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PURPOSE: To validate the association between body composition and mortality in men treated with radiation for localized prostate cancer (PCa). Secondarily, to integrate body composition as a factor to classify patients by risk of all-cause mortality. MATERIALS AND METHODS: Participants of NRG/Radiation Therapy Oncology Group (RTOG) 9406 and NRG/RTOG 0126 with archived computed tomography were included. Muscle mass and muscle density were estimated by measuring the area and attenuation of the psoas muscles on a single slice at L4-L5. Bone density was estimated by measuring the attenuation of the vertebral body at mid-L5. Survival analyses, including Cox proportional hazards models, assessed the relationship between body composition and mortality. Recursive partitioning analysis (RPA) was used to create a classification tree to classify participants by risk of death. RESULTS: Data from 2066 men were included in this study. In the final multivariable model, psoas area, comorbidity score, baseline prostate serum antigen, and age were significantly associated with survival. The RPA yielded a classification tree with four prognostic groups determined by age, comorbidity, and psoas area. Notably, the classification among older (≥70 years) men into prognostic groups was determined by psoas area. CONCLUSIONS: This study strongly supports that body composition is related to mortality in men with localized PCa. The inclusion of psoas area in the RPA classification tree suggests that body composition provides additive information to age and comorbidity status for mortality prediction, particularly among older men. More research is needed to determine the clinical impact of body composition on prognostic models in men with PCa.
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Próstata , Neoplasias da Próstata , Masculino , Humanos , Idoso , Prognóstico , Análise de Sobrevida , Composição CorporalRESUMO
BACKGROUND: The optimal treatment of adult craniopharyngioma (CP) remains controversial. Although benign, these tumors tend to recur locally. The choice between gross total resection (GTR) versus subtotal resection (STR) with adjuvant or delayed radiotherapy (RT) is debated. The objective of this study is to review our experience with adult CPs over a 20-year period and identify an optimal management strategy. METHODS: From 1999 to 2020, we reviewed all patients diagnosed with CP at our institution. We collected data regarding tumor characteristics, treatments, and toxicity. Disease progression was defined as growth on imaging. Descriptive statistics were used to assess patient characteristics. The Kaplan Meier method was used to assess progression-free survival (PFS) and corresponding 95% confidence intervals (CI) from the time since treatment initiation. RESULTS: Twenty-four patients with a median age of 50 were included in this study. The median follow-up was 85 months. Seven patients had initial GTR, 10 STR, and 7 STR + RT. The overall 5-year PFS was 56% (95% CI: 38-83%): 100% in the STR + RT group, 69% in the GTR group, and 18% in the STR group (p = 0.01). Of the 17 patients initially treated with surgery alone, 3 with GTR and 6 with STR required salvage RT at a median of 46 months, with no further progression after salvage RT. CONCLUSIONS: Our study underscores the importance of RT for local control and suggests that STR + RT should be considered a viable option in the management of these tumors as it may be associated with improved PFS compared to surgery alone.
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Craniofaringioma , Neoplasias Hipofisárias , Adulto , Humanos , Radioterapia Adjuvante/métodos , Craniofaringioma/diagnóstico por imagem , Craniofaringioma/radioterapia , Craniofaringioma/cirurgia , Recidiva Local de Neoplasia , Resultado do Tratamento , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/radioterapia , Neoplasias Hipofisárias/cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND: Randomised trials have investigated various androgen deprivation therapy (ADT) intensification strategies in men receiving radiotherapy for the treatment of prostate cancer. This individual patient data meta-analysis of relevant randomised trials aimed to quantify the benefit of these interventions in aggregate and in clinically relevant subgroups. METHODS: For this meta-analysis, we performed a systematic literature search in MEDLINE, Embase, trial registries, the Web of Science, Scopus, and conference proceedings to identify trials with results published in English between Jan 1, 1962, and Dec 30, 2020. Multicentre randomised trials were eligible if they evaluated the use or prolongation of ADT (or both) in men with localised prostate cancer receiving definitive radiotherapy, reported or collected distant metastasis and survival data, and used ADT for a protocol-defined finite duration. The Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP) Consortium was accessed to obtain individual patient data from randomised trials. The primary outcome was metastasis-free survival. Hazard ratios (HRs) were obtained through stratified Cox models for ADT use (radiotherapy alone vs radiotherapy plus ADT), neoadjuvant ADT extension (ie, extension of total ADT duration in the neoadjuvant setting from 3-4 months to 6-9 months), and adjuvant ADT prolongation (ie, prolongation of total ADT duration in the adjuvant setting from 4-6 months to 18-36 months). Formal interaction tests between interventions and metastasis-free survival were done for prespecified subgroups defined by age, National Comprehensive Cancer Network (NCCN) risk group, and radiotherapy dose. This meta-analysis is registered with PROSPERO, CRD42021236855. FINDINGS: Our search returned 12 eligible trials that provided individual patient data (10 853 patients) with a median follow-up of 11·4 years (IQR 9·0-15·0). The addition of ADT to radiotherapy significantly improved metastasis-free survival (HR 0·83 [95% CI 0·77-0·89], p<0·0001), as did adjuvant ADT prolongation (0·84 [0·78-0·91], p<0·0001), but neoadjuvant ADT extension did not (0·95 [0·83-1·09], p=0·50). Treatment effects were similar irrespective of radiotherapy dose, patient age, or NCCN risk group. INTERPRETATION: Our findings provide the strongest level of evidence so far to the magnitude of the benefit of ADT treatment intensification with radiotherapy for men with localised prostate cancer. Adding ADT and prolonging the portion of ADT that follows radiotherapy is associated with improved metastasis-free survival in men, regardless of risk group, age, and radiotherapy dose delivered; however, the magnitude of the benefit could vary and shared decision making with patients is recommended. FUNDING: University Hospitals Seidman Cancer Center, Prostate Cancer Foundation, and the American Society for Radiation Oncology.
