Hasil untuk "Neoplasms. Tumors. Oncology. Including cancer and carcinogens"

V. Devita, Samuel Hellman, S. Rosenberg

D. V. Telyashkin, Y. Anzhiganova, I. P. Safontsev et al.

Introduction . Cervical cancer, a malignant tumor that develops from the lining of the cervix. The main etiological factor in the development of this process is highly oncogenic strains of human papillomavirus type 16 and 18. Cervical cancer is 9 th ranks in the prevalence of malignant neoplasms (MNEs) worldwide and 4 th in the female population. In 2024, 426 new cases of cervical cancer were detected in the Krasnoyarsk Territory, which is 2.6% in the overall structure of oncological pathology (14 th place) and 5.0% in the structure of female cancer incidence (6 th place). In the structure of the stages of cervical cancer in the Krasnoyarsk Krai, the proportion of patients with I–II established stages of cervical cancer was 58.1% in 2022, in 2024 has increased to 66.0%. In a dynamic assessment of late stages of cervical cancer, namely III–IV, they accounted for a total of 31.0% in 2020, in 2022 this has increased to 41.9%, which makes this pathology even more actual in terms of diagnosis and choice of treatment approaches. Aim . To evaluate the effectiveness of pembrolizumab immunotherapy in a patient with PD-L1-positive status, progressive cervical cancer after radical chemoradiotherapy and platinum-containing chemotherapy and its effect on the patient’s prognosis and epidemiological parameters of oncology. Materials and methods . The analysis of GLOBOCAN data and reference books “Malignant neoplasms in Russia” is conducted. The results of the studies of KEYNOTE-158 and KEYNOTE-826 were used, as well as our own data obtained from the results of patient treatment. Results . According to GLOBOCAN, cervical cancer ranks 4th among oncological diseases in women. In 2024 16.3 thousand new cases were identified in the Russian Federation. The Krasnoyarsk Krai demonstrates a high incidence rate. Modern treatment approaches, including the use of immunotherapy, have shown effectiveness and stabilization of the process after 19 courses. Conclusions . Pembrolizumab immunotherapy is effective in patients with PD-L1-positive status, recurrent or metastatic cervical cancer, allows to achieve long-term stabilization and improve the prognosis.

L. Lyubchenko, K. M. Chernavina, I. A. Kaprin et al.

Cancer is a leading cause of mortality worldwide and the focus of priority programs and strategies for scientific and technological development in public health and health promotion. Modern screening technologies are aimed at early cancer diagnosis to improve treatment outcomes; however most of them are characterized by invasiveness and low patient compliance. Therefore, non-invasive cancer diagnosis is a promising field in molecular biology and oncology. Advances in molecular genetics and bioinformatics have enabled the identification of a wide range of diagnostic, prognostic, and predictive biomarkers, which can be analyzed not only in tumor tissue samples but also in peripheral blood. the purpose of the study was to analyze and summarize current scientific and practical data in the field of non-invasive cancer screening using molecular biological analysis, development of innovative test systems and diagnostic kits, as well as issues of legal regulation and integration into medical and social insurance programs. Material and Methods . The study was based on Russian and international scientific databases, including the National Library of Medicine using the PubMed electronic resource, Elibrary, and Google scholar search results. Open internet resources were also searched using the keywords: cancer; malignant neoplasm; tumor; diagnostic; non-invasive; early; blood; Blood-based tests; test system; screening; pancancer; multi-cancer; sequencing; PCR; marker; DNA; cfDNA; multi-cancer early detection; MCED. The analytical review included clinical trial reports, meta-analyses, systematic reviews, and cohort randomized trials for the period 2008–2025. Results. There is a steady trend worldwide towards the widespread adoption of universal, non-invasive methods for early cancer diagnosis. Retrospective and prospective multicenter studies and meta-analyses conducted over the past 15 years have demonstrated advances in interdisciplinary multimodal analysis of diverse patient data (clinical, genomic, transcriptomic, epigenomic, etc.), emphasizing the cost-effectiveness of these methods. Conclusion . Currently, large-scale population-based studies considering race and ethnicity are vital for validating methodological approaches and evaluating the effectiveness of non-invasive cancer screening methods, especially in diverse nations like Russia.

Meike Mevissen, A. Ducray, Jerrold M. Ward et al.

