Seminars in oncology最新文献

{"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}

{"title":"Prevalence, mutational spectrum and clinical implications of clonal hematopoiesis of indeterminate potential in plasma cell dyscrasias","authors":"Stefano Testa ,&nbsp;Jyoti Kumar ,&nbsp;Alex J. Goodell ,&nbsp;James L. Zehnder ,&nbsp;Kevin M. Alexander ,&nbsp;Surbhi Sidana ,&nbsp;Sally Arai ,&nbsp;Ronald M. Witteles ,&nbsp;Michaela Liedtke","doi":"10.1053/j.seminoncol.2022.11.001","DOIUrl":"10.1053/j.seminoncol.2022.11.001","url":null,"abstract":"<div><p>Clonal hematopoiesis of indeterminate potential (CHIP) is common both in healthy individuals and patients with hematological cancers. Recent studies have showed worse prognosis for patients with multiple myeloma (MM) and non-Hodgkin lymphoma undergoing stem cell transplant, that have concomitant presence of CHIP. Data regarding the clinical and biological role of CHIP in plasma cell dyscrasias (PCDs) is rapidly increasing. However, the prevalence and prognostic implication of CHIP in patients with MM outside of the transplant setting, and in those with other more indolent PCDs remains elusive. Here we explored the prevalence and clinical implications of CHIP detected through next-generation sequencing in 209 patients with PCDs including MM, light chain (AL) amyloidosis (ALA), monoclonal gammopathy of undetermined significance (MGUS), and smoldering multiple myeloma (SMM). To avoid attributing the mutations to the plasma cell clone, CHIP was defined as the presence of <em>DNMT3A, TET2,</em> or <em>ASXL1</em> mutations in the peripheral blood or bone marrow (DTA-CH). The prevalence of DTA-CH was 19% in patients with PCDs, with no difference between each PCD. <em>TET2</em> (23%) and <em>DNMT3A</em> (22%), were the most frequently mutated genes. DTA-CH correlated with older age in MM (<em>P</em> = .001) and MGUS/SMM (<em>P</em> = 0.0007), as well as with coronary artery disease or congestive heart failure in MM (<em>P</em> = .03). DTA-CH did not predict worse OS or PFS in either MM or ALA, nor it predict higher risk of progression to MM in patients with MGUS/SMM. Our results overall further elucidate the prevalence and mutational spectrum of CHIP in PCDs, providing more information regarding the clinical relevance of CHIP in this patient population.</p></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"49 6","pages":"Pages 465-475"},"PeriodicalIF":4.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9531576","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":"A narrative review of the principal glucocorticoids employed in cancer","authors":"Nerina Denaro ,&nbsp;Ornella Garrone ,&nbsp;Annamaria Morelli ,&nbsp;Benedetta Pellegrino ,&nbsp;Marco Carlo Merlano ,&nbsp;Denise Vacca ,&nbsp;Josie Pearce ,&nbsp;Daniele Farci ,&nbsp;Antonino Musolino ,&nbsp;Mario Scartozzi ,&nbsp;Chiara Tommasi ,&nbsp;Cinzia Solinas","doi":"10.1053/j.seminoncol.2023.01.004","DOIUrl":"10.1053/j.seminoncol.2023.01.004","url":null,"abstract":"<div><p>Glucocorticoids<span> (GCs) are a pharmacological class of drugs<span> widely used in oncology<span> in both supportive and palliative settings. GCs differentially impact organs with immediate and long-term effects; with suppressive effect on the immune system anchoring their use to manage the toxicities of immune checkpoint inhibitors (ICIs).</span></span></span></p><p>In addition, GCs are often used in the management of symptoms related to cancer or chemotherapy and as adjuvants in the treatment of pain in the management of other. In the palliative setting, GCs, especially administered subcutaneously can be to assist in the control of nausea, dyspnea, asthenia, and anorexia-cachexia syndrome.</p><p>In this narrative review, we aim to summarize the role of GCs in the different settings (curative, supportive, and palliative) to help clinicians use these important drugs in their daily clinical practice with cancer patients.</p></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"49 6","pages":"Pages 429-438"},"PeriodicalIF":4.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9164038","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}