Months For Stage Research Articles

Colonic Adenosquamous Carcinoma: A Single-Center Review of Patient Clinicopathologic Characteristics, Genetics, and Clinical Outcomes.

(1) Background: Adenosquamous carcinoma (ASC) is a rare subtype of colon cancer. Its rarity makes characterization challenging, although colonic ASC is believed to present at more advanced stages and have worse outcomes versus adenocarcinoma. This study aims to characterize the clinicopathological characteristics and clinical outcomes of colonic ASC. (2) Methods: This is a single-center, retrospective review of patients diagnosed with colonic ASC from 2000 to 2020. Data extracted included patient demographics, staging at diagnosis, tumor clinicopathologic and genetic characteristics, and clinical outcomes. (3) Results: Among 61,126 patients with colorectal cancer, 13 (0.02%) had colonic ASC, with a mean age at diagnosis of 48.7 years. The cecum/ascending colon was the most common primary site (6/13, 46.2%), and all except one patient was diagnosed with Stage III or IV disease. Among the eight patients with mismatch repair genetics available, only one was mismatch repair deficient. Eleven patients (84.6%) underwent surgery, and 11 likewise received some form of chemotherapy. Recurrence occurred in 7 of 13 patients (53.8%), and the overall five-year survival rate was 38.5%. The median survival rate was 39.4 months overall (30.5 months for Stage III, 23.7 months for Stage IV). (4) Conclusions: Overall, colonic ASC is rare, and this cohort of colonic ASC patients demonstrated advanced stage at diagnosis, frequent recurrence, and poor overall survival. Additional research remains to compare these characteristics with those of comparably staged adenocarcinoma and to develop specific management recommendations.

Treating lung cancer in resource limited setting: Retrospective study from Armenia.

e20055 Background: Lung cancer (LC) is second most common cancer by incidence in Armenia. Every year approximately 800-900 new cases are diagnosed, from all cases 55.5% are in the 4th stage. Methods: We have collected data from three oncology centers in Armenia: Yeolyan Hematology and Oncology Center, Mikaelyan Institute of Surgery, and Muratsan Hospital Complex of Yerevan State Medical University. In this retrospective hospital-based study the data of patients with LC who were treated at these three centers during the 01 Oct 2009 - 31 Dec 2023 period was collected․ Results: Four hundred and eighty-nine LC patients were involved in the final analysis. Male to female ratio was 6:1. From the all patients 10.6% were diagnosed at age ≤ 50, 79,6% of patients 50-70, and 9.6% ≥ 70 years. In 71.6% of all cases, LC was diagnosed in current or former smokers. Only 3% of patients were diagnosed in stage I, 9.8% in stage II, 44.8% in stage III, 41.1% in stage IV, and for 1.2% of patients' stage was unknown. From all cases 74% of patients had non small cell lung cancer (NSCLC), 22.7% small cell lung cancer (SCLC) and 3.3% had other histological types of lung cancer. Of all patients 63% are dead. The median overall survival (mOS) for all stages was 21 months for the entire cohort. Median OS was not reached for stage I ( > 100 months), was 61 months for stage II, 23 months for stage III, and 13 months for stage IV (p < 0,001). ALK mutation was checked in 22.7%, EGFR in 22%,ROS in 14.1%, KRAS in 11.2%, BRAF in 9.8% and of all patients. From all checked AKL was positive in 1.8%, EGFR in 19.4%, ROS in 2.8%, KRAS in 21.8%, BRAF in 8,3% and of cases. For patients with stage IV lung cancer (41.1%), we found a significant difference in mOS in those who received first line immunotherapy in combination with chemotherapy (19,4%) compared to those who received only chemotherapy (74.1%) (mOS: 24 months vs 11 months accordingly, p = 0.014). For stage I-III LC patients, those who received systematic therapy with cisplatin showed better overall survival than those who received systemic therapy with carboplatin (mOS 31 vs 25 months, p = 0.01), but for stage IV LC patients survival difference was not found (mOS 15 vs 12 months, p = 0.24). Conclusions: In Armenia, lung cancer is mostly diagnosed in the advanced stage where overall survival is approximately one year. In our study population, those who received immunotherapy in combination with chemotherapy showed doubled mOS, compared with only chemotherapy. In the nonmetastatic group, chemotherapy with cisplatin showed a significant increase in mOS compared with carboplatin.

Lung cancer in females from nonsmoker families in India: Observations and inferences in 5 years.

