Long term outcome and side effects in patients receiving low-dose I125 brachytherapy: a retrospective analysis

ABSTRACT Objectives: To retrospectively evaluate the disease free survival (DFS), disease specific survival (DSS),overall survival (OS) and side effects in patients who received low-dose rate (LDR) brachytherapy with I125 stranded seeds. Materials and methods: Between july 2003 and august 2012, 274 patients with organ confined prostate cancer were treated with permanent I125 brachytherapy. The median follow-up, age and pretreatment prostate specific antigen (iPSA) was 84 months (12-120), 67 years (50-83) and 7.8 ng/mL (1.14-38), respectively. Median Gleason score was 6 (3-9). 219 patients (80%) had stage cT1c, 42 patients (15.3%) had stage cT2a, 3 (1.1%) had stage cT2b and 3 (1.1%) had stage cT2c. The median D90 was 154.3 Gy (102.7-190.2). Results: DSS was 98.5%.OS was 93.5%. 13 patients (4.7%) developed systemic disease, 7 patients (2.55%) had local progression. In 139 low risk patients, the 5 year biochemical freedom from failure rate (BFFF) was 85% and 9 patients (6.4%) developed clinical progression. In the intermediate risk group, the 5 year BFFF rate was 70% and 5 patients (7.1%) developed clinical progression. Median nPSA in patients with biochemical relapse was 1.58 ng/mL (0.21 – 10.46), median nPSA in patients in remission was 0.51 ng/mL (0.01 – 8.5). Patients attaining a low PSA nadir had a significant higher BFFF (p<0.05). Median D90 in patients with biochemical relapse was 87.2 Gy (51 – 143,1). Patients receiving a high D90 had a significant higher BFFF (p<0.05). Conclusion: In a well selected patient population, LDR brachytherapy offers excellent outcomes. Reaching a low PSA nadir and attaining high D90 values are significant predictors for a higher DFS.

Toxicity of Tomotherapy-Based Simultaneous Integrated Boost in Whole-Pelvis Radiation for Prostate Cancer

PURPOSE: The validity of tomotherapy-based simultaneous integrated boost (TOMOSIB) was assessed in terms of acute intestinal/urinary toxicity by comparing with 3-dimensional conformal radiotherapy (3DCRT) in cases of whole-pelvis radiation therapy (WPRT) for prostate cancer. MATERIALS AND METHODS: Thirty-eight consecutive patients who underwent curative WPRT were retrospectively reviewed. Twenty six (68.4%) received 3DCRT and the others (31.6%) were treated with TOMOSIB. A local boost to the prostate circumferential area was added to WPRT sequentially for 3DCRT and concomitantly for TOMOSIB. The total median prostate or prostatic bed dose was 64.8 Gy including median 45.0 Gy of WPRT. Acute toxicities were assessed according to RTOG criteria. RESULTS: Overall intestinal toxicity was lower in TOMOSIB group than 3DCRT group (p=0.008). When it was divided into rectum and non-rectum intestine (NRI), TOMOSIB showed borderline superiority only in NRI toxicity (p=0.047). For the urinary toxicity, there was no significant difference between two groups (p=0.796). On dosimetric analysis for the rectum and bladder, dose delivered to 80% (p<0.001) and volume receiving 25-40 Gy (p<0.001) were remarkably higher in 3DCRT. For the NRI, only maximum dose showed significant results between two groups (p<0.001). CONCLUSION: Intestinal toxicity should be verified with more detailed anatomic categorization such as rectum and NRI. TOMOSIB could not reduce urinary toxicity because of inevitably high dose exposure to the prostatic urethra. Current dosimetry system did not properly reflect intestinal/urinary toxicity, and suitable dosimetric guidelines are needed in TOMOSIB.

