Spinal metastases from thyroid cancer: Some prognostic factors.

BACKGROUND: Spinal metastases (SpMs) from thyroid cancers (TC) significantly reduce quality of life by causing pain, neurological deficits in addition to increasing mortality. Moreover, prognosis factors including surgery remain debated. METHODS: Data were stored in a prospective French national multicenter database of patients treated for SpM between January 2014 and 2017. Fifty-one consecutive patients affected by TC with 173 secondary SpM were included. RESULTS: Mean overall survival (OS) time for all patients from the diagnosis of a thyroid SpM event was 9.1 years (SD 8.7 months). The 1-year, 5-year and 10-year survival estimates were 94% (SD 3.3), 83.8.0% (SD 5.2), and 74.5% (SD 9.9). The median period of time between primary thyroid tumor diagnosis and the SpM event was 31.4 months (SD 71.6). In univariate analysis, good ECOG-PS (status 0 and 1) (p < 0.0001), ambulatory status (Frankel score) (p < 0.0001) and no epidural involvement (p = 0.01), were associated with longer survival, whereas cancer subtype (p = 0.436) and spine surgery showed no association (p = 0.937). Cox multivariate proportional hazard model only identified good ECOG-PS: 0 [HR: 0.3, 95% CI 0.1-0.941; p < 0.0001], 1 [HR: 0.8, 95% CI 0.04-2.124; p = 0.001] and ambulatory neurological status: Frankel E [HR: 0.262, 95% CI 0.048-1.443; p = 0.02] to be independent predictors of better survival. CONCLUSION: For cases presenting SpM from TC, we highlighted that the only prognostic factors were the progression of the cancer (ECOG-PS) and the clinical neurological impact of the SpM (Frankel status). Surgery should be discussed mainly for stabilization and neurological decompression.

Are spine metastasis survival scoring systems outdated and do they underestimate life expectancy? Caution in surgical recommendation guidance.

OBJECTIVE: Survival scoring systems for spine metastasis (SPM) were designed to help surgical practice. The authors sought to validate the prognostic accuracy of the main preoperative scoring systems for SPM. METHODS: It was hypothesized that true patient survival in SPM was better than that predicted using prognosis scores. To investigate this hypothesis, the authors designed a French national retrospective study of a prospectively collected multicenter database involving 739 patients treated for SPM between 2014 and 2017. RESULTS: In this series, the median survival time for all patients from an SPM diagnosis was 17.03 ± 1.5 months. Sensitivity and specificity were estimated using the area under the curve (AUC). The AUC of Tomita's prognosis score was the lowest and poorest (0.4 ± 0.023, range 0.35-0.44), whereas the AUC of the Tokuhashi score was the highest (0.825). The Lei score presented an AUC of 0.686 ± 0.022 (range 0.64-0.7), and the Rades score showed a weaker AUC (0.583 ± 0.020, range 0.54-0.63). Differences among AUCs were all statistically significant (p < 0.001). The modified Bauer score and the Rades score had the highest rate of agreement in predicting survival, with a weighted Cohen's kappa of 0.54 and 0.41, respectively, indicating a moderate agreement. The revised Tokuhashi and Lei scores had a fair rate of agreement (weighted Cohen's kappa = 0.24 and 0.22, respectively). The van der Linden and Tomita scores demonstrated the worst performance, with only a "slight" rate of agreement (weighted Cohen's kappa = 0.19 and 0.16, respectively) between what was predicted and the actual survival. CONCLUSIONS: The use of prognostic scoring systems in the estimation of survival in patients with SPM has become obsolete and therefore underestimates survival. Surgical treatment decisions should no longer be based on survival estimations alone but must also take into account patient symptoms, spinal instability, and quality of life.

Spine Metastasis in Elderly: Encouraging Results for Better Survival.

MINI: The incidence of spinal metastasis (SpM) is increasing, and life expectancy for patients with malignancy is also rising. The "elderly" represent a population with steady growth in SpM proportion. Bracing is associated with lower survival. We believe that surgery should be considered, regardless of the patient's age.

