Cancer Outcomes Research Articles

Machine learning model using immune indicators to predict outcomes in early liver cancer

BACKGROUND Patients with early-stage hepatocellular carcinoma (HCC) generally have good survival rates following surgical resection. However, a subset of these patients experience recurrence within five years post-surgery. AIM To develop predictive models utilizing machine learning (ML) methods to detect early-stage patients at a high risk of mortality. METHODS Eight hundred and eight patients with HCC at Beijing Ditan Hospital were randomly allocated to training and validation cohorts in a 2:1 ratio. Prognostic models were generated using random survival forests and artificial neural networks (ANNs). These ML models were compared with other classic HCC scoring systems. A decision-tree model was established to validate the contribution of immune-inflammatory indicators to the long-term outlook of patients with early-stage HCC. RESULTS Immune-inflammatory markers, albumin-bilirubin scores, alpha-fetoprotein, tumor size, and International Normalized Ratio were closely associated with the 5-year survival rates. Among various predictive models, the ANN model generated using these indicators through ML algorithms exhibited superior performance, with a 5-year area under the curve (AUC) of 0.85 (95%CI: 0.82-0.88). In the validation cohort, the 5-year AUC was 0.82 (95%CI: 0.74-0.85). According to the ANN model, patients were classified into high-risk and low-risk groups, with an overall survival hazard ratio of 7.98 (95%CI: 5.85-10.93, P < 0.0001) between the two cohorts. CONCLUSION A non-invasive, cost-effective ML-based model was developed to assist clinicians in identifying high-risk early-stage HCC patients with poor postoperative prognosis following surgical resection.

Examining Geographic Disparity: Variation in Cancer Outcomes within Appalachia.

The Appalachian region of the United States (US) extends from the Mississippi delta to southern New York. Although disparities in Appalachian cancer outcomes have long been observed, recent rates and trends have not been assessed. We calculated 5-year age-adjusted US cancer incidence and mortality rates for 2017-2021, stratified into Appalachian and non-Appalachian populations, as well as Appalachian subregions, using the US Cancer Statistics Incidence Analytics Database and National Center for Health Statistics mortality files. Annual rates for 2004-2021 were also calculated. In 2017-2021, all-site cancer incidence (466.6; 95% confidence interval (CI), 465.5-467.6) and mortality rates (165.5; 95% CI, 164.9-166.1) among Appalachian residents were significantly higher (5.6% and 12.8%, respectively) than among non-Appalachian residents. Within Appalachia, the Central subregion-predominantly eastern Kentucky-had the highest rates of all-site cancer incidence (495.9) and mortality (201.9). In addition, the Central subregion had the highest rates of lung and colorectal cancer incidence, and the highest rates of lung, colorectal, and cervical cancer mortality. All-site cancer incidence and mortality rates among Appalachian individuals have decreased significantly since 2004 (-0.33%/year and -1.39%/year, respectively), with site-specific incidence rate decreases for late-stage lung (-2.19%/year), late-stage colorectal (-0.75%/year) and late-stage female breast (-0.35%/year) cancers in Appalachia. While cancer incidence and mortality rates are declining in Appalachia, they remain substantially higher and demonstrate slower progress than elsewhere in the US-particularly in the Central Appalachian subregion-indicating the need for targeted research to delineate and address the factors driving these cancer health disparities.

Discussion of Examining Geographic Disparity: Variation in Cancer Outcomes within Appalachia.

Discussion of Examining Geographic Disparity: Variation in Cancer Outcomes within Appalachia.

