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The purpose of this article is to present an updated set of American College of Radiology consensus guidelines formed from an expert panel on the appropriate use of radiation therapy in postprostatectomy prostate cancer. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Recent and relevant literature reviewed by the panel led to establishment of criteria for appropriate use of radiation therapy in postprostatectomy prostate cancer. The discussion includes treatment technique, appropriate dose, field design, and the role of prostate-specific antigen (PSA). Ratings and commentary of the panel on multiple treatment parameters were used to reach consensus. Patients with high-risk pathologic features benefit from postprostatectomy radiation therapy.
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Medicina Baseada em Evidências , Guias de Prática Clínica como Assunto/normas , Prostatectomia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Radioterapia/métodos , Ensaios Clínicos como Assunto , Humanos , Masculino , Estadiamento de Neoplasias , Radiologia/normas , Sociedades Médicas/normas , Estados UnidosRESUMO
Purpose: Quantification of integral radiation dose delivered during treatment for prostate cancer is lacking. We performed a comparative quantification of dose to nontarget body tissues delivered via 4 common radiation techniques: conventional volumetric modulated arc therapy, stereotactic body radiation therapy, pencil-beam scanning proton therapy, and high-dose-rate brachytherapy. Methods and Materials: Plans for each radiation technique were generated for 10 patients with typical anatomy. For brachytherapy plans, virtual needles were placed to achieve standard dosimetry. Standard planning target volume margins or robustness margins were applied as appropriate. A "normal tissue" structure (entire computed tomography simulation volume minus planning target volume) was generated for integral dose computation. Dose-volume histogram parameters for targets and normal structures were tabulated. Normal tissue integral dose was calculated by multiplying normal tissue volume by mean dose. Results: Normal tissue integral dose was lowest for brachytherapy. Pencil-beam scanning protons, stereotactic body radiation therapy, and brachytherapy resulted in 17%, 57%, and 91% absolute reductions compared with standard volumetric modulated arc therapy, respectively. Mean nontarget tissues receiving 25%, 50%, and 75% of the prescription dose were reduced by 85%, 76%, and 83% for brachytherapy relative to volumetric modulated arc therapy, by 79%, 64%, and 74% relative to stereotactic body radiation therapy, and 73%, 60%, and 81% relative to proton therapy. All reductions observed using brachytherapy were statistically significant. Conclusions: High-dose-rate brachytherapy is an effective technique for reducing dose to nontarget body tissues relative to volumetric modulated arc therapy, stereotactic body radiation therapy, and pencil-beam scanning proton therapy.
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PURPOSE: To report patient-reported outcomes (PROs) of a phase III trial evaluating total androgen suppression (TAS) combined with dose-escalated radiation therapy (RT) for patients with intermediate-risk prostate cancer. METHODS: Patients with intermediate-risk prostate cancer were randomly assigned to dose-escalated RT alone (arm 1) or RT plus TAS (arm 2) consisting of luteinizing hormone-releasing hormone agonist/antagonist with oral antiandrogen for 6 months. The primary PRO was the validated Expanded Prostate Cancer Index Composite (EPIC-50). Secondary PROs included Patient-Reported Outcome Measurement Information System (PROMIS)-fatigue and EuroQOL five-dimensions scale questionnaire (EQ-5D). PRO change scores, calculated for each patient as the follow-up score minus baseline score (at the end of RT and at 6, 12, and 60 months), were compared between treatment arms using a two-sample t test. An effect size of 0.50 standard deviation was considered clinically meaningful. RESULTS: For the primary PRO instrument (EPIC), the completion rates were ≥86% through the first year of follow-up and 70%-75% at 5 years. For the EPIC hormonal and sexual domains, there were clinically meaningful (P < .0001) deficits in the RT + TAS arm. However, there were no clinically meaningful differences by 1 year between arms. There were also no clinically meaningful differences at any time points between arms for PROMIS-fatigue, EQ-5D, and EPIC bowel/urinary scores. CONCLUSION: Compared with dose-escalated RT alone, adding TAS demonstrated clinically meaningful declines only in EPIC hormonal and sexual domains. However, even these PRO differences were transient, and there were no clinically meaningful differences between arms by 1 year.
