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BACKGROUND: Intermittent androgen deprivation for prostate-specific antigen (PSA) elevation after radiotherapy may improve quality of life and delay hormone resistance. We assessed overall survival with intermittent versus continuous androgen deprivation in a noninferiority randomized trial. METHODS: We enrolled patients with a PSA level greater than 3 ng per milliliter more than 1 year after primary or salvage radiotherapy for localized prostate cancer. Intermittent treatment was provided in 8-month cycles, with nontreatment periods determined according to the PSA level. The primary end point was overall survival. Secondary end points included quality of life, time to castration-resistant disease, and duration of nontreatment intervals. RESULTS: Of 1386 enrolled patients, 690 were randomly assigned to intermittent therapy and 696 to continuous therapy. Median follow-up was 6.9 years. There were no significant between-group differences in adverse events. In the intermittent-therapy group, full testosterone recovery occurred in 35% of patients, and testosterone recovery to the trial-entry threshold occurred in 79%. Intermittent therapy provided potential benefits with respect to physical function, fatigue, urinary problems, hot flashes, libido, and erectile function. There were 268 deaths in the intermittent-therapy group and 256 in the continuous-therapy group. Median overall survival was 8.8 years in the intermittent-therapy group versus 9.1 years in the continuous-therapy group (hazard ratio for death, 1.02; 95% confidence interval, 0.86 to 1.21). The estimated 7-year cumulative rates of disease-related death were 18% and 15% in the two groups, respectively (P=0.24). CONCLUSIONS: Intermittent androgen deprivation was noninferior to continuous therapy with respect to overall survival. Some quality-of-life factors improved with intermittent therapy. (Funded by the Canadian Cancer Society Research Institute and others; ClinicalTrials.gov number, NCT00003653.).
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Antagonistas de Andrógenos/administración & dosificación , Neoplasias de la Próstata/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antagonistas de Andrógenos/efectos adversos , Quimioterapia Adyuvante , Esquema de Medicación , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/radioterapia , Calidad de Vida , Testosterona/sangreRESUMEN
OBJECTIVE: To report the outcomes of >1000 men with low-risk prostate cancer treated with low-dose-rate (LDR) brachytherapy at three large UK cancer centres. PATIENTS AND METHODS: A total of 1038 patients with low-risk prostate cancer (prostate-specific antigen [PSA] ≤10 ng/mL, Gleason score 6, ≤T2b disease) were treated with LDR iodine 125 (I-125) brachytherapy between 2002 and 2007. Patients were treated at three UK centres. PSA and clinical follow-up was performed at each centre. Biochemical recurrence-free survival was reported for the cohort. RESULTS: The median (range) PSA follow-up for the whole group was 5 years (4 months to 9 years). A total of 79 patients had biochemical failure, defined by a rise in PSA level: 16 patients fulfilled the ASTRO definition of biochemical failure, 25 patients fulfilled the Phoenix definition and 38 patients fulfilled both definitions. The 5-year biochemical relapse-free survival (bRFS) rate was 94.1% by the ASTRO definition and 94.2% by the Phoenix definition. The absence of neoadjuvant hormone therapy was predictive of inferior biochemical control as defined by the Phoenix definition (P = 0.033). CONCLUSIONS: Our prospective multicentre series showed excellent bRFS with LDR I-125 brachytherapy for patients with low-risk prostate cancer. Further work is necessary to define the role of neoadjuvant androgen deprivation therapy in combination with brachytherapy.
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Adenocarcinoma/radioterapia , Braquiterapia/métodos , Neoplasias de la Próstata/radioterapia , Adenocarcinoma/diagnóstico , Adenocarcinoma/epidemiología , Adulto , Anciano , Biopsia , Supervivencia sin Enfermedad , Estudios de Seguimiento , Humanos , Radioisótopos de Yodo/uso terapéutico , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Estadificación de Neoplasias , Prevalencia , Estudios Prospectivos , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/epidemiología , Factores de Riesgo , Tasa de Supervivencia/tendencias , Factores de Tiempo , Resultado del Tratamiento , Reino Unido/epidemiologíaRESUMEN
STUDY TYPE: Preference (prospective cohort). LEVEL OF EVIDENCE: 1b. What's known on the subject? and What does the study add? In general the literature suggests that there is a need for improvement in aiding men diagnosed with early prostate cancer in their decision making about treatment options and that our understanding of this process is inadequate. There is limited data analyzing the reasons why these men decide between potentially curative or observational treatments and data evaluating patients' views before and after definitive therapy are scarce. This study begins the process of understanding the reasons underlying a patient's final treatment decision. Being a prospective study, it looks at the thought processes of these men before treatment during the time the decision is made. It also documents how satisfied patients are with their choice after their treatment and whether they would choose the same treatment again. OBJECTIVE: To identify the reasons for patients with localised prostate cancer choosing between treatments and the relationship of procedure type to patient satisfaction post-treatment. PATIENTS AND METHODS: 768 men with prostate cancer (stage T1/2, Gleason≤7, PSA<20 ug/L) chose between four treatments: radical prostatectomy, brachytherapy, conformal radiotherapy and active surveillance. Prior to choosing, patients were counselled by a urological surgeon, clinical (radiation) oncologist and uro-oncology specialist nurse. Pre-treatment reasons for choice were recorded. Post-treatment satisfaction was examined via postal questionnaire. RESULTS: Of the 768 patients, 305 (40%) chose surgery, 237 (31%) conformal beam radiotherapy, 165 (21%) brachytherapy and 61 (8%) active surveillance. Sixty percent of men who opted for radical prostatectomy were motivated by the need for physical removal of the cancer. Conformal radiotherapy was mainly chosen by patients who feared other treatments (n=63, 27%). Most men chose brachytherapy because it was more convenient for their lifestyle (n=64, 39%). Active surveillance was chosen by patients for more varied reasons. Post-treatment satisfaction was assessed in a subgroup who took part in the QOL aspect of this study. Of the respondents to the questionnaire, 212(87.6%) stated that they were satisfied/extremely satisfied with their choice and 171(92.9%) indicated they would choose the same treatment again. CONCLUSION: Men with early prostate cancer have clear reasons for making decisions about treatment. Overall, patients were satisfied with the treatment and indicated that despite different reasons for choosing treatment, they would make the same choice again.
