Dynamic and Static 18F-FDG PET/CT Imaging in SMARCA4-Deficient Non-Small Cell Lung Cancer and Response to Therapy: A Case Report

SMARCA4-deficient non-small cell lung cancer (NSCLC) is a more recently recognized subset of NSCLC. We describe the 18F-fluorodeoxyglucose (FDG) PET/CT findings in a rare case of SMARCA4-deficient NSCLC and response to therapy. A 45-year-old male patient with a history of heavy smoking (10 years) underwent an 18F-fluorodeoxyglucose (FDG) PET/CT dynamic (chest) + static (whole-body) scan for diagnosis and pre-treatment staging. 18F-FDG PET/CT showed an FDG-avid mass in the upper lobe of the left lung (SUVmax of 22.4) and FDG-avid lymph nodes (LN) in the left pulmonary hilar region (SUVmax of 5.7). In addition, there were multiple metastases throughout the body, including in the distant LNs, adrenal glands, bone, left subcutaneous lumbar region, and brain. Pathological findings confirmed SMARCA4-deficient NSCLC. After four cycles of chemotherapy and immune checkpoint inhibitors (ICI), the patient underwent again an 18F-FDG PET/CT scan (including a dynamic scan) for efficacy evaluation. We report a case that deepens the understanding of the 18F-FDG PET/CT presentation of SMARCA4-deficient NSCLC as well as dynamic imaging features and parametric characteristics.

SMARCA4-deficient non-small cell lung cancer (NSCLC) accounts for 3-6% of all NSCLCs [1]. It is only in recent years has emerged as a distinct NSCLC subset [2]. SMARCA4-deficient NSCLC is prevalent in men aged 40-50 years and shows a strong association with smoking [3]. Deficient SMARCA4 leads to an increased incidence of tumor metastasis [4]. It is highly aggressive, rapidly progressive, and has a poor prognosis [1,[4][5][6]. Previous studies have reported that approximately 83% of SMARCA4-deficient NSCLCs are already in stage IV at the time of detection and have a progression-free survival of only 30 days [4,7]. There are very limited descriptions of SMARCA4-deficient NSCLC morphology as well as 18 F-FDG PET/CT features. To our knowledge, we are the first to present a dynamic imaging and metabolic parameter profile for SMARCA4-deficient NSCLC.
Effective treatment for SMARCA4-deficient NSCLC has not been established. Little is known about the efficacy of ICIs in SMARCA4-deficient NSCLC. In 2019, Tomoyuki Naito et al. reported the first case of SMARCA4-deficient NSCLC successfully treated Diagnostics 2023, 13, 2048 2 of 7 with nivolumab [8]. In the case, we reported, based on the 18 F-FDG PET/CT findings (Figure 1), the patient's pathological and immunohistochemical findings confirmed SMARCA4deficient NSCLC (Figure 2), and clinical stage was T2N3M1, stage IVB. Then the patient received four cycles of ICIs (Tislelizumab, 200 mg) and chemotherapy (Paclitaxel 0.2 g + Carboplatin 450 mg). The review 18 F-FDG PET/CT after four cycles of treatment (4 months later, April 2023, Figure 3) showed that the primary lung cancer foci, distant metastases, and retroperitoneal LN were significantly smaller than before, and the SUV max was reduced. Other than that, tumor markers reviewed regularly during treatment were negative. However, the MRI (brain, follow up to March 2023) results at follow-up showed that the brain metastases did not shrink significantly, and enhanced on enhancement scans. Therefore, the clinical efficacy evaluation after four cycles of treatment was rated as stable disease (SD). As of our last follow-up (May 2023), the patient was on cycle 6 of treatment. So far, the general condition is good and no recurrent/metastatic lesions have been observed. We will follow up further on the patient's condition.
Dynamic 18 F-FDG PET/CT (dPET/CT) extracts physiological parameters which can better reveal the pathophysiological mechanisms of diseases. Many previous studies have confirmed that the K i values of malignant lesions are higher than those of benign lesions [9][10][11]. Our previous study also concluded that in lung cancer, the K i of metastatic LNs was higher than that of non-metastatic LNs (0.019 vs. 0.016/mLg/min, p = 0.001) [11]. However, studies evaluating the efficacy of ICIs in lung cancer were seldom seen. In this case, the enlarged LNs in the mediastinum and pulmonary hilar region after treatment raised our attention, and these LNs are more clearly seen from the K i images ( Figure 3E). Therefore, we studied the pre-treatment and post-treatment ratios of static and dynamic parameters ( Table 1) for chest lesions (including the upper lobe of the left lung, LN in the left pulmonary hilar region, and the right eighth rib). The results showed that both the primary left lung cancer focus (∆SUV max of 90.18%, and ∆K i of 85.52%) and the right eighth rib ratio were high (∆SUV max of 70.21%, and ∆K i of 68.22%), but the left hilar LN ∆SUV max was low (29.83%) and ∆K i was high (74.03%), and the trend of ∆K i remained consistent with the primary focus. As the patient did not undergo further puncture biopsy for enlarged LNs after the second 18 F-FDG PET/CT scan. It is not known at this time whether these enlarged LNs are metastatic LNs or benign LNs associated with ICI treatment. Therefore, we propose to hypothesize whether dynamic metabolic parameters (K i ) could provide additional metabolic information for the assessment of ICI efficacy. This deserves further investigation and is something we are studying.
duced. Other than that, tumor markers reviewed regularly during treatment were negative. However, the MRI (brain, follow up to March 2023) results at follow-up showed that the brain metastases did not shrink significantly, and enhanced on enhancement scans. Therefore, the clinical efficacy evaluation after four cycles of treatment was rated as stable disease (SD). As of our last follow-up (May 2023), the patient was on cycle 6 of treatment. So far, the general condition is good and no recurrent/metastatic lesions have been observed. We will follow up further on the patient's condition.

