Testicular Cancer Research Articles

Long term sequelae of testicular cancer and treatment: A point prevalence observational study.

e17015 Background: Testicular cancer (TC) is a highly curable solid organ tumour, which usually occurs in the early years of life. Recent studies have observed an increase in the incidence of TC coupled with improvement in cure rates all around the world, especially in Western Europe and North America. Consequently, we have a growing population living in the survivorship phase. Many researchers have highlighted the late complications in TC survivors, linked with the different treatment modalities used for treatment. In this study, we aim to determine the point prevalence of morbidity and mortality in TC survivors at a tertiary care cancer centre in Ireland. Methods: Participants were assessed in a purpose built survivorship clinic and informed consent was obtained. All participants were 18 years or more of age at the time of assessment with a histologically confirmed diagnosis of testicular cancer over 5 years ago. Assessments included a thorough symptom review, clinical examination, blood tests and other investigations (e.g., X-ray, ECG) if required. Results: A total of 81 patients were recruited in the study from March 2023 to January 2024, with a median follow up of more than a 10 years (129 months). Chemotherapy had been given to 85% of patients and radiotherapy to 5%. All except one patient underwent orchiectomy while RPLND was performed in 17% of patients. There were 3 deaths in the survivorship phase, all related to second malignant neoplasms (SMNs). Hyperlipidaemia was the most common condition found in 55% of TC survivors, followed by raised gonadotropins (47%), low testosterone (34%) and hypertension (40%). Other conditions prevalent in our cohort were hearing impairment (26%), abnormal high glucose (8%) and renal impairment(7%). The majority of these co-morbidities were previously undiagnosed before assessment in our survivorship clinic, including 2 cases of coronary artery disease. Over 70% of hypogonadism, hyperlipidaemia, hypertension, renal impairment and high abnormal glucose were initially diagnosed in our clinic. Conclusions: Results from our study are comparable to the studies conducted in other cancer centres across Europe and the US. Second malignant neoplasms remain the major cause of mortality in this cohort but many modifiable risk factors can be diagnosed early and potentially treated to prevent morbidity. Our data strongly supports the need for specialised survivorship clinics to improve the prognosis and quality of life in TC survivors. [Table: see text]

Testicular germ cell tumor survival among children, adolescents, and young adults: A population-based retrospective cohort study.

10035 Background: While testicular germ cell tumor (TGCT) overall survival (OS) exceeds 90%, some patient groups, such as adolescents, have inferior event free survival (EFS) outcomes. There is a paucity of granular, population-derived data about outcomes in children, adolescents, and young adults (CAYA) with TGCT, limiting a deeper understanding of the factors that impact their survival. Methods: All male CAYA (ages 11-21 years) in Ontario, Canada diagnosed with TGCT between 1992-2021 were identified using provincial cancer registries. Detailed disease and treatment characteristics were chart abstracted for ~2/3 of the cohort and determined through health administrative databases for the remainder. We assessed 5-year OS and EFS (first of death, recurrence/progression, or subsequent malignant neoplasm [SMN]) using Kaplan-Meier analysis and the log rank test. Follow-up started at TGCT diagnosis, except for survival after SMN or recurrence, where follow-up started at event date. Results: 748 TGCT patients were identified; 521 were chart abstracted and thus had EFS data available. Median age at diagnosis was 19 years (interquartile range:18-21) and 83.6% had non-seminoma histology. OS and EFS ± standard error (SE) were (94.7 ± 0.8 %, n=748) and (76.4 ± 1.9%, n=521), respectively. Among patients with chart abstracted data, OS and EFS differed by cancer extent at diagnosis and were lowest among CAYA with non-lung organ metastases (Table). Patients who underwent retroperitoneal lymph node dissection (RPLND) for initial treatment (91/521) had higher survival than those who did not (OS 96.6 ± 1.9% vs 93.7 ± 1.2%, p=0.04; EFS 87.6 ± 3.5 % vs 74.1 ± 2.1 %, p=0.0008), particularly CAYA with lung-only organ metastases. OS post SMN (n=28) was 77.3 ± 8.2%, with lower OS after non-TGCT SMN (50.8 ± 14.4%, n=13) than second primary TGCT (100 ± 0%, n=15), p=0.002. OS after recurrence/progression (n=116) was superior in the 59 who did not receive chemotherapy at initial diagnosis (89.7 ± 4%) compared to the 57 who had initial chemotherapy (65.9 ± 6.4%; p=0.0001). Conclusions: CAYA with TGCT have low EFS, consistent with previous studies. The extent of metastasis is a significant predictor. Efforts are needed to improve the survival outcomes of young TGCT patients with organ metastasis at diagnosis, and those who recur or develop a non-TGCT SMN. [Table: see text]

Molecular characterization of growing teratoma syndrome in patients with testicular germ cell tumor.