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Braquiterapia/tendencias , Observación/métodos , Prostatectomía/tendencias , Neoplasias de la Próstata/terapia , Radioterapia Conformacional/tendencias , Adulto , Factores de Edad , Anciano , Braquiterapia/métodos , Estudios de Cohortes , Toma de Decisiones , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Prioridad del Paciente , Estudios Prospectivos , Prostatectomía/métodos , Neoplasias de la Próstata/patología , Radioterapia Conformacional/métodos , Medición de Riesgo , Encuestas y Cuestionarios , Reino UnidoRESUMEN
The purpose of this study was to determine the impact of water exchange on tracer kinetic parameter estimates derived from T(1)-weighted dynamic contrast-enhanced (DCE)-MRI data using a direct quantitative comparison with DCE-CT. Data were acquired from 12 patients with bladder cancer who underwent DCE-CT followed by DCE-MRI within a week. A two-compartment tracer kinetic model was fitted to the CT data, and two versions of the same model with modifications to account for the fast exchange and no exchange limits of water exchange were fitted to the MR data. The two-compartment tracer kinetic model provided estimates of the fractional plasma volume (v(p)), the extravascular extracellular space fraction (v(e)), plasma perfusion (F(p)), and the microvascular permeability surface area product. Our findings suggest that DCE-CT is an appropriate reference for DCE-MRI in bladder cancers as the only significant difference found between CT and MR parameter estimates were the no exchange limit estimates of v(p) (P = 0.002). These results suggest that although water exchange between the intracellular and extravascular-extracellular space has a negligible effect on DCE-MRI, vascular-extravascular-extracellular space water exchange may be more important.
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Agua Corporal/metabolismo , Gadolinio DTPA/farmacocinética , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Rayos X/métodos , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/metabolismo , Anciano , Anciano de 80 o más Años , Humanos , Cinética , Masculino , Tasa de Depuración Metabólica , Persona de Mediana Edad , Proyectos PilotoRESUMEN
BACKGROUND AND PURPOSE: To report on the incidence of benign prostate-specific antigen bounce following permanent I(125) prostate brachytherapy, to describe the associations in our population and review the relationship of bounce to subsequent biochemical failure. MATERIALS AND METHODS: From February 2000 to May 2005, 374 patients with localised prostate cancer were treated with I(125) permanent prostate brachytherapy at a single institution. A prospectively collected database was used to identify cases of prostate-specific antigen (PSA) bounce, defined as a rise of 0.2 ng/ml above an initial PSA nadir with subsequent decline to or below that nadir without treatment. The patients who received neo-adjuvant or adjuvant hormone manipulation were excluded. Biochemical failure was determined using the both the ASTRO consensus definition and Phoenix (nadir +2 ng/mL) definition. RESULTS: Two hundred and five patients were identified with a median follow-up of 45 months (24-85). PSA bounce was noted in 79 (37%) men, occurring at a median of 14.8 months (1.7-40.6) following implant. The median peak PSA was 1.8 ng/ml (0.4-7.4) with a bounce magnitude of 0.91 ng/ml (0.2-5.8). When pre- and post-implant factors were assessed for association to bounce, only younger age was statistically significant (p=0.002). The threshold for biochemical failure as defined by the ASTRO consensus definition (1997) was met in 4 (5%) patients after experiencing bounce as opposed to 19 (15%) non-bounce patients (p=0.01). The threshold for Phoenix (nadir +2 ng/mL) was met in 6 (7.5%) patients following bounce versus 22 (17%) of non-bounce patients (p=0.003). Both definitions are prone to false positive calls during bounce. Median PSA velocity during the bounce was 0.08 ng/mL/month (0.02-0.98) and was statistically significantly lower than the median velocity prior to the Phoenix biochemical failure at 0.28 ng/mL/month (0.07-2.04) (p=0.0005). CONCLUSION: PSA bounce is a common finding in our population and is associated with a lower rate of subsequent biochemical failure. The noted differences in PSA velocity will require verification in a future analysis to reduce the influence of median follow-up on this finding. Patients should be advised of the potential of bounce in PSA follow-up after permanent I(125) prostate brachytherapy and physicians involved in follow-up of prostate brachytherapy patients should be aware of this phenomenon, allowing them to commit to appropriate PSA surveillance, avoiding the premature and inappropriate initiation of salvage therapy during PSA bounce.
