High Risk Of Cancer Recurrence Research Articles

Combined Aerobic and Resistance Training Improves Body Composition, Alters Cardiometabolic Risk, and Ameliorates Cancer-Related Indicators in Breast Cancer Patients and Survivors with Overweight/Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Breast cancer survivors with obesity are at a high risk of cancer recurrence, comorbidity, and mortality. This review aims to systematically evaluate the effects of combined aerobic and resistance training (CART) on body composition, lipid homeostasis, inflammation, adipokines, cancer-related fatigue, sleep, and quality of life in breast cancer patients and survivors with overweight/obesity. An electronic search was conducted in PubMed, Web of Science, Scopus, Science Direct, Cochrane, and Google Scholar databases from inception up to January 8, 2024. Randomized controlled trials (RCTs) meeting the inclusion criteria were selected for the analysis. The Cochrane risk of bias tool was used to assess eligible studies, and the GRADE method to evaluate the quality of evidence. A random-effects model was used, and data were analyzed using mean (MD) and standardized mean differences (SMD) for continuous variables with 95% confidence intervals (CI). We assessed the data for risk of bias, heterogeneity, sensitivity, reporting bias, and quality of evidence. A total of 17 randomized controlled trials were included in the systematic review involving 1,148 female patients and survivors (mean age: 54.0 ± 3.4 years). The primary outcomes showed significant improvements in body mass index (SMD -0.57 kg/m2, p = 0.04), body fat (SMD -0.50%, p = 0.02), fat mass (SMD -0.63 kg, p = 0.04), hip circumference (MD -3.14 cm, p = 0.02), and fat-free mass (SMD 1.03 kg, p < 0.001). The secondary outcomes indicated significant increases in high-density lipoprotein cholesterol (MD -0.05 mmol/L, p = 0.008), natural killer cells (SMD 0.42%, p = 0.04), reductions in triglycerides (MD -81.90 mg/dL, p < 0.01), total cholesterol (SMD -0.95 mmol/L, p < 0.01), tumor necrosis factor α (SMD -0.89 pg/mL, p = 0.03), and leptin (SMD -0.63 ng/mL, p = 0.03). Also, beneficial alterations were found in cancer-related fatigue (SMD -0.98, p = 0.03), sleep (SMD -1.17, p < 0.001), and quality of life (SMD 2.94, p = 0.02) scores. There was very low to low confidence in the estimated effect of most of the outcomes. The present findings reveal that CART could be considered an adjunct therapy in supporting the conventional clinical approach observed following exercise. However, further high-quality research is needed to evaluate whether CART would be a valuable intervention to lower aggressive pharmacologic use in breast cancer patients with overweight/obesity.

Abstract PO2-01-13: Clinico-Pathological and Molecular Characterization of Early Hormone Receptor-Positive Breast Cancer in Young Women

