Chinese clinical oncology最新文献

Background: Complete resection of contrast-enhanced lesions [gross total resection (GTR)] without severe neurological deficits has been generally accepted as the goal of surgery. However, it remains unclear if additional resection of surrounding fluid-attenuated inversion recovery (FLAIR) hyper-intense lesions combined with GTR (FLAIRectomy) has survival advantage of primary glioblastoma patients. Multicenter, open-label, randomized phase III trial was commenced to confirm the superiority of FLAIRectomy to GTR alone followed by radiotherapy with concomitant and adjuvant temozolomide in terms of overall survival (OS) for primary glioblastoma IDH-wildtype patients. This trial investigates not only survival but also postoperative neurological and neurocognitive deficits in detail.

Methods: We assumed a 2-year OS of 50% in the GTR arm and expected a 15% improvement in the FLAIRectomy arm. A total of 130 patients is required with a one-sided alpha of 5%, power of 70%, and will be accrued from 49 Japanese institutions in 4 years and follow-up will last 2.5 years. Patients aged 18-75 years will be registered and randomly assigned to each arm with 1:1 allocation. The primary endpoint is OS, and the secondary endpoints are progression-free survival, frequency of adverse events, proportion of Karnofsky performance status preservation, proportion of National Institutes of Health stroke scale preservation, proportion of mini-mental state examination preservation and proportion of health-related quality of life preservation. The Japan Clinical Oncology Group Protocol Review Committee approved this study protocol in May 2023. Ethics approval was granted by the National Cancer Center Hospital Certified Review Board. Patient enrollment began in July 2023.

Results: If FLAIRectomy is superior to GTR alone, aggressive surgery will become a standard surgical treatment for glioblastoma with resectable contrast-enhanced lesion.

Conclusions: Registry number: jRCT1031230245. Date of registration: 19/July/2023. Date of first participant enrollment: 28/July/2023.

Background: Glioblastoma (GBM) is the most aggressive type of brain tumor with heterogeneity and strong invasive ability. Treatment of GBM has not improved significantly despite the progress of immunotherapy and classical therapy. Epidermal growth factor receptor variant III (EGFRvIII), one of GBM-associated mutants, is regarded as an ideal therapeutic target in EGFRvIII-expressed GBM patients because it is a tumor-specific receptor expressed only in tumors. Flagellin B (FlaB) originated from Vibrio vulnificus, is known as a strong adjuvant that enhances innate and adaptive immunity in various vaccine models. This study investigated whether FlaB synergistically could enhance the anti-tumor effect of EGFRvIII peptide (PEGFRvIII).

Methods: EGFRvIII-GL261/Fluc cells were used for GBM-bearing mouse brain model. Cell-bearing mice were inoculated with phosphate-buffered saline (PBS), FlaB alone, PEGFRvIII alone, and PEGFRvIII plus FlaB. Tumor growth based on magnetic resonance imaging (MRI) and the survival rate was investigated. T cell population was examined by flow cytometry analysis. Both cleaved caspase-3 and CD8+ lymphocytes were shown by immunohistochemistry (IHC) staining.

Results: The PEGFRvIII plus FlaB group showed delayed tumor growth and increased survival rate when compared to other treatment groups. As evidence of apoptosis, cleaved caspase-3 expression and DNA disruption were more increased in the PEGFRvIII plus FlaB group than in other groups. In addition, the PEGFRvIII plus FlaB group showed more increased CD8+ T cells and decreased Treg cells than other treatment groups in the brain.

Conclusions: FlaB can enhance the anti-tumor effect of PEGFRvIII by increasing CD8+ T cell response in a mouse brain GBM model.

Background: Recurrent high-grade glioma (HGG) is a challenge with limited treatment options and a poor prognosis. We conducted an open-label phase II study: neoadjuvant camrelizumab and apatinib in patients with recurrent high-grade gliomas (NCT04588987), and interim analysis showed very promising results. We are further searching for evidence of the effectiveness of this strategy.

Methods: Patients with recurrent HGG received neoadjuvant treatment with camrelizumab (intravenous injection 200 mg on day 1) and apatinib (oral 250 mg per day on days 1-7), and 14 days later received surgery for recurrent tumor resection. Sequential therapy began 2 weeks after surgery with the biweekly camrelizumab (200 mg) and 4 weeks after surgery with the daily apatinib (250 mg) until investigator assessed progressive disease or unable to tolerate toxicity. The primary endpoint was overall survival (OS). When patients suspected progress during per-protocol treatment, re-surgery for resection of lesion was done, and the tissue was further examined.

