Risk Of Cancer Recurrence Research Articles

Abstract A008: Adaptive immune receptor repertoire characterization highlights the importance of interplay between B and T cells in disease progression

Abstract Understanding the adaptive immune system is integral to disease progression studies, development of diagnostic biomarkers, identification of therapeutic targets, and discerning varied treatment responses. Despite growing interest in profiling B and T cells in cancer research, the interaction between these cells and also the crucial roles of γδ T cells often go overlooked. In this research project, we explored the role of crucial yet frequently ignored γδ T cells in cancer research, using immune repertoire data from bladder cancer patients. We also studied the synergy between B and T cells in the immune repertoires of COVID-19 patients.Roche has developed immunoPETE (immune repertoire Primer Extension Target Enrichment), a DNA- based target enrichment assay to capture adaptive immune repertoire data*. immunoPETE efficiently identifies the heavy chains of B cells, alongside αβ and γδ T cells in one reaction, facilitating normalized clone counts across the adaptive immune system. To explore the significance of γδ T cells, we profiled the immune repertoires of 24 Non-Muscle Invasive Bladder Cancer patients treated with Bacillus Calmette-Guerin (BCG). Additionally, we evaluated the interplay between B and T cells in 117 peripheral blood immune repertoire from healthy and COVID-19 afflicted individuals, ranging from mild to severe cases.Immune repertoire data analysis indicates that underrepresentation of T cell receptor delta locus (TRD) is associated with higher risk of bladder cancer recurrence or progress. Urine pellet DNA was available for a subset of the patients in this study. Comparing immune repertoires from PBMC and urine revealed that urine repertoires represent the tumor repertoire more accurately than PBMC. Analysis of the immune repertoires from the COVID-19 patients linked disease severity with immune repertoire measures across all three cell types, highlighting the importance of multiple lymphocyte classes in disease progression. Using immunoPETE technology, which is capable of capturing the heavy chain of multiple immune cell types simultaneously in a single reaction, we have demonstrated that both B cell and T cell compartments provide distinct and valuable information in cancer and infectious diseases, each responding uniquely to the disease. Additionally, we emphasized the significance of γδ T cells in predicting cancer prognosis. Note: immunoPETE is for Research Use Only. Not for use in diagnostic procedures. Citation Format: Hossein Asgharian, Hamid Mirebrahim, Dilduz Telman, Hahn Zhao, Ulrich Schlecht, Sylvie McNamara, Rajiv Dua, Jan Berka, Patrick Bogard, Dinesh Kumar. Adaptive immune receptor repertoire characterization highlights the importance of interplay between B and T cells in disease progression [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 A008.

Prognostic value of surgical treatment in elderly patients with ulcerative colitis‐associated colorectal cancer: A subanalysis of a nationwide Japanese multicenter study

AbstractAimOur study aimed to examine the characteristics of elderly patients diagnosed with ulcerative colitis‐associated colorectal cancer (UAC) and evaluate the impact of surgical intervention on prognosis.MethodsA total of 1086 patients diagnosed with UAC between 1980 and 2020 were retrospectively enrolled. Data were collected through the Japanese Society for Cancer of the Colon and Rectum project. The patients were divided into two groups: 248 elderly patients in the E‐UAC group and 838 nonelderly patients in the NE‐UAC group. Patients aged >65 y at cancer diagnosis were considered elderly.ResultsThe recurrence rate did not differ between the two groups. Segmental resection was the only common independent risk factor for recurrence in both the E‐UAC and the NE‐UAC groups. The E‐UAC patients had significantly better 5‐y disease‐specific survival (DSS) than the NE‐UAC patients (94.7% vs 91.0%, p = 0.04). There were no differences in 5‐y recurrence‐free survival (RFS; 89.3% vs 86.6%, respectively, p = 0.24) or overall survival (OS; 88.8% vs 89.6%, p = 0.50). The E‐UAC patients who underwent segmental resection had poorer RFS than those who underwent total proctocolectomy, but there were no significant differences in DSS or OS.ConclusionDespite the elevated risk of cancer recurrence observed in the UAC patients who underwent segmental resection in both the E‐UAC the NE‐UAC groups, our findings suggested that segmental resection may be a viable alternative to total proctocolectomy in terms of survival rate for the E‐UAC patients.

