Oncology and Therapy最新文献

{"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}

{"title":"Long-Term Survival and Stable Disease in a Patient with Extensive-Stage Small-Cell Lung Cancer after Treatment with Carboplatin, Etoposide and Atezolizumab.","authors":"Reyes Bernabé, Stephen V Liu, Amparo Sánchez-Gastaldo, Miriam Alonso García","doi":"10.1007/s40487-023-00257-0","DOIUrl":"10.1007/s40487-023-00257-0","url":null,"abstract":"<p><p>Survival beyond 2 years is rare in patients with extensive-stage small-cell lung cancer (ES-SCLC) treated with chemotherapy alone. We describe a patient with ES-SCLC who was treated with carboplatin, etoposide and the programmed death-ligand 1 inhibitor atezolizumab in the IMpower133 study (ClinicalTrials.gov registration: NCT02763579) and who achieved exceptionally long-term survival. Treatment-naïve patients with ES-SCLC (n = 403) were included in the IMpower133 study, and the identified patient had been randomised to the investigational treatment arm, where patients received induction therapy with carboplatin and etoposide plus atezolizumab for four 21-day cycles, followed by ongoing maintenance therapy with atezolizumab. The patient had achieved a partial response after induction therapy, and then received seven cycles of atezolizumab maintenance therapy until immune-related toxicities necessitated discontinuation. The patient was alive with an ongoing response and excellent performance status more than 6 years after starting treatment and 5 years after discontinuing atezolizumab maintenance. In conclusion, this patient with ES-SCLC from the IMpower133 study is a rare example of ongoing survival more than 6 years beyond diagnosis and the start of treatment with first-line atezolizumab. This demonstrates the potential durability of response with immunotherapy.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"175-182"},"PeriodicalIF":2.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10881916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139571631","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":"Small Molecule Menin Inhibitors: Novel Therapeutic Agents Targeting Acute Myeloid Leukemia with KMT2A Rearrangement or NPM1 Mutation.","authors":"Xavier Thomas","doi":"10.1007/s40487-024-00262-x","DOIUrl":"10.1007/s40487-024-00262-x","url":null,"abstract":"<p><p>Recent advances have included insights into the clinical value of genomic abnormalities in acute myeloid leukemia (AML) and consequently the development of numerous targeted therapeutic agents that have improved clinical outcome. In this setting, various clinical trials have recently explored novel therapeutic agents either used alone or in combination with intensive chemotherapy or low-intensity treatments. Among them, menin inhibitors could represent a novel group of targeted therapies in AML driven by rearrangement of the lysine methyltransferase 2A (KMT2A) gene, previously known as mixed-lineage leukemia (MLL), or by mutation of the nucleophosmin 1 (NPM1) gene. Recent phase 1/2 clinical trials confirmed the efficacy of SNDX-5613 (revumenib) and KO-539 (ziftomenib) and their acceptable tolerability. Several small molecule menin inhibitors are currently being evaluated as a combination therapy with standard of care treatments. The current paper reviews the recent progress in exploring the inhibitors of menin-KMT2A interactions and their application prospects in the treatment of acute leukemias.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"57-72"},"PeriodicalIF":2.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10881917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139651875","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":"From Incidence to Intervention: A Comprehensive Look at Breast Cancer in South Africa.","authors":"Zodwa Dlamini, Thulo Molefi, Richard Khanyile, Mahlori Mkhabele, Botle Damane, Alexandre Kokoua, Meshack Bida, Kamal S Saini, Nkhensani Chauke-Malinga, Thifhelimbilu Emmanuel Luvhengo, Rodney Hull","doi":"10.1007/s40487-023-00248-1","DOIUrl":"10.1007/s40487-023-00248-1","url":null,"abstract":"<p><p>The formidable impact of breast cancer extends globally, with South Africa facing pronounced challenges, including significant disparities in breast cancer screening, treatment and survival along ethnic and socioeconomic lines. Over the last two decades, breast cancer incidence has increased and now accounts for a substantial portion of cancers in women. Ethnic disparities in terms of screening, incidence and survival exacerbate the issue, leading to delayed diagnosis among Black patients and highlighting healthcare inequities. These concerning trends underscore the urgency of enhancing breast cancer screening while mitigating treatment delays, although obstacles within the healthcare system impede progress. The intersection of breast cancer and human immunodeficiency virus (HIV) further complicates matters and particularly affects the Black population. Tackling the aforementioned disparities in breast cancer in South Africa mandates a multifaceted strategy. Robust screening efforts, particularly those targeting marginalised communities, are crucial for early detection. Concurrently, expedited treatment initiation is imperative. Addressing HIV-related complexities requires tailored interventions to ensure effective care. These multifaceted disparities require pan African research and cooperation as well as tailored interventions to enhance breast cancer care within the African region.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"1-11"},"PeriodicalIF":2.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10881925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71427723","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":"Patient Versus Physician Perspective in the Management of Chronic Myeloid Leukemia During Treatment with Tyrosine Kinase Inhibitors.","authors":"Hong Chen, Yan Wen, Yun Zeng, Lie Lin, Bihong Sun, Hongqian Zhu, Huiqing He, Xiaotao Wang, Waiyi Zou, Caifeng Zheng, Liling Zheng, Jinxiong Huang, Liping Pang, Jixian Huang, Yuming Zhang, Haiqing Lin, Zelin Liu, Wanshou Zhu, Qiang Wang, Xuan Zhou, Xiaoli Liu, Hong Qu, Zhenfang Liu, Xin Du, Na Xu","doi":"10.1007/s40487-023-00255-2","DOIUrl":"10.1007/s40487-023-00255-2","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic myeloid leukemia (CML) is a chronic disease with treatment-free remission (TFR) increasingly regarded as a feasible goal of treatment. However, various factors may influence adherence to international guidelines for CML management. This study aimed to compare the reporting of care between patients with CML and their treating doctors.