Prospective Study of Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma on Waitlist for Liver Transplant.

BACKGROUND AND AIMS: There are no prospective data on stereotactic body radiation therapy (SBRT) as a bridge to liver transplantation for HCC. This study aimed to evaluate the efficacy and safety of SBRT as bridging therapy, with comparison with transarterial chemoembolization (TACE) and high-intensity focused ultrasound (HIFU). APPROACH AND RESULTS: Patients were prospectively enrolled for SBRT under a standardized protocol from July 2015 and compared with a retrospective cohort of patients who underwent TACE or HIFU from 2010. The primary endpoint was tumor control rate at 1 year after bridging therapy. Secondary endpoints included cumulative incidence of dropout, toxicity, and posttransplant survival. During the study period, 150 patients were evaluated (SBRT, n = 40; TACE, n = 59; HIFU, n = 51). The tumor control rate at 1 year was significantly higher after SBRT compared with TACE and HIFU (92.3%, 43.5%, and 33.3%, respectively; P = 0.02). With competing risk analysis, the cumulative incidence of dropout at 1 and 3 years after listing was lower after SBRT (15.1% and 23.3%) compared with TACE (28.9% and 45.8%; P = 0.034) and HIFU (33.3% and 45.1%; P = 0.032). Time-to-progression at 1 and 3 years was also superior after SBRT (10.8%, 18.5% in SBRT, 45%, 54.9% in TACE, and 47.6%, 62.8% in HIFU; P < 0.001). The periprocedural toxicity was similar, without any difference in perioperative complications and patient and recurrence-free survival rates after transplant. Pathological complete response was more frequent after SBRT compared with TACE and HIFU (48.1% vs. 25% vs. 17.9%, respectively; P = 0.037). In multivariable analysis, tumor size <3 cm, listing alpha-fetoprotein <200 ng/mL, Child A, and SBRT significantly reduced the risk of dropout. CONCLUSIONS: SBRT was safe, with a significantly higher tumor control rate, reduced the risk of waitlist dropout, and should be used as an alternative to conventional bridging therapies.

Utilization of stereotactic ablative radiotherapy in oligometastatic & oligoprogressive skeletal metastases: Results and pattern of failure.

AIM: To evaluate the outcome and toxicities of stereotactic ablative radiotherapy (SABR) for skeletal metastasis in a tertiary cancer center. METHODS: This is a retrospective review of 22 patients treated with SABR for skeletal metastases for oligometastases (OM) or oligoprogression (OP) since October 2012. There are a total of 27 treatments with 20 spinal and seven non-spinal metastases. Treatment outcome including local control (LC), progression-free survival (PFS), overall survival (OS), pain control, treatment-related toxicity and failure pattern are described. Patients are assessed by interval computed tomography (CT), positron emission tomography-CT, magnetic resonance imaging or bone scintigraphy by physicians' discretion. Toxicities are graded by common toxicities criteria version 4.03. RESULT: The median age of the patients is 64 years. Primary sites include lung (50%), breast (32%), nasopharynx (9%), prostate (4.5%) and colon (4.5%). Twelve patients with OM and 10 with OP are included. Dose to most spinal and non-spinal metastases is 35 and 50 Gy, respectively, in five fractions. With a median follow up of 15.6 months, there are three local failures (1-year LC 91.2%). The median PFS and OS are 10.1 and 37.3 months, while PFS of OP and OM group is 6.6 and 10.6 months, respectively. Two-third of symptomatic patients have at least 1-year complete pain control. There are two vertebral fractures and one grade 3 esophagitis. CONCLUSION: Our series shows excellent LC of SABR to skeletal metastases with limited toxicities in OM and OP diseases. However, its benefit of survival warrants further studies.

Sustained response to standard dose osimertinib in a patient with plasma T790M-positive leptomeningeal metastases from primary lung adenocarcinoma.

