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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Diversity within the Neurosurgical Oncology Workforce in the United States: A Cross-Sectional Study with Proposed Strategies to Pave the Path Forward.

Neuro-Oncology

Improving and fostering diversity within the neurosurgical workforce has become a high priority. This cross-sectional study aims to provide data on the diversity of neurosurgical oncology faculty (NSOF) in the US.

All 115 neurosurgery (NS) ACGME accredited programs were included in this study. The academic rank, academic and clinical title(s), gender, race, and hiring date of neurosurgical faculty with a primary focus on neurosurgical oncology (NSOF) were recorded. Geographical distribution and "top 10" programs were tabulated according to published data. Underrepresented minorities in medicine (URiM) faculty were identified according to the AAMC definition.

The NSOF workforce constitute 21% of the total NS faculty. Of these, 10.1% are women and 9.9% are URiM (p<0.001). Currently, 58% of neurosurgery programs (NSP) do not have URiM and/or women NSOF. The top 10 ranked NSP, according to Blue Ridge Institute for Medical Research, had a significantly less URiM NSOF (p= 0.019) than non-top 10 ranked programs. There was a decreasing trend in the proportion of URiM at higher academic ranks (p= 0.019). All of the URiM department chairs (3/113)- all men- and 1/3 women department chairs nationwide subspecialized in neurosurgical oncology.

Neurosurgical oncology is a sought-after subspecialty attracting a fifth of neurosurgeons practicing in ACGME-accredited training programs. Changing demographics and the benefits of workforce diversity represent a great opportunity for our field to continue leading inclusion efforts and attracting the best and brightest.

Investigational PET tracers in neuro-oncology-What's on the horizon? A report of the PET/RANO group.

Neuro-Oncology

Many studies in patients with brain tumors evaluating innovative PET tracers have been published in recent years, and the initial results are promi...

Long-term outcomes and late toxicity of adult medulloblastoma treated with combined modality therapy: a contemporary single-institution experience.

Neuro-Oncology

Medulloblastoma (MB) is a rare central nervous system malignancy of adults, with limited contemporary studies to define treatment guidelines and expected late toxicity.

A single-center, retrospective study was conducted of patients age ≥18-years from 1997-2019 with MB and who were treated with postoperative radiotherapy. Late toxicity was defined as a minimum of 18-months from diagnosis. Overall survival (OS) and progression-free survival (PFS) were characterized using Kaplan-Meier and Cox regression analyses.

Fifty-nine patients met criteria, with median age of 25-years (range 18-62y) and median follow-up of 6.5-years (range 0.7-23.1y). At diagnosis, 68% were standard-risk, 88% Chang M0, and 22% with anaplastic histology. Gross total resection was achieved in 75%; median craniospinal irradiation dose was 30.6Gy(relative biological effectiveness [RBE]), median total dose was 54.0Gy(RBE), 80% received proton radiotherapy; 81% received chemotherapy. 5-year PFS and OS were 86.5% and 95.8%, respectively; 10-year PFS and OS were 83.9% and 90.7%, respectively. Anaplastic histology was associated with worse PFS (p=0.04). Among eight recurrences, 25% presented after 5-years. Most common grade ≥2 late toxicities were anxiety/depressive symptoms (30%), motor dysfunction (25%), and ototoxicity (22%). Higher posterior fossa radiation dose was associated with increased risk of late toxicity, including worse cognitive dysfunction (p = 0.05).

Adults with MB have favorable survival outcomes, but late failures and toxicity are not uncommon. Better understanding of prognostic factors, possibly from molecular subtyping, may help to define more personalized treatments for patients with high risk of recurrence and long-term treatment sequelae.

The Combination Treatment of Fosmanogepix and Liposomal Amphotericin B Is Superior to Monotherapy in Treating Experimental Invasive Mold Infections.

Antimicrobial Agents and Chemotherapy

Invasive pulmonary aspergillosis (IPA), invasive mucormycosis (IM), and invasive fusariosis (IF) are associated with high mortality and morbidity. ...

