Treatment Response In Patients Research Articles

Glutamate Signaling in Patients With Parkinson Disease With REM Sleep Behavior Disorder.

Clinical heterogeneity of patients with Parkinson disease (PD) is well recognized. PD with REM sleep behavior disorder (RBD) is a more malignant phenotype with faster motor progression and higher nonmotor symptom burden. However, the neural mechanisms underlying this clinical divergence concerning imbalances in neurotransmitter systems remain elusive. Combining magnetic resonance (MR) spectroscopy and [11C]ABP688 PET on a PET/MR hybrid system, we simultaneously investigated two different mechanisms of glutamate signaling in patients with PD. Patients were grouped according to their RBD status in overnight video-polysomnography and compared with age-matched and sex-matched healthy control (HC) participants. Total volumes of distribution (VT) of [11C]ABP688 were estimated with metabolite-corrected plasma concentrations during steady-state conditions between 45 and 60 minutes of the scan following a bolus-infusion protocol. Glutamate, glutamine, and glutathione levels were investigated with single-voxel stimulated echo acquisition mode MR spectroscopy of the left basal ganglia. We measured globally elevated VT of [11C]ABP688 in 16 patients with PD and RBD compared with 17 patients without RBD and 15 HC participants (F(2,45) = 5.579, p = 0.007). Conversely, glutamatergic metabolites did not differ between groups and did not correlate with the regional VT of [11C]ABP688. VT of [11C]ABP688 correlated with the amount of REM sleep without atonia (F(1,42) = 5.600, p = 0.023) and with dopaminergic treatment response in patients with PD (F(1,30) = 5.823, p = 0.022). Our results suggest that patients with PD and RBD exhibit altered glutamatergic signaling indicated by higher VT of [11C]ABP688 despite unaffected glutamate levels. The imbalance of glutamate receptors and MR spectroscopy glutamate metabolite levels indicates a novel mechanism contributing to the heterogeneity of PD and warrants further investigation of drugs targeting mGluR5.

Synovial fluid monocyte-to-lymphocyte ratio in knee osteoarthritis patients predicts patient response to conservative treatment: a retrospective cohort study

BackgroundBiomarkers that predict the treatment response in patients with knee osteoarthritis are scarce. This study aimed to investigate the potential role of synovial fluid cell counts and their ratios as biomarkers of primary knee osteoarthritis.MethodsThis retrospective study investigated 96 consecutive knee osteoarthritis patients with knee effusion who underwent joint fluid aspiration analysis and received concomitant intra-articular corticosteroid injections and blood tests. The monocyte-to-lymphocyte ratio (MLR) and neutrophil-to-lymphocyte ratio (NLR) were calculated. After 6 months of treatment, patients were divided into two groups: the responder group showing symptom resolution, defined by a visual analog scale (VAS) score of ≤ 3, without additional treatment, and the non-responder group showing residual symptoms, defined by a VAS score of > 3 and requiring further intervention, such as additional medication, repeated injections, or surgical treatment. Unpaired t-tests and univariate and multivariate logistic regression analyses were conducted between the two groups to predict treatment response after conservative treatment. The predictive value was calculated using the area under the receiver operating characteristic curve, and the optimal cutoff value was determined.ResultsSynovial fluid MLR was significantly higher in the non-responder group compared to the responder group (1.86 ± 1.64 vs. 1.11 ± 1.37, respectively; p = 0.02). After accounting for confounding variables, odds ratio of non-responder due to increased MLR were 1.63 (95% confidence interval: 1.11–2.39). The optimal MLR cutoff value for predicting patient response to conservative treatment was 0.941.ConclusionsMLR may be a potential biomarker for predicting the response to conservative treatment in patients with primary knee osteoarthritis.

The fibroid phenotype of biological naïve patients with rheumatoid arthritis are less likely to respond to anti-IL-6R treatment

Type III collagen gene expression is upregulated in the synovium of patients with rheumatoid arthritis (RA) presenting the fibroid phenotype. The soluble type III collagen formation biomarker, PRO-C3, is known to measure fibrogenesis in fibrotic diseases. In this exploratory study, we aimed to investigate the association between fibrogenesis (PRO-C3) and the disease- and treatment response in patients with RA. We measured PRO-C3 in subsets of two clinical trials assessing the effect of the anti-interleukin-6 (IL-6) receptor treatment tocilizumab (TCZ) as monotherapy or polytherapy with methotrexate. PRO-C3 levels had weak or very weak correlations with the clinical parameters (Spearman’s). However, when the patients were divided into Disease Activity Score-28 groups characterized by the erythrocyte sedimentation rate (DAS28-ESR), there was a statistical difference between the PRO-C3 levels of the different groups (p < 0.05). To determine the response in relation to PRO-C3, a cut-off based on PRO-C3 levels and patients in remission (DAS28-ESR ≤ 2.6) was identified. This showed that a reduction in PRO-C3 after treatment initiation was associated with decreased DAS28-ESR and a higher response rate in patients with low PRO-C3 levels than in those with high PRO-C3 levels. This indicates that a fibrotic component affects the responsiveness of patients.

Cancer-associated fibroblast-derived gene signature discriminates distinct prognoses by integrated single-cell and bulk RNA-seq analyses in breast cancer.

Cancer-associated fibroblasts (CAFs) are one of the most predominant cellular subpopulations in the tumor stroma and play an integral role in cancer occurrence and progression. However, the prognostic role of CAFs in breast cancer remains poorly understood. We identified a number of CAF-related biomarkers in breast cancer by combining single-cell and bulk RNA-seq analyses. Based on univariate Cox regression as well as Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, a novel CAF-associated prognostic model was developed. Breast cancer patients were grouped according to the median risk score and further analyzed for outcome, clinical characteristic, pathway activity, genomic feature, immune landscape, and drug sensitivity. A total of 341 CAF-related biomarkers were identified from single-cell and bulk RNA-seq analyses. We eventually screened eight candidate prognostic genes, including CERCAM, EMP1, SDC1, PRKG1, XG, TNN, WLS, and PDLIM4, and constructed the novel CAF-related prognostic model. Grouped by the median risk score, high-risk patients showed a significantly worse prognosis and exhibited distinct pathway activities such as uncontrolled cell cycle progression, angiogenesis, and activation of glycolysis. In addition, the combined risk score and tumor mutation burden significantly improved the ability to predict patient prognosis. Importantly, patients in the high-risk group had a higher infiltration of M2 macrophages and a lower infiltration of CD8+ T cells and activated NK cells. Finally, we calculated the IC50 for a range of anticancer drugs and personalized the treatment regimen for each patient. Integrating single-cell and bulk RNA-seq analyses, we identified a list of compositive CAF-associated biomarkers and developed a novel CAF-related prognostic model for breast cancer. This robust CAF-derived gene signature acts as an excellent predictor of patient outcomes and treatment responses in breast cancer.

