Safety and Efficacy of CT-Guided Iodine-125 Brachytherapy for Portal Vein Tumor Thrombus in Hepatocellular Carcinoma.

RATIONALE AND OBJECTIVES: Portal vein tumor thrombus (PVTT) seriously reduces the survival of patients with hepatocellular carcinoma (HCC). CT-guided iodine-125 (125I) brachytherapy has the advantage of a high local control rate and is minimally invasive. This study aims to evaluate the safety and efficacy of 125I brachytherapy for treating PVTT in HCC patients. MATERIALS AND METHODS: Thirty-eight patients diagnosed with HCC complicated with PVTT and treated with 125I brachytherapy for PVTT were included in this retrospective study. The local tumor control rate, local tumor progression-free survival, and overall survival (OS) were analyzed. Cox proportional hazards regression analysis was performed to identify predictors affecting survival. RESULTS: The local tumor control rate was 78.9% (30/38). The median local tumor progression-free survival was 11.6 (95% confidence interval [CI]: 6.7, 16.5) months, and the median overall survival was 14.5 (95% CI: 9.2, 19.7) months. Multivariate Cox analysis showed that age <60 years (hazard ratio [HR] = 0.362; 95% CI: 0.136, 0.965; p = 0.042), type I+II PVTT (HR = 0.065; 95% CI: 0.019, 0.228; p < 0.001), and tumor diameter <5 cm (HR = 0.250; 95% CI: 0.084, 0.748; p = 0.013) were significant predictors of OS. There were no serious adverse events related to 125I seed implantation during the follow-up period. CONCLUSION: CT-guided 125I brachytherapy is effective and safe for treating PVTT of HCC, with a high local control rate and no severe adverse events. Patients younger than 60 years old with type I+II PVTT and a tumor diameter less than 5 cm have a more favorable OS.

Clinical outcomes of benign brain tumors treated with single fraction LINAC-based stereotactic radiosurgery: Experience of a single institute.

Objectives: Accelerator-based stereotactic radiosurgery (SRS) is a noninvasive and effective treatment modality widely used for benign brain tumors. This study aims to report 20-year treatment outcomes in our institute. Materials and Methods: From May 2001 to December 2020, 127 patients treated with LINAC-based single-fraction SRS for their benign brain lesions were included. A neurosurgeon and two radiation oncologists retrospectively reviewed all data. Computed tomography (CT) simulation was performed after head-frame fixation under local anesthesia. All planning CT images were co-registered and fused with gadolinium-enhanced magnetic resonance imaging taken within 3 months for lesions targeting and critical organs delineation. The marginal dose was prescribed at 60%-90% isodose lines, respectively, to cover ≥95% planning target volume. Outcome evaluations included clinical tumor control rate (TCR), defined as the need for salvage therapy, and radiological response, defined as no enlargement of >2 cm in the maximal diameter. Overall survival (OS) and adverse reaction (defined according to CTCAE 5.0) were also analyzed. Results: The present study included 76 female and 51 male patients for analysis. The median age was 59 years (range, 20-88 years). Their diagnoses were vestibular schwannoma (VS, n = 54), nonvestibular cranial nerve schwannoma (n = 6), meningioma (n = 50), and pituitary adenoma (n = 17). Totally 136 lesions were treated in a single fraction, predominantly skull base tumors, accounting for 69.1%. Median and mean follow-up duration was 49 and 61 months (range, 1-214 months), Overall TCR was 92.9%. The 5-year disease-specific TCR for VS, nonvestibular schwannoma, meningioma, and pituitary adenoma were 97.4%, 91.7%, 93.8%, and 83.3%. Salvage therapy was indicated for eight patients at 4-110 months after SRS. Among symptomatic patients, post-SRS symptom(s) was improved, stable, and worse in 68.2%, 24.3%, and 3.6%, respectively. Radiological response rate for 111 evaluable patients was 94.6% (shrinkage, 28.8%; stable, 65.8%). OS was 96.1% without treatment-related mortality. One patient with post-SRS cranial nerve injury (0.8%, involving the trigeminal nerve, grade 2 toxicities). No grade 3-4 acute or late toxicity was found. Conclusion: Our results suggested that LINAC-based SRS effectively controls tumor growth and tumor-related neurological symptoms for patients with benign brain tumors. SRS is less aggressive, associated with low neurological morbidity and no mortality. Continuous follow-up is indicated to conclude longer outcomes.

