Exploration of targeted anti-tumor therapy最新文献

{"title":"Recent preclinical and clinical advances in radioimmunotherapy for non-Hodgkin's lymphoma.","authors":"Hiroki Goto, Yoshioki Shiraishi, Seiji Okada","doi":"10.37349/etat.2024.00213","DOIUrl":"10.37349/etat.2024.00213","url":null,"abstract":"<p><p>Radioimmunotherapy (RIT) is a therapy that combines a radioactive nucleotide with a monoclonal antibody (mAb). RIT enhances the therapeutic effect of mAb and reduces toxicity compared with conventional treatment. The purpose of this review is to summarize the current progress of RIT for treating non-Hodgkin's lymphoma (NHL) based on recent preclinical and clinical studies. The efficacy of RIT targeting the B-lymphocyte antigen cluster of differentiation 20 (CD20) has been demonstrated in clinical trials. Two radioimmunoconjugates targeting CD20, yttrium-90 (⁹⁰Y)-ibritumomab-tiuxetan (Zevalin) and iodine-131 (¹³¹I)-tositumomab (Bexxar), have been approved in the USA Food and Drug Administration (FDA) for treating relapsed/refractory indolent or transformed NHL in 2002 and 2003, respectively. Although these two radioimmunoconjugates are effective and least toxic, they have not achieved popularity due to increasing access to novel therapies and the complexity of their delivery process. RIT is constantly evolving with the identification of novel targets and novel therapeutic strategies using newer radionuclides such as alpha-particle isotopes. Alpha-particles show very short path lengths and high linear energy transfer. These characteristics provide increased tumor cell-killing activities and reduced non-specific bystander responses on normal tissue. This review also discusses reviewed pre-targeted RIT (PRIT) and immuno-positron emission tomography (PET). PRIT potentially increases the dose of radionuclide delivered to tumors while toxicities to normal tissues are limited. Immuno-PET is a molecular imaging tracer that combines the high sensitivity of PET with the specific targeting capability of mAb. Immuno-PET strategies targeting CD20 and other antigens are currently being developed. The theragnostic approach by immuno-PET will be useful in monitoring the treatment response.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 1","pages":"208-224"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10918239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140095255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the function of myeloid cells in promoting metastasis in head and neck cancer.","authors":"Dakota Dike Dimegwu Okwuone, Deri Morgan, Gregory N Gan","doi":"10.37349/etat.2024.00208","DOIUrl":"10.37349/etat.2024.00208","url":null,"abstract":"<p><p>Head and neck cancer (HNC) is a challenging disease that lacks effective treatment, particularly in the cases that spread locoregionally and metastasize distantly, dramatically reducing patient survival rates. Expanding the understanding of the mechanisms of the metastatic cascade is critical for creating more effective therapeutics that improve outcomes for HNC patients. A true grasp of cancer metastasis requires the consideration of all cell types that contribute to the inflammatory HNC microenvironment as drivers of this process. More emphasis now is being placed on exploring the roles of the different immune cells in cancer control, tumorigenesis and metastasis. Myeloid cells are the most numerous immune cell types in the body, and they are actively recruited and reprogrammed by tumor cells to behave in a variety of ways. These cells are remarkably diverse in phenotype and function, and the part they play in tumor spread greatly differs based on the cell type. This review will focus on summarizing the roles of macrophages, neutrophils, myeloid derived suppressor cells (MDSCs), and dendritic cells (DCs) in driving HNC metastasis by examining the current knowledge base and offering potential new routes through which to target and treat this deadly process.