Figure 5: Daily blood glucose levels over the course of 4 months after redebulking
Mean daily blood glucose levels (black) over the course of 4 months after redebulking surgery and under monthly treatment with Lanreotide. Interquartile-range (dark blue) containing 50% and interdecile-range (light blue) containing 80% of measured blood glucose levels. No more hypoglycemic episodes have been reported since redebulking surgery.

Discussion

DPS is defined as hypoglycemia caused by paraneoplastic secretion of Big-IGF-II associated with intrathoracic SFT. This condition is relatively rare, occurring in only 5% of patients with an SFT [6][7]. Locally recurrent DPS is particularly uncommon, reported in only 10 % of cases [3]. As their name implies, these tumors are usually solitary and fibrous. However, the patient presented with multiple recurrent lesions of the lung, pleura and pericardial fat tissue. Gross tumor morphology had transformed into an atypical gelatinous, liquified tissue, with now increased proliferation rate up to 15% underlying the early recurrence, which has not yet been described in the literature.
Early symptoms of hypoglycemia in patients with DPS include nervousness, sweating, tachycardia, and tremors, among others. In advanced stages, patients may develop headaches, confusion, syncopes, seizures, and central respiratory/circulatory disorders [23]. Elevated IGF-II levels may also lead to acromegaloid skin changes [10][11]. In November 2022 the advanced age of the patient combined with late hypoglycemic symptoms such as confusion and syncopes required immediate symptomatic treatment.
Complete resection is considered the most promising treatment for patients with DPS. In this case however, due to the unique tumor morphology and the pericardial involvement, an R0 resection was deemed unfeasible. The advanced age of the patient and her personal preferences rendered chemotherapy or radiotherapy untenable, as well. Instead, we started a symptomatic treatment with intravenous glucose infusions to bridge the time until a second debulking surgery. In many cases this has been reported as a sufficient strategy to prevent further hypoglycemia [3].
Although described as ineffective in current literature [20] an adjuvant treatment with Octreotide was initiated, because [68Ga]DOTATATE/PET-CT scanning revealed SSTR-expression of parts of the tumor lesions. Only in combination with Octreotide, intravenous glucose infusions successfully prevented fatal hypoglycemic episodes below 30 mg/dl (1.7 mmol/l) (Figure 3). These findings are consistent with the reduced intensity and frequency of hypoglycemic episodes in a 67-year-old patient with DPS treated with Octreotide [21]. Octreotide was later changed to Lanreotide, a longer-acting analogue of somatostatin after repeated surgical reduction of tumor mass.
Octreotide and Lanreotide bind to SSTR (preferentially type 2 and 5) and significantly inhibit proliferation and paraneoplastic secretion of SSTR-expressing neuroendocrine tumors [24][25]. [68Ga]DOTATATE/PET-CT enables especially the visualization of SSTR-2-expression in tumors [26]. Previous case reports described increased uptake in SSTR-PET/CT in a SFT [27]. To identify SSTR-positive lesions, a [68Ga]DOTATATE/PET-CT was performed prior to initiation of somatostatin-analogue treatment. This scan revealed variable SSTR positivity in parts of the tumor mass (Figure 2). Therefore, it was not inconceivable that somatostatin-analogue treatment could be potentially effective in reducing paraneoplastic secretion of IGF-II-derivatives and hypoglycemic tendency, and even slow down tumor progression in an SSTR expressing SFT as well. Due to the inability to achieve R0 resection and the rapid tumor progression after her first debulking surgery, the patient therefore continued somatostatin-analogue treatment after the second debulking surgery with the aim to potentially suppress rapid tumor proliferation and recurrence of hypoglycemia. Since then, no further hypoglycemic episodes have been reported (Figure 5). The influence of somatostatin-analogues on tumor progression of intrathoracic SFT remains elusive, and further research is needed to investigate their efficacy in recurrent DPS. The unique tumor-morphology of the patient and the successful mitigation of symptoms using Octreotide in combination with intravenous glucose will help clinicians to deal with similar cases in the future.
We conclude that somatostatin-analogues hold the potential of being effective in conjunction with limited surgical approaches for the treatment of hypoglycemia in recurrent or non-totally resectable SFT entities underlying DPS.

Declarations

Ethical statement: We declare that the work submitted to Cancer Reports has been done in accordance to „Wiley’s Publication Ethics“ guidelines and that is has been performed in an ethical and responsible way, with no research misconduct, which includes, but is not limited to data fabrication and falsification, plagiarism, image manipulation, unethical research, biased reporting, authorship abuse, redundant or duplicate publication, and undeclared conflicts of interest.