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Androgênios , Neoplasias da Próstata , Masculino , Humanos , Androgênios/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Antagonistas de Androgênios/uso terapêutico , Medidas de Resultados Relatados pelo Paciente , Qualidade de VidaRESUMO
PURPOSE: External beam radiation therapy (EBRT) dose escalation has been tested in multiple prospective trials. However, the impact on patient reported outcomes (PROs) associated with higher doses of EBRT remain poorly understood. We sought to assess the differences in PROs between men treated with a dose of 70.2 Gy versus 79.2 Gy of EBRT for prostate cancer. METHODS AND MATERIALS: The phase 3 clinical trial RTOG 0126 randomized 1532 patients with prostate cancer between March 2002 and August 2008 to 79.2 Gy over 44 fractions versus 70.2 Gy over 39 fractions. Eligible patients participated in the PRO data collection. PROs completed included the International Index of Erectile Function Questionnaire (IIEF), Functional Alterations due to Changes in Elimination (FACE), and the Spitzer Quality of Life Index (SQLI). The timepoints for the IIEF were collected pre-entry and at 6, 12, and 24 months. The FACE and SQLI were collected pre-entry and at 3, 6, 12, 18, and 24 months. The impact of EBRT dose to normal structures (penile bulb, rectum, and bladder) on PROs was also examined. Mixed effects models were used to analyze trends across time. RESULTS: In total, 1144 patients completed baseline IIEF forms and of these, 56%, 64%, and 61% completed the IIEF at 6, 12, and 24 months, respectively; 1123 patients completed the FACE score at baseline and 50%, 61%, 73%, 61%, and 65% completed all 15 items for the FACE metric at timepoints of 3, 6, 12, 18, and 24 months, respectively. Erectile dysfunction at 12 months based on the single question was not significantly different between arms (38.1% for the standard dose radiation therapy arm vs 49.7% for the dose escalated radiation therapy arm; P = .051). Treatment arm (70.2 vs 79.2) had no significant impact on any PRO metrics measured across all collected domains. Comprehensive dosimetric analyses are presented and reveal multiple significant differences to regional organs at risk. CONCLUSIONS: Compliance with PRO data collection was lower than anticipated in this phase 3 trial. Examining the available data, dose escalated EBRT did not appear to be associated with any detriment to PROs across numerous prospectively collected domains. These data, notwithstanding limitations, add to our understanding of the implications of EBRT dose escalation in prostate cancer. Furthermore, these results illustrate challenges associated with PRO data collection.
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Braquiterapia , Neoplasias da Próstata , Braquiterapia/métodos , Humanos , Masculino , Estudos Prospectivos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Qualidade de Vida , Dosagem RadioterapêuticaRESUMO
Purpose: In this study, we investigate linac volumetric-modulated arc therapy (VMAT) planning strategies for bilateral hip prostheses prostate patients with respect to plan quality and deliverability, while limiting entrance dose to the prostheses. Methods: Three VMAT plans were retrospectively created for 20 patients: (1) partial arcs (PA), (2) 2 full arcs optimized with 500â cGy max prostheses dose (MD), and (3) 2 full arcs optimized with max dose-volume histogram (DVH) constraint of 500â cGy to 10% prostheses volume (MDVH). PA techniques contained 6 PA with beam angles that avoid entering each prosthesis. For each patient, other than prostheses constraints, the same Pinnacle VMAT optimization objectives were used. Plans were normalized with PTV D95% = 79.2â Gy prescription dose. Organ-at-risk DVH metrics, monitor units (MUs), conformality, gradient, and homogeneity indices were evaluated for each plan. Mean entrance prosthesis dose was determined in Pinnacle by converting each arc into static beams and utilizing only control points traversing each prosthesis. Plan deliverability was evaluated with SunNuclear ArcCheck measurements (gamma criteria 3%/2â mm) on an Elekta machine. Results: MD and MDVH had similar dosimetric quality, both improved DVH metrics for rectum and bladder compared to PA. Plan complexities among all plans were similar (average MUs: 441-518). Conformality, homogeneity, and gradient indices were significantly improved in MD and MDVH versus PA (P < .001). Gamma pass rates for MD (99.0 ± 1.2%) and MDVH (99.2 ± 0.99%) were comparable. A significant difference over PA was observed (96.8 ± 1.6%, P < .001). Field-by-field analysis demonstrated 12/20 PA plans resulted in fields with pass rates <95% versus 1/20 plans for MD and none for MDVH. Cumulative mean entrance doses to each prosthesis were 62.9 ± 17.7â cGy for MD plans and 83.4 ± 27.5â cGy for MDVH plans. Conclusion: MD and MDVH plans had improved dosimetric quality and deliverability over PA plans with minimal entrance doses (â¼1% of prescription) to each prosthesis and are an improved alternative for bilateral prostheses prostate patients.