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Antagonistas de Androgênios/uso terapêutico , Neoplasias da Próstata/terapia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Dosagem Radioterapêutica , Fatores de TempoRESUMO
PURPOSE: Glioblastoma, the most common malignant brain tumor, was associated with a median survival of <1 year in the pre-temozolomide (TMZ) era. Despite advances in molecular and genetic profiling studies identifying several predictive biomarkers, none has been translated into routine clinical use. Our aim was to investigate the prognostic significance of a panel of diverse cellular molecular markers of tumor formation and growth in an annotated glioblastoma tissue microarray (TMA). METHODS AND MATERIALS: A TMA composed of archived glioblastoma tumors from patients treated with surgery, radiation, and non-TMZ chemother-apy, was provided by RTOG. RAD51, BRCA-1, phosphatase and tensin homolog tumor suppressor gene (PTEN), and miRNA-210 expression levels were assessed using quantitative in situ hybridization and automated quantitative protein analysis. The objectives of this analysis were to determine the association of each biomarker with overall survival (OS), using the Cox proportional hazard model. Event-time distributions were estimated using the Kaplan-Meier method and compared by the log-rank test. RESULTS: A cohort of 66 patients was included in this study. Among the 4 biomarkers assessed, only BRCA1 expression had a statistically significant correlation with survival. From univariate analysis, patients with low BRCA1 protein expression showed a favorable outcome for OS (p = 0.04; hazard ratio = 0.56) in comparison with high expressors, with a median survival time of 18.9 versus 4.8 months. CONCLUSIONS: BRCA1 protein expression was an important survival predictor in our cohort of glioblastoma patients. This result may imply that low BRCA1 in the tumor and the consequent low level of DNA repair cause vulnerability of the cancer cells to treatment.
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Proteína BRCA1/metabolismo , Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Estudos de Coortes , Terapia Combinada , Feminino , Glioblastoma/patologia , Glioblastoma/terapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Análise Serial de Tecidos , Adulto JovemRESUMO
PURPOSE: Radiotherapy (RT), as part of trimodal therapy, is an attractive alternative treatment in patients with urothelial muscle-invasive bladder cancer (MIBC). There is accumulating evidence suggesting the immunomodulatory effects of RT and its potential synergy when combined with immunotherapy. The aim of this review was to report on the most recent advances on this combination, including the mechanisms of RT immunomodulation, practical approach to combining RT and immunotherapy, and ongoing clinical trials in bladder cancer. METHODS: Using the PubMed database, we identified articles published between March 2004 and April 2020 on the combination of RT with immunotherapy in localized or metastatic MIBC. A search of the Clinicaltrials.gov and Clinicaltrialsregister.eu/ retrieved ongoing clinical trials on the topic as well. RESULTS: Combination of RT with immunotherapy leads to immunogenic cell death and an increase in immune markers thus leading to improved tumor control. For localized MIBC, there are safety concerns related to the use of concurrent immunotherapy with hypofractionated RT, thus neoadjuvant or adjuvant immunotherapy is preferred. In the metastatic setting, the combination of multi-site RT with SBRT-like doses (≥ 6 Gy per fraction) and concurrent immunotherapy seems most efficacious at harnessing the abscopal effect. At least 25 clinical trials combining immunotherapy and RT in MIBC are currently ongoing and will answer pending questions on safety, efficacy, and practical considerations on RT scheduling, fractionation, and targets volumes. CONCLUSION: RT has the potential to synergize with immunotherapy to improve oncological outcomes in patient with localized or metastatic MIBC. Clinical trials results are eagerly awaited.
