Primary Malignant Cancer Research Articles

ZSTK474 targeting PIK3R3 inhibits the Wilms' tumor through G0 / G1 phase arrest.

Wilms' tumor (WT), also known as nephroblastoma, is the predominant form of primary malignant renal cancer. The unfavorable prognoses linked to anaplastic nephroblastoma and recurrent nephroblastoma emphasize the crucial requirement for the exploration of innovative treatment modalities for WT. Our study conducted one-way Cox regression and Kaplan-Meier analyses using TARGET-WT nephroblastoma data to identify differentially expressed genes in nephroblastoma and evaluate their prognostic relevance. Utilizing the Connectivity Map database, ZSTK474 emerged as a viable therapeutic option for WT. The effect of ZSTK474 on WT and related underlying mechanisms were further investigated through in vitro and in vivo investigations. The in vivo experiment results indicated that ZSTK474 effectively inhibited subcutaneous tumor growth in WT mice. CCK-8 assays revealed two nephroblastoma cell lines exhibited half-inhibitory concentrations of 2μM and 2.51μM for ZSTK474, respectively. ZSTK474 was shown to inhibit the migration and invasion capabilities of WT cells in both Transwell and wound healing assays. Flow cytometry apoptosis and TUNEL assays demonstrated that ZSTK474 induced apoptosis in WT cells. Cell cycle analysis revealed that ZSTK474 led to the induction of G0/G1 phase arrest. Sequencing of ZSTK474-treated WiT49 cells suggested that the impact of ZSTK474 on WT might be mediated by the PI3K/Akt pathway, specifically by inhibiting PIK3R3. Knock-down of PIK3R3 confirmed that ZSTK474 downregulated PIK3R3, reducing Akt phosphorylation, cyclin D and CDK4 levels and elevating P21 expression in nephroblastoma cells. However, current research has limitations, including a lack of understanding of the long-term effects and potential resistance mechanisms of new therapies. This research provides insight into the potential of ZSTK474 and other PI3K inhibitors for treating nephroblastoma.

Changes in cancer diagnoses and stage distribution during the second year of the COVID-19 pandemic in the US.

130 Background: During 2020, the first year of the COVID-19 pandemic, cancer diagnoses decreased, especially early-stage disease, with largest decreases in medically underserved populations. It is unknown whether this pattern continued during 2021, the second year of the COVID-19 pandemic. With newly released cancer surveillance data, this study examined nationwide changes in adult cancer diagnoses and stage distribution from 2019 to 2021 in the US. Methods: Adults aged ≥18 years who were newly diagnosed with first primary malignant cancers between 2019 and 2021 from 50 US states and the District of Colombia were identified from the National Cancer Database. We calculated monthly cases, stage distribution, and adjusted odds ratios (aOR) of stage I vs. stage II–IV cancer and stage IV vs. stage I–III cancer diagnoses in 2021 compared with 2019, controlling for sociodemographic and clinical factors and stratified by cancer type. Results: We identified 864,430 individuals diagnosed in 2019, 780,478 diagnosed in 2020, and 819,791 diagnosed in 2021. The proportion of diagnoses at stage I decreased from 39.6% in 2019 to 31.1% in April 2020, and were 39.2% overall in 2021. The decrease in stage I diagnoses was mirrored by an increase in stage IV diagnoses. The pattern was most prominent for female breast, lung, colorectal, and prostate cancers, and melanoma. Overall, compared to 2019, we found a 5.98% decrease in stage I diagnoses and a 4.55% decrease in stage IV diagnoses in 2021 (Table). Lower odds of diagnosis at stage I were most prominent among individuals who were male, aged 18-44, Hispanic, from Mid-Atlantic region, and for the cancers of melanoma, non-Hodgkin lymphoma, prostate, esophagus, and cervical cancer. Higher odds of diagnosis at stage IV in 2021 vs. 2019 were most prominent among individuals who were Hispanic, diagnosed with cancers of prostate, thyroid, liver, esophagus and cervix. Conclusions: Decreases in cancer diagnoses and proportion of early-stage diagnoses continued in 2021 in the US. The proportion of late-stage diagnoses were lower in 2021 than 2020 but have not returned to pre-pandemic levels. Changes in stage I distribution among major cancer sites 2021 vs. 2019. 2019 2021 2021 vs. 2019 Cases Cases Percent Change AdjustedOR* (95%CI) All Cancers 341971 321514 -5.98% 0.978 (0.972-0.985) Female breast 116828 116780 -0.04% 1.023 (1.007-1.038) Prostate 26323 21012 -20.18% 0.826 (0.809-0.843) Lung cancer and bronchus 28258 25966 -8.11% 1.033 (1.012-1.053) Colon and rectum 14258 12992 -8.88% 0.942 (0.918-0.968) Melanoma 21005 19542 -6.97% 0.936 (0.907-0.966) Data source: National Cancer Database 2019-2021. *Stage I vs. II-IV, models adjusted for age group, sex, race/ethnicity, zip-code level social deprivation index, comorbidity score, state-level COVID-19 age adjusted mortality rate, MSA, state, insurance status.

