Significant Difference In Median Overall Survival Research Articles

Effects of brain radiotherapy strategies on survival in the era of MRI for patients with limited stage small cell lung cancer

Background and purposeIn the context of the widespread availability of magnetic resonance imaging (MRI) and aggressive salvage irradiation techniques, there has been controversy surrounding the use of prophylactic cranial irradiation (PCI) for small-cell lung cancer (SCLC) patients. This study aimed to explore whether regular brain MRI plus salvage brain irradiation (SBI) is not inferior to PCI in patients with limited-stage SCLC (LS-SCLC).MethodsThis real-world multicenter study, which was conducted between January 2014 and September 2020 at three general hospitals, involved patients with LS-SCLC who had a good response to initial chemoradiotherapy and no brain metastasis confirmed by MRI. Overall survival (OS) was compared between patients who did not receive PCI for various reasons but chose regular MRI surveillance and followed salvage brain irradiation (SBI) when brain metastasis was detected and patients who received PCI.Results120 patients met the inclusion criteria. 55 patients received regular brain MRI plus SBI (SBI group) and 65 patients received PCI (PCI group). There was no statistically significant difference in median OS between the two groups (27.14 versus 33.00 months; P = 0.18). In the SBI group, 32 patients underwent whole brain radiotherapy and 23 patients underwent whole brain radiotherapy + simultaneous integrated boost. On multivariate analysis, only extracranial metastasis was independently associated with poor OS in the SBI group.ConclusionThe results of this real-world study showed that MRI surveillance plus SBI is not inferior to PCI in OS for LS-SCLC patients who had a good response to initial chemoradiotherapy.

Survival of patients with lymph node versusbone versus visceral metastases according to CHAARTED/LATITUDE criteria in the era of intensified combination therapies for metastatic hormone-sensitive prostate cancer.

The first approvals of novel systemic therapies within recent years for metastatic hormone-sensitive (mHSPC) were mainly based on improved overall survival (OS) and time to castration resistance (ttCRPC) in mHSPC patients stratified according to CHAARTED low (LV) versus high volume (HV) and LATITUDE low (LR) versus high-risk (HR) disease. Relying on our institutional tertiary-care database we identified all mHSPC stratified according to CHAARTED LV versus HV, LATITUDE LR versus HR and the location of the metastatic spread (lymph nodes (M1a) versus bone (M1b) versus visceral/others (M1c) metastases. OS and ttCRPC analyses, as well as Cox regression models were performed according to different metastatic categories. Of 451 mHSPC, 14% versus 27% versus 48% versus 12% were classified as M1a LV versus M1b LV versus M1b HV versus M1c HV with significant differences in median OS: 95 versus 64 versus 50 versus 46 months (p < 0.001). In multivariable Cox regression models HV M1b (Hazard Ratio: 2.4, p = 0.03) and HV M1c (Hazard Ratio: 3.3, p < 0.01) harbored significant worse than M1a LV mHSPC. After stratification according to LATITUDE criteria, also significant differences between M1a LR versus M1b LR versus M1b HR versus M1c HR mHSPC patients were observed (p < 0.01) with M1b HR (Hazard Ratio: 2.7, p = 0.03) and M1c HR (Hazard Ratio: 3.5, p < 0.01), as predictor for worse OS. In comparison between HV M1b and HV M1c, as well as HR M1b versus HR M1c no differences in ttCRPC or OS were observed. Significant differences exist between different metastatic patterns of HV and LV and HR and LR criteria. Best prognosis is observed within M1a LV and LR mHSPC patients.

The association between proton-pump inhibitor use and recurrence of hepatocellular carcinoma after hepatectomy.

The association between long-term proton-pump inhibitors (PPIs) use and malignancies had long been discussed, but it still lacks consensus. Our study investigated the association between PPI use and hepatocellular carcinoma (HCC) recurrence following curative surgery. We retrospectively enrolled 6037 patients with HCC who underwent hepatectomy. Patients were divided into four groups according to their PPI usage. (non-users: <28 cumulative defined daily dose [cDDD]; short-term users: 28-89 cDDD; mid-term users: 90-179 cDDD, and long-term users: ≥180 cDDD, respectively). Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Kaplan-Meier method and Cox proportional hazard models. Among the 6037 HCC patients, 2043 (33.84%) were PPI users. PPI users demonstrated better median RFS (3.10years, interquartile range [IQR] 1.49-5.01) compared with non-users (2.73years, IQR 1.20-4.74; with an adjusted hazard ratio [aHR] of 0.57, 95% confidence interval [CI] 0.44-0.74, P<0.001). When considering the cumulative dosage of PPI, only long-term PPI users had significant lower risk of HCC recurrence than non-PPI group (adj-HR: 0.50; 95% CI: 0.35-0.70; P<0.001). Moreover, the impact of long-term PPIs use on improving RFS was significant in most of the subgroup analysis, except in patients with advanced tumor stages, with non-cirrhosis, or with a history of chronic kidney disease. However, there were no significant differences in median OS between PPI users and non-users (4.23years, IQR 2.73-5.86 vs 4.04years, IQR 2.51-5.82, P=0.369). Long-term PPI use (≥180 cDDD) may be associated with a better RFS in HCC patients after hepatectomy.

Clinical features and outcomes of patients with breast cancer with leptomeningeal carcinomatosis.

