Salvage Therapy for Local Progression following Definitive Therapy for Skull Base Chordomas: Is There a Role of Stereotactic Radiosurgery?

摘要

Objective?The objective of this study was to identify factors associated with improved tumor control at individual sites of recurrence and to define the role of stereotactic radiosurgery (SRS) in the management of local or distant progression following prior radiotherapy.Study Design?Clinical data of patients with recurrent skull base chordoma following prior radiotherapy were retrospectively reviewed.Setting and Participants?This is a single-center retrospective study including 16 patients from the University of Texas MD Anderson Cancer Center Houston, Texas, United States.Main Outcome Measures?Each site of recurrence was considered independently, and the primary outcome was freedom from treatment site progression (FFTSP).Results?There were 40 episodes of either local or distant progression treated in 16 patients with skull base chordoma. Tumor recurrence was classified as either local, distant, or both local and distant involving the skull base, spinal column, or leptomeninges. Patients were treated with repeat surgical resection ( n ?=?16), SRS ( n ?=?21), or chemotherapy ( n ?=?25). In multivariate analysis, SRS was the only treatment modality associated with improved FFTSP ( p ?=?0.006). For tumors treated with SRS, there was no evidence of tumor progression or adverse radiation events. Other factors associated with worse FFTSP included the number of progressive episodes (>3), tumor histology, and leptomeningeal disease.Conclusions?For local recurrence following prior radiotherapy, SRS was associated with improved FFTSP. SRS may represent an effective palliative treatment offering durable tumor control at the treated site without significant treatment-related morbidity. Keywords: chordoma, clivus, skull base, radiation, stereotactic radiosurgeryIntroductionChordomas follow a malignant course defined by local invasiveness and destruction, a tendency to recur, and occasional distant metastases. Although a consensus approach on the multimodal treatment of newly diagnosed skull base chordomas exists,~(1)there is a paucity of outcomes data directing management of locally and systemically recurrent/progressive skull base chordomas. The surgical treatment of skull base chordomas has advanced with improvements in endoscopic and open cranial approaches, and the development of salvage reconstruction techniques has led to the consideration of repeat surgery at the time of tumor recurrence. Treatment of progressive disease, however, is currently complicated by a lack of effective systemic therapeutic options and the unknown efficacy of re-irradiation. In general, the ability to offer curative treatment at the time of recurrence is rare for skull base malignancies, and selecting an optimal therapy requires a multidisciplinary approach focused on striking a balance between local control, quality of life, and potential morbidity of further interventions.We recently described factors affecting overall disease control and survival in patients with progressive skull base chordoma at our institution.~(2)In this study, it was noted that disease progression after radiation therapy was more difficult to control than after surgery alone, and the presence of distant metastases or leptomeningeal disease conferred a poorer disease-specific survival and freedom from progression (subsequent progression at any local or systemic site). Moreover, repeat surgical resection followed by adjuvant radiotherapy (RT) at the time of progression significantly improved both local and systemic disease control in patients presenting after previous surgical resection alone. In the case of postradiation disease progression, no single treatment paradigm was found to be effective in reducing the risk of local or distant disease progression.In this study, we focused on our ability to offer palliative interventions for local and distant recurrences in patients previously treated with surgery and radiation therapy. The nature of the advanced disease in these patients prevents a cure. To our knowledge, this is the only report systematically examining rates of site-specific control by treatment modality in the treatment of local or distant chordoma recurrence. The aim of this study was to identify factors influencing the ability to control individual areas of disease independent of whether or not there is progression at either local or distant sites. We hypothesized that treatment with stereotactic radiosurgery (SRS) provides effective tumor control in skull base and spine recurrences, with acceptable morbidity in patients with few remaining treatment options. To our knowledge, this is the first report specifically addressing the role of SRS in the management of locally progressive skull base chordomas in the post-RT setting.MethodsStudy PopulationA retrospective review of all patients treated at our institution for skull base chordomas between 1993 and 2016 was performed. The study was performed under an Institutional Review Board approved protocol in