Toxicity of Tomotherapy-Based Simultaneous Integrated Boost in Whole-Pelvis Radiation for Prostate Cancer

PURPOSE: The validity of tomotherapy-based simultaneous integrated boost (TOMOSIB) was assessed in terms of acute intestinal/urinary toxicity by comparing with 3-dimensional conformal radiotherapy (3DCRT) in cases of whole-pelvis radiation therapy (WPRT) for prostate cancer. MATERIALS AND METHODS: Thirty-eight consecutive patients who underwent curative WPRT were retrospectively reviewed. Twenty six (68.4%) received 3DCRT and the others (31.6%) were treated with TOMOSIB. A local boost to the prostate circumferential area was added to WPRT sequentially for 3DCRT and concomitantly for TOMOSIB. The total median prostate or prostatic bed dose was 64.8 Gy including median 45.0 Gy of WPRT. Acute toxicities were assessed according to RTOG criteria. RESULTS: Overall intestinal toxicity was lower in TOMOSIB group than 3DCRT group (p=0.008). When it was divided into rectum and non-rectum intestine (NRI), TOMOSIB showed borderline superiority only in NRI toxicity (p=0.047). For the urinary toxicity, there was no significant difference between two groups (p=0.796). On dosimetric analysis for the rectum and bladder, dose delivered to 80% (p<0.001) and volume receiving 25-40 Gy (p<0.001) were remarkably higher in 3DCRT. For the NRI, only maximum dose showed significant results between two groups (p<0.001). CONCLUSION: Intestinal toxicity should be verified with more detailed anatomic categorization such as rectum and NRI. TOMOSIB could not reduce urinary toxicity because of inevitably high dose exposure to the prostatic urethra. Current dosimetry system did not properly reflect intestinal/urinary toxicity, and suitable dosimetric guidelines are needed in TOMOSIB.

A new problem in inflammatory bladder diseases: Use of mobile phones!

Purpose Technological developments provide a lot of conveniences to our lives. This issue is one of the risks that arise along with these conveniences. In our study we tried to understand the impact of electromagnetic waves from mobile phones on bladder tissue. Materials and Methods Twenty-one adult male albino rats were divided into three equal groups. Group 1 was exposed to electromagnetic wave for 8 hours per day for 20 days and then their bladders were taken off immediately. Group 2 was firstly exposed to electromagnetic wave for 8 hours per day for 20 days then secondly another for 20 days without exposition to electromagnetic wave and then their bladders were taken off. Group 3 was the control group and they were not exposed to electromagnetic wave. Results Under microscopic examination of bladder tissue, in the first group severe inflammatory cell infiltration was seen in lamina propria and muscle layer in contrast to intact urothelium. In the second group mild inflammatory cell infiltration was seen in lamina propria and muscle layer. The mean scores for the three groups were 5.5 ± 2.5, 0.8 ± 1.3 and 1.2 ± 1.5 respectively. Mean score of group 1 was statistically higher than others (p = 0.001). Conclusion Intensive use of mobile phones has negative impact on bladder tissue as well as the other organs. Keeping a minimum level of mobile phone use makes it easy to be kept under control of diseases in which inflammation is an etiologic factor. .

Efeito radioprotetor da L-Glutamina na parede da bexiga de ratos submetidos à irradiação pélvica / Protective effects of L-Glutamine on the bladder wall of rats submitted to pelvic radiation

