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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Varied presentations of primary cutaneous lymphoma: A case series from a tertiary care center in South India.

Indian Journal of Cancer

Recent studies indicate an upsurge of primary cutaneous lymphoma (PCL) in the Indian population. Of late, we too have come across varied presentations of PCL in relatively younger individuals. Hence, we decided to study the clinical and immunohistological profile of patients with PCL in our department.

All cases diagnosed as PCL from October 2016 to October 2019 were included. Clinical details, complete blood count, peripheral smear, imaging, histopathology, and immunohistochemistry of skin specimens were analyzed. Lymph node biopsy and bone marrow studies were done in most cases. Human T lymphotropic virus-1 (HTLV1) serology was done in 10 cases.

Of the 24 patients with PCL, 12 were below 50 years of age. Twenty-three patients (95.8%) had T-cell lymphoma and only one had B-cell PCL. Mycosis fungoides (MF) (n = 17; 71%) was the most common type of PCL. There were two (8.3%) cases each of adult T-cell lymphoma/leukemia (ATLL) and Sezary syndrome. MF had varied clinical morphology at presentation and variable clinical outcomes. Both cases of ATLL had features of immunosuppression in the form of infective dermatoses.

We observed an increased proportion of T-cell type of PCL, with the age of onset being relatively early. HTLV-1 positivity was noted in three out of the 10 cases tested. More studies are needed to determine the factors responsible for the younger age of onset of PCL and the role of HTLV-1 infection in the development of PCL.

Very long-term outcomes of pediatric patients treated for optic pathway gliomas: A longitudinal cohort study.

Neuro-Oncology

Optic pathway gliomas (OPG) represent 5% of childhood brain tumors. Successive relapses lead to multiple treatments exposing to late complications.

We included patients treated at Gustave Roussy (GR) between 01.1980 and 12.2015 for OPG, before 18 years-old and alive at 5 years from diagnosis. Mortality and physical health conditions data were extracted from medical data files and updated thanks to the GR long-term follow-up program and French national mortality registry for patients included in the French Childhood Cancer Survivor Study.

We included 182 5y-OPG-childhood survivors in the analysis (sex-ratio M/F 0.8, 35% with NF1). With a median follow-up of 17.2y (range=5-41), we registered 82 relapses, 9 second malignancies and 15 deaths as first events after 5 years, resulting in 20-y conditional overall survival (C-OS) and late events-free survival (LEFS) of 79.9% (95%CI=71-86) and 43.5% (95%CI=36-51) respectively. NF1 (Hazard ratio HR=3, 95%CI=1.4-6.8), hypothalamic involvement (HR=3.2, 95%CI=1.4-7.3), and radiotherapy (HR=2.8, 95%CI=1.1-6.7) were significantly associated with C-OS in multivariable analyses. Ninety-five percent of 5y-OPG survivors suffered from any health condition, especially visual acuity "<1/10" (n=109), pituitary deficiency (n=106) and neurocognitive impairment (n=89). NF1 (HR 2.1) was associated with precocious puberty. With a median time post diagnosis of 4.2 years, 33 cerebrovascular events were observed in 21 patients.

Late relapses, second malignancies and cerebrovascular diseases are severe late events resulting in premature mortality. Morbidity is high and needing after-cancer care to improve quality of life. Risk factors could be considered to better stratify long-term follow-up.

Comprehensive analysis of MYB/MYBL1-altered pediatric-type diffuse low-grade glioma.

Neuro-Oncology

Pediatric-type diffuse low-grade gliomas (pLGG) harboring recurrent genetic alterations involving MYB or MYBL1 are closely related tumors. Detailed treatment and outcome data of large cohorts are still limited. This study aimed to comprehensively evaluate pLGG with these alterations to define optimal therapeutic strategies.

We retrospectively reviewed details of pLGG with MYB or MYBL1 alterations from patients treated or referred for pathologic review at St. Jude Children's Research Hospital. Tumor specimens were centrally reviewed, and clinical data were collated.

