Clinical Outcomes In Cancer Patients Research Articles

Unveiling the influence of SGLT2 inhibitors on clinical outcomes in patients with cancer with therapy-related cardiac dysfunction: A meta-analysis and systemic review.

e24003 Background: Cancer patients undergoing chemotherapy suffer from a variable degree of cancer therapy–related cardiac dysfunction and heart failure (HF). It is known that sodium glucose co-transporter 2 (SGLT2) inhibitors improve outcomes in patients with HF independent of diabetes mellitus and left ventricular ejection fraction; our study aims to investigate the potential benefits of SGLT2 inhibitory therapy specifically in cancer patients undergoing chemotherapy. Methods: We performed an electronic search on PubMed, Embase, and Cochrane, from the inception of databases till January 29, 2024, to identify all the articles that compared the use of SGLT2 inhibitors in adult (≥18 years) with type 2 diabetes mellitus and exposure to cardiotoxic antineoplastic therapy, subsequently diagnosed with cardiomyopathy, heart failure, or LVEF < 40%. The data was extracted and pooled using a random effects model to calculate the odds ratio (OR) with a respective 95% confidence interval (CI). R software (v.4.3) was used for all statistical analyses. Results: Our search identified three observational studies with a total of 3,164 patients (SGLT2- inhibitor group: 1,550; Control group: 1,614). We found that the use of SGLT2 inhibitors was associated with a lower risk of all-cause mortality (OR: 0.25 [0.20, 0.31]; I2 = 16%; p < 0.001), hospitalizations from heart failure (OR: 0.25 [0.10, 0.62]; I2 = 0%; p = 0.003), and acute exacerbation of heart failure (OR: 0.35 [0.27, 0.47]; I2 = 0%; p < 0.001). Conclusions: Our findings suggest a favorable association between the use of SGLT2 inhibitors and reduced mortality, as well as improved cardiac clinical outcomes in cancer patients undergoing chemotherapy. However, further validation through large-scale studies and randomized controlled trials across diverse malignancies is warranted to establish the efficacy of these drugs. [Table: see text]

Posttranslational regulatory mechanism of PD-L1 in cancers and associated opportunities for novel small-molecule therapeutics.

Despite the tremendous progress in cancer research over the past few decades, effective therapeutic strategies are still urgently needed. Accumulating evidence suggests that immune checkpoints are the cause of tumor immune escape. PD-1/PD-L1 are among them. Posttranslational modification is the most critical step for protein function, and the regulation of PD-L1 by small molecules through posttranslational modification is highly valuable. In this review, we discuss the mechanisms of tumor cell immune escape and several posttranslational modifications associated with PD-L1 and describe examples in which small molecules can regulate PD-L1 through posttranslational modifications. Herein, we propose that the use of small molecule compounds that act by inhibiting PD-L1 through posttranslational modifications is a promising therapeutic approach with the potential to improve clinical outcomes for cancer patients.

Multiomics approach towards characterization of tumor cell plasticity and its significance in precision and personalized medicine.

Cellular plasticity refers to the ability of cells to change their identity or behavior, which can be advantageous in some cases (e.g., tissue regeneration) but detrimental in others (e.g., cancer metastasis). With a better understanding of cellular plasticity, the complexity of cancer cells, their heterogeneity, and their role in metastasis is being unraveled. The plasticity of the cells could also prove as a nemesis to their characterization. In this review, we have attempted to highlight the possibilities and benefits of using multiomics approach in characterizing the plastic nature of cancer cells. There is a need to integrate fragmented evidence at different levels of cellular organization (DNA, RNA, protein, metabolite, epigenetics, etc.) to facilitate the characterization of different forms of plasticity and cell types. We have discussed the role of cellular plasticity in generating intra-tumor heterogeneity. Different omics level evidence is being provided to highlight the variety of molecular determinants discovered using different techniques. Attempts have been made to integrate some of this information to provide a quantitative assessment and scoring of the plastic nature of the cells. However, there is a huge gap in our understanding of mechanisms that lead to the observed heterogeneity. Understanding of these mechanism(s) is necessary for finding targets for early detection and effective therapeutic interventions in metastasis. Targeting cellular plasticity is akin to neutralizing a moving target. Along with the advancements in precision and personalized medicine, these efforts may translate into better clinical outcomes for cancer patients, especially in metastatic stages.

The relationship between baseline nutritional status with subsequent parenteral nutrition and clinical outcomes in cancer patients undergoing cytoreductive surgery: a retrospective study.

