[show abstract][hide abstract] ABSTRACT: Objective To report outcomes and late toxicity for a hypofractionated dose-escalated radiotherapy schedule in patients treated using intensity-modulated radiotherapy (IMRT) for localised prostate cancer.Materials and methods Eighty-eight men with localised prostate cancer were treated with 57 Gy in 19 daily fractions over 4 weeks. A total of 70 out of 88 had high-risk disease. Overall survival, cause-specific survival and biochemical progression-free survival (bPFS, Phoenix definition) were reported. Toxicity was measured retrospectively using Radiation Therapy Oncology Group (RTOG) criteria and assessed prospectively with a validated Late Effects in Normal Tissues Subjective, Objective, Management and Analytic (LENT/SOMA) patient questionnaire.Results At 5 years, overall survival was 84%, cause-specific survival 88% and bPFS 65%. In patients with high-risk disease, 5-year bPFS was 62%. There was no RTOG toxicity above grade III. LENT/SOMA questionnaires were returned by 74% patients. Median scores for bowel and urinary function were <1. Maximum bowel and urinary toxicity scores ≥2 were reported by 64% and 59% of patients, respectively. The median score for sexual function was 1·5, but nearly all (96%) patients recorded a toxicity score ≥2 for at least one question.Conclusions Dose-escalated hypofractionated radiotherapy delivered using IMRT has promising outcomes and acceptable late toxicity. This fractionation schedule is being compared with conventional treatment within an on-going multicentre phase III clinical trial.
Journal of Radiotherapy in Practice 12/2013; 12(04).
[show abstract][hide abstract] ABSTRACT: Treatment of muscle-invasive bladder cancer with chemotherapy results in haemorrhagic inflammation, mimicking residual tumour on conventional MR images and making interpretation difficult. The aim of this study was to use dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to estimate descriptive and tracer kinetic parameters post-neoadjuvant chemotherapy and to investigate whether parameters differed in areas of residual tumour and chemotherapy-induced haemorrhagic inflammation (treatment effect, Tr-Eff).
Twenty-one patients underwent DCE-MRI scans with 2.5s temporal resolution before and following neoadjuvant chemotherapy. Regions-of-interest (ROIs) were defined in areas suspicious of residual tumour on T2-weighted MRI scans. Data were analysed semi-quantitatively and with a two-compartment exchange model to obtain parameters including relative signal intensity (rSI80s) and plasma perfusion (Fp) respectively. The bladder was subsequently examined histologically after cystectomy for evidence of residual tumour and/or Tr-Eff. Differences in parameters measured in areas of residual tumour and Tr-Eff were examined using Student's t-test.
Twenty-four abnormal sites were defined after neoadjuvant chemotherapy. On pathology, 10 and 14 areas were identified as residual tumour and Tr-Eff respectively. Median rSI80s and Fp were significantly higher in areas of residual tumour than Tr-Eff (rSI80s=2.9 vs 1.7, p<0.001; Fp=20.7 vs 9.1ml/100ml/min, p=0.03). The sensitivity and specificity for differentiating residual tumour from Tr-Eff were 70% and 100% (rSI80s), 60% and 86% (Fp), and 75% and 100% when combined.
DCE-MRI parameters obtained post-treatment are capable of distinguishing between residual tumour and treatment effect in patients treated for bladder cancer with neoadjuvant chemotherapy.
European journal of radiology 08/2013; · 2.65 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background. The benefit of dose-escalated hypofractionated radiotherapy using intensity-modulated radiotherapy (IMRT) in prostate cancer is not established. We report 5-year outcome and long-term toxicity data within a phase II clinical trial. Materials and Methods. 60 men with predominantly high-risk prostate cancer were treated. All patients received neoadjuvant hormone therapy, completing up to 6 months in total. Thirty patients were treated with 57 Gy in 19 fractions and 30 patients with 60 Gy in 20 fractions. Acute and 2-year toxicities were reported and patients followed longitudinally to assess 5 year outcomes and long-term toxicity. Toxicity was measured using RTOG criteria and LENT/SOMA questionnaire. Results. Median followup was 84 months. Five-year overall survival (OS) was 83% and biochemical progression-free survival (bPFS) was 50% for 57 Gy. Five-year OS was 75% and bPFS 58% for 60 Gy. At 7 years, toxicity by RTOG criteria was acceptable with no grade 3 or above toxicity. Compared with baseline, there was no significant change in urinary symptoms at 2 or 7 years. Bowel symptoms were stable between 2 and 7 years. All patients continued to have significant sexual dysfunction. Conclusion. In high-risk prostate cancer, dose-escalated hypofractionated radiotherapy using IMRT results in encouraging outcomes and acceptable late toxicity.
[show abstract][hide abstract] ABSTRACT: 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).
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.
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%.
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.
Journal of Clinical Oncology 02/2011; 29(6):733-8. · 18.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: To investigate potential differences in zibotentan pharmacokinetics between Japanese and Caucasian patients with hormone-resistant prostate cancer (HRPC) following single and multiple dosing.
