Post-operative small pelvic field radiation therapy in patients with intermediate risk early stage cervix cancer: a safe and efficient treatment modality

BackgroundThe treatment of early stage cervical cancer has different therapeutic options. Adjuvant external beam radiotherapy for surgically treated intermediate risk cervical cancer patients has shown acceptable oncological outcomes with a low incidence of toxicity. The aim of this study was to analyze the oncological outcomes and safety of adjuvant small pelvic field radiotherapy in surgically treated stage IB1-2 cervical cancer patients who met the Sedlis intermediate-risk criteria.Materials and methodsA retrospective cohort study was carried out with 28 patients treated from 2007 to November 2019 with biopsy proven intermediate risk stage IB1–2 cervical cancer previously treated with radical hysterectomy and bilateral lymphadenectomy who received adjuvant small pelvic field radiotherapy. The primary endpoints were local and distant control and overall survival. Secondary endpoints were acute and late gastrointestinal and genitourinary toxicity. Survival curves were analyzed using the Kaplan-Meier method.ResultsAfter a median follow up period of 41.5 (27.5–80.5) months, adjuvant small pelvic field radiotherapy showed a 100% overall survival rate, 81.82% disease free survival and 86.36% local recurrence-free survival with no incidence of grade 3 or 4 acute or late toxicity. Three patients suffered from relapse, 1 in the vaginal cuff, 1 in the retrovesical area and 1 patient in the retroperitoneal area.ConclusionsAdjuvant small pelvic field radiotherapy is an efficient and safe treatment option that offers excellent oncological outcomes to surgically treated intermediate-risk stage IB1–2 cervical cancer patients with an excellent toxicity profile.     

老年宫颈癌50例临床及预后分析

目的：探讨老年宫颈癌的临床病理特征及预后影响因素。方法：对50例老年宫颈癌患者的临床特点及生存情况进行回顾性分析。结果：鳞状细胞癌45例（90．0％）,腺癌4例（8．0％）,透明细胞癌1例（2．0％）;≤Ⅱa期占16．0％,≥Ⅱb期占84．0％;主要临床症状为绝经后不规则阴道流血,全组1、3、5年生存率分别为82．0％,66．0％,54．0％。多因素分析结果显示病理类型、临床分期及淋巴结转移情况是老年宫颈癌患者预后的独立影响因素（均P〈0．05）。结论：KPS评分≥70分、鳞癌、临床分期为Ⅰ期、Ⅱ期,无淋巴结转移的患者预后较好,病理类型、临床分期及淋巴结转移情况是老年宫颈癌患者预后的独立影响因素。     

Which factors account for the ethnic inequalities in stage at diagnosis and cervical cancer survival in New Zealand?

Objective: There are substantial ethnic inequalities in stage at diagnosis and cervical cancer survival in New Zealand. We assessed what proportions of these differences were due to screening history (for the analyses of late stage diagnosis), stage at diagnosis (for the analyses of survival), comorbid conditions (for the analyses of survival), and travel time to the nearest General Practitioner and cancer centre. Methods: The study involved 1594 cervical cancer cases registered during 1994–2005. We used G-computation to assess the validity of the estimates obtained by standard logistic regression methods. Results: Māori women had a higher risk of late stage diagnosis compared with ‘Other’ (mainly European) women (odds ratio (OR) = 2.71; 95% confidence interval 1.98, 3.72); this decreased only slightly (OR 2.39; 1.72, 3.30) after adjustment for screening history, and travel time to the nearest General Practitioner and cancer centre. In contrast, the (non-significantly) elevated risk in Pacific women (1.39; 0.76, 2.54) disappeared almost completely when adjusted for the same factors (1.06; 0.57, 1.96). The hazard ratio of mortality for cervical cancer for Māori women was 2.10 (1.61, 2.73) and decreased to 1.45 (1.10, 1.92) after adjustment for stage at diagnosis, comorbid conditions, and travel time to the nearest General Practitioner and cancer centre; the corresponding estimates for Pacific women were 1.96 (1.23, 3.13) and 1.55 (0.93, 2.57). The G-computation analyses gave similar findings. Conclusions: The excess relative risk of late stage diagnosis in Māori women remains largely unexplained, while more than half of the excess relative risk of mortality in Māori and Pacific women is explained by differences in stage at diagnosis and comorbid conditions.     

