Carbon Chemist

Tag: Carcinoma

  • Research reveals potential target for enfortumab vedotin therapy in urothelial carcinoma

    Research reveals potential target for enfortumab vedotin therapy in urothelial carcinoma

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    Under the leadership of PD Dr. Niklas Klümper, Assistant Physician at the Department of Urology at the University Hospital Bonn (UKB) and Clinician Scientist of the BMBF-funded ACCENT program and PD Dr. Markus Eckstein, senior physician at the Institute of Pathology at the Uniklinikum Erlangen of the Friedrich-Alexander-University Erlangen-Nürnberg (FAU), an interdisciplinary research team has published new findings that indicate which patients with advanced urothelial carcinoma could benefit in particular from the new targeted therapy with the antibody-drug conjugate enfortumab vedotin. The study, published yesterday in the prestigious Journal of Clinical Oncology, identifies NECTIN4 amplification as a promising genomic biomarker for predicting treatment response to enfortumab vedotin. These findings could represent a significant advance in the improved treatment of this cancer.

    As an alternative to chemotherapies used to treat aggressive advanced and metastatic urothelial carcinoma, a new class of drugs, known as antibody-drug conjugates, has recently become available. Enfortumab vedotin (EV) is the first drug in this new class to be approved by the EMA at for the treatment of patients and patients with metastatic urothelial carcinoma. Given the extremely promising results of the EV-302 trial, which showed a near doubling of survival with the combination therapy of EV and pembrolizumab, an immune checkpoint inhibitor, compared to conventional platinum-based chemotherapy in untreated patients with metastatic urothelial carcinoma, it is expected that the use of EV will increase significantly in the future.

    Modern targeted oncology therapy

    Antibody-drug conjugates consist of an antibody directed against a target structure on tumor cells and combined with a highly toxic chemotherapeutic agent. This combines the selectivity of targeted antibody therapy with the cytotoxic potential of conventional chemotherapy, which represents an innovative and new oncological therapeutic approach.

    Research for more targeted therapy: precision oncology

    Long-term efficacy of the new drug EV has so far been shown in an uncharacterized group of patients with metastatic urothelial carcinoma. The research team led by PD Dr. Niklas Klümper (UKB) and PD Dr. Markus Eckstein (Uniklinikum Erlangen) therefore wanted to analyze in more detail which patients benefit effectively from EV therapy in order to be able to use it in a more targeted manner – and conversely to identify patients who benefit less or not from EV, as they could possibly be treated more effectively with other therapies.

    Nectin-4, the target structure of EV, is localized on chromosome 1q23.3. This gene segment is increased in about 20-25 percent of urothelial carcinomas, which is referred to as amplification. The new study aimed to investigate NECTIN4 amplifications as a potential genomic biomarker to predict treatment response to the drug EV in patients with advanced urothelial carcinoma.

    “We have successfully developed and applied a simple FISH test (fluorescence in situ hybridization) that is specific for NECTIN4. This test proved to be a reliable method for identifying NECTIN4 amplification. Our studies showed that the presence of NECTIN4 amplification is a robust biomarker for response to EV therapy. In fact, over 90 percent of patients with NECTIN4 amplification showed tumor response to EV therapy, compared to about 30 percent of patients without this amplification”, says PD Dr. Markus Eckstein. These new findings can help to better select patients for this promising therapy in the future. “NECTIN4 amplification is a promising biomarker for predicting treatment response to EV. Excitingly, NECTIN4 amplification is also common in other solid tumors besides urothelial carcinoma, e.g. lung and breast cancer. The consideration of NECTIN4 amplification could therefore also be an exciting option for other tumor types in order to select patients for anti-NECTIN4-directed therapy in a more targeted manner. Further studies on this topic are needed, but our work could be the starting signal for the establishment of new targeted treatment strategies “, says PD Dr. Niklas Klümper.

    Both study PIs also agree that without the great support of all the colleagues involved from the numerous oncology centers in Germany, Austria, the Netherlands and the USA, and of course without the patients’ consent to participate in the study, it could never have been carried out successfully.