BACKGROUND More than ten years ago, the World Health Organization's (WHO) International Agency for Research on Cancer (IARC) published a monograph concluding there was limited evidence in experimental animals for carcinogenicity of Radio Frequency Electromagnetic Field (RF EMF). OBJECTIVE The objective of this review was to systematically evaluate the effects of RF EMF exposure on cancer in experimental animals. METHODS Eligibility criteria: Based on pre-established Populations, Exposures, Comparators, Outcomes, and Study Type (PECOS) criteria, studies in experimental animals of the following study types were included: chronic cancer bioassays, initiation-(co-)promotion studies, and studies with tumor-prone animals. INFORMATION SOURCES MEDLINE (PubMed), Science Citation Index Expanded and Emerging Sources Citation Index (Web of Science), and the EMF Portal. Data abstraction and synthesis: Data are publicly available online as interactive visuals with downloadable metadata. We adapted the risk-of-bias (RoB) tool developed by Office of Health Assessment and Translation (OHAT) to include considerations pertinent to the evaluation of RF EMF exposure and cancer bioassays. Study sensitivity was assessed with a tool adopted from the Report on Carcinogens (RoC). We synthesized studies using a narrative approach. Effect size was calculated as the 1% Bayesian Average benchmark dose (BMD) of a respective study when dose-response or a trend was identified (see BMDAnalysisSupplementaryMaterial) (Supplement 1). Evidence Assessment: Certainty of the evidence (CoE) was assessed using the Grading of Recommendations, Assessment, Developing and Evaluations (GRADE) approach, as refined by OHAT. Evidence from chronic cancer bioassays was considered the most directly applicable to evaluation of carcinogenicity. RESULTS We included 52 studies with 20 chronic bioassays No studies were excluded based on risk of bias concerns. Studies were not considered suitable for meta-analysis due to heterogeneity in study design, species, strain, sex, exposure characteristics, and cancer outcome. No or minimal evidence of RF EMF exposure-related cancer outcomes was found in most systems or organs in any study (these included gastrointestinal/digestive, kidney, mammary gland, urinary, endocrine, musculoskeletal, reproductive, and auditory). For lymphoma (18 studies), with 6 chronic bioassays (1,120 mice, 1,780 rats) inconsistency between two chronic bioassays was not plausibly explainable, and the CoE for lymphoma was rated 'moderate'. For brain tumors (20 studies), including 5 chronic bioassays (1,902 mice, 6,011 rats), an increase in glial cell-derived neoplasms was reported in two chronic bioassays in male rats. The CoE for an increased risk in glioma was judged as high. The BMD analysis was statistically significant for only one study and the BMD was 4.25 (95% CI 2.70, 10.24). For neoplasms of the heart (4 chronic bioassays with 6 experiments), 3 studies were performed in rats (∼2,165 animals), and 1 in mice (∼720 animals). Based on 2 bioassays, statistically significant increases in malignant schwannomas was judged as high CoE for an increase in heart schwannomas in male rats. The BMDs from the two positive studies were 1.92 (95 %CI 0.71, 4.15) and 0.177 (95 %CI 0.125, 0.241), respectively. Twelve studies reported neoplasms in the adrenal gland (5 chronic bioassays). The CoE for an increased risk in pheochromocytoma was judged as moderate. None of these findings were dose-dependent when compared to the sham controls. Sixteen studies investigated tumors of the liver with 5 of these being chronic bioassays. The CoE was evaluated as moderate for hepatoblastomas. For neoplasms of the lung (3 chronic bioassays), 8 studies were conducted in rats (∼1,296 animals) and 23 studies in mice (∼2,800 animals). In one chronic bioassay, a statistically significant positive trend was reported for bronchoalveolar adenoma or carcinoma (combined), which was rated as moderate CoE for an increase in lung neoplasms with some evidence from 2 initiation-(co-)promotion studies. DISCUSSION Meta-analysis was considered inappropriate due to the heterogeneity in study methods. The GRADE/OHAT CoE framework has not been frequently applied to animal studies and experience to date suggests refinements are needed. We referred to standard methods in environmental health where CoE is framed in the context of strength of the evidence providing positive support for carcinogenicity. High CoE can be interpreted as the true effect is highly likely to be reflected in the apparent relationship. Moderate CoE indicates the true effect may be reflected in the apparent relationship. Cancer bioassays conducted in experimental animals are commonly used to identify potential human carcinogens. We note that the two tumor types with high CoE in animals in this systematic review are the same as those identified with limited evidence in humans by the IARC Working Group. However, even in cases where the animal evidence demonstrates high CoE, the extrapolation of risk from cancer bioassays to humans is particularly complex for RF EMF. Without a better understanding of the mechanism of the carcinogenicity of RF-EMF, the choice of exposure metric for risk extrapolation (whole body versus localized), intensity or cumulative exposure, whether or not a monotonic dose-response holds for carcinogenic effects, and whether SAR is the appropriate dose metric for adverse effects induced by RF-EMF, may be critical. OTHER This review was partially funded by the WHO radioprotection programme. The protocol for this review was registered in Prospero reg. no. CRD42021265563 and published in Environment International 2022 (Mevissen et al. 2022).