Matched-Case Comparisons in a Single Institution to Determine Critical Points for Inexperienced Surgeons’ Successful Performances of Laparoscopic Radical Hysterectomy versus Abdominal Radical Hysterectomy in Stage IA2-IIA Cervical Cancer

This is a retrospective study which aims to identify major determinants of successful laparoscopic radical hysterectomy (LRH) versus abdominal radical hysterectomy (ARH) performed by inexperienced surgeons for stage IA2-IIA cervical cancer. A total of 161 consecutive patients with stage IA2–IIA cervical cancer who underwent RH were grouped into 2 groups according to the surgeons’ experience with LRH: experienced surgeon versus inexperienced surgeon. After matching for age and risk factors, surgical and survival outcomes were compared. Experienced surgeon selected patients with earlier-stage and fewer risk factors for LRH than ARH, but inexperience surgeons did not. After matching, the vaginal tumor-free margin of LRH was shorter than that of ARH in experienced surgeon group (1.3 versus 1.7 cm, p=0.007); however, the vaginal tumor-free margin was longer than that of ARH in the inexperienced surgeon group (1.8 versus 1.3 cm, p=0.035). The postoperative hospital stay of LRH was shorter than that of ARH in experienced surgeon group (5.5 versus 7.7 days, p<0.001), but not different from that of ARH in the inexperienced surgeon group. Vaginal tumor-free margin >1.8 cm (OR 7.33, 95% CI 1.22–40.42), stage >IB1 (OR 8.83, 95% CI 1.51–51.73), and estimated blood loss >575 mL (OR 33.95, 95% CI 4.87–236.79) were independent risk factors for longer postoperative hospital stay in the inexperienced surgeon group. There was no difference of 5-year-profression-free survival of LRH patients between experienced surgeon and inexperienced surgeon groups after matching (55.1 versus 33.3%, p=0.391). Selection of earlier-stage disease and moderate vaginal tumor-free margin might be important for an inexperienced surgeon to successfully perform LRH with minimal complications in stage IA2–IIA cervical cancer.     

Young age as a prognostic factor in cervical cancer: analysis of population based data from 10 022 cases

The effect of young age on survival in cervical cancer is not fully known, although evidence has suggested that it is a poor prognostic factor and that young patients should therefore be treated differently from older patients. All 10 022 cases of invasive cervical cancer in the west Midlands during 1957-81, which comprised 10% of the cases in England and Wales, were analysed to determine the prognostic effect of age. Univariate analysis showed a median survival time of 54 months for all cases, with survival rates at five years of 69% for patients aged under 40 and 45% for those aged 40 or older (χ₁² (log rank)=331·4; p<0·0001). This difference remained significant after stratification for stage (χ₁² (log rank)=7·1; p=0·008). Cox regression analysis with nine covariables, including age and year of registration, reaffirmed the importance of conventional prognostic factors such as stage of disease, size of tumour, state of lymph nodes, and differentiation of the tumour. After allowance was made for the effects of other prognostic factors young age was found to be a small but significant favourable factor that did not change during the period of the study. Estimated survival distributions obtained from the Cox model showed that for women presenting with the common characteristics associated with stage Ib disease who were treated with radical radiotherapy the survival rate at five years fell non-linearly from 71% in the group aged 25-29 to 65% in the group aged 65-69.Young age alone is not a reason to alter existing policies for treatment for patients with invasive cervical cancer.     

