Reduction of Glucose Metabolic Activity Is More Accurate than Change in Size at Predicting Histopathologic Response to Neoadjuvant Therapy in High-Grade Soft-Tissue Sarcomas

Purpose: Change in tumor size as classified by Response Evaluation Criteria in Solid Tumors poorly correlates with histopathologic response to neoadjuvant therapy in patients with soft-tissue sarcomas. The aim of this study was to prospectively evaluate whether positron emission tomography with 18F-fluorodeoxyglucose (FDG-PET) allows for a more accurate evaluation of histopathologic response. Experimental Design: From January 2005 to January 2007, 42 patients with resectable biopsy-proven high-grade soft-tissue sarcoma underwent a FDG-PET/computed tomography scan before and after neoadjuvant treatment. Relative changes in tumor FDG uptake and size from the baseline to the follow-up scan were calculated, and their accuracy for assessment of histopathologic response was compared by receiver operating characteristic curve analysis. Histopathologic response was defined as ≥95% tumor necrosis. Results: In histopathologic responders (n = 8; 19%), reduction in tumor FDG uptake was significantly greater than in nonresponders (P < 0.001), whereas no significant differences were found for tumor size (P = 0.24). The area under the receiver operating characteristic curve for metabolic changes was 0.93, but only 0.60 for size changes (P = 0.004). Using a 60% decrease in tumor FDG uptake as a threshold resulted in a sensitivity of 100% and a specificity of 71% for assessment of histopathologic response, whereas Response Evaluation Criteria in Solid Tumors showed a sensitivity of 25% and a specificity of 100%. Conclusion: Quantitative FDG-PET was significantly more accurate than size-based criteria at assessing histopathologic response to neoadjuvant therapy. FDG-PET should be considered as a modality to monitor treatment response in patients with high-grade soft-tissue sarcoma.

[1]  M. Schwaiger,et al.  Metabolic imaging predicts response, survival, and recurrence in adenocarcinomas of the esophagogastric junction. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  J. Sanfridsson.  Orthopaedic measurements with computed radiography: Methodological development, accuracy, and radiation dose with special reference to the weight-bearing lower extremity and the dislocating patella , 2001, Acta radiologica. Supplementum.

[3]  H. Wanebo,et al.  Soft tissue sarcoma. , 1997, Medicine and health, Rhode Island.

[4]  Thomas Beyer,et al.  Acquisition protocol considerations for combined PET/CT imaging. , 2004, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[5]  T. Delaney,et al.  Neoadjuvant chemotherapy and radiotherapy for large extremity soft-tissue sarcomas. , 2001, International journal of radiation oncology, biology, physics.

[6]  Wolfgang A Weber,et al.  Time course of tumor metabolic activity during chemoradiotherapy of esophageal squamous cell carcinoma and response to treatment. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  J. Hanley,et al.  A method of comparing the areas under receiver operating characteristic curves derived from the same cases. , 1983, Radiology.

[8]  H. Bauer,et al.  Pre-operative radiotherapy in soft tissue tumors: Assessment of response by static post-contrast MR imaging compared to histopathology , 2001, Acta radiologica.

[9]  G. Demetri,et al.  Soft tissue sarcoma. , 2010, Journal of the National Comprehensive Cancer Network : JNCCN.

[10]  Rabiya S Tuma,et al.  Sometimes size doesn't matter: reevaluating RECIST and tumor response rate endpoints. , 2006, Journal of the National Cancer Institute.

[11]  D. Ettinger,et al.  Phase II study of neoadjuvant chemotherapy and radiation therapy in the management of high-risk, high-grade, soft tissue sarcomas of the extremities and body wall: Radiation Therapy Oncology Group Trial 9514. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  S. Dry,et al.  Validation of the postoperative nomogram for 12‐year sarcoma‐specific mortality , 2004, Cancer.

[13]  G. Rosen,et al.  Treatment-induced pathologic necrosis: a predictor of local recurrence and survival in patients receiving neoadjuvant therapy for high-grade extremity soft tissue sarcomas. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  J. Cameron.  Current Surgical Therapy , 2001 .

[15]  S. Ferrari,et al.  Chemotherapy-induced tumor necrosis as a prognostic factor in localized Ewing's sarcoma of the extremities. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  M. Kimura,et al.  Outstanding problems with Response Evaluation Criteria in Solid Tumors (RECIST) in breast cancer , 2002, Breast cancer.

[17]  M. Schwaiger,et al.  Positron emission tomography in non-small-cell lung cancer: prediction of response to chemotherapy by quantitative assessment of glucose use. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  M Van Glabbeke,et al.  New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. , 2000, Journal of the National Cancer Institute.