A radioterapia é frequentemente utilizada no tratamento de tumores da próstata, porém durante esse procedimento a bexiga sadia usualmente sofre efeitos colaterais. Através do uso de um modelo animal para irradiação pélvica, avaliamos se a suplementação nutricional com L-glutamina poderia prevenir possíveis danos na parede da bexiga, especialmente em suas camadas mais superficiais. Ratos Wistar adultos machos com idade entre 3 e 4 meses foram separados em grupos de 8 animais: grupo controle que não recebeu a irradiação; grupos somente irradiados que foram mortos 7 (R7) e 15 dias (R15) após a irradiação (dose única de 10 Gy na região pélvico-abdominal); grupos irradiados e suplementados com L-glutamina (0,65g/kg de peso por dia), que foram mortos 7 (RG7) ou 15 após a irradiação. Células e vasos sanguíneos da lâmina própria, bem como o urotélio, foram avaliados com métodos histológicos. No urotélio foram feitas análises da altura e densidade nuclear e na lâmina própria densidade celular, densidade vascular e o número de mastócitos. Os resultados mostraram que em R7, a altura e densidade nuclear do urotélio e a densidade celular da lâmina própria não foram alterados significativamente. Entretanto a densidade dos vasos sanguíneos foi reduzida em 48% (p<0,05) e essa alteração foi evitada pela glutamina (p <0,02). No grupo R15, a densidade celular do epitélio aumentou em 35% (p<0,02). A densidade celular da lâmina própria não apresentou diferença estatística entre os grupos. Os mastócitos na lâmina própria foram reduzidos em R7 e R15. Apesar de ainda reduzidos em RG7 em RG15 houve aumento no número desse tipo celular o que sugere uma ação positiva da glutamina. Células α-actina positivas na lâmina própria formam uma camada suburotelial e foram identificadas como miofibroblastos. A espessura dessa camada aumentou em R7, mas foi semelhante ao controle em RG7, enquanto alterações em R15 e RG15 foram menos evidentes. Esses resultados mostraram que a utilização ...

Radiotherapy is often used to treat prostate tumors, but the normal bladder is usually adversely affected. Using an animal model of pelvic radiation, we investigated whether glutamine nutritional supplementation can prevent radiation-induced damage to the bladder, especially in its more superficial layers. Male rats aged 3 to 4 months were divided into groups of 8 animals each: controls, which consisted intact animals; radiated-only rats, which were sacrificed 7 (R7) or 15 (R15) days after a radiation session (10 Gy aimed at the pelvico-abdominal region); and radiated rats receiving L-glutamine supplementation (0.65 g/kg body weight/day), which were sacrificed 7 (RG7) or 15 (RG15) days after the radiation session. Morphological and morphometric analysis of the urothelium were made. Nuclear density, lamina propria cell density and mast cells numbers per area were counted. The results showed that, in R7, epithelial thickness, epithelial cell density, and cell density in the lamina propria were not significantly affected. However, density of blood vessels in R7 was reduced by 48% (p < 0.05) and this alteration was mostly prevented by glutamine (p < 0.02). In R15, density of blood vessels in the lamina propria was not significantly modified. However, epithelial thickness was reduced by 25% (p < 0.05) in R15, and this effect was prevented by glutamine (p < 0.01). In R15, epithelial cell density was increased by 35% (p < 0.02), but glutamine did not protect against this radiation-induced increase. Cell density in the lamina propria was likewise unaffected in R15. Density of mast cells in the lamina propria was markedly reduced in R7 and R15. The density was still reduced in RG7, but a higher density in RG15 suggested a glutamine-mediated recovery. Alpha-actin positive cells in the lamina propria formed a suburothelial layer and were identified as myofibroblasts. Thickness of this layer was increased in R7, but was similar to controls in RG7, while changes in R15 ...

[ dosimetric evaluation of organs at risk in prostate radiation therapy using a MAGIC gel dosimeter]

Multiple fields and presence of hetrerogeneities create complex dose distributions that need three dimentisonal dosimetry. In this work, we investigated MR-based MAGIC gel dosimetry as a three-dimentional dosimetry technique to measure the delivered dose to bladder and rectum in prostate radiation therapy. A heterogeneous slab phantom including bones was made. Paired cubes in the phantom representing bladder and prostate and a cylindrical container representing rectum were filled with MAGIC gel and placed in the anthropomorphic pelvic phantom. The phantom was irradiated with four beams as planned using a treatment planning system [TPS]. Magnetic resonance transverse relaxation rate images were acquired and turned into dose distribution maps using a calibration curve. This calibration curve was obtained by linear fitting to R2 values of 4 test tubes against their given known doses. Image processing and data analysis were preformed in MATLAB 7 software. The gel dosimeter was validated using an ionization chamber. Dose maps and dose volume histograms [DVHs] were compared with dose distributions and DVHs of the TPS. Mean "distance-to-agreement" and mean "does difference" were 2.98 mm and 6.2%, respectively, in the comparison of profiles obtained from ionization chamber and gel dostimetry. Mean relative difference of DHVs between gel dosimetry and TPs data were 3.04%, 10.4% and 11.7%,for prostate, bladder and rectum, respectively. Gel dosimetry is a good method for three dimensional dosimetry although it has a low precision in high close gradient regions. This method can be used for evaluation of complicated dose distribution accuracy in 3D conformal radiotherapy, especially in presence of heterogeneities

