Late-stage Cancer Research Articles

Unequal racial distribution of immunotherapy for late-stage non-small cell lung cancer.

Immunotherapy has increased survival for non-small cell lung cancer (NSCLC), especially for those diagnosed with late-stage disease. However, it is not known if its use is equally distributed across races. We assessed immunotherapy use in 21 098 pathologically confirmed stage IV NSCLC patients according to race in the Surveillance Epidemiology, and End Results-Medicare linked dataset. Multivariable models were conducted to evaluate the independent association of receipt of immunotherapy with race and overall survival according to race. Black patients had statistically significantly lower odds of receiving immunotherapy (adjusted odds ratio = 0.60, 95% confidence interval = 0.44 to 0.80); receipt of immunotherapy was lower in Asian and Hispanic patients but not statistically significant. When immunotherapy was received, survival was similar across races. Immunotherapy for NSCLC is not used equally among races, underscoring the racial disparities that exist in access to the newest cancer treatment. Efforts should be directed toward expanding access to novel, efficacious treatments for advanced stage lung cancer.

Development and External Validation of Partial Proportional Odds Risk Prediction Models for Cancer Stage at Diagnosis among Males and Females in Canada.

Risk prediction models for cancer stage at diagnosis may identify individuals at higher risk of late-stage cancer diagnoses. Partial proportional odds risk prediction models for cancer stage at diagnosis for males and females were developed using data from Alberta's Tomorrow Project (ATP). Prediction models were validated on the British Columbia Generations Project (BCGP) cohort using discrimination and calibration measures. Among ATP males, older age at diagnosis was associated with an earlier stage at diagnosis, while full- or part-time employment, prostate-specific antigen testing, and former/current smoking were associated with a later stage at diagnosis. Among ATP females, mammogram and sigmoidoscopy or colonoscopy were associated with an earlier stage at diagnosis, while older age at diagnosis, number of pregnancies, and hysterectomy were associated with a later stage at diagnosis. On external validation, discrimination results were poor for both males and females while calibration results indicated that the models did not over- or under-fit to derivation data or over- or under-predict risk. Multiple factors associated with cancer stage at diagnosis were identified among ATP participants. While the prediction model calibration was acceptable, discrimination was poor when applied to BCGP data. Updating our models with additional predictors may help improve predictive performance.

The intention of utilization and experience toward traditional Chinese medicine among breast cancer patients in the early and late stages: a qualitative study

BackgroundIn Taiwan, breast cancer patients usually take conventional medicine and traditional Chinese medicine simultaneously. The utilization of traditional Chinese medicine among breast cancer patients at various stages has not been examined. This study aims to compare the intention of utilization and experience toward traditional Chinese medicine among early- and late-stage breast cancer patients.MethodThis qualitative research collected data from breast cancer patients through focus groups interview by convenience sampling. Conducted in 2 branches of Taipei City Hospital, a public hospital managed by the Taipei City government. Breast cancer patients > 20 years old and had used TCM for breast cancer therapy for at least 3 months were included in the interview. A semi-structured interview guide was adopted in each focus group interview. In the following data analysis, stages I and II were considered early-stage, and stages III and IV were late-stage. For analyzing the data and reporting the results, we used qualitative content analysis as the approach for data analysis, assisted by NVivo 12. Categories and subcategories were identified through content analysis.ResultsTwelve and seven early- and late-stage breast cancer patients were included in this study, respectively. The side effects were the main intention of utilizing traditional Chinese medicine. Improving side effects and constitution was the main benefit for patients in both stages. Additionally, early-stage breast cancer patients used traditional Chinese medicine to prevent recurrence or metastasis. Late-stage breast cancer patients responded more frequently to the use of traditional Chinese medicine due to the side effects of western medicine. However, some of their symptoms were not fully relieved.ConclusionsBreast cancer staging may influence the intention and utilization of traditional Chinese medicine. Health policymakers should consider the results of this research and the evidence-based illustrations to establish guidelines for integrating traditional Chinese medicine among various stages of breast cancer to improve the outcome and quality of care for cancer patients.

Clinical Presentation and Management of Malignant Psoas Syndrome: A Scoping Review of Case Reports and Case Series.

