La Protonterapia nel paziente adulto

Presentazione sul tema: "La Protonterapia nel paziente adulto"— Transcript della presentazione:

1 La Protonterapia nel paziente adulto
Protontherapie: eine Chance zur Cooperation in der Europaregion Protonterapia: un’opportunità di cooperazione nell’Euregio La Protonterapia nel paziente adulto U.O. Protonterapia-APSS Marco Cianchetti

2 Vantaggi della protonterapia
Minor dose ai tessuti normali Minore tossicità ai tessuti normali Migliore radiotolleranza (< interruzioni) Migliore integrazione con terapia sistemica Riduzione effetti tardivi Possibile dose-escalation Maggior controllo tumorale

3 Vantaggi della protonterapia
Vantaggio dosimetrico dimostrato dagli studi in-silico dei protoni rispetto ai fotoni per diverse patologie Studi prospettici randomizzati: spesso non fattibili, eticamente ingiustificati (?) Studi prospettici osservazionali più indicati per gli studi con protoni Vantaggio clinico su cui ancora non c’è completo accordo tra i ricercatori

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6 Astro model 1 Approved May, 20, 2014

7 Astro model 2 Approved May, 20, 2014

8 Category A: number of patients treatable with protons in Italy (strongly indicated)
Tumor types Patients / year Treatable with protons Uveal Melanoma 310 % Skull base Chordoma 45 % Skull base Chondrosarcoma 90 % Skull base Meningioma 250 % Paraspinal Tumors 140 % Cranial nerves Schwannoma 300 % Hypophysis Adenoma 750 10% TOTAL 1.885 %

9 Category B: number of patients treatable with protons in Italy with potential gain
Tumor types patients / year treatable with protons Brain neuroepithelial tumors % Brain Metastases % Head neck tumors % Thyroid tumors % NSCLC % Tymomas % Esophageal tumors % Biliary tract tumors % Hepatocellular tumors % Pancreatic tumors % Rectal tumors % Cervix tumors % Bladder tumors % Prostate tumors % Pelvic recurrences after surgery >500 >250 50% Pediatric solid tumors % Non-neoplastic lesions AVMs % Macular degeneration ? ? ? TOTAL > > %

10 Cordomi della base del cranio
Reference Pts RT regimen OS (%) LC (%) FU (months) Serious side effects Hug ‘99 33 Frac PT+/-P (64-79 GyE) 5y 79 5y 59 7-75 5% Munzenrider ‘99 290 Frac PT+P (66-83 GyE) 10y 54 1-254 4-13% Igaki ‘04 13 Frac PT+/-P (63-95 GyE) 5y 67 5y 46 15-123 15% Noel ‘05 100 Frac PT+P (60-71 GyE) 5y 80 4y 54 0-87 3-16% Ares ‘09 42 Frac PT (67-74 GyE) 86 (Abs.) 5y 81 14-92 6% Deraniyagala ‘14 Frac PT (70-79 GyE) 2 y 92% 2 y 86% 3-58 18% (G2) No>G2 Grosshans ‘14 10 SIB, Frac (2) (68-70 GyE) 2 y 80 (Abs) (FFS) 2 y 90 (Abs.) (LFFS) 13-42 No>G2 Frac PT: fractionated proton therapy SIB: simoultaneous integrated boost P: fractionated photon RT: radiotherapy GyE: GyEquivalent y: years Abs.: absolute FFS: Failure Free Survival LFFS: Local Failure Free Survival

11 Condrosarcomi della base del cranio
Reference Pts RT regimen OS (%) LC (%) FU (months) Serious side effects Hug ‘99 25 Frac PT+/-P (64-79 GyE) 5y 100 5y 75 7-75 5% Rosenberg ‘99 200 Frac PT+P (64-80 GyE) 10y 99 10y 98 2-222 NR Noel ‘04 26 Frac PT+P (60-70 GyE) 4y 86 3y 91 3-74 6% Ares ‘09 22 Frac PT (63-74 GyE) 95 (Abs) 5y 94 14-92 Grosshans ‘14 5 SIB PT (66-70 GyE) 2 y 100 FFS(Abs) 2 y LFFS (Abs) 13-42 No>G2 Frac PT: fractionated proton therapy SIB: simoultaneous integrated boost P: fractionated photon RT: radiotherapy GyE: Gy Equivalent y: years Abs.: absolute FFS: Failure Free Survival LFFS: Local Failure Free Survival

