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49 citation(s) found for "Fox, W Christopher".

Resolution of atlanto-occipital cyst with conservative management: A case report and review of the literature
Rivas, Gabriella , Hurdle, Mark Friedrich B., Chen, Selby , Rivas, Gabriella A., Hurdle, Mark, Biase, Gaetano De , Domingo, Ricardo A. , Fox, W Christopher

Mayo Clinic

Surgical Neurology International | October 21, 2022 | Volume: 13 | Issue: No issue available | Pages: 478

10.25259/sni_841_2022 | PMID 36324942 Get It

Background: Spinal synovial cysts are cystic dilatations of synovial sheaths that extrude into the spinal canal. Despite their generally benign behavior, they can cause severe symptoms due to compression of neural structures. They are most commonly found in the lumbar spine and are rare in the cervical region, especially at the atlanto-occipital junction. Case Description: A 65-year-old presented with neck pain and headaches. The magnetic resonance imaging (MRI) revealed a degenerative cyst within the anterior foramen magnum causing anterior spinal cord and brainstem compression. Multiple surgical treatment options were discussed, and he was prescribed methylprednisolone and immobilization of his cervical spine with a rigid collar. One month later, the patient reported dramatic improvement of his symptoms, and no surgery was performed. One year later, his pain had remained much improved with the continued use of the collar and pain management (i.e., using anti-inflammatories and muscle relaxants). The 1-year follow-up MRI showed the atlanto-occipital cyst compressing the cervicomedullary junction had completely resolved along with the brainstem compression. Conclusion: A 65-year-old presented with myelopathy attributed to a large anterior foramen magnum atlanto-occipital cyst compressing the cord. Conservative management for 1 month with a rigid cervical collar and steroids resulted in marked neurological improvement; at 1 year follow-up, the patient was markedly improved with an MR that demonstrated spontaneous cyst regression.
Intracranial Aneurysms in Loeys–Dietz Syndrome: A Multicenter Propensity-Matched Analysis
Perez‐Vega, Carlos , Tripathi, Shashwat , Santos, Jaime L. Martínez , Rahme, Rudy J. , Miller, David A. , Brinjikji, Waleed , Quiñones‐Hinojosa, Alfredo , Meyer, Fredric B. , Fox, W Christopher , Domingo, Ricardo A. , Ramos‐Fresnedo, Andres , Freeman, William D. , Sandhu, Sukhwinder J.S. , Bendok, Bernard R. , Tawk, Rabih G.

Mayo Clinic

Neurosurgery | July 12, 2022 | Volume: 91 | Issue: 4 | Pages: 541-546

10.1227/neu.0000000000002070 | PMID 35876667 Get It

BACKGROUND: Loeys–Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder characterized by a classic triad of hypertelorism, bifid uvula and/or cleft palate, and generalized arterial tortuosity. There are limited data on the prevalence and rupture risk of intracranial aneurysms (IAs) in the setting of LDS, with no established guidelines. OBJECTIVE: To analyze the prevalence and rupture risk of IA in LDS. METHODS: Electronic medical records of patients with a confirmed diagnosis of LDS and available cerebrovascular imaging were reviewed. Patients were divided into 2 groups based on the presence of IA. Unmatched and propensity-matched analyses were used to identify potential risk factors for aneurysm formation. RESULTS: Records of 1111 patients were screened yielding a total of 60 patients with a diagnosis of LDS. Eighteen (30%) patients had IA, 4 (22.2%) of whom had multiple aneurysms for a total of 24 IAs. Twenty-three (95.8%) aneurysms were located in the anterior circulation; none of them were ruptured. On unmatched analysis, age ( P = .015), smoking history ( P = .034), hypertension ( P = .035), and number of extracranial aneurysms ( P < .001) were significantly higher in patients with IA. After matching for age, sex, race, stroke history, family history, and extracranial aneurysms, smoking history ( P = .009) remained significant. CONCLUSION: Patients with LDS have an increased risk of IAs, especially with a history of smoking. The prevalence rate of IAs in our series was 30%. Screening imaging should be considered at diagnosis, and patients should be encouraged to abstain from smoking. Further studies are needed to elucidate the risk of IA rupture and treatment considerations in this unique population.
MIS lateral retroperitoneal transpsoas approach allows gross total resection of a giant L4 schwannoma
Perez‐Vega, Carlos , Ravindran, Krishnan , Perez-Vega, Carlos, Ramos‐Fresnedo, Andres , Fox, W Christopher

