Adolescent idiopathic scoliosis treated by posterior spinal segmental instrumented fusion : When is fusion to L3 stable?

OBJECTIVE: The purpose of this study was to identify risk factors for distal adding on (AO) or distal junctional kyphosis (DJK) in adolescent idiopathic scoliosis (AIS) treated by posterior spinal fusion (PSF) to L3 with a minimum 2-year follow-up. METHODS: AIS patients undergoing PSF to L3 by two senior surgeons from 2000–2010 were analyzed. Distal AO and DJK were deemed poor radiographic results and defined as >3 cm of deviation from L3 to the center sacral vertical line (CSVL), or >10° angle at L3–4 on the posterior anterior- or lateral X-ray at ultimate follow-up. New stable vertebra (SV) and neutral vertebra (NV) scores were defined for this study. The total stability (TS) score was the sum of the SV and NV scores. RESULTS: Ten of 76 patients (13.1%) were included in the poor radiographic outcome group. The other 66 patients were included in the good radiographic outcome group. Lower Risser grade, more SV-3 (CSVL doesn’t touch the lowest instrumented vertebra [LIV]) on standing and side bending films, lesser NV and TS score, rigid L3–4 disc, more rotation and deviation of L3 were identified risk factors for AO or DJK. Age, number of fused vertebrae, curve correction, preoperative coronal/sagittal L3–4 disc angle did not differ significantly between the two groups. Multiple logistic regression results indicated that preoperative Risser grade 0, 1 (odds ratio [OR], 1.8), SV-3 at L3 in standing and side benders (OR, 2.1 and 2.8, respectively), TS score -5, -6 at L3 (OR, 4.4), rigid disc at L3–4 (OR, 3.1), LIV rotation >15° (OR, 2.9), and LIV deviation >2 cm from CSVL (OR, 2.2) were independent predictive factors. Although there was significant improvement of the of Scoliosis Research Society-22 average scores only in the good radiographic outcome group, there was no significant difference in the scores between the groups. CONCLUSION: The prevalence of AO or DJK at ultimate follow-up for AIS with LIV at L3 was 13.1%. To prevent AO or DJK following fusion to L3, we recommend that the CSVL touch L3 in both standing and side bending, TS score is -4 or less, the L3/4 disc is flexible, L3 is neutral (<15°) and ≤2 cm from the midline and the patient is ≥ Risser 2

The incidence of adding-on or distal junctional kyphosis in adolescent idiopathic scoliosis treated by anterior spinal fusion to L3 was significantly higher than by posterior spinal fusion to L3

OBJECTIVE: To compare and identify risk factors for distal adding-on (AO) or distal junctional kyphosis (DJK) in adolescent idiopathic scoliosis (AIS) treated by anterior- (ASF) and posterior spinal fusion (PSF) to L3. METHODS: AIS patients undergoing ASF versus PSF to L3 from 2000-2010 were analyzed. Distal AO and DJK were deemed poor radiographic results. New stable (SV) and neutral vertebra (NV) scores were defined for this study. The total stability (TS) score was the sum of the SV and NV scores. RESULTS: Twenty of 42 (ASF group: 47.6%) and 8 of 72 patients (PSF group: 11.1%) showed poor radiographic outcome. Fused vertebrae, correction rate of main curve, coronal reduction rate of L3 were significantly higher in PSF group. Multiple logistic regression results indicated that preoperative SV-3 at L3 in standing and side benders (odds ratio [OR], 2.7 and 3.7, respectively), TS score -5, -6 at L3 (OR, 4.9), rigid disc at L3-4 (OR, 3.7), lowest instrumented vertebra (LIV) rotation \u3e 15° (OR, 3.3), LIV deviation \u3e 2 cm from center sacral vertical line (OR, 3.1) and ASF (OR, 13.4; p \u3c 0.001) were independent predictive factors. There was significant improvement of the Scoliosis Research Society (SRS)-22 average scores only in PSF group. Furthermore, the ultimate scores of PSF group were significantly superior to ASF group. CONCLUSION: The prevalence of AO or DJK at ultimate follow-up for AIS with LIV at L3 was significantly higher in ASF group. Ultimate SRS-22 scores were significantly better in PSF group

