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Magnetic resonance imaging findings of the posterior fossa in 47 patients with mucopolysaccharidoses: A cross‐sectional analysis
Reichert, Roberta , Pérez, Juliano Adams , Corte, Amauri Dalla , Isolan, Gustavo Rassier , Stefani, Marco Antônio , Pinto E Vairo, Filippo, Vairo, Filippo Pinto e , Souza, Carolina Fischinger Moura de , Giugliani, Roberto

Mayo Clinic

JIMD Reports | March 21, 2021 | Volume: 60 | Issue: 1 | Pages: 32-41

10.1002/jmd2.12212 | PMID 34258139 Get It

AbstractBackgroundMucopolysaccharidoses (MPS) is a group of hereditary multisystemic lysosomal disorders. Most neuroimaging studies in MPS have focused on the supratentorial compartment and craniocervical junction abnormalities, and data regarding posterior fossa findings are scarce in the literature. Thus, our purpose is to describe posterior fossa findings on magnetic resonance imaging (MRI) of MPS patients.MethodsWe reviewed routine MRI scans of MPS patients being followed up at our institution (types I, II, III, IV, and VI), focusing on posterior fossa structures.ResultsForty‐seven MPS patients were included. MRI‐visible perivascular spaces were commonly found in the midbrain and adjacent to the dentate nuclei (85% and 55% of patients, respectively). White‐matter lesion was not identified in most cases. Its most frequent localizations were in the pons and cerebellum (34% and 30% of patients, respectively). Enlargement of cerebrospinal fluid (CSF) spaces in the posterior fossa was present in 55% of individuals and was more frequent in neuronopathic patients (73% vs 40%; P = .02). Cerebellar volume was classified as normal, apparent macrocerebellum, atrophic, and hypoplastic in 38%, 38%, 21%, and 3% of patients, respectively. A depression of the posterior fossa floor in the midline sagittal plane was found in 22 patients (47%), which was statistical significantly associated with enlargement of CSF spaces (P = .02) and with apparent macrocerebellum (P = .03).ConclusionThe present study compiled the main posterior fossa findings in MPS patients. Classically described in the supratentorial compartment, MRI‐visible perivascular spaces, white matter lesions, and enlarged perivascular spaces were also found in the posterior fossa. However, atrophy, which commonly affects cerebral hemispheres, was not the most frequent cerebellar morphology found in our study. Moreover, potential findings for future research were described.
Hemispherectomy Outcome Prediction Scale: Development and validation of a seizure freedom prediction tool
Weil, Alexander G. , Lewis, Evan , Ibrahim, George M. , Tseng, Chi‐Hong , Zhou, Xinkai , Lin, Kao‐Min, Cai, Lixin , Liu, Qingzhu , Lin, Jiuluan , Mathern, Gary W. , Smyth, Matthew D. , O’Neill, Brent R., Dudley, Roy , Ragheb, John , Bhatia, Sanjiv, Delev, Daniel , Ramantani, Georgia , Zentner, Josef , Dorfer, Christian , Feucht, Martha , Czech, Thomas , Bollo, Robert J. , Issabekov, Galymzhan , Zhu, Hongwei , Connelly, Mary Shane, Steinbok, Paul , Zhang, Kai , Hidalgo, Eveline Teresa , Weiner, Howard L. , Lapalme‐Remis, Samuel , Tripathi, Manjari , Chandra, P. Sarat , Hader, Walter , Wang, Feng‐Peng , Champagne, Pierre Olivier, Budke, Marcelo , Pérez-Jiménez, María Ángeles, Raftapoulos, Christian, Finet, Patrice, Michel, Pauline, Schaller, Karl , Malone, Christian Cantillano, Pociecha, Juan , Chamorro, Noelia, Muro, Valeria L., Lehe, Marec von , Vieker, Silvia, Oluigbo, Chima , Gaillard, William D. , Khateeb, Mashael Al, Alotaibi, Faisal , Krayenbühl, Niklaus , Bolton, Jeffrey , Ramantani, Georgia , Dorfer, Christian , Feucht, Martha , Wong-Kisiel, Lily, Tripathi, Manjari , Sarat Chandra, Poodipedi , Gaillard, William D , Fallah, Aria , von Lehe, Marec , Weil, Alexander G , Oluigbo, Chima O , Kola, Olivia , Zhou, Wen-Jing , Ojemann, Jeffrey G. , Wang, Anthony , Connelly, Mary, Zhang, Jianguo , Wong‐Kisiel, Lily C. , Wang, Feng‐Peng, Yao, Yi , Guo, Qiang , Li, Shao‐Chun, Stienen, Martin Nikolaus , Baro, Valentina , Pearl, Phillip L. , Fallah, Aria