Figure 1. Initial scan:
We report the case of a 45-year-old male patient with a history of heavy smoking (10 years, 20 cigarettes/day) underwent an 18 F-fluorodeoxyglucose (FDG) PET/CT dynamic (chest, C,E,G) + static (whole-body, A,B,D,F) scan (December 2022) for diagnosis and pre-treatment staging. The abnormal serum tumor markers associated with lung cancer before 18 F-FDG PET/CT were CYFRA21-1 18.57 ng/mL (<3.3) and CA125 64.60 U/mL (<35.0). Before the 18 F-FDG injection, the patient had fasted for at least 6 h and had a pre-scan glucose level of 4.4 mmol/L. According to the body mass index, the chest region PET scans (dynamic) were initiated immediately after the injection of 18 F-FDG (7.07 mCi) from an intravenous indwelling needle. The total dynamic scans lasted for 65 min. Dynamic scan data were partitioned into 28 frames as follows: 6 × 10 s, 4 × 30 s, 4 × 60 s, 4 × 120 s, and 10 × 300 s. An additional whole-body static PET/CT scan was performed at the end of the dynamic acquisition. Quantitative parameters (Ki) were obtained through applying the irreversible two-tissue compartment model using in-house Matlab software. 18  . Before the 18 F-FDG injection, the patient had fasted for at least 6 h and had a pre-scan glucose level of 4.4 mmol/L. According to the body mass index, the chest region PET scans (dynamic) were initiated immediately after the injection of 18 F-FDG (7.07 mCi) from an intravenous indwelling needle. The total dynamic scans lasted for 65 min. Dynamic scan data were partitioned into 28 frames as follows: 6 × 10 s, 4 × 30 s, 4 × 60 s, 4 × 120 s, and 10 × 300 s. An additional whole-body static PET/CT scan was performed at the end of the dynamic acquisition. Quantitative parameters (K i ) were obtained through applying the irreversible two-tissue compartment model using in-house Matlab software. 18      , ∆SUV max (pretreatment SUV max − treatment SUV max /pre-treatment SUV max ) of 90.18%, and ∆K i (pre-treatment K i − treatment K i /pre-treatment K i ) of 86.67%. For the LNs, most of the LNs in the mediastinal region and pulmonary hilar regions were larger and FDG-avid than before treatment. Among them, although the left pulmonary hilar LN was larger than before, the FDG uptake and K i were reduced than before, size of 1.2 × 0.8 cm, SUV max of 4.0 (D), K i of 0.0060 /mLg/min (E), ∆SUV max of 29.83%, and ∆K i of 74.03%. The right eighth rib was also significantly smaller than before treatment, and FDG uptake was reduced, size of 4.5 × 1.8 cm, SUV max of 2.8 (F), K i of 0.0068 /mLg/min (G), ∆SUV max of 70.21%, and ∆K i of 68.22%. In addition, distant metastases were smaller than before and FDG uptake was reduced, including the retroperitoneal LN (not clearly shown), left adrenal gland (size of 1.8 × 1.2 cm, SUV max of 2.1, ∆SUV max of 75.0%), bone of the sacrum (size of 3.5 × 3.0 cm, SUV max of 2.1, ∆SUV max of 80.73%), left subcutaneous lumbar region (size of 0.9 × 0.8 cm, SUV max of 1.4, ∆SUV max of 81.58%), and brain (size of 1.0 × 0.8 cm, not uptake seen).

Conflicts of Interest:
All the authors have participated in the writing and revision of this article and take public responsibility for its content. The present publication is approved by all authors and by the responsible authorities where the work was carried out. All the authors confirm the fact that the article is not under consideration for publication elsewhere and has no conflict of interest.