[Five-year results of IMRT for prostate cancer - toxicity]. / Petileté výsledky IMRT karcinomu prostaty - toxicita.

BACKGROUND: Intensity modulated radiotherapy (IMRT) plays a crucial role in the treatment of prostate cancer thanks to its capacity for healthy tissue sparing. This work reports on the acute and late toxicity rates among 233 patients treated with high-dose IMRT. MATERIAL AND METHODS: From June 2003 to December 2007, 233 men with clinically localized prostate cancer underwent radical radiotherapy. One hundred sixty patients were treated with IMRT to the prostate and the base of seminal vesicles to 78 Gy in 39 fractions, 73 patients underwent simultaneous integrated boost. Prescribed doses were 82 Gy and 73,8 Gy in 41 fractions to the prostate and seminal vesicles, respectively. Late toxicity was evaluated prospectively using a RTOG/FC-LENT score. RESULTS: Thirty patients (12.8%) experienced acute Grade 2 gastrointestinal (GI) toxicity. No acute Grade 3 or 4 GI toxicity developed. Forty two patients (18.1%) experienced acute Grade 2 genitourinary toxicity and 23 patients (9.9%) had Grade 3 GU toxicity. Grade 4 Genitourinary toxicity was observed in nine (3.8%) patients, due to a need of short-term urinary catheterization. With a median follow-up of 49.2 months, the estimated 5-year cumulative incidence of Grade 2 gastrointestinal toxicity was 22.4%. The estimated 5-year cumulative incidence of Grade 2 genitourinary toxicity was 17.7%. CONCLUSION: Intensity modulated radiotherapy enables dose escalation to 78-82 Gy with an acceptable toxicity.

Neoadjuvant hormonal therapy in prostate cancer - impact of PSA level before radiotherapy.

PURPOSE: To retrospectively investigate the impact of prostate specific antigen (PSA) level after neoadjuvant androgen- deprivation therapy (ADT) on biochemical relapse-free survival in patients with prostate cancer who received radical radiotherapy (RT). METHODS: Between March 2003 and March 2008, 128 men with localized prostate cancer underwent neoadjuvant ADT for 4-6 months followed by radical RT. Biochemical relapse-free survival was compared between patients with pre-RT PSA ≤ 0.1 vs > 0.1 ng/mL. RESULTS: At a median follow up of 47.3 months, biochemical relapse-free survival was significantly higher in patients with a pre-RT PSA ≤ 0.1 ng/mL compared with pre-RT PSA > 0.1 ng/mL (85.6 vs 63.2%, p = 0.0025). CONCLUSION: The current analysis demonstrating better treatment outcome in patients with excellent biochemical response to neoadjuvant ADT, supports an individualized treatment strategy.

[Changes in target volumes definition by using MRI for prostate bed radiotherapy planning--preliminary results]. / Zmeny cílových objemu pri pouzití magnetické rezonance pro plánování radioterapie luzka prostaty--predbezné výsledky.

BACKGROUNDS: Magnetic resonance imaging (MRI) is used quite routinely in radiotherapy treatment planning in the primary radiotherapy of prostate cancer as it provides more contrast imaging of soft tissues in the small pelvis than planning CT, thanks to which it allows more exact delineation of target volumes and thus the saving of organs at risk We tried to verify whether it is possible to use MRI by analogy in the planning of prostate bed radiotherapy. PATIENTS AND METHODS: Twentyone patients indicated for prostate bed radiotherapy were considered in this study. Here we present the preliminary results of 10 of them. Four patients were indicated for adjuvant, 6 for salvage radiotherapy. All the patients underwent, besides standard planning CT, MRI in the same position. Target volumes and organs at risk were delineated into CT,T1 and T2 MRI images - clinical target volume (CTV), planning target volume (PTV), urinary bladder and rectum. Based on the merging of images, the volumes delineated in MRI were copied into planning CT, where the evaluation was done. We evaluated the volumes of each structure, agreement in contouring with the help of the rate of union and intersection of the volumes and with Cohen's kappa, and 3D differences between volumes of CTV on CT, T1 and T2 MRI. RESULTS: Statistically, volumes of CTV and PTV are not significantly different. The volume of the rectum is significantly smaller on T1 and also T2 MRI images. The index of agreement (union/intersection) is statistically significantly different from 1 for CTV and PTV as well. Cohen's kappa indicates moderate agreement for CTV CT and T1, T1 and T2 MRI, fair agreement for CTV CT and T2 MRI, and substantial agreement for PTV. In the superior and superolateral direction, the CTV volume on MRI in the central plane is smaller on T1 and T2 images. In the area of seminal vesicles (SV) the cranial border is similar on CT and MRI. In the superoposterior direction, the volume of CTV is smaller on CT than on T1 and T2 MRI, which means, that seminal vesicles are delineated larger in the posterior direction on MRI (about 0.24cm on T1; by about 0.20cm on T2 images). In the posterior direction, there are no differences in CTV on CT and T1 while on T2 the CTV is larger (a difference of 0.29 cm). In the posterolateral direction, CTV is smaller on T1 MRI than on CT on both sides, on the right as well as on the left. CONCLUSION: Preliminary results suggest that clinical target volume defined with the help of MRI is shifted compared with CTV defined on planning CT. The agreement of CTV delineation by one radiation oncologist is moderate to fair and is similar to interobserver variability in the contouring of the prostate bed in the planning CT. MRI provides more contrast imaging of the anterior rectal wall, where we have confirmed the most differences in contouring. Moreover, it provides better imaging of local recurrences and seminal vesicles, where the most differences in our group of patients were seen in comparison with planning CT.

