Contrast enhanced CT and PET-CT play a key role in radiological follow-up after RFA.
There is no standard imaging protocol after RFA which has been widely adopted.
However,
within the first month after the procedure,
contrast-enhanced CT is usually preferred because PET uptake in this timeframe is not specific.
Later evaluations generally involve alternating CT and PET-CT every 3 months for up to 2 years.
Contrast enhanced CT allows early detection of recurrences or residual tumor tissue proliferation.
Generally a contrast enhancement greater than 15 HU is associated with proliferation of residual tumor tissue.
Localization of contrast enhancement is also important: central or nodular (>10 mm in thickness) contrast enhancement can be a clue to the diagnosis of progression of incompletely ablated tumor.
PET-CT can be especially useful and provide additional information when tumor progression at the ablation zone or locoregionally is suspected on CT,
in order to assess extrathoracic disease spread,
or in patients who have contraindications to contrast material.
As to PET or PET-CT,
as mentioned before,
studies published in literature concluded that they are best performed at least 3 months after radiofrequency ablation because FDG uptake in the early phase is not specific.
In this poster,
we analyzed CT radiological findings after RFA through our experience of 30 patients who underwent RFA in our center.
CT patterns after RFA are classified according to the time of onset,
distinguishing three different phases: early (≤ 1 week),
intermediate (> 1 week – 2 months) and late phase (> 2 months) [5-6].
For each phase,
information about the size of the lesion,
appearance and contrast enhancement was provided (table 1).
1.
EARLY PHASE ( ≤1 week)
Size of the ablation zone
Due to the onset of edema,
inflammation and hemorrhage,
the ablation zone in the early phase appears larger than the original size of the tumor and enlarges during the first 24 hours (figures 1-5,
10,
11).
Because the ablated lesion initially increases its size,
RECIST (Response evaluation Criteria in Solid Tumors) which are currently used to provide an objective evaluation of the response to treatment cannot be applied immediately following ablation of lung cancers.
Appearance
During the late intraprocedural or immediate postprocedural period,
ground glass opacities (GGO) and intralesional bubbles [7] are frequently observed.
GGO represents an area of hyperemia induced by the thermal damage to the surrounding lung parenchyma (figures 1,
2).
An interesting histological correlation to these ground glass opacities was provided by Yamamoto [8] who described three concentric layers,
namely an inner one of preserved architecture,
an intermediate one of alveolar effusion and an outer one of congested – yet still vital - lung with hemorrhage and neutrophil infiltration.
GGO can extend circumferentially or only partially around the ablated lesion; its extension has a fundamental prognostic value.
It is worth remembering that whereas surgery allows a histopathologic evaluation in order to establish whether resection margins are clear,
this is not possible with thermal ablation,
therefore the evaluation of the effectiveness of the procedure relies solely on the radiologically measured GGO dimensions.
In particular,
in a study [9] no recurrence in a 22.2 month follow-up period was observed if a circumferential GGO with an extension greater than 5 mm beyond the tumor margins was present.
Another study,
led by De Baerè et al.
[10],
stated that complete ablation can be predicted when the ablative area is four times larger than the original lesion.
On the opposite,
in another study [11] 85% of the patients who later developed recurrence were found to have no perilesional GGO in the immediate follow-up CT.
In conclusion,
because peripheral GGO on CT overestimates the true area of coagulation necrosis by 4.1 mm [8],
a 5 mm-cut-off is used: GGO with an extension greater than 5 mm predict effective treatment,
while GGO smaller than 5 mm may indicate incomplete tumor ablation.
At CT performed in the late intraprocedural or immediate postprocedural period,
a “cockade phenomenon” [7] of concentric rings of varying attenuation can be observed (figures 3-5,
11).
It consists of a central area of consolidation - which represents the ablated lesion and necrotic perilesional parenchyma - surrounded by two concentric layers of GGO,
with the outer layer denser than the inner one; as reported above,
intralesional bubbles may be present in the central area.
From a pathologic point of view,
with the increasing distance from the point where the radiofrequency is applied,
lung tissues undergo different tissue changes [12].
From the center to the periphery they are: a vacuolated core,
coagulated tumor,
coagulated lung parenchyma,
coagulated and hemorrhagic parenchyma,
peripheral inflammatory response.
Among other radiological findings observed in the early phase,
the most frequent complication is pneumothorax,
whose reported rate in different studies ranges between 30 and 50% of patients after thermal ablation [13]; however,
only <25% pneumothoraces need chest tube placement [14].
The second most common complication is pleural effusion,
with an incidence of 14,8% according to a meta-analysis of 46 studies which included a total of 2905 patients [15].