A possible association between survival time and transfusion in cervical cancer

Some studies suggest that transfusion may be associated with an increased risk of recurrence of and death due to malignant human neoplasms. We examined retrospective data from patients with cervical cancer to see if any association between transfusion of blood at the time of initial treatment and the time interval to recurrence and death could be detected in this cancer. In 130 patients with cervical cancer, seen over a ten-year period at our institution, there was a trend toward earlier recurrence in transfused patients, but this trend did not achieve statistical significance. Death due to cervical cancer recurrence occurred after a median of Death due to cervical cancer recurrence occurred after a median of 12 months in the transfused patients and a median of 68 months in the non-transfused individuals, which was statistically significant. Transfused patients had, on average, more favorable prognostic factors than those not transfused, such as less advanced clinical stage of disease. Analysis using a proportional hazards risk model failed to demonstrate a significant association between transfusion and time to recurrence when other prognostic factors were considered, but a significant association between transfusion and time to cancer-related death (p less than 0.05) was found. While these results cannot be viewed as conclusive due to the small number and heterogeneity of the patients analyzed, our data support the possibility of an association between transfusion and cervical cancer survival. Further studies are warranted to confirm or refute this relationship.     

新辅助化疗在局部晚期宫颈癌治疗中的疗效观察

目的：探讨新辅助化疗联合手术治疗较传统手术治疗Ib2、IIa2局部晚期宫颈癌的临床疗效。方法：选取2008年6月～2011年12月在黑龙江省哈尔滨医科大学附属第三医院初治宫颈癌患者120例,临床分期为Ib2期、IIa2期,术前均经病理证实为宫颈鳞癌,将其分为两组：研究组（新辅助化疗联合手术治疗组）;对照组（单纯手术治疗组）。研究组给予1～2个疗程的新辅助化疗后评估其化疗疗效,有效者化疗结束后行广泛性子宫切除＋盆腔淋巴结清扫术;对照组直接行手术治疗。结果：新辅助化疗能够使肿瘤体积较化疗前缩小或消失,临床有效率高达81.43%,从而降低了宫颈癌的临床分期,提高手术的切除率,扩大手术适应征,降低术后病理高危因素,同时手术治疗能保留卵巢功能,提高年轻宫颈癌患者生活质量。结论：术前新辅助化疗可以提高手术治疗局部晚期宫颈癌的临床疗效。     

宫颈癌术后复发的危险因素及SCC-Ag、HR-HPV对复发的预测价值分析

目的:分析宫颈癌术后复发的危险因素,探讨鳞状细胞癌抗原(SCC-Ag)、高危型人乳头瘤病毒(HR-HPV)对宫颈癌术后复发的预测价值。方法:对2010年1月至2017年12月我院收治的宫颈癌患者300例进行回顾性分析,收集其临床资料,所有患者随访2年,定期检测SCC-Ag表达情况及HR-HPV感染情况,根据患者复发情况分为复发组与未复发组,应用单因素和多因素Logistic回归分析宫颈癌术后复发的危险因素,以病理诊断为金标准,分析SCC-Ag、HR-HPV对宫颈癌术后复发的预测价值。结果:随访期间出现12例失访,300例患者中完成随访288例,出现复发40例,未复发248例。单因素分析结果显示宫颈癌术后复发与肿瘤直径、分化程度、肿瘤间质浸润情况、临床分期、淋巴结转移、SCC-Ag阳性表达、HR-HPV持续感染有关(P0.05),而与发病年龄、体质量指数(BMI)、吸烟史、性行为开始年龄、宫颈癌家族史、病理类型、术后放化疗无关(P0.05)。多因素Logistic回归分析显示:中低分化、深肌层浸润、临床分期IIA1-IIA2期、有淋巴结转移、SCC-Ag阳性、HR-HPV持续感染是宫颈癌术后复发的危险因素(P0.05)。SCC-Ag联合HR-HPV预测宫颈癌术后复发的灵敏度、特异度、阳性预测值、阴性预测值分别为92.50%、87.50%、54.41%、98.64%。结论:中低分化、深肌层浸润、临床分期IIA1-IIA2期、有淋巴结转移、SCC-Ag阳性、HR-HPV持续感染是宫颈癌术后复发的危险因素,SCC-Ag联合HR-HPV预测宫颈癌术后复发具有一定价值,值得临床关注。     

