Late Recurrence Research Articles

Recurrence of Glomerulonephritis After Kidney Transplantation - Experience of One Center from 2020 to 2023

Glomerulonephritis (GN) after kidney transplantation is a common problem. Many of them are recurrences of the primary disease in the transplanted kidney. The course and prognosis of individual types of glomerulonephritis (GN) are very different and their appearance may worsen the graft survival. World statistics show significant discrepancies regarding the incidence of GN recurrence depending on the adopted protocol (protocolar biopsy or due to symptoms). We analyzed the transplanted kidney biopsy results that are performed only in symptomatic patients. A group of 125 patients transplanted and treated in one medical center were observed. In this group, in 32 patients, the primary kidney disease was GN, confirmed by kidney biopsy before transplantation. Twenty three kidney biopsies were performed; in 8, cases the primary disease was GN. The indication for biopsy were hematuria and/or proteinuria and/or graft failure. We diagnosed 5 cases of GN, including 4 cases of GN recurrence (12.5% in whole GN group, 50% in symptomatic GN group). In the relapse group, there was 1 case of IgA nephropathy (the earliest recurrence 1 month after transplantation), 1 case of focal segmental glomerulosclerosis, 1 case of membranous nephropathy, and 1 case of lupus nephritis (the latest recurrence 1 year and 4 months after transplantation). Our observation showed a high percentage of GN recurrences in symptomatic patients. This indicates the need to specify data regarding the diagnosis of recurrence depending on the adopted research method (protocolar or due to symptoms biopsy) to know which patients should be treated.

Duodenal Adenocarcinoma: The Relationship between Type of Surgery and Site of Recurrence in a Spanish Cohort

We present a multicenter retrospective study of patients undergoing surgery for duodenal adenocarcinoma, from January 2010 to August 2020, in order to determine the epidemiological characteristics and the oncological results after surgical resection obtained in this rare tumor. Variables: demographics; tumor location; surgical intervention and immediate postoperative period; and post-surgical follow-up information, such as recurrence, overall survival (OS), and disease-free survival (DFS). A total of 32 patients underwent surgery. The median age was 69.74 years (IQR 60.47–79.09) and the male/female distribution was 3:1. The surgeries performed were: pancreaticoduodenectomy (PD) in 16 (50%) patients, segmental resection in 13 (40.6%), and the local excision of the lesion in three (9.4%). The R0 rate was higher in PD (86.7% vs. 42.9%; p = 0.013). The OS and DFS rate at one, three and five years was 95%, 70%, and 60% and 86%, 55%, and 48%, respectively. There was a greater trend towards recurrence in patients who did not undergo PD (53.8% vs. 25%; p = 0.14) and conservative surgery seemed to be associated with more local recurrence than PD (57.1% vs. 33.3%; p = 0.49). PD and limited resection are both valid options in the cases of non-ampullary duodenal adenocarcinoma, although PD presented lower rates of loco-regional recurrence.

A Late Testicular Relapse in an Adult with Acute Lymphoblastic Leukemia, 5 Years after the Diagnosis and 4 Years after Allotransplant-A Rare Case.

Acute lymphoblastic leukemia (ALL) is a malignant disorder of lymphoid progenitor cells that affects both pediatric and adult populations. Although isolated testicular or any other organ recurrence can occur in the pediatric population, it is rare in adults. We present images for an atypical case of the late testicular recurrence of acute lymphoblastic leukemia in a 56-year-old man previously diagnosed with ALL pro-T who was in remission following polychemotherapy (GMALL 2013 protocol) and the allotransplantation of peripheral blood stem cells from a related donor. Five years later (2022), the unilateral testicular relapse of ALL was suspected by imaging and diagnosed by immunophenotyping from sperm fluid infiltrated with atypical cells with an immunophenotype concordant with that of the underlying disease (ALL T). Bone marrow aspiration and biopsy showed no evidence of systemic leukemia relapse. Testicular ablation or chemotherapy and irradiation were considered. Given the strictly testicular relapse, orchiectomy would have been useful, but given the abdominal adenopathy, a chemotherapy course with HyperCVAD Block A was first required. Testicular relapse can occur at any age, and the recognition of this is important as it may be the first manifestation of systemic relapse.

Pathological Pleural Invasion is a Risk Factor for Late Recurrence in Long-Term Survivors of Non-small Cell Lung Cancer after Complete Resection.

