PET-TAC: INDICACIONES E INTERPRETACIÓN EN MIELOMA MÚLTIPLE

Presentación del tema: "PET-TAC: INDICACIONES E INTERPRETACIÓN EN MIELOMA MÚLTIPLE"— Transcripción de la presentación:

1 PET-TAC: INDICACIONES E INTERPRETACIÓN EN MIELOMA MÚLTIPLE
M.Simó H.U.Vall d’Hebrón

2 PET-TAC: INDICACIONES E INTERPRETACIÓN EN MIELOMA MÚLTIPLE
INDICE: Consideraciones generales Radiofármacos 18F-FDG-PET en la detección / estadificación inicial M.M Mieloma Quiescente / Plasmocitoma Solitario Pronóstico Respuesta a la terapia Conclusiones

3 PET scan (C-PET ADAC). Any 2000

4 C-PET ADAC. Any 2000. “Sin CT/ resolución anatómica ~ 1.5cm”

5 PET-CT SIEMENS mCT (64 slices). Any 2012

6 “CT 64slices// resolución mm”
PET-CT SIEMENS mCT (64 slices). Any 2012

7 2. RADIOFÁRMACOS: 18F-FDG 11C-Metionina 11C-Acetate 18F-Timidina
Receptor chemokine 4 se expresa en células plasmáticas Acetato: Síntesis acidos grasos esta sobreexpresada en MM. Mayor sensibilidad que FDG en la detección de infiltración difusa y lesiones focales (84.6% vs 57.7%) 11C/18F-Colina 68Ga-Pentixafor

8 Radiofármaco Características Autor
18F-Colina vs FDG Más sensible que FDG en MM en recaída/refractario Cassou-Mounat. 2016 11C-Colina Más sensible que FDG para lesiones en calota Nanni. 2007 11C-Metionina Alta captación en lesiones con MM Luckerath. 2015 Correlación infiltración M.O/parámetros clínicos Lapa. 2016 18F-Timidina Captación relacionada con síntesis DNA y elevada prolif. Agool. 2006 18FNA Captación en relación con el flujo vasc óseo y Ak. 2015 correlación con remodelamiento. FDG >> FNA detección lesiones de M.M FNA >> FDG detección fracturas/cambios degenerativos 11C-Acetato Captación depende síntesis lípidica en la membrana Ho. 2014 así como de la AcetilCoa. Lin. 2014 Posibles ventajas en pacientes recién diagnosticados 68Ga-Pentixafor Excelente imagen PET y dosimetría favorable Hermann. 2016 Acetato: Síntesis acidos grasos esta sobreexpresada en MM. Mayor sensibilidad que FDG en la detección de infiltración difusa y lesiones focales (84.6% vs 57.7%) “Theranostics”

9 PET-F18- Fluorodesoxiglucosa (FDG)
2. RADIOFÁRMACOS: PET-F18- Fluorodesoxiglucosa (FDG) FDG FDG-P Hexoquinasa Glucose-6-asa Glut 1-3 Lo único que nos muestra un estudio PET es el metabolismo de la glucosa. Para ciertos tumores y subtipos puede tener o no el mismo significado. METABOLISMO GLUCOSA..viabilidad celular... ......≠ “células tumorales” ...

10 Indicaciones PET/CT en M.M
Estadificación: Mieloma quiescente Plasmacitoma solitario Mieloma múltiple: Detección enfermedad extra-medular Valor pronóstico Estudio de respuesta terapéutica (“estudio basal”) After this brief review of imaging techniques, let me introduce the indications of PET in MM: So, current available data indicate PET/CT in Staging of SMM and SP And in MM, PET may be used in: Extramedullary disease As a prognostic factor and in the evaluation of treatment response

