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Erschienen in: Annals of Nuclear Medicine 9/2019

13.06.2019 | Original Article

The use of molecular volumetric parameters for the evaluation of Lu-177 PSMA I&T therapy response and survival

verfasst von: Emine Acar, Özhan Özdoğan, Ayşegül Aksu, Erkan Derebek, Recep Bekiş, Gamze Çapa Kaya

Erschienen in: Annals of Nuclear Medicine | Ausgabe 9/2019

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Abstract

Purpose

The primary aim of this study was to evaluate the volumetric therapy response via Ga-68 PSMA I&T PET/CT in patients treated with Lu-177 PSMA I&T therapy. The secondary purpose was to determine the impact of volumetric parameter responses to overall survival.

Methods

PSMA tumor volumes (PSMA-TV) and tumor lesion PSMA expressions (TL-PSMA) were calculated with a semi-automatic program on Ga-68 PSMA I&T PET/CT images that were obtained before and after Lu-177 PSMA I&T therapies with 19 patients. The median overall survival was compared with PSMA-TV, TL-PSMA, SUVmax, PSA, and alteration in PERCIST criteria.

Results

PSMA-TV values were decreased in 12 patients (63%), and TL-PSMA values were decreased in 15 patients (79%) following the therapy. The SUVmax and the PSA values were also decreased in 14 (74%) and 10 (53%) patients, respectively. The complete remission (CR) was observed in two patients (10%). The partial response (PR) and progressive disease were observed in 6 (32%) and 11 (58%) patients, respectively, according to PRECIST criteria. The survival rates were statistically significant in patients with a decrease in PSMA-TV and TL-PSMA values than patients without any decrease (p 0.001, p < 0.001, respectively). However, the survival rates did not differ in responders (PR or CR) and non-responders according to the PERCIST criteria (p 0.232). The survival rates did not also differ in responders and non-responders according to the SUVmax and PSA values (p 0.140, p 0.206, respectively).