Information regarding late recurrence after pulmonary resection for non-small cell lung cancer (NSCLC) is limited. This study aimed to analyze the risk factors for late recurrence after surgery for NSCLC in the current era. We conducted a retrospective study of patients who underwent complete resection for pathological I-III NSCLC between 2006 and 2015. Late recurrence was defined as a recurrence that met the following conditions: (1) the patient underwent chest computed tomography (CT) at or after 54 months after surgery and recurrence was not detected at that time, and (2) recurrence that occurred more than 5 years after surgery. The factors influencing late recurrence, relapse-free survival (RFS), and overall survival (OS) after surgery were analyzed. A total of 1275 with 5-year relapse-free survival after surgery were enrolled in this study. The mean age of the patients was 66.4 years and 54% of the patients were men. The median interval between surgery and the latest follow-up examination was 98 months. In total, 35 patients (2.7%) experienced late recurrence and 138 patients have died thus far. The cumulative recurrence, RFS, and OS rates at 10 years were 3.9%, 84.9%, and 86.3%, respectively. A multivariate analysis revealed that pleural invasion was an independent risk factor for late recurrence. Pleural invasion was a poor prognostic factor for both RFS and OS. Pleural invasion was a predictor of late recurrence. Age>67 years, preoperative serum carcinoembryonic antigen (CEA)>5 ng/ml, non-adenocarcinoma, and pleural invasion were poor prognostic factors for RFS.

Analyses of lncRNA and mRNA profiles in recurrent atrial fibrillation after catheter ablation

BackgroundAtrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. Catheter ablation has become a crucial treatment for AF. However, there is a possibility of atrial fibrillation recurrence after catheter ablation. Our study sought to elucidate the role of lncRNA‒mRNA regulatory networks in late AF recurrence after catheter ablation.MethodsWe conducted RNA sequencing to profile the transcriptomes of 5 samples from the presence of recurrence after AF ablation (P-RAF) and 5 samples from the absence of recurrence after AF ablation (A-RAF). Differentially expressed genes (DEGs) and long noncoding RNAs (DE-lncRNAs) were analyzed using the DESeq2 R package. The functional correlations of the DEGs were assessed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein‒protein interaction (PPI) network was constructed using STRING and Cytoscape. We also established a lncRNA‒mRNA regulatory network between DE-lncRNAs and DEGs using BEDTools v2.1.2 software and the Pearson correlation coefficient method. To validate the high-throughput sequencing results of the hub genes, we conducted quantitative real-time polymerase chain reaction (qRT‒PCR) experiments.ResultsA total of 28,528 mRNAs and 42,333 lncRNAs were detected. A total of 96 DEGs and 203 DE-lncRNAs were identified between the two groups. GO analysis revealed that the DEGs were enriched in the biological processes (BPs) of “regulation of immune response” and “regulation of immune system process”, the cellular components (CCs) of “extracellular matrix” and “cell‒cell junction”, and the molecular functions (MFs) of “signaling adaptor activity” and “protein–macromolecule adaptor activity”. According to the KEGG analysis, the DEGs were associated with the “PI3K–Akt signaling pathway” and “MAPK signaling pathway.” Nine hub genes (MMP9, IGF2, FGFR1, HSPG2, GZMB, PEG10, GNLY, COL6A1, and KCNE3) were identified through the PPI network. lncRNA-TMEM51-AS1-201 was identified as a core regulator in the lncRNA‒mRNA regulatory network, suggesting its potential impact on the recurrence of AF after catheter ablation through the regulation of COL6A1, FGFR1, HSPG2, and IGF2.ConclusionsThe recurrence of atrial fibrillation after catheter ablation may be associated with immune responses and fibrosis, with the extracellular matrix playing a crucial role. TMEM51-AS1-201 has been identified as a potential key target for AF recurrence after catheter ablation.

Three-Year Outcomes of Oral Antibiotics vs Intravenous and Oral Antibiotics for Uncomplicated Acute Appendicitis

