Large Series Research Articles

Management of low-risk papillary thyroid cancer. Minimally-invasive treatments dictate a further paradigm shift?

Current management options for PTMC include lobo-isthmectomy and active surveillance (AS). Recently, ultrasound-guided minimally invasive procedures (MITs) are offered as a nonsurgical therapy for PTMC because they do not require hospitalization and general anaesthesia, and do not result in loss of thyroid function or cosmetic damage. MITs are reported to consistently provide, mostly in large retrospective series of patients, a rapid, safe, and cost-effective way to eradicate low-risk thyroid malignancies. However, conclusive data from well-conducted prospective studies on the histologically-proven completeness of tumor ablation and the long-term clinical advantages versus AS are still lacking. This study aimed to evaluate the efficacy and safety of ultrasound-guided minimally invasive treatments (MITs) for PTMC in comparison to traditional surgical methods and active surveillance, and to assess their role in current clinical practice. A structured literature review was conducted using keywords related to PTMC, MIT, and comparative techniques. Studies were evaluated based on treatment modality, patient selection, follow-up duration, complication rates, and clinical outcomes. MITs have shown promising results in the management of PTMC. These treatments offer several advantages over surgery, such as reduced use of surgical resources, lower costs, minimal work disruption, and fewer major complications. However, there are still limitations, including the need for long-term surveillance and the potential risk of incomplete tumor ablation. MITs represent a promising non-surgical option for managing low-risk PTMC, especially for patients ineligible for or refusing surgery. Despite favorable outcomes, more robust prospective data are needed to confirm their long-term benefits and completeness of tumor ablation. Interdisciplinary discussions and thorough patient education on the advantages and limitations of MITs are crucial for informed decision-making.

Evaluating the Safety of Retrograde Intrarenal Surgery (RIRS): Intra- and Early Postoperative Complications in Patients Enrolled in the Global Multicentre Flexible Ureteroscopy Outcome Registry (FLEXOR).

To assess the incidence of the most common intra- and early postoperative complications following RIRS in a large series of patients with kidney stones. We conducted a retrospective analysis of patients with kidney stones who underwent RIRS across 21 centers from January 2018 to August 2021, as part of the Global Multicenter Flexible Ureteroscopy Outcome (FLEXOR) Registry. Among 6669 patients undergoing RIRS, 4.5% experienced intraoperative pelvicalyceal system bleeding without necessitating blood transfusion. Only 0.1% of patients, required a blood transfusion. The second most frequent intraoperative complication was ureteric injury due to the ureteral access sheath requiring stenting (1.8% of patients). Postoperatively, the most prevalent early complications were fever/infections requiring antibiotics (6.3%), blood transfusions (5.5%), and sepsis necessitating intensive care unit admission (1.3%). In cases of ureteric injury, a notably higher percentage of patients exhibited multiple stones and stone(s) in the lower pole, and these cases were correlated with prolonged lasing and overall surgical time. Hematuria requiring a blood transfusion was associated with an increased prevalence of larger median maximum stone diameters, particularly among patients with stones exceeding 20 mm. Furthermore, these cases exhibited a significant prolongation in surgical time. Sepsis necessitating admission to the intensive care unit was more prevalent among the elderly, concomitant with a significantly larger median maximum stone diameter. Our analysis showed that RIRS has a good safety profile but bleeding requiring transfusions, ureteric injury, fever, and sepsis are still the most common complications despite advancements in technology.

Red blood cell distribution width as a surrogate biomarker of damage and disease activity in patients with systemic lupus erythematosus.

Red blood cell distribution width (RDW) is a measure of variability in mean corpuscular volume. Alterations in RDW can be observed in a variety of human disorders, including inflammatory, cardiovascular, and hepatic or renal diseases. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect virtually any organ in the body. In this work, our objective was to analyse how a complete characterisation of disease characteristics in a large series of patients with SLE is related to RDW values. 284 patients with SLE and 181 age- and sex-matched healthy controls were recruited. Complete blood count including RDW was assessed. Multivariable analysis was performed to analyse the relationship between RDW and SLE disease characteristics, including composite scores of disease activity and damage. After multivariable adjustment, RDW was higher in patients with SLE compared to controls (beta coefficient 0.8 [95% confidence interval: 0.3-1] %, p=0.003). Several disease characteristics, such as the presence of extractable nuclear antibodies and antiphospholipid syndrome, and the use of prednisone and azathioprine, were significantly associated with higher levels of RDW after adjustment for confounders. Of note, cumulative disease damage and disease activity scores were associated with higher RDW values after controlling for covariates. RDW may serve as a surrogate biomarker of accrual disease damage and activity in patients with SLE.

