Lambros Tselikas

GEP-NETS UPDATE: Interventional radiology: role in the treatment of liver metastases from GEP-NETs

Neuroendocrine tumors from gastro-pancreatic origin (GEP-NET) can be responsible for liver metastases. Such metastases can be the dominant part of the disease as well due to the tumor burden itself or the symptoms related to such liver metastases. Intra-arterial therapies are commonly used in liver only or liver-dominant disease and encompass trans-arterial chemoembolization (TACE), trans-arterial embolization (TAE), and radioembolization (RE). TACE performed with drug emulsified in Lipiodol has been used for the past 20 years with reported overall survival in the range of 3-4 years, with objective response up to 75%. Response to TACE is higher when treatment is used as a first-line therapy and degree of liver involvement is lower. Benefit of TACE over TAE is unproven in randomized study, but reported in retrospective studies namely in pancreatic NETs. RE provides early interesting results that need to be further evaluated in terms of benefit and toxicity. Radiofrequency ablation allows control of small size and numbered liver metastases, with low invasiveness. Ideal metastases to target are one metastasis <5 cm, or three metastases <3 cm, or a sum of diameter of all metastases below 8 cm. Ablation therapies can be applied in the lung or in the bones when needed, and more invasive surgery should be probably saved for large-size metastases. Even if the indication of image-guided therapy in the treatment of GEP-NET liver metastases needs to be refined, such therapies allow for manageable invasive set of treatments able to address oligometastatic patients in liver, lung, and bones. These treatments applied locally will save the benefit and the toxicity of systemic therapy for more advanced stage of the disease.

Intratumoral immunotherapy: using the tumor as the remedy

Immune checkpoint-targeted monoclonal antibodies directed at Programmed Death Receptor 1 (PD-1), Programmed Death Ligand 1 (PD-L1) and Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA-4) are currently revolutionizing the prognosis of many cancers. By blocking co-inhibitory receptors expressed by antitumor T cells, these antibodies can break the immune tolerance against tumor cells and allow the generation of durable cancer immunity. Benefits in overall survival over conventional therapies have been demonstrated for patients treated with these immunotherapies, leading to multiple approvals of such therapies by regulatory authorities. However, only a minority of patients develop an objective tumor response with long-term survival benefits. Moreover, the systemic delivery of immunotherapies can be responsible for severe auto-immune toxicities. This risk increases dramatically with anti-PD(L)1 and anti-CTLA-4 combinations and currently hampers the development of triple combination immunotherapies. In addition, the price of these novel treatments is probably too high to be reimbursed by health insurances for all the potential indications where immunotherapy has shown activity (i.e. in more than 30 different cancer types). Intratumoral immunotherapy is a therapeutic strategy which aims to use the tumor as its own vaccine. Upon direct injections into the tumor, a high concentration of immunostimulatory products can be achieved in situ, while using small amounts of drugs. Local delivery of immunotherapies allows multiple combination therapies, while preventing significant systemic exposure and off-target toxicities. Despite being uncertain of the dominant epitopes of a given cancer, one can therefore trigger an immune response against the relevant neo-antigens or tumor-associated antigens without the need for their characterization. Such immune stimulation can induce a strong priming of the cancer immunity locally while generating systemic (abscopal) tumor responses, thanks to the circulation of properly activated antitumor immune cells. While addressing many of the current limitations of cancer immunotherapy development, intratumoral immunotherapy also offers a unique opportunity to better understand the dynamics of cancer immunity by allowing sequential and multifocal biopsies at every tumor injection.

Polytetrafluoroethylene-covered nitinol stent graft for treatment of carotid artery blowout syndrome in head and neck cancer patients.

To evaluate the efficacy, tolerance, and outcomes of covered stents in the treatment of carotid blowout syndrome (CBS) in head and neck cancer patients.

Prevention of serious skeletal-related events by interventional radiology techniques in patients with malignant paraganglioma and pheochromocytoma

PurposeBone metastases (BM) and skeletal-related events (SRE) are frequent in patients with malignant pheochromocytoma and paraganglioma (PPM) and the best modality of prevention unknown. The role of interventional radiology (IR) techniques for the prevention of SRE in the multidisciplinary management of malignant PPM has not been evaluated in that setting.MethodsSingle referral center retrospective review of all patients with malignant PPM with BM from 2000 to 2016. The primary endpoint was the time to first serious SRE (TTSRE). At time of inclusion, patients with high bone tumor burden disease were defined as those having more than five BM with the biggest exceeding 2 cm (Group A) and patients with moderate bone tumor burden disease were defined as those having five or less BM or no BM exceeding 2 cm (Group B).ResultsA total of 28 patients were included in this study. Thirteen were treated by IR techniques for prevention of first serious SRE. After a median follow-up of 48.2 months, the median TTSRE was not reached in patients treated by IR techniques and was 26.0 months in patients without IR procedures (p = .058). When comparing patients in group B, TTSRE was significantly higher in patients treated by IR (10 patients) when compared to patients without IR procedures (12 patients) (p = .021).ConclusionsIR techniques may help to delay the occurrence of first serious SRE in patients with malignant PPM with moderate bone tumor burden disease. Prospective studies are expected to confirm these results.

