10 research outputs found
Imaging tumour hypoxia with positron emission tomography.
Hypoxia, a hallmark of most solid tumours, is a negative prognostic factor due to its association with an aggressive tumour phenotype and therapeutic resistance. Given its prominent role in oncology, accurate detection of hypoxia is important, as it impacts on prognosis and could influence treatment planning. A variety of approaches have been explored over the years for detecting and monitoring changes in hypoxia in tumours, including biological markers and noninvasive imaging techniques. Positron emission tomography (PET) is the preferred method for imaging tumour hypoxia due to its high specificity and sensitivity to probe physiological processes in vivo, as well as the ability to provide information about intracellular oxygenation levels. This review provides an overview of imaging hypoxia with PET, with an emphasis on the advantages and limitations of the currently available hypoxia radiotracers.Cancer Research UK (CRUK) funded the National Cancer Research Institute (NCRI) PET Research Working party to organise a meeting to discuss imaging cancer with hypoxia tracers and Positron Emission Tomography. IF was funded by CRUK and is also supported by the Chief Scientific Office. ALH is supported by CRUK and the Breast Cancer Research Foundation. RM is funded by NIHR Cambridge Biomedical Research Centre.This is the accepted manuscript. The final version is available from Nature Publishing at http://www.nature.com/bjc/journal/vaop/ncurrent/full/bjc2014610a.html
Evaluation of the proliferation marker Ki-67 in a large prostatectomy cohort
The tumor proliferation index marker Ki-67 is strongly associated with tumor cell proliferation,
growth and progression, and is widely used in routine clinicopathological investigation.
Prostate cancer is a complex multifaceted and biologically heterogeneous disease, and
overtreatment of localized, low volume indolent tumors, is evident. Here, we aimed to
assess Ki-67 expression and related outcomes of 535 patients treated with radical prostatectomy.
The percentage of tumor epithelial cells expressing Ki-67 was determined by
immunohistochemical assay, both digital image analysis and visual scoring by light microscope
were used for quantification. The association of Ki-67 and prostate cancer was
evaluated, as well as its prognostic value. There was a positive correlation between high
expression of Ki-67 and Gleason score > 7 (p < 0.001) as well as tumor size ( 20 mm,
p = 0.03). In univariate analyses, a high expression of Ki-67 in tumor epithelium was significantly
associated with biochemical failure (BF) (digital scoring, p = 0.014) and (visual scoring,
p = 0.004). In the multivariate analyses, a high level of Ki-67 was an independent poor
prognostic factor for biochemical failure-free survival (BFFS) (Visual scoring, Ki67, p =
0.012, HR:1.50, CI95% 1.10±2.06). In conclusion, high Ki-67 expression is an independent
negative prognostic marker for biochemical failure. Our findings support the role of Ki-67 as
a significant, poor prognostic factor for in prostate cancer outcome
[18F]Fluoromisonidazole PET in rectal cancer
Abstract Background There is an increasing interest in developing predictive biomarkers of tissue hypoxia using functional imaging for personalised radiotherapy in patients with rectal cancer that are considered for neoadjuvant chemoradiotherapy (CRT). The study explores [18F]fluoromisonidazole ([18F]FMISO) positron emission tomography (PET) scans for predicting clinical response in rectal cancer patients receiving neoadjuvant CRT. Methods Patients with biopsy-proven rectal adenocarcinoma were imaged at 0â45 min, 2 and 4 h, at baseline and after 8â10 fractions of CRT (week 2). The first 6 patients did not receive an enema (the non-enema group) and the last 4 patients received an enema before PET-CT scan (the enema group). [18F]FMISO production failed on 2 occasions. Static PET images at 4 h were analysed using tumour-to-muscle (T:M) SUVmax and tumour-to-blood (T:B) SUVmax. The 0â45 min dynamic PET scans were analysed using Casciari model to report hypoxia and perfusion. Akaike information criteria (AIC) were used to compare data fittings for different pharmacokinetic models. Pathological tumour regression grade was scored using American Joint Committee on Cancer (AJCC) 7.0. Shapiro-Wilk test was used to evaluate the normality of the data. Results Five out of eleven (5/11) patients were classed as good responders (AJCC 0/1 or good clinical response) and 6/11 as poor responders (AJCC 2/3 or poor clinical response). The median T:M SUVmax was 2.14 (IQR 0.58) at baseline and 1.30 (IQR 0.19) at week 2, and the corresponding median tumour hypoxia volume was 1.08 (IQR 1.31) cm3 and 0 (IQR 0.15) cm3, respectively. The median T:B SUVmax was 2.46 (IQR 1.50) at baseline and 1.61 (IQR 0.14) at week 2, and the corresponding median tumour hypoxia volume was 5.68 (IQR 5.86) cm3 and 0.76 (IQR 0.78) cm3, respectively. For 0â45 min tumour modelling, the median hypoxia was 0.92 (IQR 0.41) minâ1 at baseline and 0.70 (IQR 0.10) minâ1 at week 2. The median perfusion was 4.10 (IQR 1.71) ml gâ1 minâ1 at baseline and 2.48 (IQR 3.62) ml gâ1 minâ1 at week 2. In 9/11 patients with both PET scans, tumour perfusion decreased in non-responders and increased in responders except in one patient. None of the changes in other PET parameters showed any clear trend with clinical outcome. Conclusions This pilot study with small number of datasets revealed significant challenges in delivery and interpretation of [18F]FMISO PET scans of rectal cancer. There are two principal problems namely spill-in from non-tumour tracer activity from rectal and bladder contents. Emphasis should be made on reducing spill-in effects from the bladder to improve data quality. This preliminary study has shown fundamental difficulties in the interpretation of [18F]FMISO PET scans for rectal cancer, limiting its clinical applicability