Potential Molecular Biomarkers of Vestibular Schwannoma Growth: Progress and Prospects

Vestibular schwannomas (VSs, also known as acoustic neuromas) are relatively rare benign brain tumors stem from the Schwann cells of the eighth cranial nerve. Tumor growth is the paramount factor for neurosurgeons to decide whether to choose aggressive treatment approach or careful follow-up with regular magnetic resonance imaging (MRI), as surgery and radiation can introduce significant trauma and affect neurological function, while tumor enlargement during long-term follow-up will compress the adjacent nerves and tissues, causing progressive hearing loss, tinnitus and vertigo. Recently, with the deepening research of VS biology, some proteins that regulate merlin conformation changes, inflammatory cytokines, miRNAs, tissue proteins and cerebrospinal fluid (CSF) components have been proposed to be closely related to tumor volume increase. In this review, we discuss advances in the study of biomarkers that associated with VS growth, providing a reference for exploring the growth course of VS and determining the optimal treatment strategy for each patient.

Prediction of clinical efficacy by plasma concentration of apatinib in patients with solid tumor.

e15000 Background: To explore the correlation between plasma concentration of apatinib and clinical efficacy. Methods: 42 patients were enrolled. Plasma specimens of all patients were collected. At 7:40 am, fasting blood was drawn as plasma trough concentration (Ctrough). At 8 am, apatinib mesylate (APA-M, 250mg qd) was orally administrated. At 11 am, venous blood was drawn as plasma peak concentration (Cpeak). Each patient has Ctrough and Cpeak samples. A total of 84 plasma samples were obtained. The concentration of APA-M in plasma was determined by UPLC-MS/MS. Results: 1) 42 patients were evaluable. Treatment response was assessed by RECIST1.1. 2 patients achieved complete response (CR), 16 partial response (PR), 12 stable disease (SD) (tumor shrinks), 5 SD (tumor enlargement), 7 progressive disease (PD). Objective response rate (ORR) was 42.9% (18/42) and disease control rate (DCR) was 83.3% (35/42). 2) On day 1 and 456 after oral APA-M from different patients, median trough concentration (Ctrough median) was 264.38 ng/ml (1.18 ng/ml-918 ng/ml), and median peak concentration (Cpeak median) was 543.61 ng/ml (71.11 ng/ml-1609.4 ng/ml), respectively. 3) The Ctrough median in patients with CR, PR and SD (tumor shrinks) was significantly higher than that SD (tumor enlargement) and PD ( P＜0.05). There was significantly difference between CR and PR with SD (tumor shrinks) ( P＜0.05). But there was no significantly difference between CR and PR ( P＞0.05). (Table) 4) The Cpeak median in patients with CR, PR, SD (tumor enlargement) and PD was significantly higher than that SD (tumor shrinks) ( P＜0.05). But there was no significantly difference between CR and PR with SD (tumor enlargement) ( P＞0.05). (Table). Conclusions: The plasma Ctrough of Apatinib can predict the clinical efficacy of patients with solid tumor. Perspective clinical studies with adequate sample size are required to validate our results. [Table: see text]

Prognosis of hepatocellular carcinoma metastasizing to the oral cavity

Background Oral metastasis by hepatocellular carcinoma (OMHCC) is extremely rare, and the prognosis had been reported quite poor due to simultaneous multiple organ metastases. In this study, we report clinical features and survival of 10 new cases of OMHCC and suggest the criteria for palliative surgery. Methods A retrospective clinical study including 10 new cases of oral OMHCC between 2006 and 2016 was performed. Clinical features and survival analysis were examined. The recorded variables were age, sex, site of oral metastases, size of oral tumor (largest diameter), and survival after oral histopathologic diagnosis. Results There was male (n=8) predilection of OMHCC. The mean survival time was 16.9 months. Patient age ranged from 40 to 71 years (mean 56.5). Eight mandibular and two maxillary lesions were found. One patient showed simultaneously the maxilla and the oral tongue involvement. The most often encountered symptoms were swelling (80%) followed by pain (60%), numbness (60%), bleeding (10%), and tooth mobility (10%). Four patients underwent operation due to spontaneous bleeding and swelling of the cancer. Overall (from onset of hepatocellular carcinoma) and truncated survival (from onset of OMHCC) were 71.9 and 13.1 months respectively. Conclusion The prognosis of OMHCC was quite poor. Oral and jaw bone examination should be included in patients with multiple metastasis of HCC. Palliative surgery might be performed in patients who reported spontaneous bleeding, severe pain, and oral dysphasia due to tumor enlargement.

