Skip to main content
Erschienen in: BMC Cancer 1/2018

Open Access 01.12.2018 | Case report

Mixed response on regorafenib treatment for GIST (gastro-intestinal stromal tumor) according to 18F–FDG-PET/CT

verfasst von: Donatienne Van Weehaeghe, Olivier Gheysens, Vincent Vandecaveye, Patrick Schöffski, Koen Van Laere, Christophe M. Deroose

Erschienen in: BMC Cancer | Ausgabe 1/2018

Abstract

Background

Gastro-intestinal stromal tumors (GISTs) are very rare tumors of the gastro-intestinal tract, originating from the interstitial cells of Cajal or a common cell precursor which both express type III tyrosine kinase receptors. Regorafenib is an oral multi-kinase inhibitor used to treat gastro-intestinal stromal tumors. To our knowledge this is the first case in literature to show the response of regorafenib on PET.

Case presentation

A 37-year-old male with lower abdominal pain and weight loss was referred to our hospital. Abdominal ultrasound and computed tomography (CT) showed diffuse peritoneal implants. Surgical specimen histology showed a GIST with c-KIT exon 11 deletion (c.1708_1728del) and treatment with imatinib 400 mg/day was initiated. Due to disease progression illustrated on baseline versus follow-up 18F–FDG-PET/CT scans therapy was switched to imatinib 800 mg/day and later to sunitinib 50 mg/day. Upon further disease progression 10 months later, third line treatment with regorafenib 160 mg/day was initiated. 18F–FDG-PET/CT showed the metabolic responses after 4 months regorafenib treatment ranging from complete response to the appearance of a new lesion in the liver. The new hypermetabolic lesion was only seen on the non-attenuation-corrected images because of breathing motion artifact.

Conclusion

This case illustrates that metabolic response can occur in GIST lesions without morphological response after third line regorafinib treatment. Furthermore this is the first case in literature to show regorafinib response on PET.
Abkürzungen
18F-FDG PET
[18]Fluor-Fluorodeoxyglucose Positron Emission Tomography
AC
Attenuation-corrected
c.1708_1728del
c-KIT exon 11 deletion
CR
Complete metabolic response
CT
Computed tomography
GISTs
Gastro-intestinal stromal tumors
MIP
Maximal intensity projection
NAC
Non-attenuation-corrected
PMR
Partial metabolic response
RECIST
Respons Evaluation Criteria in Solid Tumours
SD
Stable disease
Δdiammax
Maximal diameter
ΔSUVmax
Maximal standardized uptake value

Background

Gastro-intestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastro-intestinal tract. However they are very rare, accounting for about 1% of the tumors of the gastro-intestinal tract. These tumors originate from the interstitial cells of Cajal or other common cell precursors which express tyrosine kinase receptors (type III). They are sometimes called the pacemaker cells of the gut. Treatment consists of surgical resection with or without adjuvant/neo-adjuvant therapy with an oral multi-kinase inhibitor like regorafinib [13].
Regorafenib is an oral multi-kinase inhibitor used to treat metastatic GISTs after progression on standard treatment. It significantly improve progression-free survival compared with placebo in patients [3]. To our knowledge this is the first case in literature to show the response of regorafenib on 18F–FDG PET/CT.

Case presentation

A 37-year-old male complaining about lower abdominal pain and weight loss was referred to our hospital. He reported a weight loss of 5 kg in the last 3 months. An abdominal ultrasound and computed tomography (CT) were performed as work-up. Both examinations showed diffuse peritoneal implants.