Combined neurokinin-1 receptor antagonist and sorafenib is a promising approach for hepatocellular carcinoma therapy

BackgroundHCC (Hepatocellular carcinoma) is the most common primary malignant cancer in the liver. Treatment options to incurable HCC such as sorafenib, an oral multikinase inhibitor, had numerous side effects and questionable effectiveness. Neurokinin-1 receptor (NK1R) have a major role in inflammation and tumour environment including the resistance to cell death, the induction of angiogenesis and the promotion of cell migration and proliferation. Additionally, NK-1R is over-expressed in human tumour cells including HCC. Moreover, Aprepitant, one of the NK-1R antagonists exerts multiple antitumor activities (antiproliferative, apoptotic, antimigration, and antiangiogenesis) in vivo and in vitro.Study aimTo analyze the effectiveness of combining sorafenib with aprepitant in the management of HCC (experimental).Patients and methodsIn this retrospective experimental study, the human HCC cell line, HepG2, cells were exposed to increasing concentrations of sorafenib alone, aprepitant alone and combination of both sorafenib and aprepitant evaluation of cytotoxicity, apoptosis, MMP-9, VEGF, NF-kB p-65, p-AKT and p-ERK were done. Moreover, The extent of the NK-1 receptor expression was assessed by immunocytochemistry on 50 HCC paraffin blocks of Egyptian HCC patients and another 50 paraffin blocks of liver cirrhosis only as a control.ResultsDecreased levels of MMP-9, VEGF, NF-kB p-65, p-AKT and p-ERK was more substantial in the combination therapy compared to sorafenib alone and aprepitant alone. Moreover, the rate of apoptosis and cytotoxicity were significantly higher in the combination treatment group than the monotherapy groups with more anti inflammatory, anti angiogentic and anti metastatic effects. Also, among the 50 HCC paraffin blocks, the majority (60%) showed a strong NK-1 expression; which significantly (p < 0.05) correlated with the progression free survival (PFS) but not the overall survival (OS) of the patients when applying multivariate analysis.ConclusionHCC had strong expression and immunostaining for NK1R.Therefore, combined aprepitant and sorafenib may be a promising approach in HCC treatment compared to each one alone.

Historic redlining, modern neighborhood structures, and mortality in children, adolescents, and young adults with cancer.

11037 Background: Historic redlining, referring to the Home Owners Loan Corporation (HOLC) program’s racially biased risk monitoring maps in the 1930’s, has indelible impacts on modern day neighborhood characteristics and health outcomes. The impact of redlining, a form of structural racism, on children, adolescents, and young adults with cancer (CAYACs) is unknown. This retrospective cohort study evaluates the association between redlining and mortality in CAYACs. Methods: Using the California Cancer Registry, we identified cases &lt;25 years old diagnosed with first primary malignant cancer between 2000-2019. Using merged HOLC maps and U.S. Census data we determined case redlining status (A “Best”, B “Still Desirable”, C “Declining”, D “Hazardous”, and N “Not graded”) by residence at diagnosis. We defined residents of D neighborhoods redlined-exposed and residents of A or B neighborhoods unexposed or referent. Kaplan Meier methods and multivariable Cox proportional hazard models were applied to calculate overall survival. Additional models accounted for census tract-level neighborhood SES (nSES, a composite measure incorporating seven SES domains), neighborhood racial and ethnic composition (or typology) and racialized economic segregation (via index of concentration at the extremes). Results: In total 8,210 cases were HOLC-graded, the median age was 16 years, 46% were female, and 48% had solid tumors. Overall survival at 5 years was inferior for D cases vs. A or B cases (OS 80.2%, 95% CI: 78.5-81.7 vs. OS 88.2, 95% CI: 84.0-91.3). Adjusting for individual clinical characteristics (age, sex, year of diagnosis, and cancer stage), D cases experienced greater mortality (HR 1.32, 95% CI: 1.12-1.55) compared to A or B cases. Additional adjustment for insurance and nSES attenuated the relationship (HR 1.17, 95%CI: 1.00-1.36 and HR 1.07, 95% CI: 0.92-1.24 respectively). Similar patterns were observed in models adjusting for racialized economic segregation (HR 1.07, 95% CI: 0.92-1.24) and typology (HR 1.10, 95% CI: 0.94-1.28) in place of nSES. Conclusions: In this population-based study, redlined-exposed CAYACs experienced greater mortality compared to unexposed CAYACs. Adjusting for insurance and contemporary nSES attenuated the association between redlining and mortality. Findings suggest current neighborhood attributes may be downstream manifestations of structural racism with survival implications for CAYACs.

Trends in primary malignant bone cancer incidence and mortality in the United States, 2000–2017: A population-based study

BackgroundPrimary malignant bone cancers have extremely low incidence, resulting in poor evaluation of their epidemiological characteristics. The objective of this study was to investigate trends in the incidence of primary malignant bone cancers and related mortality. Materials and methodsData from patients diagnosed with malignant bone cancers from 2000 to 2017 in the Surveillance Epidemiology and End Results database were retrospectively analyzed. Annual age-adjusted incidence and mortality were calculated, and the annual percentage change analyzed. Further, characteristics including patient age and sex, as well as the primary site and stage of different tumor types, were analyzed. ResultsThe overall age-adjusted incidence rate of primary malignant bone cancers was 7.70 per million people per year, and incidence rates had increased in patients between 60 and 79 years old, or with tumor size ≥ 8 cm. The incidence of chordoma increased significantly (annual percentage change (APC), 3.0 % per year), while those of WHO grade I and II primary bone cancers decreased. During 2000–2017, the mortality rate attributable to malignant bone cancers across the entire United States was 4.41 per million people per year. A positive mortality trend was observed during the study period (APC = 0.7 %, 95 % confidence interval: 0.0 %–1.5 %). Patients with osteosarcoma, and those who were female or of white ethnicity showed significant increasing trends in mortality rate. ConclusionsDifferent tumor types have variable epidemiological manifestations, in terms of incidence and mortality, and exhibited altered trends over recent years. These variables can provide guidance to inform allocation of medical resources.

