Risk of treatment-altering haematological toxicity and its dependence on bone marrow doses in peptide receptor radionuclide therapy.

BACKGROUND: Peptide receptor radionuclide therapy is effective in treating neuroendocrine tumours, but treatment may be limited by kidney and bone marrow toxicity. In this work, the absorbed dose burden to the bone marrow was estimated using image-based dosimetry and its potential use for predicting treatment-altering toxicity was studied. Peripheral blood samples taken before and after 229 treatments with 177 Lu-DOTATATE in 59 patients were studied. In connection to the treatments, a total of 940 blood sample occasions provided data on white blood cell, neutrophil granulocyte, platelet, erythrocyte and haemoglobin concentrations. SPECT/CT image data were collected at two or three time points after each treatment. Absorbed doses to bone marrow were calculated from the activity concentration in a metastasis-free lumbar vertebra. The rate of delayed and aborted treatments was analysed based on medical records.

RESULTS: The average absorbed dose to the bone marrow was 0.42 Gy (median 0.33 Gy, SD 0.27 Gy) per treatment. Dose-response relationships between white blood cells, neutrophil granulocytes and haemoglobin concentrations were observed, most prominently at 31-45 days after each treatment. The correlations were stronger in patients with skeletal metastases. The rates of haematological toxicity-related delays and aborted treatments were 6% and 12%, respectively. None of the studied bone marrow dosimetric parameters could clearly predict treatment-related toxicity. However, patients with skeletal metastases had higher risk of treatment-altering toxicity (odds ratio = 6.0).

CONCLUSIONS: Treatment-altering haematological toxicity in peptide receptor radionuclide therapy is relatively rare and appears difficult to fully predict from post-therapeutic image-based dosimetry. However, for patients with skeletal metastases, the haematological dose-response relationships are stronger. Future studies may focus on this patient group, to further investigate the usefulness of dosimetry in predicting decreases in blood values.