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Joe H Chang,
Morikatsu Wada,
Nigel J Anderson,
Daryl Lim Joon,
Sze Ting Lee,
Sylvia J Gong,
Dishan H Gunawardana,
John Sachinidis,
Graeme O'keefe,
Hui K Gan, Vincent Khoo,
Andrew M Scott
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ABSTRACT: Background. This study investigates the use of (18)F-fluoromisonidazole (FMISO) PET-guided radiotherapy dose painting for potentially overcoming the radioresistant effects of hypoxia in head and neck squamous cell carcinoma (HNSCC). Material and methods. The study cohort consisted of eight patients with HNSCC who were planned for definitive radiotherapy. Hypoxic subvolumes were automatically generated on pre-radiotherapy FMISO PET scans. Three radiotherapy plans were generated for each patient: a standard (STD) radiotherapy plan to a dose of 70 Gy, a uniform dose escalation (UDE) plan to the standard target volumes to a dose of 84 Gy, and a hypoxia dose-painted (HDP) plan with dose escalation only to the hypoxic subvolume to 84 Gy. Plans were compared based on tumor control probability (TCP), normal tissue complication probability (NTCP), and uncomplicated tumor control probability (UTCP). Results. The mean TCP increased from 73% with STD plans to 95% with the use of UDE plans (p < 0.001) and to 93% with HDP plans (p < 0.001). The mean parotid NTCP increased from 26% to 44% with the use of UDE plans (p = 0.003), and the mean mandible NTCP increased from 2% to 27% with the use of UDE plans (p = 0.001). There were no statistically significant differences between any of the NTCPs between the STD plans and HDP plans. The mean UTCP increased from 48% with STD plans to 66% with HDP plans (p = 0.016) and dropped to 37% with UDE plans (p = 0.138). Conclusion. Hypoxia-targeted radiotherapy dose painting for head and neck cancer using FMISO PET is technically feasible, increases the TCP without increasing the NTCP, and increases the UTCP. This approach is superior to uniform dose escalation.
Acta oncologica (Stockholm, Sweden) 01/2013; · 2.27 Impact Factor
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Joe H Chang,
Daryl Lim Joon,
Sze Ting Lee,
Sylvia J Gong,
Nigel J Anderson,
Andrew M Scott,
Ian D Davis,
David Clouston,
Damien Bolton,
Christopher S Hamilton, Vincent Khoo
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ABSTRACT: To demonstrate the technical feasibility of intensity modulated radiation therapy (IMRT) dose painting using (11)C-choline positron emission tomography PET scans in patients with localized prostate cancer.
This was an RT planning study of 8 patients with prostate cancer who had (11)C-choline PET scans prior to radical prostatectomy. Two contours were semiautomatically generated on the basis of the PET scans for each patient: 60% and 70% of the maximum standardized uptake values (SUV(60%) and SUV(70%)). Three IMRT plans were generated for each patient: PLAN(78), which consisted of whole-prostate radiation therapy to 78 Gy; PLAN(78-90), which consisted of whole-prostate RT to 78 Gy, a boost to the SUV(60%) to 84 Gy, and a further boost to the SUV(70%) to 90 Gy; and PLAN(72-90), which consisted of whole-prostate RT to 72 Gy, a boost to the SUV(60%) to 84 Gy, and a further boost to the SUV(70%) to 90 Gy. The feasibility of these plans was judged by their ability to reach prescription doses while adhering to published dose constraints. Tumor control probabilities based on PET scan-defined volumes (TCP(PET)) and on prostatectomy-defined volumes (TCP(path)), and rectal normal tissue complication probabilities (NTCP) were compared between the plans.
All plans for all patients reached prescription doses while adhering to dose constraints. TCP(PET) values for PLAN(78), PLAN(78-90), and PLAN(72-90) were 65%, 97%, and 96%, respectively. TCP(path) values were 71%, 97%, and 89%, respectively. Both PLAN(78-90) and PLAN(72-90) had significantly higher TCP(PET) (P=.002 and .001) and TCP(path) (P<.001 and .014) values than PLAN(78). PLAN(78-90) and PLAN(72-90) were not significantly different in terms of TCP(PET) or TCP(path). There were no significant differences in rectal NTCPs between the 3 plans.
IMRT dose painting for localized prostate cancer using (11)C-choline PET scans is technically feasible. Dose painting results in higher TCPs without higher NTCPs.
