Cancer Cases Research Articles

Metformin (The Miracle Drug) Kinetics in Different Diseases such as Cancer

: Metformin, a miracle drug that was introduced a century ago, could be considered for various aspects of diseases such as diabetes (type 1 and 2), cancer prevention or chemotherapy, metabolic and neurodegenerative disease. It is well known that the frequency of cancer is higher in patients with type 2 diabetes mellitus. This review aims to provide updated information regarding clinical pharmacokinetics and the mechanism of action of Metformin in different diseases such as cancer. Diabetes type 1 is another chronic autoimmune disease detected usually in early childhood due to immune-mediated devastation of insulin-producing pancreatic beta-cells. Because of the lack of effective therapeutic approaches, its prevalence is increasing. Regarding cancer, an estimated 19.3 million new cancer cases and almost 10.0 million cancer deaths were reported in 2020 worldwide. By 50-60% bioavailability, the main route of metformin excretion is through urine. Its mechanism of action is based on 1) initiation of adenosine monophosphate-activated kinase, 2) block proinflammatory paths in perivascular adipose tissue, 3) decrease in monocyte-to-macrophage differentiation in vascular tissues, and 4) improvement in endothelial function. Metformin induces adenosine monophosphate-activated protein kinase signaling and suppresses gluconeogenesis. Antitumor properties of Metformin include a decrease in reactive oxygen species generation and inducing autophagy. In addition to glucose-lowering effects, Metformin has moderate anti-inflammatory and antioxidative effects. It could improve lipid profile and reduce overweight individuals' body mass and arterial blood pressure. In type 1 diabetes, Metformin reduces the requirement for daily insulin and improves glycemia. Its long-term use decreases cardiovascular events. In addition to inhibiting the synthesis of lipids via a reduction in oxidative stress, Metformin inhibits inflammation and increases energy metabolism. Finally, by reducing micro- and macro-vascular consequences, mortality-related diabetes and cancer decline by metformin administration. Therefore, in addition to diabetes, Metformin could reduce the proliferation of cancer cells and the possibility of malignancies in different types of cancer.

Evaluation of Cyclin D1 protein and its association with the clinicopathological characteristics and prognosis of lung cancer: A retrospective study from Southern Kerala, India.

Cyclin D1 is a protein that can enhance the proliferation of cancer cells and has been detected in various malignancies, including lung cancer. However, routine examinations for Cyclin D1 in lung cancer cases have not been conducted in Kerala. This study sought to evaluate the links between cyclin D1 expression, clinicopathological characteristics, and 2-year survival rates in lung cancer. This retrospective cohort study used medical records and paraffin blocks of lung cancer patients at the Regional Cancer Centre in Kerala, India, between 2015 and 2018. The data were collected from 61 subjects, comprising of lung adenocarcinoma (18%), lung squamous cell carcinoma (27.9%), non-small-cell lung carcinoma (18%), poorly differentiated carcinoma (19.7%), and negative for malignant cells (16.4%). Data analysis was conducted using SPSS. The study revealed that 31.10% of the lung cancer patients exhibited overexpression of cyclin D1. A significant correlation was observed between cyclin D1 expression and histopathological results (P = 0.002), indicating that the level of cyclin D1 might be linked to specific histopathological subtypes of lung cancer. Despite this significant finding, cyclin D1 expression did not show any association with the clinical stage of the cancer or other clinical characteristics of the patients. Furthermore, when examining the 2-year survival rates of the patients, the study found no significant difference between those who had overexpression of cyclin D1 and those who did not (P = 0.145). Cyclin D1 expression was associated with histology type of lung cancer with no significant association to prognosis.

Skin cancer incidence in Mexican renal transplant recipients: a cohort over 56 years.

Skin cancer is a primary health concern in renal transplant recipients (RTRs). Existing research mainly stems from North America, Europe, and Australia, with limited data from Latin America. This 56-year (1967-2023) retrospective cohort study explores skin cancer incidence in Mexican RTRs. Our objective was to assess the long-term incidence of malignant cutaneous neoplasms in Mexican RTRs. Over 56 years, 1642 RTRs (58% male) were studied. Median follow-up was 8.4 years; median age at transplantation was 32.6 years. Skin cancer incidence was 6.6% (95% CI: 5.5-7.9), with an incidence density rate of 6.5 (95% CI: 5.4-7.9) per 1000 person-years and a median latency of 9.8 years. Incidence increased with longer transplantation-related immunosuppression (TRI), with a relative risk for >30 years of TRI of 4.8 (95% CI: 2.6-9.1) for any skin cancer and 7.5 (95% CI: 3.8-14.6) for squamous cell carcinoma (SCC). SCC was the most common malignancy (76.1%), followed by basal cell carcinomas (BCC), with a 3.6:1 ratio. Metastatic SCC occurred in 6.5% of skin cancer patients, with a skin cancer-related mortality rate of 2.7%. Limitations of the study include its single-center and retrospective design and unassessed factors such as human papillomavirus infection and sun exposure. Our study provides unique insights into the epidemiology of skin cancer among Mexican RTRs. It constitutes the largest cohort of skin cancer cases among RTRs in Mexico and, to our knowledge, in Latin America. Despite the lack of recognition of a high skin cancer incidence in non-White RTRs, our 6.6% incidence underscores the need to enhance surveillance programs.

