1 Introduction
2 Imaging assessment of tumor response
2.1 Conventional imaging modalities
Imaging modality | Principle/target | Mechanism/radiotracer | Biological correlation | Advantages | Limitations |
---|---|---|---|---|---|
US | Tissue perfusion and vascularity: – Blood flow – Peak intensity – Time to peak intensity – Area under the curve | DCE: enhanced representation of the vasculature following the administration of microbubbles | – No ionizing radiation – Real-time imaging – Short acquisition time – Inexpensive – Availability | – Whole-body imaging not possible – Contrast agents are limited to vasculature – Operator dependency – Assessment limited to selected targets | |
CT | Tissue perfusion and vascularity: – Relative blood volume – Relative blood flow – Mean transit time | DCE: changes in density following the administration of iodinated contrast agent | – Vessel density – Vascular permeability – Perfusion | – High spatial resolution – Short acquisition time – Moderately expensive – Availability | – Radiation burden – Poor soft tissue contrast – Assessment limited to selected targets |
MRI | Tissue perfusion and vascularity: – Initial curve under the gadolinium curve – Transfer rate and constants – Leakage space fraction – Fractional plasma volume | DCE: contrast average uptake rate in tissues Influenced by transfer rate, extracellular volumes, plasma volume fraction | – Vessel density – Vascular permeability – Perfusion – Tissue cell fraction – Plasma volume | – No ionizing radiation – Excellent soft tissue contrast | – Expensive – Long acquisition time – Low availability – Assessment limited to selected targets – Good patient cooperation required |
Scintigraphy | SSTR2 |
111In-pentetreotide | – SSTR2 density | – Whole-body scan possible – Availability – Sensitivity and specificity for staging superior to conventional imaging | – High to moderate affinity to SSTR2 – Low resolution; planar views – Long acquisition time – Evaluation of organs with high physiological uptake (e.g., liver, gut) |
SPECT or SPECT/CT | SSTR2 |
111In-pentetreotide | – SSTR2 density | – Tomographic imaging – Combines functional and structural information (SPECT/CT) | – Lower spatial resolution than PET – Long acquisition time – Suboptimal physical resolution of isotopes used for SPECT |
PET/CT | SSTR2 |
68Ga-DOTA-TATE | – SSTR2 density | – Whole-body scan possible – High spatial resolution of PET – Short acquisition time – Very high affinity to SSTR – Rapid extraction and clearance – Combines functional and structural information | – Limited to SSTR2 expression – Tumor dedifferentiation and loss of SSTR expression |
SSTR2, SSTR5 |
68Ga-DOTA-TOC | – SUV with IRS of SSTR2A – SUV with tumor-absorbed doses after PRRT | Idem | – Limited to SSTR2 and SSTR5 expression – Tumor dedifferentiation and loss of SSTR expression | |
SSTR2, SSTR3, SSTR5 |
68Ga-DOTA-NOC | – SUV with IRS of SSTR2A and SSTR5 | Idem – Superior to other 68Ga-radiolabeled peptides | – Tumor dedifferentiation and loss of SSTR expression | |
Catecholamine transporter and synthesis |
18F-DOPA | – Urinary levels of 5-HIAA – No correlation with SSTR | – Whole-body scan possible – Greater sensitivity than SRS – Role in negative SRPET and inconclusive conventional imaging – Greater sensitivity in functioning tumors | – Lower sensitivity than 68Ga-labeled PET | |
Catecholamine transporter and synthesis |
11C-5-HTP | – Urinary levels of 5-HIAA – No correlation with SSTR | – Same as 18F-DOPA | – Very short half-life of radiotracer – Very low availability | |
Glucose transporter |
18F-FDG | – Ki-67 % | – Whole-body scan possible – Poorly differentiated and/or highly proliferative tumors | – Useless in well-differentiated tumors |
2.2 Standard size-based evaluation criteria
WHO | RECIST 1.0 | RECIST 1.1 | |
---|---|---|---|
Method to assess tumor burden | Sum of products of the longest and greatest perpendicular diameters of all measured lesions (bidimensional) | Sum of longest diameters of target lesions (one-dimensional) | Sum of longest diameters for nonnodal and short axis for nodal target lesions (one-dimensional) |
Definition of measurable disease | Not specified | CT: ≥10 mm with spiral CT ≥20 mm with nonspiral CT Clinical: ≥20 mm LN, not specified | CT: ≥10 mm longest diameter for nonnodal ≥15 mm short axis for nodal lesions Clinical: ≥10 mm (measured with calipers) Special considerations for bone and cystic lesions |
