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Clinical score helps gauge benefit from radionuclide therapy for NETs

JAMA Network Open
Reuters Health - 19/01/2022 - A validation study supports the use of a clinical scoring system to anticipate whether patients with well-differentiated neuroendocrine tumors (WD NETs) will benefit from peptide receptor radionuclide therapy (PRRT) with lutetium-177 (177Lu)-dotatate.

Despite the benefit from 177Lu-dotatate for patients with WD NETs, "questions remain about when to sequence the therapy for patients in relation to other available therapies, and which patients are optimal candidates for the therapy," Dr. Satya Das of Vanderbilt-Ingram Cancer Center and University Medical Center in Nashville, Tennessee, and colleagues point out in JAMA Network Open.

The clinical score (CS) they developed includes five factors (each given a score of zero, one or two): 1) symptoms necessitating treatment (two points for Grade 2+ symptoms, one point for Grade 1 symptoms); 2) tumor bulk in critical organs; 3) non-PRRT treatments available based on primary tumor origin; 4) peritoneal carcinomatosis presence; 5) prior system therapy.

The CS was associated with progression-free survival (PFS) in the original cohort of 122 patients with WD NETs treated with 177Lu-dotatate at Vanderbilt-Ingram Cancer Center.

The validation cohort included the original 122 patients plus 126 additional patients with WD NETs treated at three other high-volume NET centers.

Increases in CS were associated with worsening PFS in the validation cohort, validating findings from the original cohort and demonstrating that the CS is "the first established clinical metric to prognosticate the anticipated benefit from PRRT with lutetium dotatate for an individual patient," Dr. Das told Reuters Health by email.

For each two-point increase in CS, patients were 2.5 times as likely to experience disease progression or death, the researchers found.

Among patients receiving three to four doses of PRRT, patients with lower CS (<= 4) derive a significant benefit from the therapy compared to patients with a higher CS (>4).

"This suggests that utilizing PRRT when patients are less pretreated and possess less extensive metastatic disease, may improve the efficacy of the treatment," Dr. Das said.

"Further, patients who received one to two doses of PRRT experienced the worst outcomes, suggesting that perhaps a minimum of three doses of PRRT are necessary to create the essential degree of DNA damage in NETs," Dr. Das said.

"The CS is ready for clinical use in my view and we are already using it in the clinic at Vanderbilt-Ingram Cancer Center to inform patients. The paper will be open access so figure 1 (which shows how to derive the CS) and Figure 2/Figure3 (which have the anticipated outcomes based on CS score) are all readily available online," Dr. Das told Reuters Health.

This work was supported by grants from the Vanderbilt-Ingram Cancer Center Gastrointestinal SPORE Career Enhancement Program and the Vanderbilt Digestive Disease Research Center. The authors have no relevant disclosures.

SOURCE: https://bit.ly/3nDkP5S JAMA Network Open, online January 19, 2022.

By Megan Brooks

© 2023 The Author(s). Published by Medicom Medical Publishers.
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