e20610 Background: Incidence in lung cancer in last two decades has been changing drastically in terms of gender, age, smoking behaviour of patients, stage at presentation, histopathology, genetic abnormalities, operability at presentation and survival. More perplexing is the increase in its occurrence in females from non smoker families, mitigating the sole importance of the traditional risk factors of tobacco and smoking in the recent times. This highlights the need to investigate other risk factors like radon exposure from indoor pollution where females stay most of the time, exposure to arsenic and other chemicals in daily life, particle pollution, physical inactivity and inflammatory diseases of airways. Methods: It was an observational study of patients who were diagnosed and treated at a high volume cancer centre in Karnataka state of India. 89 never smoker female patients under 50 years of age from non smoker families with no obvious exposure to second hand or third hand smoke were enrolled from October, 2018 to June, 2023. It was a longitudinal prospective cohort study where the demographic data, symptoms with duration, histopathology including genetic abnormalities, treatment details and survival were noted. Results: 89 never smoker females from non smoker families with ages ranging from 36 to 50 years had a median age of 46 years. About 70% of the ladies were from houses closely associated with farm in past or present. 55% of them had overweight and obese body habitus. Most common presenting symptom was dry cough with median duration of about 3 months in about 89%. Other symptoms were pleuritic chest pain(39%), breathlessness (19%), generalized body ache(9%) and jaundice(2%). Stage of disease was IV(69%), IIIC(12.3%), IIIB(11.2%), IIIA(5.6%) and II in just one patient. Most common sites of metastasis were contralateral lung(45%), bone(20%), liver(20%), adrenal glands(10%) and brain (15%). Most common histopathology was adenocarcinoma(87.6%), adenosquamous carcinoma(7.8%), squamous cell carcinoma(3.3%), large cell neuroendocrine carcinoma in just one patient. EGFR was mutated in 56(62.9%) with deletion 19( 33%) and L858R(21%) being the most common abnormalities. ALK rearrangements and ROS1 fusion were seen in about 9(3.3%) and 3(3.3%) patients respectively. Surgery was done in only 3 patients and chemoradiation after neoadjuvant chemotherapy was given in 8(8.9%) patients. Median overall survival was about 42 months in stage IV patients. Conclusions: Changing demographic profile of lung cancer warrants more research into the other causes of lung cancer. More stage IV disease highlights the emphasis on prevention and screening for the disease.

Phase II trial of vaccination with autologous, irradiated melanoma cells engineered by adenoviral mediated gene transfer to secrete granulocyte-macrophage colony stimulating factor in patients with stage III and IV melanoma.

In the era of immune checkpoint blockade, the role of cancer vaccines in immune priming has provided additional potential for therapeutic improvements. Prior studies have demonstrated delayed type hypersensitivity and anti-tumor immunity with vaccines engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF). The safety, efficacy and anti-tumor immunity of GM-CSF secreting vaccine in patients with previously treated stage III or IV melanoma needs further investigation. In this phase II trial, excised lymph node metastases were processed to single cells, transduced with an adenoviral vector encoding GM-CSF, irradiated, and cryopreserved. Individual vaccines were composed of 1x106, 4x106, or 1x107 tumor cells, and were injected intradermally and subcutaneously at weekly and biweekly intervals. The primary endpoints were feasibility of producing vaccine in stage III patients and determining the proportion of patients alive at two years in stage IV patients. GM-CSF vaccine was successfully developed and administered in all 61 patients. Toxicities were restricted to grade 1-2 local skin reactions. The median OS for stage III patients (n = 20) was 71.1 (95% CI, 43.7 to NR) months and 14.9 (95%CI, 12.1 to 39.7) months for stage IV patients. The median PFS in stage III patients was 50.7 (95%CI, 36.3 to NR) months and 4.1 (95% CI, 3.0-6.3) months in stage IV patients. In the overall population, the disease control rate was 39.3% (95%CI, 27.1 to 52.7%). In stage III patients, higher pre-treatment plasma cytokine levels of MMP-1, TRAIL, CXCL-11, CXCL-13 were associated with improved PFS (p<0.05 for all). An increase in post-vaccination levels of IL-15 and TRAIL for stage III patients was associated with improved PFS (p=0.03 for both). Similarly, an increase in post-vaccination IL-16 level for stage IV patients was associated with improved PFS (p=0.02) and clinical benefit. Vaccination with autologous melanoma cells secreting GM-CSF augments antitumor immunity in stage III and IV patients with melanoma, is safe, and demonstrates disease control. Luminex data suggests that changes in inflammatory cytokines and immune cell infiltration promote tumor antigen presentation and subsequent tumor cell destruction. Additional investigation to administer this vaccine in combination with immune checkpoint inhibitors is needed.

Abstract 2488: The penile cancer tumor microenvironment and immunotherapy response: Results from the PERICLES trial