e13162 Background: Leptomeningeal carcinomatosis (LMC) is a rare, but deadly complication in breast cancer, with prior studies showing median overall survival (OS) of 15 weeks. There is a paucity of data on histologic and receptor subtype-specific survival, and there is no standard of care currently for treatment of LMC in breast cancer. We reviewed the outcomes of a contemporary cohort of breast cancer patients (pts) with LMC. Methods: This is a single-institution retrospective analysis of 38 female breast cancer pts diagnosed with LMC between 2016-2023, based on radiographic features and/or positive cerebrospinal fluid (CSF) cytology or CSF circulating tumor cells (CTCs). Patients consented to share information with a research biorepository, and we conducted a chart review of their clinical features and OS with LMC. Results: 25 pts (65.8%) had invasive ductal carcinoma (IDC), 7 pts (18.4%) had invasive lobular carcinoma (ILC), 4 (10.5%) had metaplastic carcinoma, and 2 (5.3%) had mixed IDC/ILC. 22 pts (57.9%) had triple-negative breast cancer (TNBC), 12 (31.6%) had estrogen receptor positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-), and 4 (10.5%) had HER2+ disease. Median age at LMC diagnosis was 50 years. Median time between Stage IV and LMC diagnosis was 11 months. Pts received a median of 2 lines of systemic therapy for metastatic disease prior to LMC diagnosis. 11 pts (28.9%) had parenchymal brain metastasis prior to LMC diagnosis. 32 pts (84.2%) had signs of LMC on Magnetic Resonance Imaging of the brain and/or spine at diagnosis. 25 pts underwent CSF cytology and 13 pts underwent CSF CTC evaluation at LMC diagnosis; 14/25 pts (56%) had positive CSF cytology and 10/13 pts (76.9%) had detectable CSF CTCs. 21 pts (55.3%) underwent whole-brain radiotherapy, and 2 pts (5.3%) received proton craniospinal irradiation. 21 pts (55.3%) received IT therapy. 27 pts (71.1%) received at least 1 line of systemic therapy post-LMC diagnosis. Median OS between LMC diagnosis and death or last oncology follow up for the entire cohort was 5 months (range 0-57 months, 95% CI 3.0-8.0). There was a significant difference in median OS with LMC by receptor subtype: TNBC 3.5 months, ER+/HER2- 8 months, and HER2+ 23 months (p=0.0047). Two HER2+ pts survived ≥ 3 years post-LMC diagnosis with anti-HER2 antibody-drug conjugates and tyrosine kinase inhibitors +/- stereotactic radiosurgery (SRS) to parenchymal brain metastases. Amongst 9 pts with ER+/HER2-low disease, longer survival with LMC (≥ 16 months) was observed with trastuzumab deruxtecan, IT topotecan +/- IT trastuzumab, and SRS to parenchymal brain metastases. Conclusions: This study highlights heterogeneity in outcomes amongst breast cancer pts with LMC by receptor subtype, as well as improvement in outcomes for selected pts treated with novel therapeutics and a multidisciplinary approach. Larger prospective studies are needed to inform treatment paradigms for LMC.

Predictors of endocrine immune-related adverse events (irAEs) in patients treated with immune checkpoint inhibitors (ICI) in routine clinical practice.

e14713 Background: Endocrine irAEs have been reported in association with various ICI and are characterized by their correlation with improved survival outcomes. A growing clinical comprehension of endocrine irAEs has facilitated the development of effective treatment strategies involving hormone replacement, which has been shown to enhance patients' quality of life. This study aims to evaluate outcomes in patients (pts) experiencing endocrine irAEs and identify predictive factors for their occurrence. Methods: This retrospective cohort study comprised 214 adult pts with solid malignant tumors who underwent ICI, either as monotherapy or in combination with other chemotherapeutic agents, at the SBIH Moscow Clinical Scientific and Practical Center named after A.S. Loginov of DHM. Results: Between June 2016 and January 2023, 214 pts were included in the study (46.3% female, 53.7% male). The median age was 62.6 years (range 32–91). At the data cut-off (1 February 2024) the median overall survival (OS) for the analyzed population was 34,5 months (95%CI 21,15-43,91). No significant difference in median OS was observed between pts with overall endocrine irAEs and those exhibiting specific manifestations, such as hypocortisolism and destructive diabetes mellitus. However, thyroid irAEs were associated with improved median OS: 27.5 months compared to 22.6 months in those without (p=0.037); RR=1.39 (95%CI 1.025-1.89; p=0.036). The grade of endocrine irAEs did not impact the survival benefit. A significant association was observed between age group and endocrine irAEs (Pearson’s χ2=9.92, p=0.019), with a left-skewed age distribution due to a higher proportion of participants aged 32–44 years among those developing endocrine irAEs. Pts with nodular goiter had a 2.91 times higher risk of developing thyroiditis (95%CI 1.03–8.25), although this did not reach statistical significance (p=0.067). Calcium channel blockers were associated with an increased risk of developing thyroid irAEs (RR=1.54, 95%CI 1.09–2.19; p=0.036). Antihistamine use was a robust predictor of hypothyroidism with a RR=1.68 (95%CI 1.05–2.7, p=0.04). Initial derived neutrophil-to-lymphocyte ratio (dNLR) ≥3 predict the development of endocrine irAEs (Pearson χ2=4.02; p=0.045) as well as dNLR&gt;2.2 (Pearson χ2=4.22, p=0.04). Conclusions: Thyroid irAEs are correlated with improved OS. Predictors of endocrine irAEs may include young age (32-44 years), calcium channel blocker or antihistamine use, dNLR ≥3, or dNLR &gt;2.2. Prospective trials are warranted to validate these findings.

Comparing the efficacy and safety of TACE combined with donafenib or lenvatinib in the treatment of unresectable hepatocellular carcinoma.

e16153 Background: For unresectable Intermediate/Advanced-Stage Hepatocellular Carcinoma (uHCC), the efficacy of TACE monotherapy has been unsatisfactory. Studies have shown that TACE combined with molecular targeted drugs exhibits potential synergistic effects, which can prolong the overall survival (OS) of uHCC patients (pts). Donafenib and lenvatinib are small molecule targeted drugs approved as first-line treatments for HCC. The aim of this study is to evaluate the efficacy and safety of TACE combined with donafenib or lenvatinib in the treatment of uHCC. Methods: A retrospective analysis was conducted on the clinical data of uHCC pts treated with donafenib combined with TACE (Dona-TACE) or lenvatinib combined with TACE (Lenva-TACE) at The First Affiliated Hospital of USTC from January 2018 to October 2022. The OS, progression free survival (PFS), objective response rate (ORR), and disease control rate (DCR) of two groups of pts were evaluated according to the mRECIST, and the incidence of adverse events (AEs) was evaluated using CTCAE 5.0. Pts with complete baseline information and at least one follow-up evaluation were incorporated in the final analysis. Results: A total of 105 pts treated with donafenib and 59 pts treated with lenvatinib met the study criteria. After matching with a 1:1 propensity score, 35 pts in the Dona-TACE group and 35 pts in the Lenva-TACE group were included in this study. The baseline characteristics of the two groups are similar (males, 85.7% vs. 85.7%; ECOG PS of 1, 74.3% vs. 71.4%; Exceeding up-to-seven criteria, 74.3% vs. 62.9%; BCLC stage C, 42.9% vs. 40.0%; Combination immunotherapy, 62.9% vs. 54.3%). There was no significant difference in median OS (29.0 vs. 27.3m, P = 0.748) and median PFS (10.5 vs. 10.3m, P = 0.869) in the Dona-TACE and Lenva-TACE groups. The ORR (85.7% vs. 74.3%, P = 0.969) and DCR (94.3% vs. 97.1%, P = 0.280) of the Dona-TACE and Lenva-TACE group were equivalent. Compared with the Lenva-TACE group, pts in the Dona-TACE group had a lower incidence of grade 3-4 adverse events (any grade, 94.3% vs. 91.4%; grade 3 or 4, 34.3% vs. 57.1%, P &lt; 0.05). Among them, pts in the Dona-TACE group had a lower incidence of proteinuria (any grade, 22.9% vs 42.9%; grade 3 or 4, 0 vs17.1%, P &lt; 0.05) and hypertension (any grade, 42.9% vs 71.4%; grade 3 or 4, 2.9% vs 25.7%, P &lt; 0.05) than those in the Lenva-TACE group. Multivariate analysis showed that ECOG PS score, up-to-seven criteria, and tumor blood supply were independent prognostic factors affecting OS (HR, 3.470, 3.619, 3.067; P &lt; 0.05). Conclusions: The efficacy of donafenib and lenvatinib combined with TACE in the treatment of uHCC is equivalent. Furthermore, compared to lenvatinib combined with TACE, donafenib combined with TACE has higher safety.