Gamma Knife Radiosurgery for Large Vestibular Schwannoma More Than 10 cm 3 : A Single-Center Indian Study.

Introduction Gamma Knife radiosurgery (GKRS) is an effective treatment for benign vestibular schwannomas (VSs). The established cutoffs have recently been challenged, as recent literature expanded the horizon of GKRS to larger tumors. Even though microsurgery remains the primary option for large VS, GKRS can provide reasonable tumor control and is more likely to avoid cranial neuropathies associated with open surgery. Methods We analyzed patients with VS with volume exceeding 10 cm 3 who underwent GKRS at our center from January 2006 to December 2016. Clinicoradiological and radiosurgical data were collected from medical records for statistical analysis. Follow-up was performed every 6 months with a clinical assessment along with magnetic resonance imaging (MRI) of the brain and audiometric evaluation in patients with serviceable hearing. Results The study included 34 patients (18 males and 16 females) with an average age of 45.5 years. The mean tumor volume was 10.9 cm 3 (standard deviation [SD], ± 0.83), with a median tumor dose of 12 Gy (interquartile range, 11.5-12) and a mean follow-up of 34.7 months (SD, ± 23.8). Tumor response was graded as regression in 50%, stable in 44.1%, and increase or GKRS failure in 2 cases (5.8%). Treatment failure was noted in five cases (14.7%), requiring microsurgical excision and a ventriculoperitoneal shunt post-GKRS. The tumor control rate for the cohort is 85.3%, with a facial preservation rate of 96% (24/25) and hearing loss in all (5/5), while three patients developed new-onset hypoesthesia. We noted that gait ataxia and involvement of cranial nerve V or VII at initial presentation were associated with GKRS failure in univariate analysis. Conclusion Microsurgery should remain the first-choice treatment option for large VSs. GKRS is a viable alternative with good tumor control and improved or stabilized cranial neuropathies with a low complication rate.

Long-term outcomes of rotating gamma knife for vestibular schwannoma: A 4-year prospective longitudinal study of 89 consecutive patients in Vietnam.

BACKGROUND: Microsurgical total removal of vestibular schwannoma (VS) is the definitive treatment but has a high incidence of postoperative neurological deficits. Rotating Gamma Knife (RGK) is a preferred option for a small tumor. This study aims to evaluate long-term neurological outcomes of RGK for VS. METHODS: This prospective longitudinal study was conducted at the Nuclear Medicine and Oncology Center, Bach Mai Hospital, Hanoi, Vietnam. Eighty-nine consecutive patients were enrolled from October 2011 to October 2015 and followed up to June 2017. RGK was indicated for VS measuring <2.2 cm, while RGK for tumors measuring 2.2-3 cm was considered in patients with severe comorbidities, high-risk surgery, and who denied surgery. Concurrently, VS consisted of newly diagnosed, postoperative residual, and recurrent tumors. Patients with neurofibromatosis type 2 were excluded from the study. Primary outcomes were radiological tumor control rate, vestibulocochlear functions, facial and trigeminal nerve preservation. Stereotactic radiosurgery was performed by the Rotating Gamma System Gamma ART 6000. RESULTS: The tumors were measured 20.7 ± 5.6 mm at pre treatment and 17.6 ± 4.1 mm at 3-year post treatment. The mean radiation dose was 13.5 ± 0.9 Gy. Mean follow-up was 40.6 ± 13.3 months. The radiological tumor control rate was achieved 95.5% at 5-year post treatment. The hearing and vestibular functions were preserved in 70.3% and 68.9%, respectively. The facial and trigeminal nerve preservation rates were 94.4% and 73.3%, respectively. CONCLUSION: RGK is an effective and safe treatment for VS measuring ≤3 cm with no significant complications during long-term follow-up.

