Analysis of Once-Daily Thoracic Radiotherapy Dose According to the Underlying Lung Disease in Patients with Limited-Stage Small Cell Lung Cancer Undergoing Concurrent Chemoradiotherapy / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#In the treatment of concurrent chemoradiotherapy (CCRT) in limited-stage small cell lung cancer, the optimal once-daily radiotherapy (RT) dose/fractionation remain unclear although it is the most frequently used. Therefore, this study aimed to compare the treatment outcomes and toxicities of modest dose RT (≤ 54 Gy) with those of standard dose RT (> 54 Gy) and investigate the benefit of the high dose based on patient factors. @*Materials and Methods@#Since 2004, our institution has gradually increased the thoracic RT dose. Among the 225 patients who underwent CCRT, 84 patients (37.3%) received > 54 Gy. Because the patients treated with RT > 54 Gy were not randomly assigned, propensity score matching (PSM) was performed. @*Results@#The proportion of patients treated with > 54 Gy increased over time (p=0.014). Multivariate analysis revealed that the overall tumor stage and dose > 54 Gy (hazard ratio, 0.65; p=0.029) were independent prognostic factors for overall survival (OS). PSM confirmed that thoracic RT doses of > 54 Gy showed significantly improved progression-free survival (3-year, 42.7% vs. 24.0%; p 54 Gy was not observed but considerable rates of severe pulmonary toxicities were observed (p=0.001). @*Conclusion@#Our analysis supports that the 60 Gy RT dose should be considered in the once-daily regimen of CCRT for limited-stage small cell lung cancer without underlying lung disease, but RT dose > 54 Gy did not seem to benefit for patients with chronic obstructive pulmonary disease or interstitial lung disease. Further study is needed to validate these results.

Image-Guided Versus Conventional Brachytherapy for Locally Advanced Cervical Cancer: Experience of Single Institution with the Same Practitioner and Time Period / Journal of the Korean Cancer Association, 대한암학회지

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

Exploring the past, present, and future of postoperative radiotherapy for N2 stage non-small cell lung cancer

Despite conventionally applied postoperative radiotherapy (PORT) in pathological N2 (pN2) stage non-small cell lung cancer (NSCLC) considering high locoregional recurrence, its survival benefit has been a continuous topic of debate. Although several randomized clinical trials have been conducted, many of them have been withdrawn or analyzed without statistical significance due to slow accrual, making it difficult to determine the efficacy of PORT. Recently, the results of large-scale randomized clinical trials have been published, which showed some improvement in disease-free survival with PORT, but finally had no impact on overall survival. Based on these results, it was expected that the debate over PORT in pN2 patients with NSCLC would come to an end. However, since pN2 patients have different clinicopathologic features, it has become more important to carefully select the patient population who will benefit from PORT. In addition, given the development of systemic treatments such as molecular-targeted therapy and immunotherapy, it is crucial to evaluate whether there is any benefit to PORT in the midst of these recent changes. Therefore, determining the optimal treatment approach for NSCLC pN2 patients remains a complex issue that requires further research and evaluation.

Clinical outcomes of radical radiotherapy for pulmonary sarcomatoid carcinoma

Purpose@#Pulmonary sarcomatoid carcinoma (PSC) is recognized for its aggressiveness and poor prognosis. The role of radical radiotherapy in PSC remains uncertain due to its scarcity and limited data. In the absence of an effective systemic agent, this study aims to explore the possibility of cure and to investigate potential prognostic factors and treatment outcomes. @*Materials and Methods@#From January 2005 to December 2021, 149 PSC patients were identified. Among 62 patients who received radiotherapy for lung lesions, 25 who underwent palliative radiotherapy and 16 who underwent surgery were excluded. @*Results@#The median patient age was 71 years. The majority were male, and 17 patients (81.0%) were diagnosed at an advanced stage. After radical radiotherapy, distant metastasis (47.6%) was the most common site of failure, while the local recurrence rate was quite low (9.5%). Eventually, five patients (26.3%) demonstrated either a partial response or complete remission, including three complete remissions with durable responses. The median progression-free survival (PFS) and overall survival were 4.6 months and 7.9 months, respectively. Univariate and multivariate analyses revealed that a tumor size >5 cm was associated with a worse prognosis (p = 0.045), while a radiation dose >58 GyEQD2 was significantly associated with better PFS (p = 0.038). @*Conclusion@#This study demonstrates clinical outcomes after radical radiotherapy in managing PSC, suggesting tumor size and radiation dose could be a predictor of a systemic response. Given the known bad prognosis but complete remission could be achieved in certain subgroups, future research should explore the potential strategies using radical radiotherapy for this challenging patient population.

