Tumor Prognosis Research Articles

Inflammatory myofibroblastic tumor of urinary bladder in young male: A case report and literature review

The objective of this study is to present a rare case of inflammatory myofibroblastic tumor (IMT) of the urinary bladder in young male, detailing its clinical presentation, diagnostic approach, treatment strategy, and outcome. Additionally, the objective includes conducting a literature review to provide insights into the characteristics, management, and prognosis of this uncommon tumor entity.A 20-year-old male presenting with dysuria and dribbling of urine underwent diagnostic workup including imaging studies, cystoscopy. On cystoscopy there was a presence of 5x4 cm sized pedunculated mass in the urinary bladder. Partial cystectomy is done and specimen is examined for histopathology. Histopathological examination and Immunohistochemistry study of the tumor specimen was performed to confirm the diagnosis of inflammatory myofibroblastic tumor. A thorough literature review was conducted to gather relevant studies on IMT of the urinary bladder, focusing on clinical presentations, diagnostic modalities, treatment approaches, and outcomes. Diagnostic evaluation revealed a mass lesion in the urinary bladder, and histopathological examination following partial cystectomy confirmed the diagnosis of inflammatory myofibroblastic tumor. The patient underwent surgical excision of the tumor followed by adjuvant therapy. Regular follow-up examinations showed no evidence of tumor recurrence. The literature review identified a limited number of reported cases of IMT of the urinary bladder in young male, emphasizing its rarity and diverse clinical presentations. Various diagnostic modalities and treatment options, including surgery, chemotherapy, and targeted therapy, were discussed in the reviewed literature. Inflammatory myofibroblastic tumor of the urinary bladder is a rare neoplasm at younger age that can present with nonspecific symptoms, making its diagnosis challenging. However, timely recognition and appropriate management, including surgical resection and adjuvant therapy, can lead to favorable outcomes with low recurrence rates. This case report highlights the importance of considering IMT in the differential diagnosis of bladder masses in young patient and underscores the need for further research to better understand the pathogenesis and optimal treatment strategies for this rare tumor entity.

EMP1 correlated with cancer progression and immune characteristics in pan-cancer and ovarian cancer.

This study examines the prognostic role and immunological relevance of EMP1 (epithelial membrane protein-1) in a pan-cancer analysis, with a focus on ovarian cancer. Utilizing data from TCGA, CCLE, and GTEx databases, we assessed EMP1 mRNA expression and its correlation with tumor progression, prognosis, and immune microenvironment across various cancers. Our results indicate that EMP1 expression is significantly associated with poor prognosis in multiple cancer types, including ovarian, bladder, testicular, pancreatic, breast, brain, and uveal melanoma. Immune-related analyses reveal a positive correlation between EMP1 and immune cell infiltration, particularly neutrophils, macrophages, and dendritic cells, as well as high expression of immune checkpoint such as CD274, HAVCR2, IL10, PDCD1LG2, and TGFB1 in most tumors. In vivo experiments confirm that EMP1 promotes ovarian cancer cell proliferation, metastasis, and invasion. In conclusion, EMP1 emerges as a potential prognostic biomarker and therapeutic target in various cancers, particularly ovarian cancer, due to its influence on tumor progression and immune cell dynamics. Further research is warranted to elucidate the precise mechanisms of EMP1 in cancer biology and to translate these findings into clinical applications.

The collaborative project "Personalized medicine for oncology" (PM4Onco) as part of the Medical Informatics Initiative (MII)

The collaborative project Personalized Medicine for Oncology (PM4Onco) was launched in 2023 as part of the National Decade against Cancer (NKD) and is executed within the Medical Informatics Initiative (MII). Its aim is to establish asustainable infrastructure for the integration and use of data from clinical and biomedical research and therefore combines the experience and preliminary work of all four consortia of the MII and the leading oncology centers in Germany. The data provided by PM4Onco will be prepared in asuitable form to support decision making in molecular tumor boards. This concept and infrastructure will be extended to 23 participating partner sites and thus improve access to targeted therapies based on clinical information and analysis of molecular genetic alterations in tumors at different stages of the disease. This will help to improve the treatment and prognosis of tumor diseases.Clinical cancer registries are involved in the project to improve data quality through standardized documentation routines. Clinical experts advise on the expansion of the core datasets for personalized medicine (PM). Information on quality of life and treatment outcomes reported by patients in questionnaires, which is rarely collected outside of clinical trials, will make asignificant contribution. Patient representatives are involved from the onset to ensure that the important perspective of patients is taken into account in the decision-making process. PM4Onco thus creates an alliance between the MII, oncological centers of excellence, clinical cancer registries, young scientists, patients, and citizens to strengthen and advance PM in cancer therapy.

A nomogram based on the SII3 and clinical indicators predicts survival in patients with nasopharyngeal carcinoma treated with PD-1 inhibitors.

Numerous inflammatory indicators have been demonstrated to be strongly correlated with tumor prognosis. However, the association between inflammatory indicators and the prognosis of patients with nasopharyngeal carcinoma (NPC) receiving treatment with programmed death receptor-1 (PD-1) immunosuppressant monoclonal antibodies remains uncertain. Inflammatory indicators in peripheral blood were collected from 161 NPC patients at 3 weeks after initial PD-1 treatment. Through univariate and multivariate analyses, as well as nomogram and survival analyses, we aimed to identify independent prognostic factors related to 1-year progression-free survival (PFS). Subsequently, a prognostic nomogram was devised, and its predictive and discriminating abilities were assessed utilizing calibration curves and the concordance index. Our univariate and multivariate analyses indicated that age (P = .012), M stage (P < .001), and systemic immune-inflammation index (SII) during the third week following initial PD-1 treatment (SII3, P = .005) were independently correlated with the 1-year PFS of NPC patients after PD-1 treatment. Notably, we constructed a novel nomogram based on the SII3, age, and M stage. Importantly, utilizing the derived cutoff point from the nomogram, the high-risk group exhibited significantly shorter PFS than did the low-risk group (P < .001). Furthermore, the nomogram demonstrated a greater concordance index for PFS than did the tumor node metastasis stage within the entire cohort. We successfully developed a nomogram that integrates the SII3 and clinical markers to accurately predict the 1-year PFS of NPC patients receiving PD-1 inhibitor treatment.