Malignant psoas syndrome (MPS) is a rare and underreported clinical syndrome that significantly impacts the quality of life of cancer patients throughmetastatic infiltration of the iliopsoas muscle. Patients suffering from MPS often present with painful hip flexion, loss of mobility, and immense pain in their legs and back. The current literature describing the clinical presentation, management, and prognosis of MPS is limited primarily to case reports and outdated literature reviews. There remains a gap in the current knowledge of MPS and in the management of this complex cancer-related pain syndrome. Thus, this scoping review aimed to map current case reports and case series on MPS for clinical presentation, treatment modalities, and resulting prognoses of MPS in late-stage cancer patients. A systemized search using the databases Embase and PubMed (Medline) was conducted to access case reports and case series published between January 1990 and October 2022 that met the study's inclusion criteria: (1) adult patients with metastatic cancer; (2) MPS symptoms secondary to infiltration of iliopsoas; (3) clinical presentation, treatment modality, and prognosis; and (4) English-language text. Our search strategy yielded 1926 citations. After removing 629 duplicates, 1,283 reports were excluded due to failure to meet eligibility criteria (n=1,271) or inaccessibility (n=12). Using the JBI appraisal tools for case reports and case series, a total of 14 articles remained for the final review. With histories of either genitourinary, hepatic, gastric, or skin cancer, each case reported new onset intense pain in the legs, back, abdomen, or pelvis with associated symptoms such as flexion of the hip or gait disorder. A computerized tomography (CT) scan, magnetic resonance imaging (MRI), orpositron emission tomography (PET) scantypically confirmed metastasis into the iliopsoas causing these symptoms, which suggested MPS. Each case utilized two to seven different pain management strategies to alleviate MPS symptoms. Many cases first used opioids for pain relief. Following a necessitated increase in morphine equivalent daily dose, a subsequent increase in the strength of analgesic, change in route of administration, and integration of combination drug therapy were generally added to the treatment regime. Many cases reported successful management of symptoms through utilizing methadone, radiation therapy, botulinum toxin injection, increased opioid dosage, or epidural catheter administration of opioids. A unified clinical definition of MPS may be required to inform physicians of this syndrome to help support clinical decisions regarding treatments for patients. The studies indicated that a clearer guideline for treatment protocol may be warranted as most cases reported utilizing various treatment medication dosages and procedures with vastly differing results.

Colon cancer epidemiology, race and socioeconomic status: Comparing trends in counties served by an urban hospital in Newark, NJ with overall NJ-state and nation-wide patterns

PurposeDisparities in colorectal cancer (CRC) trends are linked with socioeconomic status (SES) and race. To better understand the colon cancer trends at our medical center, this study characterizes the racial and socioeconomic profile of the population served by our center to identify modifiable risk factors amenable to interventions. MethodsColon cancer data from our center as well as New Jersey (NJ) and United States (US) were obtained from National Cancer Database. Demographic data on race and SES for NJ counties were obtained from public databases that sourced data from the American Community Survey and the US census. We compared the odds of being diagnosed with early-onset and late-stage colon cancer (III or IV), respectively in NJ and US, across different racial groups. We also quantified the association between Social Vulnerability Index (SVI) and age-adjusted CRC mortality in NJ counties, with and without accounting for the racial composition of each county. ResultsIn 2015, our center recorded higher proportions of late-stage and early-onset colon cancer diagnoses compared to all hospitals in NJ and US. Trends for stage and patient age at diagnosis of colon cancer for NJ and the US (2010–2019) showed that Black, Hispanic, and Asian/Pacific Islander individuals had greater odds of being diagnosed with early-onset (age<50) and late-stage colon cancer (Stage III/IV) when compared to White population. NJ counties served by our center showed an overrepresentation of either Black or Hispanic-Latino populations and reported significant disadvantage in SES. For NJ counties, each 25 percentile increase in social vulnerability was associated with 1.04 times the rate of age-adjusted colorectal cancer death (95 % CI: 1.00–1.07). ConclusionPublic data on race and SES of the target population can help identify areas of social disparities at the county-level to guide targeted interventions such as improving healthcare access and screening rates.

Utilization of Circulating Tumor DNA in the Surveillance Setting.