Long-term estrogen-deprived estrogen receptor α-positive breast cancer cell migration assisted by fatty acid 2-hydroxylase.

The risk of breast cancer (BC) recurrence is high in postmenopausal women, though the underlying molecular mechanisms are not yet fully understood. We developed a long-term estrogen-deprived (LTED) cell line from MCF-7 cells, which we used as an in vitro model for aromatase inhibitor (AI)-resistant estrogen receptor α (ERα)-positive postmenopausal BC. We also describe the involvement of fatty acid 2-hydroxylase (FA2H) in the modulation of LTED cell migration. Small interfering RNA specific to FA2H (siFA2H) could reduce cell migration, whereas the introduction of plasmid expressing FA2H, but not its inactive mutant, resulted in enhanced migration. Moreover, proliferation of the LTED cells was not affected by modulation of FA2H expression. Fulvestrant (FUL), a selective estrogen receptor degrader used to treat AI-resistant ERα-positive postmenopausal BC, was found to induce degradation of ERα together with a decrease in ER-mediated transcription; however, FA2H protein expression and migration remained unchanged. Overall, the findings of this study suggest that FA2H is one of the drivers of LTED cell migration, and that LTED cells resistant to FUL therapy may be involved in malignancy and metastatic mechanisms.

Hepatocellular carcinoma recurrence after liver transplantation: risk factors, targeted surveillance and management options

Hepatocellular carcinoma (HCC) represents a well-recognized indication for liver transplantation (LT), with improving graft and patient survival rates due to medical and surgical advancements over time. Despite the implementation of selection criteria to ensure the highest transplant benefit, post-LT recurrence of HCC is not uncommon and is often associated with poor outcomes. Therefore, a post-transplant surveillance strategy appears to be a cost-effective approach, particularly in the early post-surgery period when the recurrence rate is high. Although specific guidelines are still lacking, emerging strategies tailored to pre-transplant tumor history and explant pathology show promise. Moreover, new immunosuppressive therapy schemes and aggressive management of post-transplant medical complications can be implemented to reduce the risk of cancer recurrence. Finally, multimodal oncological strategies are increasingly used to improve survival even after cancer recurrence. This paper reviews the evidence on HCC recurrence after LT, providing insights into risk factors, targeted surveillance, and management strategies.

Narrative Review of Lifestyle Interventions in Breast Cancer Survivors: Current Evidence and Future Directions.

One in eight females will be diagnosed with breast cancer in their lifetime. While medical advances have increased the likelihood of survival, up to 90% of females will gain weight during and after treatment increasing the risk of breast cancer recurrence and obesity related co-morbidities in survivorship. Behavioral lifestyle interventions focused on diet with or without physical activity can provide breast cancer survivors non-pharmacological options to decrease weight gain and cardiometabolic risk. A PubMed search was conducted to identify all behavioral lifestyle interventions focused on diet or diet combined with physical activity longer than 4 weeks of duration in breast cancer survivors that included body weight as an outcome. This review aims to summarize the effects on body weight, body composition and cardiometabolic risk markers are summarized. Based on the review, there is high heterogeneity in type and duration of the intervention to affect weight and cardiometabolic risk in survivorship. Calorie restriction with and without physical activity appears to promote weight loss among breast cancer survivors. However, the effects on cardiometabolic factors are less clear. Future studies should be powered for both body weight and cardiometabolic effects. Researchers should also consider interventions that are: 1) less complex, 2) recruit a more racially and ethnically diverse sample, 3) integrate resistance training, 4) implement the intervention in closer proximity to diagnosis, 5) target weight management in this population before it occurs and 6) analyze body composition in addition to body weight measurements.