11 Indicaciones PET/CT en M.M
Nova proposta de la Agencia Avaluadora de Tecnologies Sanitaries (2016) Indicacions de la PET o la PET/TAC en adults (oncologia) F18-FDG Càncer colorectal: diagnòstic/ estadificació Càncer colorectal: recidiva/ reestadificació Càncer colorectal: avaluació de la resposta al tractament Limfoma: diagnòstic/ estadificació Limfoma: recidiva/ reestadificació Limfoma: avaluació de la resposta al tractament Limfoma: Previ a trasplantament de medul·la òssia per avaluar el volum de la malaltia i si és candidat per a trasplantament Càncer de mama: diagnòstic/ estadificació Càncer de mama: recidiva/ reestadificació Càncer de mama: avaluació de la resposta al tractament Càncer de pulmó: diagnòstic/ estadificació Càncer de pulmó: recidiva/ reestadificació Càncer de pulmó: avaluació de la resposta al tractament Càncer de pulmó: planificació de radioteràpia Mieloma: diagnòstic/estadificació Mieloma: recidiva/reestadificació Nòdul pulmonar solitari: diagnòstic/ estadificació After this brief review of imaging techniques, let me introduce the indications of PET in MM: So, current available data indicate PET/CT in Staging of SMM and SP And in MM, PET may be used in: Extramedullary disease As a prognostic factor and in the evaluation of treatment response

12 Recommended in smouldering M.M and solitary plasmocytoma
2014 * 18F-FDG Increased uptake on PET is not adequate for diagnosis M.M. Underlying osteolytic bone desctruction is needed. Recommended in smouldering M.M and solitary plasmocytoma “Each focal lesion must be 5mm or more in size”

13 Vs Whole-body CT PET-CT FDG
MRI Conventional whole body skeletal radiography “30-50% destrucción ósea” Vs 1. Nuevas técnicas tienen una mayor sensibilidad que seriada ósea * (Detectan ≥ 80% lesiones con respecto WBXR) 2. CT≈ MRI (PET-CT) Más sensibles en todas las localizaciones a excepción calota/costillas (WBXR > RMI in skull “43vs10%”.Walker et al) 4. FDG-PET y RMI detectan patrón infiltración medular FDG-PET es la técnica más sensible en la detección enfermedad extra-medular A diferencia del CT, la MRI y la PET tienen valor prónostico documentado

14 PET sensitivity - compared XR and MR
Systematic review: van Lammeren-Venema D et al, Cancer 2012;15: PET vs XR: PET > 46 – 63% (Lytic lesions XR > 30% bone mineral density) PET vs MR: MR > PET Diffuse bone marrow involvement Spine: small size lesions MRI > PET 30% PET > FOV of MR 30% Moreau P et al, 2016 (abstract Menton Sept 2016) 134 patients (trial IFM/DFCI 2009): PET vs MRI spine and pelvis PET sensitivity has been recently compared with XR and MR in a systrematic review that demonstrates that: PET usually indicates more lesions than XR would. This is because Lytic lesions only become evident on XR when more than 30% of bone mineral density has been lost Four studies compared PET with MRI and MRI was usually superior to PET , Thi is specially evident in: Diffuse bone marrow involvement And in the small lesions of the spine, where MR detects more lesions in 30% of patients However, PET localized lesions beyond the FOV of MRI in other 30% of cases. In the recent meting of Menton, last week, Moreau presented a comparison between PET and MRI of spine and pelvis, and both imaging techniques demonstrate similar results in patients with MM. PET MRI Lesion Sensitivity 91% 94% No significant differences

15 PET compared MRI PET RMI - >> Enf extra-medular (Sensib ≈ 96)
- Enf activa antes y después del tratamiento - Pronóstico - Plasmocitoma Solitario/ Mieloma Quiescente - Predictor de supervivencia RMI - Infiltración M.O - Pacientes neurológicos / Compresión medular - > Sensib detección masas partes blandas - Pronóstico - Guía de biopsia CT, cirugía o RT PET sensitivity has been recently compared with XR and MR in a systrematic review that demonstrates that: PET usually indicates more lesions than XR would. This is because Lytic lesions only become evident on XR when more than 30% of bone mineral density has been lost Four studies compared PET with MRI and MRI was usually superior to PET , Thi is specially evident in: Diffuse bone marrow involvement And in the small lesions of the spine, where MR detects more lesions in 30% of patients However, PET localized lesions beyond the FOV of MRI in other 30% of cases. In the recent meting of Menton, last week, Moreau presented a comparison between PET and MRI of spine and pelvis, and both imaging techniques demonstrate similar results in patients with MM.

