The Lugano Classification provides standardized guidelines for lymphoma staging, response assessment, and follow-up. Key points include: 1. PET-CT is the standard imaging modality for staging FDG-avid lymphomas. Bone marrow biopsy is no longer routinely required for HL and DLBCL. 2. Response is assessed using a 5-point scale based on PET-CT findings. A decrease in FDG uptake defines complete or partial response. 3. For immunotherapies, 'indeterminate response' is introduced to account for immune-related flares or delayed responses. Biopsies are encouraged to distinguish true progression from immune phenomena.

1. LYMPHOMA STAGING AND RESPONSE
EVOLUTION WITH CURRENT
RECOMMENDATIONS

3. • 1st staging system in lymphoma : by PETERS in
1950
• Rye classification in 1966
• Ann arbor 1974/1988
(Initially developed for Hodgkins lymphoma for RT planning)
• COTSWOLD MODIFICATION

4. • CURRENT STAGING SYSTEM : LUGANO
• BASIS : ANN ARBOR STAGING SYSTEM ( 1974,
1988)
• FOCUS : NUMBER OF TUMOR SITES(
NODAL/EXTRANODAL); LOCATION

5. ORIGINAL ANN ARBOR

6. PART OF STAGING EVALUATION….
• IVP
• USG
• LIVER / SPLEEN SCANS
• LYMPHANGIOGRAM
• STAGING LAPAROTOMY

7. PART OF STAGING EVALUATION….
• IVP
• USG
• LIVER / SPLEEN SCANS
• LYMPHANGIOGRAM
• STAGING LAPAROTOMY
• DUE TO ADVENT OF CT SCANS , COTSWOLD
INCORPORATED CT SCANS FOR STAGING
• Also incorporated X for bulky disease and term
CRu

8. RESPONSE
• 1999, IWG ( NCI), made first
recommendations for response assessment
for NHL(also adopted for HL)

9. • Codification of terms CR, PR, Cru, SD, RD , PD
• Widely accepted subsequently
• CRu
• Visual BM evaluation
• Assessment of extranodal disease

10. PET SCAN IN LYMPHOMAS
 Invented in 1987
 First applied to lymphomas in 1990
 Advantage over CT :
Distinguish viable tumor from scar and fibrosis
Potential to eliminate CRu

11. • International Harmonization Project : German
Competence Network Malignant Lymphoma
• Subcommittes :
 Response criteria
 End points for clinical trials
 Imaging
 c/f
 Pathology/biology

12. • Led to guidelines published in 2007

14. IMAGING
 To update relevance of existing
imaging for staging,
 Reassess role of interim PET
CT,
 Standardise PET CT reporting
 Evaluate potential prog value
of quantitative analysis using
PET & CT
CLINICAL
 Assess the potential of PET
CT to modify initial staging
 Current relevance of Ann
Arbor staging system
 To evaluate role of BMB and
CXR
 Improve organ assessment
 Redefine PD
 Standardise follow up
Workshop held at the 11th ICML in June 2011 to determine further needed
changes
Two task forces created

15. • Subsequent workshop held at ICML 12 in
June, 2013 in Lugano, Switzerland
• The results of those deliberations was
THE NEW LUGANO
CLASSIFICATION

16. Ref : ESMO

17. INITIAL PATIENT EVALUATION
STAGING
RESPONSE ASSESSMENT
FOLLOW UP
WHAT’S THE LUGANO CLASSIFICATION DEALING WITH?

18. INITIAL PATIENT EVALUATION
• FNAC
• EXCISION BIOPSY
• CORE BIOPSY
• H&PE
• RECORD DISEASE RELATED SYMPTOMS
• MEASURE NODES/SPLEEN SIZE
• LABS (LDH,UA,RFT,LFT,CBC/DC, VM)
• PROGNOSTIC SCORING

19. STAGING
• PET CT formally included as
standard imaging study for staging
for FDG avid lymphomas
• NON AVID
• Subscript “E’’ used if limited
extranodal extension is
documented; more extensive
extranodal disease is stage IV.
• Disease involving spleen is nodal
CLL
MYCOSID FUNGOIDES
MARGINAL ZONE LYMPHOMAS
LYMPHOPLASMACYTIC LYMPHOMAS
• Term ‘’X’’ eliminated ( to record largest
diameter)
• For Rx purpose criteria for bulky
disease vary by histology , with no cut
off being validated using modern Rx
• However cut off mentioned for FL :
6cm; DLBCL : 6-10cm
• Systemic B symptoms not incorporated
into staging system for NHL, retained for
HL

