discussion: The aim of this trial is to evaluate acute toxicities using both physician- and patient-reported outcomes and short-term biochemical control with SBRT boost following WPRT. Additionally, chronic toxicities and long-term biochemical control will be evaluated as secondary endpoints in this trial. Based on the generated results, we will plan the full-scale phase II study for selecting the SBRT boost dose.Trial Registration: ClinicalTrials.gov, ID; NCT03322020 . Retrospectively registered on 26 October 2017. [ABSTRACT FROM AUTHOR]

Purpose This study retrospectively evaluated the clinical outcomes and complications of proton beam therapy (PBT) in a single institution in Korea and quantitatively analyzed the change in tumor volume after PBT using magnetic resonance imaging (MRI). Materials and Methods Twenty-four treatment-naïve patients who underwent PBT for choroidal melanoma between 2009 and 2015 were reviewed. Dose fractionation was 60-70 cobalt gray equivalents over 5 fractions. Orbital MRIs were taken at baseline and 3, 6, and 12 months after PBT and annually thereafter. The tumor volume was reconstructed and evaluated by stacking the tumor boundary in each thin-sliced axial T1-weighted image using MIM software. Results The median follow-up duration was 36.5 months (range, 9 to 82 months). One patient had suspicious local progression and two patients had distant metastasis. The 3-year local progression- free survival, distant metastasis-free survival, and overall survival rates were 95.8%, 95.8%, and 100%, respectively. Five Common Terminology Criteria for Adverse Event ver. 4.03 grade 3-4 toxicities were observed in four patients (16.7%), including one with neovascular glaucoma. The mean tumor volume at the baseline MRI was 0.565±0.084 mL (range, 0.074 to 1.610 mL), and the ratios of the mean volume at 3, 6, and 12 months to that at baseline were 81.8%, 67.3%, and 60.4%, respectively. Conclusion The local control rate and complication profile after PBT in patients with choroidal melanoma in Korea were comparable with those reported in a previous PBT series. The change in tumor volume after PBT exhibited a gradual regression pattern on MRI. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study was to evaluate the impact of postmastectomy radiotherapy (PMRT) on loco-regional recurrence-free survival (LRRFS), disease-free survival (DFS), and overall survival (OS) in pT1-2N1 patients treated with taxane-based chemotherapy. Materials and Methods We retrospectively reviewed the medical data of pathological N1 patients who were treated with modified radical mastectomy and adjuvant taxane-based chemotherapy in 12 hospitals between January 2006 and December 2010. Results We identified 714 consecutive patients. The median follow-up duration was 69 months (range, 1 to 114 months) and the 5-year LRRFS, DFS, and OS rates were 97%, 94%, and 98%, respectively, in patients who received PMRT (PMRT [+]). The corresponding figures were 96%, 90%, and 96%, respectively, in patients who did not receive PMRT (PMRT [-]). PMRT had no significant impact on survival. Upon multivariable analysis, only the histological grade (HG) was statistically significant as a prognostic factor for LRRFS and DFS. In a subgroup analysis of HG 3 patients, PMRT (+) showed better DFS (p=0.081). Conclusion PMRT had no significant impact on LRRFS, DFS, or OS in pT1-2N1 patients treated with taxane- based chemotherapy. PMRT showed a marginal benefit for DFS in HG 3 patients. Randomized studies are needed to confirm the benefit of PMRT in high risk patients, such as those with HG 3. [ABSTRACT FROM AUTHOR]