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Prótese de Quadril , Neoplasias da Próstata/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Tomada de Decisão Clínica , Diagnóstico por Imagem , Gerenciamento Clínico , Humanos , Masculino , Órgãos em Risco , Neoplasias da Próstata/complicações , Neoplasias da Próstata/diagnóstico , Radiometria , Dosagem Radioterapêutica , Radioterapia Guiada por ImagemRESUMO
PURPOSE: To report the long-term outcome of patients with prostate cancer treated with external beam radiation therapy and high dose rate (HDR) brachytherapy from a prospective multi-institutional trial conducted by NRG Oncology/RTOG. METHODS AND MATERIALS: Patients with clinically localized (T1c-T3b) prostate cancer without prior history of transurethral resection of prostate or hip prosthesis were eligible for this study. All patients were treated with a combination of 45 Gy in 25 fractions from external beam radiation therapy and one HDR implant delivering 19 Gy in 2 fractions. Adverse events (AE) were collected using Common Toxicity Criteria for Adverse Events, version 3. Cumulative incidence was used to estimate time to severe late gastrointestinal (GI)/genitourinary (GU) toxicity, biochemical failure, disease-specific mortality, local failure, and distant failure. Overall survival was estimated using the Kaplan-Meier method. RESULTS: One hundred and twenty-nine patients were enrolled from July 2004 to May 2006. AE data was available for 115 patients. Patients were National Comprehensive Cancer Network (NCCN) intermediate to very high risk. The median age was 68, T1c-T2c 91%, T3a-T3b 9%, PSA ≤10 70%, PSA >10 to ≤20 30%, GS 6 10%, GS 7 72%, and GS 8 to 10 18%. Forty-three percent of patients received hormonal therapy. At a median follow-up time of 10 years, there were 6 (5%) patients with grade 3 GI and GU treatment-related AEs, and no late grade 4 to 5 GI and GU AEs. At 5 and 10 years, the rate of late grade 3 gastrointestinal and genitourinary AEs was 4% and 5%, respectively. Five- and 10-year overall survival rates were 95% and 76%. Biochemical failure rates per Phoenix definition at 5 and 10 years were 14% and 23%. The 10-year rate of disease-specific mortality was 6%. At 5 and 10 years, the rates of distant failure were 4% and 8%, respectively. The rates of local failure at 5 and 10 years were 2% at both time points. CONCLUSIONS: Combined modality treatment using HDR prostate brachytherapy leads to excellent long-term clinical outcomes in this prospective multi-institutional trial.
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Adenocarcinoma/radioterapia , Braquiterapia , Neoplasias da Próstata/radioterapia , Idoso , Idoso de 80 Anos ou mais , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Resultado do TratamentoRESUMO
BACKGROUND: Using a prospectively collected institutional database, we compared rectal toxicity following high dose rate (HDR) brachytherapy as monotherapy relative to dose-escalated external beam radiotherapy (EBRT) for patients with localized prostate cancer. METHODS: 2683 patients treated with HDR or EBRT between 1994 and 2017 were included. HDR fractionation was 38 Gy/4 fractions (n = 321), 24 Gy/2 (n = 96), or 27 Gy/2 (n = 128). EBRT patients received a median dose of 75.6 Gy in 1.8 Gy fractions [range 70.2-82.8 Gy], using either 3D conformal or intensity modulated radiotherapy (IMRT). EBRT patients underwent 3D image guidance via an off-line adaptive process. RESULTS: Median follow-up was 7.5 years (7.4 years for EBRT and 7.9 years for HDR). 545 patients (20.3%) received HDR brachytherapy and 2138 (79.7%) EBRT. 69.1% of EBRT patients received IMRT. Compared to EBRT, HDR was associated with decreased rates of acute grade ≥2 diarrhea (0.7% vs. 4.5%, p < 0.001), rectal pain/tenesmus (0.6% vs. 7.9%, p < 0.001), and rectal bleeding (0% vs. 1.6%, p = 0.001). Rates of chronic grade ≥2 rectal bleeding (1.3% vs. 8.7%, p < 0.001) and radiation proctitis (0.9% vs. 3.3%, p = 0.001) favored HDR over EBRT. Rates of any chronic rectal toxicity grade ≥2 were 2.4% vs. 10.5% (p < 0.001) for HDR versus EBRT, respectively. In those treated with IMRT, acute and chronic rates of any grade ≥2 GI toxicity were significantly reduced but remained significantly greater than those treated with HDR. CONCLUSIONS: In appropriately selected patients with localized prostate cancer undergoing radiation therapy, HDR brachytherapy as monotherapy is an effective strategy for reducing rectal toxicity.
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Braquiterapia , Neoplasias da Próstata , Radioterapia de Intensidade Modulada , Braquiterapia/efeitos adversos , Fracionamento da Dose de Radiação , Humanos , Masculino , Neoplasias da Próstata/radioterapia , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/efeitos adversosRESUMO
Inhibition of mutant IDH1 is being evaluated clinically as a treatment option for oncology. Here we describe the structure-based design and optimization of quinoline lead compounds to identify FT-2102, a potent, orally bioavailable, brain penetrant, and selective mIDH1 inhibitor. FT-2102 has excellent ADME/PK properties and reduces 2-hydroxyglutarate levels in an mIDH1 xenograft tumor model. This compound has been selected as a candidate for clinical development in hematologic malignancies, solid tumors, and gliomas with mIDH1.
