Mayo Clinic Campuses Research Articles

Sunset Over Flint Hill, 2023 by Hong Chun Zhang

Art is integrated into the Mayo Clinic environment. Since the original Mayo Clinic Building was finished in 1914, many pieces have been donated or commissioned for patients and staff to enjoy. Each issue of Mayo Clinic Proceedings features a work of art (as interpreted by the author) that is displayed in a building or on the grounds of Mayo Clinic campuses.

Prognostic factors of grade 4 IDH-mutant astrocytoma.

e14019 Background: The data on the prognostic factors of grade 4 IDH-mutant astrocytoma remains limited since the 2021 update of the WHO classification of Central Nervous System tumors. This update recognizes the importance of molecular characteristics and confers a grade 4 diagnosis based on the presence of at least one of either necrosis, microvascular proliferation, or CDKN2A/B homozygous deletion. This study sought to determine the factors that impact prognosis of patients with grade 4 IDH-mutant astrocytoma. Methods: A retrospective review was performed on all patients diagnosed with grade 4 IDH-mutant astrocytoma on initial diagnosis (as defined by the 2021 WHO classification) across the three Mayo clinic campuses (Minnesota, Florida, Arizona) between 2002 and 2023. Datapoints collected included demographic, clinical, imaging, histological and molecular variables. Factors impacting survival outcomes (overall survival [OS] and progression free survival [PFS]) were evaluated using Cox regression models. Results: Sixty-two patients with grade 4 IDH-mutant astrocytoma were identified (43 based on histological criteria alone, 10 based on molecular criteria alone, and 9 based on both). The median age of the patients was 36 years, with 64.5% of the patients identified as male and 93.3% as white. 100% (n=58) of these patients received standard treatment after surgery (radiation/temozolomide). The median follow up was 3.3 years. The median PFS and OS were 3.2 and 6.9 years, respectively. The OS was impacted by an unfavorable tumor location (either tumor involving the midline or at least 3 brain lobes; 2.4 years vs. 12.8 years, HR 10.8 [95% CI 3.29-35.6], p<0.001) and CDKN2A/B homozygous deletion (2.5 years vs. NR, HR=4.3 [95% CI 1.5-12.3], p=0.0065). The PFS was impacted by an unfavorable tumor location (1.4 years vs. 4.6 years, HR=5.3 [95% CI 2.21-12.7], p=0.002), CDKN2A/B homozygous deletion (1.4 years vs. 4.6 years, HR=6.2 [95% CI 2.71-14.2], p<0.001) and MGMT promoter hypermethylation (4.6 years vs. 1.4 years, HR=0.369 [95% CI 0.154-0.883], p=0.025). Age, sex, tumor size and the use of tumor-treating fields did not significantly affect survival outcomes. Using multivariable analyses, PFS remained significantly impacted by CDKN2A/B homozygous deletion (HR=11.3 [95% CI 3.23-39.0], p=0.0001) and MGMT promoter hypermethylation (HR=0.243 [95% CI 0.082-0.717], p=0.0104), but not by an unfavorable tumor location (p=0.819). Conclusions: Both CDKN2A/B homozygous deletion and MGMT status may independently influence the progression-free survival of patients with grade 4 IDH-mutant astrocytoma.

Prevalence of “HER2 ultra-low” among patients with advanced breast cancer with historical IHC0 status.