Risks of Cervical Cancer Recurrence After Fertility-Sparing Surgery and the Role of Human Papillomavirus Infection Types

Cervical cancer is a largely preventable malignancy of the uterine cervix. The tendencies in cervical cancer morbidity and mortality have remained similar for the past decade, albeit with increasing frequency in low- and middle-income countries (LMICs). Moreover, in the majority of LMICs, cervical cancer is the second most prevalent cancer and the second most common cause of cancer-related death among reproductive-age women. High-risk human papillomavirus (HR-HPV) infections have been proven to be associated with up to 95% of cervical cancer cases, with HPV-16 and HPV-18 types being responsible for approximately 70% of all cervical cancers, with the other high-risk HPV types accounting for up to a further 25%. More recently, the latest data appear to confirm there is a change in the frequency of HR-HPV occurrence, especially HPV-16 and HPV-18, as a reflection of the implementation of preventive vaccination programs. Owing to the growing incidence of cervical cancer among reproductive-age women and with the development of cancer management approaches, fertility-sparing options have been proposed for early-stage cervical cancer management as an option for young women, especially those with unaccomplished reproductive desires. However, methods applied for this purpose (cold-knife conization, loop electrosurgical excision, trachelectomy) have variable outcomes and do not prevent risks of relapse. Multiple factors are involved in cervical cancer recurrence, even in cases treated at the early stage of the disease. In this review, the authors unveil whether HPV infection and virus type could be one of the key factors associated with cervical cancer recurrence after fertility-sparing surgery. Reviews of the literature reveal that recurrent and persistent HR-HPV infection is a strong predictor of cervical lesions’ relapse. In particular, HPV-16 and HPV-18 infections and their persistence have been reported to be associated with cervical cancer recurrence. HR-HPV genotyping before and after fertility-sparing surgery for cervical cancer could facilitate a personalized approach and improve the overall survival rate. Screening for HR-HPV is essential during the follow-up of cervical cancer-treated women and will help to predict possible cancer recurrence.

Menopausal hormone therapy for breast cancer survivors.

The global incidence of breast cancer continues to increase and increasing efficacy of treatments has improved overall prognosis and survival with a resulting requisite focus on improving quality of life after cancer. Treatment inevitably results in symptoms of menopause and these symptoms may be more severe after cancer treatment compared to natural menopause and may pose a potential risk of early treatment discontinuation. Consequently, the global burden of successfully managing these symptoms is significant. There is a discordance between randomized and observational data regarding the risk of systemic menopausal hormone therapy and breast cancer recurrence; hormone receptor status is significant to recurrence risk in this setting. The systemic absorption of local oestrogen is not a consistent surrogate marker for cancer recurrence and clinical data has not demonstrated a consistent increase in the risk of cancer recurrence with local therapy. Nonhormonal treatments remain first-line management of menopause symptoms in breast cancer survivors to minimize the risk of cancer recurrence. However, severe symptoms not responding to nonhormonal interventions require a multidisciplinary, patient-centred approach to discuss the evidence base for hormonal treatments.

A multi-model approach integrating whole-slide imaging and clinicopathologic features to predict breast cancer recurrence risk.

Breast cancer is the most common malignancy affecting women worldwide and is notable for its morphologic and biologic diversity, with varying risks of recurrence following treatment. The Oncotype DX Breast Recurrence Score test is an important predictive and prognostic genomic assay for estrogen receptor positive/HER2 negative breast cancer that guides therapeutic strategies; however, such tests can be expensive, delay care, and are not widely available. The aim of this study was to develop a multi-model approach integrating the analysis of whole-slide images and clinicopathologic data to predict their associated breast cancer recurrence risks and categorize these patients into two risk groups according to the predicted score: low-risk and high-risk. The proposed novel methodology uses convolutional neural networks for feature extraction and vision transformers for contextual aggregation, complemented by a logistic regression model that analyzes clinicopathologic data for classification into two risk categories. This method was trained and tested on 956 hematoxylin and eosin-stained whole-slide images of 950 ER+/HER2- breast cancer patients with corresponding clinicopathological features that had prior Oncotype DX testing. The model's performance was evaluated using an internal test set of 192 patients from Dartmouth Health and an external test set of 405 patients from the University of Chicago. The multi-model approach achieved an AUC of 0.91 (95% CI: 0.87-0.95) on the internal set and an AUC of 0.84 (95% CI: 0.78-0.89) on the external cohort for predicting low- and high-breast cancer recurrence risk categories based on the Oncotype DX recurrence score. With further validation, the proposed methodology could provide an alternative to assist clinicians in personalizing treatment for breast cancer patients and potentially improving their outcomes.

