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.