1、Functional Imaging for Radiation Treatment Planning,Response Assessment,and Adaptive Therapy in Head and Neck CancerRole of routine and functional Imaging(FI)Screening and diagnosis of neoplasms Precise staging of malignancy Response assessment of cancer treatment Monitor recurrencesBenefit of FI Ma
2、jor modalities of FI:1.positron emission tomography(PET)combined with CT or magnetic resonance(MR)imaging2.fMRI:DWI,DCE-MRI,BOLD,spectroscopy etc.3.Emerging techniques:PET-MRI,DKI,IVIM,APT,CEST etc.Offer complementary information including 1.metabolism of FDG,proliferation,hypoxia,and cell membrane
3、synthesis by PET2.hypoxia and permeability by DCE MRI and IVIM,cell proliferation and apoptosis by DWI,IVIM and DKI,and epidermal growth factor receptor status.About this articlePart I:Discusses the practical aspects of integrating functional imaging into head-and-neck radiation therapy planning.Par
4、t II:Reviews the potential of molecular imaging biomarkers for response assessment and therapy adaptation.Authors concluded that FI allowed more individualized treatment planning in patients with head and neck SCCs in the emerging era of personalized medicine.Part I Role of Functional Imaging in Rad
5、iation Therapy Planning There was a 20%decrease in OS among patients who underwent radiation therapy with a protocol that did not comply with established institutional standards.Reasons:1.Inaccuracies in tumor target delineation 2.Inter-observer variability in clinical practice based on CT for targe
6、t delineation Functional MRI and PET techniques provide different and potentially complementary information about the tumor extent and biologic activity.PET-based Tumor Target Contouring Tumor uptake of PET radioactive tracers can provide excellent contrast resolution between neoplastic and normal t
7、issues.There are two DOSE CONTOURING methods:visual interpretation and automated delineation methods.Example of automated delineation Figure 2.SCC arising from the epiglottis(T2N2bM0)in a 67-year-old man.Axial fused FDG PET/CT image shows tumor contours automatically generated with diagnostic softwa
8、re by using percentages of the maximum SUV(20%,30%,40%,and 50%)and a fixed SUV cutoff of 2.5.Automated delineation is believe to be more objective than visual delineation.Because,an alteration of the SUV scale can change the apparent tumor volume and lead to increased inter-observer variability.Stat
9、us of PET-contouring at present At present,there is no consensus regarding the optimal contouring method.The most practical approach to defining the tumor target is to rely on expert visual interpretations by nuclear medicine physicians and radiologists And rely on knowledge of the likely patterns o
10、f disease infiltration within strict SUV scale limits.However,limited spatial resolution and partial volume effects blur the edges of FDG-avid tumors at PET.PET-based Radiation Therapy Planning the FDG PETdefined gross tumor volume(GTV)was found to be smaller and more accurate than the CT-or MR imag
11、ingdefined GTV and closer to the tumor volume at pathologic analysis.however,no single imaging modality allowed perfectly accurate three-dimensional estimation of the tumor volume.All modalities failed to detect about 10%of the tumor volume,mainly because of superficial tumor extension.PET was found
12、 to allow the identification of potential disease extension beyond the CT-defined GTV in 29%64%of cases.PET-based Radiation Therapy Planning Duprez et al(24)demonstrated the feasibility of applying dose escalation to an FDG PETavid GTV with dose painting by numbers instead of with GTV contouring.The
13、 use of multimodality imaging raises the question of whether the GTV should be defined on the basis of imaging with only one or with several modalities？The lack of concordance found between various imaging modalities suggests that the safest approach when defining a target is to use all imaging moda
14、lities along with physical examination.Anatomic and functional imaging modalities could provide different but complementary information during contouring and planning for cancer RT treatment.Contour lines are color coded to show the imaging modality on which they are based(green=CT,blue=MR imaging,o
15、range=PET).Adaptive Radiation Therapy Planning There is considerable interest in personalizing treatment in an attempt to optimize the therapeutic ratio for individual patients.One avenue for achieving this is to alter the delivery of radiation therapy on the basis of changes in the tumor and/or nor
16、mal organs during a course of treatment.Mainly current radiation therapy is planned at a single pretreatment time-point to delineate the target volume and any organs at risk,with no account taken of anatomic changes during the course of fractionated radiation therapy.Adaptive Radiation Therapy Plann
17、ing Geets et al showed reductions of 51%in the clinical target volume and 48%in the planning target volume after a partial course(45-Gy dose)of radiation therapy.In a subsequent study of patients receiving CRT therapy for laryngopharyngeal cancer,PET-based and CT-based primary tumor GTVs were found
18、to decrease at a mean rate of 3.2%and 3.9%per treatment day,respectively while nodal GTVs decreased at a rate of 2.2%per treatment day.In addition,positional shifts were noted in the GTV.Adaptive Radiation Therapy Planning It provides an opportunity to improve the therapeutic ratio by minimizing the
19、 overall dose to organs at risk and escalating the dose to areas of tumor tissue.18F-fluorothymidine(FLT)PET/CT is a noninvasive method for monitoring proliferation during treatment.Troost et al showed that decreases in tumor-related FLT uptake occurred early after the administration of the fifth ra
20、diation dose fraction.By contrast,changes in the CT-defined GTV were detectable only after 4 weeks of radiation therapy.These data demonstrated the feasibility of escalating the radiation dose administered to tumor sub-volumes with high proliferative activity in the 2nd week of treatment.Figure 6.Ad