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Braquiterapia/métodos , Radioisótopos de Yodo/uso terapéutico , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/radioterapia , Adulto , Anciano , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estadísticas no Paramétricas , Análisis de Supervivencia , Resultado del Tratamiento , Ultrasonografía IntervencionalRESUMEN
BACKGROUND AND PURPOSE: To use quantitative MRI to detect changes in the vascular and MR relaxation characteristics of the prostate gland 1 year after external beam radiotherapy. MATERIALS AND METHODS: Twenty-one patients underwent MRI before and after external beam radiotherapy for prostatic adenocarcinoma. Tracer kinetics analysis was applied to data from regions of interest in prostate tumour, normal prostate peripheral zone and muscle to obtain estimates of blood flow, extravascular-extracellular volume, blood volume and capillary permeability surface area product. T(1) and T(2) were also measured in these regions. RESULTS: Significant changes (p<0.05) after radiotherapy were found in all three tissues examined. Tumour blood flow was 0.34 and 0.14 ml (ml tissue)(-1) min(-1) before and after treatment, respectively, and T(1) increased from 922 to 1,070 ms. In normal peripheral zone, extravascular-extracellular volume increased from 0.21 to 0.52 ml (ml tissue)(-1), and T(2) decreased from 126 to 106 ms. In muscle, both permeability surface area product and T(2) rose, from 0.02 to 0.06 ml (ml tissue)(-1) min(-1) and from 50 to 56 ms, respectively. CONCLUSIONS: Quantitative MRI can be used to measure significant changes in both vascular and MR relaxation properties of the prostate and nearby muscle following treatment for prostate cancer using external beam radiotherapy.
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Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/radioterapia , Antineoplásicos Hormonales/administración & dosificación , Imagen por Resonancia Magnética/métodos , Próstata/irrigación sanguínea , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/radioterapia , Anciano , Quimioterapia Adyuvante , Terapia Combinada , Medios de Contraste , Humanos , Masculino , Microcirculación , Persona de Mediana Edad , Estudios Prospectivos , Próstata/efectos de los fármacos , Próstata/efectos de la radiación , Resultado del TratamientoRESUMEN
The treatment of metastatic castrate-resistant prostate cancer (mCRPC) has grown over the past decade. The majority of patients develop bone metastases, which pose a significant burden on morbidity and mortality, especially skeletal-related events. Whilst demonstrating a favourable safety profile and improving symptoms, radiopharmaceuticals have until recently failed to show a survival benefit. However, since the large phase III randomized ALSYMPCA trial, the calcium mimetic properties of radium-223 (Ra223) have improved patients' quality of life and improved survival whilst keeping toxicities to a minimum. This review article summarizes the clinical data including our real life experience on the usage of the alpha emitter Ra223 in mCRPC, paying particular attention to how clinicians should best monitor response.
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Advances in radiation treatment planning, verification, and delivery provide a means to optimize radiation treatment for bladder cancer and overcome difficulties which have previously limited the success of this treatment. They offer the opportunity to enhance the therapeutic ratio by reducing the volume of normal tissue irradiated and by increasing radiation dose or using more intensive fractionation and synchronous chemotherapy regimes. In this review, we aim to present a practical overview of radiation protocols for bladder cancer, covering issues relating to patient selection, choice of target volumes, verification, dose, and fractionation. Alternative methods of improving treatment accuracy such as image-guided radiotherapy and intensity modulated radiotherapy are also discussed.