Mayo Clinic

Epilepsia | March 13, 2021 | Volume: 62 | Issue: 5 | Pages: 1064-1073

10.1111/epi.16861 | PMID 33713438 Get It

AbstractObjectiveTo develop and validate a model to predict seizure freedom in children undergoing cerebral hemispheric surgery for the treatment of drug‐resistant epilepsy.MethodsWe analyzed 1267 hemispheric surgeries performed in pediatric participants across 32 centers and 12 countries to identify predictors of seizure freedom at 3 months after surgery. A multivariate logistic regression model was developed based on 70% of the dataset (training set) and validated on 30% of the dataset (validation set). Missing data were handled using multiple imputation techniques.ResultsOverall, 817 of 1237 (66%) hemispheric surgeries led to seizure freedom (median follow‐up = 24 months), and 1050 of 1237 (85%) were seizure‐free at 12 months after surgery. A simple regression model containing age at seizure onset, presence of generalized seizure semiology, presence of contralateral 18‐fluoro‐2‐deoxyglucose–positron emission tomography hypometabolism, etiologic substrate, and previous nonhemispheric resective surgery is predictive of seizure freedom (area under the curve = .72). A Hemispheric Surgery Outcome Prediction Scale (HOPS) score was devised that can be used to predict seizure freedom.SignificanceChildren most likely to benefit from hemispheric surgery can be selected and counseled through the implementation of a scale derived from a multiple regression model. Importantly, children who are unlikely to experience seizure control can be spared from the complications and deficits associated with this surgery. The HOPS score is likely to help physicians in clinical decision‐making.
Basing Information on Comprehensive, Critically Appraised, and Up-to-Date Syntheses of the Scientific Evidence: An Update from the International Patient Decision Aid Standards
Hoffmann, Tammy , Bakhit, Mina , Durand, Marie‐Anne , Saunders, Catherine , Brito, Juan P. , Hoffmann, Tammy C , Brito, Juan P , Perestelo‐Pérez, Lilisbeth

Mayo Clinic

Medical Decision Making | March 4, 2021 | Volume: 41 | Issue: 7 | Pages: 755-767

10.1177/0272989x21996622 | PMID 33660539 Get It

Background Patients and clinicians expect the information in patient decision aids to be based on the best available research evidence. The objectives of this International Patient Decision Aid Standards (IPDAS) review were to 1) check the currency of, and where needed, update evidence for the domain of “basing the information in decision aids on comprehensive, critically appraised, and up-to-date syntheses of the evidence”; 2) analyze the evidence characteristics of decision aids; and 3) propose updates to relevant IPDAS criteria. Methods We searched MEDLINE and PubMed to inform updates of this domain’s definitions, justifications, and components. We also searched 5 sources to identify all publicly available decision aids ( N = 471). Two assessors independently extracted each aid’s evidence characteristics. Results Minor updates to the definitions and theoretical justifications of this IPDAS domain are provided and changes to relevant IPDAS criteria proposed. Nearly all aids (97%) provided a year of creation/update, but most (81%) did not report an explicit update or expiration policy. No scientific references were cited in 33% of aids. Of the 314 that cited at least 1 reference, 39% cited at least 1 guideline, 44% cited at least 1 systematic review, and 23% cited at least 1 randomized trial. In 35%, it was unclear what statement in the aid the citations referred to. Only 14% reported any of the processes used to find and decide on evidence inclusion. Only 14% reported the evidence quality. Many emerging issues and future research areas were identified. Conclusions Although many emerging issues need to be addressed, this IPDAS domain is validated and criteria refined. High-quality patient decision aids should be based on comprehensive and up-to-date syntheses of critically appraised evidence.
Choroidal melanoma treatment in times of coronavirus disease 2019
Domínguez‐Varela, Irving Armando , Perez-Ramos, Erik, Ancona‐Lezama, David , Dalvin, Lauren A.

