1
Mol Cancer Ther
. 2019 Oct;18(10):1852-1862. doi: 10.1158/1535-7163.MCT-18-0965. Epub 2019 Jul 18.
Genomic Profiling of Blood-Derived Circulating Tumor DNA From Patients With Colorectal Cancer: Implications for Response and Resistance to Targeted Therapeutics
In Sil Choi # 1 2, Shumei Kato # 3, Paul T Fanta 1, Lawrence Leichman 1, Ryosuke Okamura 1, Victoria M Raymond 4, Richard B Lanman 4, Scott M Lippman 1, Razelle Kurzrock 1
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PMID: 31320401
DOI: 10.1158/1535-7163.MCT-18-0965Free article
Abstract
Molecular profiling of circulating tumor DNA (ctDNA) is a promising noninvasive tool. Here, next-generation sequencing (NGS) of blood-derived ctDNA was performed in patients with advanced colorectal cancer. We investigated ctDNA-derived genomic alterations, including potential actionability, concordance with tissue NGS, and serial dynamics in 78 patients with colorectal cancer using a clinical-grade NGS assay that detects single nucleotide variants (54-73 genes) and selected copy-number variants, fusions, and indels. Overall, 63 patients [80.8% (63/78)] harbored ctDNA alterations; 59 [75.6% (59/78)], ≥1 characterized alteration (variants of unknown significance excluded). All 59 patients had actionable alterations potentially targetable with FDA-approved drugs [on-label and/or off-label (N = 54) or with experimental drugs in clinical trials (additional five patients); University of California San Diego Molecular Tumor Board assessment]: 45, by OncoKB (http://oncokb.org/#/). The tissue and blood concordance rates for common specific alterations ranged from 62.3% to 86.9% (median = 5 months between tests). In serial samples from patients on anti-EGFR therapy, multiple emerging alterations in genes known to be involved in therapeutic resistance, including KRAS, NRAS, BRAF, EGFR, ERBB2, and MET were detected. In conclusion, over 80% of patients with stage IV colorectal cancer had detectable ctDNA, and the majority had potentially actionable alterations. Concordance between tissue and blood was between 62% and 87%, despite a median of 5 months between tests. Resistance alterations emerged on anti-EGFR therapy. Therefore, biopsy-free, noninvasive ctDNA analysis provides data relevant to the clinical setting. Importantly, sequential ctDNA analysis detects patterns of emerging resistance allowing for precision planning of future therapy.
©2019 American Association for Cancer Research.
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2
Multicenter Study
Transfusion
. 2019 Oct;59(10):3113-3119. doi: 10.1111/trf.15495. Epub 2019 Sep 3.
Evaluating Emergency-Release Blood Transfusion of Newborn Infants at the Intermountain Healthcare Hospitals
Timothy M Bahr 1, Tara L DuPont 1, Thomas R Christensen 2, Terry Rees 3, Elizabeth A O'Brien 1 4, Sarah J Ilstrup 3, Robert D Christensen 1 4 5
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PMID: 31479169
DOI: 10.1111/trf.15495
Abstract
Background: An emergency-release blood transfusion (ERBT) protocol (uncrossmatched type O-negative red blood cells, AB plasma, AB platelets) is critical for neonatology practice. However, few reports of emergency transfusions are available. We conducted an ERBT quality improvement project as a basis for progress.
Study design and methods: For each ERBT in the past 8 years, we logged indications, products, locations and timing of the transfusions, and outcomes.
Results: One hundred forty-nine ERBTs were administered; 42% involved a single blood product, and 58% involved two or more. The incidence was 6.25 ERBT per 10,000 live births, with a higher rate (9.52 ERBT/10,000) in hospitals with a Level 3 neonatal intensive care unit (NICU) (p < 0.001). Seventy percent of ERBTs were administered in a NICU and 30% in a delivery room, operating room, or emergency department. Indications were abruption/previa (32.2%), congenital anemia (i.e., fetomaternal hemorrhage; 15.4%), umbilical cord accident (i.e., velamentous insertion; 15.0%), and bleeding/coagulopathy (12.8%). Fifty-eight percent of those with hemorrhage before birth did not have a hemoglobin value reported on the umbilical cord gas; thus, anemia was not recognized initially. None of the 149 ERBTs were administered using a blood warmer. The mortality rate of recipients was 35%.
Conclusion: Based on our findings, we recommend including a hemoglobin value with every cord blood gas after emergency delivery to rapidly identify fetal anemia. We also discuss two potential improvements for future testing: 1) the use of a warming device for massive transfusion of neonates and 2) the use of low-titer group O cold-stored whole blood for massive hemorrhage in neonates.
© 2019 AABB.
31 references
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3
Mol Cancer Ther
. 2019 Oct;18(10):1775-1786. doi: 10.1158/1535-7163.MCT-18-0864. Epub 2019 Jul 29.
Tyrosine Threonine Kinase Inhibition Eliminates Lung Cancers by Augmenting Apoptosis and Polyploidy
Lin Zheng # 1, Zibo Chen # 1 2, Masanori Kawakami 1 2, Yulong Chen 1, Jason Roszik 3 4, Lisa Maria Mustachio 1, Jonathan M Kurie 1, Pamela Villalobos 5, Wei Lu 5, Carmen Behrens 5, Barbara Mino 5, Luisa M Solis 5, Jennifer Silvester 6, Kelsie L Thu 6, David W Cescon 6, Jaime Rodriguez-Canales 5, Ignacio I Wistuba 5, Tak W Mak 6, Xi Liu 1 2, Ethan Dmitrovsky 7 2 8
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PMID: 31358662
DOI: 10.1158/1535-7163.MCT-18-0864
Abstract
The spindle assembly checkpoint maintains genomic integrity. A key component is tyrosine threonine kinase (TTK, also known as Mps1). TTK antagonism is hypothesized to cause genomic instability and cell death. Interrogating The Cancer Genome Atlas revealed high TTK expression in lung adenocarcinomas and squamous cell cancers versus the normal lung (P < 0.001). This correlated with an unfavorable prognosis in examined lung adenocarcinoma cases (P = 0.007). TTK expression profiles in lung tumors were independently assessed by RNA in situ hybridization. CFI-402257 is a highly selective TTK inhibitor. Its potent antineoplastic effects are reported here against a panel of well-characterized murine and human lung cancer cell lines. Significant antitumorigenic activity followed independent treatments of athymic mice bearing human lung cancer xenografts (6.5 mg/kg, P < 0.05; 8.5 mg/kg, P < 0.01) and immunocompetent mice with syngeneic lung cancers (P < 0.001). CFI-402257 antineoplastic mechanisms were explored. CFI-402257 triggered aneuploidy and apoptotic death of lung cancer cells without changing centrosome number. Reverse phase protein arrays (RPPA) of vehicle versus CFI-402257-treated lung cancers were examined using more than 300 critical growth-regulatory proteins. RPPA bioinformatic analyses discovered CFI-402257 enhanced MAPK signaling, implicating MAPK antagonism in augmenting TTK inhibitory effects. This was independently confirmed using genetic and pharmacologic repression of MAPK that promoted CFI-402257 anticancer actions. TTK antagonism exerted marked antineoplastic effects against lung cancers and MAPK inhibition cooperated. Future work should determine whether CFI-402257 treatment alone or with a MAPK inhibitor is active in the lung cancer clinic.
©2019 American Association for Cancer Research.
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4
Meta-Analysis
Ann Oncol
. 2019 Aug 1;30(8):1370-1380. doi: 10.1093/annonc/mdz176.
Meta-analysis in Metastatic Uveal Melanoma to Determine Progression Free and Overall Survival Benchmarks: An International Rare Cancers Initiative (IRCI) Ocular Melanoma Study
L Khoja 1, E G Atenafu 2, S Suciu 3, S Leyvraz 4, T Sato 5, E Marshall 6, U Keilholz 7, L Zimmer 8, S P Patel 9, S Piperno-Neumann 10, J Piulats 11, T T Kivelä 12, C Pfoehler 13, S Bhatia 14, P Huppert 15, L B J Van Iersel 16, I J M De Vries 17, N Penel 18, T Vogl 19, T Cheng 20, G Fiorentini 21, F Mouriaux 22, A Tarhini 23, P M Patel 24, R Carvajal 25, A M Joshua 26
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PMID: 31150059
DOI: 10.1093/annonc/mdz176
Abstract
Background: Despite the completion of numerous phase II studies, a standard of care treatment has yet to be defined for metastatic uveal melanoma (mUM). To determine benchmarks of progression free survival (PFS) and overall survival (OS), we carried out a meta-analysis using individual patient level trial data.
Methods: Individual patient variables and survival outcomes were requested from 29 trials published from 2000 to 2016. Univariable and multivariable analysis were carried out for prognostic factors. The variability between trial arms and between therapeutic agents on PFS and OS was investigated.
Results: OS data were available for 912 patients. The median PFS was 3.3 months (95% CI 2.9-3.6) and 6-month PFS rate was 27% (95% CI 24-30). Univariable analysis showed male sex, elevated (i.e. > versus ≤ upper limit of normal) lactate dehydrogenase (LDH), elevated alkaline phosphatase (ALP) and diameter of the largest liver metastasis (≥3 cm versus <3 cm) to be substantially associated with shorter PFS. Multivariable analysis showed male sex, elevated LDH and elevated ALP were substantially associated with shorter PFS. The most substantial factors associated with 6-month PFS rate, on both univariable and multivariable analysis were elevated LDH and ALP. The median OS was 10.2 months (95% CI 9.5-11.0) and 1 year OS was 43% (95% CI 40-47). The most substantial prognostic factors for shorter OS by univariable and multivariable analysis were elevated LDH and elevated ALP. Patients treated with liver directed treatments had statistically significant longer PFS and OS.
Conclusion: Benchmarks of 6-month PFS and 1-year OS rates were determined accounting for prognostic factors. These may be used to facilitate future trial design and stratification in mUM.
Keywords: meta-analysis; survival benchmarks; trial design; uveal melanoma.
© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Cited by 5 articles
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5
Clinical Trial
Eur J Cancer
. 2019 Oct;120:107-113. doi: 10.1016/j.ejca.2019.07.023. Epub 2019 Sep 9.
Can Radiomics Help to Predict Skeletal Muscle Response to Chemotherapy in Stage IV Non-Small Cell Lung Cancer?
E E C de Jong 1, K J C Sanders 2, T M Deist 1, W van Elmpt 3, A Jochems 1, J E van Timmeren 1, R T H Leijenaar 1, J H R J Degens 2, A M W J Schols 2, A-M C Dingemans 4, P Lambin 5
Affiliations expand
PMID: 31514107
DOI: 10.1016/j.ejca.2019.07.023Free article
Abstract
Background: Muscle depletion negatively impacts treatment efficacy and survival rates in cancer. Prevention and timely treatment of muscle loss require prediction of patients at risk. We aimed to investigate the potential of skeletal muscle radiomic features to predict future muscle loss.
Methods: A total of 116 patients with stage IV non-small cell lung cancer included in a randomised controlled trial (NCT01171170) studying the effect of nitroglycerin added to paclitaxel-carboplatin-bevacizumab were enrolled. In this post hoc analysis, muscle cross-sectional area and radiomic features were extracted from computed tomography images obtained before initiation of chemotherapy and shortly after administration of the second cycle. For internal cross-validation, the cohort was randomly split in a training set and validation set 100 times. We used least absolute shrinkage and selection operator method to select features that were most significantly associated with muscle loss and an area under the curve (AUC) for model performance.
Results: Sixty-nine patients (59%) exhibited loss of skeletal muscle. One hundred ninety-three features were used to construct a prediction model for muscle loss. The average AUC was 0.49 (95% confidence interval [CI]: 0.36, 0.62). Differences in intensity and texture radiomic features over time were seen between patients with and without muscle loss.
Conclusions: The present study shows that skeletal muscle radiomics did not predict future muscle loss during chemotherapy in non-small cell lung cancer. Differences in radiomic features over time might reflect myosteatosis. Future imaging analysis combined with muscle tissue analysis in patients and in experimental models is needed to unravel the biological processes linked to the radiomic features.
Keywords: Cachexia; Computed tomography; Muscle; Non-small cell lung cancer; Radiomics.
Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.
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6
Ann Surg Oncol
. 2020 Jan;27(1):188-195. doi: 10.1245/s10434-019-07934-3. Epub 2019 Oct 15.