    The study was funded and initiated by the German Research Foundation (DFG) as part of the DFG Young Investigator Academy UroAgeCare of the German Society of Urology (DGU). “This underlines the high relevance of funding clinician scientist programs for medical progress,” says Prof. Michael Hölzel, mentor of PD Dr. Klümper within the program.

    Source:

    University Hospital Bonn (UKB)

    Journal reference:

    Klümper, N., et al. (2024) NECTIN4 Amplification Is Frequent in Solid Tumors and Predicts Enfortumab Vedotin Response in Metastatic Urothelial Cancer. Journal of Clinical Oncology. doi.org/10.1200/JCO.23.01983.

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  • Childhood obesity not linked to adult skin cancer risk, study says

    Childhood obesity not linked to adult skin cancer risk, study says

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    A recent Scientific Reports study investigates whether genetically predicted childhood adiposity influences the risk of developing skin cancer in adulthood.

    Study: Genetic predisposition to childhood obesity does not influence the risk of developing skin cancer in adulthood. Image Credit: Gorodenkoff / Shutterstock.com

    Background

    Several studies have reported that childhood obesity increases the risk of several types of cancers in adulthood. Although a causal link between body mass index (BMI) and melanoma has been established, no studies have evaluated whether childhood obesity influences the risk of developing basal cell carcinoma (BCC) or cutaneous squamous cell carcinoma (cSCC) in adulthood.

    Several mechanisms have been proposed to contribute to the potential causal link between BMI and melanoma. For example, some studies have suggested that obesity increases the risk of melanoma due to greater body surface area (BSA) that subsequently increases the number of target cells at risk. This hypothesis has been supported by some observational studies indicating that BSA positively correlates with increased melanoma risk.

    Nevertheless, other studies have hypothesized that obese people receive less sunlight exposure than their non-obese counterparts due to limited outdoor recreational activity. This reduced sunlight exposure could indirectly reduce the risk of melanoma. 

    About the study

    The current study utilized a Mendelian randomization (MR) approach to determine the effect of genetically predicted childhood adiposity on the development of skin cancer in adulthood. MR uses genetic variation to investigate potential relationships that may exist between exposures and outcomes documented in observational studies.

    Generic variants and other relevant data associated with childhood obesity were obtained from a recently published genome-wide association study (GWAS) meta-analysis. The analysis included 61,111 children of European descent between two and ten years of age.

    Importantly, these data were pooled from 40 individual studies from the original meta-analysis. The final analyses comprised 10,557 SCC cases, 36,479 BCC cases, and controls.

    Study findings

    Of the twenty-five genome-wide significant variants for childhood obesity, five were not associated with cSCC, BCC, or melanoma GWAS datasets. Therefore, twenty variants were eligible for the analysis, which explained 2.3% of the variance of BMI in childhood.

    The calculated risk estimates did not identify any significant association between genetically predicted childhood BMI and the risk of skin cancer development. Sensitivity analyses were performed to determine any breaches of MR assumptions that resulted in null findings. However, this result was also consistent with the risk estimates obtained in the MR inverse-variance-weighted (IVW) method.

    No pleiotropic variants for melanoma or cSCC were detected through the MR pleiotropy residual sum and outlier (MR-PRESSO) method. Here, three outlier variants for BCC were detected. Taken together, genetically predicted childhood obesity exhibited no significant effect on the development of skin cancer, including melanoma, cSCC, or BCC later in life.

    The lack of an observed association between genetically predicted childhood obesity and the risk of skin cancer development in adulthood indicates that body size is not likely to increase the risk of different types of skin cancer. Thus, the current study failed to validate whether obesity reduced the risk of melanoma due to limited outdoor activities. However, future studies could further analyze this potential association using pigmentation genes as a proxy for sun exposure.

    Strengths and limitations

    Key strengths of the current study include the consideration of vital confounding factors and the utilization of a large dataset to determine potential causal effects. Since the childhood GWAS meta-analysis encompassed thousands of children of European descent, population stratification could be effectively performed.