BIFURCATION: A CLINICAL CASE IN ACUTE CORONARY SYNDROME

Abstract Bifurcation A clinical case in acute coronary syndrome. Coronary bifurcation lesions are considered one of challenging entities in the field of coronary intervention due to the risk of side branch loss and higher risk of stent thrombosis. There are limited data on the preferred treatment strategy in ST–segment elevation myocardial infarction (STEMI) patients with bifurcation lesions as most dedicated study excluded patients with acute coronary syndrome. In all comers population a 10–20% of STEMI patients had bifurcation culprit lesion. In 2018 guideline suggested a provisional approach by stenting the main vessel and implanting a second stent only if necessary as a bailout strategy. This reccomandation was supported by a large series of study that uniquely documented the superiority of one versus two stent technique. The same message could also be exported in the context of acute patients, as our clinical case, thanks to registry like COBIS 2 including ST–segment elevation patient. But this precious advice cannot be applied in all clinical subsets. Especially when we manage with a relevant side–branch and when the risk of loosing the side branch is very high. In this subgroup of patient, bifurcation lesion may benefit from a 2 stent approach. Different technical option are available. Among these, DK–crush and inverted Main Branch stenting across Side Branch (Invertend Culotte or inverted T technique) could be the best choice. Our patient was a young lady presenting with a lateral STEMI (D1 and aVL). The culprit lesion was a Medina 1.1.1 bifurcation lesion involving left anterior descending and first–diagonal. Since our side branch had thrombus inside, the vessel was relevant by definition. Other anatomical characteristique to take into account: relevant size and covering a large myocardial territory. Planning the strategy to treat our LAD–D1 bifurcation we consider the angle and the difference in size between main and side branch. We decided to proceed with DK–crush and its recent evolution DK–nano crush. In conclusion “do it provisional” guideline message is not always possible, 2 stent technique seems to be the best choice in presence of a relevant side–branch / high risk to loose it. Our take home message is, if the clinical scenario allow it, don’t hesitate to perform a multistep two vessel strategy technique and to try to reconstruct perfect anatomical carina even in STEMI context.

Effectiveness and safety of systemic therapy for moderate-to-severe atopic dermatitis in children and adolescent patients: a systematic review

ImportanceDue to comorbidities and associated safety risks, the management of severe atopic dermatitis (AD) in pediatric and adolescent patients poses significant challenges.ObjectiveTo examine the efficacy and safety of systemic therapies for the treatment of moderate-to-severe atopic dermatitis in children and adolescents.Evidence reviewOn Feb 29, 2024, a systematic literature search was conducted in Embase, PubMed, and the Cochrane Central Register of Controlled Trials (Central). No date restrictions were applied. Randomized clinical trials, cohort studies, large case series, and meta-analyses were assessed to evaluate the efficacy (or effectiveness) and/or safety of systemic treatments for moderate-to-severe atopic dermatitis in children and adolescents.FindingsA preliminary search yielded 1457 results, from which 19 unique articles with a total of 3741 patients were included in the analysis. Overall, the available data for each systemic medication are limited, and the overall quality of the included studies on conventional systemic treatments is relatively low. When Dupilumab was used as a standalone treatment, 30%-40% of infants and toddlers aged 6 months to 2 years achieved EASI-75, while 50% of patients aged 2 to 6 years achieved EASI-75. In children aged 6 to 12 years, 33.0%-59.0% of atopic dermatitis patients achieved EASI-75, and when combined with topical corticosteroids (TCS), 69.7%-74.6% achieved EASI-75. Long-term data showed EASI-75 rates ranging from 75.0% to 94.0% for this age group. For adolescents aged 12 to 18 years, 40%-71% of patients achieved EASI-75 within 12 to 16 weeks, and by week 52, 80.8% of patients achieved EASI-75.Abrocitinib treatment resulted in 68.5%-72.0% of patients achieving EASI-75. Omalizumab treatment at week 24 showed a percentage change in SCORAD scores of -12.4%. In the Methotrexate treatment group, there was a SCORAD change of -26.25% at week 12, while the Cyclosporine A group had a SCORAD change of -25.01%. Patients treated with IVIG (Intravenous Immunoglobulin) showed a -34.4% change in SCORAD percentage scores at week 4, which further decreased by 47.12% at week 24. Patients receiving 4mg of Baricitinib and TCS had a 52.5% rate of EASI-75 at 16 weeks, and patients receiving different doses of upadacitinib had a 63-75% rate of EASI-75 at 16 weeks. The rate of EASI-75 at 16 weeks was around 28% in patients who received various doses of Tralokinumab.The most common adverse events observed were nasopharyngitis, respiratory events and dermatitis atopic.Conclusions and relevanceAwareness of adverse events and concomitant medications is crucial, and appropriate dosing and frequent laboratory and clinical monitoring are also essential. More real-world evidence and prospective cohort studies analyzing the effectiveness and safety of systemic therapies in children and adolescents are of paramount importance for optimizing personalized, effective, and safe management of the growing population of patients with atopic dermatitis in this age group.

Removals and Revisions of Cervical Total Disc Replacement Devices in a Consecutive Series of 1,626 Patients Beginning with the First Case Experience in 2003.

Retrospective cohort study. The purpose of this study was to investigate the rate of cervical total disc replacement (TDR) device removal or revision. Cervical TDR has gained acceptance as an alternative to anterior cervical discectomy and fusion (ACDF) in appropriately selected patients. There have been concerns over device safety, one measure of which is subsequent surgery related to device problems. A consecutive series of 1,626 cervical TDR patients from 2003 to June 2021 were included, consisting of TDRs up to 3 levels and hybrids (TDR and fusion). TDR removal or revision surgeries and reasons for these surgeries, procedures performed, and duration from index procedure were recorded. Data were analyzed to determine removal/revision rate and factors possibly related to these events. There were 24 removals/revisions (1.48%) in the 1,626 patients. Removal was performed in 23 cases (1.41%) and revision in 1 (0.06%). Among removal cases, ACDF was performed in 18 and TDR was replaced with another TDR in 5. Removals with fusion included 5 cases of osteolysis with/without C. acnes, 4 device displacement/migration, 4 posterior spinal pathology, and one for each of the following: metal allergy, approach-related complications, malpositioning, subsidence, and hypermobility. The revision involved TDR repositioning 3 days after index surgery. There were 66 patients for whom minimum of 10year follow-up was confirmed, and none had removal/revision surgery 10 or more years after index surgery. There was no relationship between occurrence of removal/revision and age, gender, body mass index, or physician experience (learning curve). The removal/revision rate was significantly higher in FDA trials vs. post-approval (4.1% vs. 1.3%, P<0.05). In this large consecutive series of patients, 1.48% of cervical TDRs were removed/revised. The low rate of removals/revisions over a long period of time provides support for the devices' safety.

