RESUMEN
PURPOSE: To assess the impact of PSA bounce (PB) on biochemical failure (BF) and clinical failure (CF) in brachytherapy patients treated with or without neoadjuvant androgen deprivation (AD). METHODS AND MATERIALS: From 1987 to 2003, 691 patients with clinical stage T1-T3N0M0 prostate cancer were treated with external beam radiotherapy (EBRT) and high-dose-rate (HDR) brachytherapy boost (n=407), HDR brachytherapy alone (n=93), or permanent seed implant (n=191). Three hundred seventeen patients (46%) received neoadjuvant/adjuvant AD with RT. BF was scored using 3 definitions (ASTRO--3 rises, nadir+2 ng/ml, and threshold 3 ng/ml) based on current and absolute nadir (AN) methodologies. PB was defined as any increase in PSA followed by a decrease to the prior baseline or lower. The median followup was 4.0 years. RESULTS: Forty-six patients (7%) experienced CF at 5 years. PB of >or=0.1, >or=1.0, and >or=2.0 ng/ml at any time after RT occurred in 330 (48%), 60 (9%), and 22 patients (3%) respectively. The use of an AN definition reduced the likelihood of scoring PB as BF across all levels. The patients receiving AD experienced significantly longer bounce duration. Bounce <1.0 ng/ml showed no association with CF. For bounce >or=1.0 ng/ml, 10% demonstrated CF vs. 6% without bounce of this amplitude (p=0.27). Bounces >or=1.0 ng/ml were more likely to be scored as BFs for definitions based on current nadir (3 rises: 20% vs. 13%, nadir+2: 43% vs. 11%, 3 at/after nadir: 57% vs. 12%) than those based on AN (3 rises: 8% vs. 10%, nadir+2: 18% vs. 11%, 3 at/after nadir: 13% vs. 11%). CONCLUSIONS: Bounces >or=1.0 ng/ml are rare after brachytherapy with or without neoadjuvant AD, occurring in less than 10% of patients. Low PBs have little impact on BF, but as PB amplitude increases, the BF rate increases. BF definitions based on AN are less sensitive to PB after brachytherapy.
Asunto(s)
Antagonistas de Andrógenos/uso terapéutico , Braquiterapia/estadística & datos numéricos , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/terapia , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Hormonales/uso terapéutico , Terapia Combinada/estadística & datos numéricos , Humanos , Masculino , Michigan/epidemiología , Persona de Mediana Edad , Terapia Neoadyuvante/estadística & datos numéricos , Prevalencia , Neoplasias de la Próstata/epidemiología , Medición de Riesgo/métodos , Factores de Riesgo , Resultado del TratamientoRESUMEN
PURPOSE: To determine the gross tumor volume (GTV) to clinical target volume margin for non-small-cell lung cancer treatment planning. METHODS: A total of 35 patients with Stage T1N0 adenocarcinoma underwent wedge resection plus immediate lobectomy. The gross tumor size and microscopic extension distance beyond the gross tumor were measured. The nuclear grade and percentage of bronchoalveolar features were analyzed for association with microscopic extension. The gross tumor dimensions were measured on a computed tomography (CT) scan (lung and mediastinal windows) and compared with the pathologic dimensions. The potential coverage of microscopic extension for two different lung stereotactic radiotherapy regimens was evaluated. RESULTS: The mean microscopic extension distance beyond the gross tumor was 7.2 mm and varied according to grade (10.1, 7.0, and 3.5 mm for Grade 1 to 3, respectively, p < 0.01). The 90th percentile for microscopic extension was 12.0 mm (13.0, 9.7, and 4.4 mm for Grade 1 to 3, respectively). The CT lung windows correlated better with the pathologic size than did the mediastinal windows (gross pathologic size overestimated by a mean of 5.8 mm; composite size [gross plus microscopic extension] underestimated by a mean of 1.2 mm). For a GTV contoured on the CT lung windows, the margin required to cover microscopic extension for 90% of the cases would be 9 mm (9, 7, and 4 mm for Grade 1 to 3, respectively). The potential microscopic extension dosimetric coverage (55 Gy) varied substantially between the stereotactic radiotherapy schedules. CONCLUSION: For lung adenocarcinomas, the GTV should be contoured using CT lung windows. Although a GTV based on the CT lung windows would underestimate the gross tumor size plus microscopic extension by only 1.2 mm for the average case, the clinical target volume expansion required to cover the microscopic extension in 90% of cases could be as large as 9 mm, although considerably smaller for high-grade tumors. Fractionation significantly affects the dosimetric coverage of microscopic extension.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Carga Tumoral , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/patología , Adenocarcinoma/radioterapia , Adenocarcinoma/cirugía , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Humanos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirugía , Radiografía , Radiocirugia , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por ComputadorRESUMEN
