Impact of season of diagnosis on mortality among breast cancer survivors.

INTRODUCTION: There is mounting evidence that the time of breast cancer diagnosis and the start of treatment can improve survival rates. The aim of this study was to test the relationship between the season of breast cancer diagnosis and the survival of women patients receiving standard surgery treatment with radiotherapy. MATERIALS AND METHODS: The nonmetastatic breast cancer patients (n = 991) were followed from the date of diagnosis until death. Cox proportional hazards models were used to calculate multivariate hazard ratios (HRs) for all-cause mortality. HRs and 95% confidence intervals (CIs) were estimated in models adjusted for clinicopathologic and treatment factors. RESULTS: After adjusting for independent prognostic variables, we found that patients diagnosed in summer and autumn had a 40% reduced risk for 0-3-year mortality when compared to those diagnosed in spring. Among women aged <50 years, HRs comparing autumn with spring diagnosis categories were 0.53 (95% CI: 0.31-0.91) for 0-5-years and 0.68 (95% CI: 0.46-0.89) for 5-10-years after diagnosis. Diagnosis in autumn was associated with improving survival in younger patients treated with adjuvant chemotherapy (HR = 0.61, 95% CI: 0.39-0.96, P = 0.003). CONCLUSIONS: The diagnosis in summer and autumn was associated with a better overall prognosis. The effect of season of diagnosis on survival rate was most pronounced in the young age patients receiving chemotherapy.

Second primary malignancies after high-dose-rate 60Co photon or 252Cf neutron brachytherapy in conjunction with external-beam radiotherapy for endometrial cancer.

PURPOSE: Second primary malignancies (SPMs) may occur in organs after radiotherapy (RT). This study aimed to determine the rate and distribution of SPMs for photon- or neutron-emitting radiotherapy sources for patients treated for primary endometrial cancer. METHODS AND MATERIALS: The cohort comprised 426 patients with 5334 patient-years of observation. Patients were treated by different methods of RT from 1990 to 2000. Patients received postoperative 60Co external-beam radiotherapy (43.4%), external-beam radiotherapy + high-dose-rate (HDR) intracavitary brachytherapy with 60Co or 252Cf (42.3%), or HDR intracavitary brachytherapy alone with 60Co or 252Cf (14.3%). RESULTS: Over a 25-year period, 47 SPMs were observed (21 for HDR 60Co and 26 for HDR 252Cf). SPMs were observed for 13 patients in the high-intermediate risk group for each radiation source. Patients treated with 60Co developed SPMs in the urinary tract (1.2%) and in lymphoid/hematopoietic tissues (1.2%). Only three SPM cases (0.7%) were observed in digestive tract. In comparison, the patient group treated with 252Cf developed SPMs in the digestive tract (1.4%) with the majority in the colon (1.2%), urinary tract (0.9%) primarily the kidneys, and vulva (0.7%). All other SPMs (4.9%) were in the low-risk group. Of these, SPMs in the skin were most prevalent (1.6%) for 60Co, and breast (1.6%) for 252Cf, but believed to be caused by factors other than treatment. SPM incidence in the digestive and urinary tracts were similar (2.1%), regardless of radiation source. CONCLUSIONS: For followup at 25 years, 47 SPMs were observed with no differences in the high-intermediate risk group depending on the RT source.

The changes of radiotherapy in Lithuania: infrastructure, utilization rate, and cost.

Background. The aim of this study was to evaluate radiation therapy (RT) productivity, capacity, and cost in Lithuania. Materials and methods. An electronic questionnaire was prepared and sent to the country's RT centres. The data was collected for the years 2011-2014. The early data of the RT infrastructure was obtained from the QUARTS Project (2001). Results. In Lithuania the external beam RT was applied to 32.6% of new cancer cases (non-melanomatous skin cancer and benign conditions were excluded). In 2014, RT was more frequently applied for breast and prostate carcinomas, 23 and 20%, respectively. The country owned 11 units of linear accelerators (linacs) and this accounts for 3.7 linacs per one million population. 3D conformal RT is the standard approach in all four RT centres in Lithuania. IMRT practices were established in three centers and VMAT or stereotactic RT in two of them. 73% of linacs were capable of IGRT, while only 27% were equipped with CBCT. The average linac workload was 567 patients per year and showed a 10% decrease compared with the 2011 data. During a ten-year period, the average cost per patient for RT treatment increased 7.6 times - from EUR 129 to 974. The reimbursement system in Lithuania is not favourable for application of RT. Conclusions. During the recent thirteen years, RT services in Lithuania have dramatically improved, but we are still behind the average of European countries and benchmark rates. It is important to continue optimising the efficiency of RT services, and further evidence-based studies on RT infrastructure assessment and planning are needed.

