RESUMEN
PURPOSE/BACKGROUND: Validating a predictive model for late rectal bleeding following external beam treatment for prostate cancer would enable safer treatments or dose escalation. We tested the normal tissue complication probability (NTCP) model recommended in the recent QUANTEC review (quantitative analysis of normal tissue effects in the clinic). MATERIAL AND METHODS: One hundred and sixty one prostate cancer patients were treated with 3D conformal radiotherapy for prostate cancer at the British Columbia Cancer Agency in a prospective protocol. The total prescription dose for all patients was 74 Gy, delivered in 2 Gy/fraction. 159 3D treatment planning datasets were available for analysis. Rectal dose volume histograms were extracted and fitted to a Lyman-Kutcher-Burman NTCP model. RESULTS: Late rectal bleeding (>grade 2) was observed in 12/159 patients (7.5%). Multivariate logistic regression with dose-volume parameters (V50, V60, V70, etc.) was non-significant. Among clinical variables, only age was significant on a Kaplan-Meier log-rank test (p=0.007, with an optimal cut point of 77 years). Best-fit Lyman-Kutcher-Burman model parameters (with 95% confidence intervals) were: n = 0.068 (0.01, +infinity); m =0.14 (0.0, 0.86); and TD50 = 81 (27, 136) Gy. The peak values fall within the 95% QUANTEC confidence intervals. On this dataset, both models had only modest ability to predict complications: the best-fit model had a Spearman's rank correlation coefficient of rs = 0.099 (p = 0.11) and area under the receiver operating characteristic curve (AUC) of 0.62; the QUANTEC model had rs=0.096 (p= 0.11) and a corresponding AUC of 0.61. Although the QUANTEC model consistently predicted higher NTCP values, it could not be rejected according to the χ(2) test (p = 0.44). CONCLUSIONS: Observed complications, and best-fit parameter estimates, were consistent with the QUANTEC-preferred NTCP model. However, predictive power was low, at least partly because the rectal dose distribution characteristics do not vary greatly within this patient cohort.
Asunto(s)
Carcinoma/radioterapia , Hemorragia Gastrointestinal/epidemiología , Hemorragia Gastrointestinal/etiología , Modelos Estadísticos , Neoplasias de la Próstata/radioterapia , Traumatismos por Radiación/epidemiología , Traumatismos por Radiación/etiología , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Simulación por Computador , Directrices para la Planificación en Salud , Humanos , Masculino , Persona de Mediana Edad , Radioterapia/efectos adversos , Radioterapia/métodos , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Recto , Factores de RiesgoRESUMEN
PURPOSE: The presence of intrinsic radiosensitivity within prostate cancer patients may be an important factor contributing to development of radiation toxicity. We investigated whether variants in genes responsible for detecting and repairing DNA damage independently contribute to toxicity following prostate brachytherapy. EXPERIMENTAL DESIGN: Genomic DNA was extracted from blood samples of 41 prostate brachytherapy patients, 21 with high and 20 with low late toxicity scores. For each patient, 242 PCR amplicons were generated containing 173 exons of eight candidate genes: ATM, BRCA1, ERCC2, H2AFX, LIG4, MDC1, MRE11A, and RAD50. These amplicons were sequenced and all sequence variants were subjected to statistical analysis to identify those associated with late radiation toxicity. RESULTS: Across 41 patients, 239 sites differed from the human genome reference sequence; 170 of these corresponded to known polymorphisms. Sixty variants, 14 of them novel, affected protein coding regions and 43 of these were missense mutations. In our patient population, the high toxicity group was enriched for individuals with at least one LIG4 coding variant (P = 0.028). One synonymous variant in MDC1, rs28986317, was associated with increased radiosensitivity (P = 0.048). A missense variant in ATM, rs1800057, associated with increased prostate cancer risk, was found exclusively in two high toxicity patients but did not reach statistical significance for association with radiosensitivity (P = 0.488). CONCLUSIONS: Our data revealed new germ-line sequence variants, indicating that existing sequence databases do not fully represent the full extent of sequence variation. Variants in three DNA repair genes were linked to increased radiosensitivity but require validation in larger populations.
