Introduction
The NIC defines hematological cancers as those that begin in blood forming tissue
such as bone marrow or cells of the immune system and these broadly include three
groups leukemias, lymphomas, and myelomas.[1] The role of imaging is also fundamentally different between the three main groups
of hematological malignancies. While imaging is the main tool for staging as well
as treatment response assessment in lymphoma,[2]
[3] it represents one of several key criteria for the diagnosis and follow-up of myeloma[4]; whereas in leukemia, imaging has a role to play in the detection and management
of treatment-related complications which is a crucial part of post-transplant treatment.
In myeloma, whole-body magnetic resonance imaging (WB-MRI) is recognized as a highly
sensitive test for the assessment of myeloma, and is also endorsed by clinical guidelines,
especially for detection and staging. In lymphoma, WB-MRI is presently not recommended,
and merely serves as an alternative technique to the current standard imaging, Flourine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT),
especially in pediatric patients.[5]
Even for lymphomas with variable FDG avidity, such as extranodal mucosa-associated
lymphoid tissue lymphoma (MALT), contrast-enhanced CT, but not WB-MRI, is presently
recommended, despite the high sensitivity of diffusion-weighted MRI and its ability
to capture treatment response that has been reported in the literature.[5] In leukemia, neither MRI nor any other cross-sectional imaging test (including PET)
is currently recommended outside of clinical trials.[5]
Epidemiology, Clinical Presentation in India and Global
Almost all of these cancers occur almost a decade earlier in India compared with the
West. Possible reasons proposed have included the demographics of the Indian population
(largely younger), increased incidence of chronic infections and antigenic stimulation,
genetics, and socioeconomic status. The average ASR for multiple myeloma (MM) is 0.1
to 1.9 in India, and around 2.8 to 3.9 in the US, with similar figures for Hodgkin's
lymphoma (HL).[6] Incidence of leukemias is between 2.4 and 4.6 per 100,000 when compared with 9.6
to 11 in Canada.[6]
Imaging Guidelines
Lymphomas
PET-CT is recommended for the routine staging of FDG-avid, nodal lymphomas (essentially
all histologies except chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL),
lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia, mycosis fungoides, and
marginal zone non-Hodgkin's lymphomas (NHLs), unless there is a suspicion of aggressive
transformation) as the gold standard.[7]
CT scan is preferred in the other lymphomas. A chest X-ray is no longer required in
lymphoma staging because it less accurate than CT.[8] Moreover, CT identifies more hilar nodes and may better discriminate between a single
large nodal mass and an aggregate of individual nodes.[3]
Definition of bulky disease: A single nodal mass, in contrast to multiple smaller
nodes, of 10 cm or greater than a third of the transthoracic diameter at any level
of thoracic vertebrae as determined by CT is retained as the definition of bulky disease
for HL.[9] A chest X-ray is not required to determine bulk because of its high concordance
with CT.[8] However, a variety of sizes have been suggested for NHL[10] with limited evidence suggesting 6 cm as best for follicular lymphoma15 and 6 to
10 cm in the rituximab era for diffuse large-B-cell lymphoma (DLBCL).[11] However, none of the proposed sizes have been validated in the current therapeutic
era. Therefore, the recommendation for HL and NHL is to record the longest measurement
by CT scan, with the term X no longer necessary.[3]
If a PET-CT is performed, a bone marrow aspirate/biopsy is no longer required for
the routine evaluation of patients with HL. In DLBCL, PET-CT is also more sensitive
than bone marrow biopsy (BMB) but has been reported to miss low-volume diffuse involvement
of 10 to 20% of the marrow.[12] If the scan is negative, a BMB is indicated to identify involvement by discordant
histology if relevant for a clinical trial or patient management.[13]
Response Assessment
Lugano's criteria are used for response assessment as summarized in [Table 1].[18] End-of-treatment assessment is more accurate with PET-CT, especially for patients
with radiologic (CT) CRu or partial response (PR) in HL, DLBCL, and follicular lymphoma.[3] PET-CT-based criteria eliminate CRu and improve the prognostic value of PR. In early-
and advanced-stage patients with HL, a negative predictive value of 95 to 100% and
a positive predictive value of more than 90% have been reported.[14]