Comparative effectiveness of immunotherapy and chemotherapy in patients with metastatic colorectal cancer stratified by microsatellite instability status.

Immunotherapy have demonstrated promising outcomes in patients with high microsatellite instability (MSI) (MSI-H) metastatic colorectal cancer. However, the comparative effectiveness of Immunotherapy and chemotherapy for patients with low MSI (MSI-L), and microsatellite stable (MSS) metastatic colorectal cancer remains unclear. To investigate immunotherapy vs chemotherapy for treatment of MSI-L/MSS metastatic colorectal cancer, and to evaluate the success of immunotherapy against chemotherapy in managing MSI-H metastatic colorectal cancer during a follow-up of 50 months. We conducted a retrospective cohort study using the National Cancer Database (NCDB) to evaluate the overall survival (OS) of patients with metastatic colorectal cancer treated with immunotherapy or chemotherapy. The study population was stratified by MSI status (MSI-H, MSI-L, and MSS). Multivariable Cox proportional hazard models were used to assess the association between treatment modality and OS, adjusting for potential confounders. A total of 21951 patients with metastatic colorectal cancer were included in the analysis, of which 2358 were MSI-H, and 19593 were MSI-L/MSS. In the MSI-H cohort, immunotherapy treatment (n = 142) was associated with a significantly improved median OS compared to chemotherapy (n = 860). After adjusting for potential confounders, immunotherapy treatment remained significantly associated with better OS in the MSI-H cohort [adjusted hazard ratio (aHR): 0.57, 95% confidence interval (95%CI): 0.43-0.77, P < 0.001]. In the MSS cohort, no significant difference in median OS was observed between immunotherapy treatment and chemotherapy (aHR: 0.94, 95%CI: 0.69-1.29, P = 0.715). In this population-based study using the NCDB, immunotherapy treatment was associated with significantly improved OS compared to chemotherapy in patients with MSI-H metastatic colorectal cancer, but not in those with MSI-L/MSS metastatic colorectal cancer. Further studies are warranted to determine the optimal therapeutic approach for patients with MSI-L/MSS metastatic colorectal cancer.

Abstract 6851: The genomic, transcriptomic, and immunologic landscape of TEM8 (ANTXR1) in neuroendocrine neoplasms (NENs)

Abstract Introduction: TEM8 (coded by ANTXR1) is overexpressed in malignant tissues, with oncolytic viruses such as SVV-01 uniquely binding to this receptor on tumor-associated angiogenic endothelial cells, pericytes, fibroblasts, and immune inflammatory cells. Recent pre-clinical data suggest that TEM8-targeting therapies may convert immunologically “cold” tumor microenvironments (TME) into “hot” milieu more amenable to treatment with immune checkpoint inhibitors (ICIs). Methods: NextGen sequencing of DNA (592 genes or WES) and RNA (WTS) was performed on neuroendocrine neoplasms (NENs; N = 1724), excluding small-cell lung cancer, submitted to Caris Life Sciences (Phoenix, AZ). Mutations were defined as pathogenic SNVs/indels. ANTXR1 expression was divided by ANTXR1-expression quartiles (transcripts per million [TPM];Q4:H;Q1:L). PD-L1 expression (SP142; Positive (+): ≥2+,≥%5) was assessed by IHC. High tumor mutational burden (TMB-H) was defined as ≥10 mutations per MB. Cell infiltration in the TME was estimated by QuantiSEQ. Gene expression profiles were analyzed for transcriptional signatures predictive of response to immunotherapy (T cell-inflamed) and MAPK pathway activation score (MPAS). Overall survival (OS) data was obtained from insurance claims, and Kaplan-Meier estimates were calculated for molecularly defined subpopulations of patients. Mann-Whitney U and X2/Fisher-Exact tests were applied where appropriate, with p-values adjusted for multiple comparisons (p&amp;lt;0.05). Results: NENs from the adrenal gland had the highest median ANTXR1 expression (50 TPM), followed by those from the colon and rectum (43.5), genitourinary organs (43.3), and small bowel (excluding appendix) (39.2). The lowest median ANTXR1 expression was observed in NENs from the pancreas (31.5). No pathogenic mutations were significantly associated with ANTXR1H vs L tumors (p&amp;gt;0.05 for all), along with no differences in the prevalence of TMB-H (8.6% vs 12.6%, p=1) or PD-L1+ (5.8%: vs 3.1%, p=1). A greater proportion of B cells (5.34 % vs 3.78%, p&amp;lt;0.001), M1 (1.46% vs 0.15%, p&amp;lt;0.001) and M2 macrophages (3.92% vs 2.67%, p&amp;lt;0.001), and T-regulatory cells (1.77% vs 1.08%, p&amp;lt;0.001) was observed in ANTXR1H TMEs, which were more frequently classified as T cell-inflamed compared to ANTXR1L (42% vs 8%, p&amp;lt;0.001). ANTXR1H tumors also had higher MPAS compared to ANTXR1L (1.16 vs -1.61 arbitrary units, p&amp;lt;0.001). There was no significant difference in median OS between ANTXR1H vs L tumors (18.8 mo. vs 21.2 months, Hazard Ratio:1.18, p=0.114). Conclusion: The increased immune cell infiltrate and prevalence of T-cell inflamed status among ANTXR1H NENs suggests these tumors might be more responsive to treatment with ICIs. As trials incorporating intratumoral injections of SVV-01 in combination with ICIs are underway, further investigation of clinical and molecular associations with ANTXR1 expression in NENs is warranted. Citation Format: Samuel A. Kareff, Harris Krause, Andrew Elliott, Peter Hosein, Emil Lou, Heloisa Soares, Matthew Oberley, Aman Chauhan. The genomic, transcriptomic, and immunologic landscape of TEM8 (ANTXR1) in neuroendocrine neoplasms (NENs) [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 6851.

