Safety of Hemorrhoid Procedures in Patients Who Are Immunocompromised: The Mayo Clinic Experience.

Mayo Clinic Proceedings

Renal Cell Carcinoma with Thrombus Extension into the Inferior Vena Cava and the Right Atrium: A Case Report

Intraoperative Abandonment of Ileal Pouch to Anal Anastomosis—The Mayo Clinic Experience

Background: Two poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi) are currently FDA-approved for the treatment of HER2-negative metastatic breast cancer (MBC) in carriers of germline pathogenic variants (PVs) in BRCA1 or BRCA2 (BRCA1/2). This study explores the clinical outcomes of MBC patients treated with a PARPi. Methods: In this retrospective study, we included MBC patients treated with a PARPi between January 2017 and February 2022 at Mayo Clinic (Minnesota, Arizona, Florida, and Mayo Clinic Health Systems). We used the Kaplan Meier method to estimate the time-to-treatment-failure (TTF) and the log-rank test to compare different subsets. In addition, predictors of TTF were identified in a multivariate cox-proportional hazard regression model, including age at PARPi initiation, race, ethnicity, histology, estrogen receptor (ER), progesterone receptor (PR), and HER2 expression of the tumor, the number of prior therapies, type of PARPi, and PV carrier status (germline BRCA1/2 or PALB2 vs. somatic BRCA1/2 vs. other). Results: Sixty-five patients treated with PARPi (olaparib: 51; talazoparib: 14) were included in the final analysis. Fifty-five patients were carriers of germline PVs in BRCA1 (n=24, 37%), BRCA2 (n=27, 42%) or PALB2 (n=4, 6%), whereas ten patients (15%) had no germline PVs but the tumor had a somatic mutation in the homologous recombination-related (HRR) genes (7 in BRCA1/2, 2 in ATM, and 1 in CDKN2A and CDH1). At the data cutoff, 48 (74%) patients had discontinued PARPi due to progression or death. Fifteen (23%) patients required a dose reduction due to side effects. Occurrence of grade ≥ 3 side effects: anemia in 8, fatigue in 4, neutropenia in 2, and thrombocytopenia in 2 patients. Eight (15.7%) patients in the olaparib group and seven (50%) patients in the talazoparib group required a dose reduction for side effects. No patient on olaparib required drug discontinuation due to side effects, whereas two patients on talazoparib were switched to olaparib due to cytopenias and could tolerate olaparib. Median TTF in the overall population was 8 months (95% confidence interval [CI]: 6.4 – 9.6), and there was no difference (p=0.64) in TTF between the olaparib and talazoparib groups. Median TTF in the germline BRCA1, BRCA2, and PALB2 PV carriers were 7, 8, and 11 months, respectively (p=0.57). Among patients with somatic BRCA1/2 mutations, the median TTF was 4 months. Numerically, patients with HER2-positive tumors (n=8) had a shorter TTF compared to HER2-negative tumors (Median TTF: 4 vs. 8 months, p=0.098). No significant difference in TTF was observed by ER or PR status of the tumor, age at initiation of PARPi, the number of prior therapies, and prior use of platinum-based chemotherapy or CDK4/6 inhibitors. In multivariate analysis, HER2 positivity (hazard ratio [HR]: 8.0, 95% CI: 2.2 – 29.4, p=0.002), somatic BRCA1/2 mutations (HR: 7.6, 95% CI: 1.2 – 50.0, p=0.03) and somatic mutations in other HRR genes (HR: 19.1, 95% CI: 3.1 – 118.6, p=0.002) were associated with worse TTF. Conclusions: In the real world, PARPi were well-tolerated with promising time-to-treatment-failure (TTF) benefits comparable to data from clinical trials. Notably, relatively shorter TTF was observed in patients with somatic BRCA1/2 and other HRR gene mutations and HER2-positive MBC. These findings improve our understanding of the role of PARPi in MBC and will help to guide treatment decisions with PARPi in the clinical setting. Citation Format: Nusrat Jahan, Jodi Taraba, Karthik V. Giridhar, Roberto A. Leon-Ferre, Amye J. Tevaarwerk, Elizabeth Cathcart-Rake, Ciara C. O’Sullivan, Prema Peethambaram, Timothy J. Hobday, Kathryn Ruddy, Lida A. Mina, Pooja Advani, Felipe Batalini, Matthew P. Goetz, Tufia C. Haddad, Fergus J. Couch, Siddhartha Yadav. Clinical outcomes of metastatic breast cancer patients treated with poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi): the Mayo Clinic experience [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-01-22.

