LETTER TO THE EDITOR Treatment of chordoma with imatinib complicated by intracranial hemorrhage: a case showing dissociation between biological effect and therapeutic outcome Franc¸ois Mercier • Marie-Christine Guiot • Michel W. Bojanowski Received: 19 May 2011 / Accepted: 14 November 2011 / Published online: 26 November 2011 Ó Springer Science+Business Media, LLC. 2011 To the Editor: Chordomas are malignant tumors which originate from notochord remnants and generally grow slowly. Their management is challenging, because complete resection is often impossible, relapses are common, and the tumors rarely respond to conventional chemotherapy. Activated tyrosine kinase receptors, including platelet-derived growth factor receptor beta (PDGFRB) [1], have recently been identified in chordomas. Because PDGFRB is not mutated in chordomas, its activation is postulated to be because of an autocrine/paracrine loop. In small series of patients, i- matinib, an oral drug with anti-PDGFRB activity, has led to disease stabilization and improvement of symptoms, suggesting the possibility of targeted therapy for this type of tumor [1]. In this report we describe a patient who developed intracranial hemorrhage in the setting of imati- nib treatment for chordoma. Patient history A 32-year-old woman with no hematological disorder or previous intracranial hemorrhage had presented six years earlier with severe cervical pain. Investigation revealed a chordoma involving the clivus, the nasopharynx, and the vertebral bodies of C1 and C2. Initial treatment consisted of gross total excision, followed by adjuvant proton beam therapy. Follow-up imaging one year later revealed residual tumor at the initial site in the clivus; this was deemed unsuitable for complete resection and was man- aged conservatively. Four years after the initial diagnosis, the patient presented with pharyngeal dysfunction owing to disease progression. Further investigation also revealed distinct epidural metastasis within the cervical spine with associated impending compression of the spinal cord. Both tumors were resected for palliative reasons. Immu- nohistochemistry performed on the tumor sample con- firmed overexpression of PDGFRB. Because of the limited conventional treatment options, a trial of imatinib with palliative intent was offered outside a clinical trial. At that time, the patient had a good functional status and was not on concomitant anticoagulant or antiplatelet therapy. Imatinib was provided on a compassionate basis by Novartis Canada. Three months after the last surgery, imatinib was initiated at 400 mg daily and escalated over 1 month to 800 mg daily. Although the treatment was well tolerated overall, ten weeks after initiation of the treatment the patient presented with a three-day history of gradually worsening headache, vomiting, and altered mental status. CT scan showed hydrocephalus in associ- ation with subacute intraventricular hemorrhage (Fig. 1a, b). She underwent emergent placement of a ventriculos- tomy. Angiography performed to investigate possible sources of bleeding did not reveal any vascular lesion. MRI revealed tumor progression, accompanied by a decrease in contrast enhancement, compared with the study performed before imatinib initiation (Fig. 1c, d). Imatinib was discontinued because of lack of therapeutic F. Mercier (&) Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA e-mail: francois.mercier@mail.mcgill.ca M.-C. Guiot Montreal Neurological Institute, Montreal, Canada M. W. Bojanowski Centre Hospitalier de l’Universite de Montreal, Montreal, Canada 123 J Neurooncol (2012) 107:435–437 DOI 10.1007/s11060-011-0767-2