Actuarial Analysis of Survival after Breast Cancer Diagnosis among Lithuanian Females.

Breast cancer is the most common cause of mortality due to cancer for women both in Lithuania and worldwide. The chances of survival after diagnosis differ significantly depending on the stage of disease at the time of diagnosis and other factors. One way to estimate survival is to construct a Kaplan-Meier estimate for each factor value separately. However, in cases when it is impossible to observe a large number of patients (for example, in the case of countries with lower numbers of inhabitants), dividing the data into subsets, say, by stage at diagnosis, may lead to results where some subsets contain too few data, thus causing the results of a Kaplan-Meier (or any other) method to become statistically incredible. The problem may become even more acute if researchers want to use more risk factors, such as stage at diagnosis, sex, place of living, treatment method, etc. Alternatively, Cox models can be used to analyse survival data with covariates, and they do not require the data to be divided into subsets according to chosen risks factors (hazards). We estimate the chances of survival for up to 5 years after a breast cancer diagnosis for Lithuanian females during the period of 1995-2016. Firstly, we construct Kaplan-Meier estimates for each stage separately; then, we apply a (stratified) Cox model using stage, circumstance of diagnosis, and year of diagnosis as (potential) hazards. Some directions of further research are provided in the last section of the paper.

Evaluation of antihypertensive medications use and survival in patients with ovarian cancer: a population-based retrospective cohort study.

BACKGROUND: Despite declining mortality in most countries and in Lithuania, ovarian cancer burden has remained high. Studies have indicated that antihypertensive medications use may help to improve ovarian cancer survival, however findings remain controversial. The aim of the study was to analyse the association between post-diagnosis antihypertensive medications intake and cancer-specific survival in ovarian cancer patients. METHODS: This retrospective cohort study included 588 ovarian cancer cases diagnosed between 2013 and 2015. Hazard ratios (HR) and corresponding 95% confidence intervals (95%CI) were estimated using multivariable Cox proportional hazards models to assess associations between antihypertensive medications and ovarian cancer-specific mortality. RESULTS: In total, 279 (47%) patients died during the follow-up; 242 (87%) of them died due to ovarian cancer. The risk of ovarian cancer death was reduced in angiotensin-converting enzyme inhibitors (ACE inhibitors) users vs. non-users (HR 0.55, 95% CI: 0.36-0.83). Subgroup analysis showed better ovarian cancer survival in higher dose ACE inhibitors users (HR 0.46, 95% CI: 0.28-0.77, p for trend 0.002); the effect was also stronger in age 51-65 years, stage I-III, surgery or chemotherapy treatment, pre-diagnosis ACE inhibitor users' and pre-diagnosis hypertension subgroups. The risk of cancer-specific death was slightly lower among calcium-channel blocker and angiotensin-receptor blocker users and higher among beta-blocker users as compared to non-users, however chance and confounding could not be ruled out. We found no association between the use of centrally and peripherally acting antiadrenergic agents and diuretics and risk of ovarian cancer-specific mortality. CONCLUSIONS: Our findings imply that post-diagnosis use of ACE inhibitors may be associated with reduced ovarian cancer-specific mortality; however, further research is needed for the comprehensive assessment.

Changing epidemiology and age-specific incidence of cutaneous malignant melanoma in Lithuania: an analysis of national cancer registration data by gender and anatomical site, 1991-2015.