Prevalence and associated risk factors of cervical cancer among women in a Nigerian cohort

ABSTRACT Background: Cervical cancer is the fourth most common cancer in women worldwide. This study examined the prevalence of cervical cancer and associated factors among patients in a tertiary health facility in Edo state in Nigeria. Methods: A retrospective descriptive cross-sectional survey design was adopted including 3654 female patients who visited the oncology unit between 2016 and 2021. Their clinical files were selected through purposive sampling, and a validated checklist was used as instrument for data collection. Data analyses included descriptive and inferential statistics and multiple logistics regression. Results: Cervical cancer prevalence was highest in 2021 (10.8%). Oral contraceptives (23.8%), immunosuppression (19.3%), the number of sexual partners (8.3%), lack of human papillomavirus (HPV) vaccination (18.8%), diabetes (13.3%), and cardiovascular diseases (9.4%) were among the factors associated cervical cancer. A significant association (P = 0.000) was observed between risk factors and the clinical outcomes of cervical cancer. Women aged 30–59 were 25% more likely (odds ratio [OR] =1.25; 95% confidence interval [CI] = 0.55–2.86) to survive compared to those aged 60 and above. Women with only secondary education were also less likely (OR = 0.45; 95% CI = 0.21–0.99) to survive compared to those with tertiary education. Finally, multiparous women were less likely to survive compared to nulliparous women (OR = 0.30; 95% CI = 0.005–1.79). Conclusion: These results underscore the rising prevalence of cervical cancer and its association with age, supporting advocacy for increased HPV vaccination efforts targeting young girls before sexual maturity, as well as catchup vaccinations for high-risk older women.

Prognostic value of circulating Chromogranin A in prostate cancer: a systematic review and meta-analysis

BackgroundThere are discrepancies between the results of different studies regarding the prognostic role of circulating Chromogranin A (CgA) in prostate cancer. Therefore, we conducted a meta-analysis of the available findings to explore the value of circulating Chromogranin A in the prognosis of prostate cancer.MethodsWe systematically searched the PubMed, Embase, Web of Science, Cochrane Library, and Clinical Trials databases for studies on the relationship between CgA and survival outcomes in prostate cancer from inception until December 2024, and we focused on articles detecting circulating CgA, with the primary endpoints of the studies being overall survival (OS), and progression-free survival (PFS).ResultsOf the 2049 articles retrieved, 10 articles met our inclusion criteria, involving a total of 1445 patients. Elevated circulating CgA was associated with poorer OS (HR=1.82, 95% CI: 1.38–2.41; p<0.001) and PFS (HR=2.04, 95% CI: 1.42–2.94; p<0.001). However, no correlation was found between post-treatment circulating CgA changes and OS (HR=0.95, 95% CI: 0.66–1.37; p=0.767).ConclusionCirculating CgA is a predictive marker of poor survival outcomes in prostate cancer However, the sample size of the current study is small and larger studies are needed to further validate this in the future.

The Role of the DNA Methyltransferase Family and the Therapeutic Potential of DNMT Inhibitors in Tumor Treatment

Members of the DNA methyltransferase (DNMT) family have been recognized as major epigenetic regulators of altered gene expression during tumor development. They establish and maintain DNA methylation of the CpG island of promoter and non-CpG region of the genome. The abnormal methylation status of tumor suppressor genes (TSGs) has been associated with tumorigenesis, leading to genomic instability, improper gene silence, and immune evasion. DNMT1 helps preserve methylation patterns during DNA replication, whereas the DNMT3 family is responsible for de novo methylation, creating new methylation patterns. Altered DNA methylation significantly supports tumor growth by changing gene expression patterns. FDA-approved DNMT inhibitors reverse hypermethylation-induced gene repression and improve therapeutic outcomes for cancer. Recent studies indicate that combining DNMT inhibitors with chemotherapies and immunotherapies can have synergistic effects, especially in aggressive metastatic tumors. Improving the treatment schedules, increasing isoform specificity, reducing toxicity, and utilizing genome-wide analyses of CRISPR-based editing to create personalized epigenetic therapies tailored to individual patient needs are promising strategies for enhancing therapeutic outcomes. This review discusses the interaction between DNMT regulators and DNMT1, its binding partners, the connection between DNA methylation and tumors, how these processes contribute to tumor development, and DNMT inhibitors’ advancements and pharmacological properties.