Asunto(s)
Braquiterapia/efectos adversos , Reparación del ADN/genética , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/radioterapia , Tolerancia a Radiación/genética , Exones/genética , Humanos , Masculino , Mutación Missense , Polimorfismo de Nucleótido SimpleRESUMEN
PURPOSE: To describe the frequency of acute and late Radiation Therapy Oncology Group (RTOG) urinary toxicity, associated predictive factors, and resolution of International Prostate Symptom Score (IPSS) in 712 consecutive prostate brachytherapy patients. METHODS AND MATERIALS: Patients underwent implantation between 1998 and 2003 (median follow-up, 57 months). The IPSS and RTOG toxicity data were prospectively collected. The patient, treatment, and implant factors were examined for an association with urinary toxicity. The time to IPSS resolution was examined using Kaplan-Meier curves, and multivariate modeling of IPSS resolution was done using Cox proportional hazards regression analysis. Logistic regression analysis was used to examine the factors associated with urinary toxicity. RESULTS: The IPSS returned to baseline at a median of 12.6 months. On multivariate analysis, patients with a high baseline IPSS had a quicker resolution of their IPSS. Higher prostate D90 (dose covering 90% of the prostate), maximal postimplant IPSS, and urinary retention slowed the IPSS resolution time. The rate of the actuarial 5-year late urinary (>12 months) RTOG Grade 0, 1, 2, 3, and 4 was 32%, 36%, 24%, 6.2%, and 0.1%, respectively. At 7 years, the prevalence of RTOG Grade 0-1 was 92.5%. Patients with a larger prostate volume, greater number of needles, greater baseline IPSS, and use of hormonal therapy had more acute toxicity. On multivariate analysis, the significant predictors for late greater than or equal to RTOG toxicity 2 were a greater baseline IPSS, maximal postimplant IPSS, presence of acute toxicity, and higher prostate V150 (volume of the prostate covered by 150% of the dose). More recently implanted patients had less acute urinary toxicity and patients given hormonal therapy had less late urinary toxicity (all p < 0.02). CONCLUSION: Most urinary symptoms resolved within 12 months after prostate brachytherapy, and significant long-term urinary toxicity was very low. Refined patient selection and greater technical experience in prostate brachytherapy were associated with less urinary toxicity.
Asunto(s)
Braquiterapia/efectos adversos , Neoplasias de la Próstata/radioterapia , Trastornos Urinarios/etiología , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Braquiterapia/métodos , Colombia Británica , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Dosificación Radioterapéutica , Análisis de Regresión , Trastornos Urinarios/epidemiologíaRESUMEN
PURPOSE: To evaluate the incidence and factors predictive of acute urinary retention (AUR) in 805 consecutive patients treated with prostate brachytherapy monotherapy and to examine the possible effect of a learning curve. METHODS AND MATERIALS: Between July 1998 and November 2002, 805 patients were treated with prostate brachytherapy. Low-risk patients (Gleason Score (GS) < or = 6; prostate specific antigen (PSA) < or = 10, and < or = T2b [UICC 1997]) received implant alone. Patients with prostate volume of 50 cc or more, GS = 7, or PSA = 10 to 15 received 6 months of androgen suppression (AS) with brachytherapy. Patient, treatment, and dosimetric factors examined include baseline prostate symptom score (IPSS), diabetes, vascular disease, PSA, Gleason score, clinical stage, AS, ultrasound planning target volume (PUTV), postimplant prostate volume (obtained with "Day 30" postimplant CT), CT:PUTV ratio (surrogate for postimplant edema), number of seeds, number of needles, number of seeds per needle, dosimetric parameters (V100, V150, and D90), date of implant (learning curve), and implanting oncologists. Univariate and multivariate analyses were carried out. RESULTS: Acute urinary retention in the first 200 patients was 17% vs. 6.3% in the most recently treated 200 patients (p = 0.002). Overall AUR was 12.7%, and prolonged urinary obstruction incidence (> 20 days) was 5%. On multivariate analysis, factors predictive of any AUR include baseline IPSS (p = < 0.004), CT:PUTV ratio (p = < 0.001), PUTV (p = < 0.001), and implant order (learning curve) (p = 0.001). Factors predictive for "prolonged" catheterization (> 20 days) on multivariate analysis include IPSS (p < 0.01), number of needles (p < 0.001), diabetes mellitus (p = 0.048), and CT:PUTV ratio (p < 0.001) CONCLUSION: Over the years, our AUR rate has fallen significantly (from 17% to 6.3%). On multivariate analysis, highly significant factors include IPSS, PUTV, CT:PUTV ratio (i.e., degree of prostate edema), and order of implant (learning curve). Over the course of the program, we have deliberately reduced the number of needles and OR time per patient, which have potentially minimized intraoperative trauma and may have contributed to less toxicity. A learning curve in prostate brachytherapy programs affect not only the outcome but also the toxicity from the treatment.