Hyperthermic Intraperitoneal Chemotherapy (HIPEC) with Cytoreductive Surgery (CRS) is the preferred treatment for peritoneal malignancies. This highly complex operation is associated with a high incidence of complications, particularly due to malnutrition. This study aimed to investigate the potential association between preoperative nutritional status and postoperative clinical outcomes in adult cancer patients who underwent CRS/HIPEC for peritoneal malignancy. A retrospective study with 140 adult cancer patients, on parenteral nutrition (PN) (n = 40) and not on PN (n = 100) who underwent CRS with or without HIPEC, was conducted. Patients who received PN had significantly longer post-operative, hospital, and ICU LOS than those who did not (p = 0.001). ICU admission was significantly higher in the non-PN receiving group compared to the PN receiving group. When compared to the PN group, the majority of patients not receiving PN were at low risk of malnutrition (91% vs. 75%, p = 0.020), whereas 17.5% of PN patients were at risk of malnutrition during hospitalization. Multiple regression analyses revealed a strong positive relationship between patients with increased risk of malnutrition and ICU LOS (p = 0.047). Routine preoperative nutrition assessment is essential to identify patients who are at higher nutritional risk, and nutrition support should be provided preoperatively.

An insight into the use of telemedicine technology for cancer patients during the Covid-19 pandemic: a scoping review

BackgroundThe use of telemedicine technology has significantly increased in recent years, particularly during the Covid-19 pandemic. This study aimed to investigate the use of telemedicine technology for cancer patients during the Covid-19 pandemic.MethodsThis was a scoping review conducted in 2023. Various databases including PubMed, Web of Science, Scopus, Cochrane Library, Ovid, IEEE Xplore, ProQuest, Embase, and Google Scholar search engine were searched. All quantitative, qualitative, and mixed-method studies published in English between 2020 and 2022 were included. Finally, the needed data were extracted, and the results were synthesized and reported narratively.ResultsA total of 29 articles were included in this review. The results showed that teleconsultation, televisit, and telerehabilitation were common telemedicine services, and video conferencing and telephone were common technologies used in these studies. In most cases, patients and healthcare providers preferred these services compared to the face-to-face consultations due to their convenience and advantages. Furthermore, the findings revealed that in terms of clinical outcomes, telemedicine could effectively reduce anxiety, pain, sleep disorders, and hospital admission rates.ConclusionThe findings provided valuable insights into the various telemedicine technologies, services, users’ perspectives, and clinical outcomes in cancer patients during the Covid-19 pandemic. Overall, the positive outcomes and users’ satisfaction showed that the use of telemedicine technology can be expanded, particularly in cancer care. Future research needs to investigate both clinical and non-clinical effectiveness of using various telemedicine services and technologies for improving cancer care delivery, which can help to develop more successful strategies for implementing this technology.

Impact of concurrent medications on clinical outcomes of cancer patients treated with immune checkpoint inhibitors: analysis of Health Insurance Review and Assessment data

PurposeMedications regulating immune homeostasis and gut microbiota could affect the efficacy of immune checkpoint inhibitors (ICIs). This study aimed to investigate the impact of concurrent medications on the clinical outcomes of patients with cancer receiving ICI therapy in South Korea.MethodsWe identified patients newly treated with ICI for non-small cell lung cancer (NSCLC), urothelial carcinoma (UC), and malignant melanoma (MM) between August 2017 and June 2020 from a nationwide database in Korea. The effect of concurrent antibiotics (ATBs), corticosteroids (CSs), proton-pump inhibitors (PPIs), and opioids prescribed within 30 days before ICI initiation on the treatment duration and survival was assessed.ResultsIn all, 8870 patients were included in the ICI cohort (NSCLC, 7,128; UC, 960; MM, 782). The patients were prescribed ATBs (33.8%), CSs (47.8%), PPIs (28.5%), and opioids (53.1%) at the baseline. The median overall survival durations were 11.1, 12.2, and 22.1 months in NSCLC, UC, and MM subgroups, respectively, since starting the ICI mostly as second-line (NSCLC and UC) and first-line (MM) therapy. Early progression was observed in 34.2% of the patients. Opioids and CS were strongly associated with poor survival across all cancer types. A high number of concurrent medications was associated with early progression and short survival. Opioid and CS use was associated with poor prognosis in all patients treated with ICIs. However, ATBs and PPIs had a cancer-specific effect on survival.ConclusionA high number of concurrent medications was associated with poor clinical outcomes.