Predictive value of FCGBP expression for treatment response and survival in rectal cancer patients undergoing chemoradiotherapy.

Despite neoadjuvant chemoradiotherapy (CRT) being the established standard for treating advanced rectal cancer, clinical outcomes remain suboptimal, necessitating the identification of predictive biomarkers for improved treatment decisions. Previous studies have hinted at the oncogenic properties of the Fc fragment of IgG binding protein (FCGBP) in various cancers; however, its clinical significance in rectal cancer remains unclear. In this study, we first conducted an analysis of a public transcriptome comprising 46 rectal cancer patients. Focusing on cell adhesion during data mining, we identified FCGBP as the most upregulated gene associated with CRT resistance. Subsequently, we assessed FCGBP immunointensity using immunohistochemical staining on 343 rectal cancer tissue blocks. Elevated FCGBP immunointensity correlated with lymph node involvement before treatment (p = 0.001), tumor invasion, and lymph node involvement after treatment (both p < 0.001), vascular invasion (p = 0.001), perineural invasion (p = 0.041), and reduced tumor regression (p < 0.001). Univariate analysis revealed a significant association between high FCGBP immunoexpression and inferior disease-specific survival, local recurrence-free survival, and metastasis-free survival (all p ≤ 0.0002). Furthermore, high FCGBP immunoexpression independently emerged as an unfavorable prognostic factor for all three survival outcomes in the multivariate analysis (all p ≤ 0.025). Enriched pathway analysis substantiated the role of FCGBP in conferring resistance to radiation. In summary, our findings suggest that elevated FCGBP immunoexpression in rectal cancer significantly correlates with a poor response to CRT and diminished patient survival. FCGBP holds promise as a valuable prognostic biomarker for rectal cancer patients undergoing CRT.

Abstract PO1-16-02: Correlation of Circulating Tumor Cells (CTC) with Clinical Characteristics, Pathological Factors, and Treatment Response in Patients with Metastatic Breast Cancer (MBC)

Abstract Background: Circulating Tumor Cells (CTC) can be isolated in 40-80% of patients with metastatic breast cancer (MBC). High levels of CTC, defined as ≥5/7.5 ml of blood are associated with shorter progression-free survival and overall survival. CTC can be tested for clinically relevant biomarkers, such as ER, and HER2 status, and have the potential to guide therapy as well as help with disease monitoring. We investigated CTC detection rate, its correlation with clinical characteristics, pathological characteristics, and response to treatment in patients with any type of metastatic breast cancer who progressed on at least one line of therapy. Methods: Eligible patients with MBC were enrolled in the IMAGE-II study (Individualized Molecular Analyses Guide Efforts in Breast Cancer) NCT02965755, in which we obtained archival tissue as part of the standard of care, and prospectively collected serial blood samples for CTC analysis. We compared CTC levels and biomarker status with clinical factors, tissue-based pathology, and molecular biomarkers. We assessed whether changes in CTC count correlated with treatment response. Blood samples were collected at baseline (Day 1), after 1-2 weeks of therapy, after 8-12 weeks, and at subsequent restaging (every 8-12 weeks). Medical records were reviewed every 3 months for ongoing treatment response, and death. Samples were processed at the Biocept CLIA-certified Laboratory. CTC were enumerated by the presence of CD45- and DAPI+ cells. Further CTC characterization was performed by antibody staining of specific protein biomarkers (ER, HER2). Fisher’s exact test was used to evaluate the association between baseline CTC &amp;lt; 5 and ≥5/7.5ml with patient characteristics. McNemar’s test was used to assess discordance between tissue-based and CTC-defined markers. Results: Between 1/26/2018 and 12/31/22 baseline samples were collected from 70 women with a median age of 56 (36-82) who were enrolled at four study sites. CTC was detected in 59 (84%) of participants. Baseline CTC counts were &amp;lt; 5/7.5 ml in 37/59 (63%) and ≥5/7.5 ml in 22/59 (37%) of participants. Differences between breast cancer subtype and CTC-receptor status were observed (Table 1). Among the 41 patients who were ER-positive, 31 (76%) were CTC ER-negative(p&amp;lt; 0.001). Among 29 patients who were ER-negative, 4 (14%) were CTC ER-Positive (P&amp;lt; 0.001). Among the 7 patients who were HER2 positive, 2(29%) were HER2 positive on CTC. Among 63 patients who were HER2 negative, 7(11%) had HER2 expression on their CTC. The discordance in the classification of HER2 wasn't statistically significant (p=0.77). Elevated CTC at baseline was more frequently detected in younger participants (&amp;lt; 50 years old) (55% vs 27%; P=0.22), in Black women compared to White (60 % vs 29 %, P=0.27), and in participants with visceral vs non-visceral metastasis (52% vs 28 %, P=0.40). Patients with CTC ≥5 vs &amp;lt; 5/7.5mL at baseline had a shorter duration of anti-HER2-based therapy (61.5 vs 836 days, p=0.04). There were no statistically significant differences among participants who received chemotherapy agents (316.5 vs 365.5 days, P=0.88), endocrine therapy (376 vs 490 days, P=0.89), or overall therapy (272 vs 390 days, P=0.21). Conclusions: We observed significant differences in the expression of ER between tumor tissue and CTC, which can be partly due to tumor evolution over time. Additionally, participants who are young, Black, and those who have visceral metastasis may have higher CTC counts. Higher CTC counts were associated with a shorter duration of anti-HER2 therapy. Although it didn’t meet statistical significance, a similar trend was observed in patients who received chemotherapy and endocrine therapy. Table 1: MBC Tissue-Based Subtype and CTC-receptor status at baseline Citation Format: Asnakech Bayable, Tingchang Wang, Amanda Blackford, Jessica Tao, Jenna Canzoniero, Seoho Lee, Faith Too, Barbara Blouw, Mary Wilkinson, Rima Couzi, Antonio Wolff, Christie Hiton, Ben Park, Vered Stearns, Cesar Santa-Maria. Correlation of Circulating Tumor Cells (CTC) with Clinical Characteristics, Pathological Factors, and Treatment Response in Patients with Metastatic Breast Cancer (MBC) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-16-02.