De-escalation of Radiation Therapy in the Treatment Plan of Patients with Stage I-IIV Breast Cancer after Subcutaneous/Skin-Sparing Mastectomies with Immediate Reconstruction

Introduction. Indications for radiation therapy after mastectomies with/without reconstruction at T1­2N0­1M0 remain unclear; treatment standards contain references to the possible administration of radiation therapy for factors that increase breast cancer recurrence. Materials and methods. A retrospective single­center, non­randomized study enrolled 984 breast cancer patients treated at P.A. Gertsen Moscow Cancer Research Institute from 2014 to 2022. Patients were divided into 2 groups: a radiotherapy group and a non­radiotherapy group. Results and discussion. The paper presents an analysis of patients’ age, the histological structure of the tumor, immunohistochemical characteristics, tumor grade, multicentricity, presence of lymphovascular invasion, tumor cells, the state of R1 and R0 margins, and the tumor stage at risk of recurrence. Overall survival in the recurrence group accounted for 95.1%, in the non­recurrence group – 98.4%. In the radiotherapy group (group I), the overall survival comprised 98.4%; metastases were diagnosed in 4.9% of cases. In thenon­radiotherapy group (group II), the overall survival amounted to 98.2%; metastases were revealed in 5.9% of cases. Conclusion. Univariate analysis in the study groups showed that radiation therapy reduced the risk of relapse by 3.5%. In case of positive R1 margin, radiotherapy is recommended, which was confirmed in our study, the difference accounted for 14.5%, and in the presence of R1, radiotherapy is claimed to be necessary in the postoperative period. When analyzing the stage of breast cancer and the risk of recurrence, the statistical difference was revealed only at stage IIA (T1N1M0); radiation therapy reduced the risk of breast cancer recurrence. The statistical difference in groups I and II was detected at Grade 2 tumor, Ki­67 level less than 50%, presence of tumor embolism and age of patients under 40 years. Radiation therapy after subcutaneous/skin­sparing mastectomy reduces the recurrence risk by 3.2%; however, the overall survival in group I and group II accounted for 98.4 and 98.2%, respectively; the difference is not statistically significant. In our study, the criteria for prescribing radiation therapy in the postoperative period include: young age of the patients, R1 resection margin, luminal/non­luminal HER2 positive type, cN1, presence of tumor embolism.

Alcohol consumption and smoking history at time of diagnosis, and risk of colorectal cancer recurrence and mortality: Results from the ColoCare Study.

Findings from studies investigating the impacts of alcohol use and smoking on colorectal cancer (CRC) outcomes are inconclusive. This study aimed to investigate associations between alcohol use and smoking status at the time of diagnosis on recurrence and overall mortality among patients with CRC. The present study included 2,216 stage I-IV patients with CRC from the longitudinal multi-center ColoCare study, with available data on recurrence and CRC-specific mortality. Cox proportional hazards models adjusted for age, sex, race, ethnicity, stage, tumor site, treatment, comorbidities, body mass index, and study site were fit, with imputations for missing data. We observed 235 recurrences and 308 CRC-specific deaths over an average of 3 years of follow-up. After adjusting for confounders, current alcohol consumption and ever smoking, relative to not current consumption and never smoking, respectively, were not statistically significantly associated with CRC recurrence (Alcohol - HR: 0.95. 95% CI: 0.71-1.29; Ever smoking - HR: 0.98, 95% CI: 0.75-1.29) or CRC-specific mortality (Alcohol - HR: 0.95. 95% CI: 0.74-1.22; Ever smoking - HR: 0.98, 95% CI: 0.77-1.24). No associations were observed between alcohol and smoking at diagnosis and clinical outcomes in this well-annotated longitudinal cohort. Our cohort study reports no significant associations; however, limiting alcohol use and avoiding smoking are health behaviors recommended for CRC survivors for prevention of other cancers and chronic conditions.