The transcatheter arterial chemoembolization combined with targeted nanoparticle delivering sorafenib system for the treatment of microvascular invasion of hepatocellular carcinoma.

to explore the value of transcatheter arterial chemoembolization (TACE) combined with targeted nanoparticle delivery system for sorafenib (SFB) to treat hepatocellular carcinoma (HCC) with microvascular invasion. 42 HCC patients with microvascular invasion after liver cancer surgery were selected from our hospital from December 2020 and February 2021. Patients were divided into experimental group and control group based on their willingness. Patients in experimental group (18 cases) were treated with combination therapy of TACE and Ab-SFB-NP system; while patients in control group (24 cases) took TACE and non-nano drug delivery system. There was no obvious difference in liver function and blood test results between two groups of patients before treatment and one month after treatment (P > 0.05). Three months after treatment, differences of alanine aminotransferase (ALT) were statistically significant (P < 0.05); while differences of other test results were not (P > 0.05). The disease control rate (DCR) of patients in experimental group was higher slightly (P > 0.05). The incidence of adverse reactions of patients in experimental group was lower than the control group and the differences were statistically significant (P < 0.05). After three months of TACE, the DCR in the experimental group was significantly higher compared to control group. The toxic reactions of taking SFB with Ab-SFB-NP nano-drug delivery system mainly included hand-foot syndrome, diarrhea, and bleeding, the toxic reactions were mainly at level 1 ~ 2. After symptomatic treatment, the toxicity was effectively controlled, so the security was high.

Stereotactic radiosurgery as the first-line treatment for intracanalicular vestibular schwannomas.

OBJECTIVE: This report evaluates the outcomes of stereotactic radiosurgery (SRS) as the first-line treatment of intracanalicular vestibular schwannomas (VSs). METHODS: Between 1987 and 2017, the authors identified 209 patients who underwent SRS as the primary intervention for a unilateral intracanalicular VS. The median patient age was 54 years (range 22-85 years); 94 patients were male and 115 were female. Three patients had facial neuropathy at the time of SRS. One hundred fifty-five patients (74%) had serviceable hearing (Gardner-Robertson [GR] grades I and II) at the time of SRS. The median tumor volume was 0.17 cm3 (range 0.015-0.63 cm3). The median margin dose was 12.5 Gy (range 11.0-25.0 Gy). The median maximum dose was 24.0 Gy (range 15.7-50.0 Gy). RESULTS: The progression-free survival rates of all patients with intracanalicular VS were 97.5% at 3 years, 95.6% at 5 years, and 92.1% at 10 years. The rates of freedom from the need for any additional intervention were 99.4% at 3 years, 98.3% at 5 years, and 98.3% at 10 years. The serviceable hearing preservation rates in GR grade I and II patients at the time of SRS were 76.6% at 3 years, 63.5% at 5 years, and 27.3% at 10 years. In univariate analysis, younger age (< 55 years, p = 0.011), better initial hearing (GR grade I, p < 0.001), and smaller tumor volumes (< 0.14 cm3, p = 0.016) were significantly associated with improved hearing preservation. In multivariate analysis, better hearing (GR grade I, p = 0.001, HR 2.869, 95% CI 1.569-5.248) and smaller tumor volumes (< 0.14 cm3, p = 0.033, HR 2.071, 95% CI 1.059-4.047) at the time of SRS were significantly associated with improved hearing preservation. The hearing preservation rates of patients with GR grade I VS were 88.1% at 3 years, 77.9% at 5 years, and 38.1% at 10 years. The hearing preservation rates of patients with VSs smaller than 0.14 cm3 were 85.5% at 3 years, 77.7% at 5 years, and 42.6% at 10 years. Facial neuropathy developed in 1.4% from 6 to 156 months after SRS. CONCLUSIONS: SRS provided sustained tumor control in more than 90% of patients with intracanalicular VS at 10 years and freedom from the need for additional intervention in more than 98% at 10 years. Patients with initially better hearing and smaller VSs had enhanced serviceable hearing preservation during an observation interval up to 10 years after SRS.

Stereotactic radiosurgery as the primary management for patients with Koos grade IV vestibular schwannomas.