International journal of radiation oncology, biology, physics 05/2012; 83(5):e691-6. · 4.59 Impact Factor
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David Dearnaley,
Isabel Syndikus,
Georges Sumo,
Margaret Bidmead,
David Bloomfield,
Catharine Clark,
Annie Gao,
Shama Hassan,
Alan Horwich,
Robert Huddart, [......],
Helen Mayles,
Philip Mayles,
Olivia Naismith,
Chris Parker,
Helen Patterson,
Martin Russell,
Christopher Scrase,
Chris South,
John Staffurth,
Emma Hall
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ABSTRACT: Prostate cancer might have high radiation-fraction sensitivity, implying a therapeutic advantage of hypofractionated treatment. We present a pre-planned preliminary safety analysis of side-effects in stages 1 and 2 of a randomised trial comparing standard and hypofractionated radiotherapy.
We did a multicentre, randomised study and recruited men with localised prostate cancer between Oct 18, 2002, and Aug 12, 2006, at 11 UK centres. Patients were randomly assigned in a 1:1:1 ratio to receive conventional or hypofractionated high-dose intensity-modulated radiotherapy, and all were given with 3-6 months of neoadjuvant androgen suppression. Computer-generated random permuted blocks were used, with risk of seminal vesicle involvement and radiotherapy-treatment centre as stratification factors. The conventional schedule was 37 fractions of 2 Gy to a total of 74 Gy. The two hypofractionated schedules involved 3 Gy treatments given in either 20 fractions to a total of 60 Gy, or 19 fractions to a total of 57 Gy. The primary endpoint was proportion of patients with grade 2 or worse toxicity at 2 years on the Radiation Therapy Oncology Group (RTOG) scale. The primary analysis included all patients who had received at least one fraction of radiotherapy and completed a 2 year assessment. Treatment allocation was not masked and clinicians were not blinded. Stage 3 of this trial completed the planned recruitment in June, 2011. This study is registered, number ISRCTN97182923.
153 men recruited to stages 1 and 2 were randomly assigned to receive conventional treatment of 74 Gy, 153 to receive 60 Gy, and 151 to receive 57 Gy. With 50·5 months median follow-up (IQR 43·5-61·3), six (4·3%; 95% CI 1·6-9·2) of 138 men in the 74 Gy group had bowel toxicity of grade 2 or worse on the RTOG scale at 2 years, as did five (3·6%; 1·2-8·3) of 137 men in the 60 Gy group, and two (1·4%; 0·2-5·0) of 143 men in the 57 Gy group. For bladder toxicities, three (2·2%; 0·5-6·2) of 138 men, three (2·2%; 0·5-6·3) of 137, and none (0·0%; 97·5% CI 0·0-2·6) of 143 had scores of grade 2 or worse on the RTOG scale at 2 years.
Hypofractionated high-dose radiotherapy seems equally well tolerated as conventionally fractionated treatment at 2 years.
Stage 1 was funded by the Academic Radiotherapy Unit, Cancer Research UK programme grant; stage 2 was funded by the Department of Health and Cancer Research UK.
The lancet oncology 12/2011; 13(1):43-54. · 14.47 Impact Factor
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ABSTRACT: To evaluate the accuracy of (11)C-choline PET scans in defining dominant intraprostatic lesions (DILs) for radiotherapy target volume definition.
Eight men with prostate cancer who had (11)C-choline PET scans prior to radical prostatectomy were studied. Several methods were used to contour the DIL on the PET scans: visual, PET Edge, Region Grow, absolute standardised uptake value (SUV) thresholds and percentage of maximum SUV thresholds. Prostatectomy specimens were sliced in the transverse plane and DILs were delineated on these by a pathologist. These were then compared with the PET scans. The accuracy of correlation was assessed by the Dice similarity coefficient (DSC) and the Youden index.
The contouring method resulting in both the highest DSC and the highest Youden index was 60% of the maximum SUV (SUV(60%)), with values of 0.64 and 0.51, respectively. However SUV(60%) was not statistically significantly better than all of the other methods by either measure.
Although not statistically significant, SUV(60%) resulted in the best correlation between (11)C-choline PET and pathology amongst all the methods studied. The degree of correlation shown here is consistent with previous studies that have justified using imaging for DIL radiotherapy target volume definition.
