Size-Based Clinical Response Evaluation is Insufficient to Assess Clinical Response of Sarcomas Treated with Isolated Limb Perfusion with TNF-α and Melphalan

Grabellus, Florian; Stylianou, Eleni; Umutlu, Lale; Sheu, Sien‐Yi; Lehmann, Nils; Taeger, G.; Lauenstein, Thomas C.

doi:10.1245/s10434-012-2408-1

Cited by 16 publications

(23 citation statements)

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“…To date, the largest studies have adjusted these clinical data downward to an overall response rate of approximately 70% and a complete response rate of 20% [36]. Interestingly, clinical and pathological response evaluations have often differed substantially, which we have recently demonstrated to be the result of an insufficiency in size-based clinical response criteria that would indicate actual tumor responses (measured by a pathological investigation as the gold standard) [37]. The SS cohort exhibited a mean pathological response rate that was approximately identical to that of the STS −SS in this cohort of resected STS.…”

Section: Discussionmentioning

confidence: 99%

The pathologic response of resected synovial sarcomas to hyperthermic isolated limb perfusion with melphalan and TNF-α: a comparison with the whole group of resected soft tissue sarcomas

et al. 2013

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BackgroundHyperthermic isolated limb perfusion with tumor necrosis factor-α and melphalan (TM-HILP) has been successfully used to treat limb soft tissue sarcomas (STSs) with high response rates. The data on the effectiveness of HILP-TM for the treatment of STSs are mainly based on various STS types. The aim of this study was to investigate the responses of synovial sarcomas (SS) to TM-HILP.MethodsA total of 125 TM-HILP-treated tumors (STSall), including 14 SSs, were included in the study. The tumors were subdivided into proximal and distal limb localizations. Tumor typing (using the WHO classification), resection status (using the UICC classification), and response to therapy were assessed using light microscopy. The SSs were tested for the SYT-SSX translocation using RT-PCR. The following tests were applied: a chi-squared test, a t test, and the Mann-Whitney U test.ResultsThe SSs were localized distally more often than were the STS cohort (STS−SS) (85.7% vs. 32.4%) and were smaller (5.8 cm vs. 10.7 cm). There were no differences in the responder/nonresponder ratios or the mean percentages of pathological regression between the SS and STS−SS cohorts (74.0% vs. 76.0%). A general localization-dependent difference in the tumor responses to TM-HILP could not be detected in the STSall cohort (distal, 72.0% vs. proximal, 78.0%); however, a UICC R0 status was more often observed in proximal tumors (distal, 50.0% vs. proximal, 71.4%). There was no association between the SYT-SSX type and SS responses to TM-HILP.ConclusionsBecause of the high response rates, TM-HILP is recommended for the treatment of SSs. The distal limb localization of TM-HILP-treated STSs was generally (STSall cohort) associated with fewer R0 resections.

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Section: Discussionmentioning

confidence: 99%

The pathologic response of resected synovial sarcomas to hyperthermic isolated limb perfusion with melphalan and TNF-α: a comparison with the whole group of resected soft tissue sarcomas

et al. 2013

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“…These results are similar to those reported by other studies ( de Wilt et al , 2000 ; Hoving et al , 2006 ). In contrast, soft tissue sarcomas have been reported to not shrink significantly after pre-treatment with TM-ILP or chemotherapy ( Stacchiotti et al , 2009 ; Grabellus et al , 2012b ). In agreement with these findings, despite the positive response to TM-ILP, there was still a sufficiently significant residual tumour in all patients of the present study (between 20 and 100% of the original size) to allow measurement by O2C.…”

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confidence: 99%

TNF-alpha and melphalan-based isolated limb perfusion: no evidence supporting the early destruction of tumour vasculature

Podleska¹,

Funk

Umutlu

et al. 2015

Br J Cancer

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Background:Isolated limb perfusion with TNF-alpha and melphalan (TM-ILP) is a highly effective treatment for locally advanced tumours of the extremities. Previous research suggests an almost immediate disintegration of the blood supply of the tumour. The aim of the present study was to verify this hypothesis using non-invasive measurements of microvascular perfusion and tissue oxygenation.Methods:A total of 11 patients were included in the study. TM-ILP was performed under mildly hyperthermic conditions (39 °C) in the extremities via proximal vascular access. Capillary-venous microvascular blood flow, haemoglobin level (Hb) and oxygen saturation (SO2) were determined using laser Doppler and white-light spectroscopy, respectively, before TM-ILP and at 30 min, 4 h, 1 day, 4 days, 1 week, 2 weeks and 6 weeks after TM-ILP from tumour and healthy muscle tissues.Results:Blood flow and Hb were mostly higher, whereas SO2 was lower, in tumour tissue compared with muscle tissue. In both tumour and muscle tissues, blood flow significantly increased immediately after TM-ILP and remained elevated for at least 2 weeks, followed by a return to the initial values 6 weeks after the procedure.Conclusion:No signs were found of early destruction of the tumour vasculature. The observations suggest that an inflammatory reaction is one of the key elements of TM-ILP.