Purpose This study was conducted to evaluate the impact of supraclavicular lymph node radiotherapy (SCNRT) on N1 breast cancer patients receiving post-lumpectomy whole-breast irradiation (WBI) and anthracycline plus taxane-based (AT) chemotherapy. Materials and Methods We performed a case-control analysis to compare the outcomes of WBI and WBI plus SCNRT (WBI+SCNRT). Among 1,147 patients with N1 breast cancer who received post-lumpectomy radiotherapy and AT-based chemotherapy in 12 hospitals, 542 were selected after propensity score matching. Patterns of failure, disease-free survival (DFS), distant metastasis-free survival (DMFS), and treatment-related toxicity were compared between groups. Results A total of 41 patients (7.6%) were found to have recurrence. Supraclavicular lymph node (SCN) failure was detected in three patients, two in WBI and one in WBI+SCNRT. All SCN failures were found simultaneously with distant metastasis. There was no significant difference in patterns of failure or survival between groups. The 5-year DFS and DMFS for patients with WBI and WBI+SCNRT were 94.4% versus 92.6% (p=0.50) and 95.1% versus 94.5% (p=0.99), respectively. The rates of lymphedema and radiation pneumonitis were significantly higher in the WBI+SCNRT than in the WBI. Conclusion We did not find a benefit of SCNRT for N1 breast cancer patients receiving AT-based chemotherapy. [ABSTRACT FROM AUTHOR]

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Purpose: The concentration of capecitabine peaks at 1-2 hours after administration. We therefore assumed that proper timing of capecitabine administration and radiotherapy would maximize radiosensitization and influence survival among patients with locally advanced rectal cancer. Materials and Methods: We retrospectively reviewed 223 patients with locally advanced rectal cancer who underwent preoperative chemoradiation, followed by surgery from January 2002 to May 2006. All patients underwent pelvic radiotherapy (50 Gy/25 fractions) and received capecitabine twice daily at 12-hour intervals (1,650 mg/m2/day). Patients were divided into two groups according to the time interval between capecitabine intake and radiotherapy. Patients who took capecitabine 1 hour before radiotherapy were classified as Group A (n = 109); all others were classified as Group B (n = 114). Results: The median follow-up period was 72 months (range, 7 to 149 months). Although Group A had a significantly higher rate of good responses (44% vs. 25%; p = 0.005), the 5-year local recurrence-free survival rates of 93% in Group A and 97% in Group B did not differ significantly (p = 0.519). The 5-year disease-free survival and overall survival rates were also comparable between the groups. Conclusions: Despite the better pathological response in Group A, the time interval between capecitabine and radiotherapy administration did not have a significant effect on survivals. Further evaluations are needed to clarify the interaction of these treatment modalities. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to determine whether breast cancer subtype can affect locoregional recurrence (LRR) and ipsilateral breast tumor recurrence (IBTR) after neoadjuvant chemotherapy (NAC) and breast-conserving therapy (BCT). Materials and Methods: We evaluated 335 consecutive patients with clinical stage II-III breast cancer who received NAC plus BCT from 2002 to 2009. Patients were classified according to six molecular subtypes: luminal A (hormone receptor [HR]+/HER2-/Ki-67 < 15%, n=113), luminal B1 (HR+/HER2-/Ki-67 ≽ 15%, n=33), luminal B2 (HR+/HER2+, n=83), HER2 with trastuzumab (HER2[T+]) (HR-/HER2+/use of trastuzumab, n=14), HER2 without trastuzumab (HER2[T-]) (HR-/HER2+, n=31), and triple negative (TN) (HR-/HER2-, n=61). Results: After a median follow-up period of 7.2 years, 26 IBTRs and 37 LRRs occurred. The 5-year LRR-free survival rates were luminal A, 96.4%; B1, 93.9%; B2, 90.3%; HER2(T+), 92.9%; HER2(T-), 78.3%; and TN, 79.6%. The 5-year IBTR-free survival rates were luminal A, 97.2%; B1, 93.9%; B2, 92.8%; HER2(T+), 92.9%; HER2(T-), 89.1%; and TN, 84.6%. In multivariate analysis, HER2(T-) (IBTR: hazard ratio, 4.2; p=0.04 and LRR: hazard ratio, 7.6; p < 0.01) and TN subtypes (IBTR: hazard ratio, 6.9; p=0.01 and LRR: hazard ratio, 8.1; p < 0.01) were associated with higher IBTR and LRR rates. A pathologic complete response (pCR) was found to show correlation with better LRR and a tendency toward improved IBTR controls in TN patients (IBTR, p=0.07; LRR, p=0.03). Conclusion: The TN and HER2(T-) subtypes predict higher rates of IBTR and LRR after NAC and BCT. A pCR is predictive of improved IBTR or LRR in TN subtype. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to identify risk factors for transient lymphedema (TLE) and persistent lymphedema (PLE) following treatment for breast cancer. Materials and Methods: A total of 1,073 patients who underwent curative breast surgery were analyzed. TLE was defined as one episode of arm swelling that had resolved spontaneously by the next followup; arm swelling that persisted over two consecutive examinations was considered PLE. Results: At a median follow-up period of 5.1 years, 370 cases of lymphedema were reported, including 120 TLE (11.2%) and 250 PLE (23.3%). Initial grade 1 swelling was observed in 351 patients, of which 120 were limited to TLE (34%), while the other 231 progressed to PLE (66%). All initial swelling observed in TLE patients was classified as grade 1. In multivariate analysis, chemotherapy with taxane and supraclavicular radiation therapy (SCRT) were associated with development of TLE, whereas SCRT, stage III cancer and chemotherapy with taxane were identified as risk factors for PLE (p < 0.05). The estimated incidence of TLE among initial grade 1 patients was calculated using up to three treatment-related risk factors (number of dissected axillary lymph nodes, SCRT, and taxane chemotherapy). The approximate ratios of TLE and PLE based on the number of risk factors were 7:1 (no factor), 1:1 (one factor), 1:2 (two factors), and 1:3 (three factors). Conclusion: One-third of initial swelling events were transient, whereas the other two-thirds of patients experienced PLE. Estimation of TLE and PLE based on known treatment factors could facilitate prediction of this life-long complication. [ABSTRACT FROM AUTHOR]

