Oncology and Therapy最新文献

{"title":"Gene Therapy for Neurofibromatosis Type 2-Related Schwannomatosis: Recent Progress, Challenges, and Future Directions.","authors":"Ruofei Yuan, Bo Wang, Ying Wang, Pinan Liu","doi":"10.1007/s40487-024-00279-2","DOIUrl":"10.1007/s40487-024-00279-2","url":null,"abstract":"<p><p>Neurofibromatosis type 2 (NF2)-related schwannomatosis is a rare autosomal dominant monogenic disorder caused by mutations in the NF2 gene. The hallmarks of NF2-related schwannomatosis are bilateral vestibular schwannomas (VS). The current treatment options for NF2-related schwannomatosis, such as observation with serial imaging, surgery, radiotherapy, and pharmacotherapies, have shown limited effectiveness and serious complications. Therefore, there is a critical demand for novel effective treatments. Gene therapy, which has made significant advancements in treating genetic diseases, holds promise for the treatment of this disease. This review covers the genetic pathogenesis of NF2-related schwannomatosis, the latest progress in gene therapy strategies, current challenges, and future directions of gene therapy for NF2-related schwannomatosis.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"257-276"},"PeriodicalIF":3.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11187037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140958428","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":"A Podcast on Pre- or Perioperative Chemoimmunotherapy for Stage III Non-Small Cell Lung Cancer: Shared Agreement from the Thoracic Surgeon and Oncologist Perspectives.","authors":"Luca Bertolaccini, Andrea De Giglio, Eleonora Gariazzo, Giulio Metro","doi":"10.1007/s40487-024-00267-6","DOIUrl":"10.1007/s40487-024-00267-6","url":null,"abstract":"<p><p>Management of stage II-III non-small cell lung cancer (NSCLC) has been dramatically revolutionized by studies testing the addition of immunotherapy (IO) to chemotherapy in the pre- or perioperative setting. That is because the integration of chemoimmunotherapy (chemo-IO) with surgery has consistently shown a significant improvement in pathological complete response (path CR) rate, event-free survival, and, more recently, overall survival, versus preoperative chemotherapy alone. Particularly, resectable stage III NSCLCs represent a disease entity with a high risk of distant recurrence after radical surgery, for whom pre- or perioperative chemo-IO should be considered as the preferential treatment option. However, owing to the heterogeneity of stage III NSCLC, a standard definition of resectability is not established yet, being often subjective according to the expertise and clinical background of the thoracic surgeon. In addition, careful patient selection on the basis of tumor biomarkers, meticulous staging of the disease, and accurate monitoring of treatment-related adverse events are critical factors that could prevent the ineligibility for surgery of patients treated with pre- or perioperative chemo-IO. Finally, the impact of downstaging for initially borderline resectable tumors, as well as the exact number of preoperative chemo-IO cycles needed and the indications for adjuvant IO, still need to be fully elucidated. In this podcast, we will touch upon the above-mentioned topics from the perspectives of the thoracic surgeon and the oncologist, and suggest a shared agreement between two of the main actors involved in the treatment of resectable stage III NSCLCs.Podcast audio available for this publication.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"207-215"},"PeriodicalIF":3.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11187012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140132776","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":"Adjuvant CDK4/6 Inhibitors for Early Breast Cancer: How to Choose Wisely?","authors":"Elisa Agostinetto, Luca Arecco, Evandro de Azambuja","doi":"10.1007/s40487-023-00250-7","DOIUrl":"10.1007/s40487-023-00250-7","url":null,"abstract":"","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"19-29"},"PeriodicalIF":2.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10881905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138292029","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":"A Retrospective Study of Cemiplimab Effectiveness in Elderly Patients with Squamous Cell Carcinoma of the Skin: Insights from a Real-Life Scenario.","authors":"Giuseppe Di Lorenzo, Aieta Michele, Leo Silvana, Domenico Bilancia, Rossella Di Trolio, Michela Rosaria Iuliucci, Concetta Ingenito, Roberta Rubino, Arianna Piscosquito, Michele Caraglia, Marianna Donnarumma, Ferdinando Costabile, Raffaele Conca, Marco Pisino, Angelo Vaia, Luca Scafuri, Antonio Verde, Carlo Buonerba","doi":"10.1007/s40487-023-00256-1","DOIUrl":"10.1007/s40487-023-00256-1","url":null,"abstract":"<p><strong>Introduction: </strong>This retrospective study investigates the efficacy of cemiplimab, a monoclonal antibody targeting the PD-1 receptor, in treating squamous cell carcinoma (SCC) of the skin.