Mayo Clinic

Neurosurgical Focus: Video | July 1, 2022 | Volume: 7 | Issue: 1 | Pages: V10

10.3171/2022.3.focvid2220 | PMID 36284729 Get It

In this surgical video, the authors present a successful minimally invasive (MIS) lateral retroperitoneal transpsoas approach for resection of an L4 nerve root schwannoma. They describe the surgical approach in detail, with special emphasis on patient positioning for an orthogonal view, as well as technical nuances throughout the procedure. Using a sequential tubular retractor, they performed a microscopic dissection of the lesion. The tumor was debulked and the tumor capsule was disconnected from the surrounding tissue. During dissection, direct stimulation identified a functional nerve root that was carefully dissected from the tumor capsule. The tumor was then removed en bloc. The video can be found here: https://stream.cadmore.media/r10.3171/2022.3.FOCVID2220
PB2113: FRONTMIND: A PHASE III, RANDOMIZED, DOUBLE-BLIND STUDY OF TAFASITAMAB + LENALIDOMIDE + R-CHOP VS R-CHOP ALONE FOR NEWLY DIAGNOSED HIGH-INTERMEDIATE AND HIGH-RISK DIFFUSE LARGE B-CELL LYMPHOMA
Nowakowski, Grzegorz S. , Burke, John M. , Waldron-Lynch, Maeve, Hadar, Nira, Pachori, Alok, Lenz, Georg , Vitolo, Umberto , Fox, Christopher P. , Trněný, Marek , Chiappella, Annalisa

Mayo Clinic

HemaSphere | June 24, 2022 | Volume: 6 | Issue: No issue available | Pages: 1984-1985

10.1097/01.hs9.0000851284.83380.89 Get It

frontMIND: A phase III, randomized, double-blind study of tafasitamab + lenalidomide + R-CHOP versus R-CHOP alone for newly diagnosed high-intermediate and high-risk diffuse large B-cell lymphoma.
Nowakowski, Grzegorz S. , Burke, John M. , Waldron-Lynch, Maeve, Hadar, Nira, Pachori, Alok, Lenz, Georg , Vitolo, Umberto , Fox, Christopher P. , Trněný, Marek , Chiappella, Annalisa

Mayo Clinic

Journal of Clinical Oncology | June 6, 2022 | Volume: 40 | Issue: 16_suppl | Pages: TPS7590-TPS7590