Introduction: The purpose of this study was to investigate the gender-specific and anatomical site-specific incidence of cutaneous melanoma. Material and methods: All cases of primary skin melanoma reported to the Lithuanian Cancer Registry during the period 1991-2015 were included. For the analyses, patients were categorized by sex and melanoma site. Results: Overall age-standardized rate (ASR) of melanoma in the trunk increased 0.8-3.3, while in limbs the ASR increased 1.0-3.4. The highest increase in new cases per 100,000 population (in both sexes) was detected in limbs and it increased over time (from 2.01 per 100,000 in 1991 to 3.65 per 100,000 in 2015). The highest increase in the number of new cases was in limbs with ASR, with a more than 3-fold increase from 1991-2015 (1.4-4.6). A statistically significant increase was observed in mortality of skin melanoma between 1991 and 2015, with the highest annual percentage change (APC) of 5.5 in the trunks of men (95% CI: 5.2-5.9; p < 0.05) and women with APC 3.9 (95% CI: 3.5-4.4, p < 0.05). Conclusions: In our study, we found higher incidence rates of skin melanoma in females. Melanoma was more commonly diagnosed in the trunk of males and limbs of females, with the highest mortality increase in trunk melanoma in both genders.

The Impact of the COVID-19 Pandemic on Cancer Patient's Management-Lithuanian Cancer Center Experience.

The pandemic spread of the COVID-19 virus significantly affected daily life, but the highest pressure was piled on the health care system. Our aim was to evaluate an impact of COVID-19 pandemic management measures on cancer services at the National Cancer Institute (NCI) of Lithuania. We assessed the time period from 1 February 2020 to 31 December 2020 and compared it to the same period of 2019. Data for our analysis were extracted from the NCI Hospital Information System (HIS) and the National Health Insurance Fund (NHIF). Contingency table analysis and ANOVA were performed. The COVID-19 pandemic negatively affected the cancer services provided by NCI. Reductions in diagnostic radiology (-16%) and endoscopy (-29%) procedures were accompanied by a decreased number of patients with ongoing medical (-30%), radiation (-6%) or surgical (-10%) treatment. The changes in the number of newly diagnosed cancer patients were dependent on tumor type and disease stage, showing a rise in advanced disease at diagnosis already during the early period of the first lockdown. The extent of out-patient consultations (-14%) and disease follow-up visits (-16%) was also affected by the pandemic, and only referrals to psychological/psychiatric counselling were increased. Additionally, the COVID-19 pandemic had an impact on the structure of cancer services by fostering the application of modified systemic anticancer therapy or hypofractionated radiotherapy. The most dramatic drop occurred in the number of patients participating in cancer prevention programs; the loss was 25% for colon cancer and 62% for breast cancer screening. Marked restriction in access to preventive cancer screening and overall reduction of the whole spectrum of cancer services may negatively affect cancer survival measures in the nearest future.

The impact of incomplete registration on survival rate of children with very rare tumors.

Pediatric very rare tumors (VRTs) represent a heterogeneous subset of childhood cancers, with reliable survival estimates depending dramatically on each (un)registered case. The current study aimed to evaluate the number of VRTs among Lithuanian children, to assess the impact of the registration status on survival rates and to track changes in treatment outcomes over the 16-year study period. We performed a population-based retrospective study across children below 18 years old diagnosed with VRTs in Lithuania between the years 2000 and 2015. The identified cases were cross-checked with the Lithuanian Cancer Registry-a population-based epidemiology cancer registry-for the fact of registration and survival status. The overall survival was calculated in relation to the registration status and treatment period. Thirty-seven children with VRTs were identified within the defined time frame. Six of them (16.2%) were not reported to the Lithuanian Cancer Registry at diagnosis. The probability of overall survival at 5 years (OS5y) differed significantly between the registered (n = 31) and unregistered (n = 6) cohorts: 51.6% versus 100%, respectively (p = 0.049). A 5-year survival estimate for children diagnosed with a VRT at the age of 0-14 years differed by 10 percentage points according to the registration completeness: 52.1% calculated for the entire cohort versus 42.1% for registered patients only. The OS5y has not improved over the analyzed period: 61.1% in 2000-2007 versus 57.9% in 2008-2015 (p = 0.805). The survival continued to decline beyond 5 years post-diagnosis due to late cancer-related adverse events: 59.5% of patients were alive at 5 years as compared to 44.3% at 10 years. The OS5y of children affected by VRT was lower than in more common childhood cancers. The survival rate of the unregistered patients may lead to misinterpretation of treatment outcomes. Meticulous registration of VRTs is crucial for correct evaluation of treatment outcomes, especially across small countries with few cases.