</p><p><strong>Methods: </strong>The study analyzes data from 50 patients with SCC, focusing on various clinical parameters, including patient demographics, tumor characteristics, treatment history, disease status at the beginning of therapy, and survival outcomes.</p><p><strong>Results: </strong>Of the patients who received at least one cycle of cemiplimab, 42% showed a clinical response. Adverse reactions were generally low, with the safety profile deemed excellent. During a median follow-up of 9.6 months, 17 patients experienced progression or death. Among these, 15 patients had died at the time of the analysis. The median progression-free survival (PFS) for the entire cohort was approximately 20.8 months, while median overall survival (OS) was not reached. Univariate Cox regression analysis for PFS showed that tumors in the arms and legs were associated with higher progression risk, while age above 65 years was not statistically significant. Distant metastasis exhibited a trend towards improved PFS. In terms of OS, distant metastasis was a significant predictor of reduced survival, while age above 65 years was not statistically significant. In a multivariate model, only the absence of distant metastasis remained significant, with an adjusted odds ratio (OR) of 12.3 (95% confidence interval 1.3-112.1).</p><p><strong>Conclusion: </strong>These findings provide valuable insights into the real-world effectiveness of cemiplimab in SCC management.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"147-155"},"PeriodicalIF":2.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10881452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138811194","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":"Repotrectinib's Clinical Benefit and Its Brain Penetration in a Patient with Meningeal Carcinomatosis from G2032R-Mutated ROS-1 Positive Non-Small Cell Lung Cancer.","authors":"Giulio Metro, Eleonora Gariazzo, Silvia Costabile, Sara Baglivo, Fausto Roila, Francesca Colamartini, Barbara Palumbo, Pietro Chiarini, Stefania Gori, Antonio Conti, Luca Marcomigni, Guido Bellezza, Gianluigi Lunardi","doi":"10.1007/s40487-023-00251-6","DOIUrl":"10.1007/s40487-023-00251-6","url":null,"abstract":"<p><p>In this work, we report on a clinically significant response of meningeal carcinomatosis to repotrectinib in a woman with a heavily pretreated ROS1-rearranged non-small cell lung cancer (NSCLC) that harbored the concomitant solvent front G2032R mutation. Meningeal carcinomatosis has a higher incidence in oncogene addicted NSCLC due to increased life expectancy, yet no report has ever documented the activity of repotrectinib in this context. In line with its activity, we documented the presence of the drug at potentially active concentrations in the cerebrospinal fluid. Nevertheless, the short-lived response reported by our patient highlights the importance for novel ROS1-tyrosine kinase inhibitors (TKIs) to be specifically developed to be able to penetrate the blood-brain barrier.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"163-171"},"PeriodicalIF":2.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10881448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136399696","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":"Is HER2-Low a New Clinical Entity or Merely a Biomarker for an Antibody Drug Conjugate?","authors":"Heidi Ko, Rebecca A Previs, Kyle C Strickland, Jonathan Klein, Brian Caveney, Chiara Chiruzzi, Marcia Eisenberg, Eric A Severson, Shakti Ramkissoon, Kamal S Saini","doi":"10.1007/s40487-023-00249-0","DOIUrl":"10.1007/s40487-023-00249-0","url":null,"abstract":"","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"13-17"},"PeriodicalIF":2.