Abstract PO4-15-12: Personalized circulating tumor DNA monitoring to predict response to neoadjuvant therapy in patients with early-stage breast cancer

Abstract Introduction Longitudinal ctDNA testing offers a minimally invasive approach for monitoring treatment response in patients with breast cancer (BC). In this study, we evaluated whether serial ctDNA testing during neoadjuvant therapy (NAT) can provide an early indication of treatment response or resistance and disease progression. Methods In this real world study, longitudinal blood samples collected from 159 patients with stage I-III BC were analyzed using a personalized, tumor-informed ctDNA assay (SignateraTM bespoke mPCR-NGS assay). Of the 159 patients, 157 received standard of care NAT; the remaining 2 patients were treated with endocrine therapy only in the neoadjuvant setting. Blood samples were collected at the time of diagnosis from 71 patients (baseline) and longitudinally during treatment from 159 patients (median time between time points: 1.5 months). ctDNA status and dynamics were correlated with clinicopathological features and surgical outcomes available at the time of data cut off. Results At baseline, ctDNA was detected in 72% (51/71) of patients. Baseline ctDNA detection rates varied based on histologic subtypes: 82% (28/34) in patients with triple negative breast cancer, 88% (15/17) in patients with HER2+ disease and 40% (8/20) in patients with ER+HER2- BC. ctDNA was detectable at baseline in 72% (26/36) of patients with clinical T1-2 disease and 92% (11/12) of patients with T3-4 disease. ctDNA was detected in 64% (16/25) of patients with clinical N0, whereas among patients with at least one positive lymph node, ctDNA was detected in 92% (22/24). At baseline, 65% (31/48) of patients with low/intermediate-grade disease were ctDNA-positive, while 81% (25/31) of patients with high-grade disease were ctDNA-positive. Similarly, 83% (24/29) of patients with high levels (&amp;gt;20%) of Ki67 expression had detectable ctDNA prior to treatment initiation, while only 22% (2/9) of those with low level (&amp;lt; 20%) of Ki67 expression had ctDNA detected. Surgical outcomes were available for 22 patients of whom 16 had achieved pathologic complete response (pCR). While 3/16 pts were ctDNA negative at baseline, all of the remaining cases except one patient with baseline ctDNA detection and serial measurements (11/12) became ctDNA negative by the end of two months of treatment. Despite achieving pCR, one patient with inflammatory ER+HER2+ BC remained ctDNA positive before and after the surgery, which informed a change in the adjuvant treatment strategy. Among those with residual disease (pT1c-T3), 28% (7/25) remained ctDNA positive after two months of NAT. Association between ctDNA dynamics and surgical outcomes of the remaining 137 patients will be presented at the time of the conference. Conclusions This real world study demonstrates the prevalence of ctDNA detection and dynamics in patients with eBC treated with NAT. ctDNA monitoring during NAT can facilitate real-time assessment of treatment response and serve as an early indicator of subsequent pCR to NAT. Citation Format: Mridula George, Trishala Meghal, Coral Omene, Ekaterina Kalashnikova, Janie Fielder, Nisha Ohri, Shicha Kumar, Valeria Burkovskaya, Preena Patel, Ashley Young, Melanie Racenstein, Tinamarie Bauman, Wassim Mchayleh, Deborah Toppmeyer, Shridar Ganesan, Barry Rosen, Angel Rodriguez, Minetta Liu. Personalized circulating tumor DNA monitoring to predict response to neoadjuvant therapy in patients with early-stage breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-15-12.

Abstract PO2-25-03: Deciphering the immune molecular signature associated with pembrolizumab efficacy in the neoadjuvant setting of Triple-Negative Breast Cancer patients: a single-centre experience