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Planificación de la Radioterapia Asistida por Computador , Neoplasias de la Vejiga Urinaria/radioterapia , Fraccionamiento de la Dosis de Radiación , Humanos , Invasividad Neoplásica , Selección de Paciente , Radioterapia Asistida por Computador , Radioterapia ConformacionalRESUMEN
PURPOSE: A prospective phase I trial was conducted to determine the maximal tolerated dose of gemcitabine given once weekly during hypofractionated conformal radiotherapy to patients with locally advanced transitional cell carcinoma of the bladder. Eight male patients, median age 69 years, with Stage T2 (n = 4) or T3 (n = 4) N0M0, were enrolled in cohorts of 3. Treatment comprised conformal radiotherapy (52.5 Gy in 20 fractions) within 4 weeks, with concurrent gemcitabine once weekly for four cycles. The weekly gemcitabine dose was escalated from 100 mg/m(2) in increments of 50 mg/m(2) per cohort. Dose-limiting toxicity was defined as any acute Radiation Therapy Oncology Group (RTOG) toxicity Grade 3 or greater arising in >1 of 3 patients in each cohort. Tumor response was assessed cystoscopically and radiologically at 3 months. RESULTS: All 8 patients completed radiotherapy, and 6 of 8 completed chemoradiotherapy. No acute toxicity greater than RTOG Grade 1 was seen with gemcitabine at 100 mg/m(2). Dose-limiting toxicity was observed at 150 mg/m(2) with Grade 3 toxicity seen in 2 of 2 patients (one bladder, one bowel). An additional 3 patients received 100 mg/m(2) with minimal toxicity. No hematologic toxicity was encountered. A complete response was seen in 7 (87.5%) of 8 patients, all of whom were disease free at a median follow-up of 19.5 months (range, 14-23 months). No late toxicity (greater than RTOG Grade 0) has been observed. CONCLUSION: The maximal tolerated dose for gemcitabine given once weekly with concurrent hypofractionated conformal bladder radiotherapy was 150 mg/m(2), with a maximal recommended dose of 100 mg/m(2). This dose regimen has now entered Phase II clinical trials.
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Antimetabolitos Antineoplásicos/administración & dosificación , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/radioterapia , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Fármacos Sensibilizantes a Radiaciones/administración & dosificación , Radioterapia Conformacional , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/radioterapia , Anciano , Antimetabolitos Antineoplásicos/efectos adversos , Carcinoma de Células Transicionales/patología , Terapia Combinada , Desoxicitidina/efectos adversos , Humanos , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Estudios Prospectivos , Fármacos Sensibilizantes a Radiaciones/efectos adversos , Neoplasias de la Vejiga Urinaria/patología , GemcitabinaRESUMEN
PURPOSE: To determine the outcome in men with Stage I seminoma treated with low-dose para-aortic radiation. MATERIALS AND METHODS: Between January 1988 and December 2000, 431 men with Stage I seminoma were treated with para-aortic radiation to a midplane dose of 20 Gy in 8 fractions over 10 days. RESULTS: At a median follow-up of 62 months, 15 patients (3.5%) had relapsed, with a median time to relapse of 13 months (range: 9 to 39 months). Nine patients had pelvic nodal relapse; in addition, 1 patient had para-aortic involvement, and 2 had distant disease. Four had metastatic disease only (mediastinum 2, lung 2). One patient had scrotal recurrence, and 1 was treated for progressive rise in human chorionic gonadotrophin without identifiable disease. Initial treatment at relapse was chemotherapy (12), radiation (2), and surgery (1). One patient died from progressive disease. Thirteen men (3%) have developed second malignancies, including 7 contralateral testicular tumors, 5 solid malignancies, and 1 leukemia. The overall 5-year survival was 98%, and the estimated recurrence-free survival at 5 years was 96.3%. On log-rank univariate analysis, lymphovascular invasion, involvement of the tunica, and a preoperative human chorionic gonadotrophin level of greater than 5 were found to be of prognostic significance for recurrence. CONCLUSIONS: These data support short-duration, limited-field radiation as an optimal safe and effective protocol in the management of Stage I seminoma patients.
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Seminoma/radioterapia , Neoplasias Testiculares/radioterapia , Adolescente , Adulto , Anciano , Análisis de Varianza , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Primarias Secundarias/etiología , Seminoma/patología , Neoplasias Testiculares/patologíaRESUMEN
PURPOSE: Many studies have described the quantitated differences between clinicians in target volume definition in prostate cancer. However, few studies have looked at the clinical effects of this. We aimed to assess the relevance and sequelae of such differences. METHODS AND MATERIALS: Five experienced radiation oncologists were given the clinical details of 5 patients with early-stage prostate cancer and asked to define the clinical target volume, consisting of the prostate and seminal vesicles (CTV1) and the prostate alone (CTV2), on specified planning CT scans of the pelvis. Planning target volumes (PTV1) were generated by automatic expansion of the CTV1 by a 1-cm margin. The PTV2 was defined as the CTV2. The rectum and bladder were defined by a single experienced clinician for each plan without knowledge of the involved clinician marking the CTVs. The Pinnacle planning system was used to generate the plans, using four-field conformal radiotherapy, to deliver 64 Gy in 32 fractions to the PTV1 followed by a boost of 10 Gy to the PTV2 (Medical Research Council RT01 trial protocol). Dose-volume histograms were generated for the whole bladder and rectum for each plan and the volume receiving a specific percentage of the dose (e.g., V(90)) calculated for 74 Gy, followed by estimates of normal tissue complication probabilities (NTCPs) for the bladder and rectum. RESULTS: Statistically significant differences were found in the CTV1 and CTV2 and, consequently, the PTV1 among the 5 clinicians (p < 0.0005). Most of the discrepancies occurred at the delineation of the prostatic apex and seminal vesicles, with the smallest variance noted at the rectum-prostate and bladder-prostate interfaces. No statistically significant differences were found among clinicians for the rectal V(90), V(85), V(80), V(70), or V(50) or for the bladder V(85), V(80), V(70), or V(50). A difference was noted among consultants for the bladder V(90) (p = 0.015), although no correlation was found between the bladder V(90) and the size of the outlined volumes. No statistically significant differences were found between the estimates of bladder (p = 0.1) and rectal (p = 0.09) NTCPs. CONCLUSION: The statistically significant difference in outlined volumes of the CTV1, CTV2, and PTV1 among the 5 clinicians is in keeping with the findings of previous studies. However, the interclinician variability did not result in clinically relevant outcomes with respect to the irradiated volume of rectum and bladder or NTCP. This may have been because the outlined areas in which interclinician differences were smallest (the rectal-prostate and prostate-bladder interfaces) are the areas that have the greatest effect on normal tissue toxicity. For the areas in which the interclinician correlation was lowest (the prostatic apex and distal seminal vesicles), the effects on normal tissue toxicity are smallest. The results of this study suggest that interclinician outlining differences in prostate cancer may have less clinical relevance than was previously thought.