Clinical calculator based on CT and clinicopathologic characteristics predicts short-term prognosis following resection of microsatellite-stabilized diffuse gastric cancer.

Although microsatellite stability/Epithelial-mesenchymal transition (MSS/EMT) subtypes have been reported in multiple cancer prognosis studies, strong confounding factors between MSS/EMT (usually with Lauren's diffuse phenotype) and diffuse gastric cancer (GC) may obscure the independent prognostic value of diffuse GC. Additionally, recent studies suggest a strong correlation between mural stratification based on CT and diffuse GC. This study aims to investigate potential prognostic factors of MSS diffuse GC using mural stratification and to develop a risk assessment model. This retrospective study included 131 patients with MSS diffuse GC who underwent radical surgery. Univariate and multivariate Cox proportional hazards regression analysis was used to identify model predictors and construct a nomogram for overall survival (OS) and recurrence-free survival (RFS) risks. The model's performance was evaluated using ROC, accuracy, and C-index. Internal validation of the model was conducted using the bootstrap resampling method. Among 131 cases, 60 cases (45.8%) exhibited grade 2 mural stratification, which correlated with a poorer tumor prognosis and a more invasive phenotype. Furthermore, a nomogram for predicting OS and RFS prognosis was established based on multivariate results (age, extranodal invasion, mural stratification, and/or P53). The nomogram demonstrated excellent performance, with an AUC of 0.859 (95% CI 0.794-0.924) for OS and 0.859 (95% CI 0.789-0.929) for RFS. Internal validation using 1000 bootstrap samples yielded AUC values of 0.845 and 0.846 for OS and RFS, respectively. Grade 2 mural stratification based on CT imaging revealed a more aggressive invasive phenotype, characterized by increased LN metastasis, higher rates of peritoneal metastasis, and a poorer short-term prognosis. Furthermore, the CT phenotype-based nomogram demonstrates favorable discrimination and calibration, enabling convenient individual short-term prognostic evaluation following resection of MSS diffuse GC.

Abstract PO1-17-01: Surgical Margins and prognosis of borderline and malignant phyllodes tumors of breast

Abstract Background. To determine the appropriate surgical margin and identify predictive factors for recurrence and prognosis of borderline and malignant phyllodes tumor (PT) of the breast. Methods. A retrospective review of patients with borderline and malignant PT treated from March 2011 to December 2022 at the First Affiliated Hospital of Chongqing Medical University were conducted. The main endpoints of this research were local recurrence-free survival (LRFS) and disease-free survival (DFS). Univariate and multivariate Cox proportional hazard models were used to examine the impacts of different variables on LRFS and DFS, and to calculate hazard ratios (HR) and 95% confidence intervals (CI). Results. Of 155 patients with phyllodes tumors, 87 (56.1%) were classified as borderline while 68 (43.9%) were malignant. All patients included underwent operation, with a median age of 47 years (range,12-66 years) and a median tumor size of 60 mm (range,15-300 mm). Initial surgical margins &amp;lt; 1cm in 72 (46.5%) patients, of which 28 (38.9%) underwent reoperation, resulting in 45 (28.4%) patients with a margin &amp;lt; 1cm and 111 (71.6%) patients with a margin ≥1cm. At a median follow-up period of 66 months (range 3-146 months), local recurrence was observed in 36 patients (23.2%), and distant metastasis occurred in 10 patients (6.5%). In this cohort, the rates of 5-year LRFS was significantly higher in the surgical margin ≥1 cm group than in the surgical margin &amp;lt; 1 cm group (83.8% vs 50.4%, log-rank P&amp;lt; 0.001), both for the borderline (log-rank P=0.010) and the malignant PT (log-rank P&amp;lt; 0.001).Similarly, for both borderline (log-rank P=0.019) and malignant PT (log-rank P&amp;lt; 0.001), the rates of 5-year DFS was significantly higher in the surgical margin ≥1 cm group than in the surgical margin &amp;lt; 1 cm group (80.3% vs 47.5%, log-rank P=0.002). For 72 patients with the initial margin &amp;lt; 1 cm, 5-year DFS for undergoing reoperation to achieve a margin ≥1 cm and remaining with a margin &amp;lt; 1 cm were84.1% and 47.5%, respectively (P=0.008). In univariate analysis of the entire cohort, age, fibroadenoma surgery history, surgical methods, and surgical margins emerged as predictive factors for LRFS (P=0,003, 0.019, 0.026, and0.001, respectively), whereas age, reproductive history, fibroadenoma surgery history, tumor size and surgical margins were predictors of DFS (P= 0,011, 0.025, 0.039, 0.022, and0.002, respectively).In multivariate analysis, age&amp;lt; 45 years (HR=2.186, 95%CI:1.105-4.328, P=0.025)and surgical margins&amp;lt; 1cm (HR=2.181, 95%CI:1.021-4.659, P=0.044) were independent risk factors of LRFS. Independent risk factors for DFS included tumor size&amp;gt;5cm (HR=2.265, 95%CI:1.113-4.606, P=0.024) and surgical margins &amp;lt; 1cm (HR=2.689, 95%CI:1.438-5.027, P=0.002). Conclusion. For borderline and malignant PT, surgical margins of at least 1 cm should be achieved for a better prognosis. Patients aged &amp;lt; 45 years with a high risk of local recurrence and larger tumor patients with poor prognosis, multiple therapy modalities may be required for these high-risk patients. Survival curves for impact of variables on LRFS and DFS Table 1 Univariate and multivariate analysis of LRFS of PTs of the breast (n=155) Table 2 Univariate and multivariate analysis of DFS of PTs of the breast (n=155) Citation Format: lu Gan, Jialin Su. Surgical Margins and prognosis of borderline and malignant phyllodes tumors of breast [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 PO1-17-01.