    Nevertheless, the current study is associated with certain limitations, such as the inclusion of participants exclusively of European descent, which limits the generalizability of the findings to a broader ethnic population. The genetic predictors of childhood obesity could also differ based on geography and ethnicity.

    Conclusions

    Despite the limitations, the current study strongly indicated that genetically predicted childhood adiposity does not influence skin cancer risks.

    Even if genetically predicted adiposity has an effect on risk of skin cancer, the magnitude of the effect would be very low so would likely have limited public health implications or clinical relevance.”

    Future studies are needed to understand whether genetic differences may impact the risk of developing skin cancer. Although genetically predicted adiposity provides essential information, it is not a faultless proxy, as genetic predisposition interacts with lifestyle and environmental factors that might influence childhood BMI.

    Journal reference:

    • Keatley, J., Law, M. H., Seviiri, M., et al. (2024) Genetic predisposition to childhood obesity does not influence the risk of developing skin cancer in adulthood. Scientific Reports 14(1); 1-5. doi:10.1038/s41598-024-58418-8

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  • Pembrolizumab enhances breast cancer treatment regardless of age or menopausal status

    Pembrolizumab enhances breast cancer treatment regardless of age or menopausal status

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    New data from the KEYNOTE-756 phase 3 clinical trial show that adding the immunotherapy drug, pembrolizumab, to chemotherapy before and after surgery for breast cancer leads to better outcomes for patients regardless of their age or menopausal status.

    The findings, presented at the 14th European Breast Cancer Conference (EBCC 14) today (Wednesday), add to information available on the effect of pembrolizumab in patients with early-stage breast cancer that is at high risk of recurring or spreading further, and that is oestrogen receptor positive (ER positive) and HER2 negative.

    KEYNOTE-756 is an international trial, which has been running for eight years. It randomised 1278 patients to receive pembrolizumab or placebo in addition to neoadjuvant chemotherapy (given before surgery) followed by adjuvant (given after surgery) pembrolizumab or placebo in combination with an endocrine therapy. The patients had invasive ductal carcinoma (IDC), meaning the cancer had started to spread out of the milk ducts into the surrounding breast tissues.

    Professor Javier Cortés, Director of the International Breast Cancer Centre in Barcelona, Spain, said: “We have already reported that there was a statistically significant increase in the pathological complete response rate in patients receiving pembrolizumab compared to those receiving the placebo. The pathological complete response rate, meaning that no cancer cells remained in the breast or lymph nodes, was 24.3% in patients treated with pembrolizumab compared to 15.6% in patients treated with the placebo.

    “Now we can show that these pCR rates occurred regardless of the patients’ age or menopausal status. In patients younger than 50 years old, the pCR rate was 23.8% in those on pembrolizumab (76 out of 319 patients) compared to 16.9% (55 out of 326) for those receiving placebo, and was 24.7% (78 of 316 patients) versus 14.2% (45 of 317) respectively in those aged 50 or older. In pre-menopausal women, the pCR rate was 23.4% (83 out of 354 patients) versus 16.1% (57 out of 353) respectively, and in post-menopausal women, it was 24.8% (69 out of 278 patients) versus 14.6% (42 out of 287), respectively.

    “We also found that adding pembrolizumab to neoadjuvant chemotherapy did not delay the time to surgery. The average time to surgery in both groups of patients was about a month. The average time after surgery to the start of adjuvant treatment was 1.2 months in both groups.”

    The study found there were similar rates of breast-conserving surgery and mastectomy in both groups. Among the patients who had breast-conserving surgery, 41.3% (262 patients) received pembrolizumab and 43.7% (281 patients) received placebo. Among those who had a mastectomy, 55.3% (351 patients) were treated with pembrolizumab and 54.4% (350 patients) had the placebo.”

    Tissue collected at the time of surgery was analysed to see if any cancer cells remained after the neoadjuvant treatment, known as residual cancer burden (RCB). Neoadjuvant pembrolizumab resulted in a lower RCB for more patients, regardless of how well the immunotherapy had blocked a protein called PD-L1, which also drives some breast cancers.

