Clinical & Translational Oncology最新文献

{"title":"Expression of vesiculation-related genes is associated with a tumor-promoting microenvironment: a pan-cancer analysis.","authors":"Luisa Westermann, Brenda Diergaarde, Simon Heidegger, Hendrik Poeck, Mirosław J Szczepański, Torsten E Reichert, Silvia Spoerl, Theresa L Whiteside, Steffen Spoerl, Nils Ludwig","doi":"10.1007/s12094-024-03796-8","DOIUrl":"10.1007/s12094-024-03796-8","url":null,"abstract":"<p><strong>Background: </strong>Small extracellular vesicles (sEV) released by tumor cells (tumor-derived sEV; TEX) mediate intercellular communication between tumor and non-malignant cells and were shown to impact disease progression. This study investigates the relationship between the expression levels of the vesiculation-related genes linked to sEV production and the tumor microenvironment (TME).</p><p><strong>Methods: </strong>Two independent gene sets were analyzed, both previously linked to sEV production in various non-malignant or malignant cells. Expression profiles were compared among 28 tumor types listed in the Cancer Genome Atlas (TCGA). Gene expression and survival analysis (GEPIA2), immunogenomic analysis (TISIDB), and genomic analysis (GSCA) were performed.</p><p><strong>Results: </strong>Vesiculation-related genes were overexpressed in tissues of most tumor types compared to healthy tissues, and high expression levels were associated with worse overall survival in cervical squamous cell carcinoma, kidney chromophobe, lower grade glioma, hepatocellular carcinoma, lung squamous cell carcinoma, and pancreatic adenocarcinoma but with improved overall survival in kidney renal clear cell carcinoma. Expression of these signatures correlated with an increased abundance of infiltrating CD4( +) T cells and dendritic cells, a decreased abundance of B cells and eosinophils, and activation of tumor cell apoptosis and epithelial-mesenchymal transition pathways in all tumor types. 17-AAG was identified as a potential drug candidate to target tumors with elevated expression of vesiculation-related genes.</p><p><strong>Conclusions: </strong>Vesiculation-related genes were associated with distinct immunological and genomic landscapes further emphasizing the important role of TEX in cancer progression.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3163-3174"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recommendations for the management of cutaneous squamous cell carcinoma: a systematic multidisciplinary Delphi consensus approach.","authors":"Eva Muñoz Couselo, Javier Cañueto, Vanessa Jerviz Guía, Ana María López López, Josep Oriol Bermejo Segú, Almudena García Castaño, Susana Puig Sardá, Onofre Sanmartín Jiménez, Ainara Soria Rivas, Paula Gratal, María Teresa Pardo, Álvaro Rogado, Alfonso Berrocal Jaime","doi":"10.1007/s12094-024-03826-5","DOIUrl":"10.1007/s12094-024-03826-5","url":null,"abstract":"<p><strong>Background: </strong>There are gaps and unanswered questions in clinical guidelines regarding several aspects of the management of patients with cutaneous squamous cell carcinoma (cSCC).</p><p><strong>Methods: </strong>A scientific committee of ten cSCC specialists in Spain (dermatology, medical oncology, oral and maxillofacial surgery, plastic surgery, and radiotherapy) used ADAPTE methodology to develop recommendations by: (i) identifying clinical questions not fully answered by clinical practice guidelines; (ii) systematically reviewing the literature (published between November 2017 and July 2023 in PubMed and the Cochrane database) and grading the evidence (using Oxford levels); (iii) developing recommendations and assessing those with no consensus among the scientific committee or with evidence level 3-5 or strength of recommendation under C or D in a two-round Delphi method; and (iv) developing the final recommendations in the form of answers to key clinical questions, grading the strength of recommendation. An external group of 32 experts plus the members of the committee participated in both Delphi rounds, evaluating the appropriateness and need of the recommendations.</p><p><strong>Results: </strong>Initially, 33 recommendations were made for 26 questions; 19 recommendations were evaluated with the Delphi method. All 19 recommendations were deemed appropriate and necessary. A total of 27 final recommendations were made, concerning initial patient management, treatment of the primary tumour, management of advanced disease, specific populations, supportive and palliative care, and follow-up.</p><p><strong>Conclusion: </strong>We developed 27 recommendations that answer clinical questions on the management of patients with cSCC, providing guidance on aspects that are unclear in clinical guidelines or on which guidelines differ.