Selecting the touched vertebra as the lowest instrumented vertebra in patients with Lenke type-1 and 2 curves: Radiographic results after a minimum 5-year follow-up

BACKGROUND: The selection of the lowest instrumented vertebra (LIV) in patients with adolescent idiopathic scoliosis (AIS) is still controversial. Although multiple radiographic methods have been proposed, there is no universally accepted guideline for appropriate selection of the LIV. We developed a simple and reproducible method for selection of the LIV in patients with Lenke type-1 (main thoracic) and 2 (double thoracic) curves and investigated its effectiveness in producing optimal positioning of the LIV at 5 years of follow-up. METHODS: The radiographs for 299 patients with Lenke type-1 or 2 AIS curves that were included in a multicenter database were evaluated after a minimum duration of follow-up of 5 years. The touched vertebra (TV) was selected on preoperative radiographs by 2 independent examiners. The LIV on postoperative radiographs was compared with the preoperative TV. The final LIV position in relation to the center sacral vertical line (CSVL) was assessed. The CSVL-LIV distance and coronal balance in patients who had fusion to the TV were compared with those in patients who had fusion cephalad and caudad to the TV. The sagittal plane was also reviewed. RESULTS: In 86.6% of patients, the LIV was selected at or immediately adjacent to the TV. Among patients with an A lumbar modifier, those who had fusion cephalad to the TV had a significantly greater CSVL-LIV distance than those who had fusion to the TV (p = 0.006) or caudad to the TV (p = 0.002). In the groups with B (p = 0.424) and C (p = 0.326) lumbar modifiers, there were no differences among the TV groups. CONCLUSIONS: We recommend the TV rule as a third modifier in the Lenke AIS classification system. Selecting the TV as the LIV in patients with Lenke type-1 and 2 curves provides acceptable positioning of the LIV at long-term follow-up. The position of the LIV was not different when fusion was performed caudad to the TV but came at the expense of fewer motion segments. Patients with lumbar modifier A who had fusion cephalad to the TV had greater translation of the LIV, putting these patients at risk for poor long-term outcomes. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence

A multicenter phase II trial of ipilimumab and nivolumab in unresectable or metastatic metaplastic breast cancer: Cohort 36 of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART, SWOG S1609)

Purpose: Metaplastic breast cancer (MpBC) is a rare aggressive subtype that responds poorly to cytotoxics. Median survival is approximately eight months for metastatic disease. We report results for advanced MpBC treated with ipilimumab+nivolumab, a cohort of S1609 for rare cancers (DART: NCT02834013). Methods: Prospective, open-label, multicenter phase II (two-stage) trial of ipilimumab (1mg/kg IV q6weeks) plus nivolumab (240mg IV q2weeks) for advanced MpBC. Primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS) and toxicity. Results: Overall, 17 evaluable patients enrolled. Median age was 60 years (26-85); median number of prior therapy lines, 2 (0-5). ORR was 18%; 3/17 patients achieved objective responses (1 complete, 2 partial responses) (2 spindle cell, 1 chondromyxoid histology), which are ongoing at 28+, 33+ and 34+ months, respectively. Median PFS and OS were 2 and 12 months, respectively. Altogether, 11 patients (65%) experienced adverse events (AEs), including one grade 5 AE. Eight patients (47%) developed an immune-related AE (irAE); with adrenal insufficiency observed in all three responders. Responses occurred in tumors with low tumor mutational burden, low PD-L1 and absent TILs. Conclusion: The ipilimumab and nivolumab combination showed no new safety signals and met its primary endpoint with 18% ORR in advanced, chemotherapy-refractory MpBC. All responses are ongoing at >2 to almost 3 years later. The effect of ipilimumab and nivolumab was associated with exceptional responses in a subset of patients versus no activity. This combination warrants further investigation in MpBC, with special attention to understanding mechanism of action, and carefully designed to weigh against the significant risks of irAEs