National guidelines give recommendations regarding cancer surveillance follow-up. In many early staged cancers radiographic imaging and labs are not routinely recommended unless patients are symptomatic. This can cause a gap in care because commonly when patients present symptomatically, they have progressed and transitioned to later-stage cancer. This study demonstrates how circulating tumor DNA (ctDNA) can be used alongside current guidelines to help screen patients for recurrence in the surveillance setting. A retrospective chart review was performed. Fifty-five charts were reviewed of patients who received ctDNA testing drawn in follow-up after their primary tumor or metastatic disease was rendered surgically or radiographically disease-free. A customized signature profile, using the sixteen most prevalent genomic markers from a patient's primary tumor or biopsy, is developed by whole-exome sequencing. Serial blood draws are then drawn to assess for specific DNA markers using polymerase chain reaction (PCR) assays. Fifty-five charts were reviewed in patients who had stage I-III breast, pancreatic, melanoma, and colorectal cancer. Of the fifty-five, a total of seven had a positive test. Of the seven positive tests, six patients were found to have recurrent/metastatic disease. One positive test was performed four weeks postoperatively but by the second draw ten weeks postoperatively had non-detectable ctDNA. The remaining forty-eight patients had non-detectable ctDNA levels and to date have not had any evidence of recurrence based on standard follow-up guidelines. The utilization of ctDNA in the surveillance setting can be used to help detect recurrence in the surveillance setting.

Radiomic signature accurately predicts the risk of metastatic dissemination in late-stage non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, and the median overall survival (OS) is approximately 2-3 years among patients with stage III disease. Furthermore, it is one of the deadliest types of cancer globally due to non-specific symptoms and the lack of a biomarker for early detection. The most important decision that clinicians need to make after a lung cancer diagnosis is the selection of a treatment schedule. This decision is based on, among others factors, the risk of developing metastasis. A cohort of 115 NSCLC patients treated using chemotherapy and radiotherapy (RT) with curative intent was retrospectively collated and included patients for whom positron emission tomography/computed tomography (PET/CT) images, acquired before RT, were available. The PET/CT images were used to compute radiomic features extracted from a region of interest (ROI), the primary tumor. Radiomic and clinical features were then classified to stratify the patients into short and long time to metastasis, and regression analysis was used to predict the risk of metastasis. Classification based on binarized metastasis-free survival (MFS) was applied with moderate success. Indeed, an accuracy of 0.73 was obtained for the selection of features based on the Wilcoxon test and logistic regression model. However, the Cox regression model for metastasis risk prediction performed very well, with a concordance index (C-index) score equal to 0.84. It is possible to accurately predict the risk of metastasis in NSCLC patients based on radiomic features. The results demonstrate the potential use of features extracted from cancer imaging in predicting the risk of metastasis.

Beyond traditional therapy: Mucoadhesive polymers as a new frontier in oral cancer management.

In recent times mucoadhesive drug delivery systems are gaining popularity in oral cancer. It is a malignancy with high global prevalence. Despite significant advances in cancer therapeutics, improving the prognosis of late-stage oral cancer remains challenging. Targeted therapy using mucoadhesive polymers can improve oral cancer patients' overall outcome by offering enhanced oral mucosa bioavailability, better drug distribution and tissue targeting, and minimizing systemic side effects. Mucoadhesive polymers can also be delivered via different formulations such as tablets, films, patches, gels, and nanoparticles. These polymers can deliver an array of medicines, making them an adaptable drug delivery approach. Drug delivery techniques based on these mucoadhesive polymers are gaining traction and have immense potential as a prospective treatment for late-stage oral cancer. This review examines leading research in mucoadhesive polymers and discusses their potential applications in treating oral cancer.

Hospital surgical volume and colorectal cancer survival in Norway: A nationwide cohort study