e13156 Background: Breast Cancer (BC) patients are classified as HER2-positive (IHC3+ or IHC2+/ISH+) or HER2-negative (IHC0, IHC1+ and 2+/ISH-). Within the HER2-negative category, patients who meet HER2-low (IHC1+ or IHC2+/ISH-) criteria can benefit from HER2 targeted therapy like trastuzumab deruxtecan. Patients who meet IHC0 criteria with incomplete and faint membrane staining in >0 but ≤10% of tumor cells — defined as “HER2 Ultra-low”, may also benefit from HER2 targeted therapy. This study aimed to assess the prevalence of “HER2 Ultra-Low” expression based on re-scored HER2 IHC biopsy slides. Methods: This study utilized EHR data from all three US Mayo Clinic campuses. A total of 300 patients with advanced BC (stages III-IV), and clinically documented HER2 IHC0 status between Jan 2017 and Jan 2023, were identified. One biopsy slide per patient (IHC assay: VENTANA Pathway anti-HER2/neu (4B5) rabbit monoclonal primary antibody) was digitized and scanned at 40x magnification. Two Mayo Clinic pathologists independently scored and reported HER2 status according to 2023 ASCO-CAP guidelines and included tumor stain percentage for each slide. Patients were considered “HER2 Ultra-Low” if their slide was scored as IHC0 with >0% but ≤10% staining. Cohen’s κ was used to quantify agreement between pathologists. Results: The re-scored patients (n=300) had a mean age of 57.8 years (SD=13.5), with ~97% having IHC0 documentation within 30 days of the reviewed biopsy slide. A total of 285 (95%) patients remained classified as IHC0 by at least one pathologist. Of these, 60% (n=171) were determined as “HER2 Ultra-low” by at least one pathologist. The rate of “HER2 Ultra-Low” per pathologist ranged from 43% (n=121) to 45% (n=104). The overall inter-pathologist concordance was 57%; patients with no observable HER2 IHC staining accounted for majority of the concordant patients (Table). Conclusions: About 3 in 5 advanced BC patients originally classified as HER2 IHC0 met the “HER2 Ultra-Low” criteria by at least one pathologist, implying that significant number of additional patients may benefit from HER2 targeted therapy. The relatively low concordance between HER2 expert pathologists in identifying lower levels of HER2 expression suggests the need for increased precision enabled by digital tools, leveraging AI, training for community practice pathologists, and continuing to follow best practice recommendations in determining HER2 IHC status. [Table: see text]

Umbra RM8, 2013 by Laura Crehuet Berman

Art is integrated into the Mayo Clinic environment. Since the original Mayo Clinic Building was finished in 1914, many pieces have been donated or commissioned for patients and staff to enjoy. Each issue of Mayo Clinic Proceedings features a work of art (as interpreted by the author) that is displayed in a building or on the grounds of Mayo Clinic campuses.

Oracle, Merakai, Appollo, Yang by Claire Roche

Art is integrated into the Mayo Clinic environment. Since the original Mayo Clinic Building was finished in 1914, many pieces have been donated or commissioned for patients and staff to enjoy. Each issue of Mayo Clinic Proceedings features a work of art (as interpreted by the author) that is displayed in a building or on the grounds of Mayo Clinic campuses.

Floating World by Charles Munch

Art is integrated into the Mayo Clinic environment. Since the original Mayo Clinic Building was finished in 1914, many pieces have been donated or commissioned for patients and staff to enjoy. Each issue of Mayo Clinic Proceedings features a work of art (as interpreted by the author) that is displayed in a building or on the grounds of Mayo Clinic campuses.

The Changes of Summer, Swiftly Go the Days, and Fields and Trees, by Rob van Hoek.

Art is integrated into the Mayo Clinic environment. Since the original Mayo Clinic Building was finished in 1914, many pieces have been donated or commissioned for patients and staff to enjoy. Each issue of Mayo Clinic Proceedings features a work of art (as interpreted by the author) that is displayed in a building or on the grounds of Mayo Clinic campuses.

Beyond the Primary: Unveiling the Prognostic Value of Secondary Cytogenetic Abnormalities in Multiple Myeloma