Asunto(s)
Braquiterapia/efectos adversos , Práctica Psicológica , Neoplasias de la Próstata/radioterapia , Refuerzo en Psicología , Retención Urinaria/epidemiología , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Braquiterapia/métodos , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Dosificación Radioterapéutica , Retención Urinaria/etiologíaRESUMEN
BACKGROUND AND PURPOSE: To describe the incidence of urinary incontinence among prostate cancer patients treated with external beam radiotherapy (RT) and to investigate associated risk factors. PATIENTS AND METHODS: One thousand and hundred ninety-two patients with >or=24 months follow-up were the subjects of this series. All patients received between 50 and 72 Gy in 20-37 fractions (median 66 Gy/33#). Post-RT urinary incontinence was scored by direct patient interviewing according to the modified RTOG/SOMA scale: Grade 1--occasional use of incontinence pads, Grade 2--intermittent use of incontinence pads, Grade 3--persistent use of incontinence pads, and Grade 4--permanent catheter. Risk-factors investigated were: age, diabetes, TURP prior to RT, elapsed time from TURP to RT, clinical stage, RT dose and presence of Grade >or=2 acute GU and GI toxicity. Non-parametric, actuarial univariated (Kaplan-Meier) and multivariated tests (MVA, Cox regression) were performed. RESULTS: Median follow-up for the group is 52 months (24-109). Thirty-four patients (2.9%) had incontinence prior to RT, which was more common in TURP patients (7.8% vs 1.6% P<0.001). These are excluded from further analysis. Fifty-seven patients (4.9%) developed Grade 1 incontinence, 7 (0.6%) Grade 2, and 7 (0.6%) Grade 3. There was no Grade 4 incontinence. Actuarial rates for Grade >or=1 and >or=2 incontinence at 5 years are 7 and 1.7%, respectively. Risk factors on MVA associated with the development of Grade 1 or worse incontinence are pre-RT TURP (5-year rates 10% vs 6%, P=0.026), presence of Grade >or=2 acute GU toxicity (5-year rates 11% vs 5%, P=0.002). Age, diabetes, clinical stage, elapsed time from TURP to RT, RT dose or fraction size, acute GI toxicity were not significant. Patients who underwent post-RT TURP or dilatation for obstructive symptoms (4.3%), were more likely to develop Grade 2-3 incontinence (5-year rate 8 vs 1.5%, P=0.0015). CONCLUSIONS: Grade 2 or greater urinary incontinence is rare among patients who have been treated with external beam radiotherapy. Associated risk factors are pre-RT TURP and the presence of increased acute GU toxicity. Post-radiaton TURP increases the risk of incontinence five-fold.
