Clinical Effectiveness and Safety of Chinese Herbal Medicine Compound Kushen Injection as an Add-On Treatment for Breast Cancer: A Systematic Review and Meta-Analysis

Objective. To systematically evaluate the effect and safety of compound Kushen injection (CKI) as an add-on treatment on the treatment for breast cancer. Methods. We searched eight major electronic databases from their inception to November 1, 2021, for randomized clinical trials (RCTs) comparing CKI plus chemotherapy with chemotherapy alone. Primary outcomes included objective response rate (ORR) and disease control rate (DCR), health-related quality of life (HRQoL), progression-free survival (PFS), and overall survival (OS). Secondary outcomes included adverse drug reactions (ADRs) and tumor marker level. We used Cochrane’s RevMan 5.3 for data analysis. The GRADEpro was used to appraise the certainty of evidence. Trial sequential analysis (TSA) was applied to estimate the required sample size in a meta-analysis and test the robustness of the current results. Results. Thirty RCTs with 2556 participants were totally included. CKI plus chemotherapy showed significant effects in increasing ORR (RR 1.30, 95%CI [1.18, 1.43], I2 = 27%, n = 1694), increasing DCR (RR 1.21, 95%CI [1.15, 1.28], I2 = 16%, n = 1627), increasing HRQol as measured by Karnofsky Performance Scale (KPS) score improvement rate (RR 1.42, 95% CI [1.26, 1.61], I2 = 37%, n = 1172), increasing the PFS (MD 2.24 months, 95%CI [1.26, 3.22], n = 94) and the OS (MD 2.24 months, 95%CI [1.45, 3.43], n = 94), compared to chemotherapy alone. The results showed that CKI plus chemotherapy had a lower risk of ADRs than that of chemotherapy alone group. The certainty of evidence of the included trials was generally low to very low. TSA for ORR and KPS score improvement rate demonstrated that the current results reached a sufficient power regarding both numbers of trials and participants. Conclusions. Low certainty of evidence suggested that the combination of CKI and conventional chemotherapy appeared to improve ORR, DCR, and KPS score in breast cancer patients. Conclusions about PFS and OS could not be drawn due to lack of evidence. Additionally, CKI appeared to relieve the risk of ADRs in patients with breast cancer receiving chemotherapies. However, due to weak evidence, the findings should be further confirmed in large and rigorous trials.

Long-Term Survival after Linac-Based Stereotactic Radiosurgery and Radiotherapy with A Micro-Multileaf Collimator for Brain Metastasis

Purpose: To evaluate the prognostic factors associated with long-term survival after linear accelerator (linac)-based stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) with a micro-multileaf collimator for brain metastasis (BM). Methods: This single-center retrospective study included 226 consecutive patients with BM who were treated with linac-based SRS or fSRT with a micro-multileaf collimator between January 2011 and December 2018. Long-term survival (LTS) was defined as survival for more than 2 years after SRS/fSRT. The tumors originated from the lung (n =189, 83.6%), breast (n = 11, 4.9%), colon (n = 9, 4.0%), stomach (n = 4, 1.8%), kidney (n = 3, 1.3%), esophagus (n = 3, 1.3%), and other regions (n = 7, 3.1%). Results: The median pretreatment Karnofsky performance scale (KPS) score was 90 (range: 40–100). The median follow-up time was 13 (range: 0–120) months. Out of the 226 patients, 72 (31.8%) were categorized in the LTS group. The median survival time was 43 months and 13 months in the LTS group and in the entire cohort, respectively. The 3-year, 4-year, and 5-year survival rate in the LTS group was 59.1%, 49.6%, and 40.7%, respectively. Multivariate regression logistic analysis showed that female sex, a pre-treatment KPS score ≥80, and the absence of extracranial metastasis were associated with long-term survival. Conclusions: Female sex, a favorable pre-treatment KPS score, and the absence of extracranial metastasis were associated with long-term survival in the current cohort of patients with BM.