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3058-3072"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of the CXCL12/CXCR4 axis in the immunotherapy of non-small cell lung cancer.","authors":"Jacobo Rogado, Fernando Pozo, Kevin Troule, María Pacheco, Magdalena Adrados, José Miguel Sánchez-Torres, Fátima Al-Shahrour, Javier Aspa, Arantzazu Alfranca, Nuria Romero-Laorden, Ramon Colomer","doi":"10.1007/s12094-024-03828-3","DOIUrl":"10.1007/s12094-024-03828-3","url":null,"abstract":"<p><strong>Introduction: </strong>Peripheral blood mononuclear cells (PBMCs) trafficking is regulated by chemokines, which modulate leukocyte migration toward tumors and may collaborate in the efficacy of immunotherapy. In our study, we investigated whether the CXCL12/CXCR4 axis plays a role in the efficacy of immunotherapy in non-small cell lung cancer (NSCLC) by analyzing CXCR4 expression for CXCR4 in peripheral blood (PB), and the expression of its ligand CXCL12 in tumor.</p><p><strong>Methods: </strong>We identified PBMCs expressing CXCR4 using flow cytometry in a prospective cohort of NSCLC patients before starting anti-PD-1 immunotherapy. As a control, we studied patients with advanced cancer before starting any non-immunotherapy treatment. The relative frequency of PBMCs was correlated with treatment outcomes. Uni- and multivariate survival analyses were performed. The expression of CXCL12 in tumor tissue was studied and correlated with the expression of its receptor (CXCR4) in PBMCs.</p><p><strong>Results: </strong>The experimental group included 39 patients and the control group included 40. Low expression of CXCR4-expressing CD8 + T lymphocytes was correlated with a greater benefit from immunotherapy: median OS NR vs. 22.0 months, HR 0.6, p < 0.01; and median PFS 14.2 vs. 5.0 months, HR 0.38, p = 0.05. These differences were not observed in controls. Low expression in PB of these lymphocytes was correlated with a higher expression of CXCL12 in tumor (trend toward significance: p = 0.14).</p><p><strong>Conclusion: </strong>Patients diagnosed with advanced NSCLC with low percentage of cytotoxic T lymphocytes expressing CXCR4 in PB, show greater benefit from immunotherapy, probably due to increased tumor infiltration by lymphocytes in response to CXCL12 produced by the tumor.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"2970-2981"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical characteristics and survival outcomes in patients with pulmonary sarcomatoid carcinoma: a multicenter retrospective study.","authors":"Zhijuan Du, Yuhui Qin, Yahui Lv, Jie Gao, Siyuan Chen, Xiangyu Du, Tao Li, Yi Hu, Zhefeng Liu","doi":"10.1007/s12094-024-03823-8","DOIUrl":"10.1007/s12094-024-03823-8","url":null,"abstract":"<p><strong>Purpose: </strong>The clinicopathologic features, mutational status, immunohistochemical markers, and prognosis of Pulmonary sarcomatoid carcinoma (PSC) remain uncertain.</p><p><strong>Methods: </strong>This study included 81 PSC and 337 lung adenocarcinomas (LUAD). Progression-free survival (PFS), overall survival (OS), and other clinical data were examined.</p><p><strong>Results: </strong>46% PSC patients harbored KRAS mutation and 23% harbored EGFR mutation. Univariable analysis identified type and cTNM stage as significant predictor of PFS (type: HR 0.216; 95% CI 0.133-0.349; P < 0.001, cTNM stage: HR 0.483; 95% CI 0.269-0.846; P = 0.014) and OS (type: HR 0.269; 95% CI 0.156-0.465; P < 0.001, cTNM stage: HR 0.435; 95% CI 0.219-0.865; P = 0.018). Multivariable analysis confirmed sex, type and cTNM stage as independent predictors of PFS (sex: HR 2.026; 95%CI 1.027-3.996; P = 0.042; type: HR0.140; 95% CI 0.083-0.238; P < 0.001, cTNM stage: HR0.305; 95% CI 0.165-0.564; P < 0.001) and OS (type: HR0.231; 95% CI 0.132-0.404; P < 0.001, cTNM stage: HR 0.394; 95% CI 0.194-0.797; P = 0.010). Significant differences in PFS (P < 0.0001) and OS (P = 0.022) were observed between PSC and LUAD, and for PC compared with SCC (PFS: P = 0.00036, OS: P = 0.0053). Additionally, PSC patients treated with immunotherapy showed significantly better OS (P = 0.0019) compared with those treated without immunotherapy.</p><p><strong>Conclusions: </strong>PSC exhibits high KRAS and EGFR mutation rates, and spindle cell carcinoma has a worse prognosis. Immunotherapy shows potential as a treatment for advanced PSC.