21、aptive therapy planning in a 68-year-old man with a supraglottic SCC(T2N2bM0)treated with chemoradiation therapy.(a)Axial fused PET/CT image obtained before the start of therapy shows marked metabolic activity(SUVmax,22.2)in the tumor(arrowhead).(b)Axial fused PET/CT image obtained after 11 fraction
22、s of radiation therapy shows a reduction in tumor size and metabolic activity(SUVmax,9.7).(c)Axial fused PET/CT image,obtained after 21 fractions of radiation therapy,shows continued reduction in tumor size and metabolic activity(SUVmax,7.9).Adaptive Radiation Therapy PlanningOther limited fMRI data
23、 also suggest that changes on diffusion-weighted or dynamic contrast-enhanced MR images could be used to guide adaptive dose escalation strategies.a and b beforec and d after 21 fractionshow the tumor(arrow)and node(arrowhead)with reduced signal intensity in c and increased signal intensity in d,fin
24、dings indicative of response to treatment.Mainly issues of FI to guide A-RT planning1、the choice of imaging modality.2、imaging characteristics may not be reproducible at successive imaging evaluations.3、the optimal timing of imaging assessments during the course of treatment is unknown.4、the optimal
25、 method for defining tumor contours is unclear.PART II Functional Imaging for Disease Response Assessment functional imaging appears to be a promising addition to clinical examination and anatomic imaging for assessing the response of head and neck SCC tumors to radiation therapy.This is particularl
26、y true in the clinical scenario of residual masses,where anatomic imaging techniques are inaccurate.The use of FDG PET is now supported by considerable data.A role also may be established for other PET-and MR imagingbased techniques.I selected fMRI as my favorite lecture today.While leave PET for co
27、lleague from nuclear medicine department.Functional MR Imaging Techniques Advanced MR imaging techniques such as 1.dynamic contrast-enhanced imaging,diffusion-weighted imaging2.blood oxygenation leveldependent(BOLD)imaging3.spectroscopy hold the promise of providing functional information about dise
28、ase.These techniques can be used for planning,monitoring,and assessing the results of radiation therapy in patients with head and neck SCCs.Dynamic Contrast-enhanced Imaging it is a noninvasive technique that helps characterize the microvasculature,thereby providing markers specific to perfusion,per
29、meability of blood vessels,and the volume of extracellular space.Abnormal microvessels seen at dynamic contrast-enhanced MR imaging themselves may be a marker of hypoxiaTumor angiogenesis is associated with chaotic vessel formation and incompetent arteriovenous shunts,which lead to less effective pe
30、rfusion and a more hypoxic environment than exists in normal tissues.Previous studies of DCE MRI Newbold et al demonstrated a statistically significant correlation between various DCE-MRI parameters,particularly Ktrans(which represents the permeability of blood vessels)and pimonidazole staining(an e
31、xogenous marker for hypoxia).The appearance of head and neck SCCs at dynamic contrast-enhanced MR imaging also has been used to successfully predict treatment response to chemoradiation therapy in the tumors(85).(a)Axial T1-weighted MR image obtained for planning of chemoradiation therapy in a 62-ye
32、ar-old man shows a primary SCC in the left aspect of the tongue base(T4N2bM0)(arrow)and a nodal metastasis(arrowhead).(b,c)Axial dynamic contrast-enhanced MR images before and after RT show increased vascular permeability(Ktrans)before radiation therapy in the primary tumor(arrow in b)and cervical n
33、ode(arrowhead in b)decreased permeability after 11 fractionated doses of radiation therapy in the tumor(arrow in c)and node(arrowhead in c).These findings are indicative of therapeutic response.Diffusion-weighted Imaging Diffusion-weighted MR imaging is a noninvasive imaging technique that facilitat
34、es tissue characterization on the basis of the molecular motion of water molecules.Diffusion is quantified by using the ADC,which is inversely correlated with cellularity and is a potential biomarker for apoptosis.The increased density of cells within malignant lymph nodes reduces their ADC at diffu
35、sion-weighted MR imaging.Studies have shown that DWI can be useful for differentiating small malignant lymph nodes from nonmalignant ones In one study,a sensitivity of 76%was obtained with the use of ADC at diffusion-weighted imaging for detecting subcentimetric lymph node metastases,in comparison w
36、ith a sensitivity of 7%obtained with the use of morphologic features and size depicted at conventional MR imaging In another study,in 33 patients with head and neck SCCs,change in ADC was used as a marker of tumor response just 1 week after chemoradiation therapy.Dirix et al(31)evaluated the usefuln
37、ess of DWI for radiation therapy planning and found that patients with local-regional recurrence had lower ADC values within the tumor after 4 weeks of radiation therapy.This finding suggests that DWI would be useful for identifying patients who might benefit from adaptive escalation of the radiatio
38、n dose.ADC values also are associated with a lower false-positive rate for both primary and nodal disease than uptake at FDG PET.Other fMRI techniques The use of blood oxygenation leveldependent(BOLD)imaging in patients with head and neck SCCs is still under development,and further research must be
39、performed before the technique may be validated and standardized to ensure reproducibility.As well as phosphorus 31 MR spectroscopy and proton(hydrogen 1)MR spectroscopy Perfusion CT is gradually replaced by fMRI because of radiation exposure.Conclusions Noninvasive imaging of molecular biomarkers h
40、as the potential to transform the management of head and neck cancers.PET/CT,MR imaging,and perfusion CT provide unique and complementary information about the tumor microenvironment at baseline,during therapy,and after treatment.These complementary data can be used to provide therapy that is truly personalized and adaptive.
