• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7533-7537
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• 2014

Background: Breast cancer (BC) is the most frequent cancer type, and the leading cause of death from cancer among women in Israel. The Bedouin-Arab (BA) population in southern Israel is characterized by a high rate of consanguinity, common hereditary disorders, and transition from a semi-nomadic, traditional society to a more sedentary and urbanized society. In this hospital-based study, the demographic and the clinicopathological characteristics of BC in BA were compared with Jewish patients. Materials and Methods: 85 BA patients treated at the Soroka Medical Center, Beer Sheba, during the years 2004-2012, were studied and compared with 180 consecutive Jewish patients treated during the year 2007. Clinicopathological features compared included age, menopausal state, number of births, a history of BC in first-degree relatives, tumor size (T), extent of lymph-node involvement (N), distant metastases (M), stage, grade, estrogen and progesterone receptor (ER/PR), and Her2 status. Types of treatment, relapse rate and site, as well as outcome were also studied. Cox's regression models were applied for studying disease-free, and overall survival. Results: Compared with Jewish patients, BA patients were younger (average age $49{\pm}12$ yrs vs $59{\pm}13$, p<0.001), had a lower rate of BC in first-degree relatives (p<0.001), and a larger number of births ($6{\pm}4.2$ vs $2.5{\pm}1.9$, p<0.001). BA patients had larger tumors (p=0.02), more extensive lymph-node involvement (p=0.002), and more advanced stage (p=0.003). Grade, ER, PR, and Her2 status were similar in the two ethnic groups. Relapse type was most commonly systemic in BA patients (p=0.05), and loco-regional in Jewish patients (p=0.02). Median survival was 63, and 35 months for Jewish and BA patients, respectively (log-rank test, p=0.02). In Cox multivariate analysis, stage and PR status (HR-0.14, p<0.0001; HR-3.11, p=0.046), but not ethnicity, influenced overall survival. Conclusions: BC presents a decade earlier, and with more advanced disease in BA compared with Jewish patients. Biologic parameters including grade, ER, PR, and Her2 status were similar in both groups. Although prognosis was worse in BA than in Jewish patients, it was affected only by stage and PR status, but not by ethnicity.

• Tuberculosis and Respiratory Diseases
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• v.52 no.3
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• pp.230-240
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• 2002

Background : The majority of chemotherapy-treated small cell lung cancers(SCLC) patients eventually recur. Although many patients are in excellent physical condition at the time of recurrence, few drugs or drug combinations are capable of effecting a tumor regression in this setting. Topotecan, a topoisomerase I inhibitor, is one of the more widely studied single afents in SCLC. The aim of this study was to determine the response rate, survival and toxicity of topotecan as a second line traeatment SCLC. Materials and Methods : 19 patients with measurable SCLC, progressive during the first line chemotherapy (9 cases) or recurrent after the first line chemotherpy(10 cases), were enrolled in this study. Topotecan was administered as a 30-minute daily infusion at a dose of 1.5mg/$m^2$ for 5 consecutive days, every 3 weeks. Results : The overall response rate was 26.3%(5/19, CR 2, PR 3, SD 3, PD 11). The median survival was 24 weeks. The response rate and survival were poor in the nonresponders during first chemotherapy, those who were refractory to the first chemotherapy(recurrent within 3 months after completion of first chemotherapy) and extensive disease, but the results were not statistically significant. The toxicities were mainly hematologic and anemia grade III 1/90, leukopenia grade III 6/90 IV 4/90, thrombocytopenia grade III 1/90 IV 1/90, vomiting grade III 1/90 of cycles were occurred. There was no treatment-related deaths due to severe myelosuppression. Conclusion : Topotecan can be an active second line chemotherapeutic agent for treating SCLC.

• The Korean Journal of Applied Statistics
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• v.34 no.2
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• pp.255-266
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• 2021

The purpose of this study is to compare the effects of treatment on stage III stomach cancer data obtained from the SEER program of the National Cancer Institute and to identify the significant risk factors for the survival rates of stage III stomach cancer. Since the proportional hazards assumption was violated for treatment, we used the restricted mean survival time as an alternative to the proportional hazards model. The restricted mean survival time was estimated using pseudo-observations, and the effects of treatment were compared using a test statistic based on the estimated restricted mean survival times. We conducted the regression analysis using a generalized linear model to investigate the significant predictors for the restricted mean survival time of patients with stage III stomach cancer. We found that there was a significant difference between the restricted mean survival times of treatment groups. Age at diagnosis, race, substage, grade, tumor size, surgery, and treatment were significant predictors for the restricted mean survival time of patients with stage III stomach cancer. Surgery was the most significant predictor for increasing the restricted mean survival time of patients with stage III stomach cancer.