Identification and classification of glioma subtypes based on RNA-binding proteins

BackgroundGlioma is a common and aggressive primary malignant cancer known for its high morbidity, mortality, and recurrence rates. Despite this, treatment options for glioma are currently restricted. The dysregulation of RBPs has been linked to the advancement of several types of cancer, but their precise role in glioma evolution is still not fully understood. This study sought to investigate how RBPs may impact the development and prognosis of glioma, with potential implications for prognosis and therapy. MethodsRNA-seq profiles of glioma and corresponding clinical data from the CGGA database were initially collected for analysis. Unsupervised clustering was utilized to identify crucial tumor subtypes in glioma development. Subsequent time-series analysis and MS model were employed to track the progression of these identified subtypes. RBPs playing a significant role in glioma progression were then pinpointed using WGCNA and Lasso Cox regression models. Functional analysis of these key RBP-related genes was conducted through GSEA. Additionally, the CIBERSORT algorithm was utilized to estimate immune infiltrating cells, while the STRING database was consulted to uncover potential mechanisms of the identified biomarkers. ResultsSix tumor subgroups were identified and found to be highly homogeneous within each subgroup. The progression stages of these tumor subgroups were determined using time-series analysis and a MS model. Through WGCNA, Lasso Cox, and multivariate Cox regression analysis, it was confirmed that BCLAF1 is correlated with survival in glioma patients and is closely linked to glioma progression. Functional annotation suggests that BCLAF1 may impact glioma progression by influencing RNA splicing, which in turn affects the cell cycle, Wnt signaling pathway, and other cancer development pathways. ConclusionsThe study initially identified six subtypes of glioma progression and assessed their malignancy ranking. Furthermore, it was determined that BCLAF1 could serve as an RBP-related prognostic marker, offering significant implications for the clinical diagnosis and personalized treatment of glioma.

Hypoxia drives shared and distinct transcriptomic changes in two invasive glioma stem cell lines

Glioblastoma (GBM) is the most common primary malignant cancer of the central nervous system. Insufficient oxygenation (hypoxia) has been linked to GBM invasion and aggression, leading to poor patient outcomes. Hypoxia induces gene expression for cellular adaptations. However, GBM is characterized by high intertumoral (molecular subtypes) and intratumoral heterogeneity (cell states), and it is not well understood to what extent hypoxia triggers patient-specific gene responses and cellular diversity in GBM. Here, we surveyed eight patient-derived GBM stem cell lines for invasion phenotypes in 3D culture, which identified two GBM lines showing increased invasiveness in response to hypoxia. RNA-seq analysis of the two patient GBM lines revealed a set of shared hypoxia response genes concerning glucose metabolism, angiogenesis, and autophagy, but also a large set of patient-specific hypoxia-induced genes featuring cell migration and anti-inflammation, highlighting intertumoral diversity of hypoxia responses in GBM. We further applied the Shared GBM Hypoxia gene signature to single cell RNA-seq datasets of glioma patients, which showed that hypoxic cells displayed a shift towards mesenchymal-like (MES) and astrocyte-like (AC) states. Interestingly, in response to hypoxia, tumor cells in IDH-mutant gliomas displayed a strong shift to the AC state, whereas tumor cells in IDH-wildtype gliomas mainly shifted to the MES state. This distinct hypoxia response of IDH-mutant gliomas may contribute to its more favorable prognosis. Our transcriptomic studies provide a basis for future approaches to better understand the diversity of hypoxic niches in gliomas.

Morin Inhibits Cell Proliferation and Induces Caspase-mediated Apoptotic Cell Death in Glioma C6 Cell Line

Background Glioma is a recurrent form of primary malignant cancer that occurs in the brain and central nervous system. The adults are the major victims of gliomas, and the men are mostly affected. At present, gliomas are treated with surgical resection followed by radiation and the administration of chemodrugs such as temozolomide. The invasive and high recurrence rate of gliomas often reduces the effectiveness of treatment, which leads to poor recovery. Hence, more potent drugs without side effects on long-term treatment need to be discovered to treat gliomas. Morin is one such promising phytochemical that possesses immense pharmacological properties. It is proven to exert anti-inflammatory, antioxidant, anticancer, antibacterial, antidiabetic, and neuroprotective properties. The current research focuses on examining the growth inhibition and apoptosis-inducing potency of morin against glioma C6 cells. Materials and Methods Rat C6 glioma cells were treated with different concentrations of morin and analyzed for cytotoxicity using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The intracellular reactive oxygen species (ROS) production and alteration of mitochondrial membrane potential (MMP) by morin in glioma cells were examined with dichlorodihydrofluorescein diacetate (DCHF-DA) and rhodamine 123 staining. The apoptotic induction in glioma cells was analyzed with dual staining and it was confirmed by quantifying the apoptotic protein using the enzyme-linked immunosorbent assay (ELISA) technique. The anti-inflammatory property of morin was assessed by the inflammatory cytokines tumor necrosis factor-α (TNF-α), nuclear factor-kappa B (NF-κB), cyclooxygenase-2 (COX-2), and interleukin-6 (IL-6) using the ELISA technique. Results Our MTT results show that morin treatment significantly reduced the cell viability of rat C6 glioma cells. It also significantly increased ROS generation and decreased MMP in rat C6 glioma cells. Morin treatment also effectively increased caspase-3 and caspase-9, the proapoptotic protein Bax, and decreased the antiapoptotic protein Bcl-2. The induction of apoptosis by morin in glioma cells was evident with our acridine orange/ethidium bromide (AO/EtBr) staining results. Morin also decreased the inflammatory cytokine levels in rat C6 glioma cells. Conclusion Our findings have proven that morin significantly induces apoptosis by increasing the levels of apoptotic protein via the generation of ROS. It also effectively reduced inflammatory cytokine levels, thereby exerting anticancer activity against glioma cells. Therefore, morin can be subjected to further research to be designed as a potent anticancer drug to treat gliomas.