20. Modified from Weiler-Sagie M, et
al. J Nucl Med.2010;51(1):25-30

21. • Bone marrow biopsy role questioned for HL/DLBCL
El-Galaly et al :
454 patients with newly Dx HL
18%, BM lesions s/o PET , only 8% by BMB
No patient with stage I/II by PET had positive
biopsy
Patients with positive biopsy also haf other
evidence of advanced disease
All patients upstaged by biopsy from stage III
to IV
No treatment plan change
Khan et al study :
130 patients of DLBCL
BM involvement s/i 27% of 130 patients
with DLBCL;
33 by PET, 14 by BMB
Pet identified all patients with a positive
biopsy
Cases with a positive PET had an
outcome comparable to other pts with
stage IV withou positive bm

22. • New recommendation : BMB is no longer
needed for routine staging of HL and DLBCL
• For DLBCLs with a negative PET for whom
identification of occult discordant histology is
clinically important.
• BMB remains a standard test for staging
other lymphomas

23. Response assessment
• Restaging scan :6 – 8 weeks after Rx
completion
• To interpret scans based on D-5PS for FDG
avid histologies
• CT scans for variably avid or non avid
histologies

24. Follow up
• After response assessment, further imaging studies sould be
performed judiciously
• Surveillance scans not justified esp in HL/DLBCL
– Not cost effective
– High false positive result leading to unnecessary imaging and
biopsies
• Repeat study may be needed if postRx scan was equivocal , or
conservatively in pts with an indolent NHL and intraabd/RP
disease

25. WHAT’S NEW IN THE LUGANO
CLASSIFICATION: RECAP
• FDG-PET-CT : Standard staging for FDG-avid lymphomas
• Response assessment using the 5-point scale
• Progressive disease evaluation : PPD progression of single site defines progression.
• SPD eliminated for progression
• Spleen evaluation : Quantified: >13 cm is enlarged on CT
• Modification of the Ann Arbor Classification
• Bone marrow biopsy : No longer indicated for the routine staging of HL and most
DLBCL
• Scan frequency : Routine surveillance scans discouraged

26. Criteria for site inolvement

28. CRITERIA FOR EXTRANODAL INVOLVEMENT

32. CLINICAL EVALUATION :Systemic symptoms rarely direct treatment,
their recurrence may herald disease relapse
Lugano Classification: The presence of residual symptoms in the absence of
detectable disease by imaging does not preclude the designation CR

33. Response assessment
• PET-CT is recommended for response assessment
using 5-Point Scale (5-PS)
• If mid therapy imaging is performed, PET-CT is
superior to CT
• Trials are currently evaluating the role of PET
response adapted therapy
• Meantime it is not recommended to change
treatment based solely on PET-CT unless there is
clear evidence of progression
• Most data relate to HL, DLBCL & high tumour
burden FL

34. 5-POINT SCALE (DEAUVILLE CRITERIA)
• 1. i.e., maximum standardized uptake value (SUVmax) of the lesion >2x liver uptake

35. FDG-PET EVALUATION

37. CT VS. PET: CMR/CR

38. RESPONSE ACCORDING TO 5-PS
• Score 1, 2 is Complete Metabolic Response (CMR)
• Score 3 is also CMR with standard treatment
• But in response-adapted trials exploring de-escalation, score 3 may be
deemed inadequate response to avoid under-treatment
• Interpretation of score 3 depends on timing of assessment, clinical
context & treatment

39. HIGH PHYSIOLOGICAL FDG UPTAKE
• Can occur in some sites… e.g., Waldeyers ring, gut, bone marrow after
chemotherapy or GCSF treatment with ‘physiologic’ uptake > normal liver
• In this case, CMR may be inferred if uptake at sites of initial involvement is
no greater than surrounding normal tissue

40. RESPONSE ACCORDING TO 5-PS
• Score 4, 5 with reduced uptake from baseline is partial metabolic response
(PMR)
• At interim this suggests responding disease
• At end of treatment this indicates residual disease Score 4, 5 with no
change in uptake from baseline means no metabolic response (NMR)
• Score 4, 5 with an increase in uptake from baseline &/or new lesions is
progressive metabolic disease (PMD)
• At interim and end of treatment NMR and PMD indicates treatment failure

41. Recent situations with the use of
newer agents
CLL/SLL/LYMPHOMA : started on Lenalidomide
2-3 weeks later develops fever , painful LAP,
increase in size of existing nodal disease, rashes
Imp : tumor flare
Reason : TNF/NK Cell activation/ immune
mechanisms
Result : incorrectly assumed as PD

42. • Waldenstorm Macroglobulinemia patient
started on Rituximab
• Paradoxical increase in IgM , hence increased
viscosity
• Imp : Flare
• Result : misdx as PD

43. • Patient of CLL recently started on Ibrutinib
• Rapid Decrease in nodal/spleen disease
burden0
• Lymphocytosis ( bec of redistribution from
tissue to blood)

44. • Incorrect designation of PD in many patients ,
leading to premature discontinuation of drug
despite other e/o clinical improvement.