Pharmaco-virological outcomes and genotypic resistance profiles among children and adolescents receiving a DTG-based regimen in Togo.

Few data are available on the real-world efficacy of receiving tenofovir-lamivudine-dolutegravir (DTG) as HIV treatment, particularly among young people in West Africa. Here, we evaluated pharmaco-virological outcomes and resistance profiles among Togolese children and adolescents. A cross-sectional study was conducted in Lomé, Togo, enrolling antiretroviral-treated people with HIV aged from 18 months to 24 years. Plasma HIV-1 viral load and antiretroviral concentrations were measured. Next-Generation Sequencing (NGS) of protease, Reverse Transcriptase (RT) and integrase was performed on all samples with viral load >200 c/mL. Drug resistance mutations (DRMs) were identified and interpreted using the ANRS-MIE algorithm. 264 participants were enrolled (median age=17 years), 226 received a DTG-based regimen for a median of 20.5 months. Among them, virological suppression at the 200 c/mL threshold in 80.0% of the participants. Plasma DTG concentrations were adequate (i.e., >640 ng/mL), suboptimal and below the limit of quantification in 74.1%, 6.7% and 19.2% of participants receiving DTG, respectively. Overall, viruses resistant to any of Nucleoside RT Inhibitors, Non-NRTIs, and protease inhibitors were found in 52%, 66% and 1.6% of participants, respectively. A major integrase inhibitor DRM was observed in 9.4% (n=3/32, R263K, E138A-G140A-Q148R, and N155H) of participants with a viral load >200 c/mL. These first findings in such a large series of adolescents in a low-income country, showed a good virological response of 80% and the presence of an integrase DRM in 9.4% of the virological failures, supporting the need to monitor DTG drug resistance to reduce the risk of resistance acquisition.

Coronary Embolism Among Patients With ST-Segment-Elevation Myocardial Infarction and Atrial Fibrillation: An Underrecognized But Deadly Association.

The prevalence and impact of coronary emboli (CE) in patients with ST-segment-elevation myocardial infarction (STEMI) and atrial fibrillation (AF) have not been specifically studied. The objective was to describe the clinical characteristics and outcomes of patients with AF and CE in a large series of patients with STEMI. We investigated 2292 consecutive patients with STEMI and among them 225 patients with AF: 46 patients with a STEMI related to CE (group A) and 179 patients with a STEMI related to an atherosclerotic cause (group B). Compared with the 2067 patients without AF and CE (group C), patients with AF and CE were older (73 versus 59 years, P<0.05), more likely to be female (43% versus 22%, P<0.05), and presented more frequently with cardiogenic shock at admission (26% versus 9%, P<0.05). The baseline characteristics of patients with AF (group A versus B) did not differ significantly according to STEMI pathogenesis. In the unadjusted analysis, the 45-day mortality was higher in patients with CE and AF (group A versus group C: 20% versus 4%; P<0.05 and group A versus group B: 20% versus 8%, P=not significant); this trend persisted at 2-year follow-up (group A versus group C: 24% versus 6%; P<0.05 and group A versus group B: 24% versus 17%, P=not significant). After stabilized inverse exposure probability weighting adjustment, a higher 45-day mortality rate was confirmed in patients with CE and AF (group A versus group C: 18% versus 5%, P<0.05). In patients presenting with STEMI and AF, CE was associated with excess early mortality. URL: clinicaltrials.gov. Identifier: NCT05679843.

Assessing the change in the epidemiology of seasonal respiratory viruses with the onset of the COVID-19 pandemic.

Background. Respiratory tract infections are among the most important causes of mortality and morbidity in children worldwide. The COVID-19 pandemic has affected the distribution of seasonal respiratory viruses as in all areas of life. In this study, we have aimed to evaluate the changes in the rates of seasonal respiratory viruses with the onset of the pandemic.Methods. This study included patients who were admitted to the Pediatrics Clinic of Eskisehir Osmangazi University Faculty of Medicine Hospital between December 2018 and February 2022 with respiratory tract infections and in whom pathogens were detected from nasopharyngeal swab samples analysed by multiplex PCR method.Results. A total of 833 respiratory tract pathogens were detected in 684 cases consisting of male (55.3 %), and female (44.7 %), patients with a total mean age of 42 months. Single pathogen was revealed in 550, and multiple pathogens in 134 cases. Intensive care was needed in 14 % of the cases. Most frequently influenza A/B, rhinovirus and respiratory syncytial virus (RSV) were detected during the pre-pandemic period, while rhinovirus, RSV, and adenovirus were observed during the lockdown period. In the post-lockdown period, the incidence rates of rhinovirus, RSV, human bocavirus (HboV) (12 %), influenza virus infections increased, and patients with RSV and bocavirus infections required intensive care hospitalization.Conclusion. It is thought that the COVID-9 pandemic lockdown measures may have an impact on the distribution of seasonal respiratory viruses, especially RSV and influenza. Current, prospective and large case series regarding the mechanism of action and dynamics are needed.

