Alterations of Sexual and Erectile Functions after Brachytherapy for Prostate Cancer Based on Patient-Reported Questionnaires.

The aim of the study was to compare the side effects of high-dose-rate brachytherapy (HDRBT) and low-dose-rate brachytherapy (LDRBT), with a particular focus on the effects on sexual functions and sexual well-being (PROMOBRA study, NCT02258087). Localized low-risk and low-intermediate-risk prostate cancer patients were treated with mono LDR (N = 123, 145 Gy dose) or mono HDR brachytherapy (N = 117, 19/21 Gy). Prior to the treatment and during follow-up (at 3, 6, 9, 12, 18, and 24 months after treatment, and then annually after two years), patients completed patient-reported outcome measurement (PROM) questionnaires EORTC QLQ-PR-25, International Index of Erectile Function (IIEF), and IIEF-5 (SHIM). We compared the patients in different group breakdowns (HDR vs. LDR, hormone naïve and hormone-receiving HDR vs. LDR, hormone naïve and hormone-receiving patients in general, and 19 Gy HDR vs. 21 Gy HDR). In the hormone-naive LDR group, erectile function, orgasm function, sexual desire, satisfaction with intercourse, and overall satisfaction functions significantly decreased compared to baseline throughout the whole follow-up period. However, there were significant decreases in function at a maximum of three time points after HDR therapy without hormone therapy. In hormone-receiving patients, the orgasm function was significantly better in the HDR group at multiple time points compared to the baseline, and sexual desire improved at four time points. According to our results, both LDRBT and HDRBT can be safely administered to patients with localized prostate cancer. In hormone-naive patients, the HDR group showed only recovering decreases in sexual functions, while the LDR group showed a lasting decline in multiple areas. Thus, HDR appears to be more advantageous to hormone-naive patients.

Prostate Cancer Survivors Present Long-Term, Residual Systemic Immune Alterations.

BACKGROUND: The development of cancer and anti-tumor therapies can lead to systemic immune alterations but little is known about how long immune dysfunction persists in cancer survivors. METHODS: We followed changes in the cellular immune parameters of prostate cancer patients with good prognostic criteria treated with low dose rate brachytherapy before and up to 3 years after the initiation of therapy. RESULTS: Patients before therapy had a reduced CD4+ T cell pool and increased regulatory T cell fraction and these alterations persisted or got amplified during the 36-month follow-up. A significant decrease in the total NK cell number and a redistribution of the circulating NK cells in favor of a less functional anergic subpopulation was seen in patients before therapy but tumor regression led to the regeneration of the NK cell pool and functional integrity. The fraction of lymphoid DCs was increased in patients both before therapy and throughout the whole follow-up. Increased PDGF-AA, BB, CCL5 and CXCL5 levels were measured in patients before treatment but protein levels rapidly normalized. CONCLUSIONS: while NK cell dysfunction recovered, long-term, residual alterations persisted in the adaptive and partly in the innate immune system.

Relationship between biodosimetric parameters and treatment volumes in three types of prostate radiotherapy.

Brachytherapy (BT) and external beam radiotherapy (EBRT) apply different dose rates, overall treatment times, energies and fractionation. However, the overall impact of these variables on the biological dose of blood is neglected. As the size of the irradiated volume influences the biological effect as well, we studied chromosome aberrations (CAs) as biodosimetric parameters, and explored the relationship of isodose surface volumes (ISVs: V1%, V1Gy, V10%, V10Gy, V100%, V150%) and CAs of both irradiation modalities. We performed extended dicentrics assay of lymphocytes from 102 prostate radiotherapy patients three-monthly for a year. Aberration frequency was the highest after EBRT treatment. It increased after the therapy and did not decrease significantly during the first follow-up year. We showed that various types of CAs 9 months after LDR BT, 3 months after HDR BT and in a long time-range (even up to 1 year) after EBRT positively correlated with ISVs. Regression analysis confirmed these relationships in the case of HDR BT and EBRT. The observed differences in the time points and aberration types are discussed. The ISVs irradiated by EBRT showed stronger correlation and regression relationships with CAs than the ISVs of brachytherapy.

[Trimodal, organ-preserving treatment of organ-confined, muscle-invasive bladder cancer]. / Szervre lokalizált, izominvazív húgyhólyagrák trimodális, szervmegtartó kezelése.

