Male Cancer Research Articles

Real-World Data-Derived Pharmacovigilance on Drug-Induced Cognitive Impairment Utilizing a Nationwide Spontaneous Adverse Reporting System.

Background and Objectives: Despite high incidences of cognitive impairment with aging, evidence on the prevalence and the seriousness of drug-induced cognitive impairment is limited. This study aims to evaluate the prevalence and the severity of drug-induced cognitive impairment and to investigate the clinical predictors of increased hospitalization risk from serious drug-induced cognitive impairment. Materials and Methods: Adverse drug events (ADEs) regarding drug-induced cognitive impairment reported to the Korean Adverse Event Reporting System Database (KAERS DB) from January 2012 to December 2021 were included (KIDS KAERS DB 2212A0073). The association between the etiologic classes and the reporting serious adverse events (SAEs) was evaluated using disproportionality analysis, and the effect was estimated with reporting odds ratio (ROR). Clinical predictors associated with increased risk of hospitalization from SAEs were identified via multivariate logistic analysis, and the effect was estimated with odds ratio (OR). Results: The most etiologic medication class for drug-induced cognitive impairment ADEs was analgesics, followed by sedative-hypnotics. Anticancer (ROR 57.105, 95% CI 15.174-214.909) and anti-Parkinson agents (ROR 4.057, 95% CI 1.121-14.688) were more likely to report serious drug-induced cognitive impairments. Male sex (OR 19.540, 95% CI 2.440-156.647) and cancer diagnosis (OR 18.115, 95% CI 3.246-101.101) are the major clinical predictors for increased risk of hospitalizations due to serious drug-induced cognitive impairment. Conclusions: This study highlights the significant prevalence and severity of drug-induced cognitive impairment with cancer diagnosis and anticancer agents. However, further large-scaled studies are required because of the potential underreporting of drug-induced cognitive impairments in real practice settings, which is further contributed to by the complexity of multiple contributing factors such as comorbidities.

Antiproliferative, apoptotic and anti-inflammatory potential of 5H-benzo[h]thiazolo[2,3-b]quinazoline analogues: Novel series of anticancer compounds

Lung cancer (LC) is the most common cancer in males. As per GLOBOCAN 2020, 8.1 % of deaths and 5.9 % of cases of LC were reported in India. Our laboratory has previously reported the significant anticancer potential of 5H-benzo[h]thiazolo[2,3-b]quinazoline analogues. In this study, we have explored the anticancer potential of 7A {4-(6,7-dihydro-5H-benzo[h]thiazolo[2,3-b]quinazolin-7-yl)phenol} and 9A {7-(4-chlorophenyl)-9-methyl-6,7-dihydro-5H-benzo[h]thiazolo[2,3-b]quinazoline}by using in-vitro and in-vivo models of LC. In this study, we investigated the antiproliferative potential of quinazoline analogues using A549 cell line to identify the best compound of the series. The in-vitro and molecular docking studies revealed 7A and 9A compounds as potential analogues. We also performed acute toxicity study to determine the dose. After that, in-vivo studies using urethane-induced LC in male albino Wistar rats carried out further physiological, biochemical, and morphological evaluation (SEM and H&E) of the lung tissue. We have also evaluated the antioxidant level, inflammatory, and apoptotic marker expressions. 7A and 9A did not demonstrate any signs of acute toxicity. Animals treated with urethane showed a significant upregulation of oxidative stress. However, treatment with 7A and 9A restored antioxidant markers near-normal levels. SEM and H&E staining of the lung tissue demonstrated recovered architecture after treatment with 7A and 9A. Both analogues significantly restore inflammatory markers to normal level and upregulate the intrinsic apoptosis protein expression in the lung tissue. These experimental findings demonstrated the antiproliferative potential of the synthetic analogues 7A and 9A, potentially due to their anti-inflammatory and apoptotic properties.

Case-control study: Unveiling human polyomaviruses and papillomavirus in Egyptian colorectal cancer patients.

Colorectal cancer (CRC) is a cancer type that is thought to be influenced by human papillomaviruses (HPVs) and human polyomaviruses (HPyVs). In Egypt, CRC ranks as the 7th most common cancer, accounting for 3.47% of male cancers and 3% of female cancers. However, there is currently a lack of information regarding the presence of PyVs and HPVs co-infection specifically in CRC cases in Egypt. Therefore, the aim of this study was to investigate the occurrence of HPVs and HPyVs (JCPyV, BKPyV, and SV40) infections, as well as co-infections, among CRC patients in Egypt. Additionally, the study aimed to assess any potential association between these viral infections and tumor stages. In the present study, we analyzed a total of 51 tissue samples obtained from Egyptian CRC patients, along with 19 polyps' samples. Our investigation focused on the detection and genotyping of HPyVs using Real-Time PCR. Additionally, we employed real-time PCR for the detection of HPVs, and for their genotyping, we utilized a combination of PCR amplification followed by sequencing. In our study, we found evidence of HPyVs infection in the CRC patients, specifically SV40 (25.5%) and BKPyV (19.6%). However, JCPyV was not detected in the samples that were examined. Additionally, we discovered that HPV was present in 43.1% of the CRC patients. When considering viral co-infections, 19.6% of the CRC samples showed coexistence of multiple viruses, while no co-infections were found in the polyps samples. Importantly, we observed a significant correlation between the presence of HPVs and advanced colorectal tumor grades B2 and D. Our findings provide valuable data for the detection of oncogenic viruses in colorectal cancer (CRC) and underscore the association of viral co-infections with advanced tumor stages. However, further research with larger cohorts is necessary to validate these findings and strengthen their significance in the field of CRC.