D. Nardozi, Valeria Lucarini, V. Angiolini et al.

Gastrointestinal (GI) cancers represent a heterogeneous group of malignant neoplasms arising from the digestive tract, including gastric, colorectal, hepatic, pancreatic, and biliary cancers. These tumors represent a major public health challenge due to their aggressive nature and poor prognosis. Although significant progress has been made in diagnostic imaging, endoscopy, and multimodal therapies, early detection remains difficult. Conventional serum biomarkers often lack sufficient sensitivity and specificity for reliable diagnosis, prompting a growing interest in identifying novel, minimally invasive biomarkers. In this context, liquid biopsy is emerging as a revolutionary tool in oncology. Among its components, extracellular vesicles (EVs) have gained increasing attention because they carry a wide range of molecular cargoes that reflect the biological state of their tumor of origin. In particular, EV-associated microRNAs (miRNAs) hold great promise as biomarkers for early cancer detection, real-time monitoring of disease progression, and assessment of therapeutic response. This review discusses the diagnostic and prognostic potential of EVs as novel biomarkers in GI cancers, emphasizing EV-contained miRNAs as a key resource for the development of personalized and precision medicine strategies.

Kholoud Alqasem, Sakhr Alshwayyat, Salsabeel Aljawabrah et al.

Abstract Background Small cell carcinoma (SCC) is a neuroendocrine tumor that usually originates in the lungs but can also arise from extrapulmonary sites. Extrapulmonary small cell carcinomas (EPSCCs) are aggressive and rare, with limited data guiding their management. This case report contributes to the literature by presenting the diagnosis and treatment of primary peritoneal SCC. Case presentation This case describes a 69-year-old man who presented with abdominal distension and pain, raising concerns for metastasis. He had a history of prostate cancer treated with radical prostatectomy and pelvic lymph node dissection. Biopsy and imaging revealed metastatic SCC involving the peritoneum and omentum. A diagnosis of primary peritoneal SCC or SCC of unknown primary origin was made due to the absence of a detectable primary tumor in typical sites. The patient underwent three separate courses of carboplatin/etoposide chemotherapy (6 cycles each), with each course resulting in significant disease regression and symptom relief. Recurrence was managed effectively with repeated chemotherapy cycles, but long-term follow-up showed the need for continued treatment to maintain disease control and quality of life. Conclusion This case underscores the importance of a multidisciplinary approach and patient-centered care in managing rare cancers like primary peritoneal SCC. Further research is essential to clarify its molecular characteristics and improve therapeutic options. Graphical abstract

Xue Luo, Xingxing Bie, Na Luo et al.

Primary hepatic neuroendocrine neoplasms (PHNENs) are a rare type of neuroendocrine tumors originating in the liver. These tumors are characterized by non-specific clinical symptoms and atypical imaging features, making differentiation from other primary hepatic masses, such as hepatocellular carcinoma (HCC) and parasitic lesions, challenging. The diagnosis of PHNENs is based on characteristic histological features associated with this condition and results from immunohistochemistry assays. Here, we report on a case of a 22-year-old female presenting with a large hepatic neoplastic lesion. Computed tomography (CT) imaging results revealed a highly vascularized mass with clear boundaries located in the right lobe of the liver, suggesting a diagnosis of HCC. The patient underwent a fine-needle aspiration biopsy and subsequent complete surgical resection of the tumor. Results from both the fine-needle aspiration and histology of the surgically resected specimen showed that the tumor cells were arranged in a solid structure with a trabecular pattern. The tumor cells exhibited positive expressions for the epithelial cell markers AE1/AE3, along with the neuroendocrine markers, synaptophysin (Syn), chromogranin (CgA), and CD56 as based on results from immunohistochemical staining. The Ki-67 proliferation index was > 20%, and the mitotic count was > 20 per 2 square millimeters, leading to a final diagnosis of a hepatic neuroendocrine neoplasms, Grade 3 (G3). PHNENs are extremely rare, and, to our knowledge, there have been no reports in the literature of adolescents or young adults diagnosed with the G3-type.

