The latest medical research on Oncology
The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about oncology gathered by our medical AI research bot.
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Core Antibiotic-Induced Transcriptional Signatures Reflect Susceptibility to All Members of an Antibiotic Class.Antimicrobial Agents and Chemotherapy
Current growth-based antibiotic susceptibility testing (AST) is too slow to guide early therapy. We previously developed a diagnostic approach that...
Experience with Liposomal Amphotericin B in Outpatient Parenteral Antimicrobial Therapy (OPAT).Antimicrobial Agents and Chemotherapy
Outpatient parenteral antimicrobial therapy (OPAT) is a safe, effective, and convenient treatment strategy for patients receiving intravenous antimicrobials in the outpatient setting; however, data is limited describing the use and safety of liposomal amphotericin B (L-AMB).
Records of patients receiving L-AMB OPAT between 1/1/2015 and 7/31/2018 were retrospectively reviewed. The primary objective was to describe the OPAT patient population discharged on L-AMB and evaluate factors associated with readmission and adverse events (AE). Analysis was performed to evaluate for predictors of worse outcomes.
Forty-two patients (67% male, median age 50 years) were identified, most commonly treated for histoplasmosis. The most common doses of L-AMB were 3 mg/kg (n=16, 38%) or 5 mg/kg (n=14, 33%) based on actual body weight. Twenty-six (62%) patients completed their anticipated course of L-AMB. Twenty-two (52%) patients were readmitted within 30 days of discharge, median time to readmission was 11 days (Interquartile range [IQR] 5-18). While hypokalemia and acute kidney injury (AKI) were common, occurring in 26 (62%) and 20 (48%), respectively, only 5 (12%) were readmitted to the hospital due L-AMB-associated AE. Ninety percent of patients achieved at least partial renal recovery within 30 days after L-AMB discontinuation. Factors significantly associated with AKI include higher L-AMB dose, lower serum potassium levels after therapy initiation, and receipt of potassium supplementation at discharge.
L-AMB is associated with significant AEs; however, these results suggest treatment is feasible in the outpatient setting with close monitoring, as the majority of AEs were managed effectively as an outpatient without long-term sequelae.
E. coli GyrA Tower Domain Interacts with QnrB1 Loop B and Plays an Important Role in QnrB1 Protection from Quinolone Inhibition.Antimicrobial Agents and Chemotherapy
The Qnr pentapeptide repeat proteins interact with DNA gyrase and protect it from quinolone inhibition. The two external loops, particularly the la...
Compound FC-10696 Inhibits Egress of Marburg Virus.Antimicrobial Agents and Chemotherapy
Marburg virus (MARV) VP40 protein (mVP40) directs egress and spread of MARV, in part, by recruiting specific host WW-domain containing proteins via...
The long noncoding RNA lnc-HLX-2-7 is oncogenic in Group 3 medulloblastomas.Neuro-Oncology
Medulloblastoma (MB) is an aggressive brain tumor that predominantly affects children. Recent high-throughput sequencing studies suggest that the noncoding RNA genome, in particular long noncoding RNAs (lncRNAs), contributes to MB subgrouping. Here we report the identification of a novel lncRNA, lnc-HLX-2-7, as a potential molecular marker and therapeutic target in Group 3 MBs.
Publicly available RNA sequencing (RNA-seq) data from 175 MB patients were interrogated to identify lncRNAs that differentiate between MB subgroups. After characterizing a subset of differentially expressed lncRNAs in vitro and in vivo, lnc-HLX-2-7 was deleted by CRISPR/Cas9 in the MB cell line. Intracranial injected tumors were further characterized by bulk and single-cell RNA-seq.
Lnc-HLX-2-7 is highly upregulated in Group 3 MB cell lines, patient-derived xenografts, and primary MBs compared with other MB subgroups as assessed by quantitative real-time, RNA-seq, and RNA fluorescence in situ hybridization. Depletion of lnc-HLX-2-7 significantly reduced cell proliferation and 3D colony formation and induced apoptosis. Lnc-HLX-2-7-deleted cells injected into mouse cerebellums produced smaller tumors than those derived from parental cells. Pathway analysis revealed that lnc-HLX-2-7 modulated oxidative phosphorylation, mitochondrial dysfunction, and sirtuin signaling pathways. The MYC oncogene regulated lnc-HLX-2-7, and the small-molecule bromodomain and extraterminal domain family‒bromodomain 4 inhibitor Jun Qi 1 (JQ1) reduced lnc-HLX-2-7 expression.