The high costs of anticancer therapies in the USA: challenges, opportunities and progress.

The USA spent $99 billion on orally administered and clinician-administered anticancer therapies (excluding supportive care) in 2023 and spending is projected to increase to $180 billion by 2028. This increased spending on anticancer therapies largely reflects the high launch prices of novel therapeutics and increases in the prices of existing products, even in the absence of new evidence of clinical benefit or changes in use. Consequently, high prices have impeded Americans' access to and affordability of necessary anticancer therapies and thus increased their risk of cost-related non-adherence, cancer recurrence and mortality. To address the rising prices and concerns regarding Americans' spending on anticancer therapies, state and federal governments have, over the past decade, enacted legislation that caps out-of-pocket spending, expands subsidies and requires drug price negotiations. In this Perspective, we summarize US policies aimed to lower the costs of anticancer therapies, discuss the implications of such reforms and propose additional solutions needed to reduce costs and increase value.

Vaccination generates functional progenitor tumor-specific CD8 T cells and long-term tumor control

BackgroundImmune checkpoint blockade (ICB) therapies are an important treatment for patients with advanced cancers; however, only a subset of patients with certain types of cancer achieve durable remission. Cancer vaccines...

B-149 Diverse glycosylation of circulating alpha fetoprotein in chronic liver diseases profiled by intact mass high resolution mass spectrometry

Abstract Background Alpha fetoprotein (AFP) is a circulating tumor marker utilized clinically to detect liver cirrhosis, liver cancer and testicular seminomas. AFP molecule contains one single N-glycosylation site, with highly variable glycan structures, resulting in diverse AFP glycoforms in circulating blood. The core fucosylation of AFP (AFP-L3) is a clinical biomarker to monitor and predict risks of liver cancer progression and recurrence. Clinical testing for AFP-L3 utilizes lectin-binding and gel-shift electrophoresis. We developed a novel method to measure AFP glycoforms, based on immune-enrichment and liquid chromatography with high resolution mass spectrometry (LC-HRMS). Methods Immune enrichment of AFP was achieved by anti-AFP antibody, immobilized to magnetic beads. After binding and enrichment, the magnetic beads were washed, AFP was eluted, and the samples were analyzed by LC-HRMS (Exploris 480 MS and Vanquish UHPLC, Thermo Fisher Scientific), using full scan, positive polarity acquisition mode. Chromatographic separation was performed on PLRP column (Agilent); flow rate 200 µL/min. The HRMS data were processed and deconvoluted with intact mass analysis workflow in Biopharma Finder 5.1 (Thermo Fisher Scientific) to derive the intact AFP masses. The method’s sensitivity and imprecision were assessed by replicate analysis of serial diluted patient serum samples. AFP and its associated glycoforms were matched and identified with an in-house developed bioinformatics workflow. The deconvoluted intact masses and the sum intensity of detected charged species for each AFP glycoform were used to quantify relative abundance of AFP glycoforms. Results The method specificity for AFP was confirmed by bottom-up analysis after immune-enrichment with observed peptide sequence coverage over 35%. The recovery of the immune enrichment was shown to be independent of the AFP glycoform compositions. The identified AFP glycoforms and their relative abundance were consistent among replicates between AFP concentration 100 ng/mL and 5000 ng/mL. Analysis of authentic serum specimens from patients with different chronic liver diseases and liver cancer (n=102), revealed multiple complex biantennary branched AFP glycan modifications, with different numbers of terminal sialic acid and core fucose. Four AFP glycoforms were identified in over 60% patient samples with elevated AFP concentrations. Although occurring consistently, relative abundance of these AFP glycoforms varied significantly among patients. Assessment of the AFP fucosylation and sialylation features suggested that the two are orthogonal processes. Clinical correlations suggested that fewer terminal sialic acids were associated with impaired liver functions, while the fucosylation was linked to inflammatory responses and presence of liver malignancy. Strong linear correlation (Spearman’s rs=0.952, N=35) was observed between AFP-L3% quantitated by the LC-HRMS method, and AFP-L3% determined by the lectin-binding based isotachophoresis assay (Wako Diagnostics). Discrepancies between the two methods were observed in specimens containing < 400 ng/mL of AFP, in which the LC-HRMS method detected only a single predominant glycoform. Conclusions We developed and evaluated the LC-HRMS method for profiling circulating AFP glycoforms in patients with chronic liver diseases and liver cancer. The detected AFP glycoforms and their relative abundance were used to establish glycan features, which can be further linked to cancer development, impaired liver function, and inflammation.