Abstract Introduction: The phase II PERICLES trial investigated the efficacy of atezolizumab (anti-PD-L1) for advanced penile cancer, with or without radiotherapy. As previously published, durable responses (progression-free at 12 months) were observed in 4 out of 32 enrolled patients. Here, we present the final overall survival (OS) results and an analysis of potential biomarkers for immunotherapy response. Methods: Preplanned analysis projected that at 27/32 events, the study would have 80% power (2-sided α=0.05) to assess whether the OS for the entire cohort significantly differed from the hypothesized historical median for stage IV patients. Baseline tumor tissue samples were subjected to bulk-RNA sequencing (n=31), fluorescent (n=28) and chromogenic (n=30) multiplex immunohistochemistry. We quantified the densities of CD3+CD8+ cytotoxic T-cells, CD3+CD8−FoxP3− T-helper cells, CD3+CD8−FoxP3+ regulatory T-cells, CD68+ macrophages and CD20+ B-cells in both the tumor and stromal compartments and assessed spatial relationships. We also quantified CD8+PD1+ (potentially enriched for tumor reactivity) and CD8+PD1− T-cells. Differential expression and gene set enrichment analysis (GSEA) were performed using the hallmarks gene sets. Results: The median OS for the entire study cohort was 11.3 months (95% CI, 5.5-16.7), which is an improvement compared to the hypothesized historical median of 7.8 months for stage IV patients (one sample log-rank p=0.033). Biomarker analyses showed an increased density of stromal macrophages (p&amp;lt;0.001) and intratumoral cytotoxic T-cells (p=0.035) in durable responders compared to non-responders. Additionally, we observed an increased density of intratumoral CD8+PD1+ in durable responders (p&amp;lt;0.001). In contrast, intratumoral CD8+PD1− densities were comparable between durable and non-responders (p=0.057). Patients with a high density of intratumoral CD8+PD1+ also had an improved progression-free survival (PFS) (log-rank, p&amp;lt;0.001) and OS (log-rank, p=0.002). Analysis of the spatial relationships in the tumor microenvironment (TME) showed that durable responders had larger distances between cytotoxic T-cells and T-helper cells (p=0.034). GSEA revealed significant (FDR≤5%) up-regulation of IFN-α/γ responses in durable responders. In contrast, non-responders showed up-regulation of epithelial-mesenchymal transition, KRAS signaling and angiogenesis, suggesting potential barriers to an anti-tumor response. Conclusion: In the final clinical analysis, OS was improved with atezolizumab compared to the historical population of stage IV patients. CD8+PD1+ T-cells, a common proxy for tumor-reactive T-cells, and spatial relationships in the TME might serve as biomarkers of durable response to immunotherapy in advanced penile cancer. Citation Format: Tynisha S. Rafael, Alberto Gil-Jimenez, Hielke M. de Vries, Iris M. Seignette, Elise Bekers, Marta Lopez-Yurda, Dennis Peters, Erik Hooijberg, Annegien Broeks, Oscar R. Brouwer, Eva Schaake, Daniel J. Vis, Tanja D. de Gruijl, Lodewyk F.A. Wessels, Michiel S. van der Heijden. The penile cancer tumor microenvironment and immunotherapy response: Results from the PERICLES trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2488.

Adrenocortical Cancer in the Real World: A Comprehensive Analysis of Clinical Features and Management from the Turkish Oncology Group (TOG)

IntroductionAdrenocortical carcinoma (ACC) is a rare yet highly malignant tumor associated with significant morbidity and mortality. This study aims to delineate the clinical features, survival patterns, and treatment modalities of ACC, providing insights into the disease's prognosis. Materials and MethodsA retrospective analysis of 157 ACC patients was performed to assess treatment methodologies, demographic patterns, pathological and clinical attributes, and laboratory results. The data were extracted from the hospital's database. Survival analyses were conducted using the Kaplan–Meier method, with univariate and multivariate analyses being performed through the log-rank test and Cox regression analyses. ResultsThe median age was 45, and 89.4% had symptoms at the time of diagnosis. The median tumor size was 12 cm. A total of 117 (79.6%) patients underwent surgery. A positive surgical border was detected in 26 (24.1%) patients. Adjuvant therapy was administered to 44.4% of patients. The median overall survival for the entire cohort was 44.3 months. Median OS was found to be 87.3 months (95% confidence interval [CI] 74.4-100.2) in stage 2, 25.8 (95% CI 6.5-45.1) months in stage 3, and 13.3 (95% CI 7.0-19.6) months in stage 4 disease. Cox regression analysis identified age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as significant factors associated with survival in patients with nonmetastatic disease. In metastatic disease, only patients who underwent surgery exhibited significantly improved overall survival in univariate analyses. ConclusionACC is an uncommon tumor with a generally poor prognosis. Understanding the defining prognostic factors in both localized and metastatic diseases is vital. This study underscores age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as key prognostic determinants for localized disease, offering critical insights into the complexities of ACC management and potential avenues for targeted therapeutic interventions.

The prognostic role of PD-L1 expression and the presence of polyomavirus in Merkel cell carcinoma cases

BackgroundMerkel cell carcinoma (MCC) comprises a rare malignant primary skin tumor presenting neuroendocrine differentiation. Recently, agents blocking the programmed cell death protein 1 and programmed cell death protein ligand 1 pathway (PD-1/PD-L1) have demonstrated objective and durable tumor regressions in patients presenting advanced MCC. This study aimed to describe the sociodemographic, clinical, and histopathological characteristics of MCC patients, also assessing the prevalence of PD-L1 expression and Merkel cell Polyomavirus (MCPyV), as well as their prognostic roles.MethodsData from patients diagnosed with MCC between 1996 and 2019 at a reference cancer center in Rio de Janeiro, southeastern Brazil, were evaluated in a retrospective study. Tumor samples were tested for MCPyV and PD-L1 employing immunohistochemistry. Survival analyses were carried out employing the Kaplan–Meier method and curves were compared using the log-rank test. A multiple semiparametric Cox model was used. Values p < 0.05 were considered significant.ResultsA total of 65 patients were included in the study, with a mean age at diagnosis of 72 (standard deviation 13.9). A total of 56.9% (37/65) of the patients were male, 86.2% (56/65) were white, and 56.9% (37/64) were illiterate or with incomplete elementary school. MCPyV immunohistochemistry was positive in 29 cases (44.6%) and PD-L1 positivity was ≥ 1% in 42 cases (64.6%). Significant associations between MCPyV and PD-L1 expression ≥ 1% (p = 0.003) and PD-L1 expression ≥ 5% (p = 0.005) were noted. Concerning the multivariate analysis, only education level and advanced MCC stage indicated statistically significant worse progression-free survival. Regarding overall survival (OS), being male, education level and advanced stage comprised risk factors. The estimated OS at 60 months for stages I to III was of 48.9% and for stage IV, 8.9%.ConclusionsThis is the first large Brazilian cohort to assess the prevalence of MCPyV in MCC tumors, as well as PD-L1 expression and their associations. No correlations were noted between MCPyV infection or PD-L1 expression and survival rates.