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Carcinoma de Células de Transição/imunologia , Carcinoma de Células de Transição/terapia , Imunoterapia , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/terapia , Carcinoma de Células de Transição/radioterapia , Terapia Combinada , Humanos , Neoplasias da Bexiga Urinária/radioterapiaRESUMO
BACKGROUND: Salvage radiation therapy is often necessary in men who have undergone radical prostatectomy and have evidence of prostate-cancer recurrence signaled by a persistently or recurrently elevated prostate-specific antigen (PSA) level. Whether antiandrogen therapy with radiation therapy will further improve cancer control and prolong overall survival is unknown. METHODS: In a double-blind, placebo-controlled trial conducted from 1998 through 2003, we assigned 760 eligible patients who had undergone prostatectomy with a lymphadenectomy and had disease, as assessed on pathological testing, with a tumor stage of T2 (confined to the prostate but with a positive surgical margin) or T3 (with histologic extension beyond the prostatic capsule), no nodal involvement, and a detectable PSA level of 0.2 to 4.0 ng per milliliter to undergo radiation therapy and receive either antiandrogen therapy (24 months of bicalutamide at a dose of 150 mg daily) or daily placebo tablets during and after radiation therapy. The primary end point was the rate of overall survival. RESULTS: The median follow-up among the surviving patients was 13 years. The actuarial rate of overall survival at 12 years was 76.3% in the bicalutamide group, as compared with 71.3% in the placebo group (hazard ratio for death, 0.77; 95% confidence interval, 0.59 to 0.99; P=0.04). The 12-year incidence of death from prostate cancer, as assessed by means of central review, was 5.8% in the bicalutamide group, as compared with 13.4% in the placebo group (P<0.001). The cumulative incidence of metastatic prostate cancer at 12 years was 14.5% in the bicalutamide group, as compared with 23.0% in the placebo group (P=0.005). The incidence of late adverse events associated with radiation therapy was similar in the two groups. Gynecomastia was recorded in 69.7% of the patients in the bicalutamide group, as compared with 10.9% of those in the placebo group (P<0.001). CONCLUSIONS: The addition of 24 months of antiandrogen therapy with daily bicalutamide to salvage radiation therapy resulted in significantly higher rates of long-term overall survival and lower incidences of metastatic prostate cancer and death from prostate cancer than radiation therapy plus placebo. (Funded by the National Cancer Institute and AstraZeneca; RTOG 9601 ClinicalTrials.gov number, NCT00002874 .).
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Antagonistas de Androgênios/uso terapêutico , Anilidas/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/radioterapia , Nitrilas/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Compostos de Tosil/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/efeitos adversos , Anilidas/efeitos adversos , Terapia Combinada , Método Duplo-Cego , Seguimentos , Ginecomastia/induzido quimicamente , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/mortalidade , Estadiamento de Neoplasias , Nitrilas/efeitos adversos , Prostatectomia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/cirurgia , Radioterapia/efeitos adversos , Taxa de Sobrevida , Compostos de Tosil/efeitos adversosRESUMO
OBJECTIVE: To review outcomes of patients with stage III endometrial cancer confined to the pelvis treated with adjuvant pelvic radiotherapy (RT) or sequential chemoradiotherapy (CRT). METHODS: Between 1990 and 2012, 144 patients diagnosed with stage IIIA, B or C1 endometrial cancer were treated in our institution. All were treated with total hysterectomy, bilateral salpingo-oophorectomy⯱â¯lymph node dissection. Post-operatively, 67 patients received adjuvant RT alone, 37 CRT, 21 chemotherapy alone and 19 had no adjuvant therapy. This analysis focuses on the 104 patients treated with RT or CRT. RESULTS: The median follow-up was 61â¯months. Forty-six patients (44%) were stage IIIA, 6 (6%) were stage IIIB and 52 (50%) stage IIIC1. The 5-year overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS) for patients treated by RT alone vs. CRT were, respectively, 67% vs. 61% (pâ¯=â¯0.55); 67% vs. 51% (pâ¯=â¯0.35); and 76% vs. 65% (pâ¯=â¯0.21). Grade 3 disease was an independent predictor for worse OS (HRâ¯=â¯6.01, pâ¯=â¯0.001), DFS (HRâ¯=â¯3.16, pâ¯=â¯0.03), and DSS (HRâ¯=â¯3.77, pâ¯=â¯0.02). In patients with grade 3 disease (nâ¯=â¯49), the 5-year OS was superior for the CRT (42% vs. 56%, pâ¯=â¯0.007). CONCLUSIONS: In patients with stage III endometrial cancer confined to the pelvis, the addition of adjuvant chemotherapy with RT significantly improved OS in grade 3 disease. Grade 3 histology is a strong predictor for poor outcome. Further randomized studies aiming specifically at stage III disease are warranted.