Magnetic resonance imaging of intracranial anomalies in pregnancies complicated by twin anemia-polycythemia sequence.

To describe fetal brain Magnetic Resonance Imaging (MRI) findings in a large series of monochorionic (MC) pregnancies complicated by Twin Anemia-Polycythemia Sequence (TAPS)prenatally diagnosed, so to characterize the potential intracranial complications associated with this condition, their frequency and potential treatment options. This is a retrospective study of MC twin pregnancies complicated by TAPS and undergone fetal MRI in a single institution from 2006 to 2023. MRI control was performed and post-natal ultrasound (US) or MRI were available. 1250 MCpregnancies were evaluated in our institution. 50 pregnancies (4%) were diagnosed with TAPS, 29 underwent a fetal brain MRI. 13/29 pregnancies (44.8%) demonstratedbrain findings at MRI in at least a twin. Neuroradiological findings were detected in 14/57 twins (24.6%). We detected four main categories of findings: hemorrhagic lesions, T2-weighted white-matter hyperintensities (WMH), brain edema-swelling and venous congestion. Nineteen findings were present in the anemic and three in the polycythemic twins, with a statistically significant ratio between the two groups (p-value = 0.01). Intrauterine MRI follow-up demonstrated the sequalae of hemorrhagic lesions. A complete regression of brain swelling, veins prominence and T2-WMHs was demonstrated after treatment. Postnatal imaging confirmedprenatal features. Our work demonstrates that TAPS-related MRI anomalies consisted in edematous/hemorrhagic lesions that occur mostly in anemic rather than in polycythemic twins. Fetoscopic laser surgery could have a potential decongestant role. Therefore, prenatal MRI may help in counselling and management in TAPS pregnancies, especially for the planning of therapy and the monitoring of its efficacy.

Revision Total Ankle Arthroplasty Using a Novel Modular Fixed-Bearing Revision Ankle System.

Large bone defects such as those encountered after failed total ankle replacement have previously been a relative contraindication to revision ankle replacement due to inadequate bone stock. We describe our experience and patient reported outcomes with a modular ankle replacement system with tibial and talar augments. This is a retrospective case series analysis of patients who underwent a total ankle replacement using the INVISION system across 2 centers between 2016 and 2022. Patients completed the Manchester-Oxford Foot Questionnaire (MOXFQ), Ankle Osteoarthritis Scale (AOS), and EQ-5D pre-operatively and then post-operatively at 6 months, 1 year, 2 years, 3 years, and 5 years. Medical records were reviewed for complications and re-operations. X-rays were reviewed for lucencies and alignment. A total of 17 patients were included in the study; 14 men and 3 women with an average age at the time of surgery of 67.9 years (range 56-80 years). The average follow-up post-operatively was 40.5 months (range 7-78) at the time of this study. The indication for surgery was revision of failed total ankle replacement (TAR) in 16 and revision of failed ankle fusion in 1. An augmented tibia was used in 13, an augmented talus in 13, and both augmented tibia and talus in 9 cases. There were no early surgical complications. One patient required debridement and implant retention for late deep infection. No implants have been revised. The average MOXFQ score improved by 19.3 points at most recent follow-up. The average AOS score improved by 25.2 points. The early results of a modular augmented ankle arthroplasty system have shown satisfactory patient outcomes with a low complication and re-operation rate and present another option for patients with larger bone defects. This is a small series, and a larger series with long-term follow-up would be beneficial. Level IV: Case series.

Proximal Medial Gastrocnemius Recession for Recalcitrant Plantar Fasciitis.

Recalcitrant plantar fasciitis (RPF) is characterized by its unresponsiveness to conservative treatments, and its surgical management remains controversial. Although there is some evidence to suggest that gastrocnemius recession can be an effective treatment for RPF, no large series of patients with mid- to long-term follow-up has been published. The objective of this study was to compare physical performance, as measured by the Foot and Ankle Ability Measure activities of daily living score (FAAM-ADL), and pain levels before and 1 year after undergoing proximal medial gastrocnemius recession (PMGR) as a treatment for RPF. Additionally, we aimed to assess this cohort of patients in the mid- to long-term follow-up. This retrospective cohort study included 167 patients who underwent PMGR to address RPF between 2009 and 2021. Patients were examined with the FAAM ADL, visual analog scale (VAS) and satisfaction scores at baseline, 1 year, and at the end of follow-up. Other variables recorded were weight, duration of symptoms until surgery, time between surgery to substantial clinical improvement, calf power and Silfverskiold test, and postoperative complications. We observed that before surgery patients had an FAAM-ADL score of 22.5 (SD 11.1) and a VAS score of 8.6 (SD 9.3). One year after surgery, patients had an FAAM-ADL score of 89 (SD 17) and VAS of 1.33 (SD 2) (P < .01). We also observed that the FAAM-ADL score in the long-term follow-up (>12.5 years) group had a median of 86.4 (SD 22.6), the VAS score was 1.90 (SD 2.84), and the patient satisfaction score had a median of 1 (interquartile range 0-1). Regarding complications, we observed 1 lateral gastrocnemius recession and 1 sural nerve neuritis. Our study provides substantial evidence supporting the use of PMGR as an effective treatment for RPF. The long-term follow-up and large sample size of our series contribute to the existing literature on this topic. Level IV, case series.