Low-Risk Meningioma: Initial Outcomes from NRG Oncology/RTOG 0539.

Neuro-Oncology

Three- and five-year progression-free survival (PFS) for low-risk meningioma managed with surgery and observation exceeds 90%. Herewith we summarize outcomes for low-risk meningioma patients enrolled on NRG/RTOG 0539.

This phase II trial allocated patients to 1 of 3 groups per WHO grade, recurrence status, and resection extent. Low-risk patients had either gross total (GTR) or subtotal resection (STR) for a newly diagnosed grade 1 meningioma and were observed after surgery. The primary endpoint was 3-year PFS. Adverse events (AEs) were scored using CTCAE version 3.

Among 60 evaluable patients, median follow-up was 9.1 years. The 3, 5, and 10 year rates were 91.4% (95% CI:84.2-98.6), 89.4% (95% CI:81.3-97.5), 85.0% (95% CI:75.3-94.7) for PFS and 98.3% (95% CI:94.9-100), 98.3%, (95% CI:94.9-100), 93.8% (95% CI:87.0-100) for overall survival (OS), respectively. With centrally confirmed GTR, 3/5/10y PFS and OS rates were 94.3/94.3/87.6% and 97.1/97.1/90.4%. With STR, 3/5/10y PFS rates were 83.1/72.7/72.7% and 10y OS 100%. Five patients reported 1 grade 3, 4 grade 2, and 5 grade 1 adverse events. There were no grade 4 or 5 adverse events.

These results prospectively validate high PFS and OS for low-risk meningioma managed surgically but raise questions regarding optimal management following STR, a subcohort that could potentially benefit from adjuvant therapy.

Management of Neurofibromatosis Type 1-Associated Plexiform Neurofibromas.

Neuro-Oncology

Plexiform Neurofibromas (PN) are a common manifestation of the genetic disorder neurofibromatosis type 1 (NF1). These benign nerve sheath tumors of...

Phase II study of alisertib as a single agent for treating recurrent or progressive atypical teratoid/rhabdoid tumor.

Neuro-Oncology

Recurrent atypical teratoid/rhabdoid tumor (AT/RT) is, most often, a fatal pediatric malignancy with limited curative options.

We conducted a phase II study of Aurora kinase A inhibitor alisertib in patients aged <22 years with recurrent AT/RT. Patients received alisertib once daily (80 mg/m 2 as enteric-coated tablets or 60 mg/m 2 as liquid formulation) on Days 1-7 of a 21-day cycle until progressive disease (PD) occurred. Alisertib plasma concentrations were measured in cycle 1 on Days 1 (single dose) and 7 (steady state) and analyzed with noncompartmental pharmacokinetics. Trial efficacy end point was ≥10 participants with stable disease (SD) or better at 12 weeks.

SD (n=8) and partial response (PR) (n=1) were observed among 30 evaluable patients. Progression-free survival (PFS) was 30.0% ± 7.9% at 6 months and 13.3% ± 5.6% at 1 year. One-year overall survival (OS) was 36.7% ± 8.4%. Two patients continued treatment for >12 months. PFS did not differ by AT/RT molecular groups. Neutropenia was the most common adverse effect (n=23/30, 77%). The 22 patients who received liquid formulation had a higher mean maximum concentration (Cmax) of 10.1 ± 3.0 µM and faster time to Cmax (Tmax = 1.2 ± 0.7 h) than those who received tablets (Cmax = 5.7 ± 2.4 µM, Tmax = 3.4 ± 1.4 h).

Although the study did not meet pre-determined efficacy end point, single agent alisertib was well tolerated by children with recurrent AT/RT, and SD or PR was observed in approximately a third of the patients.

Comparative Transcriptomics Reveal Possible Mechanisms of Amphotericin B Resistance in Candida auris.

Antimicrobial Agents and Chemotherapy

Candida auris is an emerging multidrug-resistant human fungal pathogen often refractory to treatment by all classes of antifungal drugs. Amphoteric...

