Clinical Evaluation of Neoadjuvant Chemotherapy for Primary Malignant Sarcomas That Originate in Bone

Completed

• Conditions: Clinical Response; Histopathological Response; Prognosis
• Interventions: Drug: first-line chemotherapy

• Registration Number: NCT03742063
• Lead Sponsor: Peking University People's Hospital

Brief Summary

For bone lesions treated with chemotherapy or targeted therapy, particularly for sarcomas that originate in bones, Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 is spurious because bone lesions are typically located in irregularly shaped bones, are difficult to measure accurately, and usually respond more slowly to treatment than soft tissue lesions. Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) allows for response to be measured in the absence of anatomic changes through assessment of metabolic activity. It does not, however, account for morphologic changes. This study evaluated whether clinical imaging findings of sarcomas after preoperative chemotherapy correlate with tumor responses by pathological evaluation using the rate of necrosis to develop reliable and quantitative clinical response criteria.

Detailed Description

We reviewed a total of 190 primary lesions by clinical imaging, including X-ray, computed tomography (CT), magnetic resonance imaging, and bone scan or PET/CT in patients who received neoadjuvant chemotherapy. All patients had curative surgery of those lesions at Peking University People's Hospital or Peking University Shougang Hospital. Pathological evaluation was completed by determination of the tumor necrosis rate following Huvos' description. We also performed statistical diversity analysis for different pathological groups and generated receiver operating characteristic curves (ROC) to define the thresholds to distinguish different pathological groups.

Study Timeline

• Study Start: 2017-06-01
• Primary Completion: 2017-12-31
• Study Completion: 2018-10-30
• Study First Submitted: 2018-11-11
• Study First Submitted QC: 2018-11-11
• Study First Posted: 2018-11-15
• Status Verified: 2019-04
• Last Update Submitted: 2019-04-08
• Last Update Posted: 2019-04-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 190

Inclusion Criteria

• (1) patients with high-grade sarcoma that originated in bone and confirmed histologically;
• (2) patients who routinely received neoadjuvant chemotherapy according to Peking University People's Hospital chemo-protocols (PKUPH-OS and PKUPH-ES);
• (3) patients who had primary tumor resection with assessment of histological response according to literatures;
• (4) patients who had intact pre- and post-neoadjuvant chemotherapy imaging, which included X-ray, contrasted computed tomography (CT), and magnetic resonance imaging (MRI) of the primary lesions as well as chest CT (with each layer ≤5 mm), bone scan, or [18F]2-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET);
• (5) patients for whom follow-up information and evaluation after chemotherapy were available.

Exclusion Criteria

• patients with incomplete medical materials;
• patients without surgery of the primary site/ without pathological analysis of the specimens;

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Huvos group IV	first-line chemotherapy	Upon histopathological examination, the tumor response was assessed on the basis of the presence and extent of necrosis, which was assessed by a combination of gross and microscopic observations. Tumor necrosis was graded as per Picci et al. tumor histopathological response grading (Huvos classification), where grade IV is 100% necrosis.
Huvos group I	first-line chemotherapy	Upon histopathological examination, the tumor response was assessed on the basis of the presence and extent of necrosis, which was assessed by a combination of gross and microscopic observations. Tumor necrosis was graded as per Picci et al. tumor histopathological response grading (Huvos classification), where grade I is 0% to 49%.
Huvos group II	first-line chemotherapy	Upon histopathological examination, the tumor response was assessed on the basis of the presence and extent of necrosis, which was assessed by a combination of gross and microscopic observations. Tumor necrosis was graded as per Picci et al. tumor histopathological response grading (Huvos classification), where grade II is 50% to 89%.
Huvos group III	first-line chemotherapy	Upon histopathological examination, the tumor response was assessed on the basis of the presence and extent of necrosis, which was assessed by a combination of gross and microscopic observations. Tumor necrosis was graded as per Picci et al. tumor histopathological response grading (Huvos classification), where grade III is 90% to 99%.

Primary Outcome Measures

Name	Time	Method
Tumor necrosis rate	2-3 months	We evaluated all surgical resection specimens and were blinded to the clinical status. Upon histopathological examination, the tumor response was assessed on the basis of the presence and extent of necrosis, which was assessed by a combination of gross and microscopic observations. Tumor necrosis was graded as per Picci et al. tumor histopathological response grading (Huvos classification), where grade I is 0% to 49%, grade II is 50% to 89%, grade III is 90% to 99%, and grade IV is 100% necrosis.

Trial Locations

Locations (2)

Peking University Shougang Hospital; 🇨🇳 Beijing, Beijing, China

Peking University People's Hospital; 🇨🇳 Beijing, Beijing, China