Abstract PO5-02-08: Prognostic value of serum lipid levels in breast cancer patients who received neoadjuvant chemotherapy: A retrospective exploratory analysis of the prospective cohort

Abstract 【Background】 Lipid metabolism is one of the most conspicuous metabolic changes in malignant tumors. Previous studies confirmed that higher levels of “adverse lipids” might lead to poor outcomes and lipid-lowering drugs could act as a protective role in improving the prognosis of breast cancer patients. Nevertheless, few studies have clarified the impact of serum lipid levels and their changes on the tumor prognosis. Particularly for breast cancer patients treated with neoadjuvant chemotherapy, little has been studied whether their lipid levels or changes during neoadjuvant chemotherapy can serve as a valid prognostic factor. 【Methods】This study enrolled patients who received surgical treatment after neoadjuvant chemotherapy in Renji Hospital from March 2016 to December 2020. Patients were included if they were female aged 18 years or older; had pathologically confirmed unilateral invasive breast cancer; had tumor of at least 2cm in size without distant metastasis (T1-4, N0-3, M0); and underwent radical surgery for breast cancer successfully after neoadjuvant chemotherapy. We retrospectively gathered the baseline clinicopathological information and lipid metabolism-related biomarkers from electronic medical records. The study endpoints were disease free survival (DFS), overall survival (OS), relapse free survival (RFS), distance recurrence free survival (DRFS), and local recurrence free survival (LRFS). The prognostic value of each lipid levels and their variation levels were systematically evaluated and the importance of lipid biomarkers were ranked by Random Forest. 【Results】 The baseline clinicopathological information and lipid metabolism biomarkers were available from 200 eligible patients. As of the last follow-up in March 2023, 11 patients died, 24 experienced DFS events and 20 underwent RFS events. It showed no significant correlations of lipid levels before (baseline) and after (preoperative) neoadjuvant chemotherapy with any survival outcome. However, we found that the relative increase of low-density lipoprotein (LDL) led to poorer DFS (P=0.003), RFS (P=0.01), DRFS (P=0.01), and LRFS (P=0.0039), meanwhile the relative increase of total cholesterol (TC) and non-high-density lipoprotein (NHDL) during neoadjuvant period was significantly related to the worse prognosis (TC, DFS P=0.0084; NHDL, DFS P=0.031, RFS P=0.009) as well. After adjusted by multiple factors, the adverse impacts of increasing TC (DFS P=0.005; RFS P=0.026), LDL (DFS P=0.004; RFS P=0.006) and NHDL (DFS P=0.032; RFS P=0.014) on DFS or RFS were still maintained. The results of Random Forest revealed that LDL changes and Body Mass Index (BMI) ranked higher in terms of predicting survival outcomes. Based on these data, BMI &amp;gt;25.4 kg/m2 or LDL elevation &amp;gt;0.54 mmol/L were defined as High-risk Lipid Metabolism (HLM), while BMI ≤ 25.4 kg/m2 and LDL elevation ≤ 0.54 mmol/L were regarded as Low-risk Lipid Metabolism (LLM). Compared to LLM, HLM had a worse OS (P=0.026), DFS (P=0.0011) and RFS (P=0.0011). 【Conclusion】Our study demonstrated that the relative elevation of LDL, TC and NHDL levels during neoadjuvant chemotherapy is an independent prognostic risk factor for breast cancer patients. It was also the first time to propose the concept of high-risk lipid metabolism (HLM). 【keywords】Breast cancer, Lipid metabolism, Low-density lipoprotein (LDL), Body Mass Index (BMI), Prognosis. Citation Format: Xinru Chen, Wenjin Yin, Yingying Zhao, Jinsong Lu. Prognostic value of serum lipid levels in breast cancer patients who received neoadjuvant chemotherapy: A retrospective exploratory analysis of the prospective cohort [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 PO5-02-08.

Abstract PO2-20-05: Onco-Genome Brazil: Mapping Breast and Prostate Cancer in the Brazilian Public Health System

Abstract Background: Breast and prostate cancers are the most common malignancies diagnosed in women and men respectively, and present with great clinical heterogeneity, even in tumors with the same phenotypic characteristics. Somatic and germline molecular alterations in DNA may have prognostic and predictive impact, influencing response to therapies and overall survival. In addition, the evaluation of germline mutations can help identify individuals and families at higher risk for developing cancer. Aims: Our aim is to characterize the somatic and germline genomic landscape of women with locally advanced HER2-positive breast cancer and men with metastatic prostate cancer from Brazil. Secondarily, we aim to identify genetic variants associated with tumor prognosis and treatment response, identify patients carrying pathogenic alterations in cancer-predisposing genes, and characterize the genetic ancestry of the population included in the study. Trial design: This observational multicenter cohort study (NCT05306600) will include 550 adult patients from the five macro-regions of Brazil, divided into two arms: 1) breast cancer and 2) prostate cancer. Clinical and pathological data will be collected, as well as DNA samples from peripheral blood and tumor tissue. Whole-exome sequencing (WES) will be performed to identify variants that may be drivers and/or actionable in a specific patient or tumor. These variants will be interpreted and classified according to their population frequencies, in silico predictors, functional studies, and literature data, following international guidelines proposed by expert societies. This trial is supported by the Ministry of Health in Brazil and includes patients of the Public Health System. Eligibility criteria: In arm 1, the inclusion criteria are patients with a histological diagnosis of breast carcinoma with overexpression of HER-2, clinical stage II or III, and undergoing neoadjuvant treatment with chemotherapy plus trastuzumab. In arm 2, the criteria are patient with histological diagnosis of prostate adenocarcinoma, currently in clinical stage IV. Patients without availability of biological material collection are excluded from the study, as well as patients in whom there was no central confirmation of required histology. Statistical methods: Univariate and multivariate analyses will be conducted to evaluate the possible effect of specific genes or mutations on the investigated outcomes, including tumor prognosis and treatment response. Discussion: Currently, 265 participants have already been included in the study, 150 in arm 1 and 115 in arm 2. This trial will contribute to the construction of a robust database that should provide a better understanding of the genomic profile of patients with breast and prostate cancer in Brazil. For more information about the trial, please contact Daniela Rosa (daniela.rosa@hmv.org.br). Citation Format: Jaqueline Schuch, Cláudia Bordignon, Mahira Rosa, Angélica de Baumont, Marina Bessel, Gabriel Macedo, Daniela Rosa. Onco-Genome Brazil: Mapping Breast and Prostate Cancer in the Brazilian Public Health System [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 PO2-20-05.