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“…In clinical practice, therapy response is routinely monitored by changes in tumor size according to RECIST (10). However, exclusive size-based criteria have been shown insufficient for reliable response evaluation of neoadjuvant treatment effects of STS (11,12). Therefore, Stacchiotti et al introduced the MR-adapted Choi criteria, comprising modified size criteria for tumor response with, in addition, quantification of therapy-related changes in contrast-enhancing tumor parts (13,14).…”

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¹⁸F-FDG PET/MRI for Therapy Response Assessment of Isolated Limb Perfusion in Patients with Soft-Tissue Sarcomas

et al. 2019

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Our purpose was to assess the diagnostic potential of simultaneously acquired 18 F-FDG PET and MRI data sets for therapy response assessment of isolated limb perfusion (ILP) in patients with soft-tissue sarcomas (STS). Methods: In total, 45 patients with histopathologically verified STS were prospectively enrolled for an integrated 18 F-FDG PET/MRI examination before and after ILP. Therapy response was assessed based on different MRI-and PET-derived morphologic (RECIST and the MR-adapted Choi criteria) and metabolic (PERCIST) criteria. In addition, a regression model was used combining relative changes in quantitative variables to predict treatment response under ILP. Histopathologic results after subsequent tumor resection served as the reference standard, and patients were categorized as responders or nonresponders on the basis of the 6-stage regression scale by Salzer-Kuntschik. Results: Histopathologic analysis categorized 27 patients as responders (grades I-III) and 18 patients as nonresponders (grades IV-VI). Calculated sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy were 22%, 89%, 75%, 43%, and 49% for RECIST; 70%, 44%, 66%, 50%, and 60% for the Choi criteria; and 85%, 78%, 85%, 78%, and 82% for PERCIST. Receiver-operating-characteristic analysis revealed an area under the curve (AUC) of 0.56 for RECIST, 0.57 for the Choi criteria, and 0.82 for PERCIST. The combined regression model revealed higher values (AUC, 0.90) than for the standalone analysis, however, differences to metabolic parameters did not reach significance (P value: 0.067). Conclusion: Our study demonstrates the superiority of 18 F-FDG PET over MRI data sets for response assessment of STS under neoadjuvant ILP. In a clinical setting, MRI delivers valuable information for presurgical assessment. Therefore, combining 18 F-FDG PET and MRI data may enable more reliable treatment planning and therapy monitoring of STS.

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Size-Based Clinical Response Evaluation is Insufficient to Assess Clinical Response of Sarcomas Treated with Isolated Limb Perfusion with TNF-α and Melphalan

Abstract: Size-based clinical response evaluation is insufficient to assess clinical response in TM-ILP-treated sarcomas. The size changes of tumors after therapy reflect the type of regression rather than the extent of destruction.

Cited by 16 publications

References 29 publications

The pathologic response of resected synovial sarcomas to hyperthermic isolated limb perfusion with melphalan and TNF-α: a comparison with the whole group of resected soft tissue sarcomas

The pathologic response of resected synovial sarcomas to hyperthermic isolated limb perfusion with melphalan and TNF-α: a comparison with the whole group of resected soft tissue sarcomas

TNF-alpha and melphalan-based isolated limb perfusion: no evidence supporting the early destruction of tumour vasculature

¹⁸F-FDG PET/MRI for Therapy Response Assessment of Isolated Limb Perfusion in Patients with Soft-Tissue Sarcomas

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Size-Based Clinical Response Evaluation is Insufficient to Assess Clinical Response of Sarcomas Treated with Isolated Limb Perfusion with TNF-α and Melphalan

Abstract: Size-based clinical response evaluation is insufficient to assess clinical response in TM-ILP-treated sarcomas. The size changes of tumors after therapy reflect the type of regression rather than the extent of destruction.

Cited by 16 publications

References 29 publications

The pathologic response of resected synovial sarcomas to hyperthermic isolated limb perfusion with melphalan and TNF-α: a comparison with the whole group of resected soft tissue sarcomas

The pathologic response of resected synovial sarcomas to hyperthermic isolated limb perfusion with melphalan and TNF-α: a comparison with the whole group of resected soft tissue sarcomas

TNF-alpha and melphalan-based isolated limb perfusion: no evidence supporting the early destruction of tumour vasculature

18F-FDG PET/MRI for Therapy Response Assessment of Isolated Limb Perfusion in Patients with Soft-Tissue Sarcomas

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¹⁸F-FDG PET/MRI for Therapy Response Assessment of Isolated Limb Perfusion in Patients with Soft-Tissue Sarcomas