Abstract PR009: Discovery of covalent NRAS inhibitors targeting the Palmitoylation site through imaging-based high-throughput screening

Abstract NRAS mutations play a crucial role as oncogenic drivers of tumor cell growth and chemo-resistance in melanoma and acute myeloid leukemia (AML). In melanoma, NRAS mutations occur in approximately 25% of cases, and are generally mutually exclusive with BRAF-mutations. NRAS mutant tumors often exhibit an aggressive phenotype, such as thicker lesions, increased mitotic activity, and higher rates of lymph node metastasis. Surgical resection of NRAS mutant melanoma has a poor prognosis with a lower median overall survival (OS) compared to non-NRAS-mutant melanoma (8.2 vs. 15.1 months for stage IV disease). Current treatment strategies for stage III/IV non-resectable metastatic NRAS mutant melanoma include immunotherapy and indirect targeting of NRAS associated signaling pathways, highlighting the urgent need to develop small molecule NRAS inhibitors. NRAS palmitoylation is essential for its oncogenic function by regulating its trafficking and anchoring to the plasma membrane. Unlike other RAS isoforms, NRAS relies on a single palmitoylation site (C181) for its plasma membrane localization and this unique dependency makes NRAS more sensitive to palmitoylation inhibitors. To identify selective NRAS inhibitors that covalently modify C181 and prevent its palmitoylation, we employed an imaging-based NRAS translocation high-throughput screen using a library of 23,000 covalent molecules. We identified a set of covalent inhibitors that selectively target NRAS translocation but do not affect HRAS localization. We further confirmed the direct binding of these compound hits to NRAS at its palmitoylation site (C181) using intact mass spectrometry and chemo-proteomic peptide mapping techniques. Moreover, we validated the functional impact of these compound hits by demonstrating their selective inhibition of cell growth in mutant NRAS-driven melanoma cell lines. In conclusion, our study presents the first direct inhibitor for NRAS, discovered through a high-throughput covalent screening approach. This finding holds promising implications for the development of novel targeted therapies for NRAS mutant tumors. Citation Format: Zhao Wang, Keith Moore, Simon Ng, Chao Wang, Ronald Tomlinson, Huay-Keng Loke, Jamie Rice, Ivan Cornella. Discovery of covalent NRAS inhibitors targeting the Palmitoylation site through imaging-based high-throughput screening [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr PR009.

Is staging for cardiac damage in aortic stenosis associated with MACE in cancer patients with prior radiotherapy or chemotherapy that underwent transcatheter aortic valve replacement?

Abstract Background Staging classification for severe aortic stenosis (AS) based on the extent of cardiac damage has been correlated with outcomes in the general population. This is categorized based on the following echocardiographic findings: stage 1 (increase in the left ventricular mass index; E/e’&amp;gt;14; and left ventricular ejection fraction &amp;lt;50%); stage 2 (left atrial volume index &amp;gt;34ml/m2; moderate to severe mitral regurgitation and atrial fibrillation), stage 3 (systolic pulmonary hypertension&amp;gt; 60mmHg and moderate to severe tricuspid regurgitation) and stage 4 (moderate to severe right ventricular dysfunction); its applicability in a cancer population exposed to chemo+/- radiotherapy and its correlation with MACE has not been explored. Purpose To evaluate if this staging system predicts MACE (cardiovascular death, myocardial infarction, coronary revascularization, stroke, and hospitalization for heart failure) at 18 months after TAVR in cancer patients who were previously exposed to cardiotoxic therapies. Methods We retrieved data of patients that underwent TAVR from 2013 to 2021. 544 patients were included in this study and divided in 3 groups: 187 patients with prior chest Radiotherapy and Chemotherapy (RT/CT), 155 with CT only, and 202 cancer patients not exposed to CT or RT control group. This was further subdivided in two groups based on the staging system in: stage ≤ 2 and ≥3. Fisher's exact test or chi-square was used to compare categorical variables and clinical outcomes among groups and ANOVA for continuous variables. Echocardiographic findings and correlation with the outcome were evaluated by a multivariable Cox model analysis and assessed by a proportional hazards model for time to event. Kaplan–Meier curves were performed to determine the event-free survival rate. Significance was considered as a p&amp;lt;0.05. Results RT/CT had a higher prevalence of moderate to severe mitral regurgitation (11.8%) p &amp;lt;0.001 and tricuspid regurgitation (13.9%) p=0.02. Stage ≥3 was (24.1%) in the RT/CT, (9.4%) in CT, and (16.1%) in controls p= 0.004. Additionally, stage ≥3 was a predictor of MACE at 18 months: RT/CT group HR 6.43 (3.06 – 13.1) p&amp;lt;0.001, CT HR 4.49 CI (2.27 – 8.89) p&amp;lt;0.001 and control HR 2.20 CI (1.13 – 4.26) p=0.02 (Table 1). MACE at 18 months for stage ≥3 was higher for all groups vs. stage ≤ 2. MACE at 18 months after TAVR was significantly higher in stage &amp;gt;3 for RT/CT (57.4%) and CT only (61.2%) vs. CL (27.2%) p&amp;lt;0.001 (Figure 1B). Conclusions In addition to predicting aortic stenosis risk in cancer patients before TAVR, cardiac damage staging is a strong predictor of MACE at 18 months in patients post-RT/CT and CT and suggests that these patients may benefit from earlier stratification for TAVR prior to reaching stage 3. Future studies with longer follow-up should be explored to evaluate its usefulness in this complex population.