PURPOSE: Minimal data are available regarding selection of an optimal biochemical failure (BF) definition for patients treated with brachytherapy, external beam radiotherapy (EBRT), and combinations of these treatments with or without androgen deprivation (AD). We retrospectively analyzed our institution's experience treating localized prostate cancer in an attempt to determine a BF definition that could be applied for these various treatment modalities. METHODS AND MATERIALS: A total of 2376 patients with clinical stage T1-T3 N0 M0 prostate cancer were treated with conventional dose (median, 66.6 Gy) EBRT (n = 1201), high-dose (median, 75.6 Gy) adaptive radiation therapy (n = 465), EBRT + high-dose-rate brachytherapy boost (n = 416), or brachytherapy alone (n = 294) between 1987 and 2003. A total of 496 patients (21%) received neoadjuvant AD with radiation therapy. There were 21924 posttreatment prostate-specific antigen (PSA) measurements. Multiple BF definitions were tested for their sensitivity, specificity, positive predictive value (+PV), and negative PV (-PV) in predicting subsequent clinical failure (CF) (any local failure or distant metastasis), overall survival (OS), and cause-specific survival (CSS). Median follow-up was 4.5 years. The date of BF was the date BF criteria were met (e.g., date of third rise). RESULTS: A total of 290 patients (12%) experienced CF at a median interval of 3.6 years (range, 0.2-15.2 years). The 5- and 10-year CF rates were 12% and 26%, respectively. Three consecutive rises yielded a 46% sensitivity and 84% specificity for predicting CF. The 10-year CF for those 475 patients who experienced three rises (BF) was 37% vs. 17% for those patients who did not meet these criteria (biochemically controlled [BC]). For all patients, the following definitions were superior to three rises for predicting CF for both +PV, and -PV: n + 1 (> or =1 ng/mL above nadir), n + 2, n + 3, threshold 2 (any PSA > or =2.0 ng/mL at or after nadir), threshold 3, threshold 4, and threshold 5. For the subset of patients treated with EBRT alone, the n + k definitions and threshold k definitions maintained superior predictive capacity. However, the threshold k definitions seemed to maintain a slightly greater separation in 10-year CF rates (43% for BF vs. 13% for BC = 30% difference for threshold 3). Surprisingly, all definitions generally had better predictive capacity for those patients who received brachytherapy or neoadjuvant AD vs. EBRT alone. The endpoints appeared similar for n + 1 vs. threshold 3 and n + 2 vs. threshold 4 in EBRT alone patients, but for brachytherapy or neoadjuvant AD patients, there were similarities for n + 2 vs. threshold 3 and n + 3 vs. threshold 4. This may be a reflection of the lower nadir levels in patients receiving AD (median <0.1 ng/mL vs. 0.2 ng/mL for brachytherapy vs. 0.8 ng/mL for EBRT alone, p < 0.01). When examining CF correlation for the various classes of BF definitions, the threshold k definitions clearly demonstrated the greatest area under the receiver operating characteristic curve, followed by the n + k definitions. For OS, the threshold k definitions again demonstrated the greatest area under the curve, followed by definitions based on specific nadir cutoffs (nadir > or =k ng/mL). CONCLUSIONS: Biochemical failure definitions applying a PSA threshold at or after the nadir (e.g., threshold 3) demonstrated the highest association with CF, OS, and CSS for all assessed treatment modalities. Definitions incorporating a PSA increase above the nadir value (e.g., nadir + 2 ng/mL) were also superior for all modalities. In general, BF definitions have greater predictive capacity for clinical outcome with brachytherapy or neoadjuvant AD than EBRT alone, possibly because of less "noise" from production of background PSA.