16 Mieloma Múltiple Diferentes patrones de captación por PET:
Afectación difusa y homogénea compatible con infiltración M.O (bx: 20-50%) (> al hígado) The main application of PET in SM is to demonstrate the absence of bone lesions that confirm a SM Diagnosis criteria consensus of IMWG indicate one of theses imaging procedures when a SM is confirmed. These recommendations come from the work of Hillegans, that studied 149 patients with SM with WBMRI and FL were detected in 42 patients and more than one lesion in 15%, demonstrating that the presence of 2 or more FL was associated with a substantial increase the risk of progression to MM. These has not so well evaluated with PET, where only small series of cases have been reported. In this sense, Spanish societies of myeloma and NM have recently started a Prospective multicenter study that includes PET/TC at initial evaluation and every 6 months during 3 years to evaluate the Role of PET/TC in the evaluation of risk to progression to MM in patients with smouldering Myeloma”

17 Afectación ósea poliostótica + medular
NHC: Afectación ósea poliostótica + medular

18 Afectación extra-medular
NHC:

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20 ExtraSp “outside the spine”
BM3: Bone marrow uptake (3 means > Med pero < Liver) F2: Focal lesions 2 means 1 to 3 lesions ExtraSp “outside the spine” L “LIVER”, EM “extramedullary” EN “extranodal”

21 Mieloma Quiescente “Descartar presencia lesiones óseas”
Criterios consenso de IMWG ; Lancet Oncology 2014;15:38-48 CT cuerpo entero (WBCT) MRI de cuerpo entero o MRI de columna 18F-PET/TC RMI: Hillengas et al. (J Clin Oncol 2010;28: ) 149 pacientes con MQ con whole-body RMI Lesiones focales en 42 pacientes (28%) Más de una lesión en 23 patients (15%) – Alto riesgo de progresión to M.M The main application of PET in SM is to demonstrate the absence of bone lesions that confirm a SM Diagnosis criteria consensus of IMWG indicate one of theses imaging procedures when a SM is confirmed. These recommendations come from the work of Hillegans, that studied 149 patients with SM with WBMRI and FL were detected in 42 patients and more than one lesion in 15%, demonstrating that the presence of 2 or more FL was associated with a substantial increase the risk of progression to MM. These has not so well evaluated with PET, where only small series of cases have been reported. In this sense, Spanish societies of myeloma and NM have recently started a Prospective multicenter study that includes PET/TC at initial evaluation and every 6 months during 3 years to evaluate the Role of PET/TC in the evaluation of risk to progression to MM in patients with smouldering Myeloma”

22 Mieloma Quiescente Zamagni E. (Leukemia 2016;30:417-422)
Prospective study PET : 120 patients with MQ Without bone lytic lesions Risk of progression to MM The group of Bolonia have studied with PET 120 patients with SM all without bone lesions PET was positive in 19 patients (16%) 1 FL in 8, 2 FL in 2 and more than 2 in 3 and diffuse in 6 PET positive patients had a higher risk to progression to MM in terms of Time to progression and Probability of progression PET - PET + 2 years Time to Progression (y) 4,5 1,1 Probability of Progression (%) 33 58

23 Mieloma Quiescente PETHEMA y SEMNIM:
“Role of PET/TC in the evaluation of risk to progression to MM in patients with smoldering Myeloma” Prospective multicenter study that includes PET/TC at initial evaluation and every 6 months during 3 years. The main application of PET in SM is to demonstrate the absence of bone lesions that confirm a SM Diagnosis criteria consensus of IMWG indicate one of theses imaging procedures when a SM is confirmed. These recommendations come from the work of Hillegans, that studied 149 patients with SM with WBMRI and FL were detected in 42 patients and more than one lesion in 15%, demonstrating that the presence of 2 or more FL was associated with a substantial increase the risk of progression to MM. These has not so well evaluated with PET, where only small series of cases have been reported. In this sense, Spanish societies of myeloma and NM have recently started a Prospective multicenter study that includes PET/TC at initial evaluation and every 6 months during 3 years to evaluate the Role of PET/TC in the evaluation of risk to progression to MM in patients with smouldering Myeloma”