Background: The authors conducted this prospective study to analyze the amount of interfractional prostate bed motion (PBM) and quantify its components with the use of an endorectal balloon (ERB). Methods: A total of 1,348 cone beam computed tomography images from 46 patients who underwent postprostatectomy radiotherapy were analyzed. For the pilot image, electronic portal imaging, guided by skin marks was performed to ensure proper positioning and inflation of the ERB. Then, for bone matching, manual or automatic registration of the planning and each cone beam computed tomography was performed, based on the bony anatomy of the pelvis. Shifts (bony misalignment [BM]) in three directions were recorded at each treatment session. For prostate bed matching, manual matching was conducted based on the anterior rectal wall and the shift (PBM) was recorded. Total setup error was defined as the shift from the skin mark to the prostate bed matching, based on anterior rectal wall stretched by the ERB. PBM was defined as the difference between the total setup error and BM. Results: Systematic errors for the total setup error were 1.0, 1.3, and 1.0 mm in the right-left, anterior-posterior, and superior-inferior directions, with random errors of 1.9, 2.4, and 1.9 mm, respectively. Systematic errors were 1.6, 1.6, and 0.3 mm for BM and 0.8, 1.1, and 0.9 mm for PBM, with random errors of 2.4, 2.5, and 1.1 mm for BM and 1.8, 2.2, and 1.9 mm for PBM. Conclusion: The BM was the main component of the total setup error, suggesting that interfractional PBM was well controlled by the ERB device. Planning target volume margins of <5 mm were needed to include 95% of the interfractional variations when using an ERB. [ABSTRACT FROM AUTHOR]