Abstract PO4-15-10: HER2-low Status among Patients with Li-Fraumeni Syndrome and Breast Cancer

Abstract Background: The HER2-low status has gained significance as a target for HER2-directed antibody drug conjugates in breast cancer. It is observed in approximately 60% of hormone receptor-positive (HR+) tumors and 30% of hormone receptor-negative (HR-) tumors. Some studies suggest that the HER2-low status by itself does not influence tumor biology or prognosis. Breast cancer in the context of Li-Fraumeni (LFS) syndrome has been characterized by an enrichment in HER2-positive (HER2+, defined as +3 in the immunohistochemistry [IHQ] or +2 in the IHQ with positive in situ hybridization [ISH]) disease. Considering this, we aimed to evaluate whether LFS patients with breast cancer also exhibit a higher frequency of HER2-low status. Methods: This retrospective-prospective cohort study included patients diagnosed with breast cancer who had a pathogenic/likely pathogenic TP53 germline variant and were treated at two cancer institutions between 1999 and 2023. The primary objectives were to determine the overall proportion of HER2-low status and its distribution according to hormone receptor status. HER2-low was defined as IHQ +1 or IHQ +2 with negative ISH. Results: Fifty-three patients (52 female and 1 male) were included in the study. The most common germline TP53 variant was the TP53 R337H (71.7%). The median age at breast cancer diagnosis was 39 years (range 21–62). The majority of patients had breast cancer of no special type (79%) or lobular carcinoma (11.3%), grade 2 (54.7%) or grade 3 (24.5%), and stage I-II (67.9%). Breast cancer subtypes would classically be classified as HER2+ in 34%, HR+HER2- in 58.5%, and triple-negative breast cancer (TNBC) in 7.5% of the patients. Biopsy samples were obtained from the primary tumor in 96.3% of the cases and from lymph nodes in 3.7%. Overall, 15.1% of the cases exhibited HER2-low status, 34% were HER2-negative, and 17% were HER2-negative without IHC details (Table). In a hypothetical scenario assuming all cases without IHC details were HER2-low, the maximum estimated frequency of HER2-low status would be 32.1%. Among HR+ patients, 25.8% had HER2-low status, 45.2% were HER2-negative, and 29% were HER2-negative without IHC details. All four patients with TNBC exhibited HER2-zero status. Conclusion: Contrary to our initial hypothesis, the frequency of HER2-low status in this cohort of LFS patients with breast cancer was lower than anticipated. These results suggest that while breast cancer developing in the context of germline TP53 variants appears to be associated with HER2 amplification, it does not impact lower expressions of HER2. This observation reinforces the concept that HER2-low status does not seem to play a significant role as a driver of tumorigenesis. Further expansion of the study cohort and pathology analysis is planned to confirm these findings. Table HER2 status overall and according to hormone receptor-status (for HER2-negative patients). Abbreviations: IHQ, immunohistochemistry; HR+HER2- BC, hormone receptor-positive HER2-negative breast cancer; TNBC, triple-negative breast cancer. Citation Format: Luciana Auresco, Renata Colombo Bonadio, Vanessa Petry, Laura Testa, Camila Moniz, Jennifer Dos Santos, Maria Del Pilar Estevez-Diz, Rodrigo Santa Cruz Guindalini. HER2-low Status among Patients with Li-Fraumeni Syndrome and 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 PO4-15-10.

A clinicopathological study of non-functioning pituitary neuroendocrine tumours using the World Health Organization 2022 classification

BackgroundThe 2022 World Health Organization (WHO) classification of pituitary neuroendocrine tumour (PitNET) supersedes the previous one in 2017 and further consolidates the role of transcription factors (TF) in the diagnosis of PitNET. Here, we investigated the clinical utility of the 2022 WHO classification, as compared to that of 2017, in a cohort of patients with non-functioning PitNET (NF-PitNET).MethodsA total of 113 NF-PitNET patients who underwent resection between 2010 and 2021, and had follow-up at Queen Mary Hospital, Hong Kong, were recruited. Surgical specimens were re-stained for the three TF: steroidogenic factor (SF-1), T-box family member TBX19 (TPIT) and POU class 1 homeobox 1 (Pit-1). The associations of different NF-PitNET subtypes with tumour-related outcomes were evaluated by logistic and Cox regression analyses.ResultsBased on the 2022 WHO classification, the majority of NF-PitNET was SF-1-lineage tumours (58.4%), followed by TPIT-lineage tumours (18.6%), tumours with no distinct lineage (16.8%) and Pit-1-lineage tumours (6.2%). Despite fewer entities than the 2017 classification, significant differences in disease-free survival were present amongst these four subtypes (Log-rank test p=0.003), specifically between SF-1-lineage PitNET and PitNET without distinct lineage (Log-rank test p&amp;lt;0.001). In multivariable Cox regression analysis, the subtype of PitNET without distinct lineage (HR 3.02, 95% CI 1.28-7.16, p=0.012), together with tumour volume (HR 1.04, 95% CI 1.01-1.07, p=0.017), were independent predictors of a composite of residual or recurrent disease.ConclusionThe 2022 WHO classification of PitNET is a clinically useful TF and lineage-based system for subtyping NF-PitNET with different tumour behaviour and prognosis.