Time course of late rectal toxicity after radiation therapy for prostate cancer.

Rectum and bladder are the crucial organs at risk for curative radiation therapy of localized prostate cancer. We analyzed the incidence, profile and time course of late rectal radiation toxicity. A total of 320 patients with T1-3 prostate cancer were treated with three-dimensional conformal radiation therapy (3D-CRT). The prescription dose was 70 Gy for T1 and T2 patients (n=230) and 74 Gy for patients with locally advanced T3 tumors (n=90). Late rectal toxicity was graded according to the Fox Chase modification of the Radiation Therapy Oncology Group (RTOG) and Late Effects Normal Tissue Task Force (LENT) criteria. The median follow-up time was 6.2 years (range 0.2-10.7 years). At 5 years, the risk for the development of grade 2 and 3 rectal toxicities was 15.6 and 7.0%, respectively. All new cases of grade 2 and 3 rectal toxicities were observed within 5 years after treatment. Prevalence of grade 2 and 3 rectal symptoms showed fluctuation with maximum at 1.5 years and the minor peak at 4.5 years. Toxicity profile changed significantly over time. The proportion of rectal bleeding within grade 2 and 3 toxicity decreased from 85% at 1.5 years to 46% at 4.5 years. Conversely, the proportion of fecal incontinence among grade 2 and 3 rectal symptoms gradually increased (0% at 1.5 years vs 27% at 4.5 years). Late rectal radiation toxicity represents a dynamic process. Rectal bleeding decreases and fecal incontinence increases over time.

[Tumor stem cells and "niche"--a limiting factors of the carcinogenesis]. / Nádorové kmenové bunky a "niche"--jako limitující faktor karcinogeneze.

Presently, the view of tumor development is increasingly linked up with disorders of stem cells, no matter whether they are normal tissue stem cells or early progenitor cells. There is much evidence now that microenvironment regulates tissue specificity, reparation process as well as process of carcinogenesis. The aim of this paper is to enlarge the basic knowledge of carcinogenesis and show the role of stem cells and tumor stem cells as potential primary source of tumor development. We support the view that tumor may be considered an abnormal "organ" where the growth of tumor cells is controlled by a rare subpopulation of tumor stem cells giving rise to both greater number of tumor cells and non-tumorigenic tumor cells. This all is complementary and in connection with microenvironment we can speak about limiting factors of carcinogenesis. This insight into the tumor biology shows the shortcomings of recent tumor therapy. Therefore, most likely for effectual tumor therapy, attention should be given to both tumor stem cells and microenvironment. Consequently, this complementary relationship should be considered a limiting factor for understanding of carcinogenesis and also for further therapeutic strategy--homing therapy (tailored therapy) with the use of stem cells.

High dose rate versus low dose rate brachytherapy in the treatment of tongue carcinoma - a radiobiological study.