Mayo Clinic

Melanoma Research | February 27, 2021 | Volume: 31 | Issue: 2 | Pages: 194-195

10.1097/cmr.0000000000000718 | PMID 33625101 Get It

Genetic architectures of proximal and distal colorectal cancer are partly distinct
Huyghe, Jeroen R. , Harrison, Tabitha A. , Figueiredo, Jane C. , Schmit, Stephanie L. , Chen, Sai , Barfield, Richard , Cross, Amanda J. , Diergaarde, Brenda , Duggan, David , Harlid, Sophia , Imaz, Liher , Kang, Hyun Min , Levine, David , Perduca, Vittorio , Perez‐Cornago, Aurora , Slattery, Martha L. , Duijnhoven, Fränzel J.B. van , Guelpen, Bethany Van , Anderson, Kristin E. , Arnau‐Collell, Coral, Banbury, Barbara L. , Berndt, Sonja I. , Bishop, D. Timothy , Boehm, Juergen , Boeing, Heiner , Brenner, Hermann , Buch, Stephan , Burnett‐Hartman, Andrea N. , Carr, Prudence R. , Castells, Antoni , Chang‐Claude, Jenny , Curtis, Keith R. , Chapelle, Albert de la , Easton, Douglas F. , English, Dallas R. , Gala, Manish , Gallinger, Steven , Gauderman, W. James, Goodman, Phyllis J. , Grove, John, Gsur, Andrea , Gunter, Marc J. , Haile, Robert W. , Hampe, Jochen , Hoffmeister, Michael , Hsu, Wan‐Ling, Huang, Wen‐Yi , Joshi, Amit D. , Kühn, Tilman , Küry, Sébastien , Lejbkowicz, Flavio, Li, Li , Lindblom, Annika , Lindor, Noralane M. , Markowitz, Sanford D. , Moreno, Lorena , Murphy, Neil , Nassir, Rami , Offit, Kenneth, Parfrey, Patrick S. , Pearlman, Rachel , Phipps, Amanda I. , Prentice, Ross L. , Qi, Lihong , Rennert, Gad , Rennert, Hedy S., Ríboli, Elio , Schafmayer, Clemens, Seminara, Daniela, Song, Mingyang , Su, Yu‐Ru, Thibodeau, Stephen N. , Thomas, Duncan C. , Trichopoulou, Antonia , Visvanathan, Kala, Vodička, Pavel , Vodičková, Ludmila, Weigl, Korbinian , Weinstein, Stephanie J. , Woods, Michael O. , Wu, Anna H. , Nickerson, Deborah A. , Scacheri, Peter C. , Kundaje, Anshul , Casey, Graham , Gruber, Stephen B. , Hayes, Richard B. , Peters, Ulrike , Visvanathan, Kala , Brenner, Hermann , Buchanan, Daniel D , Chan, Andrew T , Gsur, Andrea , Hampe, Jochen , Hoffmeister, Michael , Huang, Wen-Yi , Jenab, Mazda , Murphy, Neil , Peters, Ulrike , Rennert, Gad , English, Dallas R , Gunter, Marc J , Haile, Robert W , Harrison, Tabitha A , Van Guelpen, Bethany , Visvanathan, Kala , Kury, Sebastien , Bishop, D Timothy , Song, Mingyang , Hayes, Richard B , Perez-Cornago, Aurora , Nassir, Rami , Kundaje, Anshul , Riboli, Elio , Vodicka, Pavel , Diergaarde, Brenda , Lindblom, Annika , Bien, Stephanie A. , Hampel, Heather , Conti, David V. , Qu, Conghui , Lin, Yi , Baron, John A. , Sakoda, Lori C. , Schumacher, Fredrick R. , Toland, Amanda Ewart , Agudo, Antonio , Albanes, Demetrius , Alonso, M. Henar , Arndt, Volker , Bassik, Michael Cory , Bezieau, Stéphane , Boutron‐Ruault, Marie‐Christine , Brezina, Stefanie , Buchanan, Daniel D. , Caan, Bette J. , Campbell, Peter T. , Castellvı́-Bel, Sergi , Chan, Andrew T. , Chanock, Stephen Jacob , Feskens, Edith J. M. , Giles, Graham G. , Grady, William M. , Hopper, John L. , Hudson, Thomas J , Jenab, Mazda , Jenkins, Mark A. , Keku, Temitope O , Kooperberg, Charles , Marchand, Loı̈c Le , Li, Christopher I , Lieb, Wolfgang , Männistö, Satu , Milne, Roger L. , Ogino, Shuji , Panico, Salvatore , Pharoah, Paul D.P. , Platz, Elizabeth A. , Potter, John D. , Raskin, Leon , Schoen, Robert E. , Tangen, Catherine M. , Ulrich, Cornelia M. , Vymetalkova, Veronika Polakova , White, Emily E. , Wolk, Alicja , Abecasis, Gonçalo R. , Hsu, Li , Moreno, Vı́ctor , Newcomb, Polly A.

Mayo Clinic

Gut | February 25, 2021 | Volume: 70 | Issue: 7 | Pages: 1325-1334

10.1136/gutjnl-2020-321534 | PMID 33632709 Get It

Objective An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined. Design To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling. Results We identified 13 loci that reached genome-wide significance (p<5×10 −8 ) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer. Conclusion Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.
Abstract PS7-01: Characteristics and outcomes of SARS-CoV-2 infection in patients with invasive breast cancer (BC) from the COVID-19 and cancer consortium (CCC19) cohort study
Accordino, Melissa , Rivera, Donna R. , Perez, Edith A. , Tolaney, Sara M. , Peppercorn, Jeffrey , Grivas, Petros , Lopes, Gilberto , Thompson, Michael A, Kuderer, Nicole M. , Vinayak, Shaveta , Khaki, Ali Raza , Shah, Dimpy P. , Lustberg, Maryam B. , Stover, Daniel G. , Nagaraj, Gayathri , Warner, Jeremy L. , Painter, Corrie , Peters, Solange , Choueiri, Toni K. , Rini, Brian I. , Lyman, Gary H

Mayo Clinic

Cancer Research | February 15, 2021 | Volume: 81 | Issue: 4_Supplement | Pages: PS7-01-PS7-01

