Zuzana Macingova

Dose escalation in prostate radiotherapy up to 82 Gy using simultaneous integrated boost: direct comparison of acute and late toxicity with 3D-CRT 74 Gy and IMRT 78 Gy.

Purpose:To compare acute and late toxicity after three-dimensional conformal radiotherapy to the prostate to 74 Gy (3D-CRT) with intensity-modulated radioterapy to 78 Gy (IMRT 78) and IMRT using simultaneous integrated boost to 82 Gy (IMRT/SIB 82).Patients and Methods:94 patients treated with 3D-CRT to the prostate and base of seminal vesicles to 74 Gy represented the first group. The second group consisted of 138 patients subjected to IMRT covering the prostate and base of seminal vesicles to 78 Gy. The last group was treated with IMRT using SIB. The prescribed doses were 82 Gy and 73.8 Gy in 42 fractions to the prostate and seminal vesicles. Late toxicity was prospectively scored according to the RTOG/FC-LENT scale.Results:Acute gastrointestinal toxicity ≥ grade 2 occurred in 35.1% of patients treated with 3D-CRT, in 16% subjected to IMRT 78, and in 7.7% receiving IMRT/SIB 82. Acute genitourinary toxicity ≥ grade 2 was observed in 26.6% (3D-CRT), 33% (IMRT 78), and 30.7% (IMRT/SIB 82). At 3 years, the estimated cumulative incidence of grade 3 late gastrointestinal toxicity was 14% for 3D-CRT, 5% for IMRT 78, and 2% for IMRT/SIB 82. The difference became significant (log rank p = 0.02). The estimated cumulative incidence of grade 3 late genitourinary toxicity was 9% (3D-CRT), 7% (IMRT 78), and 6% (IMRT/SIB 82) without statistical differences (log rank p = 0.32)Conclusion:SIB enables dose escalation up to 82 Gy with a lower rate of gastrointestinal toxicity grade 3 in comparison with 3D-CRT up to 74 Gy.ZusammenfassungZiel:Vergleich der Akut- und Spättoxizität nach dreidimensionaler konformaler Strahlentherapie der Prostata bis 74 Gy (3D-CRT) mit intensitätsmodulierter Radiotherapie bis 78 Gy (IMRT 78) und mit IMRT mit simultanem integrierten Boost bis 82 Gy (IMRT/ SIB 82).Patienten und Methodik:Die erste Gruppe bestand aus 94 Patienten, die eine 3D-CRT der Prostata und der Bläschendrüsenbasis bis 74 Gy erhielten. Die zweite Gruppe umfasste 138 Patienten, welche mit IMRT der Prostata und der Bläschendrüsenbasis bis 78 Gy behandelt wurden. Die letzte Gruppe erhielt eine IMRT mit SIB. Die verschriebenen Strahlendosen betrugen 82 Gy und 73,8 Gy in 42 Fraktionen auf die Prostata und die Bläschendrüsenbasis. Die Spättoxizität wurde anhand der RTOG/FC-LENT-Skala bewertet.Ergebnisse:Akute gastrointestinale Nebenwirkungen ≥ Grad 2 entwickelten 35,1% der Patienten mit 3D-CRT, 16% mit IMRT 78 und 7,7% mit IMRT/SIB 82. Akute urogenitale Nebenwirkungen ≥ Grad 2 traten bei 26,6% der Patienten mit 3D-CRT, 33% mit IMRT 78 und 30,7% mit IMRT/SIB 82 auf. Nach 3 Jahren betrug die geschätzte kumulative Inzidenz gastrointestinaler Spättoxizität Grad 3 14% für 3D-CRT, 5% für IMRT 78 und 2% für IMRT/SIB 82. Der Unterschied war signifikant (Log-Rank p = 0,02). Die geschätzte kumulative Inzidenz urogenitaler Spättoxizität Grad 3 lag bei 9% (3D-CRT), 7% (IMRT 78) und 6% (IMRT/ SIB 82) und zeigte keine Signifikanz (Log-Rank p = 0,32).Schlussfolgerung:Die Dosissteigerung auf 82 Gy mit SIB führt im Vergleich mit der 3D-CRT bis 74 Gy zu einer geringeren Rate an gastrointestinaler Spättoxizität Grad 3.

High-dose rate brachytherapy in the treatment of penile carcinoma--first experience.