Leveraging metformin to combat hepatocellular carcinoma: its therapeutic promise against hepatitis viral infections

Hepatocellular carcinoma (HCC) is categorized among the most common primary malignant liver cancer and a primary global cause of death from cancer. HCC tends to affect males 2-4 times more than females in many nations. The main factors that raise the incidence of HCC are chronic liver diseases, hepatotropic viruses like hepatitis B (HBV) and C (HCV), non-alcoholic fatty liver disease, exposure to toxins like aflatoxin, and non-alcoholic steatohepatitis (NASH). Among these, hepatitis B and C are the most prevalent causes of chronic hepatitis globally. Metformin, which is made from a naturally occurring compound called galegine, derived from the plant Galega officinalis (G. officinalis ), has been found to exhibit antitumor effects in a wide range of malignancies, including HCC. In fact, compared to patients on sulphonylureas or insulin, studies have demonstrated that metformin treatment significantly lowers the risk of HCC in patients with chronic liver disease. This article will first describe the molecular mechanism of hepatitis B and C viruses in the development of HCC. Then, we will provide detailed explanations about metformin, followed by a discussion of the association between metformin and hepatocellular carcinoma caused by the viruses mentioned above.

Utility of the "All of Us" Database for Radiation Oncology Research.

We provide an overview the All of Us Research Program, a National Institutes of Health funded research database, and report on the utility of this database for Radiation Oncology research. The All of Us Research Program aims to create a large and diverse health database with participants from across the US. Patients consent to join the database and agree to share electronic health records, complete surveys, provide physical measurements, and donate at least one biospecimen. In this observational study, we used the public data browser feature of the All of Us Dataset to evaluate utility for future radiation oncology research. Within the database, we report on the number of cases of common cancers in the US, using ICD10 codes, and also the number of patients treated with common radiotherapy procedures, using CPT4 codes. We then qualitatively report on additional data of interest. Of note, public patient counts in All of Us is rounded to the nearest interval of 20. Additional tiers of data access exist, including individual level data, which were not used in this survey of public data. The database includes 372,380 participants, of which 46,380 patients have a diagnosis of cancer. Within the identified top 10 cancers according to ACS, there were a total of 26,540 primary malignant cancers. The most common type of cancers were breast cancer (ICD10 - c50 [n = 6,960]), Prostate (ICD10 - c61 [n = 4,500]), Non-Hodgkin lymphoma (ICD10 - c85 [n = 2860]), Lung & bronchus (ICD10 - c34 [n = 2000]), Colon (ICD10 - c18 [n = 1940]), Melanoma of the skin (ICD10 - c43 [n = 1740]), Thyroid(ICD10 - c73 [n = 1720]), Kidney (ICD10 - c64 [n = 1300]), Urinary bladder (ICD10 - c67 [n = 1140]). The most common radiation therapy procedures were Computerized Tomography simulation (CPT - 77290 [n = 4,040]), Intensity Modulated Radiation Therapy (CPT - 77386 [n = 780]), 3D conformal radiation therapy (CPT - 77412 [n = 1,720]), Stereotactic Body Radiation Therapy (CPT - 77373 [n = 400]), Brachytherapy (CPT - 77770- 77772 [n = 240]), and Proton Therapy (CPT - 77520-77525 [n = 140]). Qualitatively, other data within All of Us include labs values, drug exposures, comorbidities, other procedures, physical measurements, and wearable biometrics (Fitbit) data. Genomic data typically includes germline testing using whole genome sequencing or genotyping array. Patient surveys include data on personal medical history, family health history, lifestyle, social determinants of health, COVID19 experience, and overall health. Potential outcome variables of interest to oncology research in the database include survival, cause of death, additional procedures or diagnoses after cancer treatment, and quality of life metrics derived from the survey instruments. The All Of Us Research Database includes a large number of cancer cases, of which a substantial number received radiotherapy. Future work will focus on focused hypothesis-driven research questions.

Association of radiotherapy for stage I-III breast cancer survivors and second primary malignant cancers: a population-based study.