Colorectal cancer incidence, mortality, and stage distribution in European countries in the colorectal cancer screening era: an international population-based study.

BACKGROUND: Colorectal cancer screening programmes and uptake vary substantially across Europe. We aimed to compare changes over time in colorectal cancer incidence, mortality, and stage distribution in relation to colorectal cancer screening implementation in European countries. METHODS: Data from nearly 3·1 million patients with colorectal cancer diagnosed from 2000 onwards (up to 2016 for most countries) were obtained from 21 European countries, and were used to analyse changes over time in age-standardised colorectal cancer incidence and stage distribution. The WHO mortality database was used to analyse changes over time in age-standardised colorectal cancer mortality over the same period for the 16 countries with nationwide data. Incidence rates were calculated for all sites of the colon and rectum combined, as well as the subsites proximal colon, distal colon, and rectum. Average annual percentage changes (AAPCs) in incidence and mortality were estimated and relevant patterns were descriptively analysed. FINDINGS: In countries with long-standing programmes of screening colonoscopy and faecal tests (ie, Austria, the Czech Republic, and Germany), colorectal cancer incidence decreased substantially over time, with AAPCs ranging from -2·5% (95% CI -2·8 to -2·2) to -1·6% (-2·0 to -1·2) in men and from -2·4% (-2·7 to -2·1) to -1·3% (-1·7 to -0·9) in women. In countries where screening programmes were implemented during the study period, age-standardised colorectal cancer incidence either remained stable or increased up to the year screening was implemented. AAPCs for these countries ranged from -0·2% (95% CI -1·4 to 1·0) to 1·5% (1·1 to 1·8) in men and from -0·5% (-1·7 to 0·6) to 1·2% (0·8 to 1·5) in women. Where high screening coverage and uptake were rapidly achieved (ie, Denmark, the Netherlands, and Slovenia), age-standardised incidence rates initially increased but then subsequently decreased. Conversely, colorectal cancer incidence increased in most countries where no large-scale screening programmes were available (eg, Bulgaria, Estonia, Norway, and Ukraine), with AAPCs ranging from 0·3% (95% CI 0·1 to 0·5) to 1·9% (1·2 to 2·6) in men and from 0·6% (0·4 to 0·8) to 1·1% (0·8 to 1·4) in women. The largest decreases in colorectal cancer mortality were seen in countries with long-standing screening programmes. INTERPRETATION: We observed divergent trends in colorectal cancer incidence, mortality, and stage distribution across European countries, which appear to be largely explained by different levels of colorectal cancer screening implementation. FUNDING: German Cancer Aid (Deutsche Krebshilfe) and the German Federal Ministry of Education and Research.

Trends in Incidence and Mortality of Skin Melanoma in Lithuania 1991-2015.

BACKGROUND: We aimed to investigate age-specific and sex-specific incidence trends of melanoma in Lithuania from 1991 to 2015. METHODS: Analysis was based on data from the population-based Lithuanian Cancer Registry database for 1991-2015, and 6024 cases of skin melanoma were identified. Age-adjusted rates (ASRs) by sex and age group were calculated. Adjustment for ASRs was done using the old European standard population, where a total of three age groups were considered: 0-39, 40-59 and 60+. Additionally, the annual percent change (APC) was calculated, and 95% confidence intervals for APC were calculated. RESULTS: Between 1991 and 2015, the overall melanoma rates increased by an annual percent change (APC) of 3.9% in men (95% CI, 3.6-4.1%) and 2.3% in women (95% CI, 2.1-2.5%). The highest incidences of new cutaneous melanoma cases were observed between old adults (60+) of both sexes, while the lowest incidence rates were observed in the young adult group (up to 39 years old), with the lowest APC (1.6% in males and 0.4% in females). The overall number of melanoma deaths during 1991 and 2015 increased from 64 to 103 deaths per year, and the age-standardized rate (ASR) increased 1.3 times (from 1.8 to 2.4). CONCLUSIONS: The incidence and mortality of skin melanoma seem to be increased in all age groups. These trends indicate that skin protection behavior is not sufficient in our population and more efforts need to be taken in order to decrease incidence and mortality rates.

