Cancer Outcomes Research Articles

The effects of muscle factors irisin on lipid metabolism in breast cancer: A possible mechanism anti-tumor mechanism of physical activity

Breast cancer is the most prevalent cancer in the female population and is a significant cause of global cancer deaths in this group. Obesity increases a woman’s risk of developing breast cancer and has a negative impact on prognosis. Metabolic alterations are an important part of the process of cancer migration; invasion and proliferation, with lipids being a major metabolic substrate for rapid cancer progression, capable of influencing the metabolic crosstalk between tumor cells and other cells in the tumor microenvironment. Physical activity-induced irisin affects the progression of obesity-associated breast cancer and is a new indicator for breast cancer diagnosis. Existing evidence suggests a potential inhibitory effect of physical activity-induced irisin on the progression of breast cancer. A strong association exists between obesity and breast cancer progression and outcomes. This paper discusses how physical activity-induced irisin may achieve cancer suppression by affecting lipid metabolic processes between breast cancer cells and cancer-associated adipocytes, and elucidates the molecular pathways involved in the effects of irisin on cancer lipid reprogramming, thereby helping to prevent the metastatic progression of breast cancer, and ultimately improving the survival rate of this patient group.

Assessing the impact of contraceptive use on reproductive cancer risk among women of reproductive age—a systematic review

BackgroundContraceptives play a crucial role in women's reproductive health, their hormonal components may be linked to cancer risks, specifically breast, and gynecological cancers. Given the high usage rates of hormonal contraceptives, it is vital to systematically evaluate their potential impact on cancer outcomes, especially among women with a family history of gynecological cancers.ObjectivesThis study aims to evaluate the evidence on the association between modern contraceptive use and the risk of breast and reproductive cancers (ovarian, endometrial, and cervical cancer) among women of reproductive age, to inform healthcare providers, women, and program managers about cancer outcomes related to contraceptive use.MethodsA systematic review was conducted according to PRISMA guidelines. Searches were performed in databases such as CINAHL, OVID Medline, EMBASE, and more from inception to February 2022. Eligible studies included randomized controlled trials, cohort studies, and case-control studies that compared cancer outcomes between contraceptive users and non-users. Data extraction, quality assessment, and meta-analyses were conducted following predefined protocols. Subgroup and sensitivity analyses examined variations in contraceptive methods, doses, and duration.ResultsA total of 51 studies were included, comprising 2 RCTs and 49 observational studies. The review identified a significant reduction in ovarian and endometrial cancer incidence among contraceptive users. Hormonal contraceptive users had a 36% lower risk of ovarian cancer (RR 0.64, 95% CI 0.60–0.68), with specific reductions seen in combined oral contraceptive users (RR 0.62, 95% CI 0.57–0.68) and hormonal IUD users (RR 0.68, 95% CI 0.48–0.96). The rate ratio of cervical cancer was higher among non- users compared to hormonal contraceptive users when we pooled the results (1.28, 95% CI 1.21, 1.35). No significant association was found between contraceptive use and breast cancer risk among healthy women (RR 1.00, 95% CI 0.94–1.06). However, BRCA1/2 mutation carriers using oral contraceptives showed a heightened risk of breast cancer (HR 1.39, 95% CI 1.15–1.67).ConclusionThis systematic review highlights the protective effects of modern contraceptives against ovarian and endometrial cancers while identifying an increased risk of cervical. No significant breast cancer risk was found for healthy women, but BRCA1/2 mutation carriers faced increased risks. These findings underscore the need for personalized contraceptive counselling that considers cancer risk factors. Further research is needed to explore contraceptive impacts across different genetic profiles and dosing regimens.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, Prospero (CRD42022332647).

OGC SO25 - Tumour Regression Grade (TRG) and Completeness of Resection in patients under esophagectomy for oesophageal Cancer

Abstract Background Oesophageal cancer, including squamous cell carcinoma (SCC) and adenocarcinoma, is challenging due to its aggressive nature and delayed presentation. Neoadjuvant chemotherapy aims to downstage the tumour thus aids in surgery and improves patient outcomes. Complete resection with tumour free resection margins is crucial for cure and survival. Understanding the relationship between tumour regression grade (TRG) and completeness of resection helps improve outcomes in patients with oesophageal cancer. Method This retrospective study was conducted over a period of 4 years (2019-2023). It included all patients over 18 years of age who underwent oesophagectomy for either squamous cell carcinoma (SCC) or adenocarcinoma following neoadjuvant chemotherapy. Tumour Regression Grade (TRG) was defined by the histological report while R1 resection was defined as any margin less than 1 mm. Statistical analysis was performed to evaluate the incidence of complete and incomplete resections across the various TRG groups. Results Study included 214 patients (178 males, 36 females) with a median age of 67 (31-82) years. Of the 214 patients, 201 (93.9%) had adenocarcinoma and 13 (6.1%) had SCC. Complete resection was achieved in 136 patients (63.6%), while 78 (36.4 %) had incomplete resections. TRG distribution in the complete resection group was-TRG 1 (97.6 %), TRG 2 (76.5 %), TRG 3 (67.2 %), TRG 4 (56.1 %), and TRG 5 (31.9 %). The Chi-Square test indicated significant associations between TRG and resection completeness (Chi-Square = 44.229, p < .001; Likelihood Ratio = 51.804, p < .001; Fisher's Exact Test p < .001). Conclusion The study demonstrates a significant correlation between higher TRG scores and incomplete resections in esophagectomy patients’ post-neoadjuvant chemotherapy. We conclude TRG is an important prognostic indicator for surgical outcomes in oesophageal cancer.