新辅助化疗对ⅠB2～ⅡB期宫颈癌近期疗效的观察

目的：探讨新辅助化疗对ⅠB2～ⅡB期宫颈癌的近期疗效。方法：对哈尔滨医科大学附属第二医院2005年9月-2007年1月间ⅠB2～ⅡB期宫颈癌82例进行前瞻性研究,其中42例在根治性手术前行新辅助化疗（Neoadjuvant Chemotherapy,NACT）2～3个疗程,为NACT组,40例在术前未行新辅助化疗,为直接手术组。评价NACT组化疗疗效及影响疗效的相关因素,比较两组手术后的病理结果。结果：NACT的总有效率为76．2％,化疗效果与临床分期和分化程度无关（P〉0．05）,与病理类型及肿瘤的大小有关,鳞癌的有效率明显高于非磷癌（P〈0．05）,肿瘤直径〉8cm的疗效明显低于≤8cm（P〈0．05）。两组术后盆腔淋巴结阳性率及宫旁侵润率之间的差异有统计学意义（P〈0．05）;在NACT组中化疗有效组与无效组术后盆腔淋巴结阳性率及宫旁侵润率之间的差异有统计学意义（P〈0．05）。结论：新辅助化疗可改善宫颈癌的临床分期,提高宫颈癌的手术疗效,成为治疗ⅠB2～ⅡB期宫颈癌一种新手段,有较大的临床应用价值。     

Time since childbirth and prognosis in primary breast cancer: population based study.

OBJECTIVE: To investigate whether time since birth of last child was of prognostic importance in women with primary breast cancer. DESIGN: Retrospective cohort study based on a population based database of breast cancer diagnoses with detailed information on tumour characteristics, treatment regimens, reproductive factors, and vital status. SETTING: Denmark. SUBJECTS: 5652 women with primary breast cancer aged 45 years or less at the time of diagnosis. MAIN OUTCOME MEASURES: 5 and 10 year survival; relative risk of dying. RESULTS: Women diagnosed in the first 2 years after last childbirth had a crude 5 year survival of 58.7% and 10 year survival of 46.1% compared with 78.4% and 66.0% for women whose last childbirth was more than 2 years before their diagnosis. After adjustment for age, reproductive factors, and stage of disease (tumour size, axillary nodal status, and histological grading), a diagnosis sooner than 2 years since last childbirth was significantly associated with a poor survival (relative risk 1.58, 95% confidence interval 1.24 to 2.02) compared with women who gave birth more than 5 years previously. Further analyses showed that the effect was not modified by age at diagnosis, tumour size, and nodal status. CONCLUSIONS: A diagnosis of breast cancer less than 2 years after having given birth is associated with a particularly poor survival irrespective of the stage of disease at debut. Therefore, a recent pregnancy should be regarded as a negative prognostic factor and should be considered in counselling these patients and in the decisions regarding adjuvant treatment.     

Clinical significance of peritumoral lymphatic vessel density and lymphatic vessel invasion detected by D2-40 immunostaining in FIGO Ib1-IIa squamous cell cervical cancer