PURPOSE Interstitial low-dose rate brachytherapy (BRT) allows a conservative treatment of T1-T2 penile carcinoma. High-dose rate (HDR) BRT is often considered as a dangerous method for interstitial implants because of higher risk of complications. However, numerous reports suggest that results of HDR-BRT may be comparable to low-dose rate BRT. There are no data available in the literature regarding HDR interstitial BRT for carcinoma of the penis. METHODS AND MATERIALS Ten patients with early penile carcinoma were treated by interstitial hyperfractionated HDR-BRT at the dose of 18 times 3Gy twice daily between years 2002 and 2009. Breast interstitial BRT template was used for fixation and precise geometry reconstruction of stainless hollow needles. RESULTS Median followup was 20 months. Our BRT technique and fractionation schedule was well tolerated by all patients. Acute reaction consisted predominantly of penis edema and Grade 2 radiation mucositis that dissolved during 8 weeks after the treatment. We neither observed any postradiation necrosis nor urethral stenosis. The worst late side effects recorded were mild telanagiectasias in the treatment region. At the last followup, all patients were alive without evidence of the tumor and with fully functional organ. CONCLUSIONS Hyperfractionated interstitial HDR-BRT with 18 times 3 Gy per fraction twice daily is a promising method in selected patients of penile carcinoma and deserves further evaluation in a larger prospective study.

Magnetic Resonance Imaging in Postprostatectomy Radiotherapy Planning

PURPOSE To investigate whether the use of magnetic resonance imaging (MRI) in prostate bed treatment planning could influence definition of the clinical target volume (CTV) and organs at risk. METHODS AND MATERIALS A total of 21 consecutive patients referred for prostate bed radiotherapy were included in the present retrospective study. The CTV was delineated according to the European Organization for Research and Treatment of Cancer recommendations on computed tomography (CT) and T(1)-weighted (T(1)w) and T(2)-weighted (T(2)w) MRI. The CTV magnitude, agreement, and spatial differences were evaluated on the planning CT scan after registration with the MRI scans. RESULTS The CTV was significantly reduced on the T(1)w and T(2)w MRI scans (13% and 9%, respectively) compared with the CT scans. The urinary bladder was drawn smaller on the CT scans and the rectum was smaller on the MRI scans. On T(1)w MRI, the rectum and urinary bladder were delineated larger than on T(2)w MRI. Minimal agreement was observed between the CT and T(2)w images. The main spatial differences were measured in the superior and superolateral directions in which the CTV on the MRI scans was 1.8-2.9 mm smaller. In the posterior and inferior border, no difference was seen between the CT and T(1)w MRI scans. On the T(2)w MRI scans, the CTV was larger in these directions (by 1.3 and 1.7 mm, respectively). CONCLUSIONS The use of MRI in postprostatectomy radiotherapy planning resulted in a reduction of the CTV. The main differences were found in the superior part of the prostate bed. We believe T(2)w MRI enables more precise definition of prostate bed CTV than conventional planning CT.

Dose Escalation in Prostate Radiotherapy up to 82 Gy Using Simultaneous Integrated Boost