Advancing a Universal European Cancer Prevention Methodology for People With Intellectual Disability: Findings From CUPID Workshops in Ireland and Türkiye

ABSTRACTBackgroundPeople with intellectual disability have higher rates of cancer mortality than the general population. Cancer prevention programmes and screenings are recommended in adults, including those with intellectual disability. The opinions of relevant parties are important to ensure that people with intellectual disability can achieve equity in cancer outcomes. The aim of this paper is to report the findings of two workshops held in Ireland and Türkiye in 2023, which identified key issues affecting prevention, diagnosis and management of cancer in people with intellectual disability.MethodsResearchers, practitioners, policymakers and other stakeholders with a role in cancer prevention programmes or cancer care (n = 44) participated in ‘World Café’ workshop meetings in Dublin and Ankara. The findings were synthesised under the Dahlgren and Whitehead (1991) Social Determinants of Health framework.ResultsBoth workshops identified that people with intellectual disability face challenges including: limited available cancer data in this population, health issues overshadowing cancer diagnosis, and social barriers such as low health literacy. Involving families, professionals and promoting self‐advocacy, while tailoring health services with inclusive decision making were prominent themes in both workshops as solutions. Research and person‐centered healthcare were identified as critical for developing effective cancer prevention programmes.ConclusionFor people with intellectual disability to benefit from effective cancer prevention programmes, reasonable adjustments must be made by policymakers, health institutions, primary healthcare professionals and non‐government organisations, and research evidence must underpin decisions.

Changes in breast reconstruction over the COVID-19 pandemic: a single centre experience

Introduction: Approximately 4000 Australians undergo mastectomy annually, yet there is a paucity of published Australian data on how the COVID-19 pandemic affected breast reconstruction services. The aim of this study is to determine the impact of the COVID-19 pandemic on the breast reconstructive service of a busy metropolitan hospital in Melbourne, Australia. Challenges in clinical service provision and surgical outcomes are discussed and compared with the published literature. Methodology: A single centre retrospective review of breast reconstruction over a four-year period (April 2018 to March 2022 inclusive) was conducted. Data collected include patient demographics, oncological attributes, surgical management and outcomes. Data was compared before (April 2018 to March 2020, inclusive) and during the COVID-19 pandemic (April 2020 to March 2022, inclusive). Results: Resection rates were comparable before and during the COVID-19 pandemic (240 versus 248 patients). There was an increase in the rate of mastectomies compared to breast-conserving operations between the two periods (30.4% versus 45.6%, p <0.001). Breast reconstruction post-mastectomy increased from 39.7 per cent to 46.0 per cent (not statistically significant, p = 0.68). The rate of immediate breast reconstruction (79% versus 81%) and autologous reconstruction (62% versus 70%) were statistically similar between the two periods. There was no difference in total pre-COVID-19 and post-COVID-19 complication rates. Conclusion: Our experience demonstrates that acceptable oncological and reconstructive outcomes for breast cancer can be achieved in the middle of a pandemic without compromising outcomes.

The Impact of Preoperative Radiotherapy and Chemotherapy on Autologous Breast Reconstruction Outcomes—A Retrospective Single-Center Study