Abstract PO4-18-09: SMALL: Open Surgery versus Minimally invasive vacuum-Assisted excision for smaLL screen-detected breast cancer – a UK phase III randomised multi-centre trial

Abstract Background: Mammographic screening programmes reduce breast cancer mortality but detect many small good-prognosis tumours which may not progress. Screen-detected cancers are currently treated with standard surgery and adjuvant therapies, with associated morbidities. There is a need to reduce overtreatment of good prognosis tumours and numerous studies are evaluating omission of radiotherapy in low-risk disease. However, there is little evidence to support surgical de-escalation, although percutaneous minimally invasive treatment approaches have been described. Vacuum-assisted excision (VAE) is in widespread use for management of lesions of uncertain malignant potential and benign lesions. SMALL (ISRCTN 12240119) is designed to determine the feasibility of using this approach to treat small invasive tumours detected within the UK NHS Breast Screening Programme. Methods: SMALL is a phase III multicentre randomised trial comparing standard surgery with VAE for screen-detected cancers. Main eligibility criteria are age ≥47 years, unifocal grade 1 tumours with maximum diameter 15mm, strongly ER/PR+ve and HER2-ve, with negative axillary staging. Patients are randomised 2:1 to VAE or surgery, with no axillary surgery in the VAE arm. Completeness of excision is assessed radiologically, and if excision is incomplete, patients undergo surgery. Adjuvant radiotherapy and endocrine therapy are mandated in the VAE arm but may be omitted following surgery. Co-primary end-points are: 1. Non-inferiority comparison of the requirement for a second procedure following excision 2. Single arm analysis of local recurrence (LR) at 5 years following VAE Recruitment of 800 patients will permit demonstration of 10% non-inferiority of VAE for requirement of a second procedure. This ensures sufficient patients for single arm analysis of LR rates, where expected LR free survival is 99% at 5 years, with an undesirable survival probability after VAE of 97%. To ensure that the trial as a whole only has 5% alpha, the significance level for each co-primary outcome is set at 2.5% with 90% power. The Data Monitoring Committee will monitor LR events to ensure these do not exceed 3% per year. Secondary outcome measures include time to ipsilateral recurrence, overall survival, complications, quality of life and health economic analysis. A novel feature of SMALL is the integration of a QuinteT Recruitment Intervention (QRI), which aims to optimise recruitment to the study. Recruitment challenges are identified by analysing recruiter/patient interviews and audio-recordings of trial discussions, and by review of trial screening logs, eligibility and recruitment data and study documentation. Solutions to address these are developed collaboratively, including individual/group recruiter feedback and recruitment tips documents. Results: SMALL opened in December 2019, but recruitment halted in 2020 for 5 months due to COVID-19. At 6th July 2023, 39 centres are open, with 300 patients randomised from 32 of these, with a randomisation rate of approximately 45%, and a per site recruitment rate of 0.4-0.5 patients/month. Despite the pandemic, SMALL achieved the internal pilot feasibility targets and continues to recruit to the main study, with estimated completion of recruitment in June 2025. Drawing from preliminary QRI findings and insights from patient representatives, a recruitment tips document has been circulated (on providing balanced information about treatments, encouraging recruiters to engage with patient preferences, and explaining randomisation). Individual recruiter feedback has commenced and wider feedback is being delivered across sites via recruitment training workshops. Conclusion: Despite pandemic-related challenges, SMALL has excellent recruitment to date and is expected to have a global impact on treatment of breast cancer within mammographic screening programmes. SMALL is funded by the UK NIHR HTA programme award 17/42/32 Citation Format: Stuart McIntosh, Charlotte Coles, David Dodwell, Kenneth Elder, Jessica Foster, Claire Gaunt, Amanda Kirkham, Iain Lyburn, Sangeetha Paramasivan, Jenna Morgan, Sarah Pinder, Shelley Potter, Tracy Roberts, Nisha Sharma, Hilary Stobart, Elizabeth Southgate, Sian Taylor-Phillips, Matthew Wallis, Daniel Rea. SMALL: Open Surgery versus Minimally invasive vacuum-Assisted excision for smaLL screen-detected breast cancer – a UK phase III randomised multi-centre trial [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 PO4-18-09.

Abstract PO5-23-04: Clinical utility of sentinel lymph node biopsy in women ≥ 70 years with early breast cancer – an international, retrospective multi-center cohort study

