Intensity-modulated radiotherapy in the treatment of subhepatic carcinomas.

BACKGROUND/AIMS: The aim of our study was to evaluate preliminary results of intensity modulated radiotherapy (IMRT) in patients with inoperable subhepatic tumors. METHODOLOGY: Thirteen patients with inoperable cholangiocarcinoma or gall bladder carcinoma were treated by biliary drainage and intensity modulated radiotherapy. In patients with tumors limited to the biliary duct only tumor stenosis was irradiated to the dose of 50-60 Gy. In patients with bulky extraductal tumors the dose was 50 Gy/25 fractions to the whole tumor and an integrated boost was used to raise the dose to the malignant stenosis to 60 Gy/25 fractions. RESULTS: Doses to organs at risk (duodenum, small intestine, liver) were in tolerable limits. In four patients transient fever occurred; one patient had duodenal bleeding that resolved after conservative treatment. Recurrent dilatation of the biliary tract was observed in 4 patients and was managed by exchange of the internal biliary drainage. Median survival was 10.4 months, 5 patients survived for more than one year following diagnosis. CONCLUSIONS: IMRT of inoperable extrahepatic biliary tract tumors allows application of high doses of radiation to the tumor with effective sparing of healthy tissues. The control of jaundice is good. In selected cases IMRT may prolong overall survival.

Perioperative hyperfractionated high-dose rate brachytherapy for the treatment of soft tissue sarcomas: multicentric experience.

BACKGROUND: Low-dose rate brachytherapy is a well-established adjuvant treatment for soft tissue sarcomas (STS). The experience with high-dose rate brachytherapy (HDR BT) in this indication is limited. The purpose of our study was to evaluate the viability of perioperative hyperfractionated HDR BT for STS. METHODS: Forty-five patients with primary (17 cases) or recurrent (28 cases) STS were treated with resection and HDR BT between 1998 and 2007. Eleven patients were treated with HDR BT alone (mean dose 40 Gy; 30-54 Gy) and 34 were treated with a combination of HDR BT (mean dose 24 Gy; 15-30 Gy) and external beam radiotherapy (EBRT) (40-50 Gy). Hyperfractionation, 3 Gy twice daily, was used for HDR BT with plastic tubes. Adjuvant chemotherapy was indicated for patients with high risk of dissemination. RESULTS: Local control (LC) was achieved in 17 patients (100%) treated for primary tumor and in 18 of 28 patients (64%) treated for recurrence; this difference was statistically significant (p = 0.004). Distant metastases occurred in seven patients (15.6%). The 5-year overall survival was 70%; the 5-year local control was 74%. LC was significantly better for extremities sarcomas in comparison with trunk tumors, for patients treated with EBRT and BT in comparison with BT alone, and for doses >65 Gy. CONCLUSIONS: Our study suggests that perioperative HDR BT is a promising method for achieving high biological doses with good LC in the postoperative radiotherapy of STS and that combination of BT and EBRT provides better tumor control than BT alone.

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.

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 radiotherapy 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 >or= 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 >or= 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.

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.

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.

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.

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.

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 Hodgkin’s and non-Hodgkin’s 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 percent and among ML respondents it was 82.7 percent. 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.

CONTEXTO E OBJETIVO: O transplante de células tronco hematopoiéticas (TCTH) é um método a ser utilizado na terapêutica das doenças hemato-oncológicas e tumores sólidos, assim como no tratamento de doenças não-malignas. O TCTH tem influência na evolução da doença e na qualidade de vida do doente, assim como outros métodos curativos. TIPO ESTUDO E LOCAL: Este estudo é retrospectivo. Foi desenvolvido no Departamento Clínico de Hematologia do 2º Departamento de Medicina Interna do Hospital da Universidade de Charles em Hradec Kralove, República Checa. MÉTODOS: Amostra de 36 adultos sujeitos ao tratamento com transplante autólogo de células tronco do progenitor, sendo 12 com leucemia mielóide aguda: sete homens e cinco mulheres, e 24 com linfoma maligno: 11 homens e 13 mulheres. Foi utilizada a versão checa do questionário internacional de qualidade de vida européia versão EQ - 5D. RESULTADOS: Houve associação estastiticamente significante entre qualidade de vida e idade, fumantes, pacientes com baixo nível educacional em ambos os sujeitos com leucemia mielóide aguda (p < 0.05). Houve associacão estatisticamente significante entre qualidade de vida e idade em ambos os sujeitos com linfoma maligno (p < 0.05). CONCLUSÃO: A qualidade de vida dos pacientes com linfoma maligno e leucemia mielóide aguda, submetidos a transplante autólogo do progenitor, mantém-se preservada na maioria dos pacientes. Pacientes com idade acima de 50 anos, baixo nível educacional e fumantes têm pior qualidade de vida. Estes fatores devem ser melhor avaliados em estudos longitudinais e com amostras maiores.