Individualized Cerebral Artery Protection Strategies for the Surgical Treatment of Parasellar Meningiomas on the Basis of Preoperative Imaging

ObjectiveParasellar meningiomas (PMs) represent a cohort of skull base tumors that are localized in the parasellar region. PMs tend to compress, encase, or even invade the cerebral arteries and their perforating branches. The surgical resection of PMs without damaging neurovascular structures is challenging. This study aimed to analyze functional outcomes in a series of patients who underwent surgery with individualized cerebral artery protection strategies based on preoperative imaging.MethodsA retrospective review was performed on a single surgeon’s experience of the microsurgical removal of PMs in 163 patients between January 2012 and March 2020. Individualized approaches with a bidirectional dissection strategy were used. Cerebral artery invasion classification, neurological outcomes, MRC Scale for muscle strength, and Karnofsky performance scale were used to assess tumor vascular invasion, functional outcome, and patient quality-of-life outcomes, respectively.ResultsTotal resection (Simpson grade I or II) was achieved in 114 patients (69.9%) in our study. A total of 44.7% of patients had improved vision at consecutive follow-ups, 51.1% were stable, and 3.8% deteriorated. Improvements in cranial nerves III, IV, and VI were observed in 41.1%, 36.2%, and 44.8% of patients, respectively. The mean follow-up time was (38.8 ± 27.9) months, and the KPS at the last follow-up was 89.6 ± 8.5. Recurrence was observed in eight patients (13.8%) with cavernous sinus meningiomas, and the recurrence rates in anterior clinoid meningiomas and medial sphenoid wing meningiomas were 3.8% and 2.8%, respectively.ConclusionsPreoperative imaging is important in the selection of surgical approaches. Maximum tumor resection and cerebral artery protection can be achieved concurrently by utilizing the bidirectional dissection technique. Individualized cerebral artery protection strategies provide great utility in improving a patient’s quality of life.

STMO-21 The Outcome of tumor resection followed by photodynamic therapy for recurrent glioblastoma

Recurrent glioblastoma remains a clinical problem with no standard treatment and quite a few effective treatment options. We evaluated the efficacy of photodynamic therapy (PDT) using talaporfin sodium (TS) as a treatment for recurrent glioblastoma in a retrospective analysis of 70 patients who underwent PDT with surgery (PDT group) between 2014 and 2018, and 38 patients who underwent surgery alone (control group) during the same period. The median overall survival (OS) of the PDT and control groups were 16.03 and 12.75 months, respectively (P=0.0311). The median progression-free survival (PFS) of these two groups were 5.67 and 2.2 months, respectively (P=0.00428). Univariate and multivariate analyses showed PDT with surgery and preoperative Karnofsky Performance Scale as significant independent prognostic factors for both PFS and OS.On the other hand, IDH mutation and previous pathology before recurrence were not significant prognostic factors in this study. In the PDT group, there was no significant difference in PFS and OS between patients with GBM from the previous pathology before recurrence and those with malignant transformation to GBM from lower-grade glioma. Furthermore, there was also no significant difference in TS accumulation in the tumor between these two groups. These results suggest that additional PDT treatment for recurrent glioblastoma can have potential survival benefits and that its efficacy is independent of the pathology before recurrence or IDH status.

COMPLICATIONS OF SURGICAL TREATMENT OF SPINAL METASTASES

ABSTRACT Objectives: To evaluate the complications of surgical treatment in a group of patients with spinal metastasis with epidural compression, undergoing surgical treatment. Methods: This is a comparative retrospective study (level of evidence III), which evaluated 96 patients with spinal metastases undergoing surgical treatment. Intra- and postoperative complications were obtained from the patients’ medical records and correlated with the following clinical characteristics: tumor type, tumor location, neurological deficit, age, number of affected vertebrae, Tokuhashi scale, Tomita scale, Karnofsky performance scale, and type of approach. Results: Complications of surgical treatment were observed in 29 (30.20%) patients. Surgical wound infection was the most frequent complication, observed in 15% of patients. Conclusions: Surgical treatment of spinal metastases presents complications in about 30% of patients and their occurrence should be considered in the treatment planning, weighing the risks and benefits for achieving the treatment goals. Level III evidence; Retrospective Study.

Supratotal Resection of Periventricular Glioblastomas and Pathomorphological Rationale for Extensive Removal of Subventricular Zone

The aim of the research was to reveal the pathomorphological patterns of periventricular glioblastoma (PVG) dissemination and assess the rationale for extended surgical removal of subventricular zone (SVZ) as a step towards supratotal resection.A total of 54 patients (16 females and 38 males, mean age 48.9 ± 13.4 years, range 22–69) with PVG were prospectively included in the study. Standard preoperative evaluation included an MRI using 3D T1 with Gd-enhancement, T2, and T2-FLAIR series. The neuronavigation system was used to identify the SVZ and to remove of ventricular wall, additionally to image-guided total tumor resection. The pathomorphological assessment of PVG features with the description of the SVZ and changes in perifocal brain matter was performed by two pathologists.The median Karnofsky Performance Scale (KPS) score raised from 67.8 to 81.9 in the postoperative period. The overall median survival was 13.0 ± 2.7 months. The low postoperative KPS score (p = 0.05) and basal ganglia invasion (p = 0.008) significantly decreased survival rates.Microscopically, the typical multilayer structure of SVZ was disrupted. The invasive spread of tumor cells in thesubventricular space was identified. The ependymal layer had prominent dystrophic alterations of cells and destruction of intracellular connections. The hyperplastic reaction on neoplastic process was typical for adjacent ependyma.The pathomorphological identification of periventricular glioblastoma invasion in the subependymal space supports the supratotal tumor resection with removal of adjacent SVZ as a potential source for relapse.