Impact of interventions to reduce racial disparities in receipt of breast cancer guideline-concordant treatment: A statewide simulation analysis.

160 Background: Inequities in the receipt of guideline-concordant treatment contribute to worse survival in Black breast cancer (BCa) patients. Inequity reduction interventions (e.g., navigation, bias training, and real-time treatment tracking) may close such treatment gaps. However, evidence to date has been derived from small-scale interventional studies, and the potential impact of these interventions on population-level disparities is unclear. The aim of this study was to simulate the effect of implementing inequity reduction interventions on observed racial inequities in treatment and downstream outcomes after BC diagnosis. Methods: We used data from the North Carolina (NC) Cancer Information and Population Health Resource - which links multi-payer claims to state cancer registry data, for women diagnosed with BCa in 2004-2017 - to calculate Black/non-Black inequities in the receipt of chemotherapy (CTx) within 4 months for women ages &lt;70 with hormone receptor-negative stage Ib-III BCa (n=2,223) and endocrine therapy (ET) within 12 months for stage I-III hormone receptor-positive BCa (n=16,220) in NC. Using effect estimates from trials of inequity-reducing interventions, we simulated the potential increase in the proportion of patients receiving CTx or ET if such interventions were implemented statewide. We estimated the effect of this potential increase in CTx and ET receipt on 10-year BCa mortality by building cohort-, race-, and treatment receipt-stratified simulation Markov models. We report confidence bounds representing 95% of simulation results. Results: Only 70.7% and 72.9% of Black patients in our cohorts received guideline-recommend ET and CTx, respectively, in 2004-2017 (versus 74.3 and 79.4% of non-Black patients, respectively; p&lt;.005). Statewide implementation of inequity reduction interventions could increase ET and CTx receipt among Black patients to 84.3% (79.1-89.3%) and 86.8% (81.5-91.9%), respectively. This would be expected to reduce 10-year BCa mortality among Black patients from 14.2% to 13.6% (13.3-13.9%) in the ET cohort and from 29.4% to 28.7% (28.3-29.1%) in the CTx group. As a result, the racial mortality gap would decrease from 5.7 to 5.2 (4.9-5.5) from 7.0 to 6.6 (6.2-6.9) in the CTx cohorts, respectively. Conclusions: Implementation of interventions designed to reduce treatment inequities are likely to improve cancer care equity. However, increases intreatment receipt alone will not close the BCa mortality gap. Inequities at other points on the cancer continuum, such as in pre-diagnostic risk factors, screening, diagnostic work-up, and post-treatment factors, may explain residual gaps which will require more comprehensive interventions to achieve full equity in breast cancer outcomes.

Symptom Clusters and Quality of Life among Women Living with Cancer

The prevalence of cancer in Indonesia has increased and is one of the biggest causes of death. Symptom clusters, a collection of symptoms in cancer patients that appear together and are related to one another, can affect the quality of life of cancer patients. This study aims to identify the relationship between symptom clusters and the quality of life of advanced cancer patients. This research used cross-sectional quantitative survey data from a cancer patient care unit at a referral hospital in West Java Province with a total of 140 respondents. Consecutive sampling was conducted for three months in stage III or IV cancer patients who were undergoing therapy. This study used descriptive analysis, factor analysis with the Principal Components Analysis (PCA) approach, and multiple linear regression analysis. Five symptom clusters were identified: the psychological cluster, the gastrointestinal cluster, the numbness cluster, the pain cluster, and the respiratory distress cluster. The results showed that symptom clusters influence the quality-of-life dimension. The symptom clusters’ coefficient of determination (R2) for the physical dimension was 0.231 (weak), the role dimension was 0.191 (very weak), the emotional dimension was 0.484 (moderate), the cognitive dimension was 0.011 (very weak), the social dimension was 0.420 (moderate), and the general-health dimension was 0.202 (weak).

