title: Splenic Enlargement and Bone Marrow Hyperplasia in Patients Receiving Trastuzumab-Emtansine for Metastatic Breast Cancer.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.affiliation: Breast Cancer Research Unit, Mount Vernon Cancer Centre, Rickmansworth Road, Northwood, Middlesex, HA6 2RN, UK. michael.kosmin@nhs.net.
authors.forename: Michael
authors.initials: M
authors.lastname: Kosmin
authors.affiliation: Breast Cancer Research Unit, Mount Vernon Cancer Centre, Rickmansworth Road, Northwood, Middlesex, HA6 2RN, UK.
authors.forename: Andreas
authors.initials: A
authors.lastname: Makris
authors.affiliation: Paul Strickland Scanner Centre, Mount Vernon Cancer Centre, Rickmansworth Road, Northwood, Middlesex, HA6 2RN, UK.
authors.forename: Noorulhuda
authors.initials: N
authors.lastname: Jawad
authors.affiliation: Breast Cancer Research Unit, Mount Vernon Cancer Centre, Rickmansworth Road, Northwood, Middlesex, HA6 2RN, UK.
authors.forename: David
authors.initials: D
authors.lastname: Woolf
authors.affiliation: Breast Cancer Research Unit, Mount Vernon Cancer Centre, Rickmansworth Road, Northwood, Middlesex, HA6 2RN, UK.
authors.forename: David
authors.initials: D
authors.lastname: Miles
authors.affiliation: Paul Strickland Scanner Centre, Mount Vernon Cancer Centre, Rickmansworth Road, Northwood, Middlesex, HA6 2RN, UK.
authors.forename: Anwar R
authors.initials: AR
authors.lastname: Padhani
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001853:Bone Marrow / Q000473:pathology*; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000209:etiology*; D008453:Maytansine / Q000009:adverse effects / Q000031:analogs & derivatives*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D013154:Spleen / Q000473:pathology*; D000068878:Trastuzumab / Q000009:adverse effects*
chemical_list: D000970:Antineoplastic Agents; D008453:Maytansine; D000068878:Trastuzumab