Purpose: We identified the predictive factors for locoregional failure after definitive chemoradiation in patients with locally advanced cervical cancer. Methods: Altogether, 397 patients with locally advanced cervical cancer (stage IB2-IVA) were treated with definitive chemoradiation between June 2001 and February 2010. Platinum-based concurrent chemotherapy was given to all patients with median radiation dose of external beam radiotherapy 50.4 Gy in 28 fractions and intracavitary radiotherapy 30 Gy in 6 fractions. Competing risk regression analysis was used to reveal the predictive factors for locoregional failure. Results: During the median follow-up of 7.2 years, locoregional failure occurred in 51 (12.9%) patients. The estimated 3-year rate of locoregional control was 89%, whereas the overall survival rate was 82%. After univariate and multivariate analyses, large tumor size (95 cm), young age (≤ 40 years), nonsquamous histology, positive lymph node on magnetic resonance imaging, and advanced stage (III-IV) were identified as risk factors for locoregional failure (P = 0.003, P = 0.075, P = 0.005, P = 0.055, and P < 0.001, respectively). After risk grouping according to the coefficients from the multivariate model, we identified a high-risk group for locoregional failure after treatment with definitive chemoradiation as follows: (1) tumor size larger than 5 cm, and at least 1 other risk factor or (2) tumor size 5 cm or less, and at least 3 other risk factors. The cumulated estimated 3-year rate of locoregional failure of the high-risk group was 26%, which was significantly higher than that of the low-risk group (7%, P < 0.001). The 3-year overall survival rates of the 2 groups were also significantly different (57% vs 86%, P < 0.001). Conclusions: Large tumor size (95 cm), young age (≤ 40 years), nonsquamous histology, positive lymph node on magnetic resonance imaging, and advanced stage are all risk factors for locoregional failure after definitive platinum-based chemoradiation in patients with locally advanced cervical cancer. In the high-risk group, further clinical trials are warranted to improve the locoregional control rate. [ABSTRACT FROM AUTHOR]

Purpose This study was conducted to investigate the incidence and survival outcomes of second primary cancers after the diagnosis of cervical cancer. Materials and Methods Data from the Korea Central Cancer Registry between 1993 and 2010 were reviewed and analyzed. Standardized incidence ratios (SIRs) of second primary cancers among women with cervical cancer were analyzed. Kaplan-Meier survival curves were constructed for cervical cancer patients with or without a second primary cancer. Results Among 72,805 women with cervical cancer, 2,678 (3.68%) developed a second primary cancer within a mean follow-up period of 7.34 years. The overall SIR for a second cancer was 1.08 (95% confidence interval, 1.04 to 1.12). The most frequent sites of second primary cancers were the vagina, bone and joints, vulva, anus, bladder, lung and bronchus, corpus uteri, and esophagus. However, the incidence rates of four second primary cancers (breast, rectum, liver, and brain) were decreased. The 5-year and 10-year overall survival rates were 78.3% and 72.7% in all women with cervical cancer, and for women with a second primary cancer, these rates were 83.2% and 65.5% from the onset of cervical cancer and 54.9% and 46.7% from the onset of the second primary cancer, respectively. Conclusion The incidence rates of second primary cancers were increased in women with cervical cancer compared to the general population, with the exception of four decreasing cancers. The 10-year overall survival rates were decreased in cervical cancer patients with a second primary cancer. [ABSTRACT FROM AUTHOR]

Purpose: To compare the acute intestinal toxicity of whole pelvic (WP) and small field (SF) intensity-modulated radiotherapy (IMRT) for prostate cancer using dosimetric and metabolic parameters as well as clinical findings. Methods: Patients who received IMRT in either a definitive or postoperative setting were prospectively enrolled. Target volume and organs at risk including intestinal cavity (IC) were delineated in every patient by a single physician. The IC volume that received a 10-50 Gy dose at 5-Gy intervals (V10-V50) and the percentage of irradiated volume as a fraction of total IC volume were calculated. Plasma citrulline levels, as an objective biological marker, were checked at three time points: baseline and after exposure to 30 Gy and 60 Gy. Results: Of the 41 patients, only six experienced grade 1 acute intestinal toxicity. Although all dose-volume parameters were significantly worse following WP than SF IMRT, there was no statistically significant relationship between these dosimetric parameters and clinical symptoms. Plasma citrulline levels did not show a serial decrease by radiotherapy volume difference (WP versus SF) and were not relevant to the irradiated doses. Conclusion: Given that WP had comparable acute intestinal toxicities to those associated with SF, WP IMRT appears to be a feasible approach for the treatment of prostate cancer despite dosimetric disadvantages. [ABSTRACT FROM AUTHOR]