Conclusions

Molecular and volumetric parameters are beneficial in the assessment of Lu-177 PSMA I&T therapy response. Although the number of patients is small, TL-PSMA response, which includes both the tumor volume and PSMA expression in tumor, may be considered as the most valuable parameter for the evaluation of the therapy response and the prediction of survival rate.
Literatur
1.
Zurück zum Zitat Mottet N, Bellmunt J, Bolla M, Briers E, Cumberbatch MG, De Santis M, et al. EAU-ESTRO-SIOG guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent. Eur Urol. 2017;71(4):618–29.CrossRefPubMed Mottet N, Bellmunt J, Bolla M, Briers E, Cumberbatch MG, De Santis M, et al. EAU-ESTRO-SIOG guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent. Eur Urol. 2017;71(4):618–29.CrossRefPubMed
2.
Zurück zum Zitat Afshar-Oromieh A, Babich JW, Kratochwil C, Giesel FL, Eisenhut M, Kopka K, et al. The rise of PSMA ligands for diagnosis and therapy of prostate cancer. J Nucl Med. 2016;57(Suppl 3):79s–89s.CrossRefPubMed Afshar-Oromieh A, Babich JW, Kratochwil C, Giesel FL, Eisenhut M, Kopka K, et al. The rise of PSMA ligands for diagnosis and therapy of prostate cancer. J Nucl Med. 2016;57(Suppl 3):79s–89s.CrossRefPubMed
3.
Zurück zum Zitat Ringheim A, Campos Neto GC, Martins KM, Vitor T, da Cunha ML, Baroni RH. Reproducibility of standardized uptake values of same-day randomized (68)Ga-PSMA-11 PET/CT and PET/MR scans in recurrent prostate cancer patients. Ann Nucl Med. 2018;32(8):523–31.CrossRefPubMed Ringheim A, Campos Neto GC, Martins KM, Vitor T, da Cunha ML, Baroni RH. Reproducibility of standardized uptake values of same-day randomized (68)Ga-PSMA-11 PET/CT and PET/MR scans in recurrent prostate cancer patients. Ann Nucl Med. 2018;32(8):523–31.CrossRefPubMed
4.
Zurück zum Zitat Emmett L, Willowson K, Violet J, Shin J, Blanksby A, Lee J. Lutetium (177) PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy. J Med Radiat Sci. 2017;64(1):52–60.CrossRefPubMedPubMedCentral Emmett L, Willowson K, Violet J, Shin J, Blanksby A, Lee J. Lutetium (177) PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy. J Med Radiat Sci. 2017;64(1):52–60.CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Haberkorn U, Eder M, Kopka K, Babich JW, Eisenhut M. New strategies in prostate cancer: prostate-specific membrane Antigen (PSMA) ligands for diagnosis and therapy. Clin Cancer Res. 2016;22(1):9–15.CrossRefPubMed Haberkorn U, Eder M, Kopka K, Babich JW, Eisenhut M. New strategies in prostate cancer: prostate-specific membrane Antigen (PSMA) ligands for diagnosis and therapy. Clin Cancer Res. 2016;22(1):9–15.CrossRefPubMed
6.
Zurück zum Zitat Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47.CrossRefPubMed Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47.CrossRefPubMed
7.
Zurück zum Zitat 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;50(Suppl 1):122s–50s.CrossRefPubMed 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;50(Suppl 1):122s–50s.CrossRefPubMed
8.
Zurück zum Zitat Jh O, Lodge MA, Wahl RL. Practical PERCIST: a simplified guide to PET response criteria in solid tumors 10. Radiology. 2016;280(2):576–84.CrossRef Jh O, Lodge MA, Wahl RL. Practical PERCIST: a simplified guide to PET response criteria in solid tumors 10. Radiology. 2016;280(2):576–84.CrossRef
9.
Zurück zum Zitat Kim JH. Comparison of the EORTC criteria and PERCIST in solid tumors: a pooled analysis and review. Oncotarget. 2016;7(36):58105–10.PubMedPubMedCentral Kim JH. Comparison of the EORTC criteria and PERCIST in solid tumors: a pooled analysis and review. Oncotarget. 2016;7(36):58105–10.PubMedPubMedCentral
10.
Zurück zum Zitat Pinker K, Riedl C, Weber WA. Evaluating tumor response with FDG PET: updates on PERCIST, comparison with EORTC criteria and clues to future developments. Eur J Nucl Med Mol Imaging. 2017;44(Suppl 1):55–66.CrossRefPubMedPubMedCentral Pinker K, Riedl C, Weber WA. Evaluating tumor response with FDG PET: updates on PERCIST, comparison with EORTC criteria and clues to future developments. Eur J Nucl Med Mol Imaging. 2017;44(Suppl 1):55–66.CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Seitz AK, Rauscher I, Haller B, Kronke M, Luther S, Heck MM, et al. Preliminary results on response assessment using (68)Ga-HBED-CC-PSMA PET/CT in patients with metastatic prostate cancer undergoing docetaxel chemotherapy. Eur J Nucl Med Mol Imaging. 2018;45(4):602–12.CrossRefPubMed Seitz AK, Rauscher I, Haller B, Kronke M, Luther S, Heck MM, et al. Preliminary results on response assessment using (68)Ga-HBED-CC-PSMA PET/CT in patients with metastatic prostate cancer undergoing docetaxel chemotherapy. Eur J Nucl Med Mol Imaging. 2018;45(4):602–12.CrossRefPubMed