The Potential of Plant Polysaccharides and Chemotherapeutic Drug Combinations in the Suppression of Breast Cancer

Breast cancer is the most common cancer affecting women worldwide. The associated morbidity and mortality have been on the increase while available therapies for its treatment have not been totally effective. The most common treatment, chemotherapy, sometimes has dangerous side effects because of non-specific targeting, in addition to poor therapeutic indices, and high dose requirements. Consequently, agents with anticancer effects are being sought that can reduce the side effects induced by chemotherapy while increasing its cytotoxicity to cancer cells. This is possible using natural compounds that are safe and biologically active. There are many reports on plant polysaccharides due to their bioactive and anticancer properties. The use of plant polysaccharide together with a conventional cytotoxic drug may offer wide benefits in cancer therapy, producing synergistic effects, thereby reducing drug dose and, so, its associated side effects. In this review, we highlight an overview of the use of plant polysaccharides and chemotherapeutic drugs in breast cancer preclinical studies, including their mechanisms of anticancer activities. The findings emphasize the potential of plant polysaccharides to improve chemotherapeutic outcomes in breast cancer, paving the way for more effective and safer treatment strategies.

AHP SO07 - Dietetic Outpatient Service to Patients undergoing Oesophagogastric (OG) Surgery for Cancer

Abstract Background Nutrition is a modifiable risk factor impacting surgical outcomes in OG cancer. Its key role influencing health related quality of life is emerging with improved survivorship. Guidelines depicting optimal timing and type of dietetic intervention for this patient group are unclear. In order to best direct dietetic care, optimise timing of nutritional interventions and understand demand for service it is important to reflect on current provision. This audit aimed to describe the dietetic outpatient service to patients undergoing OG Surgery for cancer in a national centre for treatment of oesophageal cancer. Method A retrospective review of dietetic records and statistics. Patients who underwent oesophagectomy (O), gastrectomy (G) or subtotal gastrectomy (STG) for cancer between May 2022- May 2023 were included. Results 63 patients were included: 38 O, 17 TG, 8 STG. 11 were seen by the dietitian at first visit to OG Clinic (9 O, 1 TG, 1 STG) – 6 had an elective feeding tube (FT) inserted for neoadjuvant treatment (5 O, 1 STG). 83% attended a surgical pre-assessment dietetic appointment (36 O, 14 TG, 2 STG). 86% were reviewed within 1 month post O or TG, 75% post STG. 258 dietetic interventions occurred in the first year post-op (median 3.5, range 0-14). 64% in the first 3 months(m) post op, 16% at 3-6m, 10% at 6-9m, 10% at 9-12m. Conclusion In this high nutritional risk group only 18% are assessed by a dietitian at first visit to UGI MDT clinic. There is a successful pathway for immediate peri-operative dietetic care in patients post O and TG. The pathway for STG is less well established. Dietetic interventions are concentrated in the first 3 months after surgery. There is no established protocol to support longer term nutritional needs into survivorship. To inform practice a measure of patient experience and needs would be useful, to explore best delivery format and access routes to future services.

HPB SO27 - Reconsidering Routine Histopathological Examination of Gallbladder Specimens in Cholecystectomy: Optimizing Clinical Practice and Resource Management