CDK12 is a potential biomarker for diagnosis, prognosis and immunomodulation in pan-cancer

Cell cycle-dependent protein kinase 12 (CDK12) plays a key role in a variety of carcinogenesis processes and represents a promising therapeutic target for cancer treatment. However, to date, there have been no systematic studies addressing its diagnostic, prognostic and immunological value across cancers. Here, we found that CDK12 was significantly upregulated in various types of cancers, and it expression increased with progression in ten cancer types, including breast cancer, cholangiocarcinoma and colon adenocarcinoma. Moreover, the ROC curves indicated that CDK12 showed diagnostic value in eight cancer types. High CDK12 expression was associated with poor prognosis in eight types of cancer, including low-grade glioma, mesothelioma, melanoma and pancreatic cancer. Furthermore, we conducted immunoassays to explore the exact mechanisms underlying CDK12-induced carcinogenesis, which revealed that increased expression of CDK12 allowed tumours to evade immune surveillance and upregulate immune checkpoint genes. Additionally, mutational studies have shown that amplification and missense mutations are the predominant mutational events affecting CDK12 across cancers. These findings establish CDK12 as a significant biological indicator of cancer diagnosis, prognosis, and immunotherapeutic targeting. Early surveillance and employment of CDK12 inhibitors, along with concomitant immunotherapy interventions, may enhance the clinical outcomes of cancer patients.

Comprehensive analysis of zinc and ring finger 3 in prognostic value and pan-cancer immunity.

Zinc and ring finger 3 (ZNRF3) is a negative suppressor of Wnt signal and newly identified as an important regulator in tumorigenesis and development. However, the pan-cancer analysis of ZNRF3 has not been reported. We found that ZNRF3 was significantly decreased in six tumors including CESC, KIRP, KIRC, SKCM, OV, and ACC, but increased in twelve tumors, namely LGG, ESCA, STES, COAD, STAD, LUSC, LIHC, THCA, READ, PAAD, TGCT, and LAML. Clinical outcomes of cancer patients were closely related to ZNRF3 expression in ESCA, GBM, KIRC, LUAD, STAD, UCEC, LGG, and SARC. The highest genetic alteration frequency of ZNRF3 occurred in ACC. Abnormal expression of ZNRF3 could be attributed to the differences of copy number variation (CNV) and DNA methylation as well as ZNRF3-interacting proteins. Besides, ZNRF3 were strongly associated with tumor heterogeneity, tumor stemness, immune score, stromal score and ESTIMATE score in certain cancers. In terms of immune cell infiltration, ZNRF3 was positively correlated to infiltration of cancer-associated fibroblasts in CESC, HNSC, OV, PAAD, PRAD, and THYM, but negatively associated with infiltration of CD8 T cells in HNSC, KIRC, KIRP and THYM. Moreover, ZNRF3 expression was correlated with most immune checkpoint genes in SARC, LUSC, LUAD, PRAD, THCA, UVM, TGCT, and OV, and associated with overwhelming majority of immunoregulatory genes in almost all cancers. Most RNA modification genes were also remarkably related to ZNRF3 level in KIRP, LUAD, LUSC, THYM, UVM, PRAD, and UCEC, indicating that ZNRF3 might have an important effect on cancer epigenetic regulation. Finally, we verified the expression and role of ZNRF3 in clinical specimens and cell lines of renal cancer and liver cancer. This study provides a comprehensive pan-cancer analysis of ZNRF3 and reveals the complexity of its carcinogenic effect.

Hypoxia-activated ADCC-enhanced humanized anti-CD147 antibody for liver cancer imaging and targeted therapy with improved selectivity.

Therapeutic antibodies (Abs) improve the clinical outcome of cancer patients. However, on-target off-tumor toxicity limits Ab-based therapeutics. Cluster of differentiation 147 (CD147) is a tumor-associated membrane antigen overexpressed in cancer cells. Ab-based drugs targeting CD147 have achieved inadequate clinical benefits for liver cancer due to side effects. Here, by using glycoengineering and hypoxia-activation strategies, we developed a conditional Ab-dependent cellular cytotoxicity (ADCC)-enhanced humanized anti-CD147 Ab, HcHAb18-azo-PEG5000 (HAP18). Afucosylated ADCC-enhanced HcHAb18 Ab was produced by a fed-batch cell culture system. Azobenzene (Azo)-linked PEG5000 conjugation endowed HAP18 Ab with features of hypoxia-responsive delivery and selective targeting. HAP18 Ab potently inhibits the migration, invasion, and matrix metalloproteinase secretion, triggers the cytotoxicity and apoptosis of cancer cells, and induces ADCC, complement-dependent cytotoxicity, and Ab-dependent cellular phagocytosis under hypoxia. In xenograft mouse models, HAP18 Ab selectively targets hypoxic liver cancer tissues but not normal organs or tissues, and has potent tumor-inhibiting effects. HAP18 Ab caused negligible side effects and exhibited superior pharmacokinetics compared to those of parent HcHAb18 Ab. The hypoxia-activated ADCC-enhanced humanized HAP18 Ab safely confers therapeutic efficacy against liver cancer with improved selectivity. This study highlights that hypoxia activation is a promising strategy for improving the tumor targeting potential of anti-CD147 Ab drugs.