Abstract Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancers and is characterized by a high rate of recurrence, despite the improvement of the therapeutic approaches in recent years. Neoadjuvant chemotherapy (NACT) is the standard treatment for early-stage TNBC. Achieving a pathological complete response (pCR) is considered an essential prognostic factor for long-term outcomes. However, the percentage of pCR patients after NACT is limited to 30-40%, thus requiring the implementation of novel therapeutic strategies. Recently, by applying a morphology-guided spatial transcriptomic approach on Tru-Cut biopsies, we showed that intratumoral infiltrating lymphocytes (iTILs) and stromal Natural Killer (NK) cells are major determinants of chemotherapy efficacy in TNBC. These data highlight a complex three-dimensional organization of the tumor landscape and underline how spatiality and molecular activation of immune cells are essential to enhance the efficacy of neoadjuvant NACT in TNBC. The fact that immune cells are important players in this setting is corroborated by the clinical success shown by the KEYNOTE-522 study. This trial paved the way for the use of immunotherapy in neoadjuvant settings, obtaining a significant improvement in the patient’s overall response compared to standard NACT. Still, the implementation of chemotherapy with immunotherapy in the TNBC neoadjuvant treatment implicates several compelling questions, including how to further increase the percentage of patients with a complete response, overcoming resistance mechanisms, and how to improve the personalization of treatment, evaluating which patients can benefit from a therapy de-scalation or another combined therapeutic strategy. In this prospective cohort study, we decided to define the relevance of different immune populations in affecting pembrolizumab efficacy in the neoadjuvant treatment of TNBC patients. We treated 40 patients with an early-TNBC diagnosis with the KEYNOTE-522 regimen that consists of four cycles of an intravenous infusion of pembrolizumab plus paclitaxel and carboplatin, followed by four cycles of pembrolizumab plus epirubicin and cyclophosphamide. Only patients with evident side effects to immunotherapy administration were a priori excluded. Currently, 18 patients ended the neoadjuvant schedule and underwent surgical excision. Our data indicate that 15 patients displayed a pCR at the end of the therapy, whereas 3 patients displayed only partial response. To further clarify the immune dynamics that lead to a complete response to pembrolizumab in these patients, we collected peripheral blood before and after neoadjuvant treatment to isolate peripheral blood mononucleated cells (PBMCs). We applied a single-cell transcriptome analysis to shape any variations in circulating immune cells occurring during neoadjuvant treatment and associated with patient response. In addition, we collected residual tumors at surgery from partial responders and derived three-dimensional organoids that recapitulate the characteristics of the original patient tumor. These ex vivo organoid-based platforms are applied to clarify the molecular mechanisms driving neoadjuvant resistance. To this aim, we are performing co-cultures with autologous immune cells to identify novel combined therapeutic strategies to rescue pembrolizumab efficacy in these models. Overall, our study is defining the immune-related molecular mechanisms driving pembrolizumab and chemotherapy response in the neoadjuvant treatment of TNBC patients. Our findings can improve our understanding of which immune populations are determinant players in anti-TNBC immune response and can be proposed as novel biomarkers of pembrolizumab efficacy during the neoadjuvant treatment. Citation Format: Elisa Gasparini, Gloria Manzotti, Moira Ragazzi, Benedetta Donati, Federica Torricelli, Elisa Salviato, Alessandra Bisagni, Eleonora Zanetti, Alessandra Bologna, Saverio Coiro, Rita Vacondio, Guglielmo Ferrari, Giancarlo Bisagni, Carmine Pinto, Alessia Ciarrocchi, Francesca Reggiani. Deciphering the immune molecular signature associated with pembrolizumab efficacy in the neoadjuvant setting of Triple-Negative Breast Cancer patients: a single-centre experience [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-25-03.

Abstract PO4-16-06: From Real-World Data to Improved Outcomes: Examining the Impact of Trastuzumab Disparities on Pathological Complete Response and Long-Term Survival in HER-2 Positive Breast Cancer Patients within the Brazilian Public Health System

Abstract Introduction: Equitable access to healthcare is a fundamental principle of public health, aiming to ensure that all individuals have the opportunity to receive effective treatments. However, disparities in access to healthcare still persist in many countries, including Brazil. These disparities can have significant impacts on the health and well-being of patients, particularly in the case of breast cancer treatment. Neoadjuvant chemotherapy (NAC) has been increasingly used for the treatment of breast cancer, encompassing conditions ranging from locally advanced tumors to early-stage triple-negative and HER-2 positive tumors. Objectives: The aim of this study is to evaluate the impact of disparities in the use of trastuzumab (Herceptin) within the Brazilian public health system on pathological complete response (pCR), overall survival (OS), and disease-free survival (DFS). We aim to investigate whether variations in access to trastuzumab treatment influence the achievement of pCR and impact long-term survival outcomes in breast cancer patients. Methods: This retrospective, multicenter cohort study included female patients over 18 years of age with a diagnosis of non-metastatic breast cancer undergoing NAC. pCR was defined as the absence of residual invasive or in situ tumor in the breast and axilla. As an exploratory real-world data study, no confirmatory hypothesis was established, thus no corrections for multiple comparisons were necessary. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method, calculated at five years. The study was approved by the Research Ethics Committee with registration number CAAE 64633422.4.0000.5463. Results: Between 2011 and 2020, a total of 1,891 patients were included in the study, of whom 454 (22.9%) were HER-2 positive. The pCR rate was 25.7%. Trastuzumab was accessed by 291 (64.1%) patients (p &amp;lt; 0.001). Among those who received trastuzumab, pCR was observed in 105 (36.1%) patients, compared to 12 (7.6%) in those who did not have access to trastuzumab (p &amp;lt; 0.001). OS in HER-2 positive patients was 90.1% with pCR and 64.5% without pCR (log-rank p &amp;lt; 0.001), while DFS was 89.2% with pCR and 68.2% without pCR (log-rank p = 0.003). Evaluating OS and DFS in patients who received trastuzumab versus those who did not, OS with trastuzumab and pCR was 94.3% and without pCR was 89.5% (log-rank p &amp;lt; 0.001); OS without trastuzumab and pCR was 83.3% and without pCR was 58.2% (log-rank p &amp;lt; 0.001). DFS in patients who received trastuzumab and achieved pCR was 94.5% and without pCR was 90.5% (log-rank p = 0.05), whereas without trastuzumab and pCR was 79.9% and without pCR was 62.1% (log-rank p = 0.001). Conclusion: These findings underscore the significant impact of disparities in trastuzumab utilization within the Brazilian public health system on pCR rates and long-term survival outcomes in HER-2 positive breast cancer patients. Access to trastuzumab was associated with higher pCR rates and improved overall and disease-free survival rates. Ensuring equitable access to targeted therapies is crucial for improving treatment response and long-term outcomes in breast cancer patients. Table 1 Clinicopathological characteristics of patients Legend: AJCC, American Joint Committee on Cancer; IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma; HR hormonal receptor. Table 2 - NAC schemas and correlation with pCR. AC-T, doxorubicin + cyclophosphamide – taxane; AC-TH, doxorubicin + cyclophosphamide – taxane+herceptin. Citation Format: Marcelo Antonini, Andre Mattar, Gabriel Pannain, Fernanda Grace Bauk Richter, Andressa Amorim, Marina Diogenes, Odair Ferraro, Luiz Gebrim, Reginaldo Coelho Lopes, Juliana Real. From Real-World Data to Improved Outcomes: Examining the Impact of Trastuzumab Disparities on Pathological Complete Response and Long-Term Survival in HER-2 Positive Breast Cancer Patients within the Brazilian Public Health System [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-16-06.