Background: While radiotherapy (RT) and chemotherapy (CT) significantly improve breast cancer outcomes, they may affect breast reconstruction by causing vascular damage and delayed wound healing. This retrospective study evaluates how preoperative RT, CT, or the combination of both impacts intraoperative and postoperative outcomes in immediate or delayed deep inferior epigastric perforator (DIEP) flap breast reconstructions. Methods: We conducted a single-center review of all patients undergoing autologous DIEP flap reconstruction after mastectomy between 2018 and 2024. Patients were divided into four groups: RT only, CT only, a combination of RT and CT, and a control group with no preoperative therapies. Intraoperative and postoperative outcomes were then compared among these groups, with statistical significance defined as p < 0.05. Results: We included 114 patients representing 141 DIEP-flap breast reconstructions. Flap survival rate was 98.5%. In the univariate analysis, total microvascular recipient site complications were significantly higher in the RT + CT group (14.0%, p = 0.021). Donor-site complication rates differed significantly among the four groups (p = 0.025), with the highest rate observed in the RT + CT group (44.7%). In the logistic regression analysis, ischemia time was found as an independent risk factor for total recipient site complications, but not for microvascular complications (OR = 1.019, 95%-CI = 1.004–1.035, p = 0.014). Conclusions: Combined RT + CT significantly increased microsurgical complications. Ischemia time correlated with higher odds of total recipient site complications. Individualized patient management and diminished ischemia time are likely to improve flap survival.

End-of-life care quality for American Indians with cancer.

American Indians (AI) experience disparities in cancer outcomes. Little is known about the quality of end-of-life (EOL) care in AI patients with cancer. We retrospectively analyzed EOL care for North Carolina patients who died (decedents) diagnosed with any cancer (2003-2018) using the Cancer Information and Population Health Resource. Measures of EOL care quality were informed by existing literature and included in-hospital death, hospice use and other healthcare utilization within the last 30 days of life. Associations between race/ethnicity and EOL outcomes were evaluated to estimate adjusted risk ratios (aRRs). Because within group heterogeneity can influence health outcomes and intervention effectiveness, we also evaluated associations among AI individuals only. We identified 163,285 (1,769 AI and 161,516 White) decedents. The majority (60%) of AIs lived in a geographic area characterized by non-federally recognized tribes. AI decedents had greater proportions of rural residence than White decedents (54.5% AI vs 30.4% White) and dual Medicaid/Medicare enrollment (37.4% AI vs 17.7% White). Compared with White decedents, AI decedents had increased hospital admission (aRR, 1.10, 95% confidence interval [CI], 1.06-1.15), ICU admission (aRR, 1.21; 95% CI, 1.11-1.32), and >1 ED visit (aRR, 1.31; 95% CI, 1.20-1.44) in the last 30 days of life. We observed significant within-group variation in EOL care quality among AI patients. Structural barriers to care and rurality may contribute to lower quality EOL care among AI decendents, when compared with White patients. High-quality, culturally appropriate EOL care will require a better understanding of care decision-making and access.

Colorectal Cancer Racial Equity Post Volume, Content, and Exposure: Observational Study Using Twitter Data.

Racial inequity in health outcomes, particularly in colorectal cancer (CRC), remains one of the most pressing issues in cancer communication and public health. Social media platforms like Twitter (now X) provide opportunities to disseminate health equity information widely, yet little is known about the availability, content, and reach of racial health equity information related to CRC on these platforms. Addressing this gap is essential to leveraging social media for equitable health communication. This study aims to analyze the volume, content, and exposure of CRC racial health equity tweets from identified CRC equity disseminator accounts on Twitter. These accounts were defined as those actively sharing information related to racial equity in CRC outcomes. By examining the behavior and impact of these disseminators, this study provides insights into how health equity content is shared and received on social media. We identified accounts that posted CRC-related content on Twitter between 2019 and 2021. Accounts were classified as CRC equity disseminators (n=798) if they followed at least 2 CRC racial equity organization accounts. We analyzed the volume and content of racial equity-related CRC tweets (n=1134) from these accounts and categorized them by account type (experts vs nonexperts). Additionally, we evaluated exposure by analyzing follower reach (n=6,266,269) and the role of broker accounts-accounts serving as unique sources of CRC racial equity information to their followers. Among 19,559 tweets posted by 798 CRC equity disseminators, only 5.8% (n=1134) mentioned racially and ethnically minoritized groups. Most of these tweets (641/1134, 57%) addressed disparities in outcomes, while fewer emphasized actionable content, such as symptoms (11/1134, 1%) or screening procedures (159/1134, 14%). Expert accounts (n=479; 716 tweets) were more likely to post CRC equity tweets compared with nonexpert accounts (n=319; 418 tweets). Broker accounts (n=500), or those with a substantial portion of followers relying on them for equity-related information, demonstrated the highest capacity for exposing followers to CRC equity content, thereby extending the reach of these critical messages to underserved communities. This study emphasizes the critical roles played by expert and broker accounts in disseminating CRC racial equity information on social media. Despite the limited volume of equity-focused content, broker accounts were crucial in reaching otherwise unexposed audiences. Public health practitioners should focus on encouraging equity disseminators to share more actionable information, such as symptoms and screening benefits, and implement measures to amplify the reach of such content on social media. Strengthening these efforts could help bridge disparities in cancer outcomes among racially minoritized groups.

