Outcome analyses for patients with gastroenteropancreatic neuroendocrine tumors (GEP NET) after peptide receptor radionuclide therapy (PRRT) are still limited, especially with regard to the impact of the Ki-67 index. Using a single-center analysis, we aimed to establish predictors of survival. Methods: We retrospectively analyzed a consecutive cohort of 74 patients who had metastatic GEP NET and underwent PRRT with 177Lu-octreotate (mean activity of 7.9 GBq per cycle, aimed at 4 treatment cycles at standard intervals of 3 mo). Patients (33 with pancreatic NET and 41 with nonpancreatic GEP NET) had unresectable metastatic disease graded as G1 or G2 (G1/G2) and documented morphologic or clinical progression within less than 12 mo or uncontrolled disease under somatostatin analog treatment. Responses were evaluated according to modified Southwest Oncology Group criteria. Potential predictors of survival were analyzed with the Kaplan–Meier curve method (log-rank test) and multivariate analysis (P < 0.05). Results: The response rates were 36.5% partial response, 17.6% minor response, 35.1% stable disease, and 10.8% progressive disease for the entire cohort; 54.5% partial response, 18.2% minor response, 18.2% stable disease, and 9.1% progressive disease for pancreatic NET; and 22.0% partial response, 17.1% minor response, 48.8% stable disease, and 12.2% progressive disease for nonpancreatic GEP NET. The median progression-free survival and overall survival were 26 mo (95% confidence interval, 18.3–33.7) and 55 mo (95% confidence interval, 48.8–61.2), respectively. Besides the Ki-67 index, a Karnofsky performance score of less than or equal to 70%, a hepatic tumor burden of greater than or equal to 25%, and a baseline plasma level of neuron-specific enolase of greater than 15 ng/mL independently predicted shorter overall survival (hazard ratio, 2.1–3.1). Patients with a Ki-67 index of greater than 10% still had median progression-free survival and overall survival of 19 and 34 mo, respectively. Conclusion: The results of this study demonstrated the favorable response and long-term outcome of patients with G1/G2 GEP NET after PRRT. Independent predictors of survival were the Ki-67 index, the patient’s performance status (Karnofsky performance scale score), the tumor burden, and the baseline neuron-specific enolase level. Even patients with a Ki-67 index of greater than 10% seemed to benefit from PRRT, with a good response and a notable long-term outcome. We present the first evidence, to our knowledge, that even in patients with metastatic disease the distinction between G1 and G2—in particular, between G1 (Ki-67 index of 1%–2%) and low-range G2 (Ki-67 index of 3%–10%)—provides prognostic stratification.

e14565 Background: Outcome analyses of G1/2 NEN stage IV after peptide receptor radionuclide therapy (PRRT) are still limited, especially with regard to the impact of the Ki-67 index. This study aims to establish predictors of survival. Methods: Retrospective analysis of 74 consecutive GEP NET patients undergoing PRRT with 177Lu-octreotate. Patients had unresectable metastatic disease and a G1/2 grading (33 pancreatic, 41 non-pancreatic GEP- NET), documented morphologic or clinical progression within < 12 months and/or uncontrolled disease. Response (modified SWOG criteria) was correlated with potential impact factors: origin, function, burden, and uptake of tumor, age, Ki-67-index, Karnofsky score, baseline tumor marker levels. Predictors for survival were analyzed with Kaplan-Meier curves (log-rank test) and multivariate analysis (p<0.05). Results: The response rates were 36.5% PR, 17.6% MR, 35.1% SD, and 10.8% PD for the entire cohort, 54.5% PR, 18.2% MR, 18.2% SD, and 9.1% PD for pancreatic NET, and 22.0% PR, 17.1% MR, 48.8% SD, and 12.2% PD for non-pancreatic GEP-NET. The median progression-free (PFS) and overall (OS) survival was 26 months (95% CI, 18.3 - 33.7) and 55 months (95% CI, 48.8–61.2), respectively. The only factor associated with decreased PFS was a Ki-67 index >10% (p=0.002). For OS, besides the Ki-67 index, a Karnofsky score ≤70% and a baseline NSE of >15 ng/ml independently predicted shorter survival (each p<0.005, HR 3.0 - 3.4). Patients with a Ki-67 index >10% still had a median PFS and OS of 19 and 34 months, respectively. Conclusions: This study confirms the favorable outcome of G1/2 NET after PRRT. Independent predictors of survival are the Ki-67 index, the patient‘s performance status and the baseline NSE level. Nevertheless, patients with a Ki-67 >10% may still benefit from PRRT as demonstrated by the long-term outcome.

