• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.12
• /
• pp.6311-6318
• /
• 2012

Background: HER2/neu overexpression due to gene amplification is an important factor in breast cancer, modifying the sensitivity to anti-HER2 monoclonal antibody therapy. The clinical significance of HER2 expression in non small cell lung carcinoma (NSCLC) is currently under evaluation. The tumor suppressor gene PTEN negatively regulates the HER2/PI3K/Akt signalling pathway. The purpose of this study was to evaluate the role of simultaneous alteration in HER2 and PTEN protein expression in relation to biological behaviour of NSCLCs. Materials and Methods: Protein expression was determined by immunohistochemistry in sixty-one (n=61) NSCLC cases along with CISH for HER2 gene analysis and detection of chromosome 17 aneuploidy. Patients were followed-up for a period of 34 to 41 months after surgery. Results: HER2 overexpression (2+/3+score) was detected in 17 (27.9%) patients while loss of PTEN expression was observed in 24 (39.3%) cases, low expression in 29 (47.6%) and overexpression in 8 (13.1%). Simultaneous HER2 overexpression and PTEN low/loss of expression were correlated with metastasis (71.4% vs 36.2% p=0.03). Analysis in the subgroup of 22 patients of pTNM stage III with lymph node status N1 or N2 revealed that there was a relationship between the number of positive regional lymph node groups and simultaneous deregulation of the two genes (p=0.04). Multivariate analysis determined that HER2 overexpression was associated with an increasing risk of developing metastases (OR: 4.3; 95%CI: 1.2-15.9; p: 0.03) while PTEN overexpression was associated with lower risk (OR: 0.1; 95%CI: 0.1, 1.0; p: 0.05). Conclusions: Simultaneous HER2/PTEN deregulation is a significant genetic event that leads to a more aggressive phenotype of NSCLC.

• Korean Journal of Radiology
• /
• v.22 no.3
• /
• pp.344-353
• /
• 2021

Objective: The mitotic count of gastrointestinal stromal tumors (GIST) is closely associated with the risk of planting and metastasis. The purpose of this study was to develop a predictive model for the mitotic index of local primary GIST, based on deep learning algorithm. Materials and Methods: Abdominal contrast-enhanced CT images of 148 pathologically confirmed GIST cases were retrospectively collected for the development of a deep learning classification algorithm. The areas of GIST masses on the CT images were retrospectively labelled by an experienced radiologist. The postoperative pathological mitotic count was considered as the gold standard (high mitotic count, > 5/50 high-power fields [HPFs]; low mitotic count, ≤ 5/50 HPFs). A binary classification model was trained on the basis of the VGG16 convolutional neural network, using the CT images with the training set (n = 108), validation set (n = 20), and the test set (n = 20). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated at both, the image level and the patient level. The receiver operating characteristic curves were generated on the basis of the model prediction results and the area under curves (AUCs) were calculated. The risk categories of the tumors were predicted according to the Armed Forces Institute of Pathology criteria. Results: At the image level, the classification prediction results of the mitotic counts in the test cohort were as follows: sensitivity 85.7% (95% confidence interval [CI]: 0.834-0.877), specificity 67.5% (95% CI: 0.636-0.712), PPV 82.1% (95% CI: 0.797-0.843), NPV 73.0% (95% CI: 0.691-0.766), and AUC 0.771 (95% CI: 0.750-0.791). At the patient level, the classification prediction results in the test cohort were as follows: sensitivity 90.0% (95% CI: 0.541-0.995), specificity 70.0% (95% CI: 0.354-0.919), PPV 75.0% (95% CI: 0.428-0.933), NPV 87.5% (95% CI: 0.467-0.993), and AUC 0.800 (95% CI: 0.563-0.943). Conclusion: We developed and preliminarily verified the GIST mitotic count binary prediction model, based on the VGG convolutional neural network. The model displayed a good predictive performance.