12.
Zurück zum Zitat Baum RP, Kulkarni HR, Schuchardt C, Singh A, Wirtz M, Wiessalla S, et al. 177Lu-labeled prostate-specific membrane antigen radioligand therapy of metastatic castration-resistant prostate cancer: safety and efficacy. J Nucl Med. 2016;57(7):1006–13.CrossRefPubMed Baum RP, Kulkarni HR, Schuchardt C, Singh A, Wirtz M, Wiessalla S, et al. 177Lu-labeled prostate-specific membrane antigen radioligand therapy of metastatic castration-resistant prostate cancer: safety and efficacy. J Nucl Med. 2016;57(7):1006–13.CrossRefPubMed
13.
Zurück zum Zitat Fendler WP, Reinhardt S, Ilhan H, Delker A, Boning G, Gildehaus FJ, et al. Preliminary experience with dosimetry, response and patient reported outcome after 177Lu-PSMA-617 therapy for metastatic castration-resistant prostate cancer. Oncotarget. 2017;8(2):3581–90.CrossRefPubMed Fendler WP, Reinhardt S, Ilhan H, Delker A, Boning G, Gildehaus FJ, et al. Preliminary experience with dosimetry, response and patient reported outcome after 177Lu-PSMA-617 therapy for metastatic castration-resistant prostate cancer. Oncotarget. 2017;8(2):3581–90.CrossRefPubMed
14.
Zurück zum Zitat Oh JR, Seo JH, Hong CM, Jeong SY, Lee SW, Lee J, et al. Extra-thoracic tumor burden but not thoracic tumor burden on (18)F-FDG PET/CT is an independent prognostic biomarker for extensive-disease small cell lung cancer. Lung Cancer. 2013;81(2):218–25.CrossRefPubMed Oh JR, Seo JH, Hong CM, Jeong SY, Lee SW, Lee J, et al. Extra-thoracic tumor burden but not thoracic tumor burden on (18)F-FDG PET/CT is an independent prognostic biomarker for extensive-disease small cell lung cancer. Lung Cancer. 2013;81(2):218–25.CrossRefPubMed
15.
Zurück zum Zitat Winther-Larsen A, Fledelius J, Sorensen BS, Meldgaard P. Metabolic tumor burden as marker of outcome in advanced EGFR wild-type NSCLC patients treated with erlotinib. Lung Cancer. 2016;94:81–7.CrossRefPubMed Winther-Larsen A, Fledelius J, Sorensen BS, Meldgaard P. Metabolic tumor burden as marker of outcome in advanced EGFR wild-type NSCLC patients treated with erlotinib. Lung Cancer. 2016;94:81–7.CrossRefPubMed
16.
Zurück zum Zitat Yamamoto M, Tsujikawa T, Fujita Y, Chino Y, Kurokawa T, Kiyono Y, et al. Metabolic tumor burden predicts prognosis of ovarian cancer patients who receive platinum-based adjuvant chemotherapy. Cancer Sci. 2016;107(4):478–85.CrossRefPubMedPubMedCentral Yamamoto M, Tsujikawa T, Fujita Y, Chino Y, Kurokawa T, Kiyono Y, et al. Metabolic tumor burden predicts prognosis of ovarian cancer patients who receive platinum-based adjuvant chemotherapy. Cancer Sci. 2016;107(4):478–85.CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Zhang C, Liao C, Penney BC, Appelbaum DE, Simon CA, Pu Y. Relationship between overall survival of patients with non-small cell lung cancer and whole-body metabolic tumor burden seen on postsurgical fluorodeoxyglucose PET images. Radiology. 2015;275(3):862–9.CrossRefPubMed Zhang C, Liao C, Penney BC, Appelbaum DE, Simon CA, Pu Y. Relationship between overall survival of patients with non-small cell lung cancer and whole-body metabolic tumor burden seen on postsurgical fluorodeoxyglucose PET images. Radiology. 2015;275(3):862–9.CrossRefPubMed
18.
Zurück zum Zitat Schmuck S, von Klot CA, Henkenberens C, Sohns JM, Christiansen H, Wester HJ, et al. Initial experience with volumetric (68)Ga-PSMA I&T PET/CT for assessment of whole-body tumor burden as a quantitative imaging biomarker in patients with prostate cancer. J Nucl Med. 2017;58(12):1962–8.CrossRefPubMed Schmuck S, von Klot CA, Henkenberens C, Sohns JM, Christiansen H, Wester HJ, et al. Initial experience with volumetric (68)Ga-PSMA I&T PET/CT for assessment of whole-body tumor burden as a quantitative imaging biomarker in patients with prostate cancer. J Nucl Med. 2017;58(12):1962–8.CrossRefPubMed
19.
Zurück zum Zitat Nioche C, Orlhac F, Boughdad S, Reuze S, Goya-Outi J, Robert C, et al. LIFEx: a freeware for radiomic feature calculation in multimodality imaging to accelerate advances in the characterization of tumor heterogeneity. Cancer Res. 2018;78(16):4786–9.CrossRefPubMed Nioche C, Orlhac F, Boughdad S, Reuze S, Goya-Outi J, Robert C, et al. LIFEx: a freeware for radiomic feature calculation in multimodality imaging to accelerate advances in the characterization of tumor heterogeneity. Cancer Res. 2018;78(16):4786–9.CrossRefPubMed