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Antineoplásicos/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Isocitrato Desidrogenase/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Piridinas/uso terapêutico , Quinolinas/uso terapêutico , Quinolonas/uso terapêutico , Animais , Antineoplásicos/síntese química , Antineoplásicos/metabolismo , Linhagem Celular Tumoral , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/metabolismo , Feminino , Humanos , Isocitrato Desidrogenase/metabolismo , Camundongos Endogâmicos BALB C , Estrutura Molecular , Ligação Proteica , Piridinas/síntese química , Piridinas/metabolismo , Quinolinas/síntese química , Quinolinas/metabolismo , Quinolonas/síntese química , Quinolonas/metabolismo , Relação Estrutura-Atividade , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
PURPOSE: To update outcome and toxicity results of a prospective trial of 19-Gy single-fraction high-dose-rate (HDR) brachytherapy for men with low- and intermediate-risk prostate cancer. METHODS AND MATERIALS: Patients were treated on a prospective study of single-fraction HDR brachytherapy. All patients had low- or intermediate-risk prostate cancer. Patients with prostate volumes >50 cm3, taking alpha-blockers for urinary symptoms, or with baseline American Urologic Association symptom scores >12 were ineligible. Patients underwent transrectal ultrasound-guided interstitial implant of the prostate followed by single-fraction HDR brachytherapy to a prescription dose of 19 Gy. RESULTS: Sixty-eight patients were enrolled with a median follow-up of 3.9 years. Median age was 62 years. Median gland volume at the time of treatment was 35 cm3, 92.6% of patients had T1 disease, 63.2% had a Gleason score of 6, and median pretreatment prostate-specific antigen was 5.0 ng/mL. Chronic grade 2 genitourinary toxicity was 14.7%. No grade 3 urinary toxicity occurred. A single patient experienced grade 2+ rectal toxicity (grade 3 diarrhea) that was transient and resolved with medical management. The 5-year estimated disease-free survival was 77.2% with no significant difference between low- and intermediate-risk patients. A single patient developed distant metastases during the follow-up period. Biopsy-proven local failure at 5 years was 18.8%, occurring at a median interval of 4.0 years posttreatment. No deaths occurred during follow-up. CONCLUSIONS: With extended follow-up, toxicity rates after single-fraction 19-Gy HDR brachytherapy remain low. Higher-than-expected rates of biochemical and local failure, however, raise concerns regarding the adequacy of this dose. Additional investigation to define the optimal single-fraction HDR brachytherapy dose is warranted, and single-fraction treatment currently should not be offered outside the context of a clinical trial.
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Braquiterapia/métodos , Neoplasias da Próstata/radioterapia , Radioterapia Guiada por Imagem/métodos , Adulto , Idoso , Braquiterapia/efeitos adversos , Intervalo Livre de Doença , Humanos , Calicreínas/sangue , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/sangue , Tamanho do Órgão , Estudos Prospectivos , Próstata/patologia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Dosagem Radioterapêutica , Radioterapia Guiada por Imagem/efeitos adversos , Risco , Fatores de Tempo , Falha de Tratamento , Resultado do Tratamento , Ultrassonografia de IntervençãoRESUMO
Mutations at the arginine residue (R132) in isocitrate dehydrogenase 1 (IDH1) are frequently identified in various human cancers. Inhibition of mutant IDH1 (mIDH1) with small molecules has been clinically validated as a promising therapeutic treatment for acute myeloid leukemia and multiple solid tumors. Herein, we report the discovery and optimization of a series of quinolinones to provide potent and orally bioavailable mIDH1 inhibitors with selectivity over wild-type IDH1. The X-ray structure of an early lead 24 in complex with mIDH1-R132H shows that the inhibitor unexpectedly binds to an allosteric site. Efforts to improve the in vitro and in vivo absorption, distribution, metabolism, and excretion (ADME) properties of 24 yielded a preclinical candidate 63. The detailed preclinical ADME and pharmacology studies of 63 support further development of quinolinone-based mIDH1 inhibitors as therapeutic agents in human trials.
