Hypofractionated Radiotherapy for Early-Stage Breast Cancer: A Propensity Score Matched Analysis.

BACKGROUND: In patients with early-stage breast cancer, the treatment results of hypofractionated radiation therapy (RT) and conventional RT are evaluated in efficacy and cost. METHODS: We retrospectively evaluated 280 patients with early-stage (Tis-2N0M0) breast cancer (including 100 hypofractionated RT patients) with regards to treatment outcomes according to the RT schedule. The median whole-breast RT dose was 42.56 Gy/16 fractions for hypofractionated RT and 50.4 Gy/28 fractions for conventional RT. Most patients (n = 260, 92.9%) additionally received a tumor bed boost RT. We used propensity score matching (PSM) analysis to balance the baseline risk factors for recurrence. The co-primary endpoints of this study were disease-free survival (DFS) and ipsilateral breast tumor recurrence (IBTR). DFS or IBTR was analyzed using the Kaplan-Meier survival curve and log-rank test. RESULTS: Total 89 pairs of matched patients (1:1 matching, n = 178) were finally evaluated. The median follow-up was 23.6 months. After matching, the 3-year DFS was 100% in the hypofractionated RT group and 98.4% in the conventional RT group; there was no significant difference in DFS between the groups (P = 0.374). Furthermore, the IBTR did not differ between the hypofractionated RT and conventional RT groups (P = 0.374) after matching. The 3-year overall survival was not different between two groups (both 100%). Hypofractionated RT saved 26.6% of the total cost of RT compared to conventional RT. Additionally, the acute skin toxicity rate (≥ grade 2) was also not significantly different between the groups (hypofractionated RT: 10.1% vs. conventional RT: 2.2%). CONCLUSION: Hypofractionated RT showed good IBTR and DFS, which were compatible to those in conventional RT in breast cancer. Hypofractionated RT is expected to be used more widely because of its low cost and convenience.

Feasibility Study of Phosphor Screen Containing Nano-Scale Anti-Reflection Layer for Improved Optical Properties in Indirect X-ray Detector.

With increasingly strict regulations regarding patient exposure, research on digital radiography technology has recently focused on indirect methods that can produce high-quality images for a low radiation dose. In particular, medical imaging systems based on indirect methods universally use rare-earth metal phosphors, because of their high atomic number and excellent luminescence efficiency. Thus, various studies aiming to improve the luminescence efficiency of phosphors have been conducted. Despite this research, however, the current luminescence efficiencies are insufficient. Here, we report a basic study aiming to develop a phosphor screen containing a three-quarter-wave optical-thickness layer to improve the light transmission efficiency. Specifically, the fabrication and measurement of a Gd2O2S:Tb phosphor screen containing a single three-quarter-wave optical-thickness layer is presented. The screen is fabricated via a screen-printing and spin-coating method. Based on histograms of the degree of luminescence and the pixel values, we demonstrate that the light transmission efficiency is improved by the three-quarter-wave optical-thickness layer. Note that analysis of the full width at half maximum of the pixel value distribution reveals the possibility of resolution loss when obtaining medical images. Overall, the results of this study confirm that the light transmission efficiency can be improved through use of a single-layer anti-reflection coating. However, because the emission spectrum of the Gd2O2S:Tb screen is in the 480-600-nm band, it is necessary to expand the areas exhibiting the lowest reflectance to the wavelengths at the edge of this band. Thus, further study should be conducted to optimize the optical thickness.

Human soluble delta-like 1 homolog exerts antitumor effects in vitro and in vivo.

Proteolysis of delta-like 1 homolog (DLK1), a cell-surface transmembrane protein, produces an active soluble form of DLK1 (sDLK1). Both membrane-bound DLK1 and sDLK1 modulate multiple developmental processes including adipogenesis, osteogenesis, chondrogenesis and myogenesis. However, cancer-related functions of DLK1 have not yet been established. We thus evaluated the roles of extracellular sDLK1, comprising six EGF-like domains and juxtamembrane regions, in human pancreatic cancer MIA PaCa-2 cells in vitro and in vivo. We observed that sDLK1 exerted antitumor effects not only in cancer cell migration and anchorage-independent cell growth but also in in vivo tumor growth.