Thirty-three patients (18 male; median age, 5 y) were identified. Two tumors had MYBL1 alterations; 31 had MYB alterations, MYB::QKI fusion being the most common (n=10, 30%). Most tumors were in the cerebral hemispheres (n=22, 67%). Two patients (6%) had metastasis at diagnosis. The median follow-up was 6.1 years. The 5-year event-free survival (EFS) rate was 81.3±8.3%; the 5-year overall survival (OS) rate was 96.4±4.1%. Patients receiving a near-total or gross-total resection had a 5-year EFS of 100%; those receiving a biopsy or subtotal resection had a 5-year EFS rate of 56.6±15.2% (p<0.01). No difference in EFS was observed based on location, histology, or molecular alterations. However, the tumors that progressed or metastasized may have distinct methylation profiles with evidence of activation of the MAPK and PI3K/AKT/mTOR pathways.

pLGG with MYB/MYBL1 alterations have good outcomes. Our findings suggest that surgical resectability is a crucial determinant of EFS. Further characterization is required to identify optimal treatment strategies for progressive tumors.

Challenges, Limitations and Pitfalls of PET and Advanced MRI in Patients with Brain Tumors - A Report of the PET/RANO Group.

Neuro-Oncology

Brain tumor diagnostics have significantly evolved with the use of PET and advanced MRI techniques. In addition to anatomical MRI, these modalities...

Executive Summary of the American Radium Society Appropriate Use Criteria for Brain Metastases in EGFR-mutated and ALK-fusion Non-Small Cell Lung Cancer.

Neuro-Oncology

The American Radium Society (ARS) Central Nervous System (CNS) committee reviewed literature on epidermal growth factor receptor mutated (EGFRm) and ALK-fusion (ALK+) tyrosine kinase inhibitors (TKIs) for the treatment of brain metastases (BrMs) from non-small cell lung cancers (NSCLC) to generate appropriate use guidelines addressing use of TKIs in conjunction with or in lieu of radiotherapy (RT).

The panel developed three key questions to guide systematic review: can radiotherapy be deferred in patients receiving EGFR or ALK TKIs at 1) diagnosis or 2) recurrence? Should TKI be administered concurrently with RT (3)? Two literature searches were performed (May 2019 and December 2023). The panel developed 8 model cases and voted on treatment options using a 9-point scale, with 1-3, 4-6 and 7-9 corresponding to usually not appropriate, may be appropriate, and usually appropriate (respectively), per the UCLA/RAND Appropriateness Method.

Consensus was achieved in only 4 treatment scenarios, all consistent with existing ARS-AUC guidelines for multiple BrM. The panel did not reach consensus that RT can be appropriately deferred in patients with BrM receiving CNS penetrant ALK or EGFR TKIs, though median scores indicated deferral may be appropriate under most circumstances. Whole brain RT with concurrent TKI generated broad disagreement except in cases with 2-4 BrM, where it was considered usually not appropriate.

We identified no definitive studies dictating optimal sequencing of TKIs and RT for EGFRm and ALK+ BrM. Until such studies are completed, the committee hopes these cases guide decision-making in this complex clinical space.

LncRNA LUCAT1 Promotes Glioblastoma Progression by Enhancing HIF1α Activity.

Neuro-Oncology

Hypoxia is associated with poor prognosis in many cancers including glioblastoma (GBM). Glioma stem-like cells (GSCs) often reside in hypoxic regions and serve as reservoirs for disease progression. Long non-coding RNAs (lncRNAs) have been implicated in GBM. However, the lncRNAs that modulate GSC adaptations to hypoxia are poorly understood. Identification of these lncRNAs may provide new therapeutic strategies to target GSCs under hypoxia.

lncRNAs induced by hypoxia in GSCs were identified by RNAseq. LUCAT1 expression was assessed by qPCR, RNAseq, Northern blot, single molecule FISH in GSCs, and interrogated in IvyGAP, TCGA, and CGGA databases. LUCAT1 was depleted by shRNA, CRISPR/Cas9, and CRISPR/Cas13d. RNAseq, Western blot, immunohistochemistry, co-IP, ChIP, ChIPseq, RNA immunoprecipitation, and proximity ligation assay were performed to investigate mechanisms of action of LUCAT1. GSC viability, limiting dilution assay, and tumorigenic potential in orthotopic GBM xenograft models were performed to assess the functional consequences of depleting LUCAT1.