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 1","pages":"108-119"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10925485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140102966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The rapidly changing treatment landscape of first-line advanced urothelial cancer (aUC) or metastatic urothelial cancer (mUC).","authors":"Minira Aslanova, Eun-Mi Yu, Jeanny B Aragon-Ching","doi":"10.37349/etat.2024.00258","DOIUrl":"https://doi.org/10.37349/etat.2024.00258","url":null,"abstract":"<p><p>The landscape of treatment for first-line therapy in advanced urothelial cancer (aUC) and metastatic urothelial cancer (mUC) has rapidly changed in the last year alone. Maintenance avelumab remains a viable treatment option for many patients across the globe for those who have responded or have achieved stable disease after platinum-based chemotherapy. However, the recent FDA approvals based on EV-302 for enfortumab vedotin (EV) and pembrolizumab, as well as CheckMate-904 with gemcitabine and cisplatin with nivolumab (GC+N) followed by maintenance nivolumab have left clinicians with the complicated decision of determining which regimen is most appropriate for their individual patients with untreated aUC. This commentary highlights the key trials that have set the standard-of-care for front-line aUC treatment and suggestions for choosing different regimens for the appropriate patient.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 4","pages":"971-980"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11390289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood-based circulating biomarkers for prediction of immune-checkpoint inhibitors efficacy in renal cell carcinoma.","authors":"Loubna Omri, Marie Naigeon, Ronan Flippot, Javier Gavira-Díaz, Jesus Poveda-Ferriols, Dan Nguyen, Chaimae Abdi, Alvaro Arroyo-Salgado, Nathalie Chaput, Guillermo de Velasco, Laurence Albigès, Lucía Carril-Ajuria","doi":"10.37349/etat.2024.00271","DOIUrl":"10.37349/etat.2024.00271","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICI)-based combinations have become the standard first-line treatment for advanced clear cell renal cell carcinoma (ccRCC). Despite significant improvements in survival and the achievement of sustained long-term responses, a subset of patients remains refractory to ICI, and most will eventually develop resistance. Thus, identifying predictive biomarkers for ICI efficacy and resistance is essential for optimizing therapeutic strategies. Up to now, tissue-based biomarkers have not been successful as predictive biomarkers in RCC. Circulating blood-based biomarkers offer a promising alternative. These biomarkers, including circulating immune cells, soluble factors, tumor-derived markers, and those based on metabolomics, are less invasive, offer reproducibility over time, and provide a comprehensive assessment of tumor biology and patient immune status, as well as allow dynamic monitoring during treatment. This review aims to evaluate the current evidence on the different candidate circulating biomarkers being investigated for their potential to predict ICI efficacy in RCC patients.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 6","pages":"1199-1222"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-PD-1/L1 antibody plus anti-VEGF antibody <i>vs.</i> plus VEGFR-targeted TKI as first-line therapy for unresectable hepatocellular carcinoma: a network meta-analysis.","authors":"Yiwen Zhou, Jingjing Li, Jieer Ying","doi":"10.37349/etat.2024.00236","DOIUrl":"10.37349/etat.2024.00236","url":null,"abstract":"<p><strong>Background: </strong>This article is based on our previous research, which was presented at the 2023 ASCO Annual Meeting I and published in <i>Journal of Clinical Oncology</i> as Conference Abstract (<i>JCO</i>. 2023;41:e16148. doi: 10.1200/JCO.2023.41.16_suppl.e16148). Both anti-programmed death 1/ligand-1 (PD-1/L1) antibody + anti-vascular endothelial growth factor (VEGF) antibody (A + A) and anti-PD-1/L1 antibody + VEGF receptor (VEGFR)-targeted tyrosine kinase inhibitor (A + T) are effective first-line therapies for unresectable hepatocellular carcinoma. However, there lacks evidence from head-to-head comparisons between these two treatments. We conducted a network meta-analysis on the efficacy and safety of them.</p><p><strong>Methods: </strong>After a rigorous literature research, 6 phase III trials were identified for the final analysis, including IMbrave150, ORIENT-32, COSMIC-312, CARES-310, LEAP-002, and REFLECT. The experiments were classified into three groups: A + A, A + T, and intermediate reference group. The primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and incidence of treatment-related adverse events (TRAEs). Hazard ratio (HR) with 95% confidence intervals (CI) for OS and PFS, odds ratio (OR) for ORR, and relative risk (RR) for all grade and grade ≥3 TRAEs were calculated. Under Bayesian framework, the meta-analysis was conducted using sorafenib as intermediate reference.