Chinese clinical oncology最新文献

Background: Awake craniotomy (AC) allows intraoperative brain mapping (ioBM) for maximum lesion resection while monitoring and preserving neurological function. Conventionally, language, visuospatial assessment, and motor functions are mapped, while assessment of executive functions (EFs) is uncommon. Impaired EF may lead to occupational, personal, and social limitations, thus, a compromised quality of life.

Methods: A comprehensive literature search was conducted through Scopus, Medline, and Cochrane Library using a pre-defined search strategy. Articles were selected after duplicates removal, initial screening, and full-text assessment. The demographic details, ioBM techniques, intraoperative tasks, and their assessments, the extent of resection (EOR), post-op EF and neurocognitive status, and feasibility and potential adverse effects of the procedure were reviewed. The correlations of tumor locations with intraoperative EF deficits were also assessed.

Results: A total of 13 studies with intraoperative EF assessment of 351 patients were reviewed. Awake-asleep-awake protocol was most commonly used. Most studies performed ioBM using bipolar stimulation, with a frequency of 60 Hz, pulse durations ranging 1-2 ms, and intensity ranging 2-6 mA. Cognitive function was monitored with the Stroop task, spatial-2 back test, line-bisection test, trail-making-task, and digit-span tests. All studies reported similar or better EOR in patients with ioBM for EF. When comparing the neuropsychological outcomes of patients with ioBM of EF to those without it, all studies reported significantly better EF preservation in ioBM groups. Most authors reported EF mapping as a feasible tool to obtain satisfactory outcomes. Adverse effects included intraoperative seizures which were easily controlled.

Conclusions: AC with ioBM of EF is a safe, effective, and feasible technique that allows satisfactory EOR and improved neurocognitive outcomes with minimal adverse effects.

Background: Blood loss is an important consideration in metastatic spine tumour surgery (MSTS). Allogeneic blood transfusion (ABT) is the current standard of blood replenishment for MSTS despite known complications. Salvaged blood transfusion (SBT) through intraoperative cell salvage addresses the majority of complications related to ABT. However, the use of SBT in MSTS still remains controversial. We aim to conduct a prospective propensity-score (PS) matched analysis to evaluate the long-term clinical outcomes of intraoperative cell salvage (IOCS) in MSTS.

Methods: Our study included 98 patients who underwent MSTS from 2014-2017. A PS matched cohort was created using the relevant and available predictors of treatment assignment and outcomes of interest. Clinical outcomes consisting of overall survival (OS), as well tumour progression (TP) that was evaluated using RECIST (v1.1) were compared in the matched cohort.

Results: Our study had a total of 98 patients with a mean age of 60 years old. A total of 33 patients received SBT. Overall median blood loss was 600 mL [interquartile range (IQR): 300-1,000 mL] and overall median blood transfusion (BT) was 620 mL (IQR: 110-1,600 mL). Group PS matching included 30 patients who received ABT and 28 patients who received SBT. There was also no significant difference between the OS of patients who underwent ABT or SBT (P=0.19). SBT did not show any significant increase in 4-year tumour progression [PS matched hazard ratio (HR) 3.659; 95% confidence interval (CI): 0.346-38.7; P=0.28].

Conclusions: SBT has been shown to have similar clinical outcomes to that of ABT in patients undergoing MSTS, with potential benefits of avoiding complications and costs of ABT. This will be the first long-term PS matched analysis to report on the clinical outcomes of SBT and affirms the clinical role of SBT in MSTS today.

Background: Congenital infantile brainstem high-grade gliomas (HGGs) are extremely rare. Given the limited literature characterizing this disease, management of these tumors remains challenging. Brainstem HGGs are generally associated with extremely poor prognosis. Limited reports of spontaneous regression of radiologically diagnosed infantile brainstem tumors exist in published literature. We aim to report a unique case of spontaneous regression of a rare infantile HGG brainstem glioma and to review the current literature.

Case description: In this case report, we document the first histologically proven congenital brainstem HGG with molecular characteristics that did not fall under any previously well-defined pediatric brain tumor classifications. The patient is a full-term female delivered uneventfully via normal vaginal delivery with unremarkable antenatal and fetal abnormality scans. Neuroimaging revealed a relatively focal dorsally located pontomedullary tumor. She subsequently underwent suboccipital craniotomy and biopsy of the lesion. Formal histopathology revealed features consistent with HGG. Methylation profiling classified the neoplasm closest to either "glioblastoma, IDH wildtype, subclass midline" or "pediatric type diffuse HGG". The patient's post-operative recovery was uneventful. The initial plan was to consider safe surgical debulking when the child reaches 6 months of age. However, subsequent neuroimaging revealed spontaneous tumor regression after biopsy, up to 2 years of age. A review of the literature was also performed to identify previously reported infantile brainstem HGGs and the management for such tumors.

