BMC Cancer最新文献

{"title":"Association of B cells and the risk of Esophageal cancer: a bidirectional two-sample mendelian randomization study.","authors":"Jinzhou Guo, Gao Si, Xuejie Song, Fuchun Si","doi":"10.1186/s12885-024-13166-w","DOIUrl":"10.1186/s12885-024-13166-w","url":null,"abstract":"<p><strong>Background and objectives: </strong>Currently, research on the role of B cells in esophageal cancer (EC) is limited, and existing studies on their impact are controversial. Therefore, this study was conducted to elucidate the complex causal relationship between B cells and EC, expand the understanding of esophageal cancer immunology.</p><p><strong>Methods: </strong>Bidirectional two-sample Mendelian randomization (MR) was performed to assess the causal relationships between 190 B cell phenotypes and EC. To complement the MR analysis, Bayesian Weighted Mendelian Randomization (BWMR) was employed, and sensitivity analyses were conducted to evaluate the robustness of the findings. Positive results were further validated in independent cohorts of esophageal cancer studies. In addition, RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) were utilized for validation, incorporating B cell-related gene expression analysis and functional enrichment analysis to support the MR findings.</p><p><strong>Results: </strong>In the primary analysis, significant causal relationships were observed between 5 B cell types and the risk of EC; the onset of EC was causally linked to 3 B cell phenotypes. Validation in other cohorts revealed that 4 outcomes aligned with the primary analysis, included were CD19 on IgD + CD38-, CD20 on IgD- CD27-, CD20 on IgD- CD38br, and CD38 on PB/PC. Further validation using RNA-seq data showed that CD38 mRNA was significantly overexpressed in EC tissues, whereas CD19 and MS4A1 mRNA levels did not differ significantly between tumor and normal tissues. Functional enrichment analysis revealed that CD19, MS4A1, and CD38 are involved in multiple tumor-related immune pathways, suggesting their pivotal role in regulating the tumor immune microenvironment.</p><p><strong>Conclusions: </strong>Our study suggests a potential connection between B cell phenotypes and EC through bidirectional two-sample MR combined with BWMR analysis, providing a preliminary basis for future research.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"24 1","pages":"1416"},"PeriodicalIF":3.4,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11569605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the correlation between Tom1L1 and the efficacy of neoadjuvant chemotherapy for locally progressive mid-low rectal cancer.","authors":"Meng Li, Zeyu Li, Xueliang Wu, Yubo Pan, Likun Wang, Jun Xue, Tian Li","doi":"10.1186/s12885-024-13154-0","DOIUrl":"10.1186/s12885-024-13154-0","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the specificity of Target of Myb1-Like1 (Tom1L1) expression in colorectal adenocarcinoma tissues and analyze the predictive value of Tom1L1 in the efficacy of neoadjuvant chemotherapy for patients with rectal adenocarcinoma.</p><p><strong>Methods: </strong>The cancerous tissues and paracancerous normal tissues of 102 patients diagnosed with colorectal adenocarcinoma without treatment were selected; quantitative polymerase chain reaction (qPCR), Western blot and immunohistochemistry (IHC) were adopted to validate the expression level of Tom1L1 in the two groups. Furthermore, 34 patients with locally progressive mid-low rectal adenocarcinoma, who were treated with neoadjuvant Xelox chemotherapy prior to the operation, IHC was adopted to detect the expression of Tom1L1 protein in patients before and after neoadjuvant chemotherapy and to analyze the relationship between the expression level of Tom1L1 and the sensitivity of neoadjuvant therapy.</p><p><strong>Results: </strong>The results of qPCR, Western blot and IHC showed that the expression of Tom1L1 in colorectal adenocarcinoma tissues was significantly higher than that in paracancerous normal tissues, with a statistically significant difference (P < 0.01); Neoadjuvant chemotherapy was significantly more effective in patients with low expression of Tom1L1 protein than in those with high expression of Tom1L1 protein, with a statistically significant difference (P < 0.05).</p><p><strong>Conclusions: </strong>Tom1L1 is highly expressed in colorectal adenocarcinoma tissues; neoadjuvant Xelox chemotherapy can have an impact on Tom1L1 expression in progressive rectal cancer; patients with locally progressive mid-low rectal adenocarcinoma who have low Tom1L1 expression are more sensitive to neoadjuvant chemotherapy.