Practical Management of Oligometastatic Non–Small-Cell Lung Cancer

Local ablative therapies, including surgery or stereotactic radiotherapy (SABR), are becoming an integral component in the treatment of oligometastatic disease in non–small-cell lung cancer. In this review, we summarize recent randomized evidence supporting progression-free survival and overall survival benefits of local ablation in these patients, as well as upcoming phase III data which should help us better understand the ideal treatment conditions and provide more insight into the oligometastatic state. Since practical management of oligometastatic disease in non–small-cell lung cancer can be challenging, we discuss a modern framework to identify patient, tumor, and treatment characteristics that can best guide management.

Recent Advances in the Diagnosis and Management of Multiple Primary Lung Cancer

With the wide application of computed tomography in lung cancer screening, the incidence of multiple primary lung cancer (MPLC) has been increasingly reported. Despite the established criteria, the differentiation between MPLC and intrapulmonary metastasis remains challenging. Although histologic features are helpful in some circumstances, a molecular analysis is often needed. The application of next-generation sequencing could aid in distinguishing MPLCs from intrapulmonary metastasis, decreasing ambiguity. For MPLC management, surgery with lobectomy is the main operation method. Limited resection does not appear to negatively affect survival, and it is a reasonable alternative. Stereotactic ablative radiotherapy (SABR) has become a standard of care for patients refusing surgery or for those with medically inoperable early-stage lung cancer. However, the efficacy of SABR in MPLC management could only be found in retrospective series. Other local ablation techniques are an emerging alternative for the control of residual lesions. Furthermore, systemic therapies, such as targeted therapy for oncogene-addicted patients, and immunotherapy have shown promising results in MPLC management after resection. In this paper, the recent advances in the diagnosis and management of MPLC are reviewed.

Temporal Variability of Surface Reflectance Supersedes Spatial Resolution in Defining Greenland’s Bare-Ice Albedo

Ice surface albedo is a primary modulator of melt and runoff, yet our understanding of how reflectance varies over time across the Greenland Ice Sheet remains poor. This is due to a disconnect between point or transect scale albedo sampling and the coarser spatial, spectral and/or temporal resolutions of available satellite products. Here, we present time-series of bare-ice surface reflectance data that span a range of length scales, from the 500 m for Moderate Resolution Imaging Spectrometer’s MOD10A1 product, to 10 m for Sentinel-2 imagery, 0.1 m spot measurements from ground-based field spectrometry, and 2.5 cm from uncrewed aerial drone imagery. Our results reveal broad similarities in seasonal patterns in bare-ice reflectance, but further analysis identifies short-term dynamics in reflectance distribution that are unique to each dataset. Using these distributions, we demonstrate that areal mean reflectance is the primary control on local ablation rates, and that the spatial distribution of specific ice types and impurities is secondary. Given the rapid changes in mean reflectance observed in the datasets presented, we propose that albedo parameterizations can be improved by (i) quantitative assessment of the representativeness of time-averaged reflectance data products, and, (ii) using temporally-resolved functions to describe the variability in impurity distribution at daily time-scales. We conclude that the regional melt model performance may not be optimally improved by increased spatial resolution and the incorporation of sub-pixel heterogeneity, but instead, should focus on the temporal dynamics of bare-ice albedo.

Solitary colorectal liver metastasis: overview of treatment strategies and role of prognostic factors

The following is an overview of the treatment strategies and the prognostic factors to consider in the therapeutic choice of patients characterized by solitary colorectal liver metastasis. Liver resection is the only potential curative option; nevertheless, only 25% of the patients are considered to be eligible for surgery. To expand the potentially resectable pool of patients, surgeons developed multidisciplinary techniques like portal vein embolization, two-stage hepatectomy or associating liver partition and portal vein ligation for staged hepatectomy. Moreover, mini-invasive surgery is gaining support, since it offers lower post-operative complication rates and shorter hospital stay with no differences in long-term outcomes. In case of unresectable disease, various techniques of local ablation have been developed. Radiofrequency ablation is the most commonly used form of thermal ablation: it is widely used for unresectable patients and is trying to find its role in patients with small resectable metastasis. The identification of prognostic factors is crucial in the choice of the treatment strategy. Previous works that focused on patients with solitary colorectal liver metastasis obtained trustable negative predictive factors such as presence of lymph-node metastasis in the primary tumour, synchronous metastasis, R status, right-sided primary colon tumor, and additional presence of extrahepatic tumour lesion. Even the time factor could turn into a predictor of tumour biology as well as further clinical course, and could be helpful to discern patients with worse prognosis.

