Positron Emission Tomography in Gastrointestinal malignancies

SHANKAR ZANWAR

History and principle

While 1st human PET image was made in 1950, Michael Phelps in 1975 was first to detail the medical importance of PET scan

PET uses compounds that closely resemble natural substances like glucose - Fluoro-Deoxy Glucose(FDG)

These are labelled with radioactive atoms like fluorine (18F) emits positrons

Positron collide with nearby e- , to form ƴ rays at diametrically opp. direction that are detected & localized detector gantry.

After FDG injection activity of patient is restricted for at least 20 min. to minimize the uptake by sk. muscles.

PET can be fused with CT to give a better localization of pathology

The up take of contrast is quantified in SUV-Standardized uptake value

Warburg effect – Cancer cells utilize more glucose and differently so from normal cells and are not ATP efficient.

Esophageal carcinoma

Role of PET in staging Deeper tumor a/w with higher nodal and distant mets

Nodal mets beyond loco-regional – unresectable

T2 or less primary resection, T3 and beyond pre-op chemo/chemo-radiotherapy

Sensitivity of PET in various studies to detect T1 lesion range from – 43%- 55%.

Kato Cancer 2005

Larger lesions can be picked up with greater sensitivity

Conclusion from the various studies – PET is inadequate modality for assessing the tumor depth

PET cannot distinguish carcinoma in situ from invasive disease

Also false +ve results may occur d/t chemo, radiation induced esophagitis, candidiasis

EUS is a better modality depth assessment 90% sens, 99% specific, but it may not able to pass stenotic tumors – PET-CT may be useful here

Puli WGJ – EUS staging for esop can, metaanalysis 2005

Role of nodal staging in esop. ca

CT, EUS and PET in synergy did not improve yield

Low yield could be d/t selection bias (only early stages with micromets)

PET role – better as adjunct to conventional imaging than a comprehensive test

PET combined with CT showed greater accuracy compared with PET alone (sensitivity 70% vs 62%)

Roedl et al Abd Imaging 2009

Dual time PET may help differentiating benign vs malignant lesions

Role in detecting mets in esoph ca

Better results than in depth detection

PET correctly upstaged 15-20% of pt. from M0 to M1 in studies detecting distant mets by Flamen et al and Lowe et al

Prediction of survival in esoph ca

Meta- analysis of 12 studies reported higher SUV max was a/w inferior survival

Hazard ratio for recurrence and death when SUV was above median – 2.52 and 1.86 respectively

Pan L, Eur J Gasent and Hep 2009

Survival for 5 year SUV max, Sq C C (contrast with adeno ca.) <4.5 - 76% >4.5 – 47% Kato Cancer 2005

Role in predicting chemo-radio reponse

Mandard system of evaluation after neoadjuvant chemo– >10% tumor cells remnant – non responder 0-10% - partial response 0% - complete response

Ott et al (J Clin Onco – 2006), metabolic responders (defined as 35% ↓ from base line SUV) were a/w pathologic response in 44% of pts. compared with 5% metabolic non responders

Confirmed similarly by van Vliet ,Br J cancer 2007

Primary utility of change in SUV from baseline response to chemo is guides in future management.

MUNICON trial metabolic responders achieved higher histological response in 58% of pts.

R0 resection could be achieved in 96% of metabolic responders

Event free survival in metab. Responder 29.4mon compared with 14.1 mon in non responders

Lordick Lancet Onco 2007

All above data does not hold true if pt gets neo adjuvant chemo-radio

No difference in pathological response w.r.t. SUV changes on PET, possibly due to stunning effect of radiation on cancer cells

Conclusion - PET is promising modality for chemo response detection,

Role in detection of recurrence

A follow-up study of 112 pts. sensitivity for local, regional and distant recurrences – 50%, 92% and 89.9%

Guo H J Nuc Med 2007 Another study for loco regional recurrence PET vs

CT sensitivity and specificity 100vs 65% and 85% vs 91%

PET in this study had 100% predictive value but reviews(WGJ) say its too early to recommend for general use.

Teyton J Gastroint Surg 2009

NCCN Guidelines, 2015 – PET only for assessment of chemo response

before surgery PET should not be used for selection of pts. to

surgery following pre-op chemo-radiation

Comparison of FDG PET with other molecules like FLT – fluorothymidine showed that FDG is better than FLT, thus FLT has no role at present.

van Westreenen J Nuc Med 2006

Gastric adenocarcinoma

Unlike esophageal tumors gastric lesions less well imaged

Various series ranging from 21-100% sensitivityLatest – Kameyama R Eur J Nuc Med

2009

FDG uptake may also be seen in superficial and erosive gastritis

Role in tumor size and depth

Sensitivity is lower for size <3cm – 21%

T1 lesions less likely to be detected

Histological sub type variation is also noted

Non intestinal type – 0-77% sensitivity

Intestinal type 44- 92% sensitivity

This variation may be related to variability in GLUT-1 receptor expression

But variation in histological subtype does not correlate with SUV

Takahashi Ann Nuc Med 2009

Role in screening- Not effective, sensitivity only 10% compared to OGDscopy, PPV 8.3%

Shoda H Br J Cancer 2007 similar in other studies

Lymph node status assessment – Sensitivity is generally low – 22-60%

Kamimura Nuc Med Commun – 2009

PET compared with CT, sensitivity of CT 52-77%, specificity 62-94% vs PET specificity – 62-100%

