Diabetes Mellitus and Its Effects on All-Cause Mortality After Radiopeptide Therapy for Neuroendocrine Tumors

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FIGURE 1.
(A) DOTATOC comprises somatostatin analog TOC and chelator DOTA for radiolabeling. Radiolabeled DOTATOC is injected intravenously and binds to G-protein–coupled somatostatin receptor subtype 2 on cell surface (B), internalizes via clathrin-mediated endocytosis (C), and enables tumor treatment via β⁻-emission (D). (E) Detection of γ-emission allows visualization of tumor uptake and biodistribution of radiolabeled DOTATOC. Potential adverse events may result from biodistribution of DOTATOC.
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FIGURE 2.
Study profile.
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FIGURE 3.
(A) Estimation of difference between binomial- and Aalen–Johansen estimator comparing incidence of diabetes mellitus before and after DOTATOC treatment showing significant peak before treatment and no significant increase after treatment. (B) Survival after DOTATOC in patients with and without diabetes mellitus showing no significant difference. (C) Cumulative hazard of diabetes mellitus after 3 treatment modalities showing cumulative hazard of 0 after ¹⁷⁷Lu-DOTATOC and similar cumulative hazard after treatments with ⁹⁰Y-DOTATOC and ⁹⁰Y plus ¹⁷⁷Lu DOTATOC.

TABLE 1

Patient Baseline Characteristics (n = 1,535)

Characteristic	⁹⁰Y-DOTATOC (n = 1,093)	¹⁷⁷Lu-DOTATOC (n = 141)	¹⁷⁷Lu-DOTATOC plus ⁹⁰Y-DOTATOC (n = 301)	All patients (n = 1,535)
Sex
Female	471 (43.1%)	59 (41.8%)	120 (39.9%)	650 (42.3%)
Male	622 (56.9%)	82 (58.2%)	181 (60.1%)	885 (57.7%)
Age (y)
Median	58.9	62.4	59.0	59.2
Range	11.2–86.5	14.8–83.4	23.2–82.1	11.2–86.5
Disease duration (mo)
Median	22.8	16.6	18.7	21.8
Range	0.0–460.0	1.2–374.7	0.8–623.4	0.0–623.4
Pretreatment
Surgery	597 (54.6%)	79 (56.0%)	194 (64.5%)	870 (56.7%)
Chemotherapy	344 (31.5%)	46 (32.6%)	82 (27.2%)	472 (30.7%)
Radiation	143 (13.1%)	17 (12.1%)	31 (10.3%)	191 (12.4%)
Pancreas surgery	301 (27.5%)	25 (17.7%)	81 (26.9%)	407 (26.5%)
DOTATOC cycles
Median	2	2	3	2
Range	1–10	1–5	2–11	1–11
Cumulative activity in MBq (mCi)
Median	12,950 (350)	14,800 (400)	22,200 (600)	14,060 (380)
Range	1,665–62,160 (45–1,680)	7,400–37,000 (200–1,000)	11,840–60,310 (320–1,630)	1,665–62,160 (45–1,680)
Histology
Carcinoids	482 (44.1%)	61 (43.3%)	145 (48.2%)	688 (44.8%)
pNET	326 (29.9%)	26 (18.4%)	88 (29.2%)	440 (28.7%)
Rare NET	100 (9.1%)	24 (17.0%)	26 (8.6%)	150 (9.8%)
Unknown primary	185 (16.9%)	30 (21.3%)	42 (14.0%)	257 (16.7%)
Diabetes mellitus at baseline	124 (11.3%)	24 (17.0%)	38 (12.6%)	186 (12.1%)

TABLE 2

Predictors for Diabetes Mellitus (n = 1,535)

Variable	HR^*	P
Sex (female vs. male)	1.102 (0.767–1.795)	0.698
Age (per y)	0.998 (0.978–1.017)	0.806
Duration of disease (per mo)	1.002 (0.997–1.007)	0.393
Previous surgery (vs. no surgery)	0.973 (0.579–1.633)	0.916
Previous chemotherapy (vs. no chemotherapy)	0.712 (0.394–1.287)	0.261
Previous radiation (vs. no radiation)	0.679 (0.251–1.840)	0.447
¹⁷⁷Lu-DOTATOC (vs. ⁹⁰Y-DOTATOC)	0.000 (0.000–0.498)	—
Combination treatment (vs. ⁹⁰Y-DOTATOC)	1.023 (0.542–1.931)	0.945
Cumulative activity (per 1 mCi/37MBq)	1.000 (0.999–1.001)	0.622
pNET (vs. carcinoid)	2.306 (1.364–3.897)	0.002
Rare NET (vs. carcinoid)	0.796 (0.261–2.431)	0.688
Unknown primary (vs. carcinoid)	0.586 (0.222–1.550)	0.282

↵* Estimates for each variable have been adjusted for all other variables listed.
pNet = pancreatic neuroendocrine tumors.
Data in parentheses are 95% CIs.