Bioethical and Medical-Legal Challenges in Multimodal Cancer Treatment: Addressing Misinformation and Informal, Unregistered Advice

This article addresses the bioethical and medico-legal challenges in the multimodal treatment of cancer, emphasizing the growing gap between therapeutic advances and their clinical implementation. Many patients remain uninformed or lack access to advanced therapies, such as immunotherapy or targeted treatments, due to outdated practices in their healthcare centers. This situation often leads to frustration, as patients feel that not all potential treatment options have been explored. The right of patients to receive clear, informed, and transparent guidance on their treatment is highlighted, as well as the necessity for proper documentation of medical decisions to ensure traceability and protect both the patient and the medical professionals involved. The lack of information or bias directly impacts patient autonomy, limiting their ability to make well-founded decisions. The article also highlights the significant benefits of multimodal therapies, such as cytoreductive surgery and personalized immunotherapy, which have been shown to improve outcomes and quality of life in advanced cancer cases. It calls for treating physicians to act as guides or, when necessary, defer to specialized centers with proven expertise, thus avoiding limiting patients to conventional protocols. The need for a multidisciplinary approach is clear, with a committee of clinical oncologists, radiation-oncologists, surgical oncologists, and pathologists, alongside immuno- oncopathology specialists, being essential to the development of personalized, biologically driven therapies. Advances in cancer treatment confirm the importance of this integrated approach, particularly through collaboration between pathologists and clinical oncologists who have specialized in biotechnology and precision medicine.

Correlation of MMP-9 (Matrix Metalloproteinase 9) and SMA (Smooth Muscle Actin) expression with Basal Cell Carcinoma’s risk of recurrence

Basal Cell Carcinoma (BCC) is the most common cancer in many countries, with its incidence steadily rising. Data from the Indonesian Pathologists Association show that among 1,530 skin cancer cases, BCC was the most frequent (39.93%), followed by Squamous Cell Carcinoma (23%) and Malignant Melanoma (7.9%). According to the 2018 WHO classification, BCC is divided into Low-Risk and High-Risk groups based on the risk of recurrence. BCC invades surrounding tissues through extracellular matrix degradation and enhanced cell motility, driven by the expression of MMP-9 (Matrix Metalloproteinase 9) and SMA (Smooth Muscle Actin). This study aims to evaluate the expression of MMP-9 and SMA in BCC using immunohistochemistry and analyze their correlation with the risk of recurrence. A total of 40 paraffin blocks from BCC patients diagnosed between 2019 and 2021 at Dr. Saiful Anwar General Hospital in Malang, Indonesia, were sampled. The blocks were sectioned, stained with MMP-9 and SMA antibodies, and examined for positive expression indicated by brown staining in the cytoplasm of tumor cell and peritumoral stroma. Spearman correlation showed r = 0.811 for MMP-9 and r = 0.857 for SMA (p < 0.05, CI: 95%), indicating a significant relationship between these markers and the risk of recurrence. Higher MMP-9 and SMA expression corresponded to a higher risk of BCC recurrence, suggesting their potential as prognostic biomarkers. However, further research is needed to assess recurrence risk more accurately and determine the most appropriate therapy.

Maximising the potential of National Cancer Mission Hub-like structures: A SWOT analysis approach

