Clinical Trial: Preoperative vs Postoperative IMRT for Extremity/Truncal STS

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Phase III Study of Preoperative vs Postoperative Intensity Modulated Radiation Therapy For Truncal/Extremity Soft Tissue Sarcoma

Brief Summary: This study is designed to determine if preoperative image guided radiation therapy (IGRT) delivered using intensity modulated radiation therapy (IMRT) followed by surgery results in similar short-term wound healing complications as surgery followed by postoperative IGRT in patients with extremity or truncal soft tissue sarcoma. Half of the patients will receive preoperative radiotherapy, half will receive postoperative radiotherapy.

Detailed Summary: Perioperative RT in addition to surgery is widely accepted as standard management for soft tissue sarcoma (STS) of the extremity and trunk. However, controversy remains as to whether RT should be delivered preoperatively or postoperatively. While both confer similar rates of local control, preoperative RT leads to a decrease in late tissue morbidities such as fibrosis, limb edema, joint stiffness and fracture as compared to postoperative RT. The reasons for this are likely multifactorial, but are in part related to total dose delivered (50 Gray (GY) preoperatively and 60-66 Gy postoperatively) and, based on a previous National Cancer Institute (Canada) Phase III randomized controlled trial, the much larger volume treated in the postoperative setting compared to that in the preoperative setting. The optimal radiation dose used in the postoperative setting is unknown but has been developed empirically and doses of 60-66 Gy are generally employed.However, investigators in Norway/Sweden and France have found equivalent local control rates for patients with negative surgical margins treated with 50 GY postoperativelyThe main concern with preoperative RT has centered on the risk of an increased rate of delayed wound healing and major wound complications. Although some studies suggest it may be possible to reduce the incidence of acute wound healing complications associated with pre-operative radiation than previously seen in the 2D RT era, this has yet to be tested in the phase III setting. IG-IMRT allows a much higher degree of conformality and accurate delivery of dose to the tumour while sparing surrounding normal tissue. This may allow similar rates of acute wound healing complications for pre- and postoperative RT in the treatment of STS.
Sponsor: Mount Sinai Hospital, Canada

Current Primary Outcome: Incidence of acute wound healing complications [ Time Frame: 120 days post surgery ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Acute Radiation Toxicity [ Time Frame: Once per week from the start of radiotherapy until its completion (5 weeks in total), then 1 week preop for Group 1; 4 weeks post completion of treatment for Group 2 ]
  Acute radiation skin toxicity will be documented according to the Radiotherapy Oncology Group (RTOG) Acute Radiation Morbidity Scoring Criteria.
• Late Radiation Toxicity- RTOG Late Radiation Morbidity [ Time Frame: Every 3 months, from 3 months postop for Group 1 and 3 months post RT for Group 2, for 2 years, then 4 monthly for 1 year, then 6 monthly to 5 years. ]
  Late radiation morbidity to skin, subcutaneous tissue, bone and joints will be documented according to the RTOG/EORTC Late Radiation Morbidity Scoring Scheme.
• Late Radiation Toxicity- Common Toxicity Criteria [ Time Frame: Every 3 months, from 3 months postop for Group 1 and 3 months post RT for Group 2, for 2 years, then 4 monthly for 1 year, then 6 monthly to 5 years. ]
  Late radiation morbidity to skin, subcutaneous tissue, bone and joints will be documented according to the Common Toxicity Criteria v4.0
• Late Radiation Toxicity- Limb Edema [ Time Frame: Every 3 months, from 3 months postop for Group 1 and 3 months post RT for Group 2, for 2 years, then 4 monthly for 1 year, then 6 monthly to 5 years. ]
  Peripheral limb edema will be documented according to the Late Limb Edema Scoring Criteria.
• Limb Function [ Time Frame: Within 14 days of randomization, then at 3 and 6 months, 1, 2, 3 and 5 years postop. ]
  Limb function will be documented according to the Musculoskeletal Tumor Society Rating Scale.
• Patient function [ Time Frame: Within 14 days of randomization, then at 3 and 6 months, 1, 2, 3 and 5 years postop. ]
  Patient function will be documented according to the patient completed Toronto Extremity Salvage Score (TESS)
• Overall Survival [ Time Frame: Surgery Date until 5 years postoperative or death, whichever occurs first ]
  Overall patient survival in months during the study period
• Local recurrence-free survival [ Time Frame: Surgery date until 5 years postoperative or local recurrence, whichever occures first. ]
  Patient survival without a local recurrence in months during the study period.
• Metastasis-free survival [ Time Frame: Surgery date until 5 years postoperative or systemic recurrence, whichever occures first. ]
  Patient survival without systemic metastases in months during the study period.

Original Secondary Outcome:

• Acute Radiation Toxicity [ Time Frame: Once per week for during RT, 1 week preop for Group 1; 4 weeks post completion of treatment for Group 2 ]
  Acute radiation skin toxicity will be documented according to the Radiotherapy Oncology Group (RTOG) Acute Radiation Morbidity Scoring Criteria.
• Late Radiation Toxicity- RTOG Late Radiation Morbidity [ Time Frame: Every 3 months, from 3 months postop for Group 1 and 3 months post RT for Group 2, for 2 years, then 4 monthly for 1 year, then 6 monthly to 5 years. ]
  Late radiation morbidity to skin, subcutaneous tissue, bone and joints will be documented according to the RTOG/EORTC Late Radiation Morbidity Scoring Scheme.
• Late Radiation Toxicity- Common Toxicity Criteria [ Time Frame: Every 3 months, from 3 months postop for Group 1 and 3 months post RT for Group 2, for 2 years, then 4 monthly for 1 year, then 6 monthly to 5 years. ]
  Late radiation morbidity to skin, subcutaneous tissue, bone and joints will be documented according to the Common Toxicity Criteria v4.0
• Late Radiation Toxicity- Limb Edema [ Time Frame: Every 3 months, from 3 months postop for Group 1 and 3 months post RT for Group 2, for 2 years, then 4 monthly for 1 year, then 6 monthly to 5 years. ]
  Peripheral limb edema will be documented according to the Late Limb Edema Scoring Criteria.
• Limb Function [ Time Frame: Within 14 days of randomization, then at 3 and 6 months, 1, 2, 3 and 5 years postop. ]
  Limb function will be documented according to the Musculoskeletal Tumor Society Rating Scale.
• Patient function [ Time Frame: Within 14 days of randomization, then at 3 and 6 months, 1, 2, 3 and 5 years postop. ]
  Patient function will be documented according to the patient completed Toronto Extremity Salvage Score (TESS)
• Overall Survival [ Time Frame: Surgery Date until 5 years postoperative or death, whichever occurs first ]
  Overall patient survival in months during the study period
• Local recurrence-free survival [ Time Frame: Surgery date until 5 years postoperative or local recurrence, whichever occures first. ]
  Patient survival without a local recurrence in months during the study period.
• Metastasis-free survival [ Time Frame: Surgery date until 5 years postoperative or systemic recurrence, whichever occures first. ]
  Patient survival without systemic metastases in months during the study period.

Information By: Mount Sinai Hospital, Canada

Dates:
Date Received: September 18, 2015
Date Started: June 2016
Date Completion: December 2020
Last Updated: June 28, 2016
Last Verified: June 2016