Radical cystectomy is the gold standard treatment in localized muscle-invasive bladder cancer according to today's guidelines. However, in many cases, surgery is not possible due to the patient's general condition, or the patient refuses bladder removal. In such cases, as well as in some selected patients suitable for surgery, trimodal organ preservation therapy is an alternative, which provides the patient with similar survival, local tumor control, so that 80% of patients retain their bladder. In some cases, due to complications or a muscle-invasive local recurrence in the bladder, the bladder may not be retained. At this point, a salvage cystectomy can still save the patient's quality of life and life. Adequate patient selection is a prerequisite for effective trimodal therapy. We summarize the components of organ-preserving treatment, including radiation therapy, its state-of-the-art technology, results and side effects. The results and toxicity of trimodal treatment are compared with those of radical cystectomy.

Comparative dosimetrical analysis of intensity-modulated arc therapy, CyberKnife therapy and image-guided interstitial HDR and LDR brachytherapy of low risk prostate cancer.

BACKGROUND: The objective of the study was to dosimetrically compare the intensity-modulated-arc-therapy (IMAT), Cyber-Knife therapy (CK), single fraction interstitial high-dose-rate (HDR) and low-dose-rate (LDR) brachytherapy (BT) in low-risk prostate cancer. MATERIALS AND METHODS: Treatment plans of ten patients treated with CK were selected and additional plans using IMAT, HDR and LDR BT were created on the same CT images. The prescribed dose was 2.5/70 Gy in IMAT, 8/40 Gy in CK, 21 Gy in HDR and 145 Gy in LDR BT to the prostate gland. EQD2 dose-volume parameters were calculated for each technique and compared. RESULTS: EQD2 total dose of the prostate was significantly lower with IMAT and CK than with HDR and LDR BT, D90 was 79.5 Gy, 116.4 Gy, 169.2 Gy and 157.9 Gy (p < 0.001). However, teletherapy plans were more conformal than BT, COIN was 0.84, 0.82, 0.76 and 0.76 (p < 0.001), respectively. The D2 to the rectum and bladder were lower with HDR BT than with IMAT, CK and LDR BT, it was 66.7 Gy, 68.1 Gy, 36.0 Gy and 68.0 Gy (p = 0.0427), and 68.4 Gy, 78.9 Gy, 51.4 Gy and 70.3 Gy (p = 0.0091) in IMAT, CK, HDR and LDR BT plans, while D0.1 to the urethra was lower with both IMAT and CK than with BTs: 79.9 Gy, 88.0 Gy, 132.7 Gy and 170.6 Gy (p < 0.001). D2 to the hips was higher with IMAT and CK, than with BTs: 13.4 Gy, 20.7 Gy, 0.4 Gy and 1.5 Gy (p < 0.001), while D2 to the sigmoid, bowel bag, testicles and penile bulb was higher with CK than with the other techniques. CONCLUSIONS: HDR monotherapy yields the most advantageous dosimetrical plans, except for the dose to the urethra, where IMAT seems to be the optimal modality in the radiotherapy of low-risk prostate cancer.

Acute side effects after definitive stereotactic body radiation therapy (SBRT) for patients with clinically localized or locally advanced prostate cancer: a single institution prospective study.

BACKGROUND: The aim of the study was to evaluate acute side effects after extremely hypofractionated intensity-modulated radiotherapy (IMRT) with stereotactic body radiation therapy (SBRT) for definitive treatment of prostate cancer patients. PATIENTS AND METHODS: Between February 2018 and August 2019, 205 low-, intermediate- and high-risk prostate cancer patients were treated with SBRT using "CyberKnife M6" linear accelerator. In low-risk patients 7.5-8 Gy was delivered to the prostate gland by each fraction. For intermediate- and high-risk disease a dose of 7.5-8 Gy was delivered to the prostate and 6-6.5 Gy to the seminal vesicles by each fraction with a simultaneous integrated boost (SIB) technique. A total of 5 fractions (total dose 37.5-40 Gy) were given on every second working day. Acute radiotherapy-related genitourinary (GU) and gastrointestinal (GI) side effects were assessed using Radiation Therapy Oncology Group (RTOG) scoring system. RESULTS: Of the 205 patients (28 low-, 115 intermediate-, 62 high-risk) treated with SBRT, 203 (99%) completed the radiotherapy as planned. The duration of radiation therapy was 1 week and 3 days. The frequencies of acute radiotherapy-related side effects were as follows: GU grade 0 - 17.1%, grade I - 30.7%, grade II - 50.7%, grade III - 1.5%; and GI grade 0 - 62.4%, grade I-31.7%, grade II-5.9%, grade III-0%. None of the patients developed grade ≥ 4 acute toxicity. CONCLUSIONS: SBRT with a total dose of 37.5-40 Gy in 5 fractions appears to be a safe and well tolerated treatment option in patients with prostate cancer, associated with slight or moderate early side effects. Longer follow-up is needed to evaluate long-term toxicity and biochemical control.

