This is Dr. Zohair Gogowalla. It's a great pleasure to participate in the neurosurgery and press virtual seminar with my colleagues. I would like to thank Fred Barker for the opportunity to speak once again today, where I will summarize some of the key clinical reports from the SPINE 2021. In terms of disclosure, I have a commercial disclosure for intellectual property and shares in a commercial entity, NIDUS, which has nothing to do with this presentation, federal funding from PCORI, which does pertain to this presentation, and independent foundation support from the Alan and Jackie Stewart SPINE Research Fund, Gina David Wallace Foundation, Lucinda B. Watson, and Lawrence and Stephanie Flynn, private donations to support scientific research. I would characterize the SPINE in 2021 as the return of the randomized control trial. There are two major papers that I'd like to focus on, the CSMS trial and the Nordsten DS trial. In terms of the first, a paper on cervical myelopathy, which I was involved in, published in JAMA in March of 2021, was a randomized clinical trial examining the effect of ventral versus dorsal spinal surgery for patient-reported outcome, physical component summary score in patients with cervical spondylotic myelopathy. This study is important because cervical myelopathy is obviously a prevalent condition. Surgery to treat cervical myelopathy is common. They're both ventral and dorsal approaches. In this particular study, the treatment arms were defined in a randomized control trial with 2-3 weighted allocation ventral to dorsal to permit a planned comparison between laminoplasty and fusion strategies. Ventral surgery included multilevel anterior cervical discectomy infusion or corpectomy. Dorsal surgery included laminoplasty or laminectomy and vital mass fusion. In this trial, a preliminary set of data was examined and a sample size estimate was calculated with 90 percent power at 159 randomized patients. These patients were accrued from 15 major centers. NIH funded study protocol development, and PCORI funded the study's actual execution. Study aims. Primary outcome was the one-year change in SF36 physical component summary score with an MCID, minimal clinically important difference, of five points. Secondary outcomes included mean change in SF36 physical component summary score, neck disability index, Uroqual 5D, and modified JOA measured 3, 6, and 12 months after surgery, as well as preoperatively. Secondary outcomes also included complications, as well as productivity, return to work, and health resource utilization, radiology utilization, physical therapy utilization, and opioid utilization. In terms of baseline characteristics, ventral surgery, laminectomy and fusion, and laminoplasty all had comparable baseline demographics, age, gender, as well as the baseline scores for SF36, modified JOA, EQ5D, NDI, and importantly, from a radiographic perspective, the levels of stenosis were comparable at 2.8 levels across all three groups. Primary outcome was the SF36 physical component summary score change over one year. You can see on this mountain plot, the ventral surgery arm shows baseline to one-year outcome score along this plot with improvement as a plot above this gray line, and a clinical decline after surgery as a plot below the line. In a similar way, dorsal fusion surgery is depicted in red, and dorsal laminoplasty is depicted in gray. You can see improvement in the dorsal surgery cases as well as a clinical decline in the dorsal fusion cases primarily. In terms of the randomized comparison of ventral versus dorsal intent to treat, there was no clinical difference between these groups as randomized. Looking carefully at the primary outcome and separating patients treated with dorsal laminoplasty versus dorsal fusion versus ventral fusion, there was superior outcomes observed at one year and at two years for patients treated with laminoplasty as opposed to ventral or dorsal fusion surgery. This was the case of both one and two years. Laminoplasty was associated with fewer complications. Ventral fusion surgery was associated with the most complications, although nearly half of the complications in that cohort were associated with minor dysphagia, which resolved within three months. Dorsal fusion surgery with a 27.5 percent complication rate and laminoplasty with a 10.7 percent complication rate. There were no significant differences in major complications among all groups. Major complications had a 16 percent rate in this study. Looking at return to work, there was a comparable rate of return to work at one year for all three strategies. However, return to work was faster for patients treated with either ventral fusion or with laminoplasty compared with dorsal fusion, which had the worst return to work rate at three months. Overall, laminoplasty returned to work more quickly than patients treated with either ventral or dorsal fusion. Also in the secondary outcome category, health resource utilization, there was less overall health resource utilization associated with laminoplasty for diagnostic testing, plane radiograph evaluation, ongoing physical therapy at one year, and opioid utilization at one year. For an economics analysis, we looked at hospital charges. These will ultimately be converted into hospital costs through an ongoing economic analysis. But looking at hospital charges, laminoplasty was associated with less hospital charges compared with dorsal fusion and ventral fusion, as you see here in this bar graph. There are limitations associated with this randomized controlled study. The promising results for laminoplasty should be interpreted with caution because patients treated with laminoplasty were selected by the treating surgeon among patients randomized to the dorsal arm of the trial, with therefore a potential for selection bias. A future randomized controlled trial would be important to validate these observations. Nevertheless, CSMS is the first randomized controlled study comparing ventral and dorsal surgery for CSM. In terms of that randomized comparison, ventral versus dorsal, there was no difference in SF36 physical component summary score outcome. As treated, however, in a non-randomized secondary analysis, laminoplasty was associated with superior health-related quality of life, measured with SF36 physical component summary score, fewer complications, and less outpatient health resource utilization at one year. Switching gears now to the lumbar spine, the NORDSTEN-DS trial was a non-inferiority randomized controlled study comparing decompression alone versus decompression and fusion. There has been substantial controversy associated with this topic of degenerative spondylolisthesis, where two previous New England Journal of Medicine papers were published in 2016. The Swedish study, which demonstrated no difference between patients treated with decompression versus decompression and fusion, and the SLIP study performed in the United States, which demonstrated that patients treated with decompression and fusion were associated with superior outcomes over time relative or compared with patients treated with decompression alone. This study is another randomized controlled study published in the New England Journal of Medicine just a few weeks ago. In this trial, decompression alone was a midline sparing procedure, and decompression and fusion included either MIS or open techniques with an inner body being optional. The patient population was pre-specified as single-level lumbar spondylolisthesis with symptomatic stenosis, with primary outcome measure being the two-year change in ODI score with a pre-specified non-inferiority margin of 15 points on the ODI score. The study randomized 267 patients where decompression alone was associated with a 20.6 point reduction in ODI score. Decompression and fusion was associated with a 21.3 point reduction in ODI score. Overall, 75 percent of patients had an ODI reduction of 30 points or more in both groups. The overall conclusion being that there's no significant difference between patients treated with decompression alone versus decompression and fusion. Looking at re-operations, decompression alone had a slightly higher rate of re-operation, 12.5 percent versus 9.1 percent for patients treated with decompression and fusion. Note that re-operations were not included in the primary analysis of this trial. Lumbar spondylolisthesis, where do we go from here? A couple of key points are worth noting as we evaluate these different studies. The American population may be different from the European population. The BMI was 27 in the Norwegian trial. Many of us, I think, would agree that patients treated in the United States for degenerative lumbar spondylolisthesis often have a BMI significantly higher than 27. In the Norwegian trial, follow-up was two years. By comparison, the slip study, the American study which found a major difference between the patients treated with decompression and fusion versus decompression alone, followed patients for four years in which the difference in re-operation rate was significantly different at that time. It is worth noting that in the slip study, the difference in re-operation rate at two years was not clinically significantly different. In summary, for this year, neurosurgery and PRESS, the return of the randomized control trial included a new trial on cervical spondylotic myelopathy, as well as a new trial on lumbar degenerative grade 1 spondylolisthesis. Thank you so much for the opportunity to speak with all of you today about these clinical trials in spine care. I look forward to talking more next year. Thanks again.

Dr. Zohair Gogowalla

neurosurgery

SPINE 2021

CSMS trial

Nordsten DS trial