Citations

Abstract Background Accurate assessments of patient response to therapy are a critical component of personalized medicine. In glioblastoma (GBM), the most aggressive form of brain cancer, tumor growth dynamics are heterogenous across patients, complicating assessment of treatment response. This study aimed to analyze days gained (DG), a burgeoning model-based dynamic metric, for response assessment in patients with recurrent GBM who received bevacizumab-based therapies. Methods DG response scores were calculated using volumetric tumor segmentations for patients receiving bevacizumab with and without concurrent cytotoxic therapy (N = 62). Kaplan–Meier and Cox proportional hazards analyses were implemented to examine DG prognostic relationship to overall (OS) and progression-free survival (PFS) from the onset of treatment for recurrent GBM. Results In patients receiving concurrent bevacizumab and cytotoxic therapy, Kaplan–Meier analysis showed significant differences in OS and PFS at DG cutoffs consistent with previously identified values from newly diagnosed GBM using T1-weighted gadolinium-enhanced magnetic resonance imaging (T1Gd). DG scores for bevacizumab monotherapy patients only approached significance for PFS. Cox regression showed that increases of 25 DG on T1Gd imaging were significantly associated with a 12.5% reduction in OS hazard for concurrent therapy patients and a 4.4% reduction in PFS hazard for bevacizumab monotherapy patients. Conclusion DG has significant meaning in recurrent therapy as a metric of treatment response, even in the context of anti-angiogenic therapies. This provides further evidence supporting the use of DG as an adjunct response metric that quantitatively connects treatment response and clinical outcomes.

Background: Donor site morbidity after anterior cruciate ligament (ACL) reconstruction with a bone–patellar tendon–bone (BTB) autograft is clinically significant, but evidence with contemporary techniques is lacking. Purpose: To (1) evaluate donor site morbidity at a single institution using modern techniques of BTB autograft harvest at 2-year follow-up, (2) develop a 10-question donor site morbidity instrument, and (3) compare this instrument against traditional outcome tools. Study Design: Case series; Level of evidence, 4. Methods: We analyzed the 2-year follow-up outcomes of 200 consecutive patients who underwent ACL reconstruction with a BTB autograft performed by 2 surgeons at a single institution. The surgical technique utilized modern and consistent BTB autograft harvest, including graft sizing, patellar tendon and peritenon closure, and patellar and tibial donor site bone grafting. There were 187 patients included, with 13 patients undergoing revision ACL reconstruction excluded. An original 10-question scoring instrument evaluating donor site morbidity was administered to each patient (score, 0-100) and compared against each patient’s International Knee Documentation Committee (IKDC) and Lysholm scores. Results: Overall, 13.9% of patients were noted to have anterior knee pain with activity at 2-year follow-up. Moreover, 3.7% of patients reported an inability to kneel on hard surfaces but had no problems on soft surfaces; 5.9% of patients reported mild discomfort but were able to kneel on all surfaces. Additionally, 75.4% of patients had a perfect (100/100) donor site morbidity score. The mean donor site morbidity score at 2-year follow-up was 98.3 ± 3.4. There was a very strong correlation between the IKDC and Lysholm scores but only a strong and moderate correlation when the donor site morbidity score was compared with the IKDC and Lysholm scores, respectively. Conclusion: Donor site morbidity after ACL reconstruction with a BTB autograft was less frequent than reported in the existing literature. Some patients developed anterior knee pain; therefore, an informed discussion is advised. IKDC and Lysholm scores may not capture donor site symptoms after surgery. The 10-question donor site morbidity instrument may provide a more accurate assessment.

Abstract Despite the widespread clinical use of dynamic susceptibility contrast (DSC) MRI, DSC-MRI methodology has not been standardized, hindering its utilization for response assessment in multicenter trials. Recently, the DSC-MRI Standardization Subcommittee of the Jumpstarting Brain Tumor Drug Development Coalition issued an updated consensus DSC-MRI protocol compatible with the standardized brain tumor imaging protocol (BTIP) for high-grade gliomas that is increasingly used in the clinical setting and is the default MRI protocol for the National Clinical Trials Network. After reviewing the basis for controversy over DSC-MRI protocols, this paper provides evidence-based best practices for clinical DSC-MRI as determined by the Committee, including pulse sequence (gradient echo vs spin echo), BTIP-compliant contrast agent dosing (preload and bolus), flip angle (FA), echo time (TE), and post-processing leakage correction. In summary, full-dose preload, full-dose bolus dosing using intermediate (60°) FA and field strength-dependent TE (40–50 ms at 1.5 T, 20–35 ms at 3 T) provides overall best accuracy and precision for cerebral blood volume estimates. When single-dose contrast agent usage is desired, no-preload, full-dose bolus dosing using low FA (30°) and field strength-dependent TE provides excellent performance, with reduced contrast agent usage and elimination of potential systematic errors introduced by variations in preload dose and incubation time.