Refined Temporal-to-Frontal Horn Shunt for Treatment of Trapped Temporal Horn After Surgery of Peri- or Intraventricular Tumor: A Case Series Study

BackgroundTrapped temporal horn (TTH) is a localized hydrocephalus that can be treated with cerebrospinal fluid diversion. Refined temporal-to-frontal horn shunt (RTFHS) through the parieto-occipital approach is rarely reported in the literature and its effectiveness remains unclear. The aim of the present study is to investigate the efficacy and outcome of RTFHS for treatment of TTH.Materials and MethodsWe consecutively enrolled 10 patients who underwent RTFHS for TTH after surgical resection of peri- or intraventricular tumors from February 2018 to March 2021. Clinical, radiological, and follow-up data were collected and analyzed. The most common underlying pathology was meningioma (n=4), followed by central neurocytoma (n=3), thalamic glioblastoma (n=2), and anaplastic ependymoma (n=1).ResultsThe mean Karnofsky performance scale (KPS) score and TTH volume at onset were 54.0 ± 15.1 (range 40-80) and 71.3 ± 33.2cm3 (range 31.7-118.6cm3), respectively. All patients (10/10, 100.0%) presented with periventricular brain edema (PVBE), while midline shift was observed in 9 patients (9/10, 90.0%). RTFHSs were implanted using valveless shunting catheters. No patients developed acute intracranial hemorrhage or new neurological deficit postoperatively. During the follow-up of 17.2 ± 13.7 months (range 3-39 months), all patients showed clinical and radiological improvement. The mean KPS score at the last follow-up was significantly increased to 88.0 ± 10.3 (range 70-100, p<0.0001). RTFHS resulted in significant complete remission in PVBE and midline shift in 8 (80.0%, p=0.0007) and 9 (100.0%, p=0.0001) patients, respectively. As the postoperative follow-up duration prolonged, the mean TTH volume decreased in a consistent, linear trend (p<0.0001). At last follow-up, the mean TTH volume was significantly reduced to 15.4 ± 11.5 cm3 (range 5.6-44.1 cm3, p=0.0003), resulting in a mean relative reduction of 77.2 ± 13.1% compared with the volume of TTH at onset. Over drainage was not observed during the follow-up. No patient suffered from proximal or distal shunt obstruction or shunt related infection, and the revision rate was 0%.ConclusionRTFHS seems to be safe and effective for the treatment of TTH with favorable outcomes. Advantages of this technique could be technically less complex and invasive, cost-effective, avoidance of various intraperitoneal complications, and maintaining a near-physiological CSF pathway.

A functional artificial neural network for noninvasive pretreatment evaluation of glioblastoma patients

Background Pretreatment assessments for glioblastoma (GBM) patients, especially elderly or frail patients, are critical for treatment planning. However, genetic profiling with intracranial biopsy carries a significant risk of permanent morbidity. We previously demonstrated that the CUL2 gene, encoding the scaffold cullin2 protein in the cullin2-RING E3 ligase (CRL2), can predict GBM radiosensitivity and prognosis. CUL2 expression levels are closely regulated with its copy number variations (CNVs). This study aims to develop artificial neural networks (ANNs) for pretreatment evaluation of GBM patients with inputs obtainable without intracranial surgical biopsies. Methods Public datasets including Ivy-GAP, The Cancer Genome Atlas Glioblastoma (TCGA-GBM), the Chinese Glioma Genome Atlas (CGGA) were used for training and testing of the ANNs. T1 images from corresponding cases were studied using automated segmentation for features of heterogeneity and tumor edge contouring. A ratio comparing the surface area of tumor borders vs. the total volume (SvV) was derived from the DICOM-SEG conversions of segmented tumors. The edges of these borders were detected using the canny edge detector. Packages including Keras, Pytorch, and TensorFlow were tested to build the ANNs. A 4-layered ANN (8-8-8-2) with a binary output was built with optimal performance after extensive testing. Results The 4-layered deep learning ANN can identify a GBM patient’s overall survival (OS) cohort with 80-85% accuracy. The ANN requires 4 inputs, including CUL2 copy number, patients’ age at GBM diagnosis, Karnofsky Performance Scale (KPS), and SvV ratio. Conclusion Quantifiable image features can significantly improve the ability of ANNs to identify a GBM patients’ survival cohort. Features such as clinical measures, genetic data, and image data, can be integrated into a single ANN for GBM pretreatment evaluation.