Predictors of Post-chemoradiotherapy Pulmonary Complication in Locally Advanced Non–Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We investigated the clinical effects and predictive factors of severe post-chemoradiotherapy pulmonary complications (PCPC) in locally advanced non–small cell lung cancer (LA-NSCLC). @*Materials and Methods@#Medical records of 317 patients who underwent definitive concurrent chemoradiation (CCRT) for LA-NSCLC were reviewed retrospectively. PCPC was defined as an event of admission or emergency department visit for acute or subacute pulmonary inflammatory complications, including pneumonitis and pneumonia, within 6 months after CCRT initiation. Patient characteristics, baseline lung function tests, radiation dosimetric parameters, and laboratory tests were analyzed to investigate their association with PCPC. Prognostic endpoints were disease progression rate (DPR) and overall survival (OS). @*Results@#PCPC was reported in 53 patients (16.7%). The OS of patients with PCPC was significantly worse (35.0% in 2 years) than that of patients without PCPC (67.0% in 2 years, p < 0.001). However, 2-year DPRs were 77.0% and 70.7% in patients with and without PCPC, respectively, which were not significantly different (p=0.087). In multivariate logistic regression, PCPC was independently associated with grade ≥ 1 hypoalbuminemia during CCRT (odds ratio [OR], 5.670; 95% confidence interval [CI], 2.487 to 13.40; p < 0.001), lower diffusing capacity of carbon monoxide (DLCO) (per mL/min/mmHg; OR, 0.855; 95% CI, 0.743 to 0.974; p=0.022), and higher lung V5 (per 10%; OR, 1.872; 95% CI, 1.336 to 2.699; p < 0.001). @*Conclusion@#PCPC might be a clinical endpoint to evaluate complications and predict the survival of patients subjected to CCRT for LA-NSCLC. Hypoalbuminaemia, DLCO, and lung V5 might predict PCPC in LA-NSCLC.

Efficacy of Prophylactic Cranial Irradiation According to the Risk of Extracranial Recurrence in Limited-Stage Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We aimed to evaluate the effectiveness of prophylactic cranial irradiation (PCI) for “early brain metastasis”, which occurs before extracranial recurrence (ECR), and “late brain metastasis”, which occurs after ECR, in limited-stage small cell lung cancer (LS-SCLC). @*Materials and Methods@#We retrospectively analyzed 271 LS-SCLC patients who underwent definitive chemoradiation. All patients were initially staged with brain magnetic resonance imaging and positron emission tomography. Intracranial recurrence (ICR), ECR, progression-free rate (PFR), and overall survival (OS) were analyzed as clinical endpoints. The competing risk of the first recurrence with ICR (ICRfirst) was evaluated. Significantly associated variables in multivariate analysis of ECR were considered as ECR risk factors. Patients were stratified according to the number of ECR risk factors. @*Results@#The application of PCI was associated with higher PFR (p=0.008) and OS (p=0.045). However, PCI was not associated with any of the clinical endpoints in multivariate analysis. The competing risk of ICRfirst was significantly decreased with the application of PCI (hazard ratio, 0.476; 95% confidence interval, 0.243 to 0.931; p=0.030). Stage III disease, sequential, and stable disease after thoracic radiation were selected as ECR risk factors. For patients without these risk factors, the application of PCI was significantly associated with increased OS (p=0.048) and a decreased risk of ICRfirst (p=0.026). @*Conclusion@#PCI may play a role in preventing early brain metastasis rather than late brain metastasis after ECR, suggesting that only patients with a low risk of ECR may currently benefit from PCI.