Clinical Impact and Management of Incidental Renal Findings on Pre-TAVI CT Scan from the Urologist’s Perspective

Introduction: The aim of the study was to investigate prevalence and impact of incidental renal masses (IRMs) accompanying increasing computed tomography (CT) work-up for symptomatic aortic valve stenosis (sAVS) of the elderly with regard to the relevance of urological consultation for overall survival (OS). Methods: A retrospective analysis of pre-transcatheter aortic-valve implantations (TAVIs) CT scans of patients with sAVS (N = 1,253) harboring IRM was performed for 2014–2019. According to the clinical management, groups 1 (urologic consultation) and 2 (findings ignored) were formed and analyzed in terms of OS. Results: The prevalence of IRM was 9% (119/1,253). In 19% (23/119), urological advice was sought (group 1). At baseline, group 1 showed a significantly higher rate of malignancy-specific lesions compared to 2 (p < 0.01). Other clinical parameters (e.g., age, cardiological scores, comorbidities) did not differ between groups (p > 0.05). In group 1, 4 (17%) findings were histologically confirmed, of which 3 (13%) underwent surgery. There was no significant difference in median OS at a median follow-up of 24.7 months between groups 1 and 2 with 35.7 (95% CI, 5.9; 65.4) and 47.4 months (95% CI, 33.0; 61.7), respectively (p = 0.4). In Cox regression analysis, chronic kidney disease but not urologic work-up or chronic obstructive pulmonary disease or heart failure emerged as an independent unfavorable predictor of OS (HR 2.44, 95% CI 1.37; 4.36, p = 0.003). Conclusion: For the first time, a TAVI population with IRM was analyzed from the urologist’s perspective. Urologic co-evaluation and work-up does not confer a significant benefit in terms of OS in this particular population.

Outcomes for patients with mCRPC and liver metastasis receiving 177-Lu-PSMA-617 treatment.

175 Background: It is well-known that patients with liver metastases from metastatic castration resistant prostate cancer (mCRPC) have poorer or transient responses to many forms of systemic therapy. Data on outcomes following treatment with Lutetium-177–PSMA-617 is scarce. The VISION trial reports hazard ratios for overall survival in the subgroup of patients with liver metastases without disclosing the absolute duration of survival. Using real-world clinical data, we examine this important subgroup of patients, describing their PSA response rates and survival. Methods: A single institution database was assembled to include all patients receiving 177-Lu-PSMA-617 at Mayo Clinic Rochester, MN, and starting treatment in the interval of March 2022 to March 2023. Baseline clinicopathologic and imaging characteristics were abstracted. Patients were categorized based on the presence or absence of measurable liver metastases on their baseline PSMA PET scan. Best PSA response while on treatment was annotated and reported as percent decline from baseline. Survival was calculated from date of first cycle of 177-Lu-PSMA-617. PSA50 response and overall survival (OS) outcomes for the two groups (liver metastases versus no liver metastases) were compared using Chi square test and Kaplan-Meier method, respectively. Those with available pre-treatment circulating tumor DNA (ctDNA) genomic profiling, performed by Guardant (83 gene panel), were assessed for the presence of pathogenic and likely pathogenic alterations. Findings are summarized using descriptive statistics. Results: The overall cohort consisted of 212 patients, including 29 (14%) with liver metastases on pre-treatment PSMA PET/CT. The median number of cycles received was 4 (range, 1-6) for patients with liver metastases and 6 (range, 1-6) for those without hepatic involvement. The observed PSA50 response trended lower for those with liver metastases (34.5% [10/29] versus 51% [94/183], p= 0.091). At median (IQR) follow-up of 10 (8-12) months, there was a numerical but not statistically significant difference in median OS (11.28 months versus NR, p=0.066). In the exploratory analysis of baseline ctDNA, BRCA2 copy number loss was relatively enriched among patients with liver metastases (4 of 19, 21%) versus patients without liver disease (5.7%, 9/158). Conclusions: Our data suggest that the presence of liver metastases predict poorer outcomes in patients receiving Lutetium-177–PSMA-617 treatment, which is similar to data reported with other forms of systemic therapy for mCRPC. To maximize the anti-tumor activity of radioligand therapy in the liver, combination approaches should be explored.

Co-Mutational Patterns with BCOR Influences Biological Characteristics and Clinical Outcomes of Myeloid Neoplasms

Introduction BCL6 co-repressor ( BCOR), a tumor suppressor gene located on chromosome X (locus Xp11.4) is involved in hematopoiesis via non-canonical polycomb repressive complex 1 (PRC1). The prevalence of BCOR mutation in myeloid neoplasms (MN) is approximately 5%, and it is also implicated in clonal hematopoiesis. In the 2022 ELN, WHO, and ICC classifications, BCOR is categorized as a myelodysplasia-related gene. Mutational patterns include frequent co-occurrence with DNMT3A and RUNX1 in AML and mutual exclusivity with NPM1 mutations. Although it has been theorized that BCORMT may cooperate preferentially with certain groups of genes, the prognostic significance of the BCOR co-mutational landscape has yet to be fully studied. Methods The total cohort (n = 20149) consists of 624 MN patients (169 primary (p) AML, 136 secondary (s) AML, 84 MDS, 34 MDS/MPN, 66 MPN, and 135 with other MN) from Karmanos Cancer Institute, publicly available metanalytic cohort consisting of various sub-studies (Awada et al., 2021; Kewan et al., 2023), and cohorts from open-access cancer genomics resource cBioPortal and AACR GENIE (v13.1) (Cerami et al., 2012; Gao et al., 2013). Clinical and genomic characteristics were reviewed. Chi-square and T-tests were used for analysis of various parameters as described, and Kaplan-Meier and log-rank methods were used to estimate overall survival (OS). The prevalence of BCORMT, co-occurring mutations, and their outcomes were analyzed based on co-mutational patterns. Results A total of 745 (3.7%) patients carried BCORMT. Male: Female ratio was 1.48, with a median age of 68 ys.(IQR 59-75). BCORMTshowed a trend to be most frequent in pAML compared to other MN (54 vs 46%, p=0.33). BCORMT was less associated with abnormal karyotype vs. BCORWT [41 vs. 51%, p=0.0002]. Median variant allele frequency (VAF) was 45% (IQR 22-69), and most mutations were frameshift (41%) followed by nonsense (27%), and missense (22%). Median OS was not different between BCORWT and BCORMT patients [21.9 vs. 19.6 mo., p=0.089] in the entire cohort. Oncoprint analysis centered around BCOR revealed frequent co-mutations with RUNX1, DNMT3A, TET2 and ASXL1. As a result, the patients were divided into 10 groups (groups A-J), and the OS was analyzed between groups and compared with BCORWT. Patients with BCOR/TET2, BCOR/RUNX1/TET2, and BCOR/ASXL1 (groups G, B, and H resp.) had the lowest median OS with 14.5 mo., 16.7 mo., and 17.4 mo., resp. However, no significant differences in median OS were observed between the compared groups except those involving BCOR/ASXL1 vs. BCOR/Others and BCORWT. BCOR/ASXL1 patients had significantly lower median OS compared to BCOR/Others [17.4 vs. 22.5 mo., p=0.022] and BCORWT [17.4 vs. 21.9 mo., p=0.017]. Further BCORMT and ASXL1MT comutational analysis irrespective of other co-occurring mutations, revealed that in those with BCORMT, ASXL1 co-mutation was seen in 143 (19.2%) patients. BCOR and ASXL1 co-mutation were primarily enriched in primary AML (49%), followed by sAML (25%). Median BCOR VAF was higher than ASXL1 [39 vs. 31%, p&amp;lt;0.0001]. The most associated mutational categories in this subgroup were related to myeloid transcription factors (TF) ( RUNX1, CEBPA; 62%), spliceosome ( SRSF2, U2AF1, SF3B1, ZRSR2; 22%), and DNA methylation family ( DNMT3A, TET2, IDH1/2; 8%). BCORMT/ ASXL1MT/DNA Methylation mutations had poorer median OS compared to BCORMT/ ASXL1MT/Spliceosome mutations [9.2 vs. 17.4 mo., p=0.044]. Whereas BCORMT/ ASXL1MT/Myeloid TF and BCORMT/ ASXL1MT/Spliceosome mutations had no significant survival difference compared to BCORWT, patients with BCORMT/ ASXL1MT/DNA Methylation had worse median OS [9.2 vs. 21.9 mo., p=0.007]. Conclusion This large cohort study confirms common BCOR co-mutation patterns and reveals prognostic differences in patients with co-occurring ASXL1 mutation. We demonstrated BCORMT with ASXL1MT without concurrent RUNX1MT, DNMT3AMT, and TET2MT had poorer overall survival. Furthermore, patients with BCORMT, ASXL1MT, and concomitant DNA methylation-related gene mutations had worse outcomes compared to those with concomitant spliceosome mutation and BCORWT. Our findings suggest that co-mutational patterns of BCOR may further clarify diagnosis and classification schemes, highlighting potential synergies among subcategories of gene mutations and their prognostic value.