Association between coronary artery disease and clinical outcome in cancer patients: A propensity score matching analysis

ObjectiveThe aim of this study was to evaluate the prognostic value of coronary artery disease (CAD) detected by coronary computed tomography angiography (CTA) to predict the risk of all-cause mortality in cancer patients in a propensity score matching (PSM) analysis. MethodsA total of 331 patients who previously had cancer and underwent coronary CTA from January 2015 to December 2019 were included. Multivariate Cox proportional hazards regression analysis and propensity-score matching analysis were performed. The primary endpoint was all-cause of mortality. ResultsIn total, 125 with CAD and 206 with no CAD during a median follow-up of 3.3 years were included in this study. After PSM, age (HR, 1.040; 95%CI, 1.001–1.081; p = 0.014) and CAD (HR, 2.164; 95%CI, 1.057–4.430; p = 0.035) remained significant factors for all-cause mortality. ConclusionCAD evaluated by coronary CTA was found to be at higher risk for all-cause mortality in cancer patients. Due to the retrospective design and lack of information on some medical history and treatments, especially immune checkpoint inhibitors, a large-scale prospective study is needed to further determine the prognostic value of coronary CTA in cancer patients.

FFAR2 expressing myeloid-derived suppressor cells drive cancer immunoevasion

BackgroundEmerging evidences suggest that aberrant metabolites contributes to the immunosuppressive microenvironment that leads to cancer immune evasion. Among tumor immunosuppressive cells, myeloid-derived suppressor cells (MDSCs) are pathologically activated and extremely immunosuppressive, which are closely associated with poor clinical outcomes of cancer patients. However, the correlation between MDSCs mediated immunosuppression and particular cancer metabolism remained elusive.MethodsSpontaneous lung adenocarcinoma and subcutaneous mouse tumor models, gas chromatography–mass spectrometry (GC–MS) and immunofluorescence assay of patient-derived lung adenocarcinoma tissues, and flow cytometry, RNA sequencing and Western blotting of immune cells, were utilized.ResultsMetabolite profiling revealed a significant accumulation of acetic acids in tumor tissues from both patients and mouse model, which contribute to immune suppression and cancer progression significantly through free fatty acid receptor 2 (FFAR2). Furthermore, FFAR2 is highly expressed in the myeloid-derived suppressor cells (MDSCs) from the tumor of lung adenocarcinoma (LUAD) patients which is greatly associated with poor prognosis. Surprisingly, whole or myeloid Ffar2 gene deletion markedly inhibited urethane-induced lung carcinogenesis and syngeneic tumor growth with reduced MDSCs and increased CD8+ T cell infiltration. Mechanistically, FFAR2 deficiency in MDSCs significantly reduced the expression of Arg1 through Gαq/Calcium/PPAR-γ axis, which eliminated T cell dysfunction through relieving L-Arginine consumption in tumor microenvironment. Therefore, replenishment of L-Arginine or inhibition to PPAR-γ restored acetic acids/FFAR2 mediated suppression to T cells significantly. Finally, FFAR2 inhibition overcame resistance to immune checkpoint blockade through enhancing the recruitment and cytotoxicity of tumor-infiltrating T cells.ConclusionAltogether, our results demonstrate that the acetic acids/FFAR2 axis enhances MDSCs mediated immunosuppression through Gαq/calcium/PPAR-γ/Arg1 signaling pathway, thus contributing to cancer progression. Therefore, FFAR2 may serve as a potential new target to eliminate pathologically activated MDSCs and reverse immunosuppressive tumor microenvironment, which has great potential in improving clinical outcomes of cancer immunotherapy.