Structure Determination of Heishuixiecaoline A from Valeriana fauriei and Its Content from Different Cultivated Regions by HPLC/PDA Analysis

A germacrane-type sesquiterpenoid was isolated and purified from a methanol extract of the roots of Valeriana fauriei (RVF) through open column chromatography using silica gel. This compound was verified to be heishuixiecaoline A by spectroscopic analysis. This compound was isolated for the first time from RVF.Quantitative analysis of heishuixiecaoline A from RVF cultivated from three different regions (Eumseong, Jinbu, and Jinan regions) was performed by combining high-performance liquid chromatography with a photodiode array detector. The extract of RVF cultivated in the Jinbu region showed the highest content (9.23 mg/g). In addition, a significant amount of the compound was detected in all RVF samples, which could be expected since it is a characteristic compound of RVF. The sesquiterpenoid group heishuixiecaoline A was isolated from RVF, a resource for various pharmacological substances, and quantitative analysis of RVF cultivated from three different regions was performed. As a result of these experiments, basic data on RVF that can be used in the development and application of pharmaceuticals and health functional foods in the future were obtained.

Alteration in Cngb1 Expression upon Maternal Immune Activation in a Mouse Model and Its Possible Association with Schizophrenia Susceptibility

Objective@#The cyclic nucleotide-gated channel (Cng) regulates synaptic efficacy in brain neurons by modulating Ca2＋ levels in response to changes in cyclic nucleotide concentrations. This study investigated whether the expression of Cng channel, cyclic nucleotide-gated channel subunit beta 1 (Cngb1) exhibited any relationship with the pathophysiology of schizophrenia in an animal model and whether genetic polymorphisms of the human gene were associated with the progression of schizophrenia in a Korean population. @*Methods@#We investigated whether Cngb1 expression was related to psychiatric disorders in a mouse model of schizophrenia induced by maternal immune activation. A case-control study was conducted of 275 schizophrenia patients and 410 controls with single-nucleotide polymorphisms (SNPs) in the 5′-near region of CNGB1. @*Results@#Cngb1 expression was decreased in the prefrontal cortex in the mouse model. Furthermore, the genotype frequency of a SNP (rs3756314) of CNGB1 was associated with the risk of schizophrenia. @*Conclusion@#Our results suggest that CNGB1 might be associated with schizophrenia susceptibility and maternal immune activation. Consequently, it is hypothesized that CNGB1 may be involved in the pathophysiology of schizophrenia.

The Feasibility of Spinal Stereotactic Radiosurgery for Spinal Metastasis with Epidural Cord Compression / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to investigate the effectiveness and safety of spinal stereotactic radiosurgery (SRS) in treating spinal metastasis with epidural spinal cord compression (ESCC). MATERIALS AND METHODS: During 2013-2016, 149 regions of spinal metastasis in 105 patients treated with singlefraction (12-24 Gy) spinal SRS were reviewed. Cord compression of Bilsky grade 2 (with visible cerebrospinal fluid [CSF]) or 3 (no visible CSF) was defined as ESCC. Local progression (LP) and vertebral compression fracture (VCF) rates after SRS were evaluated using multivariate competing-risk regression analysis. RESULTS: The 1-year cumulative incidences of LP for Bilsky grades 0 (n=80), 1 (n=39), 2 (n=21), and 3 (n=9) were 3.0%, 8.4%, 0%, and 24.9%, respectively. Bilsky grade 2 ESCC did not significantly increase the LP rate (no LP for grade 2). The 1-year cumulative incidences of VCF for Bilsky grades 0, 1, 2, and 3 were 6.6%, 5.2%, 17.1%, and 12.1%, respectively. ESCC may increase VCF risk (subhazard ratio [SHR] for grade 2, 5.368; p=0.035; SHR for grade 3, 2.215; p=0.460). Complete or partial pain response rates after SRS were 79%, 78%, 53%, and 63% for Bilsky grades 0, 1, 2, and 3, respectively (p=0.008). No neurotoxicity of grade ≥ 3 was observed. CONCLUSION: Spinal SRS for spinal metastasis with Bilsky grade 2 ESCC did not increase the LP rate, was not associated with severe neurotoxicity, and showed moderate VCF and pain response rates. Bilsky grade 3 had a high LP rate.