Results: Between October 9, 2020, and March 30, 2024, 24 patients were enrolled [19 glioblastomas, one World Health Organization (WHO) grade 4 diffuse astrocytoma, three anaplastic astrocytoma, and one anaplastic oligodendroglioma]. Nineteen patients with interim analysis data, and showed the median progression-free survival (PFS) was 4.8 months [95% confidence interval (CI): 4.4-5.2], the median OS was 12.9 months (95% CI: 9.3-16.4) respectively, with a median follow-up time of 17.5 months (95% CI: 9.0-26.1). There were two patients who suspected progress and received second surgery. One patient showed real tumor progression with active tumor cells. While another patient the histology revealed mainly necrosis with inflammatory cells. Five patients initially showed increased enhancement on magnetic resonance imaging (MRI) but without increased symptoms, and showed continuous improvement when receiving further treatment.

Conclusions: This immuno-target combination neoadjuvant therapy in recurrent HGG demonstrated encouraging efficacy and revealed some evidence of efficacy, and worth to further investigate.

Background: Spine is the most common site for metastases in the skeletal system. Longer lifespans of patients with common cancers are translating into increasing incidence of patients with symptomatic spinal metastases. Surgery for spinal metastases offers immediate neurological decompression with stabilization and preservation of quality-of-life parameters. The objectives of the study were to assess the effect of pre-operative neurological condition, timing, and type of surgery on postoperative neurological function and long-term outcome as well as to analyze the various sources of primary in cases of symptomatic spinal metastases and the spinal level involved in terms of postoperative neurological function and ambulation.

Methods: A retrospective analysis of all operated cases of symptomatic spinal metastases at our institute over a period of 5 years was performed. Parameters such as neurological presentation, timing of surgery, source of primary, and radiological features of the metastases were assessed and compared with the type of surgery performed, post-operative neurological function, and long-term outcome. The in-house hospital information system was to collect data.

Results: A total of 94 patients were operated on for symptomatic spinal metastases, the dorsal spine was the most common location and hematological malignancies were the most common primary overall and among men whereas breast was the most common primary in females. Overall, 64.8% of the patients had neurological motor deficits of which 72% had an improvement in motor power. We found that patients with a pre-operative motor power of 3/5 or more likely to have an improvement in post-operative neurological function and ambulatory status.

Conclusions: Surgery for symptomatic spinal metastases plays a vital role in preserving the quality of life of the patients. Patients with preoperative motor power of 3/5, spastic tone, and features of mechanical back pain alone have good ambulatory outcomes post-spine surgery.

Background: Oligodendroglioma, the third most common glioma, accounts for 5% of primary brain tumors and around 20% of all glial neoplasms. It is a rare brain tumor that develops from glial cells called oligodendrocytes, which cover nerve cells. Oligodendroglioma is classified as an adult diffuse glioma in the fifth edition of the World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS). Patients may present with cognitive impairment, aphasia, behavioral changes, and seizures. The symptoms at presentation are often related to the anatomic location of the tumor.

Case description: A 55-year-old female presented with episodes of facial seizure with drooping on the right side of her face 4 months before coming to our hospital. Her seizures lasted around one minute, causing her to be unable to speak during the seizure. She also complained of chronic headaches in the last 1 year. She initially underwent a non-contrast computed tomography (CT) scan of the brain. The scans showed an isodense calcified mass on the perifalcine anterior left lobe with surrounding peritumoral edema. Magnetic resonance imaging (MRI) brain confirmed the presence of an intraaxial white matter mass involving the left frontal lobe. This tumor did not demonstrate any contrast enhancement. MRI findings were suggestive of a low-grade astrocytoma. Histopathological examination following craniotomy and tumor removal surgery confirmed the diagnosis of oligodendroglioma not otherwise specified (NOS) CNS WHO grade II. Molecular analysis revealed to be isocitrate dehydrogenase (IDH) wildtype, inconsistent with the classic molecular profile of oligodendroglioma. The patient underwent adjuvant radiotherapy following surgery. Subsequent follow-up assessments demonstrated stable disease with improvement in symptoms.

Conclusions: Differentiating between oligodendroglioma and astrocytoma poses a significant challenge due to their overlapping clinical and radiological features, yet understanding their key differences is crucial for accurate diagnosis. On MRI, calcification strongly favors oligodendrogliomas, while T2/fluid-attenuated inversion recovery (FLAIR) mismatch sign favors astrocytoma. Only 50% of oligodendrogliomas appear to be contrast-enhanced. While oligodendrogliomas and astrocytomas share some similarities, careful consideration is essential for accurate differentiation, even though histopathological and molecular findings are the final determinants of diagnosis.

Background: Autophagy is a self-renewing process of the cell having a dual role in gliomagenesis depending on the tumor stage. Several microRNAs play a key role in the regulation of autophagy and the outcome of cancer. We investigated the potential relevance of autophagy in gliomagenesis and survival by exploring the association of the basal gene expression of autophagy-associated markers LC3, ULK1/2, UVRAG, Beclin1, mTOR, UVRAG, PI3K, AKT, PTEN and their target microRNAs miR-126, miR-374, miR-21, miR-7, miR-204 and miR-100 in low- and high-grades of gliomas.