Targeting ODC1 inhibits tumor growth through reduction of lipid metabolism in human hepatocellular carcinoma.

Ornithine decarboxylase 1 (ODC1), a metabolic enzyme critically involved in the polyamine biosynthesis, is commonly upregulated in hepatocellular carcinoma (HCC). Despite its altered expression in human HCC tissues, the molecular mechanism by which ODC1 alters the course of HCC progression and functions in HCC cell survival is unknown. Here we identified that silencing of ODC1 expression with small interfering (si) RNA causes inhibition of HCC cell growth through blockade of cell cycle progression and induction of apoptosis. Next, to obtain insights into the molecular changes in response to ODC1 knockdown, global changes in gene expression were examined using RNA sequencing. It revealed that 119 genes show same directional regulation (76 up- and 43 down-regulated) in both Huh1 and Huh7 cells and were considered as a common ODC1 knockdown signature. Particularly, we found through a network analysis that KLF2, which is known to inhibit PPARγ expression and adipogenesis, was commonly up-regulated. Subsequent Western blotting affirmed that the downregulation of ODC1 was accompanied by a decrease in the levels of PPARγ as well as of PARP-1, cyclin E1 and pro-caspase 9 delaying cell cycle progression and accelerating apoptotic signaling. Following the down-regulation of PPARγ expression, ODC1 silencing resulted in a strong inhibition in the expression of important regulators of glucose transport and lipid biogenesis, and caused a marked decrease in lipid droplet accumulation. In addition, ODC1 silencing significantly inhibited the growth of human HCC xenografts in nude mice. These findings indicate that the function of ODC1 is correlated with HCC lipogenesis and suggest that targeting ODC1 could be an attractive option for molecular therapy of HCC.

Being Overweight or Obese Increases the Risk of Progression in Triple-Negative Breast Cancer after Surgical Resection.

This study aimed to evaluate the association between body mass index (BMI) and progression in triple-negative breast cancer (TNBC). We retrospectively reviewed the medical records of 50 patients with TNBC who underwent breast-conserving surgery or mastectomy between 2007 and 2014. All patients were classified according to BMI (median 23.5 kg/m(2), range 17.2-31.6 kg/m(2)): 31 patients (62%) were classified as being overweight or obese (BMI ≥ 23 kg/m(2)) and 19 patients (38%) were classified as having a normal body weight (BMI < 23 kg/m(2)). The median follow-up for patients was 31.1 months (range, 6.7-101.9 months). Progression occurred in 7 patients (14%), including 5 ipsilateral breast tumor recurrences, 2 regional lymph node metastases, and 5 distant metastases. Progression was significantly correlated with overweight or obese patients (P = 0.035), while none of the normal weight patients showed progression. The 3-year disease-free survival (DFS) and overall survival (OS) rates were 85.0% and 87.7%, respectively. DFS was significantly reduced in overweight or obese patients compared to that in normal weight patients (P = 0.035). However, OS was not significantly compromised by being overweight or obese (P = 0.134). In conclusion, being overweight or obese negatively affects DFS in TNBC patients.

Dose escalation using helical tomotherapy improves local control in spine metastases from primary hepatic malignancies.

BACKGROUND & AIMS: This study was designed to reveal the prognostic significance of dose-escalated radiotherapy with tomotherapy in local control for spine metastases of primary hepatic tumours. METHODS: From April 2006 to May 2012, 23 hepatocellular carcinoma patients and 7 intrahepatic cholangiocellular carcinoma patients (total 30 patients, 42 spinal lesions) were treated for metastatic spine lesions with helical tomotherapy (HT). The gross tumour volume (GTV) was defined as a tumour evident from computed tomography and magnetic resonance imaging. Median values were as follows: GTV total dose of 48 Gy (range 21-51), fraction size of 6 Gy (range 3-8) and eight fractions (range 3-17). Pain response was checked according to visual analogue scale (from 0 to 10). RESULTS: The median follow-up was 5.6 months. Six events of local failure occurred, including five lesions in which spinal canals were involved at radiotherapy. Local control rate at 3 months was 86.6%. Biological equivalent dose (BED) was correlated with local control (AUC = 0.833). Higher BED (>56.0 Gy10 ) was associated with increased local control (P = 0.004). The median time to local progression in patients receiving ≤56.0 Gy10 and >56.0 Gy10 were 3 and 20.8 months respectively. Dose escalation (BED > 56.0 Gy10 ) was also associated with improved progression-free survival (median 14.7 vs. 2.8 months, P = 0.010). Pain reduction was observed in 90.9% (20/22) of patients with painful bone metastases. CONCLUSIONS: Dose-escalated radiotherapy (BED > 56.0 Gy10 ) using HT improved local control in spinal metastases of hepatic malignancies.