Abstract PO5-25-03: Immune cell infiltrate profiles in primary Triple Negative Breast Cancer and co-relation with treatment response and survival outcomes

Abstract Introduction Tumor microenvironment (TME) in breast cancer is a heterogeneous landscape with multiple cell types, each modulating the tumor progression and the disease prognosis. These cell types include lymphocytes, RBCs, stromal cells, macrophages, cancer-associated fibroblasts (CAFs), and cancer stem cells. Each cell type in the TME influences tumor progression and clinical outcomes for patients in a good or bad way, depending on the interaction with tumor cells. Tumor-infiltrating lymphocytes (TILs) are shown to be prognostic for therapy response in many cancers in the western cohorts. Our recent study showed that a higher proportion of Indian TNBC patients had intra-tumoral TILs compared to Western cohorts, and these are predictive of better response to NACT and longer disease-free survival in patients, making it a distinct finding from Western reports. In the follow-up study, we are characterizing infiltrating immune cell subtypes and their comparative association with treatment response in TNBC patients. Results from preliminary analysis and comparative analysis between responders and non-responders will be presented here. We speculate that the pro- and anti-tumorigenic immune cell population and its spatial information would help us understand TME and its precise role in response to therapy. Methods A retrospective cohort of breast cancer patients from a single one-surgeon breast cancer clinic with a uniform treatment strategy was evaluated for this study. FFPE primary tissue samples with variable TILs scores (moderate to high), taken from patients who showed complete response to the NACT treatment (n=6) and non-responding group (n=8) determined by H&amp;E stained slides from our cohort, were further stained for immune cells (Pan-B cell, Pan-T cells, Pan-macrophages) and T cells (CD4; Helper T cell marker, CD8; Cytotoxic T cell marker), FOXP; Regularly CD4+ cell marker) and PanCK (Pan-tumor marker) and counterstained with DAPI for multiplex imaging. Multispectral images for these slides were obtained using the Leica Aperio Versa system. Parameters such as individual cell types of identification and scoring, spatial proximity to tumor cells, and individual cell types will be determined by HALO software using the High plex module. Results A total of 14 TNBC samples were stained for the T-cell subtypes panel and Immune cell subtype s panel to determine the TIME. DAPI stain was used for nuclear counting based the parameters such as threshold intensity, nuclear size, roundness, and aggressiveness. The cytoplasmic size was selected as 2um beyond the outside nuclear boundary. Using Halo-Indica software, around 50000-300000 cells/tissue were evaluated across all samples from mIF whole slide scans of biopsy samples. Cell count was validated by cross-checking individual ROIs and manual cell count using Fiji. A Highplex module was used to identify individual signal positivity for each marker based on threshold intensity and cell completeness percent. Preliminary data showed a higher proportion of CD8+ cells and macrophages population are spatially closer to the tumor cells in Responders compared to non-responders. Conclusion Immune profiles are distinct among responding and non-responding patients in the Indian TNBC cohort. The association of these profiles with long-term survival in patients and various clinical and pathological parameters will help us determine the clinical relevance of these profiles and identify distinct immune subgroups as prognostic in Indian TNBCs. Citation Format: Pooja Vaid, Devaki Kelkar, LS Shashidhara, C B Koppiker, Madhura Kulkarni. Immune cell infiltrate profiles in primary Triple Negative Breast Cancer and co-relation with treatment response and survival outcomes [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-25-03.

Abstract PO5-13-12: Personalized circulating tumor DNA testing for recurrence detection and treatment response monitoring in patients with metastatic invasive lobular carcinoma

Abstract Introduction Metastatic invasive lobular carcinoma (mILC) presents unique challenges during treatment response monitoring. A higher frequency of metastases to the bone, gastrointestinal tract, uterus, meninges, ovary, and diffuse serosal involvement is observed in mILC. The challenge with mILC is that they can be difficult to detect clinically and radiographically, and consequently clinical progression can be difficult to determine with conventional imaging modalities like CT Scans, thus precluding many patients with mILC from enrolling into clinical trials. Therefore more accurate biomarkers are needed to better assess response to treatment in real time. In this study, we demonstrate the feasibility of longitudinal ctDNA testing for treatment response monitoring in patients with mILC. Methods In this real-world study, longitudinal plasma samples (n=219) from 60 patients with mILC, treated across 52 independent clinics between 7/22/21 and 6/15/23, were analyzed. A personalized, tumor-informed ctDNA assay (SignateraTM bespoke, mPCR-NGS assay) was used for detection and quantification of ctDNA in plasma samples. Results In this cohort, the median patient age at diagnosis of metastatic disease (baseline) was 62.9 years (range: 32.2-79.7). Of the 60 patients, 41 (68%) had ER+PR+HER2-, 7 (12%) ER+PR-HER2-, 4 (7%) ER+PR+HER2+, 2 (3%) ER+PR-HER2+, 1 (2%) triple negative breast cancer; receptor status was not available for 5 (8%) patients. CDH1 (75%) and PIK3CA (42%) were observed to be the top two genes with somatic, nonsynonymous mutations. Mutations in TP53 and TBX3 were observed in 13% of patients, mutations in AKAP9, IGFN1, RBM26, and RFC3 in 10% of patients, and mutations in ESR1 in 6.7% of patients. At variant level, PIK3CA p.H1047R (22%) and RBM26 p.Q701Tfs*23 (10%) were the top two somatic variants identified. The most common CDH1 variant, p.Q23*, was found in 5% of the cases. Of the 60 patients, 37 (61.7%) were ctDNA-positive at all time points while on treatment (chemotherapy/endocrine therapy/targeted therapy) with the first time point collected at a median of 6.7 months (range: 2.5-2307 months) from baseline. Of these 37, imaging/biopsy results after baseline were available for 32 patients, 86% (27/32) of whom progressed. Thirty-two of 37 persistently ctDNA-positive patients had serial ctDNA measurements available, of which 14 (43%) had significant increase in ctDNA levels (average: 47-fold increase, standard deviation: 98) from first to last time points. At some point during their care ctDNA was detectable in all (n=51) patients with evidence of clinical progression. Of the 60 patients, 14 (23.3%) were ctDNA-negative at all time points tested. None of the 14 persistently ctDNA-negative patients had evidence of disease recurrence or progression at the time of initial testing or throughout ctDNA monitoring. The first ctDNA time point was collected at a median of 33.1 months (range: 0.68-92 months) from baseline for these patients,a median of 3 time points was tested per patient (1-12). Of the remaining 9/60 patients, 3 (33%) had sustained ctDNA clearance for a median of 46 days (range: 0-224 days) in response to treatment, and 2 (22%) were initially ctDNA-negative but turned positive 105 and 156 days later, indicating potential resistance to treatment and molecular progression. Additional 4/9 (44%) had ctDNA levels consistently low levels (average: 0.42 mean tumor molecules/mL) while on treatment for a median of 260 days (range: 217-442) and showed no evidence of progression. Conclusions ctDNA status and dynamics correlate well with clinical status of patients with mILC, as determined by conventional monitoring tools such as imaging and biopsy. Our results indicate that personalized, tumor-informed, longitudinal ctDNA testing may serve as a useful tool for detection of progression and monitoring treatment response in mILC patients. Citation Format: Steffi Oesterreich, Antony Tin, Samuel Rivero-Hinojosa, Janie Fielder, Jenifer Ferguson, Ekaterina Kalashnikova, Angel Rodriguez, Minetta Liu, Adrian Lee. Personalized circulating tumor DNA testing for recurrence detection and treatment response monitoring in patients with metastatic invasive lobular carcinoma [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-13-12.