BackgroundStudies of hospital surgical volume and colorectal cancer survival are inconclusive. We investigated whether surgical volume was associated with survival of patients operated for colorectal cancer in Norway. MethodsUsing Cancer Registry of Norway data, we compared excess mortality from colorectal cancer by hospital surgical volume among 26,989 colon and 9779 rectal cancer patients diagnosed 2009–2020 and followed-up to 31.12.2021. Hospitals were divided into terciles according to their three-year average annual surgical volume; colon: low (< 22), middle (22–73), high (> 73); rectal: low (< 17), middle (17–38), high (> 38). We estimated excess hazard ratios (EHR) with flexible parametric models adjusted for age, year, stage, surgical urgency and surgery location (within/outside patient’s residential health trust). ResultsLow-volume hospitals had the highest proportion of late-stage or acutely operated colon cancer patients. Colon cancer patients operated at low- versus high-volume hospitals had significantly increased crude excess mortality (EHR = 1.30; 95 % CI = 1.14–1.48) but no difference after adjustment for age, year, and stage (EHR = 0.97; 0.85–1.11). High-volume hospitals had the highest proportion of late-stage rectal cancer patients and patients operated outside their residential area. Rectal cancer patients operated at low- versus high-volume hospitals did not have significantly different excess mortality before (EHR = 0.84; 0.64–1.10) or after (EHR = 1.03; 0.79–1.35) adjustment for age, year, stage, surgical urgency and surgery location. After accounting for case-mix, hospital surgical volume was not associated with excess mortality from colon (P = 0.40) or rectal cancer (P = 0.22). ConclusionLow hospital surgical volume was not associated with poorer colorectal cancer survival.

Prognostic value of absolute lymphocyte count in oral cavity squamous cell carcinoma.

Absolute lymphocyte count (ALC) has been shown to be a prognostic indicator in other solid tumors. Given this, we aimed to evaluate the prognostic value of ALC in oral cavity squamous cell carcinoma (OSCC). Using our institutional tumor registry data, we identified patients ≥18 years old who were diagnosed with OSCC between 2012 and 2018. Preoperative ALC values within 30 days of surgery were collected through retrospective chart review. American Joint Committee on Cancer, 7th-edition best stage was used to categorize cancers as early stage (stages 1 and 2) or late-stage (stages 3 and 4). Primary outcomes were likelihood of recurrence and survival rates after 3 years. Of the 412 patients identified, 262 patients had available ALC data and met inclusion criteria. Early stage cancer patients who had lymphopenia did not have any significant difference in their rate of death ([OR], 1.71, CI: 0.54-5.45, p = .36) or likelihood recurrence ([OR], 0.60, CI: 0.06-5.87, p = .66) after controlling for age, tobacco use, alcohol use, positive margins, and adjuvant therapy. Late-stage cancer patients who had lymphopenia also showed no difference in their rate of death ([OR], 2.74, CI: 0.65-11.6, p = .17) or likelihood of recurrence ([OR], 0.38, CI: 0.04-3.36, p = .38). This study evaluates the prognostic value of ALC in oral cavity cancers. Our findings demonstrate that pretreatment ALC is not significantly associated with recurrence and survival outcomes patients with OSCC. III. Absolute lymphocyte count (ALC) has been associated with prognosis in several cancers. We found that preoperative ALC was not associated with likelihood of survival or recurrence in patients with early stage or late-stage oral cavity cancer.

Diabetes and Prostate Cancer Outcomes in Men with Nonmetastatic Castration-Resistant Prostate Cancer: Results from the SEARCH Cohort.

The prognosis of diabetic men with advanced prostate cancer is poorly understood and understudied. Hence, we studied associations between diabetes and progression to metastases, prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) in men with nonmetastatic castration-resistant prostate cancer (nmCRPC). Data from men diagnosed with nmCRPC between 2000 and 2017 at 8 Veterans Affairs Health Care Centers were analyzed using Cox regression to determine HRs and 95% confidence intervals (CI) for associations between diabetes and outcomes. Men with diabetes were classified according to: (i) ICD-9/10 codes only, (ii) two HbA1c values > 6.4% (missing ICD-9/10 codes), and (iii) all diabetic men [(i) and (ii) combined]. Of 976 men (median age: 76 years), 304 (31%) had diabetes at nmCRPC diagnosis, of whom 51% had ICD-9/10 codes. During a median follow-up of 6.5 years, 613 men were diagnosed with metastases, and 482 PCSM and 741 ACM events occurred. In multivariable-adjusted models, ICD-9/10 code-identified diabetes was inversely associated with PCSM (HR, 0.67; 95% CI, 0.48-0.92) while diabetes identified by high HbA1c values (no ICD-9/10 codes) was associated with an increase in ACM (HR, 1.41; 95% CI, 1.16-1.72). Duration of diabetes, prior to CRPC diagnosis was inversely associated with PCSM among men identified by ICD-9/10 codes and/or HbA1c values (HR, 0.93; 95% CI, 0.88-0.98). In men with late-stage prostate cancer, ICD-9/10 'code-identified' diabetes is associated with better overall survival than 'undiagnosed' diabetes identified by high HbA1c values only. Our data suggest that better diabetes detection and management may improve survival in late-stage prostate cancer.