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Neoplasias do Endométrio/terapia , Neoplasias Pélvicas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia/efeitos adversos , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de NeoplasiasRESUMO
We aimed to test any association between authors' conclusions and self-reported COI or funding sources in central nervous system (CNS) studies. A review was performed for CNS malignancy clinical trials published in the last 5 years. Two investigators independently classified study conclusions according to authors' endorsement of the experimental therapy. Statistical models were used to test for associations between positive conclusions and trials characteristics. From February 2010 to February 2015, 1256 articles were retrieved; 319 were considered eligible trials. Positive conclusions were reported in 56.8% of trials with industry-only, 55.6% with academia-only, 44.1% with academia and industry, 77.8% with none, and 76.4% with not described funding source (p = 0.011). Positive conclusions were reported in 60.4% of trials with unrelated COI, 60% with related COI, and 60% with no COI reported (p = 0.997). Factors that were significantly associated with the presence of positive conclusion included trials design (phase 1) [OR 11.64 (95 CI 4.66-29.09), p < 0.001], geographic location (outside North America or Europe) [OR 1.96 (95 CI 1.05-3.79), P = 0.025], primary outcomes (non-overall or progression free survival) [OR 3.74 (95 CI 2.27-6.18), p < 0.001], and failure to disclose funding source [OR 2.45 (95 CI 1.22-5.22), p = 0.011]. In a multivariable regression model, all these factors remained significantly associated with trial's positive conclusion. Funding source and self-reported COI did not appear to influence the CNS trials conclusion. Funding source information and COI disclosure were under-reported in 14.1 and 17.2% of the CNS trials. Continued efforts are needed to increase rates of both COI and funding source reporting.
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Pesquisa Biomédica/economia , Pesquisa Biomédica/ética , Neoplasias do Sistema Nervoso Central/economia , Ensaios Clínicos como Assunto/economia , Ensaios Clínicos como Assunto/ética , Conflito de Interesses/economia , Neoplasias do Sistema Nervoso Central/terapia , Humanos , Oncologia/economia , Neurologia/economia , Publicações Periódicas como Assunto , Projetos de Pesquisa , Pesquisadores/economia , Pesquisadores/ética , Pesquisadores/psicologiaRESUMO
PROPOSE: To examine the association between trial sponsorship sources, self-reported conflicts of interest (COI), and study and author characteristics in central nervous system (CNS) oncology clinical trials (CT). METHODS: MEDLINE search was performed for original CT on "Central Nervous System Neoplasms"[Mesh]. The investigators assessed for relationships between funding source (industry, academic or cooperative, none, not described), COI (presented, none, or not reported), CT, and author characteristics. RESULTS: From 2010 to 2015, 319 CT were considered eligible. The majority of the studies involved primary gliomas (55.2%) and were Phase II CT (59.2%). Drug therapy was investigated in 83.0% of the CT. The remaining studies investigated surgery or radiotherapy. A minority of papers were published in journals with impact factor (IF) higher than > 10 (16%) or in regions other than North America and Europe (20.4%). Overall, 83.1% of studies disclosed funding sources: 32.6% from industry alone, 33.9% from an academic or cooperative group, and 10.7% from a mixed funding model. COI data was reported by 85.9% of trials, of which 56.2% reported no COI and 43.8% reported a related COI. Significant predictors for sponsorship (industry and/or academia) on univariate analysis were study design, type of intervention, journal impact factor, study conclusion, transparency of COI and presence of COI. On multivariate analysis, type of intervention, (P < 0.001), journal impact factor (IF) (P = 0.003), presence of COI (P < 0.001) and study conclusion (P = 0.003) remained significant predictors of sponsorship. For predicting COI, significant variables on univariate analysis were disease type, type of intervention, journal IF, funding source, and intervention arm being related to sponsor. On multivariate analysis, disease type (P = 0.003), journal IF (P < 0.001), type of intervention (P = 0.001), and funding source (P = 0.008) remained significant. CONCLUSIONS: The majority of CNS CT reported some external funding sources and non-related COI. We identified that drug trials, higher IF, presence of COI, and a neutral or negative study conclusion are associated with external funding. Likewise drug trials, higher IF, and glioma trials are associated with presence of COI.
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Autoria , Neoplasias do Sistema Nervoso Central/terapia , Ensaios Clínicos como Assunto/economia , Conflito de Interesses/economia , Pesquisadores/psicologia , Comunicação Acadêmica/economia , Humanos , Oncologia/economia , Neurologia/economia , Pesquisadores/economia , AutorrelatoRESUMO
INTRODUCTION: Ultrastaging in endometrial cancer (EC) led to increased detection of isolated tumor cells (ITC, ≤0.2 mm) and micrometastases (MM, 0.2-2 mm), with unclear effect on prognosis. Our aim was to characterize the impact of ITC and MM on the outcome of these patients. METHODS: Grade 1 to 2 stage I endometrioid EC patients with nodal ITC (n = 11) or MM (n = 12) between 2012 and 2018 were retrospectively compared to a matched group of lymph node negative (n = 18) patients based on age, body mass index, grade, myometrial invasion, and lymphovascular space invasion (LVI) status using propensity score analysis (1:1). Mann-Whitney U tests were performed on continuous variables and χ2 tests on categorical variables. Progression-free survival (PFS) was the main endpoint. RESULTS: All MM and 81% of ITC had LVI. More ITC/MM patients received RT and chemotherapy (91.7% vs 18.4%; 70.8% vs 4.5%, respectively; P < 0.01) without significant difference in treatment-related toxicities (25% vs 27.3% grade 1%-2% and 20.8% vs 9.1% grade 2-3; P = 0.538) or PFS (29.2 vs 25 months; P = 0.828). Two distant recurrences occurred in MM patients after 2.5 years; one lung and one para-aortic lymph node. CONCLUSION: With adjuvant treatment, ITC/MM in otherwise well-differentiated stage I endometrial cancer have similar outcomes to matched LN- patients.