WITHDRAWN: A Survey on the Attitude and Willingness of Chinese Cancer Patients toward a COVID-19 Booster Vaccine

ObjectiveThe 2019 novel coronavirus is still rapidly mutating and spreading worldwide, posing a great global health challenge, especially vulnerable groups, including cancer patients. Studies comparing the clinical outcomes of cancer patients receiving or not receiving the 2019 coronavirus disease (COVID-19) vaccines have not yet shown significant benefits. Therefore, this study mainly focused on the attitudes and willingness of cancer patients toward COVID-19 booster vaccines and to distinguish independent predictors that may impact the vaccination of cancer patients. MethodsAn online cross-sectional study was conducted between July 1, 2022 and January 1, 2023 in China. Patients were selected using a convenience sampling method, and a self-reporting questionnaire was developed based on a literature review to evaluate the attitude of cancer patients towards the intensive use of COVID-19 vaccines and the willingness of patients to accept the COVID-19 vaccine. Independent predictors associated with accepting a COVID-19 booster vaccine were determined through multivariate logistic regression. ResultsA total of 1055 participants were included in this study. The vaccine acceptance rate was 56.11% (592/1055), while the hesitancy rate was 43.89% (463/1055). Frequent smoking, those who had received two doses of the COVID-19 vaccine, belief that the COVID-19 booster vaccine was necessary, belief that the COVID-19 booster vaccine was safe and effective, willingness to pay for the COVID-19 booster vaccine, and recommendation of COVID-19 booster vaccine by friends and family were contributing factors for vaccine acceptance. ConclusionThis study recommends developing healthcare policies appropriate for cancer patients to facilitate their acceptance of vaccines, such as publishing the safety and effectiveness of vaccines, providing individualized treatment options after adequate risk assessment and developing specific COVID-19 vaccines suitable for cancer patients.

Malnutrition prevalence in cancer patients in Belgium: The ONCOCARE study

RationaleUnintentional weight loss and malnutrition are common among cancer patients. Malnutrition has been associated with impaired health-related quality of life, less well-tolerated chemotherapy regimens and shorter life duration. In Belgium there is a lack of epidemiological data on malnutrition in oncology patients at advanced stages of the disease.MethodsMalnutrition assessment data was collected through a prospective, observational study in 328 patients who started a neoadjuvant anticancer therapy regimen or who started 1st, 2nd or 3rd line anticancer therapy for a metastatic cancer via 3 visits according to regular clinical practice (baseline visit (BV) maximum 4 weeks before start therapy, 1st Follow up visit (FUV1) ± 6 weeks after start therapy, FUV2 ± 4 months after start therapy). Malnutrition screening was evaluated using the Nutritional Risk Screening score 2002 (NRS-2002)and the diagnosis of malnutrition by the GLIM criteria. In addition, SARC-F questionnaire and Fearon criteria were used respectively to screen for sarcopenia and cachexia.ResultsPrevalence of malnutrition risk at BV was high: 54.5% of the patients had a NRS ≥ 3 (NRS 2002) and increased during the study period (FUV1: 73.2%, FUV2: 70.1%). Prevalence of malnutrition based on physician subjective assessment (PSA) remained stable over the study period but was much lower compared to NRS results (14.0%—16.5%). At BV, only 10% of the patients got a nutrition plan and 43.9% received ≤ 70% of nutritional needs, percentage increased during FU period (FUV1: 68.4%, FUV2: 67.6%). Prevalence of sarcopenia and cachexia were respectively 12.4% and 38.1% at BV and without significant variation during the study period, but higher than assessed by PSA (11.6% and 6.7% respectively). Figures were also higher compared to PSA. There were modifications in cancer treatment at FUV1 (25.2%) and at FUV2 (50.8%). The main reasons for these modifications at FUV1 were adverse events and tolerability. Patient reported daily questionnaires of food intake showed early nutritional deficits, preceding clinical signs of malnutrition, and therefore can be very useful in the ambulatory setting.ConclusionsPrevalence of malnutrition and cachexia was high in advanced cancer patients and underestimated by physician assessment. Earlier and rigorous detection of nutritional deficit and adjusted nutritional intake could lead to improved clinical outcomes in cancer patients. Reporting of daily caloric intake by patients was also very helpful with regards to nutritional assessment.

EP2 and EP4 blockade prevents tumor-induced suppressive features in human monocytic myeloid-derived suppressor cells.

