Nyflot MJ, Harari PM, Yip S, Perlman SB, Jeraj RCorrelation of PET images of metabolism, proliferation and hypoxia to characterize tumor phenotype in patients with cancer of the oropharynx. Radiother Oncol 105(1): 36-40
Spatial organization of tumor phenotype is of great interest to radiotherapy target definition and outcome prediction. We characterized tumor phenotype in patients with cancers of the oropharynx through voxel-based correlation of PET images of metabolism, proliferation, and hypoxia.
Patients with oropharyngeal cancer received (18)F-fluorodeoxyglucose (FDG) PET/CT, (18)F-fluorothymidine (FLT) PET/CT, and (61)Cu-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) PET/CT. Images were co-registered and standardized uptake values (SUV) were calculated for all modalities. Voxel-based correlation was evaluated with Pearson's correlation coefficient in tumor regions. Additionally, sensitivity studies were performed to quantify the effects of image segmentation, registration, noise, and segmentation on R.
On average, FDG PET and FLT PET images were most highly correlated (R(FDG:FLT) = 0.76, range 0.53-0.85), while Cu-ATSM PET showed greater heterogeneity in correlation to other tracers (R(FDG:Cu-ATSM) = 0.64, range 0.51-0.79; R(FLT:Cu-ATSM) = 0.61, range 0.21-0.80). Of the tested parameters, correlation was most sensitive to image registration. Misregistration of one voxel lead to ΔR(FDG) = 0.25, ΔR(FLT) = 0.39, and ΔR(Cu-ATSM) = 0.27. Image noise and reconstruction also had quantitative effects on correlation. No significant quantitative differences were found between GTV, expanded GTV, or CTV regions.
Voxel-based correlation represents a first step into understanding spatial organization of tumor phenotype. These results have implications for radiotherapy target definition and provide a framework to test outcome prediction based on pretherapy distribution of phenotype.
"Furthermore, even if tumors are categorized to a similar phenotype based on one characteristic, they can display discordances regarding other cellular mechanisms. For instance, equally hypoxic HNC tumors can show discrepant proliferation rates [7,8]. This may even apply for different regions within one tumor . "
[Show abstract][Hide abstract] ABSTRACT: Quantification of molecular cell processes is important for prognostication and treatment individualization of head and neck cancer (HNC). However, individual tumor comparison can show discord in upregulation similarities when analyzing multiple biological mechanisms. Elaborate tumor characterization, integrating multiple pathways reflecting intrinsic and microenvironmental properties, may be beneficial to group most uniform tumors for treatment modification schemes. The goal of this study was to systematically analyze if immunohistochemical (IHC) assessment of molecular markers, involved in treatment resistance, and 18F-FDG PET parameters could accurately distinguish separate HNC tumors.
Several imaging parameters and texture features for 18F-FDG small-animal PET and immunohistochemical markers related to metabolism, hypoxia, proliferation and tumor blood perfusion were assessed within groups of BALB/c nu/nu mice xenografted with 14 human HNC models. Classification methods were used to predict tumor line based on sets of parameters.
We found that 18F-FDG PET could not differentiate between the tumor lines. On the contrary, combined IHC parameters could accurately allocate individual tumors to the correct model. From 9 analyzed IHC parameters, a cluster of 6 random parameters already classified 70.3% correctly. Combining all PET / IHC characteristics resulted in the highest tumor line classification accuracy (81.0%; cross validation 82.0%), which was just 2.2% higher (p = 5.2x10-32) than the performance of the IHC parameter / feature based model.
With a select set of IHC markers representing cellular processes of metabolism, proliferation, hypoxia and perfusion, one can reliably distinguish between HNC tumor lines. Addition of 18F-FDG PET improves classification accuracy of IHC to a significant yet minor degree. These results may form a basis for development of tumor characterization models for treatment allocation purposes.