Californium versus cobalt brachytherapy combined with external-beam radiotherapy for IIB stage cervical cancer: long-term experience of a single institute.

PURPOSE: The purpose of this paper was to observe and compare long-term curative effects and complications of FIGO stage IIB cervical cancer patients (n = 232) treated with high-dose-rate (HDR) californium ((252)Cf) neutron or cobalt ((60)Co) photon intracavitary brachytherapy (ICBT) combined with external-beam radiotherapy (EBRT). MATERIAL AND METHODS: The EBRT dose to the small pelvis was 50 Gy in both groups. The brachytherapy component of (252)Cf or (60)Co was added in the 3(rd) week of EBRT, 5 fractions were performed once per week resulting in a total ICBT dose of 40 Gy/Gyeq (point A). RESULTS: Overall survival (OS) at 5, 10 and 15 years was 63.6%, 50.4% and 38.8% in the (252)Cf group and 62.2%, 50.5%, 39.9%, in the (60)Co group, respectively (p = 0.74). The percentage of tumour recurrence was statistically significantly lower in the (252)Cf group with 7.4% versus 17.1% in the (60)Co group (p = 0.02). Second primary cancers have developed similarly 9.1% and 8.1% cases for (252)Cf and (60)Co groups, respectively. CONCLUSIONS: Our long-term retrospective study comparing (252)Cf and (60)Co isotopes with brachytherapy in combined treatment of FIGO IIB stage cervix carcinoma patients shows, that overall survival in the both groups are similar. However, the recurrence of tumour was significantly lower in the (252)Cf group. The incidence of second primary cancers was similar in both groups.

Second primary malignancies after radiotherapy including HDR (252)Cf brachytherapy for cervical cancer.

PURPOSE: Second primary malignancies (SPMs) are among the most serious late adverse effects after radiotherapy experienced over time by the increasing population of cancer survivors worldwide. The study aim was to determine the rate and distribution of SPMs for neutron- and photon-emitting brachytherapy (BT) sources for patients treated for cervical cancer. METHODS AND MATERIALS: The cohort comprised 662 patients with invasive cervical cancer (Stages IIB and IIIB) and contributed 5,224 patient-years (PY) of observation. These patients were treated by radiotherapy during the 1989-1999 year period with cobalt-60 source ((60)Co) teletherapy. The first group of patients (N = 375; 3,154 PY) received high-dose-rate (HDR) californium-252 source ((252)Cf) BT, whereas the second group (N = 287; 2,070 PY) received HDR (60)Co BT. RESULTS: Over a 25-year period, 35 SPMs were observed, amounting to 5.3% of all observed patients: in 16 (2.4%) heavily, 2 (0.3%) moderately, 14 (2.1%) lightly irradiated body sites, and 3 (0.5%) other sites. Of these, 21 cases (5.6%) were observed in the HDR (252)Cf BT group, whereas 14 cases (4.9%) were observed in the HDR (60)Co BT group. Exposures received during (60)Co teletherapy and HDR BT with either (252)Cf or (60)Co had statistically equivalent (p = 0.68) effects on SPM development. CONCLUSIONS: Cure rates are improving, and therefore, there are more long-term survivors from cervical cancer. This study shows no significant difference in rates or distribution of SPMs in women treated with neutron BT compared with photon BT (p = 0.68). After reviewing related literature and our research results, it is evident that a detailed investigation of SPM frequency, localization, and dose to adjacent organs is a suitable topic for further research.

Assessment of annual average effective dose status in the cohort of medical staff in Lithuania during 1991-2013.