Background: Male breast cancer (MBC) is rare, and usually managed by extrapolation from female breast cancer. We report on the characteristics and survival outcomes of MBC patients from Mayo Clinic Rochester (MCR). Methods: Medical records of MBC patients treated at MCR during a 25-year period (1990-2015) were reviewed. Demographic variables, tumor characteristics, recurrences, and overall survival (OS) were collected. Progression free survival (PFS) and OS were estimated by the Kaplan-Meier method. Multivariate Cox-proportional hazard regression was used to identify predictors of OS. Results: One hundred sixty-seven patients were included in the final analysis, with a median follow-up of 58 months after diagnosis. Baseline characteristics are presented in Table 1. Eighty percent of patients with ER-positive tumors received endocrine therapy. Among men with stage I-III disease, approximately 90% underwent mastectomy, and 44% received adjuvant chemotherapy. The 5-year locoregional and distant recurrence rates for patients with stage I-III disease were 4.4% and 21.5%, respectively. The 5-year PFS and OS for patients with stage I-III disease were 65.5% and 80.1%, respectively. In a multivariate analysis assessing predictors of OS in patients with stage I-III disease, older age (HR 1.05; 95% CI: 1.02 – 1.09), stage II (HR 11.06; 95% CI: 3.84 – 31.85) or stage III disease (HR 14.74; 95% CI (3.99 – 54.45), and omission of surgery (HR 45.33; 95% CI: 3.97 – 517.32) were associated with poorer OS, while endocrine therapy (HR 0.21, 95% CI: 0.09 – 0.51) was associated with better OS. ER, PR, HER2 and grade were not independently prognostic. The median OS for stage IV patients was 10 months, though this 11-man cohort was too small to allow assessment of prognostic factors in advanced male breast cancer. Conclusions: MBC remains an understudied condition. Prognostic factors in this stage I-III disease are consistent with those identified in other MBC retrospective cohorts. Prospective studies are needed to better understand the unique clinical features of MBC, and to improve outcomes, particularly for advanced disease. Table 1:Baseline characteristics N=167 Median age at diagnosis (Years)64.4 Ethnicity/Race: Caucasian131 (78.4%)African American4 (2.4%)Other or unknown32 (19.2%) Overall AJCC 7th edition stage: Stage I39 (23.4%)Stage II80 (47.9%)Stage III32 (19.2%)Stage IV11 (6.6%)Unknown5 (3.0%) Grade: 18 (4.8%)247 (28.1%)3101 (60.5%)Unknown12 (7.1%) ER status: Negative8 (4.8%)Positive153 (91.6%)Unknown6 (3.6%) PR status: Negative17 (10.2%)Positive141 (84.4%)Unknown9 (5.4%) HER-2 status: Negative70 (41.9%)Positive12 (7.2%)Unknown85 (50.9%) Citation Format: Yadav S, Leon-Ferre RA, Jimenez RE, Hawse JR, Hieken TJ, Couch FJ, Boughey JC, Ruddy KJ. Clinical characteristics and survival of patients with male breast cancer: The Mayo Clinic experience [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-19-05.

Mitral valve repair for patients with degenerative or functional mitral valve regurgitation improves symptoms and prognosis, and several techniques have been described. Important principles in operation are simplicity, reproducibility, and durability of repair. At Mayo Clinic, we have operated on more than 6000 patients with degenerative mitral valve disease and valve prolapse, and this review details our approach to mitral valve repair, including robotic and minimally invasive techniques. Most patients with isolated leaflet prolapse can be managed with leaflet plication or triangular resection, and chordal replacement is reserved for repair of anterior leaflet prolapse. Posterior annuloplasty with a standard-sized flexible band is used to reduce annular circumference and improve leaflet coaptation. With these methods, early risk of mortality for mitral valve repair is low in the current era (< 1%), and rate of recurrent valve leakage is 1.5 per 100 patient-years during the first year post-repair and 0.9 per 100 patient-years thereafter. This paper also briefly summarizes important considerations for patients with mitral valve regurgitation and severe calcification, perforations due to endocarditis, and rheumatic heart disease.