J. Pitasari, J. Kenmoe, Aanchal Gupta et al.

Introduction: Primary cardiac sarcomas are exceedingly rare and aggressive malignancies, with limited epidemiological data due to their low incidence. This study aims to characterize the incidence trends of cardiac sarcomas over a 21-year period using a population-based cancer registry and to assess differences in incidence by sex. Methods: We conducted a retrospective cohort study using data from the Surveillance, Epidemiology, and End Results (SEER) Program, accessed through SEER*Stat software version 8.4.5. Eligible cases were identified using the International Classification of Diseases for Oncology (ICD-O-3) site code C38.0 (Heart) and histology codes corresponding to soft tissue tumors and sarcomas, including: NOS (8800–8809), fibromatous neoplasms (8810–8839), myxomatous neoplasms (8840–8849), lipomatous neoplasms (8850–8889), myomatous neoplasms (8890–8929), complex mixed and stromal neoplasms (8930–8999), synovial-like neoplasms (9040–9049), and blood vessel tumors (9120–9169). The study period spanned from 2000 to 2021. Only first primary tumors were included, and no duplicate cases were identified. Incidence rates were age-adjusted to the 2000 U.S. standard population and stratified by sex. Temporal trends were evaluated using joinpoint regression. Results: A total of 264 cases of primary cardiac sarcomas were identified between 2000 and 2021. The overall age-adjusted incidence rate remained relatively stable throughout the study period, with no significant annual percent change observed. Males demonstrated a higher incidence rate compared to females (0.0065 vs. 0.0053 per 100,000 person-years, respectively), but this difference did not reach statistical significance (p > 0.05). There were no notable shifts in the incidence of specific sarcoma subtypes over time. Conclusion: This study provides one of the most comprehensive analyses of primary cardiac sarcoma incidence trends in the U.S. to date. Despite the rarity of this malignancy, the incidence has remained stable over the past two decades. While males appear to be more affected than females, the observed sex difference is not statistically significant. Continued surveillance and larger datasets are necessary to better understand risk factors and inform early detection strategies for this rare and often fatal disease.

Garima Pandey, Tegan Rowsell, Lucia Mazzacurati et al.

The classical myeloproliferative neoplasms (MPNs) polycythemia vera, essential thrombocythemia, and primary myelofibrosis (MF) are driven by aberrant JAK2 signaling induced by mutations in JAK2, MPL, or CALR. MPN patients exhibit constitutional symptoms that impair quality of life, and they live with an elevated risk of deadly cardiovascular complications, bone marrow failure, and developing an incurable acute leukemia. While FDA-approved JAK2 inhibitors can improve patient quality of life they are unable to readily reduce driver allele burden/induce remission. However, MPN mouse model studies have demonstrated that MPN phenotypes require continued aberrant JAK2 signaling, indicating MPN patients may benefit from improved JAK2 inhibitors or approaches to antagonize this signaling. As suggested by numerous studies, the RAS/MEK/ERK pathway may play a role in the persistent survival of MPN-driving cells during JAK2 inhibitor therapy. Indeed, ruxolitinib combined with MEK, ERK, or SHP2 inhibitors can improve the efficacy of JAK2 inhibitor monotherapy in preclinical studies. MEK and ERK kinase inhibitors have presented significant challenges in clinical oncology, including inefficacy, toxicity, and the development of drug resistance. Recent advances in the development of small molecule RAS inhibitors have been translated to clinical studies in solid tumors but the potential of such anti-RAS targeted therapies in blood cancers remains under explored. Given aberrant JAK2 signaling in MPN signals in part through RAS activation, which activates multiple downstream pathways, direct RAS inhibition and subsequent suppression of multiple RAS controlled pathways could provide a significant advantage over RAS pathway selective kinase inhibitors such as MEK or ERK inhibitors. We hypothesized that direct inhibition of RAS may antagonize the growth and viability of MPN cells and enhance the effectiveness of anti-JAK2 therapy. We employed the recently developed RAS(ON) multi-selective inhibitor, RMC-7977, which inhibits signaling mediated by the active GTP-bound forms of wildtype H-RAS, K-RAS, and N-RAS, alone and in combination with the JAK2 inhibitor ruxolitinib in preclinical MPN models. We found that RMC-7977 suppressed levels of active ERK (pERK) in JAK2-driven MPN model SET2 and UKE1 cells at concentrations as low as 10 nM, with RMC-7977 exhibiting GI50 concentrations of 0.4 and 0.1 μM in these cells, respectively. While the MEK inhibitor binimetinib readily suppressed pERK levels, its GI50 was > 5 μM in these cells, suggesting direct inhibition of RAS may more efficiently suppress signaling requisite for JAK2-driven growth. Combining RMC-7977 with ruxolitinib synergistically compromised growth and survival of MPN model cells, mediated in part through enhanced apoptosis. Combined RMC-7977 and ruxolitinib treatment resulted in enhanced inhibition of pERK, pRSK3, and DUSP6 levels compared to monotherapies. These signaling and growth effects of RMC-7977 and ruxolitinib were not evident in non-MPN model cells, suggesting potential selectivity of this combination. Notably, RMC-7977 effectively suppressed pERK levels in, and growth of, ruxolitinib persistent MPN model cells suggesting in vitro mechanisms of JAK2 inhibitor persistence do not provide cross-resistance to direct inhibition of RAS. RMC-7977 suppressed the levels of pERK in primary MF patient cells, as well as the neoplastic growth of primary MPN progenitor cells, and could synergistically enhance growth inhibitory responses in combination with ruxolitinib. In an MPN mouse model driven by MPL-W515L, oral RMC-7977 treatment suppressed MPN phenotypes including leukocytosis, hepatosplenomegaly, and extramedullary hematopoiesis, and enhanced survival. RMC-7977 in combination with ruxolitinib further suppressed MPN phenotypes beyond the inhibitory effects of monotherapies, and significantly enhanced survival beyond ruxolitinib and RMC-7977 treatment alone. RMC-7977 treatment suppressed inflammatory cytokine levels including TNFα and IL-6, two cytokines implicated in MPN pathogenesis, among others. Importantly, treatment of healthy mice concurrently with RMC-7977 and ruxolitinib was well tolerated as evidenced by the absence of impact on hematologic parameters and body weight. Our results reveal that direct inhibition of RAS and JAK2 may represent a promising therapeutic strategy for MPN patients and provide evidence RAS inhibition has potential beyond solid tumor indications.

