Hypofractionated Pre-operative Radiation Therapy for Soft Tissue Sarcomas of the Extremity and Chest-wall

BACKGROUND OVERVIEW: Hypofractionation has several potential advantages over conventional
radiation. First, the biological equivalent dose to the tumor is higher with
hypofractionation than it is with conventional radiation. In between radiation treatments
there is repair of the radiation damaged cancer cells (on a cell survival curve this region
of repair is referred to as the "shoulder" of the curve). Some cell lines are better at
repair than others. Sarcoma is often referred to as a "radioresistant" tumor, which means
that sarcoma cell lines have a larger capacity for radiation repair than do other cell lines.
A treatment that can deliver a high dose in fewer fractions can potentially overcome some of
this repair. There is a concept in radiation known as "biologically equivalent dose" (BED)
which states that a higher dose per fraction results in more tumor kill than a lower dose per
fraction. For example, radiation delivered to a total of 60 Gy in three 20 Gy fractions is
the equivalent of 150 Gy in 2 Gy fractions.

BACKGROUND RATIONALE: It is important to conduct this study because hypofractionation not
only decreases treatment package time and cost of care, but it also potentially improves
patient convenience and quality of life and could impact radiologic and pathologic variables
in a positive way by leading to more tumor cell kill. This could potentially change the
paradigm of the current management of STS of the extremity and chest-wall.

HYPOTHESIS: Preoperative hypofractionated radiation therapy for localized soft tissue
sarcomas (STS) will result in local control and toxicity similar to conventional
fractionation with less cost, more patient convenience and decreased overall treatment time.

TREATMENT: Image-guided radiation therapy is mandatory. PREOPERATIVE: (1) Either 3D conformal
radiotherapy or intensity modulated radiation therapy (IMRT). (2) A prescription dose of 35
Gy in 5 fractions given every other day with at least 48 hours in between each fraction will
be prescribed to cover 95% of the planning target volume. TREATMENT SCHEDULE: Treatments will
have a minimum of a 48-hour interfraction interval. Treatments will be completed over 20 days
maximum.

Inclusion Criteria:

i. ≥ 18 years of age

ii. Core needle biopsy obtained

iii. Pathologic confirmation of primary soft tissue sarcoma of the upper or lower extremity
or chest-wall. As per protocol per the STS tumor group, if biopsy was done at an outside
hospital, then it will be reviewed by the pathologists at Froedtert and the Medical College
of Wisconsin.

iv. Stage I-III Soft Tissue Sarcoma of the extremity without evidence of metastatic disease
(Appendix II)

v. Medically operable

vi. No prior radiotherapy to primary site or adjacent site that results in overlapping
radiation fields.

vii. MRI obtained of the affected extremity or chest-wall

viii. CT chest acquired to assess distant disease

ix. KPS 60 or above

x. Informed consent obtained prior to study entry

Exclusion Criteria:

i. Patients who have metastatic disease

ii. Pregnant women

iii. Women of childbearing potential and male participants must practice adequate
contraception.

iv. Disease pathology other than sarcoma subtypes

v. Patients with a history of metastatic disease from a primary other than sarcoma

vi. Patients who cannot undergo MRI as part of pre-treatment or treatment planning process

vii. STS of non-extremity or chest-wall regions

viii. Tumor size ≥ 20 cm maximal dimension