Prediction of Recurrence Patterns From Hepatic Parenchymal Disease After Resection of Colorectal Liver Metastases
Raja R Narayan 1 2, Jennifer W Harris 1, Joanne F Chou 3, Mithat Gönen 3, Fei Bao 4, Jinru Shia 5, Peter J Allen 1, Vinod P Balachandran 1, Jeffrey A Drebin 1, William R Jarnagin 1, Nancy E Kemeny 6, T Peter Kingham 1, Michael I D'Angelica 7
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PMID: 31617122
PMCID: PMC7061284 (available on 2021-01-01)
DOI: 10.1245/s10434-019-07934-3Free PMC article
Abstract
Background: Obesity and metabolic syndrome are associated with inflammatory hepatic parenchymal disease (HPD) and increased risk for recurrence after resection of colorectal liver metastases (CRLM). The independent impact of HPD on recurrence patterns has not been well defined.
Methods: The nonalcoholic fatty liver disease activity score (NAS) was used to quantify HPD including steatosis and fibrosis for all patients with completely resected CRLM between April 2003 and March 2007. Clinicopathologic factors, perioperative history, and outcomes were compared with the NAS. Fisher's exact test was used to examine the association between severe HPD (NAS ≥ 3) with clinical and perioperative characteristics. Kaplan-Meier methods were used to estimate recurrence-free survival (RFS). The cumulative incidences of recurrence [any intrahepatic recurrence (IHR), extrahepatic recurrence only (EHR), and death without recurrence (DWR)] were estimated using competing risks methods.
Results: Among the 357 patients included in this study, microsteatosis was noted in 124 (35%) patients, severe HPD in 31 (9%), steatohepatitis in 14 (4%), and sinusoidal injury in 36 (10%). After median follow-up of 127 months (range 4-175 months), 10-year RFS was 22% [95% confidence interval (CI) 17-27%]. Ten-year cumulative incidence for IHR, EHR, and DWR was 37%, 30%, and 12%, respectively. After controlling for confounders, NAS ≥ 3 was independently associated with higher risk of IHR [hazard ratio (HR) 1.76, 95% CI 1.07-2.90, p = 0.027] and lower risk of EHR (HR 0.18, 95% CI 0.04-0.75, p = 0.019) on multivariable analysis.
Conclusions: Severe HPD was associated with increased IHR risk and decreased EHR risk. Future investigation into whether improving HPD from reversible etiologies can reduce the risk for IHR is warranted.
Conflict of interest statement
DISCLOSURES: The authors have no conflicts of interest to report.
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7
Review
Curr Oncol Rep
. 2020 Jun 8;22(7):66. doi: 10.1007/s11912-020-00931-w.
Proteasome Inhibitor-Related Cardiotoxicity: Mechanisms, Diagnosis, and Management
Perry Wu 1, Ohad Oren 2, Morie A Gertz 2, Eric H Yang 3
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PMID: 32514632
DOI: 10.1007/s11912-020-00931-w
Abstract
Purpose of review: Multiple myeloma is the second most common hematologic malignancy in the USA, with over 32,000 new cases and nearly 13,000 deaths expected in 2019. The past few decades in myeloma research have yielded significant advances, leading to the expansion of novel anti-myeloma agents. This review describes the incidence and mechanisms of cardiotoxicity for the FDA-approved proteasome inhibitors in myeloma and proposes strategies to assess and manage resultant cardiovascular adverse events.
Recent findings: Proteasome inhibition precipitates protein aggregation and alters transcriptional activation of NF-κB targets which contributes to a pro-apoptotic signaling cascade in myeloma cells. Similar effects in cardiomyocytes and vascular smooth muscle endothelium, along with off-target downregulation of autophagy and signaling alterations of nitric oxide homeostasis, may be linked to observed cardiotoxic effects. There is preliminary evidence for cardioprotective potential for rutin, dexrazoxane, and apremilast that could have clinical applicability in the future. Of the proteasome inhibitors used in clinical practice, carfilzomib is the most strongly associated with cardiotoxicity. Patients with anticipated carfilzomib treatment should undergo assessment and optimization of baseline cardiovascular risk, with close monitoring during treatment. Previous clinical trials were not specifically designed to assess proteasome inhibitor-related cardiotoxicity, creating a need for future studies to identify and risk stratify vulnerable individuals and to develop potential cardioprotective strategies in attenuating cardiac injury.
Keywords: Bortezomib; Carfilzomib; Chemotherapy-induced cardiomyopathy.
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8
Review
Crit Rev Oncol Hematol
. 2020 May 19;152:102980. doi: 10.1016/j.critrevonc.2020.102980. Online ahead of print.
Double Immune Checkpoint Blockade in Advanced NSCLC
Annapaola Mariniello 1, Silvia Novello 2, Giorgio V Scagliotti 2, Suresh S Ramalingam 3
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PMID: 32516722
DOI: 10.1016/j.critrevonc.2020.102980
Abstract
Immunotherapy-based options for patients with advanced non-small cell lung cancer (NSCLC) are increasing at an unprecedented pace, carrying the promise to prolong survival of this deadly disease. To maximize responses and extend benefit to a larger portion of patients, immunotherapy combination strategies are currently under investigation, with chemo-immunotherapy already in use. Combinations of programmed death-1/ligand-1 (PD-1/L1) and cytotoxic T lymphocytes antigen-4 (CTLA-4) were developed with the rationale of targeting complementary pathways involved in T cell activation, and already showed to be highly active in other malignancies. Recently, the phase III Checkmate 227 trial showed that combination of nivolumab and ipilimumab provided survival benefit in untreated advanced NSCLC patients. However, accurate patients' selection and appropriate sequencing of different immunotherapy-based approaches remain unsolved. In this review, we provide an overview of the currently available evidence on double immune checkpoint inhibition (ICI) for NSCLC treatment and discuss current issues and future perspectives.
Keywords: Durvalumab; Immune checkpoint inhibitors; Ipilimumab; NSCLC; Nivolumab; Tremelimumab.
Copyright © 2020 Elsevier B.V. All rights reserved.
Conflict of interest statement
Declaration of Competing Interest None.
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9
J Neurooncol
. 2020 Jan;146(1):111-120. doi: 10.1007/s11060-019-03342-5. Epub 2019 Nov 19.
Brachytherapy With Surgical Resection as Salvage Treatment for Recurrent High-Grade Meningiomas: A Matched Cohort Study
Michael A Mooney 1 2, Wenya Linda Bi 3, Jonathan M Cantalino 4, Kyle C Wu 3, Thomas C Harris 4, Lucas L Possatti 3, Parikshit Juvekar 3, Liangge Hsu 5, Ian F Dunn 3, Ossama Al-Mefty 3, Phillip M Devlin 4
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PMID: 31745706
DOI: 10.1007/s11060-019-03342-5
Abstract
Purpose: To evaluate surgical resection with brachytherapy placement as a salvage treatment in patients with recurrent high-grade meningioma who exhausted prior external beam treatment options.
Methods: Single-center retrospective review of our institutional experience of brachytherapy implantation from 2012 to 2018. The primary outcome of the study was progression free survival (PFS). Secondary outcomes included overall survival (OS) and complications. A matched cohort of patients not treated with brachytherapy over the same time period was evaluated as a control group. All patients had received prior radiation treatment and underwent planned gross total resection (GTR) surgery.
Results: A total of 27 cases were evaluated. Compared with prior treatment, brachytherapy implantation demonstrated a statistically significant improvement in tumor control [HR 0.316 (0.101 - 0.991), p = 0.034]. PFS-6 and PFS-12 were 92.3% and 84.6%, respectively. Compared with the matched control cohort, brachytherapy treatment demonstrated improved PFS [HR 0.310 (0.103 - 0.933), p = 0.030]. Overall survival was not statistically significantly different between groups [HR 0.381 (0.073 - 1.982), p = 0.227]. Overall postoperative complications were comparable between groups, although there was a higher incidence of radiation necrosis in the brachytherapy cohort.
Conclusion: Brachytherapy with planned GTR improved PFS in recurrent high-grade meningioma patients who exhausted prior external beam radiation treatment options. Future improvement of brachytherapy dose delivery methods and techniques may continue to prolong control rates and improve outcomes for this challenging group of patients.
Keywords: Anaplastic; Atypical; Brachytherapy; Meningioma; Radiation; Recurrence.
39 references
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10
Review
Cancers (Basel)
. 2020 Jun 4;12(6):E1472. doi: 10.3390/cancers12061472.
The Expression, Functions and Mechanisms of Circular RNAs in Gynecological Cancers
Peixin Dong 1, Daozhi Xu 1, Ying Xiong 2, Junming Yue 3 4, Kei Ihira 1, Yosuke Konno 1, Hidemichi Watari 1
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PMID: 32512912
DOI: 10.3390/cancers12061472
Abstract
Circular RNAs (circRNAs) are covalently closed, endogenous non-coding RNAs and certain circRNAs are linked to human tumors. Owing to their circular form, circRNAs are protected from degradation by exonucleases, and therefore, they are more stable than linear RNAs. Many circRNAs have been shown to sponge microRNAs, interact with RNA-binding proteins, regulate gene transcription, and be translated into proteins. Mounting evidence suggests that circRNAs are dysregulated in cancer tissues and can mediate various signaling pathways, thus affecting tumorigenesis, metastasis, and remodeling of the tumor microenvironment. First, we review the characteristics, biogenesis, and biological functions of circRNAs, and describe various mechanistic models of circRNAs. Then, we provide a systematic overview of the functional roles of circRNAs in gynecological cancers. Finally, we describe the potential future applications of circRNAs as biomarkers for prognostic stratification and as therapeutic targets in gynecological cancers. Although the function of most circRNAs remains elusive, some individual circRNAs have biologically relevant functions in cervical cancer, ovarian cancer, and endometrial cancer. Certain circRNAs have the potential to serve as biomarkers and therapeutic targets in gynecological cancers.
Keywords: biomarker; cancer diagnosis; cancer treatment; circular RNA; gynecological cancer; non-coding RNA.
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11
J Geriatr Oncol
. 2020 Jun 5;S1879-4068(20)30064-3. doi: 10.1016/j.jgo.2020.05.013. Online ahead of print.
Efficacy and Safety of Frontline Regimens for Older Transplant-Ineligible Patients With Multiple Myeloma: A Systematic Review and Meta-Analysis
Smith Giri 1, Madan Raj Aryal 2, Han Yu 3, Alyssa Grimshaw 4, Ranjan Pathak 5, Scott P Huntington 5, Binod Dhakal 6
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PMID: 32513568
DOI: 10.1016/j.jgo.2020.05.013
Abstract
Introduction: Several treatment options are available for the management of older adults with newly diagnosed patients with Multiple Myeloma (MM) who are ineligible for hematopoietic cell transplantation (tiMM). We aimed to identify treatment options that provide the best balance in terms of efficacy and safety.
Methods: We searched bibliographic databases and meeting libraries for search terms reflecting newly diagnosed and older and/or transplant-ineligible patients from inception to October 21, 2018. Phase II/III randomized trials comparing at least two first line treatment regimens for newly diagnosed tiMM were included. We extracted data on efficacy (progression free survival, PFS, overall survival and overall response rate) and safety (grade ¾ toxicities) and conducted network meta-analysis using Bayesian methods and random effects models. Relative ranking of treatment regimens was assessed using Surface under the cumulative ranking (SUCRA) probabilities.
Results: We identified 27 trials involving 12,194 patients. For PFS, the four most effective regimens were: Daratumumab, Bortezomib, Melphalan and Prednisone (SUCRA 0.960) followed by Daratumumab, lenalidomide and dexamethasone (Dara_RD, SUCRA 0.847), Bortezomib, melphalan, prednisone, thalidomide maintenance with bortezomib-thalidomide (SUCRA 0.834) and Bortezomib, Lenalidomide and Dexamethasone (SUCRA 0.739). Among these four most efficacious regimens, toxicity profile was most favorable for Dara_RD (median additional AEs per patient vs dexamethasone = 0.74; 95% CrI 0.51-1.17; SUCRA 0.430).
Conclusion: Among first line tiMM regimens, increasing efficacy is associated with increased toxicity. We provide relative ranking of these regimens for both efficacy and safety. Future studies should incorporate geriatric assessments and frailty biomarkers to refine treatment decision-making for each individual patient.
Keywords: First-line therapy; Meta-analysis; Multiple myeloma; Systematic review; Transplant ineligible.
Copyright © 2020 Elsevier Inc. All rights reserved.
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12
J Oncol Pharm Pract
. 2020 Mar;26(2):279-285. doi: 10.1177/1078155219841424. Epub 2019 Apr 3.
