Safety and efficacy of re-treatment with [177Lu]Lu-DOTA-Octreotate radionuclide therapy in progressive gastro-entero-pancreatic neuroendocrine tumours - a single centre experience.European journal of nuclear medicine and molecular imaging • February 10, 2025
Raghava Kashyap, Ramin Alipour, Emma Boehm, Kerry Jewell, Aravind Ravikumar, Anthony Cardin, Javad Saghebi, Michael Hofman, Michael Fahey, Michael Michael, Tim Akhurst, Rodney Hicks, Grace Kong
Objective: Patients with gastro-entero-pancreatic neuroendocrine tumours (GEP NET) who retain somatostatin receptor (SSTR) expression after initial response to [177Lu]Lu-DOTA-Octreotate (LuTate) peptide receptor radionuclide therapy (PRRT) are amenable to re-treatment (R-PRRT) upon progression. We assessed the safety and efficacy of R-PRRT in patients with progressive metastatic GEP NET.
Methods: A retrospective analysis, approved by institutional ethics board, was performed in patients with GEP NET who received R-PRRT for either symptomatically or radiologically progressive disease. Safety was assessed by renal and haematological parameters at 3 months post R-PRRT (CTCAE v5.0). Molecular imaging response was evaluated on [68Ga]Ga-DOTA-Octreotate (GaTate) PET/CT using pre-defined criteria. RECIST 1.1 responses 3 months post R-PRRT were documented when feasible. Progression-free and overall survival analysis were performed.
Results: A total of 63 patients had R1-PRRT (1-3 cycles). The majority (70%) had Grade 2 NET and small intestinal primary (51%). A second re-treatment course (R2-PRRT) was given in 20 patients and a third course (R3-PRRT) in 6 patients. Glomerular filtration rate (GFR) was stable following R1-PRRT. Following R2-PRRT, worsening GFR from CTCAE G2 to G3 was seen in 10% (2/20) of patients, but none after R3-PRRT. Grade 3 thrombocytopenia occurred in 2 patients after R1-PRRT and in 1 patient after R3-PRRT. Grade 4 thrombocytopenia was observed in 1 patient post R1-PRRT. Following R1-PRRT, RECIST 1.1 responses CR, PR, SD was 0%, 10%, 76%, respectively. Disease control rate on GaTate PET/CT was 52/58 (89%) post R1-PRRT. Median progression free survival (PFS) following R1-PRRT was 1.6 years (95% CI:1.2-2.3).
Conclusions: R-PRRT is feasible, tolerable and efficacious in achieving disease control in patients with progressive GEP NET.
International Consensus Statement on Diagnosis, Evaluation, and Research of Richter Transformation: the ERIC Recommendations.Blood • January 17, 2025
Adam Kittai, Monia Marchetti, Othman Al Sawaf, Ohad Benjamini, Alexey Danilov, Matthew Davids, Barbara Eichhorst, Toby Eyre, Anna Frustaci, Michael Hallek, Paul Hampel, Yair Herishanu, Rodney Hicks, Arnon Kater, Rebecca King, JosĂ©-ignacio MartĂn Subero, Carolyn Owen, Erin Parry, Maurilio Ponzoni, Davide Rossi, Tanya Siddiqi, Stephan Stilgenbauer, Constantine Tam, Elisa Ten Hacken, Philip Thompson, William Wierda, Gianluca Gaidano, Jennifer Woyach, Paolo Ghia
Richter transformation (RT) is defined as an aggressive lymphoma emerging in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL). Despite novel therapeutics developed in CLL, RT is associated with poor outcomes. In light of recent progress regarding the diagnostic procedures and therapeutic concepts of RT, an international group of experts, under the coordination of the European Research Initiative on CLL (ERIC), has developed consensus recommendations for clinical procedures and future research on this disease. Patients with RT typically present with a rapid clinical decline, worsening B-symptoms, elevated LDH, and/or rapidly enlarging lymphadenopathy. Workup should include a PET-CT for patients with suspected RT. An excisional biopsy should be taken from an accessible lesion, preferably with the highest FDG avidity, and analyzed for the presence of aggressive lymphoma. The molecular relationship to the original CLL clone(s) should be defined. As no effective standard treatment for RT exists, patients should be treated in a clinical trial. Response of both RT and CLL should be assessed at an early time point, and survival endpoints should be prioritized in trial design. We hope that these recommendations can help to harmonize clinical and translational research and improve outcomes for patients with RT.