45. Response assessment with immune
checkpoint inhibitors
• Wolchok et al prposed immune related
response criteria (IRC) (for solid tm)
• The Lymphoma Research Foundation in
partnership with the Cancer Research Institute
convened a workshop focussing on dev of
guidelines for lymphomas in setting of
immunotherapy

47. LYRIC (LYMPHOMA RESPONSE TO
IMMUNOMODULATORY THERAPY
CRITERIA)
• INTRODUCTION OF NEW RESPONSE
CATEGORY
• INDETERMINATE RESPONSE

48. • The term IR does not make any direct
reference to the underlying mechanism,
recognizing that a delayed response and an
immune mediated flare can both occur in
early treatment period and may be difficult to
distinguish from progression by physical
examination or imaging alone

49. • The term provides flexibility to allow pts to
continue Rx past IR in some circumstances
with a mandatory subsequent evaluation
within 12 weeks to confirm or refute true PD

50. 1. Increase in overall tumor burden
(as assessed by SPD of >50% of up to 6 measurable lesions in the first 12
weeks of therapy, without clinical deterioration

51. IR 1
A delayed response
Early immune mediated flare
Recommended : biopsy
If not feasible : decision based on rpt scan 12 weeks after initial
determination of IR

52. IR 2. Appearance of new lesions or growth of one or more existing lesion(s)
>50% at any time during treatment; occurring in the context of lack of overall
progression (<50% increase) of overall tumor burden, as measured by SPD of
up to 6 lesions at any time during the treatment

53. • This phenomenon may occur early or late in the
treatment course
• Both within and outside the context of clinical trials, a
biopsy is strongly encouraged in such cases.
• If the biopsy does not confirm the presence of viable
tumor in the new or enlarging lesions then the lesions
are not considered active disease and should not be
used in subsequent SPD assessments

54. IR 3
Increase in FDG uptake of 1 or more lesion without a
concomitant increase in lesion size or number

55. • Increased immune activity at the site of tumor may
manifest as an increase in FDG uptake.
• Therefore, by itself, changes in uptake should not
trigger an assignment of PD with checkpoint
inhibitors.
• It is important to investigate this finding, especially in
conjunction with biopsies of the lesion in question.

56. Follow up of patients with IR
• In patients categorized as having any of the
above types of IR, it ismandatory to obtain a
repeat imaging after an additional 12
weeks(or earlier if clinically indicated). re-
evaluated, and the patient should be
considered to have true PD if the SPD of target
lesion has increased further

57. IR 1
• Comparison should be between the first IR(1) and the current SPD,
with an increase of >10% constituting PD.
• In addition, there should be an increase of >5 mm (in either
dimension) of >1 lesion for lesions < 2 cm and 10 mm for lesions >2
cm, to be consistent with the Lugano classification
• The 10% threshold is empiric
• If the target SPD increase is 10%, the response would still be
categorized as IR(1), and the patient could continue treatment until
a subsequent scan shows either true PD [>10% increase from first
IR(1) timepoint and an increase of >5 mm in either dimension of >1
lesion or response (>50% decrease from baseline).
• In this situation, it is reasonable to repeat imaging in 4 to 8 weeks
of the original IR(1) time point to ensure absence of significant
further increase

58. IR2
• the new or growing lesions (unless biopsy
proven to be benign) should be added to the
target lesions, upto a total of no more than 6
total lesions. If the SPD of the newly defined
set of target lesions has increased >50% from
their nadir, value (which may precede the IR
time point), the patient should be considered
to have PD

59. • Because inflammatory responses may result in an increase
in the SUV of a lesion, the patient will not be considered to
have PD unless there is evidence of PD by an increase in
lesion size or the development of new lesions, as noted
above.
• Importantly, if a patient is assessed as having IR and then
“true” PD at a subsequent time point (without an
intervening objective response between IR and PD), the IR
assessment should subsequently be corrected to PD for
reporting purposes to the date of the prior designation of
IR.
• These lesions may remain stable during the time of
observation, but, even if this is the case, the initial
designation of IR should be changed to PD.

60. CR PR PD