Vestibular Schwannoma Tumor Size and Growth Rate Predict Response with Gamma Knife Stereotactic Radiosurgery

Objective The aim of this study is to determine if pretreatment growth of sporadic vestibular schwannomas (VS) predicts postradiosurgery response. Methods This study was a retrospective chart review at a tertiary referral center of patients with VS that had at least two pretreatment magnetic resonance imaging (MRI) studies at least 6 months apart and underwent Gamma Knife radiosurgery with a minimum of 14 months postradiosurgery imaging surveillance. Tumor linear measurements and volumetric segmentation were assessed before and after radiosurgery. The main outcome measure was persistent enlargement following radiosurgery, defined as 2 mm enlargement in greatest axial diameter or 20% enlargement in volume without size regression. Results Thirty-five patients met the inclusion criteria. Patients were observed for median pre- and posttreatment intervals of 29.5 and 40.6 months, respectively. Median dose to the tumor margin was 13 Gy. Postradiosurgery enlargement occurred in six (17.1%) and nine (25.7%) patients based on linear and volumetric enlargement definitions, respectively. Pseudoprogression—defined as tumor enlargement—followed by linear or volumetric regression that occurred in 34.3% of tumors, reaching a maximum size at a median time of 6.3 months (3.3–8.4) postradiosurgery. When controlling for age, gender, and radiation dose, preradiosurgery tumor volume less than 0.3 cm3 (odds ratio [OR]: 59.7, p = 0.012) and preradiosurgery tumor diameter growth rate greater than or equal to 2.5 mm/year (OR: 19.3, p = 0.045) were associated with persistent postradiosurgery tumor enlargement. Conclusion Smaller pretreatment tumor volume and greater linear tumor growth rates were associated with postradiosurgery tumor enlargement when controlling for age, gender, and radiation dose. Level of Evidence :This study indicates that the level of evidence is V.

MRI-guided Radiotherapy Identifies Early Pseudoprogression of Glioblastoma

Background The standard glioblastoma treatment paradigm consists of surgery, pre-radiotherapy MRI, six weeks of chemoradiotherapy, followed by post-radiotherapy MRI and continued adjuvant temozolomide. In a significant proportion of patients, post-radiotherapy MRI demonstrates tumor enlargement due to either treatment failure (true progression) or treatment response (pseudoprogression). Recently introduced MRI-guided radiotherapy systems obtain daily MRI of glioblastoma patients, and we hypothesized that progression can be identified early during radiotherapy.Methods Fourteen glioblastoma patients underwent tri-Cobalt-60 MRI-guided radiotherapy in 30 fractions over 6 weeks delivered with concurrent temozolomide. The tumor target volume was delineated on MRI before each of the 30 fractions. The images obtained by the 0.35 T MRI-guided system is shown to be similar to T2-weighted images obtained by a clinical diagnostic MRI-scanner. Hyperintense volumes were measured over time through radiotherapy.Results Four of fourteen patients demonstrated increases of at least 25% and 1.5 cc in T2 hyperintense volume through radiation therapy. This volume expansion correlated with both T2/FLAIR and contrast-enhanced volume expansion on post-radiotherapy diagnostic MRIs. In three of four cases, significant volume growth only started at week three of treatment, with the most prominent changes occurring during weeks four and five. While patient numbers are limited, patients with growth during therapy exhibited excellent survival, consistent with the known improved survival of patients with pseudoprogression.Conclusions Daily MRI acquisition during radiotherapy identifies early pseudoprogression typically starting during week 3 or 4 of treatment. This and other daily MRI techniques during radiotherapy could enable early adaptation of therapy in glioblastoma patients.

MRI appearance change during stereotactic radiotherapy for large brain metastases and importance of treatment plan modification during treatment period

Purpose We aimed to evaluate the magnetic resonance imaging (MRI) appearance changes during stereotactic radiotherapy (SRT) for large sized brain metastases, and analyze the lesions necessitating treatment plan modification. Materials and methods A total of 23 patients (27 lesions, >2 cm in tumor diameter) underwent SRT and all lesions were evaluated the appearance changes which had the necessity of the treatment plan modification. The appearance change of tumor during SRT was evaluated using gadolinium-enhanced MRI. The reasons of the modification were classified into tumor reduction, tumor enlargement, displacement, and shape change. Results Among the 27 lesions, 55.6% required the treatment plan modification. The reasons were tumor reduction in six lesions, tumor enlargement in three lesions, displacement in three lesions, and shape change in three lesions. The planning target volume (PTV) size changed up to 43.0% and the shift of center of PTV was a maximum of 1.7 mm. The pathological status (adenocarcinoma vs others) and timing of steroid administration (prior vs after SRT start) were the predictive factors of tumor changes required the modification. Conclusions As tumor changes might occur even during short period of SRT, the treatment plan evaluation and modification were important in SRT for large brain metastases.

Tumors Sharply Increased after Ceasing Pazopanib Therapy for a Patient with Advanced Uterine Leiomyosarcoma: Experience of Tumor Flare

Pazopanib has activity in patients with soft-tissue sarcoma. We report an advanced uterine leiomyosarcoma case that suddenly worsened after cessation of pazopanib therapy. A 47-year-old woman had a primary uterine leiomyosarcoma tumor and multiple lung metastases, which progressed during her initial treatment. In subsequent treatment with pazopanib for 3 months, the sum of her tumor diameters after cessation sharply increased for two weeks. Symptoms such as dyspnea suddenly worsened also. She died of the disease one month after cessation of pazopanib therapy. Given the poor prognosis of recurrent uterine leiomyosarcoma and the rapid tumor enlargement after ending pazopanib therapy, control of this disease is especially important. Therefore, the decision to discontinue pazopanib therapy requires careful consideration.