Androgen-deprivation therapy and risk of death from cardio-vascular disease in prostate cancer patients: a nationwide lithuanian population-based cohort study.

Purpose: The main purpose of this study was to evaluate the risk of CVD mortality in the national cohort of patients diagnosed with prostate cancer and treated with ADT compared with the ADT non-users.Materials and methods: We performed a retrospective cohort study of patients aged 40-79 years and diagnosed with prostate cancer between 1 January 2012 and 31 December 2016 using the Lithuanian Cancer registry data. In total, 13 343 prostate cancer patients were included in the final study cohort who exclusively used gonadotropin-releasing hormone agonists. The primary outcomes that were registered during the follow-up of this study were overall CVD death.Results: There was a higher risk of CVD death in the cohort of patients treated with ADT than in ADT non-users (HR 2.14, 95% CI [1.86-2.45], p < 0.001). Moreover, there was an increased risk of death from ischemic heart disease and stroke (HR 1.42, 95% CI [1.16-1.73] and 1.70, 95% CI [1.18-2.45], respectively) among ADT users. Finally, the risk of CVD-related mortality was highest in the 70-79 age group of ADT users (HR 4.78, 95% CI [3.79-6.04]).Conclusions: This study shows that ADT usage is associated with increased CVD-related mortality risk for patients diagnosed with prostate cancer compared with ADT non-users. The highest mortality risk was found for ischemic heart disease and stroke. CVD-related mortality was increased in the elder group of patients also.

Development of a benchmark tool for cancer centers; results from a pilot exercise.

BACKGROUND: Differences in cancer survival exist between countries in Europe. Benchmarking of good practices can assist cancer centers to improve their services aiming for reduced inequalities. The aim of the BENCH-CAN project was to develop a cancer care benchmark tool, identify performance differences and yield good practice examples, contributing to improving the quality of interdisciplinary care. This paper describes the development of this benchmark tool and its validation in cancer centers throughout Europe. METHODS: A benchmark tool was developed and executed according to a 13 step benchmarking process. Indicator selection was based on literature, existing accreditation systems, and expert opinions. A final format was tested in eight cancer centers. Center visits by a team of minimally 3 persons, including a patient representative, were performed to verify information, grasp context and check on additional questions (through semi-structured interviews). Based on the visits, the benchmark methodology identified opportunities for improvement. RESULTS: The final tool existed of 61 qualitative and 141 quantitative indicators, which were structured in an evaluative framework. Data from all eight participating centers showed inter-organization variability on many indicators, such as bed utilization and provision of survivorship care. Subsequently, improvement suggestions for centers were made; 85% of which were agreed upon. CONCLUSION: A benchmarking tool for cancer centers was successfully developed and tested and is available in an open format. The tool allows comparison of inter-organizational performance. Improvement opportunities were successfully identified for every center involved and the tool was positively evaluated.

Acute toxicity and quality of life in high risk prostate cancer patients: Updated results of randomized hypofractionation trial.

PURPOSE: The aim of our study was to perform the final analysis of acute toxicity and quality of life data obtained from 221 consecutive patients who suffered from intermediate-to-high risk prostate cancer. METHODS: In this trial, 221 patients were randomized to receive either hypofractionated (63 Gy in 20 fractions, 4 fractions/week) or conventionally fractionated (76 Gy in 38 fractions, 5 fractions/week) radiotherapy to the prostate and seminal vesicles. Elective pelvic lymph node irradiation with 46 Gy in 23 fractions sequentially and 44 Gy in 20 fractions simultaneously was also applied. RESULTS: There was no statistically significant difference in acute GU and GI toxicity in men treated with hypofractionated (SIB) (Arm 2) in comparison with patients who had conventional fractionation (Arm 1) radiation therapy. Multivariate analysis using logistic regression showed statistical significant association between acute GU ≥ 1 and PTV(LN) (p = 0.008) only. We found out that clinically relevant decrease (CRD) was significantly higher only in the urinary domain of Arm 1 at month 3 (p = 0.02). CONCLUSION: Our study demonstrated that hypofractionated radiotherapy was associated with a small but insignificant increase of acute toxicity. The reduction of overall treatment time has no significant influence on patients' QOL in any domain.