BMC Cancer 02/2014; 14(1):130. DOI:10.1186/1471-2407-14-130 · 3.36 Impact Factor
"The more widespread use and associated research based on advanced functional imaging modalities like positron emission tomography (PET) and magnetic resonance imaging or spectroscopy will help to visualize and localize, those tumour subvolumes that are characterized by poor prognostic factors (e.g. high metabolism, hypoxia and elevated cell proliferation) [29, 30]. This concept of incorporating such information in the treatment-planning process and applying selective dose boosts (dose painting) will require more interdisciplinary research but has large potential to further improve radiotherapy . "
[Show abstract][Hide abstract] ABSTRACT: The purpose of the study was to determine the dosimetric difference between three emerging treatment modalities—volumetric-modulated arc therapy (VMAT), intensity-modulated proton beam therapy (IMPT) and intensity-modulated carbon ion beam therapy (IMIT)—for two tumour sites where selective boosting of the tumour is applied. For 10 patients with locally advanced head and neck (H&N) cancer and 10 with high-risk prostate cancer (PC) a VMAT plan was generated for PTVinitial that included lymph node regions, delivering 50 Gy (IsoE) for H&N and 50.4 Gy (IsoE) for PC patients. Furthermore, separate boost plans (VMAT, IMPT and IMIT) were created to boost PTVboost up to 70 Gy (IsoE) and 78 Gy (IsoE) for H&N and PC cases, respectively. Doses to brainstem, myelon, larynx and parotid glands were assessed for H&N cases. Additionally, various OARs (e.g. cochlea, middle ear, masticator space) were evaluated that are currently discussed with respect to quality of life after treatment. For PC cases, bladder, rectum and femoral heads were considered as OARs. For both tumour sites target goals were easily met. Looking at OAR sparing, generally VMAT + VMAT was worst. VMAT + IMIT had the potential to spare some structures in very close target vicinity (such as cochlea, middle ear, masticator space ) significantly better than VMAT + IMPT. Mean doses for rectal and bladder wall were on average 4 Gy (IsoE) and 1.5 Gy (IsoE) higher, respectively, compared to photons plus particles scenarios. Similar results were found for parotid glands and larynx. Concerning target coverage, no significant differences were observed between the three treatment concepts. Clear dosimetric benefits were observed for particle beam therapy as boost modality. However, the clinical benefit of combined modality treatments remains to be demonstrated.
Journal of Radiation Research 07/2013; 54(Suppl 1)(Suppl 1):i97–i112. DOI:10.1093/jrr/rrt067 · 1.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose:
The outcome of biologic image-guided radiotherapy depends on the definition of the biologic target. The purpose of the current work was to extract hyperperfused and hypermetabolic regions from dynamic positron emission tomography (D-PET) images, to dose escalate either region and to discuss implications of such image guided strategies.
Eleven patients with soft tissue sarcomas were investigated with D-PET. The images were analyzed using a two-compartment model producing parametric maps of perfusion and metabolic rate. The two image series were segmented and exported to a treatment planning system, and biological target volumes BTVper and BTVmet (perfusion and metabolism, respectively) were generated. Dice's similarity coefficient was used to compare the two biologic targets. Intensity-modulated radiation therapy (IMRT) plans were generated for a dose painting by contours regime, where planning target volume (PTV) was planned to 60 Gy and BTV to 70 Gy. Thus, two separate plans were created for each patient with dose escalation of either BTVper or BTVmet.
BTVper was somewhat smaller than BTVmet (209 ± 170 cm(3) against 243 ± 143 cm(3), respectively; population-based mean and s.d.). Dice's coefficient depended on the applied margin, and was 0.72 ± 0.10 for a margin of 10 mm. Boosting BTVper resulted in mean dose of 69 ± 1.0 Gy to this region, while BTVmet received 67 ± 3.2 Gy. Boosting BTVmet gave smaller dose differences between the respective non-boost DVHs (such as D98).
Dose escalation of one of the BTVs results in a partial dose escalation of the other BTV as well. If tumor aggressiveness is equally pronounced in hyperperfused and hypermetabolic regions, this should be taken into account in the treatment planning.
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