Lnc-HLX-2-7 is oncogenic in MB and represents a promising novel molecular marker and a potential therapeutic target in Group 3 MBs.
Systemic immunity in cancer.Nature Reviews Cancer
Immunotherapy has revolutionized cancer treatment, but efficacy remains limited in most clinical settings. Cancer is a systemic disease that induce...
The incidence of major subtypes of primary brain tumours in adults in England 1995-2017.Neuro-Oncology
Primary brain tumours are a complex heterogenous group of benign and malignant tumours. Reports on their occurrence in the English population by sex, age, and morphological subtype and on their incidence are currently not available. Using data from the National Cancer Registration and Analysis Service (NCRAS), the incidence of adult primary brain tumour by major subtypes in England will be described.
Data on all adult English patients diagnosed with primary brain tumour between 1995 and 2017, excluding spinal, endocrinal and other CNS tumours, were extracted from NCRAS. Incidence rates were standardised to the 2013 European Standard Population. Results are presented by sex, age, and morphological subtype.
Between 1995 and 2017, a total of 133,669 cases of adult primary brain tumour were registered in England. Glioblastoma was the most frequent tumour subtype (31.8%), followed by meningioma (27.3%). The age-standardised incidence for glioblastoma increased from 3.27 per 100,000 population per year in 1995 to 7.34 in men in 2013 and from 2.00 to 4.45 in women. Meningioma incidence also increased from 1.89 to 3.41 per 100,000 in men and from 3.40 to 7.46 in women. The incidence of other astrocytic and unclassified brain tumours declined between 1995 and 2007 and remained stable thereafter.
Part of the increase in the incidence of major subtypes of brain tumours in England could be explained by advances in clinical practice including the adoption of new diagnostic tools, classifications and molecular testing, and improved cancer registration practices.
MEVITEM - A Phase I/II of vismodegib + temozolomide vs temozolomide in patients with recurrent/refractory medulloblastoma with Sonic Hedgehog pathway activation.Neuro-Oncology
Vismodegib specifically inhibits Sonic Hedgehog (SHH). We report results of a Phase I/II evaluating vismodegib + temozolomide in immunohistochemically defined SHH recurrent/refractory adult medulloblastoma.
Temozolomide naïve patients were randomized 2:1 to receive vismodegib + temozolomide (Arm A) or temozolomide (Arm B). Patients previously treated with temozolomide were enrolled in an exploratory cohort of vismodegib (Arm C). If the safety run showed no excessive toxicity, a Simon's two-stage Phase II design was planned to explore the 6-month progression free survival (PFS-6). Stage II was to proceed if arm A PFS-6 was ≥3/9 at the end of Stage I.
A total of 24 patients were included: Arm A (10), Arm B (5), and Arm C (9). Safety analysis showed no excessive toxicity. At the end of Stage I, the PFS-6 of arm A was 20% (2/10 patients, 95% Unilateral Lower Confidence Limit: 3.7%) and the study was prematurely terminated. The overall response rates (ORR) were 40% [95% CI: 12.2; 73.8] and 20% [95% CI: 0.5; 71.6] in arm A and B, respectively. In arm C, PFS-6 was 37.5% (95% CI: 8.8; 75.5) and ORR was 22.2% [95% CI: 2.8; 60.0]. Among 11 patients with an expected sensitivity according to NGS, 3 had partial response (PR), 4 remained stable (SD) while out of 7 potentially resistant patients, 1 had PR and 1 SD.
Addition of vismodegib to temozolomide did not add toxicity but failed to improve PFS-6 in SHH recurrent/refractory medulloblastoma. Prediction of sensitivity to vismodegib needs further refinements.
Report of National Brain Tumor Society Roundtable Workshop on Innovating Brain Tumor Clinical Trials: Building on Lessons Learned from COVID-19 Experience.Neuro-Oncology
On July 24, 2020, a workshop sponsored by the National Brain Tumor Society was held on innovating brain tumor clinical trials based on lessons lear...
Evaluation of mid-term (6-12 months) neurotoxicity in B-cell lymphoma patients treated with CAR T-cells: a prospective cohort study.Neuro-Oncology
CAR T-cells are profoundly changing the standard of care in B-cell malignancies. This new therapeutic class induces a significant number of acute neurotoxicity, but data regarding mid and long-term neurological safety are scarce. We evaluated mid-term neurological safety, with special emphasis on cognitive functions, in a series of adults treated with CAR T-cells.
Patients treated in a single centre with CD19-targeted CAR T-cells for a relapsing B-cell lymphoma were prospectively followed-up by neurologists. Before CAR T-cells infusion, all patients underwent neurological examinations with neuropsychological testing, and filled out questionnaires assessing anxiety, depression and cognitive complains. Patients surviving without tumour progression were re-evaluated similarly, six to 12 months later.
