Current Status of Radiotherapy in Soft Tissue Sarcomas

Martin Keisch, MD

Cancer Healthcare Associates

Miami Brachytherapy Center

University of Miami Hospital

Outline

• Review Sarcoma Treatment Data – Retrospective Data – Randomized Data

• Technique – Discuss various techniques – External Beam

• Preoperative • Postoperative

– Brachytherapy alone – Brachytherapy boost + external beam – Treatment volume

• Toxicity and Function:

– Acute Wound Issues – Fibrosis

Background • History and Natural History

– Amputation as the standard surgical technique until last 40 years

– Local Failure common after conservative surgery alone-Relative radioresistance necessitates pushing dose intensity

– Hematogenous metastasis common

– Systemic management still questionable benefit

– Pathologic Classifications Evolving continually

– Group of diseases with low incidence

Pre-operative Therapy

•Used at some institutions to improve resectability

•Probably increases surgical complications

•Radiobiology is unclear due to potential for long break if post op boost needed

Post-Operative External Beam

•Bread and Butter of STS radiation

•“Easy”, Noninvasive, Least Targeted

•Probably increases late complication

Post-Operative Radiation

Brachytherapy

Major advantages are probably targeting accuracy and dose intensity/timing

Operator dependent

Probably increases acute wound complications

Post-operative XRT

after IORT

14-20 Gy

•Complex, Highly targeted

•Mobile Linear accelerator, or patient transport

•Few centers with capability

Basic Tenets of Radiotherapy

• More dose is better, Less volume is better

• No radiation is best

• The last 2 weeks of XRT are the hardest and most important

• Patient selection is key

• Techniques are local technology driven and sometimes user dependent

The Role of Radiation in Conservative Surgery

• 2 Randomized trials 1980’s-90’s

• NCI High Grade extremities

– 43 patients

– 4/27 LF CS vs. 0 in amputated group

– No diferrence in DFS or OS at five years

– + margins bad

• MSKCC mixed Grade

– 126 patients Brachytherapy vs. Conservative surgery only

– Decreased LF in BRT group for High Grade lesions

– No difference in DFS or Overall survival

From

Pisters et al

JCO Review 2007

Randomized trials for Modern Chemotherapy

• Adria/Ifos based- mid 1990’s

• 4 studies, small numbers (59-134 pts) -Frutasci et al, Petrioli et al, Brodawicz et al, Gortzak et al

• 2 positive, 2 negative

• Modest benefits at best

• Confounded by heterogeneous pathologic subtypes

Conservation Surgery and Radiation Grade 2/3

Study site Pt. # FUP yrs. LF % LF/DM % DM % RT Type

NCI 271 1-8 6 3 28 Post-op

MDA 190 5-16 21 7 25 Post-op

MGH 180 2-16 4 7 25 Pre-op

UCLA 255 2-15 5 2 24 Pre-op +Doxo

MSK 557 2-10 15 14 Pre/post/BRT+/-CT

Volumes - EBRT

Kim et al IJROBP

2D Radiation

Volumes - EBRT

• Reductions indicated? In the modern era of IMRT/IGRT

• Preoperatively on the the tumor NOT the operative bed (more like Brachytherapy)

• Postoperatively Much larger field sizes historically – need to target like Brachytherapy (need to go to the Operating Room)

Going to the OR

• But don’t want to do Brachytherapy?

• NOVAC 7: An IORT dedicated electron accelerator

• Conventional OR (no shielding needed)

• Mobile and easily docked

• Electron beams of 4 different energies: 3, 5, 7, 9 MeV

IORT MOBILE ACCELERATOR

Collimator

Skin separator

Foley catheter

Target

High Grade Retroperitoneal Liposarcoma

Resect ………..with IORT

Not going to the OR

• Didn’t think so…….

Wound healing after preoperative radiation for sarcoma of soft tissues.