Abstract Cancer is a significant and urgent concern in public health, particularly in the context of an aging population like in Europe. It is estimated that new cancer cases will increase by 21% by 2040 in Europe. With the ambition of improving the lives of 3 million people by 2030, the European Commission launched 2 major initiatives: Europe’s Beating Cancer Plan (EBCP) and the Mission on Cancer (MoC). The EBCP is a policy-driven initiative aimed at supporting Member States in addressing the whole cancer continuum. It is supported by the MoC, a research driven initiative. Member States are implementing the EBCP and MoC in a way that fits their national contexts. This can take different forms, such as ‘cancer hub,’ ‘mirror group,’ or other similar structures. The role of these entities can vary, ranging from purely coordinating activities to involving more technical work. We performed a SWOT (Strengths, Weaknesses, Opportunities, and Threats) analysis with different national mission-hub-like (NCMH-like) structures to explore their strategic positioning. We collected results from 6 countries (Belgium, Italy, the Netherlands, Portugal, Poland, and Sweden) as part of the EU project ECHoS on setting NCMHs. Participants perceived that formal government endorsement, existing stakeholder mapping, and good stakeholder engagement as strengths for the structure. Whilst, they identified overlap with other ongoing initiatives and low stakeholder engagement as weaknesses that need to be addressed, the future of existing structures could be threatened by financial and human resources as well changing political landscape. National, regional alignment and the leverage of EU funding were recurrent opportunities to build on. Ultimately, NCMH-like structures can be leveraged to achieve national and European alignment on cancer initiatives, if they succeed in building a sustainable financial and governance structure. Key messages • National Cancer Mission Hub-like structures can build on existing initiatives to support the implementation of EU cancer initiatives if they achieve sustainable financial and governance structures. • SWOT framework is a good tool for a comprehensive overview of the strategic positioning of National Cancer Mission Hub-like structures in different European countries.

Investigation of IDO1 and TDO2 expression in breast tumors by immunohistochemistry and real-time polymerase chain reaction methods

Although diagnostic and therapeutic advances have been made in the treatment of breast cancer, the challenge of effectively controlling tumor progression persists. The objective of this study was to determine the relationship between IDO1 and TDO2 expression in breast cancer by immunohistochemistry and real-time polymerase chain reaction, hormone receptor status, Ki67 proliferation index, molecular classification, metastasis, and to investigate whether IDO1 and TDO2 expression can be used in combination with targeted therapy or as a marker to increase treatment efficacy in selected cases. The study included 74 cases of breast cancer and 14 cases of normal breast tissue as controls. All cases were analyzed for IDO1 and TDO2 by both immunohistochemistry and real-time polymerase chain reaction. The immunohistochemical analysis revealed that IDO1 immunoreactivity was significantly higher in tumor tissue compared to normal breast tissue. A statistically significant correlation was observed between IDO1 immunoreactivity and histologic subtypes. Furthermore, IDO1 gene expression was correlated with IDO1 immunoreactivity. TDO2 immune reactivity did not differ between tumor and non-tumor tissues and no correlation was found between histological subtypes. There was no correlation between TDO2 immunoreactivity and gene expression. The significant increase in IDO1 levels in tumor tissue and high positivity in age, HER2 positive and triple negative cases compared to other cases suggest that IDO1 inhibitors may be suitable for the target patient group in treatment selection.

Case report: Immune checkpoint inhibitor-induced paraneoplastic neurological syndrome in two patients: a case series

Immune checkpoint inhibitors (ICIs) combined with chemotherapy have improved overall survival in patients with small-cell lung cancer, but have also led to an increase in adverse effects. The incidence of ICI-induced paraneoplastic neurological syndrome (PNS) is relatively low when the primary lung lesion is well controlled. However, it is associated with high mortality and disability rates. In this report, we present two cases of extensive-stage small-cell lung cancer with neurological symptoms and positive paraneoplastic antibodies in the serum and cerebrospinal fluid (CSF) following ICI therapy. Although the symptoms improved after treatment with systemic high-dose immunoglobulin and glucocorticoids, one patient, unfortunately, succumbed to tumor progression four months later, whereas the other patient experienced persistent difficulty in standing and walking despite improved muscle strength. In cases where neurological symptoms that cannot be explained by tumor metastases arise during ICI treatment, paraneoplastic syndromes should be considered and testing for antineuronal antibodies is crucial, as early detection and intervention can help mitigate their impact. Further research is needed to develop better predictive strategies and treatment protocols for these adverse reactions.

Characteristics and outcomes of patients with a history of cancer enrolled in our prospective HFpEF registry

