FDG-PET Metabolic Vs CT Anatomical
Monitoring of Tumor Response to Anterior Chemotherapy in Breast Carcinoma-The Uncertainties
Krithikaa Sekar, Bindiya Vijayan, Ancy Mathew, C K Fareena Taj, Radheyshyam Naik, Kruthika Murugan, B S Ajai Kumar, B J Srinivas, Ramesh S Bilimagga, Shekar Patil, Sateesh Chirondoni Thungappa, Veena Ramaswamy, Shivakumar swamy, Sudhakar Sampangi, Kumar Kallur, Somrat Bhattacharjee, M S Belliappa, Mahesh Bandemagal, K Govind Babu, Amritanshu Ram and G Lohith*
Department of Radiation Oncology, HCG Hospitals, India
Submission: June 04, 2021; Published: June 21, 2021
*Corresponding Address:Dr G Lohith, Consultant Radiation Oncologist, HCG Hospitals-Bangalore, India
How to cite this article:Krithikaa S, Bindiya V, Ancy M, C K Fareena T, Radheyshyam N, et al. FDG-PET Metabolic Vs CT Anatomical Monitoring of
Tumor Response to Anterior Chemotherapy in Breast Carcinoma-The Uncertainties. Canc Therapy & Oncol Int J. 2021; 19(1): 556003.
Purpose: To compare the metabolic tumor response and volumetric tumor response to pathological tumor response to NACT and to predict the sensitivity, specificity, positive predictive value and negative predictive value of FDG PET to neoadjuvant chemotherapy.
Material and method: The study was performed after institutional ethical committee clearance.35 consecutive eligible patients treated between January 2015 to May 2016 were included in the study. PETCT was acquired at baseline and post neoadjuvant chemotherapy, prior to surgery. The SUV max of tumor and involved nodes at baseline and post neoadjuvant chemotherapy was compared to pathological tumor size and nodal status. Response was assessed using PRECIST and RECIST criteria. Statistical methods used for analysis were software SPSS version 13, calculations for Sensitivity, specificity, positive predictive value and negative predictive value.
Results: The median age was 51.3 years (range 33 to 68 years). The patients were generally healthy with ECOG PS 0-1. FDG PET tumor to HPE correlation -sensitivity, specificity, PPV, NPV SENSITIVITY 88.8% SPECIFICITY 50% PPV 85.7% NPV 57.1% our results show the high sensitivity and low specificity of PETCT in detecting residual tumor. Overall PCR was in 22.6% (8/35). Pathological Complete Response Rates In The Axillary Node Luminal wise:Total:23/35 – 65.7%. Luminal A PCR Rate -14.4%; Luminal B PCR Rate-8.5%; TNBC PCR Rate-31.4%; HER 2-11.4%.
Conclusion: Although PETCT aids in differentiating necrotic area from viable tumor area and a decrease in SUV uptake post NACT is an indication of treatment response, there appears to be uncertainties in the sensitivity and specificity of PETCT detection of pathological tumor and nodal status. Further analysis onto to same is recommended to infer strategies to improve prediction of pathological outcome.
The spectrum of utility of FDG-PETCT in Breast cancer extends from, staging, early assessment of response to treatment, monitoring metastatic tumors for evaluating disease status at follow up . Neoadjuvant chemotherapy in breast carcinoma aids in downsizing tumor, improves chances of breast conservation surgery and eliminates micro-metastasis . Monitoring metabolic response post neoadjuvant chemotherapy has been a useful tool to plan surgery, predict response to therapy and outcomes . Literature suggests PETCT to be more accurate for NACT response monitoring because of its superiority to current imaging studies for distinguishing tumor tissue from necrotic or fibrotic tissue . Several studies have reported the usefulness of volumetric monitoring of treatment response in Breast carcinoma
using MRI . Our study compares the FDG PET and CT response predictivity to pathological tumor response.
To compare the metabolic tumor response and volumetric tumor response to pathological tumor response to NACT and to predict the sensitivity, specificity, positive predictive value and negative predictive value of FDG PET to neoadjuvant chemotherapy.
The study was performed after institutional ethical committee
clearance.35 consecutive eligible patients treated between January
2015 to May 2016 were included in the study. PETCT was acquired
at baseline and post neoadjuvant chemotherapy, prior to surgery.
The SUV max of tumor and involved nodes at baseline and post
neoadjuvant chemotherapy was compared to pathological tumor
size and nodal status. Response was assessed using PRECIST
and RECIST criteria. Statistical methods used for analysis were
software SPSS version 13, calculations for Sensitivity, specificity,
positive predictive value, and negative predictive value.