Conclusions: Our case highlights the value of performing histopathological confirmation to guide management and the possible existence of a subcategory of a congenital brainstem HGG with better prognosis.

Background: Boron neutron capture therapy (BNCT) is a unique cancer treatment modality that enables precise targeting of tumors at the cellular level. Based on the success observed in nuclear reactors, BNCT now holds promise as a therapeutic approach for treating invasive brain tumors or head and neck cancers. Metastatic spinal tumors have been treated with multidisciplinary interventions such as surgical resection and radiation therapy. Despite recent advantages of radiation therapy, it remains challenging to achieve better quality of life and activity of daily living. The purpose of this study was to evaluate the efficacy and safety of BNCT in metastatic spinal tumor using a mouse model.

Methods: For the in vitro, neutron and photon irradiation was applied to A549 human lung adenocarcinoma cells. The cells were irradiated neutrons with or without p-boronophenylalanine (BPA) 10 µg Boron/mL for a 24-h exposure before neutron irradiation. The difference of biological effect between neutrons and photons was evaluated by colony forming assay. For in vivo, the tumor-bearing mice were intravenously administered BPA (250 mg/kg), followed by measuring biodistribution of boron using inductively coupled plasma atomic emission spectroscopy (ICP-AES). For in vivo BNCT, the mice were randomly assigned to untreated (n=10), neutron irradiation only (n=9), and BNCT groups (n=10). Overall survival and hindlimb function were analyzed. Histopathological examination was also performed to assess the influences of neutron irradiation.

Results: Neutron irradiation showed a stronger cell-killing effect than that exhibited by photon irradiation in vitro. For in vivo biodistribution, the highest boron accumulation in the tumor was seen at 2.5-h time point (10.5 µg B/g), with a tumor to normal spinal cord and blood ratios were 3.6 and 2.9, respectively. For the in vivo BNCT, BNCT had significantly prolonged survival (vs. untreated, P=0.002; vs. neutron only, P=0.01, respectively, log-rank test) and preserved mice hindlimb function compared to the other groups (vs. untreated, P<0.001; vs. neutron only, P=0.005, respectively, MANOVA). No adverse events and apparent histopathological changes were observed among three groups.

Conclusions: These findings indicate that BNCT may represent a novel therapeutic option in the management of metastatic spinal tumors.

Background: Glioblastoma cells preferentially use de-novo purine synthesis pathway, whereas normal brain prefers salvage pathway. Mycophenolate mofetil (MMF), a commonly used oral immunosuppressant that inhibits inosine-5'-monophosphate dehydrogenase (IMPDH), a key enzyme in the de-novo purine pathway. Pre-clinical suggested MMF can improve radiation and temozolomide efficacy in glioblastoma which led to this phase 0/1 trial (NCT04477200) to assess MMF's tolerability with chemoradiation in glioblastoma, mycophenolic acid accumulation, and purine synthesis inhibition in tumor.

Methods: In the phase 0 study, eight recurrent glioblastoma patients received MMF at doses ranging 500-2,000 mg BID for 1-week before surgery. The tissues were analyzed using mass spectrometry for drug accumulation and purine synthesis inhibition. In the phase 1 study, adult patients were given MMF starting at 1,000 mg orally (PO) twice daily (BID), with the possible dose ranging 500-2,000 PO BID. Nineteen recurrent glioblastoma patients (target N=30) received MMF 1-week prior to and concurrently with re-irradiation (40.5 Gy). Thirty newly diagnosed glioblastoma patients received MMF 1-week prior to and concurrently with chemoradiation, followed by MMF 1-day before and during 5 days of each adjuvant temozolomide cycle.

Results: Both enhancing and non-enhancing tumors from phase 0 subjects yielded >1 µM active drug metabolite, and the guanosine triphosphate: inosine monophosphate ratio was decreased by 75% in enhancing tumors in MMF-treated patients compared to untreated controls (P=0.009), indicating effective target engagement and inhibition of purine synthesis. In the phase 1 study, no dose-limiting toxicities (DLTs) were observed at the interim analysis at MMF 1,000-1,500 mg BID combined with chemoradiation. At 2,000 mg BID, there was no DLT combined with temozolomide alone, however, there were four DLTs noted (hemiparesis, cognitive disturbance, fatigue, thrombocytopenia) when combined with radiotherapy and temozolomide together, though all were reversible. Interim median overall survival in recurrent phase 1 is 15.6 months, and not reached yet in newly diagnosed phase 1.