Abstract Background Along with the aging population, the incidence of concomitant heart failure with preserved ejection fraction (HFpEF) and cancer, is increasing. However, little is known about the typical characteristics of patients with both HFpEF and a history of oncologic disease. Aim We aimed to characterize the distinctive characteristics and outcomes of patients with a history of cancer within a prospective HFpEF registry. Methods We analyzed data from 491 unselected HFpEF patients from our tertiary university center between 2010 and 2022 and followed the patients until 2023. Laboratory parameters and comorbidities were assessed. Patients were categorized into those with and without a history of cancer, including various malignancies, survivors of childhood cancer, radiation therapy, with or without chemotherapy. Kaplan-Meier estimates were used to explore the association between cancer history, as well as previous radiotherapy, and a combined endpoint of heart failure hospitalization and/or all-cause death. Results In this analysis of 491 HFpEF patients, a total of 101 patients (21%); had a history of cancer [mean age 74±7 years; female 72 (72%), male 29 (29%)]. The median time from cancer diagnosis to the initial HFpEF visit was 7.0 years (IQR 13-0.5 years). The most prevalent primary cancer sites included the chest wall (32%) comprising 4 adenocarcinomas of the lung and 28 cases of breast cancer, followed by the gastric (28%), urogenital system (18%), hematologic and lymphatic system (16%), cancers located at the head and neck (5%) and endocrine malignancies (1%). Radiotherapy (39%) and chemotherapy (26%) were common. Notably, no significant differences were observed, between patients with or without a history of cancer, in terms of median NT-proBNP levels [1037 (IQR 416-2075) vs. 1060 pg/ml (IQR 462-2013)] and the frequency of key cardiovascular comorbidities (all p>0.05, see Table 1). Over the study period [median follow-up 50 months (IQR 18-76)], 64 (64%) of cancer patients met the combined endpoint, with no statistically significant difference in outcomes between HFpEF patients with and without a cancer history (log-rank p=0.222, see Figure 1). Furthermore, there was no significant difference in the combined endpoint between patients who had undergone radiotherapy and those without (log-rank p=0.162). Conclusion Our findings highlight a high coexistence of cancer and HFpEF, which can frequently occur after oncology therapies. The data suggest that the presence of a history of cancer or previous radiotherapy did not significantly impact overall outcomes in HFpEF patients compared to those without cancer during the study period. Further research is needed to characterize patients with both disease entities in detail. Due to modern cardiovascular therapy in a university and cardio-oncology clinic setting, outcomes for cancer patients appear better than expected.

Treatment approaches and survival outcomes in elderly colorectal cancer patients: a single-center comparative study.

Geriatric patients account for nearly half of new colorectal cancer (CRC) cases. This study compares clinicopathological features, treatments, outcomes, and frailty in elderly (≥ 70) and younger (< 70) CRC patients at our center. Patients diagnosed with non-metastatic or de novo metastatic CRC between January 2015 and April 2024 were included. Demographic, pathological, and survival data were retrospectively collected. Analyses were performed using SPSS version 25, with statistical significance set at P < 0.05. Of the 414 non-metastatic CRC patients, 26.6% were aged ≥ 70. Elderly patients received less perioperative chemotherapy (60% vs. 81.6%, P < 0.001) and had more dose reductions (41.6% vs. 19.2%, P < 0.001). Frailty reduced perioperative chemotherapy in elderly non-metastatic patients (54.5% vs. 92.1%, P < 0.001) but did not affect dose reduction (37.9% vs. 33.3%, P = 0.764) or treatment duration (median 24weeks for both groups, P = 0.909). In metastatic patients, frailty shortened chemotherapy duration (9.5 vs. 15.5weeks, P = 0.129). Elderly patients had lower 5- and 8-year overall survival (OS) rates (64.7%, 60.1% vs. 83.0%, 78.8%, P = 0.004). In the de novo metastatic cohort (135 patients), age did not affect OS (19.4 vs. 17.3months, P = 0.590) or PFS (9.8 vs. 7.5months, P = 0.209). Rectal cancer (HR: 2.751, P = 0.005) and early chemotherapy termination (HR: 4.138, P < 0.001) worsened OS in non-metastatic CRC, while absence of RAS (HR: 2.043, P = 0.047), BRAF mutations (HR: 8.263, P = 0.010), and metastasectomy (HR: 3.650, P = 0.036) improved OS in metastatic CRC. Age does not independently worsen CRC survival, though early chemotherapy discontinuation impacts outcomes. Reduced-dose chemotherapy or monotherapy can help minimize adverse effects in elderly patients.

Oncofertility in primary health care: the role of the Portuguese family doctor

Abstract Background The increasing number of cancer cases diagnosed at young ages and the impact of the disease and treatments on reproductive function have led to the development of Oncofertility. While oncologists typically lead these discussions, family doctors, as primary care providers, also play a crucial role. This study aims to assess family doctors’ knowledge, attitudes, and practices regarding fertility preservation in cancer patients. Methods This cross-sectional study, conducted between April 2023 and March 2024, surveyed 351 General and Family Medicine doctors from the Portuguese Northern Regional Health Administration. The questionnaire, consisting of 15 questions, assessed sociodemographic profiles, knowledge, attitudes, and practices. Data were analyzed using descriptive statistics and multivariate logistic regression. Results Most participants were female (80.5%) and under 40 years old. The majority (91.5%) had treated fewer than 10 cancer patients under 40 in the past two years. Key barriers included lack of knowledge (63.3%), time constraints (57.0%), and patient age (18.5%). Male physicians were more likely to address specific fertility concerns (OR 2.239) and less likely to view patient age as a barrier (OR 0.459). Physicians aged 31-35 were less likely to discuss fertility preservation (OR 0.553) but more likely to address it in the first consultation (OR 2.969). Urban-based physicians were less likely to discuss fertility preservation (OR 2.099). Only 9.1% always discussed fertility preservation before treatment, 27.6% did so sometimes, and 63.3% never discussed it. Conclusions There are significant gaps in the knowledge and practices of family doctors regarding fertility preservation for cancer patients. Targeted training and resources are urgently needed to support family doctors in effectively discussing fertility preservation, crucial for improving the quality of life of young cancer patients wishing to preserve their fertility. Key messages • Empowering Portuguese family doctors to address fertility concerns in cancer patients contributes to comprehensive oncofertility care, improving patient outcomes and quality of life. • Integrating oncofertility support with Portuguese family doctors strengthens primary care, ensuring discussion of fertility preservation is considered as part of cancer treatment planning.