12 De Laney, JSO 2014;110:115–122

13 Boost di brachiterapia di 7.5-10 Gy su dura, se chirurgia at MGH
Erogati 19,8-50,4 Gy(RBE) pre-operativamente per ridurre il rischio di disseminazione chirurgica Massima resezione chirurgica possibile, evitando di posizionare barre metalliche (Ti) Boost di brachiterapia di Gy su dura, se chirurgia at MGH Follow up mediano 7.3 anni (2,8-14,5) De Laney, JSO 2014;110:115–122

14 Complicanze di Grado 3-4: a 5 anni 10%; a 8 anni 13%
De Laney, JSO 2014;110:115–122

15 Cordomi extracranici Reference Pts RT regimen OS (%) LC (%)
FU (months) Serious side effects DeLaney 2014 50 Frac PT+/-P ( GyE) (pre-post-operatoria) 5y 84 8y 65 5y 81 8y 74 5 y 10% (G3-4) 8 y 13% (G3-4) Staab 2011 40 Frac PT (59.4–75.2 GyE) 5y 80 5y 62 24-91 G3: 2 G5: 1 Mina 2014 23 PT/C (70.4/16-32fr GyE) 3y 94 3y 83 7-78 G3-4: 39% Frac PT: fractionated proton therapy P: fractionated photon C: Carbon Ion RT: radiotherapy GyE: Gy Equivalent y: years

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17 Pts Sede Chirurgia Dose erogata Risultati Tossicità FU in mesi 16
Clivale: 8 Cervicale: 2 Toraco/lombare: 3 Sacrale: 3 8 eseguita 8 non resecabili 75.6 GyE ( ) Acuta: G3-G4: 2 Cronica: G3-G4: 2 23 (6-63) McDonald, IJROBP, 87,5,2013

18 Protonterapia per le neoplasie testa-collo: seni paranasali
Reference Pts RT regimen OS (%) LC (%) FU (months) Serious side effects Tokuye 2004 11 Frac PT+/-P 72 GyE (42-98) 5/11 (Abs.) 9/11 (Abs) 23 (6-58) G3: 1 Resto 2008 102 Frac PT +/- P GyE (55.4–79.4) 5y CR: 90% PR: 53% Bx: 49% (P = 0.02) CR: 95% PR: 82% Bx: 87% (P = 0.32) 43.2 ( ) - Zenda 2011 39 PT 65 GyE (60-70) 5y 55 1y 77 45.4 ( ) G3: 4 G5: 1 Frac PT: fractionated proton therapy P: fractionated photon RT: radiotherapy GyE: Gy Equivalent Abs: absolute y: years

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20 Carcinoma adenoideo cistico del distretto testa collo
Reference Pts RT regimen Surgery (%) OS (%) LC (%) FU (months) Serious side effects Takagi 2014 40 EQD10/ GyE (67.7–74.3) Chirurgia: 30 N. chirurgia: 70 5y 63.3 5y 75.8 6-80 (38) G3: 36 G4: 9 G5: 3 Linton 2015 26 72 GyE Chirurgia: 77 N. chirurgia: 33 2y 82 2y 92 7-50 (25) G3: 2 G4: 1 G5: 1 EQD: Equivalent Dose GyE: Gy Equivalent y: years

21 Nasofaringe re-irradiazione
16 pazienti trattati per recidiva di carcinoma del rinofaringe 9 pazienti hanno sviluppato una recidiva loco-regionale ad una media di 9.6 mesi dalla fine del trattamento (range: 0-26 mesi) 2 year - Overall Survival: 50% (6 pazienti morti per malattia, 1 per cause intercorrenti) 2 year - Local Control: 50% 2 year - Disease Free-Survival: 50% Tossicità G3: 3 pazienti Lin R. et al, Radiology, 1999, 213:

22 Nasofaringe re-irradiazione
Fattori prognostici Qualità del piano Significativo per OS anche all’analisi multivariata (p=0.028) Lin R. et al, Radiology, 1999, 213:

23 Nasofaringe-Ghiandole lacrimali
17 pazienti, 1990 – 2002, tecnica mista fotoni/protoni Stadio T4 N0-4, 12 pazienti (71%) con WHO II-III Dose media prescritta al GTV 73.6 Gy(RBE), range Gy(RBE) Ghiandole lacrimali 11 pazienti con ACC trattati a Boston con chirurgia conservativa (MEEI) e protonterapia (MGH) per ACC. 3 recidive A. W. Chan et al, JCO, 22, 14S, 2004:5574; Ahmad et al., Opht, 116 (6), 2009