Purpose:To compare acute and late toxicity after three-dimensional conformal radiotherapy to the prostate to 74 Gy (3D-CRT) with intensity-modulated radioterapy to 78 Gy (IMRT 78) and IMRT using simultaneous integrated boost to 82 Gy (IMRT/SIB 82).Patients and Methods:94 patients treated with 3D-CRT to the prostate and base of seminal vesicles to 74 Gy represented the first group. The second group consisted of 138 patients subjected to IMRT covering the prostate and base of seminal vesicles to 78 Gy. The last group was treated with IMRT using SIB. The prescribed doses were 82 Gy and 73.8 Gy in 42 fractions to the prostate and seminal vesicles. Late toxicity was prospectively scored according to the RTOG/FC-LENT scale.Results:Acute gastrointestinal toxicity ≥ grade 2 occurred in 35.1% of patients treated with 3D-CRT, in 16% subjected to IMRT 78, and in 7.7% receiving IMRT/SIB 82. Acute genitourinary toxicity ≥ grade 2 was observed in 26.6% (3D-CRT), 33% (IMRT 78), and 30.7% (IMRT/SIB 82). At 3 years, the estimated cumulative incidence of grade 3 late gastrointestinal toxicity was 14% for 3D-CRT, 5% for IMRT 78, and 2% for IMRT/SIB 82. The difference became significant (log rank p = 0.02). The estimated cumulative incidence of grade 3 late genitourinary toxicity was 9% (3D-CRT), 7% (IMRT 78), and 6% (IMRT/SIB 82) without statistical differences (log rank p = 0.32)Conclusion:SIB enables dose escalation up to 82 Gy with a lower rate of gastrointestinal toxicity grade 3 in comparison with 3D-CRT up to 74 Gy.ZusammenfassungZiel:Vergleich der Akut- und Spättoxizität nach dreidimensionaler konformaler Strahlentherapie der Prostata bis 74 Gy (3D-CRT) mit intensitätsmodulierter Radiotherapie bis 78 Gy (IMRT 78) und mit IMRT mit simultanem integrierten Boost bis 82 Gy (IMRT/ SIB 82).Patienten und Methodik:Die erste Gruppe bestand aus 94 Patienten, die eine 3D-CRT der Prostata und der Bläschendrüsenbasis bis 74 Gy erhielten. Die zweite Gruppe umfasste 138 Patienten, welche mit IMRT der Prostata und der Bläschendrüsenbasis bis 78 Gy behandelt wurden. Die letzte Gruppe erhielt eine IMRT mit SIB. Die verschriebenen Strahlendosen betrugen 82 Gy und 73,8 Gy in 42 Fraktionen auf die Prostata und die Bläschendrüsenbasis. Die Spättoxizität wurde anhand der RTOG/FC-LENT-Skala bewertet.Ergebnisse:Akute gastrointestinale Nebenwirkungen ≥ Grad 2 entwickelten 35,1% der Patienten mit 3D-CRT, 16% mit IMRT 78 und 7,7% mit IMRT/SIB 82. Akute urogenitale Nebenwirkungen ≥ Grad 2 traten bei 26,6% der Patienten mit 3D-CRT, 33% mit IMRT 78 und 30,7% mit IMRT/SIB 82 auf. Nach 3 Jahren betrug die geschätzte kumulative Inzidenz gastrointestinaler Spättoxizität Grad 3 14% für 3D-CRT, 5% für IMRT 78 und 2% für IMRT/SIB 82. Der Unterschied war signifikant (Log-Rank p = 0,02). Die geschätzte kumulative Inzidenz urogenitaler Spättoxizität Grad 3 lag bei 9% (3D-CRT), 7% (IMRT 78) und 6% (IMRT/ SIB 82) und zeigte keine Signifikanz (Log-Rank p = 0,32).Schlussfolgerung:Die Dosissteigerung auf 82 Gy mit SIB führt im Vergleich mit der 3D-CRT bis 74 Gy zu einer geringeren Rate an gastrointestinaler Spättoxizität Grad 3.

Aplastic Anemia as a Cause of Death in a Patient with Glioblastoma Multiforme Treated with Temozolomide

Background:Standard treatment of glioblastoma multiforme consists of postoperative radiochemotherapy with temozolomide, followed by a 6-month chemotherapy. Serious hematologic complications are rarely reported.Case Report and Results:The authors present the case of a 61-year-old female patient with glioblastoma multiforme treated with external-beam radiation therapy and concomitant temozolomide. After completion of treatment, the patient developed symptoms of serious aplastic anemia that eventually led to death due to prolonged neutro- and thrombocytopenia followed by infectious complications.Conclusion:Lethal complications following temozolomide are, per se, extremely rare, however, a total of four other cases of aplastic anemia have been reported in the literature so far.ZusammenfassungHintergrund:Die Standardbehandlung des Glioblastoma multiforme ist die postoperative Radiochemotherapie mit Temozolomid, gefolgt von einer 6-monatigen Erhaltungschemotherapie. Schwerwiegende hämatologische Toxizitäten werden selten berichtet.Fallbericht und Ergebnisse:Die Autoren präsentieren den Fall einer 61-jahrigen Patientin mit Glioblastoma multiforme, die mit externer Strahlentherapie und begleitender Temozolomidchemotherapie in Standarddosierung behandelt wurde. Nach Abschluss der Behandlung zeigte die Patientin Symptome einer schweren aplastischen Anämie, die infolge prolongierter Neutro- und Thrombopenie durch infektiöse Komplikationen zum Tode führte.Schlussfolgerung:Letale Komplikationen einer Temozolomidchemotherapie sind selten, bislang wurden insgesamt vier Fälle einer aplastischen Anämie in der Literatur berichtet.