Asunto(s)
Neoplasias de la Próstata/radioterapia , Traumatismos por Radiación/etiología , Incontinencia Urinaria/etiología , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Traumatismos por Radiación/epidemiología , Factores de Riesgo , Índice de Severidad de la Enfermedad , Resección Transuretral de la Próstata , Incontinencia Urinaria/epidemiologíaRESUMEN
PURPOSE: To determine the relationship between prostate-specific antigen (PSA) failure and cause-specific and overall survival in prostate cancer patients treated with radical radiotherapy. METHODS AND MATERIALS: Patients with and without PSA failure were compared with respect to overall survival and cause-specific survival in a cohort of 1786 patients. The relationship between PSA failure and survival was further investigated among six subgroups defined by three tumor risk groups (high, intermediate, and low risk based on T stage, Gleason score, and presenting PSA) and two age groups (<75 years and >/=75 years). RESULTS: The 5-year overall survival among patients who had PSA failure was 79.5% vs. 87.5% among patients who had not failed (p = 0.0003). The corresponding 5-year cause-specific survival was 84.4% vs. 99.0% (p <0.0001). When the six subgroups are considered separately, PSA failure was associated with a worse cause-specific survival in the groups with intermediate- and high-risk disease. PSA failure was only associated with a worse overall survival in one subgroup: patients younger than 75 with high-risk disease. Deaths from nonprostate causes made the survival curves of patients with and without PSA failure in the other subgroups almost identical. CONCLUSION: PSA failure in prostate cancer patients treated with radiotherapy was associated with a poorer overall survival, which is seen mainly in younger patients with high-risk disease.
Asunto(s)
Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/mortalidad , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/mortalidad , Anciano , Causas de Muerte , Estudios de Seguimiento , Humanos , Esperanza de Vida , Masculino , Estadificación de Neoplasias , Estudios Prospectivos , Neoplasias de la Próstata/radioterapia , Dosificación Radioterapéutica , Tasa de Supervivencia , Insuficiencia del TratamientoRESUMEN
PURPOSE: In this case report, we describe 7 patients with suboptimal dosimetry after (125)I prostate brachytherapy who underwent a second implant procedure to improve the dosimetric coverage of the prostate. METHODS AND MATERIALS: Seven patients underwent second (125)I implants for suboptimal dosimetry after their initial implant for prostate cancer. The pretreatment characteristics (clinical stage, Gleason score, initial prostate-specific antigen level, location of positive cores, International Prostate Symptom Score, potency, use of androgen suppression, initial implant planning characteristics) were noted. The "Day 30" CT-based dosimetry parameters after the first implant and "Day 0" CT-based dosimetry after the reimplant were recorded (volumes of prostate and rectum covered by 100% and 150% of the dose and dose covering 90% of the prostate volume). The toxicity of the second procedure, International Prostate Symptom Scores before and after reimplantation, the clinical course, and prostate-specific antigen outcomes after reimplant were examined. We described our reimplant planning and intraoperative procedure. RESULTS: In all 7 patients, we were able to achieve very favorable dosimetry after the second procedure. The acute toxicity of the reimplant procedure was reasonably low, and the short-term prostate-specific antigen outcome has been favorable. CONCLUSION: It is possible to add more seeds safely to the dosimetrically cool area after the initial brachytherapy procedure and achieve excellent postimplant dosimetry with acceptable acute toxicity. The ultimate benefits and long-term toxicity of reimplantation are unknown.
Asunto(s)
Braquiterapia/métodos , Radioisótopos de Yodo/uso terapéutico , Neoplasias de la Próstata/radioterapia , Anciano , Humanos , Masculino , Persona de Mediana Edad , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/diagnóstico por imagen , Dosificación Radioterapéutica , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: To evaluate the late toxicity profile of prostate cancer patients treated with external beam radiotherapy, to investigate the possible risk factors for late toxicity, and to determine whether neoadjuvant androgen ablation (NAA) is a factor. METHODS AND MATERIALS: The study population consisted of 1192 patients with > or =24 months' follow-up. Late GI and GU toxicities were scored with a modified Radiation Therapy Oncology Group/Subjective, Objective, Management, and Analytic scale. All patients were treated with external beam radiotherapy (52.5 Gy in 20 fractions to 72 Gy in 36 fractions), using either conventional or three-dimensional conformal techniques. Of the 1192 patients, 40% received NAA (median 5 months). Risk factors investigated on multivariate analysis were age, past medical history, use of pelvic fields, dose, fractionation, use and duration of neo- and adjuvant androgen ablation, and acute toxicity (Grade 2 or greater). RESULTS: The median follow-up for the group was 49 months (range 24-105). The incidence of late Grade 2-3 GI or GU toxicity was 30% at 5 years (GI 12% and GU 20%). The incidence of late Grade 3 GI or GU toxicity was 8% at 5 years (GI 2.7% and GU 5.5%). No Grade 4 toxicity occurred. The risk factors of significance in relation to the development of late Grade 3 GU toxicity were coexisting GU disease (p = 0.02), prior transurethral resection of the prostate or transurethral resection of bladder tumor (p <0.0001), and presence of acute GU toxicity (p = 0.012). For late Grade 3 GI toxicity, short-term (< or =2 months) NAA (p = 0.0002) and coexisting GI disease (p = 0.017) were risk factors. CONCLUSION: Short-term (< or =2 months) NAA, but not longer durations of NAA, increases the risk of developing Grade 3 GI late toxicity. The possible mechanism of this phenomenon is unclear.