    Pathology reports found that 35% of patients (222 patients) treated with pembrolizumab had no or very small amounts of cancer cells remaining (RCB 0-1) versus 23.6% of patients (152) receiving placebo. A moderate amount of RCB (RCB-2) was found in 40.8% of patients treated with pembrolizumab versus 45.3% (259 versus 291 patients), and extensive RCB (RCB-3) was found in 20.5% versus 28.9% of patients respectively (130 versus 186 patients).

    When the researchers looked at the effect of pembrolizumab according to whether patients had cancer that was ER positive in less than 10% of cells or in 10% or more, they found that 64.7% of patients (22 out of 34) with less than 10%, who were treated with pembrolizumab, had an RCB status of 0-1, compared to 37.2% of patients treated with placebo (16 out of 43). In patients with 10% or more ER positive cells, 33.3% compared to 22.7% had an RCB 0-1 status (200 out of 601 patients versus 136 out of 600 patients respectively).

    Dr Fatima Cardoso, Director of the Breast Unit of the Champalimaud Clinical Centre, Lisbon, Portugal, is the principal investigator for the trial. Speaking before EBCC 14, she said: “Keynote 756 trial showed that the addition of pembrolizumab to neoadjuvant chemotherapy significantly increased pathological response at the time of surgery, and this was true regardless of PD-L1 levels and estrogen receptor positivity. However, we saw a bigger benefit with higher PD-L1 levels and in ER-low tumors.

    “Keynote-756 is also the only trial that is powered to analyze the impact of immunotherapy in long-term outcomes for this subtype of breast cancer.”

    Adverse events from the treatments were unchanged from previous reports from the trial and were consistent with what is known already about each regimen.

    The trial continues to follow the patients, and information is being collected on survival rates and whether there are any recurrences of cancer or other related symptoms.

    Professor Michail Ignatiadis from the Institut Jules Bordet in Brussels, Belgium, is Chair of the 14th European Breast Cancer Conference and was not involved in the research.

    We have heard more data from the KEYNOTE-756 trial about which ER positive / HER2 negative patient subgroups benefit most from pembrolizumab in terms of pathological complete response. Longer follow-up is needed in order to see whether the improvement in pCR rates will result in more patients living for longer without their disease recurring, and we look forward to these data in due course.”


    Professor Michail Ignatiadis, Institut Jules Bordet in Brussels, Belgium

    Source:

    European Organisation for Research and Treatment of Cancer

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  • Inherited genetic factors may predict elevated risk of new cancers among childhood cancer survivors

    Inherited genetic factors may predict elevated risk of new cancers among childhood cancer survivors

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    Common inherited genetic factors that predict cancer risk in the general population may also predict elevated risk of new cancers among childhood cancer survivors, according to a study led by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health. The findings, published March 7, 2024, in Nature Medicine, provide additional evidence that genetics may play an important role in the development of subsequent cancers in survivors of childhood cancer and suggest that common inherited variants could potentially inform screening and long-term follow-up of those at greatest risk. 

    Childhood cancer survivors are known to have a higher risk of developing a new cancer later in life due to adverse effects of cancer treatment or rare inherited genetic factors. In the new study, the researchers evaluated the combined effect of common variants with history of radiation treatment and found the resulting elevated cancer risk was greater than the sum of the individual associations for treatment and genetic factors alone. 

    Knowledge about a person’s genetic makeup could potentially be useful in managing their risk of subsequent cancers. The hope would be that, in the future, we can incorporate genetics along with treatment exposures and other risk factors to provide a more complete picture of a survivor’s risk of subsequent cancers to help guide their long-term follow-up care.” 