Combination of Ablation and Immunotherapy for Hepatocellular Carcinoma: Where We Are and Where to Go

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide and is increasing in incidence. Local ablative therapy plays a leading role in HCC treatment. Radiofrequency (RFA) is one of the first-line therapies for early local ablation. Other local ablation techniques (e.g., microwave ablation, cryoablation, irreversible electroporation, phototherapy.) have been extensively explored in clinical trials or cell/animal studies but have not yet been established as a standard treatment or applied clinically. On the one hand, single treatment may not meet the needs. On the other hand, ablative therapy can stimulate local and systemic immune effects. The combination strategy of immunotherapy and ablation is reasonable. In this review, we briefly summarized the current status and progress of ablation and immunotherapy for HCC. The immune effects of local ablation and the strategies of combination therapy, especially synergistic strategies based on biomedical materials, were discussed. This review is hoped to provide references for future researches on ablative immunotherapy to arrive to a promising new era of HCC treatment.

Sublimation-driven morphogenesis of Zen stones on ice surfaces

In this article, the formation of Zen stones on frozen lakes and the shape of the resulting pedestal are elucidated. Zen stones are natural structures in which a stone, initially resting on an ice surface, ends up balanced atop a narrow ice pedestal. We provide a physical explanation for their formation, sometimes believed to be caused by the melting of the ice. Instead, we show that slow surface sublimation is indeed the physical mechanism responsible for the differential ablation. Far from the stone, the sublimation rate is governed by the diffuse sunlight, while in its vicinity, the shade it creates inhibits the sublimation process. We reproduced the phenomenon in laboratory-scale experiments conducted in a lyophilizer and studied the dynamics of the morphogenesis. In this apparatus, which imposes controlled constant sublimation rate, a variety of model stones consisting of metal disks was used, which allows us to rule out the possible influence of the thermal conduction in the morphogenesis process. Instead, we show that the stone only acts as an umbrella whose shade hinders the sublimation, hence protecting the ice underneath, which leads to the formation of the pedestal. Numerical simulations, in which the local ablation rate of the surface depends solely on the visible portion of the sky, allow us to study the influence of the shape of the stone on the formation of the ice foot. Finally, we show that the far-infrared black-body irradiance of the stone itself leads to the formation of a depression surrounding the pedestal.

How Immunotherapy Has Changed the Continuum of Care in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the leading causes of death worldwide. The use of local treatment, such as surgical resection, liver transplant, and local ablation, has improved the survival of patients with HCC detected at an early stage. Until recently, the treatment of patients with metastatic disease was limited to the use of the multikinase inhibitor (MKI) sorafenib with a marginal effect on survival outcome. New target approaches, such as the oral MKI lenvatinib in first-line treatment and regorafenib, ramucirumab, and cabozantinib in later lines of therapy, have demonstrated efficacy in patients with preserved liver function (Child–Pugh class A) and good performance status. On the other hand, the implementation of immune checkpoint inhibitors directed against PD-1 (nivolumab and pembrolizumab), PD-L1 (atezolizumab), and anti-CTLA4 (ipilimumab) in the management of advanced HCC has strongly changed the continuum of care of HCC. Future research should include the evaluation of molecular biomarkers that can help patient selection and provide new insight on potential combined approaches. In this review, we provide an overview of the clinical evidence of the use of immune checkpoint inhibitors in HCC, and discuss how immunotherapy has been implemented into the continuum of HCC care.

Feasibility of a Drug-Releasing Radiofrequency Ablation System in a Porcine Liver Model

The objective of this study was to investigate the feasibility of a newly developed anticancer drug-releasing radiofrequency ablation (RFA) system in a porcine liver model. A 15-gauge drug-releasing cooled wet electrode (DRCWE) was newly developed to improve the RFA efficacy for creating a large ablation as well as for simultaneously delivering an anticancer drug to the tumor margin. Nine ablations in three pigs were performed by the DRCWE. The sectioned liver specimens were evaluated by measuring the ablation zone by a positron emission tomography/magnetic resonance imaging examination to investigate whether 18F-fluorodeoxyglucose was exactly diffused. Volumes of the ablation zones released drug injection volumes, circularity, retention rate defined as the ratio between an estimated and injection dose, and the standard uptake value were assessed. The drug-releasing RFA was technically successful without procedural-related complications. During the procedure, the color changes of the ablated zones of the liver were observed in all specimens. The mean drug injection volume was higher than the ablated volumes (17.21 ± 2.85 vs. 15.22 ± 2.30 cm3) and the circularity was 0.72 ± 0.08. Moreover, the retention rate was 72.89% ± 4.22% and the mean standard uptake value was 0.44 ± 0.05. The drug-releasing RFA system was feasible not only for local ablation but also for the delivery of anticancer drugs. The results of this study indicate that this novel strategy of localized RFA with a drug delivery system could be a promising option for the prevention of local recurrence rates.