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1.
PLoS One ; 14(1): e0210785, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30650143

RESUMO

BACKGROUND: Pure squamous cell carcinoma (SCC) of the urinary tract is rare in the UK and has a poor prognosis compared with transitional cell carcinoma (TCC). Cisplatin based chemotherapy has been shown to be effective in TCC. METHODS: Patients with T3-T4, pelvic relapsed, nodal or metastatic SCC of the urinary tract were recruited into an open-label, single-arm, non-randomised, phase 2 trial evaluating the activity and safety of cisplatin, methotrexate and vinblastine (CMV) chemotherapy. CMV was given as three 21-day cycles of methotrexate 30mg/m2 (day 1 & 8), vinblastine 4mg/m2 (day 1 & 8) and cisplatin 100mg/m2 (day 2). RESULTS: 38 patients were recruited. Overall response was 39% (95% CI 24%, 55%)-13% CR and 26% PR. Median OS was 7.8 months (95% CI 3.4, 12.6) with 39% 1-year survival. Toxicity was acceptable. CONCLUSION: CMV is well tolerated and active in patients with pure SCC of the urinary tract.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Urológicas/tratamento farmacológico , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Cisplatino/administração & dosagem , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias Urológicas/mortalidade , Vimblastina/administração & dosagem
2.
Lancet Oncol ; 15(4): 464-73, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24581940

RESUMO

BACKGROUND: The aim of this trial was to compare dose-escalated conformal radiotherapy with control-dose conformal radiotherapy in patients with localised prostate cancer. Preliminary findings reported after 5 years of follow-up showed that escalated-dose conformal radiotherapy improved biochemical progression-free survival. Based on the sample size calculation, we planned to analyse overall survival when 190 deaths occurred; this target has now been reached, after a median 10 years of follow-up. METHODS: RT01 was a phase 3, open-label, international, randomised controlled trial enrolling men with histologically confirmed T1b-T3a, N0, M0 prostate cancer with prostate specific antigen of less than 50 ng/mL. Patients were randomly assigned centrally in a 1:1 ratio, using a computer-based minimisation algorithm stratifying by risk of seminal vesicle invasion and centre to either the control group (64 Gy in 32 fractions, the standard dose at the time the trial was designed) or the escalated-dose group (74 Gy in 37 fractions). Neither patients nor investigators were masked to assignment. All patients received neoadjuvant androgen deprivation therapy for 3-6 months before the start of conformal radiotherapy, which continued until the end of conformal radiotherapy. The coprimary outcome measures were biochemical progression-free survival and overall survival. All analyses were done on an intention-to-treat basis. Treatment-related side-effects have been reported previously. This trial is registered, number ISRCTN47772397. FINDINGS: Between Jan 7, 1998, and Dec 20, 2001, 862 men were registered and 843 subsequently randomly assigned: 422 to the escalated-dose group and 421 to the control group. As of Aug 2, 2011, 236 deaths had occurred: 118 in each group. Median follow-up was 10·0 years (IQR 9·1-10·8). Overall survival at 10 years was 71% (95% CI 66-75) in each group (hazard ratio [HR] 0·99, 95% CI 0·77-1·28; p=0·96). Biochemical progression or progressive disease occurred in 391 patients (221 [57%] in the control group and 170 [43%] in the escalated-dose group). At 10 years, biochemical progression-free survival was 43% (95% CI 38-48) in the control group and 55% (50-61) in the escalated-dose group (HR 0·69, 95% CI 0·56-0·84; p=0·0003). INTERPRETATION: At a median follow-up of 10 years, escalated-dose conformal radiotherapy with neoadjuvant androgen deprivation therapy showed an advantage in biochemical progression-free survival, but this advantage did not translate into an improvement in overall survival. These efficacy data for escalated-dose treatment must be weighed against the increase in acute and late toxicities associated with the escalated dose and emphasise the importance of use of appropriate modern radiotherapy methods to reduce side-effects. FUNDING: UK Medical Research Council.


Assuntos
Fracionamento da Dose de Radiação , Neoplasias da Próstata/radioterapia , Radioterapia Conformacional , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/uso terapêutico , Quimioterapia Adjuvante , Progressão da Doença , Intervalo Livre de Doença , Humanos , Análise de Intenção de Tratamento , Calicreínas/sangue , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Radioterapia Conformacional/efeitos adversos , Radioterapia Conformacional/mortalidade , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
3.
J Clin Oncol ; 29(6): 733-8, 2011 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-21205754

