Follow up della neoplasia tiroidea operata
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Presentazione a cura della Dottoressa Rosella Pasqualoni e del dottor Gregorio Reda - "TIROIDE 2018 Nuovi approcci diagnostici e terapeutici" - Roma 24/11/2018
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Follow up della neoplasia tiroidea operata
- 2. Il punto di vista del Medico Nucleare Follow up della neoplasia tiroidea operata La terapia radiometabolica
- 3. APPROCCI PERSONALIZZATI uno spettro di possibilità dalla … sorveglianza attiva alla TT + RT “ ONE-SIZE-FITS-ALL” TT + RT + OT Evoluzione del paradigma di trattamento del carcinoma della tiroide Una grande confusione !!! the role of post-operative 131 I has been reviewed and the number of patients in whom treatment was recommended has been progressively decreasing over the last decade.
- 4. VISION Precision Medicine Nuovo paradigma di cura the right treatment for the right patient, at the right time, with the right dose fornendo una terapia più mirata ed efficiente Selezionare la terapia più appropriata in base a caratteristiche paziente specifiche VISION
- 5. IL PRESENTE
- 6. ATA 2015 & BTA 2014 EANM & Italian Consensus Punti di accordo: la terapia con radiodio 1. is not routinely recommended for ATA [very ] low-risk DTC patients (as identified as very low risk according to the European Consensus Report) 2. There is an “indication for” in high-risk DTC patients. Recommendation 51 of ATA: indicazioni per l’uso del radioiodio dopo la TT in pazienti con ca tiroide differenziato - DTC Punti di disaccordo: la terapia con radiodio nelle categorie intermedie should be “considered” in “low- to intermediate-risk” only in the presence of other adverse features non ci sono indicazioni chiare riguardo l’uso del radioiodio dopo la TT nei pazienti classificati low - to - intermediate risk vs.
- 7. EANM and the EANM Thyroid Committee (2016) The reasons for declining to endorse these guidelines fall into two categories. 1. In most cases our objections are based on differences in the interpretation of the available evidence, especially where the role of nuclear medicine is concerned. In spite of solid evidence on the clinical efficacy of nuclear medicine in both the diagnostic work-up of nodular thyroid disease and the care of DTC, the 2015 ATA guidelines appear to marginalise the role of nuclear medicine in the care of DTC. 2. Some of our objections also concern the wording of some parts of the text which differ from our current viewpoint and are mostly based on a cautious, legally motivated choice of words. Pur riconoscendo lo sforzo e il carattere innovativo delle ATA tentativo di stratificare il rischio come un continuum distinzione del RAI come ablazione adiuvante e terapia NE NEGANO FORMALMENTE il recepimento
- 8. “…For the entire population of patients with DTC exceeding 1 cm in diameter, there is some evidence of the usefulness of postoperative 131I ablation. However, we do agree that not all patients who are treated with 131I will in fact benefit from it, even though we cannot yet reliably identify these patients. We therefore take this opportunity to warn our colleagues that the currently proposed strategy may not yet be based on solid evidence. It is not long since esteemed colleagues Mazzaferri and Jhiang showed in landmark studies that the introduction of postoperative 131I treatment leads to a dramatic decline in both recurrence and DTC-specific mortality rates. There are currently no prospective, controlled studies available that precisely indicate which patients with low-risk DTC may or may not benefit from postoperative 131I therapy. To that end, two well-regarded trials in the UK and France (IoN and ESTIMABL2) comparing 131I ablation and no ablation in patients with lower risk DTC are currently recruiting. A long follow-up of at least 10 years will be needed before these studies are able to provide strong, reliable prospective data on patient outcome...” Therefore we would advise caution in altering long-established and successful practice until sufficient evidence is available indicating that it is safe to omit postoperative 131I treatment – “ablation” or “adjuvant” – in patients with non-microcarcinoma….” EANM and the EANM Thyroid Committee (2016) Motivazioni specifiche