Purpose: To determine failure patterns and survival outcomes of T4N0-1 non-small cell lung cancer (NSCLC) treated with definitive radiotherapy. Materials and Methods: Ninety-five patients with T4N0-1 NSCLC who received definitive radiotherapy with or without chemotherapy from May 2003 to October 2014 were retrospectively reviewed. The standard radiotherapy scheme was 66 Gy in 30 fractions. The main concurrent chemotherapy regimen was 50 mg/m2 weekly paclitaxel combined with 20 mg/m2 cisplatin or AUC 2 carboplatin. The primary outcome was overall survival (OS). Secondary outcomes were failure patterns and toxicities. Results: The median age was 64 years (range, 34 to 90 years). Eighty-eight percent of patients (n = 84) had an Eastern Cooperative Oncology Group performance status of 0-1, and 42% (n = 40) experienced pretreatment weight loss. Sixty percent of patients (n = 57) had no metastatic regional lymph nodes. The median radiation dose was EQD2 67.1 Gy (range, 56.9 to 83.3 Gy). Seventy-one patients (75%) were treated with concurrent chemotherapy; of these, 13 were also administered neoadjuvant chemotherapy. At a median follow-up of 21 months (range, 1 to 102 months), 3-year OS was 44%. The 3-year cumulative incidences of local recurrence and distant recurrence were 48.8% and 36.3%, respectively. Pretreatment weight loss and combined chemotherapy were significant factors for OS. Acute esophagitis over grade 3 occurred in three patients and grade 3 chronic esophagitis occurred in one patient. There was no grade 3-4 radiation pneumonitis. Conclusion: Definitive radiotherapy for T4N0-1 NSCLC results in favorable survival with acceptable toxicity rates. Local recurrence is the major recurrence pattern. Intensity modulated radiotherapy and radio-sensitizing agents would be needed to improve local tumor control. [ABSTRACT FROM AUTHOR]

Purpose: The thulium laser is the most recently introduced technology for the surgical treatment of benign prostatic hyperplasia (BPH). Until recently, most thulium laser enucleation of the prostate (ThuLEP) was performed by use of the three-lobe technique. We introduce a novel one-lobe enucleation technique for ThuLEP called the "All-in-One" technique. We report our initial experiences here. Materials and Methods: From June 2013 to May 2014, a total of 47 patients underwent the All-in-One technique of ThuLEP for symptomatic BPH performed by a single surgeon. All patients were assessed with the International Prostate Symptom Score (IPSS), transrectal ultrasonography, serum prostate-specific antigen (PSA), maximal urine flow rate (Qmax), and postvoid residual urine volume (PVR) before and 1 month after surgery. We reassessed IPSS, Qmax, and PVR 3 months after surgery. To assess the efficacy of the All-in-One technique, we checked the PSA reduction ratio, transitional zone volume reduction ratio, and enucleation failure rate. Results: The mean operative time was 82.1±33.3 minutes. The mean enucleation time and morcellation time were 52.7±21.7 minutes and 8.2±7.0 minutes, respectively. The mean resected tissue weight and decrease in hemoglobin were 36.9±24.6 g and 0.4±0.8 g/dL, respectively. All perioperative parameters showed significant improvement (p<0.05). No major complications were observed. The PSA reduction ratio, transitional zone volume reduction ratio, and enucleation failure rate were 0.81, 0.92, and 4.3%, respectively. Conclusions: The All-in-One technique of ThuLEP showed efficacy and effectiveness comparable to that of other techniques. We expect that this new technique could reduce the operation time and the bleeding and improve the effectiveness of enucleation. [ABSTRACT FROM AUTHOR]