The impact of tobacco retailers density reduction on smoking status of Belgian adults

Abstract Background Smoking being one of most impactful risk factors for causing non-communicable diseases (NCD) and consequently attributable death, represents an enormous public health issue. New policy interventions aimed at reducing smoking prevalence are planned in the Belgian Tobacco Free Generation plan. Within the plan, it is aimed to reduce the number of outlets that sell tobacco products, as a higher tobacco retail density (TRD) is believed to be linked to higher smoking prevalence. Using health impact assessment (HIA), this study aims to evaluate the policy before it is set in place. Methods For this intervention a 17% reduction in density was estimated according to the scoping review would be associated with an 0.39 percentage point reduction in prevalence. The Potential Impact Fraction (PIF) was calculated to assess the change in proportion of current smokers. Time series and projections of the Belgium Health Interview Survey provided data on the smoking status from 1997 untill 2040. The relative risk were retrived from the Global Burden of Disease 2021 study. Using data from the Belgian Burden of Disease Study, the avoidable burden was estimated. Results The policy is expected to reduce the density by 17 % by 2025, which results in a PIF for lung cancer of 0.92%, decreasing to 0.82% in 2040. The smoking prevalence would decrease from 12.62% to 12.23%. We estimated that this intervention would avoid the burden of more than 300 lung cancer cases and around 100 deaths in 2040. Conclusions The HIA in this study suggests that reducing TRD has a potential to contribute to achieving the objectives in Tobacco Free Generation plan. However, it should be noted that the impact is rather small, lower than 1% for most diseases. In addition, the actual impact may vary depending on the specific implementation of the policy and future smoking trends. Further research is needed to refine the effect size estimate based on the actual policy intervention details. Key messages • Reducing tobacco retail density can reduce the burden of smoking. • Modeling limitations need further research to refine HIA results.

Referral and disease patterns of patients treated at the Nicosia General Hospital Breast Centre

Abstract Background Cyprus has one of the lowest mortality rates from breast cancer in Europe. The reasons behind this have not been investigated but it is speculated that the ease of access to Breast Centers in combination with an increased public awareness play a role. The aim of this study was to investigate referral and disease presentation patterns of patients treated at the Nicosia General Hospital (NGH) Breast Centre and define opportunities for effective public health interventions. Methods A retrospective study of all patients (585) with in situ or invasive breast cancer treated at the NGH Breast Centre between February 2017 and November 2023 was conducted. Data on referral sources, symptoms, and cancer stage at the time of diagnosis were analyzed using Stata 18. Results Most patients were referrals from the national population screening program (42.2%), followed by self-referrals (40.6%), and General Practitioner (GP)/or other specialist referrals (17.2%). Half of the patients (50.3%) were asymptomatic at diagnosis. In addition, 8% of the patients diagnosed with invasive breast cancer were Stage I, 65% Stage II, and 27% Stage III. Conclusions Our study provides important insights forming the basis of public health activities for the early detection of breast cancer based on the fact that 20% of newly diagnosed breast cancer cases in Cyprus receive treatment in NGH Breast Center. Although adherence to the national population screening program does not meet desired expectations, a significant proportion of breast cancers were detected via this program highlighting its effectiveness in early detection of asymptomatic cancers. A large proportion of patients were self-referred underlining the high degree of breast cancer awareness in Cyprus but also the media-induced anxiety which leads to early investigations. Key messages • Screening program and breast cancer awareness campaigns are effective in detecting breast cancers early. • These activities should be sustained to further reduce breast cancer mortality rate.

