Letter to the Editor: “The Inflammation-Based Index Can Predict Response and Improve Patient Selection in NETs Treated With PRRT: A Pilot Study”

We read with interest the article by Black et al. (1) in the February issue of Journal of Clinical Endocrinology & Metabolism. Black et al. (1) presented an inflammation-based index as a novel predictive biomarker for peptide receptor radionuclide therapy (PRRT) in patients with gastroenteropancreatic neuroendocrine tumors (2, 3). Their findings are of interest within the continued search for accurate predictors of response to PRRT. However, replication is needed, and several key considerations are crucial before applying this biomarker in clinical practice.

First, the circulating levels of inflammatory markers are more likely to constitute prognostic, rather than predictive, markers because they will correlate with disease severity (4). It is unclear from the report whether the differences were present in the rate of progression at baseline between the groups with a normal or an elevated inflammation-based index. Conceptually, tumors with a more aggressive phenotype will be more likely to induce systemic inflammation. However, the presence of a less favorable prognosis should not lead to refraining from a potentially effective therapy. Rather, this should be an argument for therapy. Similar thoughts have been considered for grade 3 neuroendocrine neoplasms. However, the efficacy of PRRT for these patients was, nonetheless, recently found to be superior to all other reported therapies for this subset (5).

Second, it is uncertain, at present, whether this inflammatory biomarker possesses similar predictive characteristics for the alternative neuroendocrine tumor (NET) therapies, such as everolimus and sunitinib. Importantly, the progression-free survival after treatment with these drugs was 11 months (6, 7), comparable to the 9 to 11 months obtained using PRRT for patients with an elevated inflammation-based index.

Finally, 9% of patients did not complete all four cycles because of insufficient uptake found on the post-therapy scan. This percentage would appear high if the patients had been selected by somatostatin receptor imaging before therapy. Uptake on somatostatin receptor imaging has been proven as a prerequisite for PRRT and predictive of its outcome (8). However, this was not confirmed in the study by Black et al. (1). In their study, a maximal standardized uptake value (SUVmax) of 18.7 was used as the cutoff value for the prediction of response in 42 patients. This SUVmax did not have a significant effect on survival. It remains, however, unclear on what data this SUVmax had been based and which imaging modality and tracer had been used for inclusion in their study. Also, because their study had included patients who had been treated since 2008, the routine use of gallium-68–labeled somatostatin analogs was not yet available. Their reported use of the Krenning scale is not valid for post-therapy ¹⁷⁷Lu-DOTATATE imaging, because this tool has only been validated for use with ¹¹¹In-pentetreotide (Octreoscan^®). This underscores the need for proper patient selection through somatostatin receptor imaging before the administration of PRRT. Whether the inflammation-based index possesses a similar predictive value for PRRT should be subject to further research. However, from the report by Black et al. (1), PRRT should not be withheld from patients with a high inflammation-based index. This has been further supported by the lack of a hypothesis for the reason the effect of local β-irradiation would be reduced in the presence of systemic inflammation.

Additional Information

Disclosure Summary: The authors have nothing to disclose.