“Real-Life” Data of the Efficacy and Safety of Belantamab Mafodotin in Relapsed Multiple Myeloma- the Mayo Clinic Experience

Background The current definition, prognosis, and optimal treatment (tx) for oligometastatic breast cancer (OMBC) are not fully known. With advances in multimodality breast cancer (BC) tx and overall improvement in patient (pt) outcomes, it is important to identify baseline pt factors that confer better prognosis in OMBC and assess the impact of local/regional tx and metastasis (mets)-directed tx on survival outcomes. Methods We reviewed 105 Mayo Clinic pts with OMBC (up to 5 mets) from 2003 to 2021. Pts were excluded from analysis if they were misidentified as having OMBC (n=6), did not have a primary breast mass (n=1), developed de novo BC during tx (n=1), or were lost to follow up (n=2). Categorical variables were summarized as counts. Continuous variables were reported as medians. Kaplan-Meier method was used to estimate survival and the time from diagnosis to next tx at 1, 3, and 5 years. Log-rank test was used to compare survival rates between baseline factors. Univariate Cox proportional hazards models were performed on both baseline and time-dependent factors. All tests were two-sided with p-value &amp;lt; 0.05 considered statistically significant. Results Total pts included were 95. Median age was 49 (range, 26-86), most (93.6%) pts were White, and 46.8% were postmenopausal. Invasive ductal carcinoma (89.5%) was the most common BC type. Median survival was 10.8 years; 1-, 3-, and 5-year survival rates were 98.9%, 87.7%, and 81%, respectively. 58 pts (61.1%) required a change in tx due to disease progression. No significant survival difference was observed in pre- vs. postmenopausal pts (p=0.71) or in groups based on hormone receptor and/or human epidermal growth factor receptor 2 status. 47 pts (49.5%) received local/regional tx; no significant difference in survival (HR 0.57, 95% CI 0.23-1.40; p=0.217) or time to next tx (HR 0.67, 95% CI 0.39-1.15; p=0.144) was seen in this subgroup. Of these pts, 36 (76.6%) received neoadjuvant chemotherapy and/or immunotherapy, 5 of whom (10.6%) also started endocrine tx preoperatively. Overall, 11/47 pts (23.4%) received neoadjuvant endocrine tx. 20 pts received systemic tx without eventual surgery, and 5 pts got palliative radiation (RT). Biopsy-confirmed mets were noted in 76 pts (80%), with bone-only mets in 50%, 30 pts (31.6%) with viscera-only mets and 7 pts (7.4%) with both bone and visceral mets. 18 pts had suspected mets on imaging but did not undergo biopsy. The hazard of death was 6.34 times higher in pts with both bone and visceral mets than those with bone-only mets (p=0.008). Pts with viscera-only mets had higher survival at 2 and 3 years than pts with bone-only or both bone and visceral mets (p=0.093). Pts with 3 mets (7/76, 7.4%) had decreased survival at 1, 2, and 3 years compared to pts with 1-2 (65/76, 85.5%) mets (p=0.6). 67 pts (70.5%) received mets-directed tx; RT alone was the most common modality (52/67, 77.6%), followed by surgery (6/67, 9%), RT plus surgery (5/67, 7.5%), and ablation alone (3/67, 4.5%). There was no significant difference in survival (HR 1.27, 95% CI (0.53, 3.07), p=0.589) or time to next tx (HR 0.95, 95% CI (0.56, 1.63), p=0.856) in pts who received mets-directed tx. Multivariate analysis was not performed because most findings were not statistically significant in univariate analysis. Conclusions We did not find any significant differences in survival based on characteristics like menopausal status or site or number of mets in pts with OMBC. There was a trend toward improved survival in pts with viscera-only mets, but this finding requires validation. Local/regional and mets-directed tx did not improve survival; however, survival at 1, 3, and 5 years was excellent in this OMBC pt population. Our study was limited by low pt numbers and heterogeneity in the pt population. Findings need validation in larger studies. Citation Format: Tanmayi Pai, Raza Zarrar, Zhongwei Peng, Zhuo Li, Lauren Cornell, Kostandinos Sideras, Rohit Rao, Alvaro Moreno-Aspitia, Saranya Chumsri, Sarah McLaughlin, James Jakub, Emmanuel gabriel, Sanjay Bagaria, Laura Vallow, Santo Maimone, Pooja Advani. Clinical Features and Survival Outcomes of Oligometastatic Breast Cancer Patients: The Mayo Clinic Experience [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-06-04.