Number of target lesions to follow | Not specified | Maximum of 10 lesions (up to 5 per organ) Should be those with longest diameters, representative of all involved organs, and most suitable for accurate repeated measurement | Maximum of 5 lesions (up to 2 per organ) Should be those with longest diameters, representative of all involved organs, and most suitable for accurate repeated measurement |
Response categories | |||
• CR | Disappearance of all known disease, confirmed at 4 weeks | Disappearance of all known disease, confirmed at 4 weeks | Disappearance of all target and nontarget lesions LN <10 mm short axis |
• PR | ≥50 % decrease of tumor burden, in the absence of new lesions, confirmed at 4 weeks | ≥30 % decrease of tumor burden, taking baseline sum as reference, in the absence of new lesions, confirmed at 4 weeks | ≥30 % decrease in tumor burden, taking baseline sum as reference, in the absence of new lesions, to be confirmed at 4 weeks only in nonrandomized trials with response as primary endpoint |
• SD | Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD | Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD | Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD |
• PD | ≥25 % increase in tumor burden or appearance of new lesions | ≥20 % increase in tumor burden, taking the smallest sum since treatment started as reference, or appearance of new lesions | ≥20 % increase in tumor burden, taking the smallest sum since treatment started as reference, with a minimum absolute value increase ≥5 mm or appearance of new lesions |
2.3 Pitfalls of size-based response assessment in GEP-NETs
2.4 Alternative response evaluation criteria
Response categories | Response criteria | |||
---|---|---|---|---|
Choi | mRECIST | MASS | PERCIST | |
CR | Disappearance of all lesions and no new lesions | Disappearance of any intratumor arterial enhancement in all target lesions No new lesions |
Favorable response
≥20 % decrease in tumor burden per RECIST or ≥10 % decrease in tumor burden per RECIST and ≥ half of nonlung target lesions with a ≥20 HU decreased mean attenuation or One or more nonlung target lesions with a ≥40 HU decreased mean attenuation No new lesions | Complete resolution of 18F-FDG uptake within tumor volume so that it is less than mean liver activity and indistinguishable from surrounding background blood-pool levels |
PR | ≥10 % decrease in tumor burden per RECIST or ≥15 % decrease in tumor density (HU) on CT scan and no new lesions nor unequivocal progression of nonmeasurable disease | ≥30 % decrease in tumor burden per RECIST considering only viable tumor of target lesions (that with arterial enhancement on CE radiological techniques) No new lesions | ≥30 % relative and ≥0.8 absolute decrease in 18F-FDG uptake (SUL peak of target lesion) and no >30 % increase in SUL of nontarget lesions and no PD by RECIST ROI does not need to be in precise same area as baseline scan | |
SD | Does not meet criteria for complete, partial, nor progressive disease and No clinical deterioration attributable to tumor progression | <30 % decrease to ≤20 % increase in the sum of maximum arterial enhancing diameter of target lesions No new lesions |
Indeterminate response
Does not fulfill criteria for favorable or unfavorable response No new lesions | Does not fulfill criteria for partial response nor for progressive disease |
PD | ≥10 % increase in tumor size per RECIST that does not meet criteria for PR by tumor density on CT scan or Appearance of new lesions including new intratumor nodules or increase in size of existing nodules | >20 % increase in tumor burden per RECIST considering only viable tumor of target lesions or Appearance of new lesions |
Unfavorable response
≥20 % increase in tumor burden per RECIST or Target lesion with central necrosis changing to near complete enhanced solid tumor or New enhancement in a nonenhancing lesion or Appearance of new lesions | >30 % relative and 0.8 absolute increase in 18F-FDG uptake (SUL peak of target lesion) or Unequivocal increase in extent of 18F-FDG uptake (75 % in total lesion glycolysis volume with no decline in SUL) or New 18F-FDG-avid lesions |
3 New imaging modalities for assessing GEP-NETs
3.1 Cancer-specific functional imaging
3.1.1 Somatostatin receptor imaging: SRS and 68Ga-DOTA peptides
SSTR2A (nmol/L) | SSTR3 (nmol/L) | SSTR4 (nmol/L) | SSTR5 (nmol/L) | |
---|---|---|---|---|
SRS | ||||
111In-pentetreotide | 22 | – | – | – |
SRPET | ||||
68Ga-DOTA-TOC | 2.5 | – | – | 73 |
68Ga-DOTA-TATE | 0.2 | – | – | – |
68Ga-DOTA-NOC | 1.9 | 40 | – | 7.2 |