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Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging 6/2014

01.06.2014 | Original Article

Prognostic relevance of 18F-FDG PET uptake in patients with locally advanced, extremity soft tissue sarcomas undergoing neoadjuvant isolated limb perfusion with TNF-α and melphalan

verfasst von: Dimosthenis Andreou, Henrike Boldt, Daniel Pink, Björn Jobke, Mathias Werner, Markus Schuler, Peter Reichardt, Per-Ulf Tunn

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 6/2014

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Abstract

Purpose

The objective of this study was to determine whether 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) can adequately assess the risk of systemic disease progression in patients with primary, localized, high-grade soft tissue sarcomas of the extremities undergoing neoadjuvant isolated limb perfusion (ILP) with tumour necrosis factor and melphalan.

Methods

This was a retrospective analysis of the files of 35 patients who underwent a PET or PET/CT scan prior to and after ILP followed by surgical resection with curative intent between 2006 and 2012. SUVmax1 was defined as the maximum standardized uptake value (SUV) at diagnosis, SUVmax2 as the maximum SUV after ILP and ΔSUVmax as the percentage difference between SUVmax1 and SUVmax2.

Results

The median follow-up was 40 months for all patients. The median SUVmax1 amounted to 7.6, while the median SUVmax2 was 4.7. The median ΔSUVmax was −44 %. Overall survival (OS) probability at 2 and 5 years amounted to 78 and 70 %, respectively, while metastasis-free survival (MFS) probability at 2 and 5 years was 67 and 64 %, respectively. Receiver-operating characteristic (ROC) curve analysis showed that both SUVmax2 and ΔSUVmax could predict systemic disease progression, while SUVmax1 could not adequately identify patients who went on to develop metastatic disease. The optimal cut-off value was 6.9 for SUVmax2 and −31 % for ΔSUVmax. Patients with an SUVmax2 <6.9 had a 2-year MFS of 80 %, compared to 31 % for patients with an SUVmax2 ≥ 6.9 (p < 0.001). Patients with a ΔSUVmax < −31 %, i.e. patients with a higher metabolic response, had an MFS of 76 % at 2 years, compared to 42 % for patients with a ΔSUVmax ≥ −31 % (p = 0.050).