    Todd M. Gibson, Ph.D., lead investigator of NCI’s Division of Cancer Epidemiology and Genetics

    To assess the contribution of common inherited genetic variants to risk of subsequent cancer in people who survived childhood cancer, the research team used data from genome-wide association studies, or GWAS, that had been conducted in large populations of healthy individuals. Such studies have identified thousands of common inherited variants associated with risk of different cancers. The risk associated with a single common variant is typically small, but the effects of large numbers of variants can be bundled into a summary score, or polygenic risk score, that provides a more comprehensive estimate of someone’s genetic risk. 

    Although polygenic risk scores have shown promise for predicting cancer risk in the general population, it has not been known whether such scores are also associated with the risk of subsequent cancer among childhood cancer survivors. 

    To find out, the researchers looked at the association between polygenic risk scores and risk of basal cell carcinoma, female breast cancer, thyroid cancer, squamous cell carcinoma, melanoma, and colorectal cancer among 11,220 childhood cancer survivors from two large cohort studies. For all of these cancers except colorectal cancer, polygenic risk scores derived from GWAS in the general population were associated with the risk of these same cancers among childhood cancer survivors. 

    The researchers then looked at basal cell carcinoma, breast cancer, and thyroid cancer-;malignancies that occurred most often in the combined data set and that are strongly linked to radiation therapy-;to examine the joint effect of polygenic risk score and treatment history. They found that risk associated with the combination of higher-dose radiation exposure and higher polygenic risk score was greater than would be expected based on simply adding the risk associations of each individual risk factor. 

    For basal cell carcinoma, a high polygenic risk score was associated with 2.7-fold increased risk compared with a low polygenic risk score among survivors. History of higher radiation exposure to the skin was associated with a 12-fold increase in risk, compared with lower radiation exposure to the skin. However, survivors with high polygenic risk scores and higher doses of radiation to the skin had an 18.3-fold increased risk of basal cell carcinoma, compared with those with low polygenic risk scores who had received lower radiation doses to the skin.

    Moreover, by age 50, survivors with higher polygenic risk scores and higher radiation exposure had a greater cumulative incidence of basal cell carcinoma, breast cancer, or thyroid cancer than those with lower polygenic risk scores or lower radiation exposure. For example, among female survivors who had radiation to the chest, 33.9% of those with a high polygenic risk score had been diagnosed with breast cancer by age 50, compared with 21.4% of those with a low polygenic risk score.

    One limitation of the study is that the populations included in the analysis were predominantly of European ancestry, so additional studies are needed in diverse populations. Furthermore, polygenic risk scores are not yet used routinely in the clinic, although they may one day inform screening approaches or other clinical decisions. 

    “Although these results suggest that polygenic risk scores could play a role in improving guidelines for long-term follow-up of childhood cancer survivors exposed to radiation, right now they are not sufficient on their own to alter existing guidelines,” Dr. Gibson noted. 

    Source:

    NIH/National Cancer Institute

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  • Comparing CEUS imaging features in patients with hepatic lymphoepithelioma-like carcinoma and HCC

    Comparing CEUS imaging features in patients with hepatic lymphoepithelioma-like carcinoma and HCC

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    Announcing a new article publication for BIO Integration journal. Primary hepatic lymphoepithelioma-like carcinoma (LELC) is a malignant tumor with a low incidence, but the number of case reports has increased in recent years. The prognosis of hepatic LELC is better than hepatocellular carcinoma (HCC). The differentiation between hepatic LELC and HCC has clinical value during follow-up treatment. The purpose of our study was to compare contrast-enhanced ultrasound (CEUS) imaging features in patients with hepatic LELC and HCC.

    Twelve patients with an average age of 60.1±9.5 years and histopathologically confirmed hepatic LELC were included in the study. Forty-three patients with an average age of 57.4±9.0 years and a histopathological diagnosis of HCC were designated as the control group by means of propensity score matching (1:4). The clinical data, B-mode ultrasound (BMUS), and CEUS features were retrospectively analyzed between patients with hepatic LELC and HCC.