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.

E3 ubiquitin ligases as drug targets and prognostic biomarkers in melanoma.

Melanomas are highly proliferative and invasive, and are most frequently metastatic. Despite many advances in cancer treatment over the last several decades, the prognosis for patients with advanced melanoma remains poor. New treatment methods and strategies are necessary. The main hallmark of cancer is uncontrolled cellular proliferation with alterations in the expression of proteins. Ubiquitin and ubiquitin-related proteins posttranslationally modify proteins and thereby alter their functions. The ubiquitination process is involved in various physiological responses, including cell growth, cell death, and DNA damage repair. E3 ligases, the most specific enzymes of ubiquitination system, participate in the turnover of many key regulatory proteins and in the development of cancer. E3 ligases are of interest as drug targets for their ability to regulate proteins stability and functions. Compared to the general proteasome inhibitor bortezomib, which blocks the entire protein degradation, drugs that target a particular E3 ligase are expected to have better selectivity with less associated toxicity. Components of different E3 ligases complexes (FBW7, MDM2, RBX1/ROC1, RBX2/ROC2, cullins and many others) are known as oncogenes or tumor suppressors in melanomagenesis. These proteins participate in regulation of different cellular pathways and such important proteins in cancer development as p53 and Notch. In this review we summarized published data on the role of known E3 ligases in the development of melanoma and discuss the inhibitors of E3 ligases as a novel approach for the treatment of malignant melanomas.

Efficacy of focal high-dose-rate brachytherapy in the treatment of patients diagnosed with low or favourable: intermediate-risk prostate cancer-a protocol for a randomised controlled trial.

INTRODUCTION: Prostate cancer (PCa) is men's second most predominant cancer worldwide. Because the prostate-specific antigen test is used in diagnostics, PCa is more often diagnosed in the early stages, making radical treatment of the disease possible. However, it is estimated that over a million men worldwide suffer from radical treatment-related complications. Thus, focal treatment has been proposed as a solution, which aims to destroy the predominant lesson that determines the progression of the disease. The main objective of our study is to compare the quality of life and efficacy of patients diagnosed with PCa before and after the treatment with focal high-dose-rate brachytherapy and to compare results with focal low-dose-rate brachytherapy and active surveillance. METHODS AND ANALYSIS: 150 patients diagnosed with low-risk or favourable intermediate-risk PCa who meet the inclusion criteria will be enrolled in the study. Patients are going to be randomly assigned to the study groups: focal high-dose-rate brachytherapy (group 1), focal low-dose-rate brachytherapy (group 2) and active surveillance (group 3). The study's primary outcomes are quality of life after the procedure and time without biochemical disease recurrence. The secondary outcomes are early and late genitourinary and gastrointestinal reactions after the focal high-dose and low-dose-rate brachytherapies and evaluation of the importance and significance of in vivo dosimetry used for high-dose-rate brachytherapy. ETHICS AND DISSEMINATION: Bioethics committee approval was obtained before this study. The trial results will be published in peer-reviewed journals and at conferences. TRIAL REGISTRATION NUMBER: Vilnius regional bioethics committee; approval ID 2022/6-1438-911.

OECI 2022 ONCOLOGY DAYS AND GENERAL ASSEMBLY.

The OECI 2022 Oncology Days and the OECI General Assembly were held in Valencia (Spain) on June 15-17.

The 99mTc-MIP-1404 PSMA Uptake in the Isolated Paratracheal Lymph Node From the Prostate Adenocarcinoma.