I. T. Carvalho

Cancer remains a significant challenge to public health worldwide and ranks among the leading contributors to mortality in diverse populations. This persistent impact underscores the need for proactive approaches to reduce its incidence. Chemoprevention focuses on interrupting tumor development through naturally occurring compounds, particularly plant-derived bioactive compounds. These phytochemicals exert protective effects by modulating key molecular pathways and enhancing detoxification. Of particular interest are those that regulate phase I and II enzymes, facilitating carcinogen elimination and mitigating cellular damage associated with cancer progression. This review examines phytochemicals from plant-derived functional foods that enhance detoxification pathways for cancer prevention, summarizing current evidence and future directions for their clinical application and dietary integration. Emphasis is placed on specific bioactive constituents, such as sulforaphane from cruciferous vegetables, organosulfur compounds in garlic, betanin from beetroot, a spectrum of citrus fruit flavonoids including β-cryptoxanthin, hesperidin, and nobiletin, epigallocatechin-3-gallate from green tea, and curcumin derived from turmeric. These naturally occurring compounds regulate enzymatic pathways involved in xenobiotic metabolism, underscoring their relevance in nutritional oncology. Findings from diverse experimental models show they inhibit phase I enzymes, induce phase II detox enzymes, activate the Nrf2 signaling pathway, and modulate gene expression epigenetically. Collectively, these multifaceted actions contribute to their protective role against carcinogenesis. Although natural approaches show promise for cancer prevention, they face challenges related to bioavailability, standardization, and clinical validation, necessitating further research for effective integration into evidence-based oncology.

