SPECT/CT Image-Derived Absorbed Dose to Red Marrow Correlates with Hematologic Toxicity in Patients Treated with [177Lu]Lu-DOTATATE

Johan Blakkisrud; Avery B. Peterson; Scott J. Wildermann; Griffen Kingkiner; Ka Kit Wong; Chang Wang; Kirk A. Frey; Caroline Stokke; Yuni K. Dewaraja

doi:10.2967/jnumed.123.266843

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FIGURE 1.
Overview of RM absorbed dose calculation from SPECT/CT images, via segmentation, registration, and time–activity fitting/integration and microscale/macroscale MC simulation. Arrows in example patient SPECT/CT images show vertebrae with focal uptake due to bone lesion that was not included in analysis. Created with BioRender.com.
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FIGURE 2.
Vertebral absorbed doses with patient median and 95% CI. Pnum = patient number.
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FIGURE 3.
Bland–Altman plot illustrating differences between dose metrics D_{median,lumbar} (A), D_{median,thoracic} (B), and D_{average,vertebrae} (C) compared with D_{median,vertebrae}. Each data point represents individual treatment cycle.
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FIGURE 4.
Box plots describing platelet count (A), absolute lymphocyte count (B), hemoglobin (C), and absolute neutrophil count (D) sampled before each treatment cycle and at 3- and 6-mo follow-up. Overlaid swarm plots are with individual datapoints. Dashed, dashed–dotted, and solid lines indicate levels for Common Terminology Criteria for Adverse Events of grades 2, 3 and 4, respectively. ALC = absolute lymphocyte count; ANC = absolute neutrophil count; HB = hemoglobin; PLT = platelet count.
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FIGURE 5.
Relationship between averaged absorbed dose and relative number of platelets (A–C) and neutrophils (D–F) compared with baseline. (A and D) Absorbed dose in treatment cycle 1 correlated with relative blood counts after first cycle. (B and E) Sum of first 3 absorbed dose to RM and relative blood count value before last treatment cycle. (C and F) Cumulative absorbed dose from all 4 cycles and relative blood count value 6 mo after last treatment. ANC = absolute neutrophil count; PLT = platelet count.

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TABLE 1.

Patient Characteristics

Characteristic	Data
Sex
Female	6
Male	14
⁶⁸Ga-DOTATATE-identified bone lesions
Yes	8
No	12
Age (y)	66 (48–76)
Patients with blood values between treatment fractions	20^*
Patients with blood values at 3-mo follow-up	19^†
Patients with blood values at 6-mo follow-up	14
Previous chemotherapy^‡	0 (0–4)

↵* One patient was missing platelets.
↵† Two patients were missing absolute neutrophil count.
↵‡ Four patients had previously received capecitabine plus temozolomide and everolimus; 2 patients, capecitabine plus temozolomide; 2 patients, everolimus; 1 patient, 2 cycles of PRRT; 1 patient, capecitabine plus temozolomide plus etoposide; and 1 patient, capecitabine plus temozolomide, everolimus, sunitinib, and temozolomide.
Qualitative data are number; continuous data are median and range.

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TABLE 2.

Significant Correlations Between Absorbed Dose Metrics and Hematologic Toxicity

Absorbed dose parameter^*	Toxicity parameter	r	P	n
D_{median,thoracic} (C3)	ANC_abs (before cycle 4)	−0.55	0.014	19
D_{median,thoracic} (C1)	PLT_ratio (before cycle 2)	−0.47	0.038	20
D_{median,thoracic} (C3)	PLT_ratio (before cycle 4)	−0.52	0.019	20
D_{median,thoracic} (C3)	PLT_abs (before cycle 4)	−0.45	0.049	20
D_{median,thoracic} (C1)	HB_ratio (before cycle 2)	−0.59	0.006	20
D_{median,thoracic} (C2)	HB_abs (before cycle 3)	−0.51	0.022	20
D_{median,vertebrae} (C1)	PLT_ratio (before cycle 2)	−0.51	0.023	20
D_{median,vertebrae} (C2)	HB_abs (before cycle 3)	−0.45	0.048	20
D_{median,lumbar} (C1)	PLT_ratio (before cycle 2)	−0.48	0.034	20
D_{median,lumbar} (C3)	PLT_ratio (before cycle 4)	−0.51	0.021	20
D_{median,lumbar} (C3)	PLT_abs (before cycle 4)	−0.52	0.020	20
D_{median,lumbar} (C3)	HB_ratio (before cycle 4)	−0.48	0.034	20
D_{average,vertebrae} (C1)	PLT_ratio (before cycle 2)	−0.50	0.025	20
D_{average,vertebrae} (C3)	PLT_ratio (before cycle 4)	−0.46	0.040	20
D_{average,vertebrae}	PLT_ratio (6-mo)	−0.66	0.010	14
D_{average,vertebrae}	PLT_abs (3-mo)	−0.50	0.031	19
D_{average,vertebrae}	ALC_abs (3-mo)	−0.55	0.023	17
D_{median,vertebrae}	PLT_ratio (6-mo)	−0.64	0.015	14
D_{median,vertebrae}	PLT_abs (3-mo)	−0.49	0.032	19
D_{median,vertebrae}	ALC_abs (3-mo)	−0.55	0.022	17
D_{median,lumbar}	PLT_ratio (6-mo)	−0.72	0.004	14
D_{median,lumbar}	PLT_abs (6-mo)	−0.60	0.023	14
D_{median,lumbar}	PLT_abs (3-mo)	−0.59	0.007	19
D_{median,lumbar}	ALC_abs (3-mo)	−0.53	0.029	17
D_{median,thoracic}	PLT_ratio (6-mo)	−0.58	0.029	14
D_{median,thoracic}	PLT_abs (3-mo)	−0.52	0.022	19