RESUMO

PURPOSE: The aim of this prospective, phase II trial was to determine the response of muscle-invasive bladder cancer (MIBC) to concurrent chemoradiotherapy of weekly gemcitabine with 4 weeks of radiotherapy (RT; GemX). PATIENTS AND METHODS: Fifty patients with transitional cell carcinoma, stage T2-3, N0, M0 after transurethral resection and magnetic resonance imaging, were recruited. Gemcitabine was given intravenously at 100 mg/m(2) on days 1, 8, 15, and 22 of a 28-day RT schedule that delivered 52.5 Gy in 20 fractions. Chemotherapy was stopped for Radiation Therapy Oncology Group (RTOG) grade 3 bladder or bowel toxicity. The primary end points were tumor response, toxicity, and survival. RESULTS: All patients completed RT; 46 tolerated all four cycles of gemcitabine. Two patients stopped after two cycles, and two stopped after three cycles, because of bowel toxicity. Forty-seven patients had a post-treatment cystoscopy; 44 (88%) achieved a complete endoscopic response. At a median follow-up of 36 months (range, 15 to 62 months), 36 patients were alive, and 32 of these had a functional and intact bladder. Fourteen patients died; seven died as a result of metastatic MIBC, five died as a result of intercurrent disease, and two died as a result of treatment-associated deaths. Four patients underwent cystectomy; three because of recurrent disease and one because of toxicity. One patient required a bowel resection for late toxicity. By using Kaplan-Meier analyses, 3-year cancer-specific survival was 82%, and overall survival was 75%. CONCLUSION: Concurrent gemcitabine-based chemoradiotherapy (ie, GemX) produces a high response rate in MIBC and has durable local control and acceptable toxicity, which allows patients to preserve their own bladder. This treatment modality warrants additional investigation in a phase III setting.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células de Transição/terapia , Desoxicitidina/análogos & derivados , Neoplasias Musculares/terapia , Radioterapia Conformacional/métodos , Neoplasias da Bexiga Urinária/terapia , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Terapia Combinada , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Musculares/mortalidade , Neoplasias Musculares/secundário , Invasividade Neoplásica , Estadiamento de Neoplasias , Radioterapia Conformacional/efeitos adversos , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Gencitabina
4.
BJU Int ; 107(11): 1762-8, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21083643

RESUMO

STUDY TYPE: Preference (prospective cohort). LEVEL OF EVIDENCE: 1b. What's known on the subject? and What does the study add? In general the literature suggests that there is a need for improvement in aiding men diagnosed with early prostate cancer in their decision making about treatment options and that our understanding of this process is inadequate. There is limited data analyzing the reasons why these men decide between potentially curative or observational treatments and data evaluating patients' views before and after definitive therapy are scarce. This study begins the process of understanding the reasons underlying a patient's final treatment decision. Being a prospective study, it looks at the thought processes of these men before treatment during the time the decision is made. It also documents how satisfied patients are with their choice after their treatment and whether they would choose the same treatment again. OBJECTIVE: To identify the reasons for patients with localised prostate cancer choosing between treatments and the relationship of procedure type to patient satisfaction post-treatment. PATIENTS AND METHODS: 768 men with prostate cancer (stage T1/2, Gleason≤7, PSA<20 ug/L) chose between four treatments: radical prostatectomy, brachytherapy, conformal radiotherapy and active surveillance. Prior to choosing, patients were counselled by a urological surgeon, clinical (radiation) oncologist and uro-oncology specialist nurse. Pre-treatment reasons for choice were recorded. Post-treatment satisfaction was examined via postal questionnaire. RESULTS: Of the 768 patients, 305 (40%) chose surgery, 237 (31%) conformal beam radiotherapy, 165 (21%) brachytherapy and 61 (8%) active surveillance. Sixty percent of men who opted for radical prostatectomy were motivated by the need for physical removal of the cancer. Conformal radiotherapy was mainly chosen by patients who feared other treatments (n=63, 27%). Most men chose brachytherapy because it was more convenient for their lifestyle (n=64, 39%). Active surveillance was chosen by patients for more varied reasons. Post-treatment satisfaction was assessed in a subgroup who took part in the QOL aspect of this study. Of the respondents to the questionnaire, 212(87.6%) stated that they were satisfied/extremely satisfied with their choice and 171(92.9%) indicated they would choose the same treatment again. CONCLUSION: Men with early prostate cancer have clear reasons for making decisions about treatment. Overall, patients were satisfied with the treatment and indicated that despite different reasons for choosing treatment, they would make the same choice again.