Abstract PO5-05-07: Efficacy and safety of first line CDK4/6i plus endocrine therapy for patients with HR+/HER2- metastatic breast cancer:initial real-world experience at Ho Chi Minh city oncology hospital, Viet Nam

Abstract Background The cyclin-dependent kinases (CDK)4/6 inhibitors (CDK4/6i) palbociclib and ribociclib have been available in Viet Nam since 2021 for the treatment of hormone receptor-positive metastatic breast cancer (MBC). Data regarding CDK4/6i benefit in Vietnamese MBC are sparse. This study evaluated the impact of CDK4/6i in first-line HR+/HER2− MBC using real-world experience at Ho Chi Minh City Oncology Hospital. Methods A single-institution study analyzed retrospective data from 108 patients treated with palbiciclib or ribociclib with endocrine therapy in first-line in HR+/HER2– MBC patients at Ho Chi Minh city oncology hospital. Patient characteristics, PFS, treatment response, and toxicity profiles were analyzed. Results Baseline patients’ characteristics are detailed in Table 1.The median follow-up was 12.5 months (95% CI: 10.9-13.3). Best responses by the line of therapy are in Table 2. The median PFS has still not been reached. The PFS rates at 6, 12 and 18 months were 94.4%, 93.5% and 91.5%, respectively. Patients with bone-only metastasis have a better PFS than visceral metastasis (p = 0.059). Patients with recurrent disease had shorter PFS (p = 0.083) than those presenting with de novo metastasis. The most common reasons for toxicity were neutropenia (92.6%), anemia (35.2%), thrombopenia (22.2%) and the incidence of diarrhea was only 2,8%. None were related to QTc-prolongation Conclusion The real-world effectiveness and safety with CDK4/6 inhibitors in our institution HR+/HER2– MBC patients mimics that observed in the clinical trials. This finding supports the use of CDK4/6i in combination with endocrine therapy as standard of care for HR+/HER2- MBC in Viet Nam. The study also suggests the need for more study of under-represented minority populations. Further studies are ongoing to validate these findings incorporating additional cancer centers. Keywords: advanced/metastatic breast cancer, Asia, CDK4/6 inhibitors, real world Table 1. Patient Demographics and Baseline Disease Characteristics (N=108) Characteristics N (%) Age, y: Median 52 Stage Recurrent from earlier stage, stages 0–III 67 (62) De novo, newly diagnosed stage IV at enrolment 41 (38) DFI &amp;lt; 12 months 5 (4.6) 12-24 months 12 (11.1) &amp;gt; 24 months 51 (47.2) No. of metastatic sites 1 49 (45.4) 2 37 (34.3) ≥ 3 22 (20.4) Metastasis pattern Bone only 30 (27.8) Other 78 (72.2) CDK4/6i Palbociclib 35 (32.4) Ribociclib 73 (67.6) Partner ET AIs 94 (87) Fulvestrant 14 (13) Table 2. Best responses of therapy (N=108) Best responses (N,%) CR 2 (1.9) PR 29 (26.9) SD 67 (62.1) PD 10 (9.3) Total 108 (100) ORR 31 (28.8) CBR 76 (70.3) Table. Citation Format: Hoang-Quy Nguyen, Hong-Duc Phan-Thi, Thi-Hong-Van Le. Efficacy and safety of first line CDK4/6i plus endocrine therapy for patients with HR+/HER2- metastatic breast cancer:initial real-world experience at Ho Chi Minh city oncology hospital, Viet Nam [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-05-07.

Abstract PO5-19-12: Innovative Trial Design: ARTIDIS Nanomechanical Generated Measurements for Early Breast Lesions (ANGEL) - Multicentre Study