Conclusion

SUVmax after ILP for primary, locally advanced, non-metastatic high-grade soft tissue sarcomas of the extremities appears to be significantly correlated with prognosis. Whether patients with a high SUVmax after ILP will benefit from standard or experimental adjuvant systemic treatment options should be evaluated in future studies.
Literatur
1.
Zurück zum Zitat Clarkson P, Ferguson PC. Primary multidisciplinary management of extremity soft tissue sarcomas. Curr Treat Options Oncol 2004;5:451–62.PubMedCrossRef Clarkson P, Ferguson PC. Primary multidisciplinary management of extremity soft tissue sarcomas. Curr Treat Options Oncol 2004;5:451–62.PubMedCrossRef
2.
Zurück zum Zitat Rosenberg SA, Tepper J, Glatstein E, Costa J, Baker A, Brennan M, et al. The treatment of soft-tissue sarcomas of the extremities: prospective randomized evaluations of (1) limb-sparing surgery plus radiation therapy compared with amputation and (2) the role of adjuvant chemotherapy. Ann Surg 1982;196:305–15.PubMedCentralPubMedCrossRef Rosenberg SA, Tepper J, Glatstein E, Costa J, Baker A, Brennan M, et al. The treatment of soft-tissue sarcomas of the extremities: prospective randomized evaluations of (1) limb-sparing surgery plus radiation therapy compared with amputation and (2) the role of adjuvant chemotherapy. Ann Surg 1982;196:305–15.PubMedCentralPubMedCrossRef
3.
Zurück zum Zitat Andreou D, Fehlberg S, Tiedke C, Niethard M, Tunn PU. Revolutionizing the treatment of locally advanced extremity soft tissue sarcomas: a review on TNFa-based isolated limb perfusion. Eur Surg 2009;41:176–88.CrossRef Andreou D, Fehlberg S, Tiedke C, Niethard M, Tunn PU. Revolutionizing the treatment of locally advanced extremity soft tissue sarcomas: a review on TNFa-based isolated limb perfusion. Eur Surg 2009;41:176–88.CrossRef
4.
Zurück zum Zitat Tunn PU, Kettelhack C, Durr HR. Standardized approach to the treatment of adult soft tissue sarcoma of the extremities. Recent Results Cancer Res 2009;179:211–28.PubMedCrossRef Tunn PU, Kettelhack C, Durr HR. Standardized approach to the treatment of adult soft tissue sarcoma of the extremities. Recent Results Cancer Res 2009;179:211–28.PubMedCrossRef
5.
Zurück zum Zitat Benz MR, Allen-Auerbach MS, Eilber FC, Chen HJ, Dry S, Phelps ME, et al. Combined assessment of metabolic and volumetric changes for assessment of tumor response in patients with soft-tissue sarcomas. J Nucl Med 2008;49:1579–84. doi:10.2967/jnumed.108.053694.PubMedCrossRef Benz MR, Allen-Auerbach MS, Eilber FC, Chen HJ, Dry S, Phelps ME, et al. Combined assessment of metabolic and volumetric changes for assessment of tumor response in patients with soft-tissue sarcomas. J Nucl Med 2008;49:1579–84. doi:10.​2967/​jnumed.​108.​053694.PubMedCrossRef
6.
Zurück zum Zitat Grabellus F, Stylianou E, Umutlu L, Sheu SY, Lehmann N, Taeger G, et al. Size-based clinical response evaluation is insufficient to assess clinical response of sarcomas treated with isolated limb perfusion with TNF-alpha and melphalan. Ann Surg Oncol 2012;19:3375–85. doi:10.1245/s10434-012-2408-1.PubMedCrossRef Grabellus F, Stylianou E, Umutlu L, Sheu SY, Lehmann N, Taeger G, et al. Size-based clinical response evaluation is insufficient to assess clinical response of sarcomas treated with isolated limb perfusion with TNF-alpha and melphalan. Ann Surg Oncol 2012;19:3375–85. doi:10.​1245/​s10434-012-2408-1.PubMedCrossRef
7.
Zurück zum Zitat Eary JF, Hawkins DS, Rodler ET, Conrad 3rd EU. (18)F-FDG PET in sarcoma treatment response imaging. Am J Nucl Med Mol Imaging 2011;1:47–53.PubMedCentralPubMed Eary JF, Hawkins DS, Rodler ET, Conrad 3rd EU. (18)F-FDG PET in sarcoma treatment response imaging. Am J Nucl Med Mol Imaging 2011;1:47–53.PubMedCentralPubMed
8.
Zurück zum Zitat Schuetze SM, Rubin BP, Vernon C, Hawkins DS, Bruckner JD, Conrad 3rd EU, et al. Use of positron emission tomography in localized extremity soft tissue sarcoma treated with neoadjuvant chemotherapy. Cancer 2005;103:339–48. doi:10.1002/cncr.20769.PubMedCrossRef Schuetze SM, Rubin BP, Vernon C, Hawkins DS, Bruckner JD, Conrad 3rd EU, et al. Use of positron emission tomography in localized extremity soft tissue sarcoma treated with neoadjuvant chemotherapy. Cancer 2005;103:339–48. doi:10.​1002/​cncr.​20769.PubMedCrossRef
9.