Assuntos
Braquiterapia/tendências , Observação/métodos , Prostatectomia/tendências , Neoplasias da Próstata/terapia , Radioterapia Conformacional/tendências , Adulto , Fatores Etários , Idoso , Braquiterapia/métodos , Estudos de Coortes , Tomada de Decisões , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Preferência do Paciente , Estudos Prospectivos , Prostatectomia/métodos , Neoplasias da Próstata/patologia , Radioterapia Conformacional/métodos , Medição de Risco , Inquéritos e Questionários , Reino Unido
5.
Eur J Cancer ; 46(3): 534-40, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20022742

RESUMO

We investigated the efficacy of data capture of patient-reported toxicity following radiotherapy by comparing electronic and paper formats. Patient-reported toxicity questionnaires based on items from the NCI Common Terminology Criteria for Adverse Events (CTCAE) were created for patients receiving radiotherapy. Electronic and paper questionnaires had identical questions. Thirty seven gynaecological cancer and 40 prostate cancer patients completed questionnaires. Both questionnaire formats (electronic and paper) were completed by each patient at time points before and after radiotherapy. The average questionnaire and subsection scores for each format were compared directly and by using intra-class correlation (ICC) coefficients. The internal consistency/reliability was assessed by determining Cronbach's alpha coefficient. Patient preference for questionnaire format including clarity and ease-of-use was recorded. 324 questionnaires were collected as part of this study. A similar pattern of average subsection scores was found for the electronic and paper questionnaires. ICC coefficients for the mean overall questionnaire scores and subsection scores were high (>0.8). Cronbach's alpha was generally greater than 0.6, indicating that the reliability was high. Of the patients that responded, 27.3% preferred the electronic format, 25.7% preferred the paper format and 47% had no preference. The average time taken to complete a questionnaire was about 9 minutes for each format. The different questionnaire formats measured toxicity effects consistently and were reliable for both gynaecological cancer and prostate cancer patients. The survey indicated that patients found the questionnaires clear, easy to understand and straightforward to complete. Electronic data capture of patient-reported toxicity for CTCAE is feasible and acceptable.


Assuntos
Neoplasias da Próstata/radioterapia , Lesões por Radiação/etiologia , Inquéritos e Questionários , Neoplasias do Colo do Útero/radioterapia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Preferência do Paciente , Estudos Prospectivos , Neoplasias da Próstata/patologia , Radioterapia/efeitos adversos , Fatores de Tempo , Interface Usuário-Computador , Neoplasias do Colo do Útero/patologia
6.
Int J Radiat Oncol Biol Phys ; 75(3): 664-71, 2009 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-19473781

RESUMO

PURPOSE: Organ motion is recognized as the principal source of inaccuracy in bladder radiotherapy (RT), but there is currently little information on intrafraction bladder motion. METHODS AND MATERIALS: We used cine-magnetic resonance imaging (cine-MRI) to study bladder motion relevant to intrafraction RT delivery. On two occasions, a 28 minute cine-MRI sequence was acquired from 10 bladder cancer patients and 5 control participants immediately after bladder emptying, after abstinence from drinking for the preceding hour. From the resulting cine sequences, bladder motion was subjectively assessed. To quantify bladder motion, the bladder was contoured in imaging volume sets at 0, 14, and 28 min to measure changes to bladder volumes, wall displacements, and center of gravity (COG) over time. RESULTS: The dominant source of bladder motion during imaging was bladder filling (up to 101% volume increase); rectal and small bowel movements were transient, with minimal impact. Bladder volume changes were similar for all participants. However for bladder cancer patients, wall displacements were larger (up to 58 mm), less symmetrical, and more variable compared with nondiseased control bladders. CONCLUSIONS: Significant and individualized intrafraction bladder wall displacements may occur during bladder RT delivery. This important source of inaccuracy should be incorporated into treatment planning and verification.


Assuntos
Imagem Cinética por Ressonância Magnética , Movimento , Neoplasias da Bexiga Urinária/radioterapia , Bexiga Urinária/anatomia & histologia , Idoso , Estudos de Casos e Controles , Fracionamento da Dose de Radiação , Feminino , Humanos , Intestino Delgado/anatomia & histologia , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Estudos Prospectivos , Reto/anatomia & histologia , Reprodutibilidade dos Testes , Carga Tumoral , Neoplasias da Bexiga Urinária/patologia , Urina
7.
Int J Radiat Oncol Biol Phys ; 75(4): 990-3, 2009 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-19345515

