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A R Padhani

Publications and source records attributed to A R Padhani.

At least 19 recordsLinked to original sources
PubMed2006

The relationship of the neo-angiogenic marker, endoglin, with response to neoadjuvant chemotherapy in breast cancer.

Endoglin (CD105) is upregulated in endothelial cells of tissues undergoing neovascularisation. A greater number of CD105-positive vessels predicts poor survival in breast cancer. We examine whether CD105 expression predicts response to neoadjuvant chemotherapy. Fifty-seven women (median age 50 years, range 29-70) received neoadjuvant chemotherapy for operable breast cancer. Immunohistochemical staining using monoclonal antibodies to CD105 and CD34 was performed on pretreatment biopsies and post-treatment surgical specimens. Individual microvessels were counted in 10 random fields at x 200 magnification. Median counts were correlated with clinical and pathological response using the Mann-Whitney U-test. Forty-five out of fifty-seven patients (79%) responded clinically, 22 (39%) responded pathologically. On pretreatment biopsies, clinical responders had significantly lower median CD105-positive vessel counts than nonresponders (median counts 5 and 9.3/high-power field (hpf), median difference=4.0/hpf, 95% CI 0.5-8.0/hpf, P=0.02). For pathological responders and nonresponders, median counts were 4.8 and 5.5/hpf (median difference -0.5/hpf, 95% CI=-2.5-2.0/hpf, P=0.77). CD34 expression (total microvessel density) did not correlate with response. Pretreatment CD105 expression predicts for clinical response to chemotherapy, with a lower initial count being favourable. Patients with high baseline new vessel counts or increased counts after conventional therapy may benefit from additional antiangiogenic therapy.

Adult↗
PubMed2006

Cost-effectiveness of screening with contrast enhanced magnetic resonance imaging vs X-ray mammography of women at a high familial risk of breast cancer.

Contrast enhanced magnetic resonance imaging (CE MRI) is the most sensitive tool for screening women who are at high familial risk of breast cancer. Our aim in this study was to assess the cost-effectiveness of X-ray mammography (XRM), CE MRI or both strategies combined. In total, 649 women were enrolled in the MARIBS study and screened with both CE MRI and mammography resulting in 1881 screens and 1-7 individual annual screening events. Women aged 35-49 years at high risk of breast cancer, either because they have a strong family history of breast cancer or are tested carriers of a BRCA1, BRCA2 or TP53 mutation or are at a 50% risk of having inherited such a mutation, were recruited from 22 centres and offered annual MRI and XRM for between 2 and 7 years. Information on the number and type of further investigations was collected and specifically calculated unit costs were used to calculate the incremental cost per cancer detected. The numbers of cancer detected was 13 for mammography, 27 for CE MRI and 33 for mammography and CE MRI combined. In the subgroup of BRCA1 (BRCA2) mutation carriers or of women having a first degree relative with a mutation in BRCA1 (BRCA2) corresponding numbers were 3 (6), 12 (7) and 12 (11), respectively. For all women, the incremental cost per cancer detected with CE MRI and mammography combined was pound28 284 compared to mammography. When only BRCA1 or the BRCA2 groups were considered, this cost would be reduced to pound11 731 (CE MRI vs mammography) and pound15 302 (CE MRI and mammography vs mammography). Results were most sensitive to the unit cost estimate for a CE MRI screening test. Contrast-enhanced MRI might be a cost-effective screening modality for women at high risk, particularly for the BRCA1 and BRCA2 subgroups. Further work is needed to assess the impact of screening on mortality and health-related quality of life.

Adult↗
PubMed2006

Dynamic contrast-enhanced magnetic resonance imaging is a poor measure of rectal cancer angiogenesis.

BACKGROUND: The aim of this study was to investigate the use of magnetic resonance imaging (MRI) for non-invasive measurement of rectal cancer angiogenesis and hypoxia. METHODS: Fifteen patients with rectal adenocarcinoma underwent preoperative dynamic contrast-enhanced (DCE) and blood oxygenation level-dependent (BOLD) MRI. Microvessel density (CD31 level), and expression of vascular endothelial growth factor (VEGF) and carbonic anhydrase (CA) 9 were measured immunohistochemically in histological tumour sections from 12 patients. Serum VEGF levels were also measured in 14 patients. Correlations between quantitative imaging indices and immunohistochemical variables were examined. RESULTS: There was good correlation between circulating VEGF and CD31 expression (r(S) = 0.88, P < 0.001). CD31 expression did not correlate with any dynamic MRI parameter, except transfer constant, with which it correlated inversely (r(S) = -0.65, P = 0.022). Tissue and circulating VEGF levels did not correlate, and neither correlated with any tumour DCE MRI parameter. No relationship was seen between BOLD MRI and CA-9 expression. CONCLUSION: The negative correlation between transfer constant (reflecting tumour blood flow and microvessel permeability) with CD31 expression is paradoxical. DCE MRI methods for assessing tissue vascularity correlate poorly with histological markers of angiogenesis and hypoxia, suggesting that DCE MRI does not simply reflect static histological vascular properties in patients with rectal cancer.