Efficacy of postoperative radiotherapy for high grade meningiomas.

The necessity of postoperative radiotherapy (PORT) for meningiomas remains contentious. Here, the role of PORT in patients who underwent surgical resection for WHO grade II and III meningiomas was assessed. The record of 114 patients with WHO grade II (n = 72) and III (n = 42) meningiomas treated at Samsung Medical Center between March 1995 and April 2013 were reviewed and classified according to the extent of surgical resection and implementation of PORT. Median follow-up was 55.9 months. Simpson grade (SG) I, II, III, and IV resections were achieved in 29, 56, 9 and 20 patients, respectively. The 5-year local control (LC) and overall survival rate was 65.8 and 84.2 %, respectively. Thirty patients (26.3 %) developed local failure and five patients (4.4 %) developed distant metastases. The extent of surgical resection (SG I-II vs. III-IV) was influenced by tumor location (orbital and skull base lesions vs. others, p = 0.001) and the surgeons' experience (>10 operations, p = 0.044). Extent of surgical resection was also associated with local failure, overall progression, and overall survival (p = 0.001, p < 0.001, and p < 0.001, respectively). PORT improved LC in patients with incomplete surgical resection (SG III-IV, p = 0.049). Complete resection (SG I-II) is an important prognostic factor for LC and survival, and the extent of surgical resection (SG I-II vs. III-IV) is influenced by tumor location. PORT could improve the LC in WHO grade II-III meningioma patients who underwent incomplete surgical resection (SG III-IV).

Functional Analysis of Genes Specifically Expressed during Aerial Hyphae Collapse as a Potential Signal for Perithecium Formation Induction in Fusarium graminearum.

Fusarium graminearum, the causal agent of Fusarium head blight (FHB) in cereal crops, employs the production of sexual fruiting bodies (perithecia) on plant debris as a strategy for overwintering and dissemination. In an artificial condition (e.g., carrot agar medium), the F. graminearum Z3643 strain was capable of producing perithecia predominantly in the central region of the fungal culture where aerial hyphae naturally collapsed. To unravel the intricate relationship between natural aerial hyphae collapse and sexual development in this fungus, we focused on 699 genes differentially expressed during aerial hyphae collapse, with 26 selected for further analysis. Targeted gene deletion and quantitative real-time PCR analyses elucidated the functions of specific genes during natural aerial hyphae collapse and perithecium formation. Furthermore, comparative gene expression analyses between natural collapse and artificial removal conditions reveal distinct temporal profiles, with the latter inducing a more rapid and pronounced response, particularly in MAT gene expression. Notably, FGSG_09210 and FGSG_09896 play crucial roles in sexual development and aerial hyphae growth, respectively. Taken together, it is plausible that if aerial hyphae collapse occurs on plant debris, it may serve as a physical cue for inducing perithecium formation in crop fields, representing a survival strategy for F. graminearum during winter. Insights into the molecular mechanisms underlying aerial hyphae collapse provides offer potential strategies for disease control against FHB caused by F. graminearum.

Effect of Epidermal Growth Factor Receptor Mutation on Positron Emission Tomography/Computed Tomography in Lung Cancer.