RESUMO

PURPOSE: To compare postprostatectomy clinical target volume (CTV) delineation before and after the introduction of a contouring protocol and to investigate its effect on interphysician variability METHODS AND MATERIALS: Six site-specialized radiation oncologists independently delineated a CTV on the computed tomography (CT) scans of 3 patients who had received postprostatectomy radiotherapy. At least 3 weeks later this was repeated, but with the physicians adhering to the contouring protocol from the Medical Research Council's Radiotherapy and Androgen Deprivation In Combination After Local Surgery (RADICALS) trial. The volumes obtained before and after the protocol were compared and the effect of the protocol on interphysician variability assessed. RESULTS: An increase in mean CTV for all patients of 40.7 to 53.9 cm(3) was noted as a result of observing the protocol, with individual increases in the mean CTV of 65%, 15%, and 24% for Patients 1, 2, and 3 respectively. A reduction in interphysician variability was noted when the protocol was used. CONCLUSIONS: Substantial interphysician variation in target volume delineation for postprostatectomy radiotherapy exists, which can be reduced by the use of a contouring protocol. The RADICALS contouring protocol increases the target volumes when compared with those volumes typically applied at our center. The effect of treating larger volumes on the therapeutic ratio and resultant toxicity should be carefully monitored, particularly if the same dose-response as documented in radical prostate radiotherapy applies to the adjuvant and salvage setting. Prostate cancer, Postprostatectomy, Radiotherapy, Target volume.


Assuntos
Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Radioterapia (Especialidade)/normas , Idoso , Carga Corporal (Radioterapia) , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Doses de Radiação , Radioterapia Adjuvante , Tomografia Computadorizada por Raios X
8.
Int J Radiat Oncol Biol Phys ; 74(4): 1121-7, 2009 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-19131179

RESUMO

PURPOSE: Dose escalation for prostate cancer improves biological control but with a significant increase in late toxicity. Recent estimates of low alpha/beta ratio for prostate cancer suggest that hypofractionation may result in biological advantage. Intensity-modulated radiotherapy (IMRT) should enable dose escalation to the prostate while reducing toxicity to local organs. We report late toxicity data of a hypofractionated IMRT regime. METHODS AND MATERIALS: Eligible men had T2-3N0M0 adenocarcinoma prostate, and either Gleason score >or= 7 or prostate-specific antigen 20-50 ng/L. Patients received 57-60 Gy to prostate in 19-20 fractions using five-field IMRT. All received hormonal therapy for 3 months before radiotherapy to a maximum of 6 months. Toxicity was assessed 2 years postradiotherapy using the RTOG criteria, LENT/SOMA, and UCLA prostate index assessment tools. RESULTS: Acute toxicity was favorable with no RTOG Grade 3 or 4 toxicity. At 2 years, there was 4% Grade 2 bowel and 4.25% Grade 2 bladder toxicity. There was no Grade 3 or 4 bowel toxicity; one patient developed Grade 3 bladder toxicity. UCLA data showed a slight improvement in urinary function at 2 years compared with pretreatment. LENT/SOMA assessments demonstrated general worsening of bowel function at 2 years. Patients receiving 60 Gy were more likely to develop problems with bowel function than those receiving 57 Gy. CONCLUSIONS: These data demonstrate that hypofractionated radiotherapy using IMRT for prostate cancer is well tolerated with minimal late toxicity at 2 years posttreatment. Ongoing studies are looking at the efficacy of hypofractionated regimes with respect to biological control.


Assuntos
Neoplasias da Próstata/radioterapia , Radioterapia de Intensidade Modulada/efeitos adversos , Adenocarcinoma , Idoso , Idoso de 80 Anos ou mais , Fracionamento da Dose de Radiação , Humanos , Intestinos/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Lesões por Radiação/complicações , Bexiga Urinária/efeitos da radiação
9.
Lancet Oncol ; 8(6): 475-87, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17482880

RESUMO

BACKGROUND: In men with localised prostate cancer, conformal radiotherapy (CFRT) could deliver higher doses of radiation than does standard-dose conventional radical external-beam radiotherapy, and could improve long-term efficacy, potentially at the cost of increased toxicity. We aimed to present the first analyses of effectiveness from the MRC RT01 randomised controlled trial. METHODS: The MRC RT01 trial included 843 men with localised prostate cancer who were randomly assigned to standard-dose CFRT or escalated-dose CFRT, both administered with neoadjuvant androgen suppression. Primary endpoints were biochemical-progression-free survival (bPFS), freedom from local progression, metastases-free survival, overall survival, and late toxicity scores. The toxicity scores were measured with questionnaires for physicians and patients that included the Radiation Therapy Oncology Group (RTOG), the Late Effects on Normal Tissue: Subjective/Objective/Management (LENT/SOM) scales, and the University of California, Los Angeles Prostate Cancer Index (UCLA PCI) scales. Analysis was done by intention to treat. This trial is registered at the Current Controlled Trials website http://www.controlled-trials.com/ISRCTN47772397. FINDINGS: Between January, 1998, and December, 2002, 843 men were randomly assigned to escalated-dose CFRT (n=422) or standard-dose CFRT (n=421). In the escalated group, the hazard ratio (HR) for bPFS was 0.67 (95% CI 0.53-0.85, p=0.0007). We noted 71% bPFS (108 cumulative events) and 60% bPFS (149 cumulative events) by 5 years in the escalated and standard groups, respectively. HR for clinical progression-free survival was 0.69 (0.47-1.02; p=0.064); local control was 0.65 (0.36-1.18; p=0.16); freedom from salvage androgen suppression was 0.78 (0.57-1.07; p=0.12); and metastases-free survival was 0.74 (0.47-1.18; p=0.21). HR for late bowel toxicity in the escalated group was 1.47 (1.12-1.92) according to the RTOG (grade >/=2) scale; 1.44 (1.16-1.80) according to the LENT/SOM (grade >/=2) scales; and 1.28 (1.03-1.60) according to the UCLA PCI (score >/=30) scale. 33% of the escalated and 24% of the standard group reported late bowel toxicity within 5 years of starting treatment. HR for late bladder toxicity according to the RTOG (grade >/=2) scale was 1.36 (0.90-2.06), but this finding was not supported by the LENT/SOM (grade >/=2) scales (HR 1.07 [0.90-1.29]), nor the UCLA PCI (score >/=30) scale (HR 1.05 [0.81-1.36]). INTERPRETATION: Escalated-dose CFRT with neoadjuvant androgen suppression seems clinically worthwhile in terms of bPFS, progression-free survival, and decreased use of salvage androgen suppression. This additional efficacy is offset by an increased incidence of longer term adverse events.