A 44-year-old male, never smoker, suffers from stage IV adenocarcinoma of the right lung with epidermal growth factor receptor (EGFR) exon-21 L858R point mutation on initial presentation. After 23 months of treatment with gefitinib, intercalated with multiple courses of radiotherapy, leptomeningeal metastases (LMs) developed. Acquired T790M mutation was confirmed by the droplet digital polymerase chain reaction plasma EGFR test. After switching to osimertinib at the standard dose, his neurocognitive function improved clinically, coupled with sustained radiological improvement. As this clinical entity is underrepresented in clinical trials, the practicability of plasma EGFR testing and the optimal dose-response relationship of osimertinib in T790M-positive lung cancer complicated with LM deserves further exploration.

Characterization of PD-L1 expression and immune cell infiltration in nasopharyngeal cancer.

OBJECTIVES: Locally recurrent or metastatic nasopharyngeal cancer (NPC) remains an important challenge, with more effective and durable therapeutic options needed. Cancer immunotherapy, and in particular therapies that target the PD-L1/PD-1 immune checkpoint pathway, may provide new options to treat NPC patients. This study evaluated PD-L1 and CD8 expression levels and the respective associations with clinical and histopathological characteristics of patients with NPC. MATERIALS AND METHODS: Diagnostic tumour biopsies were obtained before radical radiotherapy with or without chemotherapy from 161 patients with NPC. These biopsies were analysed for PD-L1 expression levels on tumour cells (TC) and tumour-infiltrating immune cells (IC), and for CD8 T-cell infiltration. Results were correlated with baseline characteristics and clinical outcomes with standard-of-care treatment regimens. Additionally, pre- and post-treatment-paired tumour samples were analysed (n=146). RESULTS: 75% of tumours expressed PD-L1 on IC and 24% on TC. Baseline clinical characteristics of stage, sex and age did not correlate with PD-L1 expression. Additionally, overall survival and progression-free survival of standard-of-care treatment did not correlate with baseline PD-L1 expression. CD8 levels did correlate with clinical outcomes; however, results were confounded by other baseline characteristics. After treatment, PD-L1 expression dropped a median of 1.5% on IC and a median of 2.75% on TC. Median CD8 expression dropped 1.9%. CONCLUSIONS: Majority of NPC biopsy samples demonstrated PD-L1 expression on ⩾1% of IC, with fewer expressing PD-L1 on TC. In contrast to previous smaller studies, no prognostic value was observed for PD-L1 expression levels in patients with NPC.

Induction chemotherapy with cisplatin and gemcitabine followed by accelerated radiotherapy and concurrent cisplatin in patients with stage IV(A-B) nasopharyngeal carcinoma.

BACKGROUND: The purpose of this study was to evaluate the efficacy and toxicity of cisplatin plus gemcitabine as induction chemotherapy in advanced nasopharyngeal carcinoma (NPC). METHODS: Thirty-seven patients with stage IV(A-B) NPC were treated with 3 cycles of cisplatin plus gemcitabine (cisplatin 80 mg/m(2) on day 1; gemcitabine 1250 mg/m(2) on days 1 and 8) 3-weekly as induction chemotherapy, followed by another 3 cycles of concurrent cisplatin (100 mg/m(2) on day 1) 3-weekly with accelerated radiotherapy (RT) at 70 Gy in 2-Gy fractions, 6 daily fractions per week. RESULTS: The overall response rate to induction chemotherapy was > 90%, and side effects other than uncomplicated hematologic toxicities were uncommon. All patients completed RT, with 92% receiving > or = 5 cycles of chemotherapy. At a median follow-up of 2.9 years, the 3-year overall survival (OS) and disease-free survival (DFS) rates were 76% and 63%, respectively. CONCLUSIONS: Cisplatin plus gemcitabine is a well-tolerated, effective, and convenient induction chemotherapy regimen and warrants further studies to confirm its benefit in advanced NPC.