Abstract Background Cholecystectomy, the removal of the gallbladder, is a common surgery performed globally. Routine histopathological examination (HPE) of gallbladder specimens post-surgery aims to detect pathologies like gallbladder cancer (GBC). GBC incidence varies by region and ethnicity, with higher risks in women and those over 65. Advanced GBC stages often require surgery, while early stages may only need cholecystectomy. Global HPE practices differ based on resources and GBC rates. This study evaluates the necessity of routine HPE by examining the selective processing of specimens suspected of GBC, ensuring patient safety while potentially optimizing resource use. Method This retrospective cohort study conducted at Redland Hospital, a district general hospital in Australia, investigated the necessity of routine histopathological examination (HPE) for excised gallbladder specimens. Adhering to routine HPE policy, the study encompassed all elective and emergency cholecystectomies performed from January 2023 to December 2023, excluding pediatric cases, concurrent surgical procedures, and those with suspected malignancy. Demographic data, surgery indications, intraoperative findings, histopathological results, and incidental gallbladder cancer (IGC) outcomes were analyzed. Pathology reports and case documentation were reviewed for cancerous pathology indicators. Results Over the one-year study period from January 2023 to December 2023, a total of 266 gallbladder specimens were subjected to histopathological examination (HPE) post-cholecystectomy. Of these, 201 were female and 65 were male, yielding a male-to-female ratio of 3:1. Elective cholecystectomy was performed on 56.4% (150) of patients, while 43.6% (116) underwent emergency procedures. Laparoscopic cholecystectomy (LC) was the primary surgical approach, except for one case requiring conversion to an open procedure. None of the patients exhibited gallbladder carcinoma (GBC); however, 3.3% (9) displayed premalignant histopathological features in their specimens. Conclusion In conclusion, adopting a selective approach, where only gallbladder specimens with macroscopic abnormalities undergo histopathological examination (HPE), seems prudent, especially in regions with low gallbladder cancer (GBC) incidence. Our study, which revealed no cases of GBC, supports this approach. It not only reduces the risk of missing incidental carcinoma in clinically unsuspected cases but also proves cost-effective and reduces the histopathology department workload without compromising patient outcomes. Therefore, we advocate for routine macroscopic examination of gallbladder specimens for abnormalities before HPE submission, particularly in cholecystectomy patients with gallstone disease.

Two-Year Experience of a Center of Excellence for the Comprehensive Management of Non-Small Cell Lung Cancer at a Fourth-Level Hospital in Bogota, Colombia: Observational Case Series Study and Retrospective Analysis

Background: This study aimed to provide a comprehensive analysis of 56 patients admitted to the Lung Cancer Clinical Care Center (C3) at Fundación Santa Fe de Bogotá (FSFB) between 2 May 2022 and 22 April 2024. The focus was on demographic characteristics, smoking history, comorbidities, lung cancer types, TNM classification, treatment modalities, and outcomes. Methods: This observational case series study reviewed medical records and included patients over 18 years with a confirmed diagnosis of non-small cell lung cancer (NSCLC). Data were collected and analyzed for demographics, comorbidities, treatment types, biomolecular profiling, and survival rates. Ethical approval was obtained, and data were anonymized. Results: The mean age was 71.8 years with a female predominance (53.6%). A history of smoking was present in 71.4% of patients. Adenocarcinoma was the most common type (75.0%), followed by squamous cell carcinoma (19.6%). At admission, the most frequent TNM stages were IA2 (17.9%) and IVA (16.1%). One-year survival was 68.8%, and 94.3% of stage I–IIIA patients underwent PET scans. Biomolecular profiling revealed 69.2% non-mutated EGFR, 90.4% ALK-negative, and various PDL-1 expression levels. Immunotherapy was received by 91.4% of patients, with Alectinib and Osimertinib being common. Grade III–IV pneumonitis occurred in 5.4% of patients. Conclusions: The study’s findings align with existing literature, highlighting significant smoking history, common adenocarcinoma, and substantial use of immunotherapy. Limitations include the observational design, small sample size, and short follow-up period, impacting the generalizability and long-term outcome assessment. Future research should address these limitations and explore longitudinal outcomes and emerging therapies.

A06 - OGC LAsting Symptoms after Oesophageal Resectional Surgery (LASORS): Multicentre validation cohort study

Abstract Background Patients are living longer with the long-term morbidity of oncological and surgical therapies as oesophageal cancer outcomes improve. Existing symptomatology and quality of life tools are cumbersome and moreover not designed for the post-treatment survivorship setting. The LASER study identified six key symptoms thought to predict poor health-related quality of life. The current study aimed to validate this six-symptom LAsting Symptoms after Oesophageal Resection (LASOR) clinical tool, and assess its clinical utility. Method Between 2015 and 2019, patients from UK centres who underwent curative-intent oesophageal cancer treatment, and were disease-free at least one year postoperatively, were asked to complete LASOR, EORTC QLQ-C30 and QLQ-OG25 questionnaires. LASOR symptoms (low mood, reduced energy, thoracotomy pain, heartburn, diarrhoea, and bloating after eating) were correlated with EORTC HRQOL scores. Multivariable regression analysis identified symptoms associated with poor HRQoL. Receiver operating characteristic curve analysis was used to validate the LASOR tool. Results 263 patients, spanning a combination of surgical approaches (two-stage, three-stage, left thoracoabdominal, transhiatal), techniques (open, minimally invasive, hybrid), and disease stage, completed the questionnaires. Four of the six LASOR symptoms were associated with poor HRQoL: reduced energy (OR 2.13; 95% CI 1.20-2.87), low mood (OR 1.86; 95% CI 1.4503.12), diarrhoea (OR 1.48; 95% CI 1.06-2.05), and bloating after eating (OR 1.35; 95% CI 1.03-1.77). The LASOR tool produced an area under the curve of 0.85. Conclusion The six-symptom LASOR tool generated a reliable model for identification of patients with a poor HRQOL, with an overall diagnostic accuracy of over 80%. This is the first clinical symptom and quality of life tool to be validated in esophageal cancer patients post-curative treatment. The LASOR tool is straightforward to administer and acceptable to patients. Clinical utility lies both in identifying patients at risk of poor HRQoL and in planning survivorship services.