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Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Isocitrato Desidrogenase/antagonistas & inibidores , Quinolonas/química , Quinolonas/farmacologia , Sítio Alostérico/efeitos dos fármacos , Animais , Disponibilidade Biológica , Linhagem Celular Tumoral , Cristalografia por Raios X , Cães , Descoberta de Drogas , Inibidores Enzimáticos/farmacocinética , Feminino , Humanos , Isocitrato Desidrogenase/química , Isocitrato Desidrogenase/genética , Células Madin Darby de Rim Canino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Moleculares , Mutação Puntual , Quinolonas/farmacocinéticaRESUMO
BACKGROUND: Quinoxyfen is a potent and effective fungicide, hitherto considered to control powdery mildew disease by perturbing signal transduction during early germling differentiation. The aim of this paper is to understand the mode of action of quinoxyfen by comparing the perception of host-derived signals and signal relay in a wild-type Blumeria graminis f. sp. hordei EM Marchal (Bgh) (WT/IM82) and a quinoxyfen-resistant field isolate (QR/2B11). RESULTS: QR/2B11 germinates more promiscuously on host-like and artificial surfaces than the quinoxyfen-sensitive WT/IM82. The pivotal role of host cuticle deprivation in the formation of hooked appressorial germ tubes (hAGTs) in WT/IM82 and a dramatic drop in germling differentiation in the presence of the mildewicide are demonstrated. QR/2B11 strain shows a dependence on host cuticle-like features for hAGT formation but no significant difference between germling differentiation in the presence or absence of quinoxyfen. PKC-inhibitor Ro 318220 induces morphological changes similar to those seen in quinoxyfen-treated germlings. PKC1 transcript accumulation is equivalently upregulated by quinoxyfen in QR/2B11 and WT/IM82 strains, but Bgh cutinase CUT1 transcript is 8 times more abundant in QR/2B11 conidia than in WT/IM82 conidia. Quinoxyfen inhibits serine esterase activity in WT/IM82, but not in QR/2B11. CONCLUSION: Collectively, these data suggest that quinoxyfen interferes with the perception of host-derived signals required for full germling differentiation, and that QR/2B11 bypasses the need for such signals. Moreover, quinoxyfen appears to target serine esterase activity, with a downstream perturbation in signal transduction; this represents the first demonstrable biochemical difference between the quinoxyfen-resistant and -sensitive isolates.
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Ascomicetos/efeitos dos fármacos , Esterases/antagonistas & inibidores , Fungicidas Industriais/farmacologia , Quinolinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Ascomicetos/enzimologia , Ascomicetos/genética , Hidrolases de Éster Carboxílico/metabolismo , Farmacorresistência Fúngica/genética , Indóis/farmacologia , Lactonas/farmacologia , Morfogênese/efeitos dos fármacos , Esporos Fúngicos/metabolismoRESUMO
PURPOSE: The recently published ASCENDE-RT randomized clinical trial demonstrated improved biochemical control, albeit with increased toxicity, for a prostate boost with brachytherapy versus external beam radiation therapy alone in patients with intermediate-high risk prostate cancer. In this study, we investigated the cost-effectiveness of these two modalities in the treatment of intermediate-high risk prostate cancer. METHODS AND MATERIALS: A multistate Markov model was created to model a patient with intermediate-high risk prostate cancer. The two treatment options modeled were (1) 23 fractions of intensity-modulated radiation therapy (IMRT) and two fractions of high-dose-rate prostate brachytherapy (brachytherapy boost) and (2) 44 fractions of IMRT (IMRT alone). Each patient received 1 year of hormone therapy, per the ASCENDE-RT protocol. Model assumptions, including clinical outcomes, toxicity, and utilities were derived from the medical literature. Costs of radiation therapy were estimated using Medicare reimbursement data. RESULTS: The estimated expected lifetime cost of brachytherapy boost was $68,696, compared to $114,944 for IMRT alone. Brachytherapy boost significantly lowered expected lifetime treatment costs because it decreased the incidence of metastatic castration-resistant prostate cancer, cutting the use of expensive targeted therapy for metastatic castration-resistant prostate cancer. Brachytherapy boost had an expected quality-adjusted life years of 10.8 years, compared to 9.3 years for IMRT alone. One-way sensitivity analyses of our results found brachytherapy boost to be cost-effective over a wide range of cost, utility, and cancer progression rate assumptions. CONCLUSIONS: IMRT with high-dose-rate brachytherapy boost is a cost-effective treatment for intermediate-high risk prostate cancer compared to IMRT alone.