With life span extending, breast cancer survivors may face the possibility of developing second primary cancers (SPCs). The objective of this research is to investigate the risk factors, risk attribute to radiotherapy and the survivalship for SPCs. A total of 445 523 breast cancer patients were enrolled from Surveillance, Epidemiology, and End Results database in 2000-2018. The risk factors for SPCs development were confirmed by competing risk model, and then were integrated to the nomogram establishment. The cumulative incidence of SPCs including SBC (second breast cancer), SGC (second gynecological cancer), and SLC (second lung cancer) were estimated. The radiotherapy-associated risk for SPCs were evaluated by Poisson regression in radiotherapy and no-radiotherapy. Propensity score matching was used to reduce possible bias for survival comparison. There were 57.63% patients in radiotherapy. The risk factors for developing SPCs were age, year, race, tumor size, stage, radiotherapy, grade, surgery, and histology. The cumulative incidence of SPCs was 7.75% in no-radiotherapy and 10.33% in radiotherapy. SLC, SBC, and SGC also appeared the similar results. The increased risk of developing SPCs were associated with radiotherapy in majority subgroups. The dynamic radiotherapy-associated risk for SPCs by age slightly increased risk was observed. Regardless radiotherapy or no-radiotherapy, the 10-year overall survival for SBC (radiotherapy: 59.41%; no-radiotherapy: 55.53%) and SGC (radiotherapy: 48.61%; no-radiotherapy: 35.53%) were worse than that among matched patients with only primary cancers. Breast cancer survivors remained a high radiotherapy-associated risk for developing SPCs. The prognosis in radiotherapy was better than in no-radiotherapy for some specific SPCs. Largely attention should be paid to these patients.

Changes in cancer diagnoses and stage distribution during the first year of the COVID-19 pandemic in the USA: a cross-sectional nationwide assessment

The emergence of COVID-19 disrupted health care, with consequences for cancer diagnoses and outcomes, especially for early stage diagnoses, which generally have favourable prognoses. We aimed to examine nationwide changes in adult cancer diagnoses and stage distribution during the first year of the COVID-19 pandemic by cancer type and key sociodemographic factors in the USA. In this cross-sectional study, adults (aged ≥18 years) newly diagnosed with a first primary malignant cancer between Jan 1, 2018, and Dec 31, 2020, were identified from the US National Cancer Database. We included individuals across 50 US states and the District of Columbia who were treated in hospitals that were Commission on Cancer-accredited during the study period. Individuals whose cancer stage was 0 (except for bladder cancer), occult, or without an applicable American Joint Committee on Cancer staging scheme were excluded. Our primary outcomes were the change in the number and the change in the stage distribution of new cancer diagnoses between 2019 (Jan 1 to Dec 31) and 2020 (Jan 1 to Dec 31). Monthly counts and stage distributions were calculated for all cancers combined and for major cancer types. We also calculated annual change in stage distribution from 2019 to 2020 and adjusted odds ratios (aORs) using multivariable logistic regression, adjusted for age group, sex, race and ethnicity, health insurance status, comorbidity score, US state, zip code-level social deprivation index, and county-level age-adjusted COVID-19 mortality in 2020. Separate models were stratified by sociodemographic and clinical factors. We identified 2 404 050 adults who were newly diagnosed with cancer during the study period (830 528 in 2018, 849 290 in 2019, and 724 232 in 2020). Mean age was 63·5 years (SD 13·5) and 1 287 049 (53·5%) individuals were women, 1 117 001 (46·5%) were men, and 1 814 082 (75·5%) were non-Hispanic White. The monthly number of new cancer diagnoses (all stages) decreased substantially after the start of the COVID-19 pandemic in March, 2020, although monthly counts returned to near pre-pandemic levels by the end of 2020. The decrease in diagnoses was largest for stage I disease, leading to lower odds of being diagnosed with stage I disease in 2020 than in 2019 (aOR 0·946 [95% CI 0·939-0·952] for stage I vs stage II-IV); whereas, the odds of being diagnosed with stage IV disease were higher in 2020 than in 2019 (1·074 [1·066-1·083] for stage IV vs stage I-III). This pattern was observed in most cancer types and sociodemographic groups, although was most prominent among Hispanic individuals (0·922 [0·899-0·946] for stage I; 1·110 [1·077-1·144] for stage IV), Asian American and Pacific Islander individuals (0·924 [0·892-0·956] for stage I; 1·096 [1·052-1·142] for stage IV), uninsured individuals (0·917 [0·875-0·961] for stage I; 1·102 [1·055-1·152] for stage IV), Medicare-insured adults younger than 65 years (0·909 [0·882-0·937] for stage I; 1·105 [1·068-1·144] for stage IV), and individuals living in the most socioeconomically deprived areas (0·931 [0·917-0·946] for stage I; 1·106 [1·087-1·125] for stage IV). Substantial cancer underdiagnosis and decreases in the proportion of early stage diagnoses occurred during 2020 in the USA, particularly among medically underserved individuals. Monitoring the long-term effects of the pandemic on morbidity, survival, and mortality is warranted. None.