</p><p><strong>Methods: </strong>Parallel patient and physician online surveys were conducted between September 22, 2021, and March 15, 2022, which focused on the perceptions of 1882 adult patients with CML and 305 physicians regarding tyrosine kinase inhibitor (TKI) treatment options, monitoring and toxicities, TFR, and challenges faced.</p><p><strong>Results: </strong>Among the enrolled patients, 69.9% received first-line imatinib treatment, 18.6% received nilotinib, and 4.7% received dasatinib. Among the patients treated with imatinib, 36.7% switched to other TKIs due to imatinib resistance/intolerance (71.1%), exploration of more potent TKIs to achieve TFR (8.9%), and treating physicians' recommendation (14.0%), with a median duration of initial treatment of 14 months [interquartile range (IQR) 6-36]. Most (91.8%) physicians agreed that the breakpoint cluster region-Abelson 1 (BCR::ABL1) transcript level should be assessed every 3 months, but only 42.7% of individuals committed to 3-monthly testing and only 17.8% strictly followed their treating physicians' recommendation. Half of the patients aimed for TFR; however, just 45.2% of physicians considered TFR as one of the top three goals for their patients. The major concern in obtaining TFR was patients' adherence. Fatigue was often distressing for patients with TKIs, while physicians were more concerned about platelet and neutrophil counts. A total of 12% and 20.8% of patients reported moderate/severe anxiety and depression, respectively, while only 53.7% of physicians had concerns about their patients' mental health. During the coronavirus disease 2019 (COVID-19) pandemic, 69.2% of patients reported a reduction in their income. Among these patients, 61.8% maintained their current treatment, while 7.3% switched to cheaper alternatives or discontinued treatment, with over 80% of these patients belonging to the low-income group.</p><p><strong>Conclusions: </strong>Overcoming challenges in patient-physician communication and treatment access is key to improving disease management and quality of life, especially for patients with low income.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier NCT05092048.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"131-145"},"PeriodicalIF":2.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10881939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138811282","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":"Diversity in Oncology Clinical Trials: Current Landscape for Industry-Sponsored Clinical Trials in Asia","authors":"Dany Habr, Manmohan Singh, R. Uehara","doi":"10.1007/s40487-023-00254-3","DOIUrl":"https://doi.org/10.1007/s40487-023-00254-3","url":null,"abstract":"","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":"26 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138589622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experiences and Support Needs of Caregivers of Patients with Higher-Risk Myelodysplastic Syndrome via Online Bulletin Board in the USA, Canada and UK","authors":"Pauline Frank, Anne Olshan, T. Iraca, Cindy Anthony, Sophie Wintrich, Emma Sasse","doi":"10.1007/s40487-023-00253-4","DOIUrl":"https://doi.org/10.1007/s40487-023-00253-4","url":null,"abstract":"","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":"28 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138593341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Meta-analysis of Surgical Outcomes of T4a and Infranotch T4b Oral Cancers.","authors":"Karthik Nagaraja Rao, Ripudaman Arora, Prajwal Dange, Nitin Nagarkar, Antti A Mäkitie, Luiz P Kowalski, Avraham Eisbruch, Marc Hamoir, Francisco J Civantos, Vincent Vander Poorten, Sweet Ping Ng, Sandra Nuyts, Mark Zafereo, Ameya A Asarkar, Paweł Golusinski, Ohad Ronen, Alfio Ferlito","doi":"10.1007/s40487-023-00246-3","DOIUrl":"10.1007/s40487-023-00246-3","url":null,"abstract":"<p><strong>Objective: </strong>To determine the overall surgical outcomes of infranotch T4b oral cancers and compare them with T4a oral cancers.</p><p><strong>Methods: </strong>PubMed, EMBASE and Cochrane databases from 2000 to 2022 were systematically searched. Clinical studies reporting at least one outcome following curative surgery and adjuvant therapy for comparison of patients with either infranotch T4b (IN-T4b) or T4a tumour. The heterogeneity of the included studies was determined using Tau-squared, Chi-squared, and the Higgins I² test. The random effects model was used to determine the log odds ratio (logOR).</p><p><strong>Results: </strong>The systematic review comprised 11,790 patients from 16 included studies. Seven studies were included in the meta-analysis (n = 11,381). For IN-T4b patients, the pooled 2 and 5 year overall survival (OS) were 59.3% and 53.2%, 2 and 5 year disease-free survival (DFS) 57.9% and 48.4%, 2 and 5 year disease-specific survival (DSS) 72% and 68%, and 2 and 5 year local control (LC), 47% and 56%, respectively. There was no statistically significant difference in 2 year OS [logOR = 0.28 (-0.47, 1.03), p = 0.46, confidence interval (CI) = 95%], 5 year OS [logOR = 0.7 (-0.4, 1.8), p = 0.54, CI = 95%], 2 year DFS [logOR = 0.22 (-0.35, 0.79), p = 0.45, CI = 95%], 5 year DFS [logOR = 0.17 (-0.42, 0.77), p = 0.57, CI = 95%], 2 year LC [logOR = 0.47 (-0.33, 1.26), p = 0.25, CI = 95%] and 5 year LC [logOR = 0.34 (-0.31, 0.99), p = 0.31, CI = 95%] between IN-T4b and T4a oral cancers.</p><p><strong>Conclusion: </strong>Results of this meta-analysis suggest that IN-T4b oral cancers have similar outcomes to T4a oral cancers, which supports down-staging IN-T4b cancers to T4a cancers.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"461-480"},"PeriodicalIF":2.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10673764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41137356","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}