Clinical Implications of TP53 Mutations/Allelic State in Patients (Pts) with Myelodysplastic Syndromes/Neoplasms (MDS) Treated with Hypomethylating Agents (HMA)- a Multicenter, Retrospective Analysis from the Validate Database

TK and JPB Co-first; RK, DS, and AMZ are Co-senior authors. Introduction MDS with TP53 mutations ( TP53 MT) are associated with high-risk disease features and rapid progression to AML. Effective treatment for this aggressive subtype is still not available. As compared to monoallelic TP53 MT, biallelic MT have been associated with adverse outcomes and worse overall survival (OS), but the impact of allelic status on treatment response and OS after HMA therapy are not well established. In this study, we analyzed TP53 allelic state for a large well annotated cohort of pts with MDS who were treated with HMAs. Methods The VALIDATE database includes pts with MDS treated with frontline HMA from 14 specialized centers. Pts were considered to have biallelic TP53 MT according to the ICC definition (Arber et al. 2022, Blood) if they meet any of the following: a. two TP53 MT (variant allelic frequency [VAF]&amp;gt;10% for each) b. single TP53 MT with copy neutral loss of heterozygosity (CN-LOH, available for 308 pts) c. TP53 MT with del17p and d. Single TP53 MT with VAF &amp;gt;50%. Time to event analyses were estimated using Kaplan-Meier estimator and groups were compared by the log-rank test from the time of HMA initiation. Only higher risk (HR)-MDS pts (IPSS&amp;gt;1 or IPSS-R&amp;gt;3.5) with BM biopsy within 180 days after HMA initiation were assessed for complete response (CR) and overall response rate (ORR) according to the IWG 2023 criteria (Zeidan et al, Blood 2023) (n=480). OS was calculated from time of HMA therapy initiation. This study was supported by an independent research grant from AbbVie. Results A total of 816 pts met eligibility and were included in this analysis. Median age was 68 years (IQR: 61-74) and 64% were men. MDS excess blast (EB) 1/2 was the most common MDS subtype (62%). Overall, 78% of the pts were treated with HMA monotherapy (26% decitabine [DEC] and 74% azacitidine [AZA]) and 22% received HMA as part of combination therapy. In total, 40% of the pts underwent allogenic HSCT. Median HMA treatment time was 5 months (mo), IQR:3-11. Median follow up time was 17 mo (IQR:9-31). TP53 MT were detected in 253 pts (31%) at time of MDS diagnosis, of whom 153 (60%) pts had biallelic TP53 MT and 100 (40%) pts had monoallelic TP53 MT. Missense MTs were identified in 80% of pts with monoallelic TP53 MT. TP53 MT/del17p (33%), TP53 MT/CN-LOH (28%), and multiple TP53 MT (25%) were the most common combinations in pts with biallelic TP53 MT. Pts with TP53 MT had higher rates of MDS-EB (74% vs. 61%, p&amp;lt;0.001). Complex karyotype was observed in 112 (73%) pts with biallelic TP53 MT and 81 (81%) pts with monoallelic TP53 MT (p=0.154). Median number of HMA cycles among pts with TP53 MT was 8 (IQR:5-12) and higher compared to pts without TP53 MT (5 cycles, IQR:3-9), p=0.032 ( Panel-A). In a logistic regression model for CR, TP53 MT was not associated with probability of achieving CR (1.4, 0.89-2.29). CR rates for pts with biallelic TP53 MT (18%) and monoallelic TP53 MT (14%) were not significantly different, p=0.37. There were also no significant differences in ORR observed between biallelic TP53 MT (59%) and monoallelic TP53 MT (54%) pts, p=0.39. Among TP53 MTpts treated with HMA monotherapy, pts treated with AZA compared to DEC had similar odds for ORR (OR:1.1, 95%CI: 0.7-1.6)/CR (OR: 0.8, 95%CI: 0.4-1.3) and hazard for OS (HR: 1.1, 0.9-1.4). As expected, the median OS (mo, 95%CI) for pts with TP53 MT (12, 10-13) was significantly lower than pts without TP53 MT (28, 25-31), p&amp;lt;0.001. Importantly, pts with biallelic TP53 MT (11, 9-14) had no significant difference in median OS compared to monoallelic TP53 MT (13, 11-17), p=0.268 (Panel-B). In a multivariable cox proportional hazard regression model for OS (hazards ratio, 95%CI) adjusted for age (1.0, 0.9-1.0), HSCT (0.4, 0.3-0.4), IPSS-M score (1.2, 1.1-1.3), and complex karyotype (1.4, 1.1-1.8), TP53 MT status (1.8, 1.4-2.3) was still associated with OS. However, biallelic TP53 MT had comparable risk to monoallelic TP53 MT (1.2, 0.9-1.7). Conclusions To our knowledge, VALIDATE is the largest database of MDS pts with TP53 MT who were treated with HMA. We confirm that TP53 MT have significant negative impact on survival, but not on response to HMA therapy. Importantly, we did not observe OS differences between monoallelic and biallelic TP53 MT. We also show that the type of HMA monotherapy used does not impact outcome of these pts. Overall, pts with TP53 MT have very poor outcomes and are in desperate need of new, effective therapies.