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"2993-3000"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Controversies in the use of next-generation imaging for evaluation and treatment decision-making in patients with prostate cancer after biochemical recurrence: views from a Spanish expert panel.","authors":"Xavier Maldonado, Anna Boladeras, José María Gaya, Jesús Muñoz, Jacques Planas, Gemma Sancho, José Francisco Suárez","doi":"10.1007/s12094-024-03833-6","DOIUrl":"10.1007/s12094-024-03833-6","url":null,"abstract":"<p><strong>Introduction: </strong>Diagnosing and managing biochemical recurrence (BCR) of prostate cancer (PCa) following primary radical treatment remain a challenge. Implementing next-generation imaging (NGI) techniques has improved metastases detection. However, access to these techniques is heterogeneous, and controversies surround their use and subsequent treatment decisions. In November 2023, a multidisciplinary expert meeting was organized to discuss these aspects. This information was further reviewed in November 2024.</p><p><strong>Areas covered: </strong>NGI-specific tracers' selection, evidence supporting patient selection for NGI after BRC, current treatment strategies in patients with BRC, and the role of NGIs in current and future therapeutic approaches.</p><p><strong>Expert opinion: </strong>Despite improved detection performance compared to conventional imaging techniques, the application of NGIs to treatment decision-making and the impact on patient outcomes are yet to be proven. Given the lack of guidance, opinions and recommendations from multidisciplinary expert panels are valuable for diagnosing and adequately treating patients with BRC after radical treatment.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"2876-2888"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142923598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pan-cancer analysis reveals the prognostic and immunomodulatory potential of super-enhancer-induced ANGPT2 and experimental validation in colorectal cancer.","authors":"Songyue Guo, Yanan Yu, Yulan Bu, Jiao Ren, Lu Zhang, Xiaolin Ma, Jiaqiu Li, Ao Li, Xinling Liu","doi":"10.1007/s12094-024-03818-5","DOIUrl":"10.1007/s12094-024-03818-5","url":null,"abstract":"<p><strong>Background: </strong>ANGPT2 plays important roles in cancer development. However, there is still no systematic analysis of ANGPT2 in pan-cancer.</p><p><strong>Methods: </strong>In this paper, we conducted a pan-cancer analysis to investigate the characteristics of ANGPT2. Furthermore, we investigated the impact of genetic and epigenetic factors on ANGPT2 expression by bioinformatics and assays.</p><p><strong>Results: </strong>By several TCGA and GEO databases, we identified elevated expression of ANGPT2 in various tumor types. Besides, high expression of ANGPT2 induced poor prognosis of patients in multiple tumors. Through enrichment analysis, we found that ANGPT2 participated in various biological processes, including angiogenesis and immunity. Various immune analyses indicated that high expression of ANGPT2 might suggest a propensity towards a hot tumor microenvironment, but its impact on immunotherapy was negative. Bioinformatics analysis and experiments confirmed that genetic and epigenetic factors explained part of the mechanism behind ANGPT2 abnormal expression. Finally, we screened candidate drugs targeting the ANGPT2 protein by molecular docking and molecular dynamics simulation.</p><p><strong>Conclusion: </strong>ANGPT2 has diagnostic and prognostic values in multiple tumor types. Though with a hot tumor microenvironment, ANGPT2 high expression patients are not suitable for immunotherapy because of its proangiogenic function, contributing to selecting the exact patients for immunotherapy. Both genetic and epigenetic factors influenced ANGPT2 expression, with the influence of super-enhancer being more pronounced. This paper for the first time did the systematic analysis of ANGPT2 and showed its characteristic in pan-cancer. We summarized the biomarker role of ANGPT2 on tumor diagnosis and prognosis, as well as its target role on tumor immunotherapy.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3029-3057"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic value of HER2 2 + expression in patients with TNBC receiving adjuvant capecitabine.","authors":"Tuğba Önder, Muhammet Cengiz, Sıla Soylu Koçoğlu, Öztürk Ateş, Ozan Yazıcı, Mevlüde İnanç, Ayşe Ocak Duran","doi":"10.1007/s12094-024-03812-x","DOIUrl":"10.1007/s12094-024-03812-x","url":null,"abstract":"<p><strong>Background: </strong>In triple-negative breast cancer (TNBC) patients receiving adjuvant capecitabine, the impact of HER2 expression on survival outcomes is unclear.</p><p><strong>Methods: </strong> Between June 2017 and December 2023, 112 patients with TNBC who received adjuvant capecitabine due to residual masses after neoadjuvant chemotherapy (NACT) in three hospitals were identified. HER2 is analyzed through immunohistochemistry (IHC) and/or in situ hybridization in the core biopsy and/or post-surgical histopathologies. Relapse-free survival (RFS) and overall survival (OS), according to HER2 expression (0, 1 + , 2 +) status, were calculated (Kaplan-Meier method).