Why is Mouth Self-Examination Still Not Recommended for Early Detection of Oral Cancer and Oral Potentially Malignant Disorders?

Oral self-examination still remains enigmatic considering its functionality in detecting malignant disorders in the mouth. Although this tool is not concretely implemented in any health service, several studies have considered it as a real possibility for the screening and the early diagnosis of oral cancer. However, the heterogeneity of the methodologies applied in these studies makes their results inconsistent and imprecise, making the validation of oral self-examination impossible to date. Thus, once the methodological issues that compromise the real efficacy of self-examination have been resolved, this tool should be used and perhaps be considered essential as a strategy to detect malignant lesions, contributing to more favorable outcomes for oral cancer in public health.

The Present State and Potential Applications of Artificial Intelligence in Cancer Diagnosis and Treatment.

An aberrant increase in cancer incidences has demanded extreme attention globally despite advancements in diagnostic and management strategies. The high mortality rate is concerning, and tumour heterogeneity at the genetic, phenotypic, and pathological levels exacerbates the problem. In this context, lack of early diagnostic techniques and therapeutic resistance to drugs, sole awareness among the public, coupled with the unavailability of these modern technologies in developing and low-income countries, negatively impact cancer management. One of the prime necessities of the world today is the enhancement of early detection of cancers. Several independent studies have shown that screening individuals for cancer can improve patient survival but are bogged down by risk classification and major problems in patient selection. Artificial intelligence (AI) has significantly advanced the field of oncology, addressing various medical challenges, particularly in cancer management. Leveraging extensive medical datasets and innovative computational technologies, AI, especially through deep learning (DL), has found applications across multiple facets of oncology research. These applications range from early cancer detection, diagnosis, classification, and grading, molecular characterization of tumours, prediction of patient outcomes and treatment responses, personalized treatment, and novel anti-cancer drug discovery. Over the past decade, AI/ML has emerged as a valuable tool in cancer prognosis, risk assessment, and treatment selection for cancer patients. Several patents have been and are being filed and granted. Some of those inventions were explored and are being explored in clinical settings as well. In this review, we will discuss the current status, recent advancements, clinical trials, challenges, and opportunities associated with AI/ML applications in cancer detection and management. We are optimistic about the potential of AI/ML in improving outcomes for cancer and the need for further research and development in this field.

The association between cirrhosis and outcomes among female patients undergoing surgery for breast cancer in Ontario: a population-based study.