Primary and Secondary Plasma Cell Leukemia Risk Stratification By Circulating Plasma Cells

Plasma cell leukemia (PCL) is a rare plasma cell dyscrasia associated with poor outcomes. PCL can present de novo as primary PCL (pPCL) or from preceding multiple myeloma as secondary PCL (sPCL). The International Myeloma Working Group (IMWG) in 2021 updated the diagnostic criteria for pPCL using circulating plasma cells (CPC) to ≥5% instead of ≥20% as both carry similar survival. In this single center retrospective analysis, we compared clinical features and overall survival (OS) for 104 patients: with pPCL ≥5% CPC ( N = 35), sPCL 5-19% CPC (sPCL-A) ( N = 11), sPCL ≥20% CPC (sPCL-B) ( N = 38), and spillover group 1-4% CPC regardless of newly diagnosed or secondary status ( N = 20). Mean ages were 57 - 59 years old for all groups (range: 25 - 84) with no difference in age between groups ( p = 0.90). There was a slight predominance of females (54.8%) over males and blacks (53.9%) over non-blacks. More patients with pPCL were black (65.7%) compared to sPCL and spillover groups, although this difference was not statistically significant ( p = 0.35). pPCL patients presented with the highest mean WBC at diagnosis (23.4 x10 9/L) compared to sPCL-A (5.5 x10 9/L), sPCL-B (12.2 x10 9/L), and spillover (7.2 x10 9/L) groups ( p &amp;lt;0.001). Patients in all groups were anemic (hemoglobin 7.8 - 9.3 g/dL), thrombocytopenic (platelets 60.2 - 101.2 x 10 9/L), and had abnormal renal function (creatinine 1.4 - 2.7 mg/dL), elevated LDH (918.7 - 1515.5 units/L, highest in sPCL-A), and elevated uric acid levels (5.9 - 8.2 mg/dL). sPCL patients and spillover group had more lytic lesions on skeletal survey ( p = 0.009) and positron emission tomography (PET) ( p = 0.02) compared to patients with pPCL. sPCL-A patients had higher incidences of lymphadenopathy ( N = 5/11, 62.5%, p = 0.02) and central nervous system invasion ( N = 4/11, 36.4%, p = 0.02) compared to other groups. There was no difference in incidence of extramedullary disease ( p = 0.29) between groups. Over 90% of patients with PCL had high-risk cytogenetics with 63% carrying a complex karyotype. Hypodiploidy was seen more often in patients with pPCL and sPCL-B compared to sPCL-A and spillover ( p = 0.005). There was no difference between groups in incidence of deletion 17p ( p = 0.53). All patients benefited in terms of OS from daratumumab (HR 0.44, 95% CI 0.25 - 0.76; p = 0.004), IMiDs (HR 0.13, 95% CI 0.08 - 0.23; p &amp;lt;0.001), PIs (HR 0.43, 95% CI 0.25 - 0.75; p = 0.003), chemotherapy (HR 0.56, 95% CI 0.32 - 0.98; p = 0.04), and autologous hematopoietic stem cell transplantation (HR 0.33, 95% CI 0.16 - 0.71; p = 0.004). DVT-PACE type regimens (dexamethasone-bortezomib-thalidomide-cisplatin-doxorubicin-cyclophosphamide-etoposide) are used for pPCL and may be less effective in sPCL and spillover patients who have been heavily pretreated. We noted no benefit in OS for all patients including pPCL, sPCL-A, sPCL-B, and spillover groups who received DVT-PACE (HR 0.97, 95% CI 0.62 - 1.50, p = 0.88). The lack of OS benefit in pPCL patients receiving DVT-PACE persisted on multivariate analysis when adjusting for PCL group alone (HR 0.79, 95% CI 0.50 -1.26; p = 0.33) and PCL group, age, platelet count, and presence of high-risk cytogenetics (HR 1.11, 95% CI 0.63 - 1.94; p = 0.72). After median follow-up of 6.70 months, median OS was 7.14 months for the entire cohort with 92.3% ( N = 96) deceased. On univariate analysis, male sex, age &amp;gt;58 years old, high-risk cytogenetics, LDH &amp;gt;604 units/L, creatinine &amp;gt;1.40 mg/dL, hemoglobin &amp;lt;8.3 g/dL, platelets &amp;lt;53.5 x10 9/L, lytic lesions on skeletal survey and on PET, extramedullary disease on PET, and plasmacytoma were associated with inferior median OS (Table 1). pPCL had higher median OS (13.1 months) compared to sPCL-A (3.1 months, p = 0.03) and sPCL-B (3.5 months, p = 0.003) (Figure 1). There was no statistically significant difference in median OS between pPCL (13.1 months) and spillover patients (10 months) ( p = 0.48) as well as sPCL-A (3.1 months) and sPCL-B (3.5 months) ( p = 0.80). Although the spillover group was associated with a trend towards better OS compared to sPCL-A and sPCL-B groups, this was not statistically significant, which may be due to low N which is a limitation of the study. Further research is required to better understand the clinical features, treatment responses, and outcomes of pPCL, sPCL, and spillover group (1-4% CPC).

Impact of circulating lymphoma cells at diagnosis on outcomes in patients with Waldenstrom macroglobulinemia.

Given the paucity of data surrounding the prognostic relevance of circulating lymphoma (CL) in Waldenström macroglobulinemia (WM), we sought to evaluate the impact of CL at diagnosis on outcomes in patients with WM. Patients were divided into CL+ and CL- based on the results of flow cytometry. The endpoints included assessing progression-free survival (PFS), overall survival (OS), and diagnosis-to-treatment interval (DTI) between the two groups. Among the 308 patients with WM, 69 met the eligibility criteria with 42 and 27 in CL+ and CL- groups, respectively. The two groups were well balanced in regard to all the baseline characteristics. The ORR was numerically higher in the CL+ group compared to the CL-group (81% versus 61%, respectively), however, the CR+VGPR rates were similar between the two groups. The median PFS was not significantly different between the two groups (6.3 years in the CL- group versus not reached [NR] in the CL+ group) regardless of the first-line therapy. There was no significant difference in median OS between the CL- and CL+ groups (13 years versus NR). Although the median DTI was shorter in the CL+ group compared to CL- group, the significance was lost in the multivariable analysis. In this study (largest-to-date) evaluating the impact of CL on outcomes in patients with newly diagnosed WM, we did not find the prognostic utility of CL in WM. Future studies should explore the correlation of CL with other biological factors that impact the outcomes in WM patients.