Abstract Introduction Premenopausal women diagnosed with hormone receptor-positive (HR+)/HER2-negative (HER2-) early breast cancer (EBC) face a significantly higher risk of cancer recurrence and mortality compared to older women, particularly those diagnosed under the age of 40. The underlying causes behind this disparity remain largely unknown. Material and methods We retrospectively select tumour samples from patients (pts) diagnosed with HR+/HER2- EBC at Hospital Clinic (Barcelona, Spain) from May 2014 to March 2020 who had a PAM50/Prosigna assay (Veracyte) previously performed. This assay examines the expression of 50 genes involved in important breast cancer signaling pathways, as well as the intrinsic subtypes (IS) and the Risk of Recurrence (ROR) score. Our primary objective was to compare the distinct clinicopathological and molecular characteristics of HR+/HER2- EBC between two age groups: patients under 40 years old (Young EBC or YEBC) and those 40 years old and above (Older EBC or OEBC). Disease-free survival (DFS) was defined as the time between diagnosis and the first recurrence. Comparisons between groups were carried out using chi-square tests (categorical variables). Additionally, we performed a two-class unpaired Significance Analysis of Microarrays (SAM) with a false discovery rate (FDR) less than 5% to identify genes with significantly different expression between YEBC and OEBC. The statistical significance level was set at less than 0.05. Results A total of 441 tumor samples from 420 patients were included in the analysis, with 5% (22/441) corresponding to YEBC. With a median follow-up of 64.5 months, there were 20 breast cancer (BC) recurrences (4.8%), 12 second cancers (2.9%) and 5 BC-related deaths (1.2%), all occurring in the OEBC group. Table 1 provides an overview of the main clinico-pathological and molecular characteristics. YEBC tended to have larger tumors, with 45.5% (10/22) measuring over 2 cm compared to 36.1% (151/419) in OEBC (p=0.376). YEBC also had a higher proportion of grade 3 tumors (18.18% versus 3.1% in OEBC, p=0.418) and lower expression of estrogen receptor (ER) as determined by immunohistochemistry (mean of 72.28% vs 88.36%, p=0.004). Regarding the PAM50 IS, there was a difference observed between YEBC and OEBC (p &amp;lt; 0.001). Specifically, YEBC patients exhibited a tendency towards a higher proportion of Luminal B tumors (54.6% versus 38.9% in OEBC, p=0.144), as well as non-Luminal subtypes such as Basal-like (18.2% versus 0.95% in OEBC, p&amp;lt; 0.001) and HER2E (4.6% versus 0.7% in OEBC, p=0.186). YEBC tended to have higher ROR (p=0.167), and to receive chemotherapy in a higher proportion, especially in the intermediate-risk group (p=0.004). In YEBC tumours, SAM analysis (p &amp;lt; 0.05) showed an overexpression of genes mainly related with proliferation (i.e., RRM2, MELK, MIK67), cell cycle progression (i.e., KNTC2, CDC20, MYBL2) and apoptosis inhibition (i.e., BIRC5). In OEBC there were an overexpression of genes related with the oestrogen receptor-signalling pathway (i.e., ESR1, NAT1, FOXA1, PGR). Luminal B tumours in YEBC showed an upregulation of genes related to proliferation, migration, and poor prognosis (i.e., KRT17, KRT5) compared to OEBC. However, since there were no recurrences in the YEBC group, differences in terms of DFS between the groups could not be calculated. Principio del formulario Final del formulario Conclusions YEBC exhibited a more advanced stage and a more aggressive intrinsic phenotype compared to OEBC. Additionally, these tumors showed a tendency to upregulate genes involved in proliferation, cell cycle progression, and survival, while downregulating genes related to hormone signaling pathways. These molecular characteristics may help explain the worse prognosis of YEBC compared to OEBC. However, further research is necessary to delve into the differential genomic characteristics that contribute to the unfavorable prognosis observed in patients diagnosed with HR+ EBC before the age of 40. Key clinical and molecular features in 441 biopsies Citation Format: Francisco Javier Muñoz-Carrillo, José Antonio Sola, Carme Crous, Esther Sanfeliu, Isabel Garcia-Fructuoso, Elia Seguí, Teresa Gorría, Raquel Gómez-Bravo, Barbara Adamo, Tomás Pascual, Olga Martínez-Sáez, Francesco Schettini, Pablo Rivera, Rosalía Cayuela, Montserrat Muñoz, Núria Chic, Maria Vidal. Clinico-Pathological and Molecular Characterization of Early Hormone Receptor-Positive Breast Cancer in Young Women [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 PO2-01-13.

Abstract 2584: Decoding colon cancer recurrence: Unveiling accurate predictions with attention-guided deep neural networks on histopathological whole slide images

Abstract Background: Up to 40% of colon cancer patients are at high risk of cancer recurrence, yet accurate and timely prediction tools are lacking. Leveraging whole slide images (WSIs) and deep learning models, we aimed to develop precise algorithm for prediction of colon cancer recurrence. Thus, enables risk stratification for optimized therapeutic interventions and improved health outcomes. Design: We designed an attention-based deep learning model for predicting colon cancer recurrence on paraffin-embedded, hematoxylin and eosin-stained colon tissue biopsies of digital slides. The WSIs were downloaded from the TCGA dataset, and preprocessed for color normalization, tissue segmentation, tilling, and histopathological features extraction. The entire dataset was then labeled based on cancer recurrence status, and divided into training (70%), validation (15%), and testing sets (15%). The model's performance was then evaluated by standard evaluation metrics, including receiver operating characteristic Area Under the Curve (AUC) and accuracy, on the training, validation, and testing datasets, where interpretability attention heatmaps were applied to gain insights into specific histological features and patterns involved in the model's decision-making process. The study is supported by the NIH-NCI-T32 for Next Generation Pathologists Program at our institution. Results: A total of 350 WSIs were included and labeled into two classes: post-therapeutic colon cancer recurrence and no recurrence. The tissue segmentation process involved converting RGB images to HSV color space, applying a median blur filter (kernel size: 7), and performing thresholding using Otsu's method. The extracted features were utilized to train and construct a Clustering-constrained Attention Multiple Instance Learning (CLAM) model. The model demonstrated consistent performance across the validation and testing datasets, achieving an AUC of 0.85 with an accuracy of 0.83 on the validation set, and an identical AUC of 0.85 with an accuracy of 0.83 on the testing set, indicating the model's robust ability to identify patients at risk of cancer recurrence. Conclusion: The study demonstrates the strong performance of our deep learning model in accurately identifying patients at risk for colon cancer recurrence based on H&amp;E WSIs. This capability paves the way for optimizing therapeutic interventions and implementing effective surveillance strategies. Consequently, highlighting the crucial role of pathologists in collaborating with the oncologist for optimizing the management of colon cancer care in the era of personalized medicine. Citation Format: Mohammad K. Alexanderani, Mohamed Omar, Matthew Greenblatt, Ethel Cesarman, Maria T. Diaz-Meco, Jorge Moscat, Luigi Marchionni. Decoding colon cancer recurrence: Unveiling accurate predictions with attention-guided deep neural networks on histopathological whole slide images [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 2584.