Bujko K, Suit HD, Springfield DS, Convery K. Department of Radiation Oncology, Massachusetts General Hospital

– Morbidity from wound healing retrospectively analyzed – 202 consecutive patients with tumors of the soft tissue treated with

preoperative irradiation and conservative operation – boost dose was given to 143 patients (71 percent) postoperatively.

– The overall wound complication rate was 37 percent.

– One patient died because of necrotizing fasciitis.

– In 33 instances (16.5 percent), secondary operation was necessary,

including six patients (3 percent) who required amputation.

– The wounds in the remaining 40 patients (20 percent) were treated without operation.

IMRT Case

• 42 y male with enlarging left thigh mass x 4 mo

• Pain with sitting/pressure; sometimes difficulty in extending the legs

T1

Fat sat T1

Fat sat T1 Contrast

T2 Contrast

IMRT

IMRT Example #2

Volumes - Brachytherapy

• Volume collapses

• Margin is on the tumor not the operative bed

• 2 cm distal/proximal, less radially

• Discordant to both pre and post op EBRT volumes

Technique- Low vs. High Dose Rate

• LDR vs. HDR – LDR has more data

– More staff exposure

– Less flexibility

– HDR more image guided

– No staff exposure

• Best if brachytherapist present for entire resection

Geometry is everything

• Volume collapses after resection

Wound complications of adjuvant radiation therapy in patients with soft-tissue

sarcomas Ormsby MV, Hilaris BS, Nori D, Brennan MF

• loading of the catheters with radioactive sources on the first through the fifth postoperative days results in a 48% significant wound-complication rate

• catheters loaded five or more days after operation changed wound complications to 14% significant wound complications

• 10% of the 29 patients who did not receive radiation had wound complications of similar severity

• animal experiments would suggest that delay of application of radiation to one week after wounding is accompanied by significant improvement in wound-breaking strength, new H3 hydroxyproline accumulation, and improved force-tension curves

Ann Surg. 1989 Jul;210(1):93-9

MSKCC Low Dose Rate Implants

Mostly HDR Now

STIR T1

STIR

STIR

Posterior

calf

T1 (4.7 x 3.0 cm)

T2

Excision of tumor bed-

unplanned excision

T2

Re-Irradiation

• Highly conformal irradiation can limit

Toxicity from re-irradiation

• Data for benefit is limited Most series show high DM rate, significant complication

– MDAH series

• Tolerance generally good in my experience

Retreatment Case

• 80 yo female

• Presented with a new onset painless mass in her left thigh

• Past Hx of pleomorphic liposarcoma and post op Ext beam RTX (6300 cGY) in same location in 05-06

PE

• Diffuse swelling in LLE

• Well healed 20 cm scar on the medial aspect of thigh

• Radiation changes evident

• 2.0 x 2.0 cm firm mass palpable in the lower half of surgical incision.

• Bx done in office

FS T1 C+

1.4x1.3x1.3cm

STIR

2005

2005

Boost Case

• 77 yo female with left thigh mass

• Notes increasing mass over 6 months

• Melanoma in situ removed from left thigh 12 yrs ago – No further treatment, follow up

PE

• LLE:

– Mass anterior thigh (25 x 13 cm)

– Mild TTP; negative percussion; nonpulsatile

– Longitudinal incision ant-med mid thigh; well healed (prior melanoma)

GE T2

T1 T2

26 x 10 03/06

T1

T2

STIR

05/06

Boost to close or positive margins

Non-coplanar catheters useful

University of Miami Experience

• Brachy centric

• Analysis presented in abstract CORR

• Higher wound complication rate with Brachy especially in medial thigh

• Better Late tolerance even in patients with wound complications

Conclusions

• Very poorly studied due to low incidence and broad spectrum of pathologies and anatomic locations

• Volume and dose are critical to control and complications

• No single technique is clearly superior for all settings

• It is always worth observing the surgical resection

Issues not Covered

• Effect of close vs positive surgical margin

• Impact of unplanned excision on LC and OS

• Importance of percent necrosis after neoadjuvant chemotherapy