Peptide receptor radionuclide therapy in malignant insulinoma.Endocrine-Related Cancer • January 18, 2025
David Pattison, Grace Kong, Timothy Akhurst, Matthew Burge, Cherie Chiang, Michael Hofman, Te-jui Hung, Amanda Love, Michael Michael, Satomi Okano, Aravind Ravi Kumar, Nirupa Sachithanandan, David Wyld, Rodney Hicks
The management of malignant insulinoma (MI) presents dual management challenges of hypoglycaemia and tumour control. This study aims to analyse long-term outcomes of PRRT for the treatment of MI. We retrospectively reviewed consecutive patients with MI treated with [177Lu]Lu-DOTATATE (LuTATE) at two Australian NET centres between 2004 and 2022. Follow-up for hypoglycaemia, molecular imaging, radiologic and biochemical responses, treatment-related side-effects, progression-free and overall survival were assessed. Of 15 patients (seven female; median age 60, range 26-82) treated for intractable hypoglycaemia, WHO grade (G) was known in 12 patients (three G1, six G2 and three G3). PRRT was administered in a median of seven cycles (range 1-15), with a median cumulative activity of 42 GBq (range 4-117 GBq) and radiosensitizing chemotherapy in 9/15 (60%) patients. Resolution of hypoglycaemia was observed in 14/15 (93%) patients after a median of 2.5 months (range 0.2-23.5), but recurred in 7/14 cases after a median of 17.7 months (range 7.6-48.3). Patients with recurrent hypoglycaemia had a longer time to hypoglycaemia resolution (median 3.0 vs 0.5 months), were more likely G3 (57 vs 0%) and experienced higher mortality (86 vs 29%). In all seven cases, PRRT re-treatment was successful. The mean duration of hypoglycaemia remission was 23.8 months (range 9.2-101). The median progression-free and overall survival was 17.9 months (95% CI, 8.5-43.2) and 50.1 months (95% CI, 23.0-ND), respectively. Side-effects included G3/4 myelosuppression in 4/15 patients and hypoglycaemia flare (hospitalisation >48 h) in 7/15 patients. PRRT provides durable hypoglycaemic and oncologic disease control of MI with manageable toxicity including hypoglycaemia flare requiring multidisciplinary care.
International consensus statement on diagnosis, evaluation, and research of Richter transformation: the ERIC recommendations.
Blood • January 17, 2025
Adam Kittai, Monia Marchetti, Othman Al Sawaf, Ohad Benjamini, Alexey Danilov, Matthew Davids, Barbara Eichhorst, Toby Eyre, Anna Frustaci, Michael Hallek, Paul Hampel, Yair Herishanu, Rodney Hicks, Arnon Kater, Rebecca King, Jose Martin Subero, Carolyn Owen, Erin Parry, Maurilio Ponzoni, Davide Rossi, Tanya Siddiqi, Stephan Stilgenbauer, Constantine Tam, Elisa Hacken, Philip Thompson, William Wierda, Gianluca Gaidano, Jennifer Woyach, Paolo Ghia
Richter transformation (RT) is defined as an aggressive lymphoma emerging in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL). Despite novel therapeutics developed in CLL, RT is associated with poor outcomes. In light of recent progress regarding the diagnostic procedures and therapeutic concepts of RT, an international group of experts, under the coordination of the European Research Initiative on CLL, has developed consensus recommendations for clinical procedures and future research on this disease. Patients with RT typically present with a rapid clinical decline, worsening B-symptoms, elevated lactate dehydrogenase, and/or rapidly enlarging lymphadenopathy. Workup should include a positron emission tomography-computed tomography scan for patients with suspected RT. An excisional biopsy should be taken from an accessible lesion, preferably with the highest fluorodeoxyglucose avidity, and analyzed for the presence of aggressive lymphoma. The molecular relationship to the original CLL clone(s) should be defined. Because no effective standard treatment for RT exists, patients should be treated in a clinical trial. Response of both RT and CLL should be assessed at an early time point, and survival end points should be prioritized in trial design. We hope that these recommendations can help to harmonize clinical and translational research and improve outcomes for patients with RT.