e17017 Background: Teratomas are unique neoplastic growths that encompass a diverse array of tissue types derived from multiple germ layers, often exhibiting varying degrees of differentiation. Among the phenomena associated with teratomas, the growing teratoma syndrome (GTS) stands out as a rare yet clinically significant occurrence. GTS, characterized by the persistence or regrowth of teratomatous elements despite initial treatment, poses challenges for both diagnosis and management. In this abstract, we present the results of our expression array analysis of teratomas, aiming to uncover novel insights into their molecular composition, heterogeneity, and potential implications for clinical management. Methods: This study included 53 patients with retroperitoneal teratoma (7 chemotherapy naïve and 46 with postchemotherapy teratoma) and 20 patients with viable postchemotherapy germ cell tumor from retroperitoneum that had surgery at National Cancer Institute in Slovakia and for whom formalin-fixed paraffin-embedded (FFPE) tumor tissue was available. Study also includes samples from 5 patients with normal testis as control group. Ten patients (18.9%) in this cohort had growing teratoma syndrome. Analysis was performed by HTG EdgeSeq Oncology Biomarker panel (HTG Molecular Diagnostics, Inc., Tucson, USA). Identified candidate genes associated with GTS were further validated by immunohistochemistry on FFPE. Results: Molecular profiling indicates no differences in expression profile in retroperitoneal teratomas regardless of previous chemotherapy. Expression analysis indicates 1586 genes being differently expressed with high significance ( p < 0.05) in teratomas compared to normal testis and 1571 genes differentially expressed compared postchemotherapy viable tumors. We identified 14 genes being differently expressed in growing teratoma syndrome compared to teratoma without growth (CYP4A22, IGFBP1, CXCL6, LTF, CYP2C8, CFTR, CCL20, PFKFB3, SLC2A3, LIPA, HMOX1, GPNMB, CCL18, DLK1. Pathway analysis revealed MAPK and PI3K−Akt signaling pathways are mostly dysregulated in GTS. Conclusions: This molecular profiling identify genes differentially expressed in teratomas that are potential biomarkers for prediction of teratoma element in postchemotherapy residues in testicular germ cell tumor patients. Moreover, inhibition of identified signaling pathways associated with GTS could represent potentially novel therapeutic targets in case of unresectable disease.

Substance use among individuals with cancer: A US population-based cohort study.

e23133 Background: The prevalence of concurrent substance use or comorbid substance use disorder (SUD) among individuals with a cancer diagnosis, and their participation in substance use treatment, has not yet been described in a large US population-based cohort. Methods: A population-based cohort study was conducted using cross-sectional survey data collected by the National Survey on Drug Use & Health (NSDUH) between 2015-2022. Descriptive statistics were calculated to describe two populations: those with any kind of cancer diagnosis within the preceding 12 months and either comorbid SUD as defined by the Diagnostic and Statistical Manual of Mental Illness (DSM)-5 or concurrent use of any of the following substances: alcohol, marijuana, cocaine, crack, heroin, methamphetamines, or misuse of prescription drugs. Chi-square tests were conducted to describe associations with the demographic and geographic characteristics of these individuals. Results: Between 2015-2022, 432,764 individuals (53% female) completed the survey. A total of 2,547 respondents had a cancer diagnosis in the preceding 12 months; the most common cancer types were breast cancer (17.0%), non-melanoma skin cancers (16.2%), and prostate or testicular cancer (11.0%). Among this cohort, 1,664 (65%) reported concurrent alcohol use, 354 (14%) reported marijuana use, and 82 (3%) reported illicit use of other substances. Among those with an active cancer diagnosis in the preceding 12 months, 103 (4%) met DSM-5 criteria for a comorbid SUD based on survey responses. Among individuals with a past-year cancer diagnosis, there was a statistically significant association between concurrent substance use and income bracket (X2 = 92.67, p < 0.001), concurrent substance use and race (X2=46.12, p< 0.001), and between concurrent substance use and population density (X2= 7.05, p = 0.029). Zero respondents with cancer and either concurrent substance use or comorbid SUD received outpatient treatment for substance use in the preceding year, three (0.002%) received inpatient treatment, and seven (0.004%) participated in a support group. Among respondents with comorbid SUD, many reported being recently asked by a healthcare professional about their alcohol (83%) or drug use (67%), while only 1.9% reported recently receiving information from a healthcare professional about substance use treatment. Conclusions: There is overlap between the population with a cancer diagnosis and that with concurrent substance use or comorbid SUD. Based on population-level survey data, these individuals have low rates of participation in outpatient or inpatient substance treatment, and report that they do not often receive information about substance use treatment from healthcare professionals. Describing this population may inform how providers approach their unique healthcare needs.

Longitudinal evaluation of circulating tumor DNA (ctDNA) as a prognostic biomarker to detect minimal residual disease (MRD) in testicular cancer.

Longitudinal evaluation of circulating tumor DNA (ctDNA) as a prognostic biomarker to detect minimal residual disease (MRD) in testicular cancer.

Role of military physicians in cancer screening practices: The DEPISTmed study.

