Future of Radiation Therapy

JP Morgan Healthcare Conference

January 12, 2016

Deepak Khuntia, MD,

VP of Medical Affairs

Patrick Kupelian, MD,

VP of Clinical Affairs

Cancer as a cause of death

CANCER TREATMENT MODALITY: RADIOTHERAPY

Localized Treatments:

Surgery

Ablative Treatments: Cryo

HIFU

Laser

Microwave

Systemic Treatments:Drugs: Traditional ChemoRx

Hormonal Therapy

Targeted Drugs

Radiation Therapy (RT):Spectrum of biologic effects

• Ablative: SRS/SBRT

•Biologic therapy

Organ-sparing

DNA changes

Immune modulation

: less invasive?

Very few curative therapies

Minor improvements in subsets of patients

DISEASES TREATED WITH RT

Curable Cancers with RT ALONE:

Prostate Ca

Head & Neck Ca

Lung Ca

Cervical Ca

Skin Ca

Curable Cancers with RT as part of treatment (adjuvant):Breast Ca Brain Tumors Testicular Ca

Adv. Lung Ca Rectal Ca Sarcomas

Adv. Cervical Ca Endometrial Ca Pediatric Ca

Adv. Head & Neck Ca Bladder Ca

Metastatic disease: Bone / Brain / Other…

Improving RT Delivery

1950-60s

Cobalt

Early Linacs

1970-80s

Higher

Energy

Linacs

1990s

Beam Shaping

Devices

2000s

In-room

Image

Guidance

2010s

Integration of

Better Beam

Shaping

and Aiming

Impact Explore new

indications

• Treat deeper

tumors

• Decrease

skin toxicity

• Treat smaller areas

• Individualization

• Decrease toxicity in

deeper organs

• Increase in

tumor doses

• Improve

tumor control

• Higher daily

doses

• Faster, Better,

Safer treatments

Aim: Increase Cure / Decrease Toxicity

Process: Improve RT Shaping and Targeting

Improving RT Techniques and Outcomes1995-2000

Beam shaping devices:

MLCs

2000-2005

In-room image

guidance

2005-2010

Partially integrated

systems

2010-2015

Hypofractionation,

Adaptive RT

2015-Future

Integration of Better

Beam Shaping

and Aiming

Novelty IMRT IGRT • Dedicated devices

• Multivendor

environment

• SRS

• SBRT/SABR

• ART

Need for increased

integration and/or

interoperability

Clinical Impact • Head/Neck: improve

saliva / swallowing

• Pelvis: Less bowel

toxicity

• Allows safer

chemotherapy

administration

• Prostate Ca:

Enable dose

escalation: improve

cure

• Reduce traditional

set-up errors

• Increased

complexity

• Decrease

throughput

• Increase safety

concerns.

• Lung Ca SBRT:

improve cure

• Frameless CNS

radiosurgery

• Partial breast

accelerated

irradiation

• Faster, better, safer

treatments

• Global RT:

• Simpler set-ups

• Education &

training

Andrews DW, Scott CB, Sperduto PW, et al. Whole brain radiation therapy with or without stereotactic radiosurgery boost for

patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet. 2004 May

22;363(9422):1665-72.

Brain Mets Study: Adding SRS Improves Survival

Treatment Details

• 18 Gy x 1

• 4 non-coplanar arcs

• 1-360, 3-170

• 18 min treatment

• 5 min beam-on

• 708 control points

RapidArc Radiosurgery: Treating 11 Melanoma Mets

SBRT vs. Lobectomy for Operable Stage I NSCLC

Source: Chang JY, Senan S, Paul MA, et al. Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung

cancer: a pooled analysis of two randomised trials. Lancet Oncol. 2015 Jun;16(6):630-7.

Lung Cancer:

Patients live longer with Radiosurgery than with Surgery

Zelefsky, IJROBP, 84, 125-129, 2012

PROSTATE CANCER

IMAGE GUIDANCE: IMPROVING CURE AND REDUCING TOXICITY

Memorial Sloan Kettering Cancer Center

Prostate Cancer RT: Outcome with and without Image Guidance

Cancer Control Rates Toxicity Rates

Shaping of Radiation Lowers Complications

Reduce Bowel Complications

Cancers impacted:

Prostate Ca

Rectal Ca

Anal Ca

Cervical Ca

Reduce Head & Neck Complications

Complications reduced:

Less dryness of the mouth

Less swallowing problems

Less scarring of joints / muscles

Chopra et al. ASTRO Plenary, San Antonio October 2015.

Gupta et al. Radiotherapy and Oncology. 104:3 (343-348), 2012.

Conventional RT IMRT

New Era InnovationKnowledge-Guided Oncology | Intelligent Treatment Delivery

Advanced Data Analytics

IMAGE – Not Yet Complete

RapidPlan™ Ramp Up

300+ Orders

3,800 Potential Installs

Disease Site Models

Prostate

Prostate (+lymph nodes)

Head & Neck

Lung SBRT

Breast

More Models Coming

KNOWLEDGE-GUIDED ONCOLOGY:

University of Michigan: Spine SBRT Study

Manual RapidPlan

Foy J, et al. An analysis of knowledge based planning for stereotactic body radiation

therapy of the spine [abstract]. Poster presentation at: American Association of

Physicists in Medicine (AAPM) 57th Annual Meeting & Exhibition; July 12-16,

2015; Anaheim, CA.