As per protocol, with patient fasting overnight, 3 microcurie
18 Fluor Deoxy Glucose was injected and positron emission
tomography images was acquired. SUV max was calculated based
on the formula tracer uptake in ROI / (injected activity / patient
a. Sensitivity- True Positive (TP)/True Positive False
(Proportion of patients with positive pathological node having
b. Specificity-True Negative (TN)/False Positive (FP)+True
(Proportion of patients with Negative pathological node
having PET Negativity)
c. Positive Predictive Value-True Positive/True Positive
(Patients with positive PETCT having pathological node
d. Negative Predictive Value-True Negative/False Negative
(Patients with negative PETCT having pathological node
⇒ The median age was 51.3 years (range 33 to 68 years).
⇒The patients were generally healthy with ECOG PS 0-1.
⇒ The staging information (Chart 2)
⇒ Luminal distribution (Chart 3)
⇒ Details of chemotherapy (Chart 4)
⇒ Surgery Details (Chart 5)
Correlation between presence of FDG PET residue in primary
tumor and histopathological residual primary tumor (Table 1).
Our results show the high sensitivity and low specificity of PETCT
in detecting residual tumor (Table 2). Correlation between FDG
PET Axillary nodal status and histopathological axillary nodal
status (Table 3). On the contrary, the sensitivity of PETCT in
detecting axillary node is low, however with a very high specificity.
ie) Patients with a negative axillary node in HPE have a 91.6%
chance of PET showing No SUV uptake post chemotherapy from
the baseline significant uptake (Tables 4 -7).
From our observation, in 14/35 cases (40%), had microscopic
residual tumor, however PETCT had shown size range of 2.5 to
3.8cm with a Max SUV between 3 to 5.6. On evaluating HPE
report, the size of grey, white area of the specimen correlated
with the PETCT tumor size. In 3/35 cases (8.5%), the residue in
histopathology was larger than the PET reported measurements.
Probable explanation could be microscopically infiltrative
margins, not otherwise picked up in imaging (Charts 6-8).
Screening: PETCT is not recommended imaging of choice for
screening undetected breast cancer as the sensitivity of the same
in detecting lesions less than 1cm is low. Meta-analysis evaluating
13 studies on PETCT in breast cancer detection showed that most
of the studies were unevenly weighted toward large palpable
primary lesions and typically omitted nonpalpable imagingdetected
cancers and hence did not recommend the same .
Staging: Early stage: Routine metastatic workup in earlystage
breast carcinoma is not recommended and hence is PETCT
in this setting .
Staging: Locally advanced: In locally advanced carcinoma,
PETCT is used in screening for metastatic disease and quantifying
extent of locoregional disease .
Axilla: In low risk of involvement for axillary nodes the
sensitivity was 61%, 80% specific, a positive predictive value
of 62% and a negative predictive value of 79%. However, the
sensitivity increased in patients with high risk for axillary nodal
IMR: Studies have shown that FDG PET is superior to CT
in detecting nodal disease of the Internal mammary region,
involvement of which is expected in about 25-30% of patients
with locally advanced carcinoma .
LIVER: FDG PET/CT has been shown to be very accurate
and sensitive in the detection of liver metastases derived from
a wide range of primary cancers. D’Souza et al.  showed the
superiority of PET/CT over contrast-enhanced CT in the detection
of untreated hepatic metastases in a prospective study evaluating
45 patients with suspected liver metastases from various primary
cancers. The authors found that the sensitivity and specificity
in the detection of hepatic metastases was 87.9% and 16.7%,
respectively, for contrast-enhanced CT and 97% and 75%,
respectively, for PET/CT.
LUNG: The sensitivity and specificity of FDG-PET/CT for
pulmonary metastasis were 57.1% and 99.1%, respectively,
and the positive and negative predictive values were 90.1% and
93.6%, respectively, based on literature review. The uptake of FDG
was affected by the size of the metastatic nodules; uptake was
positive and negative in pulmonary metastases with an average
size of 14.9mm and 5.75mm, respectively. The limit of positive
FDG uptake was reached in pulmonary metastases of about 9mm
BONE: Several studies have shown the superiority of FDG
PET to bone scintigraphy in detecting lytic and intramedullary
metastases of bone. Also, in equivocal bone lesions detected by
other imaging modalities, PETCT offers additional clarification
BRAIN: Based on studies, the sensitivity and specificity of
detecting brain metastasis with FDG alone was 45% and 80%.
Combined with CT it improved to 50% and 93%. However, in
addition to better sensitivity and specificity, its ability in detecting
small size lesions and leptomeningeal disease makes MRI the
investigation of choice in detecting brain metastasis .