e22502 Background: Cancer poses a significant health challenge within the military population, impacting both medical and economic aspects, as well as military operations. Despite the potential benefits of early cancer detection, adherence to organized and individual screenings remains below 50%. The pivotal role of military physicians, especially within military forces, in cancer prevention and screening is crucial.The main objective was to investigate the professional practices of military physicians in cancer screening, aiming to understand their perceptions, practices, and the role of screening in their daily routines. Methods: A prospective, observational, non-interventional cohort study was conducted, utilizing anonymous self-assessment questionnaires among military physicians practicing in army or joint military medical centers. Criteria for inclusion involved physicians engaged in patient care, including the performance of medical check-ups. Demographic data, perceptions, declared practices, and primary prevention measures were assessed through secure electronic questionnaires. Results: Between June 1, 2023, and September 30, 2023, 169 practitioners were included, with 51% were female. The median number of visits per practitioner was 400 (range 150-600). The study revealed a heightened concern among military physicians regarding cancer screening, particularly for breast, colon, and testicular cancers, with over 78% of practitioners expressing a significant level of concern (range: 59-90%). However, our investigation exposed disparities in clinical examinations and the prescription of additional tests, specifically within organized screenings among unit physicians. Less than 7% utilized recommendation sheets. Conclusions: Military physicians express a genuine concern for cancer screening, indicating the periodic medical check-up as an opportune moment for imparting screening information. The study highlights limitations such as the need for dedicated training, availability of materials, and optimizing patient care pathways. This research sheds light on the critical role of military physicians in cancer screening and provides insights into the challenges and opportunities for improving screening practices within military healthcare settings. The findings underscore the importance of targeted interventions to enhance adherence to screening guidelines and strengthen cancer prevention efforts within the military healthcare system.

Longitudinal circulating tumor DNA monitoring for detection of molecular residual disease in patients with advanced germ cell tumors.

e17022 Background: Germ cell malignancies, commonly manifesting as testicular cancer, is one of the most common malignancies in men 15 to 45 years of age, with the incidence doubling over the past 40 years. When identified promptly and treated with a multidisciplinary approach, germ cell tumors have an excellent prognosis with cure rate >90% and 5-year survival rate >95%. Treatment involves radical orchiectomy for diagnostic and therapeutic purposes. Further management includes active surveillance, adjuvant chemotherapy, retroperitoneal lymph node dissection (RLND), and radiation therapy. While AFP, B-HCG, and LDH are good biomarkers, they are not sensitive or specific for detecting molecular residual disease (MRD). B-HCG is detected in <30% of individuals with seminoma and B-HCG and AFP are detected in 50–60% of patients with non-seminomatous tumors. We describe the use of circulating tumor DNA (ctDNA) for detection of MRD in advanced germ cell malignancy, especially when baseline biomarkers are negative. Methods: This is a retrospective analysis of 20 patients with testicular cancer treated at Rush University Medical Center who monitored closely for MRD. Signatera (Natera Inc.), a personalized tumor-informed ctDNA assay, was utilized for detection and quantification of ctDNA in patients’ plasma samples, measured at MRD (1-12 weeks post-orchiectomy) and regular intervals thereafter, regardless of treatment modality. Event free survival (EFS) was determined, defined as the period from radical orchiectomy to date of radiographic progression of disease. Results: There was a total of 20 patients (35% seminoma, 65% non-seminoma) with 2 of the patients having extragonadal disease. The mean age was 32.2 years old with IQR (28-36). Post operatively, 20% underwent RLND, 10% were on surveillance, 53% received post-orchiectomy chemotherapy, 6.7% of patients underwent autologous stem cell transplant. The median follow up time is 1.14 years. Two patients had positive ctDNA despite negative baseline traditional biomarkers. There were 23.3% (7/30) of patients that had evidence of radiographic progression. Of the patients with progression, serial ctDNA monitoring had high rates of concordance (85%, 6/7) of ctDNA positivity with biomarker positivity and radiographic progression. Conclusions: Overall, ctDNA correlated with, and sometimes even preceded, traditional biomarkers and radiographic findings of disease progression. The ctDNA positivity of 2 patients in this cohort despite negative baseline AFP, B-HCG, and LDH, highlights the sensitivity and specificity of ctDNA for MRD compared to more traditional biomarkers. Serial monitoring of ctDNA offers valuable insights into germ cell tumor disease status, including presence of MRD, and there is a need for prospective studies to guide treatment escalation and de-escalation in germ cell tumors.

Impact of race and ethnicity on financial toxicity in patients with genitourinary cancers.

11077 Background: Genitourinary (GU) cancers contribute substantially to the cost of healthcare in the United States (US). While advancements in cancer treatment have improved patient outcomes, disparities in healthcare costs persist, exacerbating the financial burden on vulnerable populations. We sought to investigate the disparities in costs of inpatient hospitalizations among patients with GU cancers in the US. Methods: Eligible adult GU cases from the Medical Expenditure Panel Survey (2019–2021) were included in this study. ICD-10 CM codes were utilized to identify renal cell, prostate, urothelial, testicular, and penile cancers. In addition to the total hospital inpatient (IP) facility expenditure, questions about ability to pay for healthcare were included in the analysis after accounting for the complex survey design and sampling weights. Results: The study included a weighted sample size of 9,061,181 (wt SE = 538,502) GU cases in the US between 2019 and 2021. The mean (95% CI) age of the sample was 71.6 (70.7, 72.5) years. The sample consisted of 7.9% Hispanics, 74.8% non-Hispanic White (NHW), 13.8% non-Hispanic Black (NHB), and 3.5% Asian or other races (NHA). In 2021, NHB participants reported the lowest annual family income of $51742 (18932, 106185), followed by Hispanics with $65233 (24314, 95859), and NHW with 82035 (36298, 158863). A greater proportion of the elderly NHW population was insured compared to NHB and Hispanics (44.9% vs. 32.5% vs. 19.5%), respectively. Of note, NHB patients had worse self-perceived physical and mental health compared to NHW and Hispanics, with 18.1% reporting fair or poor physical and mental health (vs. 8.1% and 14.3%, respectively). NHB participants reported higher rates of familial financial hardship (2019: 10.2% vs. 3.6%; 2020: 6.2% vs. 3.5%; 2021: 7.1% vs. 3.3%) or not being able to afford medical care (2019: 7.2% vs. 2.1%; 2020: 2.5% vs. 0.6%; 2021: 1.9% vs. 1.7%) when compared to NHW. Overall, mean total hospital IP facility expenses were: Hispanics = $2873.30 (1434.49, 4312.12); NHW = $4213.81 (3241.05, 5186.56); and NHB = $5199.99 (2842.93, 7557.05). After accounting for sample weights, gender, family income, age, insurance status, and survey year, Poisson regression analysis showed significant differences between different racial groups. Hispanics were less likely (𝛽=-0.48; p<0.0001), while NHB (𝛽=0.152; p<0.0001) and NHA (𝛽=0.48; p<0.0001) were more likely to spend for an IP hospitalization when compared to NHW (ref.). Conclusions: Our data revealed racial disparities in the costs of inpatient hospitalizations, highlighting potential financial toxicity among patients with GU cancers. Additional investigation is warranted to elucidate factors contributing to these inequities, aiming to optimize cancer management and alleviate financial burdens. Addressing these disparities is crucial to prioritize equitable healthcare access and promote systemic change.