Discussion

Surgical exploration and debulking was performed to obtain a tumor specimen for histopathological examination. Histological examination of this specimen showed a GIST with c-KIT exon 11 deletion (c.1708_1728del). As 18F–FDG PET has been shown of significant value in evaluating treatment response in GISTs, high dose contrast-enhanced 18F–FDG PET/CT scans (374.9 ± 17.2 MBq; approximately 60 min after tracer injection) were performed both before treatment and after every therapy switch to evaluate treatment response [4]. 18FDG-PET/CT performed for tumor staging showed multiple tumor localizations in the small bowel, the sigmoid and mesenterium without signs of extra-abdominal disease. Treatment with imatinib 400 mg daily was started with follow-up 18F–FDG PET/CT 2 months later showing disease progression. The dose was increased to 800 mg daily but follow-up 18F–FDG PET/CT 3 months later again revealed disease progression. A switch to sunitinib 50 mg once a day was performed. Upon further disease progression on the 18F–FDG PET/CT 10 months later, third line treatment with regorafenib 160 mg/day was initiated with a mixed response on 18F–FDG-PET/CT 4 months after treatment initiation with regorafinib (Fig. 1). There was one lesion with a complete metabolic response (CR), one with a partial metabolic response (PMR) and one with stable disease (SD) according to the EORTC criteria for 18F–FDG-PET response [5].
Pre- and post-therapy with regorafinib fused PET/CT and CT images with the differences in maximal standardized uptake value (ΔSUVmax) and differences in maximal diameter (Δdiammax) are shown in Figs. 2 and 3. The lesion with complete metabolic response had a ΔSUVmax of − 91% and a Δdiammax of − 1.7%. The lesion with the partial metabolic response had a ΔSUVmax of − 56% and a Δdiammax of − 21%. Both lesions were stable disease on CT scan according to the RECIST1.1 criteria. [6]. The lesion with stable disease on PET had a ΔSUVmax of − 8.0% and a Δdiammax of − 3.3%. The total volume of the lesion with complete metabolic response was 19.9 cm3 pretherapy and 17.6 cm3 posttherapy. The lesions with partial metabolic response and stable disease did not change in volume and were respectively 4.1 cm3 and 3.6 cm3. The volume of the new lesion was 3.2 cm3. No histological confirmation of this new lesion was obtained due to the general condition of the patient. However, this lesion increased both in volume and metabolism on follow-up scans, compatible with a true positive new tumoral lesion.
Besides these previously known lesions, a new hypermetabolic lesion was seen on the non-attenuation-corrected (NAC) 18F–FDG-PET images. It corresponded to a new hypodense liver lesion on CT, implying a new liver metastasis. However, the lesion was not visible on the attenuation-corrected (AC) and MIP images because of breathing motion-induced misregistration and subsequent lung density attenuation correction, which strongly reduces the apparent uptake in the lesion. This lesion has important consequences for the patient with regard to further treatment options (switch to another tyrosine kinase inhibitor) and illustrates the importance to look at NAC images on all oncological scans, in particular not to miss liver lesions within the liver dome [7, 8].

Conclusion

This case illustrates that metabolic response to third line regorafinib treatment can occur in GIST lesions without morphological response. Therefore, even though it did not affect treatment decision in this case, this finding highlights the importance of 18F–FDG PET scans in the evaluation of treatment response in future GIST tumors cases.

Acknowledgements

We have no acknowledgments to be made.