Introduction Fluorescent In-Situ Hybridization (FISH) has been an indispensable tool to characterize the cytogenetic landscape of multiple myeloma (MM), mainly for identifying primary abnormalities such as heavy chain gene (IgH) translocations and odd-number chromosome trisomies. These aberrations play a crucial role in risk stratifying the disease given their correlation with disease aggressiveness, treatment response and overall prognosis. High-risk (HR) cytogenetics are identified through the presence of t(14;16), t(14;20) or loss of the p53 gene locus. Less is known about the prognostic implication of secondary abnormalities, in particular gain of 1q21. We aimed to evaluate the association between primary and secondary cytogenetic abnormalities and their impact on overall survival (OS) in MM patients. Methods We performed a retrospective analysis on a FISH records database from three Mayo Clinic campuses. Cohort included patients >18 years of age, diagnosed with multiple myeloma between 2005 and 2022, with FISH performed within two years of diagnosis. Demographics including age, date of diagnoses and OS data were retrieved from electronic medical records. Statistical analyses were done using BlueSky Statistics software. Study was conducted in accordance with the principles of the Declaration of Helsinki; informed consent was obtained from all participants. Results We analyzed a total of 2221 patients, among which 59.8% were male, with a median age of diagnosis 65 years. Hyperdiploidy was the most prevalent primary cytogenetic abnormality observed in 44.3% of patients, followed by t(11;14) as the most common translocation (23%), and t(4;14) (8.2%). Gain(1q21) was assessed in 925 patients, among which 64%, 30.3% and 5.7% had 2, 3 and ≥4 copies respectively. Furthermore, 11.4% (n=253) exhibited either mutated TP53 or del17p, and 37.8% (n=839) presented with 13q loss or monosomy 13. The median follow-up for the overall population was 102 months (8.5 years), with a median OS of 75.5 months. Patients with high-risk translocations had significantly shorter median OS of 40.01 months compared to 80.65 months for those with standard risk translocations (p <0.001). The presence of ≥4 1q copies was associated with significantly reduced overall survival (2 copies: not reached, 3 copies: 69.4 months, ≥4 copies: 40.1774; p <0.001). This was consistent even when considering the presence of high-risk translocations (Figure 1). To confirm the independent significance of these findings, we performed multivariate Cox regression models, incorporating age at diagnosis, year of diagnosis, gender, presence of hyperdiploid disease, and presence of high-risk translocations. Given that overall survival outcomes were analyzed irrespective of treatment received, we incorporated year of diagnosis as a variable to control for potential impact of evolving treatment regimens over the years. The presence of ≥4 1q copies was associated with reduced OS, with a hazard ratio (HR) of 2.12 (CI: 1.38-3.26; p <0.001). The presence of 3 copies also showed prognostic significance (HR: 1.43; p: 0.012). Similarly, both the presence of TP53mut/mon17 (HR: 1.96, CI: 1.66-2.31; p <0.001) and 13qdel/mon13 (HR: 1.21, CI: 1.08-1.38) were associated with decreased OS. On the other hand, 1p deletion did not have any significant prognostic implications (HR: 1.84, CI: 0.38-1.59; p 0.113). When incorporating all cytogenetic events into a multivariate model, variables associated with reduced OS included age at diagnosis, the presence of both of 3 and ≥4 1q copies, TP53mut/mon17, t(4;14), t(14;16) and t(14;20). However, 13qDel/mon13 lost significance when incorporated with other abnormalities (Table 1). Conclusion Our investigation sheds light on the less explored realm of secondary cytogenetic abnormalities and confirm a strong association between increasing number of 1q copies and reduced overall survival, independent of other cytogenetic abnormalities and treatment regimens. These results underscore the utility of FISH-based comprehensive cytogenetic profiling at baseline, which enables reliable identification of high-risk patients. Future prospective trials should further elucidate the pathogenic mechanism for these findings. Our analysis used OS as primary endpoint and included over 2000 MM patients, reinforcing the clinical relevance of our findings.