Clustering analysis for predicting racial disparities in genitourinary cancer–related financial burden.

e13612 Background: Healthcare costs in the United States (US) are significantly impacted by genitourinary (GU) cancers. Prostate cancer treatment alone cost the US more than $22 billion in 2020. We sought to utilize machine learning (ML)-based classification to investigate differences in the total cost of healthcare expenditure among patients with GU cancer in the US. Methods: The study included eligible adult GU cases from the 2019–2021 Medical Expenditure Panel Survey. Renal cell, prostate, urothelial, testicular, and penile cancers were identified using ICD-10 CM codes. Patients were clustered using demographic information such as age, race, sex, marital status, highest degree, insurance status, perceived health status, and perceived mental health status. The analysis accounted for the complex survey design and sampling weights. The cluster groups were taken into account when conducting descriptive and regression analyses. GU cancer cases were divided into low-, medium-, and high-risk healthcare expenditure clusters. Results: The study included a representative sample of 9,061,181 cases of GU cancer in the US between 2019 and 2021. The average age of the sample was 71.6 years (95% CI: 70.7, 72.5). There were 7.9% Hispanic (Hisp), 74.8% non-Hispanic White (NHW), 13.8% non-Hispanic Black (NHB), and 3.5% individuals from Asian or other races. Overall, the mean total healthcare expenditures within low-, med-, and high-risk clusters were $17974 (13816, 22133), $20496 (13100, 27893), and $30512 (21389, 39635), respectively. Regression analysis showed that, after adjusting for sampling weight, cluster, gender, family income, age, insurance status, and survey year, the mean total expenditure was higher by $11209.70 and $13100.81 in med- and high-risk clusters when compared to the low-risk cluster (ref.). Within each race or ethnicity, the proportion of Hisp or NHB individuals was higher in med- and high-risk clusters. Med- and high-risk clusters were more likely to contain people with cognitive impairments, poor health status, and financial difficulties in their families. Conclusions: We used an unsupervised clustering algorithm that can distinguish between GU cases with high and low expenditure based solely on sociodemographic variables. We demonstrate that our findings were consistent for all three data cohorts. This approach can predict the disparity in utilization in any insured population. [Table: see text]

A phase II multicenter study of enfortumab vedotin with or without pembrolizumab in rare genitourinary tumors (E-VIRTUE).

TPS4628 Background: Enfortumab vedotin (EV) is an antibody-drug conjugate (ADC) targeting nectin-4 with a monomethyl auristatin E (MMAE) payload, a potent microtubule inhibitor. It is standard of care (SOC) in metastatic urothelial carcinoma in combination with pembrolizumab in untreated patients and as monotherapy in post-chemotherapy, post-immune checkpoint blockade (ICB) patients. Nectin-4 expression has been retrospectively observed in 66.7-100% of urinary tract adenocarcinoma, 70-100% of urinary tract squamous cell carcinoma (SCC) (Case et al., 2022; Hoffman-Censits et al., 2021) and 36% of testicular germ cell tumors (GCTs) (The Human Protein Atlas). Metastatic urinary tract adenocarcinoma and SCC, and treatment refractory GCTs do not have an established SOC. Given the known nectin-4 expression, we hypothesize that EV with or without pembrolizumab will be active in these rare GU tumors. Methods: E-VIRTUE is an open-label, non-randomized, Phase 2 multicenter study. Eligible patients must have locally advanced or metastatic urinary tract pure adenocarcinoma, urinary tract pure SCC or refractory GCTs and have measurable disease by RECIST 1.1. Patients may have received any number of lines of prior systemic therapy except EV or other MMAE-based ADCs, and GCT patients must be refractory to all curative SOC treatments. Each histology will have an ICB-naïve and post anti-PD-1/PD-L1 ICB cohort: ICB-naïve patients will be given EV 1.25 mg/kg (maximum 125 mg) on Days 1 and 8 and pembrolizumab 200 mg on Day 1 of 21-day cycles, and post ICB patients will be given EV 1.25 mg/kg (maximum 125 mg) on Days 1, 8 and 15 of 28-day cycles. EV will be given for up to 5 years and pembrolizumab will be given for up to 2 years, or until progressive disease (PD) or unacceptable toxicity. Patients who stop pembrolizumab after achieving a complete response may resume it for 1 year after developing PD. The primary objective is to evaluate the objective response rate (ORR) in all cohorts. Secondary objectives include safety, progression-free survival (PFS) and overall survival (OS). The initial 6 cohorts will each be evaluated with exploratory intent. With 10 patients in each cohort, an exact binomial test with a 10% one-sided significance level will have 85.3% power to detect the difference between a very low (5%) ORR and a higher (30%) ORR. If there are ≥2/10 objective responses in any cohort, activity will be demonstrated. Additional histologies may be added after nectin-4 data emerges to justify their inclusion. Exploratory objectives include estimating the level of nectin-4 expression for each histology, performing DNA and RNA sequencing of tumor and blood samples, and observing changes in levels of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) with treatment and disease status. Clinical trial registration NCT06041503. Clinical trial information: NCT06041503 .