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10881909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92156925","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":"Non-Small Cell Lung Cancer Testing on Reference Specimens: An Italian Multicenter Experience.","authors":"Francesco Pepe, Gianluca Russo, Alessandro Venuta, Claudia Scimone, Mariantonia Nacchio, Pasquale Pisapia, Gaia Goteri, Francesca Barbisan, Caterina Chiappetta, Angelina Pernazza, Domenico Campagna, Marco Giordano, Giuseppe Perrone, Giovanna Sabarese, Annalisa Altimari, Dario de Biase, Giovanni Tallini, Daniele Calistri, Elisa Chiadini, Laura Capelli, Alfredo Santinelli, Anna Elisa Gulini, Elisa Pierpaoli, Manuela Badiali, Stefania Murru, Riccardo Murgia, Elena Guerini Rocco, Konstantinos Venetis, Nicola Fusco, Denise Morotti, Andrea Gianatti, Daniela Furlan, Giulio Rossi, Laura Melocchi, Maria Russo, Caterina De Luca, Lucia Palumbo, Saverio Simonelli, Antonella Maffè, Paola Francia di Celle, Tiziana Venesio, Maria Scatolini, Enrico Grosso, Sara Orecchia, Matteo Fassan, Mariangela Balistreri, Elisabetta Zulato, Daniela Reghellin, Elena Lazzari, Maria Santacatterina, Maria Liliana Piredda, Manuela Riccardi, Licia Laurino, Elena Roz, Domenico Longo, Daniela Petronilla Romeo, Carmine Fazzari, Andrea Moreno-Manuel, Giuseppe Diego Puglia, Andrey D Prjibelski, Daria Shafranskaya, Luisella Righi, Angela Listì, Domenico Vitale, Antonino Iaccarino, Umberto Malapelle, Giancarlo Troncone","doi":"10.1007/s40487-023-00252-5","DOIUrl":"10.1007/s40487-023-00252-5","url":null,"abstract":"<p><strong>Introduction: </strong>Biomarker testing is mandatory for the clinical management of patients with advanced non-small cell lung cancer (NSCLC). Myriads of technical platforms are now available for biomarker analysis with differences in terms of multiplexing capability, analytical sensitivity, and turnaround time (TAT). We evaluated the technical performance of the diagnostic workflows of 24 representative Italian institutions performing molecular tests on a series of artificial reference specimens built to mimic routine diagnostic samples.</p><p><strong>Methods: </strong>Sample sets of eight slides from cell blocks of artificial reference specimens harboring exon 19 EGFR (epidermal growth factor receptor) p.E746_AT50del, exon 2 KRAS (Kirsten rat sarcoma viral oncogene homologue) p.G12C, ROS1 (c-ros oncogene 1)-unknown gene fusion, and MET (MET proto-oncogene, receptor tyrosine kinase) Δ exon 14 skipping were distributed to each participating institution. Two independent cell block specimens were validated by the University of Naples Federico II before shipment. Methodological and molecular data from reference specimens were annotated.</p><p><strong>Results: </strong>Overall, a median DNA concentration of 3.3 ng/µL (range 0.1-10.0 ng/µL) and 13.4 ng/µL (range 2.0-45.8 ng/µL) were obtained with automated and manual technical procedures, respectively. RNA concentrations of 5.7 ng/µL (range 0.2-11.9 ng/µL) and 9.3 ng/µL (range 0.5-18.0 ng/µL) were also detected. KRAS exon 2 p.G12C, EGFR exon 19 p.E736_A750del hotspot mutations, and ROS1 aberrant transcripts were identified in all tested cases, whereas 15 out of 16 (93.7%) centers detected MET exon 14 skipping mutation.</p><p><strong>Conclusions: </strong>Optimized technical workflows are crucial in the decision-making strategy of patients with NSCLC. Artificial reference specimens enable optimization of diagnostic workflows for predictive molecular analysis in routine clinical practice.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"73-95"},"PeriodicalIF":2.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10881930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139418318","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":"Intratumoral Injection of Large Surface Area Microparticle Taxanes in Carcinomas Increases Immune Effector Cell Concentrations, Checkpoint Expression, and Synergy with Checkpoint Inhibitors: A Review of Preclinical and Clinical Studies.","authors":"Gere S diZerega, Holly A Maulhardt, Shelagh J Verco, Alyson M Marin, Michael J Baltezor, Samantha A Mauro, Marc A Iacobucci","doi":"10.1007/s40487-024-00261-y","DOIUrl":"10.1007/s40487-024-00261-y","url":null,"abstract":"<p><p>This review summarizes development of large surface area microparticle paclitaxel (LSAM-PTX) and docetaxel (LSAM-DTX) for local treatment of primary carcinomas with emphasis on immunomodulation. Intratumoral (IT) delivery of LSAM-PTX and LSAM-DTX provides continuous, therapeutic drug levels for several weeks. Preclinical studies and clinical trials reported a reduction in tumor volume (TV) and immunomodulation in primary tumor and peripheral blood with increases in innate and adaptive immune cells and decreases in suppressor cells. Increased levels of checkpoint expression of immune cells occurred in clinical trials of high-risk non-muscle-invasive bladder cancer (LSAM-DTX) and unresectable localized pancreatic cancer (LSAM-PTX). TV reduction and increases in immune effector cells occurred following IT LSAM-DTX and IT LSAM-PTX together with anti-mCTLA-4 and anti-mPD-1, respectively. Synergistic benefits from combinatorial therapy in a 4T1-Luc breast cancer model included reduction of metastasis with IT LSAM-DTX + anti-mCTLA-4. IT LSAM-PTX and LSAM-DTX are tumoricidal, immune enhancing, and may improve solid tumor response to immune checkpoint inhibitors without additional systemic toxicity.