Michael Kosmin1, Andreas Makris2, Noorulhuda Jawad3, David Woolf2, David Miles2, Anwar R Padhani3. 1. Breast Cancer Research Unit, Mount Vernon Cancer Centre, Rickmansworth Road, Northwood, Middlesex, HA6 2RN, UK. michael.kosmin@nhs.net. 2. Breast Cancer Research Unit, Mount Vernon Cancer Centre, Rickmansworth Road, Northwood, Middlesex, HA6 2RN, UK. 3. Paul Strickland Scanner Centre, Mount Vernon Cancer Centre, Rickmansworth Road, Northwood, Middlesex, HA6 2RN, UK.
Abstract
BACKGROUND: An association between trastuzumab-emtansine (T-DM1) and splenic enlargement is reported in preclinical data, and has been noted anecdotally in patients receiving T-DM1 at our institution. Use of whole-body MRI examinations (WB-MRI) allows for detailed bone marrow assessment and semi-automated splenic volume calculations. OBJECTIVE: To retrospectively evaluate changes in splenic volume versus evidence of bone marrow hyperplasia and/or changes in portal venous pressure in patients receiving T-DM1 for metastatic breast cancer. PATIENTS AND METHODS: Twelve metastatic breast cancer patients underwent 29 WB-MRIs before and during T-DM1 therapy. Splenic volume, portal vein diameter, bone marrow diffusion-weighted normalised signal intensity (nSI), quantitative water diffusivity (apparent diffusion coefficient, ADC) and fat fraction (rF%) were measured and correlated. RESULTS: Splenic volume increases were observed in 92% of patients. Mean splenic volume increased from 144 cm3 (95% CI 110-177 cm3) to 209 cm3 (95% CI 161-257 cm3) on T-DM1 therapy (p = 0.006). Splenic volume increases correlated with treatment duration (r2 = 0.43). Bone marrow hyperplasia was evidenced by an increase in bone marrow nSI (3.5 to 4.8, p = 0.12), and decreases in rF% (64.3% to 57.3%, p = 0.12) and ADC (655 μm2/s to 543 μm2/s, p = 0.11). No changes to portal vein diameter were seen. CONCLUSIONS: Previously unreported increases in splenic volume and bone marrow hyperplasia are observed on WB-MRI in patients on T-DM1 therapy. Caution must be applied to avoid misinterpreting T-DM1-induced bone marrow hyperplasia as diffuse disease progression in bone.
BACKGROUND: An association between trastuzumab-emtansine (T-DM1) and splenic enlargement is reported in preclinical data, and has been noted anecdotally in patients receiving T-DM1 at our institution. Use of whole-body MRI examinations (WB-MRI) allows for detailed bone marrow assessment and semi-automated splenic volume calculations. OBJECTIVE: To retrospectively evaluate changes in splenic volume versus evidence of bone marrow hyperplasia and/or changes in portal venous pressure in patients receiving T-DM1 for metastatic breast cancer. PATIENTS AND METHODS: Twelve metastatic breast cancerpatients underwent 29 WB-MRIs before and during T-DM1 therapy. Splenic volume, portal vein diameter, bone marrow diffusion-weighted normalised signal intensity (nSI), quantitative water diffusivity (apparent diffusion coefficient, ADC) and fat fraction (rF%) were measured and correlated. RESULTS: Splenic volume increases were observed in 92% of patients. Mean splenic volume increased from 144 cm3 (95% CI 110-177 cm3) to 209 cm3 (95% CI 161-257 cm3) on T-DM1 therapy (p = 0.006). Splenic volume increases correlated with treatment duration (r2 = 0.43). Bone marrow hyperplasia was evidenced by an increase in bone marrow nSI (3.5 to 4.8, p = 0.12), and decreases in rF% (64.3% to 57.3%, p = 0.12) and ADC (655 μm2/s to 543 μm2/s, p = 0.11). No changes to portal vein diameter were seen. CONCLUSIONS: Previously unreported increases in splenic volume and bone marrow hyperplasia are observed on WB-MRI in patients on T-DM1 therapy. Caution must be applied to avoid misinterpreting T-DM1-induced bone marrow hyperplasia as diffuse disease progression in bone.
Authors: Véronique Diéras; Nadia Harbeck; G Thomas Budd; Joel K Greenson; Alice E Guardino; Meghna Samant; Nataliya Chernyukhin; Melanie C Smitt; Ian E Krop Journal: J Clin Oncol Date: 2014-07-14 Impact factor: 44.544
Authors: Anwar R Padhani; Andreas Makris; Peter Gall; David J Collins; Nina Tunariu; Johann S de Bono Journal: J Magn Reson Imaging Date: 2014-02-10 Impact factor: 4.813
Authors: Sunil Verma; David Miles; Luca Gianni; Ian E Krop; Manfred Welslau; José Baselga; Mark Pegram; Do-Youn Oh; Véronique Diéras; Ellie Guardino; Liang Fang; Michael W Lu; Steven Olsen; Kim Blackwell Journal: N Engl J Med Date: 2012-10-01 Impact factor: 91.245
Authors: Ian E Krop; Muralidhar Beeram; Shanu Modi; Suzanne F Jones; Scott N Holden; Wei Yu; Sandhya Girish; Jay Tibbitts; Joo-Hee Yi; Mark X Sliwkowski; Fred Jacobson; Stuart G Lutzker; Howard A Burris Journal: J Clin Oncol Date: 2010-04-26 Impact factor: 44.544
Authors: Manu Lopus; Emin Oroudjev; Leslie Wilson; Sharon Wilhelm; Wayne Widdison; Ravi Chari; Mary Ann Jordan Journal: Mol Cancer Ther Date: 2010-10 Impact factor: 6.261
Authors: Anwar R Padhani; Katherine van Ree; David J Collins; Shirley D'Sa; Andreas Makris Journal: AJR Am J Roentgenol Date: 2013-01 Impact factor: 3.959