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Próstata/diagnóstico por imagen , Neoplasias de la Próstata/diagnóstico por imagen , Oncología por Radiación/normas , Planificación de la Radioterapia Asistida por Computador , Vesículas Seminales/diagnóstico por imagen , Anciano , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Próstata/patología , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/radioterapia , Radiografía , Radioterapia Conformacional , Recto/diagnóstico por imagen , Carga Tumoral , Vejiga Urinaria/diagnóstico por imagenRESUMEN
PURPOSE: Recent publications have indicated that the alpha/beta ratios for carcinoma of the prostate are much lower than had originally been thought, suggesting that prostate cancer may be highly sensitive to fraction size. We have reviewed our unique experience of the use of 3.13 Gy fractions in a large cohort of men treated homogeneously in a single institute. MATERIALS AND METHODS: The outcome for 705 men with T1-T4, N0, M0 prostate cancer who received conformal radiotherapy between 1995 and 1998 at this center was analyzed. No patient received hormonal manipulation. Mean age was 68 years (range: 49-84 years). Median pretreatment PSA was 13 ng/mL (range: 0.6-270 ng/mL). Disease characteristics were as follows: Stage T1, 125 (18%); T2, 365 (52%); T3/4, 215 (30%); Gleason 2-6, 463 (66%); Gleason 7-10, 242 (34%); pretreatment PSA < or =10 ng/mL, 291 (41%); 10 to < or =20, 228 (32%); >20, 186 (27%). Median follow-up was 48 months (range: 1-82 months). Biochemical-free survival (bNED) was defined by the American Society for Therapeutic Radiology and Oncology consensus definition. Radiotherapy was delivered to a planning target volume (prostate plus all/base of the seminal vesicles dependent on risk criteria with a 1-cm margin) with a 4-field conformal technique to a dose of 50 Gy in 16 daily fractions over 22 days. RESULTS: The 5-year bNED survival was significantly associated (p < 0.001) with pretreatment PSA, stage, and Gleason score. Five-year bNED rates with respect to pretreatment characteristics were as follows: 73% (PSA < or =10), 52% (>10-20), 35% (>20), 64% (Stage T1/2), 38% (T3/4), 61% (Gleason score 2-6), and 46% (Gleason > or =7). When patients were grouped into good (Stage T1/2, PSA < or =10 ng/mL, and Gleason score <7) (n = 181), intermediate (1 raised value) (n = 247), or poor (2 or more raised values) (n = 277) prognostic groups, the bNED was, respectively, 82%, 56%, and 39%. Radiation Therapy Oncology Group Grade > or =2 bowel toxicity was 5% and bladder 9%. CONCLUSIONS: These data indicate that the delivery of a relatively low total dose using a hypofractionated regime results in similar tumor control and normal-tissue toxicity to 65-70 Gy delivered in 1.8-2 Gy fractions. These data suggest that this is an acceptable regime for good-prognosis patients. However, because of the evidence for a dose effect at doses above 70 Gy with "conventional fractionation," we are now treating intermediate- and poor-risk patients within a hypofractionated dose escalation trial to 60 Gy in 20 fractions using intensity- modulated radiotherapy.