Adenocarcinoma↗
PubMed2005

Effects of platinum/taxane based chemotherapy on acute perfusion in human pelvic tumours measured by dynamic MRI.

Dynamic contrast enhanced MRI (DCE-MRI) is being used increasingly in clinical trials to demonstrate that vascular disruptive and antiangiogenic agents target tumour microcirculation. Significant reductions in DCE-MRI kinetic parameters are seen within 4-24 and 48 h of treatment with vascular disruptive and antiangiogenic agents, respectively. It is important to know whether cytotoxic agents also cause significant acute reductions in these parameters, for reliable interpretation of results. This study investigated changes in transfer constant (K(trans)) and the initial area under the gadolinium curve (IAUGC) following the first dose of chemotherapy in patients with mostly gynaecological tumours. A reproducibility analysis on 20 patients (using two scans performed on consecutive days) was used to determine the significance of DCE-MRI parameter changes 24 h after chemotherapy in 18 patients. In 11 patients who received platinum alone or with a taxane, there were no significant changes in K(trans) or IAUGC in either group or individual patient analyses. When the remaining seven patients (treated with a variety of agents including platinum and taxanes) were included (n=18), there were also no significant changes in K(trans). Therefore, if combination therapy does show changes in DCE-MRI parameters then the effects can be attributed to antivascular therapy rather than chemotherapy.

Adult↗
PubMed2005

The assessment of antiangiogenic and antivascular therapies in early-stage clinical trials using magnetic resonance imaging: issues and recommendations.

Vascular and angiogenic processes provide an important target for novel cancer therapeutics. Dynamic contrast-enhanced magnetic resonance imaging is being used increasingly to noninvasively monitor the action of these therapeutics in early-stage clinical trials. This publication reports the outcome of a workshop that considered the methodology and design of magnetic resonance studies, recommending how this new tool might best be used.

Angiogenesis Inhibitors↗
PubMed2005

Tumour staging using magnetic resonance imaging in clinically localised prostate cancer: relationship to biochemical outcome after neo-adjuvant androgen deprivation and radical radiotherapy.

AIMS: To evaluate the prognostic significance of magnetic resonance imaging (MRI) tumour stage in clinically localised prostate cancer. MATERIALS AND METHODS: Between 1988 and 1999, 199 men with clinically localised prostate cancer (T -T4, N0/Nx, M0) were treated with neo-adjuvant androgen deprivation and radical radiotherapy, and were staged using MRI. Concordance between clinical tumour (cT) stage, as determined by digital rectal examination, and MRI tumour (mT) stage was assessed. Univariate and multivariate analyses using the Cox proportional hazards model were used to study the prognostic role of cT stage and mT stage in addition to established prognostic factors. RESULTS: Of these 199 patients, 103 (52%) were upstaged on MRI, seven (3%) were downstaged, and in 89 (45%) cT and mT stages were concordant. With median follow-up of 3.8 years, 5-year freedom from prostate-specific antigen (PSA) failure was 48% (95% confidence interval (CI) 39-56%). On univariate analysis, freedom from PSA failure was associated with mT stage (P = 0.009) as well as Gleason score (P < 0.001) and initial PSA (P < 0.001), but not cT stage (P = 0.449). On multivariate analysis, Gleason score (P = 0.001), initial PSA (P < 0.001), but not mT stage (P = 0.112) remained independent determinants of freedom from PSA failure. For the subgroup of 149 patients with cT1-2 disease, mT stage was a significant predictor of increased risk of PSA failure on univariate analysis (P = 0.005), but not multivariate analysis (P = 0.19). CONCLUSION: Freedom from PSA failure was more closely associated with mT stage than cT stage. Future studies are warranted to determine whether mT stage is an independent determinant of treatment outcome.

Aged↗
PubMed2003

The pathway study: results of a pilot feasibility study in patients suspected of having lung carcinoma investigated in a conventional chest clinic setting compared to a centralised two-stop pathway.