[19]  B. Cheson,et al.  Positron-emission tomography and assessment of cancer therapy. , 2006, The New England journal of medicine.

[20]  Samuel Singer,et al.  Chemotherapy Is Associated With Improved Survival in Adult Patients With Primary Extremity Synovial Sarcoma , 2007, Annals of surgery.

[21]  G. Rosen,et al.  Preoperative chemotherapy for osteogenic sarcoma: Selection of postoperative adjuvant chemotherapy based on the response of the primary tumor to preoperative chemotherapy , 1982, Cancer.

[22]  Osman Ratib,et al.  Optimizing imaging protocols for overweight and obese patients: a lutetium orthosilicate PET/CT study. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[23]  M. van Glabbeke,et al.  New guidelines to evaluate the response to treatment in solid tumors , 2000, Journal of the National Cancer Institute.

[24]  S. Ferrari,et al.  Prognostic significance of histopathologic response to chemotherapy in nonmetastatic Ewing's sarcoma of the extremities. , 1993, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[25]  J. Eary,et al.  Use of positron emission tomography in localized extremity soft tissue sarcoma treated with neoadjuvant chemotherapy , 2005, Cancer.

[26]  H. Bauer,et al.  PRE‐OPERATIVE RADIOTHERAPY IN SOFT TISSUE TUMORS , 2001 .

[27]  A. Willemsen,et al.  FDG-PET to evaluate response to hyperthermic isolated limb perfusion for locally advanced soft-tissue sarcoma. , 1996, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[28]  Lawrence H Schwartz,et al.  A statistical simulation study finds discordance between WHO criteria and RECIST guideline. , 2004, Journal of clinical epidemiology.

[29]  Ludovic Ferrer,et al.  Monitoring of early response to neoadjuvant chemotherapy in stage II and III breast cancer by [18F]fluorodeoxyglucose positron emission tomography. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[30]  Osman Ratib,et al.  Impact of patient weight and emission scan duration on PET/CT image quality and lesion detectability. , 2004, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[31]  G. Steele,et al.  Cancer: Principles and Practice of Oncology , 1983 .

[32]  W. Enneking,et al.  Local host response in osteosarcoma after chemotherapy referred to radiographs, CT, tumour necrosis and patient survival , 1998, Journal of Cancer Research and Clinical Oncology.

[33]  H C Charles,et al.  Monitoring of neoadjuvant therapy response of soft-tissue and musculoskeletal sarcoma using fluorine-18-FDG PET. , 1996, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[34]  G. Rosen,et al.  The Impact of Chemotherapy on the Survival of Patients With High-grade Primary Extremity Liposarcoma , 2004, Annals of surgery.

[35]  Joel Karp,et al.  Consensus recommendations for the use of 18F-FDG PET as an indicator of therapeutic response in patients in National Cancer Institute Trials. , 2006, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[36]  W. Jarnagin,et al.  Importance of response to neoadjuvant chemotherapy in patients undergoing resection of synchronous colorectal liver metastases , 2003, Journal of Gastrointestinal Surgery.

[37]  Wolfgang A Weber,et al.  Use of PET for monitoring cancer therapy and for predicting outcome. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[38]  V. Rusch,et al.  Induction chemoradiation and surgical resection for superior sulcus non-small-cell lung carcinomas: long-term results of Southwest Oncology Group Trial 9416 (Intergroup Trial 0160). , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[39]  Wolfgang A Weber,et al.  Prediction of response to neoadjuvant chemotherapy by sequential F-18-fluorodeoxyglucose positron emission tomography in patients with advanced-stage ovarian cancer. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[40]  W. Tap,et al.  Advances in chemotherapy for patients with extremity soft tissue sarcoma. , 2006, The Orthopedic clinics of North America.

[41]  E. Gehan,et al.  Will there be resistance to the RECIST (Response Evaluation Criteria in Solid Tumors)? , 2000, Journal of the National Cancer Institute.

[42]  M Bonetti,et al.  Adjuvant chemotherapy for adult soft tissue sarcomas of the extremities and girdles: results of the Italian randomized cooperative trial. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[43]  A. Jemal,et al.  Cancer Statistics, 2006 , 2006, CA: a cancer journal for clinicians.

[44]  M. Kattan,et al.  Postoperative nomogram for 12-year sarcoma-specific death. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[45]  Su-Chun Cheng,et al.  Preoperative chemotherapy for stage IIIB extremity soft tissue sarcoma: long-term results from a single institution. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[46]  V. Devita,et al.  Cancer : Principles and Practice of Oncology , 1982 .