• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7097-7103
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• 2014

Over-expression of de novo lipogenesis (DNL) genes is associated with the prognosis of various types of cancers. However, the effects of single nucleotide polymorphisms (SNPs) in these genes on recurrence and survival of non-small cell lung cancer (NSCLC) patients after surgery are still unknown. In this study, a total of 500 NSCLC patients who underwent surgery treatment were included. Eight SNPs in 3 genes (ACACA, FASN and ACLY) of the DNL pathway were examined using the Sequenom iPLEX genotyping system. Multivariate Cox proportional hazards regression and Kaplan-Meier curves were used to analyze the association of SNPs with patient survival and tumour recurrence. We found that two SNPs in the FASN gene were significantly associated with the recurrence of NSCLC. SNP rs4246444 had a significant association with lung cancer recurrence under additive model (hazard ratio [HR], 0.82; 95% confidence interval [95%CI], 0.67-1.00; p=0.05). Under the dominant model, rs4485435 exhibited a significant association with recurrence (HR, 0.75; 95%CI, 0.56-1.01; p=0.05). Additionally, SNP rs9912300 in ACLY gene was significantly associated with overall survival in lung cancer patients (HR, 1.41; 95%CI, 1.02-1.94, p=0.04) under the dominant model. Further cumulative effect analysis showed moderate dose-dependent effects of unfavorable SNPs on both survival and recurrence. Our data suggest that the SNPs in DNL genes may serve as independent prognostic markers for NSCLC patients after surgery.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.5075-5079
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• 2015

Background: Adverse effects of treatment prolongation beyond 8 weeks with radiotherapy for cervical cancer have been established. Clinical data also show that cisplatin increases the biologically effective dose of radiotherapy. However, there are no data on the effect of overall treatment time in patients with locally advanced cervical cancer treated with concomitant chemo-radiotherapy (CCRT) in an Indian population. The present study concerned the feasibility of concurrent chemotherapy and interspacing brachytherapy during the course of external radiotherapy to reduce the overall treatment time and compare the normal tissue toxicity and loco-regional control with a conventional schedule. Materials and Methods: Between January 2009 and March 2012 fifty patients registered in the Gynaecologic Oncology Clinic of Institute Rotary Cancer Hospital with locally advanced cervical cancer (FIGO stage IIB-IIIB) were enrolled. The patients were randomly allocated to treatment arms based on a computer generated random number. Arm I (n=25) treatment consisted of irradiation of the whole pelvis to a dose of 50 Gy in 27 fractions, and weekly cisplatin $40mg/m^2$. High dose rate intra-cavitary brachytherapy (HDR-ICBT) was performed after one week of completion of external beam radiotherapy (EBRT). The prescribed dose for each session was 7Gy to point A for three insertions at one week intervals. Arm II (n=25) treatment consisted of irradiation of the whole pelvis to a dose of 50 Gy in 27 fractions. Mention HDR-ICBT ICRT was performed after 40Gy and 7Gy was delivered to point A for three insertions (days 23, 30, 37) at one week intervals. Cisplatin $20mg/m^2/day$ was administered from D1-5 and D24-28. Overall treatment time was taken from first day of EBRT to last day of HDR brachytherapy. The overall loco-regional response rate (ORR) was determined at 3 and 6 months. Results: A total of 46 patients completed the planned treatment. The overall treatment times in arm I and arm II were $65{\pm}12$ and $48{\pm}4$ days, respectively (p=0.001). At three and six months of follow-up the ORR for arm I was 96% while that for arm II was 88%. No statistically significant difference was apparent between the two arms. The overall rate of grade ${\geq}3$ toxicity was numerically higher in arm I (n=7) than in arm II (n=4) though statistical significance was not reached. None of the predefined prognostic factors like age, performance status, baseline haemoglobin level, tumour size, lymph node involvement, stage or histopathological subtype showed any impact on outcome. Conclusions: In the setting of concurrent chemoradiotherapy a shorter treatment schedule of 48 days may be feasible by interspacing brachytherapy during external irradiation. The response rates and toxicities were comparable.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.851-856
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• 2012