10.1158/1538-7445.sabcs20-ps7-01 Get It

Abstract Background: Overall, patients with cancer experience a greater risk of adverse outcomes following SARS-CoV-2 infection; however, little is known for those with BC. Methods: CCC19 (NCT04354701) is an international cohort study aimed at investigating the impact of COVID-19 in patients with a history of or active cancer using de-identified data on patient demographics, cancer history, clinical course and outcomes of COVID-19. The current analysis includes patients from U.S. and Canada with invasive BC and laboratory-confirmed SARS-CoV-2 entered between March 17, 2020 and July 2, 2020. Co-primary outcomes were hospitalization during COVID-19 illness and 30-day all-cause mortality. Frequencies for categorical variables and medians (range) for continuous variables were estimated. Final presentation will include bivariable and multivariable Cox proportional hazards regression analysis to identify risk factors (including BC subtypes and therapies, for which data collection is ongoing) associated with 30-day all-cause mortality and severe COVID-19 illness (composite of any hospitalization requiring supplemental oxygen, admission to an intensive care unit [ICU], use of mechanical ventilation, or death). Results: During the study period, a total of 2683 patients with cancer and COVID-19 were accrued in the CCC19 registry including 529 (20%) with invasive BC. Among patients with BC, 352 (67%) were 60 years or older; 518 (98%) were women; 275 (52%) non-Hispanic White, 116 (22%) non-Hispanic Black, 70 (13%) Hispanic, 56 (11%) in other categorizations; 178 (34%) had a smoking history; 75 (14%) ECOG performance status ≥2; 191 (36%) with &gt;2 active comorbidities; 64 (12%) with AJCC stage IV disease at BC diagnosis; and 267 (50%) were on anti-cancer treatment including systemic therapy, radiation, or surgery within 3 months of COVID-19 diagnosis. At least 323 (61%) patients with BC had 30-day follow-up after COVID-19 diagnosis, and 35 (7%) had 90-day follow-up. COVID-19 illness at initial diagnosis required outpatient care in 288 (54%), inpatient care in 193 (36%), and ICU care in 40 (8%). Overall, 247 (47%) were hospitalized and 30-day all-cause mortality was 9%. 30-day all-cause mortality rates by receipt of major BC treatment modalities (within past 3 months) were: 10% for those on cytotoxic systemic therapy vs 5% and 12% for noncytotoxic systemic therapy and local therapy, respectively. The table shows hospitalization and mortality outcomes by major demographic and BC treatment strata. The final presentation will incorporate the latest patient accrual and evaluate independent clinical risk factors associated with serious COVID-19 outcomes in patients with BC. Conclusions: This represents the largest study to date of COVID-19 outcomes in patients with invasive BC. Nearly half of the patients with BC required hospitalization during their COVID-19 disease course and we observed a 9% 30-day all-cause mortality. Submitted on behalf of the COVID-19 and Cancer Consortium (ccc19us.org) Table 1. COVID-19 related hospitalization and 30-day all-cause mortality for all patients with invasive BCNAny Hospitalization30-day all-cause MortalityN% [95% CI]N% [95% CI]Total population52924747 [42-51]499 [7-12]Age&lt;601774425 [19-32]21 [0-4]60-691155144 [35-54]87 [3-13]70-791206655 [46-64]1714 [8-22]80+1178674 [65-81]2219 [12-27]ECOG PS0-132212238 [33-43]165 [3-8]2+756181 [71-89]1621 [13-32]Active Comorbidities0741014 [7-23]00 [0-5]1-22239442 [36-49]178 [5-12]&gt;219112968 [60-74]2915 [10-21]Treatment IntentCurative1866434 [28-42]95 [2-9]Palliative743953 [41-64]1216 [9-27]Cancer StatusRemission/NED33115447 [41-52]247 [5-11]Active disease, stable or responding to treatment1194840 [31-50]76 [2-12]Active disease, progressing372773 [56-86]1130 [16-47]Treatment Modality (within 3 months)Cytotoxic chemotherapy833542 [31-54]810 [4-18]Noncytotoxic therapy1856435 [28-42]105 [3-10]Local therapy (surgery or radiation)341750 [32-68]412 [3-27] Citation Format: Ali Raza Khaki, Dimpy P Shah, Maryam B Lustberg, Melissa K Accordino, Daniel G Stover, Gayathri Nagaraj, Donna R Rivera, Edith A Perez, Sara M Tolaney, Jeffrey Peppercorn, Petros Grivas, Jeremy L Warner, Corrie A Painter, Gilberto de Lima Lopes, Jr, Solange Peters, Michael A Thompson, Toni K Choueiri, Brian I Rini, Gary H Lyman, Nicole M Kuderer, Shaveta Vinayak. Characteristics and outcomes of SARS-CoV-2 infection in patients with invasive breast cancer (BC) from the COVID-19 and cancer consortium (CCC19) cohort study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-01.
Abstract PS6-02: Spatially defined immune-related proteins and outcome in triple negative breast cancer in the FinXX trial and Mayo Clinic cohort
Chumsri, Saranya , Ma, Yaohua , Hinerfeld, Douglas, Brauer, Heather Ann , Warren, Sarah , Perez, Edith A. , Leon‐Ferre, Roberto A. , Liu, Minetta C. , Knutson, Keith L. , Thompson, E. Aubrey , Carter, Jodi M. , Nielsen, Torsten O. , Asleh, Karama , Joensuu, Heikki , Hillman, David W. , Boughey, Judy C. , Ingle, James N. , Kalari, Krishna R. , Couch, Fergus J. , Knutson, Keith L. , Goetz, Matthew P.