Psychosocial, health and demographic characteristics of quality of life among patients with acute myeloid leukemia and malignant lymphoma who underwent autologous hematopoietic stem cell transplantation.

CONTEXT AND OBJECTIVE This study evaluated the effect of selected psychosocial, health and demographic characteristics of quality of life (QOL) among patients treated with autologous hematopoietic stem cell transplantation (HSCT). DESIGN AND SETTING This was a retrospective study at Charles University Hospital, Hradec Kralove. METHODS The Czech version of the international generic European Quality-of-Life questionnaire (EQ-5D) was applied to evaluate QOL among patients with acute myeloid leukemia (AML) and malignant Hodgkins and non-Hodgkins lymphoma (ML). The total number of respondents was 36: 12 with AML (seven males and five females) and 24 with ML (11 males and 13 females). The mean age of AML respondents was 46 years and the mean age of ML respondents was 44.5 years. RESULTS Age, smoking status and education level had statistically significant effects on QOL among AML respondents (p < 0.05), and age had a statistically significant effect on QOL among ML respondents (p < 0.05). The overall QOL among AML and ML respondents was generally good: the mean EQ-5D score among AML respondents was 71.5% and among ML respondents it was 82.7%. CONCLUSION The QOL among AML and ML respondents treated with autologous HSCT was good. However, patients more than 50 years old, smokers and patients with lower education levels presented worse QOL. These findings need to be better evaluated in longitudinal studies, using large samples.

Sexuality of men treated with haematopoietic stem cell transplantation: a review of the literature

Summary Haematopoietic stem cell transplantation (HSCT) is a therapeutic modality used in anti-tumour treatment of haematological malignancies as well as solid tumours. Apart from that it is also used in therapy of non-malignant and hereditary diseases. As well as all the other treatments, HSCT also affects the disease process and with that also the patient’s quality of life (QoL). In the last decade of the 20 th century several studies about QoL in patients after HSCT were undertaken and the infl uence in particular dimensions of QoL was observed. One of the closely observed aspects was sexuality in patients after HSCT. Sexuality and its expression is a very important aspect of human behaviour. It is also a very sensitive aspect, so without doubt it is affected by diagnosis of neoplasm and cancer treatment. Physical and psychosocial factors of HSCT affect patients’ sexuality and sexual functioning, and with that also their QoL. They remain in focus because of the complex care concerning patients after HSCT.

Cancer stem cells--new approach to cancerogenensis and treatment.

Recently, there is an increasing evidence supporting the theory of cancer stem cells not only in leukemia but also in solid cancer. To date, the existence of cancer stem cells has been proven in acute and chronic myeloid leukemia, in breast cancer, in brain tumors, in lung cancer and gastrointestinal tumors. This review is focusing on the recent discovery of stem cells in leukemia, human brain tumors and breast cancer. A small population of cells in the tumor (less than 1%) shows the potential to give rise to the tumor and its growth. These cells have a substantial characteristic of stem cells--ability for self-renewal without loss of proliferation capacity with each cell division. Furthermore they are immortal, rather resistant to treatment and express typical markers of stem cells. The origin of these resident cancer stem cells is not clear. Whether the cancer stem cells originate from normal stem cells in consequence of genetic and epigenetic changes and/or redifferentiation from somatic tumor cells to the stem-like cells remains to be investigated. We propose the idea of the relation between normal tissue stem cells and cancer stem cells and their populations--progenitor cells. Based on this we highlight one of the major characteristic of stem cell--plasticity, which is equally important in the physiological regeneration process as well as carcinogenesis. Furthermore, we consider the microenvironment as a limiting factor for tumor genesis in AML, breast cancer and brain tumors. Thus the biological properties of cancer stem cells are just beginning to be revealed, the continuation of these studies should lead to the development of cancer stem cells target therapies for cancer treatment.