Assuntos
Neoplasias da Próstata/radioterapia , Radioterapia Conformacional , Idoso , Antagonistas de Androgênios/uso terapêutico , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Neoplasias da Próstata/tratamento farmacológico , Dosagem Radioterapêutica
10.
Int J Radiat Oncol Biol Phys ; 67(1): 84-90, 2007 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-17189065

RESUMO

PURPOSE: Vascular endothelial growth factor (VEGF) is an important hypoxia-inducible pro-angiogenic protein that has been linked with an adverse survival outcome after radiotherapy in other cancer types: we hypothesized that this may also occur in prostate cancer. A retrospective study was, therefore, carried out to evaluate the potential of tumor VEGF expression to predict radiotherapy outcome in patients with high-risk prostate cancer. METHODS AND MATERIALS: Fifty patients with locally advanced (T3 N0 M0) tumors of Gleason score > or =6, and who received radiotherapy alone as primary treatment for their disease, were studied. Vascular endothelial growth factor expression was assessed on pretreatment diagnostic tumor biopsies using a semiquantitative immunohistochemical scoring system. The results were analyzed in relation to clinicopathologic factors and patient outcome including biochemical failure and disease-specific mortality. RESULTS: High VEGF expression was associated with a poor prognosis: in univariate log rank analysis, VEGF was the only significant prognostic factor for disease-specific survival (p = 0.035). High VEGF expression also associated with increased Gleason score (p = 0.02), but not posttreatment biochemical failure. CONCLUSION: High tumor expression of VEGF identified patients at high risk of failure of treatment with radiotherapy. These patients might benefit from additional treatment approaches incorporating anti-angiogenic or hypoxia-specific agents.


Assuntos
Proteínas de Neoplasias/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/radioterapia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Idoso , Intervalo Livre de Doença , Humanos , Modelos Lineares , Masculino , Prognóstico , Próstata/metabolismo , Próstata/efeitos da radiação , Estudos Retrospectivos , Resultado do Tratamento
11.
Int J Radiat Oncol Biol Phys ; 61(2): 420-5, 2005 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-15667962

RESUMO

PURPOSE: A prospective phase I trial was conducted to determine the maximal tolerated dose of gemcitabine given once weekly during hypofractionated conformal radiotherapy to patients with locally advanced transitional cell carcinoma of the bladder. Eight male patients, median age 69 years, with Stage T2 (n = 4) or T3 (n = 4) N0M0, were enrolled in cohorts of 3. Treatment comprised conformal radiotherapy (52.5 Gy in 20 fractions) within 4 weeks, with concurrent gemcitabine once weekly for four cycles. The weekly gemcitabine dose was escalated from 100 mg/m(2) in increments of 50 mg/m(2) per cohort. Dose-limiting toxicity was defined as any acute Radiation Therapy Oncology Group (RTOG) toxicity Grade 3 or greater arising in >1 of 3 patients in each cohort. Tumor response was assessed cystoscopically and radiologically at 3 months. RESULTS: All 8 patients completed radiotherapy, and 6 of 8 completed chemoradiotherapy. No acute toxicity greater than RTOG Grade 1 was seen with gemcitabine at 100 mg/m(2). Dose-limiting toxicity was observed at 150 mg/m(2) with Grade 3 toxicity seen in 2 of 2 patients (one bladder, one bowel). An additional 3 patients received 100 mg/m(2) with minimal toxicity. No hematologic toxicity was encountered. A complete response was seen in 7 (87.5%) of 8 patients, all of whom were disease free at a median follow-up of 19.5 months (range, 14-23 months). No late toxicity (greater than RTOG Grade 0) has been observed. CONCLUSION: The maximal tolerated dose for gemcitabine given once weekly with concurrent hypofractionated conformal bladder radiotherapy was 150 mg/m(2), with a maximal recommended dose of 100 mg/m(2). This dose regimen has now entered Phase II clinical trials.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/radioterapia , Desoxicitidina/análogos & derivados , Desoxicitidina/administração & dosagem , Radiossensibilizantes/administração & dosagem , Radioterapia Conformacional , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/radioterapia , Idoso , Antimetabólitos Antineoplásicos/efeitos adversos , Carcinoma de Células de Transição/patologia , Terapia Combinada , Desoxicitidina/efeitos adversos , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Estudos Prospectivos , Radiossensibilizantes/efeitos adversos , Neoplasias da Bexiga Urinária/patologia , Gencitabina
12.
Int J Radiat Oncol Biol Phys ; 60(4): 1076-81, 2004 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-15519777