Funding

No funding for this case report was received.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
This study was approved by the Ethics Committee UZ Leuven. Informed written consent from the patient was received.
Written informed consent for publication of their clinical details and/or clinical images was obtained from the patient. A copy of the consent form is available for review by the Editor of this journal.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://​creativecommons.​org/​licenses/​by/​4.​0/​), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://​creativecommons.​org/​publicdomain/​zero/​1.​0/​) applies to the data made available in this article, unless otherwise stated.
Literatur
1.
Zurück zum Zitat Maki RG, Blay JY, Demetri GD, Fletcher JA, Joensuu H, Martin-Broto J, et al. Key issues in the clinical Management of Gastrointestinal Stromal Tumors: an expert discussion. Oncologist. 2015;20:823–30.CrossRefPubMedPubMedCentral Maki RG, Blay JY, Demetri GD, Fletcher JA, Joensuu H, Martin-Broto J, et al. Key issues in the clinical Management of Gastrointestinal Stromal Tumors: an expert discussion. Oncologist. 2015;20:823–30.CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Valsangkar N, Sehdev A, Misra S, Zimmers TA, O'Neil BH, Koniaris LG. Current management of gastrointestinal stromal tumors: surgery, current biomarkers, mutations, and therapy. Surgery. 2015;158:1149–64.CrossRefPubMed Valsangkar N, Sehdev A, Misra S, Zimmers TA, O'Neil BH, Koniaris LG. Current management of gastrointestinal stromal tumors: surgery, current biomarkers, mutations, and therapy. Surgery. 2015;158:1149–64.CrossRefPubMed
3.
Zurück zum Zitat Demetri GD, Reichardt P, Kang YK, Blay JY, Rutkowski P, Gelderblom H, et al. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381:295–302.CrossRefPubMed Demetri GD, Reichardt P, Kang YK, Blay JY, Rutkowski P, Gelderblom H, et al. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381:295–302.CrossRefPubMed
4.
Zurück zum Zitat Hassanzadeh-Rad A, Yousefifard M, Katal S, Asady H, Fard-Esfahani A, Moghadas Jafari A, et al. The value of (18) F-fluorodeoxyglucose positron emission tomography for prediction of treatment response in gastrointestinal stromal tumors: a systematic review and meta-analysis. J Gastroenterol Hepatol. 2016;31:929–35.CrossRefPubMed Hassanzadeh-Rad A, Yousefifard M, Katal S, Asady H, Fard-Esfahani A, Moghadas Jafari A, et al. The value of (18) F-fluorodeoxyglucose positron emission tomography for prediction of treatment response in gastrointestinal stromal tumors: a systematic review and meta-analysis. J Gastroenterol Hepatol. 2016;31:929–35.CrossRefPubMed
5.
Zurück zum Zitat Young H, Baum R, Cremerius U, Herholz K, Hoekstra O, Lammertsma AA, et al. Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of cancer (EORTC) PET study group. Eur J Cancer. 1999;35:1773–82.CrossRefPubMed Young H, Baum R, Cremerius U, Herholz K, Hoekstra O, Lammertsma AA, et al. Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of cancer (EORTC) PET study group. Eur J Cancer. 1999;35:1773–82.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;45:228–47.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;45:228–47.CrossRefPubMed
7.
Zurück zum Zitat Papathanassiou D, Liehn JC, Bourgeot B, Amir R, Marcus C. Cesium attenuation correction of the liver dome revealing hepatic lesion missed with computed tomography attenuation correction because of the respiratory motion artifact. Clin Nucl Med. 2005;30:120–1.CrossRefPubMed Papathanassiou D, Liehn JC, Bourgeot B, Amir R, Marcus C. Cesium attenuation correction of the liver dome revealing hepatic lesion missed with computed tomography attenuation correction because of the respiratory motion artifact. Clin Nucl Med. 2005;30:120–1.CrossRefPubMed
8.
Zurück zum Zitat Sarikaya I, Yeung HW, Erdi Y, Larson SM. Respiratory artefact causing malpositioning of liver dome lesion in right lower lung. Clin Nucl Med. 2003;28:943–4.CrossRefPubMed Sarikaya I, Yeung HW, Erdi Y, Larson SM. Respiratory artefact causing malpositioning of liver dome lesion in right lower lung. Clin Nucl Med. 2003;28:943–4.CrossRefPubMed
Metadaten
Titel
Mixed response on regorafenib treatment for GIST (gastro-intestinal stromal tumor) according to 18F–FDG-PET/CT
verfasst von
Donatienne Van Weehaeghe
Olivier Gheysens
Vincent Vandecaveye
Patrick Schöffski
Koen Van Laere
Christophe M. Deroose
Publikationsdatum
01.12.2018
Verlag
BioMed Central
Erschienen in
BMC Cancer / Ausgabe 1/2018
Elektronische ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4154-7

Weitere Artikel der Ausgabe 1/2018

BMC Cancer 1/2018 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.