Barriers to Receipt of Novel Oral Oncolytics: A Single-Institution Quality Improvement Investigation
Ann A Wang 1, Christopher Tapia 1, Yasin Bhanji 1, Christopher Campbell 2, Daniel Larsen 3, Derick Gross 2, Seema Ganatra 2, Melad Qodsi 2, Claudia Tellez 1 3, Shikha Jain 1 3
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PMID: 30943846
DOI: 10.1177/1078155219841424
Abstract
Introduction: Novel oral oncolytic agents have become the standard of care and first-line therapies for many malignancies. However, issues impacting access to these drugs are not well explored. As part of a quality improvement project in a large tertiary academic institution, we aim to identify potential barriers that delay treatment for patients who are prescribed novel oral oncolytics.
Methods: This was a retrospective review of adults who were newly prescribed a novel oral oncolytic for Food and Drug Administration-approved indications at a single tertiary care center. Patients were identified via electronic prescription data (e-Scribe). Demographics, insurance information, and prescription dates were extracted from the electronic medical record and pharmacy claims data. Statistical analyses were performed to determine whether time-to-receipt was associated with insurance category, pharmacy transfers, cost assistance, and drug prescribed.
Results: Of the 270 successfully filled prescriptions, the mean time-to-receipt was 7.3 ± 10.3 days (range: 0-109 days). Patients with Medicare experienced longer time-to-receipt (9.1 ± 13.1 days) compared to patients with commercial insurance (4.4 ± 3.3). Uninsured patients experienced the longest time-to-receipt (15.7 ± 7.8 days) overall. Pharmacy transfers and cost assistance programs were also significantly associated with longer time-to-receipt. Ten prescriptions remained unfilled 90 days after the study period and were considered abandoned.
Conclusion: Insurance has a significant effect on the time-to-receipt of newly prescribed novel oral oncolytics. Pharmacy transfers and applying for cost assistance are also associated with longer wait times for patients. Our retrospective analysis identifies areas of improvement for future interventions to reduce wait times for patients receiving novel oral oncolytics.
Keywords: Medicare; Oral oncolytics; barriers to care; cancer therapy; delays in care; health-care disparities; insurance status; medication costs; private insurance; quality improvement; specialty pharmacy.
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13
Review
Respirology
. 2020 Jun 9. doi: 10.1111/resp.13870. Online ahead of print.
Radiotherapy Treatment for Lung Cancer: Current Status and Future Directions
Shalini K Vinod 1 2, Eric Hau 3 4 5
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PMID: 32516852
DOI: 10.1111/resp.13870
Abstract
Radiotherapy is an important modality used for the treatment of lung cancer. Seventy-seven percent of all patients with lung cancer have an evidence-based indication for radiotherapy, although it is often underutilized. Radiotherapy can be used as curative or palliative treatment across all stages of disease. Technological advances have allowed better radiotherapy targeting of tumours and reduced incidental irradiation of surrounding normal tissues. This has expanded the indications for radiotherapy in lung cancer and improved outcomes both in terms of increasing survival and reducing toxicity. This review examines the current role of radiotherapy in lung cancer, discusses the evidence behind this and identifies future directions in the radiotherapy treatment of lung cancer.
Keywords: lung neoplasms; non-small cell carcinoma; radiotherapy; small cell carcinoma; therapy.
© 2020 Asian Pacific Society of Respirology.
65 references
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14
Clin Cancer Res
. 2020 Jun 8;clincanres.0945.2020. doi: 10.1158/1078-0432.CCR-20-0945. Online ahead of print.
Multicenter Phase 1 Trial of a DNA Vaccine Encoding the Androgen Receptor Ligand Binding Domain (pTVG-AR, MVI-118) in Patients With Metastatic Prostate Cancer
Christos E Kyriakopoulos 1, Jens Eickhoff 2, Anna C Ferrari 3, Michael T Schweizer 4, Ellen Wargowski 5, Brian M Olson 6, Douglas G McNeel 7
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PMID: 32513836
DOI: 10.1158/1078-0432.CCR-20-0945
Abstract
Purpose: Preclinical studies demonstrated that a DNA vaccine (pTVG-AR, MVI-118) encoding the androgen receptor ligand-binding domain (AR LBD) augmented antigen-specific CD8+ T cells, delayed prostate cancer progression and emergence of castration-resistant disease, and prolonged survival of tumor-bearing mice. This vaccine was evaluated in a multicenter phase 1 trial.
Experimental design: Patients with metastatic castration sensitive prostate cancer (mCSPC) who had recently begun androgen deprivation therapy were randomly assigned to receive pTVG-AR on one of two treatment schedules over one year, and with or without GM-CSF as a vaccine adjuvant. Patients were followed for 18 months. Primary objectives were safety and immune response. Secondary objectives included median time to PSA progression, and 18-month PSA-progression-free survival (PPFS).
Results: Forty patients were enrolled at three centers. Twenty-seven patients completed treatment and 18 months of follow-up. Eleven patients (28%) had a PSA progression event before the 18-month timepoint. No grade 3 or 4 adverse events were observed. Of 30 patients with samples available for immune analysis, 14 (47%) developed Th1-type immunity to the AR LBD, as determined by IFNγ and/or granzyme B ELISPOT. Persistent IFNγ immune responses were observed irrespective of GM-CSF adjuvant. Patients who developed T-cell immunity had a significantly prolonged PPFS compared to patients without immunity (HR=0.01, 95% CI: 0.0-0.21, p=0.003).
Conclusions: pTVG-AR was safe and immunologically active in patients with mCSPC. Association between immunity and PPFS suggests that treatment may delay the time to castration resistance, consistent with preclinical findings, and will be prospectively evaluated in future trials.
Copyright ©2020, American Association for Cancer Research.
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15
Review
Semin Oncol
. 2020 May 29;S0093-7754(20)30042-7. doi: 10.1053/j.seminoncol.2020.05.003. Online ahead of print.
Novel Radiation Therapy Approaches for Breast Cancer Treatment
Chirag Shah 1, Kristine Bauer-Nilsen 2, Ryan Hazard McNulty 2, Frank Vicini 3
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PMID: 32513420
DOI: 10.1053/j.seminoncol.2020.05.003
Abstract
The role of radiation therapy in the management of breast cancer continues to evolve. For patients with early stage breast cancer, hypofractionated whole breast irradiation following breast conserving surgery now represents the standard of care based on randomized data with long-term efficacy and toxicity outcomes. Partial breast irradiation has been found, in several randomized trials, to be effective and appropriate in selected patients with the potential to reduce toxicities as compared to whole breast irradiation. The study of tumor biology and genetics and its role in radiation therapy decision making continues to grow and the advances may help identify patients where radiation therapy can be safely omitted, with future studies looking at de-intensification approaches. Recent randomized data has demonstrated a growing role for regional nodal irradiation in patients with more advanced disease, with future studies looking to identify whether nodal radiation is indicated following neoadjuvant chemotherapy or with certain favorable tumor biologies. While postmastectomy radiation therapy represents a standard approach for patients with locally advanced breast cancer, new data supports the role of hypofractionated regimens as well as its use in patients previously considered lower risk with unfavorable tumor biology. Oligometastatic disease represents a new area of study in breast cancer with prospective trials underway and current data supporting consideration of techniques such as stereotactic body radiation therapy in appropriately selected patients.
Keywords: Breast cancer; Intraoperative radiation; Partial breast irradiation; Radiation therapy; Whole breast irradiation.
Copyright © 2020 Elsevier Inc. All rights reserved.
Conflict of interest statement
Conflict of interest Chirag Shah- Consultant, Impedimed; Travel/Grants, Varian Medical Systems; Grant- Vision RT; Grant- PreludeDx; Kristine Bauer-Nilsen- None; Ryan Hard- None; Frank Vicini- Chief medical officer, Impedimed.
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16
Radiat Oncol
. 2020 Jun 8;15(1):147. doi: 10.1186/s13014-020-01587-3.
Overlapping Volumes in Re-Irradiation for Head and Neck Cancer - An Important Factor for Patient Selection
Anna Embring 1 2, Eva Onjukka 3 4, Claes Mercke 5 3, Ingmar Lax 4, Anders Berglund 6, Sara Bornedal 4, Berit Wennberg 4, Signe Friesland 5 3
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PMID: 32513217
DOI: 10.1186/s13014-020-01587-3
Abstract
Background: There is a lack of consensus concerning the definition of re-irradiation and re-irradiation volumes in head and neck cancer (HNC). The aim of the present study is to introduce a more strict definition of the re-irradiated volume that might better predict the risk of serious side-effects from treatment.
Methods: Fifty-four consecutive patients re-irradiated for HNC cancer were retrospectively analysed. CT images were deformably registered and the dose distributions accumulated after conversion to EQD2. Patients with a cumulative dose of ≥100 Gy in the overlapping volume (V100) were included in the study. Survival data and radiation-related acute and late toxicities were recorded.
Results: The overall survival of all included patients at 2 and 5 years was 42.6 and 27.3% respectively and the progression free survival at 2 and 5 years was 32.5 and 28.5% respectively. The overall rate of any event of severe (grade ≥ 3) acute and late toxicity was 26 and 51%, respectively. We found that severe acute toxicity was more common in patients who had a larger overlapping volume (V100 > mean) where 43% of the patients experienced grade ≥ 3 acute toxicity, compared to the patients with smaller overlapping volumes (V100 < mean) where only 11% had severe toxicity (p = 0.02). The seemingly high rates of late toxicity in the present study could be due to the use of a more strict definition of re-irradiation. In previous studies also patients with low dose overlap are included and our results imply that there is a risk that previous studies might have overestimated the risk-benefit ratio in re-irradiation of HNC.
Conclusions: Our study describes the outcome of a patient material where a more strict definition of the re-irradiated volume is used. With this definition, which could better describe the volume of highest risk for serious complications, we found that larger such overlapping volumes result in an increase in severe acute side-effects. A clear definition of re-irradiation and re-irradiation volumes is of utmost importance for future studies of HNC to make results from different studies comparable.
Keywords: Cumulative dose; HNSCC; Head and neck cancer; Overlap; Re-irradiation; Re-irradiation volume.
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17
Tumori
. 2020 Jun 9;300891620929425. doi: 10.1177/0300891620929425. Online ahead of print.
Dose Prescription in SBRT for Early-Stage Non-Small Cell Lung Cancer: Are We All Speaking the Same Language?
Anna Merlotti 1, Pierluigi Bonomo 2, Riccardo Ragona 3, Marco Trovò 4, Filippo Alongi 5, Rosario Mazzola 5, Riccardo Vigna Taglianti 1, Luca Gianello 1, Alessia Reali 1, Fabrizio Bergesio 6, Francesco Lucio 6, Alberto Boriano 6, Adriano De Maggi 6, Elvio Russi 1
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PMID: 32515301
DOI: 10.1177/0300891620929425
Abstract
Introduction: Stereotactic body radiation therapy is increasingly used in the treatment of early-stage lung cancers. Guidelines provide indications regarding the constraints to the organs at risk (OARs) and the minimum coverage of the planning target volume but do not suggest optimal dose distribution. Data on dose distribution from the different published series are not comparable due to different prescription modalities and reported dose parameters.
Methods: We conducted a review of the published data on dose prescription, focusing on the role of homogeneity on local tumor control, and present suggestions on how to specify and report the prescriptions to permit comparisons between studies or between cases from different centers.
Conclusions: To identify the dose-prescription modality that better correlates with oncologic outcomes, future studies should guarantee a close uniformity of dose distribution between cases and complete dose parameters reporting for treatment volumes and OARs.
Keywords: dose; lung cancer; prescription; stereotactic ablative radiotherapy; stereotactic body radiation therapy.
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18
J Clin Med
. 2020 Jun 4;9(6):E1742. doi: 10.3390/jcm9061742.
Pre-Operative Combination of Normal BMI With Elevated YKL-40 and Leptin but Lower Adiponectin Level Is Linked to a Higher Risk of Breast Cancer Relapse: A Report of Four-Year Follow-Up Study
Kornel Bielawski 1, Piotr Rhone 2, Marek Bulsa 3, Barbara Ruszkowska-Ciastek 1
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PMID: 32512860
DOI: 10.3390/jcm9061742
Abstract
Adipokines are powerful agents involved in the development of obesity-dependent cancers. This prospective study aimed to investigate the association between pre-treatment body mass index (BMI) and serum YKL-40, leptin, and adiponectin concentrations as well as the plasma activity of tissue factor (TF) and the future prognosis of early, non-metastatic breast cancer (BrC) subjects. The serum levels of YKL-40, leptin, and adiponectin as well as plasma TF activity, anthropometric parameters, and clinicopathological parameters were analysed in 81 treatment-naïve females with invasive BrC. The predictive value of YKL-40, BMI, leptin, adiponectin, and TF was determined with a 95% confidence interval (CI). Kaplan-Meier plots and log-rank and F Cox tests were used to determine the clinical outcomes of progression-free survival (PFS). The median follow-up duration was 44 months with complete follow-up for the first event. Follow-up revealed a significantly higher incidence of disease relapse in BrC patients with a high baseline concentration of YKL-40 (22.22%) and TF activity (21.43%). Body mass index was an independent predictor of survival, with women who were overweight/obese being less prone to relapse (hazard ratio (HR): 0.75; 95% CI: 0.59 to 0.95). The recurrence rates for normal-weight BrC cases was 21.05% versus 7.14% for their overweight counterparts. The receiver operating characteristic analysis showed the strong ability of the analysed biomarkers to predict disease progression, with an area under the receiver operating characteristics (ROC) curve of 0.84 (95% CI, 0.823 to 0.931). In a prospective cohort of invasive BrC patients, overweight/obesity was associated with improved future outcomes. The combination of a normal BMI with high leptin and low adiponectin levels and high TF activity was associated with an increased risk of recurrence and decreased survival.
