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Quantitative SSTR-PET/CT for predicting response and survival outcomes in patients with pancreatic neuroendocrine tumors receiving CAPTEM

Maria Ingenerf
Maria Ingenerf
, 
Homeira Karim
Homeira Karim
, 
Christoph Auernhammer
Christoph Auernhammer
, 
Matthias Zacherl
Matthias Zacherl
, 
Vera Wenter
Vera Wenter
, 
Michael Winkelmann
Michael Winkelmann
, 
Jens Ricke
Jens Ricke
, 
Frank Berger
Frank Berger
 und 
Christine Schmid-Tannwald
Christine Schmid-Tannwald
   | 30. Nov. 2023
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Article Category: Research Article
Online veröffentlicht: 30. Nov. 2023
Seitenbereich: 436 - 445
Eingereicht: 05. Juni 2023
Akzeptiert: 25. Sept. 2023
DOI: https://doi.org/10.2478/raon-2023-0055
Schlüsselwörter
© 2023 Maria Ingenerf et al., published by Sciendo
This work is licensed under the Creative Commons Attribution 4.0 International License.

FIGURE 1.

72-year-old male with responding liver metastases of pancreatic neuroendocrine tumor. on the pretherapeutic PET/CT (A, B) there were high tumor-to-liver (t/l) ratios. after three months of treatment with CAPTEM, both liver metastases showed a shrinkage in size, but also a significantly reduced uptake of 68ga-dotatate compared to pretherapeutic PET/ CT (C, D).CAPTEM = capecitabine and temozolomide
72-year-old male with responding liver metastases of pancreatic neuroendocrine tumor. on the pretherapeutic PET/CT (A, B) there were high tumor-to-liver (t/l) ratios. after three months of treatment with CAPTEM, both liver metastases showed a shrinkage in size, but also a significantly reduced uptake of 68ga-dotatate compared to pretherapeutic PET/ CT (C, D).CAPTEM = capecitabine and temozolomide

Cox regression analysis for overall survival (OS)

Univariable Multivariable
Exp (B) 95% CI p-value Exp (B) 95% CI p-value
Baseline
Age (years) 1.059 1.003–1.118 0.039 1.054 0.996–1.115 0.071
Sex 2.326 0.486–11.4 0.291
Grading
  G1 0.64
  G2 0 0 0.988
  G3 2.137 0.442–10.325 0.345
Ki-67 1.033 0.979–1.09 0.24
Chromgranin 1 1.0–1.0 0.572
Hepatic tumor burden 1.005 0.974–1.036 0.776
SUVmax LM 0.982 0.949–1.016 0.294
SUVmean LM 0.951 0.894–1.012 0.114
SUVmax Pankreas 0.962 0.916–1.011 0.125
SUVmean Pankreas 0.912 0.813–1.023 0.115
Tmax/Lmean 0.988 0.856–1.142 0.874
Tmean/Lmean 0.879 0.653–1.184 0.396
Tmax/Smean 0.83 0.516–1.336 0.443
Tmean/Smean 0.615 0.239–1.581 0.313
% change
CgA 1.006 1.0–1.012 0.046 1.003 0.996–1.01 0.448
SUVmax LM 1.004 0.99–1.018 0.563
SUVmean LM 1.006 0.99–1.022 0.493
HU LM 0.986 0.956–1.017 0.374
SUVmax Pankreas 1.006 0.998–1.013 0.118
SUVmean Pankreas 1.007 0.998–1.015 0.132
Tmax/Lmean 1 0.989–1.011 0.986
Tmean/Lmean 1.001 0.988–1.013 0.933
Tmax/Smean 1.014 1.002–1.026 0.02 1.008 0.971–1.046 0.68
Tmean/Smean 1.017 1.003–1.032 0.02 1.011 0.973–1.05 0.58
Size LM (mm) 1.011 0.991–1.031 0.289
Size Pancreas 1.004 0.986–1.023 0.672
Size total (RECIST) 1.009 0.988–1.031 0.409