Radiotherapy and Oncology 05/2011; 99(2):187-92. · 5.58 Impact Factor
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ABSTRACT: To examine patterns of bladder wall motion during high-dose hypofractionated bladder radiotherapy and to validate a novel adaptive planning method, A-POLO, to prevent subsequent geographic miss.
Patterns of individual bladder filling were obtained with repeat computed tomography planning scans at 0, 15, and 30minutes after voiding. A series of patient-specific plans corresponding to these time-displacement points was created. Pretreatment cone-beam computed tomography was performed before each fraction and assessed retrospectively for adaptive intervention. In fractions that would have required intervention, the most appropriate plan was chosen from the patient's "library," and the resulting target coverage was reassessed with repeat cone-beam computed tomography.
A large variation in patterns of bladder filling and interfraction displacement was seen. During radiotherapy, predominant translations occurred cranially (maximum 2.5 cm) and anteriorly (maximum 1.75 cm). No apparent explanation was found for this variation using pretreatment patient factors. A need for adaptive planning was demonstrated by 51% of fractions, and 73% of fractions would have been delivered correctly using A-POLO. The adaptive strategy improved target coverage and was able to account for intrafraction motion also.
Bladder volume variation will result in geographic miss in a high proportion of delivered bladder radiotherapy treatments. The A-POLO strategy can be used to correct for this and can be implemented from the first fraction of radiotherapy; thus, it is particularly suited to hypofractionated bladder radiotherapy regimens.
International journal of radiation oncology, biology, physics 03/2011; 79(3):705-12. · 4.59 Impact Factor
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ABSTRACT: Metastases to the central nervous system may occur with tumours of any primary origin. Brain (cerebral) metastases may be either single or multiple, with or without disseminated disease elsewhere. Brain metastases may present with focal or generalised symptoms, although up to one third of people may be asymptomatic. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of interventions for managing brain metastases in adults? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
We identified 38 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review.
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: corticosteroids, surgery, radiosurgery, whole-brain radiotherapy (external beam), cytotoxic chemotherapy (systemic), surgery plus radiosurgery, surgery plus whole-brain radiotherapy (external beam), whole-brain radiotherapy plus radiosurgery, surgery plus radiosurgery plus whole-brain radiotherapy (external beam), and whole-brain radiotherapy (external beam) plus radiation sensitisers.
Clinical evidence 01/2011; 2011.
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Daisy Mak,
Daryl Lim Joon,
Michael Chao,
Morikatsu Wada,
Michael Lim Joon,
Andrew See,
Malcolm Feigen,
Patricia Jenkins,
Angelina Mercuri,
Joanne McNamara,
Aurora Poon, Vincent Khoo
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ABSTRACT: To assess the correlation of 18F-FDG-PET (PET) response to pathological response after neoadjuvant chemoradiation (CRT) for locally advanced rectal cancer.
Twenty patients with locally advanced rectal cancer were identified between 2001 and 2005. The median age was 57 years (range 37-72) with 14 males and 6 females. All patients were staged with endorectal ultrasound and/or MRI, CT, and PET. The clinical staging was T3N0M0 (16), T3N1M0 (2), and T3N0M1 (2). Restaging PET was performed after CRT, and prior to definitive surgery. The response on PET and pathology was assessed and correlated. Patient outcome according to PET response was also assessed.
Following CRT, a complete PET response occurred in 7 patients, incomplete response in 10, and no response in 3 patients. At surgery, complete pathological response was recorded in 7 patients, incomplete response in 10 and no response in 3. There was a good correlation of PET and pathological responses in complete responders (5/7 cases) and non-responders (3/3 cases). After a median follow-up of 62 months (range 7-73), twelve patients were alive with no evidence of disease. All patients achieving complete metabolic response were alive with no evidence of disease, while as those who had no metabolic response, all died as a result of metastatic disease.
PET is a promising complementary assessment tool for assessing tumor response after CRT if there is a complete or no response. PET response may also predict for outcome.
Radiotherapy and Oncology 11/2010; 97(2):205-11. · 5.58 Impact Factor
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ABSTRACT: • To test the feasibility of a self-management intervention to help men cope with lower urinary tract symptoms as a result of radiotherapy for prostate cancer.