24 Plasmocitoma Solitario
Definición “En 3 años alrededor del 10% progresan a M.M” - Única lesión ósea o de partes blandas con cel plasmáticas clonales en BX M.O normal sin evidencia de cel plasmáticas clonales No alteraciones óseas en columna ni en pelvis No evidencia de afectación visceral secundaria (Hipercalcemia, I.R, anemia, lesiones óseas) Papel de la PET-CT: Descartar otras lesiones Segundo plasmacitoma Lesiones líticas – Captación FDG “Up-staging disease” a MM Cambio de Pronóstico y Tratamiento The main goal of PET is solitary plasmocytoma is to demonstrate the absence of other lesions in either a second plasmocytoma as we can see in this patients with plasmocytomes in left humerus and in the paravertebral mussel or the presence of lytic FL with FDG uptake That upstage disease to MM Which results in a different prognostic and treatment. In this sense, I recommend this article from the French group that studied with PET/CT 43 patients diagnosed with SP 33% had 2 or more hypermetabolic lesions on initial PET/CT and these patients had a higher risk to progression to MM

25 Plasmocitoma Solitario
Fouquet et al (Clin Cancer Res 20(12) June 15, 2014) PET en 43 pacientes con Plasmacitoma Solitario * ≥ 2 lesiones focales en 33% casos * ≥ 2 lesiones focales > riesgo de progresión a MM (23 vs 71 meses) Normal serum-free light chain (sFLC) & < 2 lesiones hipermetabólicas 1 2 “41meses” The main goal of PET is solitary plasmocytoma is to demonstrate the absence of other lesions in either a second plasmocytoma as we can see in this patients with plasmocytomes in left humerus and in the paravertebral mussel or the presence of lytic FL with FDG uptake That upstage disease to MM Which results in a different prognostic and treatment. In this sense, I recommend this article from the French group that studied with PET/CT 43 patients diagnosed with SP 33% had 2 or more hypermetabolic lesions on initial PET/CT and these patients had a higher risk to progression to MM Alteración serum-free light chain (sFLC) & < 2 lesiones hipermetabólicas (o inrevés) 3 Alteración serum-free light chain (sFLC) & > 2 lesiones hipermetabólicas “21meses”

26 Plasmocitoma Solitario
Otros trabajos: PET detecta lesiones no detectadas por WBXR o fuera del campo de RMI en 30-50% Sin embargo no detectó infiltración M.O en columna y pelvis en 30% con respecto la RMI The main goal of PET is solitary plasmocytoma is to demonstrate the absence of other lesions in either a second plasmocytoma as we can see in this patients with plasmocytomes in left humerus and in the paravertebral mussel or the presence of lytic FL with FDG uptake That upstage disease to MM Which results in a different prognostic and treatment. In this sense, I recommend this article from the French group that studied with PET/CT 43 patients diagnosed with SP 33% had 2 or more hypermetabolic lesions on initial PET/CT and these patients had a higher risk to progression to MM

27 M.M: Valor Pronóstico Basal – FDG-PET/CT
PET BASAL: Bartel et al, 239 patients. (Blood 2009;114: ) Nº de lesiones activas ≤ 3 FL >3 FL 30-Month estimate 90% (86,95) 73% (64,83) Prognostic value of PET/CT has been widely analyzed in these 2 studies of Blood from Bartel and Zamagni. Baseline PET findings that may have a role a a prognostic factors are: the number of active lesions, the degree of FDG uptake and the presence of EMD We can see here that patients with more than 3 FL have worst survival And the same happens when SUV is greater than 4.2 Or here in those patients where PET demonstrate the presence of EMD

28 M.M: Valor Pronóstico Basal – FDG-PET/CT
PET BASAL: Bartel et al, 239 patients. (Blood 2009;114: ) Nº de lesiones activas ≤ 3 FL >3 FL Enf extramedular Prognostic value of PET/CT has been widely analyzed in these 2 studies of Blood from Bartel and Zamagni. Baseline PET findings that may have a role a a prognostic factors are: the number of active lesions, the degree of FDG uptake and the presence of EMD We can see here that patients with more than 3 FL have worst survival And the same happens when SUV is greater than 4.2 Or here in those patients where PET demonstrate the presence of EMD 30-Month estimate 87% (82,91) 50% (24,76)