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Braquiterapia/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Neoplasias da Próstata/radioterapia , Radioterapia de Intensidade Modulada/economia , Braquiterapia/efeitos adversos , Braquiterapia/métodos , Análise Custo-Benefício , Humanos , Masculino , Modelos Teóricos , Recidiva Local de Neoplasia , Antígeno Prostático Específico , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Resultado do TratamentoRESUMO
PURPOSE: The purpose of this study is to report the long-term outcomes and toxicity results of a prospective trial of moderately hypofractionated, image guided radiation therapy (RT) for localized prostate cancer. METHODS AND MATERIALS: Patients were enrolled between December 2006 and February 2012. Patients in group 1 were stage T1-T2b, had a Gleason score (GS) of 2 to 6 or 7 (3 + 4) with only 1 lobe involved, and had prostate-specific antigen levels ≤10 ng/mL. Group 2 patients were stage ≥T2c, had a GS ≥7 (4 + 3), a GS 7 (3 + 4) involving both lobes, or a PSA >10 ng/mL and ≤30 ng/mL. All patients underwent transrectal ultrasound guided fiducial (Visicoil) placement prior to computed tomography/magnetic resonance imaging simulation. Daily cone beam computed tomography with online correction was used. The prescribed dose was 64 Gy in 20 fractions. The primary endpoint was acute and late toxicity. The secondary endpoint was biochemical control. RESULTS: A total of 40 patients with a median age of 70 years were recruited for the study. Twenty-two patients (55%) were in group 1, and 18 patients (45%) were in group 2. Thirteen patients (32.5%) were classified as low, 26 patients (65%) as intermediate, and 1 patient (2.5%) as high risk per the National Comprehensive Cancer Network criteria. The median follow-up time was 59 months. Five-year biochemical control was 100% and 94.4% for groups 1 and 2, respectively. Thirteen patients (32.5%) developed acute gastrointestinal (GI) toxicities grade ≥2 and 3 (7.5%) developed acute grade 3 GI toxicity. A total of 17 patients (42.5%) developed grade ≥2 acute genitourinary toxicities and 1 (2.5%) developed acute grade 3 dysuria. Two patients (5%) developed late GI toxicities grade ≥2. There was 1 case (2.5%) of grade 4 fistula requiring sigmoid resection. Seven patients (17.5%) developed grade ≥2 late genitourinary toxicities; 2 patients (5%) late grade 3 urinary frequency/urgency. CONCLUSIONS: Moderately hypofractionated RT is effective with favorable toxicity and biochemical control, providing further evidence that increasing daily fractional dose can be safely and effectively delivered with contemporary RT techniques.
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PURPOSE: To identify factors predictive for chronic urinary toxicity secondary to high-dose adaptive three-dimensional conformal radiation. METHODS AND MATERIALS: From 1999 to 2002, 331 consecutive patients with clinical Stage II-III prostate cancer were prospectively treated (median dose, 75.6 Gy). The bladder was contoured, and the bladder wall was defined as the outer 3 mm of the bladder solid volume. Toxicity was quantified according to the National Cancer Institute Common Toxicity Criteria 2.0. Median follow-up was 1.6 years. RESULTS: The 3-year rates of Grade > or =2 and Grade 3 chronic urinary toxicity were 17.0% and 3.6%, respectively. Prostate volume, confidence-limited patient-specific planning target volume, bladder wall volume, and acute urinary toxicity were all found to be accurate predictors for chronic urinary toxicity. The volume of bladder wall receiving > or =30 Gy (V30) and > or =82 Gy (V82), along with prostate volume, were all clinically useful predictors of Grade > or =2 and Grade 3 chronic urinary toxicity and chronic urinary retention. Both Grade > or =2 (p = 0.001) and Grade 3 (p = 0.03) acute urinary toxicity were predictive for the development of Grade > or =2 (p = 0.001, p = 0.03) and Grade 3 (p = 0.05, p < 0.001) chronic urinary toxicity. On Cox multivariate analysis the development of acute toxicity was independently predictive for the development of both Grade > or =2 and Grade 3 chronic urinary toxicity. CONCLUSIONS: Acute urinary toxicity and bladder wall dose-volume endpoints are strong predictors for the development of subsequent chronic urinary toxicity. Our recommendation is to attempt to limit the bladder wall V30 to <30 cm(3) and the V82 to <7 cm(3) when possible. If bladder wall information is not available, bladder solid V30 and V82 may be used.
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Neoplasias da Próstata/radioterapia , Lesões por Radiação/complicações , Radioterapia Conformacional/efeitos adversos , Bexiga Urinária/efeitos da radiação , Transtornos Urinários/etiologia , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Hematúria/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Próstata/diagnóstico por imagem , Próstata/patologia , Neoplasias da Próstata/patologia , Dosagem Radioterapêutica , Radioterapia Conformacional/métodos , Tomografia Computadorizada por Raios X , Estreitamento Uretral/etiologia , Bexiga Urinária/diagnóstico por imagem , Incontinência Urinária/etiologia , Retenção Urinária/etiologiaRESUMO
PURPOSE: To report the toxicity and preliminary clinical outcomes of a prospective trial evaluating 19-Gy, single-fraction high-dose-rate (HDR) brachytherapy for men with low- and intermediate-risk prostate cancer. METHODS AND MATERIALS: A total of 63 patients were treated according to an institutional review board-approved prospective study of single-fraction HDR brachytherapy. Eligible patients had tumor stage ≤T2a, prostate-specific antigen level ≤15 ng/mL, and Gleason score ≤7. Patients with a prostate gland volume >50 cm3 and baseline American Urologic Association symptom score >12 were ineligible. Patients underwent transrectal ultrasound-guided transperineal implantation of the prostate, followed by single-fraction HDR brachytherapy. Treatment was delivered using 192Ir to a dose of 19 Gy prescribed to the prostate, with no additional margin applied. RESULTS: Of the 63 patients, 58 had data available for analysis. Five patients had withdrawn consent during the follow-up period. The median follow-up period was 2.9 years (range 0.3-5.2). The median age was 61.4 years. The median gland volume at treatment was 34.8 cm3. Of the 58 patients, 91% had T1 disease, 71% had Gleason score ≤6 (29% with Gleason score 7), and the median pretreatment prostate-specific antigen level was 5.1 ng/mL. The acute and chronic grade 2 genitourinary toxicity incidence was 12.1% and 10.3%, respectively. No grade 3 urinary toxicity occurred. No patients experienced acute rectal toxicity grade ≥2, and 2 experienced grade ≥2 chronic gastrointestinal toxicity. Three patients experienced biochemical failure, yielding a 3-year cumulative incidence estimate of 6.8%. CONCLUSIONS: Single-fraction HDR brachytherapy is well-tolerated, with favorable preliminary biochemical and clinical disease control rates.