Mayo Clinic

Cancer Research | February 15, 2021 | Volume: 81 | Issue: 4_Supplement | Pages: PS6-02-PS6-02

10.1158/1538-7445.sabcs20-ps6-02 Get It

Abstract Background: Growing data established the pivotal role of preexisting immune response in triple negative breast cancer (TNBC). Conventionally, preexisting immune response can be evaluated by quantifying tumor infiltrating lymphocytes mainly in the stroma or gene expression analysis from the whole tumor section. Due to technical challenges with these conventional methods, limited data regarding specific subtypes and spatial distribution of these immune infiltrates are currently available. Methods: NanoString IO360 gene expression analysis and Digital Spatial Profiling (DSP) were used. DSP was used to quantify 29 immune-related proteins in stromal and tumor-enriched segments from 44 TNBC samples from the FinXX trial (NCT00114816) and 335 samples from the Mayo Clinic (MC) cohort of centrally reviewed TNBC (Leon-Ferre BCRT 2018). In FinXX trial, 22 patients with recurrence and 22 patients without recurrence were included. In MC cohort, 217/335 patients received adjuvant chemotherapy while 118 patients had surgery only without adjuvant chemotherapy. Regions were segmented based on pancytokeratin staining. The general linear model was used for statistical analysis of differential expression with recurrence free survival (RFS) as a categorical variable (recur yes or no). Kaplan-Meier (KM) estimates and Cox regression models were also used for analysis. Results: In the FinXX trial, there were 12 out of 29 proteins in tumor epithelial segments (intraepithelial) which were significantly expressed at higher levels among patients who were free of recurrence. These proteins include Beta-2 microglobulin, CD11c, CD20, CD40, CD56, CD8, Granzyme B, HLA-DR, ICOS, PD-L1, PD-L2, and TGFB1. In contrast, merely 5 out of 29 proteins in stromal segments were significantly differentially expressed in these 2 groups of patients. Granzyme B, IDO1, PD-L1, and PD-L2 in stroma were significantly higher and SMA was significantly lower in patients without recurrence. Using Cox regression models, intraepithelial CD56, CD40, and HLA-DR were significantly associated with outcome. When comparing between highest and lowest intraepithelial protein expression by tertile, intraepithelial CD56 (HR 0.12, 95%CI 0.03-0.39, p &lt; 0.001), CD40 (HR 0.13, 95%CI 0.04-0.46, p = 0.002), and HLA-DR (HR 0.24, 95%CI 0.06-0.89, p = 0.032) were significantly associated with improved outcome. However, expression of these same proteins in stroma was not associated with outcome. Using KM estimates, intraepithelial CD56 (p &lt; 0.0001), CD40 (p = 0.0006), and HLA-DR (p = 0.013) were also significantly associated with improved outcome. Nonetheless, RNA expression of these proteins by IO360 from whole tumor sections were not significantly associated with outcome (CD56 p = 0.27, CD40 p = 0.21, HLA-DR p = 0.48). Similar findings with DSP were observed in MC TNBC cohort. Comparing between the highest and lowest quartiles, there were significantly fewer patients who developed recurrence with high protein expression of intraepithelial CD56 (p &lt; 0.001), CD40 (p = 0.002), and HLA-DR (p = 0.006). Conclusions: Using an in-depth analysis with spatially defined context, we identify that there were numerically more intraepithelial immune-related proteins associated with outcome compared to proteins in stroma. Specifically, intraepithelial CD56, CD40, and HLA-DR were significantly associated with improved outcome in both FinXX and MC TNBC cohorts. However, neither expression of these proteins in stroma nor RNA expression from whole tumor were associated with outcome. Our study highlights the impact of spatial biology and the importance of evaluating each potential biomarker in a spatially defined manner. Support: W81XWH-15-1-0292, BCRF 19-161, P50CA116201-9, P50CA015083 Citation Format: Saranya Chumsri, Jodi M. Carter, Yaohua Ma, Douglas Hinerfeld, Heather Ann Brauer, Sarah Warren, Torsten O. Nielsen, Karama Asleh, Heikki Joensuu, Edith A. Perez, Roberto A. Leon-Ferre, David W. Hillman, Judy C. Boughey, Minetta C. Liu, James N. Ingle, Krishna R. Kalari, Fergus J. Couch, Keith L. Knutson, Matthew P. Goetz, E. A. Thompson. Spatially defined immune-related proteins and outcome in triple negative breast cancer in the FinXX trial and Mayo Clinic cohort [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-02.
Abstract PS6-03: Prognostic value of clinical treatment score post-5 years (CTS5) and late relapse risk in hormone receptor-positive HER2-positive breast cancer in the North Central Cancer Treatment Group (NCCTG) N9831 (Alliance) and NSABP B-31 (NRG) trial
Pai, Tanyami, Gil, Angelica, Ma, Yaohua , Advani, Pooja , Moreno-Aspitia, Moreno, Colón‐Otero, Gerardo , Perez, Edith A. , Asmann, Yan W. , Pogue–Geile, Katherine L. , Thompson, E. Aubrey , Chumsri, Saranya , Li, Zhuo