Expression levels of FBXW7 and MDM2 E3 ubiquitin ligases and their c-Myc and p53 substrates in patients with dysplastic nevi or melanoma.

E3 ubiquitin ligases are of interest as drug targets due to their involvement in the regulation of the functions and interactions of several proteins. Various E3 ligase complexes are considered oncogenes or tumor suppressors associated with the development of melanoma. These proteins regulate the functions of various signaling pathways and proteins, such as p53 and Notch. The aim of the present study was to determine the expression levels of F-box and WD repeat domain-containing 7 (FBXW7), c-Myc, MDM2 and p53 proteins in samples from patients with dysplastic nevi or melanoma, and to evaluate their association with clinicopathological parameters and prognosis of the disease. Paraffin blocks with postoperative material from 100 patients diagnosed with dysplastic moles or melanoma were used in the present study. Tissue microarrays and immunohistochemistry were used to examine FBXW7, c-Myc, MDM2 and p53 protein expression. The results revealed that there was significantly lower FBXW7 expression in advanced melanoma compared with dysplastic nevus, melanoma in situ and stage pT1 melanoma (P<0.001). Additionally, there was a statistically significant association between the expression levels of FBXW7 and the morphological type of the tumor (P<0.001). In addition, there was a strong positive association between FBXW7 expression and the changes in c-Myc expression (P<0.02), and a strong trend was observed between decreased FBXW7 expression and a higher risk of death in patients, with the major factor in patient mortality being the stages of melanoma. Additionally, p53 expression was associated with the depth of melanoma invasion and the morphological type of the tumor. In summary, FBXW7 expression exhibited the highest statistically significant prognostic value and associations with advanced melanoma. As the majority of FBXW7 substrates are oncoproteins, their degradation by FBXW7 may highlight these proteins as potential targets for the treatment of melanoma.

Outcomes of Treatment for Melanoma Brain Metastases.

BACKGROUND: Historically, melanoma with brain metastases has a poor prognosis. In this retrospective medical record review, we report basic clinicopathological parameters and the outcomes of patients with melanoma and brain metastases treated with different treatment modalities before the era of immunotherapy and modern radiotherapy technique. METHODS: Patients with metastatic melanoma were treated with surgery, radiotherapy, and/or systemic therapy from 1998 to 2017. In our study, they were identified and stratified depending on treatment methods. Overall survival was defined as the time from the date of brain metastases to the death or last follow-up (2019 June 1st). Survival curves were estimated using the Kaplan-Meier method that was employed to calculate the hazard ratio. RESULTS: Six (12%) of 50 patients are still alive as of the last follow-up. The median overall survival from the onset of brain metastases was 11 months. The longest survival time was observed in patients treated by surgery followed by radiotherapy, surgery followed by radiotherapy and systemic therapy, and also radiotherapy followed by systemic therapy. The shortest survival was observed in the best supportive care group and patients treated by systemic therapy only. CONCLUSIONS: Patients with brain metastases achieved better overall survival when treated by combined treatment modalities: surgery followed by radiotherapy (26.6 months overall survival), combining surgery, radiotherapy, and systemic therapy (18.7 months overall survival), and also radiotherapy followed by systemic therapy (13.8 months overall survival).

Breast Cancer Screening Program in Lithuania: Trends in Breast Cancer Mortality Before and During the Introduction of the Mammography Screening Program.

