RESUMEN
PURPOSE: To report the toxicity profile of high-dose-rate (HDR)-brachytherapy (BT) as monotherapy in a Human Investigation Committee-approved study consisting of a single implant and two fractions (12 Gy × 2) for a total dose of 24 Gy, delivered within 1 day. The dose was subsequently increased to 27 Gy (13.5 Gy × 2) delivered in 1 day. We report the acute and early chronic genitourinary and gastrointestinal toxicity. METHODS AND MATERIALS: A total of 173 patients were treated between December 2005 and July 2010. However, only the first 100 were part of the IRB-approved study and out of these, only 94 had a minimal follow-up of 6 months, representing the study population for this preliminary report. All patients had clinical Stage T2b or less (American Joint Committee on Cancer, 5th edition), Gleason score 6-7 (3+4), and prostate-specific antigen level of ≤12 ng/mL. Ultrasound-guided HDR-BT with real-time dosimetry was used. The prescription dose was 24 Gy for the first 50 patients and 27 Gy thereafter. The dosimetric goals and constraints were the same for the two dose groups. Toxicity was scored using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. The highest toxicity scores encountered at any point during follow-up are reported. RESULTS: The median follow-up was 17 months (range, 6-40.5). Most patients had Grade 0-1 acute toxicity. The Grade 2 acute genitourinary toxicity was mainly frequency/urgency (13%), dysuria (5%), hematuria, and dribbling/hesitancy (2%). None of the patients required a Foley catheter at any time; however, 8% of the patients experienced transient Grade 1 diarrhea. No other acute gastrointestinal toxicities were found. The most common chronic toxicity was Grade 2 urinary frequency/urgency in 16% of patients followed by dysuria in 4% of patients; 2 patients had Grade 2 rectal bleeding and 1 had Grade 4, requiring laser treatment. CONCLUSIONS: Favorable-risk prostate cancer patients treated with a single implant HDR-BT to 24-27 Gy in two fractions within 1 day have excellent tolerance with minimal acute and chronic toxicity. Longer follow-up is needed to confirm these encouraging early results.
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Braquiterapia/efectos adversos , Diarrea/etiología , Neoplasias de la Próstata/radioterapia , Trastornos Urinarios/etiología , Anciano , Braquiterapia/métodos , Fraccionamiento de la Dosis de Radiación , Estudios de Seguimiento , Hemorragia Gastrointestinal/etiología , Humanos , Masculino , Persona de Mediana Edad , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Recto , Factores de Tiempo , Ultrasonografía IntervencionalRESUMEN
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.
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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 examine 10-year results of a single institution's experience with radiotherapy limited to the region of the tumor bed (i.e., accelerated partial breast irradiation, [APBI]) in selected patients treated with breast-conserving therapy (BCT) and compare them with results of matched BCT patients who underwent whole-breast irradiation (WBI). PATIENTS AND METHODS: A total of 199 patients with early-stage breast cancer were treated prospectively with BCT and APBI using interstitial brachytherapy. To compare potential differences in local recurrence rates on the basis of the volume of breast tissue irradiated, patients in the APBI group were matched with 199 patients treated with WBI. Match criteria included tumor size, nodal status, age at diagnosis, margins of excision, estrogen receptor status, and use of adjuvant tamoxifen therapy. Local-regional control, disease-free survival, and overall survival were analyzed between treatment groups. RESULTS: Median follow-up for surviving patients was 9.6 years (range, 0.3-13.6 years). Eight ipsilateral breast tumor recurrences (IBTRs) were observed in patients treated with APBI. The cumulative incidence of IBTR at 10 years was 5%. On matched-pair analysis, the rate of IBTR was not statistically significantly different between the patient groups (4%, 95% confidence interval [CI] 1.3-6.7% for WBI therapy patients vs. 5%, 95% CI 1.5-8.5% for APBI patients; p = 0.48). CONCLUSIONS: Radiation therapy limited to the region of the tumor bed (APBI) produced 10-year local control rates comparable to those from WBI in selected low-risk patients.