Developmental uterovaginal anomalies and histologic findings in transgender patients receiving gender-affirming hysterectomies: A large case series.

To describe the incidence of uterovaginal anomalies and histologic findings in transgender and nonbinary (TGNB) patients seeking hysterectomies. All patients receiving gender-affirming hysterectomies between 2013 and 2023 were retrospectively reviewed. Primary outcomes included uterovaginal anomalies and histological findings. Multivariable logistic regressions were performed to evaluate relationships between variables of interest and whether they predict findings of uterovaginal anomalies, inactive endometrium, adenomyosis, leiomyoma, endometriosis, and cervical atrophy. 278 patients received hysterectomies at an average age of 29.2 ± 8.3 years. Seven patients (2.5%) were found to have a developmental anomaly, including two bicornuate uterus (0.7%), two unicornuate uterus (0.7%), one septate uterus (0.4%), and two vaginal septum (0.7%). 60 patients (21.6%) were found to have inactive endometrium and 26 patients (9.4%) had cervical atrophy. Although 262 patients (94.2%) were on testosterone therapy, hormone duration was not a significant predictor of any uterine findings. This study describes uterovaginal anomalies in a large cohort of patients receiving gender-affirming hysterectomies. Although long-term testosterone use is commonly believed to be associated with endometrial and cervical atrophy, this study shows no such association.

Results of systematic KDM1A genotyping in a large series of Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH) patients and analysis of the genotype/phenotype correlation

Results of systematic KDM1A genotyping in a large series of Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH) patients and analysis of the genotype/phenotype correlation

Abstract PO3-04-06: A comparison of the efficacy of trastuzumab deruxtecan in advanced HER2-positive breast cancer: active brain metastasis versus progressive extracranial disease alone

Abstract Background Trastuzumab deruxtecan (T-DXd) has demonstrated efficacy in patients with brain metastasis (BM), a group historically with poor outcomes. The prevalence of BMs in patients commencing T-DXd is currently unknown. To date, no direct comparisons have been made of the activity of T-DXd in patients with active BM versus those with extracranial progression alone. This real-world study explored the prevalence of BMs at commencement of T-DXd, the efficacy of T-DXd in active BM versus extracranial progression alone and the safety of T-DXd. Methods Patients with HER2-positive advanced breast cancer treated with T-DXd between June 2021 and February 2023 at our specialist cancer hospital were identified and notes reviewed. Clinico-pathological information, prior treatment, the presence or absence of CNS disease, outcomes and treatment-emergent adverse events (TEAE) were recorded. Data cut-off was 28th February 2023. Results 29 female patients: 16 extracranial disease alone, 12 BM and 1 LMD were identified. Prevalence of BM at commencement of T-DXd was 41% (12 of 29). Median age was 52 (IQR 44-62), with a median 2 (range 2-6) prior lines of HER2 directed and chemotherapy:86% (25 of 29) had received prior trastuzumab and pertuzumab, 100% (29 of 29) T-DM1 and 3% (1 of 29) patient trastuzumab duocarmazine. At a median follow-up of 13.8 months, median progression free survival (PFS) for overall population was 13.9 months (95% CI: 12.4-NE), 16.1 months (95% CI: 15.1-NE) for active BMs, and 12.4 months (95% CI: 8.3-NE) for progressive extracranial disease alone (P=0.106). 12-month OS rate was 74% (95% CI: 59-95) in the overall population, 83% (95% CI: 58-100) and 66% (95% CI: 45-96) for active BMs, and extracranial only disease respectively (P=0.678). Objective response rates: overall population was 69% (95% CI: 52-86), active BMs was 60% (95% CI: 30-90), and progressive extracranial disease alone was 69% (95% CI: 46-91). 6% (1 of 16) with extracranial disease alone developed BM during treatment with T-DXd. Reasons for treatment discontinuation: 67% (10 of 15) disease progression or death; 33% (5 of 15) toxicity. 48% (14 of 29) remain on treatment. Most common TEAEs were fatigue (97%; 28 of 29), alopecia (76%; 22 of 29), and constipation (72%; 21 of 29). Pneumonitis occurred in 9 patients (31%, included 2 deaths). 1 pathologically confirmed case of radionecrosis was documented. An updated analysis with an additional 9 patients who commenced T-DXd since February 2023 will be presented. Conclusion In this real-world study a significant number of patients had BM at the commencement of T-DXd. We demonstrate that in advanced HER2 positive breast cancer that T-DXd is as effective, in terms of PFS and OS, in active BMs as it is in progressive extracranial disease alone. These data provide the first evidence that in contrast to the historical data that active BM may no longer be a detriment to survival as compared to progressive extracranial disease alone when treated with T-Dxd. These observations warrant further investigations in larger series. The high rate of pneumonitis warrants further consideration. Citation Format: James Pearson, Adeel Khan, Talvinder Bhogal, Helen Wong, Andrea Law, Samantha Mills, Nuria Santamaria, Joanne Cliff, Douglas Errington, Allison Hall, Clare Hart, Zafar Malik, Raj Sripadam, Helen Innes, Helen Flint, Gabriella Langton, Eliyaz Ahmed, Jill Bishop, Richard Jackson, Carlo Palmieri. A comparison of the efficacy of trastuzumab deruxtecan in advanced HER2-positive breast cancer: active brain metastasis versus progressive extracranial disease alone [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 PO3-04-06.