10.1200/jco.2022.40.16_suppl.tps7590 Get It

TPS7590 Background: Up to 40% of patients relapse or are refractory (R/R) to R-CHOP, the current standard of care for diffuse large B-cell lymphoma (DLBCL), indicating an unmet need, particularly in patients with high-intermediate and high-risk disease (IPI 3–5). POLARIX (NCT03274492) evaluated a modified regimen substituting polatuzumab vedotin for vincristine (pola-R-CHP), demonstrating modest improvement in PFS with no OS benefit between treatment arms. The addition of lenalidomide (LEN) to R-CHOP improved both PFS and OS in the ECOG-ACRIN E1412 trial but not in the Phase III ROBUST study, in which a lower dose of LEN was used, despite a positive trend toward 2-year PFS in a subgroup analysis. The chemo-free immunotherapy tafasitamab + LEN has received accelerated approval in the United States (2020), and conditional marketing authorization in Europe and Canada (2021) in adult patients with R/R DLBCL ineligible for ASCT based on L-MIND (NCT02399085). The primary analysis of First-MIND (NCT04134936), a Phase Ib randomized safety study of R-CHOP + tafasitamab ± LEN in patients with previously untreated and newly diagnosed DLBCL, demonstrated that adding tafasitamab + LEN does not impair dosing and scheduling of R-CHOP, with toxicities similar to those expected with R-CHOP alone (ASH 2021; #3556). frontMIND (NCT04824092) will investigate the efficacy and safety of R-CHOP + tafasitamab + LEN vs R-CHOP alone in previously untreated patients with high-intermediate and high-risk DLBCL. Methods: frontMIND is a Phase III, multicenter, randomized, double-blind, placebo-controlled study. Approximately 880 patients are planned to be randomized at ̃350 centers in North and South America, Europe, and Asia-Pacific. Eligible patients aged 18‒80 years with previously untreated local biopsy-proven, CD20+ DLBCL with IPI score 3–5 (age-adjusted IPI 2–3 if ≤60 years), and ECOG PS 0–2 will be enrolled. Patients with transformed lymphoma (except double or triple hit lymphoma) are excluded. Patients will be randomized 1:1 to receive six 21-day (D) cycles of either R-CHOP + tafasitamab (12 mg/kg intravenously, D 1, 8, and 15) + LEN (25 mg orally, D1–10) or R-CHOP + tafasitamab and LEN placebos. Patients will be followed for up to 5 years after the end of treatment. The primary endpoint is investigator-assessed PFS. Secondary endpoints include investigator-assessed event-free survival, OS, safety, and tafasitamab serum concentration (trough and Cmax levels). Sensitivity and specificity of minimal residual disease for early detection of disease progression is an exploratory endpoint; further MRD parameters may also be investigated. The study is funded by MorphoSys AG and conducted with the scientific support of members of the Fondazione Italiana Linfomi and the German Lymphoma Alliance. Clinical trial information: NCT04824092.
Risk of Early Versus Later Rebleeding From Dural Arteriovenous Fistulas With Cortical Venous Drainage
Durnford, Andrew , Akarca, Danyal , Culliford, David , Millar, John S. , Guniganti, Ridhima , Giordan, Enrico , Brinjikji, Waleed , Chen, Ching‐Jen , Abecassis, Isaac Josh , Levitt, Michael R. , Polifka, Adam , Derdeyn, Colin P. , Kwasnicki, Amanda , Alaraj, Ali , Potgieser, Adriaan R. E., Tada, Yoshiteru , Abla, Adib A. , Satomi, Junichiro, Starke, Robert M., Dijk, J. Marc C. van , Amin‐Hanjani, Sepideh , Hayakawa, M. , Gross, Bradley A. , Kim, Louis J. , Sheehan, Jason P. , Kansagra, Akash P. , Lai, Rosalind, Zipfel, Gregory J. , Bulters, Diederik , Piccirillo, Jay F. , Vine, Roanna , Cloft, Harry J. , Kallmes, David F. , Pollock, Bruce E. , Link, Michael J. , Patibandla, Mohana Rao, Ding, Dale , Buell, Thomas J. , Paisan, Gabriella, Meyer, R. Michael, Kelly, Cory , Duffill, Jonathan, Ditchfield, Adam, Macdonald, Jason, Laurent, Dimitri , Lockerman, Ashley, Lunsford, L. Dade , Jankowitz, Brian T. , Guerrero, Waldo R. , McGruder, Allen, Charbel, Fady T. , Aletich, Victor , Rose‐Finnell, Linda, Peterson, Eric C. , Yavagal, Dileep R. , Sur, Samir , Kanematsu, Yasuhisa , Kinouchi, T. , Korai, Masaaki , Yamaguchi, Izumi , Yamamoto, Yuki , Winkler, Ethan A. , Lawton, Michael T. , Rutkowski, Martin J. , Sultan, M. Ali Aziz, Patel, Nirav , Frerichs, Kai U., Levitt, Michael R , Polifka, Adam J , Samaniego, Edgar A , Alaraj, Ali , Tada, Yoshiteru , Phelps, Ryan , Abla, Adib , van DijK, J Marc C , Amin-Hanjani, Sepideh , Gross, Bradley , Fox, W Christopher , Kim, Louis J. , Sheehan, Jason , Lanzino, Giuseppe , Kansagra, Akash P , Du, Rose , Lai, Rosalind , Zipfel, Gregory J , Bulters, Diederik O , Ding, Dale , Chen, Ching-Jen , Derdeyn, Colin P , Abecassis, Isaac Josh , Millar, John, Chen, Stephanie , Lanzino, Giuseppe , Raman, Hari S. , Lipsey, Kim L. , Hoh, Brian L. , Smith, Jessica , Ortega-Gutierrez, Santiago , Hasan, David , Roa, Jorge A. , Rossen, James D. , Yamamoto, Nobuaki