OGC SO43 - Management of oesophageal adenocarcinoma in the Covid-19 Pandemic – What have we learnt?

Abstract Background The management of oesophageal adenocarcinoma in the UK has been standardised to neoadjuvant chemotherapy followed by surgery. However, during the early phase of the Covid-19 pandemic, oesophagectomy was considered to be too high risk, and alternative treatment options were explored . In our unit, patients were offered definitive chemoradiotherapy with a view to performing salvage oesophagectomy if there was residual disease or disease recurrence. Method We retrospectively screened all patients referred to the UGI MDT between March 2020 to February 2021. Patients included were those with first diagnosis of oesophageal carcinoma, on the curative pathway, planned neoadjuvant FLOT chemotherapy and oesophagectomy then converted to definitive CRT (dCRT). Data collected were patient demographics, cancer staging and cancer outcomes including progression to salvage surgery, disease free survival and overall survival at 1 year and 3 years post treatment. Results Ten patients with distal or junctional adenocarcinoma were included. Median age at diagnosis was 70.5 years. Five patients had T3 or T4 disease. All patients had N0 disease. After one year, one patient had undergone salvage surgery for residual disease and two for recurrent disease. One other patient was unfit for surgery and not offered salvage surgery. At three years, only two patients had no disease recurrence. Nine of 10 patients were alive at one year and seven alive at three years. Conclusion The Covid-19 pandemic was an unusual event in our most recent history that influenced the way we managed patients with oesophageal adenocarcinoma. Little data exists as to what alternative treatments were effective. Our limited data indicates that dCRT may be used as an alternative to surgery in a subgroup of patients – although disease recurrence was common, 3-year survival was high (70%). Our data appears to be comparable to 3-year survival in our own unit and that reported in NOCGA 2024 (63%). Nevertheless, these numbers are small and thus require further study.

Abstract PR007: Screening early detection of HPV-associated oropharynx cancers with multi-feature HPV whole genome sequencing liquid biopsy

Abstract Early detection of HPV-associated oropharyngeal cancer (HPV+OPSCC), the most common HPV cancer in the United States, could reduce disease-related morbidity, yet currently there are no screening tests. Circulating tumor HPV DNA (ctHPVDNA) is a sensitive and specific biomarker for HPV+OPSCC at diagnosis. It was previously unknown if ctHPVDNA is detectable prior to HPV+OPSCC diagnosis, and thus it’s potential as a screening test. We recently reported (2023 AACR-AHNS Head and Neck Cancer Conference) detection of ctHPVDNA with 79% overall sensitivity at 100% specificity in a case-control cohort of HPV+OPSCC patients with plasma samples collected 1-11 years prior to diagnosis (n=28) and age- and sex-matched controls (n=28) from the MassGeneralBrigham Biobank (MGBB) using a custom multi-feature HPV whole genome sequencing liquid biopsy, termed HPV-DeepSeek, demonstrating for the first time, the feasibility of blood-based screening for HPV+OPSCC. Here, we extend and validate these finding in a second independent cohort and generate combined metrics for estimating HPV+OPSCC screening accuracy by HPV-DeepSeek. We conducted a blinded case-control study nested within the NCI PLCO Screening Trial. PLCO enrolled 155,000 healthy participants from November 1993-July 2001 with plasma sample collected at multiple time points. All patients were followed for cancer outcomes. PLCO participants who were diagnosed with OPSCC >6 months after blood sample contribution were identified and matched 1:2 with controls based on smoking status, sex, race, year of blood collection, and year of birth. 400ul of plasma was retrieved, blinded, and transferred for testing. After quality control, the cohort included 72 OPSCC cases and 144 controls. Samples had previously underdone HPV E6 antibody testing which was used as a marker of HPV status. All samples were run on HPV- DeepSeek using pre-defined cut points and results were returned to NCI CDAS where case- control status was unblinded. 32 OPSCC cases were HPV E6 antibody positive and thus regarded as HPV16+OPSCC. 20/32 were ctHPVDNA positive and 12/32 were ctHPVDNA negative (overall sensitivity 63%). Specificity was 99%. The mean lead time of positive cases was 6.3 years, and the maximum lead time was 11.3 years. Sensitivity was highest closest to diagnosis and declined further from diagnosis (100% within 3 years of cancer diagnosis, 58% from 3-9 years, 20% from 9-12 years; p<0.001). Four additional samples were positive for non- HPV16 genotypes (31, 33, 33, 39) in the overall cohort. When combined with the MGBB cohort, overall screening sensitivity was 70% and specificity was 99%. Sensitivity within 3 years of cancer diagnosis was 100%. ctHPVDNA can be detected in the blood up to 11 years prior to diagnosis with HPV+OPSCC, with ≥99% specificity, and an overall screening sensitivity of 70% in a cohort of 100 OPSCC cases and 172 controls using a multi-feature HPV WGS liquid biopsy. ctHPVDNA detection alone, or in combination with previously identified serological biomarkers, may be a feasible approach to screening for HPV+OPSCC. Citation Format: Krystle Kuhs, Hilary Robbins, Dipon Das, Michael Bryan, Ling Aye, Yana Al-Inaya, Shun Hirayama, Viktor Adalsteinsson, Michael Lawrence, Tim Waterboer, Daniel L Faden. Screening early detection of HPV-associated oropharynx cancers with multi-feature HPV whole genome sequencing liquid biopsy [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr PR007.

