Seminars in oncology最新文献

{"title":"Tumor testing and treatment patterns in veterans with metastatic castration-resistant prostate cancer","authors":"Anna Hung ,&nbsp;Danielle Candelieri ,&nbsp;Yanhong Li ,&nbsp;Patrick Alba ,&nbsp;Brian Robison ,&nbsp;Fatai Agiri ,&nbsp;Cristina Perez ,&nbsp;Kyung-Min Lee ,&nbsp;Kara N. Maxwell ,&nbsp;Weiyan Li ,&nbsp;Himani Aggarwal ,&nbsp;Kathryn Pridgen ,&nbsp;Shelby D. Reed ,&nbsp;Scott DuVall ,&nbsp;Yu-Ning Wong ,&nbsp;Julie A. Lynch","doi":"10.1053/j.seminoncol.2023.03.001","DOIUrl":"10.1053/j.seminoncol.2023.03.001","url":null,"abstract":"<div><h3>Introduction</h3><p>In 2016, the Department of Veterans Affairs (VA) and Prostate Cancer Foundation (PCF) began a partnership to improve access to testing. The primary objective of this analysis was to describe the use of tumor testing and treatment patterns in Veterans who progressed to metastatic castration-resistant prostate cancer (mCRPC) from 2016 to 2021. Secondary objectives including identifying factors associated with receipt of tumor testing, and reporting HRR mutation results among a subset who were tested.</p></div><div><h3>Methods and Materials</h3><p>Natural language processing algorithms were applied to VA electronic health record data to identify a nationwide cohort of veterans with mCRPC. Tumor testing over time and by region were reported, alongside first-, second-, and third-line treatment patterns. Factors associated with receipt of tumor testing were identified using generalized linear mixed models with binomial distributions and logit links to account for clustering by VA facility.</p></div><div><h3>Results</h3><p>Of the 9,852 veterans analyzed, 1,972 (20%) received tumor testing, with 73% of testing occurring in 2020–2021. Factors associated with tumor testing included younger age, later diagnosis year, being treated in the Midwest, or Puerto Rico or other compared to the South, and being treated at a PCF-VA Center of Excellence. Fifteen percent of tests were positive for a pathogenic HRR mutation. Seventy-six percent of the study cohort received first-line treatment, and among those, a subsequent 52% received second-line treatment. A subsequent 46% received third-line treatment.</p></div><div><h3>Conclusion</h3><p>After the VA-PCF partnership, one-fifth of veterans with mCRPC received tumor testing, with most tests occurring in 2020–2021.</p></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"50 1","pages":"Pages 11-24"},"PeriodicalIF":4.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9659283","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":"Improved outcomes in women with BRAF-mutant melanoma treated with BRAF/MEK-targeted therapy across randomized clinical trials. A systematic review and meta-analysis","authors":"Laura Pala ,&nbsp;Tommaso De Pas ,&nbsp;Eleonora Pagan ,&nbsp;Saverio Minucci ,&nbsp;Chiara Catania ,&nbsp;Nunzio Digiacomo ,&nbsp;Emilia Cocorocchio ,&nbsp;Daniele Laszlo ,&nbsp;Antonio Di Muzio ,&nbsp;Chiara Barigazzi ,&nbsp;Erika Stucchi ,&nbsp;Laura De Grandi ,&nbsp;Sara Stucchi ,&nbsp;Giuseppe Viale ,&nbsp;Richard D. Gelber ,&nbsp;Vincenzo Bagnardi ,&nbsp;Fabio Conforti","doi":"10.1053/j.seminoncol.2023.03.003","DOIUrl":"10.1053/j.seminoncol.2023.03.003","url":null,"abstract":"<div><p>Available evidence suggests that in patients with advanced BRAF V600-mutant melanoma treated with the combination of BRAF and MEK inhibitors, gender could be associated with survival outcome. We performed a systematic review and meta-analysis of all randomized clinical trials (RCTs) testing the combination of BRAF and MEK inhibitors, to assess the interaction between treatment effect and patients’ gender. We searched PubMed, MEDLINE, Embase, and Scopus, for phase II and III RCTs up to January 30, 2022. We included all RCTs that enrolled patients with BRAF V600-mutant advanced cutaneous melanoma and assessed combinations of BRAF and MEK inhibitors versus BRAF inhibitor monotherapy. Our aim was to assess differences if any in treatment efficacy between men and women, measured in terms of the differences in progression-free survival (PFS) and overall survival (OS) log-hazard ratios (log-HRs). We calculated the pooled PFS- and OS-HRs with 95% confidence intervals (CIs) in men and women using a random-effects model and assessed the heterogeneity between the estimates using an interaction test. Five RCTs that enrolled a total of 2,113 patients were included in the analysis. In women, the combination of BRAF and MEK inhibitors halved the risk of progression or death as compared with BRAF inhibitor monotherapy with a pooled PFS-HR of 0.50 (95%CI 0.41–0.61). In men, the benefit obtained with BRAF and MEK inhibitors was smaller with a pooled PFS-HR of 0.63 (95%CI 0.54–0.74), <em>P</em>-heterogeneity = .05. A similar trend was observed for OS where the pooled OS-HR was 0.62 (95%CI 0.48–0.80) in women and only 0.78, (95%CI 0.67–0.92) in men, <em>P</em>-heterogeneity = 0.11. These results support meaningful gender-based heterogeneity of response to combination of BRAF and MEK inhibitors targeted therapy in patients with advanced BRAF-mutant melanoma, that should be considered in future research to improve treatment effectiveness.