Mayo Clinic

Stroke | April 14, 2022 | Volume: 53 | Issue: 7 | Pages: 2340-2345

10.1161/strokeaha.121.036450 | PMID 35420453 Get It

Background: Cranial dural arteriovenous fistulas with cortical venous drainage are rare lesions that can present with hemorrhage. A high rate of rebleeding in the early period following hemorrhage has been reported, but published long-term rates are much lower. No study has examined how risk of rebleeding changes over time. Our objective was to quantify the relative incidence of rebleeding in the early and later periods following hemorrhage. Methods: Patients with dural arteriovenous fistula and cortical venous drainage presenting with hemorrhage were identified from the multinational CONDOR (Consortium for Dural Fistula Outcomes Research) database. Natural history follow-up was defined as time from hemorrhage to first treatment, rebleed, or last follow-up. Rebleeding in the first 2 weeks and first year were compared using incidence rate ratio and difference. Results: Of 1077 patients, 250 met the inclusion criteria and had 95 cumulative person-years natural history follow-up. The overall annualized rebleed rate was 7.3% (95% CI, 3.2–14.5). The incidence rate of rebleeding in the first 2 weeks was 0.0011 per person-day; an early rebleed risk of 1.6% in the first 14 days (95% CI, 0.3–5.1). For the remainder of the first year, the incidence rate was 0.00015 per person-day; a rebleed rate of 5.3% (CI, 1.7–12.4) over 1 year. The incidence rate ratio was 7.3 (95% CI, 1.4–37.7; P , 0.026). Conclusions: The risk of rebleeding of a dural arteriovenous fistula with cortical venous drainage presenting with hemorrhage is increased in the first 2 weeks justifying early treatment. However, the magnitude of this increase may be considerably lower than previously thought. Treatment within 5 days was associated with a low rate of rebleeding and appears an appropriate timeframe.
Moral Distress and Moral Injury Among Attending Neurosurgeons: A National Survey
Mackel, Charles E. , Alterman, Ron L. , Buss, Mary K. , Reynolds, Renée M. , Spiotta, Alejandro M , Davis, Roger B. , Stippler, Martina , Fox, W Christopher

Mayo Clinic

Neurosurgery | March 23, 2022 | Volume: 91 | Issue: 1 | Pages: 59-65

10.1227/neu.0000000000001921 | PMID 35319531 Get It

BACKGROUND: “Moral distress” describes the psychological strain a provider faces when unable to uphold professional values because of external constraints. Recurrent or intense moral distress risks moral injury, burnout, and physician attrition but has not been systematically studied among neurosurgeons. OBJECTIVE: To develop a unique instrument to test moral distress among neurosurgeons, evaluate the frequency and intensity of scenarios that may elicit moral distress and injury, and determine their impact on neurosurgical burnout and turnover. METHODS: An online survey investigating moral distress, burnout, and practice patterns was emailed to attending neurosurgeon members of the Congress of Neurological Surgeons. Moral distress was evaluated through a novel survey designed for neurosurgical practice. RESULTS: A total of 173 neurosurgeons completed the survey. Half of neurosurgeons (47.7%) reported significant moral distress within the past year. The most common cause was managing critical patients lacking a clear treatment plan; the most intense distress was pressure from patient families to perform futile surgery. Multivariable analysis identified burnout and performing ≥2 futile surgeries per year as predictors of distress ( P < .001). Moral distress led 9.8% of neurosurgeons to leave a position and 26.6% to contemplate leaving. The novel moral distress survey demonstrated excellent internal consistency (Cronbach alpha = 0.89). CONCLUSION: We developed a reliable survey assessing neurosurgical moral distress. Nearly, half of neurosurgeons suffered moral distress within the past year, most intensely from external pressure to perform futile surgery. Moral distress correlated with burnout risk caused 10% of neurosurgeons to leave a position and a quarter to consider leaving.
Application of Color Doppler Ultrasound to Identify and Repair Postoperative Cerebrospinal Fluid Leak: A Technical Note
West, James L., Abode-Iyamah, Kingsley, Chen, Selby G., Fox, W. Christopher, Bydon, Mohamad, Miller, David A., Clendenen, Steven R., West, James L., Abode-Iyamah, Kingsley, Chen, Selby G., Fox, W. Christopher, Bydon, Mohamad, Miller, David A., Clendenen, Steven R.