R. Bomfim, L. Tourinho

INTRODUCTION. Breast cancer during pregnancy (BCGA) is a complex condition that requires careful therapeutic approaches to ensure the safety of both mother and fetus. The treatment of BCGA involves ethical and practical dilemmas, since modalities such as chemotherapy, radiotherapy, and hormonal therapy can pose risks to fetal development, especially when administered at certain times of pregnancy. In addition, physiological changes during pregnancy – such as increased mammary vascularization and hormonal changes – can make early diagnosis difficult, resulting in tumors often being identified at more advanced stages. Given this scenario, it is essential to review the available scientific evidence on therapeutic approaches, considering their efficacy, safety, and impact on maternal-fetal outcomes. OBJECTIVES. The main objective of this study is to critically analyze the therapeutic approaches available for the treatment of breast cancer during pregnancy, in light of the current scientific literature. Specifically, the aim is to: describe the epidemiology and risk factors of breast cancer diagnosed during pregnancy; identify the main diagnostic challenges of breast cancer in pregnant women, considering the clinical, radiological and histopathological aspects; review the available therapeutic options (surgery, chemotherapy, radiotherapy, hormonal therapy) and their safety during the different trimesters of pregnancy; analyze the impact of therapeutic interventions on maternal and fetal health, considering risks and benefits; explore international guidelines and consensus on the multidisciplinary management of gestational breast cancer; and evaluate the prognosis and maternal-fetal outcomes associated with the different therapeutic strategies. BACKGROUND. Breast cancer is the most common neoplasm among women of reproductive age and represents approximately 20% of cancer cases diagnosed during pregnancy, the so-called gestational breast cancer (GBC) [Amant et al., 2012]. Although rare, with an estimated incidence of 1 in 3,000 to 10,000 pregnancies, the diagnosis of breast cancer during pregnancy poses significant clinical, ethical, and therapeutic challenges, requiring a delicate balance between maternal oncological treatment and preservation of fetal health [Loibl et al., 2012; Cardonick & Iacobucci, 2004]. Pregnancy modifies breast physiology, which can mask early signs of the disease and delay diagnosis, contributing to detection at more advanced stages [Azim et al., 2010]. In addition, therapeutic management requires complex decisions regarding the type and timing of treatment—such as surgery, chemotherapy, or radiotherapy—considering gestational age and associated teratogenic risks. Despite advances in international guidelines, there are still gaps in knowledge and variations in clinical practice, especially in countries with less access to oncology referral centers. Therefore, critically reviewing therapeutic approaches to breast cancer during pregnancy is essential to contribute to evidence-based medical practice, favor multidisciplinary decision-making and, above all, ensure safer outcomes for mother and fetus. Therefore, this work is justified by the clinical, academic, social and scientific relevance of the topic, while aiming to offer updated subsidies for the ethical and therapeutic management of breast cancer, promoting comprehensive care for pregnant women with cancer. MATERIALS AND METHODS. This is a narrative literature review with a descriptive and qualitative approach, without systematization of the results. For this purpose, national and international online databases were used: Latin American and Caribbean Health Sciences Literature (LILACS), Medical Literature Analysis and Retrieval System Online (MEDLINE), Scientific Electronic Library Online (SCIELO), U.S. National Library of Medicine (PubMed), and Google Scholar. The main objective of the research is to critically analyze the therapeutic approaches available for the treatment of breast cancer during pregnancy, in light of the current scientific literature. RESULTS/DISCUSSION. It is expected that this literature review will identify and systematize the safest and most effective therapeutic approaches for the treatment of breast cancer during pregnancy, considering the different trimesters and stages of the disease. Based on the analysis of the available data, the following trends and conclusions are likely to be observed: Late diagnosis: Most cases of gestational breast cancer tend to be diagnosed at more advanced stages, due to physiological changes in the breast during pregnancy that make early detection difficult; Safety of oncological treatment during pregnancy: The literature should demonstrate that certain treatments, such as surgery and chemotherapy (mainly with anthracyclines), can be performed with relative safety from the second trimester onwards, while radiotherapy and hormonal therapies are usually postponed until the postpartum period; Individualized and multidisciplinary approach: The studies reviewed will probably reinforce the importance of individualized management, carried out by a multidisciplinary team, including an oncologist, obstetrician, neonatologist, psychologist and social worker. With these findings, the research should contribute to the improvement of medical knowledge on the subject, in addition to serving as a basis for medical education, the formulation of clinical protocols and the improvement of the quality of care for pregnant women with cancer. CONCLUSION. Breast cancer during pregnancy, although rare, represents a significant clinical challenge that requires an individualized and multidisciplinary approach. The review showed that treatments such as surgery and chemotherapy with anthracyclines can be safe during pregnancy, especially after the first trimester, while radiotherapy and hormonal therapy should be postponed. The scarcity of national protocols reinforces the need for more studies and guidelines adapted to the Brazilian reality. It is concluded that appropriate management allows for good maternal-fetal outcomes, as long as it is combined with emotional and ethical support for the pregnant woman.

D. Elsori, P. Pandey, S. Ramniwas et al.

The bioactive compounds present in citrus fruits are gaining broader acceptance in oncology. Numerous studies have deciphered naringenin’s antioxidant and anticancer potential in human and animal studies. Naringenin (NGE) potentially suppresses cancer progression, thereby improving the health of cancer patients. The pleiotropic anticancer properties of naringenin include inhibition of the synthesis of growth factors and cytokines, inhibition of the cell cycle, and modification of several cellular signaling pathways. As an herbal remedy, naringenin has significant pharmacological properties, such as anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, and anti-cancer activities. The inactivation of carcinogens following treatment with pure naringenin, naringenin-loaded nanoparticles, and naringenin combined with anti-cancer agents was demonstrated by data in vitro and in vivo studies. These studies included colon cancer, lung neoplasms, breast cancer, leukemia and lymphoma, pancreatic cancer, prostate tumors, oral squamous cell carcinoma, liver cancer, brain tumors, skin cancer, cervical and ovarian cancers, bladder neoplasms, gastric cancer, and osteosarcoma. The effects of naringenin on processes related to inflammation, apoptosis, proliferation, angiogenesis, metastasis, and invasion in breast cancer are covered in this narrative review, along with its potential to develop novel and secure anticancer medications.

Crisann Moon, Rebekah L. Wilson, P. Gonzalo-Encabo et al.