</p><p><strong>Results: </strong> Seventy-eight (69.6%) patients had HER2 zero, 20 (17.9%) patients had HER2 + 1, and 14 (12.5%) patients had HER2 + 2/ISH- BC. The 5-year OS was 62.6%, and the 5-year RFS was 55.8%. HER2 2 + expression was associated with worse OS (27.5 vs. 84.5 months; HR 4.82, 95% CI 2.15-10.80, p < 0.001) and worse RFS (11.90 months vs. not reached; HR 4.30, 95% CI 2.06-8.99, p < 0.001) compared with HER2 0/1 + expression. The 5-year OS rates were 32.7% and 72.1%, and the 5-year RFS rates were 30.6% and 64.7% in the HER2 2 + and HER2 0/1 + groups, respectively. No statistically significant differences were detected in clinicopathologic features or pathologic responses to NACT according to the HER2 expression level.</p><p><strong>Conclusions: </strong> Despite the use of the adjuvant capecitabine in HER2 2 + TNBC patients, these poor results will pave the way for further investigations of anti-HER2 therapeutic agents in adjuvant treatment.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3121-3129"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Five-year results of a prospective trial of IORT-photon boost and hypofractionated whole-breast irradiation after breast-conserving surgery.","authors":"J Burgos-Burgos, V Vega, D Macias-Verde, E Vicente, C Murias, C Santana, R Téllez, P C Lara","doi":"10.1007/s12094-024-03821-w","DOIUrl":"10.1007/s12094-024-03821-w","url":null,"abstract":"<p><strong>Aim: </strong>To assess for the first time the safety and feasibility of combining photon-IntraOperative RadioTherapy (ph-IORT) with hypofractionated whole-breast irradiation (hWBI) in patients referred to adjuvant radiotherapy after Breast-Conserving Surgery (BCS).</p><p><strong>Methods: </strong>From February 2019 to August 2020, patients referred for breast-conserving surgery (BCS) in our institution were prospectively included in the present trial. BCS was discussed in the multidisciplinary tumor board (MTB). 20 Gy were prescribed to the surface of the applicator of an Intrabeam^®ph-IORT during BCS. hWBI (40.5 Gy/2.67 Gy/15frx) was planned to be administered 3-5w after BCS. All patients were treated by hWBI VMAT-Rapid-Arc&Daily Exac-Trac-IGRT. Systemic adjuvant treatment was indicated following international guidelines. The aim of this study was to assess for the first time the local control, cancer-specific survival, and overall survival rates of BC patients treated by combined photon-IORT-boost and hWBI after BCS. Secondary endpoints include the long-term toxicity and cosmetic outcomes observed in these patients.</p><p><strong>Results: </strong>Fifty-seven patients were included in the trial. No ≥ G3 late toxicity was observed at 12 months of follow-up and thereafter. After a median follow-up of 61 months (range 54-66 months), all patients were free of local or regional relapse. Two patients had a second tumor in the contralateral breast. One triple-negative patient developed lung metastases 3 years after her initial diagnosis. Cause specific and overall survival were 100% at 5 years.</p><p><strong>Conclusion: </strong>We demonstrated for the first time that ph-IORT + hWBI is effective and safe in the long-term for patients referred to adjuvant RT after BCS.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3130-3134"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single and multitarget stereotactic radiosurgery (SRS) with single isocenter in the treatment of multiple brain metastases (BM): institutional experience.","authors":"Raquel Ciérvide, Jaime Martí, Mercedes López, Ovidio Hernando, Alejandro Prado, Leyre Alonso, Ángel Montero, Beatriz Álvarez, Miguel Angel de la Casa, Daniel Zucca, Ana Ortiz de Mendivil, Patricia Martín, Ana Martínez, Mariola García-Aranda, Emilio Sánchez, Jeannette Valero, Juan García, Xin Chen-Zhao, Rosa Alonso, Pedro Fernandez-Leton, Carmen Rubio","doi":"10.1007/s12094-024-03844-3","DOIUrl":"10.1007/s12094-024-03844-3","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;SRS for the treatment of limited brain metastases (BM) is widely accepted, but there are still limitations in the management of numerous BM. Frameless single-isocenter multitarget SRS is a novel technique that allows for rapid treatment delivery to multiple BM. We report our preliminary clinical, dosimetric, and patient´s shifts outcomes with this technique.