Conclusions: MMF with chemoradiation has been reasonably well tolerated and showed promising evidence of brain tumor target engagement and drug accumulation. This study led to a recommended phase 2 dose of MMF 1,500 mg BID and will provide a preliminary efficacy estimate for a randomized phase 2/3 trial through the Alliance for Clinical Trials in Oncology.

Background: Giant aneurysms, comprising 3-5% of all intracranial aneurysms, pose a considerable challenge due to their heterogeneity and complex vascular anatomy. Defined as aneurysms exceeding 2.5 cm in diameter, they often develop intraluminal thrombosis. Despite advancements in neurosurgical techniques, managing giant aneurysms remains complex and highly individualized. Thrombotic giant aneurysms are particularly problematic due to their size and thrombosis potential. This case report is unique as it presents the first documented instance of recurrent artery of Heubner (RAH) infarction following surgical resection of a giant thrombotic aneurysm.

Case description: A 53-year-old man with no prior systemic presented to our emergency department due to progressive left-sided weakness and slurred speech. Magnetic resonance imaging (MRI) of brain revealed a thrombotic giant intracranial aneurysm on right anterior cerebral artery (ACA). Surgical resection was performed using a right pterional craniotomy. During surgery, the aneurysm was confirmed to be completely thrombosed and was excised. Postoperatively, the patient experienced a generalized seizure and was intubated. Brain MRI revealed a new infarction in the RAH territory. Despite initial complications, the patient showed significant recovery with rehabilitation, regaining most motor functions by the 6-month follow-up.

Conclusions: This case emphasizes the critical importance of comprehensive preoperative evaluation, particularly in assessing small perforating branches and collateral circulation. It highlights the challenges in managing giant aneurysms and the necessity of anticipating potential postoperative complications. This report adds valuable insights into the clinical management and surgical planning for giant aneurysms, particularly those involving the ACA and RAH.

Background: For fluorescence-guided neurosurgery, 5-aminolevulinic acid (5-ALA) is widely used for intraoperative tumor visualization. We quantified the brightness of 5-ALA by Image J and report the pathological results of glioma, and non-tumor lesions.

Methods: From 2019 to 2023, we investigated 27 high-grade glioma patients who underwent surgery with 5-ALA. Twenty-three cases of glioblastoma (GBM) and four cases of anaplastic astrocytoma (AA) were examined. The pathological diagnosis was based on the classification of World Health Organization (WHO) 2016. The 5-ALA was administered before surgery, and the 5-ALA brightness was quantified. Other than high-grade glioma, four low-grade gliomas (LGGs), two radiation necrosis, and one inflammation patients were evaluated by Image J.

Results: In GBM, the mean brightness was 134.5±65.4, except for one negative case. AA showed the mean brightness with 180.5±51.6. All LGGs showed negative in the brightness. In two radiation necrosis cases, the mean brightness was 139.5±37.4. In one inflammatory case, the brightness was 239, but after the lesion removed, the adjacent brain parenchyma showed bright, and the border was not clear. In one GBM case, the ventricle was opened, and the brightness difference between the tumor and the ventricular wall was observed.

Conclusions: 5-ALA brightness analysis by Image J would be helpful to distinguish between malignant glioma and LGG, and other non-tumor lesions to support rapid pathological diagnosis. Also, it would be useful to distinguish between the tumor and the ventricle wall. As for radiation necrosis and inflammation, border of the lesion is unclear.

Background: Melanoma stands as a prevalent instigator of leptomeningeal disease (LMD) within the realm of cancer. Given the poor prognosis accompanying this condition, ongoing trials explore a spectrum of treatment modalities in pursuit of more effective interventions. To ascertain the most effective therapeutic strategies, we aim to compare novel treatments against the current standard of care for melanoma-associated LMD.

Methods: A comprehensive search was conducted across multiple databases, including PubMed/Medline, EMBASE, Scopus, ScienceDirect and Web of Science for relevant studies published from January 2014 to January 2024. We included primary research studies, including observational studies, randomised control trials, quasi-experimental design studies, clinical trials, and experimental studies focusing on LMD caused by metastatic melanoma. Data extraction was conducted according to PRISMA guidelines and quality assessment/risk of bias is performed individually using the GRADE method. A network meta-analysis is conducted to evaluate the effects of multiple interventions within the study. Overall survival outcomes were quantified using log hazard ratio.