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Neoplasias de la Próstata/radioterapia , Radioterapia Conformacional/métodos , Anciano , Intervalos de Confianza , Fraccionamiento de la Dosis de Radiación , Humanos , Masculino , Persona de Mediana Edad , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/mortalidad , Análisis de SupervivenciaRESUMEN
PURPOSE: To estimate the benefits of dose escalation in hypofractionated intensity-modulated radiotherapy (IMRT) for prostate cancer, using radiobiologic modeling and incorporating positional uncertainties of organs. MATERIALS AND METHODS: Biologically based mathematical models for describing the relationships between tumor control probability (TCP) and normal-tissue complication probability (NTCP) vs. dose were used to describe some of the results available in the literature. The values of the model parameters were then used together with the value of 1.5 Gy for the prostate cancer alpha/beta ratio to predict the responses in a hypofractionated 3 Gy/fraction IMRT trial at the Christie Hospital, taking into account patient movement characteristics between dose fractions. RESULTS: Compared with the current three-dimensional conformal radiotherapy technique (total dose of 50 Gy to the planning target volume in 16 fractions), the use of IMRT to escalate the dose to the prostate was predicted to increase the TCP by 5%, 16%, and 22% for the three dose levels, respectively, of 54, 57, and 60 Gy delivered using 3 Gy per fraction while keeping the late rectal complications (>/=Grade 2 RTOG scale) at about the same level of 5%. Further increases in TCP could be achieved by reducing the uncertainty in daily target position, especially for the last stage of the trial, where up to 6% further increase in TCP should be gained. CONCLUSIONS: Dose escalation to the prostate using IMRT to deliver daily doses of 3 Gy was predicted to significantly increase tumor control without increasing late rectal complications, and currently this prediction is being tested in a clinical trial.
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Adenocarcinoma/radioterapia , Simulación por Computador , Modelos Teóricos , Neoplasias de la Próstata/radioterapia , Dosificación Radioterapéutica , Radioterapia Conformacional/métodos , Ensayos Clínicos como Asunto/estadística & datos numéricos , Relación Dosis-Respuesta en la Radiación , Humanos , Imagenología Tridimensional , Masculino , Movimiento (Física) , Traumatismos por Radiación/etiología , Traumatismos por Radiación/prevención & control , Planificación de la Radioterapia Asistida por Computador , Radioterapia Conformacional/efectos adversos , Recto/lesiones , Recto/efectos de la radiación , Resultado del TratamientoRESUMEN
PURPOSE: To investigate whether analysis of MRI enhancement data using a pharmacokinetic model improved a previously found correlation between contrast enhancement and tumor oxygenation measured using PO2 histograph. To evaluate the prognostic value of gadolinium enhancement data for radiotherapy outcome, and to study the efficacy of combined enhancement and MRI volume data. METHODS AND MATERIALS: Fifty patients underwent dynamic gadolinium-enhanced MRI as part of their initial staging investigations before treatment. Gadolinium enhancement was analyzed using the Brix pharmacokinetic model to obtain the parameters amplitude and rate of contrast enhancement. Pretreatment tumor oxygen measurements (Eppendorf PO2 histograph) were available for 35 patients. RESULTS: Both standard and pharmacokinetic-derived enhancement data correlated with tumor oxygenation measurements, and poorly enhancing tumors had low tumor oxygen levels. However, only the pharmacokinetic-analyzed data correlated with patient outcome and patients with poorly (amplitude less than median) vs. well-enhancing tumors had significantly worse disease-specific survival (p = 0.024). For the 50 patients studied, no relationship was found between enhancement and volume data. Combining MRI volume and enhancement information highlighted large differences in outcome (p = 0.0054). At the time of analysis, only 55% of patients with large, poorly enhanced tumors were alive compared with 92% of patients with small, well-enhanced tumors. CONCLUSION: These preliminary results suggest that pharmacokinetic modeling of dynamic contrast-enhanced MRI provides data that reflect tumor oxygenation and yields useful prognostic information in patients with locally advanced carcinoma of the cervix. Combining MRI-derived enhancement and volume data delineates large differences in radiotherapy outcome.
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Adenocarcinoma/metabolismo , Carcinoma Adenoescamoso/metabolismo , Hipoxia de la Célula , Gadolinio/farmacocinética , Imagen por Resonancia Magnética/métodos , Oxígeno/análisis , Radioisótopos/farmacocinética , Neoplasias del Cuello Uterino/metabolismo , Adenocarcinoma/patología , Adenocarcinoma/radioterapia , Análisis de Varianza , Carcinoma Adenoescamoso/patología , Carcinoma Adenoescamoso/radioterapia , Femenino , Humanos , Persona de Mediana Edad , Resultado del Tratamiento , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/radioterapiaRESUMEN
PURPOSE: To investigate whether delivering an increased radiation dose to the tumor-bearing region of the bladder alone would improve local disease control without increasing treatment toxicity. METHODS AND MATERIALS: A total of 149 patients with unifocal T2-T3N0M0 bladder carcinoma were randomized between whole bladder conformal radiotherapy (WBRT, 52.5 Gy in 20 fractions, n = 60) and partial bladder conformal RT (PBRT) to tumor alone with 1.5-cm margins within either 4 weeks (PBRT4, 57.5 Gy in 20 fractions, n = 44) or 3 weeks (PBRT3, 55 Gy in 16 fractions, n = 45). The response was assessed cystoscopically after 4 months. RESULTS: The 5-year overall and CFS rate was 58% and 47%, respectively, for the whole population. The CR rate was 75% for WBRT, 80% for PBRT4, and 71% for PBRT3 (p = 0.6), with a 5-year local control rate of 58%, 59%, and 34%, respectively (p = 0.18). Solitary new tumors arose within the bladder, outside the irradiated volume, in 6 (7%) of 89 patients who underwent PBRT. The 5-year overall survival and cystectomy-free survival rate was 61% and 49% for WBRT, 60% and 50% for PBRT4, and 51% and 41% for PBRT3 (p = 0.81 and p = 0.59). The treatment toxicity was mild and equivalent across the three trial arms. CONCLUSION: The reduction in treatment volume allowed delivery of an increased radiation dose without a reduction in local tumor control or the development of excess toxicity. However, this dose-escalated partial bladder approach did not result in significantly improved overall survival.