</p></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"50 1","pages":"Pages 34-39"},"PeriodicalIF":4.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9659260","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":"Outcomes with panobinostat in heavily pretreated multiple myeloma patients","authors":"Darren Pan ,&nbsp;Tarek H. Mouhieddine ,&nbsp;Ranjan Upadhyay ,&nbsp;Nicole Casasanta ,&nbsp;Angela Lee ,&nbsp;Nicole Zubizarreta ,&nbsp;Erin Moshier ,&nbsp;Joshua Richter","doi":"10.1053/j.seminoncol.2023.03.006","DOIUrl":"10.1053/j.seminoncol.2023.03.006","url":null,"abstract":"<div><p>Panobinostat is an oral pan histone-deacetylase inhibitor used in the treatment of relapsed and refractory multiple myeloma. Previously published studies of panobinostat demonstrated synergy with bortezomib but included few patients exposed to newer agent combinations (ie, panobinostat plus daratumumab or carfilzomib). Here, we report outcomes of panobinostat-based combinations at an academic medical center among patients whose disease had been heavily pretreated with modern agents. We retrospectively analyzed 105 patients with myeloma treated with panobinostat at The Mount Sinai Hospital in New York City between October 2012 and October 2021. These patients had a median age of 65 (range 37–87) and had received a median of 6 prior lines of therapy while in 53% the disease was classified as triple class refractory and in 54% the disease had high-risk cytogenetics. Panobinostat was most commonly utilized at 20 mg (64.8%) as part of a triplet (61.0%) or quadruplet (30.5%). Aside from steroids, panobinostat was most commonly administered in combination with lenalidomide, pomalidomide, carfilzomib, and daratumumab in descending order of frequency. Among the 101 response-evaluable patients, the overall response rate was 24.8%, clinical benefit rate (≥minimal response) was 36.6%, and median progression-free survival was 3.4 months. Median overall survival was 19.1 months. The most common toxicities ≥grade 3 were hematologic, primarily neutropenia (34.3%), thrombocytopenia (27.6%), and anemia (19.1%). Panobinostat-based combinations produced modest response rates in patients with heavily pretreated multiple myeloma, over half of whom had triple-class refractory disease. Panobinostat warrants continued investigation as a tolerable oral option for recapturing responses in patients whose disease has progressed after receipt of standard-of-care therapies.</p></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"50 1","pages":"Pages 40-48"},"PeriodicalIF":4.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9659273","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":"Dexamethasone to prevent everolimus-induced stomatitis (Alliance MIST Trial: A221701)","authors":"Kathryn J. Ruddy ,&nbsp;David Zahrieh ,&nbsp;Jun He ,&nbsp;Blake Waechter ,&nbsp;Julianne L. Holleran ,&nbsp;Lionel D. Lewis ,&nbsp;Selina Chow ,&nbsp;Jan Beumer ,&nbsp;Matthias Weiss ,&nbsp;Nikolaos Trikalinos ,&nbsp;Bryan Faller ,&nbsp;Maryam Lustberg ,&nbsp;Hope S. Rugo ,&nbsp;Charles Loprinzi","doi":"10.1053/j.seminoncol.2023.01.001","DOIUrl":"10.1053/j.seminoncol.2023.01.001","url":null,"abstract":"<div><p>mTOR inhibitors such as everolimus may cause oral stomatitis, often a dose-limiting toxicity. Prior clinical research has suggested that a dexamethasone mouth rinse might help prevent and/or treat this. Alliance A221701 was a randomized phase III trial of patients initiating 10 mg daily oral everolimus that compared dexamethasone mouthwash taken preventively (initial dexamethasone group) versus therapeutically (initial placebo group) to assess two coprimary endpoints: the incidence of mTOR inhibitor-associated stomatitis (mIAS), and the area under the curve (AUC) of mIAS-associated pain over an 8-week treatment period. A Fisher's exact test was used to compare the incidences while a Wilcoxon rank-sum test was used to compare the AUCs. In addition, we performed an exploratory analysis of the association of everolimus trough concentrations and toxicity using a Mann-Whitney U test. Due to slow accrual, this study closed after 39 patients were randomized (19 to upfront placebo and 20 to upfront dexamethasone). There were no significant differences between groups seen in either of the coprimary endpoints; furthermore, we found no association between whole blood everolimus trough concentrations and toxicity. Although limited by poor enrollment, the results of this study do not suggest that prophylactic dexamethasone mouthwash is superior to therapeutic dexamethasone mouthwash (initiated at the first sign of mouth pain) for reducing the incidence or severity of mIAS from everolimus.