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"24 1","pages":"1413"},"PeriodicalIF":3.4,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of preoperative treatment on mismatch repair protein and HER2 expression in colorectal cancer: an analysis of paired samples.","authors":"Zhen Chen, Hui Cao, Jing Zhang, Weixiang Zhong, Xiaodong Teng","doi":"10.1186/s12885-024-13120-w","DOIUrl":"10.1186/s12885-024-13120-w","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is a leading cause of cancer-related mortality, highlighting the necessity for multifaceted treatment strategies, including preoperative treatment (PT), which can enhance surgical outcomes and provide prognostic insights. This study aims to clarify the impact of PT-induced changes in mismatch repair (MMR) and human epidermal growth factor receptor 2 (HER2) expression, potentially informing tailored treatment strategies and improving clinical outcomes for CRC patients.</p><p><strong>Methods: </strong>This retrospective study analyzed 120 paired samples from CRC patients who underwent preoperative treatment, comparing pre- and post-treatment specimens. A control group of 60 untreated surgical specimens was also included. Immunohistochemistry assessed MMR proteins (MSH6, MSH2, MLH1, PMS2) and HER2 expression. MSI status was determined in samples with low MMR expression.</p><p><strong>Results: </strong>Compared to pre-treatment samples, post-treatment samples exhibited lower levels of MSH6, MSH2, and total MMR expression, along with higher levels of HER2 expression. However, when compared to the untreated control group, there were no significant differences in the expression of MSH6, total MMR, and HER2. All samples that exhibited weak MMR expression and those that shifted to deficient mismatch repair (dMMR) status following treatment had stable microsatellite status. No clear clinicopathological characteristics or prognostic factors were found to be associated with changes in MMR and HER2 expression, except for the use of fluorouracil or capecitabine, which was related to changes in total MMR scores. ypTNM stage and TRG scores were identified as independent factors affecting disease progression in our study.</p><p><strong>Conclusions: </strong>PT is associated with a reduction in MMR expression, notably for the MSH2 protein, while it does not appear to influence HER2 expression.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"24 1","pages":"1407"},"PeriodicalIF":3.4,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adverse events after nivolumab and ipilimumab combined immunotherapy in advanced renal cell carcinoma: a multicentre experience in Poland.","authors":"Renata Pacholczak-Madej, Artur Drobniak, Łukasz Stokłosa, Anna Bidas, Jolanta Dobrzańska, Aleksandra Grela-Wojewoda, Agnieszka Roman, Daria Tusień-Małecka, Jerzy Walocha, Paweł Blecharz, Mirosława Puskulluoglu","doi":"10.1186/s12885-024-13192-8","DOIUrl":"10.1186/s12885-024-13192-8","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) have been employed in the adjuvant and metastatic setting of renal cell carcinoma (RCC) treatment. Among ICIs, combined immunotherapy has the highest risk for immune-related adverse events (irAEs). We aimed to document the incidence of irAEs in RCC patients treated with nivolumab and ipilimumab as data from the European population remain limited.</p><p><strong>Materials and methods: </strong>We analysed data from 88 RCC patients treated with nivolumab + ipilimumab between May 2022 and June 2024 across six high-volume oncology units in Poland. We reviewed irAEs and estimated their impact on survival parameters via univariate and multivariate Cox proportional hazards regression models, along with log-rank tests.</p><p><strong>Results: </strong>With a median follow-up of 11.3 months, the median overall survival (OS) was not reached, whereas the median progression-free survival (PFS) was 12.8 months (6.3-19.3). A total of 74 irAEs were recorded in 50 patients. The most frequent events were endocrine (n = 20, 27%), hepatic (n = 15, 17%), general (n = 12, 13.6%), and cutaneous (n = 11, 12.5%). The occurrence of irAEs was associated with a 60% lower risk of disease progression (hazard ratio 0.44, 95% confidence interval 0.2-0.87, p = 0.018) without impacting OS and higher disease control rate (n = 45, 90% vs. n = 24, 63.2%, p = 0.004). In contrast, patients with hepatotoxicity had poorer outcomes, with a 2.6-fold greater risk of death (p = 0.05).