Aida Muhic

Local control and survival in patients with soft tissue sarcomas treated with limb sparing surgery in combination with interstitial brachytherapy and external radiation

PURPOSE The purpose of this study was to evaluate local control, survival and complication rate after treatment of soft tissue sarcoma (STS) with limb-sparing surgery combined with pulsed-dose rate (PDR) interstitial brachytherapy (BRT) and external beam radiotherapy (EBRT). PATIENTS AND METHODS A retrospective review of 39 adult patients (female/male=25/14, mean age 51(range 21-78) years) with STS who underwent primary limb-sparing surgery combined with PDR BRT (20Gy) and additional post-operative EBRT (50Gy) during the years 1995-2004. RESULTS Five patients developed local recurrence after a mean follow-up of 3.4 (1.5-5.9) years. The probability of local recurrence free 5 years survival was 83%. At the time of follow-up 10 patients had died (mean follow-up 2.3 (0.8-7.1) years) and 29 patients were still alive (mean follow-up 5.9 (2.1-11.2) years). The overall 5-year survival rate was 76%. Nineteen (49%) patients suffered from some degree of decreased force or function of the affected extremity, 16 (41%) suffered from oedema, 12 (31%) had persistent pain, 8 (21%) suffered from wound complications, and in 4 (10%) of these patients plastic surgery were required. CONCLUSION Limb sparing surgery, combined with PDR BRT and EBRT can result in good local control in patients with soft tissue sarcomas. BRT is an effective modality with good cosmetic results and acceptable toxicity.

Neoadjuvant bevacizumab and irinotecan versus bevacizumab and temozolomide followed by concomitant chemoradiotherapy in newly diagnosed glioblastoma multiforme: A randomized phase II study

Abstract Background. Surgery followed by radiotherapy and concomitant and adjuvant temozolomide is standard therapy in newly diagnosed glioblastoma multiforme (GBM). Bevacizumab combined with irinotecan produces impressive response rates in recurrent GBM. In a randomized phase II study, we investigated the efficacy of neoadjuvant bevacizumab combined with irinotecan (Bev-Iri) versus bevacizumab combined with temozolomide (Bev-Tem) before, during and after radiotherapy in newly diagnosed GBM. Material and methods. After surgery, patients were randomized to Bev-Iri or Bev-Tem for eight weeks, followed by standard radiotherapy (60 Gy/30 fractions) and concomitant Bev-Iri or Bev-Tem followed by adjuvant Bev-Iri or Bev-Tem for another eight weeks. Bev-Iri: Bevacizumab and irinotecan were given every 14 days before, during and after radiotherapy. Bev-Tem: Bevacizumab was given as in Bev-Iri and temozolomide was given for five days every four weeks before and after radiotherapy and once daily during radiotherapy. The primary endpoint was response after neoadjuvant chemotherapy and a pre-specified response rate of 30% or more was considered of interest for future studies. Secondary endpoints were progression-free survival (PFS) and toxicity. Results. The response rate was 32% (95% CI 17–51%) for Bev-Tem (n = 32) and 23% (95% CI 9–44%) for Bev-Iri (n = 31) (p = 0.56). Median PFS was 7.7 and 7.3 months for Bev-Tem and Bev-Iri, respectively. Hematological toxicity was more frequent with Bev-Tem including one death from febrile neutropenia whereas non-hematological toxicity was manageable. Conclusions. Only the Bev-Tem arm met the pre-specified level of activity of interest. Our results did not indicate any benefit from Bev-Iri in first-line therapy as opposed to Bev-Tem in terms of response and PFS.

Vascularized Fibula Grafts for Reconstruction of Bone Defects after Resection of Bone Sarcomas

We evaluated the results of limb-sparing surgery and reconstruction of bone defects with vascularized fibula grafts in 8 consecutive patients (mean age at operation 13.6 years (range 4.1–24.2 years), female/male = 6/2) with bone sarcomas (BS) (osteosarcoma/Ewings sarcoma/chondrosarcoma= 4/3/1) operated on form 2000 to 2006. The bone defects reconstructed were proximal femoral diaphysis and epiphysis (n = 2), humeral diaphysis (n = 2), humeral proximal diaphysis and epiphysis (n = 1), femoral diaphysis (n = 1), ulnar diaphysis (n = 1), and tibial diaphysis (n = 1). One patient with Ewings sarcoma had an early hip disarticulation, developed multiple metastases, and died 9 months after the operation. The remaining patients (n = 7) are all alive 50 months (range 26–75 months) after surgery. During the follow-up the following major complications were seen: 1-2 fractures (n = 4), pseudarthrosis (n = 2), and hip dislocation (n = 1). Limb-sparing surgery with reconstruction of bone defects using vascularized fibular grafts in BS cases is feasible with acceptable clinical results, but fractures should be expected in many patients.

