A randomized trial comparing hypofractionated and conventionally fractionated three-dimensional conformal external-beam radiotherapy for localized prostate adenocarcinoma: a report on the first-year biochemical response.

OBJECTIVE: This paper describes the first-year biochemical (prostate-specific antigen [PSA]) response of 91 irradiated patients enrolled in a single-institution randomized trial comparing hypofractionated (HFRT) and conventionally fractionated (CFRT) external beam radiotherapy. MATERIAL AND METHODS: Forty-four patients in the CFRT treatment arm were irradiated with 74 Gy in 37 fractions (2 Gy per fraction), and 47 in the HFRT arm were treated with 57 Gy, given in 13 fractions of 3 Gy plus 4 fractions of 4.5 Gy. The clinical target volume includes the prostate and a base of seminal vesicles. The proportions of patients who reached PSA nadir (nPSA) lower than or equal to 1.0 ng/mL (nPSA1) and 0.5 ng/mL (nPSA05) were compared. RESULTS: There were 2 non-cancer-related deaths (1 in the CFRT and 1 in the HFRT treatment arms). Biochemical relapse after irradiation was defined in five cases (3 in the CFRT and 2 in the HFRT treatment arms) during a 12-month follow-up. The remaining 84 patients were analyzed. The proportions of patients reaching nPSA1 were 50% and 54.5% in the CFRT and HFRT treatment arms, respectively (chi-square P=0.843). The percentages of patients reaching nPSA05 were 25% and 18.2%, respectively (chi-square P=0.621). The trends toward increasing proportions of biochemical responders (both nPSA1 and nPSA05) during 12 months after radiotherapy were observed, but the difference between trends for treatment arms did not reach a statistical significance. CONCLUSION: The preliminary results presented here demonstrate that HFRT schedule induces biochemical response rates comparable to those in the CFRT schedule during the first-year follow-up.

Assessment of Correlation between Chromosomal Radiosensitivity of Peripheral Blood Lymphocytes after In vitro Irradiation and Normal Tissue Side Effects for Cancer Patients Undergoing Radiotherapy.

Patients receiving identical radiation treatments experience different effects, from undetectable to severe, on normal tissues. A crucial factor of radiotherapy related side effects is individual radiosensitivity. It is difficult to spare surrounding normal tissues delivering radiation to cancer cells during radiotherapy. Therefore, it may be useful to develop a simple routine cytogenetic assay which would allow the screening of a large number of individuals for radiosensitivity optimizing tumor control rates and minimizing severe radiotherapy effects with possibility to predict risk level for developing more severe early normal tissue adverse events after irradiation. This study was conducted to assess the correlation between in vitro radiosensitivity of peripheral blood lymphocytes from cancer patients who are undergoing radiotherapy using the cytokinesis-block micronucleus (CBMN), G2 chromosomal radiosensitivity assays, and normal tissue acute side effects. The CBMN and G2 chromosomal radiosensitivity assays were performed on blood samples taken from cancer patients before radiotherapy, after first fractionation, and after radiotherapy. Acute normal tissue reactions were graded according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer. This study suggests that there is a correlation between higher frequency of micronuclei after in vitro irradiation of blood samples and higher degree of normal tissue reactions. In addition, higher number of chromatid breaks was observed in patients with more severe normal tissue reactions. This pilot study included only 5 cancer patients, and therefore, further studies with a bigger cohort are required to identify radiosensitive patients.

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.

[A preliminary safety study of hypofractionated radiotherapy for local prostate cancer]. / Neisplitusio priesines liaukos vezio hipofrakcionuoto spindulinio gydymo saugumo tyrimas.

Institute of Oncology of Vilnius University has initiated a randomized clinical trial with the aim to evaluate the effectiveness and toxicity of conventional fractionated (37 fractions, 2.0 Gy per fraction, a total dose of 74 Gy) and hypofractionated (13 fractions, 3.0 Gy per fraction, and 4 fractions at 4.5 Gy per fraction, a total dose of 57 Gy) radiotherapy. The goal of preliminary safety analysis was to compare the acute radiation toxicity in investigated and control groups. A total of 22 patients have been enrolled in this trial; there were 11 patients in each investigated group. Grade IV acute bladder radiation toxicity according to Radiation Therapy Oncology Group (RTOG) toxicity criteria was observed in one control group patient. No grade III acute radiation toxicity was observed. Grade II acute radiation toxicity was observed in 2 patients from hypofractionated radiotherapy group and in 3 from conventional radiotherapy group. Grade I-II acute radiation toxicity was observed in all patients of investigated and control groups. A statistically significant decrease of grade I bladder and rectal toxicity in the hypofractionated arm and grade I bladder toxicity in the conventional arm was observed. Other differences were not significant. A comparatively small number of acute reactions in the patients' group treated with hypofractionated radiotherapy show the safety of the method applied and enable the continuation of this trial.

IAEA randomised trial of optimal single dose radiotherapy in the treatment of painful bone metastases.