Radon Exposure Is Associated with Breast Cancer Risk: A Long-Term Population-Based Study from Finland

Abstract Background Radon is a common environmental carcinogen. It is not known whether radon exposure and breast cancer risk are associated at the population level. Methods Women continuously living in Finland during the 1987-2016 period were linked to municipality-level indoor radon data annually to estimate their cumulative radon exposure over 30 years. Breast cancer incidence was observed over five years from 2017 onwards. Association between radon exposure and breast cancer incidence was assessed using conditional Cox models adjusted for family history of breast cancer, reproductive history, and socio-demographic covariates. Population attributable fractions (PAF) of breast cancer due to radon exposure were estimated. Robustness analyses were conducted in the population who lived only in houses. Results Among 1,335,947 women, 20,067 breast cancer cases were observed during a median follow-up period of 4.9 years. Among women who were exposed to high levels of radon (&amp;gt;100 Bq/m3), overall breast cancer incidence was 10% higher (Hazard ratio 1·10 [95% CI 1·05-1·16]), duct carcinoma incidence was 6% higher (1·06 [1·00-1·13]), lobular carcinoma incidence was 8% higher (1·08 [0·94-1·23]), and the incidence of other morphological sub-types was 34% higher (1·34 [1·17-1·53]) than among other women. Robust associations with overall breast cancer incidence (1·12 [1·05-1·20]) and the incidence of morphological sub-types in the house sample. Correspondingly, suggestive dose-response associations were observed. Conclusions High radon exposure is associated with elevated breast cancer risk at the population level, and this relationship is independent of well-established risk factors. Key messages • This study investigates the association between long-term radon exposure and breast cancer incidence based on national register data. • High radon exposure is robustly associated with breast cancer risk in general Finnish population.

Overdiagnosis of lung cancer in Chinese populations

Abstract Background Low-dose computed tomography (LDCT) has been widely-used in employee health examinations in China since 2011. This study was designed based on the Cancer Surveillance data to quantify the overdiagnosis of lung cancer due to the introduction of LDCT in Chinese populations. Methods This registry-based cohort study included 46,978 incident cases and 34,475 deaths of lung cancer from Pudong New Area of Shanghai, China, during 2002-2020. We calculated the age-standardized rates (ASR) and average annual changes (AAC) of mortality and overall, stage-specific and histological type-specific incidence by sex to evaluate the potential overdiagnosis of lung cancer. We further estimated the numbers and proportions of lung cancer cases attributable to overdiagnosis by sex and period based on the comparison between the shape of the age-specific curves with that prior to the introduction of LDCT in the populations. Results The ASR of incidence of lung cancer increased rapidly since 2011 in both men (AAC: 1.90%; 95%CI: 0.87, 2.92) and women (AAC: 4.40%; 95%CI: 3.19, 5.62), whereas the ASR of mortality declined persistently, with AAC of -0.12% (-0.64, 0.39) in men and -0.19% (-0.47, 0.09) in women. The upward trends in incidence were mainly observed in women, for early-stage cancer and for lung adenocarcinoma. Overall, the overdiagnosis rate of lung cancer grew from 22% in 2011-2015 to 50% in 2016-2020 in women. Further analysis demonstrated elevated numbers (proportions) of lung adenocarcinoma cases attributable to overdiagnosis, which increased from 182 (8%) in 2011-2015 to 827(22%) in 2016-2020 in men, and from 1,842 (85%) to 4,171 (89%) in women. Conclusions This registry-based cohort study observed considerable and increasing overdiagnosis of lung adenocarcinoma in Chinese men and women. Guideline is urgently needed to maximize the benefits of LDCT screening and reduce the potential overdiagnosis of lung cancer in the populations. Key messages • The secular trends in incidence and mortality of lung cancer in Chinese populations demonstrated the overdiagnosis since 2011, when the LDCT was used as a part of staff health examination in China. • Overdiagnosis of lung cancer in Chinese populations increased incrementally over time and was mainly observed among women.

A proteome-wide association study identifies putative causal proteins for breast cancer risk.