Testicular cancer survivorship program at National Cancer Institute in Slovakia.

e13792 Background: Testicular germ cell tumors (GCTs) are highly curable malignancies. Survivors of GCTs represent a growing population with a long life expectancy after curative cancer treatment. GCT survivors may experience a variety of late adverse effects of treatment and reduced quality of life. Therefore, National Cancer Institute in Slovakia has developed a testicular cancer survivorship program with a long-term follow-up of GCT survivors aiming to evaluate late toxicities and their underlying molecular mechanisms. Methods: The long-term annual follow-up of GCT survivors is established per our institutional guidelines for testicular cancer survivorship program. GCT survivors are referred to our testicular survivorship outpatient clinic at least 5 years after completion of curative treatment, and are followed annually throughout their lives. During each visit, patient’s history is updated, physical examination is performed, blood and urine samples are collected, and survivors complete validated questionnaires for evaluation of late toxicities (peripheral neuropathy, sexual dysfunction, cognitive impairment) and quality of life. Complete blood count, metabolic panel, lipid panel, levels of serum tumor markers, testosterone, luteinizing hormone and follicle stimulating hormone are measured at each visit. Plasma aliquots and urine samples from every visit are prospectively collected and stored in the biobank of our Translational Research Unit. Data including age, medical history, histological type, stage, prognostic group, type of treatment, laboratory values, and questionnaire scores are collected and recorded in our electronic survivorship database. In addition, information on important survivorship topics is provided and healthy lifestyle changes are suggested to all survivors. Results: From August 2015 to January 2024 our testicular survivorship outpatient clinic performed 1733 follow-up visits in 407 GCT survivors treated at our institution from 1984 to 2019. Median age at the first follow-up visit at the survivorship clinic was 41 years (range 21 - 77). Median time from the curative treatment to the first follow-up visit at the survivorship clinic was 7 years (range 4 - 32). To date, 104 patients have had at least 7 follow-ups. Eighty-six (21.13 %) patients were treated with surgery only, 278 (68.3 %) with chemotherapy, 28 (6.88 %) with radiotherapy, and 15 (3.69 %) patients with both chemotherapy and radiotherapy. To date, 18 publications (including papers and abstracts) have been published using the data from our testicular survivorship database. Conclusions: Testicular cancer survivorship program with the long-term annual follow-up of GCT survivors has been established at National Cancer Institute in Slovakia. The ongoing prospective study for evaluation of late toxicities and their underlying mechanisms is part of the program. Our large database offers valuable data for the future research.

Real-world evidence of overall survival (OS) and treatment patterns of patients (pts) with testicular germ cell tumors (GCT) receiving palliative chemotherapy in the United States.

Real-world evidence of overall survival (OS) and treatment patterns of patients (pts) with testicular germ cell tumors (GCT) receiving palliative chemotherapy in the United States.

Prognostic factors and survival in men with testicular germ cell tumors (GCT).