Relative risk of second malignant neoplasms highest among young adult cancer patients - a population-based registry study in Finland.

The objective of this study was to explore the incidence of second malignant neoplasms (SMNs) among adult cancer patients in Finland diagnosed with their first primary cancer (FPC) in 1992-2021. The study used data from the population-based Finnish Cancer Registry (FCR). Risk estimates were calculated using the standardised incidence ratio (SIR), the ratio of observed second cancers compared to the expected numbers assuming the same cancer incidence as the corresponding sex-age-calendar year -split of the general population. A total of 573,379 FPCs were diagnosed during 1992-2021. During the follow-up, 60,464 SMNs were diagnosed. Male cancer patients had neither a decreased nor an increased risk (SIR 1.00 [95% CI, 0.99-1.01]) and female patients had an 8% increased risk (SIR 1.08 [95% CI, 1.06-1.09]) of developing any SMN compared to a FPC in the general population. The highest SIR of any SMN was observed in patients aged 20-39 -years at FPC diagnosis, and the SIR decreased by increasing age at diagnosis. Patients with lymphoid and haematopoietic tissue neoplasms, cancers of the mouth and pharynx, endocrine glands, respiratory and intrathoracic organs, skin, and urinary organs had the highest SIRs, while patients with cancers of the male genital organs and the female breast had the lowest SIRs. Elevated SIRs were observed in cancer patients diagnosed at an early age and for FPCs known to be in large part attributable to lifestyle factors, which highlights the importance of monitoring and encouraging lifestyle changes.

Association of ankylosing spondylitis with the risk of cancer: a meta- analysis of cohort studies.

The potential impact of ankylosing spondylitis (AS) on cancer risk remains unclear. This study seeks to investigate the relationship between AS and different types of cancers. A literature search of the PubMed, Embase and Cochrane Library up to July 10th, 2023, was conducted. Two investigators selected eligible studies and extracted relevant data. The study used the random-effects model to explore the causality between AS and cancer, utilising relative risk (RR) as a measure for the study. A total of 20 cohorts with >330 000 participants were included. The pooling analysis shows AS being associated with a higher risk of cancers (RR = 1.16, 95% CI : 1.07-1.26, p= 0.001, I2=70.60%). In the subgroup analysis, AS has a higher cancer risk in Asia, but this association is not significant in Europe. Individual investigations indicate that AS is associated with an increased risk of bone cancer (RR = 3.41, 95% CI : 1.45-7.99, p= 0.005, I2=0.00%), thyroid gland cancer (RR = 1.76, 95% CI : 1.29-2.40, p< 0.001, I2=13.70%), multiple myeloma (RR = 1.74, 95% CI : 1.42-2.15, p< 0.001, I2=27.20%), leukaemia (RR = 1.52, 95% CI : 1.27-1.82, p< 0.001, I2=0.00%), kidney cancer (RR = 1.45, 95% CI : 1.08-1.94, p= 0.014, I2=0.00%), prostate cancer (RR = 1.43, 95% CI : 1.17-1.74, p< 0.001, I2=82.80%), and non-Hodgkin's lymphoma (RR = 1.42, 95% CI : 1.17-1.73, p< 0.001, I2=0.00%). However, there is no significant correlation with connective tissue cancer, brain cancer, testicular and other male cancers, bladder cancer, female cancers, skin cancer, and cancers of the digestive system and respiratory system. AS appears to be related to cancer development. The results highlighted the necessity for large-scale studies, considering influencing factors such as AS course, medication histories, and potential biases when examining cancer risk.

Decreasing incidence and mortality of lung cancer in Hungary between 2011 and 2021 revealed by robust estimates reconciling multiple data sources.