Objective: NBS1 plays a key role in the repair of DNA double-strand break (DSB). We conducted this study to investigate the effect of two critical polymorphisms (rs1805794 and rs13312840) in NBS1 on treatment response and prognosis of advanced non-small cell lung cancer (NSCLC) patients with platinum-based chemotherapy. Methods: Using TaqMan methods, we genotyped the two polymorphisms in 147 NSCLC patients. Odds ratios (ORs) and their 95% confidential intervals (CIs) were calculated as a measure of difference in the response rate of platinum-based chemotherapy using logistic regression analysis. The Kaplan-Meier and log-rank tests were used to assess the differences in progression-free survival (PFS) and overall survival (OS). Cox proportional hazards model was applied to assess the hazard ratios (HRs) for PFS and OS. Results: Neither of the two polymorphisms was significantly associated with treatment response of platinum-based chemotherapy. However, patients carrying the rs1805794 CC variant genotype had a significantly improved PFS compared to those with GG genotype (16.0 vs. 8.0 months, P = 0.040). Multivariable cox regression analysis further showed that rs1805974 was a significantly favorable prognostic factor for PFS [CC/CG vs. GG: Adjusted HR = 0.62, 95% CI: 0.39-0.99; CC vs. CG/GG: Adjusted HR = 0.56, 95% CI: 0.32-0.97). Similarly, rs13312840 with a small sample size also showed a significant association with PFS (CC vs. CT/TT: Adjusted HR = 25.62, 95% CI: 1.53-428.39). Conclusions: Our findings suggest that NBS1 polymorphisms may be genetic biomarkers for NSCLC prognosis especially PFS with platinum-based chemotherapy in the Chinese population.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3595-3600
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• 2016

Background: To investigate the association between preoperative pathological Ki-67 labeling index and serum tumor marker cancer antigen 15-3 (CA 15-3) with clinic-pathological parameters and treatment outcomes in early breast cancer. Materials and Methods: A retrospective study at 4 cancer centers in Saudi Arabia and Egypt was performed. Data were collected for female patients diagnosed with unilateral early breast cancer between March 2010 and October 2013. Cases treated with neoadjuvant chemotherapy (NACT) followed by surgery and radiotherapy were included. NACT included 6-8 cycles of anthracycline and taxane based regimens. Trastuzumab and hormonal treatments were added according to HER2 and hormone receptor status. Baseline serum CA15.3 and pathological Ki67 levels were evaluated and correlated with disease free survival (DFS) and overall survival (OS). Results: A total of 280 pts was included. The median age was 49 years (38-66 y) and median overall survival was 35 (20-38) months (mo). Estrogen receptors (ER), progesterone receptors (PR) and HER 2 receptors were positive in 233 (83.2%), 198 (70%) and 65 cases (23.2%), respectively. High preoperative Ki67 and CA15.3 were noted in 177 (63.2%) and 131 (46.8%). A total of 45 (16%) patients had distal or local recurrence and 24 (8.6%) died of their disease. Most of the relapsed cases had high preoperative Ki-67 (n=41, 91%) and CA15.3 (n=28, 62%) values. All of the patients who died had a high Ki-67 but CA15.3 was high in 9 (37%) only. Mean DFS/OS in patients with high preoperative Ki-67 was 32 months /32 months as compared to 37 months/35 months in those with normal Ki-67 (p<0.001). Correlation of preoperative CA15.3 and survival was statistically not significant. Conclusions:Preoperative Ki-67 can be a predictive and prognostic marker. Higher levels are associated with poor DFS and OS in patients with early BC.

• Journal of Trauma and Injury
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• v.22 no.1
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• pp.57-64
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• 2009

Purpose: Computed tomography (CT) is an accurate test for evaluating hemodynamically stable patients with blunt abdominal trauma. Until now, there have been few studies concentrating on the diagnostic and prognostic significance of the intravenous contrast extravasation (CE) site. We investigated the site of CE on abdominopelvic CT (APCT) and its effect on treating trauma patients and predicting the clinical outcome. Methods: The 50 patients admitted to our emergency department with blunt abdominal trauma showing CE on APCT from January 2004 to September 2006 were included in this study. Patients were prospectively collected, and medical records were reviewed and analyzed. The patients'clinical and lab findings, Focused Assessment with Sonography for Trauma (FAST) findings, CT findings were analyzed. CE sites were classified as intraperitoneal, retroperitoneal, and pelvic cavity and were correlated with post-treatment complications, mortality, and morbidity. Results: Of the 50 patients (mean age : $45{\pm}18years$, 29 males, 21 females) included in our study, 33 patients died (66%). There was no correlation between CE site and ICU or total hospitalization duration (p=0.553, p=0.523). During the first 24 hours of resuscitation, the pelvic cavity group required a mean of 20 units more of packed red blood cell (pRBC) transfusion compared to other groups (p=0.003). In the intraperitoneal group, more patients received operative invasive intervention - either laparotomy or embolization (p=0.025). The intraperitoneal group had the highest mortality, with 13 deaths (11/33, 39%), and the highest early mortality rate (10/13, 76%) in the first 24 hours (p=0.001). Conclusion: Intraperitoneal CE on the CT scan in cases of blunt abdominal trauma is regarded as an indication of a need for invasive intervention (either angiography or laparotomy) and of a higher mortality rate in the first 24 hours. A pelvic cavity CE rquires more aggressive transfusion with pRBC. However, the CT findings themselves showed no significant correlation with overall mortality, morbidity, or hospitalization.

