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Safety and Local Control of Radiation Therapy for Chordoma of the Spine and Sacrum: A Systematic Review.

ABSTRACT: Systematic literature review.To assess the toxicity, common radiation doses, and local control (LC) rates of radiation therapy for chordoma of the spine and sacrum and identify the difference in LC and toxicity between adjuvant, salvage, and primary therapy using radiation.Chordoma of the spine is typically a low-grade malignant tumor thought to be relatively radioresistant with a high rate of local recurrence and the potential for metastases. Improved results of modern radiation therapy in the treatment of chordoma support exploration of its role in the management of primary/de novo chordoma or recurrent chordoma.We conducted a systematic literature review using PubMed and Embase databases to assess information available regarding the toxicity, LC rates, and overall survival (OS) rates for adjuvant, salvage, and primary radiation therapy for spinal and sacral chordoma.A total of 40 articles were reviewed. Evidence quality was low or very low. The highest rates of LC and OS were with early adjuvant RT for primary/de novo disease. Salvage RT for recurrent disease has very small cohorts and thus strong conclusions were not able be made.The use of pre- and/or post-operative photon image-guided radiotherapy (IGRT), proton or carbon ion therapy should be considered for patients undergoing surgery for the treatment of primary and recurrent chordomas in the mobile spine and sacrum, since these RT modalities may improve local control. Preoperative evaluation by the surgeon and radiation oncologist should be used to formulate a cohesive treatment plan.The use of photon IGRT or carbon ion therapy as the primary treatment of chordoma, when currently in its developmental stage, shows promise and requires clear delineation of toxicity profile and long-term local control.2.

SUBMITTER: Pennicooke B

PROVIDER: S-EPMC5572655 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Safety and Local Control of Radiation Therapy for Chordoma of the Spine and Sacrum: A Systematic Review.

Pennicooke Brenton B Laufer Ilya I Sahgal Arjun A Varga Peter P PP Gokaslan Ziya L ZL Bilsky Mark H MH Yamada Yoshiya J YJ

Spine 20161001

<h4>Study design</h4>Systematic literature review.<h4>Objective</h4>To assess the toxicity, common radiation doses, and local control (LC) rates of radiation therapy for chordoma of the spine and sacrum and identify the difference in LC and toxicity between adjuvant, salvage, and primary therapy using radiation.<h4>Summary of background data</h4>Chordoma of the spine is typically a low-grade malignant tumor thought to be relatively radioresistant with a high rate of local recurrence and the pote ...[more]

PMID: 27509195

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Project description:Systematic review.To determine evidence-based guidelines for the management of locally recurrent spinal chordoma.Chordoma of the spine is a low-grade malignant tumor with a strong propensity for local recurrence. Salvage therapy is challenging due to its relentless nature and refractoriness to adjuvant therapies. There are currently no guidelines regarding the best management of recurrent chordoma.We combined the results of a systematic review with expert opinion to address the following research questions: (1) For locally recurrent chordoma of the spine without systemic disease, if surgery is planned, should en bloc resection be attempted if technically feasible with acceptable morbidity? (2) For locally recurrent chordoma without systemic disease, in which wide en bloc excision is not possible, what is the treatment of choice? (2) Should adjuvant or neoadjuvant radiation therapy be used in the treatment of locally recurrent chordoma?A total of nine surgical and seven radiation therapy articles met study criteria. Evidence quality was low or very low. Recurrent disease is associated with predominantly poor outcome, regardless of treatment modality. As for primary chordoma, resection with wide margins appears to confer an advantage with respect to local control, although this effect is attenuated in the setting of relapse. Postoperative radiation therapy likely reduces the rate of further relapse.(1) For locally recurrent chordoma of the spine without systemic disease, when surgery is planned, wide en bloc resection should be performed if technically feasible with acceptable morbidity. Strong recommendation, Low Quality of Evidence. (2) For locally recurrent chordoma without systemic disease, in which wide en bloc excision is not possible, partial resection is the treatment of choice. Weak recommendation, Very Low Quality of Evidence. (3) For the treatment of locally recurrent chordoma, high-dose conformal radiation therapy should be administered postoperatively to reduce the risk of further recurrence, and may be considered as a primary therapy. Strong recommendation, Very Low Quality of Evidence.2.