Hungary has repeatedly been shown to have the highest cancer-related mortality and incidence in Europe. Despite lung cancer being the most abundant malignant diagnosis in Hungary, numerous concerns have been raised recently regarding the bias inherent to reported incidence estimates. Re-analysis of reimbursement claims has been suggested previously by our group as an alternative approach, offering revised figures of lung cancer incidence between 2011 and 2016. Leveraging on this methodology, we aimed at updating Hungarian lung cancer incidence estimates with an additional 5years (2017-2021), including years affected by the COVID-19 pandemic. Additionally, we also attempted to improve the robustness of estimates by taking additional characteristics of the patient pathway into account. Lung cancer patients between 2011 and 2021 were identified based on reimbursement-associated ICD-10 codes, histology codes and time patterns. Multiple query architectures were tested for sensitivity and compared to official estimates of the Hungarian National Cancer Registry (HNCR). Epidemiological trends were estimated by Poisson-regression, corrected for age and sex. A total of 89,948 lung cancer patients diagnosed in Hungary between 2011 and 2021 have been identified by our study. In 2019 alone, 7,887 patients were diagnosed according to our optimized query. ESP2013 standardized rate was estimated between 92.5/100,000 (2011) and 78.4/100,000 (2019). In 2019, standardized incidence was 106.8/100,000 for men and 59.7/100,000 for women. Up until the COVID-19 pandemic, lung cancer incidence was decreasing by 3.18% (2.1%-4.3%) yearly in men, while there was no significant decrease in women. Young age groups (40-49 and 50-59) featured the largest improvement, but women aged 60-79 are at an increasing risk for developing lung cancer. The COVID-19 pandemic resulted in a statistically significant decrease in lung cancer incidence, especially in the 50-59 age group (both sexes). Our results show that using an optimized approach, re-analysis of reimbursement claims yields robust estimates of lung cancer incidence. According to this approach, the incidence rate of male lung cancer is declining in Hungary, in concordance with the trend observed for lung cancer mortality. Among women aged 60-79, the incidence of lung cancer has risen, requiring more attention in the near future.

A nomogram to predict the absence of clinically significant prostate cancer in males with negative MRI

To create a nomogram to predict the absence of clinically significant prostate cancer (CSPCa) in males with non-suspicion multiparametric magnetic resonance imaging (mpMRI) undergoing prostate biopsy (PBx). We identified consecutive patients who underwent 3T mpMRI followed by PBx for suspicion of PCa or surveillance follow-up. All patients had Prostate Imaging Reporting and Data System score 1-2 (negative mpMRI). CSPCa was defined as Grade Group ≥2. Multivariate logistic regression analysis was performed via backward elimination. Discrimination was evaluated with area under the receiver operating characteristic (AUROC). Internal validation with 1,000x bootstrapping for estimating the optimism corrected AUROC. Total 327 patients met inclusion criteria. The median (IQR) age and PSA density (PSAD) were 64 years (58-70) and 0.10 ng/mL2 (0.07-0.15), respectively. Biopsy history was as follows: 117 (36%) males were PBx-naive, 130 (40%) had previous negative PBx and 80 (24%) had previous positive PBx. The majority were White (65%); 6% of males self-reported Black. Overall, 44 (13%) patients were diagnosed with CSPCa on PBx. Black race, history of previous negative PBx and PSAD ≥0.15ng/mL2 were independent predictors for CSPCa on PBx and were included in the nomogram. The AUROC of the nomogram was 0.78 and the optimism corrected AUROC was 0.75. Our nomogram facilitates evaluating individual probability of CSPCa on PBx in males with PIRADS 1-2 mpMRI and may be used to identify those in whom PBx may be safely avoided. Black males have increased risk of CSPCa on PBx, even in the setting of PIRADS 1-2 mpMRI.

Immune checkpoint inhibitor-related reproductive adverse effects: A pharmacovigilance analysis based on the FAERS database.

e14707 Background: There exists a critical need to systematically understand the extent and magnitude of immune checkpoint inhibitor (ICI)-related reproductive adverse effects, which may not only pose long-term implications for patients who may desire future fertility, but also impact the quality of life. We aim to better understand this underexplored area. Methods: Our focus was on ICIs approved by the FDA as of June 31, 2023, including anti-PD-1 agents (nivolumab, pembrolizumab, cemiplimab, dostarlimab, retifanlimab), anti-PD-L1 agents (atezolizumab, avelumab, durvalumab), anti-CTLA-4 agents (ipilimumab, tremelimumab), and an anti-LAG-3 agent (relatlimab). We analyzed 13,702,373 cases from January 1, 2015, to June 30, 2023. We included adverse reactions under the 'Reproductive system and breast disorders' category in the SOC (System Organ Classes). For signal detection, we used the reporting odds ratio (ROR) method. Results: We identified 133,512 patients administered with ICIs, among whom 568 reported irRAEs. Abnormal spermatogenesis (ROR025: 7.91), scrotal irritation (ROR025: 3.83), scrotal oedema (ROR025: 1.90), perineal rash (ROR025: 1.38), prostatitis (ROR025: 1.25), acquired phimosis (ROR025: 1.20), and scrotal erythema (ROR025: 1.08) in males and genital tract fistula in females (ROR025: 2.72) were detected as significant irRAEs. Among them, the most commonly reported irRAEs were prostatitis (n=29), scrotal oedema (n=12), and abnormal spermatogenesis (n=6) in males and genital tract fistula (n=34) in females. Male patients had a lower risk compared to females (OR=0.68 [0.57-0.81], p&lt;0.0001). There was no marked difference between the patients on polytherapy vs. monotherapy (OR=0.90 [0.71-1.13], p=0.36). PD-1 inhibitors pose the greatest risk when compared with CTLA-4 inhibitors (OR=1.65 [1.05-2.79], p=0.045). Gynecologic cancers in females (OR=3.77 [2.82-4.99], p&lt;0.0001) and urogenital cancers in males (OR=1.56 [1.17-2.06], p=0.0018) were strong risk factors. Additional targeted therapy, particularly lenvatinib (OR=3.79 [2.71-5.15], p&lt;0.0001) and cabozantinib (OR=2.69 [1.66-4.09], p&lt;0.0001) significantly increased the risk (OR=1.87 [1.52-2.29], p&lt;0.0001) and this risk appeared to be more pronounced in females (OR=2.32 [1.76-3.02], p&lt;0.0001). Additional chemotherapy was associated with a significantly reduced risk in males (OR=0.65 [0.42-0.96], p=0.042). However, doxorubicin (OR=2.58 [1.10-5.05], p=0.013) and cyclophosphamide (OR=2.36 [0.93-4.83], p=0.038) were linked to an elevated risk. Conclusions: Our findings demonstrated that ICIs could lead to a wide range of irRAEs in both males and females. Additional therapies could change the risk of irRAEs. Despite the current lack of high-quality clinical data on this topic, it is reasonable to inform patients about the plausible risk of irRAEs.