UNLABELLED: Low dose rate (LDR) brachytherapy is a well established treatment for the early stages of tongue cancer. High dose rate (HDR) afterloading devices have replaced LDR brachytherapy in many radiotherapy departments, but the effect and safety of HDR brachytherapy in comparison with LDR brachytherapy for interstitial applications is an unresolved question. The aim of our radiobiological study was to utilize dose volume histiograms from patients treated in our institution to simulate the risk of complication of LDR and HDR brachytherapy. Normal tissue complication probabilities (NTCP) of acute mucositis, late mucosal necrosis and osteoradionecrosis of two HDR brachytherapy schedules (18 x 3 Gy bid and 10 x 6 Gy bid) and of LDR brachytherapy with identical tumor control probability were compared using data from 8 brachytherapy applications. A linear quadratic (LQ) model was used to calculate the biologically equivalent doses, the effective volume method of Kutcher and Burman and Lyman's model was used to calculate NTCP. The Student's two-tailed test was used for statistical analysis. For 18 x 3 Gy bid the risk of acute mucositis and of late mucosal necrosis was 1.48 and 1.66 times higher with HDR in comparison with LDR brachytherapy. For 10 x 6 Gy bid the risk of acute mucositis, mucosal necrosis and osteoradionecrosis was 1.3, 3.44 and 13.18 times higher with HDR brachytherapy. All differences were statistically highly significant. Our radiobiological study supported the hypothesis that HDR has a higher risk of complication in comparison with LDR brachytherapy for the same tumor control probability. KEYWORDS: tongue cancer, brachytherapy, low dose rate, high dose rate.

Tamoxifen-induced QT interval prolongation.

We report on a case of tamoxifen-induced QT interval prolongation in a 56-year-old-female patient with hormone-dependent carcinoma of the right breast, stage T2N0M0, grade 3 and HER-2 negative. Partial mastectomy with axillary lymph node excision was performed in July 2007 with adjuvant hormonal and radiation therapy. This case highlights the risk of tamoxifen causing depression of electrical impulse in the sino-atrial node, leading to symptomatic sinus bradycardia with prolonged QT interval. It indicates the necessity of regular monitoring of patients undergoing tamoxifen treatment. ECG should be performed not only before and after, but also during treatment. with an average duration of treatment of 5 years, we would advise an annual ECG for asymptomatic patients. In the presence of symptomatic sinus bradycardia, constant monitoring is necessary. We also highlight potential drug interactions, between tamoxifen and acitretin and the need to be aware of drugs which may induce QT interval prolongation.

Health-related quality of life in multiple myeloma survivors treated with high dose chemotherapy followed by autologous peripheral blood progenitor cell transplantation: a retrospective analysis.

A pilot study analyses an effect of selected demographic, psychosocial and health aspects on quality of life (QoL) in multiple myeloma survivors treated with high-dose chemotherapy followed by autologous peripheral blood progenitor cell transplantation (PBPCT). The total number of respondents with multiple myeloma treated with high-dose chemotherapy followed by autologous PBPCT between years 2001-2003 at the Department of Clinical Haematology of the 2nd Department of Internal Medicine of Charles University Hospital and Faculty of Medicine in Hradec Králové, Czech Republic was 32 (18 male, 14 female). The average age of respondents was 60 years old. The Czech version of an international generic European Quality of Life Questionnaire - Version EQ-5D was used. The effect of selected demographics, psychosocial and health aspects on QoL was determined by means of analysis of variance (ANOVA). The QoL questionnaires were evaluated by means of descriptive analysis. The above-mentioned aspects proved statistically significant dependence of QoL on respondents age and on smoking abuse. EQ-5D score (dimensions of QoL) and EQ-5D VAS (a subjective health condition) significantly decrease with increasing age and with smoking abuse. The effect of other aspects on QoL was not proven as statistically significant. Prevailing complaints in respondents with multiple myeloma were: 1. regular activity with complaints 81,2 % (26/32 respondents), 2. medium serious pain / discomfort 68,8 % (22/32 respondents), 3. movement with complaints 59 % (19/32 respondents), 4. medium serious anxiety / depression 59 % (19/32 respondents). The QoL in patients with multiple myeloma treated with high-dose chemotherapy followed by autologous PBPCT was on low level (mean EQ-5D score was 68,9 %, mean EQ-5D VAS was 66,6 %). The results had shown that with an increasing age, the QoL of patients with multiple myeloma treated with high-dose chemotherapy followed by autologous PBPCT, declines. The smokers and former smokers have lower QoL than non smokers. The global QoL in all studied patients with multiple myeloma treated with high-dose chemotherapy followed by autologous PBPCT was on low level.