The clinical significance of lymphangiogenesis in cervical cancer remains controversial. Our aim was to investigate the correlation between lymphangiogenesis, lymphatic vessel invasion (LVI) and tumor metastasis, invasion and prognosis in squamous cell cervical cancer. Paraffin sections of 90 patients with FIGO (Fédération Internationale de Gynécologie et d'Obstétrique) Ib1-IIa squamous cell cervical cancer were stained for immunohistochemistry with a D2-40 monoclonal antibody against the carcinoembryonic antigen M2A. The lymphatic vessel density (LVD) and LVI were measured, and their relationship with the clinicopathological data was analyzed. D2-40-positive lymphatic vessels were found in 75 of the 90 patients (83.3 %). All D2-40-positive vessels were located in peritumoral areas. The mean±SD of the peritumoral LVD was 10.08±4.16. The positive rate of LVI was 32.0 % (24/75). The recurrence rate of patients with LVD >10 (62.1 %, 18/29) was significantly higher than that of patients with LVD ≤10 (34.8 %, 16/46, P = 0.021). The 5-year recurrence-free survival rate of patients with LVD >10 (41.0 %) was significantly lower than that of patients with LVD ≤10 (67.0 %, P = 0.045). Univariate analysis showed that the peritumoral LVD (≤10 vs >10) was correlated with LVI (absent vs present, P = 0.016). The peritumoral LVD and LVI showed no correlation with age, FIGO stage, tumor size, tumor grade, depth of invasion, or pelvic lymph node metastasis (all: P > 0.05). Peritumoral lymphangiogenesis was correlated with the recurrence and recurrence-free survival in patients with squamous cell cervical cancer. Examination of peritumoral LVD in these patients might therefore help to estimate the risk of recurrence.     

青年妇女患宫颈癌的临床特点及预后分析

目的：探讨青年妇女患宫颈癌的临床特点并行预后分析。方法：选取2008年1月-2013年1月在我院接受治疗的青年妇女宫颈癌33例患者观察组,同期在我院接受治疗的大于35岁49例患者为对照组。对两组患者的发病相关因素及临床病理特征进行回顾性分析及对两组患者预后分析,随访患者5年内生存率及2年内复发率。结果：两组患者初次性行为差异无统计学意义（P〉0．05）;两组患者避孕方式与妊娠次数比较均有显著性差异（P〈0．05）;两组患者临床分期与宫颈形态无显著性差异（P〉0．05）;两组癌灶大小、病理分型、宫颈肌层浸润深度及盆腔淋巴转移具有显著性差异（P〈0．05）;观察组较对照组患者早期（Ⅰa—Ⅱa）与晚期（≥Ⅱb）的两年内复发率及五年生存率差异均有显著性差异（P〈0．05）。结论：青年妇女宫颈癌患者具有癌灶大、腺癌发病率高、宫颈肌层浸润深度≥1／2肌层和盆腔淋巴结转移阳性的临床特点。     

Short- and long-term survival outcomes among never smokers who developed lung cancer

BackgroundLung cancer is the leading cause of cancer death in the US. While an extensive literature exists detailing lung cancer risk factors and mortality among patients with a history of tobacco use, the data are more limited among individuals who have never smoked. The purpose of this investigation is to compare survival rates between the two groups and evaluate potential risk factors among never smokers.MethodsThis retrospective study included 3380 smokers and 334 never smokers who were diagnosed with lung cancer at Stony Brook University Hospital between 2003 and 2016. 1-, 3-, 5- and 10-year survival outcomes, stratified by smoking status, were compared and Kaplan-Meier curves for overall survival are provided. Cox Proportional Hazard models were used to evaluate factors influencing survival among never smokers.ResultsNever smokers with lung cancer were more likely to be female, be diagnosed with adenocarcinoma histology, and had fewer comorbidities than lung cancer patients who smoked. Although 60% of patients were diagnosed at a later stage of disease development, regardless of smoking status, overall short- and long-term survival was significantly higher among never smokers compared to those with a history of tobacco use. In addition to age and stage at diagnosis, a history of diabetes was found to be a significant prognostic factor for decreased survival among never smokers (HR=3.15, 95% CI (1.74, 5.71)).ConclusionsData from the present investigation suggest that, regardless of smoking status, approximately three of every five lung cancer patients are diagnosed at a later stage, and that both short- and long-term survival outcomes are significantly better among never smokers compared to those with a history of tobacco use. Additional studies are required to validate these findings and better explain the mechanistic drivers for the improved outcomes among never smokers.     