Disulfiram, a Re-positioned Aldehyde Dehydrogenase Inhibitor, Enhances Radiosensitivity of Human Glioblastoma Cells In Vitro / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Glioblastoma, the most common brain tumor in adults, has poor prognosis. The purpose of this study was to determine the effect of disulfiram (DSF), an aldehyde dehydrogenase inhibitor, on in vitro radiosensitivity of glioblastoma cells with different methylation status of O⁶-methylguanine-DNA methyltransferase (MGMT) promoter and the underlying mechanism of such effect. MATERIALS AND METHODS: Five human glioblastoma cells (U138MG, T98G, U251MG, U87MG, and U373MG) and one normal human astrocyte (NHA) cell were cultured and treated with DSF or 6MV X-rays (0, 2, 4, 6, and 8 Gy). For combined treatment, cells were treated with DSF before irradiation. Surviving fractions fit from cell survival based on colony forming ability. Apoptosis, DNA damage repair, and cell cycle distributionwere assayed bywestern blot for cleaved caspase-3, γH2AX staining, and flow cytometry, respectively. RESULTS: DSF induced radiosensitization in most of the glioblastoma cells, especially, in the cells with radioresistance as wildtype unmethylated promoter (MGMT-wt), but did not in normal NHA cell. DSF augmented or induced cleavage of caspase-3 in all cells after irradiation. DSF inhibited repair of radiation-induced DNA damage in MGMT-wt cells, but not in cells with methylated MGMT promoter. DSF abrogated radiation-induced G2/M arrest in T98G and U251MG cells. CONCLUSION: Radiosensitivity of glioblastoma cells were preferentially enhanced by pre-irradiation DSF treatment compared to normal cell, especially radioresistant cells such as MGMT-wt cells. Induction of apoptosis or inhibition of DNA damage repair may underlie DSF-induced radiosensitization. Clinical benefit of combining DSF with radiotherapy should be investigated in the future.

Influence of clozapine on neurodevelopmental protein expression and behavioral patterns in animal model of psychiatric disorder induced by low-level of lead

Exposure to lead during pregnancy is a risk factor for the development of psychiatric disorders in the offspring. In this study, we investigated whether exposure to low levels of lead acetate (0.2%) in drinking water during pregnancy and lactation causes behavioral impairment and affects the expression of proteins associated with neurodevelopment. Lead exposure altered several parameters in rat offspring compared with those unexposed in open-field, social interaction, and pre-pulse inhibition tests. These parameters were restored to normal levels after clozapine treatment. Western blot and immunohistochemical analyses of the hippocampus revealed that several neurodevelopmental proteins were downregulated in lead-exposed rats. The expression was normalized after clozapine treatment (5 mg/kg/day, postnatal day 35–56). These findings demonstrate that downregulation of several proteins in lead-exposed rats affected subsequent behavioral changes. Our results suggest that lead exposure in early life may induce psychiatric disorders and treatment with antipsychotics such as clozapine may reduce their incidence.

Survival outcomes after adjuvant radiotherapy for aggressive fibromatosis depend on time frame and nuclear β-catenin

PURPOSE: To identify prognostic factors influencing progression-free survival (PFS) of aggressive fibromatosis (AF) after postoperative radiotherapy (PORT) and assess correlations between immunohistochemistry (IHC) features of β-catenin/smooth muscle actin (SMA) and PFS. MATERIALS AND METHODS: Records of 37 patients with AF treated by PORT from 1984 to 2015 were retrospectively reviewed. Fifteen patients underwent wide excision for AF and 22 patients received debulking operation. The median total dose of PORT was 59.4 Gy. IHC staining results of β-catenin and SMA were available for 11 and 12 patients, respectively. RESULTS: The median follow-up duration was 105.9 months. Five-year PFS rate was 70.9%. Tumor size or margin status was not related to PFS in univariate analysis (p = 0.197 and p = 0.716, respectively). Multivariate analysis showed that increased interval from surgery to PORT (>5.7 weeks) was a marginal risk factor for PFS (p = 0.054). Administration of PORT at the initial diagnosis resulted in significantly improved PFS compared to deferring PORT after recurrence (p = 0.045). Patient with both risk factors of deferring PORT after recurrence and interval from surgery to PORT >5.7 weeks had significantly lower 5-year PFS than patients without risk factor (34.1% vs. 100.0%; p = 0.012). Nuclear β-catenin intensity tended to inversely correlate with 5-year PFS, although it did not reach statistical significance (62.5% at low vs. 100.0% at high; p = 0.260). SMA intensity was not related to PFS (p = 0.700). CONCLUSION: PORT should be performed immediately after surgery irrespective of margin status or tumor size especially in recurrent case. Nuclear β-catenin staining intensity of IHC might correlate with local recurrence.