#4934 HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY WITH CISPLATIN INCREASES THE RISK OF ACUTE KIDNEY INJURY COMPARED TO CONVENTIONAL INTRAPERITONEAL CISPLATIN

Abstract Background and Aims Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin is increasingly used for the treatment of ovarian and peritoneal cancer. Acute kidney injury (AKI) is a frequent complication after cisplatin containing HIPEC therapy. The aim of this study was to compare the incidence and severity of AKI and renal survival after HIPEC compared to repeated cycles of conventional high-dose intraperitoneal cisplatin in patients with ovarian and malignant peritoneal cancer. Method We conducted a retrospective study that included patients with ovarian cancer that received repeated cycles of high-dose intraperitoneal cisplatin and patients with ovarian and primary malignant peritoneal cancer that received HIPEC with cisplatin in our center between August 2006 and September 2022. Demographic and perioperative data were compared between both groups. We compared the incidence of AKI defined as a rise in serum creatinine by ≥ 0.3 mg/dL within 48 hours (KDIGO criteria), the severity of AKI defined as stages I, II and III using the KDIGO staging, the rate of kidney function recovery and need for renal replacement therapy in both groups. We performed logistic regression analysis to identify independent risk factors for experiencing AKI and conducted survival analyses and multivariate Cox regression analyses to detect independent risk factors for patient survival. Results The study included 39 patients; 20 received 76 cycles of conventional intraperitoneal cisplatin, and 19 patients (13 with ovarian cancer and 6 with primary peritoneal cancer) received HIPEC. Patients who received HIPEC were older (63.4±20 years vs 56±8 years, p = 0.002) and received a lower dose of cisplatin both in absolute values (109.2±41.1 mg vs 159.2±15.2 mg, p&amp;lt;0.001) and adjusted by body surface area (63.4±19.9 mg/m2 vs 96.8±9.2 mg/m2, p&amp;lt;0.001). AKI was significantly more frequent in patients receiving HIPEC (42.1% vs 15.8%, p = 0.012), and was more severe after HIPEC with AKIN-I, AKIN-II and AKIN-III in 50% vs 83%, 12.5% vs 16.7% and 37.5% vs 0% respectively, p = 0.042. Recovery from AKI was more frequent in patients receiving conventional intraperitoneal cisplatin (100% vs 50%, p = 0.014) and 1 patient in the HIPEC group progressed to end stage kidney disease. In the multivariate logistic regression analysis, after adjusting for age, baseline serum creatinine and cisplatin dose, treatment with HIPEC compared to conventional high-dose intraperitoneal cisplatin remained a significant risk factor for developing AKI (OR 1550, CI 95% 19-128070). Conclusion Cisplatin-based HIPEC therapy is associated with an increased risk of severe AKI compared to conventional high-dose intraperitoneal cisplatin regimens, despite the use of prophylactic measures. Hyperthermic perfusion of the abdomen might be an important contributing factor in HIPEC-induced renal injury. To reduce the incidence of AKI and its associated morbidity after HIPEC, early implementation of preventive measures with adequate fluid management and closer monitoring of hemodynamic parameters and kidney function tests should be taken into consideration.

The association between continuity of Medicaid enrollment and cancer survival in young adults diagnosed with cancer.

6538 Background: Disparities in young adult cancer survival between individuals with Medicaid and private insurance have been reported. To further understand the association between insurance-related access to healthcare and young adult cancer survival, we used Surveillance, Epidemiology, and End Results (SEER)-Medicaid linked data to test two hypotheses: 1) Those linked to Medicaid have lower cancer survival than those not linked, and 2) those with discontinuous enrollment in Medicaid around the time of diagnosis have lower survival than those with continuous enrollment. Methods: SEER-Medicaid linked data from 2006 to 2013 were obtained. Follow-up for vital status was through 2018. We included individuals diagnosed with a first malignant primary cancer diagnosed between 20 to 39 years. We excluded individuals who were linked to Medicaid enrollment records in multiple states during the same year. Individuals were defined as Medicaid-linked if they were linked to Medicaid in any U.S. state or the District of Columbia from 2006 to 2013. Medicaid enrollment was classified as continuous (enrolled within both the three months before and after diagnosis) and discontinuous (enrolled only within the 3 months before or after diagnosis or only at diagnosis). We used survival analysis methods including Kaplan-Meier (KM) curves and Cox Proportional Hazards (PH) regression models to evaluate survival differences in association with Medicaid linkage and enrollment timing after adjusting for race and a measure of census tract poverty. Results: Our analytic dataset included 137,259 young adults, among which there were 22,955 cancer deaths. KM curves showed consistently lower survival probabilities over time in young adults who linked vs. those not linked to Medicaid and in those with discontinuous vs. continuous enrollment (p &lt; .0001). Adjusted Cox PH regression models indicated that those who linked to Medicaid had a 2.19 (95% CI 2.14-2.25) times higher hazard of death vs. those who did not link. Those with continuous and discontinuous Medicaid enrollment had a 1.91 (95% CI 1.84 to 1.99) and 3.32 (95% CI 3.19 to 3.45) times higher hazard of death, respectively, vs. those not linked to Medicaid. Similar patterns were consistently observed for specific cancer types. Conclusions: These results confirm an insurance-associated disparity in a national sample of young adult cancer patients and provide additional information on risks in association with Medicaid enrollment continuity. These results further support the critical need for consistent health insurance coverage in young adults and for additional research to understand social, economic, and access-related factors leading to lower survival in the Medicaid population. Lowering administrative burdens for Medicaid enrollment, eligibility, and renewal are potentially important strategies for improving cancer outcomes.