Effect of Different Timing of Local Brain Radiotherapy on Survival of EGFR-Mutated NSCLC Patients with Limited Brain Metastases.

(1) Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been the first line therapy for EGFR-mutant lung adenocarcinoma (LAC) patients with brain metastases (BMs). However, the role and the optimal time of brain radiotherapy remains controversial. We aimed to investigate the role of upfront brain stereotactic radiotherapy (SRS) and the impact of deferral radiotherapy on patients' clinical outcomes. (2) Methods: We retrospectively studied 53 EGFR-mutant LAC patients with limited synchronous BMs between 2014 and 2020 at our institute. The limited BMs was defined with one to four BM lesions, with a maximal size of ≤4 cm. Patients were categorized into two groups: upfront brain SRS (upfront RT) and upfront TKIs. The intracranial progression-free survival (iPFS), progression-free survival (PFS), and overall survival (OS) between groups were analyzed. (3) Results: The median iPFS (21.0 vs. 12.0 months, p = 0.002) and PFS (20.0 vs. 11.0 months, p = 0.004) of the upfront RT group was longer than that of the upfront TKI group. There were no significant differences in median OS (30.0 vs. 26.0 months, p = 0.552) between the two groups. The upfront RT group is less likely to suffer from intracranial progression of the original sites than that of upfront TKIs during the disease course (36.1% vs. 0.0%, p = 0.025). Multivariate analysis showed that the Karnofsky Performance Scale and the presence of synchronous meningeal metastases were associated with overall survival. (4) Conclusions: Compared with upfront TKI, the combination of upfront SRS with TKIs can improve the iPFS and PFS in EGFR-mutant LAC with synchronous BMs. The addition of upfront brain SRS was useful for the original intracranial metastatic lesions.

Clinical score for colorectal cancer patients with lung-limited metastases undergoing surgical resection: Meta-Lung Score

BackgroundRadical resection of isolated lung metastases (LM) from colorectal cancer (CRC) is debated. Like Fong’s criteria in liver metastases, our study was meant to assign a clinical prognostic score in patients with LM from CRC, aiming for better surgery selection. MethodsWe retrospectively analyzed data from 260 CRC patients who underwent curative LM resection from December 2002 to January 2022, verifying the impact of different clinicopathological features on the overall survival (OS). ResultsAt the univariate analysis: higher baseline CEA levels (p = 0.0001), disease-free survival less than or equal to 12 months (m) (p = 0.0043), LM size larger than 2 cm (p = 0.0187), multiple resectable nodules (p = 0.0083), and positive nodal status of the primary tumor (p = 0.0011) were associated with worse prognosis. In a Cox regression model, these characteristics retained their independent role for OS (p < 0.0001) and were chosen as criteria to be assigned one point each for clinical risk score. The 5-year survival rate in patients with 0 points was 88%, while no patients with a 5-point score survived at 2 years. Based on the 0–1 vs. 2–5 score range, we obtained a significant difference in median OS: not reached vs. 40.8 months (95 %CI 36 to 87.5), respectively (p < 0.0001) stratifying patients into good and poor prognosis. The prognostic role of the score was also confirmed in terms of median RFS: not reached in 0–1 scored patients vs. 30.5 months (95 %CI 19.4 to 42) in patients with 2–5 scores (p = 0.0006). ConclusionsWhen LM from CRC is resectable, the Meta-Lung Score provides valuable prognostic information. Indeed, while upfront surgery should be considered in patients with scores of 0 to 1, it should be cautiously suggested in patients with scores of 2 to 5, for whom a prognosis comparison between preventive surgery and other treatments should be investigated in prospective randomized clinical trials.

A retrospective analysis for investigating the relationship between FIGO stage IVA/IVB and cytoreductive surgery with prognosis in epithelial ovarian cancer.

To investigate the effect of primary debulking surgery (PDS), NACT followed by interval debulking surgery (NACT-IDS), and chemotherapy alone on the prognosis of FIGO stage IV epithelial ovarian cancer (EOC) with different metastatic patterns. We retrospectively analyzed 133 cases of FIGO stage IV EOC with pleural effusion (stage IVA), parenchymal metastases (stage IVB), or extra-abdominal lymph node metastases (stage IVB) at our Hospital between January 2014 and July 2021. Among 133 cases with stage IV disease, 16.5% (n=22) presented with pleural effusion, 46.6% (n=62) with parenchymal metastases, and 36.9% (n=49) with extra-abdominal lymph node metastases. Regardless of the metastatic patterns, the 90.2% (n=120) of cases who underwent PDS/NACT-IDS exhibited a significantly superior overall survival (OS) compared to the 9.8% cases (n=13) who received chemotherapy alone (32 vs 17 months, p=0.000). The cohort was further stratified into 58 cases (48.3%) with R0, 41 cases (34.2%) with R1, and 21 cases (17.5%) with R2. The median OS of cases with R0 was significantly better than that of cases with R1/R2 (74 vs 27 months, p=0.000). There was no significant difference in median OS between PDS and NACT-IDS (43 vs 31 months, p=0.676), as well as between FIGO IVA and IVB (35 vs 31 months, p=0.582). Additionally, the metastatic patterns and the number of neoadjuvant chemotherapy cycles (≤4 or >4) did not demonstrate any prognostic significance for median OS (p=0.820 and 33 vs 26 months, p=0.280, respectively). Regardless of FIGO IVA and IVB stages or metastatic patterns, patients diagnosed with stage IV EOC may benefit from cytoreductive surgery with abdominal R0, compared with chemotherapy alone.

Demographic and clinical characteristics of patients with metastatic breast cancer and leptomeningeal disease: A single center retrospective cohort study.

