Histopathologic assessment of hot-spot microvessel density and vascular patterns in glioblastoma: Poor observer agreement limits clinical utility as prognostic factors: a translational research project of the European Organization for Research and Treatment of Cancer Brain Tumor Group.

BACKGROUND: Hot-spot microvessel density (MVD) and vascular patterns have been reported as histopathologic factors that influence prognosis in retrospective series of malignant gliomas. To investigate clinical utility, the authors systematically studied observer agreement on MVD and vascular patterns and the influence of repeatedly assessed data on patient outcomes in 2 independent glioblastoma series. METHODS: MVD and vascular patterns were assessed retrospectively by 5 observers in 1) a retrospectively compiled glioblastoma series that included 110 patients and 2) a glioblastoma series that included 233 patients who were treated within a randomized trial. MVD was determined in the field of greatest density ("hot-spot"). Predominantly classic or bizarre vascular patterns were determined by using a previously defined algorithm. RESULTS: Observer agreement on MVD was highly variable (range of kappa values, 0.464-0.901). The worst observer agreement was achieved when both the selection of hot-spots and MVD counts were performed independently. Survival analysis did not show a consistent association between repeatedly assessed MVD and patient outcome. Observer agreement on vascular patterns was poor (kappa = 0.297). Survival analysis did not show a consistent association between repeatedly assessed vascular patterns and patient outcome. CONCLUSIONS: Observer agreement on hot-spot MVD and vascular patterns in patients with glioblastoma was poor in independent assessments. MVD and vascular patterns were not associated consistently with patient outcome. Based on these findings, the authors concluded that poor observer agreement limits the clinical utility of histopathologically assessed hot-spot MVD and vascular patterns as prognostic factors in patients with glioblastoma. Improved methodologies for morphologic assessment of glioblastoma vascularization need to be identified.

Recurrent and metastatic clivus chordoma: systemic palliative therapy retards disease progression.

We report on a male patient with progressive and metastatic clivus chordoma treated over a period of 9 years by a multidisciplinary approach. Within the first 4 years, the patient underwent surgery four times. Thereafter, he received radiotherapy and subsequent chemotherapy. Stabilization of disease was achieved repeatedly for variable periods under local radiotherapy, systemic chemotherapy, immunomodulatory and anti-angiogenic therapy with isotretinoin and interferon-alpha, followed by thalidomide. Due to the occurrence of brain and lung metastases 8 years after initial diagnosis, liposomal doxorubicin was added to thalidomide. At the last follow-up control the patient had stable disease, with no progression of the intracranial tumor and regression of pulmonary metastases. He is in a good physical, psychological and neurological condition with a Karnofsky score of 80. Our observations show that multimodal therapy including a systemic palliative approach is associated with long quiescent intervals in recurrent chordoma and with regression of its metastases. Use of substances with high efficacy on tumor tissue and low toxicity, allowing long-term administration, seems promising in similar situations.