29 M.M: Valor Pronóstico Basal – FDG-PET/CT
PET BASAL: Zamagni et al, 192 patients (Blood 2011;118: ) (Tto inducción Talidomida + dexametasona plus Tx autólogo) Grado de captación FDG SUV > 4.2 Enf extramedular (5-fold higher risk) Nº lesiones (< o > 3) Haznedar et al (EJNM 2011, 38: ) < 5 year OS en todos los pacientes con lesiones captantes FDG 50% VS 92% Prognostic value of PET/CT has been widely analyzed in these 2 studies of Blood from Bartel and Zamagni. Baseline PET findings that may have a role a a prognostic factors are: the number of active lesions, the degree of FDG uptake and the presence of EMD We can see here that patients with more than 3 FL have worst survival And the same happens when SUV is greater than 4.2 Or here in those patients where PET demonstrate the presence of EMD No poner: Queda claro que en aquellos pacientes candidatos a Tx autologo el numero de lesiones, el SUV y EMD son fuertes predictores de PFS y OS Un estudio retrospectivo con pocos individuos en pacientes candidatos a trasplante alogénico muestran similares resultados...

30 VOLUMEN METABÓLICO TUMORAL (MTV)
CARGA TUMORAL!!! TMV1 TMV2 TMV3 TMV TMV global = ∑ (TMV1) + (TMV2)+ (TMV3)... Sasanelli M. EJNM 2014

31 Masa tumoral células plasmáticas

32 Papel de la FDG-PET en M.M
“VALORACIÓN DE LA RESPUESTA A LA TERAPIA” * La PET con FDG es una técnica óptima en la valoración de la respuesta a la terapia * Experiencia bien documentada en Linfoma Hodgkin & LDCGB, con numerosos estudios randomizados/prospectivos: Importante valor Pronóstico “VPN” * Masa residual normo-metabólica = Respuesta Completa (no RCIncierta)

33 Papel de la FDG-PET en M.M
“VALORACIÓN DE LA RESPUESTA A LA TERAPIA” * En MM más tardía y menos protocolizada…... * Marcador Proteína “M” * Más precoz y específica que técnicas morfológicas (RMI)…..cambios en T2…. * Identifica aquellos pacientes con Enf Mínima Residual negativa radiológica o por imagen. * 25-30% pacientes considerados en Remisión Completa (CR) por otras técnicas tienes lesiones captantes FDG y un peor pronóstico. * La NEGATIVIDAD de un estudio FDG-PET previo al trasplante autólogo (ASCT) es un Factor Pronóstico independiente de periodo libre de enfermedad (PFS) y supervivencia global (OS). “Información Pronóstica y Clínica”

34 Bibliografía:

35 Valoración Respuesta a la Terapia
Basal días post-Tto Previo Trasplante autólogo Usmani 2013 N=302. Prospectivo Bartel 2009 N=239. Prospectivo A los 3a PFS: 84% vs 36% OS: 87% vs 63% * Lesiones focales * 0 vs > 3 * Normalización FDG vs persistencia A los 30meses PFS: 89% vs 63%

36 Criterios de respuesta a la terapia: Recomendaciones
Validado en ensayos clínicos: “French criteria” Pre-tratamiento Lesión focal Positiva: Negativa: Equivocal : Captación en Fx costales o en otras FX óseas con cambios esclerosos por CT Infiltración M.O Positiva: Captación esquel axial/apendicular > hígado Negativa: Captación esquel axial/apendicular ≤ hígado Post-terapia FDG > captación fisiológica de MO “columna y pelvis” y/o > captación hepática con o sin correspondencia en CT Lesión lítica estable en CT, nueva lesión osteolítica o captación focal FDG > hígado Captación asociada a lesión lítica por CT que muestra halo escleroso captante Captación heterogénea > hígado Mesguich C. et al, Eur J Radiol 2014; 83: (Mount Sinai, NY)

37 Respuesta a la terapia:
Mujer 58años. MM stadio III ISS y IIIA Durie-Salmon Interim PET Respuesta parcial: * Resolución de la mayoría de lesiones focales (lesión esternal +) * Persiste signos de infiltración medular en húmero derecho (> hígado) “Reborde escleroso en TC es un signo de respuesta”

38 Respuesta a la terapia:
Varón de 50ª con MM IgD estadio I. Después del Tto “RC” Posteriormente dolor óseo con valores de IgD normales y leve ascenso cadenas Kappa/lambda.