Keywords: adipokines; breast cancer; disease recurrence; inflammation.
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19
Elife
. 2020 Jun 9;9:e53367. doi: 10.7554/eLife.53367.
Analysis of Pulsed Cisplatin Signalling Dynamics Identifies Effectors of Resistance in Lung Adenocarcinoma
Jordan F Hastings # 1, Alvaro Gonzalez Rajal # 1, Sharissa L Latham 1 2, Jeremy Zr Han 1, Rachael A McCloy 1, Yolande Ei O'Donnell 1, Monica Phimmachanh 1, Alexander D Murphy 3, Adnan Nagrial 3, Dariush Daneshvar 3, Venessa Chin 1 2 4, D Neil Watkins 5 6 7 8, Andrew Burgess 9 10, David R Croucher 1 2 11
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PMID: 32513387
DOI: 10.7554/eLife.53367
Abstract
The identification of clinically viable strategies for overcoming resistance to platinum chemotherapy in lung adenocarcinoma has previously been hampered by inappropriately tailored in vitro assays of drug response. Therefore, using a pulse model that closely mimics the in vivo pharmacokinetics of platinum therapy, we profiled cisplatin-induced signalling, DNA-damage and apoptotic responses across a panel of human lung adenocarcinoma cell lines. By coupling this data to real-time, single-cell imaging of cell cycle and apoptosis we provide a fine-grained stratification of response, where a P70S6K-mediated signalling axis promotes resistance on a TP53 wildtype or null background, but not a mutant TP53 background. This finding highlights the value of in vitro models that match the physiological pharmacokinetics of drug exposure. Furthermore, it also demonstrates the importance of a mechanistic understanding of the interplay between somatic mutations and the signalling networks that govern drug response for the implementation of any consistently effective, patient-specific therapy.
Keywords: P70S6K; cancer biology; chemoresistance; human; lung adenocarcinoma; p53; platinum chemotherapy; signalling dynamics.
Plain Language Summary
Lung adenocarcinoma is the most common type of lung cancer, and it emerges because of a variety of harmful genetic changes, or mutations. Two lung cancer patients – or indeed, two different sets of cancerous cells within a patient – may therefore carry different damaging mutations. A group of drugs called platinum-based chemotherapies are currently the most effective way to treat lung adenocarcinoma. Yet, only 30% of patients actually respond to the therapy. Many studies conducted in laboratory settings have tried to understand why most cases are resistant to treatment, with limited success. Here, Hastings, Gonzalez-Rajal et al. propose that previous research has been inconclusive because studies done in the laboratory do not reflect how the treatment is actually administered. In patients, platinum-based drugs are cleared from the body within a few hours, but during experiments, the treatment is continually administered to cells growing in a dish. Hastings, Gonzalez-Rajal et al. therefore developed a laboratory method that mimics the way cells are exposed to platinum-based chemotherapy in the body. These experiments showed that the lung adenocarcinoma cells which resisted treatment also carried high levels of a protein known as P70S6K. Pairing platinum-based chemotherapy with a drug that blocks the activity of P70S6K killed these resistant cells. This combination also treated human lung adenocarcinoma tumours growing under the skin of mice. However, it was ineffective on cancerous cells that carry a mutation in a protein called p53, which is often defective in cancers. Overall, this work demonstrates the need to refine how drugs are tested in the laboratory to better reflect real-life conditions. It also underlines the importance of personalizing drug combinations to the genetic background of each tumour, a concept that will be vital to consider in future clinical trials.
© 2020, Hastings et al.
Conflict of interest statement
JH, AG, SL, JH, RM, YO, MP, AM, AN, DD, VC, DW, AB, DC No competing interests declared
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20
Br J Radiol
. 2020 Jun 9;20200116. doi: 10.1259/bjr.20200116. Online ahead of print.
Staging of Bladder Cancer With Multiparametric MRI
Hiroshi Juri 1, Yoshifumi Narumi 2, Valeria Panebianco 3, Keigo Osuga 1
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PMID: 32516554
DOI: 10.1259/bjr.20200116
Abstract
The distinction of non-muscle-invasive bladder cancer and muscle-invasive bladder cancer is important for the selection of the optimal treatment. Multiparametric MRI (mp-MRI) has been an useful modality for the T staging of bladder cancer, and a systematic evaluation of mp-MRI is needed. The Vesical Imaging Reporting and Data System was designed to standardize the scanning and reporting criteria based on mp-MRI for clinical and research applications. This review briefly describes the method, interpretation, and timing of mp-MRI examinations in the clinical settings. Validation studies of Vesical Imaging Reporting and Data System and future perspectives are also considered.
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21
J Neurooncol
. 2020 Jan;146(1):55-62. doi: 10.1007/s11060-019-03334-5. Epub 2019 Nov 7.
Weak MGMT Gene Promoter Methylation Confers a Clinically Significant Survival Benefit in Patients With Newly Diagnosed Glioblastoma: A Retrospective Cohort Study
H Pinson 1, G Hallaert 2, J Van der Meulen 3, F Dedeurwaerdere 4, D Vanhauwaert 5, C Van den Broecke 6 7, J Van Dorpe 6, D Van Roost 2, J P Kalala 2, T Boterberg 8
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PMID: 31701343
DOI: 10.1007/s11060-019-03334-5
Abstract
Introduction: Quantitative methylation specific PCR (qMSP) is a frequently used technique to assess MGMT gene promoter methylation in glioblastoma patients. The optimal technical cut-off value to distinguish methylated from unmethylated samples is nevertheless still undetermined. In literature, a "grey zone" of diagnostic uncertainty has been described.
Methods: We performed a retrospective analysis of newly diagnosed glioblastoma patients treated according to the Stupp protocol. Epidemiological data were gathered from the individual patient files. MGMT gene promoter methylation status was determined on stored tumour samples using qMSP. A strong, weak or absent promoter methylation was determined based on Cq values (quantification value) of the MGMT and ACTB primers as well as a positive control sample.
Results: In total, 181 patient files were reviewed and included for statistical analysis. MGMT promoter hypermethylation was detected in 38.7% of glioblastoma patients. The median overall survival of unmethylated and strongly methylated patients was 10.1 months and 19.7 months respectively. Furthermore, 11% of the total patient cohort had a weak MGMT gene promoter methylation. The median OS in this subgroup was 15.4 months, significantly better compared to the unmethylated cohort (P < 0.001). Multivariate Cox regression analysis showed weak MGMT promoter methylation as an independent prognostic parameter for overall survival.
Conclusion: Glioblastoma patients with weak promoter methylation show a statistically significant longer overall survival when compared to clearly unmethylated patients. Patients with grey zone qMSP test results should receive additional molecular analysis in future to further direct individual therapy strategies.
Keywords: Glioblastoma; MGMT gene methylation; Prognosis; qMSP.
24 references
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22
J Neurooncol
. 2020 Jan;146(1):63-69. doi: 10.1007/s11060-019-03335-4. Epub 2019 Nov 11.
Delay in Diagnosing Patients With Right-Sided Glioblastoma Induced by Hemispheric-Specific Clinical Presentation
Claudia Baumann 1 2, Julia Tichy 3 4 5 6, Jan Hendrik Schaefer 7, Joachim P Steinbach 3 4 5 6, Michel Mittelbronn 8 9 10 11 12, Marlies Wagner 13, Christian Foerch 7
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PMID: 31713017
DOI: 10.1007/s11060-019-03335-4
Abstract
Purpose: Cognitive functions are differentially represented in brain hemispheres. Aphasia is an "easy to recognize" symptom of diseases affecting the left side. In contrast, lesions in the right hemisphere cause subtle neuropsychological deficits such as neglect and anosognosia. We evaluated whether right-sided malignant brain tumors are on average larger at the time of first diagnosis as compared to left-sided tumors, and extrapolated the delay in diagnosing right-sided tumors compared to the left side.
Methods: All first-ever diagnosed glioblastoma (GBM) patients between 2005 and 2012 were identified using our hospital-based prospective research registry. Baseline data, information on initial clinical presentation and imaging findings (including tumor volume) were collected. Extrapolation of time since tumor initiation was based on an established gompertzian growth model.
Results: We included 173 patients. Mean age of the study population was 58 ± 13 years. Tumors located in the right hemisphere (n = 96) were larger as compared to tumors located in the left hemisphere (n = 77) (median 36.4 mL [interquartile range 13.0-56.0; minimum 0.2, maximum 140.0] vs. 17.2 mL [7.7-45.1 mL; 0.4, 105.2]; p = 0.011). Right-sided tumors grew longer than left-sided tumors (378 ± 95 days vs. 341 ± 74 days; p = 0.006). Initial neuropsychological symptoms differed depending on the affected hemisphere.
Conclusion: Right-hemispheric symptoms appear to be less clinically conspicuous resulting in a delayed diagnosis of GBM, which might be improved by raising awareness for the corresponding neuropsychological deficits. Whether our findings have prognostic implications needs to be evaluated in future studies.
Keywords: Brain tumor; Growth; Neuropsychology; Side.
12 references
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23
Future Oncol
. 2020 Jun 9. doi: 10.2217/fon-2020-0315. Online ahead of print.
Incidence of Second Primary Malignancies in Metastatic Castration-Resistant Prostate Cancer: Results From Observational Studies in Three Countries
Zdravko P Vassilev 1, Montse Soriano Gabarró 2, James A Kaye 3, Catherine W Saltus 3, Oliver Riedel 4, Oliver Scholle 4, Juha Mehtälä 5, Pasi Korhonen 5, Edeltraut Garbe 4, Jihong Zong 1
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PMID: 32515225
DOI: 10.2217/fon-2020-0315
Abstract
Aim: This reports some of the first incidence rate (IR) estimates of second primary malignancies (SPMs) in men with metastatic castration-resistant prostate cancer (mCRPC) in three countries. Patients & methods: Claims data from the German Pharmacoepidemiological Research Database; registry data from the Prostate Cancer Data Base Sweden; and combined registry-claims data from the US Surveillance, Epidemiology and End Results-Medicare database were analyzed to obtain overall survival and incidence of SPMs in men with mCRPC. Results: SPMs occurred in 308 German (N = 2360), 273 Swedish (N = 2849) and 172 US (N = 2234) men with mCRPC. IRs of SPMs were 79.0 (95% CI: 70.4-88.4), 101.7 (95% CI: 90.3-114.5) and 59 (95% CI: 50-68) per 1000 person-years in German, Swedish and US cohorts, respectively. Conclusion: These studies report some of the first IR estimates of SPMs in men with mCRPC, providing a historical risk estimate of SPM in this patient population.
Keywords: healthcare data; prognosis; prostate cancer; risk estimate; second primary malignancies.
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24
Cardiovasc Intervent Radiol
. 2020 Jun 8. doi: 10.1007/s00270-020-02537-y. Online ahead of print.
90 Y-Radioembolization After Failed Portal Vein Embolization for Colorectal Liver Metastases: A Case Report
I Kurilova 1 2, V Pompa 3, R Guerrero 4, Mesa A Tapias 5, Mizrrahi D Calatayud 6, C Fondevila 7, J A González 8, J Duch 9, F M Gomez 10 11
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PMID: 32514612
DOI: 10.1007/s00270-020-02537-y
Abstract
The main limiting factor for liver resection is insufficient future liver remnant (FLR). Portal vein embolization (PVE) is a standard of care treatment to induce FLR hypertrophy, but it is not always efficient. Radioembolization (RE) has a potential to induce liver hypertrophy for PVE-refractory patients. However, this was reported only for the patients with hepatocellular carcinoma. We described two cases of lobar RE after PVE failure for the patients with colorectal liver metastases. This enabled to reach sufficient FLR, provide good local disease control and bridge the patients to extended hepatectomy.
Keywords: Ablation; Colorectal cancer; Liver metastases; Radioembolization.