</p><p><strong>Conclusions: </strong>IrAEs may serve as a predictive factor for the efficacy of the nivolumab + ipilimumab regimen in RCC patients. Special attention is needed for hepatotoxicity, as it can significantly impact survival outcomes.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"24 1","pages":"1411"},"PeriodicalIF":3.4,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Circulating levels of PCSK9, ANGPTL3 and lp(a) in stage III breast cancers.","authors":"Emilie Wong Chong, France-Hélène Joncas, Nabil G Seidah, Frédéric Calon, Caroline Diorio, Anne Ganglof","doi":"10.1186/s12885-024-13182-w","DOIUrl":"10.1186/s12885-024-13182-w","url":null,"abstract":"","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"24 1","pages":"1408"},"PeriodicalIF":3.4,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation between environmental DEET exposure and the mortality rate of cancer survivors: a large-sample cross-sectional investigation.","authors":"Lingjuan Liu, Weicheng Qin, Lixin Nie, Ximing Wang, Xiulan Dong","doi":"10.1186/s12885-024-13178-6","DOIUrl":"10.1186/s12885-024-13178-6","url":null,"abstract":"<p><strong>Background: </strong>N, N-Diethyl-meta-toluamide (DEET) is the predominant active ingredient found in insect repellents utilized by consumers. Exposure to DEET has been associated with notable risks to human health. Nonetheless, there is a scarcity of extensive cohort studies investigating the precise correlation between DEET exposure and mortality rates among cancer survivors. The objective of this study is to thoroughly evaluate the connection between DEET exposure and mortality rates in cancer survivors.</p><p><strong>Methods: </strong>This study employed individual samples obtained from the National Health and Nutrition Examination Survey (NHANES). Utilizing data from NHANES spanning 2007 to 2016, this study incorporated a cohort of 5,859 cancer survivors for subsequent analysis, following the exclusion of incomplete datasets. Through subgroup analysis, the research examined the impact of quartile levels of 3-diethyl-carbamoyl benzoic acid (DCBA), the primary metabolite of DEET, on cancer survivors across various subgroups within the broader population. Furthermore, the research utilized a multivariable Cox proportional hazards regression model and Kaplan-Meier (KM) curves to investigate the relationship between 3-diethyl-carbamoyl benzoic acid (DCBA), a principal metabolite of DEET, and mortality rates in individuals who have survived cancer.</p><p><strong>Results: </strong>The study identified an association between specific quartiles of DCBA concentration and a decreased risk of all-cause mortality among cancer survivors, specifically in the second (Q2: 0.665-1.95) and third quartiles (Q3: 1.95-6.845). Furthermore, a significant correlation was observed between the third quartile and cancer-specific mortality (Q3: 1.95-6.845), as well as between the second quartile and non-cancer mortality (Q2: 0.665-1.95). The quartiles of DCBA concentration exhibit a statistically significant correlation with total deaths (P < 0.001), cancer-specific deaths (P = 0.009), and non-cancer deaths (P < 0.001) among cancer survivors. The correlation between DCBA and reduced mortality risk in cancer survivors is particularly notable among females and individuals of non-Hispanic Black descent.</p><p><strong>Conclusion: </strong>The detection of DCBA in the urine of adult cancer survivors is strongly associated with increased mortality risks, particularly among females and non-Hispanic Black individuals, warranting further investigation and targeted interventions.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"24 1","pages":"1410"},"PeriodicalIF":3.4,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a prognostic signature for overall survival using peripheral blood biomarkers in head and neck squamous cell carcinoma treated with immune checkpoint inhibitors.","authors":"Cassie Pan, Kevin Ng, Jenna Voutsinas, Brittany Barber, Zain H Rizvi, Emily Marchiano, Rocco M Ferrandino, Neal Futran, George E Laramore, Jay J Liao, Upendra Parvathaneni, Neil Panjwani, Renato G Martins, Cristina P Rodriguez, Qian Vicky Wu","doi":"10.1186/s12885-024-13051-6","DOIUrl":"10.1186/s12885-024-13051-6","url":null,"abstract":"<p><strong>Background: </strong>We previously reported in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) treated with immune checkpoint inhibitors (ICIs), pretreatment higher lactate dehydrogenase (LDH) and absolute (abx) neutrophils as well as lower percent (%) lymphocytes correlated with worse overall survival (OS). In this study we aimed to develop a prognostic signature for HNSCC treated with ICIs using these peripheral blood biomarkers (PBBMs).