Genome-wide association studies (GWAS) have identified more than 200 breast cancer risk-associated genetic loci, yet the causal genes and biological mechanisms for most loci remain elusive. Proteins, as final gene products, are pivotal in cellular function. In this study, we conducted a proteome-wide association study (PWAS) to identify proteins in breast tissue related to breast cancer risk. We profiled the proteome in fresh frozen breast tissue samples from 120 cancer-free European-ancestry women from the Susan G. Komen Tissue Bank (KTB). Protein expression levels were log2-transformed then normalized via quantile and inverse-rank transformations. GWAS data were also generated for these 120 samples. These data were used to build statistical models to predict protein expression levels via cis-genetic variants using the elastic net method. The prediction models were then applied to the GWAS summary statistics data of 133,384 breast cancer cases and 113,789 controls to assess the associations of genetically predicted protein expression levels with breast cancer risk overall and its subtypes using the S-PrediXcan method. A total of 6388 proteins were detected in the normal breast tissue samples from 120 women with a high detection false discovery rate (FDR) p value < 0.01. Among the 5820 proteins detected in more than 80% of participants, prediction models were successfully built for 2060 proteins with R > 0.1 and P < 0.05. Among these 2060 proteins, five proteins were significantly associated with overall breast cancer risk at an FDR p value < 0.1. Among these five proteins, the corresponding genes for proteins COPG1, DCTN3, and DDX6 were located at least 1 Megabase away from the GWAS-identified breast cancer risk variants. COPG1 was associated with an increased risk of breast cancer with a p value of 8.54 × 10-4. Both DCTN3 and DDX6 were associated with a decreased risk of breast cancer with p values of 1.01 × 10-3 and 3.25 × 10-4, respectively. The corresponding genes for the remaining two proteins, LSP1 and DNAJA3, were located in previously GWAS-identified breast cancer risk loci. After adjusting for GWAS-identified risk variants, the association for DNAJA3 was still significant (p value of 9.15 × 10-5 and adjusted p value of 1.94 × 10-4). However, the significance for LSP1 became weaker with a p value of 0.62. Stratification analyses by breast cancer subtypes identified three proteins, SMARCC1, LSP1, and NCKAP1L, associated with luminal A, luminal B, and ER-positive breast cancer. NCKAP1L was located at least 1Mb away from the GWAS-identified breast cancer risk variants. After adjusting for GWAS-identified breast cancer risk variants, the association for protein LSP1 was still significant (adjusted p value of 6.43 × 10-3 for luminal B subtype). We conducted the first breast-tissue-based PWAS and identified seven proteins associated with breast cancer, including five proteins not previously implicated. These findings help improve our understanding of the underlying genetic mechanism of breast cancer development.

Five-year cancer survival rates in Monastir, Tunisia

Abstract Background Cancer is a major public health problem worldwide. To the best of our knowledge, there is no Tunisian population-based registry studies investigating cancer survival in Tunisia. The objectives of our study were to estimate the five-year cancer survival rates in the province of Monastir, Tunisia. Methods We performed a retrospective cohort study including patients originating from Monastir diagnosed with cancer between 2002 and 2014. Data were collected from the cancer register of the center. Patients were followed until December 2022. Results In total, 9318 cancer cases were identified of whom 5741 were included for the survival analysis. The 5-year cancer survival rate, all sites combined, was 46% (95% CI: 45-47.3). Among the 10 most frequent cancer sites in Monastir, cancers having the lowest 5-year survival rates were lung cancer in men (18.2% (95% CI: 15.6-20.7)) and stomach cancer in both sexes (32.1% (95% CI: 23.4-40.7) and 25.3% (95% CI: 16-34.5) in men and women respectively). The cancers with the highest 5-year survival rates among men were skin cancer (other than malignant melanoma) (64% (95% CI: 54.5-73.4)), prostate cancer (59.1% (95% CI:54.7-63.4)) and colon cancer (55.1% (95% CI: 47.7-62.4). In women, cervical cancer (70% (95% CI: 61.8-78.1), skin cancer (other than malignant melanoma) (66.2% (95% CI: 55.1-77.2) and breast cancer (63.8% (95% CI:58.8-67.7)) were those with the highest 5-year survival rates. Patients ≥ 65 years had the lowest 5-year survival rates for almost all cancer sites in both genders. Conclusions Our study has shown that cancer survival rates in Tunisia remain low compared to developed countries. The widespread implementation of cancer control programs including healthy lifestyle, education, screening and early detection are urgently needed. Key messages • The 5-year cancer survival rate, all sites combined, in Monastir was 46% (95% CI: 45-47.3). • Cancers with the lowest 5-year survival rates in Monastir were lung cancer in men and stomach cancer in both sexes.

Bias in Evaluating Trends of Thyroid Cancer Incidence between Rural and Urban Populations