Tumors educate their environment to prime the occurrence of suppressive cell subsets, which enable tumor evasion and favors tumor progression. Among these, there are the myeloid-derived suppressor cells (MDSCs), their presence being associated with the poor clinical outcome of cancer patients. Tumor-derived prostaglandin E2 (PGE2) is known to mediate MDSC differentiation and the acquisition of pro-tumor features. In myeloid cells, PGE2 signaling is mediated via E-prostanoid receptor type 2 (EP2) and EP4. Although the suppressive role of PGE2 is well established in MDSCs, the role of EP2/4 on human MDSCs or whether EP2/4 modulation can prevent MDSCs suppressive features upon exposure to tumor-derived PGE2 is poorly defined. In this study, using an in vitro model of human monocytic-MDSCs (M-MDSCs) we demonstrate that EP2 and EP4 signaling contribute to the induction of a pro-tumor phenotype and function on M-MDSCs. PGE2 signaling via EP2 and EP4 boosted M-MDSC ability to suppress T and NK cell responses. Combined EP2/4 blockade on M-MDSCs during PGE2 exposure prevented the occurrence of these suppressive features. Additionally, EP2/4 blockade attenuated the suppressive phenotype of M-MDSCs in a 3D coculture with colorectal cancer patient-derived organoids. Together, these results identify the role of tumor-derived PGE2 signaling via EP2 and EP4 in this human M-MDSC model, supporting the therapeutic value of targeting PGE2-EP2/4 axis in M-MDSCs to alleviate immunosuppression and facilitate the development of anti-tumor immunity.

Comparison of bioelectrical impedance analysis and computed tomography for the assessment of muscle mass in patients with gastric cancer

BackgroundLow muscle mass was significantly correlated with poor clinical outcomes in cancer patients. This study aimed to compare the differences between bioelectrical impedance analysis (BIA) and computed tomography (CT) in measuring skeletal muscle mass and detecting low muscle mass in patients with gastric cancer (GC). MethodThis cross-sectional study included a total of 302 consecutive patients diagnosed with GC at our institution from October 2021 to March 2023. CT images were analyzed at the L3 level to obtain the cross-sectional area of skeletal muscle, which was subsequently used for calculating whole-body skeletal muscle mass via the Shen equation and skeletal muscle tissue density. BIA was utilized to measure skeletal muscle mass using the manufacturer's proprietary algorithms. Skeletal muscle mass (kg) was divided by height squared (m2) to obtain skeletal muscle index (SMI, kg/m2). Pearson's correlation coefficient was performed to assess the correlation between SMI measured by BIA and CT. The agreement between the two methods was assessed using Bland-Altman analyses. The clinically acceptable agreement was defined as the 95% limits of agreement (LOA) for the percentage bias falling within ± 10%. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of BIA in identifying low muscle mass. ResultsA total of 59 patients (19.5%) were identified as having low muscle mass based on CT analysis, whereas only 19 patients (6.3%) met the criteria for low muscle mass according to BIA analysis. BIA-measured SMI showed a strong positive correlation with CT-measured SMI in all patients (r = 0.715, P < 0.001). With Bland-Altman analysis, there was a significant mean bias of 1.18 ± 0.96 kg/m2 (95% CI 1.07–1.29, P < 0.001) between SMI measured by BIA and CT. The 95% LOA for the percentage bias ranged from -7.98 to 33.92%, which exceeded the clinically acceptable range of ± 10%. A significant difference was observed in the mean bias of SMI measured by BIA and CT between patients with and without GLIM malnutrition (1.42 ± 0.91 kg/m2 versus 0.98 ± 0.96 kg/m2, P < 0.001). The cut-off values for BIA-measured SMI in identifying low muscle mass using CT as the reference were 10.11 kg/m2 for males and 8.71 kg/m2 for females (male: AUC = 0.840, 95% CI: 0.772–0.908; female: AUC = 0.721, 95% CI: 0.598–0.843). ConclusionsDespite a significant correlation, the values of skeletal muscle mass obtained BIA and CT cannot be used interchangeably. The BIA method may overestimate skeletal muscle mass in GC patients compared to CT, especially among those with GLIM malnutrition, leading to an underestimation of low muscle mass prevalence.

Implementing precision oncology in Latin America to improve patient outcomes: the status quo and a call to action for key stakeholders and decision-makers.