A Glimpse into the Epidemiology of Geriatric Cancers in India: Report from the Indian Population Based Cancer Registries.

Indian population is aging and the cancer rates are rising. Older adults (OAs)(≥60 years) with cancer require specialized care. However, data on geriatric cancer epidemiology is scarce. The study compiled the geriatric cancer data from the published reports(2012-2014) of Indian population-based cancer registries(PBCRs). Of the 1,61,363 cancers registered in the Indian PBCRs, 72,446(44.9%) occur in OAs, with 21,805(30.1%), 18,349(25.3%), 14,645(20.2%), and 17,647(24.4%) occurring in 60-64, 65-69, 70-74, and ≥75year age groups. The truncated incidence rates for OAs are 555.9,404.5, and 481.9 for males, females, and OA populations respectively. The common cancers are lung, prostate, and esophagus cancers in males, breast, cervix, and lung in females. The overall common cancers are lung, prostate, and breast. While >50% of the incident cases of prostate, and bladder cancers occurred in OAs, <20% of Hodgkin lymphoma and thyroid cancers occurred in OAs. OA cancer epidemiology has a regional variation, highest in South India and lowest in Western India. The current study quantifies the cancer burden in the Indian geriatric population. Understanding the epidemiology of geriatric cancers is vital to health program planning and implementation. Increased awareness, focused resource allocation, research, and national policies for streamlining care will all help to improve geriatric cancer outcomes.

Temporal trends of cancer incidence rates for the most frequent cancer sites in Cyprus (2004-2017).

Cancer is one of the leading causes of morbidity and mortality, worldwide. Little information is available for the temporal trends of cancer in the Mediterranean region, including Cyprus. We aimed to analyze cancer incidence trends overall and by sex for the period 2004-2017 regarding the five most common cancer sites for the population of Cyprus. Data were obtained from the nationwide cancer registry dataset that included 27 017 total cancer cases in Cyprus (2004-2017). We estimated the crude, sex-, and age-specific, as well as age-standardized (ASR) cancer incidence rates and we analyzed the time trends of ASR using the joinpoint regression program. For the general population (0-85+ years of age), the most common cancer sites in descending order, were breast, prostate, lung, colorectal, and thyroid cancer. During the study period, breast and thyroid cancer ASR presented a significant (p < .05) increasing temporal trend. Lung cancer ASRs seemed to stabilize (no increase or decrease) during the more recent years (2009 onwards) for both sexes; a similar pattern was observed for colorectal cancer in males. The ASRs of prostate cancer in men were in steady decline from 2012 onwards and the same was observed for the female ASRs of colorectal cancer from 2007 onwards. The colorectal cancer ASR temporal patterns overall, during the whole study period appeared unchanged. This temporal analysis would feed into cancer surveillance and control programs that focus on prevention, early detection, and treatment, particularly for cancer sites of higher mortality rates or those with temporally increasing trends.

Outcomes of colorectal cancer hospitalization with and without coexisting nutritional anemia: A National Inpatient Sample (NIS) 2016 to 2019 database study.