Abstract Background: The diagnosis of breast cancer based on histopathology of core needle biopsies and the delineation into breast cancer subtypes to drive clinical treatment decisions can be time consuming and cause patient (and clinician) anxiety. Alternative, near patient, approaches to conventional diagnostic pathways would be desirable to drive diagnostic and therapeutic planning. This study harnesses the novel concept of evaluating diagnostic cores for nanomechanical features at the time of core biopsy. Clinical manifestations of disease are often accompanied by biomechanical alterations at sub-/cellular, extracellular, tissue and organ level. Mechanical properties of cancer cells and their microenvironment play a critical role in cancer invasion, progression, and immune cell infiltration. Ultrastructural (sub-) cellular alterations (nanoscale level), including the remodulation and alteration of cellular cytoskeleton dynamics, contribute to altered mechanical state of cancer cells, and lead to increased deformability and motility of soft cancer cells to overcome stromal barrier, and spread into the adjacent tissues and distant sites in the body. This results in a direct mechanistic correlation between nanomechanical properties and clinical outcome in cancer tissues. The ARTIDIS Nanomechanical Generated measurements for Early Lesions (ANGEL) Study will prospectively evaluate the efficacy of the ARTIDIS system as an aid to diagnosis, as well as subtyping breast cancer and predicting clinical outcomes based on tissue nanomechanics, particularly in the context of neoadjuvant therapy (NAT). Methods: The study seeks to validate the predictive power of the nanomechanical signature, a unique tissue biomarker reflecting the tissue phenotype, by comparing it to standard histological assessment. A projected cohort of 2,705 patients will be enrolled, from diverse ethnic and socioeconomic backgrounds, with benign or malignant breast conditions undergoing diagnostic core biopsy. A single core biopsy (gauge agnostic) is placed in a cassette and subjected to thousands of mechanical measurements at the “nano” scale over a period of 1-3 hours. The ARTIDIS technology builds upon the Atomic Force Microscopy platform to non-disruptively detect up to 17 different nanomechanical parameters in soft tissues with a subcellular resolution. The same core biopsy can then undergo fixation and conventional histopathological analyses for comparison with the final pathology. The primary aim is to confirm the potential of the ARTIDIS system in diagnosis (benign vs malignant) and secondarily address whether the nanomechanical signature can differentiate subtypes of breast cancer, associate with clinical outcome, and guide treatment decisions. Particularly, we will investigate ARTIDIS potential as a predictor of treatment response for patients receiving NAT. Results: The multicenter ANGEL study is a prospective investigation that builds upon previous clinical data from the NANO study at the University Hospital Basel (Switzerland) and is designed to demonstrate the power of using a nanomechanical signature to evaluate breast biopsies within a routine clinical setting in a multicenter setting. The data will be used to develop ARTIDIS as an aid to diagnosis, as well as NEO Match test applications to predict and guide response to NAT. Conclusion: This study presents the first of its kind as a direct prospective, multi-center based clinical translation of the Physics of Cancer findings into clinical settings. This innovative trial design allows the prospective development of ARTIDIS as an aid to diagnosis and NAT outcome prediction and therapy guidance applications. Citation Format: Karla Sepulveda, Ashley Roark, Sagar Dhamne, Chandandeep Nagi, Ivan Marin, Iqbal Tabish, Susanne G. Hilsenbeck Hilsenbeck, Sara Nizzero, Mariam Gachechiladze, Tobias A Appenzeller, Marko Loparic, Marija Plodinec, Alastair Thompson. Innovative Trial Design: ARTIDIS Nanomechanical Generated Measurements for Early Breast Lesions (ANGEL) - Multicentre Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-19-12.

Analysis of clinical characteristics and factors affecting treatment responses in patients with pyoderma gangrenosum: a multicenter study of 239 patients☆

BackgroundPyoderma Gangrenosum (PG) is a chronic disease characterized by recalcitrant skin ulcers. ObjectiveWe aimed to evaluate the demographic, clinical characteristics, treatments and factors affecting the treatment responses of patients with PG. MethodsWe performed a multicenter study of 12 tertiary care centers. We analyzed the data of the patients who were followed up with a diagnosis of PG between the years 2012‒2022 retrospectively. ResultsWe included a total of 239 patients of whom 143 were female and 96 were male, with an average age of 54.2 ± 17.4 years. The most common treatment was systemic steroids (n = 181, 75.7%). Among these patients, 50.8% (n = 92) used systemic steroids as the sole systemic agent, while 49.2% (n = 89) used at least one adjuvant immunosuppressive agent. The independent factors determined in regression analysis to influence response to systemic steroids positively were disease onset age ≥ 30-years, negative pathergy, absence of leukocytosis, negative wound culture, presence of a single lesion, and absence of upper extremity involvement. Biological agents were used in 18.4% (n = 44) of the patients in the present study. We also analyzed pathergy positive PG and early onset (onset age < 30) PG separately due to their distinct clinical features which were revealed during statistical analysis. Study limitationsRetrospective nature of the present study. ConclusionsAnalyses of the factors influencing treatment responses are addressed in this study. Also, we concluded that investigation for accompanying autoinflammatory diseases of pathergy positive PG and early onset PG is necessary and the patients in these two groups are more resistant to treatment, necessitating more complicated treatments.

Fractional amplitude of low-frequency fluctuations in sensory-motor networks and limbic system as a potential predictor of treatment response in patients with schizophrenia

BackgroundPrevious investigations have revealed substantial differences in neuroimaging characteristics between healthy controls (HCs) and individuals diagnosed with schizophrenia (SCZ). However, we are not entirely sure how brain activity links to symptoms in schizophrenia, and there is a need for reliable brain imaging markers for treatment prediction. MethodsIn this longitudinal study, we examined 56 individuals diagnosed with 56 SCZ and 51 HCs. The SCZ patients underwent a three-month course of antipsychotic treatment. We employed resting-state functional magnetic resonance imaging (fMRI) along with fractional Amplitude of Low Frequency Fluctuations (fALFF) and support vector regression (SVR) methods for data acquisition and subsequent analysis. ResultsIn this study, we initially noted lower fALFF values in the right postcentral/precentral gyrus and left postcentral gyrus, coupled with higher fALFF values in the left hippocampus and right putamen in SCZ patients compared to the HCs at baseline. However, when comparing fALFF values in brain regions with abnormal baseline fALFF values for SCZ patients who completed the follow-up, no significant differences in fALFF values were observed after 3 months of treatment compared to baseline data. The fALFF values in the right postcentral/precentral gyrus and left postcentral gyrus, and the left postcentral gyrus were useful in predicting treatment effects. ConclusionOur findings suggest that reduced fALFF values in the sensory-motor networks and increased fALFF values in the limbic system may constitute distinctive neurobiological features in SCZ patients. These findings may serve as potential neuroimaging markers for the prognosis of SCZ patients.

Heavy-light chain pairs as an alternative method to monitor isatuximab-based treatment responses in multiple myeloma patients

Heavy-light chain pairs as an alternative method to monitor isatuximab-based treatment responses in multiple myeloma patients

Programmed Death Ligand-1 and Tumor Burden Score Dictate Treatment Responses in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma.