2518 Background: This study sought to evaluate the prognostic significance of the three WHO-defined molecular glioma subgroups ( IDHwt, IDHmt/non-codel, and IDHmt/codel) in NRG Oncology/RTOG 0424, a phase II trial of high-risk low-grade gliomas treated with radiation (RT) and concurrent and adjuvant temozolomide (TMZ) after biopsy/surgical resection. Notably, this is the first clinical study to evaluate the prognostic value of the WHO subgroups in RT + TMZ-treated high-risk grade II (G2) gliomas using prospectively-collected long-term survival data. Methods: IDH1/2 mutation status was determined by next-generation sequencing. 1p/19q co-deletion status was determined by Oncoscan and/or 450K methylation data. Overall survival (OS) and progression-free survival (PFS) by marker status were determined by the Cox proportional hazard model and tested using the log-rank test in a post-hoc analysis. Patient pre-treatment characteristics were included as covariates in multivariate analyses. Results: Of all the eligible patients (N=129), 80 (62%) had sufficient quality DNA for both IDH and 1p/19q analyses. Of these 80, 54 (67.5%) were IDHmt, and 26 (32.5%) were IDHwt. Of the 54 IDHmt patients, 26 (32.5% of total, 48% of IDHmt) were IDHmt/codel, and 28 (35% of total, 52% of IDHmt) were IDHmt/non-codel. Both IDHmt subgroups were significantly correlated with longer PFS ( IDHmt/co-del = 8.1yrs (5.2-not reached (NR)); IDHmt/non-codel = 7.5yrs (3.9-11.8); IDHwt = 1.0yr (0.6-1.7), p<0.001) and OS ( IDHmt/co-del = 9.4yrs (8.2-NR); IDHmt/non-codel = 8.8yrs (5.9-NR); IDHwt = 2.3yrs (1.4-3.4), p<0.001) relative to the IDHwt subgroup. Upon univariate and multivariate analyses, both molecular IDHmt subgroup comparisons relative to IDHwt remained significant (p<0.001) even after incorporation of known clinical variables. Conclusions: These analyses suggest that G2 glioma patients harboring IDH1/2 mutations, regardless of co-deletion status, demonstrated longer survival with RT + TMZ relative to IDHwt tumors, although sample size is limited and analyses were post-hoc. These results also support the notion that outcomes for IDHwt high-risk G2 gliomas remain dismal (median = 2.3yrs, similar to G3 anaplastic astrocytoma); these patients should be separated from IDHmt patients in future G2 glioma trials, and warrant novel treatment strategies. Funding: U10CA180868, U10CA180822, U24CA196067, CURE, PA Dept. of Health, and Merck. Also, R01CA108633, R01CA169368, RC2CA148190, U10CA180850, BTFC, OSUCCC (all to AC). Clinical trial information: NCT00114140 .

Background: Meniscal root tears and ramp lesions have been rigorously characterized in recent literature. However, one of the most common lateral meniscal injuries identified with an acute anterior cruciate ligament (ACL) disruption, a posterior horn lateral meniscal oblique radial tear (LMORT), has not been thoroughly described. Purpose: To determine the incidence of all meniscal tears and, more specifically, the incidence of posterior horn LMORTs in a multicenter cohort of consecutive, acute ACL reconstructions. Additionally, the authors aimed to develop a new classification system to help guide treatment of posterior horn LMORTs. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A multicenter retrospective cohort design was used to analyze 200 consecutive cases of acute ACL reconstruction from each of 3 different surgeons, for a total of 600 patients. The operative notes and intraoperative photos were analyzed to determine the incidence and laterality of all meniscal tears. A classification system based on tear characterization was then used to categorize tear patterns into similar groups. Results: A total of 396 (66%) of the 600 patients with acute ACL disruption had concomitant meniscal tears. Specifically, 187 (31%) had a lateral meniscal injury, 89 (15%) had a medial meniscal injury, and 122 (20%) had both medial and lateral meniscal injuries. The most common lateral meniscal tear was an LMORT; 71 (18%) patients with meniscal tears had a posterior horn LMORT. Overall, the incidence of ACL injury with a concomitant posterior horn LMORT was 12%. A classification was developed, which included type 1 tear (partial thickness <10 mm from the root attachment), type 2 tear (complete radial oblique tear that extended <10 mm from root), type 3 tear (incomplete LMORT that extended >10 mm from root), and type 4 tear (complete LMORT >10 mm from root). Conclusion: In 600 consecutive acute ACL reconstructions, the incidence of concomitant ACL injury with meniscal injury was 66%, and posterior horn LMORTs represented a large proportion of all meniscal tears (12%). A classification scheme was developed for posterior horn LMORTs to aid reporting and clinical decision making for these common tears.