Current short-term evidence has shown that uncomplicated acute appendicitis can be treated successfully with oral antibiotics alone, but longer-term results are lacking. To assess the treatment effectiveness of oral antibiotic monotherapy compared with combined intravenous (IV) and oral antibiotics in computed tomography-confirmed uncomplicated acute appendicitis at a longer-term follow-up. This secondary analysis of a predefined year 3 follow-up of the Appendicitis Acuta II (APPAC II) noninferiority, multicenter randomized clinical trial compared oral moxifloxacin with combined IV ertapenem plus oral levofloxacin and metronidazole for the treatment of uncomplicated acute appendicitis. The trial was conducted at 9 university and central hospitals in Finland from April 2017 to November 2018, with the last follow-up in November 2022. Participants included patients aged 18 to 60 years, who were randomized to receive either oral antibiotics monotherapy (n = 301) or combined IV and oral antibiotics (n = 298). Antibiotics monotherapy consisted of oral moxifloxacin, 400 mg/d, for 7 days. Combined IV and oral antibiotics consisted of IV ertapenem sodium, 1 g/d, for 2 days plus oral levofloxacin, 500 mg/d, and metronidazole, 500 mg 3 times/d, for 5 days. The primary end point was treatment success, defined as the resolution of acute appendicitis and discharge from hospital without the need for surgical intervention and no appendicitis recurrence at the year 3 follow-up evaluated using a noninferiority design. The secondary end points included late (after 1 year) appendicitis recurrence as well as treatment-related adverse events, quality of life, length of hospital stay, and length of sick leave, which were evaluated using a superiority design. After exclusions, 599 patients (mean [SD] age, 36 [12] years; 336 males [56.1%]) were randomized; after withdrawal and loss to follow-up, 582 patients (99.8%) were available for the year 3 follow-up. The treatment success at year 3 was 63.4% (1-sided 95% CI, 58.8% to ∞) in the oral antibiotic monotherapy group and 65.2% (1-sided 95% CI, 60.5% to ∞) in the combined IV and oral antibiotics group. The difference in treatment success rate between the groups at year 3 was -1.8 percentage points (1-sided 95% CI, -8.3 percentage points to ∞; P = .14 for noninferiority), with the CI limit exceeding the noninferiority margin. There were no significant differences between groups in treatment-related adverse events, quality of life, length of hospital stay, or length of sick leave. This secondary analysis of the APPAC II trial found a slightly higher appendectomy rate in patients who received oral antibiotic monotherapy; however, noninferiority of oral antibiotic monotherapy compared with combined IV and oral antibiotics could not be demonstrated. The results encourage future studies to assess oral antibiotic monotherapy as a viable treatment alternative for uncomplicated acute appendicitis. ClinicalTrials.gov Identifier: NCT03236961.

Repeat catheter ablation after very late recurrence of atrial fibrillation after pulmonary vein isolation.

Atrial fibrillation (AF) recurs in about one-third of patients after catheter ablation (CA), mostly in the first year. Little is known about the electrophysiological findings and the effect of re-ablation in very late AF recurrences (VLR) after more than 1 year. The aim of this study was to determine the characteristics and outcomes of the first repeat CA after VLR of AF after index CA. We analysed patients from a prospective Swiss registry that underwent a first repeat ablation procedure. Patients were stratified depending on the time to recurrence after index procedure: early recurrence (ER) for recurrences within the first year and late recurrence (LR) if the recurrence was later. The primary endpoint was freedom from AF in the first year after repeat ablation. Out of 1864 patients included in the registry, 426 patients undergoing a repeat ablation were included in the analysis (28% female, age 63 ± 9.8 years, 46% persistent AF). Two hundred and ninety-one patients (68%) were stratified in the ER group and 135 patients (32%) in the LR group. Pulmonary vein reconnections were a common finding in both groups, with 93% in the ER group compared to 86% in the LR group (P = 0.052). In the LR group, 40 of 135 patients (30%) had a recurrence of AF compared to 90 of 291 patients (31%) in the ER group (log-rank P = 0.72). There was no association between the time to recurrence of AF after initial CA and the characteristics and outcomes of the repeat procedure.

Impact of ABCB1 and ABCG2 Transporter in Outcome of Gallbladder Cancer

BackgroundGallbladder cancer (GBC) is a biologically aggressive malignancy requiring appropriate biomarkers to improve its outcome. Role of ABC transporters (ABCB1 and ABCG2) has been linked to cancer aggressiveness, tumorigenesis and multidrug resistance. Herein, we studied the prognostic implication of ABCB1 and ABCG2 in GBC. MethodsFresh tissue (tumour & normal) samples collected from 54 patients who underwent R0 resection, were analysed for mRNA and protein expression of ABCB1 and ABCG2 by quantitative Real-Time PCR and western blotting respectively in this prospective study. The molecular findings were correlated with clinical-pathological parameters using χ2 and fisher exact test. The molecular changes in ABCB1 and ABCG2 was analysed for predicting overall survival (OS), disease free survival (DFS) and response to chemotherapy using Kaplan Meier log rank test and Cox regression multivariate analysis. ResultsThe mean age of the cohort was 50 ±13.2 with 26 (48.1%) patients had early stage gallbladder cancer (GBC). Overexpression of ABCB1 and ABCG2 was noted in 32/54(59%) and 40/54 (74%) cases respectively. The protein expression of ABCB1(P-glycoprotein) and ABCG2 (BCRP) was higher in 27/54 (50%) and 37/54 (59%) cases respectively. The mean OS and DFS was 20.7 ±11.5 and 19.3 ± 12.2 months at median follow up 24 months. The TNM stage, lymph node metastasis, and presence of gallstone were significant factors for predicting OS and DFS on multivariate analysis. Both ABCB1 and ABCG2 did not show any significant correlation with OS and DFS with similar incidence of late death and recurrence among over-expression and down-expression. Sub- group comparison suggests that change in expression pattern of ABCB1 and ABCG2 may not affect response to chemotherapy in GBC. ConclusionAltered expression of ABCB1 and ABCG2 may not be a useful prognostic marker for survival or response to chemotherapy in GBC. Presently, histo-pathological characteristics and associated gallstones are the important predictors for survival and recurrence in GBC.