Abstract Introduction Traditionally, sentinel lymph node biopsy (SLNB) has been used to stage the axilla in early breast cancer (EBC) to guide adjuvant treatment recommendations. Following advances in tumor biology understanding, targeted systemic therapies and genomic testing, with increasing de-escalation of axillary surgery, its role may be less critical especially in selected groups of women. Aims Evaluate clinical utility of SLNB in adjuvant treatment recommendations for women ≥ 70 years with EBC. Methods Retrospective cohort study of women ≥ 70 years with cT1-2N0 EBC undergoing primary surgery and SLNB between 01/2017-12/2022 at The Royal Marsden Hospital (RMH), University Hospital Zurich (USZ) and Seoul National University Hospital (SNUH) in the United Kingdom, Switzerland and South Korea respectively. Simple descriptive statistics and non-parametric tests were performed as appropriate. Results A total of 884 patients were included in the analysis, with 584 patients from RMH, 148 from USZ and 152 from SNUH. The median age was 75 (IQR 72-79) years. Most cancers were invasive ductal (82.9%), grade 2 (61.4%), hormone receptor (HR) positive/HER2 negative (82.9%) with a median tumor size of 17 (IQR 4-50) mm. SLNB was positive in 116 (13.1%) patients. Of these 116 patients, 20 (17.2%) had completion ALND; 7/20 had further RT up to levels 3&amp;4 of the axilla. Of these 116 patients, 96 patients (82.8%) avoided ALND; 25/96 had no further treatment, and 71/96 patients had loco-regional axillary RT (8/71 had RT to levels 1&amp;2 and 63/71 had RT up to levels 3&amp;4). As per international guidelines for patients with EBC with 1-2 positive macrometastases on SLNB treated with breast conserving surgery and breast RT, 5/20 could have been spared ALND, and 50/71 axillary RT. Completion ALND was more likely to be performed at SNUH compared to the other 2 units (p&amp;lt; 0.0001). Axillary RT was more likely to be administered at SNUH and less likely at RMH (p&amp;lt; 0.0001). The multidisciplinary team (MDT) recommended adjuvant chemotherapy (AC) in 146 (16.5%) patients and 100 received it. Of those with a positive SLNB (n=116), AC was recommended in 35, and received by 29. Recommendation for AC was significantly associated with younger age (p=0.021), fewer comorbidities (p=0.003), higher tumor grade (p&amp;lt; 0.0001), increased tumor size (p&amp;lt; 0.0001), HR negative status (p&amp;lt; 0.0001), high genomic risk profile (p&amp;lt; 0.0001) and positive SLNB status (p&amp;lt; 0.0001), but not center (p=0.497). A subgroup analysis of 505 patients with cT1N0, HR+/HER2- EBC, representing a more favorable prognosis group, was performed. Here, 52/505 (10.3%) patients had positive SLNB, of whom 11 had no further axillary treatment, 9 underwent ALND and 32 axillary RT, where 4/9 could have been spared ALND and 28/32 axillary RT as per international guidelines mentioned above. AC was recommended in 26/505 (5.15%) women and 23 received it. AC was not recommended in 39/52 (75%) cases, despite a positive SLNB. MDT recommendation for AC was associated with grade 3 (p&amp;lt; 0.0001), multifocal disease (p=0.021), positive SLNB status (p&amp;lt; 0.0001), high genomic risk profile (p&amp;lt; 0.0001), lower age (p=0.044), fewer co-morbidities (p=0.001) and center (p=0.007) with SNUH being more likely than the other 2, but not ethnicity (p=0.130); AC receipt was associated with the same factors except age (p=0.347). Conclusions Real-world data demonstrates axillary overtreatment despite evidence of the safety of de-escalation of axillary management in EBC. Only a small proportion of women ≥ 70 years with EBC had positive SLNB that may influence adjuvant treatment recommendations, especially with favorable prognosis tumors. In such cases, where clinical morbidity and financial burden of SLNB may outweigh the benefits, a nuanced discussion for opting in SLNB rather than routine performance should be considered. Citation Format: Radhika Merh, Denise Vorburger, Ji-Jung Jung, Han-Byoel Lee, Marios Tasoulis. Clinical utility of sentinel lymph node biopsy in women ≥ 70 years with early breast cancer – an international, retrospective multi-center cohort study [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 PO5-23-04.

Long non-coding RNA HOTAIR: from pan-cancer analysis to colorectal cancer-related uridine metabolism.

Long non-coding RNAs (lncRNAs) are involved significantly in the development of human cancers. lncRNA HOTAIR has been reported to play an oncogenic role in many human cancers. Its specific regulatory role is still elusive. And it might have enormous potential to interpret the malignant progression of tumors in a broader perspective, that is, in pan-cancer. We comprehensively investigated the effect of HOTAIR expression on tumor prognosis across human malignancies by analyzing multiple cancer-related databases like The Cancer Genome Atlas (TCGA) and Tumor Immune Estimation Resource (TIMER). Bioinformatics data indicated that HOTAIR was overexpressed in most of these human malignancies and was significantly associated with the prognosis of patients with cancer, especially in colorectal cancer (CRC). Subsequently, this study further clarified the utility of HOTAIR that downregulation of its expression could result in reduced proliferation and invasion of CRC cells. Mechanistically, HOTAIR upregulated the metabolic enzymes UPP1 by recruiting histone methyltransferase EZH2, thereby increasing the tumor progression. Our results highlight the essential role of HOTAIR in pan-cancer and uridine bypass, suggesting that the HOTAIR/EZH2/UPP1 axis might be a novel target for overcoming CRC. We anticipate that the role of HOTAIR in metabolism could be important in the context of CRC and even exploited for therapeutic purposes.