ABSTRACT BACKGROUND: Breast cancer is the most frequent oncological disease as well as the leading cause of cancer death among women worldwide. Decline in mortality in economically strong countries is observed. This decline is mostly related to early diagnosis (an improvement in breast cancer awareness and the mammography screening program (MSP)) and a more effective treatment. In the end of 2005, MSP started in Lithuania. The main aim of this article is to evaluate the breast cancer mortality during 22 years in Lithuania, as well as changes before the start of the MSP and during its implementation, in order to assess the influence of the MSP on mortality. MATERIALS AND METHODS: Analysis is based on data from the population-based Lithuanian Cancer Registry. Analysis of changes in mortality includes the period from 1998 to 2019. Age standardized mortality rates are calculated for assessment of changes. Joinpoint regression analysis is used. RESULTS: Applying the segmental regression model, it was found that during the study period mortality was statistically significantly decreasing by -1.1% each year. Mortality among women under the age of 50 decreased both before and during the implementation of MSP. Mortality in the target population also was already decreasing until the implementation of the program, but a significant reduction in mortality was observed in this group since 2006. CONCLUSIONS: Overall breast cancer mortality is decreasing in Lithuania. After the implementation of MSP the largest reduction in mortality was observed in the target population, however, it is not as pronounced as it could be with the well-organized MSP.

Breast Cancer Screening Program in Lithuania: Interval Cancers and Program Sensitivity After 7 Years of Mammography Screening.

OBJECTIVE: Analysis of interval cancers is critical in determining the sensitivity of screening and represents an objective measure of the quality of mammography screening program (MSP). METHODS: Period analyzed: from 2006 to 2012. The rate of screen-detected, interval cancers and program sensitivity were measured. A comparison of screen-detected and interval cancers was performed. RESULTS: During the period of the study, 429 473 women were screened and 1297 were found to have cancer. The overall screen-detected cancer rate was 30.2 per 10 000 women screened. Four hundred thirty-one case of interval cancers have occurred during the period of the study. The interval cancer ratio (ICR) was 0.25. Overall sensitivity of MSP amounted to 75.1%. Slightly lower sensitivity was found among the youngest age-group, especially for those with lobular cancers. Interval cancers were bigger in size, more often with metastases in lymph nodes, than screen-detected cancers, but these differences were not statistically significant. CONCLUSIONS: Overall program sensitivity in Lithuania is about 75%, ICR is 0.25, and these parameters are comparable to other European countries.

Education predicts cervical cancer survival: a Lithuanian cohort study.

Background: : We examined inequalities in cervical cancer survival in Lithuania by education and place of residence. : The study is based on the linked dataset that includes all records of the 2001 population Census, all records from Lithuanian Cancer Registry (cancer incidence) and all death and emigration records from Statistics Lithuania for the period between 6 April 2001 and 31 December 2009. The study group includes cervical cancers registered in the Cancer Registry from 1 January 2002 to 31 December 2006. Analysis was restricted to women who were 25-64 years old at the Census date (in total 1 866 cases). : During the study period there were 671 deaths corresponding to an overall 5-year survival proportion 64.13% (95% CI 61.86-66.31). Place of residence and education of cervical cancer patients had strong impact on survival; 5-year survival was higher in women living in urban areas than in rural (68.61 and 55.93%) and survival decreased with decreasing education: from 79.77% in highest education group to 64.85 and 50.48% in groups with secondary and lower than secondary education. The effect of place of residence declined when stage of disease was included in the model and became not significant in final model with education adjustment. The effect of education declined after inclusion of stage and other variables, however, remained significant. : We found that women with higher education experienced higher survival following a cervical cancer diagnosis, and stage of disease at the time of diagnosis explains only the part of observed differences.

Basal cell skin cancer and the risk of second primary cancers: a cancer registry-based study in Lithuania.