Abstract CT271: Neoadjuvant targeted therapy in stage I-III HER2-mutant lobular breast cancer

Abstract Background: Invasive lobular carcinoma (ILC) accounts for approximately 10-15% of all breast cancers and is characterized by hormone receptor positivity (HR+), low Ki-67 score, and loss of cell adhesion receptors such as E-cadherin. While these tumors tend to be indolent initially, late recurrences and distant metastasis are common, and ILC has very low rates of pathologic complete response (pCR) to both neoadjuvant chemotherapy and endocrine therapy (ET). HER2 (ERBB2) mutations are enriched in about 10% of unselected ILC, with some reports showing the prevalence as high as 27% in pleomorphic and higher grade ILCs. HER2 mutations in ILC are associated with ET resistance and a worse prognosis. Neratinib is a HER2 tyrosine kinase inhibitor (TKI) currently FDA-approved for adjuvant treatment of HER2-amplified (HER2+) early-stage breast cancer. It has shown safety and efficacy in combination with ET in metastatic HER2-mutant HR+ breast cancer. We hypothesize that neoadjuvant treatment with neratinib and ET will improve pathologic responses in newly diagnosed HER2-mutant HR+ ILC. Methods: This study (NCT05919108) is an open label multi-site Phase II clinical trial for 30 patients with Stage I-III ILCs and a HER2 activating mutation. Patients will be identified by next generation sequencing (NGS) of the diagnostic biopsy and randomized to 4 weeks of ET +/- neratinib; a biopsy will be done at the end of the lead-in phase. All patients will then receive ET and neratinib for 20 weeks prior to proceeding to surgery. To optimize tolerability, the first cycle of neratinib will include a dose escalation and antidiarrheal prophylaxis. The primary objective of this study will be the pre-operative endocrine prognostic index (PEPI) score, which will be compared to a historical PEPI-0 rate for patients with HR+ breast cancer treated with neoadjuvant ET. Secondary objectives will include pCR, residual cancer burden, and rates of breast conserving surgery. Correlative studies will include biomarkers of tumor cell cycle arrest, apoptosis, HER2 pathway activation, and gene expression on the pre- and on-treatment (4 week) biopsy from the lead-in phase to document molecular synergy between neratinib and ET. Patient-derived organoids from the 4-week biopsies will be established and subjected to single-cell RNA, ATAC seq, and DNA sequencing to study tumor evolution and elucidate epigenetic programs and somatic alterations that allow breast cancer survival despite continuous HER2-directed therapy. This is a first in kind, mechanism-based, molecularly targeted combination of a HER2 TKI and ET in HER2-mutant ILC. We posit results from this study may generate a clear signal of clinical activity leading to a randomized Phase III trial aimed at incorporating HER2-directed therapies as a treatment for operable, early stage ILC. This signal may also suggest for the first time the added value of NGS in patients with newly diagnosed HR+ breast cancer. Citation Format: Laura C. Kennedy, Nisha Unni, Ariella B. Hanker, Carlos L. Arteaga. Neoadjuvant targeted therapy in stage I-III HER2-mutant lobular breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT271.

Late cytomegalovirus disease after hematopoietic cell transplantation: significance of novel transplantation techniques

AbstractPreemptive therapy (PET) and letermovir prophylaxis are effective in preventing cytomegalovirus (CMV) disease within the first 100 days after allogeneic hematopoietic cell transplantation (HCT) but are associated with late-onset CMV disease. We retrospectively examined the clinical manifestations, risk factors, prevention algorithm, and outcome of late CMV disease in CMV seropositive day 100 survivors transplanted between 2001-2017 (PET cohort) and 2018-2021 (letermovir cohort). There were 203 episodes of late CMV disease among 2469 day 100 survivors, and the estimated cumulative incidence of first late CMV disease was 7.2% (95% confidence interval [CI], 6.2-8.3) with no difference between the PET (7.4%; 95% CI, 6.4-8.6) and the letermovir group (5.4%; 95% CI, 3.2-8.3). Thirty-seven patients (1.5%) had a second episode of CMV disease. In multivariable Cox regression models, posttransplant cyclophosphamide was associated with an increased risk of gastrointestinal CMV disease. CMV viremia or disease detected before day 100, corticosteroid treatment after day 100 at dose ≥1 mg/kg, acute and chronic graft-versus-host disease, lymphopenia, HLA-mismatched related donor status, were also associated with late CMV disease. HLA-mismatched donor status and late use of corticosteroids (≥1 mg/kg) were risk factors for late CMV disease recurrence. Late CMV disease occurred most frequently in a setting of prolonged low-level untreated viremia and was independently associated with death by 2 years after HCT. In summary, late CMV disease continues to occur in the present era. Improved prevention strategies for late CMV disease are needed.