831. Majocchi’s Granuloma – A Single Institution Retrospective Review

Abstract Background Majocchi’s granuloma (MG) is an uncommon deep fungal folliculitis predominantly caused by dermatophytes. Available data regarding predisposing comorbidities/risk factors, clinical characteristics, offending microbiologic pathogens, diagnostics, pathologic findings, and treatment approaches has been inferred from historical cases. Given these limitations in the existing literature of MG, we sought to conduct a detailed review of our institutional experience with biopsy-confirmed cases of MG. Methods Following IRB approval, we retrospectively identified and analyzed a multicenter cohort of adult patients diagnosed with MG between September 1992 and September 2022 at Mayo Clinic campuses (Figure 1). Data extracted included demographics, comorbid conditions, presenting clinical characteristics, diagnostic, microbiologic, and biopsy characteristics, treatment details, and outcomes. Figure 1 Flow Diagram show exclusion of patients from the final cohort. Results A total of 147 patients with MG with the accompanying baseline characteristics met study criteria (Table 1). One-hundred and five patients were male with a median age of 55.6 years. Immunosuppressant and topical corticosteroid use were common prior to development of MG (Table 1). Dermatologic lesions and their sites of involvement did not differ based on the immune status of patients (Table 2). Trichophyton rubrum was the most common causative pathogen of MG, in addition to other dermatophytes and fungal organisms (Table 3a). Treatment duration for all prescribed agents was median 31.5 days. Oral terbinafine was the most frequently utilized agent and clinical resolution was achieved in 96.6% of cases (Table 3b). Baseline Characteristics of 147 Patients with Majocchi’s Granuloma Diagnostic, Microbiologic, and Biopsy Characteristics, Treatment Characteristics and Outcomes Conclusion While rare and clinically variable in presentation, the diagnosis of MG requires careful clinical examination and history-taking, histopathologic confirmation, and frequently fungal culture. Most cases of MG in our study responded well to a course of oral terbinafine at a median of 31.5 days of treatment. Disclosures All Authors: No reported disclosures

Folk Fantail, Missing you-Kotare, Sunshine Kereru, Loyal Hihi, and Morning Quails by Jane Galloway

Art is integrated into the Mayo Clinic environment. Since the original Mayo Clinic Building was finished in 1914, many pieces have been donated or commissioned for patients and staff to enjoy. Each issue of Mayo Clinic Proceedings features a work of art (as interpreted by the author) that is displayed in a building or on the grounds of Mayo Clinic campuses.

Supervised machine learning to validate a novel scoring system for the prediction of disease remission of functional pituitary adenomas following transsphenoidal surgery

Functional pituitary adenomas (FPAs) are associated with hormonal hypersecretion resulting in systemic endocrinopathies and increased mortality. The heterogenous composition of the FPA population has made modeling predictive factors of postoperative disease remission a challenge. Here, we aim to define a novel scoring system predictive of disease remission following transsphenoidal surgery (TSS) for FPAs and validate our process using supervised machine learning (SML). 392 patients with FPAs treated at one of the three Mayo Clinic campuses were retrospectively reviewed. Variables found significant on multivariate analysis were incorporated into our novel Pit-SCHEME score. The Pit-SCHEME score with a cut-off value ≥ 6 achieved a sensitivity of 86% and positive likelihood ratio of 2.88. In SML models, without the Pit-SCHEME score, the k-nearest neighbor (KNN) model achieved the highest accuracy at 75.6%. An increase in model sensitivity was achieved with inclusion of the Pit-SCHEME score with the linear discriminant analysis (LDA) model achieving an accuracy of 86.9%, which suggests the Pit-SCHEME score is the variable of most importance for prediction of postoperative disease remission. Ultimately, these results support the potential clinical utility of the Pit-SCHEME score and its prospective future for aiding in the perioperative decision making in patients with FPAs.

Young Forest by Laura Wasilowski

Art is integrated into the Mayo Clinic environment. Since the original Mayo Clinic Building was finished in 1914, many pieces have been donated or commissioned for patients and staff to enjoy. Each issue of Mayo Clinic Proceedings features a work of art (as interpreted by the author) that is displayed in a building or on the grounds of Mayo Clinic campuses.

Exotic Species and Clusters by Glenda Kronke

Art is integrated into the Mayo Clinic environment. Since the original Mayo Clinic Building was finished in 1914, many pieces have been donated or commissioned for patients and staff to enjoy. Each issue of Mayo Clinic Proceedings features a work of art (as interpreted by the author) that is displayed in a building or on the grounds of Mayo Clinic campuses.

