Radiation Effects on the Musculoskeletal System

Adam C. Olson, MD, MS

Assistant Professor

Department of Radiation Oncology

Disclosures

• None

Outline

• What is Radiation?

• Why do we use Radiation for soft tissue sarcoma?

• What are the short and long term side effects of radiation?

• What can rehabilitative services offer patients receiving radiation therapy?

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Radiation: A Brief History• 1895 – Röntgen discovers x-rays (Nobel

Prize 1901)• 1896 – Becquerel discovers natural

radioactive decay. Marie and Pierre Curie further characterize radioactive compounds

• 1896 – First patients with cancer treated with x-rays by Emil Grubbe in Chicago

• 1952 – first “linear accelerator” used for treatment (USA in 1957)

• 1968 – Radiosurgery• 1980 – Multi-leaf collimators, Proton

therapy• 1988 – Intensity modulated radiation

treatment (IMRT)• 2000’s – Image-guided RT (IGRT)

Marie Curie (1867-1934)

Radiation Treatment

Image courtesy of Varian Medical Systems, Inc. All rights reserved

Incident x-ray photon

Fast Electron

Free Radical

Cellular DNA Damage

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Biologic Effects of Radiation

Radiation For Sarcomas

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Limb-Sparing Surgery +/- EBRT

RANDOMIZE

n = 141 STS of extremity s/p limb-sparing surgery within past 4 months• 91 high-grade• 50 low-grade

Exclusion criteria:• Metastatic• H/o cancer• Contraindication

s to chemo/XRT

• Outcomes: LR-free, metastasis-free and overall survival; QOL

• Median f/u: 9.6 years

1983 – 1991

Yang et al, JCO 1998

Limb-sparing surgery + chemo• Goal 1 – 2 cm normal tissue margin

Limb-sparing surgery + chemo + XRT• EBRT: 45 Gy + 18 Gy boost to tumor bed

at 1.8 Gy/fx• XRT started w/I 1 week of cycle 1 chemo

Stratification (differed by grade):• Grade 2 vs. 3 (high) or grade 1 vs.

benign• Proximal vs. distal or primary vs. recur• Margin < 1 vs. > 1 mm

Chemo: doxorubicin/cyclophosphamide x 5 for high-grade disease

Improved Local Control with Adjuvant EBRT

Yang et al, JCO 1998

No Difference in Overall Survival

Yang et al, JCO 1998

QOL/Late Toxicity (20-Y Follow-Up)

Beane et al, Ann Surg Onc 2014

• No difference in pain, wound complications, edema, or lower extremity function

• No functional limb deficits for upper extremity STS patients

• Assistive device for walking less common in patients receiving XRT (8% vs. 15%, p = 0.065)

Summary (Yang/Beane, et al.)

• Adjuvant EBRT improves local control

• No impact on overall survival

• QoL data suggests RT effects may be transient and do not have significant impact on global QoL assessments

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CAN-NCIC-SR2: Preop vs. Postop XRT

RANDOMIZE

n = 94 patients w/resectable STS- Planned n = 266

Exclusion criteria:• Age < 16• Regional or distant

mets• Prior chemo or

overlapping XRT• Other malignancy• Histologies typically

treated with chemo

• Primary endpoint: Wound-healing complications postoperatively• Closed early due to significant difference at planned prelim analysis

• Median f/u: 3.3 years

1994 – 1997

O’ Sullivan et al, Lancet 2002

Preoperative XRT• 50 Gy in 25 fx

Postoperative XRT• 66 Gy in 33 fx

Stratification:• Size (< 10 cm vs. > 10 cm)

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Higher Postop Wound Complications after Neoadjuvant XRT

O’ Sullivan et al, Lancet 2002Trial stopped accrual early due to difference in complications

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No Difference in Local Recurrence

O’ Sullivan et al, Lancet 2002

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Similar Overall Survival

O’ Sullivan et al, Lancet 2002

No survival difference at 5-yr follow-up (73% vs.

67%) (O’Sullivan, ASCO 2004)

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NCIC Trial: Late Radiation Morbidity

Davis et al, Rad & Onc 2005

Trend towards increased late toxicity in postop arm

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Preop v Postop RT: Summary

Preop RT• Pros

– Smaller RT fields

– Lower doses

– Maybe improve R0 resection rate

• Cons

– Higher risk of wound complication (reversible)

– Loss of pathologic information

Postop RT• Pros

– Complete specimen available for margin and histologic evaluation

– Lower risk of wound complications

• Cons

– Larger volume, higher doses

– Higher chronic long term toxicities (irreversible)

Radiation Toxicities for the MSK system

Acute (0-3 months after RT)

• Dermatitis

• Pain

• Desquamation

• Edema

• These generally resolve

Long term Toxicities

• Joint Stiffness

• Soft Tissue Fibrosis

• Edema

• These generally do not resolve

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Radiation Fibrosis Syndrome

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Trismus

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Physical Therapy for Breast RT

• Randomized trial of PT 2x week during RT for breast cancer

• Kinesiotherapy: 14 exercises for C-spine and upper limbs

• SS improvement inshoulder ROM

Leal et al. Rev Lat Am Enfermagem 2016.

ASCO Guidelines• Breast

– Lymphedema• Low-level laser therapy, manual drainage, compression bandaging

– Pain• Music Therapy

• Head and Neck– Cervical Dystonia, Neuropathy, Trismus, pain, disability, ROM,

edema/facial swelling• Nerve stabilizing agents, botox, manual drainage, compression bandaging,

• Sarcoma– NCCN guidelines recommend PT/OT referral for all stages of disease

23 Stout et al. CA Cancer J Clin 2021.

Conclusions

• Radiation therapy is an integral component of treatment for many cancers

• MSK effects can be long-lasting and debilitating

• Integrating rehabilitation services into multi-disciplinary care should be considered for most patients (breast, H&N, sarcoma) with cancer

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