Multicentric prospective study. Through this study, we aimed to clarify and update the prognostic assessment of elderly with spine metastasis (SpM). The incidence SpM is rising, in parallel life expectancy is getting longer and the number of elderly patients presenting malignancy is increasing. Elderly patients with SpM constitute a growing heterogeneous population The patient data used in this study were obtained from a French national multicenter database of patients treated for SpM between 2014 and 2017. Two hundred and forty-three consecutive patients >70 years' old were diagnosed. Median overall survival (OS) time for elderly patients following the event of SpM was 16.3 months. First, we identified significantly worse survival prognostic factors for elderly patients with SpM: poor WHO status 3/4: (hazard ratio [HR]: 2.245, 95% confidence interval [CI] 1.899­2.655; P  < 0.0001), >80 years (HR: 1.758, 95% CI 1.117­2.765; P  = 0.015) no-ambulatory neurological status (Franckel A/B status [HR: 3.219, 95% CI 1.621­6.390; P  < 0.0001)], gastrointestinal cancer (HR: 3.530, 95% CI 1.75­7.1; P  < 0.0001), lung cancer (HR: 3.452, 95% CI 1.784­6.680; P  < 0.0001), orthopedic brace treatment (HR: 1.329; 95% CI 1.050­1.683; P  = 0.018), and epiduritis (HR: 1.52, 95% CI 1.041­2.22; P  = 0.03) were independently poor prognostic factors of survival. The only good prognosis factor identified was thyroid cancer (HR: 0.257, 95% CI 0.07­0.952; P  = 0.04). Prognosis factors concerning the survival of elderly patients seem to be the same as those for the general population such as primary cancer histology, neurological status, WHO status, and epiduritis. Age >80 years also appears to be an independently poor prognosis factor. Our data suggest that orthopedic brace treatment is also associated with lower survival. Level of Evidence: 2.

Spine metastasis in patients with prostate cancer: Survival prognosis assessment.

BACKGROUND: Patients presenting spine metastasis (SpM) from prostate cancer (PC) form a heterogeneous population, through this study, we aimed to clarify and update their prognostic assessment. METHODS: The patient data used in this study was obtained from a French national multicenter database of patients treated for PC with SpM between 2014 and 2017. A total of 72 patients and 365 SpM cases were diagnosed. RESULTS: The median overall survival time for all patients following the event of SpM was 28.8 months. First, we identified three significant survival prognostic factors of PC patients with SpM: good Eastern Cooperative Oncology Group/World Health Organization personnel status (Status 0 hazard ratio [HR]: 0.031, 95% confidence interval [CI]: 0.008-0.127; p < .0001) or (Status 1 HR: 0.163, 95% CI: 0.068-0.393; p < .0001) and SpM radiotherapy (HR: 2.923, 95% CI: 1.059-8.069; p < .0001). Secondly, the presence of osteolytic lesions of the spine (vs. osteoblastic) was found to represent an independent prognosis factor for longer survival [HR: 0.424, 95% CI: 0.216-0.830; p = .01]. Other factors including the number of SpM, surgery, extraspinal metastasis, synchrone metastasis, metastasis-free survival, and SpM recurrence were not identified as being prognostically relevant to the survival of patients with PC. CONCLUSION: Survival and our ability to estimate it in patients presenting PC with SpM have improved significantly. Therefore, we advocate the relevance of updating SpM prognostic scoring algorithms by incorporating data regarding the timeline of PC as well as the presence of osteolytic SpM to conceive treatments that are adapted to each patient.

Spinal metastases from lung cancer: Survival depends only on genotype, neurological and personal status, scarcely of surgical resection.