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Intervalo Livre de Doença , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Linfonodos/patologia , Metástase Linfática , Micrometástase de Neoplasia , Idoso , Estudos de Casos e Controles , Quimioterapia Adjuvante , Feminino , Humanos , Laparoscopia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Pontuação de Propensão , Radioterapia Adjuvante , Estudos Retrospectivos , Procedimentos Cirúrgicos RobóticosRESUMO
PURPOSE OF THE REVIEW: This review targets the latest literature on bladder preservation therapy with emphasis on trimodal therapy (TMT), highlighting its role in the management of muscle invasive bladder cancer (MIBC) and outlining future directions in bladder preservation research. RECENT FINDINGS: TMT is the most promising bladder preservation treatment modality. Comparable results to contemporary radical cystectomy series are seen in properly selected patients. A multidisciplinary team approach is critical in the management of these patients. Future research is directed at the integration of immunotherapy into the treatment protocol. TMT, involving maximal transurethral resection followed by chemoradiation, is an attractive alternative to radical cystectomy with urinary diversion in carefully selected patients with muscle invasive disease. In the absence of randomized trial (RCT), comparison between TMT and cystectomy, based on retrospective data from large centers, suggests comparable oncological outcomes, with a favorable impact on quality of life.
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Tratamentos com Preservação do Órgão , Neoplasias da Bexiga Urinária/terapia , Quimiorradioterapia Adjuvante , Terapia Combinada/métodos , Cistectomia/métodos , Humanos , Invasividade Neoplásica , Seleção de Pacientes , Qualidade de Vida , Estudos RetrospectivosRESUMO
INTRODUCTION: To report long term toxicity and efficacy of patients with intermediate risk prostate cancer treated with moderate hypofractionated radiotherapy (HypoRT). MATERIALS AND METHODS: We studied the first consecutive 100 men with intermediate risk (stage T2b-T2c, or PSA = 10-20 ug/L, or Gleason score = 7) adenocarcinoma of the prostate treated between October 2002 and May 2010 in our institution with moderate HypoRT. Patients were treated using three-dimensional conformal HypoRT to a dose of 66 Gy in 22 daily fractions prescribed to the isocenter. Androgen suppression was not given to any patient. A uniform 7 mm margin was created around the prostate for the planning target volume. Daily ultrasound was used to guide the radiotherapy. Common Terminology Criteria for Adverse Events, version 3.0, was used to prospectively score toxicity. Biochemical failure was defined as the nadir PSA level plus 2 ng/m. RESULTS: After a median follow up time of 80 months (range: 7-152), the 8 year actuarial freedom from biochemical relapse survival rate was 90%. The 8 year cancer specific survival and overall survival rates were 96% and 84%, respectively. Only 2 patients died from prostate cancer. The worst grade ≥ 2 late genitourinary (GU) or gastrointestinal (GI) toxicities ever documented were 19% and 20%, respectively. At the last follow up the incidence of grade ≥ 2 late GI or GU toxicity was of only 2% and 3%, respectively. No grade 4 or 5 late toxicity was seen. CONCLUSION: Our long term experience with HypoRT delivering 66 Gy/22 fractions prescribed to the isocenter using three-dimensional conformal radiotherapy shows excellent tumor control with acceptable toxicity.