• A quasi-experimental design was used incorporating a pre-post-test evaluation. In total, a population of 71 men were screened for moderate to severe urinary symptoms 3 months or longer post-radiotherapy. Of these mean, 22 were recruited into the intervention from an eligible population of 43 symptomatic men. • Urinary symptoms were measured before the intervention and again after 4 months of follow-up through International Prostate Symptom Scores (IPSS) and bladder diaries. • Health-related quality of life was measured in relation to cancer per se and prostate cancer specifically, and confidence to cope was measured by a self-efficacy questionnaire. • The self-management intervention comprised pelvic floor muscle exercises, bladder retraining, patient education and problem solving and coping strategies
• Lower urinary tract symptoms, as measured by the IPSS, showed a significant improvement, with a median score change of 5 (P < 0.005). • This was supported by objective changes in median bladder void volume of +7.5 mL (P < 0.05) and the median number of daily voids of -1 (P < 0.005). • In addition, decreases in emotional distress and problems associated with urinary function suggest that the intervention had a positive impact on health-related quality of life.
• The provision of such an intervention was feasible within the clinical setting and provided benefits for men. • Symptom change vs those of normative recovery values for IPSS showed an intervention effect. • This intervention could be applied in routine practice and further testing is required in a randomized controlled trial.
BJU International 10/2010; 107(5):783-90. · 2.84 Impact Factor
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ABSTRACT: To investigate anatomical response-related changes in the head and neck region during a course of radical radiotherapy and their impact on the planned dosimetry.
The study consisted of 10 patients with primary mucosal carcinoma. Patients' nutritional requirements were managed as per departmental protocol to minimise weight loss during treatment. Kilovoltage computed tomography (CT) scans were acquired once 40 to 50 Gy had been delivered. Gross tumour volumes (GTV) and organs at risk were delineated and the initial optimised treatment plan was overlaid on the repeat CT. Comparisons were made between scans and absolute volume variations, centres of structures, dice similarity coefficients and the subsequent dosimetric impact were assessed.
Median weight loss at second scan was 3%. Primary and lymph node GTVs reduced by 49.9% (range 21.3-82%) and 73.7% (range 61.7-88.6%), respectively, yet continued to receive the prescribed dose. Maximum dose to spinal cord and brainstem changed minimally. Spared and un-spared parotid gland volumes reduced by median 23.5% and 20.5%, respectively, with no consistent translational displacement direction and minimal change in the mean dose.
Despite some significant geometric changes, nutritional management ensured patient size and shape was maintained in these consecutively selected patients and subsequently there was no apparent under-dosing of targets or over-dosing of normal structures with this technique. Further investigations which model gradual change and allow cumulative dosimetry are required to better characterise what occurs during the treatment course.
Journal of Medical Imaging and Radiation Oncology 10/2010; 54(5):497-504. · 0.87 Impact Factor
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Roy Vergis,
Catherine M Corbishley,
Karen Thomas,
Alan Horwich,
Robert Huddart, Vincent Khoo,
Ros Eeles,
Matthew R Sydes,
Colin S Cooper,
David Dearnaley,
Chris Parker
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ABSTRACT: Established prognostic factors in localized prostate cancer explain only a moderate proportion of variation in outcome. We analyzed tumor expression of apoptotic markers with respect to outcome in men with localized prostate cancer in two randomized controlled trials of radiotherapy dose escalation.
Between 1995 and 2001, 308 patients with localized prostate cancer received neoadjuvant androgen deprivation and radical radiotherapy at our institution in one of two dose-escalation trials. The biopsy specimens in 201 cases were used to make a biopsy tissue microarray. We evaluated tumor expression of Bcl-2, p53, and MDM2 by immunohistochemistry with respect to outcome.
Median follow-up was 7 years, and 5-year freedom from biochemical failure (FFBF) was 70.4% (95% CI, 63.5-76.3%). On univariate analysis, expression of Bcl-2 (p < 0.001) and p53 (p = 0.017), but not MDM2 (p = 0.224), was significantly associated with FFBF. Expression of Bcl-2 remained significantly associated with FFBF (p = 0.001) on multivariate analysis, independently of T stage, Gleason score, initial prostate-specific antigen level, and radiotherapy dose. Seven-year biochemical control was 61% vs. 41% (p = 0.0122) for 74 Gy vs. 64 Gy, respectively, among patients with Bcl-2-positive tumors and 87% vs. 81% (p = 0.423) for 74 Gy vs. 64 Gy, respectively, among patients with Bcl-2-negative tumors. There was no statistically significant interaction between dose and Bcl-2 expression.