</p><p><strong>Results: </strong>With the rank probability of 96%, A + A showed the greatest reduction in the risk of death, without significant difference from A + T (HR: 0.82, 95% CI: 0.65-1.04). A + T showed the greatest effect in prolonging PFS and improving ORR with the rank probability of 77%, but there were no statistical differences with A + A. A + A was safer than A + T in terms of all grade of TRAEs (RR: 0.91, 95% CI: 0.82-1.00) and particularly in those grade ≥3 (RR: 0.65, 95% CI: 0.54-0.77).</p><p><strong>Conclusions: </strong>A + A had the greatest probability of delivering the longest OS, while A + T was correlated with larger PFS benefits at the cost of a lower safety rate.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 3","pages":"568-580"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11220314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel therapeutic strategies targeting myeloid-derived suppressor cell immunosuppressive mechanisms for cancer treatment.","authors":"Eric Jou, Natasha Chaudhury, Fizza Nasim","doi":"10.37349/etat.2024.00212","DOIUrl":"10.37349/etat.2024.00212","url":null,"abstract":"<p><p>Cancer is the leading cause of death globally superseded only by cardiovascular diseases, and novel strategies to overcome therapeutic resistance against existing cancer treatments are urgently required. Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells with potent immunosuppressive capacity against well-established anti-tumour effectors such as natural killer cells (NK cells) and T cells thereby promoting cancer initiation and progression. Critically, MDSCs are readily identified in almost all tumour types and human cancer patients, and numerous studies in the past decade have recognised their role in contributing to therapeutic resistance against all four pillars of modern cancer treatment, namely surgery, chemotherapy, radiotherapy and immunotherapy. MDSCs suppress anti-tumour immunity through a plethora of mechanisms including the well-characterised arginase 1 (Arg1), inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS)-mediated pathways, along with several other more recently discovered. MDSCs are largely absent in healthy homeostatic states and predominantly exist in pathological conditions, making them attractive therapeutic targets. However, the lack of specific markers identified for MDSCs to date greatly hindered therapeutic development, and currently there are no clinically approved drugs that specifically target MDSCs. Methods to deplete MDSCs clinically and inhibit their immunosuppressive function will be crucial in advancing cancer treatment and to overcome treatment resistance. This review provides a detailed overview of the current understandings behind the mechanisms of MDSC-mediated suppression of anti-tumour immunity, and discusses potential strategies to target MDSC immunosuppressive mechanisms to overcome therapeutic resistance.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 1","pages":"187-207"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10918238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140095253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of lysyl oxidase as an adipocyte-secreted mediator that promotes a partial mesenchymal-to-epithelial transition in MDA-MB-231 cells.","authors":"Cassidy M Van Stiphout, Grant Kelly, Nikitha K Pallegar, Eman Elbakry, Ana Valeria Vilchis-Celis, Sherri L Christian, Alicia M Viloria-Petit","doi":"10.37349/etat.2024.00201","DOIUrl":"10.37349/etat.2024.00201","url":null,"abstract":"<p><strong>Aim: </strong>Breast cancer (BC) is the most common cancer in women worldwide, where adiposity has been linked to BC morbidity. In general, obese premenopausal women diagnosed with triple-negative BC (TNBC) tend to have larger tumours with more metastases, particularly to the bone marrow, and worse prognosis. Previous work using a 3-dimensional (3D) co-culture system consisting of TNBC cells, adipocytes and the laminin-rich extracellular matrix (ECM) trademarked as Matrigel, demonstrated that adipocytes and adipocyte-derived conditioned media (CM) caused a partial mesenchymal-to-epithelial transition (MET). Given that MET has been associated with secondary tumour formation, this study sought to identify molecular mediators responsible for this phenotypic change.