Mayo Clinic

Operative Neurosurgery | December 15, 2021 | Volume: 22 | Issue: 1 | Pages: e12-e17

10.1227/ons.0000000000000007 | PMID 34982905 Get It

BACKGROUND: Incidental durotomy is a known complication of spinal surgery. Persistent cerebrospinal fluid (CSF) leak after unrecognized durotomy may lead to prolonged hospitalization and significant morbidity. If initial bed rest fails, the surgeon must choose between nontargeted methods such as oversewing the wound and lumbar drain placement or return to the operating room. OBJECTIVE: To report the novel use of color flow doppler (CFD) in conjunction with ultrasound (US) to localize the point of CSF leak, assist with aspiration of the pseudomeningocele, and direct the application of fibrin sealant or epidural blood patch. METHODS: This article includes a description of the technique as a technical note. RESULTS: A 72-year-old man underwent L2-5 laminectomies for spinal stenosis. During the index operation, a durotomy occurred and was repaired primarily. The patient subsequently developed leg weakness, back pain, and bulging of the incision. Using CFD, the site of durotomy was determined. Under direct visualization, 34 mL of CSF was aspirated from the pseudomeningocele and 20 mL of fibrin sealant was placed opposing the durotomy. At 2-month follow-up, CFD confirmed absent flow and MRI demonstrated pseudomeningocele resolution. CONCLUSION: This article represents the first report highlighting the utility of CFD US to guide epidural patch placement for postsurgical CSF leaks. CFD allows localization of the durotomy and direct application of blood or fibrin sealant, potentially increasing the success rate of epidural blood patch in postoperative patients. This approach is less invasive than revision surgery and does not require the prolonged hospitalization of lumbar drainage or other nontargeted interventions.
Robotic-Assisted vs Nonrobotic-Assisted Minimally Invasive Transforaminal Lumbar Interbody Fusion: A Cost-Utility Analysis
Moniz‐Garcia, Diogo , Akinduro, Oluwaseun O., Biase, Gaetano De, Sousa-Pinto, Bernardo, Jerreld, Daniel J., Dholakia, Ruchita, Borah, Bijan, Nottmeier, Eric, Deen, H. Gordon, Fox, W. Christopher, Bydon, Mohamad, Chen, Selby, Quinones-Hinojosa, Alfredo, Abode-Iyamah, Kingsley, Biase, Gaetano De , Sousa‐Pinto, Bernardo , De Biase, Gaetano , Garcia, Diogo Moniz , Akinduro, Oluwaseun O., Jerreld, Daniel J., Dholakia, Ruchita, Borah, Bijan, Nottmeier, Eric, Deen, H. Gordon, Fox, W. Christopher, Bydon, Mohamad, Chen, Selby, Quinones-Hinojosa, Alfredo, Abode-Iyamah, Kingsley