Obesity and the likelihood of sexual behavioral risk factors for HPV and cervical cancer

Obesity is associated with higher cervical cancer mortality, but its relationship with sexual behavioral risk factors that predispose women to human papilloma virus (HPV) and cervical cancer is unclear. We used data from 3,329 women participants, aged 20-59 years, of the 1999-2004 National Health and Nutrition Examination Survey, to analyze the relationship between BMI and age at first intercourse, number of sexual partners, condom use during sexual activity, history of sexually transmitted disease (STD), herpes simplex virus 2 (HSV-2) seropositivity, and HPV prevalence. BMI was not associated with the prevalence of HPV. Mildly obese women (BMI 30.0-34.9 kg/m(2)) were least likely to report a STD history (9% vs. 13% in normal weight) and >or=2 sexual partners in the previous year (8% vs. 13%) while overweight women (BMI 25.0-29.9 kg/m(2)) were least likely to report >or=10 lifetime partners; among those with multiple partners, BMI was not associated with sexual activity without condoms in the past month. After adjustment for age, race/ethnicity, and education, women with higher BMI were less likely to report sexual behavioral risk factors than normal-weight women; however, odds ratios were only significant for mildly obese women for reporting a STD history (0.74, 95% confidence interval 0.55-0.99) and having >or=2 sexual partners in the last year (0.57, 0.39-0.85). Higher BMI was not associated with HSV-2 seropositivity after adjustment. HPV and sexual behavioral risk factors for HPV and cervical cancer are not more prevalent in obese than normal-weight women and unlikely to account for higher-observed cervical cancer mortality in obese women.     

高危型HPV 感染对宫颈病变组织IFN-r、IL-10表达的影响

目的：探讨高危型人乳头瘤病毒（HPV）感染对宫颈病变组织干扰素-r(IFN-r)、白细胞介素-10(IL-10)的影响。方法：收集我 院2013 年1 月到2015 年1 月妇科门诊行宫颈活检患者150 例,根据病理检查结果,将患者分为观察组（宫颈癌33 例、CINⅠ期 26 例、CINⅡ期28 例、CINⅢ期23 例）110 例,对照组（慢性宫颈炎患者）40 例。提取两组患者宫颈组织标本,检测观察组 HPV-DNA、HPV 分型,及两组IFN-r、IL-10 蛋白及mRNA 表达,分析高危型HPV感染与宫颈病变组织IFN-r、IL-10 表达的关系。 结果：观察组HPV-DNA阳性87 例（79.1%）,其中HPV16 型47 例（42.7%）、HPV18 型20 例（18.2%）感染率最高;且HPV16、18 感 染率在CINⅠ期、CINⅡ期、CINⅢ期以及宫颈癌组中的感染率差异均有统计学意义（P<0.05）,Spearman相关性分析显示,HPV16、 18 与宫颈病变程度均呈现正相关关系（r=0.896,0.786;均P<0.05）。IFN-r、IL-10 表达水平在CINⅠ期、CINⅡ期、CINⅢ期、宫颈 癌、对照组表达水平差异均具有统计学意义（P<0.05）,Spearman 相关性分析显示,IFN-r与宫颈病变程度呈现负相关关系（r=-0. 567,P<0.05）,IL-10 呈现正相关关系（r=0.678,P<0.05）。且HPV16、HPV18 感染率与IFN-r表达呈现负相关关系（rHPV16/18=-0. 678,-0.675,均P<0.05）,与IL-10 呈现正相关关系（rHPV16/18=0.582,0.778,均P<0.05）。结论：IFN-r表达随着宫颈病变加重或者 HPV16、HPV18 感染率升高逐渐降低,IL-10 则逐渐升高。     

Relative survival analysis of gynecological cancers in an urban district of Shanghai during 2002–2013

