5 novembre 2019

Livia Ruffini

SC Medicina Nucleare

Azienda Ospedaliero-Universitaria di Parma

Il PDTA di Oncologia Toracica dell’AOU di Parma

Dal sospetto alla diagnosi di neoplasia toracica

La stadiazione PET

In contrast to commonly used clinicalimaging, it sets forth to probe themetabolic/molecular abnormalitiesunderlying the cancer rather than thestructural consequences of theseabnormalities

Functional imaging: visual representation of biological processes

Glucose utilization: FDG PET

CT PET/CTPET

PET/CT - HYBRID IMAGING

M 67 yrs, ADCStaging FDG-PET: T SUVmax 9,3; lymph nodes SUVmax 7,7

N1 Stage

M 63 yrs

ADK

N2 Stage

T SUVmax 11.7N SUVmax 6.8

N SUVmax 4.4

F 63 yrs

ADK

ALK - PDL-1 + (1%)

N3 Stage

StagingSCC with Liver MTS

FDG-PET/CT

• Providing information about size and local extent/invasion.

• Chest CT primary and most commonly used modality to achieve this task

• FDG PET/CT can accurately delineate the viable tumor from surrounding atelectasis and collapse/consolidation for accurate T staging but also provide guidance for biopsies if histological confirmation is required or prior biopsy attempts have led to inconclusive pathological results

T classification of the primary tumor

• Primary radiochemotherapy is the mainstay of treatment for patients with locally advanced NSCLC

• Appropriate performance status, functional imaging could provide important information, especially on target volumes definition for irradiation

• Volume difference is mainly due to the separation of tumor from atelectasis

T classification for target volumes definition in RT planning

Tumor volume can be better depicted by FDG-PET/CT largely affecting the precision of defining the target

volume, and decreasing the irradiated volume as well as the dose to tumor-surrounding radiation-

sensitive organs at risk.

Steenbakkers et al. Int. J. Radiation Oncology Biol. Phys. 2008

M 63 yrs

ADK

N2 Stage

T SUVmax 11.7N SUVmax 6.8

N SUVmax 4.4

PET/CT – SUV (STANDARD UPTAKE VALUE)

Higher the SUV, greater the risk of disease

Compare SUVs to monitor therapy

Cannot be used as an absolute number

before chemotherapy SUV = 17.2

chemotherapy day 7SUV = 3.9

chemotherapy day 42SUV = 1.8

ROI

Activity in ROI (MBq) / vol (ml)

Injected activity (MBq)/patient weight (g)SUV =

Reports of practical oncology and radiotherapy 2013

Primary T volume by PET–CT to evaluate risk of mediastinal nodal involvement

• Tumor area is identified and delineated on each PET–CT scan

• IzoSUV2.5 volumes, that is the volume of primary tumor inside SUV 2.5 line, is calculated automatically

• Lymph nodes greater than 10 mm in the short axis and SUV > 2.5 were interpreted as metastatic.

Risk of mediastinal nodalinvolvement and tumor volume

Factors influencing FDG uptake in NSCLC on PET/CT Expression of glucose transporters 1 and 3

Correlations between Glut-1 and Glut-3 expression at high rates and SUVmax

Lung Cancer 2010

AC showed positive expression at a high rate, as did SCC, for both Glut-1 and Glut-3, although the degree of overexpression was significantly higher for SCC than for AC

Lung Cancer 2010

Factors influencing FDG uptake in NSCLC on PET/CT Expression of glucose transporters 1 and 3

Histological differences of grades of Glut-1 and

Glut-3

Muto J. Anticancer Research 2014

Cut-off values could be set for different histological subtypes, although data from different institutions would

need to be validated

primary T (354 pts) adenocarcinoma (235 pts) lowest SUVmax 1.24

squamous cell carcinoma (94 pts)lowest SUVmax 2.05

Predicting Lymph Node Involvement in Patients with Primary NSCLC

• MTV: total volume of the FDG-avid lesions

• TLG: combines the volumetric and metabolic information of FDG PET and

reflects whole-body tumor burden

• Whole-body TLG provides a strong prognostic indicator in patients with

NSCLC and could be an important guide for making treatment decisions

Metabolic tumour burden and total lesion glycolysis

• Metabolic Tumor Volume (MTV) = total tumor volume with SUV > 2.5 or greater

• Total lesion glycolysis (TLG) = MTV x SUVmean (cm3*g/ml)