UNLABELLED: The best chance of cure in non-small cell lung cancer (NSCLC) is surgical resection, but UK rates of 8% compare poorly to 25% in the USA and Europe. Delays in diagnosis in the current UK system may be one reason for such discrepancy. To address this problem we set up a rapid diagnostic system and compared it to the conventional method of investigations in a pilot randomised trial. METHODS: Eighty-eight patients were prospectively enrolled from three District General Hospitals and randomised to either investigation locally or to the rapid system at The Royal Marsden Hospital. The pilot end-points were feasibility and audit of radical treatment rates to enable estimates for patient numbers for the full study. RESULTS: Forty-five and 43 patients were in the central and conventional arms, respectively (65% male, median age 69 years). There was a 4-week improvement in time to first treatment in those in the central arm (P=0.0025) with 13/30 (43%) and 9/27 (33%) patients having radical treatment in the central and conventional arms, respectively. Patients in the conventional arm felt the diagnostic process was too slow (P=0.02) while those in the central arm seemed to have a better care experience (P=0.01). There were significantly less visits to the general practitioner (GP) in the central arm (P=0.02). CONCLUSIONS: This pilot study demonstrates that the full study is feasible but would require the commitment and involvement of a large number of patients and physicians. The results show several advantages to investigations and diagnosis in the central arm, particularly in time to treatment initiation, patient satisfaction and rate of radical treatments. The improved rate of radical treatment could lead to an improved survival rate.

Aged↗
PubMed2003

MRI for assessing antivascular cancer treatments.

Selective antiangiogenesis and vascular targeting drugs hold out the promise of improved efficacy and tolerability for anticancer treatments. Early phase 1 drug trials have shown good tolerability for antiangiogenesis agents with biological activity below the maximum tolerated dose. Advanced clinical trials have demonstrated that morphological assessments of tumour response are of limited value in gauging the efficacy of treatment. MRI is a versatile technique which is sensitive to contrast mechanisms that can be affected by antivascular treatments; this use for MRI has been validated in xenografts and humans. Dynamic contrast-enhanced MRI (DCE-MRI), which demonstrates tissue perfusion and permeability, is being used clinically as a pharmacodynamic indicator of biological activity for antivascular cancer drugs. Early data show that DCE-MRI studies can define the biologically active dose and predict the efficacy of treatment on the basis of changes observed. MRI with macromolecular contrast media (MMCM) depicts microvessel permeability and fractional plasma volume. Xenograft studies with MMCM have shown great promise for evaluating antivascular treatments but this has not been used clinically. Intrinsic susceptibility-weighted MRI, which is sensitive to blood oxygenation and flow, is emerging as a technique that may be able to monitor vascular targeting therapies.

Angiogenesis Inhibitors↗
PubMed2002

Clinical and immunological assessment of Mycobacterium vaccae (SRL172) with chemotherapy in patients with malignant mesothelioma.

The objectives of this study were to determine the toxicity of intratumoural/intrapleural SRL172 in addition to intradermal SRL172 and standard chemotherapy (mitomycin-C, vinblastine and cisplatin) in patients with malignant mesothelioma. Patients received chemotherapy (mitomycin-C: 8 mg m(-2), vinblastine: 6 mg m(-2), cisplatin 50 mg m(-2)) on a 3-weekly basis for up to six courses. IP SRL172 injections were given 3-weekly prior to chemotherapy and escalated in groups of three patients from 1 microg to 1 mg bacilli in 10-fold increments. Patients were also given ID SRL172 at a dose of 1 mg bacilli 4-weekly. Patients were assessed for toxicity after each course of chemotherapy and for response by CT imaging. Immuno-haematological parameters were analyzed pre-treatment and 1 month after completion of treatment. There was no dose limiting toxicity with IP SRL172 although there was greater toxicity at the highest dose (n=13). There were six out of 16 partial responses (37.5%). Haemato-immunological parameters, measured in seven patients pre and post-therapy, revealed that response rate correlated with a decrease in platelet count and there was an increase in activation of natural killer cells and a decrease in the percentage of IL-4 producing T cells in all tested patients post-treatment. SRL172 can be given safely into tumour deposits and the pleural cavity in patients with malignant mesothelioma and we have established the dose for phase II testing.

Aged↗
PubMed2002

Applications of sliding window reconstruction with cartesian sampling for dynamic contrast enhanced MRI.

Applications of dynamic contrast enhanced MR imaging are increasing and require both high spatial resolution and high temporal resolution. Perfusion studies using susceptibility contrast in particular require very high temporal resolution. The sliding window reconstruction is a technique for increasing temporal resolution. It has previously been applied to radial and spiral sampling, but these schemes require extensive correction and interpolation during image reconstruction. Fourier raw data can be reconstructed simply and quickly using the fast fourier transform (FFT). This paper presents a new Fourier-based sampling scheme and sliding window reconstruction that facilitates fast scanning without needing correction or interpolation. This technique can be used on virtually any MR scanner since it requires no specialized hardware. It is implemented here as a dual gradient echo sequence providing simultaneous T(1)- and T(2)*-weighted images with a time resolution of 1.1 s.

