Renal radiation during peptide receptor radionuclide therapy (PRRT) may result in glomerular damage, a potential reduction of glomerular filtration rate (GFR) and ultimately lead to renal failure. While reported PRRT nephrotoxicity is limited to data derived from serum creatinine—allowing only approximate estimates of GFR—the aim of this study is to accurately determine PRRT-induced long-term changes of renal function and associated risk factors according to state-of-the-art GFR measurement.

UNLABELLED:Myelosuppression may be the dose-limiting toxicity in peptide receptor radionuclide therapy (PRRT). The aim of this study was to investigate the incidence, severity, and reversibility of long-term hematotoxicity in a large cohort of patient undergoing PRRT with (177)Lu-octreotate for metastatic neuroendocrine tumors. The impact of potential risk factors, including initial cytopenia, advanced bone metastatic disease, previous chemotherapy, and cumulative administered activity, and the protective effects of splenectomy were of particular interest. METHODS:A total of 632 PRRT courses were performed in 203 patients with metastatic neuroendocrine tumors. A mean activity of 7.9 GBq of (177)Lu-octreotate was administered per treatment cycle, with a goal of 4 courses at standard intervals of 3 mo. Hematologic parameters were determined before each treatment course, at 2- to 4-wk intervals between the courses, 8-12 wk after the last course of PRRT, and at 3-month intervals for further follow-up. Toxicity was recorded with Common Terminology Criteria for Adverse Events (version 3.0). RESULTS:Myelodysplastic syndrome as a delayed adverse event was documented in 3 patients (1.4%). Relevant but reversible hematotoxicity (grade 3 or 4) occurred in 23 patients (11.3%) and 29 administrations (4.6%), with leukopenia in 2.7% and thrombocytopenia in 1.7%. The mean time to blood count recovery was 12 mo after the termination of PRRT (range, 3-22 mo). The only preexisting factor that contributed to hematotoxicity was initial cytopenia (P < 0.001). A high level of cumulative administered activity (>29.6 GBq) was associated with relevant leukopenia (P < 0.001). None of the patients with a history of splenectomy developed grade 3 or 4 hematotoxicity, and splenectomy was inversely associated with the incidence and degree of leukopenia (P = 0.02) and thrombocytopenia (P = 0.03). CONCLUSION:PRRT-induced myelosuppression is almost invariably reversible and rarely requires clinical measures. Administered activity and initial cytopenia are the only factors contributing to myelosuppression, whereas splenectomy may exert a protective effect.

1186 Objectives Renal radiation during peptide receptor radionuclide therapy (PRRT) may result in glomerular damage and reduction of glomerular filtration rate (GFR) and eventually may lead to renal failure years after PRRT. Serum creatinine and creatinine clearance allow only an approximate estimation of the GFR. The aim of this study was an accurate assessment of long -term changes in GFR using the 99mTc-DTPA clearance. Of particular interest was the impact of pre-existing risk factors. Methods GFR of 75 patients with gastroenteropancreatic neuroendocrine tumours (GEP-NET) treated with 177Lu-octreotate (4 intended cycles at 3 monthly intervals and mean activity of 7.9 GBq per cycle) were retrospectively analyzed. A minimum follow-up of 12 months was required for patient inclusion. Mean follow-up duration was 20 months (range 12-48 months), with a median of 5 GFR measurements per patient. The change of GFR was analyzed by linear curve fit. Potential risk factors including DM, HTN, previous chemotherapy and decreased renal function at baseline were analyzed regarding impact on the renal function loss. Comparability of nephrotoxicity determined by 99mTc-DTPA clearance and serum creatinine (using Common Terminology Criteria for Adverse Events v3.0) was also investigated. Results A reduction of >2 ml / year in GFR was observed in 31 (42%) and > 10ml/year in 16 patients (22%). The mean and median decline in GFR was 12 and 7 ml per year respectively. However, only one patient developed serious nephrotoxicity (CTCAE grade III). Eleven patients showed an increase of > 10 ml/year in GFR following PRRT. Nephrotoxicity graded according to serum creatinine (CTCAE) was not compatible with GFR in 17% of the assessments and was underestimated by serum creatinine in 12% of patients. None of the investigated risk factors contributed to a reduction in GFR. Conclusions Severe nephrotoxicity after PRRT with 177Lu-octrotate is rare (1.3 % of patients). However, mild renal function impairment (> 2 ml/year) is common and best monitored with 99mTc-DTPA clearance