20.
Zurück zum Zitat Giesel FL, Fiedler H, Stefanova M, Sterzing F, Rius M, Kopka K, et al. PSMA PET/CT with Glu-urea-Lys-(Ahx)-[(6)(8)Ga(HBED-CC)] versus 3D CT volumetric lymph node assessment in recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2015;42(12):1794–800.CrossRefPubMedPubMedCentral Giesel FL, Fiedler H, Stefanova M, Sterzing F, Rius M, Kopka K, et al. PSMA PET/CT with Glu-urea-Lys-(Ahx)-[(6)(8)Ga(HBED-CC)] versus 3D CT volumetric lymph node assessment in recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2015;42(12):1794–800.CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Liu C, Liu T, Zhang N, Liu Y, Li N, Du P, et al. (68)Ga-PSMA-617 PET/CT: a promising new technique for predicting risk stratification and metastatic risk of prostate cancer patients. Eur J Nucl Med Mol Imaging. 2018;45(11):1852–61.CrossRefPubMed Liu C, Liu T, Zhang N, Liu Y, Li N, Du P, et al. (68)Ga-PSMA-617 PET/CT: a promising new technique for predicting risk stratification and metastatic risk of prostate cancer patients. Eur J Nucl Med Mol Imaging. 2018;45(11):1852–61.CrossRefPubMed
22.
Zurück zum Zitat Vinsensia M, Chyoke PL, Hadaschik B, Holland-Letz T, Moltz J, Kopka K, et al. (68)Ga-PSMA PET/CT and volumetric morphology of PET-positive lymph nodes stratified by tumor differentiation of prostate cancer. J Nucl Med. 2017;58(12):1949–55.CrossRefPubMedPubMedCentral Vinsensia M, Chyoke PL, Hadaschik B, Holland-Letz T, Moltz J, Kopka K, et al. (68)Ga-PSMA PET/CT and volumetric morphology of PET-positive lymph nodes stratified by tumor differentiation of prostate cancer. J Nucl Med. 2017;58(12):1949–55.CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Schmidkonz C, Cordes M, Schmidt D, Bauerle T, Goetz TI, Beck M, et al. (68)Ga-PSMA-11 PET/CT-derived metabolic parameters for determination of whole-body tumor burden and treatment response in prostate cancer. Eur J Nucl Med Mol Imaging. 2018;45(11):1862–72.CrossRefPubMed Schmidkonz C, Cordes M, Schmidt D, Bauerle T, Goetz TI, Beck M, et al. (68)Ga-PSMA-11 PET/CT-derived metabolic parameters for determination of whole-body tumor burden and treatment response in prostate cancer. Eur J Nucl Med Mol Imaging. 2018;45(11):1862–72.CrossRefPubMed
24.
Zurück zum Zitat Ahmadzadehfar H, Eppard E, Kurpig S, Fimmers R, Yordanova A, Schlenkhoff CD, et al. Therapeutic response and side effects of repeated radioligand therapy with 177Lu-PSMA-DKFZ-617 of castrate-resistant metastatic prostate cancer. Oncotarget. 2016;7(11):12477–88.CrossRefPubMedPubMedCentral Ahmadzadehfar H, Eppard E, Kurpig S, Fimmers R, Yordanova A, Schlenkhoff CD, et al. Therapeutic response and side effects of repeated radioligand therapy with 177Lu-PSMA-DKFZ-617 of castrate-resistant metastatic prostate cancer. Oncotarget. 2016;7(11):12477–88.CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Yadav MP, Ballal S, Tripathi M, Damle NA, Sahoo RK, Seth A, et al. (177)Lu-DKFZ-PSMA-617 therapy in metastatic castration resistant prostate cancer: safety, efficacy, and quality of life assessment. Eur J Nucl Med Mol Imaging. 2017;44(1):81–91.CrossRefPubMed Yadav MP, Ballal S, Tripathi M, Damle NA, Sahoo RK, Seth A, et al. (177)Lu-DKFZ-PSMA-617 therapy in metastatic castration resistant prostate cancer: safety, efficacy, and quality of life assessment. Eur J Nucl Med Mol Imaging. 2017;44(1):81–91.CrossRefPubMed
26.
Zurück zum Zitat Ahmadzadehfar H, Wegen S, Yordanova A, Fimmers R, Kurpig S, Eppard E, et al. Overall survival and response pattern of castration-resistant metastatic prostate cancer to multiple cycles of radioligand therapy using [(177)Lu]Lu-PSMA-617. Eur J Nucl Med Mol Imaging. 2017;44(9):1448–54.CrossRefPubMed Ahmadzadehfar H, Wegen S, Yordanova A, Fimmers R, Kurpig S, Eppard E, et al. Overall survival and response pattern of castration-resistant metastatic prostate cancer to multiple cycles of radioligand therapy using [(177)Lu]Lu-PSMA-617. Eur J Nucl Med Mol Imaging. 2017;44(9):1448–54.CrossRefPubMed
Metadaten
Titel
The use of molecular volumetric parameters for the evaluation of Lu-177 PSMA I&T therapy response and survival
verfasst von
Emine Acar
Özhan Özdoğan
Ayşegül Aksu
Erkan Derebek
Recep Bekiş
Gamze Çapa Kaya
Publikationsdatum
13.06.2019
Verlag
Springer Singapore
Erschienen in
Annals of Nuclear Medicine / Ausgabe 9/2019
Print ISSN: 0914-7187
Elektronische ISSN: 1864-6433
DOI
https://doi.org/10.1007/s12149-019-01376-3

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