    The serum a-fetoprotein (58.1% [25/43] vs.16.7% [2/12]; p=0.017) and des-gamma-carboxy prothrombin levels (74.4% [32/43] vs.16.7% [2/12]; p=0.001) were not significantly elevated in patients with hepatic LELCs compared to HCCs. LELCs were mainly hypoechoic based on BMUS, while the echogenicity of HCCs varied (p=0.016). A halo sign was less common in patients with hepatic LELCs than HCCs (16.7% [2/12] vs. 58.1% [25/43]; p=0.011). Of hepatic LELCs, 75% (9/12) had homogeneous hyperenhancement based on CEUS, whereas 58.1% (25/43) of HCCs had heterogeneous hyperenhancement (p=0.004). Early washout was noted in 91.7% (11/12) of hepatic LELCs compared to 46.5% (20/43) of HCCs (p=0.005). Furthermore, hepatic LELCs were more likely to exhibit peripheral rim-like hyperenhancement (83.3% [10/12] vs. 11.6% [5/43]; p < 0.001).

    BMUS and CEUS are helpful in discriminating between hepatic LELC and HCC. A hypoechoic mass, the rare halo sign, homogeneous hyperenhancement in the arterial phase, higher frequencies of early washout, and peripheral rim-like hyperenhancement are useful ultrasound features that can help differentiate hepatic LELCs from HCCs.

     

    Source:

    Journal reference:

    Qin, H., et al. (2024) Contrast-Enhanced Ultrasound Features of Primary Hepatic Lymphoepithelioma-Like Carcinoma: Comparison with Hepatocellular Carcinoma. BIO Integration. doi.org/10.15212/bioi-2023-0019.

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  • Nomogram could be a game-changer for predicting alcohol-related liver cancer risk

    Nomogram could be a game-changer for predicting alcohol-related liver cancer risk

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    Liver cancer, unfortunately, is the sixth most common cancer and the third most frequent cause of cancer-related death globally. However, its distribution and causes vary greatly across different regions. While areas like Eastern Asia and sub-Saharan Africa see the most cases, the reasons behind them differ significantly.

    In high-income countries, liver cancer has been on the decline thanks to widespread newborn hepatitis B vaccination and antiviral drugs. Meanwhile, low-income countries witness a worrying rise, often linked to increased hepatitis B and C infections and injectable drug use.

    While viral hepatitis remains a major concern, another factor is gaining attention: alcohol consumption. Studies show that chronic alcohol consumption can directly cause about 10% of cancer cases in men and 3%, respectively, in women. In fact, a study at the Mayo Clinic revealed that alcoholic cirrhosis was the main culprit in 29% of patients with hepatocellular carcinoma (HCC), the most common liver cancer type.

    But the study doesn’t just sound the alarm; it also offers a potential solution. Researchers identified key risk factors for HCC in people with alcohol-related liver disease, including heavy drinking, age, diabetes, male sex, and liver cirrhosis. Based on these factors, they developed a novel tool called a nomogram that can predict HCC risk with high accuracy and ease of use.

    This nomogram could be a game-changer for doctors, allowing them to personalize treatment plans and identify individuals at highest risk for HCC. Early intervention could save lives and prevent unnecessary suffering.

    This study underscores the growing public health concern of alcohol-related liver cancer. The newly developed nomogram offers a valuable tool for doctors to identify high-risk individuals and personalize treatment plans, potentially saving lives and preventing unnecessary suffering.

    While the study provides valuable insights, it acknowledges limitations like its retrospective nature and the need for further validation in larger, prospective studies. Additionally, incorporating other factors like smoking, genetics, and dietary habits could further improve the prediction model.

    The researchers also highlight the need for future research on non-alcoholic fatty liver disease and its link to liver cancer, as this area remains under-investigated.

    Overall, this study shines a light on the rising threat of alcohol-related liver cancer and offers a promising tool for early detection and intervention. Further research and public health efforts are crucial to combat this growing health challenge.

    Source:

    First Hospital of Jilin University

    Journal reference:

    Chang, B., et al. (2024). Prevalence and prediction of hepatocellular carcinoma in alcohol-associated liver disease: a retrospective study of 136 571 patients with chronic liver diseases. eGastroenterology. doi.org/10.1136/egastro-2023-100036.