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Adenocarcinoma/radioterapia , Próstata/patologia , Neoplasias da Próstata/radioterapia , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidade , Idoso , Idoso de 80 Anos ou mais , Biópsia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/mortalidade , Quebeque/epidemiologia , Radioterapia de Intensidade Modulada , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Fatores de TempoRESUMO
BACKGROUND: The current study was conducted to assess acute and late adverse events (AEs), overall survival (OS), pelvic failure, regional failure, distant failure, and disease-free survival in a prospective phase 2 clinical trial of bevacizumab and pelvic intensity-modulated radiotherapy (IMRT) with chemotherapy in patients with high-risk endometrial cancer. METHODS: Patients underwent a hysterectomy and lymph node removal, and had ≥1 of the following high-risk factors: grade 3 carcinoma with >50% myometrial invasion, grade 2 or 3 disease with any cervical stromal invasion, or known extrauterine extension confined to the pelvis. Treatment included pelvic IMRT and concurrent cisplatin on days 1 and 29 of radiation and bevacizumab (at a dose of 5 mg/kg on days 1, 15, and 29 of radiation) followed by adjuvant carboplatin and paclitaxel for 4 cycles. The primary endpoint was grade ≥3 AEs occurring within the first 90 days (toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). RESULTS: A total of 34 patients were accrued from November 2009 through December 2011, 30 of whom were eligible and received study treatment. Seven of 30 patients (23.3%; 1-sided 95% confidence interval, 10.6%-36.0%) developed grade ≥3 treatment-related nonhematologic toxicities within 90 days; an additional 6 patients experienced grade ≥3 toxicities between 90 and 365 days after treatment. The 2-year OS rate was 96.7% and the disease-free survival rate was 79.1%. No patient developed a within-field pelvic failure and no patients with International Federation of Gynecology and Obstetrics stage I to IIIA disease developed disease recurrence after a median follow-up of 26 months. CONCLUSIONS: Postoperative bevacizumab added to chemotherapy and pelvic IMRT appears to be well tolerated and results in high OS rates at 2 years for patients with high-risk endometrial carcinoma.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bevacizumab/administração & dosagem , Quimiorradioterapia Adjuvante , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Histerectomia , Excisão de Linfonodo , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Período Pós-Operatório , Radioterapia de Intensidade ModuladaRESUMO
We report on the long-term results of a phase II study of pre-irradiation temozolomide followed by concurrent temozolomide and radiotherapy (RT) in patients with newly diagnosed anaplastic oligodendroglioma (AO) and mixed anaplastic oligoastrocytoma. Pre-RT temozolomide was given for up to 6 cycles. RT with concurrent temozolomide was administered to patients with less than a complete radiographic response. Forty eligible patients were entered and 32 completed protocol treatment. With a median follow-up time of 8.7 years (range 1.1-10.1), median progression-free survival (PFS) is 5.8 years (95 % CI 2.0, NR) and median overall survival (OS) has not been reached (5.9, NR). 1p/19q data are available in 37 cases; 23 tumors had codeletion while 14 tumors had no loss or loss of only 1p or 19q (non-codeleted). In codeleted patients, 9 patients have progressed and 4 have died; neither median PFS nor OS have been reached and two patients who received only pre-RT temozolomide and no RT have remained progression-free for over 7 years. 3-year PFS and 6-year OS are 78 % (95 % CI 61-95 %) and 83 % (95 % CI 67-98 %), respectively. Codeleted patients show a trend towards improved 6-year survival when compared to the codeleted procarbazine/CCNU/vincristrine (PCV) and RT cohort in RTOG 9402 (67 %, 95 % CI 55-79 %). For non-codeleted patients, median PFS and OS are 1.3 and 5.8 years, respectively. These updated results suggest that the regimen of dose intense, pre-RT temozolomide followed by concurrent RT/temozolomide has significant activity, particularly in patients with 1p/19q codeleted AOs and MAOs.
Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/terapia , Dacarbazina/análogos & derivados , Oligodendroglioma/terapia , Radioterapia/métodos , Adolescente , Adulto , Idoso , Dacarbazina/uso terapêutico , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Temozolomida , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: Surgery and luteinizing hormone-releasing hormone (LHRH) analogs are standard androgen deprivation treatments (ADT) for patients with advanced prostate cancer. We performed a phase I study to explore if irradiation to the testes could be used as an alternative to ADT. MATERIALS AND METHODS: All patients had advanced prostate cancer with normal testosterone levels before treatment and indication for long term castration. Treatment started with one LHRH analog injection (to induce a fast drop of testosterone) followed by irradiation to the whole scrotum. Two fractionation regimens were tested: 17 Gy in 2 fractions, and 24 Gy in 3 fractions. Hormonal blood evaluation was performed before and every 3 months after radiotherapy. Toxicity was evaluated at each visit by the CTCv3 scoring system. This was an IRB approved prospective study. RESULTS: The first three patients received 17 Gy in 2 fractions. None of them developed acute or late skin toxicity and none became castrated, keeping normal levels of testosterone during the time they were followed at 11, 24 and 36 months post-radiotherapy. Another four patients received 24 Gy in 3 fractions. Two developed grade 1 temporary acute dermatitis and, again, none of them became castrated during follow up of 11-36 months. CONCLUSIONS: Prospective studies assessing the effect of the Leydig cells after direct irradiation to the testes are rare. The two radiotherapy regimens used in this study were well tolerated, but not capable of causing castration after 11-36 months of follow up. It is not yet clear whether radiation treatment can effectively induce castration in men.