Bcl-2 expression was a significant, independent determinant of biochemical control after neoadjuvant androgen deprivation and radical radiotherapy for prostate cancer. These data generate the hypothesis that Bcl-2 expression could be used to inform the choice of radiotherapy dose in individual patients.
International journal of radiation oncology, biology, physics 09/2010; 78(1):35-41. · 4.59 Impact Factor
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ABSTRACT: The past decade has provided many technological advances in radiotherapy. The European Institute of Radiotherapy (EIR) was established by the European Society of Therapeutic Radiology and Oncology (ESTRO) to provide current consensus statement with evidence-based and pragmatic guidelines on topics of practical relevance for radiation oncology. This report focuses primarily on 3D CT-based in-room image guidance (3DCT-IGRT) systems. It will provide an overview and current standing of 3DCT-IGRT systems addressing the rationale, objectives, principles, applications, and process pathways, both clinical and technical for treatment delivery and quality assurance. These are reviewed for four categories of solutions; kV CT and kV CBCT (cone-beam CT) as well as MV CT and MV CBCT. It will also provide a framework and checklist to consider the capability and functionality of these systems as well as the resources needed for implementation. Two different but typical clinical cases (tonsillar and prostate cancer) using 3DCT-IGRT are illustrated with workflow processes via feedback questionnaires from several large clinical centres currently utilizing these systems. The feedback from these clinical centres demonstrates a wide variability based on local practices. This report whilst comprehensive is not exhaustive as this area of development remains a very active field for research and development. However, it should serve as a practical guide and framework for all professional groups within the field, focussed on clinicians, physicists and radiation therapy technologists interested in IGRT.
Radiotherapy and Oncology 02/2010; 94(2):129-44. · 5.58 Impact Factor
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International journal of radiation oncology, biology, physics 11/2009; 75(2):632-3. · 4.59 Impact Factor
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ABSTRACT: New in vitro models of castration-resistant prostate cancer (CRPC) are urgently required.
Trans-rectal needle biopsies (TRBP) of the prostate were performed for research purposes on progressing CRPC patients who had not received prior treatment to the prostate. Biopsies were immediately digested with collagenase and plated onto collagen-coated flasks with a feeder layer of 3T6 cells and cultured in cytokine-supplemented keratinocyte serum-free medium.
Biopsies from 25 patients were collected and one of these, following an initial period of crisis, spontaneously immortalized. A series of cell lines called Bob were then established from a clone that survived CD133-selection followed by 4 weeks under adhesion-independent conditions in methylcellulose. Gains and losses previously described in clinical prostate tumors, most notably loss of 8(p) and gain of 8(q), were identified on comparative genomic hybridization and long-term growth in culture, survival in methylcellulose and invasion through matrigel confirmed the malignant phenotype of Bob. Furthermore, Bob expressed high levels of p53 and markers of early differentiation, including K8, prostatic acid phosphatase and prostate stem cell antigen. There was, however, no in vivo growth and ERG and ETV1 were not rearranged. Growth in serum permitted some differentiation.
This is the first spontaneously immortalized prostate cancer cell line to be established from a TRBP of a patient with CRPC. Bob is a novel pre-clinical model for functional studies in CRPC and especially for studying the CRPC "basal" phenotype.
The Prostate 07/2009; 69(14):1507-20. · 3.48 Impact Factor
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ABSTRACT: Prostate cancer is prevalent worldwide. In England, men living with this malignancy often report unmet psychological, informational, urological and sexual needs. Their experience of care is correspondingly lower than that of other patient groups with cancer. To address this, prostate cancer clinical nurse specialist posts were established across England and Scotland. Their intent was to support men with this form of cancer, enhance symptom management and improve quality of service provision.
The research sought to investigate prostate cancer clinical nurse specialists' roles, determine whom they targeted services at, and determine their work practices and perceived contribution.
A mixed method multi-site exploratory-descriptive design was employed.
Data were collected across four acute NHS Trusts-one in the South of England, one in the Midlands, one in Northern England and one in Scotland, respectively.
Participants included 4 prostate cancer clinical nurse specialists, 19 of their clinical colleagues and 40 men they provided care to.
Data were collected through nurse specialists' completion of a Diary and Contact Sheets. Interviews were conducted concurrently with the nurses, stakeholders they worked alongside and patients on their caseload. Data were collected between November 2004 and January 2006.