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  • Rising incidence and mortality rate of hepatocellular carcinoma in the USA: A comprehensive analysis

    Rising incidence and mortality rate of hepatocellular carcinoma in the USA: A comprehensive analysis

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    Background and Aim

    Over the past two decades, there has been a significant increase in the incidence of primary liver cancer in the USA, with higher rates observed in men. Its burden increases with age and disproportionately affects men, with mortality rates three times higher in men than in women. The higher incidence in men can be partially attributed to a greater prevalence of risk factors such as alcohol abuse and chronic HBV and HCV infections. A recent study of the Surveillance Epidemiology and End Results (SEER) database showed rising incidence and mortality of liver cancer in the USA from 1975 to 2017. The most notable increase in incidence was observed in men and older adults. Another study found varying mortality rates of HCC across different age-specific populations in recent years. While mortality rates were found to be decreasing in younger individuals, they were increasing in older adults. In addition, liver cancer trends among racial groups showed increasing incidence and mortality rates from 1975 to 2017, with variations across different race groups.

    Given the escalating incidence and mortality of HCC and the observed disparities among age and racial/ethnic groups, analyzing recent trends can aid in identifying high-risk populations, guiding early detection, intervention, and treatment, and ultimately improving patient outcomes. While current literature offers insight into the increasing incidence and mortality rates of HCC, there remains limited data pertaining to recent sex, age, and racial/ethnic group-specific incidence and mortality rates and time trends. This is especially important given the increasing incidence of several gastrointestinal cancers in younger adults, particularly in younger women. Therefore, this study aimed to evaluate recent incidence and mortality rates and time trends of HCC in the USA, focusing on specific sex, age, and race/ethnicity.

    Methods

    Age-adjusted HCC incidence rates were calculated from the Centers for Disease Control’s United States Cancer Statistics database, which combines incidence data on newly diagnosed cancer cases and covers approximately 98% of the population in the USA. Additionally, age-adjusted HCC mortality rates were obtained from the Centers for Disease Control’s National Center for Health Statistics database, which offers comprehensive coverage spanning nearly 100% of deaths attributed to HCC in the USA. Rates were stratified by sex, age (older [≥55 years] and younger [<55 years] adults), race and ethnicity (Non-Hispanic White, Non-Hispanic Black, Hispanic, Non-Hispanic Asian/Pacific Islander, and Non-Hispanic American Indian/Alaska Native), and tumor stage at diagnosis (early and late). Annual and average annual percentage change (AAPC) were calculated using joinpoint regression. A sex-specific pairwise comparison was conducted.

    Results

    Between 2001 and 2020, there were 467,346 patients diagnosed with HCC (26.0% women), with increasing incidence in both sexes without significant difference (p=0.65). In younger adults (78,169 patients), the incidence decreased in men but not in women (AAPC difference=−2.39, p=0.002). This was seen in various racial and ethnic groups, mostly driven by early-stage tumors (AAPC difference=−2.65, p=0.02). There were 329,973 deaths attributed to HCC between 2000 and 2020 (28.4% women). In younger adults (43,093 deaths), mortality decreased in men at a greater rate than in women (AAPC difference=1.61, p=0.007). This was seen in various racial and ethnic groups, most notably in non-Hispanic American Indian/Alaska Natives (AAPC difference=−4.51, p=0.01).

    Conclusions

    In conclusion, our nationwide comprehensive analysis of the USCS database, which covers nearly all patients diagnosed with HCC, shows an increasing incidence of HCC rates between 2001 and 2020. Our analysis of younger adults shows decreasing HCC incidence in younger men but not in women. This trend was seen in various racial/ethnic groups, and was mostly attributed to tumors diagnosed at an early stage. Additionally, our evaluation of the NCHS database, which covers nearly all deaths attributed to HCC in the USA, showed increasing HCC mortality between 2000 and 2020. When evaluating younger adults, HCC mortality rates were found to have improved in men at a greater rate compared to women, and this was notable in various racial/ethnic groups, especially in NHAIAN. The reason for the disparity in incidence and mortality between men and women is unclear and may be attributed to known or yet-to-be-discovered modifiable or non-modifiable risk factors that might have been disproportionately affecting younger women. Future studies are warranted to identify the risk factors associated with the occurrence and outcomes of HCC in different populations, especially in younger women.