In this prospective cohort of 56 consecutive adult patients treated with CAR T-cells, 27 were eligible for mid-term evaluation (median time 7.6 months). Twelve patients developed an acute and reversible neurotoxicity with median duration time of 5.5 days. In all patients, neurological examination on mid-term evaluation was similar to baseline. In self-assessment questionnaires, 63% of patients reported clinically meaningful anxiety, depression or cognitive difficulties at baseline, a number reduced to 44% at time of mid-term evaluation. On cognitive assessments, no significant deterioration was found when compared to baseline, in any cognitive functions assessed (verbal and visual memory, executive functions, language and praxis), even in patients who developed acute neurotoxicity.
In this cohort of patients treated with CD19-targeted CAR-T cells , we found no evidence for neurological or cognitive toxicity, 6 and 12 months after treatment.
Temozolomide-induced hypermutation is associated with distant recurrence and reduced survival after high-grade transformation of low-grade IDH-mutant gliomas.Neuro-Oncology
Chemotherapy improves overall survival after surgery and radiotherapy for newly diagnosed high-risk IDH-mutant low-grade gliomas, but a proportion of patients treated with temozolomide (TMZ) will develop recurrent tumors with TMZ-induced hypermutation. We aimed to determine the prevalence of TMZ-induced hypermutation at recurrence and prognostic implications.
We sequenced recurrent tumors from 82 patients with initially low-grade IDH-mutant gliomas who underwent re-operation and correlated hypermutation status with grade at recurrence and subsequent clinical outcomes.
Hypermutation was associated with high-grade disease at the time of re-operation (OR 12.0 95% CI 2.5-115.5, p=0.002) and was identified at transformation in 57% of recurrent LGGs previously exposed to TMZ. After anaplastic (grade III) transformation, hypermutation was associated with shorter survival on univariate and multivariate analysis (HR 3.4, 95% CI 1.2-9.9, p=0.024), controlling for tumor grade, subtype, age, and prior radiotherapy. The effect of hypermutation on survival after transformation was validated in an independent, published dataset. Hypermutated (HM) tumors were more likely to develop discontiguous foci of disease in the brain and spine (p=0.003). To estimate the overall incidence of high-grade transformation among low-grade IDH-mutant tumors, data from a phase II trial of TMZ for LGG were analyzed. 8-year transformation-free survival was 53.8% (95% CI 42.8-69.2) and 61% of analyzed transformed cases were HM.
TMZ-induced hypermutation is a common event in transformed LGG previously treated with TMZ, and is associated with worse prognosis and development of discontiguous disease after recurrence. These findings impact tumor classification at recurrence, prognostication, and clinical trial design.
Clinical features, neurologic recovery, and risk factors of post-operative posterior fossa syndrome and delayed recovery: A prospective study.Neuro-Oncology
Posterior fossa syndrome (PFS) is a known consequence of medulloblastoma resection. Our aim was to clinically define PFS, its evolution over time, and ascertain risk factors for its development and poor recovery.
Children with medulloblastoma treated at St Jude Children's Research Hospital from 6/2013-7/2019 received standardized neurological examinations, before and periodically after radiation therapy. Most (98.3%) were enrolled on the ongoing multi-institutional protocol (SJMB12; NCT01878617).
Sixty (34%) of 178 evaluated children had PFS. Forty (23%) had complete mutism (PFS1) and 20 (11%) had diminished speech (PFS2). All children with PFS had severe ataxia and 42.5% of PFS1 had movement disorders. By multivariable analysis, younger age (p=0.0005) and surgery in a low-volume surgery center (p=0.0146) increased PFS risk, while SHH tumors had reduced risk (p=0.0025). Speech and gait returned in PFS1/PFS2 children at a median of 2.3/0.7 and 2.1/1.5 months respectively, however, 12 (44.4%) of 27 PFS1 children with 12-months of follow-up were non-ambulatory at one-year. Movement disorder (p= 0.037) and high ataxia score (p< 0.0001) were associated with delayed speech recovery. Older age (p= 0.0147) and high ataxia score (p< 0.0001) were associated with delayed gait return. Symptoms improved in all children but no child with PFS had normal neurologic examination at a median of 23-months after surgery.
Categorizing PFS into types 1 and 2 has prognostic relevance. Almost half of the children with PFS1 with 12-month follow-up were non-ambulatory. Surgical experience was a major modifiable contributor to the development of PFS.