The use of radiation sources for various medical purposes is closely related to irradiation of the medical staff, which causes harmful effects to health and an increased risk of cancer. In total, 1463 medical staff who have been occupationally exposed to sources of ionising radiation (IR) had been monitored. Records with annual dose measurements (N = 19 157) were collected and regularly analysed for a 23-y period: from 01 January 1991 to 31 December 2013. The collected annual average effective dose (AAED) data have been analysed according to different socio-demographic parameters and will be used in future investigation in order to assess cancer risk among medical staff occupationally exposed to sources of IR. A thorough analysis of data extracted from medical staff's dose records allows one to conclude that the average annual effective dose of Lithuanian medical staff occupationally exposed to sources of IR was consistently decreased from 1991 (1.75 mSv) to 2013 (0.27 mSv) (p < 0.0001).

Postgraduate Cancer Education and Training in Lithuania: Harmonization According to the EU Rules.

The purpose of this article is to discuss Lithuanian postgraduate cancer education according to the data of 2013. In Lithuania, a specialization in an area called clinical oncology is absent; as independent specialities in oncology, there are both medical oncologists and radiation oncologists. These types of oncologists complete rigorous residency training in the clinics. Separate courses are provided in different residency programmes. Currently, there are two medical oncology and radiation oncology programmes for 3rd-, 4th- and 5th-year residents, one at the National Cancer Institute and another at the Lithuanian University of Health Sciences and Kaunas Clinics. Today, there are only 45 radiation oncologists and 56 medical oncologists licensed in Lithuania. This means that each radiation oncologist and medical oncologist is providing for 397 and 319 new cancer cases per year, respectively, or there are 0.3 practising in the major specialties of oncology per 10,000 population. Most other medical residency programmes expose their trainees to oncology for only 1 month either in the 1st or the 2nd year of residency. Due to the growing number of new cancer cases worldwide, these programmes have to be extended, especially for family and internal medicine residents. Lithuanian postgraduate cancer education and training is in the process of harmonization according to the EU rules. All the Lithuanian residency programmes are certificated by an independent public agency and are recognized by a number of countries, including all the countries of the EU.

Molecular alterations in signal pathways of melanoma and new personalized treatment strategies: Targeting of Notch.

Despite modern achievements in therapy of malignant melanomas new treatment strategies are welcomed in clinics for survival of patients. Now it is supposed that personalized molecular therapies for each patient are needed concerning a specificity of molecular alterations in patient's tumors. In human melanoma, Notch signaling interacts with other pathways, including MAPK, PI3K-AKT, NF-kB, and p53. This article discusses mutated genes and leading aberrant signal pathways in human melanoma which are of interest concerning to their perspective for personalized treatment strategies in melanoma. We speculate that E3 ubiquitin ligases MDM2 and MDM4 can be attractive therapeutic target for p53 and Notch signaling pathways in malignant melanoma by using small molecule inhibitors. It is possible that restoration of p53-MDM2-NUMB complexes in melanoma can restore wild type p53 function and positively modulate Notch pathway. In this review we summarize recent data about novel US Food and Drug Administration approved target drugs for metastatic melanoma treatment, and suppose model for treatment strategy by targeting Notch.

Cancer education in Lithuania.

The aim of this article is to describe cancer education in Lithuania according to the data of 2013. In Lithuania, there are the following stages of education for physicians: basic education through integrated studies of medicine (six years), postgraduate education through residency studies (four to five years), and continuing professional development. In recent years, integrated studies of medicine have been the most popular specialty. Oncology is incorporated into the teaching courses in medicine programmes. In each university, an oncology course is mandatory during these studies. In Lithuania, there are two types of specialists related to oncology: medical oncologists and radiation oncologists. These oncologists complete multidisciplinary residency study programmes in the clinics. To receive a doctoral degree, specialists may join PhD programmes at any of the accredited universities. In recent years the number of dissertations in oncology has grown. Notably, oncology is chosen not only by students in the field of medicine. It also becomes the choice of those seeking a doctorate in the fields of nursing, public health, biochemistry, and physics. The professional development of oncologists is a lifelong commitment. In Lithuania, continuing specialist medical training is mandatory. This requirement is ensured with the process of licensing of medical practice. All Lithuanian study programmes are certificated by an independent public agency and are recognised by a number of other countries as well.

Postmastectomy internal mammary nodal irradiation: a long-term outcome.