Methods: A total of 50 fresh glioma tissues were used for the extraction of RNA using TRIzol-Chloroform method and reverse transcribed cDNA. The cDNA was used to determine the expression of genes and microRNAs using quantitative real-time polymerase chain reaction (qPCR). Mann-Whitney U-test was used to determine the statistical significance.

Results: In high-grade glioma, increased expression of AKT and miR-21, coupled with reduced ULK2 and LC3 expression was distinctly observed. While correlation analysis identified a strong positive correlation between ULK2 and UVRAG, PTEN, miR-7, and miR-100 and a moderate positive correlation emerged between ULK2 and mTOR, miR-7, miR-30, miR-100, miR-204, and miR-374, also between miR-21 and miR-126 in low-grade glioma. Similarly, a positive correlation appeared between ULK2 and AKT, LC3, PI3K, PTEN, ULK1, VPS34, mTOR, Beclin1, UVRAG, miR-7 and miR-374. AKT positively correlated with LC3, PI3K, PTEN, ULK1, VPS34, mTOR, Beclin1, UVRAG, miR-7, miR-30, miR-204, miR-374, miR-126 and miR-21 weakly correlated with AKT and miR-30 in high-grade glioma. The low ULK2, UVRAG, and miR-374 expression group exhibited significantly poor overall survival in glioma, while miR-21 over-expression indicated a poor prognosis in glioma patients.

Conclusions: This study provides comprehensive insights into the molecular landscape of gliomas, highlighting the dysregulation of autophagy genes ULK2, and UVRAG and the associated miR-21, miR-126 and miR-374 as potential prognostic biomarkers and emphasizing their unique significance in shaping survival outcomes in gliomas patients.

Background: Oligodendroglioma is a part of diffusely infiltrating gliomas with poorly understood pathological aspect often manifesting histologic overlap among other intracranial tumors, though it only consisted 5% in total. Its occurrences among pediatric is a rare finding, constituted <1% of total brain tumors in the population, but with molecularly distinct properties to its adult version. Metachronous pediatric oligodendroglioma plus mediastinal mass is even more uncommon, as history of double primary tumor serves as a groundbreaking point in understanding individual pathology. This study reports a rare case of pediatric oligodendroglioma with history of mediastinal mass.

Case description: This study reports a rare case of pediatric oligodendroglioma with history of mediastinal mass. A 10-year-old female presented to our emergency department with altered consciousness level in the past couple of weeks, and progressively worsening for 3 days. Moreover, she withstands a yearlong headache, plus continuously worsens weakness on the left side of the extremities for 6 months, right sided weakness of face and visual disturbances appeared at least 4 months prior presentation; no seizures were observed. History of pericardial effusion due to mediastinal mass was also recorded in 3 years before with history of pericardial tapping, with cytology showed malignant lesion; with history of 5 times radiotherapy cycle for treatment purpose, and patient discontinued therapy due to loss of follow up. Non-contrast head computed tomography (CT)-scan observed a mix-density lesion on the frontotemporoparietal region with calcification. On magnetic resonance imaging (MRI), mix-intensity lesion was found suggesting a glioma lesion. Patient underwent removal of tumor, with gross tumor removal was achieved. Histopathology result of oligodendroglioma was found.

Conclusions: The management of pediatric oligodendroglioma in our case involves wide range of discipline to elaborate its interaction with prior metachronous mediastinal mass, and findings of double primary tumor should raise any suspicion for any tumor-related genetic mutations.

Background: Pituitary masses during pregnancy pose many challenges, requiring inputs from multidisciplinary teams. Where surgery is required, such as in cases of impending pituitary apoplexy, timing must be carefully selected. Several case reports have suggested good outcome with surgery in later trimesters or postpartum. However, insufficient data exists on surgical strategies for such patients with severe visual symptoms in early pregnancy. We report two patients with pituitary masses requiring surgical excision.

Methods: Review of patients' notes and imaging, with literature review.