The association between cirrhosis and post-operative breast cancer outcomes has not been explored. We evaluated the association between cirrhosis and surgical outcomes in female patients with breast cancer. We performed a retrospective population-based cohort study of female patients undergoing surgery for breast cancer between 2007 and 2018 using health administrative data from Ontario, Canada. Patients were stratified by cirrhosis status. Overall survival (OS) was described using the Kaplan-Meier method and the association between cirrhosis and long-term cancer-specific mortality (CSM) was evaluated using adjusted competing risks regression and subdistribution hazard ratios (sHR). A total of 902 patients with breast cancer and cirrhosis were compared to 81,514 patients with breast cancer without cirrhosis. The median age at diagnosis was 65years vs 61years in patients with and without cirrhosis, respectively (p < .001). The most common etiologies of cirrhosis were metabolic dysfunction-associated steatotic liver disease (n = 595, 66%) and alcohol-associated (n = 143, 16%) liver disease. The median model for end-stage liver disease sodium score was 8 (IQR 6-11, n = 215). Furthermore, cirrhosis was associated with a twofold higher 90-day rate of post-operative mortality (RR 2.82; 95% CI 1.49-5.33). OS was lower in patients with cirrhosis (HR 1.41, 95% CI 1.26-1.58); however, there was no association with CSM (sHR 1.11, 95% CI 0.93-1.32). This large population-based study demonstrates that patients with cirrhosis have lower OS compared to those without cirrhosis; however, there is no difference in CSM. Their outcomes remain favorable, and they should be considered for curative-intent therapies.

Low Phosphatidylserine+ Cells Within the CD34+/CD45dim/CD117(c-kit)+ Subpopulation are Associated with Poor Outcomes in Metastatic Colorectal Cancer

Background: Colorectal cancer is among the most prevalent causes of tumor-related deaths worldwide. Antiangiogenic therapy represents a cornerstone of metastatic CRC treatment, and biomarkers are advocated for the optimization of this therapeutic strategy. Methods: In this observational prospective study, we employed an optimized flow cytometry protocol to investigate the prognostic and predictive potential of blood circulating endothelial cells (CECs), circulating endothelial progenitor cells (CEPCs), and related subsets in a cohort of patients with metastatic colorectal cancer (n = 40). Results: Computational FC analysis revealed a differential enrichment of blood cell clusters with a CD34+/CD45dim/CD117(c-kit)+ phenotype between responders and non-responders both to antiangiogenic and non-antiangiogenic treatments. Intriguingly, our results show that a high percentage of annexin V-negative cells in a putative circulating progenitor population with a CD34+/CD45dim/CD117+ phenotype was correlated with a reduced response to systemic anticancer treatments (p = 0.015) and worse overall survival (log-rank p = 0.03). In addition, we observed increased blood concentrations of CD34+/CD45dim/CD117+/annexin V- cells in patients with a higher number of metastatic sites (p = 0.03). Conclusions: Overall, these findings hold promise for the identification of novel circulating biomarkers to develop more personalized treatment approaches in patients with metastatic colorectal cancer.

Association of Hospital Consolidation with Cancer Outcomes.

Hospital mergers have increased significantly since 2010, driven by factors such as healthcare policy changes, reimbursement, economies of scale, and quality improvement goals. However, limited evidence exists about how these mergers affect the quality of care and cancer outcomes. We conducted a difference-in-differences analysis to assess the impact of hospital consolidation on cancer outcomes. Using data from the Surveillance, Epidemiology, and End Results (SEER) program, we identified cancer patients diagnosed between 2008 and 2016, then used the Health Cost Institute's Healthy Marketplace Index to assess hospital consolidation as measured by the Herfindahl-Hirschman Index (HHI). The HHI is a measure of market concentration and competition between firms in a given industry. We found that increases in hospital consolidation were associated with a higher likelihood of early-stage cancer diagnosis compared to control areas (-1.1%, 95% confidence interval (CI) -2.3 to 0.0%), and improved overall survival (hazard ratio 0.94, CI 0.90-0.98). These improvements were restricted to cancers with screening recommendations. Our study suggests that hospital consolidation may have some benefits for cancer patients. However, these benefits may not be evenly distributed across all cancer types. Further research is needed to confirm these findings and to understand the mechanisms by which hospital consolidation affects cancer outcomes.

Disparities in liver cancer risk and outcomes in the LGBTQ community: A literature review.