Results: Out of 680 records screened for eligibility, seven carefully chosen studies, meeting our specific inclusion criteria, provide insights into the management of 397 patients grappling with LMD due to metastatic melanoma. These studies vary in design: one observational cohort study with 29 participants, a clinical trial with 25 patients, four retrospective cohort studies ranging from 39 to 190 participants and one experimental study with 24 patients.

Conclusions: Despite the escalating breakthroughs of treatment options in melanoma-associated LMD, further studies may be imperative to conclusively determine whether the newer therapeutic options yield superior outcomes compared to the current standard of care treatments.

Background: Skull base metastasis from follicular thyroid carcinoma (FTC) is uncommon. A single study, encompassing 473 cases of thyroid carcinoma, revealed a mere 2.5% incidence of such metastasis. Much is unknown about FTC skull base metastasis, and a streamlined algorithm is yet to be created.

Methods: We present a case of a 63-year-old female, with a history of a non-toxic goiter, complaining of a chronic history of progressive L proptosis, associated with headache and vision loss. History and radiologic findings were incompatible, hence, a biopsy was performed, revealing FTC metastasis. With this experience, we performed a systematic review of available literature for FTC skull base metastasis to help guide management for future cases. Using PRISMA guidelines, a systematic search across PubMed, Google Scholar, and Cochrane Library using MeSH keywords "Skull base", "Metastasis", and "Follicular Thyroid Carcinoma", identified 18 records. Fifteen articles were assessed for eligibility, but only eight studies met the inclusion criteria for qualitative analysis, including demographics, pathological characteristics, surgical approaches, clinical outcomes, and follow-up data.

Results: Included studies showcased a consistent age range (43 to 69 years) among patients diagnosed with FTC, with variability in management for the primary malignancy. Metastatic presentation varied depending on tumor location, with symptoms including dysphagia, proptosis, epistaxis, facial dysesthesia, and visual impairment. Tumor size ranged from 3 cm × 3 cm × 2 cm to 6.8 cm × 3.9 cm × 5.3 cm, greatly influencing surgical management strategies, from punch biopsy to complete resection and reconstruction. Adjuvant therapies included combinations of intensity-modulated radiation therapy (IMRT) with immunotherapy, I-131 therapy, oral radioiodine ablation, and radiotherapy alone, with outcomes showing improvement in most cases. Follow-up duration varied from 12 to 60 months, reflecting a wide range of outcome results.

Conclusions: FTC skull base metastasis remains to be an uncommon entity in neurosurgery. Its rarity creates a lack of established guidelines and treatment algorithms. A high index of suspicion as well as good history and physical examination skills are necessary to achieve an adequate diagnosis. Multi-disciplinary teams form the cornerstone of a patient-tailored approach to its management.

Background: Glioma characterization and follow-up are underreported from low-and-middle-income country centers within the literature. With the recent emphasis on molecular markers for survival prediction, there is a need for robust data exploring molecular epidemiology in these countries. In Pakistan particularly, there is a significant gap in glioma outcomes reporting and survival analysis.

Methods: One hundred and sixty-five consecutive glioma patients were enrolled from 2019 onwards; histopathological and molecular analysis was performed on archived formalin-fixed paraffin-embedded (FFPE) blocks for isocitrate dehydrogenase (IDH), P53, α-thalassemia retardation X-linked (ATRX) and Ki-67 immunohistochemical (IHC) markers. Survival analysis was calculated using the Kaplan-Meier method; hazard ratios are reported through a multivariate Cox regression model.

Results: Fifty-seven (35%) histopathological diagnoses were revised according to the updated criteria; 30% (n=16) glioblastoma were converted to a new category on re-analysis. IDH wild type (IDH-WT) gliomas had a significantly worse overall survival (log-rank =0.002), with a 2-year survival rate of 60% for IDH-mutant (IDH-M) and 38% for IDH-WT. Significant survival differences were seen for the Ki-67 index (log-rank =0.001) and methylguanine methyltransferase (MGMT) promotor methylation [log-rank =0.027, 2-year survival rate: 100% (methylation detected), 33% (methylation not detected)]. On Cox proportional hazards regression, gross total resection (P<0.001), IDH mutation (P<0.001), and updated histopathological diagnosis (P<0.001) were significant predictors of survival, with good sensitivity and specificity as seen on receiver operating characteristic (ROC) analysis [area under the curve (AUC) =0.86].

Conclusions: In our cohort, the revised World Health Organization (WHO) classification shows significant implications on prognosis and implications for treatment. Although these markers are not commonly used in low-and-middle-income country centers, our results strongly support their greater implementation for improved prognostication and reclassification.