Efeitos adversos tardios subseqüentes ao tratamento radioterápico para câncer de colo uterino na bexiga, reto e função sexual / Late adverse effects subsequent to radiotherapy for cervical cancer in the bladder, rectum and sexual function

O diagnóstico de câncer de colo uterino no Brasil ainda ocorre em estádios avançados, em muitos casos, o que implica na utilização da radioterapia de forma exclusiva ou combinada, com finalidade curativa ou paliativa. Os avanços tecnológicos nesta área têm propiciado melhores taxas de sobrevida e de remissão da doença. No entanto, os efeitos adversos ocasionados pela radioterapia sobre as áreas sadias adjacentes à área irradiada foram observados em muitas pesquisas realizadas em centros de radioterapia do mundo inteiro. Para mensurar a ocorrência dos efeitos adversos tardios subseqüentes à radioterapia para câncer de colo uterino na bexiga, reto e função sexual em mulheres que freqüentam o ambulatório de ginecologia do INCA, conduziu-se um estudo observacional em que foram incluídas 300 mulheres em seguimento ambulatorial em 2007, diagnosticadas entre os estágios IB e IIIB. As informações foram colhidas através de entrevistas com as pacientes no momento de comparecimento à consulta ambulatorial de seguimento e junto ao prontuário das mesmas. Os dados revelaram que a população de estudo se declarou predominantemente branca, com idade entre 40 e 60 anos, com baixa escolaridade e baixa renda. O efeito adverso mais freqüente registrado no prontuário foi a estenose vaginal. A curva de sobrevida livre de efeitos adversos tardios foi obtida através do Estimador de Kaplan - Meier. O tempo mediano até a ocorrência da estenose vaginal foi de 49,2 meses. Esse tempo variou de acordo com o estádio da doença, sendo de 59,6 meses para o grupo com estádio até IIB e de 26,3 meses para o grupo com estádios mais avançados. Só foram encontrados quatro registros de encaminhamento para o tratamento desse efeito adverso com exercícios fisioterápicos e dilatação vaginal. Levando-se em conta a diminuição da qualidade de vida das pacientes após o desenvolvimento de efeitos adversos tardios, torna-se importante o diagnóstico e o tratamento precoces dentro da rotina de seguimento ambulatorial das pacientes no HCII do INCA.

Diagnosis of cervical cancer in Brazil still occurs in advanced stages, in many cases, which implies in the use of radiotherapy for exclusive or combined treatment for curative or palliative purpose. Technological advances in this area have offered better survival rates and remission of the disease. However, side effects caused by radiation on the healthy areas adjacent to the irradiated area were observed in several studies conducted in radiotherapy centers worldwide. To measure occurrence of late side effects subsequent to radiotherapy for cervical cancer on bladder, rectum and sexual function in women attending INCA gynecology clinic during 2007, an observational study was conducted including 300 follow-up outpatients, diagnosed in stages IB to IIIB. Information was collected through patient interview during follow-up visit and by review of medical records. The results showed that the study population was predominantly white, aged between 40 and 60 years, with low education and income level. The most frequent late side effect recorded was vaginal stexnosis. Slopes of late side effects-free survival were obtained from Kaplan-Meier estimator. The median time to occurrence of vaginal stenosis was 49.2 months. This time varied according to the disease stage, with 59.6 months for the reference group (disease stage until IIB) and 26.3 months for patients in more advanced stages. Only four records were found for the vaginal stenosis treated with physiotherapy exercises and vaginal dilation. Taking into account the decrease of quality of life of patients after the development of late side effects, early diagnosis becomes very important as well as early treatment within the follow-up routine of patients in HCII of INCA.