BACKGROUND: For patients with non-small cell lung cancer (NSCLC), the spinal column is the most common site for bone metastasis. Studies that assess survival prognostic factors associated with specific lung spinal metastases (SpM) are weak and required the incorporation of genotype mutations. METHODS: A prospective French national multicenter database of patients treated for SpM between January 2014 and 2017.818 lung SpM were diagnosed over the course or at the time of diagnosis of 210 consecutive patients with NSCLC. RESULTS: Median overall survival (OS) time for all patients from the lung SpM event was 5.9 months (SD 0.609). For 122 patients (61%), lung tumor and SpM were diagnosed synchronously. In univariate analysis, good World Health Organisation (WHO) status (p < 0.0001), ambulatory status (Frankel score) (p < 0.0001), the absence of spine epiduritis (p < 0.0001), immunotherapy after SpM diagnosis (p < 0.0001), ALK gene rearrangement (p < 0.0001) and EGFR mutation (p < 0.0001) were associated with longer survival, whereas spine surgery showed no association (0.141). Cox multivariate proportional hazard model identified that EGFR + status (HR: 0.339, 95% CI 0.166-0.693; p = 0.003), good WHO status (p < 0.0001) and good neurological status (Frankel E; p < 0.001 and D; p = 0.018) were associated with higher median OS. Whereas the other factors, including ALK + status, epiduritis and immunotherapy were not independent prognostic factors of survival. CONCLUSION: Survival in SpM must be prognosticated from general health performance status: clinical (WHO) and neurological (Frankel) as well as the EGFR mutation status. Immunotherapy, surgery and epiduritis have not demonstrated prognostic value. Therefore, surgical prognostic scoring algorithms should incorporate genotype subtypes in NSCLC cancers to adapt surgical treatment.

Intra-CSF AAV9 and AAVrh10 Administration in Nonhuman Primates: Promising Routes and Vectors for Which Neurological Diseases?

The identification of the most efficient method for whole central nervous system targeting that is translatable to humans and the safest route of adeno-associated virus (AAV) administration is a major concern for future applications in clinics. Additionally, as many AAV serotypes were identified for gene introduction into the brain and the spinal cord, another key to human gene-therapy success is to determine the most efficient serotype. In this study, we compared lumbar intrathecal administration through catheter implantation and intracerebroventricular administration in the cynomolgus macaque. We also evaluated and compared two AAV serotypes that are currently used in clinical trials: AAV9 and AAVrh10. We demonstrated that AAV9 lumbar intrathecal delivery using a catheter achieved consistent transgene expression in the motor neurons of the spinal cord and in the neurons/glial cells of several brain regions, whereas AAV9 intracerebroventricular delivery led to a consistent transgene expression in the brain. In contrast, AAVrh10 lumbar intrathecal delivery led to rare motor neuron targeting. Finally, we found that AAV9 efficiently targets respiratory and skeletal muscles after injection into the cerebrospinal fluid (CSF), which represents an outstanding new property that can be useful for the treatment of diseases affecting both the central nervous system and muscle.

Survival in breast cancer patients with spine metastases: Prognostic assessment involving molecular markers.

BACKGROUND: To clarify and update the prognostic assessment for heterogeneous population of patients with breast cancer and spine metastases (SpM), using molecular markers. METHODS: The patient data used in this study was obtained from a French national multi-center database of patients treated for breast cancer with SpM between 2014 and 2017. 556 SpM cases were diagnosed. RESULTS: Median overall survival (OS) time for all patients following the SpM event was 43.9 months. First, we confirmed 3 previously known significant prognostic factors for survival of patients with SpM: young age [HR: 2.019, 95% CI 1.343-3.037; p = 0.001], good WHO status [ Status 0 HR: 2.823, 95% CI 1.231-3.345; p < 0.0001] or [ Status 1 HR: 1.956, 95% CI 0.768-2.874; p = 0.001] and no-ambulatory neurological status: Frankel A-C [HR: 0.438, 95% CI 0.248-0.772; p = 0.004]. Secondly, we determined the effect of gene mutations on survival in patients with SpM, and we identified that HER2+ cancer subtype [HR: 1.567, 95% CI 0.946-2.557; p = 0.008] was an independent predictor of longer survival, whereas basal cancer subtype [HR: 0.496, 95% CI 0.353-0.699; p < 0.0001] was associated with a poorer prognosis. Other factors including the number of SpM, surgery, extraspinal metastases, synchrone metastases, metastasis-free survival, and SpM recurrence were not identified as prognostically relevant to survival. CONCLUSION: Survival and our ability to estimate it in breast cancer patients with SpM has improved significantly. Therefore, SpM prognostic scoring algorithms should be updated and incorporate genotypic data on subtypes to make treatment more adaptive.

Approaching spinal metastases spread profile.