[15] In aggressive NHL, studies have reported a negative predictive value of 80 to 100%,
but a lower positive predictive value, ranging from 50 to 100%.[16]
Table 1
Lugano response criteria for PET-CT follow-up in lymphomas[28]
|
Modality
|
Complete response
|
Partial response
|
Stable disease
|
Progressive disease
|
|
CT
|
Lymph modes ≤ 1.5 cm in Ldi
Complete disappearance of radiologic evidence of disease
|
Single lesion: ↓ ≥ 50% in PPD
Multiple lesions: ↓ ≥
50% in SPD of up to six lymph nodes or extranodal sites
|
↓ ≤ 50% in SPD of up to six lymph nodes or extranodal sites (no criteria for progressive
disease are met)
|
1) New lymphadenopathy or ↑; single node must be abnormal with:
a) Ldi > 1.5 cm and
b) PPD ≥ 50% and
c) Ldi or Sdi ↑ 0.5 cm if ≤ 2.0 cm and ↑ 1.0 cm if > 2.0 cm
|
|
2) ↑ splenic volume:
a) with prior splenomegaly: ↑ > 50% of its prior ↑ beyond baseline
b) without prior splenomegaly: ↑> 2.0 cm
c) New or recurrent splenomegaly
|
|
3)New or Larger non measured lesions
|
|
4) Recurrent previously resolved lesions
|
|
5) New extranodal lesion > 1.0 cm in any axis (new lesions < 1.0 cm in any axis are
included if attributable to lymphoma)
|
|
FDG-PET-CT
|
Scores 1, 2, 3 in nodal or extra nodal sites with or without a residual mass
|
Scores 4 or 5 with ↓ uptake compared with baseline and residual mass(es)
|
Scores 4 or 5 with no obvious change in FDG uptake
|
Scores 4 or 5 any lesion with ↑ uptake from baseline and /or new FDG-avid foci
|
Abbreviations: FDG-PET-CT, fluorodeoxyglucose positron emission tomography/computed
tomography; LDi,—; PPD,—; SPD,—.
A CT-based response is preferred for histologies with low or variable FDG avidity
and in regions of the world where PET-CT is unavailable. However, in the absence of
a PET-CT scan, a mass that has decreased in size but persists is considered at best
a PR in the absence of a biopsy documenting the absence of lymphoma, and the former
term CRu is not to be considered.7
Summary of response and follow-up strategies as per the IWG, NCCN, and ESMO criteria
are as follows[3]:
-
1) PET-CT should be used for response assessment in FDG-avid histologies, using the
5-point scale; CT is preferred for low or variable FDG avidity.
-
2) A complete metabolic response even with a persistent mass is considered a complete
remission.
-
3) A PR requires a decrease by more than 50% in the sum of the product of the perpendicular
diameters of up to six representative nodes or extranodal lesions.
-
4) Progressive disease by CT criteria only requires an increase in the PPDs of a single
node by more than or equal to 50%.
-
5) Surveillance scans after remission are discouraged, especially for DLBCL and HL,
although a repeat study may be considered after an equivocal finding after treatment.
-
6) Judicious use of follow-up scans may be considered in indolent lymphomas with residual
intra-abdominal or retroperitoneal disease.
PET-CT is used for staging and response assessment of lymphomas, during treatment
(interim PET) and for remission assessment at the end of treatment.[7] MRI is the modality of choice for suspected central nervous system lymphoma.
Mantle-cell lymphoma is routinely FDG avid; limited data suggest that the sensitivity
and specificity of identifying bowel involvement is low and should not replace other
investigative measures.
The standard response criteria currently in use for lymphoma are the Lugano criteria
which are based on [18F]FDG-PET or bidimensional tumor measurements on computerized
tomography scans. These differ from the RECIST criteria used in solid tumors, which
use unidimensional measurements.
Imaging Guidelines of Leukemias
PET imaging is considered investigational and experimental for all indications in
acute lymphoblastic leukemia, acute myeloid leukemia, and chronic myeloid leukemia.
Routine advanced imaging is not indicated in the evaluation and management of chronic
myeloid leukemias, myelodysplastic syndromes, or myeloproliferative disorders in the
absence of specific localizing clinical symptoms or clearance for hematopoietic stem
cell transplantation.[17]
CLL/SLL: PET imaging is not indicated in the evaluation of CLL/SLL except for suspected
Richter's transformation.
Suspected transformation (Richter's) from a low-grade lymphoma to a more aggressive
type is based on one or more of the following: New B symptoms, rapidly growing lymph
nodes, development of extranodal disease, a significant recent rise in LDH above normal
range- A PETCT may be advisable in such cases.[18]
Imaging Guidelines for Post-Hematopoietic Stem Cell Transplantation (HSCT)
Selected patients of leukemias/lymphomas are offered HSCT and imaging plays a very
important role in surveillance of these patients.