Zurück zum Zitat Benz MR, Evilevitch V, Allen-Auerbach MS, Eilber FC, Phelps ME, Czernin J, et al. Treatment monitoring by 18F-FDG PET/CT in patients with sarcomas: interobserver variability of quantitative parameters in treatment-induced changes in histopathologically responding and nonresponding tumors. J Nucl Med 2008;49:1038–46. doi:10.2967/jnumed.107.050187.PubMedCrossRef Benz MR, Evilevitch V, Allen-Auerbach MS, Eilber FC, Phelps ME, Czernin J, et al. Treatment monitoring by 18F-FDG PET/CT in patients with sarcomas: interobserver variability of quantitative parameters in treatment-induced changes in histopathologically responding and nonresponding tumors. J Nucl Med 2008;49:1038–46. doi:10.​2967/​jnumed.​107.​050187.PubMedCrossRef
10.
Zurück zum Zitat Evilevitch V, Weber WA, Tap WD, Allen-Auerbach M, Chow K, Nelson SD, et al. 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. Clin Cancer Res 2008;14:715–20. doi:10.1158/1078-0432.CCR-07-1762.PubMedCrossRef Evilevitch V, Weber WA, Tap WD, Allen-Auerbach M, Chow K, Nelson SD, et al. 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. Clin Cancer Res 2008;14:715–20. doi:10.​1158/​1078-0432.​CCR-07-1762.PubMedCrossRef
12.
Zurück zum Zitat van Ginkel RJ, Hoekstra HJ, Pruim J, Nieweg OE, Molenaar WM, Paans AM, et al. FDG-PET to evaluate response to hyperthermic isolated limb perfusion for locally advanced soft-tissue sarcoma. J Nucl Med 1996;37:984–90.PubMed van Ginkel RJ, Hoekstra HJ, Pruim J, Nieweg OE, Molenaar WM, Paans AM, et al. FDG-PET to evaluate response to hyperthermic isolated limb perfusion for locally advanced soft-tissue sarcoma. J Nucl Med 1996;37:984–90.PubMed
13.
Zurück zum Zitat van Ginkel RJ, Kole AC, Nieweg OE, Molenaar WM, Pruim J, Koops HS, et al. L-[1-11C]-tyrosine PET to evaluate response to hyperthermic isolated limb perfusion for locally advanced soft-tissue sarcoma and skin cancer. J Nucl Med 1999;40:262–7.PubMed van Ginkel RJ, Kole AC, Nieweg OE, Molenaar WM, Pruim J, Koops HS, et al. L-[1-11C]-tyrosine PET to evaluate response to hyperthermic isolated limb perfusion for locally advanced soft-tissue sarcoma and skin cancer. J Nucl Med 1999;40:262–7.PubMed
14.
Zurück zum Zitat Been LB, Suurmeijer AJ, Elsinga PH, Jager PL, van Ginkel RJ, Hoekstra HJ. 18F-fluorodeoxythymidine PET for evaluating the response to hyperthermic isolated limb perfusion for locally advanced soft-tissue sarcomas. J Nucl Med 2007;48:367–72.PubMed Been LB, Suurmeijer AJ, Elsinga PH, Jager PL, van Ginkel RJ, Hoekstra HJ. 18F-fluorodeoxythymidine PET for evaluating the response to hyperthermic isolated limb perfusion for locally advanced soft-tissue sarcomas. J Nucl Med 2007;48:367–72.PubMed
15.
16.
Zurück zum Zitat Beyer T, Antoch G, Müller S, Egelhof T, Freudenberg LS, Debatin J, et al. Acquisition protocol considerations for combined PET/CT imaging. J Nucl Med 2004;45 Suppl 1:25S–35S.PubMed Beyer T, Antoch G, Müller S, Egelhof T, Freudenberg LS, Debatin J, et al. Acquisition protocol considerations for combined PET/CT imaging. J Nucl Med 2004;45 Suppl 1:25S–35S.PubMed
17.
Zurück zum Zitat Folpe AL, Lyles RH, Sprouse JT, Conrad 3rd EU, Eary JF. (F-18) fluorodeoxyglucose positron emission tomography as a predictor of pathologic grade and other prognostic variables in bone and soft tissue sarcoma. Clin Cancer Res 2000;6:1279–87.PubMed Folpe AL, Lyles RH, Sprouse JT, Conrad 3rd EU, Eary JF. (F-18) fluorodeoxyglucose positron emission tomography as a predictor of pathologic grade and other prognostic variables in bone and soft tissue sarcoma. Clin Cancer Res 2000;6:1279–87.PubMed
18.
Zurück zum Zitat Eary JF, O’Sullivan F, Powitan Y, Chandhury KR, Vernon C, Bruckner JD, et al. Sarcoma tumor FDG uptake measured by PET and patient outcome: a retrospective analysis. Eur J Nucl Med Mol Imaging 2002;29:1149–54. doi:10.1007/s00259-002-0859-5.PubMedCrossRef Eary JF, O’Sullivan F, Powitan Y, Chandhury KR, Vernon C, Bruckner JD, et al. Sarcoma tumor FDG uptake measured by PET and patient outcome: a retrospective analysis. Eur J Nucl Med Mol Imaging 2002;29:1149–54. doi:10.​1007/​s00259-002-0859-5.PubMedCrossRef
20.
Zurück zum Zitat Grabellus F, Kraft C, Sheu-Grabellus SY, Bauer S, Podleska LE, Lauenstein TC, et al. Tumor vascularization and histopathologic regression of soft tissue sarcomas treated with isolated limb perfusion with TNF-alpha and melphalan. J Surg Oncol 2011;103:371–9. doi:10.1002/jso.21724.PubMedCrossRef Grabellus F, Kraft C, Sheu-Grabellus SY, Bauer S, Podleska LE, Lauenstein TC, et al. Tumor vascularization and histopathologic regression of soft tissue sarcomas treated with isolated limb perfusion with TNF-alpha and melphalan. J Surg Oncol 2011;103:371–9. doi:10.​1002/​jso.​21724.PubMedCrossRef
21.