e15648 Background: Colorectal carcinoma (CRC) is third most commonly diagnosed cancer in males and second in females. Implications of CRC with coexisting anemia and its outcomes of hospitalization have not been studied. We aim to evaluate the outcomes of CRC hospitalization with and without coexisting nutritional anemia. Methods: A total of 504,515 patients (male: 52.61%, female: 47.39%), aged ≥18 years, admitted from 2016 to 2019 with principal admission diagnosis of CRC were identified using International Classification of Disease 10 (ICD-10) coding for NIS database. Patients were stratified into those with and without nutritional anemia (16.19% vs 83.81%) which included iron, B12, folate deficiency and other nutritional anemia per ICD-10 coding. Mortality was the primary outcome of the study whereas length of stay (LOS), total treatment cost, acute kidney injury (AKI), pulmonary embolism (PE), deep vein thrombosis (DVT), colonoscopy, abdominal surgery and lower gastrointestinal (GI) bleeding were secondary outcomes. Multivariate regression model was used to estimate the outcomes of CRC hospitalization with and without coexisting nutritional anemia after adjusting for confounders like age, sex, race, insurance provider, co-morbidities, median income, hospital region, location, etc. Results: Mean age of patients admitted with CRC with and without anemia was 69.06 and 65.77 years respectively. Among two groups, mortality was significantly lower among patients with nutritional anemia (2.05 % vs 2.64 %). Lower GI bleeding (12.24% vs 4.77%) and colonoscopy during inpatient stay (43.97% vs 23.05%) were significantly higher among CRC cohort with nutritional anemia. Similarly, LOS, cost of inpatient hospitalization, AKI, PE and DVT were also significantly higher among anemia cohort. However, the need for abdominal surgery was significantly higher among CRC patients without nutritional anemia. Table 1 summarizes the results of multivariate regression analysis. Conclusions: Nutritional anemia in CRC patients is associated with longer length of stay, increased cost, higher risk of developing venous thrombosis along with lower GI bleed and colonoscopy. Therefore, it should be corrected to optimize outcomes among CRC patients. [Table: see text]

Racial and gender disparities in the incidence of bladder cancer: A nationwide analysis.

e16623 Background: Several studies have been conducted to examine racial and gender disparities in various common malignancies. However, there remains a notable lack of comprehensive data addressing ethnic and gender disparities, specifically in relation to patients with Bladder cancer. This study sought to evaluate these disparities and their potential impact on the risk of developing bladder cancer. Methods: Using the National Inpatient Sample 2020, we identified patients diagnosed with Bladder cancer as their primary condition (local/regional and advanced metastatic).We analyzed disparities in the baseline characteristics, including age, gender, insurance status, income, comorbidities, and the risk associated with Bladder cancer. We utilized a log Binomial regression model to determine the risk ratios after adjusting for any confounding variables. Results: A total of 6,471,165 patients were analyzed, and it was found that 24,400 of them (0.4%) had bladder cancer. Among these patients, 76% were male, and 23% were female, p&lt;0.001.The mean age of patients with and without Bladder cancer was 72(SD +/- 11.39) vs. 49(SD+/- 27.18) years, respectively, p&lt;0.001. Female patients demonstrated a lower risk of developing bladder cancer than males (RR=0.31(0.24-0.27); p&lt;0.001). Compared to white females, white and black males exhibited an increased risk of bladder cancer (RR=3.45(3.20-3.73); p&lt;0.001 and RR=1.71(1.48-1.98); p&lt;0.001, respectively). Hispanic males also showed an increased risk (RR=2.20(1.88-2.58); p&lt;0.001), while Hispanic females demonstrated a decreased risk (RR=0.72(0.56-0.94); p=0.016). Males of other races had a higher risk of bladder cancer (RR=2.95(2.36-3.70); p&lt;0.001), and no significant difference was observed in the risk of bladder cancer in Asian males and females (RR=1.39(0.66-2.92); p=0.384 and RR=0.83(0.34-2.01); p=0.694, respectively). The risk of bladder cancer increased with age (36-45: RR=4.45(2.21-8.96),p&lt;0.001,46-64: RR=10.94(5.67-21.12),p&lt;0.001, &gt;65: RR =21.02(10.87-40.63), p&lt;0.001). Conclusions: Disparities in healthcare access and understanding of specific challenges faced by high-risk groups deeply impact patients with bladder cancer. Gaining a deeper knowledge of these disparities can better support this vulnerable patient population and illuminate effective preventive measures for reducing the incidence of bladder cancer among high-risk demographic segments.

Clinical characteristics and treatment outcomes of advanced penile squamous cell carcinoma: Real-world evidence from a tertiary cancer center in Brazil.

e17025 Background: Penile cancer is a rare disease worldwide. However, Brazil has an annual incidence of 1.5 cases per 100,000 inhabitants, representing 2% of male cancers. This study aims to evaluate clinical characteristics and treatment outcomes of patients (pts) with advanced penile squamous cell carcinoma (SCC) in a large tertiary cancer center in Brazil. Methods: We performed a retrospective database analysis of pts with advanced penile squamous cell carcinoma (SCC) treated at Instituto do Cancer do Estado de Sao Paulo between January 2008 and October 2023. Medical records were reviewed for demographic, clinicopathological features and treatment outcomes data. Cumulative survival probabilities were computed using the Kaplan-Meier method. Prognostic factors associated with survival were evaluated through univariate analyses, using the Cox regression model. Results: We identified 91 pts with advanced penile SCC eligible for analysis. Median age was 62 years (IQR 44.5-64.5), most were married (53.8%), diagnosed with stage T3/T4 (60.4%), and N2/N3 (64.9%) SCC. At diagnosis, 65% were classified as stage IV (T4, N3, or M1 disease). De novo metastasis occurred in 35% pts. Neoadjuvant chemotherapy was given to 30.8%, mainly ITP regimen containing paclitaxel, ifosfamide, and cisplatin (46.4%). First-line palliative chemotherapy was given to 50.5%, being carboplatin and paclitaxel the predominant choice (47.8%). Disease progression occurred in 54% pts, after a median follow-up of 21.8 months. At the last follow-up, 61.5% had nodal disease. Most common sites of metastasis were lung (50.5%) and liver (19.8%). Overall survival (OS) was 12.9 months (95% CI 9.8 - 18.3). Prognostic factors significantly correlated with OS were ECOG 0-1 (HR 0.40, 95% CI 0.21 - 0.74, p=0.003) and complete response post-chemotherapy (HR 0.14; 95% CI 0.02 - 0.80, p=0.02). No association with survival was found for region/state of origin, distance from patient’s home to the hospital, marital status, education level, and age. Conclusions: Advanced penile squamous cell carcinoma (SCC) presents significant challenges in Brazil, with high rates of advanced disease at diagnosis. OS correlated with complete response to chemotherapy and performance status.