Assuntos
Adenocarcinoma/radioterapia , Braquiterapia/métodos , Neoplasias da Próstata/radioterapia , Adenocarcinoma/sangue , Adenocarcinoma/patologia , Adulto , Idoso , Braquiterapia/efeitos adversos , Seguimentos , Humanos , Radioisótopos de Irídio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Ensaios Clínicos Controlados não Aleatórios como Assunto , Tamanho do Órgão , Próstata/patologia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Dosagem Radioterapêutica , Risco , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia de Intervenção , Transtornos Urinários/etiologiaRESUMO
BACKGROUND: Intensity-modulated proton therapy (IMPT), non-coplanar 4π intensity-modulated radiation therapy (IMRT), and volumetric-modulated arc therapy (VMAT) represent the most advanced treatment methods based on heavy ion and X-rays, respectively. Here we compare their performance for prostate cancer treatment. METHODS: Ten prostate patients were planned using IMPT with robustness optimization, VMAT, and 4π to an initial dose of 54 Gy to a clinical target volume (CTV) that encompassed the prostate and seminal vesicles, then a boost prescription dose of 25.2 Gy to the prostate for a total dose of 79.2 Gy. The IMPT plans utilized two coplanar, oblique scanning beams 10° posterior of the lateral beam positions. Range uncertainties were taken into consideration in the IMPT plans. VMAT plans used two full, coplanar arcs to ensure sufficient PTV coverage. 4π plans were created by inversely selecting and optimizing 30 beams from 1162 candidate non-coplanar beams using a greedy column generation algorithm. CTV doses, bladder and rectum dose volumes (V40, V45, V60, V65, V70, V75, and V80), R100, R50, R10, and CTV homogeneity index (D95/D5) were evaluated. RESULTS: Compared to IMPT, 4π resulted in lower anterior rectal wall mean dose as well as lower rectum V40, V45, V60, V65, V70, and V75. Due to the opposing beam arrangement, IMPT resulted in significantly (p < 0.05) greater femoral head doses. However, IMPT plans had significantly lower bladder, rectum, and anterior rectal wall max dose. IMPT doses were also significantly more homogeneous than 4π and VMAT doses. CONCLUSION: Compared to the VMAT and 4π plans, IMPT treatment plans are superior in CTV homogeneity and maximum point organ-at-risk (OAR) doses with the exception of femur heads. IMPT is inferior in rectum and bladder volumes receiving intermediate to high doses, particularly to the 4π plans, but significantly reduced low dose spillage and integral dose, which are correlated to secondary cancer for patients with expected long survival. The dosimetric benefits of 4π plans over VMAT are consistent with the previous publication.
Assuntos
Órgãos em Risco/efeitos da radiação , Neoplasias da Próstata/radioterapia , Terapia com Prótons , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Humanos , Masculino , Radiometria , Dosagem Radioterapêutica , Reto/efeitos da radiação , Estudos Retrospectivos , Bexiga Urinária/efeitos da radiaçãoRESUMO
PURPOSE: Prostate-specific antigen (PSA) bounce is a temporary elevation of the PSA level above a prior nadir. The purpose of this study was to determine whether the frequency of a PSA bounce following high-dose-rate (HDR) interstitial brachytherapy for the treatment of prostate cancer is associated with individual treatment fraction size. METHODS AND MATERIALS: Between 1999 and 2014, 554 patients underwent treatment of low- or intermediate-risk prostate cancer with definitive HDR brachytherapy as monotherapy and had ≥3 subsequent PSA measurements. Four different fraction sizes were used: 950 cGy × 4 fractions, 1200 cGy × 2 fractions, 1350 cGy × 2 fractions, 1900 cGy × 1 fraction. Four definitions of PSA bounce were applied: ≥0.2, ≥0.5, ≥1.0, and ≥2.0 ng/mL above the prior nadir with a subsequent return to the nadir. RESULTS: The median follow-up period was 3.7 years. The actuarial 3-year rate of PSA bounce for the entire cohort was 41.3%, 28.4%, 17.4%, and 6.8% for nadir +0.2, +0.5, +1.0, and +2.0 ng/mL, respectively. The 3-year rate of PSA bounce >0.2 ng/mL was 42.2%, 32.1%, 41.0%, and 59.1% for the 950-, 1200-, 1350-, and 1900-cGy/fraction levels, respectively (P=.002). The hazard ratio for bounce >0.2 ng/mL for patients receiving a single fraction of 1900 cGy compared with those receiving treatment in multiple fractions was 1.786 (P=.024). For patients treated with a single 1900-cGy fraction, the 1-, 2-, and 3-year rates of PSA bounce exceeding the Phoenix biochemical failure definition (nadir +2 ng/mL) were 4.5%, 18.7%, and 18.7%, respectively, higher than the rates for all other administered dose levels (P=.025). CONCLUSIONS: The incidence of PSA bounce increases with single-fraction HDR treatment. Knowledge of posttreatment PSA kinetics may aid in decision making regarding management of potential biochemical failures.