• Radiation Oncology Journal
• /
• v.16 no.4
• /
• pp.485-495
• /
• 1998

Purpose : The major goal of the therapy in the soft tissue sarcoma is to control both local and distant tumor. However, the technique of obtaining local control has changed significantly over the past few decades from more aggressive surgery to combined therapy including conservative surgery and radiation and/or chemotherapy. We retrospectively analyzed the treatment results of the postoperative radiation therapy of soft tissue sarcoma and its prognostic factor. Materials and Methods : Between March 1983 and June 1994, 50 patients with soft tissue sarcoma were treated with surgery and postoperative radiation therapy at Kang-Nam St. Mary's hospital. Complete follow up was possible for all patients with median follow up duration 50 months (range 6-162 months). There were 28 male and 32 female patients. Their age ranged from 6 to 83 with a median of 44 years. Extremity (58$\%$) was the most frequent site of occurrence followed by trunk (20$\%$) and head and neck (12$\%$). Histologically malignant fibrous histiocytoma (23$\%$), liposarcoma (17$\%$), malignant schwannoma (12$\%$) constitute 52$\%$ of the patients. Daily radiation therapy designed to treat all areas at a risk for tumor spread upto dose of 4500-5000 cGy. A shrinking field technique was then used and total 55-65 Gy was delivered to tumor bed. Twenty-five patients (42$\%$) received chemotherapy with various regimen in the postoperative period. Results : Total 41 patients failed either with local recurrence or with distant metastasis. There were 29 patients (48$\%$) of local recurrence. Four patients (7$\%$) developed simultaneous local recurrence and distant metastasis and 8 patients (13$\%$) developed only distant metastasis. Local recurrence rate was rather higher than of other reported series. This study included patients of gross residual, recurrent cases after previous operation, trunk and head and neck Primary This feature is likely explanation for the decreased local control rate. Five of 29 Patients who failed only locally were salvaged by re-excision and/or re-irradiation and remained free of disease. Factors affecting local control include histologic type, grade, stage, extent of operation and surgical margin involvement, lymph node metastasis (p<0.05). All 21 patients who failed distantly are dead with progressive disease at the time of this report. Our overall survival results are similar to those of larger series. Actuarial 5 year overall survival and disease free survival were 60.4 $\%$, 30.6$\%$ respectively. Grade, stage (being close association with grade), residual disease (negative margin, microscopic, gross) were significant as a predictor of survival in our series (p<0.05). Conclusion : Combined surgery and postoperative radiation therapy obtained 5 year survival rate comparable to that of radical surgery.

• Radiation Oncology Journal
• /
• v.22 no.2
• /
• pp.115-123
• /
• 2004

Purpose : This retrospective study was conducted to compare early preliminary results of breast conservation therapy (BCT) with mastectomy In early breast cancer. Materials and Methods : We evaluated 171 women with AJCC stage I and II breast cancer who had been treated at Kangnam St. Mary's Hospital from March 1989 to August 1996. Eighty-eight patients underwent mastectomy and 85 patients did conservative surgery with breast irradiation. in the BCT group, all patients received whole breast irradiation to a total dose of 45$\~$50 Gy/5$\~$6 wks, followed by a boost to the original tumor site at least 60 Gy. Chemotherapy was administered to 29 (34.1$\%$) patients in BCT and 40 (45.5$\%$) in mastectomy, with various sequencing of surgery and/or radiation. We compared survival rate, patterns of failure in each treatment group and the prognostic factors that had a significant effect on treatment failure. The median follow-up time was 63 months (19$\~$111 months). Log rank test was used to estimate the prognostic factors for treatment failure. Results : Overall survival, disease free survival, locoregional recurrence and distant metastasis rates were not significantly different between the two treatment groups. During the follow-up period, 11 patients (12.5$\%$)in the mastectomy group and 10 patients (11.8%$\%$ in the BCT group were failed. Six local recurrences occurred after mastectomy and 5 after BCT Five patients fatted at distant site in mastectomy and 4 in BCT. Of the local recurrence cases, five of 6 mastectomy patients and 3 of S BCT patients were alive with no evidence of disease after salvage surgery and/or chemoirradiation. Our results indicated that the major influence on survival was distant metastasis. Unfortunately, control of distant metastasisis was not frequently achieved. Even with salvage systemic therapy or radiotherapy, most of distant metastasis patients died or had uncontrolled disease in both treatment groups: only one of 4 BCT patients and none of mastectomy patients were alive without disease. There was no apparent difference in the incidence rate of contralateral breast cancer and non-breast 2$^{nd}$ primary tumor between the two treatment groups. Univariate Log-rank test identified the N stage and the involved axillary LN number as distinct prognostic factors that were highly predictive of treatment failure in both treatment groups. Additionally, marginal status in BCT and histologic nuclear grade In the mastectomy group were risk factors for treatment fallure (p < 0.05). Concousion : Although further careful follow-up is necessary to confirm the trends evident In this serles, it would appear that patterns of failure and survival rate following conservative surgery and radiotherapy in early breast cancer are similar to those following mastectomy. The great majority of patients with local recurrence had an exellent salvage rate in both treatment groups. Therefore, these preliminary short term results support BCT as an equally effective management for early breast cancer as an alternative to mastectomy.