Olutasidenib (FT-2102) in patients with relapsed or refractory IDH1-mutant glioma: a multicenter, open-label, phase 1b/2 trial.

Neuro-Oncology

Olutasidenib (FT2102) is a highly potent, orally bioavailable, brain-penetrant and selective inhibitor of mutant isocitrate dehydrogenase 1 (IDH1). The aim of the study was to determine the safety and clinical activity of olutasidenib in patients with relapsed/refractory gliomas harboring an IDH1  R132X mutation.

This was an open-label, multicenter, non-randomized, phase 1b/2 clinical trial. Eligible patients (≥18 years) had histologically confirmed IDH1  R132Xmutated glioma that relapsed or progressed on or following standard therapy and had measurable disease. Patients received olutasidenib, 150 mg orally twice daily (BID) in continuous 28-day cycles. The primary endpoints were dose-limiting toxicities (DLTs) (cycle 1) and safety in phase 1 and objective response rate using the Modified Response Assessment in Neuro-Oncology criteria in phase 2.

Twenty-six patients were enrolled and followed for a median 15.1 months (7.3‒19.4). No DLTs were observed in the single-agent glioma cohort and the pharmacokinetic relationship supported olutasidenib 150 mg BID as the recommended phase 2 dose. In the response-evaluable population, disease control rate (objective response plus stable disease) was 48%. Two (8%) patients demonstrated a best response of partial response and eight (32%) had stable disease for at least 4 months. Grade 3‒4 adverse events (≥10%) included alanine aminotransferase increased and aspartate aminotransferase increased (three [12%], each).

Olutasidenib 150 mg BID was well tolerated in patients with relapsed/refractory gliomas harboring an IDH1  R132X mutation and demonstrated preliminary evidence of clinical activity in this heavily pretreated population.

Trastuzumab Deruxtecan in Patients with Central Nervous System Involvement from HER2-Positive Breast Cancer: The DEBBRAH Trial.

Neuro-Oncology

Trastuzumab deruxtecan (T-DXd) has shown durable antitumor activity in pretreated patients with HER2-positive advanced breast cancer (ABC), but its efficacy has not yet been evaluated in patients with active brain metastases (BMs). DEBBRAH aims to assess T-DXd in patients with HER2-positive or HER2-low ABC and central nervous system involvement.

This ongoing, five-cohort, phase II study (NCT04420598) enrolled patients with pretreated HER2-positive or HER2-low ABC with stable, untreated, or progressing BMs and/or leptomeningeal carcinomatosis. Here, we report findings from HER2-positive ABC patients with non-progressing BMs after local therapy (n=8; cohort 1), asymptomatic untreated BMs (n=4; cohort 2), or progressing BMs after local therapy (n=9; cohort 3). Patients received 5.4 mg/kg T-DXd intravenously once every 21 days. The primary endpoint was 16-week progression-free survival (PFS) for cohort 1 and intracranial overall response rate (ORR-IC) for cohorts 2 and 3.

As of October 20, 2021, 21 patients received T-DXd. In cohort 1, 16-week PFS rate was 87.5% (95%CI, 47.3-99.7; P<.001). ORR-IC was 50.0% (95%CI, 6.7-93.2) in cohort 2 and 44.4% (95%CI, 13.7-78.8; P<.001) in cohort 3. Overall, the ORR-IC in patients with active BMs was 46.2% (95%CI, 19.2-74.9). Among patients with measurable intracranial or extracranial lesions at baseline, the ORR was 66.7% (12 out of 18 patients; 95%CI, 41.0-86.7), 80.0% (95%CI, 28.4-99.5) in cohort 1, 50.0% (95%CI, 6.7-93.2) in cohort 2, and 66.7% (95%CI, 29.9-92.5) in cohort 3. All responders had partial responses. The most common adverse events included fatigue (52.4%; 4.8% grade≥3), nausea (42.9%; 0% grade≥3), neutropenia (28.6%; 19% grade≥3), and constipation (28.6%; 0% grade≥3). Two (9.5%) patients suffered grade 1 interstitial lung disease/pneumonitis.

