e13036 Background: This study aimed to investigate the influence of insulin therapy for type 2 diabetes mellitus (T2D) on cancer development. Methods: We evaluated 4780 patients with T2D, treated at our institution, from 1994-2006, after excluding patients with 1) preexisting cancer or cancer within 1 year after T2D registration, 2) renal transplantation, and 3) follow-up period of < 5 years. The following information was collected from the patients’ electronic medical records: age; sex; registered date of T2D and cancer; last visit; use of metformin, insulin, and medications for microvascular complications; and start date of using insulin in the first year after cohort entrance. Insulin users were stratified according to insulin start date and complication as follows: < 3 months with (462 patients) or without complications (526 patients), ≥3 months with complications (852 patients) or without complications (1249 patients). The standardized incidence ratio (SIR) was calculated using the expected age-standardized incidence rate in Korea. The adjusted hazard ratio (AHR) of insulin was estimated for evaluation of all-year cancer risk and time interval of 3 years from cohort entrance. Results: SIR was > 1 in all cancer types except laryngeal and esophageal cancers. The median follow-up was 12 years (interquartile range: 9–15 years), and 679 events occurred. Insulin users had a significantly higher risk of all-time cancer. The patients with insulin use for ≥3 months without complications had a continuously increasing cancer risk 2–3, 4–6, 7–9, 10–12, and 13–15 years from cohort start (AHR [95% confidence interval {CI}]: 2.2 [0.91–5.3], P= 0.081; 2.39 [1.07–5.32], P= 0.0335; 1.98 [1.35–2.9], P= 0.0005; 2.41 [1.52–3.81], P= 0.0002; and 1.6 [0.6–2.83], P= 0.1077, respectively), while the rest did not. This was significantly associated with stomach, colorectal, lung, liver, pancreatic, and bladder cancers (AHR [95% CI]: 6.09 [2.58–14.4], P= 00001; 2.49 [1.22–5.07], P= 01188; 3.36 [1.18–9.51], P= 0.02265; 14.8 [1.97–110], P= 0.0088; 14.6 [1.88–113], P= 0.0103; and 10.4 [2.38–45.6], P= 0.00186, respectively). Conclusions: Incidences of gastrointestinal, lung, and bladder cancers could be increased in new insulin users without complications.
Radioresistance often leads to poor survival in concurrent chemoradiotherapy–treated cervical squamous cell carcinoma, and reliable biomarkers can improve prognosis. We compared the prognostic potential of hemoglobin, absolute neutrophil count, and absolute lymphocyte count with that of squamous cell carcinoma antigen in concurrent chemoradiotherapy–treated squamous cell carcinoma. We analyzed 152 patients with concurrent chemoradiotherapy and high-dose-rate intracavitary brachytherapy–treated cervical squamous cell carcinoma. Hemoglobin, absolute neutrophil count, absolute lymphocyte count, and squamous cell carcinoma antigen were quantitated and correlated with survival, using Cox regression, receiver operating characteristic curve analysis, and Kaplan–Meier plots. Both hemoglobin and absolute lymphocyte count in the second week of concurrent chemoradiotherapy (Hb2 and ALC2) and squamous cell carcinoma antigen in the third week of concurrent chemoradiotherapy (mid-squamous cell carcinoma antigen) correlated significantly with disease-specific survival and progression-free survival. The ratio of high-dose-rate intracavitary brachytherapy dose to total dose (high-dose-rate intracavitary brachytherapy ratio) correlated significantly with progression-free survival. Patients with both low Hb2 (≤11 g/dL) and ALC2 (≤639 cells/µL) showed a lower 5-year disease-specific survival rate than those with high Hb2 and/or ALC2, regardless of mid-squamous cell carcinoma antigen (mid-squamous cell carcinoma antigen: ≤4.7 ng/mL; 5-year disease-specific survival rate: 85.5% vs 94.6%, p = 0.0096, and mid-squamous cell carcinoma antigen: >4.7 ng/mL; 5-year disease-specific survival rate: 43.8% vs 66.7%, p = 0.192). When both Hb2 and ALC2 were low, the low high-dose-rate intracavitary brachytherapy ratio (≤0.43) subgroup displayed significantly lower 5-year disease-specific survival rate compared to the subgroup high high-dose-rate intracavitary brachytherapy ratio (>0.43) (62.5% vs 88.2%, p = 0.0067). Patients with both anemia and lymphopenia during concurrent chemoradiotherapy showed poor survival, independent of mid-squamous cell carcinoma antigen, and escalating high-dose-rate intracavitary brachytherapy ratio might improve survival.