39 Fractura por insuficiencia sacra
Falsos positivos: Fractura por insuficiencia sacra Estimulantes de las colonias granulocíticas

40 Negatividad Intramedular + Negatividad Extramedular
“Extramedulladry disease > 10% patients with MM” However, in the last meeting of Menton in September 2016, The IMWG consensus criteria for treatment response assessment and for MRD assessment has been presented, And this group suggests/conclude that: PET has been validated to evaluate treatment response And the definition of imaging minimal residual disease takes into account the disappearance of every area of increased trace uptake found at baseline PET/CT. This has been suported by the fact that more than 10% of patients witnh MM may develop extramedullary involvement at the time of relapse Negatividad Intramedular + Negatividad Extramedular (Citometría de flujo/Secuenciación) + (FDG-PET negativo)

41 Conclusiones: Papel de la PET en Mieloma Múltiple (M.M)
* WBXR persiste como método estandard en la detección enfermedad ósea Lesiones osteolóticas (CT) Infiltración M.O (RMI & PET-CT) Infiltracion extra-medular (PET-CT) PET-RM Plasmocitoma Solitario (PET-CT) Mieloma Quiescente In summary, Although XR remains a standard method for assessing bone disease in Myeloma, PET may be used in Solitary Plasmocytoma Extramedulary disease Smouldering Myeloma And in MM provides an accurate stage of active disease. And can be used for Assessing Prognostic value And although non yet validated and non standardized, we are convinced that PET will have a role in Treatment response assessment. Thanks for your atention Pronóstico basal/post QT (RM & PET-CT) MTV Respuesta a la terapia ESTANDARIZACIÓN

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43 PET-RMI

44 Conclusions Role of PET in multiple myeloma
X-Ray remains a standard method for assessing bone disease. PET: Allows a whole-body evaluation in a single session Solitary Plasmacytoma Extramedullary disease Smoldering Myeloma Multiple myeloma: Accurate stage of active disease Prognostic value Treatment response assessment: Non validated Non standardized Role in the future In summary, Although XR remains a standard method for assessing bone disease in Myeloma, PET may be used in Solitary Plasmocytoma Extramedulary disease Smouldering Myeloma And in MM provides an accurate stage of active disease. And can be used for Assessing Prognostic value And although non yet validated and non standardized, we are convinced that PET will have a role in Treatment response assessment. Thanks for your atention

45 Conclusiones: Papel de la PET en Mieloma Múltiple (M.M)
* WBXR persiste como método estandard en la detección enfermedad ósea Lesiones osteolóticas (CT) Infiltración M.O (RMI & PET-CT) Infiltracion extra-medular (PET-CT) PET-RM Plasmocitoma Solitario (PET-CT) In summary, Although XR remains a standard method for assessing bone disease in Myeloma, PET may be used in Solitary Plasmocytoma Extramedulary disease Smouldering Myeloma And in MM provides an accurate stage of active disease. And can be used for Assessing Prognostic value And although non yet validated and non standardized, we are convinced that PET will have a role in Treatment response assessment. Thanks for your atention Pronóstico basal/post QT (RM & PET-CT) MTV Respuesta a la terapia ESTANDARIZACIÓN

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47 Limitation PET/CT treatment response lack of an standardized level of FDG uptake Mesguich C. et al, Eur J Radiol 2014; 83: (Mount Sinai, NY) Recomendaciones Estudio PET/TC basal (previo a la terapia) Comparar todas las lesiones focales: No muestra lesiones focales activas en estudio basal: No seguimiento mediante PET Muestra lesiones focales activas en estudio inicial: PET persiste positivo: Captación FDG > Hígado PET negativo: Captación FDG ≤ Hígado Validado en ensayos clínicos: “French criteria” The main limitation to evaluated treatment response with PET is the lack of an standardized level of uptake that differentiate between response form non response. In this sense, the group of Mount Sinai in NY have develop a recommendations to analyze PET/CT in MM patients before and after treatment: After treatment, the main requirement is a baseline PET/CT to compare all focal lesions. this is particularly important in the case on non active focal lesion before treatment, where PET is not suitable to follow this lesions. In the case of active focal lesions at baseline PET: PET remain positive of tumor activity when FDG uptake is higher than the liver And PET become negative for tumor imaging when FDG uptake is inferior to the liver. (in a similar way we are using in lymphoma) Of course this must be validate in clinical trials. With French criteria that are quite similar to the American recommendation.