Programmed Cell Death Protein 1 Inhibitors and MET Targeted Therapies in NSCLC With MET Exon 14 Skipping Mutations: Efficacy and Toxicity as Sequential Therapies

IntroductionNSCLC with MET exon 14 skipping mutation (METex14) is associated with poor outcomes. Integration of novel targeted therapies is challenging because of barriers in testing and drug access. We, therefore, sought to characterize the treatment patterns, outcomes, and emerging issues of treatment sequencing in patients with METex14-mutant NSCLC. MethodsWe reviewed all NSCLC cases with METex14 alterations between 2014 and 2020 across four Canadian cancer centers. Demographics, disease characteristics, systemic therapy, overall response rates (ORRs), survival, and toxicity were summarized. ResultsAmong 64 patients with METex14-mutant NSCLC, the median overall survival was 23.1 months: 127.0 months in stage 1, 27.3 months in resected stage 2 and 3, and 16.6 months in unresectable stage 3 or 4 disease, respectively. In patients with advanced disease, 22% were too unwell for systemic treatment. MET tyrosine kinase inhibitors (TKIs) were administered to 28 patients with an ORR of 33%, median progression-free survival of 2.7 months, and 3.8 months for selective TKIs. Programmed cell death protein-1 (PD-1) inhibitors were given to 25 patients—the ORR was 44% and progression-free survival was 10.6 months. No responses were seen with subsequent MET TKIs after initial TKI treatment. Grade 3 or higher toxicities occurred in 64% of patients who received MET TKI after PD-1 inhibitors versus 8% in those who did not receive PD-1 inhibitors. ConclusionsMany patients with advanced METex14 NSCLC were too unwell to receive treatment. PD-1 inhibitors seem effective as an initial treatment, although greater toxicity was seen with subsequent MET TKIs. Thus, timely testing for METex14 skipping and initial therapy are imperative to improving patient survival.

Combination of Interferons for Advanced Renal Cell Carcinoma

Introduction: A novel formulation that combines IFN alpha-2b and gamma evidenced effectivity in cancer treatment. The poor prognosis of advanced renal cancer needs new therapeutic approaches. A retrospective study was carried out evaluating the effectivity and safety of interferon’s combination in patients with advanced renal cell carcinoma. Methods: Retrospective case-control and cohort analyzes were performed, carried out to identify patients with advanced or metastatic kidney tumors treated from May 2009 to December 2021 in a Cuban healthcare center. Patients with advanced renal cell carcinoma received a combination of IFN alpha-2b/gamma. Heberon Alpha R was used as historical control. The study was approved by the Ethics Committee and informed consent was obtained for participating patients. Results: 56 patients were included. The combination of IFNs (experimental group) and the Heberon Alpha R (historical control group) were comparable. Overall survival in stage III disease was 101.3 months with combination of IFNs versus 38.1 in Heberon Alpha R, and 70.4 months versus 30.6 months in stage IV patients. The functional capacity of patients from experimental group was higher than those from control and reached more than 75%, with favorable functional capacity at 24 months; while more than 65% of patients in the control cursed with worse capacity. No serious adverse events with proven causality occurred within the cohort of patients treated with interferon combination. The events correspond to those reported in other studies.

Treatment and outcomes of pancreatic cancer in Armenia: Hospital-based study.

e16251 Background: Pancreatic cancer is one of the deadliest cancers in the world. In Armenia, pancreatic cancer is on the 12th place by incidence. The aim of this study is to evaluate treatment and outcomes of pancreatic cancer in Armenia during the last 12 years. Methods: For this retrospective hospital-based study we have collected data from three oncology centers in Armenia: “Muratsan” Hospital of Yerevan State Medical University, “Miqaelyan institute of surgery” and “Hematology center after prof. Yeolyan”. The information about patients with pancreatic cancer who were treated at these centers during 01/01/2010 - 01/01/2022 period was collected from the medical records. Log- rank test and Kaplan-Meier curves were used for survival analysis. Cox regression analysis was done for identification of main prognostic factors. Results: 70 patients with pancreatic cancer were involved in the final analysis. From them 44.3% were female. Median age at diagnosis was 63 years. Median follow up time was 10,5 months (range 2-146). 11,4% of patients had stage I-II, 27,1% stage III, 58,6% stage IV cancer. The main independent prognostic factor for overall survival (OS) was tumor grade, while TNM stage was not significant. 23% of patients were alive before study end date. Median OS was 12 months (range 2-146 months). Median overall survival was 35 months in stage I-II, 11 months in stage III and 11 months in stage IV. In stage I-III pancreatic cancer patients, those who had undergone surgery (44.4%) lived significantly longer (35 vs 11 months, p=0.011). 38.6% of patients received chemotherapy with Gemcitabine plus Capecitabine regimen, while 41.4% with FOLFIRINOX regimen. No significant difference in survival was found between these groups (11 vs 13 months, p=0.35). Conclusions: As our results has shown survival of pancreatic cancer patients in Armenia is dismal, not exceeding 1 year. Hopefully further research in the field and new treatment modalities will improve the situation.