Utility of Sensate Pedicled Medial Thigh Perforator Flaps in Treating Recurrent Ischial Ulcers in Individuals with Cauda Equina Lesions and Spinal Dysraphism – A Retrospective Analysis

Abstract Background: Ischial pressure ulcers pose a significant challenge due to their high recurrence rates. It is imperative to provide or establish a reliable, well-vascularized soft-tissue cover over the ischial area to prevent recurrences. The objective of the study was to study the utility and complication rates associated with pedicled medial thigh perforator (P-MTP) sensate flap procedures in managing recurrent ischial ulcers and perineal lesions. Methods: A retrospective cohort study was conducted at Christian Medical College, Vellore, a tertiary care center in South India. This study involved 30 patients with ischial pressure sores. Of these, 13 patients underwent P-MTP flaps, while 17 underwent alternative surgeries for ulcer closure (January 2014–June 2020). Results: Among 13 patients who underwent P-MTP sensate flaps, 1 major complication (full-thickness flap necrosis) necessitated flap revision, while 6 minor complications occurred in the postoperative period. Three patients (23.08%) reported late recurrence of ulcers at the same postoperative site. In contrast, among the 17 patients who underwent the other (alternative) methods of surgical closure, 3 patients had wound dehiscence in the postoperative period. Four patients reported recurrence of ulcer at the postoperative site within 6 months and another four after 6 months of surgical closure. The surgical outcomes in sensate flap surgeries (P-MTP flaps) were comparable to other approaches for surgical closure. Sensation in the P-MTP flap transposed over the ischial region remained intact in all 13 patients at 6-month follow-up. Conclusion: The P-MTP sensate flap is a feasible and reliable treatment strategy for regional soft-tissue reconstruction in ischial and perineal lesions with postoperative complications comparable to other surgical methods for ischial ulcer closure. The sensate flap surgeries offer the additional benefit of maintaining intact sensation over the pressure injury vulnerable ischial region.

Long-term outcomes of neoadjuvant endocrine therapy versus chemotherapy in luminal HER2-breast cancer

Introduction. Neoadjuvant endocrine therapy (NET) is an effective treatment modality that can downsize breast tumors in a cohort of postmenopausal women with HR-positive HER2-negative breast cancer. A lack of data regarding efficacy of NET vs neoadjuvant cytotoxic chemotherapy (NCT) leads to limited usage of NET despite its favorable toxicity profile. Perioperative endocrine therapy is mainly used for the elderly or patients with comorbidities that limit their access to NCT. The COVID-19 pandemic led to increased data of NET efficacy. Nevertheless, long-term outcomes of NET application are underrepresented in literature. Objective. Assessment of long-term outcomes in patients treated with neoadjuvant endocrine therapy (NAT) versus neoadjuvant cytotoxic chemotherapy in a cohort of postmenopausal women with HR-positive HER2-negative breast cancer. Materials and methods. We retrospectively evaluated the results of treatment of 154postmenopausal patients with luminal HER2-breast cancer who were treated with neoadjuvant systemic therapy (NET or NCT) at the State Medical Institution «St. Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncological)» from 01.01.2019 to 31.11.2020. We analyzed data on radiological, pathomorphological and long-term treatment outcomes (rate of locoregional and overall recurrence) in two groups.Results. 154 patients received neoadjuvant hormone therapy (n=78) or neoadjuvant chemotherapy (n=76). The clinical response was evaluated according to the RECIST criteria after 12 weeks and after study treatment using MMG. Partial or complete radiological response was achieved in 41.0% (n=32) in the NET group vs 69.7% (n=53) in the NCT group (p<0.001). All patients included in the study underwent surgery. A complete pathologic response was observed in 9.2% (n=7) of patients in the chemotherapy group, and in 0% of patients in the endocrine therapy group (p=0.006). Median follow-up was 46.2 months. Progression was recorded in 23.2% (n=29) of participants, with no significant benefit of NCT over NET in the frequency of locoregional relapses (NET n=8 (10.3%) vs NCT n=4 (5.3%)) (p= 0.369) or the occurrence of distant metastases NAT n=8 (10.3%) vs NCT n=13 (17.1%)) (p=0.216). Multivariate analysis showed that only pathologic lymph node status (ypN2–3) was an independent predictor of progression (p=0.007, OR=3.2; 95%CI: 1.380-7.422). Conclusions. Long-term outcomes after neoadjuvant hormone therapy are comparable with chemotherapy in the group of postmenopausal women with luminal HER2-breast cancer. The small sample size and limited follow-up period are significant limitations of our work.