T-DXd showed intracranial activity with manageable toxicity and maintained quality of life in pretreated HER2-positive ABC patients with stable, untreated, or progressing BMs. Further studies are needed to validate these results in larger cohorts.

Comparative single-cell RNA-sequencing profiling of BMP4-treated primary glioma cultures reveals therapeutic markers.

Neuro-Oncology

Glioblastoma (GBM) is the most aggressive primary brain tumor. Its cellular composition is very heterogeneous, with cells exhibiting stem-cell characteristics (GSCs) that co-determine therapy resistance and tumor recurrence. Bone Morphogenetic Protein (BMP)-4 promotes astroglial and suppresses oligodendrocyte differentiation in GSCs, processes associated with superior patient prognosis. We characterized variability in cell viability of patient-derived GBM cultures in response to BMP4 and, based on single-cell transcriptome profiling, propose predictive positive and early-response markers for sensitivity to BMP4.

Cell viability was assessed in 17 BMP4-treated patient-derived GBM cultures. In two cultures, one highly sensitive to BMP4 (high therapeutic efficacy) and one with low sensitivity, response to treatment with BMP4 was characterized. We applied single-cell RNA-sequencing, analyzed the relative abundance of cell clusters, searched for and identified the aforementioned two marker types, and validated these results in all 17 cultures.

High variation in cell viability was observed after treatment with BMP4. In three cultures with highest sensitivity for BMP4, a substantial new cell subpopulation formed. These cells displayed decreased cell proliferation and increased apoptosis. Neuronal differentiation was reduced most in cultures with little sensitivity for BMP4. OLIG1/2 levels were found predictive for high sensitivity to BMP4. Activation of ribosomal translation (RPL27A, RPS27) was upregulated within one day in cultures that were very sensitive to BMP4.

The changes in composition of patient-derived GBM cultures obtained after treatment with BMP4 correlate with treatment efficacy. OLIG1/2 expression can predict this efficacy, and upregulation of RPL27A and RPS27 are useful early-response markers.

Activation of Hedgehog signaling by the oncogenic RELA fusion reveals a primary cilia-dependent vulnerability in Supratentorial Ependymoma.

Neuro-Oncology

Supratentorial RELA fusion (ST-RELA) ependymomas (EPNs) are resistant tumors without an approved chemotherapeutic treatment. Unfortunately, the molecular mechanisms that leads to chemoresistance traits of ST-RELA remains elusive. The aim of this study was to assess RELA fusion-dependent signaling modules, specifically the role of the Hedgehog (Hh) pathway as a novel targetable vulnerability in ST-RELA.

Gene expression was analyzed in EPN from patient cohorts, by microarray, RNA-seq, qRT-PCR, and scRNA-seq. Inhibitors against Smoothened (SMO) (Sonidegib) and Aurora-kinase A (AURKA) (Alisertib) were evaluated. Protein expression, primary cilia formation, and drug effects were assessed by immunoblot, immunofluorescence and immunohistochemistry.

Hh components were selectively overexpressed in EPNs induced by the RELA fusion. Single-cell analysis showed that the Hh signature was primarily confined to undifferentiated, stem-like cell subpopulations. Sonidegib exhibited potent growth-inhibitory effects on ST-RELA cells, suggesting a key role for active Hh signaling; importantly, the effect of Sonidegib was reversed by primary cilia loss. We thus tested the effect of AURKA inhibition by Alisertib, to induce cilia stabilization/reassembly. Strikingly, Alisertib rescued ciliogenesis and synergized with Sonidegib in killing ST-RELA cells. Using a xenograft model, we show that cilia loss is a mechanism for acquiring resistance to the inhibitory effect of Sonidegib. However, Alisertib fails to rescue cilia and highlights the need for other strategies to promote cilia reassembly, for treating ST-RELA tumors.

Our study reveals a crucial role for the Hh pathway in ST-RELA tumor growth, and suggests that rescue of primary cilia represents a vulnerability of the ST-RELA EPNs.