A new isoform of Lucat1 is induced by HIF1α and NRF2 in GSCs under hypoxia. LUCAT1 is highly expressed in hypoxic regions in GBM. Mechanistically, LUCAT1 formed a complex with HIF1α and its co-activator CBP to regulate HIF1α target gene expression and GSC adaptation to hypoxia. Depletion of LUCAT1 impaired GSC self-renewal. Silencing LUCAT1 decreased tumor growth and prolonged mouse survival in GBM xenograft models.

A HIF1α-LUCAT1 axis forms a positive feedback loop to amplify HIF1α signaling in GSCs under hypoxia. LUCAT1 promotes GSC self-renewal and GBM tumor growth. LUCAT1 is a potential therapeutic target in GBM.

Effectiveness of a smartphone-based virtual reality intervention on balance and functional mobility in children with acute lymphoblastic leukemia: A pre-post experimental study.

Indian Journal of Cancer

The odds of survival of children with acute lymphoblastic leukemia (ALL) has increased markedly owing to a better understanding of pathogenesis, adoption of risk stratification therapy, and availability of newer therapeutic agents. These drugs, however, may affect balance and functional mobility, leading to activity restrictions. Virtual reality (VR) is a promising rehabilitation program for motor difficulties. The study, therefore, aimed to determine the effect of a smartphone-based VR intervention on balance and functional mobility in children with ALL.

The pre-post experimental study included 32 children with ALL between 4 and 18 years of age. They received smartphone-based VR intervention every day for a period of 2 weeks, with each session lasting for 30 minutes. Each session included five VR games that were played by the child for 5 minutes each, with 1 minute rest between the games. Pre- and post-intervention, balance and functional mobility were evaluated using the balance subset of Bruininks Oseretsky Test of Motor Proficiency, second edition (BOT-2) and the Timed Up and Go (TUG) test, respectively.

Children with ALL demonstrated a significant improvement in balance post-intervention, with a mean difference of 2.22 ± 1.75 (P < 0.0001). Functional mobility improved with a mean difference of 1.12 ± 1.09 (P < 0.0001). There was an improvement of 8.04% and 11.04% in balance and functional mobility, respectively.

The study concluded that a 2-week smartphone-based VR intervention is effective in improving balance and functional mobility in children with ALL.

A young boy with a rare tumor presenting as an upper gastrointestinal bleed.

Indian Journal of Cancer

We describe an interesting upper gastrointestinal endoscopy image of a mass seen in the stomach of a 19-year-old boy who presented to us with an up...

3D volume growth rate evaluation in the EORTC-BTG-1320 clinical trial for recurrent WHO grade 2 and 3 meningiomas.

Neuro-Oncology

We previously reported that tumor 3D volume growth rate (3DVGR) classification could help in the assessment of drug activity in patients with meningioma using three main classes and a total of five subclasses: class 1: decrease; 2: stabilization or severe slowdown; 3: progression. The EORTC-BTG-1320 clinical trial was a randomized phase II trial evaluating the efficacy of trabectedin for recurrent WHO 2 or 3 meningioma. Our objective was to evaluate the discriminative value of 3DVGR classification in the EORTC-BTG-1320.

All patients with at least one available MRI before trial inclusion were included. 3D volume was evaluated on consecutive MRI until progression. 2D imaging response was centrally assessed by MRI modified Macdonald criteria. Clinical benefit was defined as neurological or functional status improvement or steroid decrease or discontinuation.

Sixteen patients with a median age of 58.5 years were included. Best 3DVGR classes were: 1, 2A, 3A and 3B in 2 (16.7%), 4 (33.3%), 2 (16.7%) and 4 (33.3%) patients, respectively. All patients with progression-free survival longer than 6 months had best 3DVGR class 1 or 2. 3DVGR classes 1 and 2 (combined) had a median overall survival of 34.7 months versus 7.2 months for class 3 (p=0.061). All class 1 patients (2/2), 75% of class 2 patients (3/4) and only 10% of class 3 patients (1/10) had clinical benefit.