ObjectiveAppraisal of cancer survival is essential for cancer control, but studies related to gynecological cancer are scarce. Using cancer registration data, we conducted an in-depth survival analysis of cervical, uterine corpus, and ovarian cancers in an urban district of Shanghai during 2002–2013.Materials and methodsThe follow-up data of gynecological cancer from the Changning District of Shanghai, China, were used to estimate the 1–5-year observed survival rate (OSR) and relative survival rate (RSR) by time periods and age groups during 2002–2013. Age-standardized relative survival rates estimated by the international cancer survival standards were calculated during 2002–2013 to describe the prognosis of cervical, uterine corpus, and ovarian cancers among women in the district.ResultsIn total, 1307 gynecological cancer cases were included in the survival analysis in the district during 2002–2013. Among gynecological cancers, the 5-year OSRs and RSRs of uterine corpus cancer were highest (5-year OSR 84.40%, 5-year RSR 87.67%), followed by those of cervical cancer (5-year OSR 73.58%, 5-year RSR 75.91%), and those of ovarian cancer (5-year OSR 53.89%, 5-year RSR 55.90%). After age adjustment, the 5-year relative survival rates of three gynecological cancers were 71.23%, 80.11%, and 43.27%, respectively.ConclusionThe 5-year relative survival rate did not show a systematic temporal trend in cervical cancer, uterine cancer, or ovarian cancer. The prognosis in elderly patients was not optimistic, and this needs a more advanced strategy for early diagnosis and treatment. The age structure of gynecological cancer patients in the district tended to be younger than the standardized age, which implies that more attention to the guidance and health education for the younger generation is needed.     

Expression of TRF2 and its prognostic relevance in advanced stage cervical cancer patients

Background

Telomeres are protective caps consisted of specific tandem repeats (5′-TTAGGG-3′). Shortening of telomeres at each cell division is known as “mitotic clock” of the cells, which renders telomeres as important regulators of lifespan. TRF2 is one of the critical members of shelterin complex, which is a protein complex responsible from the preservation of cap structure, and loss or mutation of TRF2 results in DNA damage, senescence or apoptosis. Since cancer is frequently associated with aberrant cell cycle progression, defective DNA repair or apoptosis pathways, TRF2 could be one likely candidate for cancer therapy.Here we investigated the prognostic role of TRF2 levels in cervical cancer patients. Fold-induction rates were evaluated with respect to median values after real-time PCR analysis. Overall survival, distant disease-free and local recurrence-free survival rates were calculated using Kaplan-Meier long rank test.

Results

Both five year overall- and disease-free survival rates were longer in patients with higher TRF2 expression compared to lower expression, but results were not statistically significant (69.2% vs 28.9%, respectively). Mean local recurrence-free survivals (LRF) were very close ( 58.6, CI: 44.3-72.9 vs 54.5, CI: 32.1-76.9 months) for high and low expressions, respectively. Cumulative proportion of LRF at the end of five year period was 76.9% for high and 57.1% for low TRF2 expression (P = 0.75). Statistically significant difference was found between survival ratios and Bcl-xL and p53 gene expressions, but not with TRF2. A respectable correlation between TRF2 expression and apoptosis along with distant metastasis was noted (P = 0.045 and 0.036, respectively). Additionally, high TRF2 expression levels had a positive impact in five year survival rate of stage IIIB-IVA patients (P = 0.04).

Conclusions

Our results support the role of TRF2 in apoptosis and imply a positive relation with distant metastases and survival in advanced stage patients. The remarkable difference in survival periods of patients with different TRF2 expressions suggest that TRF2 may be a candidate factor to estimate survival for cervical cancer, a preliminary observation which should further be verified with a larger cohort.     