Assuntos
Castração/métodos , Fracionamento da Dose de Radiação , Células Intersticiais do Testículo/efeitos da radiação , Neoplasias da Próstata/terapia , Lesões por Radiação/etiologia , Radiodermite/etiologia , Idoso , Hormônio Liberador de Gonadotropina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias da Próstata/sangue , Radioterapia/efeitos adversos , Testosterona/sangueRESUMO
BACKGROUND: It is not known whether short-term androgen-deprivation therapy (ADT) before and during radiotherapy improves cancer control and overall survival among patients with early, localized prostate adenocarcinoma. METHODS: From 1994 through 2001, we randomly assigned 1979 eligible patients with stage T1b, T1c, T2a, or T2b prostate adenocarcinoma and a prostate-specific antigen (PSA) level of 20 ng per milliliter or less to radiotherapy alone (992 patients) or radiotherapy with 4 months of total androgen suppression starting 2 months before radiotherapy (radiotherapy plus short-term ADT, 987 patients). The primary end point was overall survival. Secondary end points included disease-specific mortality, distant metastases, biochemical failure (an increasing level of PSA), and the rate of positive findings on repeat prostate biopsy at 2 years. RESULTS: The median follow-up period was 9.1 years. The 10-year rate of overall survival was 62% among patients receiving radiotherapy plus short-term ADT (the combined-therapy group), as compared with 57% among patients receiving radiotherapy alone (hazard ratio for death with radiotherapy alone, 1.17; P=0.03). The addition of short-term ADT was associated with a decrease in the 10-year disease-specific mortality from 8% to 4% (hazard ratio for radiotherapy alone, 1.87; P=0.001). Biochemical failure, distant metastases, and the rate of positive findings on repeat prostate biopsy at 2 years were significantly improved with radiotherapy plus short-term ADT. Acute and late radiation-induced toxic effects were similar in the two groups. The incidence of grade 3 or higher hormone-related toxic effects was less than 5%. Reanalysis according to risk showed reductions in overall and disease-specific mortality primarily among intermediate-risk patients, with no significant reductions among low-risk patients. CONCLUSIONS: Among patients with stage T1b, T1c, T2a, or T2b prostate adenocarcinoma and a PSA level of 20 ng per milliliter or less, the use of short-term ADT for 4 months before and during radiotherapy was associated with significantly decreased disease-specific mortality and increased overall survival. According to post hoc risk analysis, the benefit was mainly seen in intermediate-risk, but not low-risk, men. (Funded by the National Cancer Institute; RTOG 94-08 ClinicalTrials.gov number, NCT00002597.).
Assuntos
Antagonistas de Androgênios/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Combinada , Disfunção Erétil/etiologia , Flutamida/administração & dosagem , Flutamida/efeitos adversos , Seguimentos , Hormônio Liberador de Gonadotropina/agonistas , Hormônio Liberador de Gonadotropina/uso terapêutico , Gosserrelina/administração & dosagem , Gosserrelina/efeitos adversos , Humanos , Leuprolida/administração & dosagem , Leuprolida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Próstata/patologia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Radioterapia/efeitos adversos , Dosagem Radioterapêutica , Risco , Taxa de SobrevidaRESUMO
This investigation reports on the biochemical and clinical outcomes of a newly created pan-Canadian Prostate Cancer Risk Stratification (ProCaRS) database developed by the Genitourinary Radiation Oncologists of Canada (GUROC). GUROC ProCaRS template-compliant data on 7974 patients who underwent radiotherapy were received from 7 unique databases. Descriptive analysis, Cox proportional hazards, and Kaplan-Meier analyses were performed using American Society for Radiation Oncology (ASTRO) biochemical failure-free survival (BFFS), prostate cancer-specific survival, and overall survival. Multivariable modeling for the primary ASTRO BFFS end point showed that age, prostate-specific antigen, T stage, and Gleason score and components such as hormonal therapy, and radiation treatment (brachytherapy with better outcome than external-beam) were predictive of outcome. Kaplan-Meier analysis of the existing GUROC and new NCCN classification system both showed good separation of all clinical outcome curves. The construction of a pan-Canadian database has informed important prostate cancer radiotherapy outcomes and risk stratification.
Assuntos
Neoplasias da Próstata/sangue , Neoplasias da Próstata/radioterapia , Medição de Risco , Resultado do Tratamento , Idoso , Braquiterapia , Canadá , Intervalo Livre de Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia , Dosagem Radioterapêutica , RiscoRESUMO
BACKGROUND AND PURPOSE: To determine the rate and time of testosterone (T) recovery in patients (pts) with localised prostate cancer treated with radiotherapy plus 0-, 6-, 18- or 36-month of androgen deprivation therapy (ADT). MATERIALS AND METHODS: In 1230 pts with prostate cancer randomised into two phase III trials, serum T was measured at baseline, then regularly. T recovery rate was compared between normal vs. abnormal baseline T and with ADT duration with Chi-square test or Fisher's exact test. A multivariable logistic regression model to predict the probability of recovering normal T was performed. RESULTS: Overall, 87.4 % (167/191), 75.9 % (293/386), 54.8 % (181/330) and 43.2 % (80/185) of pts, recovered normal T on the 0-, 6-, 18- or 36-month schedule, respectively (p < 0.001). In patients recovering normal T, the median time to T recovery increased with ADT duration ranging from 0.31, 1.64, 3.06 to 5.0 years for the 0-, 6-, 18- or 36-month schedules, respectively (p < 0.001) and was significantly faster for those with a normal T at baseline (p < 0.001). On multivariable analysis, older age and longer ADT duration are associated with a lower T recovery. CONCLUSIONS: Testosterone recovery rate after ADT depends on several factors including hormonal duration, normal baseline T, age and medical comorbidities. A longer ADT duration is the most important variable affecting T recovery. The data from this report might be a valuable tool to help physicians and patients in evaluating risks and benefits of ADT.