• Journal of Trauma and Injury
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• v.27 no.4
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• pp.133-138
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• 2014

Purpose: If the survival of patients suffering from severe blunt trauma is to be improved, appropriate interventions should be taken immediately. The purpose of this study is to evaluate the clinical utility of end-tidal carbon dioxide ($ETCO_2$) as a surrogate marker for predicting both the need for intervention and the prognosis. Methods: This is a prospective observational study. Nasal cannula was applied to measure $ETCO_2$, and the following parameters, which are known to be related to the prognosis for a patient, were recorded: injury severity score (ISS), revised trauma score (RTS), arterial blood gas (ABG), lactate, and hemoglobin (Hb). To evaluate the outcome, we investigated the details of emergent interventions and expired patients. Results: A total of 93 patients were enrolled in this study. Emergent intervention was significantly associated with systolic blood pressure (sBP, p-value=0.001), $ETCO_2$ (p-value<0.001), serum lactate level (p-value<0.001), pH (p-value< 0.003), $HCO_3$ (p-value=0.004), base excess (p-value<0.002), ISS (p-value<0.001) and RTS (p-value=0.005). In the multivariate logistic regression, only $ETCO_2$ (odds ratio (OR): 0.897, 95% confidence interval (CI): 0.792-0.975, p-value= 0.048) and ISS (OR: 1.132, 95% CI: 1.053-1.233, p-value=0.002) were associated with emergent intervention whereas $ETCO_2$ (p-value=0.973) and ISS (p-value=0.511) were not statistically significant in predicting the survival of patients in the univariate analysis. An optimal ETCO cut-off of 29 mmHg on the ROC curve was determined, with the area under the ROC curve (AUC) being 0.824 (0.732-0.917)]. Conclusion: This study has revealed that $ETCO_2$, which can be rapid and easily measured through a nasal cannula, and the ISS may be prognostic indicators of emergent interventions in Emergency Departments.

• Korean Journal of Head & Neck Oncology
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• v.34 no.2
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• pp.23-28
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• 2018

Background/Objectives: Adenoid cystic carcinoma is the second most common salivary carcinoma. It occurs commonly in the submandibular gland, sublingual gland and minor salivary gland. Local recurrence and distant metastasis are the leading cause of death. The aim of this study was to evaluate long-term oncologic outcomes of patients with head and neck adenoid cystic carcinoma focusing on distant metastasis. Materials & Methods: We retrospectively studied 39 patients who were diagnosed with and treated for adenoid cystic carcinoma of the head and neck from December 1996 to May 2018. The clinicopathologic characteristics of patients such as age, sex, primary site and TNM stage, and treatment methods, recurrence and distant metastasis after treatment, survival rate, and treatment method for recurrence were analyzed. Results: Of 39 patients, 18 were males and 21 were females, and the mean age was $5.9{\pm}14.4$ (28-89) years. The most common primary site was oral cavity (12 cases), and followed by sino-nasal cavity (11 cases), parotid gland (5 cases), and etc. For treatment, 17 patients underwent surgery alone, 16 received surgery with postoperative radiation therapy, and 3 patients received radiation therapy only. Three patients refused any further treatments. Recurrence occurred in 15 patients. The most common site of recurrence was the lung. The mean time to recurrence was 31.7 months. The 5 and 10 years' overall survival rate was 79.3% and 74%, respectively. The 2 and 5 years' overall survival rate was 69.6% and 62.6% in patients with distant metastasis. Conclusion: Distant metastasis is an important prognostic factor in adenoid cystic carcinoma, and eventually one third of patients have distant metastasis, especially in the lung. An appropriate treatment for lung metastasis is necessary because some patients with pulmonary metastasis survive for a quite long time.