Factors associated with recurrence in patients with oral cancer in Mongolia

IntroductionIn Mongolia, there has been limited research on the posttreatment survival rate, recurrence, and occurrence of oral cancer. The goal of this study is to investigate the risk factors that contribute to the recurrence of oral cancer to increase survival rates, facilitate early detection, and improve treatment accuracy.MethodA retrospective cohort method was used, with medical records from 173 patients diagnosed with squamous cell carcinoma of the mouth at the National Cancer Center of Mongolia’s Department of Head and Neck Surgery, Radio, and Chemotherapy between 2012 and 2017. The Mongolian National University of Medical Sciences’ Research Ethics Committee approved the project.ResultsThe findings revealed that 109 cases (63.0%) were men and 64 (37.0%) were females, with a large proportion of patients (28.3%) falling between the ages of 61 and 70. Men had a 3.8 times higher risk of cancer recurrence than women (OR = 3.79, CI = 1.24–11.57). Furthermore, lymph node metastases and treatment were linked to oral cancer recurrence.ConclusionThis study offers light on the factors that influence the recurrence of oral cancer, giving useful insights for improving patient outcomes through early detection and proper treatment.

Identification and Economic Evaluation of Differentiated Thyroid Cancer Care Consumption Patterns Using Sequence Analysis.

Objectives: This study aims to assess the impact of care consumption patterns and individual characteristics on the cost of treating differentiated thyroid carcinoma (DTC), in France, with a specific emphasis on socioeconomic position. Methods: The methodology involved a net cost approach utilising cases from the EVATHYR cohort and controls from the French National Health Insurance database. Care consumption patterns were created using Optimal Matching and clustering techniques. The individual characteristics influence on patterns was assessed using multinomial logistic regression. The individual characteristics and patterns influence on care costs was assessed using generalised estimating equations. Results: The findings revealed an average cost of €13,753 per patient during the initial 3years. Regression models suggested the main predictors of high DTC specific care consumption tended to include having a high risk of cancer recurrence (OR = 4.97), being a woman (OR = 2.00), and experiencing socio-economic deprivation (OR = 1.26), though not reaching statistical significance. Finally, high DTC-specific care consumers also incurred higher general care costs (RR = 1.35). Conclusion: The study underscores the increased costs of managing DTC, shaped by consumption habits and socioeconomic position, emphasising the need for more nuanced DTC management strategies.

Stratification of Stage II Colon Cancer Using Recurrence Prediction Value: A Multi-institutional International Retrospective Study.

To create a recurrence prediction value (RPV) of high-risk factor and identify the patients with high risk of cancer recurrence. There are several high-risk factors known to lead to poor outcomes. Weighting each high-risk factor based on their association with increased risk of cancer recurrence can provide a more precise understanding of risk of recurrence. We performed a multi-institutional international retrospective analysis of patients with Stage II colon cancer patients who underwent surgery from 2010 to 2020. Patient data from a multi-institutional database were used as the Training data, and data from a completely separate international database from two countries were used as the Validation data. The primary endpoint was recurrence-free survival (RFS). A total of 739 patients were included from Training data. To validate the feasibility of RPV, 467 patients were included from Validation data. Training data patients were divided into RPV low (n = 564) and RPV high (n = 175). Multivariate analysis revealed that risk of recurrence was significantly higher in the RPV high than the RPV low (Hazard ratio (HR) 2.628; 95% confidence interval (CI) 1.887-3.660; P < 0.001). Validation data patients were divided into two groups (RPV low, n = 420) and RPV high (n = 47). Multivariate analysis revealed that risk of recurrence was significantly higher in the RPV high than the RPV low (HR 3.053; 95% CI 1.962-4.750; P < 0.001). RPV can identify Stage II colon cancer patients with high risk of cancer recurrence world-wide.

Association of ctDNA detection and recurrence assessment in patients with neoadjuvant treatment.

The utilization of neoadjuvant therapy is progressively expanding in various clinical settings. However, the absence of a clinically validated biomarker to evaluate the treatment response remains a significant challenge in the field. Circulating tumor DNA (ctDNA) detection, a novel and emerging monitoring approach in the field of oncology, holds promise as a potential prognostic biomarker for patients with cancer. This meta-analysis investigated the clinical significance of ctDNA detection as a predictive tool for cancer recurrence in patients receiving neoadjuvant treatment. A comprehensive systematic literature search was conducted using public databases to identify relevant studies that investigated the association between ctDNA detection and cancer recurrence in patients receiving neoadjuvant treatment. Hazard ratios (HRs) and their corresponding 95% confidence intervals (95% CI) were calculated to assess the relationship between cancer recurrence and relevant factors. Cancer recurrence was considered the primary outcome. A total of 23 studies encompassing 1590 patients across eight different cancer types were included in the final analysis. Positive ctDNA detection was significantly associated with higher cancer recurrence, especially at post-neoadjuvant treatment and post-surgery time points. The risk values for the different cancer categories and geographic areas also differed significantly. Our comprehensive meta-analysis revealed a significant positive correlation between ctDNA detection and a higher risk of cancer recurrence in patients receiving neoadjuvant treatment. In addition, the risk of recurrence was influenced by variations in cancer type, timing of detection, and geographic region. These findings highlight the promising clinical applicability of ctDNA as a prognostic marker and monitoring approach for patients with cancer. However, the precise mechanism is unknown and more evidence is needed for further research.