BACKGROUND: Spinal metastases cause significant morbidity. The vertebral column is the most common site of cancer metastasis, however predilection of metastases for the spine is not fully understood. OBJECTIVE: The aim of the present investigation was to obtain a better description of the distribution of spinal metastases. The main objective of our study was to figure out how malignant cells disseminate within the spine and determine a potent mapping or profile of the metastatic spread routes. STUDY DESIGN: A prospective French national multicenter database. METHODS: 740 consecutive patients were treated for spine metastasis (SpM) between January 2014 and 2017. A categorisation of the anatomical distribution of spine lesions was conducted. RESULTS: One hundred and seventy patients (22.9% of series) presented cervical SpM, 440 (60%) lumbar SpM, and a majority 530 (71.6%) at the thoracic vertebral level. Metastases were more often present in the vertebral body (645 patients, 87.2%) than in a posterior location (278 patients, 37.6%, p < 0.0001). 212/740 patients (28.6%) presented circumferential spine involvement (body and posterior elements). An associated epiduritis was presented in 404 patients (54.6%). Primitive neck tumors spread towards the cervical spine: ENT (34.8%, p = 0.049), thyroid (33.3%, p = 0.043) whereas pelvic tumors targeted the lumbar spine: prostate (72%, p = 0.011), bladder (75%, p = 0.047). All tumors presented a tropism for thoracic vertebrae. Significant tumor/vertebrae associations were identified: lung (p = 0.004) and thyroid (p = 0.028) for L1, bladder for L5 (p = 0.0025), breast for C6 (p = 0.006), Prostate for L1-L4 (p = 0.002-0.04), multiple myelomas for C7, p = 0.03, T3-T7 (p < 0.0001-0.025) and L1-L4 (p = 0.004-0.027). Spine was the latest organ affected by metastases with a median-free survival of 4.2 months (SD 1.8, p = 0.001). CONCLUSIONS: Although we determined that some tumors have a significant propensity to localise at certain vertebral level, it remains premature to conclude on a spinal metastases profile. To date, it is too early to provide recommendations in imaging follow-up or in preventive therapeutic based on this mapping of spine metastases.

Long-Term Follow-Up Comparative Study of Hydroxyapatite and Autologous Cranioplasties: Complications, Cosmetic Results, Osseointegration.

OBJECTIVE: A three-dimensional reconstruction technique using the CustomBone (CB) prosthesis allows custom-made cranioplasty (CP) possessing osseointegration properties owing to its porous hydroxyapatite (HA) composition. This reconstruction technique has replaced less expensive techniques such as subcutaneously preserved autologous bone (SP). Our primary objective was to evaluate complications between CB and SP CP techniques. A secondary objective was to assess cosmetic results and osseointegration of CPs. METHODS: This single-center study comprised patients undergoing delayed CB or SP CP after craniectomy between 2007 and 2014. A prospective interview was conducted to collect all data, including 2-year follow-up clinical and radiologic data. Cosmetic results were assessed by a qualitative score, and osseointegration was assessed by measuring relative fusion at the CP margins. RESULTS: Of 100 patients undergoing CB or SP CP between 2007 and 2014, 92 (CB, n = 44; SP, n = 48) participated in the prospective interview. No significant difference in complication rates was observed between the 2 groups. The main complication specific to the CB group was fracture of the prosthesis observed in 20.8% patients. A higher rate of good cosmetic results was observed in the CB group (92.5% vs. 74.3%, P = 0.031). In the CB group, 51% of patients demonstrated no signs of bone fusion of the CP. CONCLUSIONS: Although the CB prosthesis is associated with cosmetic advantages, the porous hydroxyapatite composition makes it fragile in the short-term and long-term, and effective osseointegration remains uncertain.

Non neurologic burst thoracolumbar fractures fixation: Case-control study.