Patterns of failure for patients with glioblastoma following O-(2-[18F]fluoroethyl)-L-tyrosine PET- and MRI-guided radiotherapy

BACKGROUND AND PURPOSE To evaluate the patterns of failure following clinical introduction of amino-acid O-(2-[18F]fluoroethyl)-L-tyrosine (FET)-PET-guided target definition for radiotherapy (RT) of glioblastoma patients. MATERIALS AND METHODS The first 66 consecutive patients with confirmed histology, scanned using FET-PET/CT and MRI were selected for evaluation. Chemo-radiotherapy was delivered to a volume based on both MRI and FET-PET (PETvol). The volume of recurrence (RV) was defined on MRI data collected at the time of progression according to RANO criteria. RESULTS Fifty patients were evaluable, with median follow-up of 45months. Central, in-field, marginal and distant recurrences were observed for 82%, 10%, 2%, and 6% of the patients, respectively. We found a volumetric overlap of 26%, 31% and 39% of the RV with the contrast-enhancing MR volume, PETvol and the composite MRPETvol, respectively. MGMT-methylation (p=0.03), larger PETvol (p<0.001), and less extensive surgery (p<0.001), were associated with larger PETvol overlap. CONCLUSION The combined MRPETvol had a stronger association with the recurrence volume than either of the modalities alone. Larger overlap of PETvol and RV was observed for patients with MGMT-methylation, less extensive surgery, and large PETvol on the RT-planning scans.

Presentation of Two Cases with Early Extracranial Metastases from Glioblastoma and Review of the Literature

Extracranial metastases from glioblastoma are rare. We report two patients with extracranial metastases from glioblastoma. Case 1 concerns a 59-year-old woman with multiple metastases that spread early in the course of disease. What makes this case unusual is that the tumor had grown into the falx close to the straight sinus and this might be an explanation to the early and extensive metastases. Case 2 presents a 60-year-old man with liver metastasis found at autopsy, and, in this case, it is more difficult to find an explanation. This patient had two spontaneous intracerebral bleeding incidents and extensive bleeding during acute surgery with tumor removal, which might have induced extracranial seeding. The cases presented might have hematogenous spreading in common as an explanation to extracranial metastases from GBM.

Abstract 3701: Phase II study of BIBF1120 in recurrent glioblastoma multiforme

Background: BIBF 1120, a potent, orally available triple angiokinase inhibitor targeting VEGFR 1-3, PDGFR- α/-α, and FGFR 1-3, has shown promising clinical activity with a good safety profile in patients with advanced non-small cell lung cancer or ovarian cancer. The specific and simultaneous abrogation of these three pathways results in effective growth inhibition of both endothelial and perivascular cells. This may be more effective than inhibition of endothelial cell growth via the VEGF pathway alone. In addition, signalling via FGF-receptors has been identified as a possible escape mechanism for tumour angiogenesis when the VEGF pathway is disrupted. Recurrent glioblastomas (GBM) have an extremely poor prognosis and consequently new and innovative therapies are still needed. Accordingly, the purpose of this study was to assess the efficacy and safety of BIBF 1120 in two parallel groups of patients with recurrent GBM after radiotherapy and temozolomide (STD) or the same regimen and subsequent bevacizumab based therapy (BEV). Methods: Patients were included in one of two parallel groups depending of prior exposure to bevacizumab (STD or BEV). Inclusion critieria included recurrent GBM, PS 0-1, normal organ function, available archival tissue blocks, and measurable disease according to RANO guidelines. A total of 32 patients were to be enrolled in each group in a two-stage design including a stopping rule if less than 4/16 patient responded. BIBF-1120 was administered orally 200 mg bid, with weekly plasma sampling for the first 4 weeks and MRI assessement every 8 weeks. Primary endpoint was objective response rate. Secondary endpoints were safety, PFS and plasma and tissue biomarkers. Results: The study was prematurely stopped for after inclusion of 13 patients in the STD arm and 12 patients in the BEV arm. No objective responses were seen in either arm. One patient in the BEV arm has had stable disease for 8 months while the remainder of the patients in both arms progressed within the first 4 cycles. BIBF-1120 was very well tolerated with no observed grade III or IV adverse events. Most frequent adverse events were grade I-II hypertension, diarrhoea and fatigue, with a frequency of Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3701. doi:1538-7445.AM2012-3701

PO-0651: Pattern of failure in glioblastoma patients after FET-PET and MRI-guided chemo-radiotherapy

Results: The median overall DBMFS was 12.9 months. A significant difference in median DBMFS was observed for patients with squamous cell vs. adenocarcinoma primary histology (4.57 months vs. 15.9 months, respectively, p <0.015). The initial number of metastases, total initial metastasis volume, ECD status, KPS scores, EGFR mutation status, or ALK gene rearrangement status, made no significant difference on DBMFS. None of the analyzed parameters displayed significant impact on ODBF. WBRT had no significant effect on DBMFS or ODBF in the study population, but patients with history of WBRT prior to SRS had an increased DBFR (0.396 vs. 0.089) which was borderline significant (p=0.05). There was an insufficient number of patients receiving combined WBRT with SRS to determine an effect on distant brain failure vs. SRS alone.