Over the past decade, a variety of new and innovative technologies has led to important advances in the diagnosis and management of patients with primary malignant brain tumors. New approaches to surgical navigation and tumor localization, advanced imaging to define tumor biology and treatment response, and the widespread adoption of a molecularly defined integrated diagnostic paradigm that complements traditional histopathologic diagnosis continue to impact the day-to-day care of these patients. In the neuro-oncology clinic, discussions with patients about the role of tumor treating fields (TTFields) and the incorporation of next-generation sequencing (NGS) data into therapeutic decision-making are now a standard practice. This article summarizes newer applications of technology influencing the pathologic, neuroimaging, neurosurgical, and medical management of patients with malignant primary brain tumors.

Abstract Background : Sex is recognized as a significant determinant of outcome among glioblastoma patients, but the relative prognostic importance of glioblastoma features has not been thoroughly explored for sex differences. Methods : Combining multi-modal MR images, biomathematical models, and patient clinical information, this investigation assesses which pretreatment variables have a sex-specific impact on the survival of glioblastoma patients (299 males and 195 females). Results : Among males, tumor (T1Gd) radius was a predictor of overall survival (HR=1.027, p=0.044). Among females, higher tumor cell net invasion rate was a significant detriment to overall survival (HR=1.011, p<0.001). Female extreme survivors had significantly smaller tumors (T1Gd) (p=0.010 t-test), but tumor size was not correlated with female overall survival (p=0.955 CPH). Both male and female extreme survivors had significantly lower tumor cell net proliferation rates than other patients (M p=0.004, F p=0.001, t-test). Conclusion : Despite similar distributions of the MR imaging parameters between males and females, there was a sex-specific difference in how these parameters related to outcomes.

Purpose To systematically evaluate the outcomes and complications of osteochondral autograft transfer (OAT) and osteochondral allograft transplantation (OCA) for the surgical treatment of capitellar osteochondritis dissecans (OCD). Methods A literature search was conducted across 3 databases (PubMed, Cochrane, and CINAHL [Cumulative Index to Nursing and Allied Health Literature]) from database inception through December 2019 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA) guidelines. Individual study quality was assessed using the Methodological Index for Non‐randomized Studies scale. Studies were published between 2005 and 2019. Results Eighteen studies consisting of 446 elbow OCD lesions treated with OAT surgery were included. There was a single OCA study eligible for inclusion. Patient ages ranged from 10 to 45 years. Of the OAT studies, 4 used autologous costal grafts whereas the remainder used autografts from the knee. Outcome measures were heterogeneously reported. A significant improvement in Timmerman‐Andrews scores from preoperatively to postoperatively was reported in 9 of 10 studies. Return‐to‐play rates to the preinjury level of competitive play ranged from 62% to 100% across 16 studies. Significant improvement in motion, most often extension, was noted in most studies. Reported complication, reoperation, and failure rates ranged from 0% to 11%, 0% to 26%, and 0% to 20%, respectively. When used, knee autografts resulted in low donor‐site morbidity (Lysholm scores, 70‐100). Conclusions OAT surgery for large, unstable OCD lesions of the capitellum reliably produced good outcomes, few complications, and a high rate of return to competitive play. Complications are relatively uncommon, and donor‐site morbidity is low. Less is known about the performance of OCA given the paucity of available literature. Level of Evidence Level IV, systematic review of Level II to IV studies.

Abstract Background : Sex is recognized as a significant determinant of outcome among glioblastoma patients, but the relative prognostic importance of glioblastoma features has not been thoroughly explored for sex differences. Methods : Combining multi-modal MR images, biomathematical models, and patient clinical information, this investigation assesses which pretreatment variables have a sex-specific impact on the survival of glioblastoma patients (299 males and 195 females). Results : Among males, tumor (T1Gd) radius was a predictor of overall survival (HR=1.027, p=0.044). Among females, higher tumor cell net invasion rate was a significant detriment to overall survival (HR=1.011, p<0.001). Female extreme survivors had significantly smaller tumors (T1Gd) (p=0.010 t-test), but tumor size was not correlated with female overall survival (p=0.955 CPH). Both male and female extreme survivors had significantly lower tumor cell net proliferation rates than other patients (M p=0.004, F p=0.001, t-test). Conclusion : Despite similar distributions of the MR imaging parameters between males and females, there was a sex-specific difference in how these parameters related to outcomes.