Biological dose summation of intensity-modulated arc therapy and image-guided high-dose-rate interstitial brachytherapy in intermediate- and high-risk prostate cancer.

PURPOSE: To present an alternative method for summing biologically effective doses of intensity-modulated arc therapy (IMAT) as teletherapy (TT), with interstitial high-dose-rate (HDR) brachytherapy (BT) boost in prostate cancer. Total doses using IMAT boost was compared with BT boost using our method. MATERIAL AND METHODS: Initially, 25 IMAT TT plus interstitial HDR-BT plans were included, and additional plans using IMAT TT boost were created. The prescribed dose was 2/44 Gy to the whole pelvis, 2/60 Gy to the prostate and seminal vesicles, and 1 × 10 Gy BT or 2/18 Gy IMAT TT to the prostate. Teletherapy computed tomography (CT) was registered with ultrasound (US) of BT, and the most exposed volume of critical organs in BT were identified on these CT images. The minimal dose of these from IMAT TT was summed with their BT dose, and these EQD2 doses were compared using BT vs. IMAT TT boost. This method was compared with uniform dose conception (UDC). RESULTS: D90 of the prostate was significantly higher with BT than with IMAT TT boost: 99.3 Gy vs. 77.9 Gy, p = 0.0034. The D2 to rectum, bladder, and hips were 50.3 Gy vs. 76.8 Gy (p = 0.0117), 64.7 Gy vs. 78.3 Gy (p = 0.0117), and 41.9 Gy vs. 50.6 Gy (p = 0.0044), while D0.1 to urethra was 96.1 Gy vs. 79.3 Gy (p = 0.0180), respectively. UDC overestimated D2 (rectum) by 37% (p = 0.0117), D2 (bladder) by 5% (p = 0.0214), and underestimated D0.1 (urethra) by 1% (p = 0.0277). CONCLUSIONS: Based on our biological dose summation method, the total dose of prostate is higher using BT boost than the IMAT. BT boost yields lower rectum, bladder, and hips doses, but higher dose to urethra. UDC overestimates rectum and bladder dose and underestimates the dose to urethra.

Normal tissue sparing using different techniques for prostate irradiation.

AIM: The aim of this study was to investigate normal tissue sparing through dosimetric parameters of normal tissue volumes using different irradiation techniques for conventional (CFRT) and simultaneously integrated boost (SIB) schedules. BACKGROUND: Several dose-escalation studies for localized prostate cancer (PCa) have shown advanced biochemical relapse-free (bRFS) rates and also better local control for higher total doses using either CFRT or SIB schedules. Besides the most important organs-at-risk, absorbed dose reduction of other surrounding normal tissues are also preferable. In order to analyse the normal tissue sparing, dosimetric parameters of different normal tissue volumes were examined. MATERIALS AND METHODS: Treatment plans for 15 high risk prostate cancer patients were created using RapidArc (RA), Sliding Window (SW) IMRT and 4-field box (3D-CRT) technique. In order to evaluate normal tissue sparing, the volume of pelvic region was divided into six normal tissue cylinders with 1 cm wall thickness, located in each other. RESULTS: All plans met the criteria of target coverage (V95%>95%). All techniques provided the same results for OARs except 3D-CRT for rectum and bilateral femoral heads. The values of V5, V10 and V15 increased in cases which included RapidArc technique and decreased for V20 and V30. CONCLUSIONS: The dosimetric parameters for the cylindrical normal tissue volumes show that using RapidArc technique gives equal or slightly better normal tissue sparing and SIB provided the same normal tissue sparing as CFRT planned with RapidArc.

Acute and Late Toxicity after Moderate Hypofractionation with Simultaneous Integrated Boost (SIB) Radiation Therapy for Prostate Cancer. A Single Institution, Prospective Study.

