Hot topics in Radiation Oncology for the Primary Care Providers

Transcription

1 Hot topics in Radiation Oncology for the Primary Care Providers Steven Feigenberg, MD Professor Chief, Thoracic Oncology Vice Chair of Clinical Research April 19, 2018

2 Disclosures NONE 2

3 Early Stage Disease and the Challenges from 15 years ago Radiation is used when surgery is too risky or is refused Standard is 7 weeks of daily treatment Treatment works about 70% of the time 3

4 Typical Patient seen in Radiation Oncology What Can We Do to Improve the Standard of Care? 4

5 Radiation Therapy is an outpatienttreatment: Evolved over the last 15 years 5

6 Local Control (%) / // / / / / / // / / // / / / // / /// / 36 month local control = 98% (CI: %) Fail: 1 Total: Patients Months after Start of SBRT at Risk Initial goal SBRT = 7 wks RT What we found SBRT >> 7 weeks SBRT 4 outpatient treatments in 1 week Less side effects A real WIN WIN 6

7 The Impact of Stereotactic Radiation Stereotactic Radiotherapy has dramatically changed how lung cancer is managed Improving quality of life Reducing time at a radiation facility Reducing side effects Reducing the need of surgery for high risk patients Improving cancer outcomes In addition, 7

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10 Should Surgery be Challenged as the Standard of Care? Surgery is not a perfect treatment Immediate toxicity and pain Expense - hospitalization, recovery, lost work/income, etc. Morbidity Cure Challenge for high risk patients

11 SBRT vs. Surgery Trials 3 Phase III SBRT vs surgery trials were attempted Netherlands- VU University Med Ctr- Trial of Either Surgery or Stereotactic Radiotherapy for Early Stage (IA) Lung Cancer (ROSEL) Cyberknife- International Randomized Study to Compare CyberKnife Stereotactic Radiotherapy With Surgical Resection In Stage I Non-small Cell Lung Cancer (STARS) ACOSOG Z4099 / RTOG 1021 Phase III Study of Sublobar Resection versus SBRT in High Risk Patients with Stage I Non-Small Cell Lung Cancer (NSCLC) 11

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13 SBRT vs. Surgery Trials 3 Phase III SBRT vs surgery trials ongoing or will open ACOSOG Z4099 / RTOG 1021 Phase III Study of Sublobar Resection versus SBRT in High Risk Patients with Stage I Non-Small Cell Lung Cancer (NSCLC) now re opened as STABLE MATES 272 pts SABRTOOTH UK multicenter trial (high risk) 690 pts Veterans Affairs (VALOR) superiority study 13

14 SBRT Results by Center Volume A NCDB study of ct1-2an0 NSCLC of 4,420 pts from Variable of interest: facility volume 90 th percentile (12 cases/yr) Predictors of treatment at high volume facility: academic center (most associated), race, income, histologic confirmation, BED, tumor size Before propensity score matching B After propensity score matching Median OS 41.9 months at HVF vs months at LVF, p=0.024 Park HS, et al. ASTRO For HVF vs. LVF, propensity scorematched HR 0.77 ( ), p=

15 SBRT Results by Center Volume Sensitivity analysis varying HVF definition HVF Cut-Off (cases/year) Hazard Ratio (95% Confidence Interval) P-value 6 (59 th percentile) 1.01 ( ) (66 th percentile) 0.93 ( ) (73 rd percentile) 0.91 ( ) (84 th percentile) 0.89 ( ) (87 th percentile) 0.82 ( ) (88 th percentile) 0.81 ( ) (90 th percentile) 0.83 ( ) (90 th percentile) 0.83 ( ) (93 rd percentile) 0.82 ( ) Conclusion: SBRT at high-volume facilities appears to be independently associated with improved overall survival among clinical stage I NSCLC patients Park HS, et al. ASTRO

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17 Evolution of Radiation Therapy for Advanced Disease in Lung Cancer 17

18 Better Imaging has led to Major Benefits Tumor = CT = PET = 18

19 Technology initially used for Stereotactic Radiotherapy Radiation Therapy only works of you hit the target famous Radiation Oncologist 19

20 Benefits in treatment Delivery: Intensity Modulated Radiation (IMRT) 20

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22 Can We Do Better? Why Protons Can be Superior to Photons Protons X Rays do not stop X-ray Radiotherapy Excess radiation to healthy tissue results in potentially costly side effects and secondary tumors 22

23 PROTONS Proton Delivery Therapy is Complex 23

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28 Is this Clinically Meaningful in Lung Cancer? 28

29 ? RT pneumonitis? RT lung fibrosis & cardiotoxicity Median overall survival: 28.7 months (60 Gy) vs months (74 Gy), p= Bradley JD, et al. Lancet Oncol. 2015;16(2):

30 RTOG 0617 Multivariate Cox Model - Survival Authors: heart dose might best explain why patients given 74 Gy did worse than patients given the 60 Gy Bradley JD, et al. Lancet Oncol. 2015;16(2):

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32 UNC Cardiac Data for NSCLC Cardiac dose was evaluated by V5, V30, mean heart dose, LV V5, LV V30, LV mean dose Endpoint symptomatic cardiac events 32

33 Michigan Cardiac Data for NSCLC Cardiac dose was evaluated by V5, V30, V50, mean heart dose and as a continuous variable Endpoint grade 3 and higher cardiac events 33

34 Cardiac Toxicity - Myocardial infarction - Coronary revascularization tx - Death from ischemic heart disease - Cardiac morbidity increases 7.4% with each extra Gy. - There is no safe cardiac dose Darby et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer. NEJM

35 RTOG 0617: Impact of Technology 3DCRT vs. IMRT: IMRT more commonly used for larger tumors (p<0.001), higher stage disease (p=0.04) Greater decline in QOL at 12 months for 3DCRT (46% vs. 21%, p=0.003) For a given PTV volume, IMRT was associated with lower lung V20 (p=0.08), lower heart doses (p<0.05) Heart dose predicted for survival (p<0.001) IMRT had fewer grade 3 pneumonitis (3.5% vs. 7.9%, p=0.0653) [adjusted p=0.046] IMRT was associated with higher compliance with full dose consolidative chemotherapy High volume centers had longer overall survival more likely to treat with IMRT (p=0.002) and had RT plans with lower mean esophageal dose (p=0.03), lower median heart dose (p=0.006) Movsas B, et al. JAMA Oncol. 2016, Chun SG, et al. J Clin Oncol. 2017;Eaton RB, et al. J Natl Cancer Inst

36 LA-NSCLC Proton Therapy Enrolling Studies RTOG 1308: Phase III Randomized Trial Comparing Overall Survival After Photon Versus Proton Chemoradiotherapy for Inoperable Stage II-IIIB NSCLC Protons vs. photons up to 70 Gy with concurrent chemotherapy (platinum-based doublet) +/- consolidation chemotherapy Primary outcome: overall survival Secondary outcomes: progression-free survival, grade 3 adverse events, QOL/PROs, cost-effectiveness outcomes, PFT changes 560 patient targeted accrual, enrollment started

37 Conclusions Advanced Technology has had a substantial improvement for patients with early and locally advanced disease Experience is key to the success SBRT has improved outcomes, while reducing side effects and improving QoL Advanced Technology with IMRT and Proton therapy for advanced Lung Cancer will reduce dose to surrounding critical structures 37

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