Sociodemographic differences in suicide/intentional self-harm among cancer survivors versus the general United States population.

11097 Background: Suicide is a national public health crisis, and one of the leading causes of death in the United States. Worse yet, the suicide mortality rate is at least double among cancer survivors compared to the general population. Suicide rates vary across the population, but it is unclear how sociodemographic factors explain differences in suicide rates among cancer survivors versus the general United States population. Methods: We analyzed two sets of population-based data. First, we retrieved suicide/self-harm mortality rates for the general population from the National Vital Statistics System. Next, we accessed cancer case data from the Surveillance, Epidemiology, End Results (SEER) program to estimate number of deaths due to suicide/self-harm among cancer patients, per 100,000 persons, with a 95% confidence interval. All analyses were restricted to contiguous states with full state representation in SEER (CA, CT, GA, ID, IA, KY, LA, NJ, NM, NY, TX, UT). We then compared subgroup differences by sex, race/ethnicity, age, and state. Results: In 2020, there were 15,813 deaths in the general population (12.1 suicide/100,000 persons; 95% CI: 11.9, 12.3), and 1,127 among cancer survivors (22.1 suicide/100,000 persons; 95% CI: 22.0, 22.1) due to suicide/intentional self-harm. Among racial/ethnic groups, the largest difference was found in the non-Hispanic White cancer survivors, with 10.4 more suicide/100,000 persons vs. White individuals in the general population. In contrast, two racial minority groups had higher suicide mortality rate in the general population vs. cancer survivors: Non-Hispanic Black individuals (general population = 7.4 suicide/100,000 persons vs cancer survivors = 6.9 suicide/100,000 persons), and Native American Indian (general population = 16.6 suicide/100,000 persons vs. cancer survivors = 11.3 suicide/100,000 persons). Among females, suicide mortality rate was slightly higher by 1.3 suicide/100,000 persons in cancer survivors vs. general population, and much higher among male cancer survivors vs. general population (19.9 suicide/100,000 persons more). For age groups, the lowest difference in suicide mortality between cancer survivors vs. general population was in the 65-84 age group (5.1 more suicide/100,000 persons). Across all other age groups, suicide rates were 11.9 to 14.4 higher in cancer survivors vs. the general population. Across the 12 states in our analysis, the smallest difference was in Iowa (1.9 more suicide/100,000 persons), and the largest difference was in Idaho (27.0 more suicide/100,000 persons). Conclusions: In most subgroups, people diagnosed with cancer appear to be at greater risk of death from suicide/intentional self-harm than the general population. As the number of people living with cancer continues to grow, policies increasing the quality of life for cancer patients are warranted.

Linking in with advice and supports for men impacted by metastatic cancer: The LIAM Mc trial (NCT05946993).

TPS1646 Background: Multidisciplinary supportive care interventions are key to preventing and managing adverse effects of cancer and its treatment for patients, reducing symptom and psychological burdens and enhancing quality of life (QoL). However, the optimal composition of these interventions for men with genitourinary (GU) cancers is poorly understood. The LIAM Mc Trial is an enhanced supportive care programme, funded by the Irish Cancer Society and designed with the input of patient representatives who highlighted the unmet needs of cancer survivors. An important aspect of the trial is to demonstrate how to improve the survivorship supports and services for underserved communities of men who experience disparities in cancer incidence, prognosis, outcome and QoL, and have not traditionally been the focus of such initiatives. Methods: Using an embedded mixed-method process evaluation this prospective trial aims to assess the feasibility and impact of a holistic 12-week survivorship programme amongst men with advanced GU cancers at an Irish Cancer Centre. The programme involves twice-weekly sessions with input from a dedicated physiotherapist, dietitian, and nurse specialist, along with education sessions from medical social worker and psycho-oncology specialists, and programme oversight provided by medical oncologists. Outcomes are measured at three timepoints; pre-intervention, immediately post-intervention and at 6 months post intervention, and will include EORTC QoL; muscle strength; body composition through bioelectrical impedance analysis and ultrasound; diet quality; cancer related symptom control; cancer related fatigue scores; feasibility outcomes, qualitative interviews and a process evaluation. Any man with a locally advanced or metastatic GU cancer who has recently completed a course of treatment or is stable on active anti-cancer treatment is eligible for the programme. Over the two-year study period the sample size target is 72 participants. The primary endpoint of the study is to evaluate the feasibility of introducing an enhanced supportive care programme as part of routine management for male cancer patients with metastatic disease. Acceptability, satisfaction with the programme and QoL changes are key secondary endpoints. Barriers to participation are also a key outcome under investigation. The study was activated in May 2023 with the first participants enrolled in June 2023. To date 17 men have enrolled with accrual completion anticipated in June 2025. Clinical trial information: NCT05946993 .