PURPOSE: The aim of this population-based cohort study was to determine the risk of second primary cancer in basal cell carcinoma (BCC) patients in Lithuania. METHODS: This analysis was based on patients diagnosed with BCC in Lithuania between 1998 and 2007 and followed until 2011. Standardized incidence ratios for subsequent cancers as a ratio of observed number of cancer cases in people with previous BCC diagnosis to the expected number of cancer cases in the underlying general population were calculated. RESULTS: After diagnosis of BCC, 1442 new cases of selected cancers were diagnosed. Compared with the general population, the incidence of all new primaries combined after BCC was very close to expected. Statistically meaningful increase in developing subsequent cancer was obtained for Hodgkin's lymphoma, prostate cancer, and leukemia in men, and for cancers of the lip, lung, and breast in women. Risk of melanoma and thyroid cancer was significantly elevated in both sexes. Relative risk of cancer of the eye was increased although not significant. CONCLUSIONS: In our study, we found increased cancer risk for cancers related to sun exposure. In addition, increased risks were identified for Hodgkin's lymphoma, thyroid cancer, leukemia, prostate, and breast cancer in BCC patients.

Education, survival, and avoidable deaths in Lithuanian cancer patients, 2001-2009.

Background Our aim in this study is to provide a systematic assessment of the site-specific cancer survival rates of patients with different educational levels, using population-based census-linked registry data covering the entire population of Lithuania. Material and methods The study is based on the linkage between all records of the 2001 population census and all records from Lithuanian Cancer Registry (cancer incidence) and Statistics Lithuania (deaths) for the period between 6 April 2001 and 31 December 2009. Results For the vast majority of cancer sites we found an inverse gradient in survival, with the worst survival indicators in the lowest educational group. We estimated that 18.6% of the deaths in Lithuanian cancer patients could have potentially been postponed, if all the patients had the same cancer mortality as the patients with the highest educational level. Conclusion Our findings offer a warning that although the survival rates of cancer patients are improving, this progress hides disparities between different groups of patients.

Educational differentials in cancer mortality and avoidable deaths in Lithuania, 2001-2009: a census-linked study.

OBJECTIVES: We investigate relative mortality inequalities by education for detailed cancer sites and provide estimates of deaths which could have been avoided through the elimination of these inequalities. METHODS: A census-linked dataset based on a follow-up of all residents registered in the 2001 census was used for the analysis. Mortality rate ratios were estimated by employing multivariate Poisson regression models for count data. RESULTS: An inverse educational gradient was observed for 11 cancer sites among men and for three cancer sites among women. Substantial shares of these cancer deaths would have been avoided if mortality among less educated groups had been the same as mortality among highly educated groups. CONCLUSIONS: Cancer control plans must consider socioeconomic inequalities and propose ways to improve prevention measures aimed at disadvantaged groups.

Educational differences in incidence of cancer in Lithuania, 2001-2009: evidence from census-linked cancer registry data.

This study used population-based census-linked cancer incidence data to identify patterns of educational differentials in the risk of cancer by detailed sites of cancer in Lithuania. The study is based on the linkage between all records of the 2001 population census, all records from the Lithuanian Cancer Registry (cancer incidence), and all death and emigration records from Statistics Lithuania for the period between 6 April 2001 and 31 December 2009. The study population (cohort) includes all permanent residents of Lithuania aged 30-74 years on the day of the census (6 April 2001). The study found that cancers of the lip, mouth, and pharynx, esophagus, stomach, larynx, urinary bladder, pancreas, and lung for men and cancers of the cervix uteri, lung, and colon for women show a statistically significant inverse educational gradient with excess incidence in the lowest educational group. At the same time, a reversed cancer risk gradient with the highest incidence for the higher education group was observed for thyroid cancer, melanoma, nonmelanoma skin cancers, and non-Hodgkin lymphomas. This group also includes prostate cancer, kidney cancer, and multiple myeloma for men and cancer of the pancreas, breast cancer, cancer of the colon, and cancer of the uterus for women. The associations between education and cancer incidence observed in this study reflect the concordance between social status and lifestyle-related risk factors for cancer. Cancer awareness in society has also contributed toward the observed higher risk of cancer, which is usually promoted more by patients with higher education.