Histone H2A Lys130 acetylation epigenetically regulates androgen production in prostate cancer

The testicular androgen biosynthesis is well understood, however, how cancer cells gauge dwindling androgen to dexterously initiate its de novo synthesis remained elusive. We uncover dual-phosphorylated form of sterol regulatory element-binding protein 1 (SREBF1), pY673/951-SREBF1 that acts as an androgen sensor, and dissociates from androgen receptor (AR) in androgen deficient environment, followed by nuclear translocation. SREBF1 recruits KAT2A/GCN5 to deposit epigenetic marks, histone H2A Lys130-acetylation (H2A-K130ac) in SREBF1, reigniting de novo lipogenesis & steroidogenesis. Androgen prevents SREBF1 nuclear translocation, promoting T cell exhaustion. Nuclear SREBF1 and H2A-K130ac levels are significantly increased and directly correlated with late-stage prostate cancer, reversal of which sensitizes castration-resistant prostate cancer (CRPC) to androgen synthesis inhibitor, Abiraterone. Further, we identify a distinct CRPC lipid signature resembling lipid profile of prostate cancer in African American (AA) men. Overall, pY-SREBF1/H2A-K130ac signaling explains cancer sex bias and reveal synchronous inhibition of KAT2A and Tyr-kinases as an effective therapeutic strategy.

Withaferin A Increases the Effectiveness of Immune Checkpoint Blocker for the Treatment of Non-Small Cell Lung Cancer.

Treatment of late-stage lung cancers remains challenging with a five-year survival rate of 8%. Immune checkpoint blockers (ICBs) revolutionized the treatment of non-small cell lung cancer (NSCLC) by reactivating anti-tumor immunity. Despite achieving durable responses, ICBs are effective in only 20% of patients due to immune resistance. Therefore, synergistic combinatorial approaches that overcome immune resistance are currently under investigation. Herein, we studied the immunomodulatory role of Withaferin A (WFA)-a herbal compound-and its effectiveness in combination with an ICB for the treatment of NSCLC. Our in vitro results show that WFA induces immunogenic cell death (ICD) in NSCLC cell lines and increases expression of the programmed death ligand-1 (PD-L1). The administration of N-acetyl cysteine (NAC), a reactive oxygen species (ROS) scavenger, abrogated WFA-induced ICD and PD-L1 upregulation, suggesting the involvement of ROS in this process. Further, we found that a combination of WFA and α-PD-L1 significantly reduced tumor growth in an immunocompetent tumor model. Our results showed that WFA increases CD-8 T-cells and reduces immunosuppressive cells infiltrating the tumor microenvironment. Administration of NAC partially inhibited the anti-tumor response of the combination regimen. In conclusion, our results demonstrate that WFA sensitizes NSCLC to α-PD-L1 in part via activation of ROS.

Pragmatica-Lung Trial to Mimic "Real-World" Conditions.

The phase III randomized Pragmatica-Lung trial, comparing therapies for late-stage or recurrent non-small cell lung cancer, has eased eligibility criteria, simplified primary objectives, and limited data gathering requirements. Investigators hope that the design will speed accrual, expand patient eligibility and diversity, and ease administrative burdens.

Are we missing the beat in cancer end-of-life care: Prevalence and end-of-life monitoring of implantable cardioverter defibrillators in a population-based sample of older adults diagnosed with breast, colorectal, or pancreatic cancer.