BACKGROUND AND OBJECTIVE: The internal mammary lymph nodes (IMN) have been recognized as a potential site of regional breast cancer spread. The aim of this study was to evaluate the impact of internal mammary node radiotherapy (RT) to on clinical outcomes in breast cancer patients treated with mastectomy and postoperative radiation therapy. MATERIALS AND METHODS: This cohort study included 588 patients with breast cancers located in the central and medial quadrants. IMN RT was applied to 320 patients and 268 patients did not receive it IMN RT. Inside the IMN RT group, 165 patients received external beam IMN irradiation (IMN-EB). Mastectomy combined with using Californium-252 neutron source implantation was applied to 155 patients (IMN-BT). Cox proportional hazards modeling was used to determine the influence of IMN RT on clinical outcome. Age, tumor size, lymph nodal status, adjuvant radiotherapy, chemotherapy and hormonal therapy were assessed. RESULTS: IMN-EB resulted in a significant improvement of distant metastasis-free survival, breast cancer-specific survival and overall survival (P=0.033, P=0.037 and P=0.011, respectively). The IMN-EB radiotherapy has a significant impact on event-free survival (HR, 0.67; 95% CI, 0.46-0.91; P=0.043) and breast cancer-specific survival (HR, 0.64; 95% CI, 45-0.91; P=0.013) in patients with moderate-risk (stage T1-2N1). There was no association between IMN RT and clinical outcomes of patients with high-risk disease (stage T3-4N2-3) in any of the study end points. CONCLUSIONS: The effects of IMN-EB radiotherapy on event-free survival and breast cancer-specific survival were benefit for women with moderate-risk breast cancer.

Radiotherapy equipment and departments in the European countries: final results from the ESTRO-HERO survey.

BACKGROUND: Documenting the distribution of radiotherapy departments and the availability of radiotherapy equipment in the European countries is an important part of HERO - the ESTRO Health Economics in Radiation Oncology project. HERO has the overall aim to develop a knowledge base of the provision of radiotherapy in Europe and build a model for health economic evaluation of radiation treatments at the European level. The aim of the current report is to describe the distribution of radiotherapy equipment in European countries. METHODS: An 84-item questionnaire was sent out to European countries, principally through their national societies. The current report includes a detailed analysis of radiotherapy departments and equipment (questionnaire items 26-29), analyzed in relation to the annual number of treatment courses and the socio-economic status of the countries. The analysis is based on validated responses from 28 of the 40 European countries defined by the European Cancer Observatory (ECO). RESULTS: A large variation between countries was found for most parameters studied. There were 2192 linear accelerators, 96 dedicated stereotactic machines, and 77 cobalt machines reported in the 27 countries where this information was available. A total of 12 countries had at least one cobalt machine in use. There was a median of 0.5 simulator per MV unit (range 0.3-1.5) and 1.4 (range 0.4-4.4) simulators per department. Of the 874 simulators, a total of 654 (75%) were capable of 3D imaging (CT-scanner or CBCT-option). The number of MV machines (cobalt, linear accelerators, and dedicated stereotactic machines) per million inhabitants ranged from 1.4 to 9.5 (median 5.3) and the average number of MV machines per department from 0.9 to 8.2 (median 2.6). The average number of treatment courses per year per MV machine varied from 262 to 1061 (median 419). While 69% of MV units were capable of IMRT only 49% were equipped for image guidance (IGRT). There was a clear relation between socio-economic status, as measured by GNI per capita, and availability of radiotherapy equipment in the countries. In many low income countries in Southern and Central-Eastern Europe there was very limited access to radiotherapy and especially to equipment for IMRT or IGRT. CONCLUSIONS: The European average number of MV machines per million inhabitants and per department is now better in line with QUARTS recommendations from 2005, but the survey also showed a significant heterogeneity in the access to modern radiotherapy equipment in Europe. High income countries especially in Northern-Western Europe are well-served with radiotherapy resources, other countries are facing important shortages of both equipment in general and especially machines capable of delivering high precision conformal treatments (IMRT, IGRT).

Radiotherapy staffing in the European countries: final results from the ESTRO-HERO survey.