OBJECTIVE: While extensive long-term outcome studies support the role of stereotactic radiosurgery (SRS) for smaller-volume vestibular schwannomas (VSs), its role in the management for larger-volume tumors remains controversial. METHODS: Between 1987 and 2017, the authors performed single-session SRS on 170 patients with previously untreated Koos grade IV VSs (volumes ranged from 5 to 20 cm3). The median tumor volume was 7.4 cm3. The median maximum extracanalicular tumor diameter was 27.5 mm. All tumors compressed the middle cerebellar peduncle and distorted the fourth ventricle. Ninety-three patients were male, 77 were female, and the median age was 61 years. Sixty-two patients had serviceable hearing (Gardner-Robertson [GR] grades I and II). The median margin dose was 12.5 Gy. RESULTS: At a median follow-up of 5.1 years, the progression-free survival rates of VSs treated with a margin dose ≥ 12.0 Gy were 98.4% at 3 years, 95.3% at 5 years, and 90.7% at 10 years. In contrast, the tumor control rate after delivery of a margin dose < 12.0 Gy was 76.9% at 3, 5, and 10 years. The hearing preservation rates in patients with serviceable hearing at the time of SRS were 58.1% at 3 years, 50.3% at 5 years, and 35.9% at 7 years. Younger age (< 60 years, p = 0.036) and initial GR grade I (p = 0.006) were associated with improved serviceable hearing preservation rate. Seven patients (4%) developed facial neuropathy during the follow-up interval. A smaller tumor volume (< 10 cm3, p = 0.002) and a lower margin dose (≤ 13.0 Gy, p < 0.001) were associated with preservation of facial nerve function. The probability of delayed facial neuropathy when the margin dose was ≤ 13.0 Gy was 1.1% at 10 years. Nine patients (5%) required a ventriculoperitoneal shunt because of delayed symptomatic hydrocephalus. Fifteen patients (9%) developed detectable trigeminal neuropathy. Delayed resection was performed in 4% of patients. CONCLUSIONS: Even for larger-volume VSs, single-session SRS prevented the need for delayed resection in almost 90% at 10 years. For patients with minimal symptoms of tumor mass effect, SRS should be considered an effective alternative to surgery in most patients, especially those with advanced age or medical comorbidities.

Stereotactic radiosurgery for central nervous system hemangioblastoma in von Hippel-Lindau disease: A systematic review and meta-analysis.

Von Hippel-Lindau (VHL) disease is a dominantly inherited disorder marked by multiorgan tumors, such as central nervous system benign hemangioblastomas (CHB). Stereotactic radiosurgery (SRS) has also been used to treat CHB for a long time. The purpose of this meta-analysis is to provide a long-term outcome of SRS for VHL-associated CHB by reviewing published studies. We completed a Pubmed/Embase/SCOPUS/Cochrane Library literature search to get eligible studies published from January 1990 to December 2019 about using SRS to treat VHL-associated CHB. 15 studies met eligibility for qualitative systematic review, of which nine studies were ultimately eligible for quantity meta-analysis of 5-year tumor control rates (TCR), representing 170 subjects with a total of 660 lesions. Gamma Knife was the most published SRS method for VHL-associated CHB. The pooled 5-year TCR across the nine studies was 0.919 (95 %CI: 0.881-0.957). The pooled 5-year TCR for only intracranial lesions across eight studies was 0.917 (95 %CI: 0.876-0.957). Individual patient data were extracted from 9 studies, representing 298 lesions of 70 subjects. Sex, tumor volume, radiosurgery methods, marginal doses, maximum doses, the number of tumors for radiosurgery, age at the time of radiosurgery, tumor locations were not proven to be associated with tumor progression. SRS offered a satisfactory 5-year tumor control of CHB for VHL patients. Despite the paucity of randomized control trials, SRS is recommended to patients with limited surgical alternatives. However, the long-term outcomes and underlying factors associated with tumor progression remain to be investigated.

Activity endpoints reported in soft tissue sarcoma phase II trials: quality of reported endpoints and correlation with overall survival.

BACKGROUND: Despite extensive research over the past 3 decades, few investigational drugs are considered as promising and these drugs failed to improve overall survival. Therefore we performed a systematic review of the literature to improve our understanding of the reasons that explain these failures. METHODS: We reviewed 53 phase II trial reports that investigated new treatments in patients with advanced soft tissue sarcoma from 1999 to 2011. We critically reviewed the selected primary endpoint used in these trials. RESULTS: Forty percent of trials were not interpretable because of major inherent methodological flaws. Only 3 primary endpoints were correlated with median overall survival (mOS): 3- and 6-month progression free rates and median progression-free survival. Nevertheless, the mOS was not significantly higher in the cases of active drugs. DISCUSSION: We need to improve the definition of primary active endpoints and develop better designs for future trials. The current definition of promising drugs must be refined.