Effects of Tianeptine on Adult Rats Following Prenatal Stress

OBJECTIVE: Exposing a pregnant female to stress during the critical period of embryonic fetal brain development increases the risk of psychiatric disorders in the offspring. The objective of this study was to investigate the effect of antidepressant tianeptine on prenatally stressed (PNS) rats. METHODS: In this study, a repeated variable stress paradigm was applied to pregnant rats during the last week of gestation. To investigate the effects of antidepressant tianeptine on PNS rats, behavioral and protein expression analyses were performed. Forced swim test, open field test, and social interaction test were performed to determine changes in PNS rats compared to non-stressed offspring. Haloperidol was used as a positive control as an antipsychotic drug based on previous studies. RESULTS: Behavioral changes were restored after treatment with tianeptine or haloperidol. Western blot and immunohistochemical analyses of the prefrontal cortex revealed downregulation of several neurodevelopmental proteins in PNS rats. After treatment with tianeptine or haloperidol, their expression levels were increased. CONCLUSION: Downregulation of several proteins in PNS rats might have caused subsequent behavioral changes in PNS rats. After tianeptine or haloperidol treatment, behavioral changes in PNS rats were restored. Therefore, tianeptine might decrease incidence of prenatal stress related-psychiatric disorders such as depression and schizophrenia.

Effects of tianeptine on symptoms of fibromyalgia via BDNF signaling in a fibromyalgia animal model

Previous reports have suggested that physical and psychological stresses may trigger fibromyalgia (FM). Stress is an important risk factor in the development of depression and memory impairments. Antidepressants have been used to prevent stress-induced abnormal pain sensation. Among various antidepressants, tianeptine has been reported to be able to prevent neurodegeneration due to chronic stress and reverse decreases in hippocampal volume. To assess the possible effect of tianeptine on FM symptoms, we constructed a FM animal model induced by restraint stress with intermittent cold stress. All mice underwent nociceptive assays using electronic von Frey anesthesiometer and Hargreaves equipment. To assess the relationship between tianeptine and expression levels of brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), and phosphorylated cAMP response element-binding protein (p-CREB), western blotting and immunohistochemistry analyses were performed. In behavioral analysis, nociception tests showed that pain threshold was significantly decreased in the FM group compared to that in the control group. Western blot and immunohistochemical analyses of medial prefrontal cortex (mPFC) and hippocampus showed downregulation of BDNF and p-CREB proteins in the FM group compared to the control group. However, tianeptine recovered these changes in behavioral tests and protein level. Therefore, this FM animal model might be useful for investigating mechanisms linking BDNF-CREB pathway and pain. Our results suggest that tianeptine might potentially have therapeutic efficacy for FM.

Survey of the Patterns of Using Stereotactic Ablative Radiotherapy for Early-Stage Non-small Cell Lung Cancer in Korea / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Stereotactic ablative radiotherapy (SABR) is an effective emerging technique for early-stage non-small cell lung cancer (NSCLC). We investigated the current practice of SABR for early-stage NSCLC in Korea. MATERIALS AND METHODS: We conducted a nationwide survey of SABR for NSCLC by sending e-mails to all board-certified members of the Korean Society for Radiation Oncology. The survey included 23 questions focusing on the technical aspects of SABR and 18 questions seeking the participants' opinions on specific clinical scenarios in the use of SABR for early-stage NSCLC. Overall, 79 radiation oncologists at 61/85 specialist hospitals in Korea (71.8%) responded to the survey. RESULTS: SABR was used at 33 institutions (54%) to treat NSCLC. Regarding technical aspects, the most common planning methods were the rotational intensity-modulated technique (59%) and the static intensity-modulated technique (49%). Respiratory motion was managed by gating (54%) or abdominal compression (51%), and 86% of the planning scans were obtained using 4-dimensional computed tomography. In the clinical scenarios, the most commonly chosen fractionation schedule for peripherally located T1 NSCLC was 60 Gy in four fractions. For centrally located tumors and T2 NSCLC, the oncologists tended to avoid SABR for radiotherapy, and extended the fractionation schedule. CONCLUSION: The results of our survey indicated that SABR is increasingly being used to treat NSCLC in Korea. However, there were wide variations in the technical protocols and fractionation schedules of SABR for early-stage NSCLC among institutions. Standardization of SABR is necessary before implementing nationwide, multicenter, randomized studies.