BACKGROUND/AIM: This study analyzed the effect of epidermal growth factor receptor (EGFR) mutations on fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) results in lung cancer and the pathological findings in patients subjected to surgery. PATIENTS AND METHODS: A total of 210 patients diagnosed with lung cancer by F-18 FDG PET/CT at Inje University Busan Paik Hospital between January 2018 and December 2023 were recruited. EGFR mutation tests were performed on biopsy specimens. Overall, 78 patients (37.1%) with EGFR mutations were included in this study. Twenty-seven patients (12.9%) had distant metastases at the time of diagnosis. Of all patients, 69 (32.9%) underwent surgery at our hospital, and their pathological findings were analyzed. RESULTS: The maximum standardized uptake value (SUVmax) of F-18 FDG PET/CT was <10 in patients with EGFR mutations. Patients with EGFR mutations were not commonly diagnosed with diabetes. When analyzing the pathological findings after surgery in the 69 patients, adenocarcinoma was more common in those with EGFR mutations. In contrast, perineural invasion was more common in patients without EGFR mutations. When analyzing the results of 69 patients with postoperative pathology, 25 relapsed during the median follow-up of 21.7 months (range=0.9-58.4 months). Patients who underwent surgery and had EGFR mutations (n=26) exhibited lower recurrence rates compared to those without EGFR mutations. Disease-free survival was longer in patients with EGFR mutations. CONCLUSION: In non-small-cell lung cancer with an EGFR mutation, the F-18 FDG PET/CT SUVmax value and the probability of recurrence were lower. EGFR mutations are associated with low-glucose metabolism.

Lymphedema after regional nodal irradiation for breast cancer: a retrospective cohort study.

Purpose: We aimed to analyze the occurrence of lymphedema as a side effect in patients who underwent regional nodal irradiation (RNI) following surgery for breast cancer. Methods: This retrospective study was conducted on patients with breast cancer who underwent surgery from July 2014 to October 2020 at Inje University Busan Paik Hospital. The analysis included 113 cT1-3N1-3M0 breast cancer patients who underwent RNI as part of radiotherapy (RT). Mostly, surgeries were performed using breast-conserving surgery (n = 99, 87.6%), except for 14 patients with modified radical mastectomy. The total RT dose for RNI was 45-60 Gy, and the fraction size was 1.8-2.0 Gy. Most patients underwent chemotherapy (n = 98, 86.7%), including taxanes (n = 92, 81.4%). Results: The median follow-up was 61.1 months (range, 5.0-110.5 months). Lymphedema occurred in 54 patients (47.8%) after surgery. Twenty of them (17.7%) developed a new onset of lymphedema after RT, while 34 (30.1%) detected lymphedema before the completion of RT. Over the follow-up, 16 patients (14.2%) experienced recurrence. High radiation dose (>50.4 Gy) for RNI (P = 0.003) and taxane use (P = 0.038) were related to lymphedema occurrence after RT. Moreover, lymphedema occurrence after RT was also related to recurrence after surgical resection (P = 0.026). Breast-conserving surgery was related to early-onset lymphedema before the completion of RT (P = 0.047). Furthermore, the degree of lymph node dissection (≤4) was related to the overall occurrence of lymphedema (P = 0.045). Conclusion: Considering a reduction in RNI dose may be beneficial in mitigating the incidence of lymphedema after RT in patients with breast cancer.

Low body mass index is associated with poor treatment outcome following radiotherapy in esophageal squamous cell carcinoma.

PURPOSE: We aimed to determine whether patients with esophageal cancer with a low baseline body mass index (BMI) have a poor prognosis following radiotherapy (RT). MATERIALS AND METHODS: We retrospectively analyzed data from 50 patients with esophageal cancer to determine whether a low starting BMI (before RT) was associated with a poor outcome. All study participants were diagnosed with non-metastatic esophageal squamous cell carcinoma (SCC). RESULTS: The number of patients at each T stage were as follows: 7 (14%) patients at T1, 18 (36%) at T2, 19 (38%) at T3, and 6 (12%) at T4. Based on BMI, 7 (14%) patients were defined as underweight. A low BMI was common in patients with T3/T4 stage esophageal cancer (7/43, p = 0.01). Overall, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 26.3% and 69.2%, respectively. In univariate analysis, clinical factors associated with poor PFS included being underweight (BMI <18.5 kg/m2; p = 0.011) and a positive N status (p = 0.017). Univariate analysis also revealed that being underweight was associated with a decrease in OS (p = 0.003). However, being underweight was not an independent prognostic factor for PFS and OS. CONCLUSION: Patients with esophageal SCC with a low starting BMI (BMI <18.5 kg/m2) are more prone to have a negative survival outcome following RT than patients who are considered to be normal weight or overweight. For this reason, it is important that clinicians pay more attention to BMI when treating patients with esophageal SCC.