Mayo Clinic

Neurosurgery | December 13, 2021 | Volume: 90 | Issue: 2 | Pages: 192-198

10.1227/neu.0000000000001779 | PMID 35023874 Get It

BACKGROUND: Management of degenerative disease of the spine has evolved to favor minimally invasive techniques, including nonrobotic-assisted and robotic-assisted minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). Value-based spending is being increasingly implemented to control rising costs in the US healthcare system. With an aging population, it is fundamental to understand which procedure(s) may be most cost-effective. OBJECTIVE: To compare robotic and nonrobotic MIS-TLIF through a cost-utility analysis. METHODS: We considered direct medical costs related to surgical intervention and to the hospital stay, as well as 1-yr utilities. We estimated costs by assessing all cases involving adults undergoing robotic surgery at a single institution and an equal number of patients undergoing nonrobotic surgery, matched by demographic and clinical characteristics. We adopted a willingness to pay of $50 000/quality-adjusted life year (QALY). Uncertainty was addressed by deterministic and probabilistic sensitivity analyses. RESULTS: Costs were estimated based on a total of 76 patients, including 38 undergoing robot-assisted and 38 matched patients undergoing nonrobot MIS-TLIF. Using point estimates, robotic surgery was projected to cost $21 546.80 and to be associated with 0.68 QALY, and nonrobotic surgery was projected to cost $22 398.98 and to be associated with 0.67 QALY. Robotic surgery was found to be more cost-effective strategy, with cost-effectiveness being sensitive operating room/materials and room costs. Probabilistic sensitivity analysis identified robotic surgery as cost-effective in 63% of simulations. CONCLUSION: Our results suggest that at a willingness to pay of $50 000/QALY, robotic-assisted MIS-TLIF was cost-effective in 63% of simulations. Cost-effectiveness depends on operating room and room (admission) costs, with potentially different results under distinct neurosurgical practices.
High-Dose Methotrexate Is Not Associated with Reduction in CNS Relapse in Patients with Aggressive B-Cell Lymphoma: An International Retrospective Study of 2300 High-Risk Patients
Villa, Diego , Bobillo, Sabela , Smedby, Karin Ekstroem, Eyre, Toby A. , Cwynarski, Kate , Caporn, Paris L., Zyl, Joan Van, Puckrin, Robert , Stewart, Douglas A. , Thanarajasingam, Gita , Joffe, Erel , Eloranta, Sandra , Maliske, Seth , Poonsombudlert, Kittika , Guo, Xiao, Hapgood, Greg , Manos, Kate , Gilbertson, Michael , Streit, Isaac T, Scott, Hamish W , Ku, Matthew , Mel, Sanjay De , Yong, Kar Ying , Liu, Xin , Mokoonlall, Mridula , McVilly, Nicholas L., Johnston, Anna , Brunner, Matthew, Ku, Matthew , Lewis, Katharine L. , Jakobsen, Lasse Hjort , Savage, Kerry J. , Klánová, Magdalena , Trněný, Marek , Bishton, Mark , Fox, Christopher P. , Tun, Aung M. , Djebbari, Faouzi , Harrysson, Sara , Sehn, Laurie H. , Hawkes, Eliza A. , Khwaja, Jahanzaib , Minson, Adrian , Dickinson, Michael , Øvlisen, Andreas Kiesbye , Gregory, Gareth P. , Streit, Isaac T., Talaulikar, Dipti , Brunner, Matthew J, Pophali, Priyanka A. , Maurer, Matthew J. , El‐Galaly, Tarec Christoffer , Cheah, Chan Y.