Prediction of the survival status and tumor microenvironment in colorectal cancer through genotyping analysis based on toll-like receptors.

Colorectal cancer (CRC) ranks third in both the incidence and mortality rates among male and female cancers, and it is the leading digestive system cancer. Due to the inter- and intratumor heterogeneity of cancer, the TNM system is insufficient for predicting prognosis, necessitating the use of molecular biomarkers for prognostic prediction. Toll-like receptors (TLRs) have been associated with CRC survival rates. This study focused on the investigation of the role and potential value of TLRs in CRC genotyping to aid in immunotherapy for CRC patients. Differential gene expression analysis was performed on CRC transcriptomic data from The Cancer Genome Atlas database. TLRs were referred from the literature, and their intersection with differentially expressed genes (DEGs) in CRC yielded TLR-DEGs. The expression patterns of TLR-DEGs were predicted using the STRING website, and copy number variations of TLR-DEGs were analyzed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted on TLR-DEGs. ConsensusClusterPlus R package was used for clustering CRC patients, and ESTIMATE and GSEAbase were employed to analyze immune characteristics of different subtypes. Immune phenotyping scores and tumor immune dysfunction and exclusion scores were evaluated. DEGs of different subtypes were analyzed, followed by GO and KEGG enrichment analyses, the protein-protein interaction (PPI) network analysis, and further selection of hub genes. The sensitivity of drugs was assessed using the identified hub genes. We identified 37 TLR-DEGs, and the PPI analysis revealed their coexpression, although they were distributed on different chromosomes. Enrichment analyses indicated that the 37 TLR-DEGs were linked to cancer cell immune response. Based on these TLR-DEGs, CRC patients were classified into three subtypes. Cluster2 exhibited lower survival rates and higher immune infiltration levels and predicted poorer response to immune checkpoint inhibitor therapy. The intersection of DEGs from cluster2 and cluster1 with DEGs from cluster2 and cluster3 yielded a set of 426 commonly shared DEGs. Enrichment analyses revealed that these shared DEGs might regulate immune cell viability. Eight common hub genes for different subtypes were further identified to predict drug-related correlations. The developed TLR genotyping was used to predict the survival status and tumor microenvironment of CRC, providing a foundation for understanding the molecular mechanisms of TLR signaling and deepening its clinical significance.

Association between Metabolic-Dysfunction-Associated Steatotic Liver Disease and Hepatic Cancer: Current Concepts and Future Challenges.

Background: This study systematically reviewed the association between metabolic-dysfunction-associated steatotic liver disease (MASLD) and the development of hepatic cancer. Previous research has highlighted MASLD as a predisposing condition. Aim: To collect recent global data on the relationship between MASLD and hepatic cancer. Methods: A systematic review was conducted, which included an analysis of studies on the relationship between MASLD and the incidence of hepatic cancers, focusing on the role of fibrosis and MASLD severity as predictors of cancer risk. Following standard methodological frameworks for the assessment of longitudinal studies, the review gathered information on fibrosis scores, hepatocellular carcinoma (HCC) incidence, and other types of hepatic neoplasms. Results: A total of 522 studies were initially identified, of which 6 studies were appropriate for the review. They collectively revealed that the stage of fibrosis in MASLD is a significant independent predictor of mortality and liver-related events, with higher fibrosis stages correlating with greater risk. Longitudinal data showed that increases in FIB-4 scores were linked to a higher risk of developing HCC and cirrhosis. MASLD was also associated with an increased risk of non-hepatic cancers such as colorectal cancer in males and breast cancer in females. The severity of MASLD was found to be a modifiable risk factor for biliary tract cancer (BTC), with the risk further amplified by diabetes. Moreover, lifestyle factors and comorbidities, such as smoking and diabetes, were identified as modifiers of cancer risk in MASLD patients. Conclusions: The systematic review identified the association between MASLD and an elevated risk of hepatic cancer, establishing a clear link between the severity of liver fibrosis and the incidence of HCC and other hepatic neoplasms. This supports the need for screening for hepatic cancer in patients with MASLD, particularly in the presence of advanced fibrosis or other risk-modifying factors.