University of Michigan

Equivalent Quality

Manual Rapid Plan

Time 60-90 min 15-20 min

KNOWLEDGE-GUIDED ONCOLOGY:

Royal Surrey County Hospital: Prostate Study

Manual RapidPlan™

Time 114 ± 86 min 21 ± 13 min

Equivalent

or better30% 90%

Better 10% 90%

Courtesy, Royal Surrey County Hospital NHS Foundation, Guilford, UK

Data source on file

0

50

100

150

200

250

300

350

A1A2A3A4B1B2C1D1D2D3E1E2E3F1F2F3F4F5F6

Planning time (min)

conventional RapidPlan

KNOWLEDGE-GUIDED ONCOLOGY:

High Definition Radiotherapy (HDRT)

INTELLIGENT TREATMENT DELIVERY:

Works in Progress

4π Dose Compression for Lung SBRT

INTELLIGENT TREATMENT DELIVERY:

IMRT

PATIENT 1

PATIENT 2

VMAT 4 π HDRT

64 Gy

15 Gy

Dong P et al. IJROBP 86(3):407-13, 2013Works in Progress

High Definition Radiosurgery

Coplanar RapidArc SRS 4π High Definition SRS

Brain Stem Brain Stem

50% Rx Dose50% Rx Dose

INTELLIGENT TREATMENT DELIVERY:

Works in Progress

Promise of Protons

InSightive™ Analytics

Operational Efficiencies

Referral Patterns

Clinical Outcome Analysis

ADVANCED DATA ANALYTICS

ADVANCED DATA ANALYTICS:

VelocityTM

Creates the cancer story from

imaging

Imaging informatics integrated

with our Big Data Analytics

Improve outcomes, quality, and

efficiency

ADVANCED DATA ANALYTICS:

Radio-immunotherapy for Cancer Treatment

Hodge, Guha, Neefjes, Gulley. Oncology, 2008 August, 22(9):1064-1084

Abscopal Responses in Metastatic Non-Small Cell Lung Cancer

(NSCLC) Patients Treated on a Phase 2 Study of Combined Radiation

Therapy and Ipilimumab: Evidence for the In Situ Vaccination

Hypothesis of Radiation

E.B. Golden, A. Chachoua, M.B. Fenton-Kerimian, S. Demaria, and S.C.

Formenti

New York University

ASTRO Annual Meeting

October 2016

The Abscopal Effect:

Radiotherapy in one site can potentially eradicate tumors elsewhere in the body

• Combining radiosurgery with immunotherapy

• Study of NSCLC

• Study shows that SBRT with ipilumimab could

increase tumor control and survival

• 25% remission; 100% control/no progression

Golden et al. ASTRO 2016.

Targeted Therapies and Immunotherapies:

Trend is in Combining Drugs

RT as a combination “drug”

• Available

• Cost-effective

• Reimbursed

Challenges of drug+drug combinations

• Clinical trial design

• Cost

• Commercialization

4. Radiation Medicine

Cardiac Arrhythmia

(Atrial Fibrillation)

Research opportunities in radiation

medicine:

Cardiac arrhythmias

Emphysema

Post-thoracic surgery neuropathy

Plantar fasciitis

Depression

Arthritis

NEW FRONTIERS IN

RADIATION ONCOLOGY

Works in Progress

Cardiac Arrhythmias: A New RT Frontier?

Affordable, Accessible, Quality Care

Cost of Cancer Care in US

30% increase from 2010 to 2020

Average cost for one extra year of life:

1995: $54,100

2005: $139,100

2013: $207,000

Sources: Avalere study, 2015 National Bureau of Economic Research

$0

$20,000

$40,000

$60,000

$80,000

$100,000

$120,000

Sh

ort

cou

rse

Inte

rmed

iate

Lon

g c

ou

rse

Co

lecto

my

Cyste

cto

my

Lob

ecto

my

Pa

ncre

ate

cto

my

Off

ice

Hosp

ital

RT Surgery Chemo(1 year)

Average Cost per Patient

Technology Decreasing Treatment Cost:

SBRT / SRS

Technology (SBRT) Decreasing Actual Treatment Cost

Time-driven activity-based costing (TDABC), UCLA

SBRT

Utilizing time-driven activity based costing to understand the short- and long-term costs of treating localized, low-risk prostate

cancer. Laviana et al. Cancer. 2015

Conclusion

• Advanced technology is increasing cure rates and

lowering toxicity

• Advanced technology will improve affordability,

accessibility, and quality of radiotherapy

• Radiation therapy utilization could dramatically

increase with new opportunities outside of cancer

Thank You

$3-4M?

IGRT SBRT HDRT

The Key To

Progress:

Better Dose

Delivery

INTELLIGENT TREATMENT DELIVERY:

IMRT

MR LINAC

3D CONFORMAL

Relative Clinical Value

$10M