功能影像学技术在头颈部肿瘤放疗计划制定疗效评估和个体化治疗中应用

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,功能影像学技术在头颈部肿瘤放疗计划制定疗效评估和个体化治疗中应用,Role,of,routine,and,functional,Imaging,(FI),Screening,and,diagnosis,of,neoplasms,Precise staging,of,malignancy,Response,assessment,of,cancer,treatment,Monitor,recurrences,Benefit,of,FI,Major,modalities,of,FI:,positron,emission tomography (PET) combined with CT or magnetic resonance (MR),imaging,fMRI:,DWI,DCE-MRI,BOLD,spectroscopy,etc.,Emerging,techniques:,PET-MRI,DKI,IVIM,APT,CEST,etc.,Offer complementary information including,metabolism,of,FDG, proliferation, hypoxia, and cell membrane synthesis by,PET,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,article,Part,I,:,Discusses the practical aspects of integrating functional imaging into head-and-neck radiation therapy planning.,Part,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 Radiation 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,:,Inaccuracies in tumor target delineation,Inter-observer variability in,clinical,practice,based,on,CT,for target,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 tissues.,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 software,.,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.,Status,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 of 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 imagingdefined 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 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 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 modalities 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,orange,= 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 normal 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 Planning,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 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 overall dose to organs at risk and escalating the dose to areas of tumor tissue.,18,F-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 radiation 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.,Adaptive 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 fractions,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 Planning,Other,limited,fMRI,data,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,before,c,and,d, after,21,fraction,show the tumor (arrow) and node (arrowhead) with reduced signal intensity in c and increased signal intensity in d, findings indicative of response to treatment.,Mainly,issues,of,FI,to,guide,A-RT,planning,1,、,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 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 particularly 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,colleague from,nuclear,medicine,department.,Functional MR Imaging Techniques,Advanced MR imaging techniques such as,dynamic,contrast-enhanced imaging, diffusion-weighted,imaging,blood,oxygenation leveldependent (BOLD),imaging,spectroscopy,hold the promise of providing functional information about,disease.,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, permeability of blood vessels, and the volume of extracellular space.,Abnormal microvessels seen at dynamic contrast-enhanced MR imaging themselves may be a marker of hypoxia,Tumor angiogenesis is associated with,chaotic vessel formation,and,incompetent arteriovenous shunts, which lead to less effective perfusion 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,K,trans,(which represents the permeability of blood vessels),and pimonidazole staining,(an exogenous 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-year-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 (,K,trans) before radiation therapy in the primary tumor (arrow in,b,) and cervical node (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 facilitates 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 diffusion-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 with 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 usefulness 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 radiation 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 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 has 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.,The End,谢谢您的聆听！,期待您的指正！,