RESUMO

PURPOSE: Many studies have described the quantitated differences between clinicians in target volume definition in prostate cancer. However, few studies have looked at the clinical effects of this. We aimed to assess the relevance and sequelae of such differences. METHODS AND MATERIALS: Five experienced radiation oncologists were given the clinical details of 5 patients with early-stage prostate cancer and asked to define the clinical target volume, consisting of the prostate and seminal vesicles (CTV1) and the prostate alone (CTV2), on specified planning CT scans of the pelvis. Planning target volumes (PTV1) were generated by automatic expansion of the CTV1 by a 1-cm margin. The PTV2 was defined as the CTV2. The rectum and bladder were defined by a single experienced clinician for each plan without knowledge of the involved clinician marking the CTVs. The Pinnacle planning system was used to generate the plans, using four-field conformal radiotherapy, to deliver 64 Gy in 32 fractions to the PTV1 followed by a boost of 10 Gy to the PTV2 (Medical Research Council RT01 trial protocol). Dose-volume histograms were generated for the whole bladder and rectum for each plan and the volume receiving a specific percentage of the dose (e.g., V(90)) calculated for 74 Gy, followed by estimates of normal tissue complication probabilities (NTCPs) for the bladder and rectum. RESULTS: Statistically significant differences were found in the CTV1 and CTV2 and, consequently, the PTV1 among the 5 clinicians (p < 0.0005). Most of the discrepancies occurred at the delineation of the prostatic apex and seminal vesicles, with the smallest variance noted at the rectum-prostate and bladder-prostate interfaces. No statistically significant differences were found among clinicians for the rectal V(90), V(85), V(80), V(70), or V(50) or for the bladder V(85), V(80), V(70), or V(50). A difference was noted among consultants for the bladder V(90) (p = 0.015), although no correlation was found between the bladder V(90) and the size of the outlined volumes. No statistically significant differences were found between the estimates of bladder (p = 0.1) and rectal (p = 0.09) NTCPs. CONCLUSION: The statistically significant difference in outlined volumes of the CTV1, CTV2, and PTV1 among the 5 clinicians is in keeping with the findings of previous studies. However, the interclinician variability did not result in clinically relevant outcomes with respect to the irradiated volume of rectum and bladder or NTCP. This may have been because the outlined areas in which interclinician differences were smallest (the rectal-prostate and prostate-bladder interfaces) are the areas that have the greatest effect on normal tissue toxicity. For the areas in which the interclinician correlation was lowest (the prostatic apex and distal seminal vesicles), the effects on normal tissue toxicity are smallest. The results of this study suggest that interclinician outlining differences in prostate cancer may have less clinical relevance than was previously thought.


Assuntos
Próstata/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Radioterapia (Especialidade)/normas , Planejamento da Radioterapia Assistida por Computador , Glândulas Seminais/diagnóstico por imagem , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Próstata/patologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , Radiografia , Radioterapia Conformacional , Reto/diagnóstico por imagem , Carga Tumoral , Bexiga Urinária/diagnóstico por imagem
13.
Int J Radiat Oncol Biol Phys ; 59(1): 197-207, 2004 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-15093917