BACKGROUND: The ESTRO Health Economics in Radiation Oncology (HERO) project has the overall aim to develop a knowledge base of the provision of radiotherapy in Europe and build a model for health economic evaluation of radiation treatments at the European level. The first milestone was to assess the availability of radiotherapy resources within Europe. This paper presents the personnel data collected in the ESTRO HERO database. MATERIALS AND METHODS: An 84-item questionnaire was sent out to European countries, through their national scientific and professional radiotherapy societies. The current report includes a detailed analysis of radiotherapy staffing (questionnaire items 47-60), analysed in relation to the annual number of treatment courses and the socio-economic status of the countries. The analysis was conducted between February and July 2014, and is based on validated responses from 24 of the 40 European countries defined by the European Cancer Observatory (ECO). RESULTS: A large variation between countries was found for most parameters studied. Averages and ranges for personnel numbers per million inhabitants are 12.8 (2.5-30.9) for radiation oncologists, 7.6 (0-19.7) for medical physicists, 3.5 (0-12.6) for dosimetrists, 26.6 (1.9-78) for RTTs and 14.8 (0.4-61.0) for radiotherapy nurses. The combined average for physicists and dosimetrists is 9.8 per million inhabitants and 36.9 for RTT and nurses. Radiation oncologists on average treat 208.9 courses per year (range: 99.9-348.8), physicists and dosimetrists conjointly treat 303.3 courses (range: 85-757.7) and RTT and nurses 76.8 (range: 25.7-156.8). In countries with higher GNI per capita, all personnel categories treat fewer courses per annum than in less affluent countries. This relationship is most evident for RTTs and nurses. Different clusters of countries can be distinguished on the basis of available personnel resources and socio-economic status. CONCLUSIONS: The average personnel figures in Europe are now consistent with, or even more favourable than the QUARTS recommendations, probably reflecting a combination of better availability as such, in parallel with the current use of more complex treatments than a decade ago. A considerable variation in available personnel and delivered courses per year however persists among the highest and lowest staffing levels. This not only reflects the variation in cancer incidence and socio-economic determinants, but also the stage in technology adoption along with treatment complexity and the different professional roles and responsibilities within each country. Our data underpin the need for accurate prediction models and long-term education and training programmes.

Guidelines for equipment and staffing of radiotherapy facilities in the European countries: final results of the ESTRO-HERO survey.

BACKGROUND AND PURPOSE: In planning to meet evidence based needs for radiotherapy, guidelines for the provision of capital and human resources are central if access, quality and safety are not to be compromised. A component of the ESTRO-HERO (Health Economics in Radiation Oncology) project is to document the current availability and content of guidelines for radiotherapy in Europe. MATERIALS AND METHODS: An 84 part questionnaire was distributed to the European countries through their national scientific and professional radiotherapy societies with 30 items relating to the availability of guidelines for equipment and staffing and selected operational issues. Twenty-nine countries provided full or partial evaluable responses. RESULTS: The availability of guidelines across Europe is far from uniform. The metrics used for capital and human resources are variable. There seem to have been no major changes in the availability or specifics of guidelines over the ten-year period since the QUARTS study with the exception of the recent expansion of RTT staffing models. Where comparison is possible it appears that staffing for radiation oncologists, medical physicists and particularly RTTs tend to exceed guidelines suggesting developments in clinical radiotherapy are moving faster than guideline updating. CONCLUSION: The efficient provision of safe, high quality radiotherapy services would benefit from the availability of well-structured guidelines for capital and human resources, based on agreed upon metrics, which could be linked to detailed estimates of need.

Radiation exposure received by the medical radiation workers in Lithuania at the Institute of Oncology, Vilnius University, 2004-2011.

The occupational radiation exposure of medical radiation workers at the Institute of Oncology, Vilnius University (IOVU) was analysed. Quartile dose measurements were collected and routinely analysed for a period of 8 y from 1 January 2004 to 31 December 2011. A total of 193 medical radiation workers were monitored, comprising 34 % physicians (radiologists and radiotherapists), 8 % physicists, 42 % radiological technologists and 16 % ancillary staff. A statistically significant decrease by 18 % has been detected when comparing the annual average effective doses (AAEDs) received by medical radiation workers at the IOVU during periods 2004-2007 and 2008-2011 (p < 0.0001). The main occupation categories responsible for this reduction were of Nuclear Medicine (p < 0.028) and Radiology (p < 0.0001) departments. The values of AAED in Radiology, Radiotherapy and Nuclear Medicine departments are quite low and well below the annual limit of 20 mSv, averaged over a period of 5 consecutive years.

Second malignancies following conventional or combined ²5²Cf neutron brachytherapy with external beam radiotherapy for breast cancer.