There was great variation in the qualifications and experience of nurse specialists and in the services they provided. Services ranged from generic support and information provided across the disease trajectory to provision of services to meet specific care needs, e.g. providing nurse-led clinics for erectile dysfunction. Patients and members of the multidisciplinary team welcomed the introduction of nurse specialists but were aware they could become over burdened through their rapidly growing caseloads.
Variability in services provided by the prostate cancer nurse specialists arose from differences in local demand for nursing services and the skills and experiences of those appointed. Such variability - whilst understandable - has implications for access and equity across patient groups. Further, it can compromise efforts to define clinical nurse specialists' contribution to care, can impede others' expectation of their role, and render their outcomes difficult to evaluate.
International journal of nursing studies 05/2009; 46(10):1345-54. · 1.91 Impact Factor
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ABSTRACT: Metastases to the central nervous system may occur with tumours of any primary origin. Brain (cerebral) metastases may be either single or multiple, with or without disseminated disease elsewhere. Brain metastases may present with focal or generalised symptoms, although up to a third of patients may be asymptomatic. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of interventions for managing brain metastases in adults? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2007 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare Regulatory Agency (MHRA).
We identified 18 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review.
In this systematic review we present information relating to the effectiveness and safety of the following interventions: corticosteroids; cytotoxic chemotherapy (systemic); radiation sensitisers plus whole-brain radiotherapy (external beam); surgery; radiosurgery; surgery plus radiosurgery; surgery plus radiosurgery plus whole-brain radiotherapy (external beam); surgery plus whole-brain radiotherapy (external beam); whole-brain radiotherapy (external beam); and whole-brain radiotherapy plus radiosurgery.
Clinical evidence 02/2009; 2009.
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ABSTRACT: To compare the accuracy of prostate-specific antigen (PSA) velocity (PSAV) vs PSA doubling time (DT) for predicting the repeat biopsy results in men with localized prostate cancer on active surveillance (AS), as the utility of PSAV vs PSADT in untreated prostate cancer has not been well studied.
Eligible patients had favourable-risk localized prostate cancer (T1/2a, PSA level <or=15 ng/mL, Gleason score <or=3 + 4, and percentage positive biopsy cores <or=50%), and consented to AS between 2002 and 2005. Repeat biopsies were taken after 18-24 months, with adverse histology defined as any of: primary Gleason grade >or=4, >50% cores positive, or initial Gleason score 3 + 3 upgraded to >or=3 + 4. Using all PSA values for the 2 years preceding repeat biopsy, the PSAV and PSADT were calculated using linear regression and the log-slope method (DT = ln2/slope), respectively.
In all, 199 patients were assessable; the median PSAV and PSADT were 0.71 ng/mL/year and 5.29 years, respectively. Fifty-three patients (27%) had adverse histology on repeat biopsy. On univariate analyses, PSAV (P < 0.001) and PSADT (P = 0.019) were associated with adverse histology. The area under the receiver operating characteristic curve for predicting adverse histology was 0.70 and 0.63 for PSAV and PSADT, respectively. The mean difference was 0.07 (95% confidence interval 0.03-0.12; P < 0.001).
PSAV is more accurate than PSADT for predicting adverse histology on repeat biopsies. These data suggest that PSAV should be used in preference to PSADT to describe PSA kinetics in untreated, localized prostate cancer.
BJU International 11/2008; 103(7):872-6. · 2.84 Impact Factor
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09/2008;
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Brandon T Nguyen,
Daryl Lim Joon, Vincent Khoo,
George Quong,
Michael Chao,
Morikatsu Wada,
Michael Lim Joon,
Andrew See,
Malcolm Feigen,
Kym Rykers,
Cynleen Kai,
Eddy Zupan,
Andrew Scott
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ABSTRACT: To assess the utility of FDG-PET in anal cancer for staging and impact on radiotherapy planning (RTP), response and detection of recurrent disease.
Fifty histopathological anal cancer patients were reviewed between 1996 and 2006. The median age was 58 years (range 36-85) with 19 males:31females. Clinical assessment with CT was compared to PET. Impact on management, disease response, recurrence and metastases was evaluated.