Abstract 4118018: Increased Risk of Post-Transplant Malignancy After Isolated Heart Transplant in Adult Patients with Congenital Heart Disease

Introduction: Patients with congenital heart disease (CHD) are at increased risk of cancer. In patients with CHD and advanced heart failure, isolated heart transplantation (HT) can be considered. In the overall HT population, immunosuppression after HT increases the risk of post-transplant malignancy (PTM). However, cancer outcomes among adult HT patients with CHD have not been investigated. Methods: Patients aged ≥ 18 years who received HT between January 1, 2010 and December 31, 2021 were identified using the United Network for Organ Sharing (UNOS) registry. Patients with CHD were compared to those without. Outcomes were PTM and hematologic malignancy (either leukemia, lymphoma or post-transplant lymphoproliferative disorder). Multivariable Fine-Gray competing-risk regression adjusting for age, sex, race, prior cardiac surgery, smoking, diabetes, induction immunosuppression, recipient and donor cytomegalovirus and Ebstein-Bar virus status was used to estimate subhazard ratio (SHR). Results: Of the total of 29,717 patients with HT were included, 1,017 (3.4%) had CHD. Patients with CHD were younger, more likely to be female, and more likely to have had prior cardiac surgery. After multivariable competing-risk regression, CHD was associated with higher risk of PTM (aSHR 1.44, 95% CI 1.15 – 1.80) and hematologic malignancy (aSHR 2.09, 95% CI 1.28 – 3.42). Among patients < 45 years old, CHD had an unadjusted SHR of 1.55 (95% CI 1.11 – 2.16) of PTM, Figure. Conclusions: Among adult patients with HT, CHD was associated with increased risk of PTM and hematologic malignancy. Further investigation is warranted to identify risk factors and screening strategies for malignancy in this patient population.

Shareable artificial intelligence to extract cancer outcomes from electronic health records for precision oncology research

Abstract Databases that link molecular data to clinical outcomes can inform precision cancer research into novel prognostic and predictive biomarkers. However, outside of clinical trials, cancer outcomes are typically recorded only in text form within electronic health records (EHRs). Artificial intelligence (AI) models have been trained to extract outcomes from individual EHRs. However, patient privacy restrictions have historically precluded dissemination of these models beyond the centers at which they were trained. In this study, the vulnerability of text classification models trained directly on protected health information to membership inference attacks is confirmed. A teacher-student distillation approach is applied to develop shareable models for annotating outcomes from imaging reports and medical oncologist notes. ‘Teacher’ models trained on EHR data from Dana-Farber Cancer Institute (DFCI) are used to label imaging reports and discharge summaries from the Medical Information Mart for Intensive Care (MIMIC)-IV dataset. ‘Student’ models are trained to use these MIMIC documents to predict the labels assigned by teacher models and sent to Memorial Sloan Kettering (MSK) for evaluation. The student models exhibit high discrimination across outcomes in both the DFCI and MSK test sets. Leveraging private labeling of public datasets to distill publishable clinical AI models from academic centers could facilitate deployment of machine learning to accelerate precision oncology research.