Locoregional recurrence and survival of breast-conserving surgery compared to mastectomy following neoadjuvant chemotherapy in operable breast cancer.

The risk of locoregional recurrence (LRR) and the long-term prognosis of breast-conserving surgery (BCS) after neoadjuvant chemotherapy (NAC) are still controversial. This study aimed to evaluate oncological outcomes for patients undergoing BCS after NAC and determine LRR and survival predictors. This study was a retrospective cohort study of patients with locally advanced breast cancer (LABC) who received NAC and underwent BCS or mastectomy from June 2011 to November 2020. LRR, disease-free survival (DFS), and overall survival (OS) were compared in patients undergoing BCS or mastectomy. Univariate and multivariate analyses were performed to determine LRR, DFS, and OS predictors. A total of 585 patients were included, of whom 106 (18.1%) underwent BCS and 479 (81.9%) underwent a mastectomy. The LRR rate was 11.3% in the BCS group and 16.3% in the mastectomy group, revealing no significant difference(p = 0.200). In patients who underwent BCS, clinical lymph node status, histological grade and pathological complete response (pCR) were independent factors to predict LRR. There was no significant difference in DFS and OS between the BCS and the mastectomy groups. Multivariable analysis showed that lymph node status, histological grade, molecular subtypes, pCR and Miller&Payne (M&P) classification were independent predictors of DFS. Lymph node status, molecular subtypes and pCR were independent predictors of OS. BCS or mastectomy was not an independent predictor of DFS or OS. Compared with mastectomy, BCS after NAC may not increase the risk of local recurrence or mortality, BCS can be performed in selected patients with small tumor size and good response to NAC.

PRERISK: A Personalized, Artificial Intelligence-Based and Statistically-Based Stroke Recurrence Predictor for Recurrent Stroke.

Predicting stroke recurrence for individual patients is difficult, but individualized prediction may improve stroke survivors' engagement in self-care. We developed PRERISK: a statistical and machine learning classifier to predict individual risk of stroke recurrence. We analyzed clinical and socioeconomic data from a prospectively collected public health care-based data set of 41 975 patients admitted with stroke diagnosis in 88 public health centers over 6 years (2014-2020) in Catalonia-Spain. A new stroke diagnosis at least 24 hours after the index event was considered as a recurrent stroke, which was considered as our outcome of interest. We trained several supervised machine learning models to provide individualized risk over time and compared them with a Cox regression model. Models were trained to predict early, late, and long-term recurrence risk, within 90, 91 to 365, and >365 days, respectively. C statistics and area under the receiver operating characteristic curve were used to assess the accuracy of the models. Overall, 16.21% (5932 of 36 114) of patients had stroke recurrence during a median follow-up of 2.69 years. The most powerful predictors of stroke recurrence were time from previous stroke, Barthel Index, atrial fibrillation, dyslipidemia, age, diabetes, and sex, which were used to create a simplified model with similar performance, together with modifiable vascular risk factors (glycemia, body mass index, high blood pressure, cholesterol, tobacco dependence, and alcohol abuse). The areas under the receiver operating characteristic curve were 0.76 (95% CI, 0.74-0.77), 0.60 (95% CI, 0.58-0.61), and 0.71 (95% CI, 0.69-0.72) for early, late, and long-term recurrence risk, respectively. The areas under the receiver operating characteristic curve of the Cox risk class probability were 0.73 (95% CI, 0.72-0.75), 0.59 (95% CI, 0.57-0.61), and 0.67 (95% CI, 0.66-0.70); machine learning approaches (random forest and AdaBoost) showed statistically significant improvement (P<0.05) over the Cox model for the 3 recurrence time periods. Stroke recurrence curves can be simulated for each patient under different degrees of control of modifiable factors. PRERISK is a novel approach that provides a personalized and fairly accurate risk prediction of stroke recurrence over time. The model has the potential to incorporate dynamic control of risk factors.

Adenoid Cystic Carcinoma, Clinical Presentation, Current Treatment and Approaches Towards Novel Therapies.