Reirradiation to the pelvis for recurrent rectal cancer.

OBJECTIVES: This study investigated late toxicity and infield progression-free survival in patients with locally recurrent rectal cancer (LRRC) who had previously received irradiation to the pelvis. METHODS: Twenty-two patients were treated by reirradiation to the pelvis between January 2000 and August 2007. All patients received curative surgery with preoperative or postoperative chemoradiotherapy as an initial treatment. Five patients (23%) underwent surgical resection after reirradiation. The median follow-up duration was 20 months (range, 7-91 months). RESULTS: Two patients (9%) had grade-3 acute toxicity and eight patients (36%) had grade-3 to -4 late toxicity. The incidence of grade-3 to -4 late toxicity in the gastrointestinal and urinary system was 18% and 27%, respectively. Recurrent tumor location (axial or anterior) and surgical resection after reirradiation significantly influenced severe late toxicity (P = 0.024 and P = 0.039, respectively). In the 17 patients not undergoing surgery after reirradiation, median infield progression-free survival was 16 months. Reirradiation doses exceeding 50 Gy(αß10) (equivalent dose in 2 Gy fractions) significantly increased the infield progression-free survival (P = 0.005). CONCLUSIONS: Tumor location (axial or anterior) and surgery after reirradiation may increase severe late toxicity. In addition, an EQD2 exceeding 50 Gy(αß10) may improve infield control.

18F-FDG PET/CT Parameters for Predicting Prognosis in Esophageal Cancer Patients Treated With Concurrent Chemoradiotherapy.

BACKGROUND AND AIMS: This study evaluated the prognostic value of 18F-fluorodeoxyglucose positron emission tomography with integrated computed tomography (18F-FDG PET/CT) performed before and after concurrent chemoradiotherapy (CCRT) in esophageal cancer. METHODS: We analyzed the prognosis of 50 non-metastatic squamous cell esophageal cancer (T1-4N0-2) patients who underwent CCRT with curative intent at Inje University Busan Paik Hospital and Haeundae Paik Hospital from 2009 to 2019. Median total radiation dose was 54 Gy (range 34-66 Gy). Our aim was to investigate the relationship between PET/CT values and prognosis. The primary end point was progression-free survival (PFS). RESULTS: The median follow-up period was 9.9 months (range 1.7-85.7). Median baseline maximum standard uptake value (SUVmax) was 14.2 (range 3.2-27.7). After treatment, 29 patients (58%) showed disease progression. The 3-year PFS and overall survival (OS) were 24.2% and 54.5%, respectively. PFS was significantly lower (P = 0.015) when SUVmax of initial PET/CT exceeded 10 (n = 22). However, OS did not reach a significant difference based on maximum SUV (P = 0.282). Small metabolic tumor volume (≤14.1) was related with good PFS (P = 0.002) and OS (P = 0.001). Small total lesion of glycolysis (≤107.3) also had a significant good prognostic effect on PFS (P = 0.009) and OS (P = 0.025). In a subgroup analysis of 18 patients with follow-up PET/CT, the patients with SUV max ≤3.5 in follow-up PET/CT showed longer PFS (P = 0.028) than those with a maximum SUV >3.5. CONCLUSION: Maximum SUV of PET/CT is useful in predicting prognosis of esophageal cancer patients treated with CCRT. Efforts to find more effective treatments for patients at high risk of progression are still warranted.

Pre- and Post-diagnosis Diabetes as a Risk Factor for All-Cause and Cancer-Specific Mortality in Breast, Prostate, and Colorectal Cancer Survivors: a Prospective Cohort Study.