A Randomized Pilot Trial of Virtual Reality Surgical Planning for Head and Neck Oncologic Resection

ObjectiveApplication of virtual reality (VR) for surgical planning may improve clinical outcomes for head and neck cancer (HNC) resection. There is a lack of randomized trials and meaningful metrics to assess such technological applications. Our objective was to evaluate the feasibility of a VR protocol for oncologic surgical planning and assess the impact on surgical outcomes.MethodsA randomized controlled trial utilizing a VR Case Enhancement Protocol (VRCEP) versus standard of care (SOC) surgical planning was conducted. The primary endpoint was feasibility, defined as >80% successful VRCEPs. Metrics included surgeon task‐load burden (TLB) using the NASA Task‐Load Index and “margin events,” defined as "the need for defect‐driven margins, positive frozen margins, and/or positive final margins." Margin events were used to calculate a margin event score (MES) per case and margin event rate (MER) per cohort.ResultsThirty‐four patients were included in the final analysis (17 VRCEP, 17 SOC) with 94.4% of eligible VRCEP cases completed (17/18). Surgeon TLB was unchanged with VRCEP. Cases undergoing VRCEP were associated with a lower mean MES (0.27 vs. 0.94, p = 0.014) and MER (11.6% vs. 35.6%, p = 0.0041). VRCEP was associated with decreased defect‐driven margins (10% vs. 53.3%, p = 0.032). Although not statistically significant, positive frozen and final margin rates were lower in VRCEP.ConclusionCompletion of the VRCEP was feasible with no significant increase in surgeon TLB appreciated. VRCEP yielded fewer MEs. Further investigation into the benefit of VR in HNC resection is warranted. Margin events may represent useful metrics for assessing novel surgical technologies.Level of Evidence2 Laryngoscope, 2024

The expression of keratin 17 and p27 predicts clinical outcomes in colorectal cancer

Keratin 17 (K17) is frequently overexpressed, associated with poor prognosis in various cancers, and contributes to p27 degradation during cancer progression. Using immunohistochemistry, we evaluated K17 and p27 expression and assessed their biological behavior and prognostic significance in 326 colorectal cancers. High K17 expression was associated with poorly differentiated tumors, high pT classification, and lymph node metastases. Low p27 expression was associated with large tumors, high pT classification, lymphovascular invasion, and lymph node metastases. The overall survival of patients with high K17 expression was significantly worse than that of patients with low K17 expression [hazard ratio (HR) = 1.805, 95% confidence interval (CI) 1.169–2.787; p = 0.007]. Patients with low p27 expression showed significantly worse overall survival than those with high p27 expression (HR = 3.082, 95% CI 1.722–5.517; p < 0.001). When combining the results of K17 and p27 expression, the K17highp27low expression group showed the worst overall survival. On the contrary, the K17high/lowp27high group showed the best overall survival (p < 0.001). Therefore, K17highp27low expression is an independent poor prognostic factor in colorectal cancer. Thus, high K17 and low p27 expression correlate with aggressive clinicopathologic behavior and can be used as poor prognostic markers in colorectal cancer.

Abstract 4116425: " Navigating High-Risk Terrain: Clinical Outcomes of Percutaneous Coronary Intervention (PCI) in Breast Cancer Patients - A National Inpatient Sample Analysis "

Background: Breast cancer is the most prevalent malignancy affecting women globally and is one of the leading causes of cancer-related deaths. Cardiovascular disease (CVD) holds the highest mortality rate among women. However, the prognosis of percutaneous coronary intervention (PCI) patients with underlying breast cancer has not been well-studied. Methods: The National Inpatient Sample (NIS) 2017-2020 database was used to identify PCI patients with ICD-10 codes for a retrospective analysis. PCI patients were then divided into those with and without underlying breast cancer. Multivariable logistic regression was performed for composite post-PCI outcomes analyses. Results: Among 2,815,610 patients admitted for PCI, 3,935 had breast cancer. Patients with underlying breast cancer experienced worse post-PCI outcomes, including a higher risk of major bleeding (OR, 3.7; 95% CI, 2.9 - 4.8; P < .001) and post-PCI cardiac arrest (OR, 8.003; 95% CI, 5.39 - 11.8). The need for devices such as Impella and IABP was also higher in the breast cancer subpopulation compared to those without (OR, 6.8; 95% CI, 5.7 - 8.0) and (OR, 8.4; 95% CI, 7.44 - 9.668), respectively. Although the incidence of stroke was higher in the subpopulation, intra/post-PCI stroke was lower. Breast cancer patients undergoing PCI showed no significant difference in hospitalization charges or length of stay. Conclusions: In conclusion, our study sheds light on the intricate relationship between breast cancer and percutaneous coronary intervention (PCI) outcomes. These findings underscore the importance of tailored care and close monitoring for breast cancer patients undergoing PCI.