Adenoid cystic carcinoma (AdCC) is a rare cancer originating from secretory glands with unknown aetiology. It is one of the most dominant malignant salivary tumours (MST). However, it can arise in other areas of the head and neck region and in secretory glands outside this area. It occurs at all ages, but is more frequent between 50-70 years of age and more common in females than in males. The symptoms of AdCC are generally unspecific and the clinical diagnosis of AdCC maybe challenging, partially due to its heterogenous histopathology and indolent growth. Moreover, there is a lack of good prognostic markers, and due to its rarity, it is difficult to predict which therapeutic methods are the most optimal for each patient, especially since very late recurrences occur. This review presents some major characteristics of AdCC and some current treatments for this disease.

Survival and clinical outcomes of salvage surgery in recurrent oral cavity cancer: a single institutional experience

Background: Oral cavity is the most common site of head and neck squamous cell carcinoma in India with more than 70% presenting in locally advanced stage. Recurrence in all stages of OCSCC occurs in up to 50% of patients, with most failures being local and/or regional relapses. The present study was done to analyze clinical outcomes of patients undergoing salvage surgery (SS) following recurrent OCSCC. Methods: A retrospective analysis of prospectively collected data of 82 patients with recurrent OCSCC was done in the department of head and neck surgery. Results: At the end of 1 year post SS for OCSCC 62 out of 82 (75.6%) patients were alive without disease. At the end of 2 year after SS 22 out of 45 patients were alive of which 21 were alive without disease and 1 was alive with disease (48.8%). At the end of 3 years, 10 out of 25 of which 9 were alive without disease and 1 patient was alive with disease (40%). Median disease-free survival (DFS) post SS was 13.50 months (0-47 months). DFS and overall survival (OS) post SS showed significantly better results in patients treated with surgery along with RT as primary treatment, patients with late recurrence, patients with early recurrent T stage, patients with free margins at SS and in patients who received adjuvant radiation therapy post SS. Conclusions: Salvage Surgery is one of the best treatment options for recurrent OCSCC with acceptable survival rates.

Comparison of Postprocedural P-Wave Vector Magnitude on 12-Lead Electrocardiogram Between Cryoballoon and Radiofrequency Ablation

Pulmonary vein isolation (PVI) causes changes in P-wave parameters. However, the difference in changes in P-wave parameters including P-wave vector magnitude (Pvm) between radiofrequency catheter ablation (RFCA) and cryoballoon ablation (CBA) remains unknown. Paroxysmal atrial fibrillation (PAF) patients who underwent only PVI were enrolled. Pvm was calculated by the square root of the sum of the squared P-wave amplitude in leads II and V6 and one-half of the P-wave amplitude in V2. The patients were divided into two groups: RFCA and CBA. ΔPvm was calculated as ΔPvm (mV)=(Pvm at pre-PVI)-(Pvm at post-PVI).The following factors were evaluated: (1) differences in the ΔPvm between the two groups, (2) relationship between late arrhythmia recurrence and ΔPvm in both RFCA and CBA groups and (3) the impact of relevant factors on ΔPvm. The study population included a total of 426 PAF patients (RFCA, 167 patients; CBA, 259 patients). ΔPvm was significantly larger in CBA than RFCA (p<0.001). Kaplan-Meier analysis showed late arrhythmia recurrence was significantly higher in patients with low ΔPvm (<0.019mV) than high ΔPvm (≥0.019mV) in RFCA (Log-rank p<0.001), and low ΔPvm (<0.033mV) than high ΔPvm (≥0.033mV) in CBA (Log-rank p<0.001). Multiple regression analysis showed that CBA and heart rate change were independently and significantly associated with ΔPvm (p<0.001 and p<0.001, respectively). In conclusion, ΔPvm was significantly larger in CBA than RFCA during procedure. Low ΔPvm had a higher risk of late arrhythmia recurrence in both RFCA and CBA.

Prognostic factors of palatal adenoid cystic carcinoma: A single-center analysis of 85 cases.

The purpose of this retrospective study was to describe the clinicopathological characteristics of primary adenoid cystic carcinoma (ACC) of the palate and to identify the factors affecting prognosis. The medical records of 85 patients with primary ACC of the palate treated with surgery, with or without adjuvant radiotherapy/chemotherapy, from 2009 to 2019 were reviewed. The relationship of different clinical parameters with locoregional recurrence (LR), distant metastasis (DM), and overall survival (OS) were analyzed. Median follow-up time was 44.6 months. LR and DM rates were 24.7% and 25.9%, respectively, and the 5-year OS and disease-free survival (DFS) rates were 85.9% and 55.1%, respectively. Multivariate analysis showed that positive margins were independently associated with the risk of LR (p < .001). Positive margins (p = .001) and high histological grade (p = .031) were significantly associated with shorter OS. Positive surgical margins are a strong adverse prognostic factor affecting LR and OS in patients with ACC; apart from that, high histopathological grade is an independent predictor of poor OS. Level 3 (Prognosis - Cohort study).