Cirque of the Towers by Gus Foster

Art is integrated into the Mayo Clinic environment. Since the original Mayo Clinic Building was finished in 1914, many pieces have been donated or commissioned for patients and staff to enjoy. Each issue of Mayo Clinic Proceedings features a work of art (as interpreted by the author) that is displayed in a building or on the grounds of Mayo Clinic campuses.

PO-05-056 FAILURE OF INTRINSIC ANTI-TACHYCARDIA PACING TO TERMINATE VENTRICULAR TACHYCARDIA AND POTENTIAL PROARRHYTHMIC EFFECTS

Intrinsic anti-tachycardia pacing (iATP™) is a novel, automated ATP algorithm that provides individualized therapy to terminate ventricular tachycardia (VT). If the first ATP attempt is unsuccessful, the algorithm analyzes the tachycardia cycle length and the post-pacing interval (PPI) and adjusts the subsequent sequence to successfully terminate VT. This algorithm was effective in a single clinical study without a comparator arm and case reports have corroborated this success in clinical practice. Despite the previously presented data, iATP™ failure has not been well documented in the literature. We present the first case series of iATP™ failure in routine clinical practice with detailed episode analysis and the apprise the electrophysiology community of the potential proarrhythmic effect of the algorithm. We retrospectively evaluated 262 patients with Medtronic Cobalt XT defibrillators followed at Mayo Clinic campuses in Minnesota, Florida, and Arizona. 119 patients had devices with the iATP™ feature turned on. 4 out of 119 patients (3.36%) had an acceleration of their ventricular arrhythmias within our cohort. Illustrative Case: A 74-year-old male with a history of idiopathic, non-ischemic cardiomyopathy (LVEF) 21%) status post-cardiac resynchronization therapy (CRT)-defibrillator for primary prevention, subsequent VT, and atrial fibrillation presented to our heart rhythm clinic for evaluation of syncope. The patient was riding an all-terrain vehicle when he felt a sudden onset of dyspnea and pre-syncope. His device interrogation revealed a presenting rhythm of VT at 200 beats per minute (bpm). The patient underwent four unsuccessful rounds of ATP. The 4th round of ATP resulted in acceleration (figure 1A) and degeneration into ventricular fibrillation (VF), followed by a successful 39.5 J shock (figure 1B). Figure 1C shows the dot plot for the entire episode with the blue box highlighting the acceleration in ventricular rate after the 4th ATP sequence. Given concern for a proarrhythmic effect, iATP™ was turned off. The patient was treated with amiodarone and mexiletine and underwent endocardial ablation with substrate modification in the inferolateral LV. He is currently doing well without a subsequent need for VT therapies. While the novel adaptive algorithm and its underlying concepts are intriguing, clinicians should be aware of the potential for acceleration and degeneration of VT by iATP™ and prepared to turn off the feature when this occurs.

Landscape With River by Alejos Lorenzo Vergara

Art is integrated into the Mayo Clinic environment. Since the original Mayo Clinic Building was finished in 1914, many pieces have been donated or commissioned for patients and staff to enjoy. Eachissue of Mayo Clinic Proceedings features a workof art (as interpreted by the author) that is displayed in a building or on the grounds of Mayo Clinic campuses.

Clare of Assisi by Caprice Kueffner Glaser

Art is integrated into the Mayo Clinic environment. Since the original Mayo Clinic Building was finished in 1914, many pieces have been donated or commissioned for patients and staff to enjoy. Each issue of Mayo Clinic Proceedings features a work of art (as interpreted by the author) that is displayed in a building or on the grounds of Mayo Clinic campuses.

Predictive factors for post operative seizures following meningioma resection in patients without preoperative seizures: a multicenter retrospective analysis.