Objective: The relationship between diabetes and all- and cause-specific mortality in individuals with common cancers (breast, colorectal, and prostate) remains both under-researched and poorly understood. Methods: Cancer survivors (N = 37,993) from the National Health Interview Survey with linked data retrieved from the National Death Index served as our study participants. Cox proportional-hazards models were used to assess associations between pre- and post-diabetes and all-cause and cause-specific mortality. Results: Over a median follow-up period of 13 years, 2,350 all-cause, 698 cancer, and 506 CVD deaths occurred. Among all cancer survivors, patients with diabetes had greater risk of: all-cause mortality [hazard ratio (HR) 1.35, 95% CI = 1.27-1.43], cancer-specific mortality (HR: 1.14, 95% CI = 1.03-1.27), CVD mortality (HR: 1.36, 95% CI = 1.18-1.55), diabetes related mortality (HR: 17.18, 95% CI = 11.51-25.64), and kidney disease mortality (HR: 2.51, 95% CI = 1.65-3.82), compared with individuals without diabetes. The risk of all-cause mortality was also higher amongst those with diabetes and specific types of cancer: breast cancer (HR: 1.28, 95% CI = 1.12-1.48), prostate cancer (HR: 1.20, 95% CI = 1.03-1.39), and colorectal cancer (HR: 1.29, 95% CI = 1.10-1.50). Diabetes increased the risk of cancer-specific mortality among colorectal cancer survivors (HR: 1.36, 95% CI = 1.04-1.78) compared to those without diabetes. Diabetes was associated with higher risk of diabetes-related mortality when compared to non-diabetic breast (HR: 9.20, 95% CI = 3.60-23.53), prostate (HR: 18.36, 95% CI = 6.01-56.11), and colorectal cancer survivors (HR: 12.18, 95% CI = 4.17-35.58). Both pre- and post-diagnosis diabetes increased the risk of all-cause mortality among all cancer survivors. Cancer survivors with diabetes had similar risk of all-cause and CVD mortality during the second 5 years of diabetes and above 10 years of diabetes as compared to non-diabetic patients. Conclusions: Diabetes increased the risk of all-cause mortality among breast, prostate, and colorectal cancer survivors, not for pre- or post-diagnosis diabetes. Greater attention on diabetes management is warranted in cancer survivors with diabetes.

Maximum standardized uptake value at pre-treatment PET in estimating lung cancer progression after stereotactic body radiotherapy.

PURPOSE: This study aimed to identify the feasibility of the maximum standardized uptake value (SUVmax) on baseline 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) as a predictive factor for prognosis in early stage primary lung cancer treated with stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: Twenty-seven T1-3N0M0 primary lung cancer patients treated with curative SBRT between 2010 and 2018 were retrospectively evaluated. Four patients (14.8%) treated with SBRT to address residual tumor after wedge resection and one patient (3.7%) with local recurrence after resection were included. The SUVmax at baseline PET/CT was assessed to determine its relationship with prognosis after SBRT. Patients were divided into two groups based on maximum SUVmax on pre-treatment FDG PET/CT, estimated by receiver operating characteristic curve. RESULTS: The median follow-up period was 17.7 months (range, 2.3 to 60.0 months). The actuarial 2-year local control, progressionfree survival (PFS), and overall survival were 80.4%, 66.0%, and 78.2%, respectively. With regard to failure patterns, 5 patients exhibited local failure (in-field failure, 18.5%), 1 (3.7%) experienced regional nodal relapse, and other 2 (7.4%) developed distant failure. SUVmax was significantly correlated with progression (p = 0.08, optimal cut-off point SUVmax > 5.1). PFS was significantly influenced by pretreatment SUVmax (SUVmax > 5.1 vs. SUVmax ≤ 5.1; p = 0.012) and T stage (T1 vs. T2-3; p = 0.012). CONCLUSION: SUVmax at pre-treatment FDG PET/CT demonstrated a predictive value for PFS after SBRT for lung cancer.

Diabetes as a prognostic factor in HER-2 positive breast cancer patients treated with targeted therapy.