Abstract PO2-13-03: Spatial HER2 heterogeneity on HER2-PET in HER2-low and negative disease: potential biomarker for antibody-drug conjugate effect

Abstract Background: Anti-HER2 antibody drug conjugates (ADCs) can assert an effect in part of patients with HER2-low breast cancer. In light of patient burden and financial sustainability, biomarkers to select responding patients are urgently needed, but so far, none have been identified. In the IMPACT trial (NCT01957332), patients with newly diagnosed and non-rapidly progressive metastatic breast cancer (MBC) of all subtypes (including HER2-negative, -low, and –positive disease) were included. We assessed the performance of Zirconium-89 (89Zr)-trastuzumab positron emission tomography (HER2-PET) in HER2-low and negative MBC. Methods: All patients received extensive workup, including a metastasis biopsy and HER2-PET at baseline. HER2 status was determined by immunohistochemistry (IHC) and in situ hybridization. ⁸⁹Zr-trastuzumab uptake was quantified as maximum and mean standardized uptake values (SUVmax, SUVmean) in metastases and healthy background tissue. Quantitative ⁸⁹Zr-trastuzumab uptake of all metastases and corresponding biopsied metastasis, was related to HER2 IHC status. Results: In 200 patients, ⁸⁹Zr-trastuzumab uptake was quantified in 5,163 metastases. With increasing HER2 IHC status, uptake was higher (geometric mean SUVmax 7.0, 7.6, 7.3, and 17.4 with HER2 IHC 0, 1, 2, or 3+, in respectively 71, 71, 20, and 24 biopsied metastases (P  0.001 between IHC 0 and 3+). SUVmax in lesions was heterogeneous within and between patients for all HER2 IHC groups. All HER2 IHC groups, also HER2-negative and -low, had uptake exceeding that of the healthy background (geometric mean tumor-to-background ratio SUVmax &amp;gt;1 in all groups, increasing with higher HER2 IHC). Of patients with a HER2 IHC 0 biopsy, 27.8% had at least one metastasis elsewhere in the body, with uptake exceeding the overall 90th SUVmax percentile of 14.6; in HER2 low IHC1+ and 2+, this was 31.9% and 30%. Conclusions: In this largest series with HER2-PET in patients with MBC, we show that ±30% of patients with HER2-low or -negative IHC in the biopsy, in fact, have metastases with high HER2 uptake elsewhere in the body. This spatial heterogeneity provides novel insights into HER2-negative and -low disease compared to standard HER2 IHC of a single biopsy. As HER2-PET uptake is related to ADC response in HER2 positive MBC1, HER2-PET is a potential biomarker for anti-HER2 ADC effect in HER2-low and -negative MBC as well. Reference: 1. Gebhart G, et al. Ann Oncol 2016;27(4): 619-624. Supported by the Dutch Cancer Society grant 2012-5565 Citation Format: Carolien Schroder, Jasper van Geel, Bertha Eisses, Adrienne Brouwers, Sjoerd Elias, Frederike Bensch, Evelien Kuip, Agnes Jager, Andor Glaudemans, Bert van der Vegt, Willemien Menke-van der Houven van Oordt, Elisabeth de Vries. Spatial HER2 heterogeneity on HER2-PET in HER2-low and negative disease: potential biomarker for antibody-drug conjugate effect [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 PO2-13-03.

Abstract PO5-13-04: Breast Cancer Index (BCI) results from a HER2 low breast cancer community cohort of operable stage I-II hormone receptor positive (HR+) breast cancer

Abstract Background Hormone receptor positive (HR+) breast cancer (BC) traditionally included HER2-negative or HER2-positive classifications. The BCI test is a quantitative RNA profile assay applied to HR+ early-stage breast cancers from archival pretreatment surgical specimens. The BCI assay estimates the likelihood of distant recurrence (DR) during years 5-10 (prognostic result) and predicts extended endocrine therapy benefit (ETT)(i.e., BCI (H/I)-High, yes benefit) or no benefit (i.e., BCI (H/I)- Low) for patients who have completed 5 years of adjuvant endocrine therapy (AET). Based on the Destiny Breast 04 trial, an antibody drug conjugate (ADC) anti-HER2 therapy was recently approved for treating metastatic HR+HER2 low BCs, which are currently defined as tumors with either HER2 immunohistochemical (IHC) staining of 1+ or IHC 2+ without HER2 gene amplification. Primary archival specimens were eligible for enrollment on the Destiny Breast 04 trial (35%). Quality control of IHC result categories is needed due to new clinical implications in the metastatic setting. To date, BCI results for tumors classified as HER2 low has not been reported. Objectives Determine the average BCI distant DR risk (prognostic result) and the proportion of tumors with BCI (H/I)-High, yes benefit versus BCI (H/I)-Low, no benefit (predictive result) from a small community-based retrospective study of pretreatment samples from a cohort of HER2 low, HR+ breast tumors. Methods Around completion of 5 years of AET, BCI testing was applied to 110 surgically excised archived stage I and 2 HR+ untreated tumors that were collected between 2017 and 2022. Specimens had paired HER2 local pathology IHC and in-situ hybridization (ISH) results. Results 32 tumors were identified as HER2-low including 26 specimens with HER2 IHC 1+ results and six HER2 IHC 2+ tumors with non-amplified HER2 ISH results. Given this was a small exploratory analysis, statistical significance was deliberately not evaluated. Prognostic Results: The average estimated DR risk during years 5-10 was 8% for tumors classified as HER2-low (Range 1.3-17.5%). For 26/32 patients with HER2 IHC1+, the average DR risk was 7.4% (Range 1.3-17.5%). For 6/32 patients with HER2 IHC 2+ and non-amplified HER2 ISH results, the average DR risk was 4.6% (Range 1.6-8.6%). Predictive Results: Of the 32 HER2-low tumors, 15/32 (47%) were BCI (H/I)-High (yes benefit) compared to 17/32 (53%) which were BCI (H/I)-Low (no benefit). Conclusions The prevalence of HER2 low tumors appears to be as high as 67% in reports to date. In this small series, the prevalence of HR+ HER2 low tumors was 29% (32/110). The average DR risk in these HR+ HER2 low cases was roughly 8% which represents a DR risk that is very similar to the average DR risk of 7.4% for HR+ HER2 negative tumors reported from one of the large BCI validation studies (TransATAC). In this series of HER2 low BCs, the proportions of BCI (H/I)-High (yes benefit) and BCI (H/I)-Low (no benefit) tumors were 47% and 53%, compared with 46% and 54%, respectively, in three large BCI validation studies (Trans-aTTom, B42, IDEAL) for HER2 negative tumors. Although this is a small retrospective series, these results suggest that HER2 low tumor are, by BCI testing, very similar to HER2 negative tumors in DR risk (prognostic results). Also, it appears that BCI (H/I)-High (yes benefit) and BCI (H/I)-Low (no benefit) proportions (predictive results) for HER2 low tumors appear similar to reported results for HER2 negative tumors. Follow-up data from larger series are needed to determine if BCI testing is prognostic and predictive for HER-2 low BCs. Citation Format: Milana Dolezal, Mark Pegram. Breast Cancer Index (BCI) results from a HER2 low breast cancer community cohort of operable stage I-II hormone receptor positive (HR+) breast cancer [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 PO5-13-04.