Nano selenium-doped TiO2 nanotube arrays on orthopedic implants for suppressing osteosarcoma growth.

Osteosarcoma, the most common primary malignant bone tumor, is characterized by malignant cells producing osteoid or immature bone tissue. Most osteosarcoma patients require reconstructive surgery to restore the functional and structural integrity of the injured bone. Metal orthopedic implants are commonly used to restore the limb integrity in postoperative patients. However, conventional metal implants with a bioinert surface cannot inhibit the growth of any remaining cancer cells, resulting in a higher risk of cancer recurrence. Herein, we fabricate a selenium-doped TiO2 nanotube array (Se-doped TNA) film to modify the surface of medical pure titanium substrate, and evaluate the anti-tumor effect and biocompatibility of Se-doped TNA film. Moreover, we further explore the anti-tumor potential mechanism of Se-doped TNA film by studying the behaviors of human osteosarcoma cells in vitro. We provide a new pathway for achieving the anti-tumor function of orthopedic implants while keeping the biocompatibility, aiming to suppress the recurrence of osteosarcoma.

Associations between body mass index with cancer recurrence and all-cause mortality among survivors of breast cancer.

12074 Background: It is widely recognized that obesity is associated with increased breast cancer incidence. While body mass index (BMI) does not capture measures of body composition, it is routinely collected during clinical care. However, we do not know whether BMI at breast cancer diagnosis affects cancer recurrence or all-cause mortality. This study aims to investigate the associations between clinical categories of BMI, cancer recurrence, and all-cause mortality in this population. Methods: All breast cancer survivors treated at Northwestern Medicine on or after 1/1/2005 were included. We applied the WHO classification of BMI (kg/m2): underweight ( &lt; 18.5), normal (18.5-24.9), overweight (25-29.9), class I obesity (30-34.9), class II obesity (35-39.9), and class III obesity (≥ 40). Cox proportional hazards models were used to determine the associations between BMI category at baseline and cancer recurrence plus all-cause mortality for breast cancer survivors. Models were adjusted for potential confounders including age, gender, race, ethnicity, histological grade, clinical stage, chemotherapy use, smoking, alcohol use, history of coronary artery disease, and history of Diabetes Mellitus. Results: Among all the 20,322 breast cancer survivors, 1,371 all-cause deaths and 1,183 cancer recurrences were observed. For patients aged 55 and above at diagnosis, there were 964 deaths and 632 cancer among 11,818 cases. When compared with a normal BMI (18.5-24.9), a BMI of 40 and above is associated with a higher risk of all-cause mortality among stage 1 breast cancer survivors (HR 1.90, 95 % CI 1.17-3.09), whereas a BMI of lower than 18.5 is associated with a higher risk of all-cause mortality among stage 4 breast cancer patients (HR 3.21, 95 % CI 1.24-8.30). For cancer recurrence, when compared with a normal BMI (18.5-24.9), a BMI of 40 and above is associated with a higher risk of cancer recurrence among stage 0 breast cancer survivors (HR 3.78, 95 % CI 1.21-11.81) and a BMI of 35 to 39.9 is associated with a higher risk of cancer recurrence among stage 3 breast cancer patients (HR 1.91, 95 % CI 1.01-3.61). We did not observe effect modification for either association by age at diagnosis using a cut-point of 55 years, which is considered as reaching postmenopausal status. Conclusions: Higher levels of obesity are associated with a higher mortality risk among early-stage breast cancer survivors whereas underweight is associated with a higher mortality risk for terminal-stage breast cancer. The associations between high-class obesity and increased risk of cancer recurrence were observed among stage 0 and stage 3 breast cancer survivors. These findings emphasize the importance of BMI as a tool for monitoring the health of breast cancer survivors. However, further study is needed to better understand the impact of BMI, and more importantly body composition, on the health and longevity of breast cancer survivors.

Relationship between homologous recombination deficiency and clinical features of breast cancer based on genomic scar score.