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;We have reviewed clinical and dosimetric outcomes of patients with intact BM treated with SRS using one isocenter either for single (1BM) or multiple (≥ 2BM) targets). Immobilization was based on an SRS stereotactic mask. Elements Multiple Brain Mets SRS (Brainlab AG, Munich, Germany) software was used for registration, image fusion, target contouring, and treatment planning. Exactrac Dynamic (Brainlab AG, Munich, Germany) and a 6 degree of freedom couch were used for monitoring, correcting the position and assessing and applying residual errors also when couch rotations. During dose delivery, the patient position was monitored and registered using surface tracking and stereoscopic X-rays.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;From May 2022 to December 2023, we treated 60 patients with a total of 255 BM. The 67% of patients had at least 2 BM treated and the average of treated BM per patient per course was 3.6 (range 1-13). The average total treated BM per patient (sum of all courses) was 4.4. Lung cancer was the most frequent (63%) primary tumor. 77% of cases were patients with a brain relapse and the remaining 23% had BM at diagnosis. Ninety-two percent of BM were treated with single fraction. The most used fractionations were 20 Gy (27.8%) and 21 Gy (43.5%), respectively, and the median PTV target volume (if single fraction) was 0,2 cc (range 0.016-4.32 cc). The median cumulative target volume per isocenter and the sum of all SRS courses were 1.37 and 1.46 cc, respectively. The 100% of patients completed the SRS treatment with no incidences. With an average follow-up of 8.3 months (0.1-19 months), we have not identified any local relapse, although 27% developed an intracranial relapse that was again treated with SRS in the 44% of cases. We did not find any relation between overall survival and the presence of any driver mutation (p = 0.97), presence of BM at diagnosis vs. recurrences (p = 0.113), number of courses of SRS (p = 0.688), number of isocenters (p = 0.679), or number of treated BM (1 vs. 2-3 vs. ≥ 4; p = 0.7). Healthy normal tissue constraints were adequately accomplished with a median V12 (if single dose) and V20 (if 5 fractions) of 0.2 and 5 cc, respectively. No acute toxicity &gt; G2 was reported. Regarding patient positioning, monitoring, and registration based on X-ray imaging and surface guidance, patient shifts distributions were centered at 0.0 mm with standard deviations below 0.25 mm, except for the longitudinal shift based on X-rays, which was 0.35 mm. This implies an adequate fixation system, patien","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3183-3197"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Open-label phase II clinical trial of orteronel (TAK-700) in metastatic or advanced non-resectable granulosa cell ovarian tumors: the Greko II study (GETHI2013-01).","authors":"Jesus Garcia-Donas, Laia Garrigos, Nuria Lainez, Ana Santaballa, Andres Redondo, Juan Fernando Cueva, Mª Jesus Rubio, Mario Prieto, Jose Antonio Lopez-Guerrero, Zaida Garcia-Casado, Aranzanzu Barquin, Enrique Grande, Eva Guerra Alia, Elena Sevillano, Isabel Bover, Tatiana P Grazioso, Ramón Sanchez-Escribano, Alicia Hurtado, Paloma Navarro, Juan Francisco Rodriguez-Moreno","doi":"10.1007/s12094-024-03827-4","DOIUrl":"10.1007/s12094-024-03827-4","url":null,"abstract":"<p><strong>Background: </strong>Granulosa cell ovarian tumors (GCTs) are a rare neoplasia characterized by a pathognomonic mutation in the FOXL2 gene. In vitro studies have demonstrated an overactivation of hormone activity due to this alteration. Thus, we aimed to determine the activity of orteronel, a CYP17 inhibitor, in advanced disease.</p><p><strong>Methods: </strong>We designed a multicentric open-label phase II clinical trial. Eligible patients were adult woman with advanced or unresectable GCTs. Primary objective was clinical benefit rate, defined as the average of patients with radiological response plus stable disease longer than 6 months.</p><p><strong>Results: </strong>From October 1, 2014 to May 20, 2016, ten patients were included in six participating institutions members of the GETTHI group. The study was terminated early due to a low recruitment rate. Up to 40% (CI 95% [9.6-70.4%]) cases presented a disease stabilization longer than 6 months and two of them, longer than 12 months. One patient continued on treatment at database closure 29 months after inclusion in the trial. No patient reached partial or complete response by RECIST criteria on the independent radiological review. The drug was well tolerated with nausea as the only grade 3 adverse event in one case.</p><p><strong>Conclusion: </strong>Low accrual led to an early interruption of the study. However, orteronel achieved a promising clinical benefit rate that supports further development of new hormonotherapies in this tumor.</p><p><strong>Clinicaltrials: </strong></p><p><strong>Gov identifier: </strong>NCT02101684.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3223-3231"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}