Humans↗
PubMed2002

Functional MRI for anticancer therapy assessment.

Anticancer drug discovery and development are experiencing a paradigm shift from cytotoxic therapies to more selective therapies that target underlying oncogenic abnormalities. Many newer therapies are cytostatic, for which objective tumour shrinkage is an inappropriate response parameter. There is a growing need to develop surrogate endpoints of drug efficacy to speed up the process of finding effective drug combinations for phase III trials. This review focuses on the developing field of functional magnetic resonance imaging (MRI) and its potential applications in the pharmacodynamic evaluation of existing and new cancer therapeutics. Dynamic contrast enhanced MRI, which is currently being used to evaluate anti-angiogenic, and anti-vascular agents in human trials will be reviewed in detail. The requirements that must be met before incorporating functional MRI techniques into clinical protocols are also discussed.

Antineoplastic Agents↗
PubMed2002

A multicentre phase II trial of primary chemotherapy with cisplatin and protracted venous infusion 5-fluorouracil followed by chemoradiation in patients with carcinoma of the oesophagus.

BACKGROUND: We undertook a multicentre phase II trial to evaluate the safety and efficacy of primary chemotherapy followed by chemoradiation for localised adenocarcinoma or squamous carcinoma of the oesophagus. PATIENTS AND METHODS: Chemotherapy comprised five 3-weekly cycles of cisplatin and protracted continuous infusion 5-fluorouracil, with conformally planned radiotherapy commencing at the start of the fifth cycle. RESULTS: The planned treatment programme was completed by 39 of 72 patients (54%), and a further 13% completed chemotherapy and proceeded to surgical oesophagectomy. Response rates to chemotherapy and to the entire treatment programme were 47% [95% confidence interval (CI) 34% to 60%] and 56% (CI 43% to 68%). The dysphagia score improved in 54% of patients. The median survival duration was 14.6 months with 1- and 2-year survival rates of 58.7% and 44.1%, respectively. Grade III/IV chemotherapy-related toxicity occurred in 38% of patients, and there were no treatment-related deaths. CONCLUSIONS: This is a feasible and active treatment regimen providing palliative benefits for patients with poor-prognosis localised oesophageal cancer.

Adenocarcinoma↗
PubMed2001

The prevalence of avascular necrosis in patients treated with chemotherapy for testicular tumours.

To study the prevalence of avascular necrosis in patients receiving chemotherapy for testicular cancer we invited 103 consecutive patients treated by chemotherapy to attend for MRI scan of the hips. Four of 47 (9% (CI 2-20%)) patients scanned and 4/103 (3.8% (CI 1-10%)) of patients invited to participate in the study had evidence of avascular necrosis. As not all patients in the study had completed the at risk period this equates to a 3-year actuarial risk of 6.3% (95% confidence limits (CI) 2.4-16.1). These data suggest that avascular necrosis is an uncommon but significant complication of chemotherapy including steroids as anti-emetics.

Adolescent↗
PubMed2001

Problem in diagnostic imaging: Mediastinal venous anomalies.

This article presents as a diagnostic problem a rare mediastinal venous anomaly detected in a patient with a primary intrathoracic tumor. Its appearance on computed tomography (CT) is discussed and compared with that of other developmental mediastinal venous anomalies. The individual CT characteristics of these anomalies and their clinical significance with respect to the management of patients with cancer are also reviewed.

Adult↗
PubMed2001

BOLD MRI of human tumor oxygenation during carbogen breathing.

An MRI method is described for demonstrating improved oxygenation of human tumors and normal tissues during carbogen inhalation (95% O2, 5% CO2). T2*-weighted gradient-echo imaging was performed before, during, and after carbogen breathing in 47 tumor patients and 13 male volunteers. Analysis of artifacts and signal intensity was performed. Thirty-six successful tumor examinations were obtained. Twenty showed significant whole-tumor signal increases (mean 21.0%, range 6.5-82.4%), and one decreased (-26.5 +/- 8.0%). Patterns of signal change were heterogeneous in responding tumors. Five of 13 normal prostate glands (four volunteers and nine patients with nonprostatic tumors) showed significant enhancement (mean 11.4%, range 8.4-14.0%). An increase in brain signal was seen in 11 of 13 assessable patients (mean 8.0 +/- 3.7%, range 5.0-11.7%). T2*-weighted tumor MRI during carbogen breathing is possible in humans. High failure rates occurred due to respiratory distress. Significant enhancement was seen in 56%, suggesting improved tissue oxygenation and blood flow, which could identify these patients as more likely to benefit from carbogen radiosensitization.

Aged↗