IntroductionHepatic artery pseudoaneurysm (HAP) is a rare and potentially life-threatening condition associated with high mortality. This study aims to review the etiology, clinical manifestations, management, and outcomes of patients diagnosed and treated for HAP at the Mayo Clinic.MethodologyThis study was a retrospective chart review of medical records for patients diagnosed and treated for hepatic artery pseudoaneurysm (HAP) at the Mayo Clinic (Florida, Minnesota, and Arizona) between September 1, 1998, and June 30, 2022. A total of 27 patients with HAP were identified, and their demographics, presenting symptoms, location of HAP, etiology, associated liver pathology, type of intervention, and outcomes were analyzed.ResultsThe majority of patients with hepatic artery pseudoaneurysm (HAP) were male (63%), with a median age of 57 years (range: 25–87 years). HAP was predominantly intrahepatic (85.2%) and most commonly located on the right hepatic artery (RHA) (70.4%). In 89.9% of cases, the condition was attributable to hepatobiliary procedures or trauma, while only 10.1% occurred spontaneously. Presenting symptoms at the time of HAP diagnosis varied, including gastrointestinal (GI) bleeding (29.6%), abdominal pain (14.81%), non-GI bleeding (11.1%), traumatic bodily injury (11.1%), and other symptoms (14.81%). Asymptomatic or incidental findings of HAP were observed in 18% of cases. Malignancy was identified in 52% of patients, and 26% were liver transplant recipients. Statistical analysis revealed that factors such as prior knowledge of HAP (p = 0.381), HAP rupture (p = 0.382), anticoagulation therapy (p = 0.856), hemorrhagic shock (p = 0.25), liver cirrhosis (p = 0.143), gastrointestinal bleeding (p = 0.879), hepatobiliary abscess (p = 0.079), liver transplantation (p = 0.738), spontaneous HAP (p = 0.381), and malignancy (p = 0.163) were not significantly associated with increased mortality. In contrast, the need for transfusions (p = 0.021), tumor invasion (p = 0.023), portal vein thrombosis (PVT) (p = 0.02), and liver necrosis (p = 0.02) were significantly associated with higher mortality. The overall infection rate was 3%, while the mortality rate was 18.5%.DiscussionHepatic artery pseudoaneurysm (HAP) is a rare but serious condition often associated with hepatobiliary procedures, trauma, or liver transplants, though it can also occur spontaneously. While HAP is commonly detected incidentally, its diagnosis is frequently linked to complications such as rupture and gastrointestinal bleeding. However, our study suggests that these complications do not necessarily increase mortality. Key factors associated with higher mortality include the need for blood transfusions, tumor invasion, portal vein thrombosis, and liver necrosis at the time of diagnosis. The overall infection rate was low, but the mortality rate was 18.5%, highlighting the importance of early detection and management.

Breast Conservation Therapy for Invasive Breast Cancer: A Review of Prior Trials and the Mayo Clinic Experience