Further complications include pleural thickening,
parenchymal hemorrhage,
pneumonia (1,5%) and abscess formation (0,4%).
Contrast Enhancement
A rim of contrast enhancement (benign periablational enhancement) peripheral to the ablation zone represents a normal response after RFA and may observed for as long as 6 months (figure 5) [16].
It reflects the inflammatory reaction (hyperemia and,
later,
giant cell reaction and fibrosis) to tissue damage caused by RFA; unsurprisingly,
it is also a common finding after RFA in renal and hepatic malignancies.
It is of the utmost importance to pay close attention to the ablated zone contrast enhancement features: it ought to be less than 5 mm thick,
with concentric smooth margins.
The central necrotic area on the opposite should be hypoattenuating with marked reduction in contrast enhancement due to disrupted microcirculation caused by thermal injury.
On the opposite,
contrast enhancement which is central,
nodular (> 10 mm) or greater than 15 HU at densitometry suggests the presence of residual tumor tissue.
2.
INTERMEDIATE PHASE ( > 1 week – 2 months)
Size of the ablation zone
As edema and inflammation subside,
the ablation zone should reduce its dimensions compared to its size in the early phase,
though still larger than the original tumor size.
In fact,
only in the late phase will the ablated area witness a size reduction that allows it to reach its pre-ablation original dimensions.
Any further size increase compared to the early phase size should raise the suspicion of residual or recurrent disease.
However,
although a cut-off of 25% increase compared to previous imaging studies was introduced by the WHO as a clue to recurrence/incompletely ablated disease,
size cannot be used alone to predict residual/recurrent disease as its increase in this phase might still be justified by inflammation,
hemorrhage or development of areas of cavitation.
Appearance
GGO involution often takes place in this phase,
though it may also be observed at the beginning of the late phase (i.e.
1 to 3 months after RFA).
Presumably because of the clearance of the necrotic core via bronchi,
cavitation or intralesional bubbles (defined as 1-3 mm gas bubbles within the ablated area) appear in the intermediate phase (figure 6).
Since they are related to the presence of a central necrotic area,
they represent a positive response to RFA and they can be frequently observed in the follow-up period: bubble lucencies were described in literature in as many as 31% of patients who underwent thermal ablation [17].
On the opposite,
development of new areas of consolidation – often associated with size increase – is a “red flag” for residual tumor tissue or recurrence.
Pneumothoraces which appeared in the initial phase evolve: they may become localized or,
less frequently,
form bronchopleural fistulae.
Other findings described in this phase include pleural thickening and mediastinal or hilar lymph node enlargement.
The latter finding is frequently observed (up to 63%),
has no correlation with original lesion size or its location and generally resolves within 1 year.
It must be noted,
however,
that such lymph node hyperplasia can be a confounding factor when assessing the presence of recurrence.
Contrast Enhancement
While some ablated areas show no contrast enhancement in this phase,
in some other ones a peripheral contrast enhancement,
often reduced from the early phase,
may still persist.
This is believed to represent an inflammatory response (giant cell reaction) elicited by thermal injury.
As noted before,
progression of incompletely ablated tumor is differentiated by the presence of contrast enhancement which is central,
nodular (> 10 mm) or greater than 15 HU.
3.
LATE PHASE ( >2 Months)
Size of the ablation zone
As cited above,
the trend of lesion size decrease starts during the intermediate phase,
yet the size of the ablated area still remains larger than that of the original lesion.
Such a decrease proceeds further months after treatment,
but it is only 6 months after RFA that the size eventually becomes the same or smaller than original tumor size; any size increase in this phase is associated with recurrences [14-18].
Appearance
The size and wall thickness of previously observed cavities are expected to slowly decrease over the subsequent months (figure 7),
leading ultimately to the formation of a fibrous scar (figure 8) which substitutes the cavitation.
GGO are rarely present at the beginning of the later phase and also undergo involution over the subsequent months.
Additional findings of the immediate and intermediate phase are expected to resolve; among such findings are included pleural effusion,
pleural thickening,
localized PNX and contained bronchopleural fistula.
As to the “red flags”,
development of satellite nodules along the RFA electrode track can herald the onset of local or locoregional disease which can take place months after the initial treatment.
Appearance of lymphadenopathies is another “red flag” which may be associated with recurrence.
Contrast Enhancement
Due to the recovering circulation in the ablated area,
a transient peripheral rim of contrast enhancement may be present for up to 6 months,
reaching its peak in the 3rd month [19]; as long as it does not exceed that of the original tumor,
this is an entirely benign finding after radiofrequency ablation.
However,
appearance of contrast enhancement in a previously non-enhancing lesion (figure 9),
which is central,
nodular,
or greater than 10 mm or 15 HU is related to progression of residual tumor tissue.