Purpose: We evaluated the prognostic factors and clinical outcomes of 56 patients with vulvar cancer treated with curative radiotherapy (RT) or concurrent chemoradiotherapy. Materials and Methods: Overall survival (OS) and disease-free survival (DFS) were assessed retrospectively. Prognostic factors evaluated included age, International Federation of Gynecology and Obstetrics (FIGO) stage, TNM classification, tumor size, treatment modality, RT duration, and RT field. The association between the tumor human papillomavirus (HPV) status and survival was analyzed in 35 patients. Results: During the median follow-up of 2.8 years (range, 0.3 to 18.9 years), 21 patients (37.5%) experienced treatment failure. Fifteen patients (27%) had local failure: nine (16%) local failure only, three (5%) locoregional failure, two (4%) local and distant failure, and one (2%) locoregional and distant failure. Of 56 patients, seven (13%) had persistent disease at the first follow-up at 2 months and all but one died within a year after completing RT. The 5-year OS and DFS were 51.6% and 44.0%, respectively. In multivariate analysis, clinical size =3 cm predicted a poor prognostic factor for DFS (p = 0.040) and age (≥70 years) was poor prognostic for DFS (p = 0.032) and OS (p = 0.048). Patients with HPV-positive tumors tended to have better 5-year OS and DFS, but the differences were not significant statistically. Conclusion: Clinical size ≥3 cm was a significant prognostic factor for DFS. However, age was the most important prognostic factor for DFS and OS in patients treated with curative RT. Further studies are needed to determine which treatment should be considered for old age ≥70 years. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to determine the optimal dose of proton beam therapy (PBT) in hepatocellular carcinoma (HCC) patients. Materials and Methods: Inoperable HCC patients who had naïve, recurrent, or residual tumor to treatment were considered eligible for PBT. Patients received PBT with 60 GyE in 20 fractions (dose level 1; equivalent dose in 2 Gy fractions [EQD2], 65 GyE10); 66 GyE in 22 fractions (dose level 2; EQD2, 71.5 GyE10); or 72 GyE in 24 fractions (dose level 3; EQD2, 78 GyE10). Dose-limiting toxicity was determined by grade ≥ 3 acute toxicity. Results: Twenty-seven patients were enrolled; eight, seven, and 12 patients were treated with dose levels 1, 2, and 3, respectively. Overall, treatment was well tolerated, with no dose-limiting toxicities. The complete response (CR) rates of primary tumors after PBT for dose levels 1, 2, and 3 were 62.5% (5/8), 57.1% (4/7), and 100% (12/12), respectively (p=0.039). The 3- and 5-year local progression-free survival (LPFS) rates among 26 patients, excluding one patient who underwent liver transplantation after PBT due to its probable significant effect on disease control, were 79.9% and 63.9%, respectively, and the 3- and 5-year overall survival rates were 56.4% and 42.3%, respectively. The 3-year LPFS rate was significantly higher in patients who achieved CR than in those who did not (90% vs. 40%, p=0.003). Conclusion: PBT is safe and effective and an EQD2 ≥ 78 GyE10 should be delivered for achievement of local tumor control. [ABSTRACT FROM AUTHOR]

This study investigates the impact of economic statecraft on the North Korean Government. As a totalitarian regime, which is characterized by a controlled mass media, the North Korean Government tries to contain potential problems caused by sanctions by using three types of political rhetoric: appeasement, backlash, and surveillance. Using timeseries data from 1949 to 2010 derived from a content analysis of the New Year's Day addresses by Kim II Sung, Kim Jong II, and Kim Jong Un, the empirical results suggests that the North Korean Government does alter its rhetorical strategies in response to external economic sanctions. Negative sanctions cause the regime to use appeasement strategies (or calls for reforms and internal changes). It tends to use backlash rhetoric (or blaming the sanctioning powers) in response to, interestingly, positive sanctions. Surveillance rhetoric, or the call for internal vigilance against enemies, on the other hand, does not have any statistical connection with sanctions, rather driven by other factors, such as the Korean War, external instability, and so on. [ABSTRACT FROM AUTHOR]