• Brain Tumor Research and Treatment
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• v.6 no.2
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• pp.60-67
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• 2018

Background Recently, modern technology such as diffusion tensor imaging (DTI), neuro-navigation and intraoperative neurophysiological monitoring (IOM) have been actively adopted for the treatment of thalamic tumors. We evaluated surgical outcomes and efficacy of the aforementioned technologies for the treatment of pediatric thalamic tumors. Methods We retrospectively reviewed clinical data from 37 children with thalamic tumors between 2004 and 2017. There were 44 operations (27 tumor resections, 17 biopsies). DTI was employed in 17 cases, neuro-navigation in 23 cases and IOM in 14 cases. All diagnoses were revised according to the 2016 World Health Organization Classification of Tumors of the Central Nervous System. Progression-free survival (PFS) and overall survival (OS) rates were calculated, and relevant prognostic factors were analyzed. The median follow-up duration was 19 months. Results Fifteen cases were gross total resections (GTR), 6 subtotal resections (STR), and 6 partial resections (PR). Neurological status did not worsen after 22 tumor resections. There were statistically significant differences in terms of the extent of resection between the groups with DTI, neuro-navigation and IOM (n=12, GTR or STR=12) and the group without at least one of the three techniques (n= 15, GTR or STR=9, p=0.020). The mean PFS was $87.2{\pm}38.0$ months, and the mean OS $90.7{\pm}36.1$ months. The 5-year PFS was 37%, and the 5-year OS 47%. The histological grade ($p{\leq}0.001$) and adjuvant therapy (done vs. not done, p=0.016) were significantly related to longer PFS. The histological grade (p=0.002) and the extent of removal (GTR/STR vs. PR/biopsy, p=0.047) were significantly related to longer OS. Conclusion Maximal surgical resection was achieved with acceptable morbidity in children with thalamic tumors by employing DTI, neuro-navigation and IOM. Maximal tumor resection was a relevant clinical factor affecting OS; therefore, it should be considered the initial therapeutic option for pediatric thalamic tumors.

• Journal of Trauma and Injury
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• v.34 no.1
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• pp.3-12
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• 2021

Purpose: To evaluate the severity of trauma, many scoring systems and predictive models have been presented. The quick Sequential Organ Failure Assessment (qSOFA) is a simple scoring system based on vital signs, and we expect it to be easier to apply to trauma patients than other trauma assessment tools. Methods: This study was a cross-sectional study of trauma patients who visited the emergency department of Jeju National University Hospital. We excluded patients under the age of 18 years and unknown outcomes. We calculated the qSOFA, the Modified Early Warning Score (mEWS), Revised Trauma Score (RTS), and Injury Severity Score (ISS) based on patients' initial vital signs and assessments performed in the emergency department (ED). The primary outcome was mortality within 14 days of trauma. We analyzed qSOFA scores using multivariate logistic regression analysis and compared the predictive accuracy of these scoring systems using the area under the receiver operating characteristic curve (AUROC). Results: In total, 27,764 patients were analyzed. In the multivariate logistic regression analysis of the qSOFA, the adjusted odds ratios with 95% confidence interval (CI) for mortality relative to a qSOFA score of 0 were 27.82 (13.63-56.79) for a qSOFA score of 1, 373.31 (183.47-759.57) for a qSOFA score of 2, and 494.07 (143.75-1698.15) for a qSOFA score of 3. In the receiver operating characteristic (ROC) curve analysis for the qSOFA, mEWS, ISS, and RTS in predicting the outcomes, for mortality, the AUROC for the qSOFA (AUROC [95% CI]; 0.912 [0.871-0.952]) was significantly greater than those for the ISS (0.700 [0.608-0.793]) and RTS (0.160 [0.108-0.211]). Conclusions: The qSOFA was useful for predicting the prognosis of trauma patients evaluated in the ED.

• Journal of Gastric Cancer
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• v.22 no.2
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• pp.120-134
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• 2022

Purpose: This study aimed to identify prognostic factors for patients with distant lymph node-involved gastric cancer (GC) using a machine learning algorithm, a method that offers considerable advantages and new prospects for high-dimensional biomedical data exploration. Materials and Methods: This study employed 79 features of clinical pathology, laboratory tests, and therapeutic details from 289 GC patients whose distant lymphadenopathy was presented as the first episode of recurrence or metastasis. Outcomes were measured as any-cause death events and survival months after distant lymph node metastasis. A prediction model was built based on possible outcome predictors using a random survival forest algorithm and confirmed by 5×5 nested cross-validation. The effects of single variables were interpreted using partial dependence plots. A contour plot was used to visually represent survival prediction based on 2 predictive features. Results: The median survival time of patients with GC with distant nodal metastasis was 9.2 months. The optimal model incorporated the prealbumin level and the prothrombin time (PT), and yielded a prediction error of 0.353. The inclusion of other variables resulted in poorer model performance. Patients with higher serum prealbumin levels or shorter PTs had a significantly better prognosis. The predicted one-year survival rate was stratified and illustrated as a contour plot based on the combined effect the prealbumin level and the PT. Conclusions: Machine learning is useful for identifying the important determinants of cancer survival using high-dimensional datasets. The prealbumin level and the PT on distant lymph node metastasis are the 2 most crucial factors in predicting the subsequent survival time of advanced GC.