TLG of 707.4 TLG of 196.8 TLG of 52.77

a b cStage IIIB NSCLC

a.66-year-old man PFS of 3.6 months

b.69-year-old man PFS of 1.3 years

c. 52-year-old woman PFS of 3.2

years

Prognostic Value of the Volumetric Parameters of 18F-FDG PET/CT in Non–Small Cell

Lung Cancer Treated With Definitive Radiation Therapy

AJR:213, December 2019

Volume of interest automatically rendered using standardized uptake value threshold of 2.5

Kaplan-Meier curve of disease-specific survival rate according to total lesion glycolysis of primary tumor (TLG-T) and change in TLG-T (ΔTLG-T).

ΔTLG and TLG on FDG PET were significant predictors of the local control rate (LCR) and disease-specific survival of patients with NSCLC who received definitive RT.

In particular, patients with low ΔTLG had poor outcomes in terms of LCR and disease-specific survival.

Prognostic Value of the Volumetric Parameters of 18F-FDG PET/CT in Non–Small Cell Lung Cancer Treated With Definitive Radiation Therapy

AJR:213, December 2019

pure

Texture analysis of FDG PET images of patients with lung cancer

Homogeneous tumor M, 56 yrs

Heterogeneous tumor M, 80 yrs

RadiomicsPost-processing and analysis of large amounts of quantitative imaging features derived from medical images Radiogenomics focused on defining relationships between the radiomics phenotypes and genomic information

• More heterogeneous tumors on imaging tend to be more aggressive and to be associated with poorer outcomes

• Increasing heterogeneity is linearly associated with tumor SUV - a prognosticator of poor outcome in lung cancer

• Specifically, patients with PET images showing relatively uniform tracer distribution (high contrast, low coarseness) have better outcome

Ganeshan et al. Cancer Imaging 2010

Relationship between texture features in NSCLC and the likelihood for response to chemoradiotherapy

pre-treatment imaging

second week of radiotherapy

• Manner of SUV discretization has a crucial effect on the resulting textural features and the interpretation thereof, emphasizing the importance of standardized methodology in tumor texture analysis

• Up till now no prospective clinical studies on this approach can be found on www.clinicaltrials.gov

The effect of SUV discretization in quantitative FDG-PET Radiomics

• FDG-PET at baseline and at 6 weeks• Differences in survival between patients with

a change in entropy of more than 20% and those with a change in entropy of less than 20%

• Response to erlotinib is associated with reduced heterogeneity at 18F-FDG PET• The heterogeneity of 18F-FDG uptake measured by first-order texture features on

PET images of NSCLC decreases in patients who respond to the tyrosine kinase inhibitor erlotinib (P = .01; entropy, P = .001; uniformity, P = .001).

Cook et al. Radiology 2015

Heterogeneity of 18F-FDG Uptake at PET in NSCLC Treated with Erlotinib

VP

QC

SUVmax 1.5

SUVmax 2.6

VuePoint QClear

SUV 2.2 SUV 3.2

SUV 5.2 SUV 6.8

• Type of PET-CT scanner employed is associated with different accuracy estimates

• The two main integrated PET-CT scanner manufacturers have produced products with

different characteristics

• It is of potential importance to lung cancer clinicians to know that the equipment alone

may influence the result obtained.2014 The Cochrane Collaboration

Type of PET-CT acquisition

GATED IMAGES

IMAGING 4D

GATED ACQUISITION (4D): 6 TEMPORAL PHASES

Phase IV (58%): SUVmax 4.7

phase I (8%): SUVmax 3.7

Monitoring response to treatment

M 64 yrs

ADK, ALK - PDL-1 + (10%)