24 Cortesia Dr. Dante Amelio
Adenomi Pituitari Reference Pts # RT regimen TV (cc) LC (Absolute) Hormone normalization Serious side effects Ronson ‘06 24 NON-func. 4 ACTH-secr. 11 GH-secr. 6 Prolactine-secr. Frac PT (50-56GyE) 1-9 cm (Ø) 100% - 25% (CR) 45% (CR) 39% (CR) 4.6% RION Wattson ‘14 79 ACTH-secr. 61 GH-secr. 12 Prolactine-secr. 3 TSH 10 NS SRS PT (15-24GyE) Frac PT ( GyE) 67% (CR) 49% (CR) 38% (CR) 50% (CR) 75% (CR) 2.5% Seizure Rivedere dati Boston appena usciti Frac PT: fractionated proton therapy SRS PT: proton radiosurgery #: number RT: radiotherapy TV: target volume NS: Nelson syndrome CR: complete response RION: radiation-induced optic neuropathy Class III evidence Same as photons Cortesia Dr. Dante Amelio

25 Meningiomi Cortesia Dr. Dante Amelio
Reference Pts # WHO RT regimen TV (cc) LC (%) Serious side effects Gudjonsson ‘99 19 I (Hypo)Frac PT (24GyE) 5-53 100 (Absolute) None Wenkel ‘00 46 Frac PT+P (53-74GyE) 9-287 5y 100 17% Noel ’05 51 Frac PT+P (54-61GyE) 1-120 4y 98 4% Halasz ‘11 50 SRS PT (10-15GyE) 0.5-10 3y 94 6% Vernimmen ‘01 23 NR Frac PT (54-62GyE) (Hypo) Frac PT (17-24GyE) 13-80 3-63 87 (Absolute) 13% Slater ‘12 72 I-II Frac PT (50-72GyE) 5-229 5y 99 WHO I 50 WHO II 8% Weber ’12 39 I-II-III Frac PT (52-67GyE) 1-546 5y 100 WHO I 49 WHO II-III Combs ‘13 70 Frac PT/I+P (52-68GyE) (Absolute) 100 WHO I 81 WHO II-III Hug ’00 16 II-III Frac PT+P (50-72GyE) 5y 38 WHO II 52 WHO III 9% Boskos ‘09 24 II-IIII Frac PT+P (64GyE - Median) 30-325 5y 47 #: number; RT: radiotherapy; Frac PT: fractionated proton therapy; P: fractionated photon; SRS PT: proton radiosurgery; I: fractionated ion therapy; TV: target volume; y: years; NR: not reported Cortesia Dr. Dante Amelio Class III evidence Same as photons

26 Schwannoma vestibolare
Reference Pts # RT regimen TV (cc) LC Hearing preservation Serious side effects Bush ’02 31 Frac PT (54-60GyE) 1-29 100 (Absolute) 31% None Weber ’03 88 SRS PT (10-18GyE) 1-16 5y 94 33% 9% FND 10% TND Vernimmen ‘09 51 (Hypo)Frac PT (20-42GyE) 1-46 5y 98 42% 4% FND Frac PT: fractionated proton therapy SRS PT: proton radiosurgery #: number RT: radiotherapy TV: target volume FND: facial nerve dysfunction TND: trigeminal nerve dysfunction Class III evidence Same as photons Cortesia Dr. Dante Amelio

27 Cortesia Dr. Dante Amelio
Gliomi di basso grado Reference Pts # RT regimen Outcomes Compliance FU in mts Fitzek ’01 (Boston) 20 68.2 GyRBE (1.8 GyRBE/fr) 5-yrs OS 71% 100% (Mild Tox) 54-81 Hauswald ‘12 (Heidelberg) 19 48-54 GyRBE (1.8-2 GyRBE/fr) 15 SD, 2 PR, 1 CR, 1 P 100% * 0-22 Maquilian ‘13 (Philadelphia) 23 54 GyRBE (1.8 GyRBE/fr) 23 SD 1-9 Shih ‘15 5-yrs PFS 40% 5-yrs OS 84% 100% ** Med 5.1 yrs Neurocognitive and QoL evaluationin on going. ** No neurocognitive and QoL decline Cortesia Dr. Dante Amelio