e17018 Background: The International Germ Cell Cancer Collaborative Group (IGCCCG) has recently discovered new factors for GCT in 2021. We have estimated previously known and new prognostic factors in patients with nonseminomatous germ cell tumors (NSGCT) and seminoma treated at N.N. Petrov NMRC of Oncology. Methods: From 2011 to 2021, the study included 273 adult patients receiving standard cisplatin-based chemotherapy. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Survival was estimated using the Kaplan-Meier and Cox methods. Results: 5-year OS rates were 94%, 85% and 70% in the good, intermediate, and poor prognosis groups, respectively for NSGCT and 95% and 86% in good and intermediate prognosis groups for seminoma (p<0.05). 5-year PFS rates were 74%, 51%, and 41% for NSGCT and 76% and 62% for seminoma of the above-mentioned prognostic groups, respectively (p<0,05). Presence of pulmonary metastases (mts) (HR 0.177; 95% CI: 0.051-0.612; p=0.006), non-pulmonary visceral mts (HR 4.636; 95% CI: 1.710-12.570; p= 0.003), elevated LDH of ≥ 2.5 limit of normal (≥ 2.5 × ULN) (HR 4.107; 95% CI: 1.614-10.451; p= 0.003), treatment in high-experienced clinic (HR 0.37; 95% CI: 0.147-0.919; p=0.0032), and non-compliance with guidelines (HR 3.731; 95% CI: 1.456-9.564; p= 0.006) was significantly associated with OS in NSGCT. The presence of pulmonary mts (HR 0.15; 95% CI: 0.024-0.877; p=0.035) and elevated LDH ≥ 2.5 × ULN (HR 0.109; 95% CI: 0.015-0.775; p=0.027) were the only factors associated with poor OS in seminoma. The presence of pulmonary mts (HR 0.446; 95% CI: 0.247-0,804; p=0.007), non-pulmonary visceral mts (HR 2.668; 95% CI: 1.390-5,120; p=0.003) and treatment in high-experienced clinic (HR 1.852; 95% CI: 1.059-3.238; p=0.031), were significantly associated with inferior PFS in NSGCT. Pulmonary mts were the only significant (HR 0.301; 95% CI: 0.100-0.910; p=0.033) factor in the multivariate OS analysis for all testicular GCT. The absence of non-pulmonary visceral mts (HR 0.522: 95% CI: 0.265-0.963; p=0.019) and compliance with guidelines (HR 0.565; 95% CI: 0.309-0.910; p=0.038) were significant factors in the multivariate PFS model for all patients with testicular GCT. Conclusions: The original IGCCCG classification remains the reference for treatment decisions for testicular GCT in daily practice. Non-compliance with guidelines and treatment in high-experienced clinic could become additional poor prognostic factors.

A novel oral microtubule inhibitor utidelone capsule (UTD2): A phase 1 clinical study to assess the tolerability, safety, and efficacy in advanced solid tumors.

e15014 Background: Utidelone is a potential best-in-class novel microtubule stabilizing agent that offers several advantages including improved efficacy and safety, broader anti-cancer spectrum, blood-brain barrier penetrance, and response against multidrug-resistant tumors. Utidelone injection (UTD1) has been approved for advanced breast cancer in China since 2021 (30 mg/m2/d-5day in combination with capecitabine; 35mg/m2/d-5day for monotherapy’s recommended dose). Utidelone is not susceptible to P-glycoprotein, leading to better oral bioavailability and successful development of an oral capsule. This is the first-in-human study of Utidelone Capsule (UTD2) in the United States. Methods: This is an ongoing phase I, open-label, dose escalation study (NCT05681000). Eligible patients are aged ≥18, and have an ECOG PS of 0-1, life expectancy ≥12weeks, adequate organ functions, pathologic confirmed advanced solid tumor refractory to prior standard therapies. Patients are treated with UTD2 monotherapy. The starting dose is 25 mg/m2/d-5day, with planned escalation to 50, 75, 100 mg/m2/d-5day, 70 mg/m2/d-7day and 85 mg/m2/d-7day in a 21-day cycle. The primary objective is to determine DLT and MTD. Secondary objectives include efficacy, pharmacokinetic profile and phase II dose recommendation. Results: As of 22nd January 2024, 10 advanced solid tumor patients were enrolled with median age of 62.5 years (range 52.0-81.0), 5 females and 5 males. All patients had received prior treatment in advanced settings. Dose escalation is ongoing, and 100mg/m2/d-5day cohort is under evaluation. The first 8 patients were evaluated for efficacy with an outcome of 1 CR (ovarian cancer), 5 SD (prostate adenocarcinoma, testicular Sertoli cell tumor, non-small cell lung cancer, pancreatic adenocarcinoma and appendiceal adenocarcinoma) and 2 PD (carcinoma of fallopian tube and adenocarcinoma of sigmoid colon), among whom 5 patients are still on the treatment with durations of 2 to 11 cycles. The ovarian patient with CR was enrolled to the lowest dose cohort, and is still on treatment. She is heavily pre-treated with multiple prior lines including chemotherapies. Regarding safety, most treatment-emergent adverse events (TEAEs) were Grade 1/2, manageable, and included diarrhoea, nausea, alopecia. There were two cases of Grade 3 diarrhea that recovered to Grade 1 through dose reduction or medical support. No grade 4 or 5 adverse events and no treatment discontinuations due to AE were reported. There have been no DLTs and the MTD is not yet reached. Conclusions: This study has demonstrated encouraging anti-tumor activity with good tolerance and manageable safety profile of UTD2 in patients with heavily pre-treated advanced solid tumors. This study is still actively ongoing, and further data will be provided at time of presentation. Clinical trial information: NCT05681000 .

The demographics of Sertoli cell carcinoma: A National Cancer Database analysis.