Metastatic tumors: In patients with metastatic breast cancer,
tumor response on PET/CT appears to be a superior predictor of
PFS and DSS than response on CE-CT. Study findings published
in the European Journal of Nuclear Medicine and Molecular
Imaging revealed that the differences in response assessment
with PETCT versus other modalities could have caused changes
in patient management in 25% of the cohort of 65 women with
stage IV breast cancer. The current standard for monitoring
tumor response and breast cancer progression has been based
on changes in tumor size. This is very effectively measured on
contrast-enhanced CT (CE-CT) imaging. However, the ability of
FDG PET/CT to measure glucose metabolism, assess metabolic
activity in osseous metastases, and differentiate an active tumor
from post-therapeutic change, shown by changes in FDG uptake,
have demonstrated a high accuracy for predicting histopathologic
response of breast cancer .
Monitoring at follow-up: Detecting early recurrence
has an important survival benefit because it prompts clinical
consideration for administering different therapies. However, it
is difficult to differentiate true recurrence from posttreatment
sequelae using the conventional imaging modalities . Grahek
et al.  studied 134 patients with suspected recurrence,
and they found that the sensitivity and specificity of PET for
detecting recurrence were 84% and 78%, respectively, whereas
the sensitivities and specificities of the conventional imaging
modalities were 63% and 61%, respectively
The effect of PET for evaluating the response to treatment
has already been demonstrated for different types of neoplasm,
including breast cancer . In a study by Smith et al, the mean
reduction in FDG uptake after the first cycle of chemotherapy was
significantly higher in the lesions that showed a partial, complete
macroscopic, or complete microscopic response than that of
the non-responsive lesions, as determined by histopathological
examinations . Rose et al. have also reported that after a
single cycle of chemotherapy, PETCT predicted the pathological
complete response with a 90% sensitivity and a specificity of
74%, and by using a decrease in FDG uptake at the threshold of
< 55% to the baseline PETCT, all the responders were correctly
identified after the first treatment course with a 100% sensitivity
and 85% specificity . Studies have shown that after NACT, 39
(28%) patients showed negative conversion of Axillary lymph
node on surgical specimens. The sensitivity of ultrasound, MRI
and PET/CT was 50%, 72% and 22%, respectively. The specificity of ultrasound, MRI and PET/CT was 77%, 54% and 85%,
respectively. Combination of three imaging modalities showed
the highest sensitivity, and PET/CT showed the highest specificity.
Ultrasound alone or combination of ultrasound and PET/CT
showed the highest positive-predictive value .
The rate of PCR in our study was 22.8%. Various studies have
reported PCR rates between 20 to 34% [21,22]. Of note, the PCR
rates differed between the luminal groups and the proportion
of patients in different subclassifications were altered in these
studies. Highest PCR among the luminal: Study by Kim et al
showed that the highest PCR rates were with TNBC . Another
study by Haque et al showed that highest PCR rates were in her2
positive . From our observation, in the era of Trastuzumab
based chemotherapy, the PCR rates are increasing in her2 as
previously noted in TNBC as in our study . Sensitivity of PETCT
in NACT setting in Breast Cancer for assessing tumor response,
as reported in the studies mentioned above ranges between 60-
90% and specificity up to 90%. Our study reports a sensitivity
of 88.8% in primary tumor correlation with HPE residue and a
91% specificity in detecting pathological axillary nodal status.
However, of mention, the specificity i.e., the ability of PETCT to
detect a complete pathological response in tumor appears to be
low (50%) with 8/35(22.8%), showing a PCR in primary tumor
with a contradicting PETCT significant SUV uptake and a CT
residual lesion whose size corresponds to the grey, white lesion
in Specimen. Also, in 3/35 cases (8.5%), PETCT reported decrease
in size and SUV of lesion and was contradicted with a significant
difference in size of pathological residue (later being1.7 times
larger than PET reported residue). Similarly, the sensitivity of
PETCT in detecting a pathological positive axillary node was
33% only, i.e.) with a residual pathological axillary node and a
contradicting PETCT showing NIL SUV uptake. PET&CT Showing
complete regression of axillary node with decrease in SUV from
upfront 8.7 to NIL However pathological axillary node status was
positive (Images 1-4).
Although PETCT aids in differentiating necrotic area from
viable tumor area and a decrease in SUV uptake post NACT
is an indication of treatment response, there appears to be
uncertainties in the sensitivity and specificity of PETCT detection
of pathological tumor and nodal status. Further analysis onto to
same is recommended to infer strategies to improve prediction of