Yashioka T J Nuc Med 2003 Role in peritoneal disease assessment - Inferior to

CT(sensitivity -76 -80% vs PET – 9-30%)

Response to preop chemo- Response criteria – 35%↓ in SUV value of target lesion

Metabolic response predicted histological response in 10/13 pts. sensitivity 77% and specificity 86%

Weber W A, J Clin Onco

Role in prediction of survival - At 2 year follow-up survival in metabolic responders – 90% vs 25% in nonresponders

Di Fabio gastric cancer 2007

Role in detection of recurrence

Compared with CT lesser sensitivity(87% vs 47%) but greater specificity(70-100%)

Sim SH BMC Cancer 2009

FDG PET utility in recurrence detection is dependent on prevalence of ca stomach i.e., higher prevalence a/w higher PPV

NCCN guidelines 2015

PET-CT has higher accuracy in preop staging i.e. 68% than PT(47%) and CT(53%) alone

PET alone is not adequate in staging of ca stomach, but it could be helpful when used in conjunction with CT

PET/CT is useful in predicting chemo response and recurrence prediction

PET may be also be useful in detecting occult mets, but additional studies needed to establish utility.

Pancreatic adenocarcinoma

Role in diagnosis – Sensitivity 85% for ca pancreas and 84% for chronic pancreatitis based on SUV cutoff of 4

PET has lower sensitivity than EUS but higher specificity than all other modalities

Sensitivity of PET increases when blood glucose is corrected to normal levels

Sperti J Gastrointest Surg 2005

Ability of PET is greater than CT in detecting smaller lesion

Gambhir et al J Nuc Med 2001

Role in staging – Not a preferred modality, due to poor spatial resolution.

Lymph node staging – Sensitivity ranges from 49-76% for local field involvement.

For hepatic mets - sensitivity of 97% if size >1cm but specificity <43% if <1cm.

Role in prognostication - SUV >4.0 overall survival 7 mon, compared to those with 32mon those with SUV <4.

Sperti J Gastrointestinal surg 2006

Role in chemo response prediction

Those with 50%↓ SUV from baseline, 10% had complete surgical resection

Compared to 6% for those with non respoders

Those with response had survival 23.2mon vs non responders survived – 11.3mon

Choi Am J Clin Onc 2010

PET response correlates with tumor markers fallKuwatani Int Med 2009

Role in predicting recurrence

PET is superior in predicting than CT and MRI in detection of recurrence (96% vs 39%)

CT and MRI though poor for local recurrence but sensitive for hepatic mets and better than PET.

PET is complementary to CT in recurrence detection(increases sensitivity to 94.7%)

Ruf Pancreatology 2005

NCCN guidelines 2015

Role in stagingPET/CT is not a substitute for high quality CECT but can be considered adjunct to CT in high risk with mets

Borderline resectable Markedly elevated CA 19.9 Large primary tumor Large regional LN Very symptomatic pt.

Colorectal cancer Value in preop staging – Insufficient evidence for its routine

use

Sensitivity for recurrent disease – 91% and specificity 91%.Review of 30 studies J Brush Health tech Assess 2011

Role in colorectal liver mets – PET-CT is better than CT in detecting extra hepatic mets but at least equal to CT in intrahepatic mets

The studies show that PET may change management in 10-21% of patients i.e. avoidance of surgery

Response prediction after chemo therapy – PET-CT predicts tumor response in 70% of lesions vs CT alone.

Goshen E Technol Can Res 2011

Whom to scan? – consensus in reviews – only if suspicion of mets high after CT/MRI used after multidisplinary opinion

NCCN guidelines 2015

Non metastatic ca colon No routine use

Indicated if – inconclusive imaging results on MRI or CT, not useful for sub centimeter lesions

Synchronous mets Recommended if prior imaging suggest potentially resectable M1

lesion, to identify if any unresectable mets exist

C/I for clearly unresectable mets on prior imaging

C/I in chemo response assessment since False –ve for transient period post chemo/ false +ve - if inflamed, MRI used instead

NCCN guidelines 2015

Metachronous mets – Main role in establishing extra hepatic mets if any

Preop PET changes management in ~25%

Though no impact on survival, surgical management changes in nearly 8%

Surveillance Not recommended as routine But may be indicated in pts. with high CEA and

negative good quality CECT

Hepato-biliary malignancies

HCC – only 30-50% demonstrate uptake of FDGOkazumi J Nuc Med 1992

Alternative tracer – 11C acetate has been used in conjunction with FDG

Well differentiated HCC - -ve FDG, +ve C acetate Undifferentiated - +ve FDG, -ve for C acetate Moderately differentiated mixed affinity But applicability of this uptake pattern still in abstracts level

FDG – reported to be more accurate than CT (90% vs 45%) in detecting recurrence after TACE or RFA

Zhao, WJG 2005

Cholangioca and GB ca.

Very few studies

No enough data for comparing efficiency of different modalities in evaluating PET

Most individual studies PET is better than other imaging in detecting mets, regional LNs.

PET - Poor intrahepatic mets detection vs better extra hepatic detection

NCCN for cholangio ca. – though not established PET may be used in assessment regional LN and potentially resectable disease for finding distant mets

Neuroendocrine tumours

Different radio tracers may be needed because of histological composition

Overall data shows that PET is more accurate and sensitive than CT alone or MRI.

Kayani Nuc Med Jour 2008

Intrahepatic mets lesser accuracy than other modalities

May add to diagnostic yield when used as adjunct to other modalities

Thank You

They said I will need a “PET” scan