Protones/Fotones. Dra. Berta Roth

Transcription

1 Protones/Fotones Dra. Berta Roth The Best in Proton Protect, Therapy, Enhance Today and and Save Tomorrow Lives

2 Advances in Science, biology, physics, imaging allows: More efficient and better tolerated treatments Increasing proportion of patients free of tumour with less side effects

3 Radiotherapy in 2016 Precision Individualization Organ Preservation

4 Radiotherapy. What we can do better? Field IMRT, IGRT Dose per fraction Protons Target Functional Images Radiobiology Biological Modifiers New Drugs Biology of the Tumour Biological predictors

5 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

6 Optimal Therapeutic Ratio: cure/toxicity Precision!!! To adapt the machine to the patient and not the patient to the machine Individualized versus one fits all!!!! IGRT / IMRT / SBRT / SRS/ PROTON...

7 Why heavier hadron beams? Precision therapy conformed to tumor Sparing of normal tissues Increased DNA damage in tumor Increased effect on hypoxic tumors Less repair of sublethal anf potentially lethal damage in cell cycle Short overall treatment course Use of radioactive beam component for treatment verification

8 Charged particles are being increasingly used in cancer treatment

9 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. Photons (X-Rays) Protons

10 Why Proton Therapy? The dose deposition / 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 The Best in Proton Protect, Therapy, Enhance Today and and Save Tomorrow Lives 11

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12 42 centres with protons (USA 14, Europe 12, Japan 8,..) 6 centres with carbon ions (Japan 3, Europe 2, China 1) 3 dual centres (p+ C-12) 27 new centres planned 107,792 treated patients (93,452 with p+, with C-12) + 46,000 in the past 5 years ( 10,000 patients per year )

13 Protons: Expansion Centers Worldwide 45,000 40,000 40,000 patients , , ,000 20, PT centers , Research centres 10, ,000 Hospitals

14 Growing interest in PT clinical advantages: Publications Yearly publications Pubmed search with: Proton Therapy or Proton Radiotherapy or Proton Beam Therapy From Technical and Standard indications publications (Ocular, Pediatrics, Base of Skull Chondrosarcoma and Chordoma) to New indications (Lung, Breast, Head and Neck) expending the use of PT Year The Best in Proton Protect, Therapy, Enhance Today and and Save Tomorrow Lives Number of publication up to end

15 PT Advantages: From Beam properties to Clinical benefits Tumor control Toxicity PROBABILITY Photons Protons Widening of the Therapeutic Ratio The Best in Proton Protect, Therapy, Enhance Today and and Save Tomorrow Lives DOSE OF RADIATION 16

16 PT Advantages: From Beam properties to Clinical benefits Improve Local Control Reduce Normal Tissues Complications Decrease integral dose (secondary cancer) PT is the treatment of choice for retreatment Probability Probability (%) Tumor control Photons Improvement of local tumor control Current standard (IMRT photons) Complications Local tumour control Toxicity Courtesy of Prof Lagendijk Protons Protons The Best in Proton Protect, Therapy, Enhance Today and and Save Tomorrow Lives Prevention of complications 17

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21 Growth in prospective clinical trials 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 ocular spine pancreas prostate bone soft tissues head and neck liver esophagus, anal uterus, cervix lung RCT 60 Trial type NonRandomized, comparative others Source: The Best in Proton Protect, Therapy, Enhance Today and and Save Tomorrow Lives 26

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26 Meduloblastoma

27 Meduloblastoma

28 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 The Best in Proton Protect, Therapy, Enhance Today and and Save Tomorrow Lives Secondary malignancy (Cancer generated by the RT treatment itself) 33

29 Decreased risk of 2 nd cancer with protons 503 proton patients, Matched with 1,591 photon pts, by site, year, pathology Mean F-Up 7.7 vs 6.1 y. Risk : 6.4% (protons) vs 12.8% (photons) adjusted: 2.73 (p <.0001) Chung CS et al, ASTRO, 2008, abstr 17

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37 Proton Therapy for Head and Neck The Best in Proton Protect, Therapy, Enhance Today and and Save Tomorrow Lives 44

38 Proton Therapy for H&N: Brain Stem DVH Volume (%) Dose (Gy) Photons Volume (%) Dose (Gy) Protons The Best in Proton Protect, Therapy, Enhance Today and and Save Tomorrow Lives All the lines correspond to the different patients Courtesy of Dr Nancy Lee MSKCC.

39 Proton Therapy for H&N: Spinal Cord DVH Volume (%) Dose (Gy) Photons Volume (%) Dose (Gy) Protons The Best in Proton Protect, Therapy, Enhance Today and and Save Tomorrow Lives All the lines correspond to the different patients Courtesy of Dr Nancy Lee MSKCC.

40 Proton Therapy for H&N: Oral Cavity DVH Volume (%) Dose (Gy) Photons Volume (%) Dose (Gy) Protons The Best in Proton Protect, Therapy, Enhance Today and and Save Tomorrow Lives All the lines correspond to the different patients Courtesy of Dr Nancy Lee MSKCC.

