Advances in Radiation Therapy

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1 Advances in Radiation Therapy 2017 Recent Advances in Oncology Michelle Alonso-Basanta, MD PhD Helene Blum Assistant Professor Associate Chief of Clinical Operations Director of Quality Assurance Chief, Central Nervous System April 27, 2017

2 Disclosures IBA speaker 2

3 Radiotherapy: Overview Cancer is a complex disease from an anatomic and biologic standpoint, and therapy often requires a multidisciplinary approach Radiotherapy is a non-invasive form of cancer therapy, focused to a finite anatomic site/region It can be used alone, or in conjunction with other treatment modalities such as surgery, traditional chemotherapy, or with emerging agents such as immunotherapy Innovations in Radiotherapy: leading to improved patient outcomes and new indications for therapy 3

4 Advances in Radiotherapy 1) Radiosurgery: non-invasive, high-dose radiation to treat areas for which surgery would be difficult/morbid 2) Proton therapy: highly-focused radiation, with minimal exposure to surrounding normal tissues/organs Potential for significant improvements in side effect profile normally seen with standard radiation techniques 3) Radiotherapy in combination with immunotherapy: in patients with widespread disease, using radiation to a focused area as a way to stimulate/augment the immune system in order to obtain dramatic responses to immunotherapy agents 4

5 RADIOSURGERY Advances in Radiation Therapy 5

6 Stereotactic Radiosurgery To deliver safe, high doses of radiation to a target with little to no normal tissue exposure Number of machines that can do this 6

7 Trigeminal Neuralgia 40 Gy to the 50% 7

8 8

9 9

10 Graded Prognostic Assessment (GPA) 10

11 Median Survivals 11

12 Stereotactic Radiosurgery Good for treating brain metastases Most mets are small, spherical, and radiographically distinct, making good targets for SRS Minimally invasive and displace normal brain beyond target volume Can usually encompass entire met within target volume Avoids risks of surgery Bleeding Infection Tumor seeding Minimal hospitalization Less costly than surgery 12

13 Does SRS add anything to WBRT? Andrews et al, Lancet 2004;363:

14 Median survival: 7.5 mo vs 8 mo Recurrent rate 46.8% vs 76.4% 14

15 15

16 16

17 17

18 213 patients (34 institutions) from Median follow-up was 7.2 months Clinical characteristics well balanced Decline in cognitive function: SRS: 63.5% SRS+WBRT: 91.7% p = Trend of greater progression of cognitive deterioration for SRS plus WBRT for all cognitive tests, and there were substantial differences for immediate recall, memory, and verbal fluency QOL scores were also worse with WBRT 18

19 NCCTG N0574 Increased intracranial disease progression: 3 mo 6 mo SRS 24.7% 35.4% SRS + WBRT 6.3% 11.6% p < No significant difference in median OS SRS 10.4 mo SRS + WBRT 7.4 mo Trends for worse cognitive function with WBRT persisted in long-term survivors (16%), defined as patients alive 12 months after study entry 19

20 PROTON THERAPY Advances in Radiation Therapy 20

21 Relative Dose (%) The Physics of Protons X-rays deliver a greater dose outside the target for the same dose within the target volume as protons Depth dose curves for protons and photons MeV photons Photons Additional Dose outside the target delivered with Photons compared to Protons 150 Proton Spread Out Bragg Peak Protons Tumor Depth in Water (mm)

22 22

23 Why consider proton therapy: Head and Neck Cancer as an Example Treatment is morbid Side effects Acute Mucositis Dysgeusia Dysphagia Odynophagia (requiring opioids and/or supplemental nutrition) Xerostomia Weight loss, dehydration, malnutrition Chronic Dysgeusia Xerostomia Dysphagia (risk of feeding tube dependence) Fibrosis Lymphedema Dental caries and Osteoradionecrosis RT-induced malignancy Cerebrovascular accident 23

24 Time to severe late toxicity (shown in the graph as Treatment Failure Rates): all assessable patients. Mitchell Machtay et al. JCO 2008;26:

25 Contralateral Submandibular Gland PBS Rapid Arc IMRT: Backup plan Stage 4a, T1N2b, HPV+, R tonsil SCCA 25

26 Contralateral Submandibular Gland PBS Rapid Arc IMRT: Backup plan Mean Doses: IMRT (40 Gy), PBS (33 Gy) 26

27 Contralateral Parotid PBS Rapid Arc IMRT: Backup plan Mean Doses: IMRT (18 Gy), PBS (9 Gy) 27

28 Oral Cavity PBS Rapid Arc IMRT: Backup plan Mean Doses: IMRT (19 Gy), PBS (3 Gy) 28

29 Patient-Reported Toxicity/QOL Collected at baseline, 3, 6, 12, and 24 mos 29

30 Mean Dose (Gy) Mean Dose (Gy) UPenn Experience, Adjuvant RT (n=51) Parotid Ipsilateral Parotid (p=0.759) Contralateral Parotid (p<0.0001) VMAT PBS Submandibular Ipsilateral Submandibular (p=0.941) Contralateral Submandibular (p=0.0236) VMAT PBS

31 Mean Dose (Gy) Mean Dose (Gy) Ipsilateral Sublingual (p=0.0007) Sublingual Contralateral Sublingual (p<0.0001) VMAT PBS Buccal Ipsilateral Buccal (p<0.0001) Contralateral Buccal (p<0.0001) VMAT PBS

32 Mean Dose (Gy) Hard Palate (p<0.0001) Soft Palate (p=0.0209) Tongue (p<0.0001) Upper Lip (p<0.0001) Lower Lip (p<0.0001) VMAT PBS

33 Normal Taste (p=0.10) 33% 63% Mild-Severe Appetite Changes (p=0.015) Mild-Severe Sticky Saliva (p=0.853) 13% 53% 50% 53% PBS VMAT Moderate-Severe Xerostomia (p=0.002) 19% 73% 0% 10% 20% 30% 40% 50% 60% 70% 80% 33

34 IMMUNOTHERAPY Advances in Radiation Therapy 34

35 Radiotherapy + Immunotherapy: Case 1 9/2013: Dx w/metastatic NSCLC (R hilar mass with bone mets) carbo/taxol x 6 cycles palliative RT to R lung mass (37.5 Gy) 9/2014 5/2015: nivolumab 1/2015 5/2015: progression 35

36 5/2015: taken off nivolumab and enrolled on RADVAX study Started on pembrolizumab and given 8 Gy x 3 to paraaortic mass (6/2015) Continued on pembro after 6 cycles 36

37 no RT 5/2015 (pre-radvax) 12/ Gy x 3 37

38 Radiotherapy + Immunotherapy: Case 2 9/2013: melanoma of skin of L foot 2014: L groin mass; Bx + for melanoma 9/ /2014: ipilimumab x 4 cycles 12/ /2015: pembrolizumab x 13 cycles 12/2014 3/ /2015: progression 38

39 10/2015: enrolled on RADVAX protocol Given 17 Gy to L inguinal mass 39

40 17 Gy 10/2015 (pre-radvax) 4/2016 no RT 40

41 Summary Numerous options for treatment compared to just 5 years ago PENN has every possible modality of radiation to individualize treatment Multi-disciplinary approach 41

42 42

43 Thank you 43

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