e17012 Background: Sertoli cell tumors (SCTs) are an extremely rare and lethal diagnosis responsible for roughly 1% of all testicular and ovarian carcinomas. No uniform treatment regimen with sufficient results has been established. Current combination of retroperitoneal lymph node dissection, chemotherapy, and radiation therapy provides the best known outcome. Analyzing trends in diagnosis may provide valuable information about its epidemiology. The National Cancer Database (NCDB) was analyzed to establish the demographic factors in diagnosed patients. Methods: A retrospective cohort study from 2004 to 2020 was conducted using the NCDB. 159 patients were found with a histologically confirmed diagnosis of SCTs (ICD-8640-3). Race, gender, Hispanic origin, type of treatment facility, insurance coverage, and distance from patient residence to treatment facility were analyzed via descriptive statistics, and trends in incidence were interpreted using regression analysis. Results: The number of patients diagnosed with SCTs has remained relatively consistent since 2004 (R^2 = 0.07), with approximately 9 diagnoses per year. Of the 159 patients found, the average age of diagnosis was 44.6 years (SD = 19.1, range = 2 – 89 years). A majority of patients were male (67%), while the remaining third were female (33%). Most of the patients were White (73%). Patient Hispanic status could not be reliably determined due to limited data. More patients were in the top income quartile (31%) than the second (24%), third (18%), or fourth (14%) quartiles, with 13% having unknown income status. Most patients were privately insured (59%), followed by coverage under Medicare/Medicaid (28%). More patients lived in metropolitan counties with a population of 250,000 or more (76%) compared to less-populated urban or rural regions (24%). The majority received treatment at comprehensive community cancer programs or academic/research programs (43%). Patients traveled an average of 30.2 miles (SD = 64.0, range = 0.5 – 474.9) to reach the treatment facility. Conclusions: SCTs remains a rare diagnosis. This study pursues a significant gap in existing knowledge on patient characteristics that may present with SCTs. Most patients were White, privately insured, in the top income quartile, and lived in metropolitan areas. This novel study may contribute data towards understanding the relationship between patient socioeconomic status and access to diagnosis. Further research is required to uncover the role of socioeconomic status in SCTs.

Decade of insights: Bleomycin-induced pneumonitis and use of G-CSF in chemotherapy-treated germ cell testicular tumors and Hodgkin lymphoma—Real-world outcomes from an academic cancer center.

e17013 Background: Bleomycin induced pulmonary toxicity (BIP) occurs in 4-10% of treated patients. Preclinical reports suggest G-CSF use may increase BIP risk, due to neutrophil migration to lung tissues. Limited real-world clinical data is available and G-CSF use may reduce risk of treatment related toxicity with curative bleomycin combination treatment. Methods: We conducted a retrospective study of patients with GCT (Germ cell tumor) and HL (Hodgkin’s lymphoma) receiving bleomycin containing chemotherapy and at-least on dose of G-CSF at The James Cancer Center from 2010-2022 using the institutional database. BIP was diagnosed mainly using clinical symptoms complemented by radiological evidence when possible. We reviewed 361 patients, 145 in GCT group and 216 in HL group and clinically relevant information was recorded.Descriptive statistics for the study variables were presented using frequencies and percentages overall. The bivariate associations between G-CSF use and clinical outcomes were assessed using chi-square tests or fisher’s exact tests for the overall sample, and by chemotherapy type. We used SPSS 26.0 for all the statistical analyses, and an alpha level of 0.05 (two-sided) was used for all the tests. Results: Data on 361 patients, including 145 GCT and 216 HL patients treated with at least one dose of bleomycin was available. The median age was 36.3 years in the GCT group and 44.2 years in the HL group.144 patients in the GCT and 50 patients in the HL group received at least 1 dose of G-CSF. BIP occurred in 4.8% in the GCT and 7.4% of patients in the HL group. Only 2 out of 16 patients developing BIP in the HL group received G-CSF. All patients with BIP developed symptomatic disease. On bivariate analysis, no association was noted between BIP and G-CSF in either group (p-value =1.00 in GCT and p-value = 0.32 in HL). Febrile neutropenia (FN) was reported in 4 patients in the GCT group and 29 in the HL group. In the HL subgroup, 28 (28/29) patients developing FN did not receive G-CSF (p-value=0.0008). All patients who developed FN required hospital admission. Conclusions: Use of G-CSF in patients receiving bleomycin was not associated with an increased incidence of BIP. Incidence of FN was higher in patients not receiving G-CSF leading to hospital admissions. [Table: see text]

Follow-Up of Patients Diagnosed With Germinal Testicular Tumors (Seminomas and Non-seminomatous) Treated With a Bone Marrow Transplant and a High Dose of Chemotherapy.

Germinal testicular tumors are the most common malignant neoplasm in men around 20 to 34 years. Even though they are unusual, they have increased incidence in the last decade; they have an excellent prognosis and overall survival at five years, approximately 95%. Divergent data exists regarding treatment options in patients with first, second, and third relapses with conventional therapy. Some studies describe the possible benefit of using high-dose chemotherapy associated with a bone marrow transplant with variable results. The present study describes clinical outcomes, clinical response, mortality, overall survival, and progression-free survival to two years in a group of patients with germinal malignant tumors, seminoma versus non-seminomatous with evidence of progression of the disease at first, second, or third conventional chemotherapy regimens,and who received high dose chemotherapy and bone marrow transplantation at the National Cancer Institute between 2010 and 2021. A retrospective observational study of case series showed that 57% of patients in third-line therapy received high-dose chemotherapy and bone marrow transplantation, with progression disease median time from diagnosis more than two years. Patients in the post-graft period presented infectious complications (71%). The most common were febrile neutropenia (29%) with a mortality rate of 71% (n=5), progression-free survival of 2.3 months, and overall survival of 7.4 months. These results show that in this group of patients, regimens with high-dose chemotherapy associated with bone marrow transplants, have a worse prognosis compared to other cohorts of patients, and may not be the best candidates for this rescue therapy.