Meningiomas are the most common primary brain tumor and represent 35% of all intracranial neoplasms. However, in the early post-operative period approximate 3-5% of patients experience an acute symptomatic seizure. Establishing risk factors for postoperative seizures will identify those patients without preoperative seizures at greatest risk of postoperative seizures and may guide antiseizure medications (ASMs) management. Adult seizure naïve patients who underwent primary resection of a World Health Organization (WHO) Grade 1-3 meningioma at the three Mayo Clinic Campuses between 2012-2022 were retrospectively reviewed. Multivariate regression analyses were used to identify radiological, surgical, and management features with the development of new-onset seizures in patients undergoing meningioma resection. Of 113 seizure naïve patients undergoing meningioma resection 11 (9.7%) experienced a new-onset post-operative seizure. Tumor volume ≥ 25 cm3 (Odds Ratio (OR) 5.223, 95% Confidence Interval (CI) 1.546 - 17.650, p = 0.008) and cerebral convexity meningiomas (OR 4.742, 95% CI 1.255 - 14.336, p = 0.016) were most associated with new onset postoperative seizures in multivariate analysis. ASMs and corticosteroid therapies did not display a significant difference among those with and without a new onset postoperative seizure. In the current study, a larger tumor volume (≥ 25 cm3) and/or convexity meningiomas predicted the development of new onset post-operative seizures. Those who present with these factors should be counseled for their increased risk of new onset post-operative seizures and may benefit from prophylactic ASMs therapy.

Coexistence of oral lichen planus and vulvar lichen sclerosus

Oral lichen planus (OLP) is a mucosal variant of lichen planus. Lichen sclerosus (LS) is an inflammatory disorder with a predilection for genital skin. We aimed to identify the characteristics of patients with both mucosal diagnoses. This retrospective study included 86 women with both OLP and vulvar LS diagnosed from June 1, 1991 through November 30, 2020 at a Mayo Clinic campus in Rochester, Minnesota; Scottsdale, Arizona; or Jacksonville, Florida. Data included treatments, other cutaneous diagnoses, comorbidities, and information on patch testing and malignant transformation. The median patient age at diagnosis was 64.5 years for OLP and 65.6 years for vulvar LS. A diagnosis of OLP before vulvar LS was most common (50.0%). The most frequently used treatment for both conditions was topical corticosteroids. Oral squamous cell carcinoma (SCC) did not develop in any patient, but vulvar SCC developed in 2 (2.3%). OLP and vulvar LS may coexist, commonly beginning in the patient's seventh decade. Topical corticosteroids are often used to manage both conditions. The coexistence of both diseases did not seem to portend a greater malignancy risk.

Pragmatic, Prospective Comparative Effectiveness Trial of Carbon Ion Therapy, Surgery, and Proton Therapy for the Management of Pelvic Sarcomas (Soft Tissue/Bone) Involving the Bone: The PROSPER Study Rationale and Design.

Surgical treatment of pelvic sarcoma involving the bone is the standard of care but is associated with several sequelae and reduced functional quality of life (QOL). Treatment with photon and proton radiotherapy is associated with relapse. Carbon ion radiotherapy (CIRT) may reduce both relapse rates and treatment sequelae. The PROSPER study is a tricontinental, nonrandomized, prospective, three-arm, pragmatic trial evaluating treatments of pelvic sarcoma involving the bone. Patients aged at least 15 years are eligible for inclusion. Participants must have an Eastern Cooperative Oncology Group Performance Status score of two or less, newly diagnosed disease, and histopathologic confirmation of pelvic chordoma, chondrosarcoma, osteosarcoma, Ewing sarcoma with bone involvement, rhabdomyosarcoma (RMS) with bone involvement, or non-RMS soft tissue sarcoma with bone involvement. Treatment arms include (1) CIRT (n = 30) delivered in Europe and Asia, (2) surgical treatment with or without adjuvant radiotherapy (n = 30), and (3) proton therapy (n = 30). Arms two and three will be conducted at Mayo Clinic campuses in Arizona, Florida, and Minnesota. The primary end point is to compare the 1-year change in functional QOL between CIRT and surgical treatment. Additional comparisons among the three arms will be made between treatment sequelae, local control, and other QOL measures.