Mayo Clinic

Cancer Research | February 15, 2021 | Volume: 81 | Issue: 4_Supplement | Pages: PS6-03-PS6-03

10.1158/1538-7445.sabcs20-ps6-03 Get It

Abstract Background: Although risk of late relapse in hormone receptor-positive (HR+) breast cancer is well established, most existing data pertain to the HR+ HER2-negative (HER2-) subgroup. CTS5 is one of the models for predicting risk of late relapse in HR+ HER2- breast cancer. However, the value of this model in HR+ HER2+ disease is less known, particularly in the context of adjuvant trastuzumab. Here, we evaluated CTS5 in patients with early stage HR+ HER2+ breast cancer treated in the NCCTG N9831 (Alliance for Clinical Trials in Oncology) and NSABP B-31 (NRG) trials. Methods: Stage I-III HR+ (ER+ and/or PR+) HER2+ breast cancer patients who were free of recurrence after 5 years in N9831 and B-31 trials were included. The online CTS5 calculator was used to determine CTS5 score and risk group (low, intermediate, and high) based on age, tumor size, grade, and number of involved nodes. Kaplan-Meier (KM) estimates, Cox regression models, and C index were used for analysis. N9831 and B-31 trials were analyzed separately. Results: 1,204 patients in N9831 and 658 patients in B-31 met the entry criteria. Baseline characteristics were similar between both trials, including median age, tumor size, and follow up. Similar distribution within CTS5 risk group was observed in both trials; 68.2% and 70.1% patients were high risk, 24% and 21.9% as intermediate risk, as well as 7.8% and 8.1% as low risk classified in N9831 and B-31, respectively. Using univariate Cox regression analysis, CTS5 score as a continuous variable was associated with recurrence-free survival (RFS) in the entire study cohort, including patients who received chemotherapy alone or in combination with trastuzumab, (HR 1.37, 95%CI 1.03-1.81, p=0.03, C index 0.57 in N9831 and HR 1.36, 95%CI 1.06-1.76, p=0.02, C index 0.54 in B-31), but not in patients who received concurrent trastuzumab (HR 1.19, 95%CI 0.73-1.2, p=0.49, C index 0.54 in N9831 and HR 1.35, 95%CI 0.96-1.9, p=0.08, C index 0.54 in B-31). As categorical variable in the entire study cohort, CTS5 risk group was not significantly associated with RFS among patients with intermediate vs. low (HR 0.47, 95%CI 0.18-1.22, p=0.12 and HR 1.61, 95%CI 0.66-3.92, p=0.29) and high vs. low (HR 1.23, 95%CI 0.57-2.67, p=0.6 and HR 1.93, 95%CI 0.85-4.41, p=0.12) with the C index of 0.58 and 0.53 in N9831 and B-31 respectively. There was also no significant difference in RFS among 3 CTS5 risk groups with Kaplan-Meier estimates. Among patients who received concurrent trastuzumab, similar trends were observed with no statistical difference in RFS between high vs. low (HR 0.68, 95%CI 0.24-1.97, p=0.48 and HR 1.44, 95%CI 0.52-3.96, 0.49) with the C index of 0.55 and 0.51 in N9831 and B-31, respectively. Paradoxically, patients with intermediate risk had better RFS than low risk (HR 0.18, 95%CI 0.03-0.97, p=0.05) in N9831 but no significant difference in B-31 (HR 1.31, 95%CI 0.44-3.95, p=0.63). Conclusions: While CTS5 score as a continuous variable was associated with outcome in overall HR+ HER2+ population, this model was not prognostic in patients receiving adjuvant trastuzumab in both N9831 and B-31 trials. Furthermore, the correlation (C index) was modest and CTS5 risk group as a categorical variable could not stratify outcome in this group of patients. This study underlines the need to develop a new prognostic model to better delineate the risk of late relapse in HR+ HER2+ breast cancer patients receiving trastuzumab as this model can facilitate clinical decision for extended adjuvant endocrine therapy. Support: BCRF-19-161, U10CA180821, U10CA180868 and U10CA180822 (NRG), Genentech. https://acknowledgments.alliancefound.org Citation Format: Tanyami Pai, Angelica Gil, Yaohua Ma, Zhuo Li, Pooja Advani, Moreno Moreno-Aspitia, Gerardo Colon-Otero, Edith A. Perez, Yan Asmann, Katherine Pogue-Geile, E. A. Thompson, Saranya Chumsri. Prognostic value of clinical treatment score post-5 years (CTS5) and late relapse risk in hormone receptor-positive HER2-positive breast cancer in the North Central Cancer Treatment Group (NCCTG) N9831 (Alliance) and NSABP B-31 (NRG) trials [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-03.
Abstract GS3-00: First results from a phase III randomized clinical trial of standard adjuvant endocrine therapy (ET) +/- chemotherapy (CT) in patients (pts) with 1-3 positive nodes, hormone receptor-positive (HR+) and HER2-negative (HER2-) breast cancer (
Albain, Kathy S. , Hayes, Daniel F. , Perez, Edith A. , Goldstein, Lori J. , Chia, Stephen , Dhesy-Thind, Subkhbinder, Rastogi, Priya , Gil, Miguel Gil, Arce-Salinas, Claudia , Pierga, Jean‐Yves , Lluch, Ana Hernandez, Vasquez, Manuel Ramos, Borrego, Manuel Ruíz, Ferrero, Jean-­Marc , Schott, Anne F. , Shak, S., Lew, Danika L., Miao, Jieling, Dhesy‐Thind, Sukhbinder , Dhesy-Thind, Sukhbinder , Kalinsky, Kevin M. , Barlow, William E. , Meric‐Bernstam, Funda , Gralow, Julie R. , Lin, Nancy U. , Alba, Emilio , Delaloge, Suzette , Martín, Miguel , Brain, Etienne G.C. , Park, In Hae , Jung, Kyung Hae , Sharma, Priyanka , Miao, Jieling , Tripathy, Debu , Hortobágyi, Gabriel N. , Pusztai, Lajos