28 Cortesia Dr. Dante Amelio
Gliomi di alto grado Reference Pts # RT regimen Outcomes Toxicity FU in mts Fitzek ’99 (Boston) 23 (GBM) 90 GyRBE (Hyperfr.) NO CONC. CHT in most pts Med OS 20 mts 30% Radio-necrosis NA Mizumoto ‘10 (Tokio) 21 (GBM) 96 GyRBE (Hyperfr.) CONC. CHT: ACNU 21.6 mts NO RT G3-4 5% Radio-necrosis Cortesia Dr. Dante Amelio

29 Clinical experience with proton therapy for GI cancers: a review F
Clinical experience with proton therapy for GI cancers: a review F. Dionisi, D. Amelio, M. Cianchetti, E Iannacone, D. Ravanelli, B. Rombi, S. Vennarini, L. Vinante, M. Amichetti Gastroenterol. Hepatol. Res. accepted October 2013 ……. Thus, the clinical experience is still scarce. Most of the studies regarding the use of PT in GI cancer treatment focused on HCC and reported good outcomes. A survival benefit could also be achieved in pancreatic cancer. A potential benefit can be presumed in all other malignancies by the reduction of treatment-related toxicity with a possible improvement in cancer survivors’quality of life. Several trials are currently ongoing such as ……

30 Cortesia Dr. Francesco Dionisi

31 Inoltre, negli Stati Uniti l’HCC è inserito dall’ASTRO tra le patologie elettive per protonterapia ( ursement/ASTRO%20PBT%20Model%20Policy%20FINAL.pdf) sulla base di dati di letteratura favorevoli e consistenti: Qi WX et al. Charged particle therapy versus photon therapy for patients with hepatocellular carcinoma: A systematic review and meta-analysis. Radiother Oncol Dec 9. pii: S (14) doi: /j.radonc ; Dionisi F, Ben-Josef E The use of proton therapy in the treatment of gastrointestinal cancers: liver. Cancer J (6):371-7.; Klein J, Dawson LA Hepatocellular carcinoma radiation therapy: review of evidence and future opportunities. Int J Radiat Oncol Biol Phys Sep 1;87(1):22-32. D.A. Bush et al., The safety and efficacy of high-dose proton beam radiotherapy for hepatocellular carcinoma: a phase 2 prospective trial, Cancer. 117 (2011) 3053–3059.

32 Sarcomi retroperitoneali
Esperienza del MGH nel trattamento di 28 pazienti con sarcomi retroperitoneali. Chirurgia radicale più radioterapia(Protoni e/o fotoni) Sopravvivenza libera da malattia locale a 3 anni: 90%-30% (Primitivi –Recidive) Yoon et al. Ann Surg Oncol (2010) 17:1515–1529

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35 The use of proton-beam therapy in the treatment of non-small-cell lung cancer.
Oshiro Y, Sakurai H. Expert Rev Med Devices Mar;10(2): doi: /erd  Review.

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37 ASTRO’s five recommendations 2013:
Don’t initiate whole breast radiotherapy as a part of breast conservation therapy in women age ≥50 with early stage invasive breast cancer without considering shorter treatment schedules. Don’t initiate management of low-risk prostate cancer without discussing active surveillance. Don’t routinely use extended fractionation schemes (>10 fractions) for palliation of bone metastases. Don’t routinely recommend proton beam therapy for prostate cancer outside of a prospective clinical trial or registry. Don’t routinely use intensity modulated radiation therapy (IMRT) to deliver whole breast radiotherapy as part of breast conservation therapy.

38 Melanoma della coroide

39 Risultati: Protonterapia
2,435 melanomi oculari, Marzo 1984 e Dicembre 1998; PSI Villigen/University Eye Clinic Lausanne Follow up mediano: 40 mesi Dose 60 Gy(RBE)/4 frazioni/4giorni consecutivi Gy(RBE)/4 frazioni/4giorni consecutivi Controllo Locale: 95.8% a 5 anni; 94.8% a 10 anni 90.6% ( ) 96.3% ( ) 98.9% ( ) Sopravvivenza a 10 anni: 72.6% (senza recidiva) 47.5% (con recidiva) Sopravvivenza per periodo di trattamento: : 81.8% : 83.3% : 87.9% (p=0.003) Int J Rad Onc Biol Phys, 2001,51,

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41 Attività U.O. Protonterapia-Trento Pazienti trattati

42 Accelerated partial breast irradiation with Protons
Kozak KR et al. IJROBP, 66: , 2006

43 …thank you for your attention…
October 22nd, 2014 – Trattamento del primo paziente

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