The advent of precision oncology (PO) has revolutionised diagnostic and follow up strategies and improved clinical outcomes for cancer patients. However, socio-economic inequalities in the level of implementation of PO in different countries is a prevailing issue. To improve this situation, the Latin America Patients Academy has gathered the recommendations of healthcare professionals and social civil members experienced in cancer management from Mexico, Guatemala, Costa Rica, Dominican Republic, Panama, Colombia, Chile, Ecuador, Peru and Argentina regarding the areas that need to be prioritised to improve the access to PO in Latin American (LATAM) countries. This manuscript is the culmination of a series of educational campaigns and panel discussion aimed at improving the implementations of PO in LATAM that took place from June 2021 to January 2022. the level of PO implementation is generally low with some exceptions. The number of clinical trials and articles published with keywords related to PO from LATAM countries is drastically lower than in Europe and the United States. Despite sharing many complex challenges, progress is taking place in some countries in the region. The expert panel determined the areas of PO that should be improved by LATAM countries to improve its implementation through cancer care plans, educational programs and collaborative strategies. These initiatives should increase awareness about PO in the region and eventually improve cancer control in the region.

Heterogeneity of tertiary lymphoid structures in cancer.

The success of immunotherapy approaches, such as immune checkpoint blockade and cellular immunotherapy with genetically modified lymphocytes, has firmly embedded the immune system in the roadmap for combating cancer. Unfortunately, the majority of cancer patients do not yet benefit from these therapeutic approaches, even when the prognostic relevance of the immune response in their tumor entity has been demonstrated. Therefore, there is a justified need to explore new strategies for inducing anti-tumor immunity. The recent connection between the formation of ectopic lymphoid aggregates at tumor sites and patient prognosis, along with an effective anti-tumor response, suggests that manipulating the occurrence of these tertiary lymphoid structures (TLS) may play a critical role in activating the immune system against a growing tumor. However, mechanisms governing TLS formation and a clear understanding of their substantial heterogeneity are still lacking. Here, we briefly summarize the current state of knowledge regarding the mechanisms driving TLS development, outline the impact of TLS heterogeneity on clinical outcomes in cancer patients, and discuss appropriate systems for modeling TLS heterogeneity that may help identify new strategies for inducing protective TLS formation in cancer patients.

COVID-19 in cancer patients: The impact of vaccination on outcomes early in the pandemic.

With the rapid evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the development of effective and safe vaccines was of utmost importance to protect vulnerable individuals, including cancer patients. Studies comparing the clinical outcomes of cancer patients with or without vaccination against coronavirus disease 2019 (COVID-19) have not demonstrated clear benefit. We aimed to determine the protective effects of COVID-19 vaccination by comparing vaccinated and unvaccinated cancer patients after the initial phase of vaccine roll-out and to identify risk factors associated with hospitalization, severe COVID-19, and 30-day COVID-19 attributable mortality. We performed a retrospective cohort study of cancer patients with COVID-19 diagnosed by polymerase chain reaction on nasal swabs between January 1, 2021 and July 30, 2021. Outcomes of interest included hospitalization, severe COVID-19, and 30-day COVID-19 attributable mortality. Univariate and multivariate analyses were performed to identify factors associated with clinical outcomes, using vaccination status as a variable of interest in all models. Key risk factors, such as age ≥ 60 years; comorbidities including diabetes mellitus, heart failure, and lung diseases; and specific cancer types (leukemia and lymphoma) were independently associated with hospital admission for COVID-19, severe COVID-19, and 30-day COVID-19 attributable mortality in cancer patients regardless of their vaccination status. Vaccinated patients were protected against severe COVID-19 but with no impact on hospitalization or mortality due to COVID-19. Our study highlights a significant benefit of COVID-19 vaccination for cancer patients-specifically its protection against severe COVID-19.

Abstract B097: Molecular disparities between cancer patients with normal weight and excessive body fat