Homologous recombination deficiency (HRD) phenotype will sensitize tumors to poly (ADP-ribose) polymerases inhibitors and platinum. However, previous studies did not focus on the prevalence of HRD among Chinese breast cancer (BC) patients. One hundred and forty-seven BC patients were included in this study. Their HRD status was assessed by Genomic Scar Score (GSS), which was determined according to the length, site, and type of copy number. HRD was defined as positive when a harmful BRCA1/2 mutation was detected or GSS ≥50. Our data revealed that 9.5% of the 147 patients tested positive for BRCA1/2 mutation, while approximately 34.7% were HRD-positive. For triple negative BC (TNBC), HRD positivity rate (60.5%) was higher than Luminal A (5.3%), Luminal B (HER2-) (28.8%), and Luminal B (HER2+) (31.6%) subgroups. HRD-positive tumors were more likely to be ER/PR-negative and exhibited higher Ki-67 expression. 50.0% of the HRD-positive patients achieved pathologic complete remission (pCR) after neoadjuvant therapy. HRD-positive patients tended to have a higher risk for cancer recurrence or metastasis compared to HRD-negative patients (29.4% vs. 13.5%). We investigated the HRD status among Chinese BC patients using an HRD detection tool developed based on the Chinese population. The clinical characteristics, pathological profile, family history pattern, neoadjuvant efficacy, and disease progression events of HRD-positive and negative patients were described and compared. Thus, our data provided an evidence-based basis for applying the original HRD assay in Chinese BC.

Understanding cancer treatment decision making among cancer survivors.

e24076 Background: Nearly 20% of U.S. cancer survivors develop late cardiovascular disease (CVD) as a result of cardiotoxic cancer treatments. Patients and providers may consider alternative treatment options to lower cardiotoxicity risk, which may present a trade-off between reducing relatively near-term relapse/recurrence vs. preventing long-term CVD. Patients’ decision-making processes (e.g., delay discounting, risk perceptions for CVD vs. cancer) may affect such choices. However, these decision-making factors are not well understood in this context; nor is their association with treatment selection. Methods: In a cross-sectional survey using the online survey vendor Prolific, we recruited 443 U.S. cancer survivors (any type.) Using logistic regression, we assessed how survivors’ risk perceptions (deliberative, affective, and intuitive) for cancer vs. CVD were associated with decisions between two hypothetical cancer treatments involving different risk tradeoffs: Treatment 1: 5% chance of near-term cancer recurrence &amp; 10% chance of CVD; Treatment 2: 10% chance of near-term cancer recurrence &amp; 5% chance of CVD. We explored effects of delay discounting by randomizing participants to information describing immediate vs. delayed (10 years post-treatment) development of CVD. Results: Survivors ( Mage = 48, range 18-93) were, on average, 10.8 years from diagnosis. More survivors ( 72% v. 28%) chose Treatment 1 (lower cancer recurrence risk but higher risk of cardiotoxicity) than Treatment 2 (lower risk of cardiotoxicity but higher risk of cancer recurrence) . Immediacy of CVD development (immediate vs. delayed) was not associated with treatment selection (p = 0.12.) Modeling separately, higher levels of affective risk perception (“worry”) about cancer, but not worry about CVD, was associated with increased odds of choosing Treatment 1 ( OR= 1.25, p= 0.014.). Modeled together, cancer worry was associated with increased odds, whereas CVD worry was associated with decreased odds, of choosing Treatment 1 ( OR-cancer= 1.35, p= 0.002; OR-CVD= 0.76, p= 0.011). Neither deliberative nor experiential risk perceptions were significantly associated with treatment choice. Conclusions: Cancer survivors were more likely to select treatment that minimizes cancer recurrence rather than comparative CVD—regardless of the described immediacy of cardiotoxicity. Further, treatment decision also depended upon both cancer- and CVD-related worry but not deliberative or experiential risk perceptions. Comparatively to CVD, cancer is often more affectively-laden, especially among cancer survivors. These results suggest that in treatment discussions, clinicians may need to address not only the probabilities of treatment outcomes, but patients’ relative worries about cancer and cardiotoxicity.

Abstract 86: Chemotherapy-induced microenvironmental changes promote dormant breast cancer cell outgrowth in adipose tissue

Abstract Despite the high 5-year survival rate for early-stage breast cancer patients, late recurrence of the disease remains a major challenge. Breast cancer can recur in approximately 20-25% of patients months to decades after an initial diagnosis, and there are few biomarkers that predict which patients will suffer from the recurrent disease. Unfortunately, this means clinicians and their patients must take a frustrating wait-and-see approach. Notably, disseminated tumor cells (DTCs) are frequently detected in early-stage breast cancer patients, and their presence predicts a higher chance of recurrence. However, why some patients with DTCs recur while others do not remains a mystery. Previous work has suggested that changes in the tumor microenvironment (TME) play an important role in the maintenance of tumor cell dormancy. When assessing the impact of doxorubicin (DOXO), a chemotherapeutic agent often used to treat breast cancer patients, on the TME, we noted that DOXO treatment led to the activation of dormant breast cancer cells in the visceral adipose tissue. Moreover, in accordance with the clinical observation that obese patients suffer a higher risk of cancer recurrence, we found that diet-induced obesity further exacerbated DOXO ability to reactivate dormant breast cancer cells in adipose tissue and this reactivation was associated with robust macrophage infiltration. These findings were interesting in light of our observation that tumor cells can metastasize to visceral fat depots in breast cancer patients. To understand why macrophages were recruited to the adipose tissue and how they led to tumor cell reactivation, we profiled the microenvironmental changes in visceral fat from Veh- and Doxo- treated mice using single-cell RNA-sequencing and found that the infiltrating macrophages exhibited unique pro-inflammatory and lipid-regulatory phenotypes. Our study provides novel insights into how TME impacts breast cancer dormancy and also highlights the importance of adipose tissue as a unique reservoir that potentiates cancer relapse. Citation Format: Qihao Ren, Jiayu Ye, Xiaoyu Yuan, Sheila Stewart. Chemotherapy-induced microenvironmental changes promote dormant breast cancer cell outgrowth in adipose tissue [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 86.