The role of the Ki-67 tumour proliferation index (PI) in predicting the efficacy of peptide receptor radionuclide therapy (PRRT) in gastroenteropancreatic tumours (GEP-NET) remains undetermined. This single-centre analysis focused on the potential therapeutic impact of this immunohistochemical parameter.

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

BACKGROUND:Morbus Ledderhose (ML) is a rare hyperproliferative disorder of the plantar aponeurosis which is similar in its clinical course to Morbus Dupuytren (MD). We examined whether radiotherapy (RT) can effect symptoms and prevent disease progression.PATIENTS AND METHODS:From June 1996 to December 2001, 25 patients (12 female/13 male) aged 9-76 (median: 56) years had radiotherapy (RT) for symptomatic ML. Follow-up (FU) was at least 1 year. 36 feet (16 right/20 left) were treated, as eleven patients had bilateral disease. Twelve (48%) patients had MD. There were 63 nodules (with 0,5-6,5 cm diameter) on all feet and 20 cords (with 1-4 cm length) on 13 (52%) feet prior to RT. 21 (84%) patients had one or more signs: 14 (56%) severe local pain, eight (32%) walking difficulties, twelve (48%) other symptoms, pressure or tension sensation. The RT field involved all nodules and cords plus safety margin. Two RT-series were applied (each 5 3 Gy in 1 week) separated by 8-12 weeks up to a total dose of 30 Gy. Evaluation was performed at the end of RT, after 3 and 12 months FU and in December 2002. The primary endpoint was prevention of disease progression and avoidance of surgery. Secondary endpoints were objective changes of morphological and functional parameters and patient's satisfaction measured on a visual analogue scale (VAS).RESULTS:With a median FU of 38 (12-67) months no patient experienced progression or underwent surgery: 11 of 36 (44%) feet had a reduced number (overall: -16) or size of nodules, 7 of 13 (54%) feet had a reduced number (overall: -9) or length of cords; gait was improved in six of twelve (50%) feet; pain was reduced or had completely disappeared in 9 of 15 (60%) feet, and other symptoms disappeared in 8 of 18 (44%) symptomatic feet. 20 (80%) patients regarded 28 of 36 (78%) treated feet as improved and 8 (22%) in stable condition. The median relative improvement stated by patients on the VAS was 50% (0-100%). Treatment side effects were minimal: During and within 3 months of the RT course only a slight erythema (CTC 1 degrees ) was seen in five treated lesions, while dry skin changes within the RT portal were observed in three cases (11%) in long term FU (> 12 months).CONCLUSIONS:Radiotherapy is effective in treating ML and may prevent otherwise necessary surgical interventions. Nodules, cords and symptoms regress, but long-term outcome of at least 5 years has to be awaited. Prospective phase III studies should confirm these results.

Der Morbus Ledderhose (ML) ist eine hyperproliferativeErkrankung der Plantaraponeurose, die dem Morbus Dupuytren (MD)sehr ähnlich ist. Wir prüften, ob eine Bestrahlung die Symptomelindern und die Progression der Erkrankung aufhaltenkann.

Trigeminal neuralgia (TN) is a disabling painful condition. It is characterized by sudden severe and intense attacks of stabbing or electrical-shock-like pain that are typically brief, lasting for a few seconds up to several minutes. TN pain is mostly unilateral, involving the innervation area of the trigeminal nerve. Each pain attack may come on spontaneously or be triggered by certain stimuli, usually in the affected areas of the face. Common triggers may include simple touch, talking, eating, drinking, chewing, tooth brushing and hair combing. In contrast, pinching or pressing these trigger points will not usually cause TN pain.