Assuntos
Braquiterapia/métodos , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Fracionamento da Dose de Radiação , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Probabilidade , Dosagem Radioterapêutica , Fatores de TempoRESUMO
PURPOSE: To present the most updated American College of Radiology consensus guidelines formed from an expert panel on treatment of locally advanced, high-risk prostate cancer METHODS:: The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. RESULTS: The panel summarized the most recent and relevant literature on the topic and voted on 4 clinical variants illustrating the appropriate management of locally advanced, high-risk cancer. Numerical rating and commentary reflecting the panel consensus was given for each treatment approach in each variant. CONCLUSIONS: Aggressive local approaches including surgery followed by adjuvant XRT, beam combined with androgen deprivation therapy, and beam combined with brachytherapy have resulted in unpresented success in locally advanced, high-risk prostate cancer. By combining most recent medical literature and expert opinion, this guideline can aid clinicians in the appropriate integration of available therapeutic modalities.
Assuntos
Neoplasias da Próstata/radioterapia , Terapia Combinada , Humanos , Masculino , Estadiamento de Neoplasias , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Radioterapia/métodos , Radioterapia/normas , Medição de RiscoRESUMO
PURPOSE: To present the most updated American College of Radiology (ACR) Appropriateness Criteria formed by an expert panel on the appropriate delivery of external beam radiation to manage stage T1 and T2 prostate cancer (in the definitive setting and post-prostatectomy) and to provide clinical variants with expert recommendations based on accompanying Appropriateness Criteria for target volumes and treatment planning. METHODS AND MATERIALS: The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a panel of multidisciplinary experts. The guideline development and revision process includes an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In instances in which evidence is lacking or equivocal, expert opinion may supplement available evidence to recommend imaging or treatment. RESULTS: The panel summarizes the most recent and relevant literature on the topic, including organ motion and localization methods, image guidance, and delivery techniques (eg, 3-dimensional conformal intensity modulation). The panel presents 7 clinical variants, including (1) a standard case and cases with (2) a distended rectum, (3) a large-volume prostate, (4) bilateral hip implants, (5) inflammatory bowel disease, (6) prior prostatectomy, and (7) a pannus extending into the radiation field. Each case outlines the appropriate techniques for simulation, treatment planning, image guidance, dose, and fractionation. Numerical rating and commentary is given for each treatment approach in each variant. CONCLUSIONS: External beam radiation is a key component of the curative management of T1 and T2 prostate cancer. By combining the most recent medical literature, these Appropriateness Criteria can aid clinicians in determining the appropriate treatment delivery and personalized approaches for individual patients.
RESUMO
PURPOSE: To provide updated American College of Radiology (ACR) appropriateness criteria for transrectal ultrasound-guided transperineal interstitial permanent source brachytherapy. METHODS AND MATERIALS: The ACR appropriateness criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. RESULTS: Permanent prostate brachytherapy (PPB) is a treatment option for appropriately selected patients with localized prostate cancer with low to very high risk disease. PPB monotherapy remains an appropriate and effective curative treatment for low-risk prostate cancer patients demonstrating excellent long-term cancer control and acceptable morbidity. PPB monotherapy can be considered for select intermediate-risk patients with multiparametric MRI useful in evaluation of such patients. High-risk patients treated with PPB should receive supplemental external beam radiotherapy (EBRT) along with androgen deprivation. Similarly, patients with involved pelvic lymph nodes may also be considered for such combined treatment but reported long-term outcomes are limited. Computed tomography-based postimplant dosimetry completed within 60 days of PPB is essential for quality assurance. PPB may be considered for treatment of local recurrence after EBRT but is associated with an increased risk of toxicity. CONCLUSIONS: Updated appropriateness criteria for patient evaluation, selection, treatment, and postimplant dosimetry are given. These criteria are intended to be advisory only with the final responsibility for patient care residing with the treating clinicians.