The authors apologize for the oversight in presenting incomplete affiliations for author Jin Sung Kim. Jin Sung Kim is affiliated with the Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea, and Oncosoft Inc., Seoul, Republic of Korea. The authors would like to apologize for any inconvenience caused. Assessment of deep learning-based auto-contouring on interobserver consistency in target volume and organs-at-risk delineation for breast cancer: Implications for RTQA program in a multi-institutional studyThe BreastVol. 73PreviewTo quantify interobserver variation (IOV) in target volume and organs-at-risk (OAR) contouring across 31 institutions in breast cancer cases and to explore the clinical utility of deep learning (DL)-based auto-contouring in reducing potential IOV. Full-Text PDF Open Access
4037 Background: Esophageal cancer has a relatively poor prognosis ( < 15% overall 5-year survival), owing to a lack of initial symptoms and delayed diagnosis. Also, patients with this fatal cancer tend to have a high rate of mental disorders. The psychological problems can affect treatment compliance and could increase mortality in cancer survivors. Methods: The aim of this longitudinal study was to analyze the prevalence of mental disorders in esophageal cancer survivors using claims data in South Korea. We confirmed mental disorders in a nationwide cohort of 8,879 patients who were diagnosed with esophageal cancer between January 1, 2010 and December 31, 2014. We categorized the prevalence of mental disorders based on the age and the time of diagnosis. Results: In esophageal cancer, a total of 738 patients were diagnosed with a mental disorder, 1 year prior to the cancer treatment. Of those patients, 231 were diagnosed with depression (31.3%) and 245 with anxiety (33.2%) during their first visit. The overall frequency of mental disorders peaked within 2 months after the cancer treatment. The highest rate of increase after treatment was confirmed in stress reaction/adjustment disorders. Age and sex was a significant predictive factor for mental disorders (p < 0.05). Female patients were at a higher risk for mental disorders (hazard ratio: 1.30, p = 0.002), whereas patients with initial treatment as surgery were more likely to have mental disorders compared with radiotherapy (hazard ratio: 1.33, p < 0.001). Conclusions: Mental disorders in esophageal cancer survivors showed different patterns of prevalence depending on the nature of disease. Timely diagnosis and intervention for psychological distress could increase the quality of life for esophageal cancer survivors. The frequency of mental disorders in esophageal cancer survivors (N = 8,879). Age Total number of esophageal cancer Mental disorder Substance abuse Depressive disorder Anxiety disorder Stress/ adjustment disorder Somatoform/ conversion disorder 10-39 25 2 1 1 0 0 0 40-49 367 34 14 7 8 3 2 50-59 2,072 174 51 53 41 9 20 60-69 3,212 285 50 83 91 29 32 70-99 3,203 243 13 87 92 22 29 Total 8,879 738 129 231 232 63 83
The purpose of the present study was to evaluate treatment outcomes and prognostic factors in cervical cancer patients with isolated para-aortic lymph node (PALN) metastases. We especially tried to evaluate PALN factors such as size, site and number.From August 1994 to December 2009, 40 cervical cancer patients with isolated PALN node metastases at initial diagnosis were selected for analysis. Patients underwent both extended field external beam and intracavitary brachytherapy. Fourteen patients received 5-fluorouracil and cisplatin (FP) and 16 patients received weekly concurrent cisplatin. Information of PALN, such as size, site, and number, was founded before PALN radiotherapy.The median follow-up time after primary treatment was 28.5 months (range, 2 to 213 months). The 3-year overall and progression-free survival rate after primary treatment was 44.3% and 31.3%, respectively. In multivariate analysis including tumor stage, performance status, and chemotherapy, FP regimen concurrent chemoradiotherapy was more effective than radiotherapy alone (p=0.030). The 3-year progression-free survival rate was 41.9% and 11.1% in patients with PALN numbers of ≤1 and ≥2, respectively (p=0.008). The 3-year progression-free survival rate was 42.1% and 19.2% in patients with PALN size of <1.5 cm and ≥1.5 cm, respectively (p=0.031).The radiologic features of PALN, such as number or size, can be used to determine prognosis in PALN metastatic cervical cancer patients. Furthermore, FP regimen concurrent chemoradiotherapy was associated with better patient survival than radiotherapy alone. However, more studies are required to confirm possible different treatment outcomes between FP and weekly cisplatin regimens.