</p><p><strong>Methods: </strong>Adipocytes were cultured with and without Matrigel, where semi-quantitative proteomics was used to identify proteins whose presence in the CM was induced or enhanced by Matrigel, which were referred to as adipocyte-secreted ECM-induced proteins (AEPs). The AEPs identified were assessed for association with prognosis in published proteomic datasets and prior literature. Of these, 4 were evaluated by the reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), followed by a functional and MET marker analysis of 1 AEP on MDA-MB-231 cells grown on Matrigel or as monolayers.</p><p><strong>Results: </strong>The 4 AEPs showed a positive correlation between protein expression and poor prognosis. RT-qPCR analysis reported no significant change in AEPs mRNA expression. However, lysyl oxidase (LOX) was increased in CM of ECM-exposed adipocytes. Recombinant LOX (rLOX) caused the mesenchymal MDA-MB-231 TNBC cells to form less branched 3D structures and reduced the expression of vimentin.</p><p><strong>Conclusions: </strong>The data suggest that adipocyte-secreted LOX changes the mesenchymal phenotype of BC cells in a manner that could promote secondary tumour formation, particularly at sites high in adipocytes such as the bone marrow. Future efforts should focus on determining whether targeting LOX could reduce BC metastasis in obese individuals.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 1","pages":"1-19"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10927314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140102967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic utility of prostate health index density prior to MRI-ultrasound fusion targeted biopsy.","authors":"Benjamin H Press, Soum D Lokeshwar, Lindsey Webb, Ghazal Khajir, Shayan Smani, Olamide Olawoyin, Mursal Gardezi, Syed N Rahman, Michael S Leapman, Preston C Sprenkle","doi":"10.37349/etat.2024.00269","DOIUrl":"10.37349/etat.2024.00269","url":null,"abstract":"<p><strong>Aim: </strong>Prostate biopsy can be prone to complications and thus should be avoided when unnecessary. Although the combination of magnetic resonance imaging (MRI), the prostate health index (PHI), and PHI density (PHID) has been shown to improve detection of clinically significant prostate cancer (csPCa), there is limited information available assessing its clinical utility. We sought to determine whether using PHID could enhance the detection of PCa on MRI ultrasound fusion-targeted biopsy (MRF-TB) compared to other biomarker cutoffs.</p><p><strong>Methods: </strong>Between June 2015 and December 2020, 302 men obtained PHI testing before MRF-TB at a single institution. We used descriptive statistics, multivariable logistic regression, and receiver operating characteristic curves to determine the predictive accuracy of PHID and PHI to detect ≥ Gleason grade group (GGG) 2 PCa and identify cutoff values.</p><p><strong>Results: </strong>Any cancer grade was identified in 75.5% of patients and ≥ GGG2 PCa was identified in 45% of patients. The median PHID was 1.05 [interquartile range (IQR) 0.59-1.64]. A PHID cutoff of 0.91 had a higher discriminatory ability to predict ≥ GGG2 PCa compared to PHI > 27, PHI > 36, and prostate specific-antigen (PSA) density > 0.15 (AUC: 0.707 vs. 0.549 vs. 0.620 vs. 0.601), particularly in men with Prostate Imaging Reporting and Data System (PI-RADS) 1-2 lesions on MRI (AUC: 0.817 vs. 0.563 vs. 0.621 vs. 0.678). At this cutoff, 35.0% of all the original biopsies could be safely avoided (PHID < 0.91 and no ≥ GGG2 PCa) and csPCa would be missed in 9.67% of patients who would have been biopsied. In patients with PI-RADS 1-2 lesions using a PHID cutoff of 0.91, 56.8% of biopsies could be safely avoided while missing 0 csPCa.</p><p><strong>Conclusions: </strong>These findings suggest that a PHID cutoff of 0.91 improves the selection of patients with elevated prostate-specific antigen who are referred for prostate biopsy, and potentially in patients with PI-RADS 1-2 lesions.