Beth Chasen

Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors

Background Patients with advanced midgut neuroendocrine tumors who have had disease progression during first‐line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium‐177 (177Lu)–Dotatate in patients with advanced, progressive, somatostatin‐receptor–positive midgut neuroendocrine tumors. Methods We randomly assigned 229 patients who had well‐differentiated, metastatic midgut neuroendocrine tumors to receive either 177Lu‐Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long‐acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) (177Lu‐Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression‐free survival. Secondary end points included the objective response rate, overall survival, safety, and the side‐effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a prespecified interim analysis of overall survival was conducted and is reported here. Results At the data‐cutoff date for the primary analysis, the estimated rate of progression‐free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the 177Lu‐Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the 177Lu‐Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the 177Lu‐Dotatate group and 26 in the control group (P=0.004). Grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the 177Lu‐Dotatate group as compared with no patients in the control group, with no evidence of renal toxic effects during the observed time frame. Conclusions Treatment with 177Lu‐Dotatate resulted in markedly longer progression‐free survival and a significantly higher response rate than high‐dose octreotide LAR among patients with advanced midgut neuroendocrine tumors. Preliminary evidence of an overall survival benefit was seen in an interim analysis; confirmation will be required in the planned final analysis. Clinically significant myelosuppression occurred in less than 10% of patients in the 177Lu‐Dotatate group. (Funded by Advanced Accelerator Applications; NETTER‐1 ClinicalTrials.gov number, NCT01578239; EudraCT number 2011‐005049‐11.)

The prognostic value of interim positron emission tomography scan in patients with classical Hodgkin lymphoma

The prognostic value of interim positron emission tomography (PET) was evaluated after 2 cycles of doxorubicin, bleomycin, vinblastin and dacarbazine in classical Hodgkin lymphoma patients (n = 229), based on Deauville criteria. In early stage non‐bulky disease, bulky stage II disease, advanced stage low International Prognostic Score (IPS ≤2) and advanced stage (IPS ≥3), 3‐year progression‐free survival rates in PET2‐negative vs. PET2‐positive groups were 95·9% vs. 76·9% (P < 0·0018), 83·3% vs. 20·0% (P = 0·017), 77·0% vs. 30·0% (P < 0·001) and 71·0% vs. 44·4%(P = 0·155), respectively. The outcome after positive PET2 was better than previously reported. The results from non‐randomized studies of PET2‐guided therapy would be valuable with careful interpretation.

6LBA 177-Lu-Dotatate significantly improves progression-free survival in patients with midgut neuroendocrine tumours: Results of the phase III NETTER-1 trial

177-Lu-Dotatate significantly improves progression-free survival in patients with midgut neuroendocrine tumours : Results of the phase III NETTER-1 trial

Temporary Balloon Occlusion of the Common Hepatic Artery for Administration of Yttrium-90 Resin Microspheres in a Patient with Patent Hepatoenteric Collaterals

The most common serious complication of yttrium-90 ((90)Y) therapy is gastrointestinal ulceration caused by extrahepatic microsphere dispersion. The authors describe the use of a balloon catheter for temporary occlusion of the common hepatic artery to reverse hepatoenteric flow for lobar administration of resin microspheres when coil embolization of a retroportal artery was impossible. At 9 months after treatment, the patient had no gastrointestinal side effects and showed a partial response.

Bone Windows for Distinguishing Malignant from Benign Primary Bone Tumors on FDG PET/CT

Objective. The default window setting on PET/CT workstations is soft tissue. This study investigates whether bone windowing and hybrid FDG PET/CT can help differentiate between malignant and benign primary bone tumors. Materials and methods. A database review included 98 patients with malignant (n=64) or benign primary bone (n=34) tumors. The reference standard was biopsy for malignancies and biopsy or >1 year imaging follow-up of benign tumors. Three radiologists and/or nuclear medicine physicians blinded to diagnosis and other imaging viewed the lesions on CT with bone windows (CT-BW) without and then with PET (PET/CT-BW), and separate PET-only images for malignancy or benignity. Three weeks later the tumors were viewed on CT with soft tissue windows (CT-STW) without and then with PET (PET/CT-STW). Results. Mean sensitivity and specificity for identifying malignancies included: CT-BW: 96%, 90%; CT-STW: 90%, 90%; PET/CT-BW: 95%, 85%, PET/CT-STW: 95%, 86% and PET-only: 96%, 75%, respectively. CT-BW demonstrated higher specificity than PET-only and PET/CT-BW (p=0.0005 and p=0.0103, respectively) and trended toward higher sensitivity than CT-STW (p=0.0759). Malignant primary bone tumors were more avid than benign lesions overall (p<0.0001) but the avidity of benign aggressive lesions (giant cell tumors and Langerhans Cell Histiocytosis) trended higher than the malignancies (p=0.08). Conclusion. Bone windows provided high specificity for distinguishing between malignant and benign primary bone tumors and are recommended when viewing FDG PET/CT.