PURPOSE: Recent studies revealed that metabolic stress influences the outcomes of breast cancer treatment. We sought to evaluate the prognostic effect of type 2 diabetes and find the molecular mechanism of relapses in postoperative HER-2+ breast cancer patients treated with HER-2 targeted therapy. MATERIALS AND METHODS: We evaluated 190 HER-2+ breast cancer patients (pT1-4N0-2M0) who were treated with surgical resection and trastuzumab (HER-2 targeted therapy) between 2006 and 2015. Survival outcomes and failure patterns were compared between such patients with (n = 12) and without (n = 178) type 2 diabetes. RESULTS: The median follow-up period was 42.4 months (range 12.0-124.7 months). Twenty-one patients (11.1%) showed relapse (including nine patients with locoregional failure), and three patients (1.6%) died as a result of cancer relapse. One-third of the patients with diabetes experienced relapse (4/12, 33.3%). The 3-year disease-free survival (DFS) and overall survival (OS) rates were 90.7% and 98.6%, respectively. Diabetic patients showed shorter DFS compared with non-diabetic patients (p = 0.006, 74.1% vs. 91.9%). OS was also shorter in diabetic patients compared with non-diabetic patients (p = 0.017, 91.7% vs. 99.1%). Of our interest, the levels of HER-3 and its ligand neuregulin-1 were significantly increased in the tumor specimen in HER-2+ breast cancer patients suffering with type 2 diabetes than that in the euglycemic control group. CONCLUSIONS: Type 2 diabetes was associated with detrimental effects on survival in postoperative HER-2+ breast cancer patients who were treated with trastuzumab. The poor prognostic effect of diabetes in HER-2+ breast cancer patients could be associated with the high levels of HER-3 and neuregulin 1, thus it should be considered and evaluated more.

Ki-67 labeling index as a prognostic marker in advanced stomach cancer.

PURPOSE: Proliferation marker Ki-67 is widely used in cancer prognosis prediction. We tried to investigate the role of Ki-67 as a prognostic factor in stomach cancer after surgery in this study. METHODS: We retrospectively evaluated 251 patients who underwent curative resection for gastric cancer from 2010 to 2015. In pathologic examination, Ki-67 labeling index was defined as the percentage of Ki-67 antigen positive cells. Prognostic significance of Ki-67 for gastric cancer was evaluated. Disease-free survival (DFS) was assessed as a primary end-point. RESULTS: The median follow-up period was 28.0 months. Thirty-one patients (12.4%) showed Ki-67 labeling index (LI) lower than 25%. Sixty-eight patients (26.6%) showed recurrence during follow-up period. Recurrence was associated with Ki-67 LI level (≤25%, P = 0.016), and lymph node metastasis status (P = 0.002). High Ki-67 LI level (>25%) was also related to p53 positivity (P < 0.001) and poorly cohesive type (P = 0.002). The 3-year DFS was 69.4%. Low Ki-67 LI level (≤25%) was related with low DFS (47.6% vs. 72.6%, P = 0.016). T stage (P < 0.001), N stage (P = 0.006), lymphovascular invasion (P = 0.010), and neuronal invasion (P = 0.001) also affected the DFS. In addition, T stage (P = 0.03) and Ki-67 LI (P = 0.035) were independent prognostic factors for DFS. In patients treated with adjuvant chemotherapy (n = 239, 93.4%), low Ki-67 (≤25%) was a poor prognostic factor for DFS (P = 0.013). CONCLUSION: Low Ki-67 LI predicts high rate of progression and low DFS of stomach cancer. Ki-67 LI can be a predictive marker in resected stomach cancer treated with surgery and adjuvant chemotherapy.

Prognostic Value of Ki-67 Labeling Index and Postoperative Radiotherapy in WHO Grade II Meningioma.

OBJECTIVE: This study was performed to determine the clinical significance of the Ki-67 labeling index (LI) for local control (LC) in patients with World Health Organization (WHO) grade II meningioma. We also tried to discern the effect of postoperative radiotherapy (PORT) on LC depending upon the Ki-67 LI value. MATERIALS AND METHODS: The medical records and values of Ki-67 LIs were retrospectively reviewed for 50 patients who underwent surgical resection of intracranial WHO grade II meningiomas at Samsung Medical Center from May 2001 to December 2012. Forty-three patients (86%) were treated with immediate PORT. The median total radiation dose was 60 Gy (range, 54 to 60 Gy). RESULTS: The median follow-up was 47.4 months. The mean Ki-67 LI was 13% (range, 1% to 47%). Twelve patients (24.0%) showed local failure, and 8 patients (16.0%) experienced local failure even after PORT. The mean Ki-67 LI was 15% in patients with local failure (n=12) and 12% in patients without local failure (n=38). The 3-year actuarial LC was 80.5%. The 3-year overall survival was 89.5%. Ki-67 LI>13% and PORT were significant prognostic factors for LC (P=0.015 and 0.009, respectively). In patients with Ki-67 LI>13% (n=17), PORT (n=14) improved LC (P<0.001). However, PORT (n=29) did not affect LC (P=0.412) for patients with Ki-67 LI≤13% (n=33). CONCLUSIONS: Ki-67 LI can be a useful prognostic factor for LC in WHO grade II meningioma. In patients with Ki-67 LI>13%, PORT should be recommended to improve LC.

