In-Vivo Somatostatin-Receptor Expression in Small Cell Lung Cancer as a Prognostic Image Biomarker and Therapeutic Target
by
, , , ,
Feyza Şen
1,2,3,†,
Gabriel T. Sheikh
2,4,†,
Johannes von Hinten
2,
Andreas Schindele
2,
Malte Kircher
2,
Alexander Dierks
2,
Christian H. Pfob
2,
Sebastian E. Serfling
1,
Andreas K. Buck
1,
Theo Pelzer
5,
Takahiro Higuchi
1,6,
Alexander Weich
7,
Ralph A. Bundschuh
2
,
Rudolf A. Werner
1,8,‡ and
Constantin Lapa
2,*,‡ 1
Department of Nuclear Medicine, University Hospital Wuerzburg, 97080 Würzburg, Germany
2
Nuclear Medicine, Faculty of Medicine, University of Augsburg, 86154 Augsburg, Germany
3
Department of Nuclear Medicine, Pendik Training and Research Hospital, Marmara University, 34722 İstanbul, Turkey
4
Department of Nuclear Medicine, Ludwig-Maximilians-Universität München, 81377 Munich, Germany
5
Department of Internal Medicine I, Pulmonology, University Hospital Wuerzburg, 97080 Würzburg, Germany
6
Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan
7
Department of Internal Medicine II, Gastroenterology, University Hospital Wuerzburg, 97080 Würzburg, Germany
8
Johns Hopkins School of Medicine, The Russell H Morgan Department of Radiology and Radiological Science, Division of Nuclear Medicine and Molecular Imaging, Baltimore, MD 21287, USA
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
‡
These authors contributed equally to this work.
Cancers 2023, 15(14), 3595; https://doi.org/10.3390/cancers15143595
Submission received: 16 June 2023
/
Revised: 2 July 2023
/
Accepted: 11 July 2023
/
Published: 13 July 2023
(This article belongs to the Section Cancer Therapy)
Simple Summary
Despite novel targeted treatment options, small cell lung cancer (SCLC) still has a bad prognosis. However, as a relevant number of SCLC patients show a high expression of somatostatin receptors (SSTRs), SSTR-targeted radionuclide therapy (PRRT) may be a treatment option. Therefore, we investigated whether SSTR expression assessed in positron emission tomography (PET) has prognostic value. In patients with adequate PET uptake, PRRT was performed, and the outcome was investigated. We found that SSTR-targeted PET, although not a prognostic tool for outcome, is an important tool for treatment decision. In some patients, PRRT can be a promising treatment option as a second or third line treatment of SCLC.
Abstract
Background: Given the dismal prognosis of small cell lung cancer (SCLC), novel therapeutic targets are urgently needed. We aimed to evaluate whether SSTR expression, as assessed by positron emission tomography (PET), can be applied as a prognostic image biomarker and determined subjects eligible for peptide receptor radionuclide therapy (PRRT). Methods: A total of 67 patients (26 females; age, 41–80 years) with advanced SCLC underwent SSTR-directed PET/computed tomography (somatostatin receptor imaging, SRI). SRI-avid tumor burden was quantified by maximum standardized uptake values (SUVmax) and tumor-to-liver ratios (T/L) of the most intense SCLC lesion. Scan findings were correlated with progression-free (PFS) and overall survival (OS). In addition, subjects eligible for SSTR-directed radioligand therapy were identified, and treatment outcome and toxicity profile were recorded. Results: On a patient basis, 36/67 (53.7%) subjects presented with mainly SSTR-positive SCLC lesions (>50% lesions positive); in 10/67 patients (14.9%), all lesions were positive. The median SUVmax was found to be 8.5, while the median T/L was 1.12. SRI-uptake was not associated with PFS or OS, respectively (SUVmax vs. PFS, ρ = 0.13 with p = 0.30 and vs. OS, ρ = 0.00 with p = 0.97; T/L vs. PFS, ρ = 0.07 with p = 0.58 and vs. OS, ρ = −0.05 with p = 0.70). PRRT was performed in 14 patients. One patient succumbed to treatment-independent infectious complications immediately after PRRT. In the remaining 13 subjects, disease control was achieved in 5/13 (38.5%) with a single patient achieving a partial response (stable disease in the remainder). In the sub-group of responding patients, PFS and OS were 357 days and 480 days, respectively. Conclusions: SSTR expression as detected by SRI is not predictive of outcome in patients with advanced SCLC. However, it might serve as a therapeutic target in selected patients.
Keywords:
somatostatin receptor; SSTR; SCLC; small cell lung cancer; theranostics; DOTATATE; DOTATOC; PET