Abstract Background Diagnosis of thyroid cancer is based on fine needle aspiration cytology of thyroid nodules, based on nodules’ sonographic appearance and size. The American Thyroid Association published new guidelines for management of thyroid nodules in 2009 and 2015, where in some cases, only follow-up of thyroid nodules without any other procedure is recommended. This may lead to a decrease in diagnosed thyroid cancer cases. We studied thyroid cancer trends in Israel between the Arab population who are more likely to be living in rural areas, and the Jewish population who predominantly living in urban areas, and assesses whether these guidelines were reflected in the trends. Methods Data on new thyroid cancer cases were retrieved for Jews and Arabs separately from the Israel National Cancer Registry. Trends in age standardized incidence rates between 1996-2019 were evaluated for the two population groups using joinpoint regression model. Population group was included in the regression models to compare the trends between the two groups. We also studied trends in treatment of thyroid cancer at Rambam Health Care Campus. Results In both populations, age standardized thyroid cancer incidence rate increased between 1996 and 2013. However, between 2013-2019, Annual Percentage Change continuously increased in Arabs, but decreased in Jews. In the hospital study, we found that the Arab patients were 30% more likely to have surgery for small tumors. Conclusions The decrease in thyroid cancer incidence in the Jewish population compared with the Arab population may be related to differences in implementing the 2009 guidelines, which do not recommend fine needle aspiration cytology for very small tumors. We have found evidence that these guidelines were not followed to the same extent among Arab community clinics. This may explain the persisting increasing trend among Arabs, and could be one of the possible explanations for the differences in trends between the two groups. Key messages • Updated Guidelines regarding thyroid cancer diagnosis may be differently implemented by rural and urban populations. • Trends assessment may be biased due to differences in guidelines implementation.

Developing an Evidence-Based Primary Cancer Prevention Repository: insights from the PIECES project

Abstract Introduction Up to 40% of cancer cases could be avoided through effective primary prevention. However, cancer prevention tends to be fragmented across Europe, leading to geographical health differences. The dissemination and scale-up of effective primary cancer prevention interventions may address this. Although effective cancer prevention programs exist, finding them and their materials (especially regarding implementation) can be challenging. Repositories of evidence-based interventions provide insight into “what is out there” and can support dissemination within and across national borders. The PIECES project aims to develop and disseminate a repository of evidence-based primary cancer prevention programs adaptable to European contexts, with information to aid adaptation and implementation across countries. Methods The development of the PIECES repository has been informed by established repositories such as NCI’s Evidence-Based Cancer Control Programs. The project team developed a scoring sheet with a selection of items that could be included in the repository. All participants rated each item on relevance and applicability and provided comments and suggestions. A final framework, including a set of minimal requirement items, was agreed upon during three online consensus building meetings. Results We created a repository of evidence-based primary cancer prevention interventions targeting modifiable risk factors suitable for implementation in European healthcare settings. This 22-item repository provides information about an intervention’s logic model, implementation practices, and appraisal of published evidence of effectiveness. Conclusions This repository is innovative as it includes practical information and tools to facilitate implementation. While initially built to serve the PIECES project, the repository is designed to be a valuable tool for European policymakers, researchers, and implementers. Lessons learned from this process will inform future developers. Key messages • A comprehensive cancer prevention intervention repository avoids “reinventing the wheel” and allows for more efficient use of existing interventions by building upon the best available evidence. • The ongoing efforts of the PIECES project represent a significant contribution to reduce cancer prevention disparities and to facilitate the adoption of evidence-based interventions in Europe.

The association between body mass index and vulvar and vaginal cancer incidence: findings from a large Norwegian cohort study.

There is limited evidence of potential associations between body mass index (BMI) and risk of vulvar and vaginal cancer. We explored these associations in a large cohort of Norwegian women. The analytical dataset included 889,441 women aged 16-75years at baseline in 1963-1975. Multivariable Cox regression analyses were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between BMI and vulvar and vaginal cancer incidence. During 30.1 million person-years of follow-up, 1748 incident vulvar and 408 incident vaginal cancer cases occurred. The HRs (95% CIs) for vulvar cancer for a BMI of 15- < 18.5, 18.5- < 25, 25- < 30, 30- < 35, ≥ 35 were 0.62 (0.38-1.01), 1.00 (reference), 1.23 (1.10-1.40), 1.43 (1.23-1.66) and 1.72 (1.35-2.20, ptrend < 0.001), and per 5kg/m2 increment was 1.20 (1.13-1.26). The corresponding HRs (95% CIs) for vaginal cancer were 1.05 (0.52-2.15), 1.00, 0.89 (0.71-1.12), 0.95 (0.68-1.34), and 2.01 (1.29-3.13, ptrend < 0.001), respectively, and per 5kg/m2 was 1.11 (0.99-1.25). The HR (95% CI) per 5kg/m2 increase in BMI at ages 16-29 was 1.28 (1.07-1.54, n = 250 cases) for vulvar and 1.53 (1.11-2.11, n = 66 cases) for vaginal cancers. The HR (95% CI) per 5kg/m2 for early-onset (< 50years age at diagnosis) vulvar cancer was 0.92 (0.66-1.28, n = 87 cases) and 1.70 (1.05-2.76, n = 21 cases) for vaginal cancer. These results further support the associations between higher BMI and increased risk of vulvar and vaginal cancers, with suggestive stronger associations between BMI in early adulthood for both cancers and for early-onset vaginal cancer. Further studies are needed to elucidate these findings and investigate the underlying mechanisms.