TFAIP6 facilitates hepatocellular carcinoma cell glycolysis through upregulating c-Myc/PKM2 axis

BackgroundHepatocellular carcinoma (HCC) is the most prevalent liver cancer. Despite of the improvement of therapies, the durable response rate and survival benefit are still limited for HCC patients. It’s urgent to clarify the molecular mechanisms and find therapeutic strategies to improve the clinical outcome. TNFα-stimulated gene-6 (TNFAIP6) plays a critical role in the prognosis of various tumors, but its roles in HCC are still unclear. MethodsQuantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) analysis were employed to evaluate the clinical relevance of TNFAIP6 expressions in HCC patients. Cell counting kit-8 (CCK-8), Edu assay, and transwell assay were performed to evaluate the malignancy of HCC cells. Glucose uptake, lactate production, ATP production, extracellular acidification rate (ECAR) by Seahorse XF analyzer were employed to evaluate the role of TNFAIP6 in the regulation of aerobic glycolysis. The expressions of key proteins involved in glycolysis were examined by western blot. Co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation (ChIP) were used for protein-protein interactions or protein-RNA interactions respectively. Knockdown and overexpression of TNFAIP6 in HCC cells were employed for analyzing the functions of TNFAIP6 in HCC. ResultsTNFAIP6 was significantly upregulated in HCC and predicted a poor clinical prognosis. Knockdown of TNFAIP6 inhibited in vitro cell proliferation, invasion, migration, as well as glycolysis in HCC cells. Mechanistically, we clarified that TNFAIP6 interacted with heterogeneous nuclear ribonucleoprotein C (HNRNPC), stabilized c-Myc mRNA and upregulated pyruvate kinase M2 (PKM2) to promote glycolysis. ConclusionsOur study reveals a molecular mechanism by which TNFAIP6 promotes aerobic glycolysis, which is beneficial for malignance of HCC and provides a potential clinical therapy for disease management.

Roles of lncRNA-MALAT1 in the Progression and Prognosis of Gliomas.

Long noncoding RNAs (lncRNAs) represent a large subgroup of RNA transcripts that lack the function of coding proteins and may be essential universal genes involved in carcinogenesis and metastasis. LncRNA metastasis-associated lung adenocarcinoma transcript 1 (lncRNAMALAT1) is overexpressed in various human tumors, including gliomas. However, the biological function and molecular mechanism of action of lncRNA-MALAT1 in gliomas have not yet been systematically elucidated. Accumulating evidence suggests that the abnormal expression of lncRNA-MALAT1 in gliomas is associated with various physical properties of the glioma, such as tumor growth, metastasis, apoptosis, drug resistance, and prognosis. Furthermore, lncRNAs, as tumor progression and prognostic markers in gliomas, may affect tumorigenesis, proliferation of glioma stem cells, and drug resistance. In this review, we summarize the knowledge on the biological functions and prognostic value of lncRNA-MALAT1 in gliomas. This mini-review aims to deepen the understanding of lncRNA-MALAT1 as a novel potential therapeutic target for the individualized precision treatment of gliomas.

A Nomogram for Preoperative Prediction of Vessels Encapsulating Tumor Clusters (VETC) Pattern and Prognosis of Hepatocellular Carcinoma

BackgroundVessels encapsulating tumor clusters (VETC) pattern of hepatocellular carcinoma (HCC) are associated with unfavorable prognosis. This study aimed to establish a nomogram model to predict VETC patterns based on preoperative CT imaging features. Patients and MethodsPatients who underwent surgical resection between January 1, 2016 and August 31, 2022 were retrospectively included. Predictors associated with VETC pattern were determined by using logistic regression analyses, and a nomogram model was constructed. Prognostic factors associated with recurrence-free survival (RFS) after surgical resection were identified by using Cox regression analyses. ResultsA total of 84 patients were included for CT analysis. All patients underwent radical surgical resection. AST/ALT >1.07(odds ratio [OR], 4.91; 95% CI: 1.11, 21.68; P<0.05), intratumoral necrosis (OR, 4.99; 95% CI: 1.25, 19.99; P<0.05) and enhancing capsule (OR, 3.32; 95% CI: 1.27, 8.94; P<0.05) were independent predictors of VETC pattern. These features were used for the construction of nomogram model, which showed comparable prediction performance, with AUC value of 0.767 (95%CI [0.662, 0.852]). CK19 status (Hazard ratio [HR], 2.02; 95% CI: 1.06, 3.86; P<0.05), the number of tumors (HR, 3.31; 95% CI: 1.47, 7.45; P<0.05) and VETC pattern (HR, 2.52; 95% CI: 1.31, 4.86; P<0.05) were independent predictors of postoperative RFS. ConclusionA nomogram model based on preoperative CT imaging features could be used for the characterization of VETC pattern, and has prognostic significance for postoperative RFS in patients with HCC.

Underlying bone change in oral squamous cell carcinoma observed from magnetic resonance imaging and computed tomography: Potential implications for tumor aggressiveness and prognosis

Background/purposeIn cases where oral squamous cell carcinoma (OSCC) invades the jawbone, clinicians frequently observe abnormal attenuation on computed tomography (CT) and pathologic signal intensity (SI) on magnetic resonance (MR) imaging of the affected underlying bone marrow. This study introduced a concept of “underlying bone change” to examine its association with clinicopathological features and prognosis of OSCC, as well as its correlation with medullary invasion. Materials and methodsWe enrolled 93 consecutive patients diagnosed with OSCC, who underwent mandibulectomy between 2010 and 2016. CT and MR images, along with electronic medical records, were reviewed to evaluate correlations between underlying bone changes, clinicopathological features, five-year overall survival, and medullary invasion. ResultsOf the 93 patients, 69 (74.2%) exhibited underlying bone sclerosis on CT, and 74 (79.6%) displayed pathological SI on MR images. These underlying bone changes correlated with the T stage and recurrence, but not with overall survival.Medullary invasion, observed in 61 (65.6%) patients, was strongly associated with T and TNM stages and was linked to poorer overall survival.The underlying bone changes on CT and MR images were positively associated with medullary invasion; however, no significant differences were found in the occurrence of underlying bone changes between the subtypes based on the extent of medullary invasion. ConclusionUnderlying bone changes on CT and MR images can provide valuable insights into the aggressiveness of bone invasion by OSCC. Accurate interpretation of these imaging findings might be crucial for correctly delineating surgical margins and preventing the overestimation of tumor extent.