ASBTRACT: To evaluate the acute and late toxicity using moderately hypofractionated, intensity-modulated radiotherapy (IMRT) with a simultaneous integrated boost (SIB) to prostate for patients with intermediate and high risk prostate cancer. From 2015 to 2017, 162 patients were treated with IMRT with SIB to the prostate. IMRT plans were designed to deliver 50.4Gy in 28 fractions (1.8 Gy/fraction) to the pelvic lymph nodes (whole pelvis radiotherapy, WPRT) while simultaneously delivering 57.4 Gy in 28 fractions (2.05 Gy/fraction) to the seminal vesicles and 70 Gy in 28 fractions (2.5 Gy/fraction) to the prostate for high risk patients. For intermediate risk patients the same technique was applied, without WPRT. Acute and cumulative late genitourinary (GU) and gastrointestinal (GI) toxicities were scored according to the Radiation Therapy Oncology Group (RTOG) scoring system. Of the 162 patients enrolled, 156 (96%) completed the treatment as planned. The median follow-up time was 30 months. Seventy-eight patients (48.2%) were treated with WPRT. The rate of acute grade ≥ 2 GI and GU toxicities in all patients were 22% and 58%, respectively. The rate of cumulative late grade ≥ 2 GI and GU toxicities were 11% and 17%, respectively. Acute grade 3 GI and GU toxicities occurred in 1% and 1%. Late grade 3 GI and GU side effects occurred in 5% and 4%, respectively. None of the patients developed grade ≥ 4 toxicity. IMRT with SIB technique using moderate hypofractionation to the prostate is feasible treatment option for intermediate and high risk patients, associated with low rate of severe GU and GI toxicities.

[Stereotactic body radiation therapy with CyberKnife accelerator for low- and intermediate risk prostate cancer]. / Kis és közepes kockázatú prosztatarákos betegek sztereotaxiás sugárkezelése CyberKnife gyorsítóval: korai radiogén mellékhatások.

We report implementation of stereotactic body radiotherapy (SBRT) for the treatment of early, localized prostate cancer patients, and acute side effects caused by radiation therapy. Between February 2018 and July 2018, 36 prostate cancer patients were treated with SBRT. Treatments were performed with "CyberKnife M6" linear accelerator. In low-risk patients 8 Gy was delivered to the prostate in each fraction. For intermediate risk, 8 Gy to the prostate and 6.5 Gy to the seminal vesicles were delivered by each fraction with a simultaneous integrated boost technique. A total of 5 fractions (total dose 40 Gy) were given every second working days. Acute radiogenic genitourinary (GU) and gastrointestinal (GI) side effects were assessed using the Radiation Therapy Oncology Group (RTOG) score. The duration of radiotherapy was 1 week and 3 days. The frequency of acute radiogenic side effects was as follows: GU grade 0: 13.9%, grade I: 30.6%, grade II: 52.8%, grade III: 2.7%. GI grade 0: 55.5%, grade I: 30.6%, grade II: 13.9%, grade III: 0%. Grade IV-V side effects were not observed. SBRT appears to be a safe and well tolerated treatment in patients with early stage, localized prostate cancer.

ERG expression can predict the outcome of docetaxel combinedwith androgen deprivation therapy in metastatic hormone-sensitiveprostate cancer.

BACKGROUND: Our study aimed to analyze the potential association between clinical parameters and ERG expression and the outcome of docetaxel chemotherapy among patients with metastatic hormone-sensitive prostate cancer. PATIENTS AND METHODS: Fifty-five patients with metastatic hormone-sensitive prostate cancer were treated with docetaxel in addition to androgen deprivation therapy. Patient characteristics, clinical factors, and tumor expression of ERG by immunohistochemistry were analyzed with respect to therapeutic response and survival data. RESULTS: Relapse free survival (RFS) and overal survival (OS) were 10.5 and 40.4 months, respectively, and both correlated with PSA response (RFS: 16.8 with a ≥50% decrease in PSA vs. 5.9 months in the case of <50% decrease, P < 0.001; OS: 40.4 vs. 11.6 months, respectively, P < 0.001). There was an association between OS and early progression (OS: 40.4 months with progression after 12 months vs. 17.9 months with progression within 12 months, P = 0.009). ERG expression was detected in 21 (42%) samples. ERG positivity was associated with favorable RFS (ERG pos. vs. neg.: 26.0 vs. 11.4 months, P = 0.003). CONCLUSION: ERG expression may have a potential predictive value with respect to the effectiveness and outcome of docetaxel chemotherapy combined with androgen deprivation therapy.

Transperineal gold marker implantation for image-guided external beam radiotherapy of prostate cancer : A single institution, prospective study.