• Radiation Oncology Journal
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• v.20 no.3
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• pp.215-220
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• 2002

Purpose : Preoperative radiotherapy has been used to induce tumor regression and allow complete resection of rectal cancer with a sphincter preservation surgery. This study was performed to determine the effectiveness of preoperative radiotherapy for $T_2,\;T_3$ distal rectal carcinoma. Materials and Methods : From November 1995 to June 1997, fifteen patients with invasive distal rectal cancer were treated with preoperative radiotherapy followed by sphincter preservation surgery. Classification by preoperative T stage consisted of 7 $T_2$ and 8 $T_3$ tumors. Radiation therapy was delivered with 6 MV and 15 MV linear accelerator, at 1.8 Gy fractions for 5 days per week. Total radiation doses were 45 Gy to 50.4 Gy (median : 50.4 Gy). Sphincter preservation surgery was peformed $4\~6$ weeks after the completion of radiotherapy. Median follow-up was 22 months (range : $16\~37\;months$). Results : One patient $(6.7\%)$ had a complete pathologic response. Comparing the stage at the diagnostic workup with the pathologic stage, tumor downstaging of T stages occurred in 11 of 15 patients $(73.3\%)$ and $N_1$ stages occurred in 2 of 5 patients $(40\%)$. No patient developed progressive disease undergoing treatment. Two patients suffered local recurrence at 7 and 20 months, and one a distant metastasis at 30 months. No grade 3 or 4 toxicity was observed. Conclusion : Our experience suggests that preoperative radiotherapy followed by sphincter preservation surgery is well tolerated, and can significantly reduce the tumor burden for $T_2\;T_3$ distal rectal cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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• pp.5331-5336
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• 2014

Background: Early onset breast cancer is associated with poor outcomes but variable results have been reported. It is a significant problem in Pakistani women but remains under reported. Breast conservation plays an important role in surgical management of this younger patient group. The objective of this study was to determine the outcome of breast conservative therapy in patients with early onset breast cancer in our population and compare it with their older counterparts. Materials and Methods: A review of patients with invasive breast cancer who underwent breast conservation surgery at Shaukat Khanum Cancer Hospital from 1997 to 2009 was performed. Patients were divided into two groups i.e. Group I age ${\leq}40$ and Group II >40 years. A total of 401 patients with breast cancer were identified in Group I and 405 patients in Group II. Demographics, histopathological findings and receptor status of the two groups were compared. The Chi square test was used for categorical variables. Outcome was assessed on basis of 10 year locoregional recurrence free survival (LRRFS), disease free survival (DFS) and overall survival (OS). For survival analysis Kaplan Meier curves were used and significance was determined using the Log rank test. Cox regression was applied for multivariate analysis. Results: Median follow up was 4.31 (0.1-15.5) years. Median age at presentation was 34.6 years (17-40) and 51.9 years (41-82) for the two groups. Groups were significantly different from each other with respect to grade, receptor status, tumor stage and use of neoadjuvant therapy. No significant difference was present between the two groups for estimated 10 year LRRFS (86% vs 95%) (p=0.1), DFS (70% vs 70%) (p=0.5) and OS (75% vs 63%) (p=0.1). On multivariate analysis, tumor stage was an independent predictor of LRRFS, DFS and OS. Conclusions: Early onset breast cancer is associated with a distinct biology but does not lead to poorer outcomes in our population.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3335-3341
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• 2014

Background: Severe toxicity is commonly observed in cancer patients receiving irinotecan (CPT-11) UDPglucuronosyltransferase1A1 (UGT1A1) catalyzes the glucuronidation of the active metabolite SN-38 but the relationship between UGT1A1 and severe toxicity remains unclear. Our study aimed to assess this point to guide clinical use of CPT-11. Materials and Methods: 89 cancer patients with advanced disease received CPT-11-based chemotherapy for at least two cycles. Toxicity, including GI and hematologic toxicity was recorded in detail and UGT1A1 variants were genotyped. Regression analysis was used to analyse relationships between these variables and tumor response. Results: The prevalence of grade III-IV diarrhea was 10.1%, this being more common in patients with the TA 6/7 genotype (5 of 22 patients, 22.7%) (p<0.05). The prevalence of grade III-IV neutropenia was 13.4%and also highest in patients with the TA 6/7 genotype (4 of 22 patients; 18.2%) but without significance (p>0.05). The retreatment total bilirubin levels were significantly higher in TA6/7 patients (mean, $12.75{\mu}mol/L$) with compared to TA6/6 (mean, $9.92{\mu}mol/L$) with p<0.05. Conclusions: Our study support the conclusion that patients with a $UGT1A1^*28$ allele (s) will suffer an increased risk of severe irinotecan-induced diarrhea, whether with mid-or low-dosage. However, the $UGT1A1^*28$ allele (s) did not increase severe neutropenia. Higher serum total bilirubin is an indication that patients UGT1A1 genotype is not wild-type, with significance for clinic usage of CPT-11.