- 9. Italian consensus on diagnosis and treatment of differentiated thyroid cancer: joint statements of six Italian societies. Six scientific Italian societies entitled to cure thyroid cancer patients felt the need to develop a consensus report based on significant scientific advances occurred in the field. (the Italian Thyroid Association, the Medical Endocrinology Association, the Italian Society of Endocrinology, the Italian Association of Nuclear Medicine and Molecular Imaging, the Italian Society of Unified Endocrine Surgery and the Italian Society of Anatomic Pathology and Diagnostic Cytology)
- 10. Italian consensus on diagnosis and treatment of differentiated thyroid cancer: joint statements of six Italian societies. The indication to post-surgical thyroid ablation with radioiodine should be established both on the basis of : the AJCC/UICC staging (VIII ed.) useful to predict the risk of mortality the Initial Risk Stratification System (ATA) useful to predict the risk of disease recurrence/ persistence The indication should be based on post-operative disease status evaluation with stimulated Tg (hypotiroidism or rhTSH) + [ whole body scan]
- 11. Italian consensus on diagnosis and treatment of differentiated thyroid cancer: joint statements of six Italian societies. In patients with ATA low-risk (T1a-b, N0-X, M0-X), RAI remnant ablation is not generally recommended. However, consideration of specific features could lead to consider RAI remnant ablation in individual patients. In patients with intermediate or low-to-intermediate risk (T1-2, N1a–N1b, M0-X), RAI remnant ablation should be considered, particularly in patients with adverse features such as advanced age, larger tumors, macroscopic or clinically evident lymph nodes or the presence of extranodal extension, or aggressive histology or vascular invasion. In patients with high risk or intermediate to high risk (T3-4, any N, any M), RAI ablation is routinely recommended.
- 12. The risk of structural disease recurrence associated with selected clinico-pathological features are shown as a continuum of risk with percentages (ranges, approximate values) presented to reflect our best estimates based on the published literature. Intermed LOW < 5% > 20% 5- 20% RAI agree
- 13. Ma … Quale è il RISCHIO ACCETTABILE Per il paziente ATTENZIONE Le stime del rischio ATA sono basate su popolazioni che sono state trattate con radioiodio Per il medico Per la società
- 14. RISCHIO DINAMICO Il rischio iniziale deve essere completato e aggiornato incorporando la risposta al trattamento Italian consensus on diagnosis and treatment of DTC ERGO … la vera stratificazione del rischio si ha solo dopo aver valutato la risposta alla terapia
- 15. Proposed terminology to classify response to therapy and clinical implications RECOMMENDATION 49 ATA 2015 Excellent response: no clinical, biochemical, or structural evidence of disease How should initial risk estimates be modified over time? Negative imaging and either Suppressed Tg <0.2 ng/mLbor TSH-stimulated Tg <1 ng/mLb 1% –4 % recurrencec <1% disease specific death Negative imaging and Suppressed Tg ≥1 ng/mL or Stimulated Tg ≥10 ng/mL or Rising anti-Tg antibody levels At least 30% spontaneously evolve to NED; 20% achieve NED after additional therapy; 20% develop structural disease <1% disease specific death Structural or functional evidence of disease with any Tg level with or without anti-Tg antibodies 50%–85% persistent disease despite additional therapy. Disease specific death rates as high as 11% with loco-regional metastases and 50% with structural distant metastases Nonspecific findings on imaging and/or basal thyroglobulin ≥0.2 to <1 ng/ml or stimulated thyroglobulin ≥1 to <10 ng/ml or stable or declining thyroglobulin antibodies over time 15%–20% will have structural disease identified during follow-up Biochemical incomplete response: abnormal Tg or rising anti-Tg antibody levels in the absence of localizable disease. Structural incomplete response: persistent or newly identified loco-regional or distant metastases Indeterminate response: nonspecific biochemical or structural findings that cannot be confidently classified as either benign or malignant. This includes patients with stable or declining anti-Tg antibody levels without definitive structural evidence of disease. La prognosi cambia significativamente sulla base della negatività dell’imaging post- terapia
- 16. This figure describes the follow-up protocol for patients with papillary thyroid cancer who are at a low risk of recurrence (part a), a low or intermediate risk of recurrence (part b) or a high risk of recurrence (part c). 18F-FDG–PET, 18F-fluorodeoxyglucose–PET; RRA, radioactive iodine remnant ablation. Follow-up protocols for patients with papillary thyroid cancer Lamartina. Nature Reviews Endocrinology Volume: 14 Issue 9 (2018)
- 17. ESPERIENZA IFO • maggiore casistica mondiale omogenea per trattamento • migliore sopravvivenza • minore morbilità a proposito di evidenze …. Misure di outcome overall survival (morti specifiche) progression free disease disease free survival morbidità (recidive + malattia persistente)
- 18. ESPERIENZA IFO
- 19. il fattore predittivo più significativo di aumentato rischio di mortalità per tumore è la mancata risposta al trattamento con 131I (hazard ratio = 211 , p < 0,0001) altre variabili indipendenti predittive di rischio di sono l’età, il sesso e l’istologia follicolare. Structural incomplete response: persistent or newly identified loco- regional or distant metastases 50%–85% persistent disease despite additional therapy. Disease specific death rates as high as 11% with loco-regional metastases and 50% with structural distant metastases RISPOSTA alla TERAPIA : valore prognostico
- 20. ESPERIENZA IFO Post-surgery staging Nuclear Medicine staging N+ 19,8 % 30,1 % M + 2,1 % 10,4 % I 69% II 13%III 16% IV 2% R 75% M + 25% 7 % St I e 8 % pT1 hanno M+ al WB scan post-interv. low risk High risk
- 21. Casi clinici Donna 70 anni; TT 17/09/2015 E.I ca papillare variante follicolare del lobo dx della tiroide di 0,8 cm; non invasione vascolare. pT1a VERY LOW RISK Tg in OT > 70 ng/ml. 10/2015 TB 131I riscontro di metastasi omero dx trattata con osteosintesi preventiva con chiodo endomidollare pre terapia 131I Novembre 2015 TRM 131-I (150 mCi) con TSH = 32 uUI/ml, Tg > 4000 ng/ml, Ab anti Tg neg Scintigrafia di controllo terapia : M1 su omero dx + residuo M1 - HIGH RISK
- 22. Casi clinici CDT 06/2016 Previa ristadiazione con TB131I in ipotiroidismo viene sottoposta ad ulteriori due cicli di TRM 131I (06/2016 e 06/2017) con pressochè assenza di significativa iperfissazione a livello omerale dx all’ultimo CDT con valori rispettivamente di TSH = 128 uUI/ml e 194 uUI/ml, Tg = 12,2 e 1,0 ng/ml CDT 06/2017
- 23. Casi clinici 06/2018 TB 131I con rh-TSH negativo con valore max di TSH = 367 uUI/ml, Tg < 0,1 ng/ml, AbTg <10 UI/ml Risposta eccellente LOW RISK
- 24. Casi clinici Donna 49 anni; TT 03/11/2016 con E.I. ca papillifero variante follicolare dell’istmo di 8.5 mm che giunge a meno di 1 mm dal margine di resezione; a carico del lobo sinistro nodulo di 1.5 cm sede di ca papillare var follicolare; margini indenni – pT1bm. TB/SPET gen 2018 01/2017 TB 131I iperfissazione focale regione anteriore del collo + ulteriore focalità regione latero-cervicale dx di verosimile pertinenza linfonodale confermata alla SPET/TC TSH = 41 uUI/ml; Tg = 1,7 ng/ml; Ab anti Tg < 10 IU/ml N1 LOW RISK LOW RISK
- 25. Casi clinici In data 16/01/2017 TRM 131-I TSH = 41 uUI/ml; Tg = 1,7 ng/ml; AbTg < 10 IU/ml Sorveglianza attiva O Terapia ? Ecografia ogni 6 mesi Tg dopo stimolo ? N.S.