RESUMO

PURPOSE: To investigate whether delivering an increased radiation dose to the tumor-bearing region of the bladder alone would improve local disease control without increasing treatment toxicity. METHODS AND MATERIALS: A total of 149 patients with unifocal T2-T3N0M0 bladder carcinoma were randomized between whole bladder conformal radiotherapy (WBRT, 52.5 Gy in 20 fractions, n = 60) and partial bladder conformal RT (PBRT) to tumor alone with 1.5-cm margins within either 4 weeks (PBRT4, 57.5 Gy in 20 fractions, n = 44) or 3 weeks (PBRT3, 55 Gy in 16 fractions, n = 45). The response was assessed cystoscopically after 4 months. RESULTS: The 5-year overall and CFS rate was 58% and 47%, respectively, for the whole population. The CR rate was 75% for WBRT, 80% for PBRT4, and 71% for PBRT3 (p = 0.6), with a 5-year local control rate of 58%, 59%, and 34%, respectively (p = 0.18). Solitary new tumors arose within the bladder, outside the irradiated volume, in 6 (7%) of 89 patients who underwent PBRT. The 5-year overall survival and cystectomy-free survival rate was 61% and 49% for WBRT, 60% and 50% for PBRT4, and 51% and 41% for PBRT3 (p = 0.81 and p = 0.59). The treatment toxicity was mild and equivalent across the three trial arms. CONCLUSION: The reduction in treatment volume allowed delivery of an increased radiation dose without a reduction in local tumor control or the development of excess toxicity. However, this dose-escalated partial bladder approach did not result in significantly improved overall survival.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células de Transição/radioterapia , Radioterapia Conformacional/métodos , Neoplasias da Bexiga Urinária/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Cistoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Estudos Prospectivos , Lesões por Radiação/classificação , Dosagem Radioterapêutica , Indução de Remissão , Terapia de Salvação , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia
14.
Int J Radiat Oncol Biol Phys ; 57(5): 1254-9, 2003 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-14630259

RESUMO

PURPOSE: Recent publications have indicated that the alpha/beta ratios for carcinoma of the prostate are much lower than had originally been thought, suggesting that prostate cancer may be highly sensitive to fraction size. We have reviewed our unique experience of the use of 3.13 Gy fractions in a large cohort of men treated homogeneously in a single institute. MATERIALS AND METHODS: The outcome for 705 men with T1-T4, N0, M0 prostate cancer who received conformal radiotherapy between 1995 and 1998 at this center was analyzed. No patient received hormonal manipulation. Mean age was 68 years (range: 49-84 years). Median pretreatment PSA was 13 ng/mL (range: 0.6-270 ng/mL). Disease characteristics were as follows: Stage T1, 125 (18%); T2, 365 (52%); T3/4, 215 (30%); Gleason 2-6, 463 (66%); Gleason 7-10, 242 (34%); pretreatment PSA < or =10 ng/mL, 291 (41%); 10 to < or =20, 228 (32%); >20, 186 (27%). Median follow-up was 48 months (range: 1-82 months). Biochemical-free survival (bNED) was defined by the American Society for Therapeutic Radiology and Oncology consensus definition. Radiotherapy was delivered to a planning target volume (prostate plus all/base of the seminal vesicles dependent on risk criteria with a 1-cm margin) with a 4-field conformal technique to a dose of 50 Gy in 16 daily fractions over 22 days. RESULTS: The 5-year bNED survival was significantly associated (p < 0.001) with pretreatment PSA, stage, and Gleason score. Five-year bNED rates with respect to pretreatment characteristics were as follows: 73% (PSA < or =10), 52% (>10-20), 35% (>20), 64% (Stage T1/2), 38% (T3/4), 61% (Gleason score 2-6), and 46% (Gleason > or =7). When patients were grouped into good (Stage T1/2, PSA < or =10 ng/mL, and Gleason score <7) (n = 181), intermediate (1 raised value) (n = 247), or poor (2 or more raised values) (n = 277) prognostic groups, the bNED was, respectively, 82%, 56%, and 39%. Radiation Therapy Oncology Group Grade > or =2 bowel toxicity was 5% and bladder 9%. CONCLUSIONS: These data indicate that the delivery of a relatively low total dose using a hypofractionated regime results in similar tumor control and normal-tissue toxicity to 65-70 Gy delivered in 1.8-2 Gy fractions. These data suggest that this is an acceptable regime for good-prognosis patients. However, because of the evidence for a dose effect at doses above 70 Gy with "conventional fractionation," we are now treating intermediate- and poor-risk patients within a hypofractionated dose escalation trial to 60 Gy in 20 fractions using intensity- modulated radiotherapy.