</p><p><strong>Methods: </strong>Adults with R/M HNSCC treated with ICIs at our institution from 08/2012 to 03/2021 with pretreatment PBBMs were included. Follow-up continued until 02/15/2022. The cohort (n = 151) was randomly split into training (n = 100) and testing (n = 51) datasets. A prognostic score incorporating LDH, % lymphocytes, and abx neutrophils was developed from the training dataset using Cox proportional hazards regression. In the training dataset, a grid search identified the optimal cutpoints classifying patients into high, medium, and low-risk groups (trichotomized signature) as well as high vs. low-risk groups (dichotomized signature). The prognostic score, dichotomized and trichotomized signatures were then validated in the testing dataset.</p><p><strong>Results: </strong>Training and testing datasets showed no clinically meaningful differences in clinicodemographic characteristics or PBBMs. An OS prognostic model was developed from the training dataset: Risk score = 1.24*log10(LDH) - 1.95*log10(% lymphocytes) + 0.47*log10(abx neutrophils). Optimal risk score cutpoints for the dichotomized and trichotomized signatures were defined in the training dataset, and Kaplan-Meier curves for both dichotomized and trichotomized signatures showed good separation between risk groups. Risk scores were calculated in the testing dataset, where the trichotomized signature demonstrated overlap between low and medium-risk groups but good separation from the high-risk group while the dichotomized signature showed clear separation between low and high-risk groups. Higher risk score correlated with worse OS (HR 2.08, [95%CI 1.17-3.68], p = 0.012). Progression-free survival Kaplan-Meier curves likewise showed excellent separation between dichotomized risk groups in the training and testing datasets.</p><p><strong>Conclusions: </strong>We developed a prognostic signature for OS based on 3 previously identified PBBMs for HNSCC treated with ICIs and identified a high-risk group of patients least likely to have survival benefit from ICIs. This signature may improve ICI patient selection and warrants validation in an independent cohort as well as correlation with CPS.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"24 1","pages":"1406"},"PeriodicalIF":3.4,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Randomized trial of physical activity on quality of life and lung cancer biomarkers in patients with advanced stage lung cancer: a pilot study.","authors":"Brett C Bade, Geliang Gan, Fangyong Li, Lingeng Lu, Lynn Tanoue, Gerard A Silvestri, Melinda L Irwin","doi":"10.1186/s12885-024-13183-9","DOIUrl":"10.1186/s12885-024-13183-9","url":null,"abstract":"","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"24 1","pages":"1409"},"PeriodicalIF":3.4,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical characteristics and survival of patients with de novo metastatic prostate cancer treated with androgen deprivation therapy and taxane-based chemotherapy in Uganda: a retrospective study.","authors":"Alex Bakenga, Barbra Natukunda, Fred Okuku, Kelvin Roland Mubiru, Edward Kakungulu, Eddy Kyagulanyi, Derrick Bary Abila, Jackson Orem","doi":"10.1186/s12885-024-13147-z","DOIUrl":"10.1186/s12885-024-13147-z","url":null,"abstract":"<p><strong>Background: </strong>Prostate cancer is the second most common cancer among men worldwide. Mortality is highest among patients in resource-limited settings (RLS), in part due to late-stage disease. Among patients with metastatic prostate cancer (mPCa), studies have shown significant improvement in overall survival with the use of androgen deprivation therapy (ADT) and taxane-based chemotherapy. However, outcome data among patients treated with chemo-endocrine therapy are scarce in many resource-limited settings. The aim of this study was to determine the clinical characteristics and 5-year overall survival (OS) of patients with de novo mPCa treated at the Uganda Cancer Institute (UCI).</p><p><strong>Methods: </strong>A retrospective chart review study was conducted between 2015 and 2019, and the data of patients with histologically confirmed prostate cancer and radiological evidence of metastasis were reviewed. Sample size was estimated for Cox Proportion Hazard regression. Data on clinical and laboratory characteristics, overall survival, and predictors of survival were extracted. P < 0.05 was considered to indicate statistical significance.