- 26. Casi clinici In data 19/01/2018 TB 131-I con rh-TSH risultato negativo TSH max = 205 uUI/ml; Tg = < 0,1 ng/ml; AbTg < 10 IU/ml Risposta eccellente LOW RISK
- 27. Casi clinici TB/CDT gen 2017 Donna, 67 anni; TT 07/06/2010 E.I. Ca papillifero variante follicolare del lobo sx di 1,6 cm. Capsula tiroidea esente. Non figure di invasione linfovascolare e perineurale. pT1b 01/17 TB con 131I : intensa iperfissazione regione anteriore del collo; TSH = 67,3 uUI/ml, Tg 1023; Ab anti Tg < 15 IU/ml. Segue TRM 131I con comparsa di iperfissazione emitorace sx (alla SPET/TC lesione IX arco costale sx). TSH = 72,8 uUI/ml; Tg 1161 ng/ml
- 28. Casi clinici TB/CDT dic 2017 12/17 TB con 131I: iperfissazione regione anteriore del collo + emitorace sx TSH = 72.8 uUI/ml, Tg 1165; Ab anti Tg < 11 IU/ml. Segue II ciclo di TRM 131I (200 mCi) che ha evidenziato PD di malattia per comparsa di più lesioni scheletriche di tipo litico alla SPET/TC TSH =83 uUI/ml; Tg 1428 ng/ml
- 29. Casi clinici SPET/CDT dic 2017 01/17 TB con 131I: iperfissazione regione anteriore del collo + emitorace sx TSH = 83 uUI/ml, Tg 1165; Ab anti Tg < 11 IU/ml. Segue II ciclo di TRM 131I (200 mCi) che ha evidenziato PD di malattia per comparsa di più lesioni scheletriche di tipo litico alla SPET/TC TSH = 72,8 uUI/ml; Tg 1428 ng/ml
- 30. Casi clinici CDT 09/2018 Segue III di TRM 131I (200 mCi) con sostanziale SD di malattia al CDT e Tg 1426 ng/ml CDT 12/2017 Risposta strutturale incompleta
- 31. Casi clinici CDT 10/2018 Uomo, 54 anni; TT con E.I multipli focolai di ca papillifero var follicolare (max lobo dx 1cm e paraistmo 1.1 cm); focale infiltrazione del tessuto muscolare striato peritiroideo pT3b(m) UICC 2017 TB 10/2018 10/2018 TB 131I : “alcune immagini di intensa iperfissazione regione ant collo” TSH = 87 uUI/ml, Tg 96.4 ng/ml , Ab anti Tg < 10 UI/ml. Segue TRM 131I (150 mCi)
- 32. ATA RECOMMENDATION 62 and 63 rhTSH (Thyrogen) in the follow-up of DTC During initial follow-up, serum Tg on thyroxine therapy should be measured every 6–12 months. More frequent Tg measurements may be appropriate for ATA high-risk patients. 1. In ATA low- and intermediate-risk patients that achieve an excellent response to therapy, the utility of subsequent Tg testing is not established. The time interval between serum Tg measurements can be lengthened to at least 12–24 months. 2. In ATA high-risk patients (regardless of response to therapy) and all patients with biochemical incomplete, structural incomplete, or indeterminate response should continue to have Tg measured at least every 6–12 months for several years. 3. In ATA low-risk and intermediate-risk patients who have had remnant ablation or adjuvant therapy and negative cervical US, serum Tg should be measured at 6–18 months on thyroxine therapy with a sensitive Tg assay (<0.2 ng/mL) or after TSH stimulation to verify absence of disease (excellent response). Repeat TSH-stimulated Tg testing is not recommended for low- and intermediate-risk patients with an excellent response to therapy. Subsequent TSH-stimulated Tg testing may be considered in patients with an indeterminate, biochemical incomplete, or structural incomplete response following either additional therapies or a spontaneous decline in Tg values on thyroid hormone therapy over time in order to reassess response to therapy. Subsequent stimulated testing is rarely needed for those with NED, because there are rarely benefits seen in this patient population from repeated TSH-stimulated Tg testing. The use of sensitive methods for serum Tg may obviate the need for rhTSH stimulation in low-risk patients with a Tg on LT4 treatment below 0.1–0.2 ng/mL
- 33. CONCLUSIONI la “gestione strategica” del DTC sta evolvendo da una responsabili- tà individuale a una responsabilità collegiale - DMT con expertise specifica … ma le “responsabilità” restano individuali ! Le linee- guida presentano aspetti controversi bias di interpretazione e … contraddizioni in particolare la “responsabilità clinica” della terapia (indicazioni, modalità e FUP è del Medico-Nucleare (D.Lgs. 187/00, art. 5, comma 2) Con l’idea di evitare terapie potenzialmente inutili si corre il rischio di “non verificare “ lo stato effettivo della malattia e peggiorare la prognosi a lungo termine attualmente eccellente
- 34. CONCLUSIONI Nell’attesa che le società scientifiche italiane varino le Linee-Guida ufficiali usare il buon senso utilizzare tutti gli strumenti per una stadiazione corretta (ATA, TNM, Tg, 131 I whole body basarsi sulla propria esperienza ma .. documentare le scelte informare il paziente tenere conto delle sue preferenze