Neoadjuvant ChT (3 courses Carbo+Alimta)

M, 71 yrs 2012 right lobectomy + wedge resection14.02.17 PET right hilar LN ChT26.06.17 PET: PR

SUVmax 7,5

SUVmax 4,6

Monitoring N response to treatment

18/09/19

Fig. 2

• Good response to treatment on both primary T and LNs

• Mean decrease of total lesion glycolysis (ΔTLG) 76 ± 6%

• PFS 11 months• OS 24 months

• Good response to treatment on primary T and limited response in LNs

• Mean ΔTLG 38 ± 6% • PFS 7 months• OS 21 months

Baseline Interim (second week of treatment)

TLG is a robust metric to monitor early therapy response in patients undergoing concomitant chemoradiotherapy for locally advanced NSCLC

Grootjans et al. Radiotherapy and Oncology 2016

ΔTLGs (summed Tumor + LNs) in FDG-PET during radiochemotherapy is predictive

for PFS and OS

Metabolic PET/CT Parameters for Primary Tumor and Lymph Nodes to assess response in NSCLC After Neoadjuvant Therapy

• As compared with RECIST 1.1, EORTC seems to be more appropriate to assess response.

• Post-induction parameters varied significantly between responders and non-responders

Clinical Lung Cancer Month 2019

LYMPHNODES CHARACTERIZATION

RADIOTHERAPY: treatment planning

Wouter van Elmpt et al. J Nucl Med 2012

• FDG-PET/CT at second week of radiotherapy

• EORTC response criterion • Metabolic responders (n = 13)

and nonresponders (n = 21) defined for decrease of at least 15% in mean SUV of primary tumor (P = 0.001)

A decrease in 18F-FDG uptake by the primary tumor correlates with higher long-term overall survival

Response Assessment Using FDG PET Early in the Course of Radiotherapy Correlates with Survival in Advanced-Stage Non–Small Cell Lung Cancer

Identification of residual metabolic-active areas within individual NSCLC tumours using a pre-radiotherapy FDG-PET-CT

• Post-radiotherapy FDG-PET-CT scan• 86 days (range: 49–184 days) after the end

of RT• Pre-RT scan performed after ChT for

sequential chemo-radiotherapy

Patients with residual metabolic-active areas within the tumour had a significantly worse survival compared to individuals with a complete metabolic response (p=0.002)

The location of residual metabolic-active areas within the primary tumour after therapy corresponded with the original high FDG uptake areas pre-radiotherapy

The results led to the design of a prospective multicenter phase II clinical trial, called the PET-boost trial closed at the end of 2017

van Elmpt W. The PET-boost randomised phase II dose-escalation trial in NSCLC. Radiother Oncol 2012

Aerts et al. Radiother Oncol. 2009

Transaxial, coronal, and sagittal views of fluorodeoxyglucose (FDG) target volume (TV), and hypoxic volumes in 18 F-fluoromisonidazole

Noninvasive assessment of hypoxia in tumors

[1⁸F]-fl uoromisonidazole

(FMISO)

Fluorinated radiotracer

developed from the

nitroimidazole compound

Trapped inside the cell

constituents under hypoxic

conditions.

Widely used tracers, and

tested clinically in various

tumour types

Kinetic studies showed that

the optimum time between

tracer injection and imaging

is less than 4 h

Metabolism[18F]FDG-PET standardised uptake value (SUV), total lesion glycolysis (TLG), metabolic tumor volume (MTV)

Hypoxia[18F]FMISO-PET tumour-to blood uptake ratio (TBR), standardised uptake value (SUV), hypoxic fraction (HF)

Quantitativeassessment

AIRC Grant IG 2017 Id 20074Task 2 Nuclear Medicine Unit

Metabolic assessment [18F]FDG PET/CT

Intratumoral hypoxia [18F]FMISO PET/CT