Radiation for persistent or recurrent epithelial ovarian cancer: a need for reassessment

PURPOSE: The role of radiotherapy (RT) was largely deserted after the introduction of platinum-based chemotherapy, but still survival rates are disappointingly low. This study focuses on assessing the clinical efficacy of RT in relation to chemotherapy resistance. MATERIALS AND METHODS: From October 2002 to January 2015, 44 patients were diagnosed with epithelial ovarian cancer (EOC) and treated with palliative RT for persistent or recurrent EOC. All patients received initial treatment with optimal debulking surgery and adjuvant platinum-based chemotherapy. The biologically effective dose (BED) was calculated with α/β set at 10. Ninety-four sites were treated with RT with a median BED of 50.7 Gy (range 28.0 to 79.2 Gy). The primary end-point was the in-field local control (LC) interval, defined as the time interval from the date RT was completed to the date any progressive or newly recurring disease within the RT field was detected on radiographic imaging. RESULTS: The median follow-up duration was 52.3 months (range 7.7 to 179.0 months). The 1-year and 2-year in-field LC rates were 66.0% and 55.0%, respectively. Comparisons of percent change of in-field tumor response showed similar distribution of responses among chemoresistant and chemosensitive tumors. On multivariate analysis of predictive factors for in-field LC analyzed by sites treated, BED ≥ 50 Gy (hazard ratio, 0.4; confidence interval, 0.2–0.9; p = 0.025) showed better outcomes. CONCLUSION: Regardless of resistance to platinum-based chemotherapy, RT can be a feasible treatment modality for patients with persistent of recurrent EOC. The specific role of RT using updated approaches needs to be reassessed.

Major clinical research advances in gynecologic cancer in 2016: 10-year special edition / 부인종양

In 2016, 13 topics were selected as major research advances in gynecologic oncology. For ovarian cancer, study results supporting previous ones regarding surgical preventive strategies were reported. There were several targeted agents that showed comparable responses in phase III trials, including niraparib, cediranib, and nintedanib. On the contrary to our expectations, dose-dense weekly chemotherapy regimen failed to prove superior survival outcomes compared with conventional triweekly regimen. Single-agent non-platinum treatment to prolong platinum-free-interval in patients with recurrent, partially platinum-sensitive ovarian cancer did not improve and even worsened overall survival (OS). For cervical cancer, we reviewed robust evidences of larger-scaled population-based study and cost-effectiveness of nonavalent vaccine for expanding human papillomavirus (HPV) vaccine coverage. Standard of care treatment of locally advanced cervical cancer (LACC) was briefly reviewed. For uterine corpus cancer, new findings about appropriate surgical wait time from diagnosis to surgery were reported. Advantages of minimally invasive surgery over conventional laparotomy were reconfirmed. There were 5 new gene regions that increase the risk of developing endometrial cancer. Regarding radiation therapy, Post-Operative Radiation Therapy in Endometrial Cancer (PORTEC)-3 quality of life (QOL) data were released and higher local control rate of image-guided adaptive brachytherapy was reported in LACC. In addition, 4 general oncology topics followed: chemotherapy at the end-of-life, immunotherapy with reengineering T-cells, actualization of precision medicine, and artificial intelligence (AI) to make personalized cancer therapy real. For breast cancer, adaptively randomized trials, extending aromatase inhibitor therapy, and ribociclib and palbociclib were introduced.