Assuntos
Antagonistas de Androgênios , Neoplasias da Próstata , Testosterona , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/sangue , Testosterona/sangue , Testosterona/uso terapêutico , Antagonistas de Androgênios/uso terapêutico , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Fatores de TempoRESUMO
PURPOSE: 5-FU/cisplatin and twice-daily radiation (FCT) or gemcitabine and once daily radiation (GD) are effective chemoradiation (CRT) regimens for bladder sparing treatment of muscle-invasive bladder cancer (MIBC). This trial evaluated these regimens and demonstrated efficacy with either regimen at 3 years. With further follow-up, longer term results are reported here. METHODS AND MATERIALS: Patients with cT2-4a MIBC were randomized to FCT or GD. Patients had a transurethral resection and induction CRT to 40 Gy. Patients with a complete response (CR) received consolidation CRT to 64 Gy. Others had cystectomy. Adjuvant gemcitabine/cisplatin chemotherapy was administered. The primary endpoint was freedom from distant metastasis (FDM). This updated analysis reports 7-year data. Toxicity and efficacy endpoints, including bladder intact distant metastasis free survival (BI-DMFS) were also assessed. RESULTS: From 12/2008 to 4/2014, 70 patients were enrolled; 66 eligible for analysis, 33 per arm. Median follow-up was 9.1 years for eligible living patients. At 7 years, FDM was 65% and 73% for FCT and GD, respectively. BI-DMFS was 58% (95% CI: 41 - 76) and 68% (95% CI: 51-84), respectively. The post-hoc hazard ratio of 0.75 (95% CI: 0.37-1.55) showed no difference between treatments (p=0.44). Overall survival at 7 years was 48% and 59%. There were 4 and 5 cystectomies performed for FCT and GD, respectively. In the FCT arm, there were 5 (16%), 1 (3%) and 0 grade 3, 4 and 5 late toxicities reported. In the GD arm, there were 7 (23%), 0 and 0. CONCLUSIONS: Both regimens maintained high FDM rates at 7 years. Cystectomy rates were low and overall survival rates high on both arms. Late toxicity rates were low. Either gemcitabine and daily radiation or a cisplatin-based regimen are effective bladder sparing therapies.
RESUMO
PURPOSE: A suboptimal prostate-specific antigen (PSA) response to neoadjuvant androgen deprivation therapy (ADT) among men who go on to receive definitive radiation therapy for prostate cancer might suggest the existence of castration-resistant disease or altered androgen receptor signaling. This in turn may portend worse long-term clinical outcomes, especially in men with high-risk disease. We set out to evaluate the prognostic impact of poor PSA response to neoadjuvant ADT in men with high-risk prostate cancer. METHODS AND MATERIALS: This was a post hoc analysis of the multicenter TROG 03.04 RADAR and PCS IV randomized clinical trials. Inclusion criteria for this analysis were patients with high-risk prostate cancer (defined as Gleason score ≥8, initial PSA ≥20 ng/mL, or cT3a disease or higher) who received definitive radiation therapy, at least 18 months of ADT, and had a preradiation therapy PSA level drawn after at least 3 months of neoadjuvant ADT. Poor PSA response was defined as PSA >0.5 ng/mL. Cox regression and Fine-Gray models were used to test whether poor PSA response was associated with metastasis-free survival, biochemical recurrence, prostate-cancer specific mortality, and overall survival. RESULTS: Nine hundred thirty men met inclusion criteria for this analysis. Median follow-up was 130 months (interquartile range [IQR], 89-154 months). After a median of 3 months (IQR, 3-4.2 months) of neoadjuvant ADT, the median PSA was 0.60 ng/mL (IQR, 0.29-1.59). Overall, 535 men (57%) had a PSA >0.5 ng/mL. Poor PSA response was associated with significantly worse metastasis-free survival (hazard ratio [HR], 3.93; P = .02), worse biochemical recurrence (subdistribution HR, 2.39; P = .003), worse prostate-cancer specific mortality (subdistribution HR, 1.50; P = .005), and worse overall survival (HR, 4.51; P = .05). CONCLUSIONS: Patients with PSA >0.5 mg/mL after at least 3 months of neoadjuvant ADT had worse long-term clinical outcomes and should be considered for treatment intensification.