In the Japanese study, 18 patients received a single dose of zibotentan 5, 10 or 15 mg followed by 72 h washout before 26 days' once-daily dosing. In the Caucasian study, 21 patients received a single dose of zibotentan 5, 10 or 15 mg followed by 72 h washout before 12 days' once-daily dosing.
Pharmacokinetic parameters were similar between populations. Absorption of zibotentan was rapid with maximum plasma concentrations typically achieved within 3 h of dosing. Mean clearance, 17.9 and 18.7 ml/min in Japanese and Caucasian patients, respectively (range 7.0 - 36.3 ml/min in Japanese patients and 7.8 - 29.5 ml/min in Caucasian patients) and volume of distribution, 14.0 and 15.6 l for Japanese and Caucasian patients, respectively (range 7.9 - 29.1 l in Japanese patients and 9.6 - 23.8 l in Caucasian patients) were relatively low, and t1/2 was approximately 12 h (range 5.7 - 18.8 h in Japanese patients and 5.0 - 22.9 h in Caucasian patients) following single dosing. Little accumulation was observed following daily dosing and multiple-dose pharmacokinetics were predictable. Exposure levels achieved in some Japanese patients receiving zibotentan 15 mg were higher than those observed in Caucasian patients, however, this may be due to differences in body weight, as exposure levels were similar when data were normalized for body weight. Zibotentan was well tolerated in both populations.
There are no clinically relevant differences in the disposition and pharmacokinetics of zibotentan between Japanese and Caucasian patients with HRPC.
International journal of clinical pharmacology and therapeutics 11/2010; 48(11):708-17. · 1.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: Preference (prospective cohort).
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.
To identify the reasons for patients with localised prostate cancer choosing between treatments and the relationship of procedure type to patient satisfaction post-treatment.
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.
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.
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.
BJU International 11/2010; 107(11):1762-8. · 3.05 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
European journal of cancer (Oxford, England: 1990) 12/2009; 46(3):534-40. · 4.12 Impact Factor
[show abstract][hide abstract] ABSTRACT: Supradiaphragmatic radiotherapy (SRT) to treat Hodgkin's lymphoma (HL) at a young age increases the risk of breast cancer (BC). A national notification risk assessment and screening programme (NRASP) for women who were treated with SRT before the age of 36 years was instituted in the United Kingdom in 2003. In this study, we report the implementation and screening results from the largest English Cancer Network.
A total of 417 eligible women were identified through cancer registry/hospital databases and from follow-up (FU) clinics. Screening results were collated retrospectively, and registry searches were used to capture BC cases.
Of the 417 women invited for clinical review, 243 (58%) attended. Of these 417 women, 23 (5.5%) have been diagnosed with BC, a standardised incidence ratio of 2.9 compared with the age-matched general population. Of five invasive BCs diagnosed within the NRASP, none involved axillary lymph nodes compared with 7 of 13 (54%) diagnosed outside the programme (P<0.10). The mean latency for BC cases was 19.5+/-8.35 years and the mean FU duration for those unaffected by BC was 14.6+/-9.11 years (P<0.01), suggesting that those unaffected by BC remain at high risk. Recall and negative biopsy rates were acceptable (10.5 and 0.8%, respectively).
The NRASP appears to detect BC at an early stage with acceptable biopsy rates, although numbers are small. Determination of NRASP results on a national basis is required for the accurate evaluation of screening efficacy in women previously treated with SRT.
British Journal of Cancer 09/2009; 101(4):582-8. · 5.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: Organ motion is recognized as the principal source of inaccuracy in bladder radiotherapy (RT), but there is currently little information on intrafraction bladder motion.
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.
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.
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.
International journal of radiation oncology, biology, physics 06/2009; 75(3):664-71. · 4.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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
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.
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.
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.
International journal of radiation oncology, biology, physics 05/2009; 75(4):990-3. · 4.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
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.
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.
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.
International journal of radiation oncology, biology, physics 02/2009; 74(4):1121-7. · 4.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of the study was to assess levels of chemotherapy-induced nausea and vomiting (CINV) in routine practice.
The study was an observational prospective evaluation using patient self-reports. One hundred and two patients with cancer in a single cancer centre in UK receiving their first chemotherapy treatment participated in the study and were followed up over four cycles, providing a total of 272 assessments of nausea and vomiting. Data was collected with the use of the MASCC Antiemesis Tool (MAT), which is an eight-item short clinical scale assessing acute and delayed nausea and vomiting after chemotherapy.
Results indicated that acute vomiting was experienced by 15.7% of the patients in cycle 1 and delayed vomiting by 14.7%, while acute nausea was present in 37.3% of the patients and delayed nausea in 47.1%, increasing over the subsequent cycles. Moderately emetogenic and highly emetogenic chemotherapy had the highest incidence of CINV, whereas patients receiving highly emetogenic chemotherapy showed significant levels of delayed nausea. Acute symptoms were more easily controlled than delayed symptoms.
The data suggest that, while vomiting is well controlled, nausea remains a significant problem in practice, and optimal management of CINV is yet to be achieved. Understanding more clearly the biological basis of nausea will assist in managing this complex symptom more effectively in practice.
Supportive Care Cancer 03/2008; 16(2):201-8. · 2.65 Impact Factor