Faculty Bibliography

Deeper responses are associated with improved survival in patients being treated for myeloma. However, the sensitivity of the current blood-based assays is limited. Historical studies suggested that normalisation of the serum free light chain (FLC) ratio in patients who were negative by immunofixation electrophoresis (IFE) was associated with improved outcomes. However, recently this has been called into question. Mass spectrometry (MS)-based FLC assessments may offer a superior methodology for the detection of monoclonal FLC due to greater sensitivity. To test this hypothesis, all available samples from patients who were IFE negative after treatment with carfilzomib and lenalidomide-based induction and autologous stem cell transplantation (ASCT) in the Myeloma XI trial underwent FLC-MS testing. FLC-MS response assessments from post-induction, day+100 post-ASCT and six months post-maintenance randomisation were compared to serum FLC assay results. Almost 40% of patients had discordant results and 28.7% of patients with a normal FLC ratio had residual monoclonal FLC detectable by FLC-MS. FLC-MS positivity was associated with reduced progression-free survival (PFS) but an abnormal FLC ratio was not. This study demonstrates that FLC-MS provides a superior methodology for the detection of residual monoclonal FLC with FLC-MS positivity identifying IFE-negative patients who are at higher risk of early progression.

Background: Autologous stem cell transplant (ASCT) remains standard of care for eligible newly diagnosed myeloma patients (TE NDMM). Induction prior to ASCT frequently includes lenalidomide, reported to have an adverse effect on peripheal blood stem cell (PBSC) harvest in some studies.
Aim(s): The UK NCRI Myeloma XI/+ study compared induction combinations including thalidomide or lenalidomide giving the opportunity to compare PBSC harvests between patients treated with different immunomodulatory agents.
Method(s): TE NDMM patients were randomised to triplet combinations, thalidomide or lenalidomide plus dexamethasone and cyclophosphamide (Tdc/Rdc) or the quadruplet combination carfilzomib+Rdc (KRdc). Induction was given for a min. of 4 cycles but continued to max. response. Patients who received Tdc/Rdc and achieved a max. response less than VGPR underwent response-adapted intensification therapy. PBSC harvest was planned to occur after the completion of induction+/- intensification. Stem cell mobilisation and harvest was performed according to local practice with advice to aim for the collection of sufficient cells for at least two transplants. The median number of CD34+ cells harvested was compared between patients randomised to Tdc, Rdc and KRdc and those who received 4, 5-6 or >6 cycles of induction. Mann-Whitney U Tests were used to compare groups. Only patients achieving >=VGPR to initial induction, completing >=4 cycles and proceeding directly to ASCT were included in this analysis to avoid any impact of response or intensification therapy on harvest outcome.
Result(s): Of the1543 patients included, 521 had received Tdc (51.0% of all patients randomised to Tdc), 610 Rdc (59.7%), 412 KRdc (78.3%). Of these patients 88.4% underwent harvest (Tdc 86.9%, Rdc 87.5%, KRdc 91.5%). The median number of CD34+ cells harvested was lower for those who had received lenalidomide compared to thalidomide. Patients who received Tdc harvested a median 4.6x10^6/kg CD34+ cells, Rdc 4.1, KRdc 4.2 (Rdc vs Tdc p=0.0002, KRdc vs Rdc p=0.1766, KRdc vs Tdc p=0.0210). There was also a reduction in the median CD34+ cells harvested for patients requiring >6 cycles of induction to achieve maximum response prior to harvest. 4 cycles 4.5 x10^6/kg CD34+ cells, 5-6 cycles 4.2, >6 cycles 4.1 (4 vs 5-6 p=0.1212, 5-6 vs >6 p=0.1839, 4 vs >6 p=0.0262). The reduction in CD34+ cells with increasing number of induction cycles appeared greater for those patients who received lenalidomide induction. Tdc: 4 cycles 4.9 x10^6/kg CD34+ cells, 5-6 cycles 4.6, >6 cycles 4.6. Rdc: 4 cycles 4.4, 5-6 cycles 4.0, >6 cycles 3.5. KRdc: 4 cycles 4.4, 5-6 cycles 4.1, >6 cycles 3.9. This corresponded to a reduction in the proportion of patients meeting the threshold for two ASCTs both between therapies and with increasing cycles. Tdc: 4 cycles 63.0%, 5-6 cycles 60.2%, >6 cycles 61.4%. Rdc: 4 cycles 54.3%, 5-6 cycles 47.4%, >6 cycles 46.2%. KRdc: 4 cycles 60.9%, 5-6 cycles 49.3%, >6 cycles 41.7%. Despite these differences, more than 96% of patients in all groups were considered to have enough stem cells and proceeded to first ASCT within the trial, with no differences between treatment groups. Summary/Conclusion: Lenalidomide-based induction therapy was associated with lower median CD34+ cells harvested than thalidomide-based induction. This had no impact on the proportion of patients able to undergo first ASCT. The reduction in median CD34+ cells with lenalidomide was most marked when >4 cycles were administered. This should be considered when planning the timing of harvests, especially if storage of sufficient cells for two ASCTs is desired