General Anesthetics in CAncer REsection Surgery (GA-CARES) randomized multicenter trial of propofol vs volatile inhalational anesthesia: protocol description

BackgroundStudies indicate that patients can be “seeded” with their own cancer cells during oncologic surgery and that the immune response to these circulating cancer cells might influence the risk of cancer recurrence. Preliminary data from animal studies and some retrospective analyses suggest that anesthetic technique might affect the immune response during surgery and hence the risk of cancer recurrence. In 2015, experts called for prospective scientific inquiry into whether anesthetic technique used in cancer resection surgeries affects cancer-related outcomes such as recurrence and mortality. Therefore, we designed a pragmatic phase 3 multicenter randomized controlled trial (RCT) called General Anesthetics in Cancer Resection (GA-CARES).MethodsAfter clinical trial registration and institutional review board approval, patients providing written informed consent were enrolled at five sites in New York (NY) State. Eligible patients were adults with known or suspected cancer undergoing one of eight oncologic surgeries having a high risk of cancer recurrence. Exclusion criteria included known or suspected history of malignant hyperthermia or hypersensitivity to either propofol or volatile anesthetic agents. Patients were randomized (1:1) stratified by center and surgery type using REDCap to receive either propofol or volatile agent for maintenance of general anesthesia (GA). This pragmatic trial, which seeks to assess the potential impact of anesthetic type in “real world practice”, did not standardize any aspect of patient care. However, potential confounders, e.g., use of neuroaxial anesthesia, were recorded to confirm the balance between study arms. Assuming a 5% absolute difference in 2-year overall survival rates (85% vs 90%) between study arms (primary endpoint, minimum 2-year follow-up), power using a two-sided log-rank test with type I error of 0.05 (no planned interim analyses) was calculated to be 97.4% based on a target enrollment of 1800 subjects. Data sources include the National Death Index (gold standard for vital status in the USA), NY Cancer Registry, and electronic harvesting of data from electronic medical records (EMR), with minimal manual data abstraction/data entry.DiscussionEnrollment has been completed (n = 1804) and the study is in the follow-up phase. This unfunded, pragmatic trial, uses a novel approach for data collection focusing on electronic sources.Trial registrationRegistered (NCT03034096) on January 27, 2017, prior to consent of the first patient on January 31, 2017.

Prognostic impact ofmicrometastasis in patients with esophageal cancer.

Squamous cell carcinoma (SCC) oftheesophagus and adenocarcinoma oftheesophago-gastric junction (AEG) are diseases with poor prognosis. Despite radical surgery having been carried out, many patients are at risk ofcancer recurrence, especially with thepresence ofmetastases in thelymph nodes. The study involved 60 patients suffering from SCC and AEG who had lymph nodes surgically removed between 2012 and 2018. Only lymph nodes with N0 status were subjected to immunohistochemistry examination. Histopathological criteria were used for thediagnosis ofmicrometastases (MM), defined as tumor cells or cell clusters of0.2-2 mm diameter in thelymph node and tumor cell microinvolvement defined as free-floating neoplastic cells or cell clusters within thesub-capsular sinus or intramedullary sinuses ofthelymph node. Atotal of1130 lymph nodes were removed during surgery, with an average of22 lymph nodes per patient (range 8-58). Micrometastases were found in 7 (11.66%) patients: 6 (10.0%) with AEG and 1 (1.66%) with SCC, representing astatistically significant difference p = 0.017. Multivariate analysis ofthestudy group did not confirm thedependence oftheMM on theT features ( p = 0.7) or G ( p = 0.5). In aCox regression analysis, MM were not arisk factor for death, HR: 2.57 (0.95; 7.00), p = 0.064. There was no difference in overall survival for patients with MM (N (+)) and those without (N0), p = 0.055, but there was astatistically significant difference in time ofrelapse between patients with and without MM ( p = 0.049). Patients with theN (+) status are at high risk ofcancer recurrence, and therefore we believe that complementary treatment should be considered in this group.

Study protocol of an open-label prospective phase II umbrella study of precise neoadjuvant therapy for patients with stage II-IIIB resectable non-small cell lung cancer (PURPOSE).