41 Proton Therapy for H&N: Larynx DVH Volume (%) Dose (Gy) Photons Volume (%) Dose (Gy) Protons The Best in Proton Protect, Therapy, Enhance Today and and Save Tomorrow Lives All the lines correspond to the different patients Courtesy of Dr Nancy Lee MSKCC.

42 Cost effectiveness of Proton Therapy: MD Anderson MD Anderson Head and neck 50 to 60% reduction in Gastrostomy tube IMPT for Oropharynx is cost effective Breast Proton therapy less expensive than some conventional radiotherapy techniques The Best in Proton Protect, Therapy, Enhance Today and and Save Tomorrow Lives 49

43 Cost effectiveness of proton therapy 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 The Best in Proton Protect, Therapy, Enhance Today and and Save Tomorrow Lives 50

44 Cost effectiveness of proton therapy 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 The Best in Proton Protect, Therapy, Enhance Today and and Save Tomorrow Lives 51

45 RACIONAL DE LOS PROTONES EN CÁNCER DE MAMA EL CANCER DE MAMA ES UNA ENFERMEDAD ALTAMENTE CURABLE Y POR LO CUAL LAS PACIENTES SON LARGAS SOBREVIVIENTES POR LO QUE PUEDEN EXPERIMENTAR MAS TOXICIDADES TARDIAS.

46 Breast RX-associated cardiac toxicity Estudio de 2160 mujeres desde 1958 a 2001 (Darby et al., NEJM, 2013)

47 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++)

48 SPARING HIGH DOSE RT For tangent field to cover IMN left, LAD & portion RV & LV would receive full dose. For a tangent field to cover IMN right, RCA

49 Proton Therapy for Breast IMRT PT Complication Left Breast Right Breast Chest pain 26% 12% Coronary art. dis. 25% 5810% Myocardial Infrac. 15% 5% Images Courtesy of Dr. S. Both, Penn Med. Reduction of Side Effects Reduced dose to the heart Reduced dose to the lung Reduced dose to the left anterior descending artery The Best in Proton Protect, Therapy, Enhance Today and and Save Tomorrow Lives Cardiac Death 6.4% 3.6% Post Mastectomy trial on-going : NCT

50 Protons allow for an external beam plan with non- target breast tisuue sparing more comparable to brachytherapy Modest reduction lung and heart (most patients) El-Ghamry IJROBP 2002

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

52 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 Pancreatic Cancer Facts... 43,140 Annual Cases Perhaps 50% present with localized disease Perhaps 50% of these are resectable or curable And yet the cure rate is only about 20% for these curable patients.

57 Particle therapy for locally advanced unresectable Pancreatic Cancer

58 More Facts Local control is a necessary condition for cure. Surgery is a necessary condition for local control. Surgery is not a sufficient condition for local control.

59 The problem with the Pancreaticoduodenectomy... is that even with negative nodes and negative surgical margins, 50% to 80% of patients will suffer a local failure if they do not receive postoperative radiotherapy.

60 Are you ready for the bad news? Hopkins data: Pawlik TM, Surgery, Whipples from 1995 to 2005 Node positivity was 79.3% Margin positivity was 41.1%

61 Postoperative X-Rays?

62 Problems with postoperative radiotherapy MGH data shows a 36% local/regional failure rate at 3 years after postoperative chemoradiation. RTOG shows a 23% to 28% local failure rate.

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

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

66 What about efficacy?

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

68 Summary #1 Surgical outcome data demonstrates a high rate of local failure which is only marginally improved with postoperative radiotherapy.

69 Summary #2 Our experience suggests that these fears are unjustified with proton therapy: Dosimetry Lack of acute or late radiotherapy toxicity Surgical experience showing no increase in complications for unresectable patients receiving high dose radiotherapy before surgery.

70 UFPTI protocols: PC01 Unresectable disease 59.40CGE with concomitant Capecitabine (closed) PC02... Resectable and marginally resectable disease 50.40CGE with concomitant Capecitabine. PC03 Postoperative adjuvant with weekly Gemcitabine 50.40CGE for R0 resections 54.00CGE for R1 resections 59.40CGE for R2 resections

71 UFPTI protocols: PC04 ( in development) initally unresectable disease 63CGE in 28 fractions (mimics NRG 1201) with concomitant capecitabine. +/- equivalent of 70CGE at 2CGE per fraction

72 Case #1: Which best? (LEC. Joelle) Max:105% TomoT Max:68% Max:76% 56Y old, RIII palsy Past history: RON glioma as young adult(±45 Gy) Pr Work up: B meningioma Rt ant clinoid Management: partial resection+rt(52gy) CyberK Choice: protons (sharp penumbra) Stroke at 3 m NED at

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75 Protons in choroidal melanomas: DFS BostonLarge BostonSmall Villigen Orsay Nice

76 Paraespinal Tumour K K IMRT Protons

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

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

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

80 Protontherapy for oligometastatic patients

81 Potential Number of Patients in Argentina ( Population: 40 M) RT Conventional: pt/year every 10 M Hab = patients Protontherapy: % pt RT = pt/year

82 Proton Therapy and Advanced Radiotherapy Center Instituto Roffo FCDN Protonterapia

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

84 Be positive like a proton!