Mayo Clinic

Blood | November 23, 2021 | Volume: 138 | Issue: Supplement 1 | Pages: 181-181

10.1182/blood-2021-146737 Get It

Abstract Introduction Central nervous system relapse (secondary central nervous system lymphoma -SCNS) is an uncommon but devastating complication of aggressive B-cell lymphoma. Patients (Pts) with CNS-IPI 4-6 are at greatest risk (10.2% at 2 years). Intravenous high-dose methotrexate (HD-MTX) is widely used to mitigate SCNS risk but data supporting this practice are limited. Methods We performed a multicentre, retrospective study at 21 sites in Australia, Asia, North America and Europe. Chart or registry review was performed for consecutively diagnosed pts with diffuse large B-cell lymphoma (DLBCL) and CNS-IPI 4-6, high grade B-cell lymphoma (HGBL) with rearrangements of MYC+BCL2 and/or BCL6 and primary breast/testicular DLBCL irrespective of CNS-IPI. Pts were diagnosed between 2000-2020, 18-80 years at diagnosis, and treated with curative intent anti-CD20 based chemo-immunotherapy. Pts with CNS involvement at diagnosis were excluded. HD-MTX was defined as at least one cycle of intravenous MTX at any dose. Time to SCNS was calculated from date of diagnosis (all-pts), and from the end of frontline systemic lymphoma therapy, defined as 6x21 days from diagnosis (complete response (CR-pts)), until SCNS, systemic relapse, death, or censoring, whichever came first. Cumulative risk of SCNS was computed using the Aalen-Johansen estimator treating death and systemic relapses as competing events. Adjusted cumulative risks were obtained by using an inverse probability of treatment weighting approach. The average treatment effect was computed as the difference in adjusted 5-year risk of SCNS. Results - 2300 and 1455 pts were included in the all-pts and CR-pts analyses, respectively. Baseline demographics and details of therapy are summarised in Table 1. Except for a predominance of males, pts ≤60 years and pts with ECOG 0-1 in the HD-MTX vs no HD-MTX groups, the demographics and treatments were well balanced. At a median follow up of 5.9 years (range 0.0-19.1) and 5.5 years from diagnosis (range 0.0-18.7), 201/2300 and 84/1455 pts experienced CNS events in the all-pts and CR-pts analyses respectively. For all-pts(n=2300), CNS-IPI was 4-6 in 2052(89.2%), with R-CHOP-like therapy given to 93.8%. 410 pts (17.8%) received HD-MTX (265 HD-MTX alone, 145 in combination with intrathecal methotrexate (IT-MTX);435 received IT-MTX alone;1455 received neither. There were 32/410 and 169/1890 SCNS events, with median time from diagnosis to SCNS of 8.8 and 6.7 months in the HD-MTX and no HD-MTX groups respectively. 5-year OS was 70% (95% CI, 65-76%) and 55% (95% CI 53-57%) in HD-MTX and no HD-MTX groups respectively. There was no difference in the adjusted 5-year risk of SCNS between the HD-MTX and no HD-MTX groups (8.4% vs 9.1%, adjusted hazard ratio [HR] 0.71, p=0.100) (Figure 1). For CR-pts(n=1455), CNS-IPI was 4-6 in 1267(87.0%), with R-CHOP-like therapy given to 93.3%. 284 pts (19.5%) received HD-MTX (170 HD-MTX alone, 114 with IT-MTX);298 received IT-MTX alone;873 received neither. There were 16/284 and 68/1171 SCNS events, with median time from diagnosis to SCNS of 11.0 and 10.3 months in the HD-MTX and no HD-MTX groups respectively. 5-year OS was 74%(95% CI 67-81%) and 75%(95% CI 72-78%) in the HD-MTX groups and no HD-MTX groups respectively (adjusted HR 1.08, p=0.622). There was no difference in the 5-year risk of CNS relapse between the HD-MTX and no HD-MTX groups 5.0% vs 6.0% (adjusted HR 1.03, p=0.903) (Figure 2). Exploratory analysis of the impact of HD-MTX among the highest risk groups CNS IPI 5 (n=368), CNS-IPI 6 (n=59) and CNS-IPI 6 plus all pts with testicular, renal or adrenal involvement (n=349) did not reveal differences in SCNS rates in HD-MTX treated pts. Additional subgroup analyses will be presented at the meeting. Conclusions To our knowledge, this is the largest study of the efficacy of HD-MTX in reducing SCNS events focusing exclusively on high-risk pts. The overall incidence of CNS relapse observed was consistent with previous reports in similar patient cohorts at 9%. The use of HD-MTX did not lower SCNS rates overall or when analysis was confined to CR pts at completion of curative intent therapy to compensate for potential immortal bias associated with HD-MTX therapy. Despite the limitations of the non-randomized and retrospective design, it appears unlikely that HD-MTX is associated with a clinically meaningful reduction in SCNS rates in pts with high risk for SCNS. Figure 1 Figure 1. Disclosures Lewis: AstraZeneca: Consultancy, Honoraria; Novartis: Patents & Royalties: Conference attendance; Janssen: Honoraria, Patents & Royalties: Conference