A roadmap to reduce the incidence and mortality of breast cancer by rethinking our approach to women’s health

Abstract Despite progress, breast cancer remains the most feared disease among women. In the USA alone, the incidence is now almost 300,000 new cancers per year, a rate that has nearly doubled in the last 30 years. Most women survive, but over 40,000 women a year still die of their disease National Cancer Institute [Internet]. [cited 2024 Nov 4]. Cancer of the Breast (Female) - Cancer Stat Facts. Available from: https://seer.cancer.gov/statfacts/html/breast.html. It is the most diagnosed cancer among women and the second leading cause of cancer death. Important disparities exist in breast cancer outcomes among African American women, where women die of breast cancer at higher rates, are diagnosed younger, and at a more advanced stage. We are proposing a radical shift in our thinking about breast cancer prevention with an aspiration to dramatically lower breast cancer incidence. Most breast cancers are driven by steroid hormones. Throughout the life course, women are offered an array of hormonal treatments for menstrual cycle control, family planning, in vitro fertilization, postpartum weaning, and menopausal symptom management. There are mixed data on the extent to which each of these may contribute to increased or decreased risk for breast cancer. These endocrine manipulations could represent a great opportunity to potentially reduce breast cancer incidence and improve quality of life for survivors. To date, they have not been designed to explicitly reduce breast cancer risk. A new holistic approach will require scientists, drug developers, breast oncologists, obstetricians, gynecologists, endocrinologists, radiologists, and family medicine/internists to work together toward the common goal of reducing breast cancer risk while addressing other critical issues in women’s health.

Impact of major depressive disorder on breast cancer outcomes: a national retrospective cohort study

Abstract Background Establishing whether women with major depressive disorder (MDD) who develop breast cancer (BC) have poor outcomes is key to optimizing care for this population. To address this, we examined associations between MDD and BC recurrence and mortality. Methods Using medical record data from the Veterans Affairs Healthcare System, we established a retrospective cohort of women with local or regional stage invasive BC between 2010 and 2019 and followed through 2022. We used a two-year window to identify women diagnosed with MDD prior to BC diagnosis. We used multivariable Cox-proportional hazards regression to estimate associations between MDD and BC recurrence and mortality while accounting for competing-risks and adjusting for sociodemographic, clinical, lifestyle, and tumor characteristics. Results We identified 6,051 women with BC, of whom 1,754 (29%) had MDD. The mean age at BC diagnosis was 57 years (standard deviation = 11). In multivariable analyses, women with MDD had a 37% (hazard ratio (HR)=1.37; 95% confidence interval (CI): 1.19-1.57) higher risk of recurrence and a 30% (HR = 1.30; 95% CI: 1.02-1.64) higher risk of BC mortality. The association between MDD and recurrence was stronger among women with estrogen receptor-positive BC. In secondary analyses, there were significant interactions between MDD and multiple exposures with respect to recurrence, including current smoking, substance abuse, and non-receipt of screening mammography. Conclusions Women with MDD had inferior BC outcomes compared to women without a history of MDD. Research is needed to investigate underlying mechanisms linking depression to BC progression and evaluate interventions to improve outcomes in this high-risk population.

Impact of Socioeconomic Deprivation on Care Quality and Surgical Outcomes for Early-Stage Non-Small Cell Lung Cancer in United States Veterans

Background: Socioeconomic deprivation has been associated with higher lung cancer risk and mortality in non-Veteran populations. However, the impact of socioeconomic deprivation on outcomes for non-small cell lung cancer (NSCLC) in an integrated and equal-access healthcare system, such as the Veterans Health Administration (VHA), remains unclear. Hence, we investigated the impact of area-level socioeconomic deprivation on access to care and postoperative outcomes for early-stage NSCLC in United States Veterans. Methods: We conducted a retrospective cohort study of patients with clinical stage I NSCLC receiving surgical treatment in the VHA between 1 October 2006 and 30 September 2016. A total of 9704 Veterans were included in the study and assigned an area deprivation index (ADI) score, a measure of socioeconomic deprivation incorporating multiple poverty, education, housing, and employment indicators. We used multivariable analyses to evaluate the relationship between ADI and postoperative outcomes as well as adherence to guideline-concordant care quality measures (QMs) for stage I NSCLC in the preoperative (positron emission tomography [PET] imaging, appropriate smoking management, pulmonary function testing [PFT], and timely surgery [≤12 weeks after diagnosis]) and postoperative periods (appropriate surveillance imaging, smoking management, and oncology referral). Results: Compared to Veterans with low socioeconomic deprivation (ADI ≤ 50), those residing in areas with high socioeconomic deprivation (ADI > 75) were less likely to have timely surgery (multivariable-adjusted odds ratio [aOR] 0.832, 95% confidence interval [CI] 0.732–0.945) and receive PET imaging (aOR 0.592, 95% CI 0.502–0.698) and PFT (aOR 0.816, 95% CI 0.694–0.959) prior to surgery. In the postoperative period, Veterans with high socioeconomic deprivation had an increased risk of 30-day readmission (aOR 1.380, 95% CI 1.103–1.726) and decreased odds of meeting all postoperative care QMs (aOR 0.856, 95% CI 0.750–0.978) compared to those with low socioeconomic deprivation. There was no association between ADI and overall survival (adjusted hazard ratio [aHR] 0.984, 95% CI 0.911–1.062) or cumulative incidence of cancer recurrence (aHR 1.047, 95% CI 0.930–1.179). Conclusions: Our results suggest that Veterans with high socioeconomic deprivation have suboptimal adherence to care QMs for stage I NSCLC yet do not have inferior long-term outcomes after curative-intent resection. Collectively, these findings demonstrate the efficacy of an integrated, equal-access healthcare system in mitigating disparities in lung cancer survival that are frequently present in other populations. Future VHA policies should continue to target increasing adherence to QMs and reducing postoperative readmission for socioeconomically disadvantaged Veterans with early-stage NSCLC.