Zurück zum Zitat Kaplan E, Maier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457–81.CrossRef Kaplan E, Maier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457–81.CrossRef
22.
Zurück zum Zitat Mantel N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 1966;50:163–70.PubMed Mantel N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 1966;50:163–70.PubMed
25.
Zurück zum Zitat Huth JF, Mirra JJ, Eilber FR. Assessment of in vivo response to preoperative chemotherapy and radiation therapy as a predictor of survival in patients with soft-tissue sarcoma. Am J Clin Oncol 1985;8:497–503.PubMedCrossRef Huth JF, Mirra JJ, Eilber FR. Assessment of in vivo response to preoperative chemotherapy and radiation therapy as a predictor of survival in patients with soft-tissue sarcoma. Am J Clin Oncol 1985;8:497–503.PubMedCrossRef
26.
Zurück zum Zitat Kasper B, Dietrich S, Dimitrakopoulou-Strauss A, Strauss LG, Haberkorn U, Ho AD, et al. Early prediction of therapy outcome in patients with high-risk soft tissue sarcoma using positron emission tomography. Onkologie 2008;31:107–12. doi:10.1159/000113795.PubMedCrossRef Kasper B, Dietrich S, Dimitrakopoulou-Strauss A, Strauss LG, Haberkorn U, Ho AD, et al. Early prediction of therapy outcome in patients with high-risk soft tissue sarcoma using positron emission tomography. Onkologie 2008;31:107–12. doi:10.​1159/​000113795.PubMedCrossRef
27.
Zurück zum Zitat Schwarzbach MH, Hinz U, Dimitrakopoulou-Strauss A, Willeke F, Cardona S, Mechtersheimer G, et al. Prognostic significance of preoperative [18-F] fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging in patients with resectable soft tissue sarcomas. Ann Surg 2005;241:286–94.PubMedCentralPubMedCrossRef Schwarzbach MH, Hinz U, Dimitrakopoulou-Strauss A, Willeke F, Cardona S, Mechtersheimer G, et al. Prognostic significance of preoperative [18-F] fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging in patients with resectable soft tissue sarcomas. Ann Surg 2005;241:286–94.PubMedCentralPubMedCrossRef
28.
Zurück zum Zitat Eggermont AM, de Wilt JH, ten Hagen TL. Current uses of isolated limb perfusion in the clinic and a model system for new strategies. Lancet Oncol 2003;4:429–37.PubMedCrossRef Eggermont AM, de Wilt JH, ten Hagen TL. Current uses of isolated limb perfusion in the clinic and a model system for new strategies. Lancet Oncol 2003;4:429–37.PubMedCrossRef
29.
Zurück zum Zitat Italiano A, Delva F, Mathoulin-Pelissier S, Le Cesne A, Bonvalot S, Terrier P, et al. Effect of adjuvant chemotherapy on survival in FNCLCC grade 3 soft tissue sarcomas: a multivariate analysis of the French Sarcoma Group Database. Ann Oncol 2010;21:2436–41. doi:10.1093/annonc/mdq238.PubMedCrossRef Italiano A, Delva F, Mathoulin-Pelissier S, Le Cesne A, Bonvalot S, Terrier P, et al. Effect of adjuvant chemotherapy on survival in FNCLCC grade 3 soft tissue sarcomas: a multivariate analysis of the French Sarcoma Group Database. Ann Oncol 2010;21:2436–41. doi:10.​1093/​annonc/​mdq238.PubMedCrossRef
30.
Zurück zum Zitat ESMO/European Sarcoma Network Working Group. Soft tissue and visceral sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2012;23 Suppl 7:vii92–9. doi:10.1093/annonc/mds253. ESMO/European Sarcoma Network Working Group. Soft tissue and visceral sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2012;23 Suppl 7:vii92–9. doi:10.​1093/​annonc/​mds253.
31.
Zurück zum Zitat Woll PJ, Reichardt P, Le Cesne A, Bonvalot S, Azzarelli A, Hoekstra HJ, et al. Adjuvant chemotherapy with doxorubicin, ifosfamide, and lenograstim for resected soft-tissue sarcoma (EORTC 62931): a multicentre randomised controlled trial. Lancet Oncol 2012;13:1045–54. doi:10.1016/S1470-2045(12)70346-7.PubMedCrossRef Woll PJ, Reichardt P, Le Cesne A, Bonvalot S, Azzarelli A, Hoekstra HJ, et al. Adjuvant chemotherapy with doxorubicin, ifosfamide, and lenograstim for resected soft-tissue sarcoma (EORTC 62931): a multicentre randomised controlled trial. Lancet Oncol 2012;13:1045–54. doi:10.​1016/​S1470-2045(12)70346-7.PubMedCrossRef
Metadaten
Titel
Prognostic relevance of 18F-FDG PET uptake in patients with locally advanced, extremity soft tissue sarcomas undergoing neoadjuvant isolated limb perfusion with TNF-α and melphalan
verfasst von
Dimosthenis Andreou
Henrike Boldt
Daniel Pink
Björn Jobke
Mathias Werner
Markus Schuler
Peter Reichardt
Per-Ulf Tunn
Publikationsdatum
01.06.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 6/2014
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-013-2680-8

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