High-dose-rate-intracavitary brachytherapy applications and the difference in the bladder and rectum doses: a study from rural centre of Maharashatra, India.

AIM: To report the difference in the bladder and rectum doses with different applications by the radiotherapists in the same patient of the carcinoma of the uterine cervix treated by multiple fractions of high-dose-rate (HDR) intracavitary brachytherapy (ICBT). MATERIALS AND METHODS: Between January 2003 to December 2004, a total of 60 cases of the carcinoma uterine cervix were selected randomly for the retrospective analyses. All 60 cases were grouped in six groups according to the treating radiotherapist who did the HDR-ICBT application. Three radiotherapists were considered for this study, named A, B and C. Ten cases for each radiotherapist in whom all three applications were done by the same radiotherapist. And 10 cases for each radiotherapist with shared applications in the same patient (A+B, A+C and B+C). The bladder and rectal doses were calculated in reference to point "A" dose and were limited to 80% of prescribed point "A" dose, as per ICRU-38 recommendations. Received dose grouped in three groups--less then 80% (< 80%), 80-100% and above 100% (>100%). A total of 180 applications for 60 patients were calculated for the above analyses. RESULTS: There is a lot of difference in the bladder and rectal doses with the application by the different radiotherapists, even in the same patient with multiple fractions of HDR-ICBT. Applications by 'A' radiotherapist were within the limits in the self as well as in the shared groups more number of times, by 'B' radiotherapist was more times exceeding the limit and by 'C' radiotherapist doses were in between the A and B. DISCUSSION AND CONCLUSION: For the rectal and bladder doses most important factors are patient's age, disease stage, duration between EBRT and HDR-ICRT and patient anatomy, but these differences can be minimized to some extent by careful application, proper packing and proper fixation.

Análisis dosimétrico en braquiterapia ginecológica de alta tasa de dosis / Dosimetric analysis in high dose rate gynecological brachytherapy

OBJETIVO: Analizar la dosimetría en braquiterapia ginecólogica para el dispositivo Fletcher-Suit-Delclos con alta tasa de dosis, mediante placas radiográficas ortogonales (anteroposterior y lateral) versus tomografía axial computada (TAC). MATERIAL Y MÉTODOS: Se compararon dosimetrías de 4 implantes, realizadas con placas ortogonales y TAC pélvico en la Unidad de Braquiterapia del Instituto Nacional del Cáncer durante el mes de febrero del año 2006. Se prescribieron dosis de 8 Gy/fracción a punto H y se evaluó dosis a vejiga, recto y vagina según norma internacional. RESULTADOS: Las dosimetrías por TAC mostraron puntos calientes superiores a las placas ortogonales, para recto un 133% y para vejiga un 260% más aproximadamente. El porcentaje de volumen blanco incluido es subestimado con la dosimetría efectuada por placas ortogonales. CONCLUSIONES: La dosimetría por placas ortogonales muestra menor exactitud que el TAC. Los volúmenes blanco no son satisfactoriamente cubiertos por la curva de isodosis prescrita. La dosis acumulada, probablemente, sea más relevante que la dosis fracción.

OBJECTIVE: We analyze the gynecologycal high dose rate brachytherapy dosimetry using the Fletcher-Suit-Delclos device, comparing orthogonal films (anteroposterior and lateral) versus axial computarized tomography. METHODS: 4 implants were analized with orthogonal films and axial computarized tomography in the Brachyhterapy Unit of the National Cancer Institute on February 2006. The dose/fraction was 8 Gy to the H point. The bladder, rectal and vaginal dose point were evaluated according to international specifications. RESULTS: Axial computarized tomography reveals hot points higher than orthogonal films dosimetries (133% and 260% for bladder and rectum respectively). The target volumen included was underestimated with the classical orthogonal film dosimetry. CONCLUSIONS: The orthogonal film dosimetry shows smaller accuracy than axial computarized tomography. The target volumens were not satisfactorily covered by the prescribed isodosis curve. The dose accumulated could, probably, be more prominent than the dose/fraction.