Outcome analysis of immunotherapy and possible prognostic role of pretreatment neutrophil-lymphocyte ratio in lung cancer: An Appalachian study.

e21053 Background: Immune checkpoint inhibitors (ICI) have revolutionized the treatment of lung cancer resulting in better survival benefits. We are reporting outcome analysis of lung cancer patients treated with ICI in our institution. Methods: We performed retrospective chart review of lung cancer patients treated with ICI at our institution between June 2016 and March 2022. Results: A total of 289 patients were identified- 241 had non-small cell lung cancer (NSCLC) and 48 had small cell lung cancer (SCLC). A total of 109 patients (37.7%) developed immunotherapy related adverse events (IRAE): 92 (38.1%) with NSCLC and 17 (35.4%) with SCLC. Average time to develop IRAE was 3 months in both NSCLC and SCLC. IRAE grades 1,2,3,4 were noted in 33%, 20%, 15%, 31% patients respectively. 34 of 63 (53%) patients who received Ipilimumab-Nivolumab developed more IRAE than any other ICI with fatigue and dermatitis being the most common IRAE associated with this ICI. 79 of 183 (43%) patients who received RT developed IRAE (p = 0.012). Median overall survival (OS) for NSCLC was 35 months, 41 months, 27 months, 15 months for stages 1,2,3,4, respectively (p = 0.03). Median OS for extensive stage SCLC was 14.6 months. Median OS for NSCLC with and without IRAE was 30 and 23 months, respectively (p = 0.02). Median OS for SCLC with and without IRAE was 16.7 and 16.2 months, respectively (p = 0.5). Median OS for NSCLC when steroids were used to treat IRAE was 25 months, and 63 months if no steroids were used (p = 0.027). Better median overall survival rate was noted in patients with low Neutrophil-Lymphocyte ratio (defined as NLR &lt; 5) 29.23 months vs 20.59 months (high NLR) (p = 0.019). Although demographics like male sex, smoking history, higher BMI and poor ECOG performance status had numerically increased the risk of developing IRAE, no statistical significance was noted. Conclusions: Overall results of our analysis are mostly consistent with the current literature on survival rates in Lung Cancer. IRAE may have a predictive role in survival, as we observed that patients with NSCLC developing IRAE had better survival rates. Ipilimumab-Nivolumab combination resulted in more IRAE than any other ICI. Pneumonitis was the most common IRAE among all patients receiving ICI. Also, Radiation-therapy increased the risk of developing IRAE. Our observation that steroid use in treating IRAE was associated with lower survival is concerning. This may be due to higher grade IRAE/toxicities and possible decreased ICI effectiveness. Regardless of IRAE, low pretreatment NLR resulted in better survival rates. The role of pretreatment NLR as a potential prognostic tool to assess survival outcomes requires validation in a randomized clinical trial.

CINOVA: a phase II study of CPC634 (nanoparticulate docetaxel) in patients with platinum resistant recurrent ovarian cancer

ObjectiveRecurrent platinum-resistant ovarian cancer has a poor prognosis with limited therapeutic options. Sub‐therapeutic intra-tumoral drug concentrations may add to therapy resistance. CPC634 (docetaxel entrapped in CriPec nanoparticles) was designed to...

Long-term Follow-up Results of Idiopathic Epiretinal Membrane Removal in the Eyes with Ectopic Inner Foveal Retinal Layers.

The purpose of this study was to evaluate pre- and perioperative factors related to time for the evolution of ectopic inner foveal layers (EIFL) following pars plana vitrectomy (PPV) for epiretinal membrane (ERM) peeling. This retrospective study included 81 consecutive eyes with idiopathic ERM that underwent vitrectomy surgery. Standard PPV + internal limiting membrane peeling was performed in all cases. A comprehensive ophthalmic examination was performed for all patients before and 1, 3, 6, and 12 months, and the last follow-up after surgery. We observed the postoperative improvement in EIFL severity in the short-term and longest follow-up and evaluated anatomical and functional improvement. Several parameters were assessed using the multivariate COX proportional hazard analysis. Eighty patients (81 eyes) with a mean age of 70.33 ± 7.75 years were followed for a mean of 34.37 ± 23.61 months, and 55.5% of eyes (45 eyes) with EIFL ERM showed improvement of foveal contour to a better stage at the last follow-up. The median estimated time for evolving to a better stage was 29.73 months for stage 2, 49.68 months for stage 3, and 38.67 months for stage 4 (P = 0.001, log-rank test). The severity of EIFL was the only significant factor for time to evolution of EIFL ERM to a better stage, where the eyes with stage 4 EIFL ERM showed faster foveal contour improvement compared to those with stage 3 EIFL ERM (hazard ratio: 0.317, 95% confidence interval = 0.164-0.615, P = 0.001). On assessing preoperative factors, the preoperative EIFL stage emerged as the sole significant factor for EIFL ERM improvement to a better disease stage. This study reports some of the longest follow-up durations for patients undergoing PPV for EIFL ERM, and both functional and anatomical improvements were observed across all stages of EIFL, including in the advanced stage 4 EIFL ERM.

Advances in exosome research in the management of lung cancer.

