Radiation Treatment for CRC:

How it works and what to expect

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Speaker:

Dr. Bassetti is an Assistant Professor in

the Department of Human Oncology at

the UW School of Medicine and Public

Health and a member of the UW Carbone

Cancer Center. He sees patients at UW

Carbone Cancer Center.

Dr. Bassetti is a broadly trained radiation

oncologist with specialty focus on patents

with gastrointestinal (GI) cancers

(esophagus, stomach, colorectal region,

liver and pancreas). He brings expertise

in the use of 3D conformal radiation,

intensity modulated radiation and

stereotactic ablative radiation therapy. He

is committed to multidisciplinary cancer

care and the advancement of clinical

trials.

Radiation in the Treatment of

Rectal and Colon Cancer

Michael Bassetti MD PhD

University of Wisconsin

Assistant Professor of Radiation Oncology

• Radiation treatment basics

• Rectal cancer treatment

• Metastatic Colorectal Cancer

– Lungs, liver, brain

• Future Directions

– MRI guided treatment and response

– Immunotherapy in colorectal cancer

Overview

Oncology (Cancer Medicine)

Medical Oncology Surgical Oncology Radiation Oncology

Chemotherapy Surgery Radiation

Coordination of care between all the specialties often leads to the best

outcomes, but also exposure to the risks of the different treatments.

Radiation Therapy

• High energy “x-rays” aimed at the location

of the tumor.

• x-rays damage the cancer cells DNA

causing them to die.

Radiation in Colorectal Cancer Care

• Rectal cancer treatment

• Metastatic colorectal cancer treatment

– Stereotactic Radiation for spread of colorectal

cancer (metastasis) to the liver, lung, or other

organs

Radiation in Colorectal Cancer Care

• Rectal cancer treatment

• Metastatic colorectal cancer treatment

– Stereotactic Radiation for spread of colorectal

cancer (metastasis) to the liver, lung, or other

organs

Anal Sphincter Preserving Surgery

Anatomy

• Schematic • MRI

Anal Sphincter Sacrificing Surgery:

This patient will require a permanent colostomy

Proximity to Anal Sphincter

• Far • Close

Treatment Paradigm for Rectal Cancer

Chemoradiation

5.5 wksradiation and capecitibine

(or 5-FU)

Surgery

Temporary vs Permanent Colostomy

Chemotherapy

~4 months(FOLFOX) 6-10 wks 3-4 wks

• Decrease the chance of a recurrence near

the rectum or in the adjacent lymph nodes

• Organ preservation: Decrease the chance

of an operation requiring a permanent

colostomy

• Less toxicity from chemoradiation if done

prior to surgery

Benefits of Chemoradiation

before Surgery

• Intensity Modulation lets us control the

shape of the radiation dose better than

ever before

• Improved quality of imaging both before

treatment and now during treatment with

Magnetic Resonance Image (MRI) guided

Radiation

Modern Radiation

Viewray inc

Radiation Treatment Plan

• Treat the rectum, tissue around rectum and at risk lymph nodes

• Avoid the hips, bladder, bowel and other tissues

• 5-6 weeks of daily (M-Fri) radiation

• Decreases chance of local recurrence

after surgery by half

• Organ preservation: avoid a permanent

colostomy

– One out of every five patients felt to need a

permanent colostomy was able to have avoid

it

• Less toxicity if radiation is done prior to

surgery

• Modern radiation may decrease toxicity in

some patients

Conclusions: Radiation before Surgery

• Are there situations where we could avoid

radiation?

• Do I really need to have a permanent

colostomy?

• These are questions being currently

investigated

Current Questions

Great Response!

Mass et al, Journal of Clinical Oncology 2011

Non-Operative Management?

• Can some patients avoid surgery that

requires a permanent colostomy?

• Maybe? No Randomized Data. Long

term data from Brazil, MSKCC, and

prospective data from Netherlands support

this may be possible in highly selected

patientsHabr-Gama et al, journal of Gastrointestinal Surgery, 2006

Mass et al, Journal of Clinical Oncology 2011

Smith et al, Annals of Surgery, 2012

Non-Operative Management?

Chemoradiation

8-12 wks

Evaluate response

Complete

Response

Incomplete

ResponseSurgery

Very Close Surveillance

Chemotherapy before or after

Can the lowest risk patients avoid

radiation?

Schrag et al, JCO 2014

Can I Avoid Radiation?

Chemoradiation

>20% response

< 20% response

SurgeryFOLFOX x6

Surgery FOLFOX

FOLFOX

Favorable Patients are randomized

Conclusions

• Chemoradiation decreases pelvic

recurrences, optimizes chances of anal

sphincter preserving surgery.

• Omission of radiation and/or surgery are

both unanswered questions. These are

currently being investigated in randomized

clinical trials in appropriate risk patients

Curable Stage IV Disease?