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Mol Cancer Ther
. 2019 Oct;18(10):1852-1862. doi: 10.1158/1535-7163.MCT-18-0965. Epub 2019 Jul 18.
Genomic Profiling of Blood-Derived Circulating Tumor DNA From Patients With Colorectal Cancer: Implications for Response and Resistance to Targeted Therapeutics
In Sil Choi # 1 2, Shumei Kato # 3, Paul T Fanta 1, Lawrence Leichman 1, Ryosuke Okamura 1, Victoria M Raymond 4, Richard B Lanman 4, Scott M Lippman 1, Razelle Kurzrock 1
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PMID: 31320401
DOI: 10.1158/1535-7163.MCT-18-0965Free article
Abstract
Molecular profiling of circulating tumor DNA (ctDNA) is a promising noninvasive tool. Here, next-generation sequencing (NGS) of blood-derived ctDNA was performed in patients with advanced colorectal cancer. We investigated ctDNA-derived genomic alterations, including potential actionability, concordance with tissue NGS, and serial dynamics in 78 patients with colorectal cancer using a clinical-grade NGS assay that detects single nucleotide variants (54-73 genes) and selected copy-number variants, fusions, and indels. Overall, 63 patients [80.8% (63/78)] harbored ctDNA alterations; 59 [75.6% (59/78)], ≥1 characterized alteration (variants of unknown significance excluded). All 59 patients had actionable alterations potentially targetable with FDA-approved drugs [on-label and/or off-label (N = 54) or with experimental drugs in clinical trials (additional five patients); University of California San Diego Molecular Tumor Board assessment]: 45, by OncoKB (http://oncokb.org/#/). The tissue and blood concordance rates for common specific alterations ranged from 62.3% to 86.9% (median = 5 months between tests). In serial samples from patients on anti-EGFR therapy, multiple emerging alterations in genes known to be involved in therapeutic resistance, including KRAS, NRAS, BRAF, EGFR, ERBB2, and MET were detected. In conclusion, over 80% of patients with stage IV colorectal cancer had detectable ctDNA, and the majority had potentially actionable alterations. Concordance between tissue and blood was between 62% and 87%, despite a median of 5 months between tests. Resistance alterations emerged on anti-EGFR therapy. Therefore, biopsy-free, noninvasive ctDNA analysis provides data relevant to the clinical setting. Importantly, sequential ctDNA analysis detects patterns of emerging resistance allowing for precision planning of future therapy.
©2019 American Association for Cancer Research.
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2
Multicenter Study
Transfusion
. 2019 Oct;59(10):3113-3119. doi: 10.1111/trf.15495. Epub 2019 Sep 3.
Evaluating Emergency-Release Blood Transfusion of Newborn Infants at the Intermountain Healthcare Hospitals
Timothy M Bahr 1, Tara L DuPont 1, Thomas R Christensen 2, Terry Rees 3, Elizabeth A O'Brien 1 4, Sarah J Ilstrup 3, Robert D Christensen 1 4 5
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PMID: 31479169
DOI: 10.1111/trf.15495
Abstract
Background: An emergency-release blood transfusion (ERBT) protocol (uncrossmatched type O-negative red blood cells, AB plasma, AB platelets) is critical for neonatology practice. However, few reports of emergency transfusions are available. We conducted an ERBT quality improvement project as a basis for progress.
Study design and methods: For each ERBT in the past 8 years, we logged indications, products, locations and timing of the transfusions, and outcomes.
Results: One hundred forty-nine ERBTs were administered; 42% involved a single blood product, and 58% involved two or more. The incidence was 6.25 ERBT per 10,000 live births, with a higher rate (9.52 ERBT/10,000) in hospitals with a Level 3 neonatal intensive care unit (NICU) (p < 0.001). Seventy percent of ERBTs were administered in a NICU and 30% in a delivery room, operating room, or emergency department. Indications were abruption/previa (32.2%), congenital anemia (i.e., fetomaternal hemorrhage; 15.4%), umbilical cord accident (i.e., velamentous insertion; 15.0%), and bleeding/coagulopathy (12.8%). Fifty-eight percent of those with hemorrhage before birth did not have a hemoglobin value reported on the umbilical cord gas; thus, anemia was not recognized initially. None of the 149 ERBTs were administered using a blood warmer. The mortality rate of recipients was 35%.
Conclusion: Based on our findings, we recommend including a hemoglobin value with every cord blood gas after emergency delivery to rapidly identify fetal anemia. We also discuss two potential improvements for future testing: 1) the use of a warming device for massive transfusion of neonates and 2) the use of low-titer group O cold-stored whole blood for massive hemorrhage in neonates.
© 2019 AABB.
31 references
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3
Mol Cancer Ther
. 2019 Oct;18(10):1775-1786. doi: 10.1158/1535-7163.MCT-18-0864. Epub 2019 Jul 29.
Tyrosine Threonine Kinase Inhibition Eliminates Lung Cancers by Augmenting Apoptosis and Polyploidy
Lin Zheng # 1, Zibo Chen # 1 2, Masanori Kawakami 1 2, Yulong Chen 1, Jason Roszik 3 4, Lisa Maria Mustachio 1, Jonathan M Kurie 1, Pamela Villalobos 5, Wei Lu 5, Carmen Behrens 5, Barbara Mino 5, Luisa M Solis 5, Jennifer Silvester 6, Kelsie L Thu 6, David W Cescon 6, Jaime Rodriguez-Canales 5, Ignacio I Wistuba 5, Tak W Mak 6, Xi Liu 1 2, Ethan Dmitrovsky 7 2 8
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PMID: 31358662
DOI: 10.1158/1535-7163.MCT-18-0864
Abstract
The spindle assembly checkpoint maintains genomic integrity. A key component is tyrosine threonine kinase (TTK, also known as Mps1). TTK antagonism is hypothesized to cause genomic instability and cell death. Interrogating The Cancer Genome Atlas revealed high TTK expression in lung adenocarcinomas and squamous cell cancers versus the normal lung (P < 0.001). This correlated with an unfavorable prognosis in examined lung adenocarcinoma cases (P = 0.007). TTK expression profiles in lung tumors were independently assessed by RNA in situ hybridization. CFI-402257 is a highly selective TTK inhibitor. Its potent antineoplastic effects are reported here against a panel of well-characterized murine and human lung cancer cell lines. Significant antitumorigenic activity followed independent treatments of athymic mice bearing human lung cancer xenografts (6.5 mg/kg, P < 0.05; 8.5 mg/kg, P < 0.01) and immunocompetent mice with syngeneic lung cancers (P < 0.001). CFI-402257 antineoplastic mechanisms were explored. CFI-402257 triggered aneuploidy and apoptotic death of lung cancer cells without changing centrosome number. Reverse phase protein arrays (RPPA) of vehicle versus CFI-402257-treated lung cancers were examined using more than 300 critical growth-regulatory proteins. RPPA bioinformatic analyses discovered CFI-402257 enhanced MAPK signaling, implicating MAPK antagonism in augmenting TTK inhibitory effects. This was independently confirmed using genetic and pharmacologic repression of MAPK that promoted CFI-402257 anticancer actions. TTK antagonism exerted marked antineoplastic effects against lung cancers and MAPK inhibition cooperated. Future work should determine whether CFI-402257 treatment alone or with a MAPK inhibitor is active in the lung cancer clinic.
©2019 American Association for Cancer Research.
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4
Meta-Analysis
Ann Oncol
. 2019 Aug 1;30(8):1370-1380. doi: 10.1093/annonc/mdz176.
Meta-analysis in Metastatic Uveal Melanoma to Determine Progression Free and Overall Survival Benchmarks: An International Rare Cancers Initiative (IRCI) Ocular Melanoma Study
L Khoja 1, E G Atenafu 2, S Suciu 3, S Leyvraz 4, T Sato 5, E Marshall 6, U Keilholz 7, L Zimmer 8, S P Patel 9, S Piperno-Neumann 10, J Piulats 11, T T Kivelä 12, C Pfoehler 13, S Bhatia 14, P Huppert 15, L B J Van Iersel 16, I J M De Vries 17, N Penel 18, T Vogl 19, T Cheng 20, G Fiorentini 21, F Mouriaux 22, A Tarhini 23, P M Patel 24, R Carvajal 25, A M Joshua 26
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PMID: 31150059
DOI: 10.1093/annonc/mdz176
Abstract
Background: Despite the completion of numerous phase II studies, a standard of care treatment has yet to be defined for metastatic uveal melanoma (mUM). To determine benchmarks of progression free survival (PFS) and overall survival (OS), we carried out a meta-analysis using individual patient level trial data.
Methods: Individual patient variables and survival outcomes were requested from 29 trials published from 2000 to 2016. Univariable and multivariable analysis were carried out for prognostic factors. The variability between trial arms and between therapeutic agents on PFS and OS was investigated.
Results: OS data were available for 912 patients. The median PFS was 3.3 months (95% CI 2.9-3.6) and 6-month PFS rate was 27% (95% CI 24-30). Univariable analysis showed male sex, elevated (i.e. > versus ≤ upper limit of normal) lactate dehydrogenase (LDH), elevated alkaline phosphatase (ALP) and diameter of the largest liver metastasis (≥3 cm versus <3 cm) to be substantially associated with shorter PFS. Multivariable analysis showed male sex, elevated LDH and elevated ALP were substantially associated with shorter PFS. The most substantial factors associated with 6-month PFS rate, on both univariable and multivariable analysis were elevated LDH and ALP. The median OS was 10.2 months (95% CI 9.5-11.0) and 1 year OS was 43% (95% CI 40-47). The most substantial prognostic factors for shorter OS by univariable and multivariable analysis were elevated LDH and elevated ALP. Patients treated with liver directed treatments had statistically significant longer PFS and OS.
Conclusion: Benchmarks of 6-month PFS and 1-year OS rates were determined accounting for prognostic factors. These may be used to facilitate future trial design and stratification in mUM.
Keywords: meta-analysis; survival benchmarks; trial design; uveal melanoma.
© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Cited by 5 articles
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5
Clinical Trial
Eur J Cancer
. 2019 Oct;120:107-113. doi: 10.1016/j.ejca.2019.07.023. Epub 2019 Sep 9.
Can Radiomics Help to Predict Skeletal Muscle Response to Chemotherapy in Stage IV Non-Small Cell Lung Cancer?
E E C de Jong 1, K J C Sanders 2, T M Deist 1, W van Elmpt 3, A Jochems 1, J E van Timmeren 1, R T H Leijenaar 1, J H R J Degens 2, A M W J Schols 2, A-M C Dingemans 4, P Lambin 5
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PMID: 31514107
DOI: 10.1016/j.ejca.2019.07.023Free article
Abstract
Background: Muscle depletion negatively impacts treatment efficacy and survival rates in cancer. Prevention and timely treatment of muscle loss require prediction of patients at risk. We aimed to investigate the potential of skeletal muscle radiomic features to predict future muscle loss.
Methods: A total of 116 patients with stage IV non-small cell lung cancer included in a randomised controlled trial (NCT01171170) studying the effect of nitroglycerin added to paclitaxel-carboplatin-bevacizumab were enrolled. In this post hoc analysis, muscle cross-sectional area and radiomic features were extracted from computed tomography images obtained before initiation of chemotherapy and shortly after administration of the second cycle. For internal cross-validation, the cohort was randomly split in a training set and validation set 100 times. We used least absolute shrinkage and selection operator method to select features that were most significantly associated with muscle loss and an area under the curve (AUC) for model performance.
Results: Sixty-nine patients (59%) exhibited loss of skeletal muscle. One hundred ninety-three features were used to construct a prediction model for muscle loss. The average AUC was 0.49 (95% confidence interval [CI]: 0.36, 0.62). Differences in intensity and texture radiomic features over time were seen between patients with and without muscle loss.
Conclusions: The present study shows that skeletal muscle radiomics did not predict future muscle loss during chemotherapy in non-small cell lung cancer. Differences in radiomic features over time might reflect myosteatosis. Future imaging analysis combined with muscle tissue analysis in patients and in experimental models is needed to unravel the biological processes linked to the radiomic features.
Keywords: Cachexia; Computed tomography; Muscle; Non-small cell lung cancer; Radiomics.
Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.
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6
Ann Surg Oncol
. 2020 Jan;27(1):188-195. doi: 10.1245/s10434-019-07934-3. Epub 2019 Oct 15.