528 Background: Liver cancer continues to be a significant public health concern, particularly among high-risk groups such as individuals with hepatitis infections, alcohol use disorders, and metabolic diseases. While liver cancer disparities have been well-documented among racial and ethnic minority groups, emerging research highlights significant health inequities within the LGBTQ community, including higher rates of risk factors and limited access to screening and care. This literature review aims to assess the extent of liver cancer disparities within the LGBTQ community and identify gaps in prevention, screening, and treatment. Methods: We performed a systematic search across PubMed, Scopus, and Google Scholar for peer-reviewed studies published between 2000 and 2024. The inclusion criteria focused on studies addressing liver cancer risk, prevalence, or outcomes in LGBTQ populations. Data on key liver cancer risk factors such as hepatitis B and C prevalence, alcohol use, obesity, and access to healthcare services were extracted and synthesized. Additionally, we reviewed public health reports and clinical guidelines relevant to LGBTQ health disparities. Results: The review identified significant disparities in liver cancer incidence and mortality among LGBTQ individuals. Hepatitis B infection rates were about 1.5 times higher, and hepatitis C rates up to 1.7 times higher among LGBTQ populations, particularly among gay and bisexual men. Alcohol use disorder was about 30-40% more prevalent in LGBTQ individuals, which further increases the risk of liver cancer. Screening for liver cancer in LGBTQ populations is underutilized, with rates approximately 20% lower than the general population. There were reported delays in diagnosis in LGBTQ community due to stigma, discrimination, and lack of culturally competent healthcare services. While some interventions targeting LGBTQ health have shown promise, the overall lack of targeted liver cancer prevention and treatment strategies remains a significant barrier. Conclusions: LGBTQ individuals face increased liver cancer risk due to a higher prevalence of key risk factors and inadequate healthcare access. Current screening and preventive strategies are insufficient for addressing these disparities. Targeted interventions, including enhanced screening efforts, hepatitis vaccination and treatment programs, and the development of LGBTQ-specific healthcare protocols, are needed to reduce the liver cancer burden in this underserved population. Policymakers and healthcare providers must address the unique needs of LGBTQ individuals to achieve equitable cancer outcomes. Prevalence of liver cancer risk factors in LGBTQ vs. general population. Risk Factor LGBTQ Population (%) General Population (%) Hepatitis B Infection 15 10 Hepatitis C Infection 18 12 Alcohol Use Disorder 25 16 Metabolic Syndrome 22 18 Screening Rate 40 60

AGITG SPAR: A randomized, placebo-controlled, phase II trial of simvastatin in addition to neoadjuvant chemotherapy and radiation for rectal cancer.