Imaging and clinical parameters on baseline and follow-up imaging

Responder Non-Responder Baseline R vs. NR
Baseline Follow-up p-value baseline vs. FU Baseline Follow-up p-value baseline vs. FU p-value
Age (years) 66 (56–75) 69 (57–82) 0.44
Grading 13 (7–20) 10 (4–15) 0.33
  G1 0 1
  G2 6 11
  G3 4 0
Ki-67 (%) 12.5 (7.3–20) 10 (4.3–15) 0.33
Male sex 7 (70%) 10 (83%)
Chromogranin A 796 (512–2756) 270 (102–1136) < 0.04 178 (90–845) 198 (96–1071) < 0.02 0.06
Bilirubin (mg/dl) 0.6 (0.60.88) 0.85 (0.5–1.1) 0.64 0.6 (0.43–0.9) 0.55 (0.33–0.88) > 0.99 0.45
Hepatic tumor burden (%) 35 (5–40) 13 (5–33) 0.16 13 (5–38) 15 (5–38) 0.25 0.42
SUVmax LM 47 (24–62) 21 (13–46) < 0.04 24 (13–43) 21 (11–39) 0.15 < 0.02
SUVmean LM 30 (15–38) 15 (11–24) 0.04 14 (9–22) 11 (8–17) 0.40 < 0.0004
Tmax/Lmean 6.9 (3.2–11.3) 2.8 (1.6–8.3) 0.03 3.6 (2.0–5.8) 3.2 (1.5–5.5) 0.6 0.0192
Tmean/Lmean 4.8 (2.0–6.8) 1.9 (1.2–3.9) 0.02 2.1 (1.4–2.9) 1.6 (1.1–2.6) 0.05 0.0061
Tmax/Smean 2.0 (1.4–4.1) 0.9 (0.5–3.0) 0.01 1.3 (0.5–1.9) 1.3 (0.4–2.2) 0.12 0.0469
Tmean/Smean 1.4 (0.8–2.1) 0.7 (0.4–1.5) 0.007 0.7 (0.4–1.1) 0.6 (0.3–1.1) 0.19 0.0094
Size LM (mm) 32 (24–42) 20 (14–32) < 0.0001 27 (17–36) 30 (18–43) 0.12 0.10
HU LM 106 (88–116) 106 (95–126) 0.41 92 (85–108) 90 (68 –104) 0.02 0.09
SUVmax pNET 26 (14–47) 26 (16–41) 0.94 30 (12–59) 28 (16–45) 0.2 0.68
SUVmean pNET 17 (9–22) 18 (13–28) 0.81 15 (9–33) 15 (15–30) 0.57 0.98
Size pNET 35 (25–38) 20 (14–37) 0.03 34 (20–47) 34 (23–54) 0.81 0.92
HU pNET 105 (77–113) 94 (88–98) 0.79 107 (81–117) 92 (81–100) 0.15 0.89

Cox regression analysis for progression free survival (PFS)

Univariable Multivariable
Exp (B) 95% CI p-value Exp (B) 95% CI p-value
Baseline
Age (years) 1.037 0.995–1.082 0.084
Sex 1.105 0.324–2.528 0.849
Grading
   G1 0.251
  G2 0 0 0.985
  G3 2.913 0.827–10.625 0.096
Ki-67 1.02 0.978–1.063 0.362
Chromogranin 1 1 0.989
Hepatic tumor burden 0.98 0.955–1.006 0.125
SUVmax LM 0.979 0.951–1.007 0.134
SUVmean LM 0.982 0.94–1.025 0.41
SUVmax Pancreas 0.983 0.956–1.01 0.21
SUVmean Pancreas 0.975 0.93–1.023 0.3
Tmax/Lmean 0.922 0.821–1.037 0.175
Tmean/Lmean 0.886 0.72–1.09 0.251
Tmax/Smean 0.588 0.373–0.927 0.022 0.626 0.365–1.076 0.09
Tmean/Smean 0.474 0.223–1.004 0.051
% change
CgA 1.004 1–1.008 0.056
SUVmax LM 1.002 0.99–1.013 0.792
SUVmean LM 0.998 0.986.1.009 0.686
HU LM 0.999 0.975–1.024 0.948
SUVmax Pancreas 1.002 0.996–1.008 0.451
SUVmean Pancreas 1.002 0.995–1.009 0.512
Tmax/Lmean 1.003 0.992–1.013 0.623
Tmean/Lmean 0.99 0.989–1.009 0.836
Tmax/Smean 1.006 0.99–1.013 0.079
Tmean/Smean 1.006 0.998–1.013 0.149
Size LM (mm) 0.999 0.983–1.015 0.908
Size Pancreas 1.018 1.001–1.034 0.037 1.009 0.99–1.009 0.37
Size total (RECIST) 1.014 0.993–1.036 0.183

Patient characteristics

Sex
  Male 17 (77%)
  Female 5 (23%)
Median age, years (range) 66 (40–85)
Grading
  G1 1 (5%)
  G2 17 (77%)
  G3 4 (18%)
Median Ki-67 (ng/ml, range) 12 (2–40)
Treatment with CAPTEM
  Duration of treatment (month, range) 7.5 (3–20)
  Prior treatment 16 (73%)
  pNET resected 6 (27%)
  Prior medical treatment 9 (41%)
  Prior PRRT 6 (27%)
  Prior liver targeted therapy 6 (27%)
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