Asunto(s)
Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Transicionales/radioterapia , Radioterapia Conformacional/métodos , Neoplasias de la Vejiga Urinaria/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Transicionales/mortalidad , Carcinoma de Células Transicionales/patología , Cistoscopía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Estudios Prospectivos , Traumatismos por Radiación/clasificación , Dosificación Radioterapéutica , Inducción de Remisión , Terapia Recuperativa , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
On-line imaging of prostate markers can be used to compensate for errors in radiation delivery. This study assessed the patient acceptability and morbidity associated with the trans-perineal route of implantation. A minority experienced acute pain or bleeding. Placement was accurate in all but one subject. An operator related learning curve exists. Although this is an invasive procedure most patients found it acceptable. Implementation for routine clinical practice is feasible.
Asunto(s)
Adenocarcinoma/radioterapia , Neoplasias de la Próstata/radioterapia , Humanos , Masculino , Aceptación de la Atención de Salud , Estudios Prospectivos , Radioterapia/efectos adversos , Radioterapia/métodos , Dosificación RadioterapéuticaRESUMEN
BACKGROUND AND PURPOSE: To assess the correlation between different general and organ specific quality of life and morbidity scoring methods in a cohort of men treated with radical radiotherapy for prostate cancer. MATERIALS AND METHODS: Men who had been treated with radical radiotherapy (50 Gy in 16 fractions over 21 days) for localized prostate cancer more than 3 years previously and who had no evidence of recurrent disease were invited to take part in the study. A total of 101 of 135 invited patients agreed and completed LENT/SOMA, UCLA Prostate Cancer Index, and 36 item RAND Health survey questionnaires. RESULTS: The patients had comparable results with other published series with respect to the UCLA and SF-36 indices. There was significant correlation between the corresponding parts of the UCLA and LENT/SOMA scales (P<0.0005). However, for the same symptoms, a patient tended to score lower (worse) on the UCLA scale in comparison to LENT/SOMA. The relationship between the average LENT/SOMA score and maximum score was also not straightforward with each set of data revealing different information. CONCLUSIONS: The LENT/SOMA questions were, in the main, more wide-ranging and informative than the UCLA index. It is helpful to give both the overall and maximum LENT/SOMA scores to most efficiently use all of the data. There may need to be a further LENT/SOMA question to allow both symptoms of tenesmus and faecal urgency to be fully addressed.
Asunto(s)
Neoplasias de la Próstata/psicología , Neoplasias de la Próstata/radioterapia , Radioterapia Conformacional/efectos adversos , Perfil de Impacto de Enfermedad , Anciano , Anciano de 80 o más Años , Humanos , Enfermedades Inflamatorias del Intestino/etiología , Masculino , Persona de Mediana Edad , Calidad de Vida/psicología , Disfunciones Sexuales Fisiológicas/etiología , Encuestas y Cuestionarios , Factores de Tiempo , Enfermedades de la Vejiga Urinaria/etiologíaRESUMEN
PURPOSE: The aim of this prospective, phase II trial was to determine the response of muscle-invasive bladder cancer (MIBC) to concurrent chemoradiotherapy of weekly gemcitabine with 4 weeks of radiotherapy (RT; GemX). PATIENTS AND METHODS: Fifty patients with transitional cell carcinoma, stage T2-3, N0, M0 after transurethral resection and magnetic resonance imaging, were recruited. Gemcitabine was given intravenously at 100 mg/m(2) on days 1, 8, 15, and 22 of a 28-day RT schedule that delivered 52.5 Gy in 20 fractions. Chemotherapy was stopped for Radiation Therapy Oncology Group (RTOG) grade 3 bladder or bowel toxicity. The primary end points were tumor response, toxicity, and survival. RESULTS: All patients completed RT; 46 tolerated all four cycles of gemcitabine. Two patients stopped after two cycles, and two stopped after three cycles, because of bowel toxicity. Forty-seven patients had a post-treatment cystoscopy; 44 (88%) achieved a complete endoscopic response. At a median follow-up of 36 months (range, 15 to 62 months), 36 patients were alive, and 32 of these had a functional and intact bladder. Fourteen patients died; seven died as a result of metastatic MIBC, five died as a result of intercurrent disease, and two died as a result of treatment-associated deaths. Four patients underwent cystectomy; three because of recurrent disease and one because of toxicity. One patient required a bowel resection for late toxicity. By using Kaplan-Meier analyses, 3-year cancer-specific survival was 82%, and overall survival was 75%. CONCLUSION: Concurrent gemcitabine-based chemoradiotherapy (ie, GemX) produces a high response rate in MIBC and has durable local control and acceptable toxicity, which allows patients to preserve their own bladder. This treatment modality warrants additional investigation in a phase III setting.
Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma de Células Transicionales/terapia , Desoxicitidina/análogos & derivados , Neoplasias de los Músculos/terapia , Radioterapia Conformacional/métodos , Neoplasias de la Vejiga Urinaria/terapia , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Carcinoma de Células Transicionales/mortalidad , Carcinoma de Células Transicionales/patología , Terapia Combinada , Desoxicitidina/efectos adversos , Desoxicitidina/uso terapéutico , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neoplasias de los Músculos/mortalidad , Neoplasias de los Músculos/secundario , Invasividad Neoplásica , Estadificación de Neoplasias , Radioterapia Conformacional/efectos adversos , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patología , GemcitabinaRESUMEN
We investigated the efficacy of data capture of patient-reported toxicity following radiotherapy by comparing electronic and paper formats. Patient-reported toxicity questionnaires based on items from the NCI Common Terminology Criteria for Adverse Events (CTCAE) were created for patients receiving radiotherapy. Electronic and paper questionnaires had identical questions. Thirty seven gynaecological cancer and 40 prostate cancer patients completed questionnaires. Both questionnaire formats (electronic and paper) were completed by each patient at time points before and after radiotherapy. The average questionnaire and subsection scores for each format were compared directly and by using intra-class correlation (ICC) coefficients. The internal consistency/reliability was assessed by determining Cronbach's alpha coefficient. Patient preference for questionnaire format including clarity and ease-of-use was recorded. 324 questionnaires were collected as part of this study. A similar pattern of average subsection scores was found for the electronic and paper questionnaires. ICC coefficients for the mean overall questionnaire scores and subsection scores were high (>0.8). Cronbach's alpha was generally greater than 0.6, indicating that the reliability was high. Of the patients that responded, 27.3% preferred the electronic format, 25.7% preferred the paper format and 47% had no preference. The average time taken to complete a questionnaire was about 9 minutes for each format. The different questionnaire formats measured toxicity effects consistently and were reliable for both gynaecological cancer and prostate cancer patients. The survey indicated that patients found the questionnaires clear, easy to understand and straightforward to complete. Electronic data capture of patient-reported toxicity for CTCAE is feasible and acceptable.
Asunto(s)
Neoplasias de la Próstata/radioterapia , Traumatismos por Radiación/etiología , Encuestas y Cuestionarios , Neoplasias del Cuello Uterino/radioterapia , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Prioridad del Paciente , Estudios Prospectivos , Neoplasias de la Próstata/patología , Radioterapia/efectos adversos , Factores de Tiempo , Interfaz Usuario-Computador , Neoplasias del Cuello Uterino/patologíaRESUMEN
PURPOSE: To improve a questionnaire used to collect patient-reported outcomes from patients with early stage prostate cancer treated with brachytherapy. A secondary aim was to adapt the Late Effects of Normal Tissue (LENT) subjective toxicity questionnaire for use to collect Common Terminology Criteria for Adverse Events (CTCAE) data, the current preferred platform for assessing radiation toxicity. MATERIALS AND METHODS: Three hundred and seventy-seven patients were treated with permanent iodine-125 seed implant brachytherapy for early prostate cancer. Toxicity data were collected before and at nine time points post-treatment (0-36 months). Compliance rates for patients completing individual items and item-subsection correlation coefficients were calculated. A factor analysis was carried out to analyse responses to the questionnaire and identify less informative questions, which could be removed. Cronbach's α coefficient was used to measure reliability. RESULTS: Two thousand one hundred and eighty-eight questionnaires were analysed. There was poor compliance for questions specifically relating to operations and bowel medication. We found that the division of the questionnaire into subsections based on anatomical site was reasonable and that certain items could be safely removed. The high mean value for Cronbach's α across all questionnaires (0.752; 95% CI: 0.726-0.779) indicated that the questionnaire was reliable. Fifteen of the 44 questions were removed from the original questionnaires. Questions on urinary incontinence severity, management of urinary and bowel incontinence, effects of reduced flow of urine and the effects of symptoms on activity of daily living and change in sexual function were required to adapt the LENT subjective questionnaire for use to collect CTCAE data. CONCLUSIONS: A questionnaire, validated over 6 years to collect LENT subjective data were adapted and is a reliable approach for collecting CTCAE data after prostate brachytherapy.