Lymphovascular invasion as a negative prognostic factor for triple-negative breast cancer after surgery.

PURPOSE: This study aimed to evaluate the prognostic effects of lymphovascular invasion (LVI) in triple-negative breast cancer (TNBC) patients who underwent surgical resection. MATERIALS AND METHODS: A total of 63 non-metastatic TNBC patients who underwent surgical resection were retrospectively investigated from 2007 to 2016 in Inje University Busan Paik Hospital. Pathological tests revealed that 12 patients (19.0%) had LVI. Approximately 61.9% (n = 39) of the patients' samples stained positive for p53. Additional chemotherapy and radiotherapy (RT) were performed in 53 (84.1%) and 47 (74.6%) patients, respectively. RESULTS: The median follow-up period was 39.5 months (range, 5.9 to 123.0 months). The pathological T stage (p = 0.008), N stage (p = 0.014), and p53 positivity (p = 0.044) were associated with LVI. Overall, the 3-year disease-free survival (DFS) rate and overall survival (OS) rate were 85.4% and 90.2%, respectively. Ten patients (15.9%) experienced relapse. LVI (n = 12) was associated with relapses (p = 0.016). p53 positivity was correlated with poor DFS (p = 0.048). Furthermore, LVI was related to poor DFS (p = 0.011) and OS (p = 0.001) and considered as an independent prognostic factor for DFS (p = 0.039). The 3-year DFS of patients with LVI (n = 12) was only 58.3%. Adjuvant RT minimized the negative prognostic effect of LVI on DFS (p = 0.068 [with RT] vs. p = 0.011 [without RT]). CONCLUSION: LVI was related to the detrimental effects of disease progression and survival of TNBC patients. Thus, a more effective treatment strategy is needed for TNBC patients with LVI.

Diabetes mellitus increases the risk of intrahepatic recurrence of hepatocellular carcinoma after surgical resection.

AIMS AND BACKGROUND: The relationship between cancer and metabolism has recently been receiving attention. We investigated the prognostic influence of type 2 diabetes mellitus in patients with hepatocellular carcinoma (HCC) treated with curative resection. METHODS AND STUDY DESIGN: The records of 58 patients who underwent curative resection for HCC pT1-2N0M0 between 2010 and 2014 were reviewed retrospectively. Fourteen patients (24.1%) had diabetes mellitus at diagnosis. Local control (LC) was defined as time to recurrence in the liver. RESULTS: The median follow-up was 23.3 months. Relapses occurred in 20 patients (34.5%) during the follow-up period; 17 of them developed intrahepatic recurrence, which was associated with diabetes mellitus (p = 0.013) and alpha fetoprotein (AFP) levels >500 ng/mL (p = 0.019). Overall relapses (n = 20) were related to T stage (p = 0.044), AFP level (p = 0.005), and diabetes (p = 0.044). The 3-year local control (intrahepatic control), disease-free survival, and overall survival rates were 56.7%, 50.5%, and 84.3%, respectively. LC was affected by diabetes mellitus (p = 0.046), Barcelona Clinic Liver Cancer staging (p<0.001), Milan criteria for transplantation (p = 0.041), serosal invasion (p = 0.032), and microvascular invasion (p = 0.043). Diabetes was also associated with reduced LC in the subgroup with hepatitis B-related HCC (n = 44, p = 0.028). CONCLUSIONS: Diabetes mellitus is correlated with intrahepatic HCC recurrence after surgery. Greater attention should be paid to managing patients with HCC and diabetes mellitus.