Predicting Recurrence after Sublobar Resection in Patients with Lung Adenocarcinoma Using Preoperative Chest CT Scans.

Background Sublobar resection for lung cancer is usually guided by cutoff values for consolidation size (maximal diameter of the solid tumor component) and consolidation-to-tumor ratio (CTR). The effects of these factors as continuous variables and the reason for established cutoffs are, to the knowledge of the authors, unexplored. Purpose To quantitatively assess the predictive value of CTR and consolidation size for cancer recurrence risk after sublobar resection in clinical stage IA lung adenocarcinoma. Materials and Methods This retrospective study reviewed sublobar resection for clinical stage IA lung adenocarcinoma performed between January 2010 and December 2019. A restricted cubic spline function verified linearity by estimating recurrence probabilities using CTR and consolidation size obtained on preoperative CT scans. Statistical analyses included a Cox proportional hazards model to identify risk factors for cancer recurrence and the Cochran-Armitage trend test for the association between CTR and consolidation size. Results Of 1032 enrolled patients (age, 63.9 years ± 9.9 [SD]; 464 male patients), 523 (50.7%) and 509 (49.3%) underwent wedge resection and segmentectomy, respectively. Among patients with a CTR between 1% and 50% (n = 201), 187 (93.0%) had a consolidation size of less than or equal to 10 mm (P < .001). There was a positive association between the risk of recurrence with CTR and consolidation size (r2 = 0.727; P < .001). The recurrence rate showed the greatest increase when CTR was greater than 50% or consolidation size was greater than 10 mm. Specifically, the recurrence rate increased from 2.1% (three of 146) at 26%-50% CTR to 8.3% (nine of 108) at 51%-75% CTR, and from 4.4% (eight of 183) for 6-10-mm consolidation size to 11.9% (23 of 194) for 11-15-mm consolidation size. The probability of recurrence exhibited linearity and increased with CTR and consolidation size. Conclusion Cancer recurrence risk after sublobar resection for stage IA adenocarcinoma consistently rises with CTR and consolidation size. Current guideline cutoffs for sublobar resection remain clinically relevant given observed recurrence rates. © RSNA, 2024 Supplemental material is available for this article.

MRI-based radiomics for stratifying recurrence risk of early-onset rectal cancer: a multicenter study