</p></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"50 1","pages":"Pages 7-10"},"PeriodicalIF":4.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10247389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9662656","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":"Non-pharmacologic interventions for improving cancer-related fatigue (CRF): A systematic review of systematic reviews and pooled meta-analysis","authors":"Silvia Belloni ,&nbsp;Cristina Arrigoni ,&nbsp;Irene Baroni ,&nbsp;Gianluca Conte ,&nbsp;Federica Dellafiore ,&nbsp;Greta Ghizzardi ,&nbsp;Arianna Magon ,&nbsp;Giulia Villa ,&nbsp;Rosario Caruso","doi":"10.1053/j.seminoncol.2023.03.004","DOIUrl":"10.1053/j.seminoncol.2023.03.004","url":null,"abstract":"<div><h3>Introduction</h3><p>Literature encloses numerous systematic reviews (SRs) on nonpharmacologic interventions for improving cancer-related fatigue (CRF). The effect of these interventions remains controversial, and the available SRs have not been synthesized yet. We conducted a systematic synthesis of SRs and meta-analysis to determine the effect of nonpharmacologic interventions on CRF in adults.</p></div><div><h3>Material and methods</h3><p>We systematically searched 4 databases. The effect sizes (standard mean difference) were quantitatively pooled using a random-effects model. Chi-squared (Q) and I-square statistics (I²) tested the heterogeneity.</p></div><div><h3>Results</h3><p>We selected 28 SRs, including 35 eligible meta-analyses. The pooled effect size (standard mean difference, 95% CI) was -0.67 (-1.16, -0.18). The subgroup analysis by types of interventions showed a significant effect in all the investigated approaches (complementary integrative medicine, physical exercise, self-management/e-health interventions).</p></div><div><h3>Conclusions</h3><p>There is evidence that nonpharmacologic interventions are associated with CRF reduction. Future research should focus on testing these interventions on specific population clusters and trajectories.</p></div><div><h3>Prospero registration</h3><p>CRD42020194258.</p></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"50 1","pages":"Pages 49-59"},"PeriodicalIF":4.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10032746","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":"Epidemiology and genetics of early onset colorectal cancer—African overview with a focus on Ethiopia","authors":"Chimaobi Anugwom ,&nbsp;Grace Braimoh ,&nbsp;Amir Sultan ,&nbsp;Willie Mohammed Johnson ,&nbsp;Jose D. Debes ,&nbsp;Abdulsemed Mohammed","doi":"10.1053/j.seminoncol.2023.03.007","DOIUrl":"10.1053/j.seminoncol.2023.03.007","url":null,"abstract":"<div><p>Colorectal cancer (CRC) is a common cause of cancer-related death worldwide, with high rates of late diagnosis and increased mortality in sub-Saharan Africa. Furthermore, there is an alarming uptrend in the incidence of early onset colorectal cancer (EOCRC) across the globe, thus necessitating the need for early screening in general and special populations. There is, however, limited data available on the incidence and genetic characteristics of EOCRC from resource-poor countries, particularly Africa. Moreover, there is lack of clarity if recommendations and mechanisms proposed based on data from resource-rich countries applies to other regions of the world. In this review, we appraise the literature on EOCRC, its overall incidence, and genetic components as it pertains to sub-Saharan Africa. In addition, we highlight epidemiologic and epigenetic findings of our EOCRC cohort in Ethiopia.</p></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"50 1","pages":"Pages 28-33"},"PeriodicalIF":4.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9713694","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":"Battling chronic myeloid leukemia in a resource-constrained country: A case of public-private partnerships","authors":"Rabbia Tariq ,&nbsp;Irtebaat Fatima,&nbsp;Muhammad H. Shahid,&nbsp;Samiuddin Tariq,&nbsp;Faizan Niaz,&nbsp;Syed M. Hussain","doi":"10.1053/j.seminoncol.2023.03.002","DOIUrl":"10.1053/j.seminoncol.2023.03.002","url":null,"abstract":"<div><p>Pakistan, where chronic myeloid leukemia constitutes around 80% of all myeloproliferative disorders, has been exploring multiple avenues in order to ensure the accessibility and affordability of imatinib and nilotinib. While most provinces of the country have joined hands with a pharmaceutical company to dispense free anti-CML medicines as part of a public-private partnership, the patients are still facing numerous challenges in the form of geographical disparity in the availability of these medicines, other out-of-pocket expenditures and most importantly, the uncertainty associated with the long-term continuation of this public-private endeavor due to procedural delays. In light of these predicaments, channeling resources towards research and development, fostering partnerships between government and NGOs and tapping into the domain of compulsory licensing appear to be the most sustainable solutions.