Purpose: To assess the clinical efficacy and toxicity of whole pelvic intensity-modulated radiotherapy (WP-IMRT) for high-risk prostate cancer. Materials and Methods: Patients with high-risk prostate cancer treated between 2008 and 2013 were reviewed. The study included patients who had undergone WP-IMRT with image guidance using electronic portal imaging devices and/or cone-beam computed tomography. The endorectal balloon was used in 93% of patients. Patients received either 46 Gy to the whole pelvis plus a boost of up to 76 Gy to the prostate in 2 Gy daily fractions, or 44 Gy to the whole pelvis plus a boost of up to 72.6 Gy to the prostate in 2.2 Gy fractions. Results: The study cohort included 70 patients, of whom 55 (78%) had a Gleason score of 8 to 10 and 50 (71%) had a prostate-specific antigen level > 20 ng/mL. The androgen deprivation therapy was combined in 62 patients. The biochemical failure-free survival rate was 86.7% at 2 years. Acute any grade gastrointestinal (GI) and genitourinary (GU) toxicity rates were 47% and 73%, respectively. The actuarial rate of late grade 2 or worse toxicity at 2 years was 12.9% for GI, and 5.7% for GU with no late grade 4 toxicity. Conclusion: WP-IMRT was well tolerated with no severe acute or late toxicities, resulting in at least similar biochemical control to that of the historic control group with a small field. The long-term efficacy and toxicity will be assessed in the future, and a prospective randomized trial is needed to verify these findings. [ABSTRACT FROM AUTHOR]

Background: Although capecitabine has theoretical advantages in the pharmacokinetics, such as higher intratumoral and lower systemic concentration, relative to bolus 5-fluorouracil (5-FU), outcomes of chemoradiotherapy (CRT) with capecitabine or bolus 5-FU have not been directly compared in patients with locally advanced pancreatic cancer. Therefore, we retrospectively compared the outcomes, including toxicity, tumor response, and overall survival, of oral capecitabine plus radiotherapy (RT) with bolus 5-FU plus RT, in patients with locally advanced pancreatic cancer. Methods: Between August 2006 and January 2012, 98 patients with locally advanced pancreatic cancer received CRT, with 52 receiving concurrent oral capecitabine and 46 receiving bolus injection of 5-FU. Primary tumor and overall response after CRT were evaluated radiologically, and toxicity, tumor response, and overall survival (OS) were compared in the two groups. Results: Baseline clinical parameters of the two groups were similar. The rates of ≥ Grade 3 hematologic (0% vs. 8.7%, p = 0.045) and non-hematologic (0% vs. 8.7%, p = 0.045) toxicities were significantly lower in the capecitabine group than in the 5-FU group. Primary tumor (30.7% vs. 28.2%, p = 0.658) and overall (13.7% vs. 15.2%, p = 0.273) response rates and median OS time (12.5 months vs. 11.6 months, p = 0.655) were similar in the two groups. Conclusions: Capecitabine plus RT may be a safe and feasible regimen for patients with locally advanced pancreatic cancer, with similar efficacy and low rates of toxicities compared with bolus 5-FU plus RT. [ABSTRACT FROM AUTHOR]

Purpose: We assessed the value of dose-volumetric parameters predicting rectosigmoid mucosal changes (RMC) and late rectosigmoid complications (LRC). Methods: Between January 2004 and February 2006, 77 patients with stage IB-IIIB cervical cancer underwent external beam radiotherapy and computed tomography (CT)-based intracavitary irradiation. Total dose to the rectal point and several dose-volumetric parameters for rectosigmoid colon (D20cc, D15cc, D10cc, D5cc, D2cc, D1cc, and D0.1cc , defined as the minimal doses received by the highest irradiated volumes of 20, 15, 10, 5, 2, 1, and 0.1 cc, respectively), were calculated using the equivalent dose in 2 Gy fractions (α/β = 3, Gy3). The RMC and LRC were graded by rectosigmoidoscopy and Radiation Therapy Oncology Group criteria every 6 months, respectively. Results: Of 77 patients, 27 (35.1%) patients developed RMC ≥ score 3 and 22 (28.6 %) patients developed LRC ≥ grade 2. There was a positive correlation between RMC score and LRC grade (r = 0.728, p < 0.001). In multivariate analyses, D5cc, among the dose-volumetric parameters, was significant parameter for the risks of RMC ≥ score 3 and LRC ≥ grade 2 (p < 0.05). Conclusions: D5cc may be a more reliable estimate than other dose-volumetric parameters for predicting the risk of RMC ≥ score 3 and LRC ≥ grade 2 in CT-based brachytherapy. [ABSTRACT FROM AUTHOR]