• Radiation Oncology Journal
• /
• v.26 no.4
• /
• pp.204-212
• /
• 2008

Purpose: This study was performed to evaluate the disease-free survival and risk factors of recurrence in early breast cancer patients who have undergone breast conserving surgery and radiation therapy. Materials and Methods: From March 1997 to December 2002, 77 breast cancer patients who underwent breast conserving surgery and radiation therapy were reviewed retrospectively. The median follow-up time was 58.4 months (range $43.8{\sim}129.4$ months) and the mean subject age was 41 years. The frequency distribution of the different T stages, based on the tumor characteristics was 38 (49.3%) for T1, 28 (36.3%) for T2, 3 for T3, 7 for T is and 1 for an unidentified sized tumor. In addition, 52 patients (67.5%) did not have axillary lymph metastasis, whereas 14 patients (18.1%) had $1{\sim}3$ lymph node metastases and 3 (0.03%) had more than 4 lymph node metastases. The resection margin was negative in 59 patients, close (${\leq}2\;mm$) in 15, and positive in 4. All patients received radiation therapy at the intact breast using tangential fields with a subsequent electron beam boost to the tumor bed at a total dose ranging from 59.4 Gy to 66.4 Gy. Patients with more than four positive axillary lymph nodes received radiation therapy ($41.4{\sim}60.4\;Gy$) at the axillary and supraclavicular area. Chemotherapy was administered in 59 patients and tamoxifen or fareston was administered in 29 patients. Results: The 5 year overall survival and disease-free survival rates were 98.08% and 93.49%, respectively. Of the 77 patients, a total of 4 relapses (5.2%), including 1 isolated supraclavicular relapse, 1 supraclavicular relapse with synchronous multiple distant relapses, and 2 distant relapses were observed. No cases of local breast relapses were observed. Lymph node metastasis or number of metastatic lymph nodes was not found to be statistically related with a relapse (p=0.3289) nor disease-free survival (p=0.1430). Patients with positive margins had a significantly shorter disease-free survival period (p<0.0001) and higher relapse rates (p=0.0507). However, patients with close margins were at equal risk of relapse and disease-free survival as with negative margins (p=1.000). Patients younger than 40 years of age had higher relapse rates (9.3% vs. 0%) and lower disease-free survival periods, but the difference was not statistically significant (p=0.1255). The relapse rates for patients with tumors was 14% for tumor stage T2, compared to 0% for tumor stage T1 tumors (p=0.0284). A univariate analysis found that disease-free survival and relapse rates, T stage, positive resection margin and mutation of p53 were significant factors for clinical outcome. Conclusion: The results of this study have shown that breast conservation surgery and radiation therapy in early breast cancer patients has proven to be a safe treatment modality with a low relapse rate and high disease-free survival rate. The patients with a positive margin, T2 stage, and mutation of p53 are associated with statistically higher relapse rates and lower disease-free survival.