PURPOSE: To present the feasibility and complications of transperineal fiducial marker implantation in prostate cancer patients undergoing image-guided radiotherapy (IGRT) METHODS AND MATERIALS: Between November 2011 and April 2016, three radiopaque, gold-plated markers were transperineally implanted into the prostate of 300 patients under transrectal ultrasound guidance and with local anaesthesia. A week after the procedure patients filled in a questionnaire regarding pain, dysuria, urinary frequency, nocturia, rectal bleeding, hematuria, hematospermia or fever symptoms caused by the implantation. Pain was scored on a 1-10 scale, where score 1 meant very weak and score 10 meant unbearable pain. The implanted gold markers were used for daily verification and online correction of patients' setup during IGRT. RESULTS: Based on the questionnaires no patient experienced fever, infection, dysuria or rectal bleeding after implantation. Among the 300 patients, 12 (4%) had hematospermia, 43 (14%) hematuria, which lasted for an average of 3.4 and 1.8 days, respectively. The average pain score was 4.6 (range 0-9). Of 300 patients 87 (29%) felt any pain after the intervention, which took an average of 1.5 days. None of the patients needed analgesics after implantation. Overall, 105 patients (35%) reported less, 80 patients (27%) more, and 94 patients (31%) equal amount of pain during marker implantation compared to biopsy. The 21 patients who had a biopsy performed under general anesthesia did not answer this question. CONCLUSION: Transperineal gold marker implantation under local anesthesia was well tolerated. Complications were limited; rate and frequency of perioperative pain was comparable to the pain caused by biopsy. The method can be performed safely in clinical practice.

[Intraoperative and post-implant dosimetry in patients treated with permanent prostate implant brachytherapy]. / Intraoperatív és posztimplantációs dozimetria összehasonlítása permanens implantációs prosztata-brachyterápiával kezelt betegeknél.

The purpose of our work was to compare intraoperative and four-week post-implant dosimetry for loose and stranded seed implants for permanent prostate implant brachytherapy. In our institute low-dose-rate (LDR) prostate brachytherapy is performed with encapsulated I-125 isotopes (seeds) using transrectal ultrasound guidance and metal needles. The SPOT PRO 3.1 (Elekta, Sweden) system is used for treatment planning. In this study the first 79 patients were treated with loose seed (LS) technique, the consecutive patients were treated with stranded seed (SS) technique. During intraoperative planning the dose constraints were the same for both techniques. All LSs were placed inside the prostate capsule, while with SS a 2 mm margin around the prostate was allowed for seed positioning. The prescribed dose for the prostate was 145 Gy. This study investigated prostate dose coverage in 30-30 randomly selected patients with LS and SS. Four weeks after the implantation native CT and MRI were done and CT/MRI image fusion was performed. The target was contoured on MRI and the plan was prepared on CT data. To assess the treatment plan dose-volume histograms were used. For the target coverage V100, V90, D90, D100, for the dose inhomogeneity V150, V200, and the dose-homogeneity index (DHI), for dose conformality the conformal index (COIN) were calculated. Intraoperative and postimplant plans were compared. The mean V100 values decreased at four-week plan for SS (97% vs. 84%) and for LS (96% vs. 80%) technique, as well. Decrease was observed for all parameters except for the DHI value. The DHI increased for SS (0.38 vs. 0.41) and for LS (0.38 vs. 0.47) technique, as well. The COIN decreased for both techniques at four-week plan (SS: 0.63 vs. 0.57; LS: 0.67 vs. 0.50). All differences were significant except for the DHI value at SS technique. The percentage changes were not significant, except the COIN value. The dose coverage of the target decreased significantly at four-week plans for both techniques. The decrease was larger for LS technique, but the difference between techniques was not significant at this patient number. The dose distribution was more homogenous, but the conformality was worse at four-week plans.

Loose versus stranded seeds in permanent prostate brachytherapy: dosimetric comparison of intraoperative plans.