Lumbar fusion is an accepted and effective technique for the treatment of lumbar degenerative disease. The practice has evolved continually since Albee and Hibbs independently reported the first cases in 1913, and advancements in both technique and patient selection continue through the present day. Clinical and radiological indications for surgery have been tested in trials, and other diagnostic modalities have developed and been studied. Fusion practices have also advanced; instrumentation, surgical approaches, biologics, and more recently, operative planning, have undergone stark changes at a seemingly increasing pace over the last decade. As the general population ages, treatment of degenerative lumbar disease will become a more prevalent-and costlier-issue for surgeons as well as the healthcare system overall. This review will cover the evolution of indications and techniques for fusion in degenerative lumbar disease, with emphasis on the evidence for current practices.

QUESTION:Does early surgical intervention improve outcomes for patients with thoracic and lumbar fractures? RECOMMENDATIONS:There is insufficient and conflicting evidence regarding the effect of timing of surgical intervention on neurological outcomes in patients with thoracic and lumbar fractures. Strength of Recommendation: Grade Insufficient It is suggested that "early" surgery be considered as an option in patients with thoracic and lumbar fractures to reduce length of stay and complications. The available literature has defined "early" surgery inconsistently, ranging from <8 h to <72 h after injury. Strength of Recommendation: Grade B The full version of the guideline can be reviewed at: https://www.cns.org/guideline-chapters/congress-neurological-surgeons-systematic-review-evidence-based-guidelines/chapter_10.

QUESTION 1:Are there classification systems for fractures of the thoracolumbar spine that have been shown to be internally valid and reliable (ie, do these instruments provide consistent information between different care providers)? RECOMMENDATION 1:A classification scheme that uses readily available clinical data (eg, computed tomography scans with or without magnetic resonance imaging) to convey injury morphology, such as Thoracolumbar Injury Classification and Severity Scale or the AO Spine Thoracolumbar Spine Injury Classification System, should be used to improve characterization of traumatic thoracolumbar injuries and communication among treating physicians. Strength of Recommendation: Grade B. QUESTION 2:In treating patients with thoracolumbar fractures, does employing a formally tested classification system for treatment decision-making affect clinical outcomes? RECOMMENDATION 2:There is insufficient evidence to recommend a universal classification system or severity score that will readily guide treatment of all injury types and thereby affect outcomes. Strength of Recommendation: Grade Insufficient The full version of the guideline can be reviewed at: https://www.cns.org/guideline-chapters/congress-neurological-surgeons-systematic-review-evidence-based-guidelines/chapter_2.

QUESTION:Does the active maintenance of arterial blood pressure after injury affect clinical outcomes in patients with thoracic and lumbar fractures? RECOMMENDATIONS:There is insufficient evidence to recommend for or against the use of active maintenance of arterial blood pressure after thoracolumbar spinal cord injury. Grade of Recommendation: Grade Insufficient However, in light of published data from pooled (cervical and thoracolumbar) spinal cord injury patient populations, clinicians may choose to maintain mean arterial blood pressures >85 mm Hg in an attempt to improve neurological outcomes. Consensus Statement by the Workgroup The full version of the guideline can be reviewed at: https://www.cns.org/guideline-chapters/congress-neurological-surgeons-systematic-review-evidence-based-guidelines/chapter_6.