Early-onset rectal cancer (EORC) is characterized by a unique disease process with different clinicopathological features compared with late-onset rectal cancer (LORC). Research on the risk of recurrence in EORC patients, however, is limited. We aim to develop a predictive model to accurately predict EORC recurrence risk. Rectal cancer patients who underwent radical surgery and T2-weighted imaging and diffusion-weighted imaging magnetic resonance imaging (MRI) were retrospectively enrolled from three medical institutions from November 2012 to November 2018. Differences in clinicopathological characteristics between EORC and LORC were compared. Five prediction models for disease-free survival were constructed based on clinicopathological variables and five radiomic features from pretreatment MRI of the EORC. A fixed cut-off value calculated in the training set was used to stratify EORC patients into high-risk and low-risk groups of post-operative recurrence. Model performance was evaluated by concordance index (C-index) and receiver operating characteristic curve. A total of 264 EORC patients (median age, 43 years, 163 males) and 778 LORC patients (median age, 62 years, 520 males) were enrolled. Pretreatment positive carcinoembryonic antigen [hazard ratio (HR)= 2.84, P= 0.006], pathological positive lymph node status (pN positive) [HR= 2.86, P= 0.011] and MRI-based radiomics score [HR= 2.72, P < 0.001] are independent risk factors for disease-free survival in EORC patients. The EORC-ClinPathRadiom model, constructed by integrating the clinicopathological characteristics and MRI-based radiomics features of EORC, showed C-index of 0.82, 0.82, and 0.81 in the training, internal, and external test sets, respectively. This model effectively stratified EORC patients into high risk and low risk of recurrence (HRs for the training, internal, and external test sets were 8.96, 6.81, and 7.46, respectively). The EORC-ClinPathRadiom model can effectively predict and stratify the risk of post-operative recurrence in EORC patients.

Mesoporous Polydopamine Nanotherapeutics for MRI-Guided Cancer Photothermal and Anti-Inflammatory Therapy.

As a burgeoning cancer treatment modality, photothermal therapy (PTT) has shown robust anti-tumor effects. However, it still faces numerous challenges, such as triggering an inflammatory response and potentially increasing the risk of cancer recurrence. To address these concerns, integration of PTT with anti-inflammatory therapies presents a promising approach to enhance the efficacy of cancer treatment and meanwhile reduce the risk of recurrence. In this study, Gd3+ was first chelated with dopamine to create Gd-DA chelates, and then the mesoporous dopamine nanoparticles MX@Arg-Gd-MPDA (MAGM NPs) were synthesized by combining arginine (Arg) and the anti-inflammatory medication meloxicam (MX). The photothermal properties of MAGM NPs were then defined and examined; the in vivo MRI imaging effect, as well as MAGM NPs' anti-cancer and anti-inflammatory efficiency, were tested in a mouse model of breast cancer. The incorporation of Arg doping into MAGM NPs was intended to boost its photothermal conversion efficiency and reactive oxygen species (ROS) scavenging ability. Additionally, synergizing with the anti-inflammatory agent meloxicam (MX) within the nanoparticles aimed to enhance the anti-inflammatory effect following photothermal therapy. Furthermore, gadolinium ions (Gd3+) were chelated into the nanostructure to enable precise T1-T2 dual-mode magnetic resonance imaging (MRI) of the intratumor accumulation profile. This imaging capability was leveraged to guide the implementation of photothermal therapy. Animal experiments demonstrated that MAGM NPs exerted a notable anticancer effect in a 4T1 breast cancer mouse model, under the precise guidance of MRI.

Cardio-oncology: chances and challenges.

Cardio-oncology is an emerging field that aims to ensure optimal cancer treatment while minimising cardiovascular toxicity. The management of cardiovascular toxicity is critical because it can lead to premature discontinuation of treatment, increasing the risk of cancer recurrence and mortality. The 2022 European Society of Cardiology guidelines were a milestone in advocating a patient-centred, multidisciplinary approach. Key components include risk stratification and a standardised criterion for adverse events, incorporating definitions from the International Cardio-Oncology Society. Effective risk stratification, supported by imaging and biomarkers, helps to anticipate cardiovascular problems and implement preventive measures. Future research should focus on understanding mechanisms, developing preventive strategies and implementing personalised medicine. Education and reducing disparities in care are essential to advance cardio-oncology and improve patient outcomes.