The significance of tumor burden for survival is unknown for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). The purpose of our study was to evaluate the prognostic impact of programmed death ligand-1 (PD-L1) and tumor burden score (TBS) in patients with R/M HNSCC. R/M HNSCC patients who were treated with cisplatin, 5-fluorouracil plus cetuximab (EPF) or pembrolizumab (PPF) as first-line treatment were included in our study. PD-L1 and TBS were estimated and correlated with treatment responses. Kaplan-Meier curves were plotted for outcomes estimation. A total of 252 R/M HNSCC patients were included, with 126 high tumor burden (HTB) and 126 low tumor burden (LTB) patients. Median progression-free survival (PFS) was 7.1 months in LTB and 3.9 months in HTB (p < 0.001) and median overall survival (OS) was 14.2 months in LTB and 9.2 months in HTB (p = 0.001). Patients with LTB had better PFS and OS than those with HTB independent of PD-L1 status. Subgroup analysis showed HTB patients treated with EPF had better survival than those treated with PPF, regardless of PD-L1 expression. For LTB PD-L1 positive patients, there was a longer survival with PPF than EPF, while for LTB PD-L1 negative patients, survival was similar between PPF and EPF. Multivariate analysis exhibited that tumor burden was significantly correlated with OS. Tumor burden is significantly correlated with survival in patients with R/M HNSCC. PD-L1 and TBS should be taken into consideration to determine first-line treatment.

Impact of obstructive sleep apnea risk on prognosis and treatment responses of lung cancer

Aims: Obstructive sleep apnea (OSA) may affect oncogenic processes in a specific way for each tumor type. This study was conducted to reveal the relationship between OSA risk and prognosis and treatment responses in patients with lung cancer. Methods: This prospective study included stage III and IV lung cancer patients aged between 18 and 75 years. Patients with poor performance status, cranial metastasis, congestive heart failure, surgery history, and positive airway pressure device use were excluded. STOP-BANG questionnaire was used to assess the OSA risk. The primary end-point was the differences in the survival and treatment responses of patients at intermediate/high risk of OSA compared with those at low OSA risk. Data from the patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) were analyzed separately. Results: Ninety-eight patients (34 SCLC and 64 NSCLC), mostly male (85.7%), with a mean age of 59.3±8 were included in the analysis. Overall survival was similar in the groups. However, in the SCLC group, those at low OSA risk had a shorter progression-free survival (PFS) than those at intermediate/high risk (105±31.8 days, vs 272±16.2 days, p=0.001). Cox regression analysis showed that low OSA risk was an independent risk factor for PFS in only the SCLC group (HR:4.9 CI:1.6-14.7, p=0.005). Conclusion: IOur results showed that low OSA risk was an independent poor prognostic factor for PFS in SCLC regardless of the tumor stage.

Prediction of the treatment response and local failure of patients with brain metastasis treated with stereotactic radiosurgery using machine learning: A systematic review and meta-analysis.

Stereotactic radiosurgery (SRS) effectively treats brain metastases. It can provide local control, symptom relief, and improved survival rates, but it poses challenges in selecting optimal candidates, determining dose and fractionation, monitoring for toxicity, and integrating with other modalities. Practical tools to predict patient outcomes are also needed. Machine learning (ML) is currently used to predict treatment outcomes. We aim to investigate the accuracy of ML in predicting treatment response and local failure of brain metastasis treated with SRS. PubMed, Scopus, Web of Science (WoS), and Embase were searched until April 16th, which was repeated on October 17th, 2023 to find possible relevant papers. The study preparation adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The statistical analysis was performed by the MIDAS package of STATA v.17. A total of 17 articles were reviewed, of which seven and eleven were related to the clinical use of ML in predicting local failure and treatment response. The ML algorithms showed sensitivity and specificity of 0.89 (95% CI: 0.84-0.93) and 0.87 (95% CI: 0.81-0.92) for predicting treatment response. The positive likelihood ratio was 7.1 (95% CI: 4.5-11.1), the negative likelihood ratio was 0.13 (95% CI: 0.08-0.19), and the diagnostic odds ratio was 56 (95% CI: 25-125). Moreover, the pooled estimates for sensitivity and specificity of ML algorithms for predicting local failure were 0.93 (95% CI: 0.76-0.98) and 0.80 (95% CI: 0.53-0.94). The positive likelihood ratio was 4.7 (95% CI: 1.6-14.0), the negative likelihood ratio was 0.09 (95% CI: 0.02-0.39), and the diagnostic odds ratio was 53 (95% CI: 5-606). ML holds promise in predicting treatment response and local failure in brain metastasis patients receiving SRS. However, further studies and improvements in the treatment process can refine the models and effectively integrate them into clinical practice.

Prediction of Responsiveness to PD-L1/PD-1 Inhibitors Using miRNA Profiles Associated With PD-L1 Expression in Lung Adenocarcinoma and Squamous Cell Carcinoma.

MicroRNAs (miRNAs) regulate programmed cell death ligand 1 (PD-L1) and play a crucial role in tumor immune response. However, the relationship between miRNA expression patterns and PD-L1 remains unclear in both lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). We investigated PD-L1-related miRNAs that can predict treatment response in patients treated with PD-L1/PD-1 inhibitors. We selected miRNAs that were correlated with PD-L1 expression within the LUAD and LUSC datasets obtained from The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC). We validated whether the miRNA profile could be used to predict the prognosis of patients treated with PD-L1/PD-1 inhibitors. Based on four public datasets, we selected 66 and 23 miRNAs associated with PD-L1 expression in LUAD and LUSC, respectively. From the above miRNAs, we identified 5 miRNAs in LUSC and 1 miRNA in LUAD that could predict the response to PD-L1/PD-1 inhibitors in a validation set of patients treated with PD-L1/PD-1 inhibitors. In LUSC, the miRNA profile exhibited a high predictive capability for the response to PD-L1/PD-1 treatment [area under the curve (AUC)=0.963] and accurately predicted prognosis (p=0.031). In LUAD, the miRNA profile was relatively less predictive than in LUSC (AUC=0.691 and p=0.213). Additionally, we observed variations in the PD-L1-associated miRNA profiles, as well as in the associated pathways, between LUAD and LUSC. The PD-L1-associated miRNA profile may predict treatment response in LUSC patients treated with PD-L1/PD-1 inhibitors and help select the PD-L1/PD-1 inhibitor treatment group.