Lentinan Combined with (125)I Brachytherapy for Recurrent Ovarian Cancer

Objective. To investigate the clinical value of lentinan combined with (125)I brachytherapy in the treatment of recurrent ovarian cancer. Methods. A total of 160 patients with recurrent ovarian cancer admitted at Jiaozhou Central Hospital from June 2009 to October 2015 were enrolled in this study and randomly divided into observation group (80 cases) and control group (80 cases). The control group received chemotherapy. Observation group (80 cases) was treated with lentinan combined with (125)I brachytherapy on the basis of control group, and the efficacy, adverse reactions, and Karnofsky Performance Scale (KPS) and quality of life scale (QOL) scores of the two groups were analyzed and compared. Results. After treatment, the levels of CA125, CA199, and CA724 in the 2 groups were markedly lower than those before treatment, and the observation group was lower than the control group ( P < 0.05 ). After treatment, the proportion of CD4+/CD8+ cells and helper T cells and NK cells in the control group remarkably depleted, while the proportion of CD4+/CD8+ cells, NK cells, and B cells in the observation group increased significantly compared to that before treatment, and the level of IgA, IgG, and IgM in the control group decreased, while that in the observation group showed no conspicuous difference compared with that before chemotherapy ( P > 0.05 ). The effective rate of observation group (85%) was higher than that of control group (75%) ( P < 0.05 ). The overall survival of patients in the control group was (16.2 ± 2.04) months and that of the observation group was (24.8 ± 1.8) months. KPS and QOL scores in both groups were enormously higher than those before treatment, and the observation group was higher than the control group ( P < 0.05 ). The incidence of hemoglobin reduction, leukopenia, aglobulia, granulocytopenia, nausea and vomiting, hepatorenal toxicity, and neurovirulence in the observation group was significantly lower than that in the control group. Conclusion. Lentinan combined with (125)I brachytherapy is effective in treating recurrent ovarian cancer, with mild adverse reactions and good tolerance.

NCOG-46. WHITE MATTER TRACT INVOLVEMENT BY INTRA-AXIAL BRAIN TUMORS; DIAGNOSTIC & THERAPEUTIC IMPLICATIONS

Diffusion tensor imaging (DTI) is a relatively recent modality which aids in visualization of WMT and their relation to intracranial lesions. Despite almost two decades since the beginning of its use in tumor resection, there is still dearth of data on its diagnostic and prognostic value from low- and middle-income countries. We aimed to assess the pattern of involvement of white matter tracts (WMT) by intra-axial brain tumors on DTI. Secondary objectives were to evaluate implications of involvement of WMT on surgical resection, and post-operative functional outcome. This was a retrospective study of 77 consecutive patients, who underwent DTI guided surgery for brain tumors. The involvement of WMT by tumors on DTI was assessed by a radiologist (who was blind to the pathology) using the Witwer classification. The pathology was reported by histopathologists using WHO brain tumor classification. Karnofsky Performance Scale (KPS) was used for assessing patients’ neurological status at admission, and at follow-up. Forty-five (58.4%) out of 77 tumors reviewed, caused infiltration of WMT, whereas only 22 (28.6%) tumors caused displacement of WMT (p = 0.040). Among 32 cases of astrocytoma, involvement of WMTs was influenced by the grade of tumor (p = 0.012), as high-grade tumors caused infiltration (19; 59.4%), unlike low grade tumors which commonly caused displacement (2; 50%). Oligodendroglioma caused infiltration/disruption of WMTs in most cases, irrespective of the grade (19 out of 25 cases; 76%). At last follow-up, 27 (35.1%) patients showed improvement in KPS and 14 (18.2%) reported deterioration, while there was no change observed in 36 (46.8%) patients. Infiltration of WMTs was associated with poor functional outcome. We conclude that intra-axial brain tumors mostly cause infiltration of WMTs, particularly high-grade astrocytoma, and oligodendroglioma of any grade. Infiltration of WMTs is associated with poor functional outcome at follow-up.