Tumor 3DVGR classification may be helpful to identify early signals of treatment activity in meningioma clinical trials.

ACTION: A randomized phase 3 study of ONC201 (dordaviprone) in patients with newly diagnosed H3 K27M-mutant diffuse glioma.

Neuro-Oncology

H3 K27M-mutant diffuse glioma primarily affects children and young adults, is associated with a poor prognosis, and no effective systemic therapy is currently available. ONC201 (dordaviprone) has previously demonstrated efficacy in patients with recurrent disease. This phase 3 trial evaluates ONC201 in patients with newly diagnosed H3 K27M-mutant glioma.

ACTION (NCT05580562) is a randomized, double-blind, placebo-controlled, parallel-group, international Phase 3 study of ONC201 in newly diagnosed H3 K27M-mutant diffuse glioma. Patients who have completed standard frontline radiotherapy are randomized 1:1:1 to receive placebo, once-weekly dordaviprone, or twice-weekly dordaviprone on two consecutive days. Primary efficacy endpoints are overall survival (OS) and progression-free survival (PFS); PFS is assessed by response assessment in neuro-oncology-high grade glioma criteria (RANO-HGG) by blind independent central review. Secondary objectives include safety, additional efficacy endpoints, clinical benefit, and quality of life. Eligible patients have histologically confirmed H3 K27M-mutant diffuse glioma, a Karnofsky/Lansky performance status ≥70, and completed first-line radiotherapy. Eligibility is not restricted by age; however, patients must be ≥10 kg at time of randomization. Patients with a primary spinal tumor, diffuse intrinsic pontine glioma, leptomeningeal disease, or cerebrospinal fluid dissemination are not eligible. ACTION is currently enrolling in multiple international sites.

HIF1α/ATF3 partake PGK1 K191/K192 succinylation by modulating P4HA1/succinate signaling in glioblastoma.

Neuro-Oncology

Hypoxia is a pathological hallmark in most cancers, including glioblastoma (GBM). Hypoxic signaling activation and posttranslational modification (PTM) of oncogenic proteins are well-studied in cancers. Accumulating studies indicate glycolytic enzyme PGK1 plays a crucial role in tumorigenesis, yet the underlying mechanisms remain unknown.

We first used ChIP assays to uncover the crosstalk between HIF1α and ATF3 and their roles in P4HA1 regulation. Protein degradation analysis, LC-MS/MS, and in vitro succinate production assays were performed to examine the effect of protein succinylation on GBM pathology. Seahorse assay measured the effects of PGK1 succinylation at K191/192 or its mutants on glucose metabolism. We utilized an in vivo intracranial mouse model for biochemical studies to elucidate the impact of ATF3 and P4HA1 on aerobic glycolysis and the tumor immune microenvironment.

We demonstrated that HIF1α and ATF3 positively and negatively regulate the transcription of P4HA1, respectively, leading to an increased succinate production and increased activation of HIF1α signaling. P4HA1 expression elevated the succinate concentration, resulting in the enhanced succinylation of PGK1 at the K191 and K192 sites. Inhibition of proteasomal degradation of PGK1 by succinylation significantly increased aerobic glycolysis to generate lactate. Furthermore, ATF3 overexpression and P4HA1 knockdown reduced succinate and lactate levels in GBM cells, inhibiting immune responses and tumor growth.

Together, our study demonstrates that HIF1α/ATF3 participated in P4HA1/succinate signaling, which is the major regulator of succinate biosynthesis and PGK1 succinylation at K191 and K192 sites in GBM. The P4HA1/succinate pathway might be a novel and promising target for aerobic glycolysis in GBM.

The role of radiotherapy in immunotherapy strategies in the central nervous system.

Neuro-Oncology

The clinical efficacy and relative tolerability of adverse effects of immune checkpoint immunotherapy have led to its increasingly routine use in t...