Prediction of Recurrence Patterns From Hepatic Parenchymal Disease After Resection of Colorectal Liver Metastases
Raja R Narayan 1 2, Jennifer W Harris 1, Joanne F Chou 3, Mithat Gönen 3, Fei Bao 4, Jinru Shia 5, Peter J Allen 1, Vinod P Balachandran 1, Jeffrey A Drebin 1, William R Jarnagin 1, Nancy E Kemeny 6, T Peter Kingham 1, Michael I D'Angelica 7
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PMID: 31617122
PMCID: PMC7061284 (available on 2021-01-01)
DOI: 10.1245/s10434-019-07934-3Free PMC article
Abstract
Background: Obesity and metabolic syndrome are associated with inflammatory hepatic parenchymal disease (HPD) and increased risk for recurrence after resection of colorectal liver metastases (CRLM). The independent impact of HPD on recurrence patterns has not been well defined.
Methods: The nonalcoholic fatty liver disease activity score (NAS) was used to quantify HPD including steatosis and fibrosis for all patients with completely resected CRLM between April 2003 and March 2007. Clinicopathologic factors, perioperative history, and outcomes were compared with the NAS. Fisher's exact test was used to examine the association between severe HPD (NAS ≥ 3) with clinical and perioperative characteristics. Kaplan-Meier methods were used to estimate recurrence-free survival (RFS). The cumulative incidences of recurrence [any intrahepatic recurrence (IHR), extrahepatic recurrence only (EHR), and death without recurrence (DWR)] were estimated using competing risks methods.
Results: Among the 357 patients included in this study, microsteatosis was noted in 124 (35%) patients, severe HPD in 31 (9%), steatohepatitis in 14 (4%), and sinusoidal injury in 36 (10%). After median follow-up of 127 months (range 4-175 months), 10-year RFS was 22% [95% confidence interval (CI) 17-27%]. Ten-year cumulative incidence for IHR, EHR, and DWR was 37%, 30%, and 12%, respectively. After controlling for confounders, NAS ≥ 3 was independently associated with higher risk of IHR [hazard ratio (HR) 1.76, 95% CI 1.07-2.90, p = 0.027] and lower risk of EHR (HR 0.18, 95% CI 0.04-0.75, p = 0.019) on multivariable analysis.
Conclusions: Severe HPD was associated with increased IHR risk and decreased EHR risk. Future investigation into whether improving HPD from reversible etiologies can reduce the risk for IHR is warranted.
Conflict of interest statement
DISCLOSURES: The authors have no conflicts of interest to report.
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7
Review
Curr Oncol Rep
. 2020 Jun 8;22(7):66. doi: 10.1007/s11912-020-00931-w.
Proteasome Inhibitor-Related Cardiotoxicity: Mechanisms, Diagnosis, and Management
Perry Wu 1, Ohad Oren 2, Morie A Gertz 2, Eric H Yang 3
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PMID: 32514632
DOI: 10.1007/s11912-020-00931-w
Abstract
Purpose of review: Multiple myeloma is the second most common hematologic malignancy in the USA, with over 32,000 new cases and nearly 13,000 deaths expected in 2019. The past few decades in myeloma research have yielded significant advances, leading to the expansion of novel anti-myeloma agents. This review describes the incidence and mechanisms of cardiotoxicity for the FDA-approved proteasome inhibitors in myeloma and proposes strategies to assess and manage resultant cardiovascular adverse events.
Recent findings: Proteasome inhibition precipitates protein aggregation and alters transcriptional activation of NF-κB targets which contributes to a pro-apoptotic signaling cascade in myeloma cells. Similar effects in cardiomyocytes and vascular smooth muscle endothelium, along with off-target downregulation of autophagy and signaling alterations of nitric oxide homeostasis, may be linked to observed cardiotoxic effects. There is preliminary evidence for cardioprotective potential for rutin, dexrazoxane, and apremilast that could have clinical applicability in the future. Of the proteasome inhibitors used in clinical practice, carfilzomib is the most strongly associated with cardiotoxicity. Patients with anticipated carfilzomib treatment should undergo assessment and optimization of baseline cardiovascular risk, with close monitoring during treatment. Previous clinical trials were not specifically designed to assess proteasome inhibitor-related cardiotoxicity, creating a need for future studies to identify and risk stratify vulnerable individuals and to develop potential cardioprotective strategies in attenuating cardiac injury.
Keywords: Bortezomib; Carfilzomib; Chemotherapy-induced cardiomyopathy.
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8
Review
Crit Rev Oncol Hematol
. 2020 May 19;152:102980. doi: 10.1016/j.critrevonc.2020.102980. Online ahead of print.
Double Immune Checkpoint Blockade in Advanced NSCLC
Annapaola Mariniello 1, Silvia Novello 2, Giorgio V Scagliotti 2, Suresh S Ramalingam 3
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PMID: 32516722
DOI: 10.1016/j.critrevonc.2020.102980
Abstract
Immunotherapy-based options for patients with advanced non-small cell lung cancer (NSCLC) are increasing at an unprecedented pace, carrying the promise to prolong survival of this deadly disease. To maximize responses and extend benefit to a larger portion of patients, immunotherapy combination strategies are currently under investigation, with chemo-immunotherapy already in use. Combinations of programmed death-1/ligand-1 (PD-1/L1) and cytotoxic T lymphocytes antigen-4 (CTLA-4) were developed with the rationale of targeting complementary pathways involved in T cell activation, and already showed to be highly active in other malignancies. Recently, the phase III Checkmate 227 trial showed that combination of nivolumab and ipilimumab provided survival benefit in untreated advanced NSCLC patients. However, accurate patients' selection and appropriate sequencing of different immunotherapy-based approaches remain unsolved. In this review, we provide an overview of the currently available evidence on double immune checkpoint inhibition (ICI) for NSCLC treatment and discuss current issues and future perspectives.
Keywords: Durvalumab; Immune checkpoint inhibitors; Ipilimumab; NSCLC; Nivolumab; Tremelimumab.
Copyright © 2020 Elsevier B.V. All rights reserved.
Conflict of interest statement
Declaration of Competing Interest None.
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9
J Neurooncol
. 2020 Jan;146(1):111-120. doi: 10.1007/s11060-019-03342-5. Epub 2019 Nov 19.
Brachytherapy With Surgical Resection as Salvage Treatment for Recurrent High-Grade Meningiomas: A Matched Cohort Study
Michael A Mooney 1 2, Wenya Linda Bi 3, Jonathan M Cantalino 4, Kyle C Wu 3, Thomas C Harris 4, Lucas L Possatti 3, Parikshit Juvekar 3, Liangge Hsu 5, Ian F Dunn 3, Ossama Al-Mefty 3, Phillip M Devlin 4
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PMID: 31745706
DOI: 10.1007/s11060-019-03342-5
Abstract
Purpose: To evaluate surgical resection with brachytherapy placement as a salvage treatment in patients with recurrent high-grade meningioma who exhausted prior external beam treatment options.
Methods: Single-center retrospective review of our institutional experience of brachytherapy implantation from 2012 to 2018. The primary outcome of the study was progression free survival (PFS). Secondary outcomes included overall survival (OS) and complications. A matched cohort of patients not treated with brachytherapy over the same time period was evaluated as a control group. All patients had received prior radiation treatment and underwent planned gross total resection (GTR) surgery.
Results: A total of 27 cases were evaluated. Compared with prior treatment, brachytherapy implantation demonstrated a statistically significant improvement in tumor control [HR 0.316 (0.101 - 0.991), p = 0.034]. PFS-6 and PFS-12 were 92.3% and 84.6%, respectively. Compared with the matched control cohort, brachytherapy treatment demonstrated improved PFS [HR 0.310 (0.103 - 0.933), p = 0.030]. Overall survival was not statistically significantly different between groups [HR 0.381 (0.073 - 1.982), p = 0.227]. Overall postoperative complications were comparable between groups, although there was a higher incidence of radiation necrosis in the brachytherapy cohort.
Conclusion: Brachytherapy with planned GTR improved PFS in recurrent high-grade meningioma patients who exhausted prior external beam radiation treatment options. Future improvement of brachytherapy dose delivery methods and techniques may continue to prolong control rates and improve outcomes for this challenging group of patients.
Keywords: Anaplastic; Atypical; Brachytherapy; Meningioma; Radiation; Recurrence.
39 references
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10
Review
Cancers (Basel)
. 2020 Jun 4;12(6):E1472. doi: 10.3390/cancers12061472.
The Expression, Functions and Mechanisms of Circular RNAs in Gynecological Cancers
Peixin Dong 1, Daozhi Xu 1, Ying Xiong 2, Junming Yue 3 4, Kei Ihira 1, Yosuke Konno 1, Hidemichi Watari 1
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PMID: 32512912
DOI: 10.3390/cancers12061472
Abstract
Circular RNAs (circRNAs) are covalently closed, endogenous non-coding RNAs and certain circRNAs are linked to human tumors. Owing to their circular form, circRNAs are protected from degradation by exonucleases, and therefore, they are more stable than linear RNAs. Many circRNAs have been shown to sponge microRNAs, interact with RNA-binding proteins, regulate gene transcription, and be translated into proteins. Mounting evidence suggests that circRNAs are dysregulated in cancer tissues and can mediate various signaling pathways, thus affecting tumorigenesis, metastasis, and remodeling of the tumor microenvironment. First, we review the characteristics, biogenesis, and biological functions of circRNAs, and describe various mechanistic models of circRNAs. Then, we provide a systematic overview of the functional roles of circRNAs in gynecological cancers. Finally, we describe the potential future applications of circRNAs as biomarkers for prognostic stratification and as therapeutic targets in gynecological cancers. Although the function of most circRNAs remains elusive, some individual circRNAs have biologically relevant functions in cervical cancer, ovarian cancer, and endometrial cancer. Certain circRNAs have the potential to serve as biomarkers and therapeutic targets in gynecological cancers.
Keywords: biomarker; cancer diagnosis; cancer treatment; circular RNA; gynecological cancer; non-coding RNA.
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11
J Geriatr Oncol
. 2020 Jun 5;S1879-4068(20)30064-3. doi: 10.1016/j.jgo.2020.05.013. Online ahead of print.
Efficacy and Safety of Frontline Regimens for Older Transplant-Ineligible Patients With Multiple Myeloma: A Systematic Review and Meta-Analysis
Smith Giri 1, Madan Raj Aryal 2, Han Yu 3, Alyssa Grimshaw 4, Ranjan Pathak 5, Scott P Huntington 5, Binod Dhakal 6
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PMID: 32513568
DOI: 10.1016/j.jgo.2020.05.013
Abstract
Introduction: Several treatment options are available for the management of older adults with newly diagnosed patients with Multiple Myeloma (MM) who are ineligible for hematopoietic cell transplantation (tiMM). We aimed to identify treatment options that provide the best balance in terms of efficacy and safety.
Methods: We searched bibliographic databases and meeting libraries for search terms reflecting newly diagnosed and older and/or transplant-ineligible patients from inception to October 21, 2018. Phase II/III randomized trials comparing at least two first line treatment regimens for newly diagnosed tiMM were included. We extracted data on efficacy (progression free survival, PFS, overall survival and overall response rate) and safety (grade ¾ toxicities) and conducted network meta-analysis using Bayesian methods and random effects models. Relative ranking of treatment regimens was assessed using Surface under the cumulative ranking (SUCRA) probabilities.
Results: We identified 27 trials involving 12,194 patients. For PFS, the four most effective regimens were: Daratumumab, Bortezomib, Melphalan and Prednisone (SUCRA 0.960) followed by Daratumumab, lenalidomide and dexamethasone (Dara_RD, SUCRA 0.847), Bortezomib, melphalan, prednisone, thalidomide maintenance with bortezomib-thalidomide (SUCRA 0.834) and Bortezomib, Lenalidomide and Dexamethasone (SUCRA 0.739). Among these four most efficacious regimens, toxicity profile was most favorable for Dara_RD (median additional AEs per patient vs dexamethasone = 0.74; 95% CrI 0.51-1.17; SUCRA 0.430).
Conclusion: Among first line tiMM regimens, increasing efficacy is associated with increased toxicity. We provide relative ranking of these regimens for both efficacy and safety. Future studies should incorporate geriatric assessments and frailty biomarkers to refine treatment decision-making for each individual patient.
Keywords: First-line therapy; Meta-analysis; Multiple myeloma; Systematic review; Transplant ineligible.
Copyright © 2020 Elsevier Inc. All rights reserved.
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12
J Oncol Pharm Pract
. 2020 Mar;26(2):279-285. doi: 10.1177/1078155219841424. Epub 2019 Apr 3.