Background: While anthracyclines are frequently utilized in the treatment of early-stage breast cancer (BC) patients (pts), they are associated with serious toxicities including dose-dependent cardiotoxicity and secondary myelodysplastic syndrome/acute myeloid leukemia. Neoadjuvant therapy (NAT) combining anthracycline-based chemotherapy and immunotherapy has become the standard of care for early-stage triple-negative BC per the pivotal KEYNOTE-522 study [1]. However, pts aged ≥65 represented &amp;lt;20% of KEYNOTE-522 pts. Here, we assessed the clinical and surgical outcomes of older adult pts who received anthracycline-sparing NAT for early-stage, triple-negative BC. Methods: In this retrospective case series, 34 Mayo Clinic enterprise pts aged ≥65 who were documented to have 1) received anthracycline-sparing NAT with immunotherapy +/- chemotherapy and 2) completed surgery for nonmetastatic, HER2-negative BC between 6/2019 and 3/2024 were reviewed. We did include pts with low hormone receptor (ER +/- PR) expression. One pt who had a concomitant non-BC malignancy was excluded. Demographics, baseline clinical and tumor characteristics including stromal tumor-infiltrating lymphocytes (sTILs), reasons for anthracycline omission, NAT-related toxicities, and surgical outcomes were assessed. The primary endpoint was pathological complete response (pCR). Results: Thirty-three pts were included. Median pt age was 75 (range, 65-89), and most pts (28/33, 84.8%) were Non-Hispanic White. Nine pts (27.3%) had a prior history of cancer, and 4/33 (12.1%) had a history of anthracycline use. Only 3/33 (6.1%) had documented LVEF ≤50% prior to NAT, one of whom had received an anthracycline previously. Most had grade 3 (24/33, 72.7%), cT2 (22/33, 66.7%), and cN1 (17/33, 51.5%) disease pre-NAT. Baseline sTIL % ranged from 0 to 80% for the 16 pts for whom these data were available. The most frequently administered NAT regimen was carboplatin, paclitaxel, and pembrolizumab (25/33, 75.8%). The most-often cited reasons for anthracycline omission were medical comorbidities including cardiac comorbidities (7/33, 21.2%), favorable clinical response to anthracycline-sparing NAT (7/33), and difficulty tolerating anthracycline-sparing NAT (7/33). Over half of pts (17/33, 51.5%) had a documented grade ≥3 adverse event (AE) of any type, of whom 6 pts had a grade ≥3 immune-related AE. Similarly, 17/33 pts had to discontinue all or part of NAT due to NAT-related toxicities. No pts had a documented grade 4-5 AE. pCR was achieved by 11/33 (33.3%) pts, most of whom had cT2 (7/11, 63.6%), node-positive (7/11) BC pre-NAT. None had axillary nodal disease only. 2/11 (18.2%) had a BRCA mutation or variant of unknown significance, and 3/11 had ER +/- PR-low BC. All but 1 received carboplatin as part of NAT. Most pts (8/11, 72.7%) had a documented grade ≥3 AE, half of which were immune related, and 7/11 (63.6%) had to discontinue all or part of NAT due to NAT-related toxicities. Only 4/11 received adjuvant pembrolizumab (36.4%). Conclusion: One third of elderly pts achieved pCR with a non-anthracycline-based NAT regimen. However, over half of our sample (51.5%) experienced grade ≥3 AEs, including 72.7% of pts with pCR. Our institutional experience was limited by a small sample size. Analysis of pCR based on sTILs is ongoing. Reference: 1. Schmid P, Cortes J, Pusztai L, et al. Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med. 2020;382(9):810-821. doi:10.1056/NEJMoa1910549 Citation Format: Tanmayi Pai, Blake McKinley, Sonam Sonam, Miglena K. Komforti, Rohit Rao. A real-world analysis of clinical characteristics and outcomes of early-stage, triple-negative breast cancer patients receiving anthracycline-sparing neoadjuvant chemoimmunotherapy: the Mayo Clinic experience [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-10-07.

Long-term outcomes of radiotherapy for stage II testicular seminoma–the Mayo Clinic experience

Melkersson-Rosenthal syndrome and its variants- The Mayo Clinic experience

Introduction: Atrial fibrillation (AF) is a serious complication, which occurs in 30% to 40% of patients after surgical aortic valve replacement (SAVR) and contributes to adverse outcomes. Advanced technology has enabled transcatheter aortic valve replacement (TAVR) in patients with High-risk Severe Aortic Stenosis (HRSAS). In these patients, the compliance of the systemic vasculature is an independent predictor of diastolic dysfunction, a known predictor of postoperative AF (POAF). We hypothesize that patients with HRSAS undergoing TAVR represent a population at increased risk for POAF. METHODS: The medical records of 195 TAVR patients at the Mayo Clinic from November 2008 to January 2013 were analyzed. All patient demographic, clinical, pre- and post-procedural outcomes were collected from the patients’ medical records, and reviewed to ascertain all cases of POAF (AF ≤30 days of surgery). Patients with a prior history of AF (n= 75 (38.5%)) were excluded. Logistic regression analysis was used to identify clinical predictors of POAF after TAVR. Results: The mean age of the study population was 80.8±7.8 years and 60.8% (n=73) were men. The mean STS risk score was 8.9±5.1. Of the 120 patients without prior AF, 20.8% (n=25) developed new-onset POAF after TAVR. Patients who developed POAF were more likely to have undergone a transapical or transaortic TAVR approach (OR 3.20; 95% CI (1.3-8.0), had a higher incidence of renal complications (52.0% vs 21.5%; p= 0.003), greater hospital length of stay (7.4±2.58 vs 5.0±2.6 days; p= 0.0003, and a trend toward higher 30-day mortality (28.0% vs 13.7%; p= 0.09) and pulmonary complications (16.0% vs 5.4%; p= 0.08) compared with those who did not develop POAF, respectively. Neurologic complications were not different between the 2 group (4.0% vs 3.2%; p= 0.85). Conclusions: Patients with High-risk Severe Aortic Stenosis undergoing TAVR have increased risk of POAF, primarily associated with a transapical or aortic surgical approach. Patients who develop POAF had higher incidence of post-procedural complications and longer hospitalizations. Therefore, perioperative strategies aimed at prevention of POAF are as important in TAVR patients as in those undergoing SAVR.

86 Diagnostic Yield of Targeted Gene Panels in Evaluation of Suspected Immunodeficiency - The Mayo Clinic Experience