The cumulative impact of type 2 diabetes and obstructive sleep apnoea on cardiovascular, liver, diabetes‐related and cancer outcomes

AbstractAimA bidirectional relationship exists between obstructive sleep apnoea (OSA) and type 2 diabetes (T2D). We aimed to examine the cumulative impact of having both OSA and T2D on patient outcomes, relative to having either condition alone.Materials and methodsUsing TriNetX, a global federated research network (n = 128 million), we undertook two retrospective cohort studies, using time‐to‐event analysis. Analysis 1 compared OSA with T2D versus OSA alone; analysis 2 compared T2D with OSA versus T2D alone. Propensity score matching using greedy nearest neighbour (calliper 0.1) balanced the cohorts (1:1) for significant covariates. Primary outcomes were cardiovascular, liver, diabetes‐related (microvascular) and cancer events over 1–5 years.ResultsAnalysis 1 (n = 179 688): A codiagnosis of T2D/OSA significantly increased risk of all‐cause mortality (hazard ratio [HR] 1.52; confidence interval [CI]: 1.48, 1.57), dementia (HR 1.19; CI: 1.12, 1.26), liver (HR 2.20; CI: 1.77, 2.73), pancreatic (HR 1.62; CI: 1.35, 1.93), colon, renal and endometrial cancers; all cardiovascular, microvascular and liver related outcomes versus OSA alone over 1–5 5 years following OSA diagnosis. Analysis 2 (n = 240 094): A codiagnosis of OSA/T2D significantly increased the risk of peripheral (HR 1.39; CI: 1.36, 1.43) and autonomic (HR 1.63; CI: 1.51, 1.75) neuropathy; retinopathy (HR 1.13; CI: 1.09, 1.18), CKD (HR 1.21; CI: 1.18, 1.23); all cardiovascular and liver outcomes; all‐cause mortality and several obesity related cancers versus T2D alone.ConclusionsT2D significantly potentiates risk of cardiovascular, malignancy and liver‐related outcomes in individuals with OSA. OSA, in individuals with T2D, significantly potentiates risk of cardiovascular disease, malignancy, death and several microvascular complications (retinopathy, CKD, peripheral/autonomic neuropathy).

IMMU-20. CIRCULATING CELL-FREE DNA DIRECTLY INHIBITS T CELL RESPONSES AND CONTRIBUTES TO SYSTEMIC IMMUNOSUPPRESSION IN GLIOBLASTOMA

Abstract Glioblastoma (GBM) is an aggressive form of brain cancer with poor survival despite standard of care. Checkpoint inhibitors aimed to revive dysfunctional T cells have significantly improved outcomes in other cancers, but have failed GBM. GBM patients have severe peripheral immunosuppression, including severe lymphopenia, immune organ atrophy, and defective T cell responses. This immunosuppression is a critical barrier to patient survival and the success of immunotherapies. Using parabiosis, we demonstrated that serum-derived factors were sufficient to drive hallmark features of immunosuppression, including inhibition of ex vivo T cell proliferation. This factor was nonsteroidal in nature and had molecular weights greater than 100kDa. Mass-spectrometry and pathway analysis of the suppressive serum implicated proteins involved in DNA response elements, cell death, and DNA-histone complexes. We hypothesized that the factor is cell-free DNA (cfDNA). Confirming this, serum levels of cfDNA are increased in glioma-bearing mice. Moreover, exposure to cfDNA from serum of glioma-bearing mice was sufficient to directly and potently inhibit T cell proliferation ex vivo. Interestingly, exposure to genomic DNA was not sufficient to induce proliferation defects in T cells, highlighting the unique features of cfDNA. Importantly, reducing cfDNA content using DNaseI partially restored proliferation capacity. We determined that the T cell proliferation defects were independent of DNA sensing mechanisms through AIM2, implicating a novel pathway of DNA sensing in T cells. Finally, to determine the origin of the cfDNA, we employed methyl-seq. The chromatin signature most closely represented neutrophils. This highlights a potential role for neutrophils-derived cfDNA as a targetable strategy in GBM. Together, we contend that cfDNA induces immunosuppressive effects in GBM and devising strategies to reduce circulating cfDNA could be a therapeutic approach to improve T cell functions and outcomes in GBM patients.