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"31-55"},"PeriodicalIF":2.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10881942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139576805","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":"Long Term Remission of Capillary Leak Syndrome Associated with Monoclonal Gammopathy with Progression to Multiple Myeloma After Autologous Stem Cell Transplantation: a Case Report and Review of the Literature.","authors":"Gerardo Hermida, Rodolfo Alvarez-Nuño, Jesús San Miguel-Izquierdo, Santiago González-Quijada, Tomás José González-López","doi":"10.1007/s40487-024-00263-w","DOIUrl":"10.1007/s40487-024-00263-w","url":null,"abstract":"<p><strong>Background: </strong>Clarkson's disease is a very rare entity characterised by acute episodes of systemic oedema and severe hypotension associated with paraproteinaemia. Its classical treatment relies on methylxanthine combined with terbutaline. Although this prophylactic therapy reduces the mortality rate, relapses are frequent. Eighty percent of patients with Clarkson's disease present with monoclonal gammopathy of unknown significance (MGUS). The risk of progression to multiple myeloma is 1% per year.</p><p><strong>Case description: </strong>Here, we present a 49-year-old woman who suffered multiple such episodes requiring treatment in the intensive care unit. Treatment with terbutaline and theophylline was ineffective. She was diagnosed with multiple myeloma (MM) 8 years after the first of these acute episodes. Antimyeloma treatment with bortezomib and dexamethasone was started, followed by autologous haemopoietic transplantation, with no further acute episodes since then.</p><p><strong>Conclusion: </strong>Our case is, to our knowledge, unique because eradication of MM was followed by complete disappearance of acute episodes of capillary leakage. Our case report is also the first to support the use of bortezomib and dexamethasone in this setting. Furthermore, autologous peripheral blood progenitor cell transplantation consolidated the MM stringent complete remission achieving a very long progression-free survival (> 11 years) of both MM and Clarkson's disease.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"183-188"},"PeriodicalIF":2.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10881945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139673239","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":"Acute Thrombocytopenia Complicating the Initial Administration of Obinutuzumab: Is It More Frequent Than We Think?","authors":"Umut Yılmaz, Selin Küçükyurt, Muhlis Cem Ar, Ahmet Emre Eşkazan","doi":"10.1007/s40487-023-00259-y","DOIUrl":"10.1007/s40487-023-00259-y","url":null,"abstract":"<p><p>Thrombocytopenia has been reported more frequently with obinutuzumab in clinical trials where it was directly compared with rituximab. However, more significant than the frequency, a unique form of severe thrombocytopenia manifesting very early after the first obinutuzumab infusion has been published in case reports. To further explore this subject, we went through the records of our clinic to identify similar cases of obinutuzumab-induced acute thrombocytopenia (OIAT). Among 24 patients who received obinutuzumab outside of clinical trials, we recovered three cases with OIAT. This paper describes these three cases in detail, placing emphasis on the timing, severity, and the clinical course. Notably, all three patients developed severe OIAT within 5 days of their first obinutuzumab exposure, responded well to transfusion, and recovered within a few days without severe bleeding. None of the patients experienced a similar event in the second course of the obinutuzumab-based therapy. Our observations suggest that OIAT may be a frequent, possibly non-relapsing, and unique event that deserves more attention than it currently receives.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"157-161"},"PeriodicalIF":2.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10881447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139513945","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}