Estado Actual en la Radioterapia con Protones. Dra. Berta Roth 20 de Octubre de 2017

Transcripción

1 Estado Actual en la Radioterapia con Protones Dra. Berta Roth 20 de Octubre de 2017

2 Radioterapia en 2017 Precisión Individualización Preservación de Órgano

3 Radioterapia Que podemos hacer mejor? Campo IMRT, IGRT Dosis por fracción Protones Target Imágenes funcionales Radiobiología Modificadores biológicos Nuevas drogas Biología tumoral Marcadores Predictivos biológicos

4 protons precision stereotactic radiotherapy cyberknife tomotherapy Carbon ions IGRT Image guided IMRT (XR Intensity modulation) photons «hadrons» 3D RT, conformal 2D RT >80% radiotherapy cost / sophistication

5 Por qué la protonterapia? Mayor precision en la conformación del tratamiento Menor dosis a tejidos sanos Mayor daño al DNA tumoral Mayor efecto en tumores hipoxicos Menor reparación de daño sub-letal y potencialmente mayor daño letal Tratamientos más cortos (hipofraccionamiento)

6 Las partículas cargadas están siendo cada vez mas utilizadas

7 Tumor Dose is less than the entry dose. Highest Dose is near the point of beam entry. Dose is also delivered beyond the tumor target. Fotones (X-Rays) Protones

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9 Por qué protones? Depósito de dosis/ Bragg peak Ballistic advantages No radiation beyond the Bragg Peak tumor; Homogeneous dose along the defined modulation Distal & Proximal Conformality to tumor shape (PBS) Example: Single Field Uniform Dose using in Pencil Beam Scanning 9

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15 PROBABILITY Protones: Beneficios Clínicos Tumor control Toxicity Photons Protons Widening of the Therapeutic Ratio DOSE OF RADIATION 15

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17 Probability Protones: Beneficios Clínicos Mejor control local Menores complicaciones en tejidos sanos Menos dosis integral (segundos primarios) De elección en reirradiación Probability (%) Tumor control Improvement of local tumor control Toxicity Prevention of complications 0 Photons Current standard (IMRT photons) Complications Local tumour control Protons Protons Courtesy of Prof Lagendijk 17

18 INDICACIONES CLINICAS

19 INDICACIONES CLINICAS Oct data from a leading center in the US 19

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24 Ensayos clínicos prospectivos End February prospective clinical trials on ClinicalTrials.gov with status of ongoing and/or recruiting Randomized Controlled Trials have increased to 23 Non Randomized Studies have increased to 52 Ongoing clinical trial Total Trial type 23 ocular spine pancreas prostate bone soft tissues 1 head and neck liver esophagus, anal uterus, cervix lung 52 RCT NonRandomized, comparative others Source: 24

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28 Meduloblastoma

29 Meduloblastoma

30 Portonterapia en T. Cabeza y Cuello 30

31 Proton therapy for Pediatric Tumor Side Effects* Protons Photons Restrictive Lung Disease 0% 60% Reduced exercise capability 0% 75% Abnormal EKGs 0% 31% Growth abnormality 20% 100% IQ drop of 10 points at 6 years 1.6% 28.5% Risk of IQ score < 90 15% 25% Courtesy of Newhauser et al PMB 2009 Secondary malignancy (Cancer generated by the RT treatment itself) 31

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37 Costo Efectividad de la Protonterapia: MD Anderson MD Anderson T. Cabeza y Cuello 50 to 60% reducción de gastrostomia IMPT para orofaringe es costo/efectivo Mama Protones es más económico que otras técnicas conformadas de tratamiento con fotones 37

38 Costo Efectividad de la Protonterapia CONCLUSIONS: The current results provide the first evidence-based guide for identifying children with brain tumors who may benefit the most from Proton-Therapy with respect to endocrine dys-function. Proton- Therapy may be more cost effective for scenarios in which radiation dose to the hypothalamus can be spared, but protons may not be cost effective when tumors are involving or directly adjacent to the hypothalamus if there is a high dose to this structure. Cancer 2015;121: American Cancer Society 38

39 Costo Efectividad de la Protonterapia CONCLUSIONS: With greatly limited amount of data, PBT offers promising cost-effectiveness for pediatric brain tumors, well-selected breast cancers, loco-regionally advanced NSCLC, and high-risk head/neck cancers. Heretofore, it has not been demonstrated that PBT is cost-effective for prostate cancer or early stage NSCLC. Careful patient selection is absolutely critical to assess cost-effectiveness. Together with increasing PBT availability, clinical trial evidence, and ongoing major technological improvements Cancer 2016;122: American Cancer Society 39

40 RACIONAL DE LOS PROTONES EN CÁNCER DE MAMA ES UNA ENFERMEDAD ALTAMENTE CURABLE PACIENTES LARGAS SOBREVIVIENTES EVITAR TOXICIDADES TARDIAS

41 RT en MAMA: toxicidades cardíacas asociadas Estudio de 2160 mujeres desde 1958 a 2001 (Darby et al., NEJM, 2013)

42 ANATOMIA: ARTERIAS CORONARIAS (Nilsson, JCO, 2011) = Right CA 5+6 = Left main = Left Anterior descending Lt Tangential fields = Lt breast/chest Wall ( Rt Int Mam = Rt breast = Electrons++)

43 Altas dosis de RT en OAR IMN izq, LAD, VD y VI recibirán dosis completa. IMN der, RCA recibirá altas dosis.

44 Protones en Ca Mama IMRT PT Images Courtesy of Dr. S. Both, Penn Med. Complication Left Breast Right Breast Chest pain 26% 12% Coronary art. dis. 25% 4410% Myocardial Infrac. 15% 5% Reduction of Side Effects Reduced dose to the heart Reduced dose to the lung Reduced dose to the left anterior descending artery Cardiac Death 6.4% 3.6% Post Mastectomy trial on-going : NCT

45 PROTONES Y PARRILLA COSTAL (Mac Donald S et al., Rad Oncol, 2013) XR+El XR PROTONS PROTONS PROTONS

46 Trial RADCOMP Randomized control trial for protons vs photons for patientes reciving Radiation for nonmetastatic breast cancer in reducing major cardiovascular events (MCE) PCORI sponsored total 1716 patients Dose specification 45-50Gy in 1.8-2Gy fractions with o whithout tumor bed or chest wall boost Hypothesis For patients with locally advanced breast cancer proton therapy will reduce the 10 years MCE after radiation from 6.3% to 3.8%

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56 Protons versus IMRT Small Bowel V20 (15.4% vs. 47.0% p=0.03)

57 Protons versus IMRT Right Kidney V18 (27.3% vs. 50.5% p=0.02)

58 What about efficacy?

59 PC01 Protocol (continued) 2 Year Overall Survival 31% Median Survival 18.4 months 2 Year Local Control 69%

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64 Paraespinal Tumour K K IMRT Protons

65 Treatment Plan...3DCRT Pulmonary V20 = 50% - Not Feasible

66 Treatment Plan...IMRT Mean Heart Dose 19.00Gy Pulmonary V20 = 35%

67 Treatment Plan...Protons Pulmonary V20 = 24%. Cardiac Dose Minimal

68 Protontherapy for oligometastatic patients

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70 Potencial numero de pacientes en Argentina ( Poblacion: 40 M) RT Convencional: pt/año cada 10 M Hab = pacientes Protonterapia: % pt RT = pt/año

71 CENTRO DE PROTONTERAPIA Instituto Roffo FCDN Protonterapia

72 Which future for Hadrons? Today... Tomorrow PHOTONS PROTONS PROTONS CARBON? Others?

73 Be positive like a proton!