• Radiation Oncology Journal
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• v.23 no.3
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• pp.143-156
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• 2005

Background: The best dose-fractionation regimen of the definitive radiotherapy for cervix cancer remains to be clearly determined. It seems to be partially attributed to the complexity of the affecting factors and the lack of detailed information on external and intra-cavitary fractionation. To find optimal practice guidelines, our experiences of the combination of external beam radiotherapy (EBRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT) were reviewed with detailed information of the various treatment parameters obtained from a large cohort of women treated homogeneously at a single institute. Materials and Methods: The subjects were 743 cervical cancer patients (Stage IB 198, IIA 77, IIB 364, IIIA 7, IIIB 89 and IVA 8) treated by radiotherapy alone, between 1990 and 1996. A total external beam radiotherapy (EBRT) dose of $23.4\~59.4$ Gy (Median 45.0) was delivered to the whole pelvis. High-dose-rate intracavitary brachytherapy (HDR-IBT) was also peformed using various fractionation schemes. A Midline block (MLB) was initiated after the delivery of $14.4\~43.2$ Gy (Median 36.0) of EBRT in 495 patients, while In the other 248 patients EBRT could not be used due to slow tumor regression or the huge initial bulk of tumor. The point A, actual bladder & rectal doses were individually assessed in all patients. The biologically effective dose (BED) to the tumor ($\alpha/\beta$=10) and late-responding tissues ($\alpha/\beta$=3) for both EBRT and HDR-ICBT were calculated. The total BED values to point A, the actual bladder and rectal reference points were the summation of the EBRT and HDR-ICBT. In addition to all the details on dose-fractionation, the other factors (i.e. the overall treatment time, physicians preference) that can affect the schedule of the definitive radiotherapy were also thoroughly analyzed. The association between MD-BED $Gy_3$ and the risk of complication was assessed using serial multiple logistic regression models. The associations between R-BED $Gy_3$ and rectal complications and between V-BED $Gy_3$ and bladder complications were assessed using multiple logistic regression models after adjustment for age, stage, tumor size and treatment duration. Serial Coxs proportional hazard regression models were used to estimate the relative risks of recurrence due to MD-BED $Gy_{10}$, and the treatment duration. Results: The overall complication rate for RTOG Grades $1\~4$ toxicities was $33.1\%$. The 5-year actuarial pelvic control rate for ail 743 patients was $83\%$. The midline cumulative BED dose, which is the sum of external midline BED and HDR-ICBT point A BED, ranged from 62.0 to 121.9 $Gy_{10}$ (median 93.0) for tumors and from 93.6 to 187.3 $Gy_3$ (median 137.6) for late responding tissues. The median cumulative values of actual rectal (R-BED $Gy_3$) and bladder Point BED (V-BED $Gy_3$) were 118.7 $Gy_3$ (range $48.8\~265.2$) and 126.1 $Gy_3$ (range: $54.9\~267.5$), respectively. MD-BED $Gy_3$ showed a good correlation with rectal (p=0.003), but not with bladder complications (p=0.095). R-BED $Gy_3$ had a very strong association (p=<0.0001), and was more predictive of rectal complications than A-BED $Gy_3$. B-BED $Gy_3$ also showed significance in the prediction of bladder complications in a trend test (p=0.0298). No statistically significant dose-response relationship for pelvic control was observed. The Sandwich and Continuous techniques, which differ according to when the ICR was inserted during the EBRT and due to the physicians preference, showed no differences in the local control and complication rates; there were also no differences in the 3 vs. 5 Gy fraction size of HDR-ICBT. Conclusion: The main reasons optimal dose-fractionation guidelines are not easily established is due to the absence of a dose-response relationship for tumor control as a result of the high-dose gradient of HDR-ICBT, individual differences In tumor responses to radiation therapy and the complexity of affecting factors. Therefore, in our opinion, there is a necessity for individualized tailored therapy, along with general guidelines, in the definitive radiation treatment for cervix cancer. This study also demonstrated the strong predictive value of actual rectal and bladder reference dosing therefore, vaginal gauze packing might be very Important. To maintain the BED dose to less than the threshold resulting in complication, early midline shielding, the HDR-ICBT total dose and fractional dose reduction should be considered.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5775-5781
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• 2013