Barriers to Receipt of Novel Oral Oncolytics: A Single-Institution Quality Improvement Investigation
Ann A Wang 1, Christopher Tapia 1, Yasin Bhanji 1, Christopher Campbell 2, Daniel Larsen 3, Derick Gross 2, Seema Ganatra 2, Melad Qodsi 2, Claudia Tellez 1 3, Shikha Jain 1 3
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PMID: 30943846
DOI: 10.1177/1078155219841424
Abstract
Introduction: Novel oral oncolytic agents have become the standard of care and first-line therapies for many malignancies. However, issues impacting access to these drugs are not well explored. As part of a quality improvement project in a large tertiary academic institution, we aim to identify potential barriers that delay treatment for patients who are prescribed novel oral oncolytics.
Methods: This was a retrospective review of adults who were newly prescribed a novel oral oncolytic for Food and Drug Administration-approved indications at a single tertiary care center. Patients were identified via electronic prescription data (e-Scribe). Demographics, insurance information, and prescription dates were extracted from the electronic medical record and pharmacy claims data. Statistical analyses were performed to determine whether time-to-receipt was associated with insurance category, pharmacy transfers, cost assistance, and drug prescribed.
Results: Of the 270 successfully filled prescriptions, the mean time-to-receipt was 7.3 ± 10.3 days (range: 0-109 days). Patients with Medicare experienced longer time-to-receipt (9.1 ± 13.1 days) compared to patients with commercial insurance (4.4 ± 3.3). Uninsured patients experienced the longest time-to-receipt (15.7 ± 7.8 days) overall. Pharmacy transfers and cost assistance programs were also significantly associated with longer time-to-receipt. Ten prescriptions remained unfilled 90 days after the study period and were considered abandoned.
Conclusion: Insurance has a significant effect on the time-to-receipt of newly prescribed novel oral oncolytics. Pharmacy transfers and applying for cost assistance are also associated with longer wait times for patients. Our retrospective analysis identifies areas of improvement for future interventions to reduce wait times for patients receiving novel oral oncolytics.
Keywords: Medicare; Oral oncolytics; barriers to care; cancer therapy; delays in care; health-care disparities; insurance status; medication costs; private insurance; quality improvement; specialty pharmacy.
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13
Review
Respirology
. 2020 Jun 9. doi: 10.1111/resp.13870. Online ahead of print.
Radiotherapy Treatment for Lung Cancer: Current Status and Future Directions
Shalini K Vinod 1 2, Eric Hau 3 4 5
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PMID: 32516852
DOI: 10.1111/resp.13870
Abstract
Radiotherapy is an important modality used for the treatment of lung cancer. Seventy-seven percent of all patients with lung cancer have an evidence-based indication for radiotherapy, although it is often underutilized. Radiotherapy can be used as curative or palliative treatment across all stages of disease. Technological advances have allowed better radiotherapy targeting of tumours and reduced incidental irradiation of surrounding normal tissues. This has expanded the indications for radiotherapy in lung cancer and improved outcomes both in terms of increasing survival and reducing toxicity. This review examines the current role of radiotherapy in lung cancer, discusses the evidence behind this and identifies future directions in the radiotherapy treatment of lung cancer.
Keywords: lung neoplasms; non-small cell carcinoma; radiotherapy; small cell carcinoma; therapy.
© 2020 Asian Pacific Society of Respirology.
65 references
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14
Clin Cancer Res
. 2020 Jun 8;clincanres.0945.2020. doi: 10.1158/1078-0432.CCR-20-0945. Online ahead of print.
Multicenter Phase 1 Trial of a DNA Vaccine Encoding the Androgen Receptor Ligand Binding Domain (pTVG-AR, MVI-118) in Patients With Metastatic Prostate Cancer
Christos E Kyriakopoulos 1, Jens Eickhoff 2, Anna C Ferrari 3, Michael T Schweizer 4, Ellen Wargowski 5, Brian M Olson 6, Douglas G McNeel 7
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PMID: 32513836
DOI: 10.1158/1078-0432.CCR-20-0945
Abstract
Purpose: Preclinical studies demonstrated that a DNA vaccine (pTVG-AR, MVI-118) encoding the androgen receptor ligand-binding domain (AR LBD) augmented antigen-specific CD8+ T cells, delayed prostate cancer progression and emergence of castration-resistant disease, and prolonged survival of tumor-bearing mice. This vaccine was evaluated in a multicenter phase 1 trial.
Experimental design: Patients with metastatic castration sensitive prostate cancer (mCSPC) who had recently begun androgen deprivation therapy were randomly assigned to receive pTVG-AR on one of two treatment schedules over one year, and with or without GM-CSF as a vaccine adjuvant. Patients were followed for 18 months. Primary objectives were safety and immune response. Secondary objectives included median time to PSA progression, and 18-month PSA-progression-free survival (PPFS).
Results: Forty patients were enrolled at three centers. Twenty-seven patients completed treatment and 18 months of follow-up. Eleven patients (28%) had a PSA progression event before the 18-month timepoint. No grade 3 or 4 adverse events were observed. Of 30 patients with samples available for immune analysis, 14 (47%) developed Th1-type immunity to the AR LBD, as determined by IFNγ and/or granzyme B ELISPOT. Persistent IFNγ immune responses were observed irrespective of GM-CSF adjuvant. Patients who developed T-cell immunity had a significantly prolonged PPFS compared to patients without immunity (HR=0.01, 95% CI: 0.0-0.21, p=0.003).
Conclusions: pTVG-AR was safe and immunologically active in patients with mCSPC. Association between immunity and PPFS suggests that treatment may delay the time to castration resistance, consistent with preclinical findings, and will be prospectively evaluated in future trials.
Copyright ©2020, American Association for Cancer Research.
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15
Review
Semin Oncol
. 2020 May 29;S0093-7754(20)30042-7. doi: 10.1053/j.seminoncol.2020.05.003. Online ahead of print.
Novel Radiation Therapy Approaches for Breast Cancer Treatment
Chirag Shah 1, Kristine Bauer-Nilsen 2, Ryan Hazard McNulty 2, Frank Vicini 3
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PMID: 32513420
DOI: 10.1053/j.seminoncol.2020.05.003
Abstract
The role of radiation therapy in the management of breast cancer continues to evolve. For patients with early stage breast cancer, hypofractionated whole breast irradiation following breast conserving surgery now represents the standard of care based on randomized data with long-term efficacy and toxicity outcomes. Partial breast irradiation has been found, in several randomized trials, to be effective and appropriate in selected patients with the potential to reduce toxicities as compared to whole breast irradiation. The study of tumor biology and genetics and its role in radiation therapy decision making continues to grow and the advances may help identify patients where radiation therapy can be safely omitted, with future studies looking at de-intensification approaches. Recent randomized data has demonstrated a growing role for regional nodal irradiation in patients with more advanced disease, with future studies looking to identify whether nodal radiation is indicated following neoadjuvant chemotherapy or with certain favorable tumor biologies. While postmastectomy radiation therapy represents a standard approach for patients with locally advanced breast cancer, new data supports the role of hypofractionated regimens as well as its use in patients previously considered lower risk with unfavorable tumor biology. Oligometastatic disease represents a new area of study in breast cancer with prospective trials underway and current data supporting consideration of techniques such as stereotactic body radiation therapy in appropriately selected patients.
Keywords: Breast cancer; Intraoperative radiation; Partial breast irradiation; Radiation therapy; Whole breast irradiation.
Copyright © 2020 Elsevier Inc. All rights reserved.
Conflict of interest statement
Conflict of interest Chirag Shah- Consultant, Impedimed; Travel/Grants, Varian Medical Systems; Grant- Vision RT; Grant- PreludeDx; Kristine Bauer-Nilsen- None; Ryan Hard- None; Frank Vicini- Chief medical officer, Impedimed.
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16
Radiat Oncol
. 2020 Jun 8;15(1):147. doi: 10.1186/s13014-020-01587-3.
Overlapping Volumes in Re-Irradiation for Head and Neck Cancer - An Important Factor for Patient Selection
Anna Embring 1 2, Eva Onjukka 3 4, Claes Mercke 5 3, Ingmar Lax 4, Anders Berglund 6, Sara Bornedal 4, Berit Wennberg 4, Signe Friesland 5 3
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PMID: 32513217
DOI: 10.1186/s13014-020-01587-3
Abstract
Background: There is a lack of consensus concerning the definition of re-irradiation and re-irradiation volumes in head and neck cancer (HNC). The aim of the present study is to introduce a more strict definition of the re-irradiated volume that might better predict the risk of serious side-effects from treatment.
Methods: Fifty-four consecutive patients re-irradiated for HNC cancer were retrospectively analysed. CT images were deformably registered and the dose distributions accumulated after conversion to EQD2. Patients with a cumulative dose of ≥100 Gy in the overlapping volume (V100) were included in the study. Survival data and radiation-related acute and late toxicities were recorded.
Results: The overall survival of all included patients at 2 and 5 years was 42.6 and 27.3% respectively and the progression free survival at 2 and 5 years was 32.5 and 28.5% respectively. The overall rate of any event of severe (grade ≥ 3) acute and late toxicity was 26 and 51%, respectively. We found that severe acute toxicity was more common in patients who had a larger overlapping volume (V100 > mean) where 43% of the patients experienced grade ≥ 3 acute toxicity, compared to the patients with smaller overlapping volumes (V100 < mean) where only 11% had severe toxicity (p = 0.02). The seemingly high rates of late toxicity in the present study could be due to the use of a more strict definition of re-irradiation. In previous studies also patients with low dose overlap are included and our results imply that there is a risk that previous studies might have overestimated the risk-benefit ratio in re-irradiation of HNC.
Conclusions: Our study describes the outcome of a patient material where a more strict definition of the re-irradiated volume is used. With this definition, which could better describe the volume of highest risk for serious complications, we found that larger such overlapping volumes result in an increase in severe acute side-effects. A clear definition of re-irradiation and re-irradiation volumes is of utmost importance for future studies of HNC to make results from different studies comparable.
Keywords: Cumulative dose; HNSCC; Head and neck cancer; Overlap; Re-irradiation; Re-irradiation volume.
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17
Tumori
. 2020 Jun 9;300891620929425. doi: 10.1177/0300891620929425. Online ahead of print.
Dose Prescription in SBRT for Early-Stage Non-Small Cell Lung Cancer: Are We All Speaking the Same Language?
Anna Merlotti 1, Pierluigi Bonomo 2, Riccardo Ragona 3, Marco Trovò 4, Filippo Alongi 5, Rosario Mazzola 5, Riccardo Vigna Taglianti 1, Luca Gianello 1, Alessia Reali 1, Fabrizio Bergesio 6, Francesco Lucio 6, Alberto Boriano 6, Adriano De Maggi 6, Elvio Russi 1
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PMID: 32515301
DOI: 10.1177/0300891620929425
Abstract
Introduction: Stereotactic body radiation therapy is increasingly used in the treatment of early-stage lung cancers. Guidelines provide indications regarding the constraints to the organs at risk (OARs) and the minimum coverage of the planning target volume but do not suggest optimal dose distribution. Data on dose distribution from the different published series are not comparable due to different prescription modalities and reported dose parameters.
Methods: We conducted a review of the published data on dose prescription, focusing on the role of homogeneity on local tumor control, and present suggestions on how to specify and report the prescriptions to permit comparisons between studies or between cases from different centers.
Conclusions: To identify the dose-prescription modality that better correlates with oncologic outcomes, future studies should guarantee a close uniformity of dose distribution between cases and complete dose parameters reporting for treatment volumes and OARs.
Keywords: dose; lung cancer; prescription; stereotactic ablative radiotherapy; stereotactic body radiation therapy.
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18
J Clin Med
. 2020 Jun 4;9(6):E1742. doi: 10.3390/jcm9061742.
Pre-Operative Combination of Normal BMI With Elevated YKL-40 and Leptin but Lower Adiponectin Level Is Linked to a Higher Risk of Breast Cancer Relapse: A Report of Four-Year Follow-Up Study
Kornel Bielawski 1, Piotr Rhone 2, Marek Bulsa 3, Barbara Ruszkowska-Ciastek 1
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PMID: 32512860
DOI: 10.3390/jcm9061742
Abstract
Adipokines are powerful agents involved in the development of obesity-dependent cancers. This prospective study aimed to investigate the association between pre-treatment body mass index (BMI) and serum YKL-40, leptin, and adiponectin concentrations as well as the plasma activity of tissue factor (TF) and the future prognosis of early, non-metastatic breast cancer (BrC) subjects. The serum levels of YKL-40, leptin, and adiponectin as well as plasma TF activity, anthropometric parameters, and clinicopathological parameters were analysed in 81 treatment-naïve females with invasive BrC. The predictive value of YKL-40, BMI, leptin, adiponectin, and TF was determined with a 95% confidence interval (CI). Kaplan-Meier plots and log-rank and F Cox tests were used to determine the clinical outcomes of progression-free survival (PFS). The median follow-up duration was 44 months with complete follow-up for the first event. Follow-up revealed a significantly higher incidence of disease relapse in BrC patients with a high baseline concentration of YKL-40 (22.22%) and TF activity (21.43%). Body mass index was an independent predictor of survival, with women who were overweight/obese being less prone to relapse (hazard ratio (HR): 0.75; 95% CI: 0.59 to 0.95). The recurrence rates for normal-weight BrC cases was 21.05% versus 7.14% for their overweight counterparts. The receiver operating characteristic analysis showed the strong ability of the analysed biomarkers to predict disease progression, with an area under the receiver operating characteristics (ROC) curve of 0.84 (95% CI, 0.823 to 0.931). In a prospective cohort of invasive BrC patients, overweight/obesity was associated with improved future outcomes. The combination of a normal BMI with high leptin and low adiponectin levels and high TF activity was associated with an increased risk of recurrence and decreased survival.