ABSTRACT: The oncologist consulted a 56-year-old man after receiving prostate-specific antigen screening results. Prostate-specific antigen level during the screen time was 33 ng/mL. As a result, poorly differentiated prostate adenocarcinoma with a Gleason score of 9 (5 + 4) was diagnosed. SPECT/CT scan with 99mTc-MIP-1404 PSMA tracer was performed. The 99mTc-PSMA-positive lesions were detected in the prostate, external iliac, obturator lymph nodes of the pelvis, para-aortic, and the right lower paratracheal space. The patient was prescribed androgen deprivation therapy and early chemotherapy with docetaxel (6 fractions), after which radiation therapy to prostate and seminal vesicles was planned.

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.

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.

Analysis of cardiac and pulmonary complication probabilities after radiation therapy for patients with early-stage breast cancer.

OBJECTIVE: The purpose of this study was to evaluate the radiobiological implications of clinical use of respiratory-gated techniques for postoperative radiation therapy of early-stage left-sided breast cancer after breast-conserving surgery. MATERIAL AND METHODS: Radiation therapy treatment plans of 80 patients with early-stage breast cancer (stage I-II), receiving whole breast irradiation after breast-conserving therapy, were analyzed. The control group consisting of 47 patients received standard radiation therapy, and the respiratory-gated group consisting of 33 patients received deep inspiration-gated radiation therapy. Normal tissue complication probabilities (NTCP) for cardiac mortality and for clinical radiation-induced pneumonitis were calculated for all patients included in present study, using relative seriality model. NTCP data were analyzed for 113 radiation therapy plans, which included free breathing plans for the respiratory-gated groups. RESULTS: Pneumonitis probability was 0.6% (range 0.0-2.8%) and 0.3% (0.0-1.2%) for control and respiratory-gated group, respectively. Cardiac mortality was 1.3% (0.0-5.0%) and 0.2% (0.0-2.8%) for control and respiratory-gated group, respectively. Using respiratory-gated radiation therapy, NTCP was reduced in comparison with the control group by 83% (P<0.00001) and by 55% (P=0.01270) for cardiac mortality and for clinical radiation-induced pneumonitis, respectively. CONCLUSIONS: Use of respiratory-gated radiation therapy, for postoperative treatment of early-stage breast cancer, significantly reduces excessive cardiac mortality probability and pulmonary complication probability, as compared to standard radiation therapy techniques. This is especially important from heart complication probability point of view, as cardiac mortality remains one of the important issues of postoperative breast irradiation in patients with early stage breast cancer.

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.

Investigation of Vitamin D-Binding Protein Polymorphism Impact on Coronary Artery Disease and Relationship with Longevity: Own Data and a Review.

The aim of the study was to assess the effect of vitamin D-binding protein (DBP) polymorphism on coronary artery disease (CAD). DBP phenotypes were identified in the groups: control (n = 306), men suffering from CAD (n = 154), and long-lived individuals (n = 108). Isoelectric focusing of DBP phenotypes in serum was performed on polyacrylamide gel. Distribution of DBP phenotypes in the study groups was found to be in Hardy-Weinberg equilibrium. Gc1s-1s phenotype and Gc1s allele frequency in CAD groups were significantly higher than in control, and Gc1s allele frequency was found significantly more often in CAD compared with long-lived group (p < 0.05). The Gc2 allele frequency in control was higher as compared with Gc2 frequency in CAD group (p < 0.05). The Gc2-2 phenotype was more frequent in long-lived survivors than in the CAD group (p < 0.05). It was found that the Gc1s allele significantly increased the risk of CAD with the odds ratio (OR) equal to 1.45 (p < 0.02) and showed Gc2 to be related with a decreased risk of CAD (OR = 0.69; p < 0.03). Authors review the role of DBP in resistance to atherosclerosis and cancer as the main longevity determinants.

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.

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.

A randomized hypofractionation dose escalation trial for high risk prostate cancer patients: interim analysis of acute toxicity and quality of life in 124 patients.

