Abstract
Simple SummaryWe compared the safety and efficacy of targeted radionuclide therapy between elderly (79 years old and older) and disease-matched younger patients (between 60 and 70 years of age) with metastatic neuroendocrine tumour (NET). To our knowledge, this is the first paper addressing this important clinical question of the outcome of radionuclide therapy in this particularly vulnerable population. We found that targeted radionuclide therapy did not cause increased side effects in the elderly NET population, while toxicity remains modest and comparable in both groups. We also find that survival (after adjusting for differences in life expectancy) is not inferior for the elderly compared to younger NET patients.Peptide receptor radionuclide therapy (PRRT) is a well-established treatment in somatostatin receptor-expressing neuroendocrine tumours (NETs). The safety and efficacy of PRRT in >79 years old patients (EP) have not been systematically investigated. All patients with inoperable/metastatic/progressive G1/G2 NET, >79 years (EP), treated with PRRT at the University Hospital of Basel between 2006 and 2018, were enrolled in this retrospective matched cohort study. Each patient was manually matched with ≥1 younger patient (YP = 60–70 years). The primary endpoint was toxicity. Toxicity (subacute, long-term) was graded according to the criteria for adverse events (CTCAE) v5.0. All toxicity grades ≥ 3, or whose delta (Δ) to baseline were ≥2, were considered significant. The odds ratio (OR) for developing toxicity was tested for non-inferiority of EP vs. YP. Clinical response to PRRT and overall survival (OS) were assessed as secondary outcome measures. Forty-eight EP and 68 YP were enrolled. Both cohorts were balanced regarding median time since diagnosis, tumour location, grading, treatment scheme, and baseline biochemical parameters, except for eGFR (EP: 61 ± 16 vs. YP: 78 ± 19; mL/min/1.73 m2). Twenty-two grade ≥ 3 or Δ ≥ 2 subacute hematotoxicities occurred in 10 EP (10.3% of cycles) and 37 in 19 YP (11.6% of cycles; p = NS). Long-term grade ≥ 3 renal toxicity occurred in 7 EP and 2 YP (p = NS). The median OS was 3.4 years (EP) vs. 6.0 years (YP), HR: 1.50 [0.75, 2.98], p = NS. PRRT is a valid therapeutic option in elderly NET patients with similar toxicity and non-inferior survival compared to matched younger patients.
Highlights
Neuroendocrine tumours (NETs) frequently overexpress somatostatin receptors, in particular subtype 2, on the tumour cell membrane
The main results of this study can be summarised as follows: (1) Despite a reduced haematological functional reserve, a lower estimated glomerular filtration rate (eGFR) and more comorbidities with a trend for a reduced WHO/ECOG status at the beginning of therapy, Peptide receptor radionuclide therapy (PRRT) did not result in increased toxicity in the elderly patients (EP). (2) overall survival (OS) was reduced in the EP and younger patients’ cohort (YP) compared to the reference population, the reference-related time scale was not inferior in the EP compared to the YP
Our study shows that EP with functional activity were treated with somatostatin analogues for symptom control as frequently as the YP cohort; in the case of non-secreting neuroendocrine tumours (NETs), somatostatin analogues tended to be more frequently discontinued upon tumour progression prior to PRRT
Summary
Neuroendocrine tumours (NETs) frequently overexpress somatostatin receptors, in particular subtype 2 (sst2), on the tumour cell membrane. These somatostatin receptors represent important molecular targets for imaging and therapy, using either radiolabelled or “cold” peptide analogues [1,2,3,4,5,6,7]. In the NETTER-1 trial, the mean age was only 63 ± 9 years and 83% of the patients tolerated 3 or 4 fractions of PRRT with 177 Lu-DOTATATE well with moderate, mostly reversible haematological and without significant renal toxicity [2,9]. Elderly patients (EP) more frequently have comorbidities, exhibit an impaired glomerular filtration rate, and have a reduced haematological reserve and may, be at increased risk for PRRT-induced toxicity This may explain why EP are less frequently treated with PRRT [10]
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