e18728 Background: More than 50,000 implantable cardioverter defibrillators (ICDs) are placed in adults aged 65 years and older in the United States each year to manage cardiac arrhythmias. Shared risk profiles between many cancers and heart disease, as well as cardiotoxic effects of anti-cancer treatments suggest individuals with cancer are likely to have ICD devices. Although ICDs have been studied extensively in Europe, little is known about the US population, and even less is known in populations with cancer. ICDs have critical implications for end-of-life care in patients with cancer. Many patients do not include wishes for their ICD in their advanced directives, and end-of-life shocks can cause pain and distress for patients and their families. We evaluated prevalence and end-of-life monitoring of ICDs in a national sample of older adults who had breast, colorectal, or pancreatic cancer. Methods: We analyzed Surveillance, Epidemiology and End Results (SEER) data for first incident breast, colorectal, and pancreas cancer cases linked to Medicare claims (years 2004-2016) in Medicare-beneficiaries aged ³66 years. We evaluated the prevalence of ICDs by cancer stage at diagnosis with descriptive statistics. For patients with late-stage cancer (III or IV) who died in our study period we also evaluated the prevalence of ICD monitoring at the end of life. Because ICD deactivation is not a billable code, we evaluated ICD monitoring as a proxy for having an active device, hence an opportunity to discuss device deactivation. Results: In our sample of 286,015 individuals with cancer, 6.8% of patients had evidence of an ICD in their Medicare claims (6.1% breast, 8.2% colorectal, 5.3% pancreas). Of these, 49.7% had evidence of an ICD before their cancer diagnosis. The prevalence of ICDs was lower among the 60,046 individuals diagnosed with late-stage cancer( p&lt; .001) (5.0% breast, 6.1% colorectal, 4.5% pancreas). Among individuals with late-stage cancer and evidence of an ICD, 27.0% of those who died had ICD monitoring in the last six months of life (21.1% breast, 27.9% colorectal, 29.3% pancreas, p= .001), and 6.2% had monitoring in the last month of life (5.1% breast, 6.5% colorectal, 6.3% pancreas, p= .46). Conclusions: To improve the quality of care at the end-of-life for people with advanced cancer, awareness, communication, and shared decision making about ICD device management options are important considerations. These data suggest there may be opportunities to discuss prognosis and implications of advanced-stage cancer at device monitoring visits or during cardio-oncology visits.

PCR220 Symptom Burden in Late-Stage Breast Cancer Patients Treated with CDK Inhibitors Using the PRO-CTCAE

Cyclin-Dependent Kinase Inhibitors (CDKI) are an important advancement in the treatment of Metastatic Breast Cancer. Barriers to clinician adoption, such as tolerability concerns, may limit front line use. The objective of this study is to use electronic patient-reported outcome (ePRO) and remote symptom monitoring platform to evaluate symptom differences among late-stage breast cancer patients with and without CDKI treatment.

Demographic stratification, evaluation of symptoms burden on basis of gender, and implications of G8 questionnaires in elderly patients with cancer in Bangladesh.

12060 Background: Geriatric oncology is a new concept worldwide, as well as in Bangladesh. Presently, there is a scarcity of data regarding the geriatric perspective of malignant patients in Bangladesh. Our study investigated the demographic differentiation, evaluation of symptoms burden on the basis of gender, and implications of the G8 questionaries in elderly cancer patients from a tertiary cancer care center in Bangladesh. This will help physicians to understand cancer in the elderly better, integrate their biological and epidemiological characteristics, and promote a longer life expectancy without compromising their quality of life in resource-constrained regions. Methods: This study included all the newly diagnosed and histologically confirmed primary solid tumors among age ≥60 years at the National Institute of Cancer Research &amp; Hospital (NICRH), a tertiary care center in Bangladesh, during the year 2019 and 2020. For all statistical analyses, P&lt;0.05 was considered significant. Results: Of 8057 solid tumor patients, 2823 were geriatric patients (35.04%). Male dominant patients' mean BMI was 20.23 ±SD 4.26 and 35.4% were malnourished. The low SES was 63.7%i and 68.5% of patients were illiterate. Pain was the most common symptom (37.44%), followed by GI symptoms (31.77%), whereas 33.1% suffered from more than one symptom. in the disease distribution, lung cancer was 52.4% irrespective of sex, followed by GIT 17% and HBS cancer 10%. Breast 24.58% and GIT 17.77% were the second most common malignancy in females and males, respectively. Among them, 22.1% of patients were metastatic at presentation and 25% had a comorbid condition. About 17.4% of patients were completely disabled. Low BMI with high ECOG status had more symptoms (p=.004). Gender, nutrition and socioeconomic condition strongly correlated with the patient's functional status and symptomatic presentation. Females were more comorbid with symptomatic metastases at presentation (p=0.020), and males presented with late-stage cancer (p=0.002). Compared to male elderly patients, female elderly patients suffered more from malnutrition and obesity (p=&lt;.000). Polypharmacy rates for elderly males were lower than those for elderly females (p=0.000). Food intake behavior, weight loss, mobility, and health-related perception did not differ based on gender during or after treatment. Based on G8 scoring, we found that 12.3% were in the worse group, 70.2% in the intermediate group and the good group contained 17.5%. According to the cut-off value (≤11), 71.9% of patients needed the CGA evaluation. Conclusions: A high number of elder patients with multiple symptoms makes comprehensive management more challenging. A frail elderly patient's gender, SES, education, disease type, and stage along with performance status at the time of presentation of their disease are important prognostic factors.