</p><p><strong>Results: </strong>A total of 300 patients were enrolled over the 5-year study period. The median age was 68 (IQR 61.5-74) years. At presentation, lower urinary tract symptoms were reported in nearly all patients (96.7%, n = 290), median total prostate specific antigen (PSA) was 414.75 ng/ml and 40% (n = 120) of patients had grade 5 histological scores. In addition to receiving ADT, majority of patients (70.3%, n = 211) received at least 6 cycles of chemotherapy. Overall survival at one year was 92.4% (95% CI: 88.6-94.9%), but it declined to 45.2% (95% CI: 36.8-53.2%) at 5 years. A high Gleason score, the presence of visceral metastasis and receiving less than 6 cycles of chemotherapy were predictors of poor outcomes.</p><p><strong>Conclusion: </strong>Patients with de novo mPCa in Uganda present with high histologic grades and high baseline Prostate Specific Antigen (PSA) levels but have improved 5-year overall survival with a combination of chemotherapy and ADT as a first-line treatment. We recommend interventions to reduce late presentation and prospective studies to evaluate treatment efficacy in this population.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"24 1","pages":"1404"},"PeriodicalIF":3.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interim analysis of the multinational, post-authorization safety study (NISSO) to assess the long-term safety of sonidegib in patients with locally advanced basal cell carcinoma.","authors":"Ralf Gutzmer, Ulrike Leiter, Peter Mohr, Katharina C Kähler, Paolo Antonio Ascierto, Massimiliano Scalvenzi, Ketty Peris, Gemma María Pérez-Pastor, Ricardo Fernández-de-Misa, Rafael Botella-Estrada, Robert E Hunger, Serena Martelli, Nur Güneli, Ramon Arntz, Axel Hauschild","doi":"10.1186/s12885-024-13101-z","DOIUrl":"10.1186/s12885-024-13101-z","url":null,"abstract":"<p><strong>Background: </strong>Following the pivotal phase II trial BOLT, the Hedgehog (Hh) inhibitor sonidegib was approved in the EU to treat locally advanced basal cell carcinoma (laBCC) in patients not amenable to surgery or radiotherapy. We report safety data from the interim analysis of the real-world NISSO study.</p><p><strong>Methods: </strong>NISSO is an ongoing non-interventional, multinational, post-authorization safety study (NCT04066504). Patients with laBCC are treated with sonidegib 200 mg orally once daily and followed for 3 years. Dose modifications were allowed according to the local prescribing information.</p><p><strong>Results: </strong>Between May 6, 2019, and March 15, 2022, 321 patients with laBCC were enrolled at 46 European sites (data cut-off: June 22, 2023). Treatment was discontinued in 241 (75.1%) patients, with the main reasons being the patient/guardian decision (n = 69, 28.6%), treatment success (n = 40, 16.6%) and the physician decision (n = 35, 14.5%). The median duration of sonidegib exposure was 8.8 months (4.4-13.7 months). Overall, 284 (88.5%) patients had ≥ one treatment-emergent adverse event (TEAE). Most TEAEs were ≤ grade 2 and the most common were muscle spasms (n = 141; 43.9%), dysgeusia (n = 119; 37.1%), and alopecia (n = 97; 30.2%). After 3 months of treatment, the cumulative rates of muscle spasms, dysgeusia, and alopecia were 21.8%, 16.2%, and 3.7%, respectively. TEAEs led to treatment discontinuation in 59 (18.4%) patients, while 149 (46.4%) patients had at least one TEAE leading to dose reduction or interruption. Serious drug-related TEAEs were reported in 13 (4.1%) patients.</p><p><strong>Conclusions: </strong>These results confirm the safety profile previously observed. Most patients experienced the onset of common TEAEs after 3 months of treatment, and the cumulative incidence of most common TEAEs was 10-20% lower compared to the BOLT study, except for dysgeusia and fatigue that had a similar incidence. The percentage of patients experiencing TEAEs requiring interruption or dose reduction was similar to the BOLT study, while the proportion of patients with TEAE leading to discontinuation of sonidegib was lower. This study demonstrates that the tolerability of sonidegib is manageable in routine clinical practice.</p><p><strong>Trial registration: </strong>NCT04066504.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"24 1","pages":"1401"},"PeriodicalIF":3.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}