Mayo Clinic

Cancer Research | February 15, 2021 | Volume: 81 | Issue: 4_Supplement | Pages: GS3-00-GS3-00

10.1158/1538-7445.sabcs20-gs3-00 Get It

Abstract Funding: Supported by National Cancer Institute grants U10CA180888, U10CA180819, U10CA180820, U10CA180821, U10CA180868, U10CA180863; and in part by Susan G. Komen for the Cure® Research Program, The Hope Foundation for Cancer Research, Breast Cancer Research Foundation, and Genomic Health, Inc. Acknowledgement: The authors wish to thank Dr. Ana M. Gonzalez-Angulo, MD, for her invaluable contributions to the design and implementation of this study. Background: The clinical utility of the RS to determine CT benefit is well established in pts with HR+, HER2-, axillary lymph node (LN)-negative BC. Retrospective analyses from SWOG S8814 support the potential prognostic and predictive role of RS for CT benefit in postmenopausal pts with LN+ BC. SWOG S1007 is a prospective, randomized trial of endocrine therapy (ET) vs. chemoendocrine therapy (CET) in women with 1-3 +LN and a RS &lt; 25 (NCT01272037). Methods: Eligibility criteria included women &gt; 18 years of age with HR+, HER2- BC and 1-3 +LN and no contraindications to taxane and/or anthracycline based CT. Women with a RS &lt; 25 were randomized to receive ET or CET in 1:1 randomization using 3 stratification factors: (1) RS (0-13 vs.14-25); (2) menopausal status; and (3) axillary nodal dissection vs. sentinel node biopsy. The primary objective was to determine the effect of CT on invasive disease-free survival (IDFS) and whether the effect depended on the RS. The primary analysis was to test for a significant interaction of the treatment arm and continuous RS using a Cox regression model for IDFS, adjusting for treatment, RS, and menopausal status. A total of 832 IDFS events were expected for the final analysis. Secondary objectives included overall survival (OS). The protocol specified that interaction between treatment and the stratification variables was to be tested and, if significant, separate analyses performed by stratum. Annual interim analyses were planned starting at 24% of events. At the third interim analysis with 410 IDFS events, the Data and Safety Monitoring Committee recommended reporting results, with a decision by the NCI’s Cancer Therapy Evaluation Program, the study sponsor. Results: Of the 9,383 women screened from 2/28/11-9/29/17, 5,083 pts (54.2%) were randomized. With a median follow-up of 5.1 years, 447 IDFS events have been observed. For the primary analysis, the interaction test for CT benefit and continuous RS was not statistically significant, p=0.30. In a model with CT, RS, and menopausal status (no interaction term), higher continuous RS was associated with worse IDFS [HR 1.06, 2-sided p&lt;0.001, 95% Confidence Interval (CI) 1.04-1.07], and CT was associated with an improvement in IDFS (HR 0.81, p=0.026, 95% CI 0.67-0.98). In a pre-specified analysis, a significant interaction was identified between CT and menopausal status (p=0.004), necessitating separate analyses by menopausal status. In postmenopausal pts (N=3350, 67%), adjusting for continuous RS, the HR for CET vs. ET was not significant (HR=0.97, p=0.82, 95% CI 0.78-1.22; 5-year IDFS 91.6% vs. 91.9%) indicating no benefit from CT. In premenopausal pts (N=1665, 33%), the HR (0.54) was statistically significant (p=0.0004, 95% CI 0.38-0.76; 5-year IDFS 94.2% vs. 89.0%), indicating CT benefit. In premenopausal pts, ovarian suppression was performed in 15.9% vs. 3.7% (ET vs. CET), and 47.9% vs. 26.4% reported menstruation after 6 months of treatment. Although the number of events is limited, the HR for treatment adjusted by RS for OS in premenopausal pts was 0.47 (p=0.032, 95% CI 0.24-0.94). At this time, there is no differential effect with CT in regard to other stratification factors. Conclusions: There is a significant differential treatment effect of CT benefit based on RS for premenopausal vs. postmenopausal women requiring separate analyses. While only 54% of the protocol specified events are recorded and pts will be followed for 15 years, the current data show that adjuvant therapy can be de-escalated to ET alone in postmenopausal pts with a RS &lt; 25 and 1-3 +LN. However, there is a strong IDFS benefit for CET in premenopausal pts, with an early indication of an OS improvement. Citation Format: Kevin Kalinsky, William E Barlow, Funda Meric-Bernstam, Julie R Gralow, Kathy S Albain, Daniel Hayes, Nancy Lin, Edith A Perez, Lori J Goldstein, Stephen Chia, Subkhbinder Dhesy-Thind, Priya Rastogi, Emilio Alba, Suzette Delaloge, Miguel Martín, Miguel Gil Gil, Claudia Arce-Salinas, Etienne Brain, In Hae Park, Jean-Yves Pierga, Ana Hernandez Lluch, Manuel Ramos Vasquez, Manuel Ruiz Borrego, Kyung Hae Jung, Jean-Marc Ferrero, Anne Schott, Steve Shak, Priyanka Sharma, Danika L Lew, Jieling Miao, Debu Tripathy, Gabriel Hortobagyi, Lajos Pusztai. First results from a phase III randomized clinical trial of standard adjuvant endocrine therapy (ET) +/- chemotherapy (CT) in patients (pts) with 1-3 positive nodes, hormone receptor-positive (HR+) and HER2-negative (HER2-) breast cancer (BC) with recurrence score (RS) &lt; 25: SWOG S1007 (RxPonder) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS3-00.
The Society for Obstetric Anesthesia and Perinatology Interdisciplinary Consensus Statement on Neuraxial Procedures in Obstetric Patients With Thrombocytopenia
Bauer, Melissa E. , Beilin, Yaakov, Gernsheimer, Terry , James, Allison , Yaghmour, Edward, Toledano, Roulhac D. , Turrentine, Mark , MacEachern, Mark , Madden, Hannah E., Rajasekhar, Anita, Leffert, Lisa , Arendt, Katherine, James, Andra H , Arendt, Katherine W. , Botero, Juliana Perez , Houle, Timothy T. , Segal, Scott , Wu, Christopher L , Cooper, Jason Phillip , Landau, Ruth