Abstract 464: Chromatin associated long non-coding RNAs involved in dormancy for late recurrence of ER-positive breast cancer

Abstract Late recurrence is one of the major problems for hormone receptor-positive breast cancer patients. It is suggested that the risk of recurrence may be maintained by cancer cells that have been already disseminated in the body at surgery. They enter long-term dormancy, thus evade immune surveillance and become resistant to therapies. The detailed molecular mechanism for this process is largely unknown.Nuclear long noncoding RNAs, which are not translated to proteins, often function as epigenetic regulators and determine the phenotype of cells and individuals. We found that a cluster of long noncoding RNAs, ELEANORS, is specifically expressed in ER (estrogen receptor)-positive recurrent breast cancer cells, forms a molecular condensate (RNA cloud) in the nucleus, and activates the ESR1 gene that encodes ER. ELEANORS define a large chromatin domain, the 0.7 Mb topologically associated domain (TAD), which contains the ESR1 and three other breast-cancer-associated genes. ELEANORS also regulates the three-dimensional genome architecture. They mediate a long-range chromatin interaction of ESR1 and FOXO3 genes, which are 42.9 Mb apart, and contribute to their cooperatively activate transcription, equilibrating cell proliferation (ESR1) and apoptosis (FOXO3). Upon ELEANOR knockdown, the ELEANOR clouds are disappeared, and ESR1 gene transcription is repressed. Further, the two genes are dissociated and only the FOXO3 gene remains transcriptionally active, resulting in the induction of apoptosis.Further analysis of clinical specimens revealed that ELEANOR expression in primary tumors correlates with recurrences over 5 years after surgeries, suggesting that ELEANORs are involved in late recurrence. We also found that ELEANOR activates transcription of CD44, a breast cancer stem cell marker gene. Cancer stem cell maintenance and equilibration of proliferation and apoptosis by ELEANOR may be involved in long-term tumor dormancy in late recurrence. This study suggests the possibility of ELEANORS as a biomarker to predict late recurrence, as well as a therapeutic target for ER-positive breast cancer. (References)Abdalla, MOA. et al., Nat. Commun, 10, 3778 (2019) Tomita, S. et al., Nat. Commun, 6, 6966 (2015) Citation Format: Noriko Saitoh, Maierdan Palihati, Hiroaki Tachiwana. Chromatin associated long non-coding RNAs involved in dormancy for late recurrence of ER-positive breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 464.

Abstract 3584: Context matters: Genomic profiling of PR isoform-specific actions in breast cancer stem cells reveals novel therapeutic insights for ER+ breast cancer

Abstract Exposure to progesterone is a recognized risk factor for breast cancer, and PGR polymorphisms are associated with various malignancies. The two progesterone receptor (PR) isoforms, full length PR-B and truncated PR-A, are expressed from the PGR gene in breast tissue and play crucial roles in normal physiology. An imbalance in the expression ratio of these isoforms, favoring increased levels of PR-A, is common in breast cancer and is associated with resistance to tamoxifen in Luminal A-type tumors. Notably, PRs have recently been implicated in promoting endocrine resistance and driving the expansion of cancer stem-like cell (CSC) populations implicated in early dissemination and maintenance of metastatic populations. Because prior gene expression studies were primarily conducted in 2D culture conditions, the isoform-specific molecular and epigenetic mechanisms underlying PR actions in advanced ER+ breast cancer remain elusive. Our goal was to define progesterone-driven gene expression in CSC cells by employing transcriptomic profiling of T47D cells cultivated in spheroid-culture conditions (3D) expressing exclusively PR-A or PR-B. Utilizing CUT&amp;RUN, we have mapped the genomic binding sites unique to each PR isoform and identified shared sites. This genomic data has been integrated with phenotypic studies in cells expressing a single PR isoform. Our findings indicate that PR-A acts as a regulator of the cell cycle and senescence, while PR-B plays a pivotal role in cell metabolism and intracellular signaling. We find little overlap between PR-regulated gene sets derived from the same hormone-treated cells harvested from 2D relative to 3D conditions. Our genomic profiling of PRs in this 3D model system has unveiled novel strategies to combat CSC outgrowth and late recurrence in luminal breast cancer patients. This work has shifted our prior understanding of the role of PRs in gene regulation within the CSC population, and offers potential insights for therapeutic interventions in ER+ breast cancer. Citation Format: Noelle E. Gillis, Thu H. Truong, Jessica Finlay-Schultz, Carol A. Sartorius, Carol A. Lange. Context matters: Genomic profiling of PR isoform-specific actions in breast cancer stem cells reveals novel therapeutic insights for ER+ breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3584.