Disparities in survival improvement for U.S. childhood and adolescent cancer between 1995 and 2019: An analysis of population-based data

BackgroundAlthough treatment advances have increased childhood and adolescent cancer survival, whether patient subgroups have benefited equally from these improvements is unclear. MethodsData on 42,865 malignant primary cancers diagnosed between 1995 and 2019 in individuals ≤ 19 years were obtained from 12 Surveillance, Epidemiology, and End Results registries. Hazard ratios (HRs) and 95 % confidence intervals (CIs) for cancer-specific mortality by age group (0–14 and 15–19 years), sex, and race/ethnicity were estimated using flexible parametric models with a restricted cubic spline function in each of the periods: 2000–2004, 2005–2009, 2010–2014 and 2015–2019, versus 1995–1999. Interactions between diagnosis period and age group (children 0–14 and adolescents 15–19 years at diagnosis), sex, and race/ethnicity were assessed using likelihood ratio tests. Five-year cancer-specific survival rates for each diagnosis period were further predicted. ResultsCompared with the 1995–1999 cohort, the risk of dying from all cancers combined decreased in subgroups defined by age, sex and race/ethnicity with HRs ranging from 0.50 to 0.68 for the 2015–2019 comparison. HRs were more variable by cancer subtype. There were no statistically significant interactions by age group (Pinteraction=0.05) or sex (Pinteraction=0.71). Despite non-significant differences in cancer-specific survival improvement across different races and ethnicities (Pinteraction=0.33) over the study period, minorities consistently experienced inferior survival compared with non-Hispanic Whites. ConclusionsThe substantial improvements in cancer-specific survival for childhood and adolescent cancer did not differ significantly by different age, sex, and race/ethnicity groups. However, persistent gaps in survival between minorities and non-Hispanic Whites are noteworthy.

Better survival and prognosis in SCLC survivors after combined second primary malignancies: A SEER database-based study.

With recent advances in treatment modalities, the survival time for patients with small cell lung cancer (SCLC) has increased, along with the likelihood of recurrence of a second primary tumor. However, patient treatment options and prognosis remain uncertain. This research evaluated the survival rates of patients with SCLC with a second malignancy, aiming to provide new insights and statistics on whether to proceed with more active therapy. SCLC patients were selected based on the Surveillance, Epidemiology, and End Results (SEER) database, updated on April 15, 2021. We defined those with SCLC followed by other cancers (1st of 2 or more primaries) in the sequence number as S-second primary malignant cancer (S-SPM). Those who had other cancers followed by SCLC (2nd of 2 or more primaries) were defined as OC-SCLC. We performed Kaplan-Meier survival analysis, life table analysis, univariate analysis, stratified analysis, and multiple regression analysis of patient data. We considered the difference statistically meaningful at P < .05. After selection, data for 88,448 participants from the SEER database was included in our analysis. The mean survival time for patients with S-SPM was 69.349 months (95% confidence interval [CI]: 65.939, 72.759), and the medium duration of survival was 34 months (95% CI: 29.900, 38.100). Univariate analysis showed that for overall survival, the hazard ratio (HR) of S-SPM was 0.367 (95% CI: 0.351, 0.383), which was 0.633 lower than that of patients with solitary SCLC and 0.606 lower than that of patients with OC-SCLC. For cancer-specific survival (CSS), the HR of S-SPM was 0.285 (95% CI: 0.271, 0.301), which was 0.715 lower than for patients with solitary SCLC and 0.608 lower than that for patients with OC-SCLC. Multiple regression analysis showed that the HR values of S-SPM were lower than those of patients with single SCLC and those with OC-SCLC, before and after adjustment for variables. Kaplan-Meier survival curves showed that patients with S-SPM had significantly better survival times than the other groups. The survival time and prognosis of patients with S-SPM were clearly superior to those with single SCLC and OC-SCLC.

Chemoembolization as a minimally invasive treatment of primary malignant liver cancer

Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer and one of the most malignant neoplasms with high incidence and mortality in humans worldwide. The complex nature of the disease and its high resistance to systemic therapies result in poor prognosis for patients with advanced HCC. Case Report: In March 2017, the patient was admitted to the Department of Oncological Surgery, where a non-anatomical tumor resection was performed. Three years later, the patient developed a single change in segment 8 of the liver that was a relapse of the neoplastic process. Based on the Bracelon Criteria, the patient was qualified for the 1st stage of chemoembolization using the Seldinger method. In the presented patient as a result of the applied treatment, the neoplastic process was stabilized. Conclusion: The chemoembolization treatment that was applied to the presented patient turned out to be the correct treatment option. After only the first stage of chemoembolization, the patient regressed the neoplastic lesion.

Cancer Prevention for Survivors: Incidence of Second Primary Cancers and Sex Differences-A Population-Based Study from an Italian Cancer Registry.

Background: The number of cancer survivors continues to increase, thanks to advances in cancer diagnosis and treatment. Unfortunately, the incidence of a second primary cancer (SPC) is also increasing, but limited studies reporting incidence data are available regarding multiple cancers. This study presents our observations on multiple primary malignant cancers, the associations between sites, and the inherent sex differences. Patients and methods: We report the data, disaggregated by sex, concerning the SPCs that were recorded in the “Registro Tumori Integrato” (RTI) a population-based cancer registry in Sicily, Italy, as observed in the period from 2003 to 2017, in a total population of approximately 2,300,000. SPCs were divided into synchronous and metachronous cancers. The International Classification of Diseases for Oncology, third edition (ICD-O-3), was used for topographical and morphological classifications. Multiple primary cancers with multi-organ primitiveness were selected from the database of the RTI by extracting patients with more than one diagnosis. SPCs had different histology or morphology from the particular cancer that was considered to be the index cancer case. Multicenter or multifocal cancers, or metastases, were excluded. The percentages of cancer by sex and topography, the average age of incidence, and a breakdown by age were computed. Results: Differences were observed between sexes in terms of incidence and site for SPCs. The most frequent SPC was skin cancer (20% of the SPCs observed). The associations among sites of multiple cancers are reported. Conclusion: There are many gaps in our knowledge of sex differences in cancer. The study of multiple primary cancers could bring more likely opportunities for evaluation of the cancer burden and trends that can be used to identify new research areas by population health programs, as well as for clinical researchers.