</p></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"50 1","pages":"Pages 25-27"},"PeriodicalIF":4.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10033235","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 flaws in assessing and reporting the toxicities of oral targeted therapies","authors":"Tito Fojo MD, PhD","doi":"10.1053/j.seminoncol.2023.04.001","DOIUrl":"https://doi.org/10.1053/j.seminoncol.2023.04.001","url":null,"abstract":"","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"50 1","pages":"Pages 1-6"},"PeriodicalIF":4.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50185078","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":"TOC","authors":"","doi":"10.1053/S0093-7754(23)00046-5","DOIUrl":"https://doi.org/10.1053/S0093-7754(23)00046-5","url":null,"abstract":"","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"50 1","pages":"Pages A3-A4"},"PeriodicalIF":4.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50185081","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":"Synchronous or metachronous presentation of pancreatic neuroendocrine tumor versus secondary lesion to pancreas in patients affected by renal cell carcinoma. Systematic review","authors":"Irene Persano ,&nbsp;Elena Parlagreco ,&nbsp;Anna La Salvia ,&nbsp;Marco Audisio ,&nbsp;Marco Volante ,&nbsp;Consuelo Buttigliero ,&nbsp;Giorgio Vittorio Scagliotti ,&nbsp;Maria Pia Brizzi","doi":"10.1053/j.seminoncol.2023.01.007","DOIUrl":"10.1053/j.seminoncol.2023.01.007","url":null,"abstract":"<div><p>The simultaneous or metachronous occurrence of pancreatic neuroendocrine tumor (panNET) and renal cell carcinoma (RCC) may represent a rare coincidence or a manifestation of von Hippel-Lindau disease (VHL). These two malignancies share both radiological and cytopathological features, making the differential diagnosis very challenging. In this review, we collected all cases of concurrent diagnosis of localized panNET and RCC, with or without VHL, as reported in the literature to date. We aimed to provide an insight into the differential diagnosis between panNET and RCC pancreatic metastasis with a focus on the optimal therapeutic algorithm depending on the diagnosis. We performed literature research in PubMed library databases for articles about coexisting panNET and RCC published from 2001 to 2018. We selected nine articles with a total of 13 patients, including one treated at our institution. Patients' median age was 49 years and eight out of 13 patients were women. VHL was diagnosed in nine cases. Most patients underwent radical nephrectomy for RCC (9/13) and a clear cell renal carcinoma variant was identified in six cases. The diagnosis of panNET was synchronous with RCC detection in nine cases and metachronous in four cases. The diameter of the pancreatic lesion was &gt;2 cm in six cases. In two cases the panNET was misdiagnosed as metastatic RCC by radiological tests. Somatostatin receptor scanning was performed only in our patient (Octreoscan) showing intense uptake in the pancreatic mass. Endoscopic ultrasound fine needle aspiration of the pancreatic lesion was performed in four patients: in two cases the panNET was confused with metastatic RCC by cytological analysis. Most patients underwent pancreatic surgery (10/13) without histological confirmation. Clear cell panNET was recognized in six cases, while mixed neuroendocrine non-neuroendocrine neoplasm was diagnosed in one patient. Immunohistochemistry (IHC) staining showed positivity to typical neuroendocrine markers (chromogranin A and synaptophysin) in all reported tested cases (8/8). Three patients underwent systemic treatment: two patients received sunitinib and one patient interleukin-2 (IL-2). Other neoplasms were observed in seven patients, of whom six were affected by VHL syndrome. When neoplastic lesions are recognized in both the kidney and pancreas, panNET and RCC pancreatic metastasis are often misdiagnosed due to similar radiological and cytopathological features. An accurate differential diagnosis is crucial and IHC plays a central role in distinguishing the two entities. The therapeutic algorithm may change depending on the diagnosis: while pancreatic RCC metastases benefit from resection, in panNETs and VHL the indication for surgery must be carefully evaluated.</p></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"49 6","pages":"Pages 476-481"},"PeriodicalIF":4.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10330030","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}