Lung cancer is one of the most common malignant tumors, and its death rate is much higher than that of colon, kidney, breast, and prostate cancers, and its 5-year survival rate is only 18%. Lung cancer has no specific clinical symptoms in its early stages and lacks effective detection, making early detection difficult. The survival rate for advanced lung cancer is meager, with a median survival of only 12 months for stage IIIB/IV non-small cell lung cancer treated with platinumbased chemotherapy. Exosomes could provide vital information for the early diagnosis of lung cancer and have the potential to become a tumor marker for lung cancer. In addition, scientists have proposed encouraging ways to treat lung cancer by loading drugs, proteins, microRNAs, and siRNAs into exosomes. Therefore, studying lung cancer exosomes and exosomal nano drugs will provide new ideas and approaches for the diagnosis and treatment of lung cancer. This paper reviews the progress of research on the biological functions of exosomes and exosomal nanomedicines and their applications in clinical practice.

Factors associated with the survival outcomes of patients with untreated hepatocellular carcinoma: An analysis of nationwide data.

In this study, we examined the natural course of untreated hepatocellular carcinoma (HCC) and identified predictors of survival in an area where hepatitis B is the predominant cause of HCC. We identified 1,045 patients with HCC who did not receive HCC treatment and were registered in the Korean Primary Liver Cancer Registry between 2008 and 2014, and were followed-up up to December 2018. Thereafter, we analyzed the clinical characteristics of patients who survived for <12 or ≥12 months. A Cox proportional regression model was used to identify the variables associated with patient survival. The mean age of the untreated patients at HCC diagnosis was 59.6 years, and 52.1% of patients had hepatitis B. Most untreated patients (94.2%) died during the observation period. The median survival times for each Barcelona Clinic Liver Cancer (BCLC) stage were as follows: 31.0 months for stage 0/A (n = 123), 10.0 months for stage B (n = 96), 3.0 months for stage C (n = 599), and 1.0 month for stage D (n = 227). Multivariate Cox regression analysis demonstrated that BCLC stage D (hazard ratio, 4.282; P < 0.001), model for end-stage liver disease (MELD) score ≥10 (HR, 1.484; P < 0.001), and serum alpha-fetoprotein (AFP) level ≥1,000 ng/mL (HR, 1.506; P < 0.001) were associated with poor survival outcomes in patients with untreated HCC. In untreated patients with HCC, advanced stage BCLC, serum AFP level ≥1,000 ng/mL, and MELD score ≥10 were significantly associated with overall survival.

SJLA_2024_A8: Clinical and Survival Patterns of Pulmonary Metastases in Colorectal Cancer Patients

Background: Pulmonary metastasis (PM) from colorectal cancer (CRC) is a rare and incompletely understood entity which affects 10% of CRC patients. The 5-year overall survival (OS) of Stage IV CRC is 11.3% and in pulmonary metastatectomy range from 40% to 69.7%. This study aims to evaluate the overall 5-year survival of PM from CRC and identify potential independent risk factors affecting the OS. Methods: A retrospective study was conducted in a tertiary care center (Royal Hospital). The study included all patients diagnosed with Stage IV CRC with PM aged &gt;18 years between 2008 and 2015. Patients with no follow-up and missed data were excluded. Data were retrieved from the electronic record system (Al-Shifaa) and analyzed using SPSS software. Results: The prevalence of PM in the overall CRC cases was 15.2% (84/554 patients). Seventy-one patients were included in this study after the application of exclusion criteria with the mean age of patients was 60.35 ± 16.4 years; majority male gender 64.8% (46) and most of them with no comorbidities 57.7% (42). The most common location of primary tumor is sigmoid 31% (22) and diagnosed with T3 40.8% (29) status and N2 32.4% (23) status with high CEA &gt; 5 at presentation and diagnosis. The majority of cases presented with synchronous PM 74.6% (53) and following metastasis features bilateral lung side 69.0% (49), =&gt;10 nodules 42.3% (30), &lt;1 cm size 66.2% (47), and no lymph involvement 57.7% (41). Five-year OS rate is 15.3%, and the median OS time is 15 months. There was a statistically significant difference in the OS distribution between those who received surgery and those who did not receive surgery (Log-rank test, P = 0.004) and 5-year OS rate in the surgical group is 55.6% versus 8.3% in nonsurgical. Median survival time was 71 months versus 13 months, respectively. Several factors were found to be associated with a favorable OS, which include the middle age group (P = 0.007), absence of perineural invasion (P = 0.015), and isolated PM (P = 0.003). In addition, multivariate Cox regression showed OS relatively poor in females (P0.001), metachronous (0.003), T4 (0.005), and normal CEA at diagnosis (0.011). Conclusion: The present study showed 5-year OS rate is 15.3%, and the median OS time is 15 months for Stage IV CRC with pulmonary metastasis. Surgical management, middle age group (40–59 years), absence of perineural invasion, and isolated pulmonary metastasis at diagnosis may be associated with improved survival. Female gender, tumor status T4, Carcinoembryonic &lt;=5 at diagnosis, and metachronous lung mts were associated with poorer survival outcomes. Despite the study’s limitations of retrospective design with a small sample size, the results can be considered as part of MDT-based decision-making. These findings will require future large multicenter studies.