48 Prognostic value – PET/CT
Treatment response assessment Bartel et al, Blood 2009 PET 10 days from starting the first induction cycle of VDT-PACE Zamagni et al Blood 2011 PET 3 mounts post-ASCT Patients achieve CR with conventional criteria; 23% persistent PET/CT positive PET + post - TAPH PET – post - TAPH ______ Furthermore, treatment response assessment with PET may also have prognostic value. In the Bartel study, PET was performed 10 days from starting the first induction cycle. Patients with a complete PET reduction or normalization had a longer survival than those patients where PET still shows FDG uptake Zamagni obtain similar results when PET was performed 3 months after SCT. And they also showed in a small group of patients that achieved CR with conventional criteria, that those with persistent PET/CT positive had worst prognosis compared with those with negative PET.

49 Treatment response assessment
Lytic lesions XR and CT → sclerotic rim after treatment Residual tissue XR-CT PET Size Metabolic activity Not differentiate from active disease Differentiate from tumor viability PET/TC could be useful in the assessment of treatment response: Extramedullary disease After chemo, after induccióntreatment, before and after SCT Metabolic Response: CMR; PMR; Non-MR, PMD PET not indicated/validated to evaluate treatment response in MM Uniform response criteria from IMWG: Disappearance of any soft tissue plasmacytoma > 50% reduction in size of soft tissue plasmacytoma Baseline PET Next point is te role of PET for treatment response assessment: Is well known that, Osteolytic lesions of XR and CT does not change or frequently become sclerotic after treatment. After treatment, in the presence of a residual mass or residual tissue, anatomic imaging is not optimal for differentiating active disease from residual scar tissue and, PET, on the other hand, reflect metabolic activity, rather than the size of the tissue masses, making easier to differentiate fibrosis tissue from tumoral viability, And as the metabolic changes during treatment tend to precede anatomical changes, PET can also allow an earlier and more effective treatment evaluation response. That’s way PET could be useful in the assessment of treatment response Specially in the assessment of EMD PET may be performed at different times during treatment after chemo, after induction or before and after SCT And because the response may be assessed in terms of CMR, PMR, non MR or PMD. However, PET is not indicated or validated to evaluate treatment response in MM And, the Uniform response criteria from IMWG: only recognize the Disappearance of any soft tissue plasmocytoma Or the reduction in size of soft tissue plasmocytoma But dues not include PET findings PET after treatment

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56 Valoración Respuesta a la Terapia
Enfermedad residual XR-CT PET Tamaño Actividad metabólica No diferencia Enf activa vs Enf residual Detecta viabilidad tumoral Ventajas PET/TC: Enfermedad extramedular. Después de la QT, después Tto inducción, antes y después de SCT Precoz que técnicas morfológicas (RMI) Identifica aquellos pacientes con Enf Mínima Residual negativa radiológica Respuesta metabólica: CMR; PMR; Non-MR, PMD Desventajas PET/TC: Falta de estandarización. Alto coste Disponibilidad Baseline PET Next point is te role of PET for treatment response assessment: Is well known that, Osteolytic lesions of XR and CT does not change or frequently become sclerotic after treatment. After treatment, in the presence of a residual mass or residual tissue, anatomic imaging is not optimal for differentiating active disease from residual scar tissue and, PET, on the other hand, reflect metabolic activity, rather than the size of the tissue masses, making easier to differentiate fibrosis tissue from tumoral viability, And as the metabolic changes during treatment tend to precede anatomical changes, PET can also allow an earlier and more effective treatment evaluation response. That’s way PET could be useful in the assessment of treatment response Specially in the assessment of EMD PET may be performed at different times during treatment after chemo, after induction or before and after SCT And because the response may be assessed in terms of CMR, PMR, non MR or PMD. However, PET is not indicated or validated to evaluate treatment response in MM And, the Uniform response criteria from IMWG: only recognize the Disappearance of any soft tissue plasmocytoma Or the reduction in size of soft tissue plasmocytoma But dues not include PET findings PET after treatment

57 MTV >> Bulky “10cm”