BACKGROUND: To determine the optimal single-dose radiotherapy schedule for pain from bone metastases in a multi-centre, international, randomised trial. PATIENTS AND METHODS: 651 patients were randomised to either 8Gy (n=325) or 4Gy (n=326) radiotherapy. Pain at 4, 8, 12, 24 and 52weeks was assessed using a Categorical Scale (CS) and a Visual Analogue Scale (VAS). The primary endpoint was response at 4weeks. RESULTS: There was no significant difference in patient demographics and other co-variates. The complete response (CR) rate and ORR (complete or partial response) for all follow-up times were higher after 8Gy (p=0.02). The Kaplan-Meier actuarial rate (categorical scale) at 4weeks for ORR was 80% after 8Gy compared to 68% after 4Gy (p=0.0015). 117 re-treatments were given of which 72 were in the 4Gy group and 45 in 8Gy arm (p=0.01). CONCLUSIONS: There was a marked consistent difference in pain relief at all time points in favour of 8Gy. These data reinforce the case for single dose 8Gy radiotherapy to be recommended for metastatic bone pain in all healthcare settings.

[Trends in the prevalence of risk factors of noncommunicable diseases during 1987-1999]. / Letiniu neinfekciniu ligu rizikos veiksniu paplitimo pokyciai 1987-1999 metais.

The trends in the prevalence of hypertension, hypercholesterolemia, overweight and smoking among Lithuanian rural population were assessed from 1987 to 1999. Three independent surveys in 1987, 1993 and 1999 were carried out in five rural regions of Lithuania in random samples of men and women aged 25-64 involving 2695, 1550 and 1838 persons respectively. The risk factors were defined according to the WHO criteria. During the 13 years the prevalence of hypercholesterolemia and overweight has significantly decreased among men (by 23.2% and 4.9% respectively) as well as among women (by 19.9% and 10.7% respectively). The prevalence of hypertension among women has decreased by 9.1%, with no significant changes among men. The prevalence of smoking has increased by 8.9% among women and has not changed among men. Age was positively correlated with the prevalence of all risk factors, except smoking. Younger persons smoked more often than elderly did. Prevalence of risk factors varied by educational level. Hypertension and overweight have been more prevalent among women with incomplete secondary education, than among those with university education. The prevalence of overweight and hypercholesterolaemia has been higher among highly educated men compared to low educated. The inverse relationship between smoking and education has been observed in men. In conclusion, the decreasing trends in the prevalence of some risk factors have been estimated in Lithuania within last decade. Sociodemographic differences in the prevalence of risk factors should be taken into account while developing health promotion and diseases prevention programmes.

Prevalence of dyslipidemias among Lithuanian rural population (CINDI program).

The aim of this study is to describe trends in serum total, low and high density lipoprotein cholesterol, triglycerides and nutrition habits in Lithuanian rural population between 1987 and 1999. The article presents the data of three screenings of random samples of the population aged 25-64 of five Lithuanian rural regions. Since 1987 the prevalence of hypercholesterolemia has decreased. The greatest decrease was observed in the proportion of persons with elevated level of low-density lipoprotein cholesterol. The prevalence of low level of high-density lipoprotein cholesterol decreased more significantly among women compared to men. The most remarkable changes in the prevalence of dyslipidemias were observed between 1993 and 1999. The increasing age was strongly correlated with higher prevalence of hypercholesterolemia in both genders. The prevalence of hypercholesterolemia was higher among men with higher education, overweight, hypertension and smokers than among those with low education, normal weight, normal level of blood pressure and nonsmokers. In women hypercholesterolemia was associated only with hypertension. The nutrition habits of Lithuanian rural population have changed, especially over the last five years. The consumption of animal fat has decreased and the usage of vegetable oil and margarine has increased. Women increased consumption of vegetables and fruits. The strengthening of favorable trends in nutrition habits in Lithuanian population should be one of the most important strategies in the implementation of cardiovascular disease prevention programs.

[Influence of prognostic factors on the survival of lung cancer patients]. / Serganciuju plauciu veziu prognoziniu veiksniu itaka gyvenimo trukmei.

This study presents the results of analysis of 134 lung cancer patients treated with radiotherapy in 1999-2002. The objective of the paper was to evaluate the importance of some prognostic factors on survival of lung cancer patients. We have analyzed influence of patient's age, stage of the disease, tumor size, lymphnodes status, histological type and radiotherapy dose to the survival of lung cancer patients. Among analyzed patients 87% were males and 73.9% were more than 60 years old. Locally advanced lung cancer was diagnosed in 65.6% of cases. The non-small cell lung cancer was diagnosed in 83.8% of cases. During the study period 58.2% of patients died. Statistically significant prognostic factors in our study were: stage, locally advanced lung cancer, involvement of the lymphnodes, III B and IV of the disease. The survival of the patients depends on the radiotherapy dose in our study. The better survival was associated with the bigger than 50 Gy dose (p<0.001).

[The influence of conformal radiotherapy on survival of lung cancer patients]. / Konformalios spindulines terapijos itaka serganciuju plauciu veziu gyvenimo trukmei.

The aim of this study was to analyze survival dependence on 3-D conformal radiotherapy dose applied to non-small cell lung cancer patients treated in Kaunas University of Medicine Hospital from year 1999 to 2001. One hundred fifteen patients with median age 67.3 years were analyzed. There were 101 men and 14 women. Squamous cell carcinoma was the most common type of histology (80.86% patients). Most patients (61.7%) had locally advanced lung cancer (stage III). Radiotherapy doses applied ranged from 30 Gy (3.0 Gy/10 fractions) to 70 Gy (2.0 Gy/35 fractions). After analysis of radiotherapy dose influence on survival statistically significant improvement in median survival with higher doses was found (p=0.0001 Breslow). The group of patients irradiated with higher than 50 Gy dose demonstrated better survival than patients treated with smaller doses. (Log rank p=0.0061, Breslow p=0.0013). There was a correlation between dose and conformity of dose distribution.