1667 Objectives: Assessment of response and tolerability of receptor-mediated radionuclide therapy in gastroenteropancreatic neuroendocrine tumors (GEP-NET) using Lu-177-DOTA octreotate with prolonged intervals. Methods: We analyzed n=25 consecutive pts with inoperable GEP-NET (mean age 62 y [37-77]) and ≥ 2 treatment cycles (each with 7.4 GBq Lu-177-DOTA octreotate); minimum interval of 3 mo, renal protection with co-infusion of lysine-arginine-solution; dosimetry with serial post-therapeutic whole body imaging, Picker Prism 2000 with MEGP collimator, energy peaks at 113/208 keV. At baseline and during follow-up regular lab examinations including complete blood counts, hepatic and renal function tests, tumor markers including chromogranin A and NSE, monitoring of GFR (Tc-99m-DTPA clearance). Radiological response was assessed by CT and/or MRI using RECIST. Toxicity was classified according to CTC. Results: Preliminary response was as follows: all GEP-NET (n=25; mean 2.5 [2-4] courses per pt.) PR 9/25 (36%), MR 4/25 (16%), NC 10/25 (40%), PD 2/25 (8%) pts.; pancreatic NET (P-NET; n= 12, mean age 61 y [37-77], mean 2.6 courses per pt.) PR 58%, MR 25%, NC 16%; non-pancreatic GEP-NET (GE-NET; n=13, mean age 63 y, 42-75; mean 2.5 courses per pt.) PR 15%, MR 8%, NC 62%, PD 15%. Treatments were overall well tolerated, nausea was mostly transient and self-limiting (CTC 1-2), in one case (small bowel NET) a post-therapeutic GI-bleeding originating from the site of the primary was noted, no other relevant GI-toxicities were seen, transient hematotoxicity grade 3

SCHERER, M., et al.: Extension of Generator Longevity by Use of High Impedance Ventricular Leads. The resistance of a pacing lead negatively correlates to current consumption. A prospective, randomized trial was conducted to evaluate the effect of a high impedance ventricular lead (CapSure Z) on generator longevity compared to a conventional lead (CapSure SP) eighty‐nine patients were included in the study (51 male, 37 female, age 70.0 ± 10.3 years). Forty‐six patients received a CapSure SP lead (5024 bipolar), and 43 patients received a CapSure Z lead (5034 bipolar) in a randomized fashion. Follow‐up data collected at 5 days, 3, 6, and 12 months postimplant included: lead impedance, pacing and sensing thresholds, impulse energy, and estimated time to replacement. All parameters were collected via pacemaker telemetry; the time to replacement was calculated automatically by a programmed algorithm of the pacemaker. There was no difference in the performance of the atrial lead when a dual chamber device was indicated. The CapSure Z leads displayed statistically significant higher impedance values than the CapSure SP lead in all follow‐up periods. There was no significant difference in lead related complications. No significant differences were observed between pacing and sensing thresholds in both groups. The CapSure Z leads provided a significant reduction in current drain, resulting in a reduction of mean energy consumption at the 12‐month follow‐up from 10.4 ± 5.0 μJ in the CapSure SP group to 6.6 ± 1.4 μJ in the CapSure Z group (median from 9.9 μJ to 6.9 μJ, respectively), providing an estimated increase in mean longevity of more than 1 year from 81.1 ± 23.5 months in the CapSure SP group to 94.5 ± 13.4 months in the CapSure Z group (median: 76.5 months to 95.0 months, respectively). The use of a high resistance lead for ventricular pacing appears to result in a clinically relevant extension of generator longevity.

Die meisten antibradykarden Systeme bieten erweiterte diagnostische Speicher zur Erfassung atrialer bzw. ventrikulärer Rhythmusstörungen. Jedoch fehlte bisher zur Validierung dieser gespeicherten Ereignisse ein intrakardialer EKG-Speicher. Die DISCOVERY und PULSAR Schrittmachersysteme haben die Möglichkeit bis zu 20 intrakardiale Episoden mit einer Gesamtdauer von 80 Sekunden zu speichern. Die Aktivierung des Speichers erfolgt durch Vorhofarrhythmien, ventrikuläre Tachykardien, oder kann durch den Patienten selbst ausgelöst werden. Bei 87 Patienten wurde ein DISCOVERY oder ein PULSAR Schrittmacher implantiert. Die EKG-Speicher wurden bei allen Patienten kurz nach Implantation aktiviert und nach 1 Monat abgerufen. Einen Monat nach der Implantation zeigten 88% der Patienten in den abgespeicherten intrakardialen EKGs mehr als eine Arrhythmie-Episode. Insgesamt wurden 192 EKG’s gespeichert. In 12 Fällen erbrachten die intrakardialen EKGs zusätzliche klinisch relevante Informationen: undersensing (2), oversensing (8), multiple ventrikuläre Extrasystolen (1), Kammerflimmern als Todesursache (1). Intrakardiale EKG-Speicher bieten eine neue wertvolle diagnostische Möglichkeit, um klinisch relevante Arrhythmien und Schrittmacherdysfunktionen zu erkennen.