Assuntos
Neoplasias da Próstata/radioterapia , Radioterapia Conformacional/métodos , Idoso , Intervalos de Confiança , Fracionamento da Dose de Radiação , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/mortalidade , Análise de Sobrevida
15.
Radiother Oncol ; 65(2): 109-21, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12443807

RESUMO

BACKGROUND AND PURPOSE: To assess the correlation between different general and organ specific quality of life and morbidity scoring methods in a cohort of men treated with radical radiotherapy for prostate cancer. MATERIALS AND METHODS: Men who had been treated with radical radiotherapy (50 Gy in 16 fractions over 21 days) for localized prostate cancer more than 3 years previously and who had no evidence of recurrent disease were invited to take part in the study. A total of 101 of 135 invited patients agreed and completed LENT/SOMA, UCLA Prostate Cancer Index, and 36 item RAND Health survey questionnaires. RESULTS: The patients had comparable results with other published series with respect to the UCLA and SF-36 indices. There was significant correlation between the corresponding parts of the UCLA and LENT/SOMA scales (P<0.0005). However, for the same symptoms, a patient tended to score lower (worse) on the UCLA scale in comparison to LENT/SOMA. The relationship between the average LENT/SOMA score and maximum score was also not straightforward with each set of data revealing different information. CONCLUSIONS: The LENT/SOMA questions were, in the main, more wide-ranging and informative than the UCLA index. It is helpful to give both the overall and maximum LENT/SOMA scores to most efficiently use all of the data. There may need to be a further LENT/SOMA question to allow both symptoms of tenesmus and faecal urgency to be fully addressed.


Assuntos
Neoplasias da Próstata/psicologia , Neoplasias da Próstata/radioterapia , Radioterapia Conformacional/efeitos adversos , Perfil de Impacto da Doença , Idoso , Idoso de 80 Anos ou mais , Humanos , Doenças Inflamatórias Intestinais/etiologia , Masculino , Pessoa de Meia-Idade , Qualidade de Vida/psicologia , Disfunções Sexuais Fisiológicas/etiologia , Inquéritos e Questionários , Fatores de Tempo , Doenças da Bexiga Urinária/etiologia
16.
Br J Haematol ; 119(2): 408-11, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12406078

RESUMO

Bone marrow aspirates (BMA) and trephine biopsies (BMT) are commonly performed in the staging of patients with newly diagnosed Hodgkin's lymphoma (HL) but the value of these procedures is controversial. The purpose of this study was to evaluate the predictive value of the blood count and erythrocyte sedimentation rate (ESR) for bone marrow involvement (BMI) and the influence of BMI on stage and prognostic score. A retrospective analysis of 955 patients with newly diagnosed HL entered into clinical trials in a regional cancer centre between 1975 and 1999 was performed. BMI was identified by BMT in 50 patients (5.2%) but in only five of these by BMA. The negative predictive values of a normal full blood count (FBC) and ESR for absence of BMI were 98.8% and 97.3%, respectively, and the positive predictive value of an abnormal FBC and ESR for presence of BMI were both 6.7%. BMT did not alter initial patient management in a single case but provided valuable prognostic information in certain subgroups of patients. BMA gave no additional staging information over BMT and abnormalities of blood count and ESR were poor predictors of infiltration. We conclude that BMA should be abandoned for staging purposes in HL and BMT restricted to patients with stage IIB or III disease, for whom valuable prognostic information may be obtained.


Assuntos
Exame de Medula Óssea , Doença de Hodgkin/patologia , Adulto , Contagem de Células Sanguíneas , Sedimentação Sanguínea , Institutos de Câncer , Distribuição de Qui-Quadrado , Feminino , Doença de Hodgkin/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco
17.
Br J Haematol ; 119(2): 459-66, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12406086

RESUMO

Autologous lymphocytes provide a potential vector for the delivery of a cytotoxic agent in patients with lymphoid cell malignancy. This report describes a phase I-II study using autologous lymphocytes to target the radionuclide indium-114m ((114m)In) in patients with refractory chronic lymphocytic leukaemia or small lymphocytic non-Hodgkin's lymphoma. Nineteen patients, the majority of whom had been heavily pretreated with conventional chemotherapy and radiotherapy, received between 69 and 211 MBq (114m)In-labelled autologous lymphocytes. Approximately 80% of the administered activity was localized in the liver and spleen, with around 5% accumulating in the bone marrow. Ten patients (53%) responded (one complete response and nine partial responses). The median duration of response was 7 months. The median survival for the responders was 14 months and for the non-responders was 3 months. The first notable response in every patient was a fall in peripheral lymphocyte count. The indium treatment was not associated with any subjective toxicity, although all patients suffered from myelosuppression, with thrombocytopenia being the dose-limiting factor. This study has demonstrated a significant anti-tumour effect in a group of patients with late-stage highly resistant disease.


Assuntos
Radioisótopos de Índio/uso terapêutico , Leucemia Linfocítica Crônica de Células B/radioterapia , Linfócitos , Radioimunoterapia/métodos , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/efeitos da radiação , Relação Dose-Resposta à Radiação , Feminino , Meia-Vida , Humanos , Fígado/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Baço/efeitos da radiação , Transplante Autólogo
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