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

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

This is a nonrandomized Phase II pilot protocol to determine the feasibility, toxicity and disease control (local control, overall and progression-free survival) using hypofractionated preoperative radiation therapy in patients with primary localized soft tissue sarcomas (STS).

Study Overview

• Status: Active, not recruiting
• Conditions: Soft Tissue Sarcoma
• Intervention / Treatment: Radiation: Hypofractionated Radiation Therapy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥ 18 years of age
• Core needle biopsy obtained
• Pathologic confirmation of primary soft tissue sarcoma of the upper or lower extremity or chest-wall.
• Stage I-III Soft Tissue Sarcoma of the extremity without evidence of metastatic disease
• Medically operable
• No prior radiotherapy to primary site or adjacent site that results in overlapping radiation fields.
• MRI obtained of the affected extremity or chest-wall
• CT chest acquired to assess distant disease
• Karnofsky Performance Status (KPS) 60 or above
• Informed consent obtained prior to study entry

Exclusion Criteria:

• Patients who have metastatic disease
• Pregnant women
• Women of childbearing potential and male participants must practice adequate contraception.
• Disease pathology other than sarcoma subtypes
• Patients with a history of metastatic disease from a primary other than sarcoma
• Patients who cannot undergo MRI as part of pre-treatment or treatment planning process
• STS of non-extremity or chest-wall regions
• Tumor size ≥ 20 cm maximal dimension

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hypofractionated Radiation Therapy; Radiation treatment in which the total dose of radiation is divided into large doses and treatments are given every other day. Hypofractionated radiation therapy is given over a shorter period of time (fewer days or weeks) than standard radiation therapy.	Radiation: Hypofractionated Radiation Therapy; Treatments will have a minimum of a 48-hour interfraction interval. Treatments will be completed over 20 days maximum.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local Disease Control Assessed by Physical Examination	This measure will capture the number of subjects experiencing a recurrence of the primary lesion assessed by physical examination.	2 Years
Local Disease Control Assessed by Magnetic Resonance Imaging (MRI)	This measure is the number of subjects experiencing a recurrence of the primary lesion as assessed by MRI.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Musculoskeletal Tumor Rating Scale (MSTS) Score	Toxicity will be assessed at specific times the Musculoskeletal Tumor Rating Scale. The MSTS evaluates: pain, function, emotional acceptance, hand positioning, dexterity and lifting ability, using a six-item Likert scale ranging from 0 (worst condition) to 5 (best condition). The individual scores are added for the MSTS Score, range 0 to 30. A higher score indicates better function.	Baseline (typically 2 to 4 weeks prior to surgery) and 4, 8, 12, 16, 20, and 24 months after surgery
Disease-free Survival	Disease-free survival will measure the time in months from initiation of radiation therapy until documented recurrence of disease. Patients who are disease-free and alive at the time of analysis will be censored at the time of their last follow-up. Patients will be assessed for disease-free survival at 2 years.	2 Years
Overall Survival	Overall survival will measure the time from initiation of radiation therapy until documented death from any cause. Patients who are alive at the time of analysis will be censored at the time of their last follow-up. Patients will be assessed for overall survival at 2 years.	2 Years
Radiologic Changes Due to Hypofractionated Radiation.	This measure will assess the presence or absence of enhancement of T2 imaging.	4 weeks after radiation therapy
Pathologic Changes Due to Hypofractionated Radiation.	This measure will capture the fibrosis present in tissue specimens as a percent.	2 weeks after surgery

Collaborators and Investigators

• Sponsor: Medical College of Wisconsin
• Investigators: Principal Investigator: Meena Bedi, MD, Medical College of Wisconsin

Publications and helpful links

General Publications

• Bedi M, Singh R, Charlson JA, Kelly T, Johnstone C, Wooldridge A, Hackbarth DA, Moore N, Neilson JC, King DM. Is 5 the New 25? Long-Term Oncologic Outcomes From a Phase II, Prospective, 5-Fraction Preoperative Radiation Therapy Trial in Patients With Localized Soft Tissue Sarcoma. Adv Radiat Oncol. 2022 Jan 25;7(3):100850. doi: 10.1016/j.adro.2021.100850. eCollection 2022 May-Jun.

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2016
• Primary Completion (Actual): May 18, 2022
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: November 4, 2015
• First Submitted That Met QC Criteria: December 15, 2015
• First Posted (Estimated): December 18, 2015

Study Record Updates

• Last Update Posted (Estimated): July 24, 2023
• Last Update Submitted That Met QC Criteria: July 19, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: soft tissue sarcoma
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma
• Other Study ID Numbers: 25722

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No