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

Prognosis Clinical Trial

— CESOFB-00  

Official title:

Clinical Evaluation of Neoadjuvant Chemotherapy for Primary Malignant Sarcomas That Originate in Bone: a Multi-center Retrospective Study for Standardization and Modification of Response Evaluation Criteria

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03742063
• Other study ID #: CBTRA-00
• Status: Completed
• Start date: June 1, 2017
• Est. completion date: October 30, 2018

Study information

• Verified date: April 2019
• Source: Peking University People's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 190
• Est. completion date: October 30, 2018
• Est. primary completion date: December 31, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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;

Related Conditions & MeSH terms

• Clinical Response
• Histopathological Response
• Prognosis
• Sarcoma

Intervention

Drug:
• first-line chemotherapy
patients who routinely received neoadjuvant chemotherapy according to Peking University People's Hospital chemo-protocols (PKUPH-OS and PKUPH-ES)

Locations

Country	Name	City	State
China	Peking University People's Hospital	Beijing	Beijing
China	Peking University Shougang Hospital	Beijing	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Peking University People's Hospital	Peking University Shougang Hospital

Country where clinical trial is conducted

China, 

References & Publications (15)

Bajpai J, Gamnagatti S, Kumar R, Sreenivas V, Sharma MC, Khan SA, Rastogi S, Malhotra A, Safaya R, Bakhshi S. Role of MRI in osteosarcoma for evaluation and prediction of chemotherapy response: correlation with histological necrosis. Pediatr Radiol. 2011 Apr;41(4):441-50. doi: 10.1007/s00247-010-1876-3. Epub 2010 Oct 27. — View Citation

Bajpai J, Kumar R, Sreenivas V, Sharma MC, Khan SA, Rastogi S, Malhotra A, Gamnagatti S, Kumar R, Safaya R, Bakhshi S. Prediction of chemotherapy response by PET-CT in osteosarcoma: correlation with histologic necrosis. J Pediatr Hematol Oncol. 2011 Oct;33(7):e271-8. doi: 10.1097/MPH.0b013e31820ff78e. — View Citation

Byun BH, Kim SH, Lim SM, Lim I, Kong CB, Song WS, Cho WH, Jeon DG, Lee SY, Koh JS, Chung SK. Prediction of response to neoadjuvant chemotherapy in osteosarcoma using dual-phase (18)F-FDG PET/CT. Eur Radiol. 2015 Jul;25(7):2015-24. doi: 10.1007/s00330-015-3609-3. Epub 2015 Feb 14. — View Citation

Choi H, Charnsangavej C, Faria SC, Macapinlac HA, Burgess MA, Patel SR, Chen LL, Podoloff DA, Benjamin RS. Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: proposal of new computed tomography response criteria. J Clin Oncol. 2007 May 1;25(13):1753-9. — View Citation

Costelloe CM, Chuang HH, Madewell JE, Ueno NT. Cancer Response Criteria and Bone Metastases: RECIST 1.1, MDA and PERCIST. J Cancer. 2010 Jun 28;1:80-92. — View Citation

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026. — View Citation

Hamaoka T, Madewell JE, Podoloff DA, Hortobagyi GN, Ueno NT. Bone imaging in metastatic breast cancer. J Clin Oncol. 2004 Jul 15;22(14):2942-53. Review. — View Citation

Lamuraglia M, Raslan S, Elaidi R, Oudard S, Escudier B, Slimane K, Penna RR, Wagner M, Lucidarme O. mTOR-inhibitor treatment of metastatic renal cell carcinoma: contribution of Choi and modified Choi criteria assessed in 2D or 3D to evaluate tumor response. Eur Radiol. 2016 Jan;26(1):278-85. doi: 10.1007/s00330-015-3828-7. Epub 2015 May 8. — View Citation

Moertel CG, Hanley JA. The effect of measuring error on the results of therapeutic trials in advanced cancer. Cancer. 1976 Jul;38(1):388-94. — View Citation

O JH, Lodge MA, Wahl RL. Practical PERCIST: A Simplified Guide to PET Response Criteria in Solid Tumors 1.0. Radiology. 2016 Aug;280(2):576-84. doi: 10.1148/radiol.2016142043. Epub 2016 Feb 24. Review. — View Citation

Rosen G, Caparros B, Huvos AG, Kosloff C, Nirenberg A, Cacavio A, Marcove RC, Lane JM, Mehta B, Urban C. Preoperative chemotherapy for osteogenic sarcoma: selection of postoperative adjuvant chemotherapy based on the response of the primary tumor to preoperative chemotherapy. Cancer. 1982 Mar 15;49(6):1221-30. — View Citation

Smith AD, Lieber ML, Shah SN. Assessing tumor response and detecting recurrence in metastatic renal cell carcinoma on targeted therapy: importance of size and attenuation on contrast-enhanced CT. AJR Am J Roentgenol. 2010 Jan;194(1):157-65. doi: 10.2214/AJR.09.2941. — View Citation

Smith AD, Shah SN, Rini BI, Lieber ML, Remer EM. Morphology, Attenuation, Size, and Structure (MASS) criteria: assessing response and predicting clinical outcome in metastatic renal cell carcinoma on antiangiogenic targeted therapy. AJR Am J Roentgenol. 2010 Jun;194(6):1470-8. doi: 10.2214/AJR.09.3456. — View Citation

Tsuchida Y, Therasse P. Response evaluation criteria in solid tumors (RECIST): new guidelines. Med Pediatr Oncol. 2001 Jul;37(1):1-3. — View Citation

Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: Evolving Considerations for PET response criteria in solid tumors. J Nucl Med. 2009 May;50 Suppl 1:122S-50S. doi: 10.2967/jnumed.108.057307. Review. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tumor necrosis rate	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.	2-3 months