Background: The gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) is the most common type of neuroendocrine neoplasm. We summarized data in our centre to investigate the clinicopathological features, diagnostic methods, therapeutic approaches and prognosis for this neoplasm to increase knowledge of this disease in Asian populations. Method: A total of 122 patients treated at Sun Yet-san Memorial Hospital of Sun Yat-sen University between January 2000 and December 2011 were analyzed retrospectively. Results: Pancreas was the most common site of involvement (65/122, 53.3%); this disease has no special symptoms; positive rates of chromogranin A (CgA) and synaptophysin (Syn) were 81.1% and 87.7%, respectively. The positive rate of Syn had statistical difference among the three grades, but not CgA. Some 68 patients had G1 tumors, 32 G2 tumors and 22 G3 tumors, and Chi-square test showed that higher grading was correlated with worse prognosis (${\chi}^2=32.825$, P=0.0001). A total of 32 patients presented with distant metastasis, and 8 cases emerged during following up. Cox proportional hazards regression modeling showed that the tumor grade (P=0.01), lymphatic metastasis (P=0.025) and distant metastasis (P=0.031) were predictors of unfavorable prognosis. The overall 5-year survival rate was 39.6%, the 5-year survival rate of G1 was 55.7%, and the G2 and G3 were 34.2% and 0%, respectively. Conclusions: The incidence of gastroenteropancreatic neuroendocrine tumors has risen over the last 12 years. All grades of these diseases metastasize readily, and further research regarding the treatment of patients after radical surgery is needed to prolong disease-free survival.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10643-10646
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• 2015

Background: To study the relationship between mammographic findings and clinical/pathologic features in women with 1-15mm sized invasive breast cancer. Materials and Methods: We investigated a consecutive series of 134 cases diagnosed in Tianjin Medical University Cancer Institute and Hospital in 2007. Mammographic findings were classified into five groups as follows :1) stellate mass without calcification; 2) non-stellate mass without calcification; 3) intermediate suspicious calcification with or without associated mass; 4) higher probability malignant calcification with or without associated mass; 5) focal asymmetry/distortion without associated calcification. Associations between mammographic and clinical/pathological features (menopause status/family history/histologic grade/lymph node status and ER/PR/HER2 status) was analyzed through logistic regression and chi square tests. Results: Compared to the stellate mass without calcification group, higher probability malignant calcification patients were associated significantly with a positive lymph node status, always presenting in patients who were non-menopausal and with a family history of carcinoma. Conclusions: Higher probability malignant calcifications with or without associated tumor masses are associated with clinical/pathologic features of poor prognosis.

• Radiation Oncology Journal
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• v.12 no.1
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• pp.81-90
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• 1994

Purpose : The aim of this study is to analyze the clinical results of thermo-irradiation treatment for surgically unresectable advanced hepatoma with or without hepatic arterial chemo-embolization (HACE), chemotherapy (CT) and interferon (IFN) therapy. Materials and Methods : Between February 1990 and December 1992, 45 Patients with surgically unresectable advanced hepatomas were treated by thermo-irradiation with or without hepatic arterial chemo-embolization and other treatment modalities. Among them, We analyzed retrospectively 25 patients who received more than three times of hyperthermias. Mean age was 50 years (range : 18-71 years) and male to female ratio was 20 : 5. In the study, treatment was administered as follows : 3 patients received radiation therapy(RT) and hyperthermia (HT). 3 received RT+HT+CT. 3 received RT+HT+HACE. 1 received RT+HT+CT+HACE. 2 received RT+HT+CT+IFN. 10 received RT+HT+HACE+IFN. 3 received RT+HT+CT+HACE+IFN. Radiation therapy was done by a 6 MV linear accelerator Patients were treated with daily fractions of 180 cGy to doses of 11Gy-50Gy (median 30Gy). Local hyperthermia was done by HEH-500C(Omron Co. Japan), 30-45 min/session, 2 sessions/wk and the number of HT sessions ranged from 3 to 17 (median 7 times). 15 patients of 25 were followed by abdominal CT scan or abdominal ultra-sonogram. The following factors were analyzed :Age, histologic grade, sex. number of hyperthermia, total RT dose, hepatic arterial chemo-embolization. Results : Of 25 patients. there were observed tumor regression (partial response and minimal response) in 6 (24$ \% $), no response in 8 (32$ \% $), progression in 1 (4$ \% $) and not evaluable ones in 10 (40$ \% $) radiographically. The over all 1-year survival was 25$ \% $, with a mean survival of 33 weeks. The treatment modes of partial and minimal responsive patients (PR+MR)were as follows : Two were treated with RT+HT+HACE, 2 were done with RT+HT+HACE+IFN Remaining 2 were treated with RT+HT+CT+HACE+IFN. The significant factor affecting the survival rate were RT dose (more than 25 Gy), HACE, number of HT (above 6 times), responsiveness after treatment (PR + MR). Age, sex, histologic differentiation, chemotherapy, interferon therapy were not statistically significant factors affecting the survival rate. Conclusion : Although follow-up duration was short, the thermo-irr3diBtion with/without hepatic arterial chemo-embolization was well tolerated and there were no serious complicatons. In future, it is considered the longer follow up and prospective, well controlled trials should be followed to evaluate the efficacies of survival advantage.