Project description:Background:Chordomas are rare malignant tumors of the spinal column often afflicting the upper cervical spine and sacrum. There are few large single center series on chordomas due to its rarity. The purpose of this study is to report a single center's experience with the operative and non-operative management of chordomas. Methods:We evaluated our institution's pathology database from 1994 to 2016 to identify patients diagnosed with chordomas. Inclusion criteria were chordomas of the mobile spine and sacrum. Exclusion criteria were chordomas of the clivus and resection performed at another institution. We collected patient demographics as well as the type of resection performed, intra-operative complications, wound complications and recurrence/prognosis. Results:We identified 18 patients diagnosed with chordomas at our institution, and 12 met our inclusion criteria. There were four females and eight males with an average age of 64 [32-87] years. All patients were Caucasian and 10 of the 12 had surgery. Of the two patients with sacral chordomas that did not have surgery, one received chemotherapy and the other did not elect for any treatment. One is alive 161 months following diagnosis and the second died 96 months following diagnosis. Five of the lesions were in the mobile spine (one cervical, two thoracic, two lumbar) and seven were in the sacrum. Six patients underwent an en bloc resection [two via total en bloc spondylectomy (TES)]. Average length of follow up is 60 [3-161] months and eight of 12 patients are alive at latest follow up. Intraoperative complications included cardiac arrest, pleural tear, and excessive blood loss (8 L). Two patients, with sacral chordomas, had wound complications. Recurrence occurred in one patient with piecemeal resection and one patient with incomplete resection had post-operative metastatic lesions to the liver and lung. Conclusions:We found less recurrence in patients managed with an en bloc resection as opposed to piece meal or intralesional resections. Sacral chordoma patients had higher wound complication rates as compared to chordomas of the mobile spine. The long life expectancy of non-surgically managed patients underscores the indolent nature of chordomas.

Project description:PurposeTo quantitatively evaluate published experiences with hepatic stereotactic body radiation therapy (SBRT), to determine local control rates after treatment of primary and metastatic liver tumors and to examine whether outcomes are affected by SBRT dosing regimen.Methods and materialsWe identified published articles that reported local control rates after SBRT for primary or metastatic liver tumors. Biologically effective doses (BEDs) were calculated for each dosing regimen using the linear-quadratic equation. We excluded series in which a wide range of BEDs was used. Individual lesion data for local control were extracted from actuarial survival curves, and data were aggregated to form a single dataset. Actuarial local control curves were generated using the Kaplan-Meier method after grouping lesions by disease type and BED (<100 Gy10 vs >100 Gy10). Comparisons were made using log-rank testing.ResultsThirteen articles met all inclusion criteria and formed the dataset for this analysis. The 1-, 2-, and 3-year actuarial local control rates after SBRT for primary liver tumors (n = 431) were 93%, 89%, and 86%, respectively. Lower 1- (90%), 2- (79%), and 3-year (76%) actuarial local control rates were observed for liver metastases (n = 290, log-rank P = .011). Among patients treated with SBRT for primary liver tumors, there was no evidence that local control is influenced by BED within the range of schedules used. For liver metastases, on the other hand, outcomes were significantly better for lesions treated with BEDs exceeding 100 Gy10 (3-year local control 93%) than for those treated with BEDs of ≤100 Gy10 (3-year local control 65%, P < .001).ConclusionsStereotactic body radiation therapy for primary liver tumors provides high rates of durable local control, with no clear evidence for a dose-response relationship among commonly utilized schedules. Excellent local control rates are also seen after SBRT for liver metastases when BEDs of >100 Gy10 are utilized.

Project description:Study designThis was a subanalysis of an international, multicenter, open-label study.ObjectiveThe aim of this study was to assess the efficacy and safety of denosumab in a subset of patients with giant cell tumors of bone (GCTB) of the spine including the sacrum from an international, open-label, single-arm, phase 2 study (ClinicalTrials.gov: NCT00680992).Summary of background dataStandard GCTB treatment is surgical removal, either by curettage or resection, combined with intraoperative adjuvant therapy; however, some sites may not be amenable to resection (e.g., skull, spine).MethodsAdults or skeletally mature adolescents with pathologically confirmed GCTB of the spine including the sacrum, and radiologically measurable evidence of active disease, were included. Patients received denosumab (120?mg subcutaneously) once every 4 weeks during the treatment phase, with loading doses on days 8 and 15 of the first cycle. Patients had surgically unsalvageable GCTB (Cohort 1), had planned surgery expected to result in severe morbidity (Cohort 2), or were enrolled from a previous GCTB study (Cohort 3).ResultsOverall, 132 patients were included in the safety analysis (103 in Cohort 1, 24 in Cohort 2, and five in Cohort 3); 131 patients were included in the efficacy analysis. Kaplan-Meier estimated probabilities of disease progression or recurrence were 3% (95% confidence interval [CI], 0.0-6.2) at year 1 and 7.4% (95% CI, 2.1-12.7) at years 3 and 5 in Cohort 1, and not estimable in Cohorts 2 and 3. Of 23 patients (Cohort 2) with surgery planned at baseline, 10 (43%) had on-study surgery; of these, one patient had reported disease progression or recurrence after the on-study surgery. Clinical benefit was reported in 83% of patients overall (all cohorts).ConclusionResults from the analysis suggest that denosumab is potentially effective treatment for patients with GCTB of the spine including the sacrum. The adverse event profile was consistent with the full study population.Level of Evidence: 2.

Dataset Information

Safety and Local Control of Radiation Therapy for Chordoma of the Spine and Sacrum: A Systematic Review.

Publications

Safety and Local Control of Radiation Therapy for Chordoma of the Spine and Sacrum: A Systematic Review.

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