attendance; Roche: Consultancy, Honoraria. Villa: Janssen: Honoraria; Gilead: Honoraria; AstraZeneca: Honoraria; AbbVie: Honoraria; Seattle Genetics: Honoraria; Celgene: Honoraria; Lundbeck: Honoraria; Roche: Honoraria; NanoString Technologies: Honoraria. Bobillo: F. Hoffmann-La Roche Ltd: Consultancy, Speakers Bureau; Gilead: Speakers Bureau. Ekstroem Smedby: Takeda: Consultancy; Janssen Cilag: Research Funding. Savage: Merck: Consultancy, Honoraria, Other: Institutional clinical trial funding; BMS: Consultancy, Honoraria, Other: Institutional clinical trial funding; AbbVie: Consultancy, Honoraria; Roche: Research Funding; Takeda: Other: Institutional clinical trial funding; Servier: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Astra-Zeneca: Consultancy, Honoraria; Beigene: Other: Institutional clinical trial funding; Genentech: Research Funding. Eyre: Beigene: Honoraria, Research Funding; Incyte: Consultancy; Secura Bio: Consultancy, Honoraria; Janssen: Honoraria; Gilead/KITE: Honoraria, Other: Travel support for conferences, Research Funding, Speakers Bureau; Loxo Oncology: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Other: Travel to conferences; AstraZeneca: Honoraria, Research Funding; Roche: Consultancy, Honoraria. Cwynarski: Incyte: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Atara: Consultancy; Celgene: Consultancy; Takeda: Consultancy, Other: travel to scientific conferences, Speakers Bureau; Kite, a Gilead Company: Consultancy, Other: travel to scientific conferences, Speakers Bureau; Janssen: Consultancy, Other: travel to scientific conferences; Roche: Consultancy, Other: travel to scientific conferences, Speakers Bureau; BMS/Celgene: Other: travel to scientific conferences. Stewart: Teva: Honoraria; Sandoz: Honoraria; Amgen: Honoraria; AstraZeneca: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Gilead: Honoraria; Abbvie: Honoraria; Janssen: Honoraria; Roche: Honoraria. Bishton: Gilead: Honoraria, Other: Travel grants; AbbVie: Honoraria, Other: Travel grants; Celgene/BMS: Honoraria, Other: travel grants; Celltrion: Honoraria, Other: Travel grants; Takeda.: Honoraria, Other: Travel grants . Fox: F. Hoffmann-La Roche Ltd: Consultancy, Membership on an entity's Board of Directors or advisory committees. Joffe: Epizyme: Consultancy; AstraZeneca: Consultancy. Eloranta: Janssen Pharmaceutical NV: Other: NV. Sehn: Genmab: Consultancy; Novartis: Consultancy; Debiopharm: Consultancy. Manos: Bristol-Myers Squibb: Other: Travel and meetings. Hawkes: Specialised Therapeutics: Consultancy; Gilead: Membership on an entity's Board of Directors or advisory committees; Merck Sharpe Dohme: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Antigene: Membership on an entity's Board of Directors or advisory committees; Regeneron: Speakers Bureau; Bristol Myers Squib/Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck KgA: Research Funding; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel and accommodation expenses, Research Funding, Speakers Bureau; Janssen: Speakers Bureau. Minson: Novartis: Research Funding; Hoffman La Roche: Research Funding. Dickinson: Celgene: Research Funding; Amgen: Honoraria; Takeda: Research Funding; Gilead Sciences: Consultancy, Honoraria, Speakers Bureau; MSD: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Other: travel, accommodation, expenses, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau. Øvlisen: Abbvie: Other: Travel expenses. Gregory: Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel fees, Speakers Bureau; Janssen: Consultancy; Novartis: Consultancy. Ku: Roche: Consultancy; Antegene: Consultancy; Genor Biopharma: Consultancy. Talaulikar: Roche: Honoraria, Research Funding; Jansenn: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; EUSA Pharma: Honoraria, Research Funding. Maurer: Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Genentech: Research Funding; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Morphosys: Membership on an entity's Board of Directors or advisory committees, Research Funding; Nanostring: Research Funding. El-Galaly: Abbvie: Other: Speakers fee; ROCHE Ltd: Ended employment in the past 24 months. Cheah: Roche: Consultancy, Honoraria, Other: advisory and travel expenses, Research Funding; Janssen: Consultancy, Honoraria, Other: advisory; MSD: Consultancy, Honoraria, Other: advisory, Research Funding; Gilead: Consultancy, Honoraria, Other: advisory; Ascentage pharma: Consultancy, Honoraria, Other: advisory; Beigene: Consultancy, Honoraria, Other: advisory; AbbVie: Research Funding; Celgene: Research Funding; AstraZeneca: Consultancy, Honoraria, Other: advisory; Loxo/Lilly: Consultancy, Honoraria, Other: advisory; TG Therapeutics: Consultancy, Honoraria, Other: advisory.