The non-PET staging was Stage I(8), Stage II(18), Stage III(22), and Stage IV(2)s. The primary was strongly FDG avid in 98% with non-excised tumors compared to CT (58%). PET upstaged 17% with unsuspected pelvic/inguinal nodal disease. Pre-treatment PET identified 11 additional by involved nodal groups in 48 patients causing RTP amendments in 19%. Post-treatment PETs at median 17 weeks (range 9-28) showed complete responses in 20 (80%) and 5 (20%) partial responses (PR). PRs were biopsy positive in 2 and negative in 3. Fifteen had follow-up scans of which all nine PETs detected recurrences were pathologically confirmed.
Anal cancer is FDG-PET avid. PET upstages 17% and changes the RTP in 19%. PET can aid in anal cancer staging and identification of residual disease, recurrent/metastatic disease but warrants further prospective studies.
Radiotherapy and Oncology 07/2008; 87(3):376-82. · 5.58 Impact Factor
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Roy Vergis,
Catherine M Corbishley,
Andrew R Norman,
Jaclyn Bartlett,
Sameer Jhavar,
Michael Borre,
Sara Heeboll,
Alan Horwich,
Robert Huddart, Vincent Khoo,
Ros Eeles,
Colin Cooper,
Matthew Sydes,
David Dearnaley,
Chris Parker
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ABSTRACT: Expression of intrinsic markers of tumour hypoxia and angiogenesis are important predictors of radiotherapeutic, and possibly surgical, outcome in several cancers. Extent of tumour hypoxia in localised prostate cancer is comparable to that in other cancers, but few data exist on the association of extent of tumour hypoxia with treatment outcome. We aimed to study the predictive value of intrinsic markers of tumour hypoxia and angiogenesis in localised prostate cancer, both in patients treated with radiotherapy and in those treated surgically.
We applied a new, needle biopsy tissue microarray (TMA) technique to study diagnostic samples from men with localised, previously untreated prostate cancer treated in two randomised controlled trials of radiotherapy-dose escalation. Multivariate analysis by Cox proportional hazards was done to assess the association between clinical outcome, in terms of biochemical control, and immunohistochemical staining of hypoxia inducible factor-1 alpha (HIF-1 alpha), vascular endothelial growth factor (VEGF), and osteopontin expression. The analysis was repeated on an independent series of men with localised, previously untreated prostate cancer treated by radical prostatectomy. The main outcome was time to biochemical (ie, prostate-specific antigen [PSA]) failure.
Between Oct 12, 1995, and Feb 5, 2002, 308 patients were identified from two prospective, randomised trials at the Royal Marsden Hospital, London and Sutton, UK, for the radiotherapy cohort and diagnostic biopsies were available for 201 of these patients. Between June 6, 1995, and Nov 4, 2005, 329 patients were identified from the Aarhus University Hospital, Skejby, Denmark, for the prostatectomy cohort; of these, 40 patients were excluded because the tumour was too small to sample (19 patients), because the paraffin block was too thin (19 patients), or because the blocks were missing (two patients), leaving 289 patients for analysis. For patients treated with radiotherapy, increased staining for VEGF (p=0.008) and HIF-1 alpha (p=0.02) expression, but not increased osteopontin expression (p=0.978), were significant predictors of a shorter time to biochemical failure on multivariate analysis, independent of clinical tumour stage, Gleason score, serum PSA concentration, and dose of radiotherapy. For patients treated with surgery, increased staining for VEGF (p<0.0001) and HIF-1 alpha (p<0.0001) expression, and increased osteopontin expression (p=0.0005) were each significantly associated with a shorter time to biochemical failure on multivariate analysis, independent of pathological tumour stage, Gleason score, serum PSA concentration, and margin status.
To our knowledge, this is the largest study of intrinsic markers of hypoxia and angiogenesis in relation to the outcome of radical treatment of localised prostate cancer. Increased expression of VEGF, HIF-1 alpha, and, for patients treated with surgery, osteopontin, identifies patients at high risk of biochemical failure who would be suitable for enrolment into trials of treatment intensification.
The lancet oncology 04/2008; 9(4):342-51. · 14.47 Impact Factor
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ABSTRACT: Retrospective analysis in 150 patients with metastatic prostate cancer was conducted to determine whether early detection with MRI spine and treatment of clinically occult spinal cord compromise (SCC) facilitate preservation of neurologic function. Our results suggest that prophylactic radiotherapy for patients with back pain or radiological SCC without neurologic deficit may facilitate preservation of neurologic function. Thus MRI surveillance for SCC may be important for prostate cancer patients with bone metastases.
Radiotherapy and Oncology 01/2008; 85(3):469-72. · 5.58 Impact Factor