QUESTION:Does the administration of a specific pharmacologic agent (eg, methylprednisolone) improve clinical outcomes in patients with thoracic and lumbar fractures and spinal cord injury? RECOMMENDATION:There is insufficient evidence to make a recommendation; however, the task force concluded, in light of previously published data and guidelines, that the complication profile should be carefully considered when deciding on the administration of methylprednisolone. Strength of recommendation: Grade Insufficient The full version of the guideline can be reviewed at: https://www.cns.org/guideline-chapters/congress-neurological-surgeons-systematic-review-evidence-based-guidelines/chapter_5.

BACKGROUND:The thoracic and lumbar ("thoracolumbar") spine are the most commonly injured region of the spine in blunt trauma. Trauma of the thoracolumbar spine is frequently associated with spinal cord injury and other visceral and bony injuries. Prolonged pain and disability after thoracolumbar trauma present a significant burden on patients and society. OBJECTIVE:To formulate evidence-based clinical practice recommendations for the care of patients with injuries to the thoracolumbar spine. METHODS:A systematic review of the literature was performed using the National Library of Medicine PubMed database and the Cochrane Library for studies relevant to thoracolumbar spinal injuries based on specific clinically oriented questions. Relevant publications were selected for review. RESULTS:For all of the questions posed, the literature search yielded a total of 6561 abstracts. The task force selected 804 articles for full text review, and 78 were selected for inclusion in this overall systematic review. CONCLUSION:The available evidence for the evaluation and treatment of patients with thoracolumbar spine injuries demonstrates considerable heterogeneity and highly variable degrees of quality. However, the workgroup was able to formulate a number of key recommendations to guide clinical practice. Further research is needed to counter the relative paucity of evidence that specifically pertains to patients with only thoracolumbar spine injuries. The full version of the guideline can be reviewed at: https://www.cns.org/guideline-chapters/congress-neurological-surgeons-systematic-review-evidence-based-guidelines/chapter_1.

BACKGROUND:Radiological evaluation of traumatic thoracolumbar fractures is used to classify the injury and determine the optimal treatment plan. Currently, there remains a lack of consensus regarding appropriate radiological protocol. Most clinicians use a combination of plain radiographs, 3-dimensional computed tomography with reconstructions, and magnetic resonance imaging (MRI). OBJECTIVE:To determine, through evidence-based guidelines review: (1) whether the use of MRI to identify ligamentous integrity predicted the need for surgical intervention; and (2) if there are any radiological findings that can assist in predicting clinical outcomes. METHODS:A systematic review of the literature was performed using the National Library of Medicine/PubMed database and the Cochrane Library for studies relevant to thoracolumbar trauma. Clinical studies specifically addressing the radiological evaluation of thoracolumbar spine trauma were selected for review. RESULTS:Two of 2278 studies met inclusion criteria for review. One retrospective review (Level III) and 1 prospective cohort (Level III) provided evidence that the addition of an MRI scan in acute thoracic and thoracolumbar trauma can predict the need for surgical intervention. There was insufficient evidence that MRI can help predict clinical outcomes in patients with acute traumatic thoracic and thoracolumbar spine injuries. CONCLUSION:This evidence-based guideline provides a Grade B recommendation that radiological findings in patients with acute thoracic or thoracolumbar spine trauma can predict the need for surgical intervention. This evidence-based guideline provides a grade insufficient recommendation that there is insufficient evidence to determine if radiographic findings can assist in predicting clinical outcomes in patients with acute thoracic and thoracolumbar spine injuries. QUESTION 1:Are there radiographic findings in patients with traumatic thoracolumbar fractures that can predict the need for surgical intervention? RECOMMENDATION 1:Because MRI has been shown to influence the management of up to 25% of patients with thoracolumbar fractures, providers may use MRI to assess posterior ligamentous complex integrity, when determining the need for surgery. Strength of Recommendation: Grade B. QUESTION 2:Are there radiographic findings in patients with traumatic thoracolumbar fractures that can assist in predicting clinical outcomes? RECOMMENDATION 2:Due to a paucity of published studies, there is insufficient evidence that radiographic findings can be used as predictors of clinical outcomes in thoracolumbar fractures. Strength of Recommendation: Grade Insufficient The full version of the guideline can be reviewed at: https://www.cns.org/guideline-chapters/congress-neurological-surgeons-systematic-review-evidence-based-guidelines/chapter_3.