Cancer-associated cognitive deficits following chemotherapy have received increased attention in clinical research. Exercise has been shown to preserve cognitive function in cancer patients, though the overall effect is mixed. Here we present a scoping review of the published literature summarizing methods used to assess cognitive function in exercise oncology trials. Methods: PubMed, PsycINFO and CINAHL databases were searched using keywords “cognition,” “cancer” OR “neoplasm” OR “tumor,” “chemotherapy” and “exercise” OR “physical activity.” Studies eligible for inclusion include prospective studies that were published in English in peer-reviewed journals that include a method of assessing cognitive function in adult cancer patients, in which an exercise modality or method of quantifying exercise habits was evident. Studies were excluded if they included a pediatric population, patients that were not diagnosed with cancer, or were systematic/narrative/scoping reviews, protocol papers or dissertation/theses. Results: A total of 29 studies met the inclusion criteria. In total, 29 unique assessments were used to evaluate cognitive function, including patient-reported outcomes (PROs; n = 8) and objective (n = 21) methods. More than half (n = 17) of included studies relied on PROs while 12 studies utilized objective measures of cognitive function Cognitive domains of the PROs were limited in scope, focusing on memory and attention/concentration while the objective measures were broader and inclusive of multiple domains. Conclusion: The results of this review indicate that mixed approaches to evaluating cognitive function in cancer patients pose a major limitation to understanding the role of exercise as an integrative approach. The evidence demonstrates a need for more uniform assessment of cognitive function in exercise oncology trials.

Mingyue Xiao, Jiayi Liang, Jie Ren et al.

Ectopic spleen (ES) is a rare condition. It is difficult to diagnose with conventional imaging modalities. In this case series, we presented the imaging features of three misdiagnosed ES cases in our hospital and previously reported cases to compare the consistency of enhancement patterns among different imaging modalities with varied phases. Finally, 22 cases were reviewed. We determined that variable arterial phase enhancement and persistent enhancement throughout the portal and delayed phases are present in contrast-enhanced ultrasound (CEUS) imaging of the ES and found the arterial phase of CEUS had the highest consistency compared with computerized tomography (CT) and magnetic resonance imaging (MRI).

Mengjiao Fan, Guochao Deng, Yue Ma et al.

Abstract Background Despite some therapeutic advances, improvement in survival rates of unresectable and/or metastatic pancreatic ductal adenocarcinoma (PDAC) has been minimal over recent decade. We aimed to evaluate the impact of different treatment sequences on clinical outcomes of advanced PDAC at our academic institution. Methods In this single institution retrospective analysis, we assessed characteristics and survival rates of unresectable and/or metastatic pancreatic PDAC patients who started a systemic treatment between 01/2015 and 12/2021. Survival analyses were performed by Kaplan-Meier and Cox proportional hazards model. Results The number of 285 patients received at least two lines of treatment, but only 137 patients were suitable for third-line treatment. Subgroup analysis showed that thirty-seven patients received A line (gemcitabine/nab-paclitaxel or nab-paclitaxel combined therapy to FOLFIRINOX) therapy, 37 patients received B line (nab-paclitaxel combined therapy to gemcitabine combined therapy to FOLFIRINOX) therapy, 21 patients received C line (nab-paclitaxel combined therapy to gemcitabine combined therapy to oxaliplatin or irinotecan combined therapy) therapy. Survival rates for different treatment lines were significantly different and median overall survival (OS) was 14.00, 18.00, and 14.00 months, respectively (p<0.05). Conclusion Our study provides real-world evidence for the effectiveness of different treatment sequences and underscores the treatment sequences on survival outcome when considering the entire management in advanced PDAC.

Yu Jiang Master of Engineering, Kang Wang Master of Medicine, Yu-Ran Wang Master of Engineering et al.

Microvascular invasion of hepatocellular carcinoma is an important factor affecting tumor recurrence after liver resection and liver transplantation. There are many ways to classify microvascular invasion, however, an international consensus is urgently needed. Recently, artificial intelligence has emerged as an important tool for improving the clinical management of hepatocellular carcinoma. Many studies about microvascular invasion currently focus on preoperative and prognosis prediction of microvascular invasion using artificial intelligence. In this paper, we review the definition and staging of microvascular invasion, especially the diagnosis of it by using artificial intelligence. In preoperative prediction, deep learning based on multimodal data modeling of radiomics-screened features, clinical features, and medical images is currently the most effective means. In prognostic prediction, pathology is the gold standard, and the techniques used should more effectively utilize the global features of the pathology images.

Athanasios Michas, Vasileios Michas, Evangelos Anagnostou et al.