    Source:

    Journal reference:

    Abboud, Y., et al. (2024). Hepatocellular Carcinoma Incidence and Mortality in the USA by Sex, Age, and Race: A Nationwide Analysis of Two Decades. Journal of Clinical and Translational Hepatology. doi.org/10.14218/JCTH.2023.00356.

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  • Blood biomarkers in TGF-β pathway identify hidden liver cancer risk

    Blood biomarkers in TGF-β pathway identify hidden liver cancer risk

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    A new research paper was published in Genes & Cancer on February 5, 2023, entitled, “Mechanistically based blood proteomic markers in the TGF-β pathway stratify risk of hepatocellular cancer in patients with cirrhosis.”

    Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer worldwide but is often diagnosed at an advanced incurable stage. Yet, despite the urgent need for blood-based biomarkers for early detection, few studies capture ongoing biology to identify risk-stratifying biomarkers.

    In this new study, researchers Xiyan Xiang, Krishanu Bhowmick, Kirti Shetty, Kazufumi Ohshiro, Xiaochun Yang, Linda L. Wong, Herbert Yu, Patricia S. Latham, Sanjaya K. Satapathy, Christina Brennan, Richard J. Dima, Nyasha Chambwe, Gulru Sharifova, Fellanza Cacaj, Sahara John, James M. Crawford, Hai Huang, Srinivasan Dasarathy, Adrian R. Krainer, Aiwu R. He, Richard L. Amdur, and Lopa Mishra, from The Feinstein Institutes for Medical Research, Cold Spring Harbor Laboratory, University of Maryland, University of Hawaii, University of Hawaii Cancer Center, The George Washington University, North Shore University Hospital, Northwell Health, Hofstra Northwell School of Medicine, Cleveland Clinic, and Georgetown Lombardi Comprehensive Cancer Center, address this gap using the TGF-β pathway because of its biological role in liver disease and cancer, established through rigorous animal models and human studies. 

    “Alterations in the TGF-β signaling pathway could reflect a continuum of fibrosis to cirrhosis to cancer in the liver. Thus, we hypothesize that the TGF-β pathway-enriched biomarkers may serve as biomarkers in the evolution of HCC and stratify patients at risk for HCC. In addition, we hypothesized that the integrated animal model-to-human studies program would yield new TGF-β driven mechanistic biomarkers that could be valuable in yielding additional biomarkers that could stratify the risk of HCC.”

    Using machine learning methods with blood levels of 108 proteomic markers in the TGF-β family, the team found a pattern that differentiates HCC from non-HCC in a cohort of 216 patients with cirrhosis, which they refer to as TGF-β based Protein Markers for Early Detection of HCC (TPEARLE) comprising 31 markers. Notably, 20 of the patients with cirrhosis alone presented an HCC-like pattern, suggesting that they may be a group with as yet undetected HCC or at high risk for developing HCC. 

    In addition, the researchers found two other biologically relevant markers, Myostatin and Pyruvate Kinase M2 (PKM2), which were significantly associated with HCC. They tested these for risk stratification of HCC in multivariable models adjusted for demographic and clinical variables, as well as batch and site. These markers reflect ongoing biology in the liver. 

    “They potentially indicate the presence of HCC early in its evolution and before it is manifest as a detectable lesion, thereby providing a set of markers that may be able to stratify risk for HCC.”

    Source:

    Journal reference:

    Xiang, X., et al. (2024). Mechanistically based blood proteomic markers in the TGF-β pathway stratify risk of hepatocellular cancer in patients with cirrhosis. Genes & Cancer. doi.org/10.18632/genesandcancer.234.

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