Surgery Stereotactic Radiation

Bae et al, JSO 2010Tepper et al, JCO 2003

• Surgical series show

20-40% 10 yr survival

when all metastatic

disease to liver or

lungs can be resected.

Colorectal Liver Metastasis

Anterior

Posterior

Rig

ht

Le

ft

CRC Liver Metastasis SBRT plan

6 months post treatment

6.2 cm 0.8 cm

Prospective Trial Control Rates

Rusthoven et al, JCO 2009

Colorectal Brain Metastasis

Tumor Swelling

Radiation of Resection cavity

Response

At presentation 10 months post Tx

Asymptomatic and doing well. Continues on FOLFOX for lung disease

Lung Radiation

• This patient

underwent rectal

surgery and partial

liver resection and

multiple recurrences.

• Did not tolerate

FOLFOX

• Recurrence in lung

and nearby

mediastinal lymph

node not amenable to

surgery

Lung Radiation

Lung Radiation

Before Treatment 1.5 years after treatment

• Stereotactic Radiation is an effective

treatment option for metastatic colorectal

patients to varying sites.

– Non-invasive

– Well tolerated

– Very effective

Conclusions

MRI Guided Radiation

The ViewRay

MRIdian system is a

radiation treatment

system with MRI

image guidance

7/12/2017 University of Wisconsin–Madison 42

Under the covers

7/12/2017 University of Wisconsin–Madison 43

Treatment

gantry

MRI gantry

Mark Geurts

Comparison

Standard Daily Pretreatment imaging

MRI Improves Visualization

Non MRI

Daily Image

MRI

Daily Image

Stereotactic Ablative Liver Metastasis Radiation

Radiation is only on when

tumor is in proper position

Contrast used to highlight

the tumor and allow daily

tracking

Unique to be able to see

and track actual tumor (not

a surrogate) in realtime

MRI Tracking During Treatment

An

terio

r

po

ste

rio

r

Lung

Liver

Radiation

Tumor

Superior

Inferior

Summary

• Advantages of MRI Guided Radiation

• Soft Tissue Resolution• Improved alignment/targeting

• Confidence using high dose near critical organs

• Motion management –Breath hold and Tracking

• Decreased normal tissue/increase tumor dose

• Improve image quality

• Intra-treatment Response Assessment

Mid-Treatment ResponseP

retr

eatm

ent

Mid

-tre

atm

ent

Curable Stage IV Disease?

• 20-40% 10 yr survival

when all metastatic

disease to liver or

lungs can be resected.

• SBRT also shows

potential for long term

survival in

unresectable patients

• Unfortunately, most

patients still fail!

• How can we improve?Tepper et al, JCO 2003

Immune Checkpoint Inhibition

nzmu.co.nx

Anti-PD-1 antibody

T-c

ell

Tum

or

Cell

Release the Brakes!

High Mutational Burden Cancers Respond to

Immunotherapy

Highly Mutated cancers respond to Immune Checkpoint (PD-1) Inhibition

How can we move

this curve up here?

Radiation Effects on Tumor

Microenvironment

• New Mutations Created

• New Antigens Expressed

• Dying Tumor Cells

• Release Antigens

• Pro-Inflammatory Cytokines

• Chemokines to attract immune cells

• Remove Immunosupressive Immune

Cells

• Macrophages, Regulatory T-cells

SBRT and immunotherapy in colorectal cancer

patients with liver confined metastasis and

completely resectable disease.

Dustin Deming MD

Michael Bassetti MD PhD

Eligibility

Patients with microsatellite stable metastatic colorectal cancer with the treatment goal of eradicating all known sites of disease will be enrolled. Patients may have had other treatments prior to enrollment, including chemotherapy, radiation or operations

SchemaFD

G P

ET/M

RI

FLT

PET

/CT

FDG

PET

/MR

I

FLT

PET

/CT

FDG

PET

/MR

I

FLT

PET

/CT FDG shows metabolism

FLT shows proliferation

PET/MRI images

MRI PET/MRI

Conclusions

• Radiation can stimulate a T cell response

in colorectal tumors

• The trial is using this response with an

immune checkpoint inhibitor to attempt to

help the body recognize the CRC as

foreign and attack it.

• Surgery after SBRT to clear any remaining

metastasis and give immune therapy best

chance to work against remaining possible

microscopic cancer cells

Conclusions

• Radiation plays an important role in localized

rectal cancer management

• Stereotactic radiation is an effective, non-

invasive option for treatment of metastatic

lesions.

• MRI guided radiation allows accurate treatment

and easy assessment of intra-treatment

response for individually tailored radiation

therapy

• Immotherapy is very exciting, but currently

ineffective for the majority of CRC patients. We

are currently looking for ways to help the

immune system target CRC.

Thank You

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