Abstract PO3-25-07: Characterization of tertiary lymphoid structures and its association with response to immune checkpoint inhibitors in triple negative breast cancer using spatial transcriptomics

Abstract Background Tertiary lymphoid structures (TLS) are ectopic lymphoid organs playing a role in adaptive antitumor immune response. They were shown to be associated with favorable outcome and appears to be a promising biomarker for response to immune checkpoint inhibitors (ICI). Yet, there is no consensus for their detection and quantification. Here we aimed to derive a specific TLS signature using high resolution spatial transcriptomics data from a large series of triple negative breast cancer (TNBC) samples and to assess its clinical relevance including response to ICI. Methods Spatial transcriptomics (ST) was performed on a series of 94 early-stage TNBC surgical samples with detailed clinicopathological and outcome data. TLS and tumor infiltrating lymphocytes (TILs) were scored using hematoxylin and eosin and double immunohistochemistry (CD3/CD20) stained slides by a dedicated breast pathologist. Regression based on morphological annotations and deconvolution methods estimated the fraction of gene expression related to TLS in each ST spot allowing to derive specific TLS signature. Its prognostic and predictive value of response to ICI was assessed using publicly available breast cancer (METABRIC, SCAN-B, and I-SPY2) and other tumor type datasets treated with ICI (Bareche et al. Ann Oncol, 2022) from bulk gene expression data. Results Deconvolution of the TLS compartments using the ST gene expression data showed that TLS are enriched in all B cell subsets, CD4+ (central) memory and naïve T cells, as well as mast cells. A functional analysis showed an enrichment of ‘vascular endothelial cell proliferation’, ‘mitotic G2/M transition checkpoint’, ‘V/D/J recombination’ and ‘regulation of cell chemotaxis to fibroblast growth factor’ suggesting that TLS aggregates are associated with angiogenesis, immune cell proliferation, adaptative humoral response and tissue remodeling. A comparison of gene expression data between TLS and non-aggregated TILs led to the development of a specific TLS gene signature comprising B and T cell-specific genes, immunoglobulin genes as well as genes associated with TLS initiation. Its projection on tumor slides overlapped with the regions annotated as TLS by the pathologist, demonstrating its specificity for TLS detection. As expected, the highest levels of the TLS signature were observed in the immunomodulatory TNBC molecular subtype and fully inflamed tumors, whereas the lowest levels were observed in the mesenchymal molecular subtype and immune desert tumors (p&amp;lt; 0.05). Of note, high levels of the TLS signature were associated with better prognosis in TNBC patients from METABRIC (p=6.5 10−5) and SCAN-B datasets (p=1.6 10−3) as well as with higher pathological complete response rates in all breast cancer patients treated with neoadjuvant pembrolizumab in the I-SPY2 study (p=0.026). Similar results were found in other tumor types treated with immunotherapy in the metastatic setting including metastatic melanoma, pancreatic and bladder cancers (PFS, p=6 10−6). Of interest, the TLS signature outperformed the predictive value of other immune-related signatures including TILs suggesting a key role of TLS in obtaining a sustainable, adaptive antitumor immune response in the vicinity of the tumor area. Conclusion By leveraging the potential of spatial transcriptomics, we have successfully developed a unique TLS gene signature that demonstrates a strong correlation with the response to ICI in breast cancer and various other tumor types. This TLS gene signature outperforms other immune biomarkers, underscoring the pivotal role of TLS in eliciting a robust antitumor immune response. The universality of this TLS signature makes it a potent biomarker capable of identifying patients who would benefit from immunotherapy, pending further validation. Citation Format: Xiaoxiao Wang, David Venet, Frédéric Lifrange, Denis Larsimont, Mattia Rediti, Linnea Stenbeck, Floriane Dupont, Ghizlane Rouas, Andrea Joaquin Garcia, David Gacquer, Ligia Craciun, Laurence Buisseret, Nayanika Bhalla, Yuvarani Masarapu, Kim Thrane, Eva Gracia Villacampa, Lovisa Franzén, Sami Saarenpää, Linda Kvastad, Joakim Lundeberg, Françoise Rothé, Christos Sotiriou. Characterization of tertiary lymphoid structures and its association with response to immune checkpoint inhibitors in triple negative breast cancer using spatial transcriptomics [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 PO3-25-07.