Cistitis crónica fibrótica telangectásica por ciclofosfamida / Fibrous chronic cystitis telangectasia for ciclofosfamide

Enfoque de estudio y manejo de pacientes pediátricos hematúricos, con antecedente de tratamiento previo con ciclofosfamida.Paciente femenino de 8 años, con antecedente de linfoma no Hodgkin diagnosticado a los 4 años, que es tratado durante un año en centro extranjero con quimioterapia que incluía ciclofosfamida, sin registro de protección vesical. Presenta también un síndrome atáxico de etiología desconocida. Tres años después consulta por disuria, hematuria recurrente micro y macroscópica con coágulos, presentando función renal normal. Estudio por imágenes (ecografía, pielografía y TAC), muestra imagen de defecto de llene de 4 cm a nivel del trígono vesical, sugerente de coágulo. Se descartan malformaciones vasculares y tumorales.Cistoscopía demostró una cistitis hemorrágica con telangectasias. Histología mostró cistitis crónicahemorrágica fibrosa G° III.Pacientes sometidos a terapias con ciclofosfamida o sus derivados deben recibir protección vesical con Ledoxina, para reducir al máximo este tipo de complicación. Este paciente es candidato a reemplazo vesical total, aún no operado por encontrarse en su centro de origen en el extranjero. Se discute la indicación quirúrgica y la técnica quirúrgica en este caso particular.

Evaluation de la toxicite aigue chez 50 patients atteints de cancer de la prostate traites par radiotherapie conformationnelle

Purpose: To report our experience with 3D conformal radiotherapy for prostate cancer material and methods: We reviewed our first 50 patients diagnosed with prostate cancer. Median follow-up was 27 months [16-40 m]. Median age 68 [52-74] T stage was T1c = 12 T2a = 14 T2b = 10 T2c = 2 T3a = 10 T3b = 1 and T3c = 1. Gleason score [GS] 4-6 50% and GS 7-8 50%. Pretreatment PSA.value of < 10 ng/ml 36%, 10-20 ng/ml 32% and >20 ng/ml 32%. Forty patients received androgen ablation therapy 2 to 6 months before radiation. 3D conformal radiotherapy was used to allow a smaller amount of rectum and bladder to be in the high dose volume. An 18 Mv linear accelerator was used. The first 21 patients received 66 Gy, 28 patients received 70 Gy and one 74 Gy.The mean prostate volume was 45 cc for patients who received androgen ablation and 54 for the others [p = 0.02]. The percentage of volume receiving more than 50 Gy [V50] was calculated for the rectum and bladder. The median V50 was 30% [10-55] for the rectum and 36% [5-70] for the bladder. Based on the RTOG grading [gr] for acute toxicity, there was no gr 3 gastrointestinal [GI] toxicity and only 1 gr 3 genitourinary [GU] toxicity. There were 9 gr 1 and 5 gr 2 GI toxicity, 10 gr 1 and 5 gr 2 GU toxicity. With our actual follow-up we have 2 late morbidities: gr 2 GLI and one erectile failure.3D conformal radiotherapy for prostate cancer has a good toxicity profile. Longer follow-up is needed to assess late toxicity and clinical outcome in this series

Cistopatía posradiación: análisis de 467 pacientes / Posradiation cistopaty: analysis of 467 patients

Análisis retrospectivo de 467 expedientes clínicos de pacientes radiadas por padecer cáncer ginecológico. Como resultados se señalan la mayor incidencia de complicaciones en mujeres operadas como parte de su tratamiento, sin establecer en la mayoría de los casos una correlación entre las características del tratamiento aplicado y la aparición de complicaciones.