The outcomes of locally advanced non-small cell lung cancer (LA-NSCLC) are unfavorable mainly due to a high risk of cancer recurrence. Only around 5% of patients can benefit from perioperative chemotherapy which is the current standard treatment. Recently, promising results with neoadjuvant targeted and immune-therapy therapy have been seen. However, most clinical trials are looking for patients eligible for certain drugs, instead of seeking suitable treatments for certain patients. Therefore, it is necessary to look for more efficient perioperative therapies to increase resectability, reduce recurrence and improve prognosis. The study is an open-label, prospective, phase II, umbrella trial, enrolling patients diagnosed with treatment-naïve potentially resectable Stage II-IIIB NSCLC. Next-generation sequencing (NGS) using a 68-gene panel is performed for biopsies of tumor tissues from eligible patients. Enrolled patients are then stratified into six independent cohorts based on the status of gene mutations and PD-L1 status in tumor tissues, that is, ①EGFR 19del group, ②EGFR 21 L858R group, ③EGFR rare mutation group, ④Other driver mutation group, ⑤Drive mutation-negative group with PD-L1≥1%, ⑥Drive mutation-negative group with PD-L1<1%. A Simon's two-stage design is performed in each cohort independently and patients receive corresponding standard therapies accordingly. We aim to enroll 26 patients in each cohort and totally 156 patients will be enrolled. The primary endpoint is objective response rate (ORR). Secondary endpoints include oncological prognosis and perioperative outcomes. Exploratory endpoint is to investigate patient-specific minimal residual disease (MRD) in predicting treatment efficacy and oncological prognosis. This is the first umbrella trial focusing on the safety and efficacy of precise neoadjuvant therapy for patients diagnosed with potentially resectable LA-NSCLC based on NGS results. The results of this trial would help improve overall treatment results in LA-NSCLC patients. Chinese Clinical Trial Registry. Trial registration number: ChiCTR2100053021. There is no neoadjuvant umbrella trial focusing on LA-NSCLCs. This is the first neoadjuvant umbrella trial, using a precise individualized approach and seeking suitable drugs for LA-NSCLC patients, with the aim to improve overall treatment outcomes. https://www.chictr.org.cn/, identifier ChiCTR2100053021.

169 (PB049) - Ornithine decarboxylase as a new target for improving the effect of KRAS-G12C inhibitors in non-small cell lung cancer cells

Non-small cell lung cancer (NSCLC) is the deadliest and most prevalent form of lung cancer. Mutations in the Kirsten rat sarcoma viral oncogene (KRAS) homolog gene exist in 20–30% of NSCLC and are associated with a poor prognosis and a high risk of cancer recurrence. Also, the G12C point mutation in KRAS is considered a driver mutation in NSCLC.

Long-term Recurrence and Progression Patterns in a Contemporary Series of Patients with Carcinoma In Situ of the Bladder With or Without Associated Ta/T1 Disease Treated with Bacillus Calmette-Guérin: Implications for Risk-adapted Follow-up

BackgroundLimited data are available on patients with carcinoma in situ (CIS) of the bladder managed according to current clinical practice guidelines. ObjectiveTo assess the patterns of recurrence, progression to muscle-invasive bladder cancer (MIBC), and upper tract urothelial carcinoma (UTUC) in patients with CIS, and to compare the effectiveness of adequate versus inadequate bacillus Calmette-Guérin (BCG) immunotherapy. Design, setting, and participantsA retrospective analysis of 386 patients with CIS of the bladder with or without associated pTa/pT1 disease treated with BCG between 2008 and 2015. Outcome measurements and statistical analysisKaplan-Meier estimations and an inverse probability of treatment weighting (IPTW)-Cox regression were performed to compare recurrence-free survival (RFS) and progression-free survival (PFS) and UTUC incidence over time for patients who received adequate versus inadequate BCG treatment. Results and limitationsThe median follow-up was 70.5 mo. At 5 and 10 yr, RFS was 82% and 52%, PFS was 93.6% and 75.8%, and UTUC incidence was 1.7% and 2.9%, respectively. Most recurrence (73.6%) and progression (69.1%) events occurred in the first 3 yr of follow-up, while 38.7% of UTUC incident events were recorded after 5 yr of follow-up. IPTW-Cox regression revealed that patients who received BCG treatment had a lower risk of recurrence (hazard ratio [HR] 0.21, 95% confidence interval [CI] 0.13–0.34), progression (HR 0.46, 95% CI 0.25–0.87), and UTUC incidence (HR 0.24, 95% CI 0.09–0.64). Limitations include the retrospective design and potential selection bias. ConclusionsPatients with CIS of the bladder show a high risk of recurrence, progression, and UTUC incidence. Most of these outcomes occur during the first 3 yr of follow-up, but a significant proportion of the events occur at long-term follow-up. Although receipt of adequate BCG treatment improves outcomes, intensive and long-term surveillance may be warranted. Patient summaryWe investigated the long-term cancer control outcomes for patients with carcinoma in situ (CIS; cancerous cells that have not spread from where they first formed) of the bladder. Patients with CIS have a high risk of cancer recurrence and progression. Treatment with bacillus Calmette-Guérin (BCG) improves outcomes.

Weakly supervised deep learning for prediction of treatment effectiveness on ovarian cancer from histopathology images.