Results: A 35-year-old gravida 2 para 1 female at 9 weeks gestational age (GA) presented with chronic bitemporal hemianopia, with acute left eye blurring of vision, identified during a pre-employment screening test. Imaging revealed a 38 mm × 29 mm × 33 mm sellar mass with compression onto the optic chiasm. She had no significant hormonal imbalances other than hyperprolactinemia and newly diagnosed Hashimoto's thyroiditis. She underwent transsphenoidal resection, with histology showing pituitary adenoma with blood clots. Similarly, our second patient was a 37-year-old gravida 4 para 2 female at 12 weeks GA with worsening bitemporal hemianopia with a 25 mm × 21 mm × 18 mm sellar mass displacing and compressing the optic chiasm. After resection she had marked objective improvement in her vision, but developed diabetes insipidus, and final histology revealed pituicytoma. Preoperative considerations for timing of surgery include pituitary apoplexy or acutely worsening visual field deficit. The pituitary physiologically increases in size during pregnancy, which can compress the optic chiasm and worsen visual deficit. In the case of apoplexy, delayed identification can have devastating consequences. However, major surgery in the first trimester may increase spontaneous miscarriage. The effects of imaging investigations from radiation, or gadolinium contrast administration, are also uncertain. While surgical positioning remains unaffected, other intraoperative considerations include strictly avoiding hypotension and using pregnancy-safe agents. Postoperative considerations include correcting hormonal deficiencies of hypopituitarism, including acute central hypocortisolism, diabetes insipidus and interruption of gonadotrophin production which could negatively affect pregnancy. Fetal heart rate must also be assessed.

Conclusions: Determining timing of surgery to ensure well-being of both mother and fetus involves a difficult balance of risks. In our two cases, a thorough discussion with multidisciplinary input was required to achieve good outcomes.

Background: Attributing to its deep-seated location, surrounded by significant vessels, surgical management of pineal gland lesions is still considered a challenge. Various surgical approaches are employed to access these lesions, based on patient-specific risks and benefits. Each approach has its merits and demerits. In this study, we aim to narrate our experience with trans-cortical trans-ventricular (TT) approach for pineal tumor resection. We aim to outline the procedure details, safety, efficacy, and treatment outcome of TT.

Case description: This is a single-center, consecutive case series. All patients with pineal gland tumors who underwent surgical intervention, namely biopsy or resection using TT approach from 2000 to 2023 were included. Data for the patient characteristics, intraoperative details and complications were collected from the hospital's database. Mean [standard deviation (SD)] and frequency (proportions) were calculated for continuous and discrete variables, respectively. We identified 13 patients, mean age 24 (SD: 13) years in our case series. Of them, 8 (61.5%) were male. Most common presenting complains were headaches (69%), nausea/vomiting (38.5%), seizure (23%), and visual deficit (23%). Most patients, 60%, had high grade tumor and average size of tumors were 43.5 mm (SD: 18.45 mm). Pilocytic astrocyotma (23%) and pineal parenchymal tumor of intermediate differentiation (23%) were the most common diagnoses. In total, nine patients had pineal gland lesion biopsy done using TT approach along with the cerebrospinal fluid (CSF) diversion. Of them, four had tumor resection done using the same approach. Whereas four patients had primary excision done using TT approach. There were no intra-operative complications. Two patients had post-operative seizures which were treated with anti-epileptics. We did not identify any long-term sequalae attributed to this approach.

Conclusions: We presented our data regarding the safety, efficacy, and outcomes of trans-cortical trans-ventricular approach for pineal tumor surgical management. Utilizing this novel approach for pineal lesion resection can be a great addition to surgeons' armamentarium. This unique approach allows to access the tumor for biopsy/resection and perform CSF diversion procedure, simultaneously. Moreover, the same incision can be used for the second/redo surgery.

Background: Spinal cord diffuse midline gliomas are rare, infiltrative entities with an extremely grim prognosis. Standard of care is limited and extrapolated from those for intracranial gliomas, focusing on maximal safe resection, chemotherapy and radiation therapy. These do not prolong survival significantly and while advances in molecular profiling and targeted therapy have been promising, further research still needs to be performed. Here, we present a case of a young lady with a cervical cord diffuse midline glioma, along with a literature review of the disease and treatment options.

Case description: A 35-year-old female presented with progressive neck pain and left sided weakness. MRI revealed an intramedullary cervical spinal cord lesion. The lesion progressed rapidly to the medulla, resulting in lower cranial nerve palsies and left hemiplegia. Investigations for autoimmune and infective causes were negative. Cervical laminectomy and debulking was performed. Histological analysis showed high grade diffuse glioma, IDH-wildtype, loss of H3K27me3 staining and H3K27M positivity. The patient was treated with fractionated radiation and temozolamide, followed by lomustine and bevacizumab. A literature review was performed to better understand the molecular features, natural history and treatment options for spinal cord high grade gliomas. Our case highlights the importance of maintaining broad differentials for patients exhibiting features of cervical myelopathy. Malignant spinal cord tumours could be a differential. Molecular testing can aid in achieving an accurate diagnosis to better understand prognosis and determine treatment options. Early, function-preserving debulking with neuromonitoring is feasible. Adjuvant therapy with chemotherapy and radiation can prolong survival.

Conclusions: Spinal cord diffuse midline gliomas H3 K27-altered demonstrate rapid progression and a poor prognosis. They should be considered as a differential in patients with cervical myelopathy. Molecular testing for H3 K27 alterations facilitates an accurate diagnosis. Surgical debulking and adjuvant therapy are viable treatment options.