Colorectal carcinoma (colon and rectum) is currently considered among the most prevalent malignancies of Western societies. The pathogenesis and etiological mechanisms underlying colorectal cancer (CRC) development remain complex and heterogeneous. The homeostasis and function of normal human intestinal cells is highly regulated by microRNAs. Therefore, it is not surprising that mutations and inactivation of these molecules appear to be linked with progression of colorectal tumors. Recent studies have reported significant alterations of microRNA expression in adenomas and CRCs compared with adjacent normal tissues. This observed deviation has been proposed to correlate with the progression and survival of disease as well as with choice of optimal treatment and drug resistance. MicroRNAs can adopt either oncogenic or tumor-suppressive roles during regulation of pathways that drive carcinogenesis. Typically, oncogenic microRNAs termed oncomirs, target and silence endogenous tumor-suppressor genes. On the other hand, tumor-suppressive microRNAs are critical in downregulating genes associated with cell growth and malignant capabilities. By extensively evaluating robust studies, we have emphasized and distinguished a discrete set of microRNAs that can modulate tumor progression by silencing specific driver genes crucial in signaling pathways including Wnt/b-catenin, epidermal growth factor receptor, P53, mismatch repair DNA repair, and transforming-growth factor beta.

Rosa Mallorson, Briana N. Cortez, D. Varghese et al.

TPS659 Background: Neuroendocrine neoplasms (NENs) are a rare spectrum of malignant neoplasms originating from neuroendocrine cells, most commonly affecting the gastrointestinal tract, pancreas, and lungs. Tumors may vary from low grade neuroendocrine tumors (NET) to high grade neuroendocrine carcinomas (NEC). The annual occurrence of NENs is increasing worldwide and currently the incidence in the US is about 6 cases per 100,000 people per year. A variety of therapeutic options are available for advanced NENs, however, when to apply a given option, what combination therapeutic approach should be used, how long treatment should be continued is unclear and controversial. Moreover, unlike common cancers, pre-clinical models for NENs are sorely limited. Without robust pre-clinical models our understanding of tumor pathophysiology and novel drug development can be challenging. Methods: A prospective study to evaluate the natural history and sample acquisition of NENs comprehensively and longitudinally. Patients ≥ 18 years old with histological confirmation of NENs, biochemical evidence of NENs, or by imaging studies of NENs are eligible. Participants are invited to NIH for biannual evaluations or as clinically indicated. Patients complete individual medical history, family history, and laboratory assessments including blood, saliva, and tumor for RNA/DNA analysis. A tumor analysis via a 500+ gene panel (Illumina TruSight Oncology 500 Panel) is performed for comprehensive genomic and epigenomic analysis. When feasible, fresh tissue is collected to develop pre-clinical models for drug testing. If clinically indicated, anatomic and functional imaging is performed. We aim to 1) create a repository of biological samples and conduct future investigations to understand the basic biology of NENs with the goal to develop novel treatment approaches, biomarkers of treatment response, and new prognostic and diagnostic models, 2) acquire clinical data so that the overall genomic, proteomic, and metabolomic alternations can be correlated to clinical parameters, 3) establish organoid cultures, cell line models, and xenograft models corresponding to NENs of various grades for drug screening. This protocol will evaluate the natural history of NENs, allow tissue acquisition, and study this heterogenous group of neoplasms with unique tumor biology, and current clinical management to stabilize correlations with clinical outcomes and develop novel therapies. Clinical trial information: NCT05237934 .

A. Picca, D. Guyon, O. Santonocito et al.

Simple Summary Diffuse gliomas, including the most aggressive subtype glioblastoma, represent the most frequent primary central nervous system tumors. Despite intense chemoradiation protocols that represent the current standard of care, these cancers inevitably recur, and median overall survival does not exceed 18 months. New therapeutic options are compellingly needed for these tumors, particularly those lacking the favorable prognostic marker IDH mutation. Nonetheless, potentially druggable alterations are increasingly identified in distinct subsets of patients harboring gliomas. Targeted treatments, along with improved immunotherapeutic schedules, gene therapy, cell therapy, and physical strategies to improve drug delivery to the nervous system, are currently under extensive investigation. They bring hope for more effective therapies in these diseases with currently often a dismal outcome. Abstract Diffuse gliomas, the most frequent and aggressive primary central nervous system neoplasms, currently lack effective curative treatments, particularly for cases lacking the favorable prognostic marker IDH mutation. Nonetheless, advances in molecular biology allowed to identify several druggable alterations in a subset of IDH wild-type gliomas, such as NTRK and FGFR-TACC fusions, and BRAF hotspot mutations. Multi-tyrosine kinase inhibitors, such as regorafenib, also showed efficacy in the setting of recurrent glioblastoma. IDH inhibitors are currently in the advanced phase of clinical evaluation for patients with IDH-mutant gliomas. Several immunotherapeutic approaches, such as tumor vaccines or checkpoint inhibitors, failed to improve patients’ outcomes. Even so, they may be still beneficial in a subset of them. New methods, such as using pulsed ultrasound to disrupt the blood–brain barrier, gene therapy, and oncolytic virotherapy, are well tolerated and may be included in the therapeutic armamentarium soon.

C. Kline, Nancy M. Joseph, J. Grenert et al.