Pretransplant Imaging in HSCT: This imaging generally takes place within 30 days prior
to transplant, and involves a reassessment of the patient's disease status as well
as infectious disease clearance. CT of the sinuses, neck, chest, and/or abdomen/pelvis
is recommended. Nuclear renal function study to ensure adequate renal function and
echocardiogram are routinely indicated to ensure adequate cardiac function to proceed
with the transplant.
Post-transplant Imaging in HSCT: There are many common complications from HSCT, including
infection, graft versus host disease, hepatic sinusoidal obstruction syndrome, restrictive
lung disease, among others. These can be classified into early (less than 30 days)
and delayed (more than 100 days) complications.
These patients often require several CT chest scans in the post-transplant period
due to their susceptibility to infection (most commonly lung). At the very least,
scans for disease response generally takes place at day 30 and day 100 post-transplant.
CT chest without contrast is indicated for patients with bronchiolitis obliterans
with organizing pneumonia, a delayed post-transplant complication for surveillance
and evaluation of acute changes.
Imaging Guidelines of Myelomas
Plasma cell disorders range from the spectrum of the mostly benign monoclonal gammopathy
of unknown significance to the intermediate smoldering multiple myeloma to the frankly
malignant MM.[19] Imaging of bone lesions forms a major stay in the diagnosis and management of MM.
The CRAB criteria: Hypercalcemia, Renal insufficiency, Anaemia and Bone lesions—at least one or more bone lesions on X-Ray/CT/PET-CT—form the four pillars
upon which a diagnosis is made in patients with clonal bone marrow plasma cells more
than 10%.[19]
At least one well-defined lytic lesion of diameter greater than 5mm is necessary to
satisfy the bony lesion category of CRAB lesions.[4] Advances in cross-sectional imaging have led the IMWG to form newer guidelines with
the definition of myeloma-defining events) in which at least two or more focal lesions
in the marrow of size greater than 5 mm can be used to make the diagnosis, in the
absence of focal lytic lesions on X-ray or CT.[4] Newer advanced sequences like diffusion-weighted imaging with background suppression
(DWIBS) have also helped to increase sensitivity and specificity of bony lesion detection;
however, their inclusion into a formal role as defining criteria is awaited pending
further research.
Imaging Guidelines
For screening and diagnosis:
-
1) X-ray is not to be used unless it is the only modality available. Similarly, there
is no role of technetium scans.[20]
-
2) Whole-body low-dose CT (WBLDCT) is the ideal screening tool. It is the scan with
arms over the head (to reduce beam hardening artifacts on vertebrae if arms are placed
on the side of the body).[21] Even one focal lesion of size greater than 5 mm is sufficient for diagnosis.[22]
-
3) In clinically suspected MM patients who are screening negative on WBLDT, WBMRI
is strongly advised.[23] Conventional T1 sequences pick up marrow infiltration and diffusion-weighted imaging
has been shown to be the single most sensitive sequence.[22]
-
4) Imaging of bone marrow is the opposite of imaging findings elsewhere in the body:
Normal bone marrow shows restricted diffusion with low apparent diffusion coefficient
(ADC) values, whereas disease (metastases/myeloma) leads to a facilitated diffusion
with a progressive increase in ADC values. ADCs of normal bone marrow is very low
(range, 0.2–0.5 × 10−3 mm2/sec), whereas a value greater than 0.597 × 10−3 mm2/s showed 96% sensitivity and 100% specificity for MM.[24]
-
5) DWIBS: It is a free-breathing sequence wherein multiple thin slice axial sections of the
whole body are acquired. It relies on the relatively unchanged “incoherent” motion
within a voxel during respiration where the “coherent” motion is affected. It is the
incoherent motion of the water molecules that determines diffusivity. This sequence
is commonly acquired in the coronal plane and short tau inversion recovery sequence
is the commonly employed pre-pulse fat saturating sequence that is combined with DWIBS
to achieve uniform fat suppression.[25] B values generally range from 800 to 1000 seconds mm2.
For post-treatment assessment: 18 FDG-PET-CT is the gold standard for assessing post-treatment
response. Complete suppression of FDG avidity on post-therapy scans confers increased
overall survival and serves as a good prognostic marker.[26]
Structured Reporting System
In an effort to promote standardization and diminish variations in the acquisition,
interpretation, and reporting of whole-body MRI in myeloma and allow response assessment,
the IMWG and NICE UK group together developed the Myeloma Response Assessment and
Diagnosis System (MY-RADS).[27] A sample of the reporting template is described below ([Fig. 1]).
Fig. 1 Structured reporting format of myelomas.[27] AVN,—; G-CSF,—; MY-RADS, Myeloma Response Assessment and Diagnosis System; ONJ,—;
RAC,—; WB-MRI, whole body magnetic resonance imaging.