STUDY DESIGN: Burst fractures not associated with any neurological deficits are frequent but not therapeutic agreement on their management is available to date. This case-control study was conducted to try to help guide therapeutic decision in the treatment of such fractures. MATERIALS AND METHODS: This case-control study includes consecutive retrospective evaluation of 25 case-patients treated by posterior short-segment fixation associated with kyphoplasty (SFK) in the treatment of A3 thoracolumbar unstable fractures, as compared to a control-group composed of 82 patients treated by long-segment (LF) pedicle screws. RESULTS: SFK patients bled significantly less than the LF patients (p=0.04). Assessment of deformation progression, vertebral height restoration and reduction of the regional kyphotic angle in the SFK and LF groups revealed no statistically significant superiority of one approach on another. In contrast, the height of endplates was significantly increased in the SFK group (p=0.006). The patients' pain levels were significantly improved in the SFK group (p=0.002). However, patients from the SFK group stood earlier postoperatively (1.7 vs 3.7days, p=0.001). CONCLUSION: We believe that SFK in vertebral fractures is as efficient as LF for bone consolidation and spine stabilization. In addition, SFK patients may use fewer analgesics.

Overall Survival in Spine Myeloma Metastases: Difficulties in Predicting With Prognostic Scores.

STUDY DESIGN: Fifty-one patients with spinal multiple myeloma (MM) metastases were operated and followed between January 2004 and July 2014. OBJECTIVE: The aim of this study was to consider the efficiency of surgical prognosis scores in the management of spinal metastases myelomas. SUMMARY OF BACKGROUND DATA: The spine is the most common site of bone metastases in MM. Surgery in spine metastases MM is a matter of debate and its impact on the increase of a patient's survival time is not clear. Several surgical survival scores have been developed to determine the best treatment in these patients. METHODS: We studied 51 patients operated for spinal MM metastases between January 2004 and July 2014. We determined the Tokuhashi and Tomita survival scores and compared them with documented patient survivals. The two scores were also compared with the International Staging System (ISS). RESULTS: Median survival (MS) was 108 months [standard deviation (SD) 62] for ISS I, 132.2 (SD 40) for ISS II, and 45.5 months (SD 16.3) for ISS III (P = 0.09). According to Tokuhashi survival score, 21 patients (41.2%) will survive <6 months, 6 (11.8%) 6 to 12 months, and 24 (47%) >12 months. According to Tomita et al., 50 patients (98%) will survive >49.9 months and 1 patient (2%) <15 months. Regardless of the ISS grade prognosis, Tokuhashi survival score, and to a lesser extent Tomita score, underestimated the actual survival very significantly [P < 0.0001, Log Rank (Mantel-Cox)]. CONCLUSION: We suggest that spine surgical prognosis scores are not accurate and are not able to predict the survival of patients with spine myeloma metastases. Spine surgeons have to be guided not by the initial ISS stage but rather by spinal instability and neurological status. LEVEL OF EVIDENCE: N/A.

Predictors of survival in patients with surgical spine multiple myeloma metastases.

BACKGROUND: Multiple myeloma (MM) is the most common primary malignant tumor of the spine and bone. Spinal metastases are part of the evolution and progression of the MM disease. Therefore, this study aims at investigating prognostic factors associated with overall survival (OS) in patients with symptomatic spine MM metastases. METHODS: Consecutive spine surgery procedures were performed in the largest series reported to date and comprising 51 patients with osteolytic vertebral compression fractures resulting from MM, diagnosed by either bone marrow or tumor biopsy. RESULTS: The mean age of patients was 61.1 years and mean follow-up was 31.9 months. Through univariate analyses, ISS stage (p < 0.0001), preoperative spine instability (SINS score) (p < 0.03), posterior osteosynthesis fixation (p < 0.002), preoperative adjuvant therapy (p < 0.02), postoperative adjuvant treatment (p < 0.001), bone marrow transplant (p < 0.03) and newly MM diagnosed (p < 0.03) emerged as powerful predictors of survival. Cox multivariate proportional hazard model indicated that only ISS Stage and stabilization surgery such as osteosynthesis were two independent predictive factors for OS [hazard ratio (HR): 0.268, 95% confidence interval (CI) 0.07-0.536; p < 0.006 for the former and HR: 0.184, 95% confidence interval (CI) 0.03-0.89; p < 0.04 for the latter]. CONCLUSION: Stabilization surgery combined to ISS staging should be considered as an important prognostic survival factor for patients with symptomatic MM spine metastases.