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 6","pages":"1168-1176"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hematopoietic and leukemic stem cells homeostasis: the role of bone marrow niche.","authors":"Shaimaa Khattab, Manal El Sorady, Ashraf El-Ghandour, Giuseppe Visani, Pier Paolo Piccaluga","doi":"10.37349/etat.2024.00262","DOIUrl":"10.37349/etat.2024.00262","url":null,"abstract":"<p><p>The bone marrow microenvironment (BMM) has highly specialized anatomical characteristics that provide a sanctuary place for hematopoietic stem cells (HSCs) that allow appropriate proliferation, maintenance, and self-renewal capacity. Several cell types contribute to the constitution and function of the bone marrow niche. Interestingly, uncovering the secrets of BMM and its interaction with HSCs in health paved the road for research aiming at better understanding the concept of leukemic stem cells (LSCs) and their altered niche. In fact, they share many signals that are responsible for interactions between LSCs and the bone marrow niche, due to several biological similarities between LSCs and HSCs. On the other hand, LSCs differ from HSCs in their abnormal activation of important signaling pathways that regulate survival, proliferation, drug resistance, invasion, and spread. Targeting these altered niches can help in better treatment choices for hematological malignancies and bone marrow disorders in general and acute myeloid leukemia (AML) in particular. Moreover, targeting those niches may help in decreasing the emergence of drug resistance and lower the relapse rate. In this article, the authors reviewed the most recent literature on bone marrow niches and their relations with either normal HSCs and AML cells/LSC, by focusing on pathogenetic and therapeutic implications.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 5","pages":"1027-1055"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemotherapy related changes in cfDNA levels in squamous non-small cell lung cancer: correlation with symptom scores and radiological responses.","authors":"Nithiyanandan Ravi, Parul Gupta, Amanjit Bal, Kuruswamy Thurai Prasad, Mandeep Garg, Rakesh Kapoor, Navneet Singh","doi":"10.37349/etat.2024.00232","DOIUrl":"10.37349/etat.2024.00232","url":null,"abstract":"<p><strong>Aim: </strong>There is limited data on prognostic value of baseline plasma cell free DNA (cfDNA) in advanced squamous non-small cell lung cancer (sq-NSCLC). This prospective observational study aimed to assess change in plasma cfDNA levels in locally-advanced/metastatic sq-NSCLC with chemotherapy and its correlation with symptom-scores and radiological-responses.</p><p><strong>Methods: </strong>Chemotherapy-naive patients with stages-IIIB/IIIC/IV sq-NSCLC (<i>n</i> = 59), smokers with chronic obstructive pulmonary disease [COPD, COPD-controls (CC); <i>n</i> = 27] and healthy-controls (<i>n</i> = 25) were enrolled. Respiratory symptom burden (RSB) and total symptom burden (TSB) were calculated from mean visual-analog-scores (VAS) of dyspnoea, cough, chest pain, hemoptysis RSB, anorexia and fatigue (all six for TSB). cfDNA was isolated from peripheral blood. All patients received platinum-doublet chemotherapy. RSB/TSB/cfDNA assessment and contrast-enhanced computed tomography (CECT)-thorax scans were done at baseline and post-chemotherapy.</p><p><strong>Results: </strong>At baseline, 13/59 (22%) sq-NSCLC, 3/27 (11%) CC and none (0%) healthy-controls had detectable cfDNA. All three CC were heavy smokers with no evidence of malignancy and undetectable cfDNA levels on repeat testing. In sq-NSCLC group, majority were males (95%), current-smokers (88%), heavy-smokers (70%), had metastatic disease (59%) with median age of 65 years. Eastern Co-operative Oncology Group (ECOG) performance status (PS) was 0-1 (56%) and 2 (42%). Median RSB- and TSB-scores were 9 [interquartile range (IQR) = 5-14] and 16 (IQR = 9-23), respectively. Of the 59 patients, 54 received ≥ 1 cycle while 27 underwent post-C4 evaluation with detectable cfDNA levels in 18/27 (66.7%). No baseline characteristic correlated with cfDNA detectability. Median overall survival (OS) and progression-free survival (PFS) were 262 days and 167 days, respectively. ECOG PS ≥ 2, RSB-score > 9 and TSB-score > 16 were all associated with worse OS and PFS as was cfDNA detectability [median OS = 97 days <i>vs.</i> 298 days and median PFS = 97 days <i>vs.</i> 197 days; <i>P</i> = 0.025; hazard ratio (HR) = 2.17].</p><p><strong>Conclusions: </strong>Baseline cfDNA detectability is independently associated with poor OS and PFS in patients with advanced sq-NSCLC on chemotherapy.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 3","pages":"508-521"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11222716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}