PURPOSE: To compare target volume coverage and critical organ dosimetry of intraoperative treatment plans for loose seed (LS) and stranded seed (SS) (125)I permanent implants for low and intermediate risk prostate cancer. METHODS: Two hundred and five patients who underwent permanent seed brachytherapy were included in the study. For prostate dosimetry V90, V100, V150, V200, D90 and COIN were used. The dose to urethra and rectum was determined by the maximal dose and relative doses that cover specified volumes. Means and standard deviations were calculated and statistically compared. RESULTS: On average, 54 (range, 30-78) and 48 (range, 31-67) seeds were implanted in the prostate with individual median activities of 0.62 U (range, 0.52-0.70 U) and 0.71 U (range, 0.65-0.71 U) for LS and SS technique, respectively. The target coverage was slightly better with SS (V100: 98% vs. 96%,p < 0.05; D90: 172 Gy vs. 166 Gy, p < 0.05), but more conformal dose distributions were observed with LS (COIN: 0.70 vs. 0.63, p < 0.05). The dose homogeneity did not differ significantly between the two groups. Regarding the dose to urethra and rectum all dose parameters were significantly lower with LS. CONCLUSIONS: LS resulted in less dose to the urethra and rectum compared to SS in intraoperative dosimetry. A slightly better target volume coverage with decreased conformity of dose distribution is reported with SS. More studies are necessary to determine how these results will affect postoperative dosimetry, and ultimately, clinical outcome.

[Role of radiotherapy in the treatment of retroperitoneal soft tissue sarcomas]. / A sugárterápia szerepe a retroperitoneális lágyrészszarkómák kezelésében.

Soft tissue sarcomas are rare tumors, composing 1% of all malignancies. Fifteen percent of them are situated in the retroperitoneal region. The primary curative treatment for this group of patients is complete surgical resection. In most cases, due to their large size and localization at diagnoses, complete resection (R0) is not feasible. The main cause of disease-specific death is local recurrence. Therefore, improved local control by radiotherapy (RT) may contribute to better survival results. Based on international studies, despite the frequent positive surgical margins, only 25% of the patients with retroperitoneal sarcoma (RPS) receive perioperative RT. We performed a literature review based on the available data on the role of RT in the management of RPS. The 5-year local recurrence-free survival after surgery alone, and surgery + RT has been reported in the range of 23-54% and 40-62%, respectively. The respective 5-year rate of overall survival was of 33-49% and 48-64%. There are no available results from prospective randomized studies comparing surgery to surgery + RT. The majority of studies were retrospective and the treatments were performed over a time span of several decades. The total dose, technique and timing of RT were not standardized. Gastrointestinal and genitourinary side effects of RT are common, but their incidence and severity can be significantly reduced by using modern techniques. Based on the currently available studies, RT improves local control and it may play a role in the prolongation of overall survival as well. However, prospective randomized studies are needed to clarify the role of RT in the multidisciplinary management of RPS.

[Application of image-guided radiotherapy in external beam radiation of cancer patients]. / Képvezérelt sugárterápia klinikai alkalmazása daganatos betegek külso besugárzásánál.

The aim of the study was to present the clinical application of megavoltage cone beam CT (MV-CBCT) for image-guided radiotherapy at different tumour sites in our department. Altogether 2772 CT examinations were performed to verify the accuracy of patient setup before irradiation of 462 patients with pelvic (n=281), thoracic (n=107), head and neck (n=33) and cranial (n=41) tumours. A MV-CBCT with 6 MV photon beam integrated into a linear accelerator was used for imaging. The verification CT images were registered to planning CTs using bony structures, and in the three main directions (lateral, longitudinal, vertical) deviation between treatment and planning isocentres was determined in order to characterise the accuracy of patient setup. The verifications were performed before the first four fractions, and weekly-biweekly thereafter. From data obtained during the first three measurements systematic error of patient setup was calculated "off line", and the setup was corrected with the calculated value. At errors larger than 5 mm "on line" table correction was applied. The measured data were grouped and analysed according to location, and systematic and random errors were determined. From the data safety zone around clinical target volume (CTV) was calculated to create planning target volume (PTV). Following isocentre correction after the first three fractions the patient setup became more accurate at all site locations. At pelvic irradiation the mean error in all the three directions was below 1 mm, and the range of standard deviation was 0.32-0.38. At pelvic and thoracic irradiation the CTV-PTV safety zone calculated without any correction was 9-13 mm depending on direction, while at head and neck and cranial irradiation it was 6-9 mm. After correction of systematic error these data were 7-9 mm and 3-6 mm. After on line correction of setup errors larger than 5 mm the safety zone was 5-6 mm at pelvic and thoracic irradiation, 5 mm at head and neck, and 3-5 mm at cranial irradiation. Verification of patient setup with MV-CBCT at different locations can be easily performed. The initial systematic error can be corrected with a simple verification protocol which results in a few millimeter decrease of the CTV-PTV safety zone. Use of smaller safety zone is possible only with more frequent verifications and on line corrections.