Despite the progress made during the last two decades in the surgery and chemotherapy of ovarian cancer, more than 70 % of advanced patients are with recurrent cancer and decease. Surgical debulking of tumors following chemotherapy is the conventional treatment for advanced carcinoma, but patients with such treatment remain at great risk for recurrence and developing drug resistance, and only about 30 % of the women affected will be cured. Bevacizumab is a humanized monoclonal antibody, which blocks VEGF signaling in cancer, inhibits angiogenesis and causes tumor shrinkage, and has been recently approved by FDA as a monotherapy for advanced ovarian cancer in combination with chemotherapy. Considering the cost, potential toxicity, and finding that only a portion of patients will benefit from these drugs, the identification of new predictive method for the treatment of ovarian cancer remains an urgent unmet medical need. In this study, we develop weakly supervised deep learning approaches to accurately predict therapeutic effect for bevacizumab of ovarian cancer patients from histopathological hematoxylin and eosin stained whole slide images, without any pathologist-provided locally annotated regions. To the authors' best knowledge, this is the first model demonstrated to be effective for prediction of the therapeutic effect of patients with epithelial ovarian cancer to bevacizumab. Quantitative evaluation of a whole section dataset shows that the proposed method achieves high accuracy, 0.882±0.06; precision, 0.921±0.04, recall, 0.912±0.03; F-measure, 0.917±0.07 using 5-fold cross validation and outperforms two state-of-the art deep learning approaches Coudray et al. (2018), Campanella et al. (2019). For an independent TMA testing set, the three proposed methods obtain promising results with high recall (sensitivity) 0.946, 0.893 and 0.964, respectively. The results suggest that the proposed method could be useful for guiding treatment by assisting in filtering out patients without positive therapeutic response to suffer from further treatments while keeping patients with positive response in the treatment process. Furthermore, according to the statistical analysis of the Cox Proportional Hazards Model, patients who were predicted to be invalid by the proposed model had a very high risk of cancer recurrence (hazard ratio = 13.727) than patients predicted to be effective with statistical signifcance (p<0.05).

Intraoperative radiation therapy for locally advanced and recurrent head and neck cancer.

6058 Background: Intraoperative Radiation Therapy (IORT) allows precise delivery of radiation therapy (RT) to a limited target area at high risk of cancer recurrence while minimizing RT to nearby organs at risk. IORT may be particularly beneficial for patients with locally recurrent head and neck cancer (HNC) in a previously irradiated field and for locally advanced HNC cases, in which obtaining negative surgical margins may be difficult. This study aims to present a single institution experience with IORT for HNC patients. Methods: This study included HNC patients treated consecutively with IORT at our institution between 2014 and 2018. Charts were reviewed for patients’ and tumors’ characteristics, IORT technical details, IORT-induced adverse events, and treatment outcomes. Results: The study included 23 eligible patients. Median patient age was 66 (range 33-91). Tumor sites included parotid gland (43%), lymph nodes (43%), oral tongue (9%), and ear (4%). 52% of patients received IORT upfront with or without postoperative adjuvant external beam radiation therapy (EBRT), while 48% received salvage IORT after local tumor recurrence. The median prescribed IORT dose was 7.5 Gy (range 5-14 Gy) in a single fraction prescribed to 5 mm depth with Flat applicators (median diameter of 5 cm). 92% of patients did not experience wound healing complications. One patient (4%) developed postoperative acute thromboembolic stroke, a second patient (4%) experienced protracted wound healing. At a median follow-up of 36 months (range 2-81), 42% of patients presented with no evidence of disease (NED), overall survival was 54%, 13% of patients were alive with disease, and 46% died with disease. Local-regional recurrence rate was 39% (median time to local recurrence was 18 months, range 2-60), rate of distant metastasis was 43% (median time to distant metastasis was 23 months, range 5-60), and 30% of patients had both local-regional recurrence and distant metastases. The percent of local-regional recurrence and distant metastases among patients receiving salvage IORT was 64% and 73% respectively, compared to 23%, and 15% respectively in those receiving upfront IORT with or without adjuvant EBRT. Conclusions: In this single institution chart review study, IORT to locally advanced and recurrent HN cancer patients was a safe treatment modality, with tumor control comparable to historical EBRT data. Larger prospective studies are needed to further assess the utility of IORT in the management of locally advanced and recurrent HN cancer.

Potential Refinement of Recurrence Score by pSTAT3 Status.

The likelihood of recurrence in breast cancer patients with hormone receptor-positive (HR-positive) tumors is influenced by clinical, histopathological, and molecular features. Recent studies suggested that activated STAT3 (pSTAT3) might serve as a biomarker of outcome in breast cancer patients. In the present work, we have analyzed the added value of pSTAT3 to OncotypeDx Recurrence Score (RS) in patient prognostication. We have found that patients with low RS (<26) and low pSTAT3 might represent a population at a higher risk for cancer recurrence. Furthermore, we have observed that a positive pSTAT3 score alone can be a favorable marker for patients with HR-positive breast cancer under the age of 50. In an era of personalized medicine, these findings warrant further appraisal of chemotherapy benefit in this population.