Acquired and genetic susceptibility to cervical cancer

Infection with high-risk human papilloma virus (HPV) is a necessary risk factor for the development of cervical cancer (CC). However, there are many factors that contribute to the development of CC. We have been investigating the role of polymorphisms in chemical metabolizing genes and life-style factors in the development of CC between two countries with significantly different prevalence of CC. Our data confirm that infection with high-risk HPV is the most significant risk factor for CC in both Venezuela and US. In Venezuela, having multiple sex partners and early sexual activities are significant risk factors (OR=4.7, 95% CI=1.7-13.1; OR=6.7, 95% CI=2.3-20.1, respectively). On the other hand, cigarette smoking is the significant risk factor for women in the US (OR=6.4, 95% CI=1.8-23.2). Genotype analyses were conducted using specimens from the US population only. The GSTM1 null genotype was associated with a significant 3.4 fold increase in risk (95% CI=1.0-11.8) compared with those who were GSTM1 positive, after adjustment for smoking and HPV infection. Polymorphosis in CYP2E1 and mEH are associated with a non-significant increase in risk. Our study indicates that different acquired and genetic susceptibility factors can make significant contributions to the development of environmental disease such as cervical cancer.     

Effects of war aggression in Croatia on some forms and manifestations of breast cancer

The aim of this study was to determine the differences in epidemiological and clinical manifestations of breast cancer in time of war in Croatia and in peacetime before and after the war, in the defined population of Pozesko-Slavonska County. The methods used in this study were the evaluation of relative predictive value of variables by means of chi 2-test and the analysis of variance, while the survival studies were tested by Long Rank test according to Kaplan-Meier analysis of survival. This work encompasses 660 patients who had breast cancer. The differences between three time periods were evaluated: the war period (1991-1995), and two control periods: before the war (1981-1990) and after the war (1996-2000). The patients were grouped by age, localization of tumor and survival. During the war period the patients were, on the average, 4.2 years younger than those who acquired the disease in control periods, and the mean age of patients was between 50 and 59 years (36.5% of patients). Although the difference in tumor distribution by sides (left or right breast) and quadrants was statistically significant (war period vs. control periods; p < 0.001), there was no statistically significant difference in the survival of patients according to the results of Kaplan-Meier analysis of localization of tumor (p > 0.05). The length of survival in terms of age of patients in time of surgical procedure was significantly different (p < 0.001). This study confirms the effects of war on some epidemiological and clinical manifestation of breast cancer in the defined population of Pozesko-Slavonska County.     

Identification of Risk Factors for Locoregional Recurrence in Breast Cancer Patients with Nodal Stage N0 and N1: Who Could Benefit from Post-Mastectomy Radiotherapy?

Introduction

The locoregional recurrence (LRR) rate was reported as high as approximately 20% in stage I-II breast cancer following mastectomy. To investigate the risk factors for LRR in pT1–2N0-1 breast cancer patients treated with mastectomy but not radiation, and to define a subgroup of patients at high risk of LRR who may benefit from postmastectomy radiotherapy (PMRT).

Methods and Materials

In total, 390 patients with pT1-2N0M0 (n = 307) and pT1-2N1M0 (n = 83) breast cancer who underwent total mastectomy without adjuvant radiotherapy from 2002 to 2011 were enrolled in the study.

Results

After a median follow-up period of 5.6 years (range, 0.6–11.3 years), 21 patients had 18 systemic relapses and 12 LRRs including six in the chest wall and eight in the regional nodal area. The 5-year LRR-free survival (LRRFS) rates were 97.0% in pN0, 98.8% in pN1, and 97.4% in all patients. Multivariate analysis revealed that age < 50 years (Hazard Ratio, 11.4; p = 0.01) and no adjuvant chemotherapy (Hazard Ratio, 10.2; p = 0.04) were independent risk factors for LRR in pN0 patients. Using these factors, the 5-year LRRFS rates were 100% without any risk factors, 96.4% with one risk factor, and 86.7% with two risk factors. In pN1 patients, multivariate analysis revealed that having a hormone receptor negative tumor (Hazard Ratio, 18.3; p = 0.03) was the only independent risk factor for LRR. The 5-year LRRFS rates were 100.0% for luminal type, and 92.3% for non-luminal type cancer.

Conclusion

Patients with pT1-2N0-1 breast cancer who underwent total mastectomy without PMRT could be stratified by nodal stage and risk factors for LRR. PMRT may have of value for node negative patients aged less than 50 years and who are not treated with adjuvant chemotherapy, and for non-luminal type patients with one to three positive nodes.