Dose Escalation in Prostate Radiotherapy up to 82 Gy Using Simultaneous Integrated Boost@@@Dosissteigerung bei Prostatabestrahlung durch einen simultanen integrierten Boost bis 82 Gy. Vergleich der Akut‑ und Spättoxizität nach 3D-CRT bis 74 Gy und IMRT bis 78 Gy: Direct Comparison of Acute and Late Toxicity with 3D-CRT 74 Gy and IMRT 78 Gy

Purpose:To compare acute and late toxicity after three-dimensional conformal radiotherapy to the prostate to 74 Gy (3D-CRT) with intensity-modulated radioterapy to 78 Gy (IMRT 78) and IMRT using simultaneous integrated boost to 82 Gy (IMRT/SIB 82).Patients and Methods:94 patients treated with 3D-CRT to the prostate and base of seminal vesicles to 74 Gy represented the first group. The second group consisted of 138 patients subjected to IMRT covering the prostate and base of seminal vesicles to 78 Gy. The last group was treated with IMRT using SIB. The prescribed doses were 82 Gy and 73.8 Gy in 42 fractions to the prostate and seminal vesicles. Late toxicity was prospectively scored according to the RTOG/FC-LENT scale.Results:Acute gastrointestinal toxicity ≥ grade 2 occurred in 35.1% of patients treated with 3D-CRT, in 16% subjected to IMRT 78, and in 7.7% receiving IMRT/SIB 82. Acute genitourinary toxicity ≥ grade 2 was observed in 26.6% (3D-CRT), 33% (IMRT 78), and 30.7% (IMRT/SIB 82). At 3 years, the estimated cumulative incidence of grade 3 late gastrointestinal toxicity was 14% for 3D-CRT, 5% for IMRT 78, and 2% for IMRT/SIB 82. The difference became significant (log rank p = 0.02). The estimated cumulative incidence of grade 3 late genitourinary toxicity was 9% (3D-CRT), 7% (IMRT 78), and 6% (IMRT/SIB 82) without statistical differences (log rank p = 0.32)Conclusion:SIB enables dose escalation up to 82 Gy with a lower rate of gastrointestinal toxicity grade 3 in comparison with 3D-CRT up to 74 Gy.ZusammenfassungZiel:Vergleich der Akut- und Spättoxizität nach dreidimensionaler konformaler Strahlentherapie der Prostata bis 74 Gy (3D-CRT) mit intensitätsmodulierter Radiotherapie bis 78 Gy (IMRT 78) und mit IMRT mit simultanem integrierten Boost bis 82 Gy (IMRT/ SIB 82).Patienten und Methodik:Die erste Gruppe bestand aus 94 Patienten, die eine 3D-CRT der Prostata und der Bläschendrüsenbasis bis 74 Gy erhielten. Die zweite Gruppe umfasste 138 Patienten, welche mit IMRT der Prostata und der Bläschendrüsenbasis bis 78 Gy behandelt wurden. Die letzte Gruppe erhielt eine IMRT mit SIB. Die verschriebenen Strahlendosen betrugen 82 Gy und 73,8 Gy in 42 Fraktionen auf die Prostata und die Bläschendrüsenbasis. Die Spättoxizität wurde anhand der RTOG/FC-LENT-Skala bewertet.Ergebnisse:Akute gastrointestinale Nebenwirkungen ≥ Grad 2 entwickelten 35,1% der Patienten mit 3D-CRT, 16% mit IMRT 78 und 7,7% mit IMRT/SIB 82. Akute urogenitale Nebenwirkungen ≥ Grad 2 traten bei 26,6% der Patienten mit 3D-CRT, 33% mit IMRT 78 und 30,7% mit IMRT/SIB 82 auf. Nach 3 Jahren betrug die geschätzte kumulative Inzidenz gastrointestinaler Spättoxizität Grad 3 14% für 3D-CRT, 5% für IMRT 78 und 2% für IMRT/SIB 82. Der Unterschied war signifikant (Log-Rank p = 0,02). Die geschätzte kumulative Inzidenz urogenitaler Spättoxizität Grad 3 lag bei 9% (3D-CRT), 7% (IMRT 78) und 6% (IMRT/ SIB 82) und zeigte keine Signifikanz (Log-Rank p = 0,32).Schlussfolgerung:Die Dosissteigerung auf 82 Gy mit SIB führt im Vergleich mit der 3D-CRT bis 74 Gy zu einer geringeren Rate an gastrointestinaler Spättoxizität Grad 3.