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
Disclosures IBA speaker 2
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
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
RADIOSURGERY Advances in Radiation Therapy 5
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
Trigeminal Neuralgia 40 Gy to the 50% 7
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Graded Prognostic Assessment (GPA) 10
Median Survivals 11
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
Does SRS add anything to WBRT? Andrews et al, Lancet 2004;363:1665 13
Median survival: 7.5 mo vs 8 mo Recurrent rate 46.8% vs 76.4% 14
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213 patients (34 institutions) from 2002-2013 Median follow-up was 7.2 months Clinical characteristics well balanced Decline in cognitive function: SRS: 63.5% SRS+WBRT: 91.7% p = 0.0007 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
NCCTG N0574 Increased intracranial disease progression: 3 mo 6 mo SRS 24.7% 35.4% SRS + WBRT 6.3% 11.6% p < 0.0001 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
PROTON THERAPY Advances in Radiation Therapy 20
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 300 250 200 10 MeV photons Photons Additional Dose outside the target delivered with Photons compared to Protons 150 Proton Spread Out Bragg Peak 100 50 Protons Tumor 0 0 50 100 150 200 250 Depth in Water (mm) 300 350 400 21
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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
Time to severe late toxicity (shown in the graph as Treatment Failure Rates): all assessable patients. Mitchell Machtay et al. JCO 2008;26:3582-3589 24
Contralateral Submandibular Gland PBS Rapid Arc IMRT: Backup plan Stage 4a, T1N2b, HPV+, R tonsil SCCA 25
Contralateral Submandibular Gland PBS Rapid Arc IMRT: Backup plan Mean Doses: IMRT (40 Gy), PBS (33 Gy) 26
Contralateral Parotid PBS Rapid Arc IMRT: Backup plan Mean Doses: IMRT (18 Gy), PBS (9 Gy) 27
Oral Cavity PBS Rapid Arc IMRT: Backup plan Mean Doses: IMRT (19 Gy), PBS (3 Gy) 28
Patient-Reported Toxicity/QOL Collected at baseline, 3, 6, 12, and 24 mos 29
Mean Dose (Gy) Mean Dose (Gy) UPenn Experience, Adjuvant RT (n=51) 40 35 30 25 20 15 10 5 0 Parotid Ipsilateral Parotid (p=0.759) Contralateral Parotid (p<0.0001) VMAT 33 21 PBS 34 12 70 Submandibular 60 50 40 30 20 10 0 Ipsilateral Submandibular (p=0.941) Contralateral Submandibular (p=0.0236) VMAT 60 38 PBS 60 29 30
Mean Dose (Gy) Mean Dose (Gy) 50 45 40 35 30 25 20 15 10 5 0 Ipsilateral Sublingual (p=0.0007) Sublingual Contralateral Sublingual (p<0.0001) VMAT 44 38 PBS 32 8 30 Buccal 25 20 15 10 5 0 Ipsilateral Buccal (p<0.0001) Contralateral Buccal (p<0.0001) VMAT 27 19 PBS 10 2 31
Mean Dose (Gy) 45 40 35 30 25 20 15 10 5 0 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 16 37 41 10 20 PBS 6 31 26 2 3 32
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
IMMUNOTHERAPY Advances in Radiation Therapy 34
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
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
no RT 5/2015 (pre-radvax) 12/2015 8 Gy x 3 37
Radiotherapy + Immunotherapy: Case 2 9/2013: melanoma of skin of L foot 2014: L groin mass; Bx + for melanoma 9/2014 11/2014: ipilimumab x 4 cycles 12/2014 10/2015: pembrolizumab x 13 cycles 12/2014 3/2015 10/2015: progression 38
10/2015: enrolled on RADVAX protocol Given 17 Gy to L inguinal mass 39
17 Gy 10/2015 (pre-radvax) 4/2016 no RT 40
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
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Thank you 43