Asunto(s)
Antagonistas de Andrógenos/efectos adversos , Enfermedades Gastrointestinales/etiología , Enfermedades Urogenitales Masculinas/etiología , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/radioterapia , Traumatismos por Radiación/etiología , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Antagonistas de Andrógenos/uso terapéutico , Quimioterapia Adyuvante/efectos adversos , Enfermedades Gastrointestinales/patología , Humanos , Masculino , Enfermedades Urogenitales Masculinas/patología , Persona de Mediana Edad , Análisis Multivariante , Traumatismos por Radiación/patología , Dosificación Radioterapéutica , Radioterapia Conformacional , Factores de RiesgoRESUMEN
OBJECTIVE: To review retrospectively the outcome and toxicity of Radiotherapy (RT) in the cohort of elderly patients (EP) with muscle-invasive urinary bladder carcinoma (MIUBC). METHODS: Thirty-six EP were treated with RT with radical intent. The age of the cohort ranged from 71 to 89 years with a median of 79 years. Eighty percent of the patients had Easter Cooperative Oncology Group (ECOG) 0 and 1 performance status. Conventional and accelerated fractionation RT regimen were utilized. RESULTS: With median follow up of 45.8 months, the median survival was 23.9 months. There was a trend toward better survival in patients treated with the accelerated fractionation regimen. The median survival for that group (12) has not yet been reached, where it is 9.7 months for the group (24) treated with conventional fractionation. Treatment related toxicity was low for any RT regimens. CONCLUSION: RT is well tolerated by EP with good baseline performance status. The role of accelerated fractionation should be tested by conducting randomized trials.
Asunto(s)
Neoplasias de la Vejiga Urinaria/radioterapia , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Invasividad Neoplásica , Dosificación Radioterapéutica , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
PURPOSE: To investigate postimplant dosimetry for different regions of the prostate gland in patients treated with transperineal 125Iodine brachytherapy implants for low- and intermediate-risk prostate cancer. METHODS AND MATERIALS: Two hundred eighty-four patients treated with permanent interstitial prostate brachytherapy comprised the study population. A nonuniform, urethral-sparing algorithm was used to plan all patients. Prostate contours were outlined on postimplant CT images. Prostate volumes were then divided into four quadrants: anterior-superior quadrant (ASQ), posterior-superior quadrant (PSQ), anterior-inferior quadrant (AIQ), and posterior-inferior quadrant (PIQ). Dose-volume histograms (DVHs) were calculated for the whole prostate and each quadrant. RESULTS: The mean postimplant V(100) +/- 95% confidence (the percent prostate volume encompassed within the isodose surface comprising the prescription dose = 144 Gy) for the ASQ was 78.5 +/- 1.9, which was significantly lower than that of the PSQ, AIQ, and PIQ in which the V(100) plus minus 95% confidence values were 94.9 +/- 0.8, 92.6 +/- 1.2, and 98.7 +/- 0.3, respectively. The mean V(100) +/- 95% confidence for the whole prostate was 90.4 +/- 0.8. Mean values for V(150) and D(90) (the minimum dose in Gy received by 90% of the target volume) for the four quadrants and the whole prostate showed similar results. CONCLUSIONS: Underdosed areas of the planning target volume (PTV), if present, were largely confined to the ASQ, which received a significantly lower dose, on average, compared to the other three quadrants of the prostate.