Developing a RiskScore Model based on Angiogenesis-related lncRNAs for Colon Adenocarcinoma Prognostic Prediction

Aim: We screened key angiogenesis-related lncRNAs based on colon adenocarcinoma (COAD) to construct a RiskScore model for predicting COAD prognosis and help reveal the pathogenesis of the COAD as well as optimize clinical treatment Background: Regulatory roles of lncRNAs in tumor progression and prognosis have been confirmed, but few studies have probed into the role of angiogenesis-related lncRNAs in COAD. Objective: To identify key angiogenesis-related lncRNAs and build a RiskScore model to predict the survival probability of COAD patients and help optimize clinical treatment. Methods: Sample data were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. The HALLMARK pathway score in the samples was calculated using the single sample gene set enrichment analysis (ssGSEA) method. LncRNAs associated with angiogenesis were filtered by an integrated pipeline algorithm. LncRNA-based subtypes were classified by ConsensusClusterPlus and then compared with other established subtypes. A RiskScore model was created based on univariate Cox, least absolute shrinkage and selection operator (LASSO) regression and stepwise regression analysis. The Kaplan-Meier curve was drawn by applying R package survival. The time-dependent ROC curves were drawn by the timeROC package. Finally, immunotherapy benefits and drug sensitivity were analyzed using tumor immune dysfunction and exclusion (TIDE) software and pRRophetic package. Results: Pathway analysis showed that the angiogenesis pathway was a risk factor affecting the prognosis of COAD patients. A total of 66 lncRNAs associated with angiogenesis were screened, and three molecular subtypes (S1, S2, S3) were obtained. The prognosis of S1 and S2 was better than that of S3. Compared with the existing subtypes, the S3 subtype was significantly different from the other two subtypes. Immunoassay showed that immune cell scores of the S2 subtype were lower than those of the S1 and S3 subtypes, which also had the highest TIDE scores. We recruited 8 key lncRNAs to develop a RiskScore model. The high RiskScore group with inferior survival and higher TIDE scores was predicted to benefit limitedly from immunotherapy, but it may be more sensitive to chemotherapeutics. A nomogram designed by RiskScore signature and other clinicopathological characteristics shed light on rational predictive power for COAD treatment. Conclusion: We constructed a RiskScore model based on angiogenesis-related lncRNAs, which could serve as potential prognostic predictors for COAD patients and may offer clues for the intervention of anti-angiogenic application. Our results may help evaluate the prognosis of COAD and provide better treatment strategies.

Cervical cancer subtype identification and model building based on lipid metabolism and post-infection microenvironment immune landscape

BackgroundAs the second most common gynecological cancer, cervical cancer (CC) seriously threatens women's health. The poor prognosis of CC is closely related to the post-infection microenvironment (PIM). This study investigated how lipid metabolism-related genes (LMRGs) affect CC PIM and their role in diagnosing CC. MethodsWe analyzed lipid metabolism scores in the CC single-cell landscape by AUCell. The differentiation trajectory of epithelial cells to cancer cells was revealed using LMRGs and Monocle2. Consensus clustering was used to identify novel subgroups using the LMRGs. Multiple immune assessment methods were used to evaluate the immune landscape of the subgroups. Prognostic genes were determined by the LASSO and multivariate Cox regression analysis. Finally, we perform molecular docking of prognostic genes to explore potential therapeutic agents. ResultsWe revealed the differentiation trajectory of epithelial cells to cancer cells in CC by LMRGs. The higher LMRGs expression cluster had higher survival rates and immune infiltration expression. Functional enrichment showed that two clusters were mainly involved in immune response regulation. A novel LMR signature (LMR.sig) was constructed to predict clinical outcomes in CC. The expression of prognostic genes was correlated with the PIM immune landscape. Small molecular compounds with the best binding effect to prognostic genes were obtained by molecular docking, which may be used as new targeted therapeutic drugs. ConclusionWe found that the subtype with better prognosis could regulate the expression of some critical genes through more frequent lipid metabolic reprogramming, thus affecting the maturation and migration of dendritic cells (DCs) and the expression of M1 macrophages, reshaping the immunosuppressive environment of PIM in CC patients. LMRGs are closely related to the PIM immune landscape and can accurately predict tumor prognosis. These results further our understanding of the underlying mechanisms of LMRGs in CC.

Post-surgery statin use contributes to favorable outcomes in patients with early breast cancer

BackgroundStatins are a group of lipid-lowering drugs with pleiotropic effects that include, but are not limited to the inhibition of cholesterol synthesis resulting in a wide range of anti-inflammatory, anti-tumor, immunomodulatory, and anti-thrombotic properties. This study aimed to determine the impact of the prior to- or after- breast surgery usage of statins on the tumor prognosis in breast cancer (BC) patients. MethodsA cohort of patients diagnosed with early invasive ductal BC (n=301) at the Hospital Italiano de Buenos Aires, Argentina, with a minimum follow-up period of 10 years after the surgical procedure were included and stratified according to the time of use of statins and type of statin used. Then, local relapse-free survival (RFS), metastasis-free survival (MFS), bone metastasis-free survival (BMFS), visceral metastasis-free (VMFS), mixed metastasis (bone and visceral)-free survival (mix-MFS) and overall survival (OS) were analyzed. ResultsStatins usage after breast surgery was related with lesser metastatic occurrence (p=0.017), lower number of metastatic foci (p=0.034) and fewer dead events (p=0.041), as well as longer MFS (p=0.013) and OS (p=0.027). When stratified by the nature of statins (hydrophilic or lipophilic), only the relatively hydrophilic statin rosuvastatin (ROSU) had an impact on the increase of MFS and OS (p=0.018 and p=0.030, respectively). ConclusionPost-surgery statins usage was associated with increased MFS and OS, with increased benefits of ROSU over simvastatin (SIM) or atorvastatin (ATOR). These results set the rationale for additional studies addressing the use of statins, and particularly, rosuvastatin, to improve the outcome of BC patients.