BACKGROUND: The α/ß ratio for prostate cancer is postulated being in the range of 0.8 to 2.2 Gy, giving rise to the hypothesis that there may be a therapeutic advantage to hypofractionation. To do so, we carried out a randomized trial comparing hypofractionated and conventionally fractionated image-guided intensity modulated radiotherapy (IG-IMRT) in high-risk prostate cancer. Here, we report on acute toxicity and quality of life (QOL) for the first 124 randomized patients. METHODS: The trial compares 76 Gy in 38 fractions (5 fractions/week) (Arm 1) to 63 Gy in 20 fractions (4 fractions/week) (Arm 2) (IG-IMRT). Prophylactic pelvic lymph node irradiation with 46 Gy in 23 fractions sequentially (Arm 1) and 44 Gy in 20 fractions simultaneously (Arm 2) was applied. All patients had long term androgen deprivation therapy (ADT) started before RT. Both physician-rated acute toxicity and patient-reported QOL using EPIC questionnaire are described. RESULTS: There were no differences in overall maximum acute gastrointestinal (GI) or genitourinary (GU) toxicity. Compared to conventional fractionation (Arm 1), GI and GU toxicity both developed significantly earlier but also disappeared earlier in the Arm 2, reaching significant differences from Arm 1 at week 8 and 9. In multivariate analyses, only parameter shown to be related to increased acute Grade ≥1 GU toxicity was the study Arm 2 (p = 0.049). There were no statistically significant differences of mean EPIC scores in any domain and sub-scales. The clinically relevant decrease (CRD) in EPIC urinary domain was significantly higher in Arm 2 at month 1 with a faster recovery at month 3 as compared to Arm 1. CONCLUSIONS: Hypofractionation at 3.15 Gy per fraction to 63 Gy within 5 weeks was well tolerated. The GI and GU physician-rated acute toxicity both developed earlier but recovered faster using hypofractionation. There was a correlation between acute toxicity and bowel and urinary QOL outcomes. Longer follow-up is needed to determine the significance of these associations with late toxicity.

Strain specificity of antimycobacterial immunity in whole blood culture after cure of tuberculosis.

Bactericidal assays have facilitated development of most modern vaccines, and have been proposed as indicators of protection after vaccination against tuberculosis. We examined control of intracellular growth of Mycobacterium tuberculosis in whole blood cultures of cured TB patients and tuberculin-negative healthy volunteers. Cured patients showed superior restriction of growth of the strain with which they had been infected. They similarly showed superior control of growth of a clinical strain (MP-28) that had become attenuated during passage. However, patients and healthy volunteers did not differ with regard to control of M. tuberculosis H37Ra. The ability of cured patients to control growth of the strain with which they had been infected correlated with MP-28, but not with H37Ra. These findings indicate M. tuberculosis MP-28 may be suitable to assess mycobacterial immunity as growth inhibition in whole blood culture, whereas H37Ra is not. However, additional studies will be required to confirm these observations in additional patient and microbial populations that are distinct according to geography and microbial and host genetics.

Survival and replication of clinical Mycobacterium tuberculosis isolates in the context of human innate immunity.

The initial host response to Mycobacterium tuberculosis is driven by innate immunity. For this study, we examined the ability of 18 recent clinical isolates and 5 reference strains to survive and replicate in the context of host innate immunity by using whole blood culture. Six healthy tuberculin-negative volunteers served as subjects. H(37)Ra showed the least capacity to replicate of any of the strains tested, decreasing in viability 1.3 log CFU during 72 h of whole blood culture, whereas H(37)Rv increased 0.32 log. Clinical isolates varied greatly in their ability to replicate in blood cells, ranging from -0.4 to +0.8 log (P < 0.001). Four showed significantly more growth than H(37)Rv, and one showed significantly reduced growth. Host mechanisms for restricting intracellular mycobacterial growth were more effective during the first 24 h of whole blood culture than during the 24- to 72-h period. Certain mycobacterial isolates appeared preferentially able to withstand host defenses during each of these intervals. Although there was relatively more homogeneity among subjects than among strains, one of the six subjects showed a reduced capacity to restrict intracellular mycobacterial growth due to a defect expressed during the first 24 h of culture. Our findings indicate substantial variability in the capacity of clinical tuberculosis isolates to replicate in host cells in the face of innate host immunity.