Prognostıc Factors In Testıcular Cancer

Aim: Testicular cancer is the most common cancer in men aged 15-35 years and accounts for 1% of all lifetime male cancers. There are two histologic subtypes: seminoma and nonseminoma. In our study, we aimed to investigate the factors predicting recurrence in early-stage testicular cancer. Materials and Methods: Our study is a retrospective study of early stage testicular cancer admitted to the medical oncololi clinic of our hospital between 2006-2018. During the study, 344 patient files were reviewed and 130 patients who met the study criteria were included in the study. Our primary aim in this study was to investigate the factors predictive of recurrence in early stage testicular cancer. Results: When evaluating PFS in patients with nonseminoma with and without lymphovascular invasion, no median PFS value was reached in either group. However, PFS was worse in patients with LVI (p=0.037). When comparing stage 1 with stage 2 seminoma patients, no median PFS values could be reached, but there was a statistical difference between the two groups in terms of recurrence (p=0.019). Conclusions: In our study, we found no association between tumor size, embryonal carcinoma predominance, tunica albuginea invasion, spermatic cord involvement and tumor marker values and recurrence in nonseminoma germ cell testicular tumors. PFS was shorter in patients with LVI compared to those without LVI. Lymphovascular invasion, spermatic cord involvement, tunica albuginea involvement, and rete testis involvement were not associated with disease recurrence in seminoma patients, whereas higher disease stage predicted the risk of recurrence.

Lynch syndrome in Mexican-Mestizo families: Genotype, phenotypes, and challenges in cascade testing among relatives at risk

Lynch syndrome (LS) is the most frequent cancer predisposition syndrome affecting the colon and rectum. A pathogenic variant (PV) disrupting one of the mismatch repair (MMR) genes is responsible for the disease. The spectrum of tumors in LS is heterogeneous and includes cancer of the colon and rectum (CRC), endometrium, ovaries, stomach, small bowel, urinary tract, bladder, pancreas, and skin. Knowledge of the phenotypic variation of patients with LS, the type and frequency of PVs, and cascade testing studies in the Latin American population is limited. The present study aims to recognize the PVs in MMR genes, describe the phenotype in Mexican-Mestizo patients and their relatives, and identify the acceptance rate of cascade testing of relatives at risk. We included 40 carriers of a MMR gene PV and 142 relatives that developed a LS-related neoplasm. Patients’ clinical data, number, and type of malignancies were obtained from their medical records. Amsterdam I-II, Bethesda criteria, and PREMM5® predictive model score were estimated. Available immunohistochemistry (IHC) reports were analyzed. Relatives at risk were determined from index cases pedigrees. The distribution of MMR gene mutations among 40 probands was: MLH1 (67.5 %), MSH2 (22.5 %), MSH6 (7.5 %), and PMS2 (2.5 %). Out of the 182 LS cases, 58 % exhibited the LS phenotype before age 50. The most common tumor was CRC, followed by endometrial cancer in women and gastric cancer in males. We found a 90.0 % concordance between the IHC and germline PV. The most frequent PV in our sample was MLH1 c.676C > T, occurring in 1/6 index cases. All probands disclosed their molecular test result to their family. Out of the 451 asymptomatic relatives at risk, 28.2 % underwent germline testing. Our results highlight the importance of conducting germline genetic studies in LS since it allows the establishment of appropriate cancer screening, risk-reducing measures, and genetic cascade testing among relatives at risk. Interestingly, we observed a significantly higher prevalence of the c.676C > T variant in MLH1, probably a singular characteristic of the Mexican-Mestizo population. New strategies to facilitate accurate communication between index cases and relatives should be implemented to improve the cascade testing acceptance rate.

Managing complexity with chimerism: ALT-AMT flaps for complex head and neck reconstruction

BackgroundHead and neck cancer is the most common cancer in males and fifth most common in females in India. Inadequate screening programs and non-availability of local healthcare resources leads to late diagnosis and most cases present at an advanced stage. Surgical extirpation often results in complex, large defects. The concept of chimerism is useful in dealing with such extensive defects.MethodsBetween July 2013 and May 2017, all patients who underwent primary reconstruction of head and neck defects following cancer extirpative surgery, with ALT-AMT chimera flap at a tertiary care cancer centre were included in this study. The patient data of age, sex, etiology, defect size, flap size, perforator configuration, anastomotic details, donor site closure, and complications was retrospectively collected as per the designated proforma from the hospital electronic record, departmental case record forms and the first author’s personal logs, and analyzed.ResultsChimeric flaps based on the lateral circumflex femoral artery i.e. ALT plus AMT provide the desired qualities to address the complex defects. All thirteen patients had a large intraoral mucosal defect. Nine cases had a large extra oral skin defect. The average size of ALT was (112.5 cm2 area) and of AMT was (94.9 cm2 area). The combined area of ALT AMT was 28.5 X 9 = 256.5 cm2. All AMT pedicles were joining the ALT pedicle. 1 AMT was lost and all donor sites needed skin grafting.ConclusionChimeric ALT + AMT is a valuable option when complex, large, multidimensional and multicomponent defects need to be reconstructed. The advantage of utilising a single donor site and two independent flaps with a single microvascular anastomosis.Level of Evidence: Level IV, therapeutic study