A Case of Metastatic Prostate Cancer with Neuroendocrine Differentiation with Long-Term Survival after Multidisciplinary Therapy

A 74-year-old man visited the urology clinic with the chief complaint of urinary retention in December 2014. Serum level of initial prostate specific antigen (PSA) was 50 ng/ml and he was diagnosed with Gleason Score 4＋4 prostate adenocarcinoma with regional lymphadenopathy (cT3aN1M0). PSA level had declined after the treatment with combined androgen blockade. In November 2018, he was diagnosed with castration resistant prostate cancer (CRPC) as local progression was detected by computed tomography (CT) while PSA level did not increase. Since local symptoms worsened, resulting in repeated hematuria after the treatment with enzalutamide, palliative radiation therapy to the prostate (45 Gy) was performed. Five months later, follow-up CT showed multiple metastasis in bilateral lung and left testicle. Serum level of neuron-specific enolase (NSE) was 24.4 ng/ml without an elevated in serum PSA level. He received rebiopsy of the prostate, but no malignant findings were observed. Consequently, bilateral orchiectomy was performed for diagnosis of left testicular tumor. Pathological examination revealed metastasis of neuroendocrine prostate cancer (NEPC). Chemotherapy using cisplatin and irinotecan was administered after orchiectomy. Complete response of lung lesions was achieved and serum level of NSE decreased within normal range. No recurrence has been confirmed for 4 years after the completion of chemotherapy.

Decision making in oncology: Unleashing the power of artificial intelligence—Beyond the question of feasibility.

9021 Background: This study examines how consulting artificial intelligence (Chat GPT, Bard) or electronic tools (Apps, Journal or Guidelines) affects the decision-making process in Oncology Fellows. Methods: In the OSCE IOHM-USAL 2023, Oncology Fellows (2022 and 2023 cohorts) individually answered stations I and II, both spontaneously and after AI consultation. Group responses for stations III and IV were also gathered. Sign tests compared pre- and post-consultation responses in stations I and II while the impact of AI in stations III and IV was individually assessed on a five-point scale (0= Null and 5= Extremely useful). Results: 15 Oncology Fellows participated in OSCE 2023- 14 Females. Median age: 30 (r=28-36). A) Stations I - II Cases: Case1: 70 y. Non smoker. PS 0. Stage IV NSCLC. PS 0. EGFR mutated E746 _A750. PDL1 90%. Case 2: 52 y. Postmenopausal Stage II Luminal B Her2 negative Breast cancer (pT2, pN1, M0). Case 3: 35 yo. Advanced colon cancer. Stage IV. BRAF p(V600E) c.1799 A>C. No Micorsatellite Instability. B) Station III (Ethics Committee), the following cases were addressed: 4. “BRCA1: Insured, not excluded”. 5. “Smoke vs. oath? Tough choice” 6. “Follow Lynch path, or HMO exit”. In all three cases, 3/15 students reported finding AI useful in the discussion. C) Station IV (Tumor board), the following cases were addressed: 7. “Postmenopausal NOS IBC (pT1c pNmic Luminal B Her2 negative)”. 8. “Oncology emergency in a 22 y male patient testicular tumor pending pathology”. In Case 7, 3/15 students reported finding AI useful in the discussion. In Case 8, 4/15 students reported finding AI useful. Conclusions: 1. A study of 15 oncology fellows found no appreciable influence of AI on clinical decision-making. 2. Analysis of eight cases (individual/collective) identified anchor value, optimistic denial, and confirmation bias in reasoning and processing. 3. Fellow training in critical AI analysis and outcome evaluation is imperative. [Table: see text]

Survival outcomes and molecular drivers of testicular cancer in hispanic men

ObjectiveTo examine survival outcomes and molecular drivers in testis cancer among Hispanic men using a large national sample and molecular database. MethodsWe reviewed the SEER registry for testicular cancer from 2000 to 2020. Cox proportional hazards models were used to examine the relationship between race/ethnicity and cancer-specific survival (CSS) by tumor type (seminoma vs. nonseminomatous germ cell tumors [NSGCT]). All models were adjusted for demographic, socioeconomic, and treatment variables. We accessed somatic mutations for testicular cancers through AACR Project GENIE v13.1 and compared mutational frequencies by ethnicity. ResultsOur cohort consisted of 43,709 patients (23.3% Hispanic) with median follow-up 106 months (interquartile range: 45-172). Compared to Non-Hispanic Whites (NWH), Hispanics presented at a younger age but with more advanced disease. Hispanics experienced worse CSS for NSGCT (HR 1.7, 95% CI: 1.5-2.0, P < 0.01) but not seminoma. Somatic mutation data was available for 699 patients. KIT and KRAS mutations occurred in 24.2% and 16.9% of seminoma patients (n = 178), respectively. TP53 and KRAS mutations occurred in 12.1% and 7.9% of NSGCT patients (n = 521), respectively. No differences in mutational frequencies were observed between ethnic groups. There was significant heterogeneity in primary ancestral group for Hispanic patients with available data (n = 53); 14 (26.4%) patients had primary Native American ancestry and 30 (56.6%) had primary European ancestry. ConclusionsCancer-specific survival is worse for Hispanic men with non-seminoma of the testicle. Somatic mutation analysis suggests no differences by ethnicity, though genetic ancestry is heterogeneous among patients identifying as Hispanic.