Abstract PS01-08: Management of ipsilateral breast tumor recurrence following breast conservation surgery for ductal carcinoma in situ – a data-free zone

Abstract Background: Breast-conserving surgery (BCS) is well established for the management of ductal carcinoma in situ (DCIS). Although a growing body of data support re-conservation therapy (RBCS) for ipsilateral breast tumor recurrence (IBTR) following BCS in invasive cancer, neither randomized trials nor guidelines address management of IBTR following BCS for DCIS. Here we aim to compare the outcomes of mastectomy vs RBCS for a large series of DCIS patients with IBTR. Methods: We identified women treated with BCS for DCIS at MSKCC who developed IBTR as a first event. Between those treated with mastectomy vs RBCS, we compared the clinicopathologic characteristics for the initial and recurrent tumors, the use of adjuvant RT (both upfront (“primary RT”) and post IBTR (“secondary RT”)) and/or tamoxifen, the rate of third events (local, regional, distant), breast cancer specific (BCSS) and overall survival (OS). Results: From our service databases among 3001 women treated with BCS for DCIS (1978-2010), we found 383 who developed an IBTR as a first event and were treated at our institution between 1983-2023, 186 (49%) with RBCS and 197 (51%) with mastectomy. RBCS was more frequent over time and comprised 56% of patients treated between 2014 and 2023. Among those treated with mastectomy, the initial tumors were significantly more likely to have necrosis (74% vs 59%), high grade (47% vs 28%), comedo histology (38% vs 20%), and to have received primary RT at the time of BCS (61% vs 21%). Between those who underwent mastectomy vs RBCS, there were no significant differences in disease-free interval, in the pathologic characteristics of their IBTR, or in the proportion of invasive vs in situ disease. For patients treated with RBCS, 11 (5.9%) received both primary and secondary RT and 77 (41.3%) received neither (Table 1a). For patients treated with a mastectomy only 8.5% had secondary RT (Table 1b). At a median follow-up of 5.1 years post-IBTR, third local events in total were more frequent for RBCS vs mastectomy (16.1% vs 3.0%, 0.001), but there were no differences in BCSS or OS. Among RBCS patients, third local events (breast re-recurrence) were least frequent among those who received primary and secondary RT, and comparable between with who did vs did not receive secondary RT (16% (13/82) vs 16% (117/104), Table 2). Conclusions: Our data show that for women with isolated IBTR following BCS for DCIS and treated by mastectomy vs RBCS, 1) treatment with mastectomy was associated with less favorable initial pathology and more frequent use of primary RT, 2) re-recurrence was more frequent with RBCS, and 3) BCSS and OS were comparable. In an era of increasing surgical de-escalation, our data suggest a wider role for RBCS and – as for patients having RBCS for IBTR following invasive cancer – further study of the relationship between secondary RT and the rate of third breast events. Citation Format: Brian Diskin, Varadan Sevilimedu, Kimberly Van Zee, Monica Morrow, Hiram Cody. Management of ipsilateral breast tumor recurrence following breast conservation surgery for ductal carcinoma in situ – a data-free zone [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 PS01-08.

Valvulitis: un nuevo criterio ecocardiográfico para el diagnóstico de endocarditis infecciosa de bioprótesis de válvula aórtica

Introduction and objectivesDiffuse homogeneous hypoechoic leaflet thickening, with a wavy leaflet motion documented by transesophageal echocardiography (TEE), has been described in some cases of prosthetic valve endocarditis (PVE) involving aortic bioprosthesis (AoBio-PVE). This echocardiographic finding has been termed valvulitis. We aimed to estimate the prevalence of valvulitis, precisely describe its echocardiographic characteristics, and determine their clinical significance in patients with AoBio-PVE. MethodsFrom 2011 to 2022, 388 consecutive patients with infective endocarditis (IE) admitted to a tertiary care hospital were prospectively included in a multipurpose database. For this study, all patients with AoBio-PVE (n=86) were selected, and their TEE images were thoroughly evaluated by 3 independent cardiologists to identify all cases of valvulitis. ResultsThe prevalence of isolated valvulitis was 12.8%, and 20.9% of patients had valvulitis accompanied by other classic echocardiographic findings of IE. A total of 9 out of 11 patients with isolated valvulitis had significant valve stenosis, whereas significant aortic valve regurgitation was documented in only 1 patient. Compared with the other patients with AoBio-PVE, cardiac surgery was less frequently performed in patients with isolated valvulitis (27.3% vs 62.7%, P=.017). In 4 out of 5 patients with valve stenosis who did not undergo surgery but underwent follow-up TEE, valve gradients significantly improved with appropriate antibiotic therapy. ConclusionsValvulitis can be the only echocardiographic finding in infected AoBio and needs to be identified by imaging specialists for early diagnosis. However, this entity is a diagnostic challenge and additional imaging techniques might be required to confirm the diagnosis. Larger series are needed.