Radiation Treatment (XRT)

Mylin A. Torres Director, Glenn Family Breast Center

Louisa and Rand Glenn Family Chair in Breast Cancer Resarch Associate Professor

Department of Radiation Oncology

The Old Days

“Organ Preservation”

Lumpectomy Simple Mastectomy MRM

SSM Radical mastectomy

Why would you need Radiation? • Prevent a Local Recurrence (in the breast) and

promote “breast conservation”

• Prevent a Regional Recurrence (in the draining lymph nodes)

• Improves overall survival and cure

Results – Local Regional Recurrence Following a Lumpectomy

14.3%

39.2% Significantly more patients who received radiation kept their breast because they did not develop a recurrence of breast cancer

Fisher et al. NEJM 2002

Does Radiation (XRT) Contribute More than Native Breast Preservation and

Local Control of Disease?

EBCTCG, Lancet 2005

XRT decreases the relative local

recurrence by 2/3 and improves

absolute survival by at least 5%

4 to 1 Rule

For every 4 Local Recurrences

Prevented, One Life is Saved

4 to 1 Rule

For every 4 Local Recurrences

Prevented, One Life is Saved

A 5 yr 20% absolute risk reduction in LRR

translates into at least a 5% OS improvement

Take Home Message

Persistent Local-Regional Disease

is a Cause of

Distant Metastasis and Subsequent Death

DCIS

• Risk factor and precursor to cancer

• Current standard of care is surgery

+/- XRT

+/- Tamoxifen if estrogen receptor positive

• Following lumpectomy alone, chance of recurrence within the breast is 1.5-3.5% per year

• Half of recurrences will be invasive cancer

• XRT decreases the local recurrence rate by 50%

Poor Prognostic Factors in DCIS

• Age < 50

• Size > 2cm

• Surgical margins < 2mm

• High Grade, presence of comedonecrosis

XRT decreases local recurrence by 50% relatively

Do all patients with DCIS need XRT?

Emory Practice

• Offer XRT to all high grade DCIS

• Consider observation in the following patients:

1. > 60 yo &

2. < 1.0 cm &

3. Grade 1 or 2 &

4. Margins > 2.0mm &

What about XRT in Invasive Breast Cancer?

EBCTCG, Lancet 2005

XRT decreases the relative LRR by 2/3

and improves absolute survival by

at least 5% in patients

XRT following Breast Conserving Surgery (Lumpectomy)

What about XRT following Mastectomy?

Postmastectomy Radiation Oxford: Mastectomy +/- XRT Trials

LN - Disease

LN + Disease

Local Recurrence Breast Ca Deaths

8% vs. 3%

29% vs. 8%

28% vs. 31%

60%vs. 55%

Local Recurrence

• 70% reduction

Breast Ca Survival

• none in LN-

• 5% for LN+

Lancet 366:2087, 2005

Magnitude of Survival Benefit from XRT

Survival benefit for patients with +LN

Absolute Benefit

•Chemotherapy 12%

•Tamoxifen 11%

•Radiation 9%

Current Practice at Emory

• XRT for patients with T3 and/or T4 tumors

• XRT for all patients with > 4 LN’s

• XRT for patients with 1-3LN’s with high risk features: – Young age

– Poor response to neoadjuvant chemo

• XRT for all patients with Stage III cancers regardless of response to neoadjuvant chemotherapy

Radiation Therapy

• Reduces dz recurrence in DCIS pts by 50%

• Reduces LRR after lumpectomy or mastectomy + sys rx by ~ 70%

• Improvements have overcome mortality risk

• Reduction in LRR improves OS

• Degree of overall survival benefit increases w/

improvements in systemic treatment

Conclusion

Radiation Therapy Has Many Bad Features

• Inconvenience and costs

• Short term acute effects

• Limits/affects reconstruction

• Arm edema

• Fibrosis/stiffness, soft tissue changes

• Cardiovascular effects

However….

How are we improving convenience and decreasing costs of XRT?

Shortening Treatment Time from 6 weeks to 4 weeks, NCIC Study

< 25 cm separation

Node Negative

<2cm tumor in 80% of pts

75% of pts > 50 yo

Whelan et al. NCIC 2002

• e Most tumors recur at tumor bed site

• Catheter based or IORT

• Treat limited breast volume

• Target tumor bed + 1 cm

– Allows for treating with fewer fractions

– Possible lower complications

Partial Breast Irradiation

Fractionated Brachytherapy

(Rt-image.com) (mammosite.com)

Mammosite Double Plane Implant

Intraoperative Radiation Therapy (IORT)

Local Recurrence Results

Vaidya et al. Lancet 2013

Local Recurrence Results

Vaidya et al. Lancet 2013

Radiation Treatment Technique Is Critically Important

•Significant XRT Improvements

• CT-based treatment planning

• 3-D dose modulation

•Benefits

• Avoiding missing/under-dosing target

• May improve breast aesthetics

• Can avoid cardiovascular injury

Treatment for XRT Skin Changes

Calendula and Acute XRT Toxicity

Pommier et al. JCO 2004

Pentoxifylline and Vitamin E

Jacobson et al. International Journal of Radiation Oncology, Biology and Physics 2013

Pentoxifylline and Vitamin E

Magnussen et al. European Journal of Cancer 2015

0%

20%

40%

60%

During RT 1 month Post-RT 2 months Post-RT 1 year Post-RT

Rat

io P

erc

en

tage

Ch

ange

Follow-up Time

Standard (N=15)

Hypofractionated (N=15)

Short course Whole Breast Radiation (Hypofractionation) and STRA

P<0.01

P<0.01

P<0.01

p=0.18

Torres et al. In preparation

Treatment for Fatigue

• Exercise, at least 10 minutes, 3x per week

• Massage Therapy

• Stay Hydrated

• Cognitive Behavioral Therapy

Lymphedema Treatment

Cho et al. Support Care cancer, 2015

Lymphedema and

Weight Lifting

Schmitz et al. JAMA 2010

Treatment of Lymphedema

with Surgery

Dionyssiou et al. Breast Cancer Res Treat 2016

Conclusions

• Radiation-associated changes to the skin continue long after a patient has completed radiation

• There are complex patient, treatment, physician, and biologic factors associated with skin thickening following radiation treatment making this a difficult problem to study

How are We Decreasing Rates of Long Term Cardiac Toxicity?

15-yr cardiac deaths of Left vs. Right breast ca

• sample size of 27,000

• 1973 – 1979

– 13.1% (L) vs. 10.2 (R) p = 0.02

• 1980 – 1984

– 9.4% (L) vs. 8.7 (R) p = 0.64

• 1985 - 1989

– 5.8% (L) vs. 5.2 (R) p = 0.98

SEER Data Cardiac Studies

JNCI 97:419, 2005

Deep Breath Hold Cardiac Displacement Technique

Tracking the Respiratory Cycle

Moving Heart Away From Radiation Fields

Free Breathing Breath Hold

Representative Beams

Conclusions

• One size does not fit all when it comes to breast cancer disease or treatment

• Many patients spend a full year of their life undergoing chemotherapy, surgery, and radiation

• 2/3 of women diagnosed with breast cancer will be recommended 5 to 10 years of daily endocrine therapy with either tamoxifen or an aromatase inhibitor

Conclusions

• When specific treatments are recommended, the statistical benefits outweigh the risks

• Advances in treatment have lead to significant improvements in overall cure rates