Purpose Past studies have reported that S-allylcysteine (SAC) inhibits the migration and invasion of cancer cells through the restoration of E-cadherin, the reduction of matrix metalloproteinase (MMP) and Slug protein expression, and inhibition of the production of reactive oxygen species (ROS). Furthermore, evidence is emerging that shows that ROS induced by radiation could increase Met activation. Following on these reports of SAC and Met, we investigated whether SAC could suppress Met activation. Materials and Methods Wound healing, invasion, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium (MTT), soft agar colony forming, western blotting, and gelatin zymography assays were performed in the human nasopharyngeal cancer cell lines HNE1 and HONE1 treated with SAC (0, 10, 20, or 40 mM) and hepatocyte growth factor (HGF). Results This study showed that SAC could suppress the migration and invasion of HNE1 and HONE1 cell lines by inhibiting p-Met. An increase of migration and invasion induced by HGF and its decrease in a dose dependent manner by SAC in wound healing and invasion assays was observed. The reduction of p-Met by SAC was positively correlated with p-focal adhesion kinase (p-FAK) and p-extracellular related kinase (p-ERK in both cell lines). SAC reduced Slug, MMP2, and MMP9 involved in migration and invasion with the inhibition of Met-FAK signaling. Conclusion These results suggest that SAC inhibited not only Met activation but also the downstream FAK, Slug, and MMP expression. Finally, SAC may be a potent anticancer compound for nasopharyngeal cancer treated with radiotherapy. Keywords: Nasopharyngeal cancer, Met, S-allylcysteine, Migration, Invasion
e16054 Background: The growing number of incident cases of gastric cancer along with improved survival results in a rising population of survivors at risk of second primary cancers (SPC). Aims: In this study, we analyzed SPC risk in stomach cancer survivors to compared the incidence of SPC with that expected in the general population. Methods: We selected adult ( > 19 years) patients with gastric cancer as first primary malignancy diagnosed from January 2010 to December 2014 using claims data from the Health Insurance Review and Assessment Service (HIRA) in South Korea. We analyzed the frequency and standardized incidence ratios (SIRs) to estimate the risk of SPC in gastric cancer survivors. Results: Among 115,914 patients with first primary gastric cancer, 3,165 (2.7%) developed SPC. The mean time to first SPM from the time of diagnosis of stomach cancer was 20.2 ± 12.5 months. The most common site was colorectal, which occurred in 529 patients (16.7%), and lung in 407 patients (12.9%), thyroid in 284 patients (9.0%), prostate in 270 patients (8.5%), liver in 260 patients (8.2%), and esophagus in 185 (5.8%). Among men, the most frequent were colorectal, lung, prostate and esophageal cancer; in women, colorectal cancer, thyroid and breast cancer were the most common. The SIR for all cancers was 1.24 in all patients, 1.30 in males, and 1.14 in females. Among both sexes, significantly higher SIRs were observed for cancers of the esophagus (6.94), small intestine (5.63) and Non-Hodgkin lymphoma (3.50). Interestingly, there was decreased risk of thyroid (SIR: 0.63), breast (SIR: 0.52) and skin cancer (SIR: 0.83). The risk of secondary cancer was found to be significantly higher within one year after primary cancer diagnosis (SIR: 2.42). Conclusions: Patients with gastric cancer were found to be at increased risk of developing SPC in compared to the general population. Close surveillance of these patients within one year after diagnosis was needed for early detection.
Our institution has implemented two different adjuvant protocols in treating patients with non-small cell lung cancer (NSCLC): chemotherapy followed by concurrent chemoradiotherapy (CT-CCRT) and sequential postoperative radiotherapy (PORT) followed by postoperative chemotherapy (POCT). We aimed to compare the clinical outcomes between the two adjuvant protocols.From March 1997 to October 2012, 68 patients were treated with CT-CCRT (n = 25) and sequential PORT followed by POCT (RT-CT; n = 43). The CT-CCRT protocol consisted of 2 cycles of cisplatin-based POCT followed by PORT concurrently with 2 cycles of POCT. The RT-CT protocol consisted of PORT followed by 4 cycles of cisplatin-based POCT. PORT was administered using conventional fractionation with a dose of 50.4-60 Gy. We compared the outcomes between the two adjuvant protocols and analyzed the clinical factors affecting survivals.Median follow-up time was 43.9 months (range, 3.2 to 74.0 months), and the 5-year overall survival (OS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were 53.9%, 68.2%, and 51.0%, respectively. There were no significant differences in OS (p = 0.074), LRFS (p = 0.094), and DMFS (p = 0.490) between the two protocols. In multivariable analyses, adjuvant protocol remained as a significant prognostic factor for LRFS, favouring CT-CCRT (hazard ratio [HR] = 3.506, p = 0.046) over RT-CT, not for OS (HR = 0.647, p = 0.229).CT-CCRT protocol increased LRFS more than RT-CT protocol in patients with completely resected NSCLC, but not in OS. Further studies are warranted to evaluate the benefit of CCRT strategy compared with sequential strategy.
This article reviewed new trends and controversial issues, including the intensification of chemotherapy and recent brachytherapy (BT) advances, and also reviewed recent consensuses from different societies on the management of locally advanced cervical cancer (LACC). Intensive chemotherapy during and after radiation therapy (RT) was not recommended as a standard treatment due to severe toxicities reported by several studies. The use of positron emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI) for pelvic RT planning has increased the clinical utilization of intensity-modulated radiation therapy (IMRT) for the evaluation of pelvic lymph node metastasis and pelvic bone marrow. Recent RT techniques for LACC patients mainly aim to minimize toxicities by sparing the normal bladder and rectum tissues and shortening the overall treatment time by administering a simultaneous integrated boost for metastatic pelvic lymph node in pelvic IMRT followed by MRI-based image guided adaptive BT. Keywords: Uterine cervical neoplasms, Intensity-modulated radiotherapy, Drug therapy, Brachytherapy
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