Association of Ethnicity, Sex, and Age With Cancer Diagnoses and Health Care Utilization Among Children in Inner Mongolia, China

China is experiencing a sustained increase in childhood cancer. However, whether differences exist in disease burden by ethnicity remains unclear. To compare differences in cancer diagnoses and health care utilization in Inner Mongolia among children subgrouped by ethnicity (Han vs Mongolian), sex, and age. This retrospective cohort study in Inner Mongolia, China, used data on children aged 0 to 14 years with cancer from the Inner Mongolia Regional Health Information Platform, which comprises the National Basic Medical Insurance database and the Inner Mongolia cause-of-death reporting system, from January 1, 2013, to December 31, 2019. Ethnicities analyzed included Han and Mongolian; patients of other ethnicities were not included in the analysis because of the small sample size. Cancer was broadly defined as a primary malignant tumor or hematologic cancer; benign central nervous system tumors were also included. A 2-year washout period was used to exclude prevalent cases. After diagnosis, the patients were followed up until the date of death or the end of the insured status, whichever came first. Ethnicity (Han vs Mongolian), sex (male vs female), and age (0-4, 5-9, and 10-14 years). Crude incidence, 5-year prevalence, and survival rates at 1 year and 3 years after diagnosis; health care utilization, represented by medical costs during the first year and first 3 years after diagnosis; and hospital attendance with level (tertiary vs secondary and lower-level hospitals) and location of each unique visit. From 2013 to 2019, 1 106 684 (2013), 1 330 242 (2014), 1 763 746 (2015), 2 400 343 (2016), 2 245 963 (2017), 2 901 088 (2018), and 2 996 580 (2019) children aged 0 to 14 years were registered in the NBMI database. Among the 2 996 580 children enrolled in 2019, the mean (SD) age was 6.8 (4.3) years, of whom 1 572 096 (52.5%) were male, 2 572 091 (85.8%) were Han, and 369 400 (12.3%) were Mongolian. A total of 1910 patients with cancer were identified (1048 were male [54.9%]; 1559 were Han [81.6%], and 300 were Mongolian [15.7%]). There were 764 hematologic cancers (40.0%) and 1146 solid tumors (60.0%). The overall crude incidence of cancer from 2015 to 2019 was 129.85 per million children (95% CI, 123.63-136.06), with a higher incidence among Mongolian than among Han children (155.12 [95% CI, 136.81-173.43] vs 134.39 [95% CI, 127.46-141.32]). The 5-year prevalence was 428.97 per million (95% CI, 405.52-452.42) in 2020, with a higher prevalence among Mongolian than among Han children (568.49 [95% CI, 91.62-645.36] vs 404.34 [95% CI, 379.77-428.91]). The combined 1-year (2015-2019) and 3-year (2015-2017) survival rates were 72.5% (95% CI, 67.5%-77.5%) and 66.8% (95% CI, 61.6%-71.9%), respectively. The 1-year (median [IQR], $1991 [$912-$10 181] vs $3991 [$1171-$15 425]) and 3-year (median [IQR], $2704 [$954-$13 909] vs $5375 [$1283-$22 466]) postdiagnosis costs were lower among Mongolian than among Han children. A higher proportion of Mongolian patients attended low-level hospitals (45.9% vs 17.4%). In this cohort study, Mongolian children had a higher incidence and prevalence of cancer but a lower demand for medical care, suggesting that further investigations are needed to identify mechanisms underlying ethnic disparities and ensure that care is equitable.

Shilajit potentiates the effect of chemotherapeutic drugs and mitigates metastasis induced liver and kidney damages in osteosarcoma rats

Osteosarcoma is a primary malignant cancer of the bone identified by the direct formation of osteoid tissue or immature bone by cancer cells. The liver and kidneys represent two major secondary organs to which osteosarcoma metastasizes. In this study, we assessed Shilajit, a phytomineral diffusion traditionally used in Ayurvedic medicine, for its possible protective effects against metastasis induced liver and kidney damages in an osteosarcoma rat model. Osteosarcoma rats displayed typical dysregulation of serum levels of hepatic and renal functional markers (p < 0.05) including aspartate aminotransferase (AST)* and alanine aminotransferase (ALT), alkaline phosphatase (ALP), total proteins, albumin, bilirubin, creatinine, urea, and uric acid. Changes in functional markers were also positively correlated with marked histopathological alterations in liver and kidney tissues. Whereas Shilajit's treatment of osteosarcoma rates in combination with CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) chemotherapy drug cocktail significantly (p < 0.05) reversed the studied functional markers to their near-normal levels. Co-treatment of shilajit and drug cocktails also markedly alleviated histopathological changes in liver and kidney tissues. Correlation co-efficient analysis of hepatic and renal functional markers revealed a significant inter-association among these markers. Collectively, present data indicate that shilajit may potentiate the effects of chemotherapy drugs and mitigate the metastasis-induced liver and kidney damage in osteosarcoma. Thus, the findings of this study substantiate the beneficial health effects of shilajit and promote its regular consumption.