1108 Background: Patients (pts) with metastatic breast cancer (MBC) and leptomeningeal disease (LMD) have a poor prognosis with limited therapeutic options. It is critical to better understand the risk factors and natural history of this condition, including pts in a modern cohort. Methods: In this single center retrospective cohort study, we identified pts with radiographic and/or cytologic evidence of LMD who received care at the University of California San Francisco (UCSF) from 2000-2023. To identify pts, we used the UCSF Pathology Database, the UCSF Radiation Oncology Database, and EMERSE, a searchable copy of the medical record. We conducted chart review to identify demographic and clinical characteristics, treatment history, and overall survival (OS). Results: 106 pts with MBC and radiographic and/or cytologic evidence of LMD were identified. All but one pt was female (n=105; 99.1%); most pts were non-Hispanic (n=93, 87.7%) and white (n=74, 69.8%). Median age at the time of MBC diagnosis was 51.9 years; 25 pts (20%) had de novo metastatic disease. Most pts had invasive ductal carcinoma (n=71, 66.9%), with invasive lobular carcinoma making up 21.7% (n=23) of cases. Pts presented with the following BC subtypes: Hormone receptor (HR) positive, HER2 negative (n=50, 47.1%), HR+/HER2+ (n=19, 17.9%), HR-/HER2+ (n=9, 8.5%), and triple negative (TNBC; n=23, 21.7%). Most pts had brain metastasis (n=78, 73.6%) in addition to LMD. Median time from diagnosis of MBC to LMD was 17.6 months (0-101.2 months). Pts received a median of 3.0 lines of therapy prior to the diagnosis of LMD (range 0-11.0) and 1.0 lines after the diagnosis of LMD (range 0-4.0). Many pts received intrathecal (IT) therapy (n=42, 39.6%) and/or whole brain radiation therapy or spinal radiation (n=49, 46.2%). Median OS from the diagnosis of LMD to death was 3.3 months. There was no significant difference in median OS by subtype: HR+/HER2- 3.5 months, HER2+ 4.7 months, and TNBC 2.2 months (p=0.45). There was no significant difference in median OS by histology: ductal (3.3 months) vs. lobular (4.7 months) (p=0.56). Pts who received IT therapy survived longer than those not treated with IT therapy (4.7 vs. 2.5 months, p=0.01). There was no significant difference in median OS among pts diagnosed with LMD between 2000-2015 (2.9 months) vs. 2016-2023 (3.6 months) (p=0.74). Conclusions: This study represents one of the largest reported case series of pts with MBC and LMD, including a more modern cohort. There appeared to be an over-representation of pts with lobular cancer and those with de novo metastatic disease. Most pts had brain metastases in addition to LMD. Survival was short in all pts, particularly those who did not receive IT therapy. There was no significant difference in median OS in pts diagnosed with LMD from 2000-2015 vs. 2016-2023; this remains an area of unmet clinical need.

Low dose anti-PD(L)-1: A potentially effective alternative for greater accessibility in solid malignancies.

e21523 Background: Anti-PD(L)1 agents changed the treatment landscape of multiple tumor types yielding long-term responses in a significant proportion of patients. However, these drugs are costly and not accessible to patients from most countries. Mounting data suggest that lower doses of anti-PD(L)1 can be as efficacious as label-approved doses at lower costs. Herein we compare the outcomes of patients treated with low-dose anti-PD(L)1 agents (LD) and patients treated with conventional doses (CD) at a single tertiary hospital. Methods: This is an observational historical cohort study evaluating the outcomes of patients treated with anti-PD(L)-1 agents (either at LD or CD) at Hospital de Base, São José do Rio Preto - Brazil. We included patients older than 18yo, with solid malignancies and treated with any anti-PD(L)1 agent. Patients were classified as having received LD if the dose administered at the first cycle was below the label dose. Data were abstracted from electronic medical records. Efficacy outcomes, including overall survival (OS), progression-free survival (PFS), and overall response rate (ORR), were evaluated. Log-rank test and Chi-square or Fisher's exact test were used as appropriate. A p-value of 0.05 was considered statistically significant. Results: From January 2020 to October 2022, a total of 43 patients were included: 26 (60.4%) received LD and 17 (39.6%) received CD. The mean age of LD and CD was 66.9 (SD 14.5) and 64.8 (SD 9.7), respectively. Most patients presented with ECOG 0 or 1 (64% LD and 66% CD), had metastatic disease at treatment onset (92% LD and 94.1% CD), and were treated in the first line (50% LD and 64% CD). Most frequent tumor sites were melanoma (38.5% LD, 56.3% CD) and lung (29.9% LD, 18.8% CD). Only 23.1% and 17.6% of tumours in LD and CD were tested for PD-L1 expression, of which 83% and 33% had PD-L1 &gt; 1. Most patients from both groups were treated with pembrolizumab (92.3% LD and 82.4% CD). The mean dose of pembrolizumab was 89.6 mg (1.5 mg/kg) for LD and 171 mg (2.1 mg/kg) for CD. After a median follow-up of 23 months, there was no significant difference in median OS (mOS), mPFS, and ORR between LD and CD (Table). A sensitivity analysis with patients receiving pembrolizumab was performed and had similar results (Table). Conclusions: Our study suggests there is no difference between patients treated with LD and CD anti-PD(L)1 in terms of OS, PFS, and ORR. The numerically shorter OS and PFS in the CD group may be due to selection bias and should be interpreted cautiously. LD anti-PD(L)1 could be an alternative to expand access in places where CD is not affordable. [Table: see text]

Survival Analysis of Lung Adenocarcinoma Patients with Exon 19 Del and 21 L858R Mutations Receiving EGFR-TKI Treatment

Introduction: Patients with adenocarcinoma of the lung that have a common EGFR mutation, the Exon 19 Del mutation, survive better than those with the Exon 21 L858R mutation. This study examined whether there is a significant difference in prognosis between two common EGFR mutations, namely exon 19 Del and 21 L858R. This study compared OS (overall survival) and PFS (progression-free survival) in NSCLC patients with Exon 19 Del and Exon 21 L858R mutations who received EGFR-TKI targeted therapy at H. Adam Malik Hospital Medan. Methods: This analysis study used a retrospective cohort design to evaluate the OS and PFS of NSCLC patients who underwent EGFR-TKI precision medicine at H. Adam Hospital Malik Medan between January 1, 2017, and December 31, 2020 and also had Exon 19 Del and Exon 21 L858R alterations. Results: A total of 88 people were sampled. The majority of research subjects were male (60.2%). Median OS was eleven months (95 percent CI:9.594-12,406). According to the study's data, eight people (9.1%) survived until the study's ending. The median OS of Exon 19 Del Common Mutation was 11 months (95%CI 9,064-12,936). While Exon 21 L858R group had ten months (95%CI 4,546-15,454). The log-rank test identified no statistical difference in median OS between mutation types (p=0.562). Conclusion: The findings of this study revealed that subjects with Exon 19 Del mutations had a longer median OS and PFS than those with Exon 21 L858R variants. Nevertheless, there was no significant difference in median OS and PFS between study subjects with mutation of Exon 19 Del and Exon 21 L858R, which received the targeted medication.