Survivorship in patients with cardiac metastases defined by cardiac magnetic resonance imaging in relation to lesion hypoperfusion.

e24070 Background: Cardiac metastases (CMET) can occur in late-stage cancer, but limited data exists on prognostic implications in context of current day cancer care. Cardiac magnetic resonance imaging (CMR) provides a new, well validated, means to identify CMET in vivo, and assess magnitude of lesion vascularity – which can vary in relation to tumor etiology and be compromised with tumor necrosis. Survivorship in pts with CMET and modifying impact of lesion vascularity are unknown. Methods: The population comprised adult (≥18yo) pts with metastatic cancer derived from a dual site CMR registry, including pts with and without CMET on CMR. CMR was performed via a uniform protocol for which CMET was defined using established criteria as a cardiac mass with late gadolinium enhancement; lesion vascularity was measured on perfusion-CMR. Cancer type was categorized by pathological review and follow-up was performed for all-cause mortality. Results: 330 pts (59±15 yo; 55% M) were studied, inclusive of CMET and controls matched for cancer etiology/stage. Among pts with CMET, cancer etiology varied (sarcoma 24% | GI 18% | GU 13% | lymphoma 13% | lung 10% | skin/melanoma 7% |); cases and controls were similar with respect to age, sex, anti-cancer regimen, and cardiac function on CMR (all p = NS). Median duration of post-CMR follow-up was 19 months [IQR 11.9 – 43.6]; 92% had clinical follow-up ≥ 1 year or mortality within this interval, including an aggregate 1-year mortality in pts with CMET of 53% (43% in CMET - controls; p = 0.09). Among cancer categories, pts with lymphoma were at decreased risk for death (HR 0.44 [0.26 – 0.75], p = 0.002); risk was increased in pts with GI malignancies (1.63 [1.12 – 2.37], p = 0.01) or those treated with antimetabolites or kinase inhibitors (both p &lt; 0.05): Neither age, sex, cardiac risk factors nor function granted increased risk for death (all p = NS). Regarding Cmet tissue characteristics, decreased lesion perfusion conferred increased mortality risk irrespective of whether assessed as a continuous variable (HR 1.29 [1.08 – 1.56]) or via graded tertiles (HR 1.32 [1.05 – 1.66]) of hypoperfusion (both p &lt; 0.05). Decreased CMET perfusion conferred increased mortality risk (1.30 [1.03 – 1.64], p = 0.03) independent of cancer type or anticancer regimen. Conclusions: Among systemic cancer pts with CMET, survivorship varies and nearly half are alive ≥1 year post cardiac MRI diagnosis. Prognosis in pts with CMET varies inversely to lesion perfusion, with low vascularity lesions conferring increased mortality risk.[Table: see text]

Detection of early-stage cancers using circulating orphan non-coding RNAs in blood.