• Journal of Gastric Cancer
• /
• v.6 no.2
• /
• pp.109-113
• /
• 2006

Purpose: Various minimally invasive surgical techniques, such as an endoscopic mucosal resection and a laparoscopic gastrectomy, are becoming common practice for some cases of early gastric cancer (EGC) defined in terms of the depth of invasion being limited to the mucosa or submucosa. However, there are rare cases of early gastric cancer with massive lymph-node metastasis. Materials and Methods: From 6 university hospitals of Korea, 2,772 EGC cases were resected during the various period of analysis (1,432 cases of mucosal cancer and 1,340 of submucosal cancer). Results: As control data, we used the data from a single institute, CHA University Hospital. There were nine cases of early gastric cancer (9/2,772, 0.32%) with N3 lymph node metastasis defined by more than 15 lymph nodes being metastasized according to the UICC-TNM classification (pT1N3, stage IV). Two cases were mucosal cancer (2/1,432, 0.1 4%), and seven cases were submucosal cancer (7/1,340, 0.52%). Metastasized lymph nodes varied in number from 18 to 52. There were three male and six female patients with a mean age of 57. This is a totally reversed sex ratio compared to the usual gastric cancer or EGC. Among the total of 9 EGC patients, there were 5 who had superficial spreading carcinomas with surface areas larger than $25\;cm^2$. This is a significantly higher proportion compared to the general EGC population. When we compared the tumor size according to the LN status, the N3 group was definitely larger than the other groups. 78% of the pT1N3 cases showed lymphatic invasion, which is very high compared to the 4.7% in general EGC cases. Among the 9 cases, 6 patients had too short a follow-up period to evaluate the correct prognosis, but there was one patient with a non-curative resection and two patients with early recurrence. Although the sample size is small and the follow-up period is short, we can expect a very poor prognosis when we consider the common prognosis of EGC that is widely known and accepted. Conclusion: From these results, we can a conclude that the risk factors for pT1N3 gastric cancer are female patients, submucosal invasion, larger tumor size, and lymphatic invasion. However rare, the existence of pT1N3 gastric cancer needs to be taken into consideration, especially during the diagnosis. Furthermore, minimally invasive treatment for EGC needs to be chosen with great precaution. Since the prognosis of pT1N3 gastric cancer is expected to be poor, aggressive adjuvant chemotherapy may be necessary. (J Korean Gastric Cancer Assoc 2006;6:109-113)

• Radiation Oncology Journal
• /
• v.14 no.4
• /
• pp.317-322
• /
• 1996

Purpose : Patients with cervical cancer who have positive resection margins after radical hysterectomy are at increased risk for local recurrence. The result of postoperative pelvic radiotherapy for cervix cancer with positive resection margins were analyzed to evaluate the role of radiotherapy. Materials and Methods : Between n 1979 and 1992, 60 patients of cervix carcinoma were treated with postoperative radiotherapy after radical hysterectomy and pelvic lymphadenectomy because of positive vaginal (48 patients) or parametrial resection margins (12 patients). Patients were treated with external beam radiation therapy (EBRT) alone (12 Patients) or EBRT plus vaginal ovoid irradiation (VOI) (48 patients). The median followup period was 55 months. Results : The 5-year actuarial disease free and overall survival rates for all patients were $75.2\%$, $84.1\%$, respectively. The overall recurrence rate was $23\%$ (14/60). In 48 patients with Positive vaginal resection margins, the pelvic recurrence was $8\%$ (4/48). Distant metastasis was $15\%$(7/48). Of the 43 patients with positive vaginal resection margins treated with EBRT and VOI, recurrence rate was $21\%$(9/43) , while recurrence rate was $40\%$(2/5) in the EBRT only treated group. In 12 patients with positive parametrial margins, three patients ($25\%$) had distant metastases. The most significant prognostic factor was lymph node metastasis. Complications resulting from radiotherapy occurred at a rate of $32\%$(19/60) and grade III complications occurred in three patients ($5\%$). Conclusion : Postoperative radiotherapy can produce excellent pelvic control rates in patients with positive resection margins. In patients with positive vaginal margins, whole pelvic EBRT and VOI is recommended.