We retrospectively evaluated the risk of second malignancies among 832 patients with inner or central breast cancer treated with conventional external beam schedule (CRT group), or neutron brachytherapy using Californium-252 (²5²Cf) sources and hypofractionated external beam radiotherapy (HRTC group), between 1987 and 1996 at the Institute of Oncology, Vilnius University. Patients were observed until the occurrences of death or development of a second malignancy, or until 31 December 2009, whichever was earlier. Median follow-up time was 10.4 years (range, 1.2-24.1 years). Risk of second primary cancers was quantified using standardized incidence ratios (SIRs). Cox proportional hazards regression models were used to estimate hazard ratios (HRs). There was a significant increase in the risk of second primary cancers compared with the general population (SIR 1.3, 95% CI 1.1-1.5). The observed number of second primary cancers was also higher than expected for breast (SIR 1.8, 95% CI 1.3-2.4) and lung cancer (SIR 3.8, 95% CI 2.0-6.7). For second breast cancer, no raised relative risk was observed during the period ≥10 or more years after radiotherapy. Compared with the CRT group, HRTC patients had a not statistically significant higher risk of breast cancer. Increased relative risks were observed specifically for age at initial diagnosis of <50 years (HR 2.9, 95% CI 1.6-5.2) and for obesity (HR 2.8, 95% CI 1.1-7.2).

[Microsatellite instability and loss of heterozygosity in cancer]. / Mikrosatelitu nestabilumas ir heterozigotiskumo praradimas sergant veziu.

Literature review on genetic alterations (microsatellite instability and loss of heterozygosity) in different types of cancer is presented. Microsatellite instability and loss of heterozigosity are significant processes in carcinogenesis. The evaluation of microsatellite instability in cancer patients might be of clinical importance as a prognostic and predictive factor. The most of up-to-date data available are on microsatellite instability in colorectal cancer. For other types of cancer, the number of publications on microsatellite instability is rapidly increasing.

Long-term results of high-dose-rate brachytherapy and external-beam radiotherapy in the primary treatment of endometrial cancer.

In this report we update our long-term follow-up results of the prospective study whose aim was to evaluate the efficacy of high-dose-rate (HDR) brachytherapy in combination with external-beam radiotherapy (EBRT) in the treatment of medically inoperable endometrial cancer. Between 1995 and 1998, 29 patients with stages I-III medically inoperable carcinoma of endometrium were treated with definitive irradiation. All patients underwent combined intracavitary HDR brachytherapy and EBRT. The EBRT dose was 50 Gy with midline shield from 16 Gy. The HDR brachytherapy dose was 50 Gy, delivered in 5 fractions in a weekly schedule. Overall survival (OS) at 5 and 10 years was 48.3% and 20.7%, respectively. Disease-specific survival (DSS) at 5 and 10 years was 73.5% and 67.9%, respectively. The 10-year DSS rate was 73.5% for all stages, 85.7% for Stage I disease, 71.4% for Stage II, and 16.7% for stage III disease. Late Grade 1-2 radiation complications were observed in 4 patients (13.8%). Our long-term follow-up confirms that HDR brachytherapy with EBRT appears to be an effective and safe treatment for stage I and II medically inoperable endometrial cancer.

[Treatment outcome of locally advanced stage IIIA/B lung cancer]. / Vietiskai isplitusio IIIA/B stadijos plauciu vezio gydymo rezultatai.