Cross sectional and nuclear medicine imaging of pancreatic insulinomas

Insulinomas are rare neuroendocrine tumors which occur predominantly in the pancreas. Although majority of the insulinomas are benign, over-secretion of insulin by the tumor leads to debilitating hypoglycemic symptoms. The diagnosis is based on clinical and biochemical findings. After the diagnosis is made, the principal challenge lies in locating the tumor because most tumors are solitary and small in size. Locating the tumor is of paramount importance as complete surgical excision is the only curative treatment, and incomplete resection leads to persistence of symptoms. Different preoperative and intraoperative imaging techniques have been used with varying success rates for the insulinoma imaging. Besides localizing the tumor, imaging also helps to guide biopsy, detect metastatic lesions, and perform image-guided therapeutic procedures. This review will discuss the role of different Cross sectional and nuclear medicine imaging modalities in insulinomas.

Health-Related Quality of Life in Patients With Progressive Midgut Neuroendocrine Tumors Treated With 177Lu-Dotatate in the Phase III NETTER-1 Trial

Purpose Neuroendocrine tumor (NET) progression is associated with deterioration in quality of life (QoL). We assessed the impact of 177Lu-Dotatate treatment on time to deterioration in health-related QoL. Methods The NETTER-1 trial is an international phase III study in patients with midgut NETs. Patients were randomly assigned to treatment with 177Lu-Dotatate versus high-dose octreotide. European Organisation for Research and Treatment of Cancer quality-of-life questionnaires QLQ C-30 and G.I.NET-21 were assessed during the trial to determine the impact of treatment on health-related QoL. Patients completed the questionnaires at baseline and every 12 weeks until tumor progression. QoL scores were converted to a 100-point scale according to European Organisation for Research and Treatment of Cancer instructions, and individual changes from baseline scores were assessed. Time to QoL deterioration (TTD) was defined as the time from random assignment to the first QoL deterioration ≥ 10 points for each patient in the corresponding domain scale. All analyses were conducted on the intention-to-treat population. Patients with no deterioration were censored at the last QoL assessment date. Results TTD was significantly longer in the 177Lu-Dotatate arm (n = 117) versus the control arm (n = 114) for the following domains: global health status (hazard ratio [HR], 0.406), physical functioning (HR, 0.518), role functioning (HR, 0.580), fatigue (HR, 0.621), pain (HR, 0.566), diarrhea (HR, 0.473), disease-related worries (HR, 0.572), and body image (HR, 0.425). Differences in median TTD were clinically significant in several domains: 28.8 months versus 6.1 months for global health status, and 25.2 months versus 11.5 months for physical functioning. Conclusion This analysis from the NETTER-1 phase III study demonstrates that, in addition to improving progression-free survival, 177Lu-Dotatate provides a significant QoL benefit for patients with progressive midgut NETs compared with high-dose octreotide.

Selected For Oral Presentation: Overall Survival, Progression-Free Survival, and Quality of Life Updates from the NETTER-1 Study : 177Lu-Dotatate Vs. High Dose Octreotide In Progressive Midgut Neuroendocrine Tumors

Pre-Treatment Tumor Growth Rate (TGR0) in Patients Diagnosed with Well-Differentiated Neuroendocrine Tumors (NETs) Treated with Systemic Therapies : Subgroup Analysis of the GREPONET StudySelected For Oral Presentation: Overall Survival, Progression-Free Survival, and Quality of Life Updates from the NETTER-1 Study : 177Lu-Dotatate Vs. High Dose Octreotide In Progressive Midgut Neuroendocrine TumorsSelected For Oral Presentation: Peptide Receptor Radionuclide Therapy (PRRT) in Gastroenteropancreatic Grade 3 Neuroendocrine Neoplasms : A Retrospective International Multicenter StudySelected For Poster Walks : Can Insulin-Like Growth Factor 1 (IGF-1), IGF-1 Receptor, Connective Tissue Growth Factor and Ki-67 Labelling Index Have a Prognostic Role in Pulmonary Carcinoids?Ex Vivo Activity of Cytotoxic Drugs and Targeted Agents in Small Intestinal Neuroendocrine TumorsA Prospective Nordic Study on the Use of Chromogranin A for the Prediction of Progression in Patients with Pancreatic and Small Intestinal Neuroendocrine TumorsPlasma Protein Kallikrein-14 Strongly Predicts Pronounced Chromogranin A (CgA) Response in Small Intestinal Neuroendocrine Tumor (NET) Patients after Somatostatin Analog (SSA) Treatment : The Nordic EXPLAIN Biomarker StudyIntravenous versus Oral Etoposide : Efficacy and Correlation to Clinical Outcome in Patients with High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms (WHO G3)

438PDImproved time to quality of life deterioration in patients with progressive midgut neuroendocrine tumors treated with 177Lu-DOTATATE: The NETTER-1 phase III trial

Improved time to quality of life deterioration in patients with progressive midgut neuroendocrine tumors treated with 177Lu-DOTATATE : The NETTER-1 phase III trial

177-Lu-Dotatate Significantly Improves Progression-Free Survival in Patients with Midgut Neuroendocrine Tumors : Results of the Phase III NETTER-1 Trial

177-Lu-Dotatate Significantly Improves Progression-Free Survival in Patients with Midgut Neuroendocrine Tumors : Results of the Phase III NETTER-1 Trial