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Braquiterapia/métodos , Neoplasias de la Mama/radioterapia , Carcinoma Ductal de Mama/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama/mortalidad , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/cirugía , Femenino , Humanos , Mastectomía Segmentaria , Análisis por Apareamiento , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias Primarias Secundarias/mortalidad , Estudios Prospectivos , Dosificación Radioterapéutica , Radioterapia Adyuvante , Insuficiencia del TratamientoRESUMEN
BACKGROUND: Results from numerous trials have indicated that breast-conserving therapy (BCT) produces outcomes equivalent to those produced by mastectomy in terms of both locoregional control and survival. However, conservative treatment has resulted in the dilemma of how best to address recurrences when they appear in a breast treated previously with radiation therapy. Attempts have been made to characterize ipsilateral breast tumor recurrences (IBTRs) as either true recurrences of the treated malignancy or new primary carcinomas, because cancers that represent new primary tumors may be associated with a more favorable prognosis compared with cancers that represent true recurrences. METHODS: The authors studied the clonality of IBTRs relative to the initial invasive carcinomas by using a polymerase chain reaction loss-of-heterozygosity molecular comparison assay in 29 patients who received breast-conserving therapy (BCT). RESULTS: Twenty-two IBTRs (76%) were related clonally to the initial carcinoma, and 7 IBTRs (24%) were clonally different. Clonally related IBTRs were more frequently higher grade (72.2% vs 14.3%; P = .009) and developed sooner after initial treatment (mean time to IBTR, 4.04 years in clonally related IBTRs vs 9.25 years in clonally different IBTRs; P = .002). Six patients subsequently developed distant metastases, and 5 of those patients (83.3%) had clonally related IBTRs. Clinical IBTR classification and molecular clonality assay results differed in 30% of all patients. The proportion of IBTRs that were related clonally at 5 years, 10 years, and 15 years after BCT were 93%, 67%, and 33%, respectively. CONCLUSIONS: Clinical classifications of IBTRs were unreliable methods for determining clonality in many patients. Molecular clonality assays provided a reliable means of identifying patients who may benefit from aggressive systemic therapy at the time of IBTR and also provided a more accurate assessment of the efficacy of various forms of local therapy.
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Neoplasias de la Mama/genética , Neoplasias de la Mama/cirugía , Mastectomía Segmentaria , Recurrencia Local de Neoplasia/genética , Neoplasias de la Mama/diagnóstico , Células Clonales , ADN de Neoplasias/análisis , Diagnóstico Diferencial , Femenino , Humanos , Pérdida de Heterocigocidad/genética , Metástasis Linfática , Repeticiones de Microsatélite/genética , Invasividad Neoplásica , Estadificación de Neoplasias , PronósticoRESUMEN
PURPOSE: To determine the long-term efficacy and cosmetic results of accelerated partial breast irradiation (APBI) by reviewing our institution's experience. METHODS AND MATERIALS: A total of 199 patients with early-stage breast cancer were treated prospectively with adjuvant APBI after lumpectomy using interstitial brachytherapy. All patients had negative margins, 82% had Stage I disease, median tumor size was 1.1 cm, and 12% had positive lymph nodes. The median follow-up for surviving patients was 8.6 years. Fifty-three patients (27%) have been followed for >or=10 years. RESULTS: Six ipsilateral breast tumor recurrences (IBTRs) were observed, for a 5-year and 10-year actuarial rate of 1.6% and 3.8%, respectively. A total of three regional nodal failures were observed, for a 10-year actuarial rate of 1.6%. Five contralateral breast cancers developed, for a 5- and 10-year actuarial rate of 2.2% and 5.2%, respectively. The type of IBTR (clonally related vs. clonally distinct) was analyzed using a polymerase chain reaction-based loss of heterozygosity assay. Eighty-three percent of IBTRs (n = 5) were classified as clonally related. Multiple clinical, pathologic, and treatment-related factors were analyzed for an association with the development of an IBTR, regional nodal failure, or contralateral breast cancer. On multivariate analysis, no variable was associated with any of these events. Cosmetic results were rated as excellent/good in 99% of patients. CONCLUSIONS: Long-term results with APBI using interstitial brachytherapy continue to demonstrate excellent long-term local and regional control rates and cosmetic results. According to a polymerase chain reaction-based loss of heterozygosity assay, 83% of recurrences were classified as clonally related.