OBJECTIVE: To determine survival of patients with stage IIIA/B non-small cell lung cancer considering disease stage and treatment methods. MATERIAL AND METHODS: A total of 304 patients with non-small cell lung cancer were treated at the Department of Thoracic Surgery and Oncology, Institute of Oncology, Vilnius University, in 2000-2004. Stage IIIA (T3N1-2M0) cancer was diagnosed for 193 (63.5%) patients and stage IIIB (T4N0-1M0) cancer was diagnosed for 111 (36.5%) patients. There were 277 (91.1%) males and 27 (8.9%) females. According to morphology, there were 219 (72%) patients with squamous cell lung cancer, 80 (26.3%) with adenocarcinoma, and 5 (1.7%) patients with large cell carcinoma. Surgery was performed in 145 patients: 84 (57.9%) patients underwent lung resection (T3-4N0-1M0), 51 (35.2%) patients - thoracotomy, and 10 (6.7%) patients - other palliative thoracic procedures (mediastinotomy, pleurectomy, mediastinoscopy). Forty-eight (30.2%) patients were treated with radiation therapy with total doses of >40 Gy and 58 (36.5%) patients were treated with radiation therapy with total doses of <40 Gy. Fifty-four (33.9%) patients were treated with Gemzar and cisplatin and 19 (11.9%) patients were treated with etoposide and cisplatin. RESULTS: Overall median and mean survival was 7.8 months (95% CI, 6.8 to 8.8) and 9.9 months (95% CI, 9.0 to 10.9), respectively. The median and mean survival of patients with stage IIIA cancer was 8.3 months and 10.4 months, respectively, and that of patients with stage IIIB cancer - 6.4 months and 9.0 months, respectively (P < or =0.05). The median survival of the patients with stage IIIA cancer who received a combination of operation, chemotherapy, and radiation therapy with a total dose of >40 Gy was 14.4 months (mean, 14.7 months), and the median survival of those who received operation, chemotherapy, and radiation therapy with a total dose of < or =40 Gy was 9.7 months (mean, 14.1 months); the median survival of the patients who underwent surgery alone was 4.9 months (mean, 6.7 months) (P=0.004 and P=0.007), respectively. There was a significant difference in the median survival comparing the patients with stage IIIB cancer who underwent surgery alone and those who received a combination of radiation therapy and chemotherapy (median survival of 5.0 months [mean, 8.1 months] versus 16.8 months [mean, 17.6 months], respectively; P < or =0.05). CONCLUSIONS: Disease stage had an influence on the survival of patients with non-small cell lung cancer: patients with stage IIIA (T3N0-1M0) cancer without metastases to mediastinal lymph nodes (N factor) survived longer than patients with stage IIIB (T4N1-2M0) cancer, where not only N factor had an impact but T factor as well. Better treatment outcomes, i.e. longer survival, can be achieved when a combination of three treatment types - surgery, chemotherapy, and radiation therapy - is applied to patients with stage IIIA or IIIB non-small cell lung cancer. The patients with stage IIIA disease who received surgery and radiation therapy (total dose, >40 Gy), and combinations of surgery, chemotherapy, and radiation therapy and second-line chemotherapy showed a significantly longer survival than those who received surgery alone.

Enhancement of photodynamic tumor therapy effectiveness by electroporation in vitro.

The aim of our study was to determine if electroporation could improve the efficacy of photodynamic tumor therapy. A disadvantage of photodynamic therapy is a slow and in some cases insufficient accumulation of photosensitizer in tumor tissue, which could restrict the achievement of an efficient dose. Under the action of electric pulses, cells undergo membrane electroporation, which results in an increased permeability to various exogenous molecules. In this study, murine hepatoma MH22A cells were exposed to light in vitro in the presence of a photosensitizer, either chlorin e6 or aluminum phthalocyanine tetrasulfonate, following electroporation. Accumulation of the photosensitizers was registered by fluorescence microscopy. Cell viability was determined by the MTT assay. Our results demonstrate that electroporation improves an access of chlorin e6 and aluminum phthalocyanine tetrasulfonate to MH22A cells. Electroporation in combination with photosensitization significantly reduces viability of the treated cells even at low doses of photosensitizers.

The risk of cancer among Lithuanian medical radiation workers in 1978-2004.

OBJECTIVES: To describe the cohort of Lithuanian medical radiation workers and to estimate the risk of cancer during 1978-2004. METHODS: Analysis of cancer risk evaluation was done using the retrospective cohort method, an indirect standardization. The observed numbers of cancer cases were obtained from the National Cancer Registry. The expected numbers were based on the age- and gender-specific incidence rates for the general Lithuanian population in 5-year periods. The standardized incidence ratios and 95% confidence intervals (assuming that the incidence of cancer follows the Poisson distribution) were calculated. RESULTS: During the follow-up of 1978-2004, 159 cases of cancer were observed. There was no increased overall cancer risk in men (SIR=0.92, 95% CI=0.62-1.33, based on 29 cases) and women (SIR=0.97, 95% CI=0.81-1.15, based on 130 cases). The risk of leukemia among men and women was insignificantly increased. CONCLUSIONS: During the follow-up period, the overall cancer risk among medical radiation workers was the same as in the general population of Lithuania.