Underexpression of HOXA11 Is Associated with Treatment Resistance and Poor Prognosis in Glioblastoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Homeobox (HOX) genes are essential developmental regulators that should normally be in the silenced state in an adult brain. The aberrant expression of HOX genes has been associated with the prognosis of many cancer types, including glioblastoma (GBM). This study examined the identity and role of HOX genes affecting GBM prognosis and treatment resistance. MATERIALS AND METHODS: The full series of HOX genes of five pairs of initial and recurrent human GBM samples were screened by microarray analysis to determine the most plausible candidate responsible for GBM prognosis. Another 20 newly diagnosed GBM samples were used for prognostic validation. In vitro experiments were performed to confirm the role of HOX in treatment resistance. Mediators involved in HOX gene regulation were searched using differentially expressed gene analysis, gene set enrichment tests, and network analysis. RESULTS: The underexpression of HOXA11 was identified as a consistent signature for a poor prognosis among the HOX genes. The overall survival of the GBM patients indicated a significantly favorable prognosis in patients with high HOXA11 expression (31±15.3 months) compared to the prognoses in thosewith low HOXA11 expression (18±7.3 months, p=0.03). When HOXA11 was suppressed in the GBM cell lines, the anticancer effect of radiotherapy and/or temozolomide declined. In addition, five candidate mediators (TGFBR2, CRIM1, TXNIP, DPYSL2, and CRMP1) that may confer an oncologic effect after HOXA11 suppression were identified. CONCLUSION: The treatment resistance induced by the underexpression of HOXA11 can contribute to a poor prognosis in GBM. Further investigation will be needed to confirm the value of HOXA11 as a potential target for overcoming the treatment resistance by developing chemo- or radiosensitizers.

Toxicokinetics of paraquat in Korean patients with acute poisoning

To conduct a kinetic study of paraquat (PQ), we investigated 9 patients with acute PQ intoxication. All of them ingested more than 20 ml of undiluted PQ herbicide to commit suicide and arrived at our hospital early, not later than 7 h after PQ ingestion. The urine dithionite test for PQ in all of the nine patients was strongly positive at emergency room. Blood samples were obtained every 30 min for the first 2~3 h and then every 1 or 2 h, as long as the clinical progression was stable among the patients for 30 h after PQ ingestion. The area under the plasma concentration-time curve (AUCinf), which was extrapolated to infinity, was calculated using the trapezoidal rule. Toxicokinetic parameters, such as the terminal elimination half-life, apparent oral clearance, and apparent volume of distribution (Vd/F) were calculated. The maximum PQ concentration (Cmax) and the time to reach maximum PQ concentration (Tmax) were also obtained. Plasma PQ concentrations in nine patients were well described by a bi-exponential curve with a mean terminal elimination half-life of 13.1+/-6.8 h. Cmax and AUCinf were 20.8+/-25.7 mg/l and 172.5+/-160.3 h.mg/l, respectively. Apparent volume of distribution and apparent oral clearance were 50.9+/-61.3 l/kg and 173.4+/-111.2 l/h, respectively. There were a significant correlation (r =0.84; p<0.05) between the PQ amount ingested and Cmax. AUCinf also showed a significant correlation (r =0.83; p<0.05) with the PQ amount ingested. These correlations provide evidence that PQ has dose-linear toxicokinetic characteristics.

Current status of brachytherapy in Korea: a national survey of radiation oncologists / 부인종양

OBJECTIVE: The aim of the present study was to acquire information on brachytherapy resources in Korea through a national survey of radiation oncologists. METHODS: Between October 2014 and January 2015, a questionnaire on the current status of brachytherapy was distributed to all 86 radiation oncology departments in Korea. The questionnaire was divided into sections querying general information on human resources, brachytherapy equipment, and suggestions for future directions of brachytherapy policy in Korea. RESULTS: The response rate of the survey was 88.3%. The average number of radiation oncologists per center was 2.3. At the time of survey, 28 centers (36.8%) provided brachytherapy to patients. Among the 28 brachytherapy centers, 15 (53.5%) were located in in the capital Seoul and its surrounding metropolitan areas. All brachytherapy centers had a high-dose rate system using (192)Ir (26 centers) or (60)Co (two centers). Among the 26 centers using (192)Ir sources, 11 treated fewer than 40 patients per year. In the two centers using (60)Co sources, the number of patients per year was 16 and 120, respectively. The most frequently cited difficulties in performing brachytherapy were cost related. A total of 21 centers had a plan to sustain the current brachytherapy system, and four centers noted plans to upgrade their brachytherapy system. Two centers stated that they were considering discontinuation of brachytherapy due to cost burdens of radioisotope source replacement. CONCLUSION: The present study illustrated the current status of brachytherapy in Korea. Financial difficulties were the major barriers to the practice of brachytherapy.