Mayo Clinic

Anesthesia & Analgesia | February 13, 2021 | Volume: 132 | Issue: 6 | Pages: 1531-1544

10.1213/ane.0000000000005355 | PMID 33861047 Get It

Because up to 12% of obstetric patients meet criteria for the diagnosis of thrombocytopenia in pregnancy, it is not infrequent that the anesthesiologist must decide whether to proceed with a neuraxial procedure in an affected patient. Given the potential morbidity associated with general anesthesia for cesarean delivery, thoughtful consideration of which patients with thrombocytopenia are likely to have an increased risk of spinal epidural hematoma with neuraxial procedures, and when these risks outweigh the relative benefits is important to consider and to inform shared decision making with patients. Because there are substantial risks associated with withholding a neuraxial analgesic/anesthetic procedure in obstetric patients, every effort should be made to perform a bleeding history assessment and determine the thrombocytopenia etiology before admission for delivery. Whereas multiple other professional societies (obstetric, interventional pain, and hematologic) have published guidelines addressing platelet thresholds for safe neuraxial procedures, the US anesthesia professional societies have been silent on this topic. Despite a paucity of high-quality data, there are now meta-analyses that provide better estimations of risks. An interdisciplinary taskforce was convened to unite the relevant professional societies, synthesize the data, and provide a practical decision algorithm to help inform risk-benefit discussions and shared decision making with patients. Through a systematic review and modified Delphi process, the taskforce concluded that the best available evidence indicates the risk of spinal epidural hematoma associated with a platelet count ≥70,000 × 10 6 /L is likely to be very low in obstetric patients with thrombocytopenia secondary to gestational thrombocytopenia, immune thrombocytopenia (ITP), and hypertensive disorders of pregnancy in the absence of other risk factors. Ultimately, the decision of whether to proceed with a neuraxial procedure in an obstetric patient with thrombocytopenia occurs within a clinical context. Potentially relevant factors include, but are not limited to, patient comorbidities, obstetric risk factors, airway examination, available airway equipment, risk of general anesthesia, and patient preference.