Keywords: adipokines; breast cancer; disease recurrence; inflammation.
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19
Elife
. 2020 Jun 9;9:e53367. doi: 10.7554/eLife.53367.
Analysis of Pulsed Cisplatin Signalling Dynamics Identifies Effectors of Resistance in Lung Adenocarcinoma
Jordan F Hastings # 1, Alvaro Gonzalez Rajal # 1, Sharissa L Latham 1 2, Jeremy Zr Han 1, Rachael A McCloy 1, Yolande Ei O'Donnell 1, Monica Phimmachanh 1, Alexander D Murphy 3, Adnan Nagrial 3, Dariush Daneshvar 3, Venessa Chin 1 2 4, D Neil Watkins 5 6 7 8, Andrew Burgess 9 10, David R Croucher 1 2 11
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PMID: 32513387
DOI: 10.7554/eLife.53367
Abstract
The identification of clinically viable strategies for overcoming resistance to platinum chemotherapy in lung adenocarcinoma has previously been hampered by inappropriately tailored in vitro assays of drug response. Therefore, using a pulse model that closely mimics the in vivo pharmacokinetics of platinum therapy, we profiled cisplatin-induced signalling, DNA-damage and apoptotic responses across a panel of human lung adenocarcinoma cell lines. By coupling this data to real-time, single-cell imaging of cell cycle and apoptosis we provide a fine-grained stratification of response, where a P70S6K-mediated signalling axis promotes resistance on a TP53 wildtype or null background, but not a mutant TP53 background. This finding highlights the value of in vitro models that match the physiological pharmacokinetics of drug exposure. Furthermore, it also demonstrates the importance of a mechanistic understanding of the interplay between somatic mutations and the signalling networks that govern drug response for the implementation of any consistently effective, patient-specific therapy.
Keywords: P70S6K; cancer biology; chemoresistance; human; lung adenocarcinoma; p53; platinum chemotherapy; signalling dynamics.
Plain Language Summary
Lung adenocarcinoma is the most common type of lung cancer, and it emerges because of a variety of harmful genetic changes, or mutations. Two lung cancer patients – or indeed, two different sets of cancerous cells within a patient – may therefore carry different damaging mutations. A group of drugs called platinum-based chemotherapies are currently the most effective way to treat lung adenocarcinoma. Yet, only 30% of patients actually respond to the therapy. Many studies conducted in laboratory settings have tried to understand why most cases are resistant to treatment, with limited success. Here, Hastings, Gonzalez-Rajal et al. propose that previous research has been inconclusive because studies done in the laboratory do not reflect how the treatment is actually administered. In patients, platinum-based drugs are cleared from the body within a few hours, but during experiments, the treatment is continually administered to cells growing in a dish. Hastings, Gonzalez-Rajal et al. therefore developed a laboratory method that mimics the way cells are exposed to platinum-based chemotherapy in the body. These experiments showed that the lung adenocarcinoma cells which resisted treatment also carried high levels of a protein known as P70S6K. Pairing platinum-based chemotherapy with a drug that blocks the activity of P70S6K killed these resistant cells. This combination also treated human lung adenocarcinoma tumours growing under the skin of mice. However, it was ineffective on cancerous cells that carry a mutation in a protein called p53, which is often defective in cancers. Overall, this work demonstrates the need to refine how drugs are tested in the laboratory to better reflect real-life conditions. It also underlines the importance of personalizing drug combinations to the genetic background of each tumour, a concept that will be vital to consider in future clinical trials.
© 2020, Hastings et al.
Conflict of interest statement
JH, AG, SL, JH, RM, YO, MP, AM, AN, DD, VC, DW, AB, DC No competing interests declared
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20
Br J Radiol
. 2020 Jun 9;20200116. doi: 10.1259/bjr.20200116. Online ahead of print.
Staging of Bladder Cancer With Multiparametric MRI
Hiroshi Juri 1, Yoshifumi Narumi 2, Valeria Panebianco 3, Keigo Osuga 1
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PMID: 32516554
DOI: 10.1259/bjr.20200116
Abstract
The distinction of non-muscle-invasive bladder cancer and muscle-invasive bladder cancer is important for the selection of the optimal treatment. Multiparametric MRI (mp-MRI) has been an useful modality for the T staging of bladder cancer, and a systematic evaluation of mp-MRI is needed. The Vesical Imaging Reporting and Data System was designed to standardize the scanning and reporting criteria based on mp-MRI for clinical and research applications. This review briefly describes the method, interpretation, and timing of mp-MRI examinations in the clinical settings. Validation studies of Vesical Imaging Reporting and Data System and future perspectives are also considered.
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21
J Neurooncol
. 2020 Jan;146(1):55-62. doi: 10.1007/s11060-019-03334-5. Epub 2019 Nov 7.
Weak MGMT Gene Promoter Methylation Confers a Clinically Significant Survival Benefit in Patients With Newly Diagnosed Glioblastoma: A Retrospective Cohort Study
H Pinson 1, G Hallaert 2, J Van der Meulen 3, F Dedeurwaerdere 4, D Vanhauwaert 5, C Van den Broecke 6 7, J Van Dorpe 6, D Van Roost 2, J P Kalala 2, T Boterberg 8
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PMID: 31701343
DOI: 10.1007/s11060-019-03334-5
Abstract
Introduction: Quantitative methylation specific PCR (qMSP) is a frequently used technique to assess MGMT gene promoter methylation in glioblastoma patients. The optimal technical cut-off value to distinguish methylated from unmethylated samples is nevertheless still undetermined. In literature, a "grey zone" of diagnostic uncertainty has been described.
Methods: We performed a retrospective analysis of newly diagnosed glioblastoma patients treated according to the Stupp protocol. Epidemiological data were gathered from the individual patient files. MGMT gene promoter methylation status was determined on stored tumour samples using qMSP. A strong, weak or absent promoter methylation was determined based on Cq values (quantification value) of the MGMT and ACTB primers as well as a positive control sample.
Results: In total, 181 patient files were reviewed and included for statistical analysis. MGMT promoter hypermethylation was detected in 38.7% of glioblastoma patients. The median overall survival of unmethylated and strongly methylated patients was 10.1 months and 19.7 months respectively. Furthermore, 11% of the total patient cohort had a weak MGMT gene promoter methylation. The median OS in this subgroup was 15.4 months, significantly better compared to the unmethylated cohort (P < 0.001). Multivariate Cox regression analysis showed weak MGMT promoter methylation as an independent prognostic parameter for overall survival.
Conclusion: Glioblastoma patients with weak promoter methylation show a statistically significant longer overall survival when compared to clearly unmethylated patients. Patients with grey zone qMSP test results should receive additional molecular analysis in future to further direct individual therapy strategies.
Keywords: Glioblastoma; MGMT gene methylation; Prognosis; qMSP.
24 references
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22
J Neurooncol
. 2020 Jan;146(1):63-69. doi: 10.1007/s11060-019-03335-4. Epub 2019 Nov 11.
Delay in Diagnosing Patients With Right-Sided Glioblastoma Induced by Hemispheric-Specific Clinical Presentation
Claudia Baumann 1 2, Julia Tichy 3 4 5 6, Jan Hendrik Schaefer 7, Joachim P Steinbach 3 4 5 6, Michel Mittelbronn 8 9 10 11 12, Marlies Wagner 13, Christian Foerch 7
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PMID: 31713017
DOI: 10.1007/s11060-019-03335-4
Abstract
Purpose: Cognitive functions are differentially represented in brain hemispheres. Aphasia is an "easy to recognize" symptom of diseases affecting the left side. In contrast, lesions in the right hemisphere cause subtle neuropsychological deficits such as neglect and anosognosia. We evaluated whether right-sided malignant brain tumors are on average larger at the time of first diagnosis as compared to left-sided tumors, and extrapolated the delay in diagnosing right-sided tumors compared to the left side.
Methods: All first-ever diagnosed glioblastoma (GBM) patients between 2005 and 2012 were identified using our hospital-based prospective research registry. Baseline data, information on initial clinical presentation and imaging findings (including tumor volume) were collected. Extrapolation of time since tumor initiation was based on an established gompertzian growth model.
Results: We included 173 patients. Mean age of the study population was 58 ± 13 years. Tumors located in the right hemisphere (n = 96) were larger as compared to tumors located in the left hemisphere (n = 77) (median 36.4 mL [interquartile range 13.0-56.0; minimum 0.2, maximum 140.0] vs. 17.2 mL [7.7-45.1 mL; 0.4, 105.2]; p = 0.011). Right-sided tumors grew longer than left-sided tumors (378 ± 95 days vs. 341 ± 74 days; p = 0.006). Initial neuropsychological symptoms differed depending on the affected hemisphere.
Conclusion: Right-hemispheric symptoms appear to be less clinically conspicuous resulting in a delayed diagnosis of GBM, which might be improved by raising awareness for the corresponding neuropsychological deficits. Whether our findings have prognostic implications needs to be evaluated in future studies.
Keywords: Brain tumor; Growth; Neuropsychology; Side.
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23
Future Oncol
. 2020 Jun 9. doi: 10.2217/fon-2020-0315. Online ahead of print.
Incidence of Second Primary Malignancies in Metastatic Castration-Resistant Prostate Cancer: Results From Observational Studies in Three Countries
Zdravko P Vassilev 1, Montse Soriano Gabarró 2, James A Kaye 3, Catherine W Saltus 3, Oliver Riedel 4, Oliver Scholle 4, Juha Mehtälä 5, Pasi Korhonen 5, Edeltraut Garbe 4, Jihong Zong 1
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PMID: 32515225
DOI: 10.2217/fon-2020-0315
Abstract
Aim: This reports some of the first incidence rate (IR) estimates of second primary malignancies (SPMs) in men with metastatic castration-resistant prostate cancer (mCRPC) in three countries. Patients & methods: Claims data from the German Pharmacoepidemiological Research Database; registry data from the Prostate Cancer Data Base Sweden; and combined registry-claims data from the US Surveillance, Epidemiology and End Results-Medicare database were analyzed to obtain overall survival and incidence of SPMs in men with mCRPC. Results: SPMs occurred in 308 German (N = 2360), 273 Swedish (N = 2849) and 172 US (N = 2234) men with mCRPC. IRs of SPMs were 79.0 (95% CI: 70.4-88.4), 101.7 (95% CI: 90.3-114.5) and 59 (95% CI: 50-68) per 1000 person-years in German, Swedish and US cohorts, respectively. Conclusion: These studies report some of the first IR estimates of SPMs in men with mCRPC, providing a historical risk estimate of SPM in this patient population.
Keywords: healthcare data; prognosis; prostate cancer; risk estimate; second primary malignancies.
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24
Cardiovasc Intervent Radiol
. 2020 Jun 8. doi: 10.1007/s00270-020-02537-y. Online ahead of print.
90 Y-Radioembolization After Failed Portal Vein Embolization for Colorectal Liver Metastases: A Case Report
I Kurilova 1 2, V Pompa 3, R Guerrero 4, Mesa A Tapias 5, Mizrrahi D Calatayud 6, C Fondevila 7, J A González 8, J Duch 9, F M Gomez 10 11
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PMID: 32514612
DOI: 10.1007/s00270-020-02537-y
Abstract
The main limiting factor for liver resection is insufficient future liver remnant (FLR). Portal vein embolization (PVE) is a standard of care treatment to induce FLR hypertrophy, but it is not always efficient. Radioembolization (RE) has a potential to induce liver hypertrophy for PVE-refractory patients. However, this was reported only for the patients with hepatocellular carcinoma. We described two cases of lobar RE after PVE failure for the patients with colorectal liver metastases. This enabled to reach sufficient FLR, provide good local disease control and bridge the patients to extended hepatectomy.
Keywords: Ablation; Colorectal cancer; Liver metastases; Radioembolization.
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