141 Background: Retrospective clinical studies and preclinical studies demonstrated that statin use during preoperative (chemo)radiation (pCRT) for rectal cancer is associated with improved survival, response, and toxicity. Tumor regression following pCRT has strong prognostic significance and can be assessed using MRI-based tumor regression grading (mrTRG), including with non-operative management. SPAR was designed to prospectively evaluate the benefits of adding simvastatin (SIM) to pCRT on tumor regression and gastrointestinal (GI) adverse events (AE). Methods: SPAR is a double-blind randomized phase 2 trial investigating SIM/placebo (PBO) in addition to long-course fluoropyrimidine-based pCRT for rectal adenocarcinoma. Stratification included trial site, clinical T stage (&lt;4 vs 4), clinical N stage (&lt;2 vs 2), either mesorectal fascia involvement (MRFI) or extramural venous invasion (EMVI) on MRI (yes vs no), and total neoadjuvant therapy (TNT): induction vs consolidation chemotherapy vs none. Study treatment was SIM 40mg/PBO daily for 90 days, starting 1 week prior to pCRT; recent statin use was excluded. Pelvic MRI was repeated 6-8 weeks after pCRT to determine mrTRG. An amendment in January 2022 allowed TNT with either induction or consolidation chemotherapy; the timing of post-pCRT MRI remained unchanged. The design was amended to open-label due to PBO supply issues. Primary objective: rate of centrally assessed grade 1-2 mrTRG. Secondary objectives include centrally assessed favorable pathologic TRG (pathTRG), safety and cancer outcomes. Analysis was by intention-to-treat. Results: Between April 2018 - November 2023, 135 of 222 planned participants from 17 sites in Australia and New Zealand were randomized (68 SIM; 67 no SIM). Recruitment was hampered by the COVID-19 pandemic and adoption of TNT as standard care before the protocol amendment. Participant characteristics: median age 59 years; 85 (63%) males; 118 (87%) T2-3 disease, 80 (59%) N0-1 disease; 55 (41%) MRFI or EMVI; 25 (19%) had TNT. Rates of grades 1-2 mrTRG with SIM vs no SIM were 38.5% and 29.7% (X 2 = 1.09, p = 0.30), respectively. There was no significant difference in rates of &gt; grade 2 GI and non-GI AE. Four serious AE were recorded, none related to study treatment. Median follow-up was 3.2 years. 3-year local recurrence rates (LRR) were low: 1 (2.2%) and 3 (5.5%) with SIM vs no SIM, respectively (HR: 0.29, 95% CI: 0.03 to 2.67, p = 0.26). 3-year disease-free survival (DFS) with SIM vs no SIM was 84% and 72%, respectively (HR 0.48; 95% CI: 0.21–1.08, p = 0.07). Conclusions: The rates of favorable mrTRG, 3-year LRR and DFS were numerically better with the addition of SIM to pCRT, though the differences were not statistically significant. SIM was well tolerated. Interpretation is limited by reduced sample size and statistical power. PathTRG and other key outcomes will be presented at the meeting. Clinical trial information: ACTRN12617001087347 .

In Search of Representative Translational Cancer Model Systems.

Racial disparities in cancer outcomes are well documented across tumor types. For patients with breast cancer, Black women are more likely to present with more aggressive molecular features and more likely to die from disease, even after accounting for those features. Recent efforts have been aimed at developing translational model systems for precision medicine strategies, and a major focus has been on patient-derived organoids. Organoids allow for robust in vitro experimental platforms, including drug and CRISPR screens while maintaining more complex cancer and tumor microenvironment subpopulations than cell lines. For results that are broadly translationally relevant, it is important that cancer models are derived from the spectrum of human disease and humans with disease. In this issue of Cancer Research, Madorsky Rowdo and colleagues derive breast cancer organoids from patients with African ancestry and use CRISPR-Cas9 screens to identify novel therapeutic vulnerabilities. These findings demonstrate the promise of representative cancer model systems to facilitate discoveries that are most likely to translate to improved therapy for all patients. See related article by Madorsky Rowdo et al., p. 551.

The effect of the type of anaesthesia on long-term outcomes after cancer resection surgery: a narrative review.

The peri-operative period may create a biological environment conducive to cancer cell survival and dissemination. Microscopic residual tumours (micrometastases) can be dislodged even with excellent surgical technique. At the same time, the stress response from surgery can temporarily impair immune function and activate inflammatory processes, increasing the risk of tumour proliferation. This narrative review investigates how peri-operative anaesthetic and analgesic interventions may influence cancer recurrence and metastasis by exploring evidence from both experimental and clinical studies. A comprehensive review of the literature was conducted to identify relevant preclinical and clinical studies published. While surgery remains the best curative option for many cancers, metastasis remains the leading cause of death. Numerous studies have suggested that different anaesthetic drugs and techniques could impact cancer outcomes including volatile anaesthetic agents; total intravenous anaesthesia with propofol; local anaesthetics; regional anaesthesia; and opioids. This review focuses on these five commonly used anaesthetic approaches and evaluates their potential impact on cancer progression. There is a complex interplay between anaesthetic and analgesic techniques and cancer outcomes. Despite promising data from laboratory experimental models, the balance of available clinical trials indicates an equivalent influence of all evaluated anaesthetic techniques on long-term oncologic outcomes, except, possibly, for peritumoral or intraperitoneal local anaesthetic infiltration.