• Nuclear Medicine and Molecular Imaging
• /
• v.43 no.5
• /
• pp.402-410
• /
• 2009

Purpose: The aim of this study was to determine the incidence and malignant rate of incidental asymmetric palatine tonsillar uptake (ATU) on $^{18}F$-FDG PET/CT in various clinical indications and to evaluate the clinical and PET/CT findings suggesting malignancy. Materials and Methods: We retrospectively reviewed a total of 2,901 patients ($58.4{\pm}12.3$ yrs, range 20~88 yrs, M:F = 1,841:1,060) who underwent $^{18}F$-FDG PET/CT during an 1-year period with various indications except primary tonsillar cancer and lymphoma evaluation. On $^{18}F$-FDG PET/CT, metabolic abnormality of the palatine tonsil and cervical lymph node were visually assessed. ATU was defined as increased palatine tonsillar uptake with diffuse, focal, or irregular pattern compared to contralateral side. The incidence and malignant ratio of ATU were evaluated according to clinical and PET/CT findings. Results: Of 2,901 cases, 290(10,0%) showed ATU. The incidence of ATU showed seasonal variation and was high in the winter (12.1%). Of 209 cases with ATU confirmed pathologically and/or clinically, five (2.4%) were malignant lesions. ATU with irregular uptake pattern (2/2) and in cases referred for cervical lymph node metastasis of unknown origin (3/5) were frequently associated with malignant lesion (p<0.05). Conclusion: ATU was not infrequently observed on $^{18}F$-FDG PET/CT, and the malignant risk of ATU was low. However, ATU with cervical lymph node metastasis or with irregular pattern on PET/CT would be further evaluated by the histopathologic examination.

• Radiation Oncology Journal
• /
• v.31 no.2
• /
• pp.97-103
• /
• 2013

Purpose: To investigate the patterns of locoregional recurrence of pathologic T3N0 (pT3N0) lower rectal cancer omitting postoperative radiotherapy (RT) and explore the potential of modification of a RT field. Materials and Methods: From Jan 2003 to Nov 2011, 35 patients omitting preoperative or postoperative RT for pT3N0 lower rectal cancer were included. We defined the lower rectal cancer as the tumor with the inferior margin located below the virtual line-a convergent level between rectal wall and levator ani muscle. All patients had radiologic examinations for recurrence evaluation during the follow-up duration. Results: The median follow-up duration was 66.4 months (range, 1.4 to 126.1 months). Eight (22.9%) of the 35 patients had recurrence. Three (8.6%) was local recurrence (LR) only, 3 (8.6%) was distant metastasis (DM) only, and 2 (5.7%) was LR with DM. All LR were located at primary tumor sites. The overall survival rate, LR-free survival rate, and DM-free survival rate at 5 years was 79.8%, 83%, and 87%, respectively. All LR developed from tumors over 5 cm. However, there was no statistical significance (p = 0.065). There was no other risk factor for LR. Conclusion: Even though the patients included in this study had pathologically favorable pT3N0 rectal cancer, LR developed in 14.3% of patients. Most of the LR was located at primary tumor sites prior to surgery. Based on these findings, it might seem reasonable to consider postoperative RT with a smaller radiation field to the primary tumor site rather than the conventional whole pelvic irradiation.

• Journal of Life Science
• /
• v.22 no.7
• /
• pp.964-969
• /
• 2012

Genistein, a predominant isoflavone, has been shown to inhibit the growth of various cancer cells in vitro and in vivo without toxicity to normal cells. In the present study, we investigated the effects of genistein on the activity and the expression of matrix metalloproteinases (MMPs) in MCF-7 and MDA-MB-231 human breast adenocarcinoma cells. Our findings showed that MMP-9 and -2 activation was significantly increased in response to 12-O-tetradecanoyl phorbol-13-acetate (TPA). However, the increased activities of MMP-9 and -2 in TPA-treated cells were concentration-dependently inhibited by treatment with genistein, and this was also correlated with a decrease in the expression of their mRNA and proteins. In addition, a matrigel invasion assay showed that genistein reduced TPA-induced invasion of MCF-7 and MDA-MB-231 cells. Although further in vivo studies are needed, these results suggest that genistein treatment may inhibit tumor cell invasion and, therefore, act as a dietary source to decrease the risk of cancer metastasis.