Abstract Overweight and obesity, as measured by high body mass index (BMI), can have significant negative impacts on human health due to associated co-morbidities. Epidemiological data have demonstrated strong associations between overweight/obesity and 13 different types of cancer. However, the molecular features underlying the relationship between body weight and cancer remain poorly understood. In this study, we conducted a comprehensive analysis of molecular differences between patients with overweight/obesity and normal-weight patients across 14 different cancer types from The Cancer Genome Atlas (TCGA). By employing the propensity score weighting algorithm to balance confounding factors, we identified obesity-specific mutational features in multiple cancer types, such as a higher mutation burden in rectal cancer, biased mutational signatures, and overweight/obesity-specific significantly mutated genes in several cancer types. The biased mutation signatures are caused by the activity of AID/APOBEC family of cytidine deaminases and their contribution to DNA damage, ect, which suggest that obesity may contribute to the development of cancer by promoting the accumulation of specific types of mutations. Most of these biased genes have not been reported as significantly mutated genes in previous TCGA large cohort, implying these biased genes may be due to the environment of excessive body fat. We also found that differential expression genes (DEGs) and dysmethylated genes in overweight and obese tumors were predominantly upregulated and enriched in inflammatory and hormone-related pathways. These DEGs were significantly associated with survival rates in various cancer types, highlighting the impact of excessive body fat on gene expression profiles and clinical outcomes in cancer patients. Interestingly, while high BMI seemed to have a negative impact on most cancer types, it may be beneficial to endometrial cancers, as reflected by normal weight-biased mutational and gene expression patterns, suggesting the presence of an "obesity paradox" in this context. Moreover, our analysis revealed that excessive body fat significantly impacted the tumor microenvironment by altering immune cell infiltration, emphasizing the importance of understanding the complex interplay between obesity and immune response in cancer progression and treatment. Overall, our results provide the most comprehensive understanding of the molecular differences including mutational patterns, gene expression, and immune features between normal-weight and overweight/obese cancer patients. Such systematic understanding of the molecular basis for body weight disparities in multiple cancer types may provide critical insights into the future development of precision cancer therapy for cancer patients with overweight/obesity. Citation Format: Fengyuan Huang, Peng Xu, Zongliang Yue, Yuwei Song, Kaili Hu, Xinyang Zhao, Min Gao, Zechen Chong. Molecular disparities between cancer patients with normal weight and excessive body fat [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B097.

Novel Drug to Target HK2 Overcomes Therapeutic Resistance in Preclinical B-Cell Lymphoma Models

Background: The Warburg's effect is a hallmark in cancer. Hexokinase II (HK2) is a glycolic kinase to phosphorylate glucose to glucose-6-phosphate, which can be utilized as the energy source for cells. HK2 is predominantly overexpressed in cancer cells and has been associated with poor clinical outcomes in cancer patients. Previously, we demonstrated that HK2 mRNA and protein levels were increased in diffuse large B-cell lymphoma patients, and were significantly associated with inferior progression free survival (PFS) and overall survival (OS). In our rituximab and chemotherapy-resistant cell lines (TRCL), we demonstrated an upregulation of HK2 expression level is association with voltage-dependent anion channel (VDAC) resulting in a) repress mitochondrial potential and b) global therapy resistance. Knocking out HK2 overcame the chemo-resistance phenotype observed in TRCL. Here, we designed a novel specific inhibitor of HK2 and tested its activity in lymphoma pre-clinical models. Material and Methods: A HK2 specific inhibitor (HK2-001) was designed and generated according to antisense peptide technology, CABS-docking system and ROSWTTA analyzing. A panel of B-cell lymphoma cell lines including rituximab/chemo-sensitive and resistant cell lines (Raji, Raji 4RH, RL and RL 4RH), diffuse large B-cell lymphoma (DLBCL) (DHL4, DOHH2, TMD8 and U2932) and mantle cell lymphoma (MCL) (HBL2, Granta, Mino and Z138) were used. In addition, primary tumor cells isolated from chronic lymphocytic lymphoma (CLL) or other B-cell lymphoma patients were used. Briefly, cell lines or primary tumor cells were exposed to escalating doses of HK2-001 alone or in combination with different chemotherapy agents (doxorubicin, dexamethasone), targeted agents (i.e. burton tyrosine kinase inhibitors, BH3 mimetics) or monoclonal anti-CD20 antibodies. Cell viability was evaluated using the Presto Blue assay in experiments testing pharmacological interactions between HK2-001 and chemotherapy or targeted agents. All experiments were performed in triplicates in three separate experiments. The coefficient of synergy was calculated using CalcuSyn. Results: In vitro exposure of lymphoma cell lines to HK2-001 induced cell death in a panel of B-cell lymphoma cell lines representing rituximab/chemo-sensitive and resistant lymphoma. In addition, synergistic activity was observed between HK2-001 and doxorubicin, ibrutinib, and Venetoclax. These effects were also observed in primary tumor cells isolated from B-cell lymphoma patients. In addition, HK2-001 potentiated the anti-tumor activity of Rituximab and Obinutuzumab ex vivo. Conclusion: We developed a novel peptide targeting HK2. Pre-clinical studies suggested anti-tumor activity as a single agent. More importantly, HK2-001 enhanced the anti-tumor activity of chemotherapy agents, BTK inhibitors, BH3 mimetics and monoclonal antibodies targeting CD20. HK2-001 is a promising novel therapeutic strategy for against B-cell lymphoma, especially in refractory or relapsed patients. Future studies aimed to evaluate the effects of HKII-001 drug combinations in lymphoma animal models are planned and to evaluate its effects on Chimeric antigen receptor T-cells (CART) or bi-specific antibodies.