Lu177-DOTATATE therapy for NET: Does tumor dose predict response?

Objectives Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-DOTATATE is used to treat neuroendocrine tumors (NETs) which express somatostatin receptors. Though PRRT is an effective treatment (Tt) in many patients (pts), in others disease (ds) progression is seen. Post-Tt 177Lu image based personalized dosimetry can be used to monitor dose to tumors and organs and avoid bone marrow and renal toxicity. However, little has been reported about the radiation dose to tumors. In this study we examine whether low dose to tumor might be a factor in PRRT failure in pts with metastatic NET.

Methods 57 pts (21F/36M, mean age 59 ± 14, range 18-89 years) received a total of 146 177Lu-DOTATATE Tts (mean Tt dose 7.2±0.8 GBq, range 3.6-7.9 GBq, 1-5 Tts per pt). Tumor VOI’s were defined on post-Tt 177Lu images using GE Dosimetry Toolkit software, and beta dose to tumor was estimated and correlated with response as seen in clinical, laboratory and imaging follow-up.

Results 32/57 pts had a partial response, 15 stable ds and 10 progressed. Mean dose to tumor was 1.63 mGy/MBq (range 0.06-9.78). Tumor dose tended to change little over repeat Tts in the same pt (variance between pts 1.64, within pt 0.77). Distribution of mean tumor dose for each Tt in 57 pts in relation to Tt response is shown in the table. Higher tumor dose was not necessarily associated with favorable response. Low cumulative dose over serial Tts was also not a predictor of ds progression.

Conclusions This study found very variable radiation dose to tumor in PRRT, with no simple relation between dose and response to therapy. The results suggest that high dose may be unnecessary in some NET’s, where lower tumor dose may achieve adequate response while reducing dose to critical organs. For optimization of therapy, further work may elucidate factors determining tumor dose and its effect on success of PRRT.