Severe carbohydrate restriction augments the antiproliferative effect of hormonal therapy in a murine model of Ehrlich breast adenocarcinoma: histological and immunohistochemical investigations

BackgroundMalignant tumors of the breast are the most diagnosed cancers in females globally. Recent evidence suggests that carbohydrate restriction (CR), especially ketogenic diets, has become a potential treatment approach for many malignancies, including breast cancer. Tamoxifen (TAX) is a selective estrogen receptor modulator (ERM) that can reduce the risk of cancer recurrence. The current work was designed to assess the impact of CR on the proliferation of breast adenocarcinoma cells and to compare this impact with that of TAX. Study groups included: group 1: vehicle-treated mice; group 2: the Ehrlich group: injected Ehrlich ascites carcinoma (EAC) cells (2.5 × 106) in 0.25 ml isotonic saline; group 3: CR group: mice were supplied with a diet regimen of severe CR throughout the study and injected EAC at week 7; group 4: hormonal therapy (HT) group: mice in this group injected with EAC at week 7 and then received TAX at a dose of 20 mg/kg 3 times/week orally for 3 weeks; and lastly group 5: the group of combined intervention. The mice in the CR, HT, and the combined groups received Ehrlich cancer cells at the same dose and route as the Ehrlich group.ResultsCR and HT groups demonstrated a significant decrease in levels of insulin-like growth factor (IGF-1), carbohydrate antigen (CA 15–3), hexokinase 2 (HK2), hypoxia-inducible factor-1 (HIF-1) α, and malondialdehyde (MDA) compared to the Ehrlich group. Additionally, the mean area % of caspase-3 was significantly increased, and the mean area % of Ki67 and estrogen receptor (ER)α was significantly decreased.ConclusionsThe combined treatment demonstrated the most advantageous outcome, as evidenced by reduced CA 15–3 levels, tumor size, and the mean area % of Ki67. This suggests that the addition of severe CR to the conventional therapy of breast cancer has a beneficial effect.

Vulvovaginal Atrophy Following Treatment for Oncogynecologic Pathologies: Etiology, Epidemiology, Diagnosis, and Treatment Options.

Vulvovaginal atrophy, characterized by the thinning of vaginal mucosa typically resulting from reduced estrogen levels, is frequently exacerbated by oncogynecologic treatments such as chemotherapy, hormonal therapy, radiotherapy, or surgery. This condition significantly impacts the quality of life for cancer survivors, leading to persistent discomfort, heightened infection risk, and negative effects on sexual function and self-esteem. Despite being a relatively common complication, vulvovaginal atrophy is not always discussed before the start of treatment. Treatments typically mirror those used for natural menopause; however, efficacy and safety data specific to this population are limited due to the exclusion of these patients from clinical trials. A major safety concern is the risk of hormone-sensitive cancer recurrence associated with estrogen therapy, which drives a preference for non-hormonal alternatives. Newer treatments, such as laser therapy, radiofrequency, and vaginal injections, show promise with minimal side effects and hormone-independent mechanisms, though efficacy data varies, highlighting the need for further research. This narrative review explores the epidemiology, risk factors, diagnosis, and management of vulvovaginal atrophy after the treatment for oncogynecologic disorders.

Menopausal Hormone Therapy in Breast Cancer Survivors.

Menopausal symptoms negatively impact quality of life in breast cancer survivors. The paucity of data on the impact of Menopausal Hormone Therapy (MHT) on oncological outcomes in these patients limits informed clinical discussion. Defining the risk of cancer recurrence with MHT is central to the appraisal of risk/benefit, particularly with low-risk disease (based on genomic profile). The aim of this review is to summarize the current data evaluating MHT in breast cancer patients. A systematic review of the literature was performed to evaluate the impact of MHT on oncological outcomes in breast cancer survivors. Three major databases (PubMed, EMBASE and Medline) were searched. The review included all prospective studies published in English. Four randomized control trials and four non-randomized prospective studies were identified. An increase in breast cancer recurrence with MHT was observed in the early randomized trials whilst no increased risk of recurrence was reported in the observational studies. There remains a need to quantify MHT-related recurrence risk in patients with molecularly favorable disease.