3051 Background: Orphan non-coding RNAs (oncRNAs) are a novel category of small RNAs (smRNAs) that are present in tumors and largely absent in healthy tissue. We investigated the utility of oncRNAs extracted from serum for early cancer detection across seven cancer types. Methods: We collected 2,882 serum samples from individuals with known cancers of the bladder ( n=152), breast (220), colon and rectum (141), kidney (283), lung (281), pancreas (287), and stomach (280) as well as donors with no history of cancer (1,238). We used 0.5 mL serum aliquots to generate and sequence smRNA libraries at an average depth of 20 million 50-bp single-end reads. Samples were split into age-, sex-, and smoking status-matched training (1,232 cancer; 922 control) and validation (412 cancer; 316 control) cohorts. A large catalog of oncRNAs specific to each cancer was created using tumor and adjacent normal samples from The Cancer Genome Atlas (TCGA) smRNA-seq database. Using TCGA-derived oncRNAs, we trained a machine learning model to predict cancer presence and tissue of origin (TOO) in a 5-fold cross validation setup using our training cohort. For the validation cohort, we averaged the predictions from the five training cohort models. Results: The model ROC-AUC for detecting cancer was 0.95 (95% CI: 0.94–0.95 for training and 0.94–0.97 for validation cohorts). Sensitivities for detecting cancer at 95% specificity were 0.74 (0.70–0.76) for early stage (I/II) and 0.80 (0.76–0.84) for late stage (III/IV) cancers in the training cohort, and 0.77 (0.71–0.81) and 0.81 (0.73–0.87) in the validation cohort. Sensitivities of detection for each cancer type are shown. For samples with cancer and TOO predictions, our top 1 and top 2 TOO accuracy was 0.76 (0.68–0.84) and 0.83 (0.76–0.90) for the validation set. Conclusions: These results demonstrate that oncRNAs detected in serum can be used for accurate, early detection, and localization of multiple cancers. [Table: see text]

PolyPEPI1018 vaccine in combination with TAS-102 in participants with late-stage microsatellite-stable metastatic colorectal cancer (MSS mCRC): A phase Ib study to evaluate safety, tolerability, immunogenicity and efficacy (OBERTO-201).

3595 Background: PolyPEPI1018 is an off-the-shelf, multi-peptide vaccine containing 12 immunogenic epitopes derived from 7 tumor-specific antigens frequently expressed in patients with mCRC. Following early evidence of clinical activity of PolyPEPI1018 in first-line MSS mCRC, here we report the results of a phase Ib study of PolyPEPI1018 vaccine plus trifluridine/tipiracil (TAS-102) in late-stage mCRC patients. Methods: Patients with MSS mCRC who have progressed on ≤2 lines of prior chemotherapy regimen for mCRC received PolyPEPI1018 subcutaneously on days 1 and 15 and TAS-102 orally twice daily on days 1-5 and 8-15 of a 28-day cycle. Treatment continued for up to 7 cycles, until disease progression or unacceptable toxicity. Immunomonitoring was performed at both blood and tumor levels prior to and on study treatment. The primary endpoint of the study was safety and tolerability. Data on objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and correlation studies will be presented. Results: 15 patients started treatment. Median age was 55 years (range 31–71), 73% had liver metastases (mets), 73% had KRAS mutant tumors. The most common side effect related to PolyPEPI1018 was Grade (Gr) 1-2 local skin reactions in 93% of patients. Gr 3 events (n = 15) at least possibly related to treatment were fatigue, decreased white blood cell, lymphocyte and neutrophil counts, nausea, diarrhea, myalgia, and maculo-papular rash. There were no Gr 4 or 5 events. The ORR was 0%. The DCR was 53.3% in the overall population and 36% and 100% for the patients with liver mets and without liver mets, respectively. The mPFS was 4 months (95%CI 2.2-6.1) in the overall population and 2.3 months (95%CI 2.1-NE) and 7.6 months (95%CI 4.4-NE) for the patients with liver mets and without liver mets, respectively (HR = 5.73 (95%CI 1.21, 27.06); p = 0.015). At the data cut-off date (Feb 10, 2023), the mOS was 8.7 months (95%CI 6.9-NE; not mature) in the overall population and it was not reached in patients without liver mets. Patients with increased PFS (≥ 24 weeks) had more robust vaccine-specific humoral and T cell responses induced by higher number of vaccine peptides than patients with PFS &lt; 24 weeks. Conclusions: To our knowledge, this is the first study investigating combination of a cancer vaccine with TAS-102 chemotherapy in advanced MSS mCRC. Our results show that PolyPEPI1018 plus TAS-102 was well-tolerated with few grade 3 AEs beyond what is expected with TAS-102 monotherapy. Despite no objective tumor responses could be detected, correlative data suggest contribution of PolyPEPI1018-induced immunological responses to the improved clinical benefit and the combination warrants further testing. Clinical trial information: NCT05130060 .