Percutaneous hepatic perfusion (chemosaturation) with melphalan in patients with intrahepatic cholangiocarcinoma: European multicentre study on safety, short-term effects and survival

ObjectivesCholangiocarcinoma is the second most common primary liver tumour with a poor overall prognosis. Percutaneous hepatic perfusion (PHP) is a directed therapy for primary and secondary liver malignancies, and its efficacy and safety have been shown in different entities. The purpose of this study was to prove the safety and efficacy of PHP in patients with unresectable intrahepatic cholangiocarcinoma (iCCA).Patients and methodsWe retrospectively reviewed data from 15 patients with unresectable iCCA treated with PHP in nine different hospitals throughout Europe. Overall response rates (ORR) were assessed according to response evaluation criteria in solid tumours (RECIST1.1). Overall survival (OS), progression-free survival (PFS) and hepatic PFS (hPFS) were analysed using the Kaplan-Meier estimation. Adverse events (AEs) and toxicity were evaluated.ResultsFifteen patients were treated with 26 PHPs. ORR was 20%, disease control was achieved in 53% after the first PHP. Median OS was 26.9 months from initial diagnosis and 7.6 months from first PHP. Median PFS and hPFS were 122 and 131 days, respectively. Patients with liver-only disease had a significantly longer median OS compared to patients with locoregional lymph node metastases (12.9 vs. 4.8 months, respectively; p < 0.01). Haematological toxicity was common, but manageable. No AEs of grade 3 or 4 occurred during the procedures.DiscussionPHP is a standardised and safe procedure that provides promising response rates and survival data in patients with iCCA, especially in non-metastatic disease.Key Points• Percutaneous hepatic perfusion (PHP) offers an additional locoregional therapy strategy for the treatment of unresectable primary or secondary intrahepatic malignancies.• PHP is a standardised and safe procedure that provides promising response rates and survival data in patients with intrahepatic cholangiocarcinoma (iCCA), especially in non-metastatic disease.• Side effects seem to be tolerable and comparable to other systemic or local treatment strategies.

Immuno-Oncology in Cancer Care is a Fantastic Opportunity for Interventional Oncology: IO4IO (Interventional Oncology for Immuno-Oncology) Initiative

Immuno-oncology is a rapidly expanding weapon in the anti-cancer arsenal of modern oncology. The revolution of immuno-oncology in cancer care is the result of intense research over the past decade in cancer immunology that has provided solid evidence that tumours can be recognised and controlled by the host immune system, a process known as immunosurveillance [1, 2]. Systemic immuno-targeted therapies are now approved treatment options in many cancer types because of their clinical efficacy even in relapsing/refractory patients through different primary cancer locations. These novel immuno drugs allow an enhancement of patients’ anti-cancer immunity, namely by blocking inhibitory pathways and inhibitory cells in the tumour microenvironment. The most common strategy is to use checkpoint inhibitors such as antibodies against cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed death-1 (PD-1) or its ligand, programmed death ligand-1 (PDL-1). Other strategies aim to enhance the specificity of anti-tumour immunity using antibodies directed to well-defined tumour antigens with the help of either cancer vaccines, potent adjuvants or various types of immunomodulating agents, such as pattern recognition receptor agonists, recognising pathogen-associated molecular patterns or immunostimulatory monoclonal antibodies. Oncolytic viruses and peptides are used to release tumour antigens in order to stimulate immunity [3, 4]. Furthermore, in vitro expansion of the patient’s own T-cells, which can be genetically modified for specificity towards a specific tumour-associated antigen called chimeric antigen receptor T cell (CAR T-cells), is also now an FDA-approved therapy in blood cancer. Those therapies are currently used systemically, and experience in their local application mainly refers to melanoma, while local application for solid organ tumours is still insufficiently explored. Immuno-oncology carries new opportunities for interventional oncology, and it is vital for interventional radiologists/ oncologist to actively engage in enhancing immuno-oncology. A critical value of interventional oncology is the expertise in target selection, sampling and treatment administration. Image guidance ensures safe access and precise distribution to the tumour or peri-tumoural environment through either direct puncture or intra-arterial routes, even when deeply located or adjacent to vulnerable structures. Interventional oncology treats tumours locally, including percutaneous ablation (radiofrequency, microwave and cryoablation, and irreversible electroporation), but also intra-arterial therapies delivering drugs, embolics or radio isotopes selectively to the tumour-feeding arteries with excellent tolerance, rendering treatment easily repeatable if needed. Even if complete destruction of some targeted tumours can be achieved with interventional oncology treatments, such therapy is often limited due to the tumour size or the number of tumour lesions.

Advances in transarterial therapies for hepatocellular carcinoma: is novel technology leading to better outcomes?

Conventional transarterial chemoembolization (c-TACE) was validated in 2002 for intermediate stage hepatocellular carcinoma (HCC). Recent improvements in overall survival after c-TACE in HCC is linked to both better patient selection, and improvement in treatment technologies: catheter, image guidance and new drug delivery platforms. Drug eluting beads (DEBs) demonstrated a benefit over c-TACE in pharmacokinetic studies; however, two randomized studies comparing c-TACE and DEB-TACE demonstrated no benefit of DEB-TACE in response rate or overall survival. Delivery platforms loaded with yttrium-90 deliver selective internal radiation therapy, which opens a new field of therapy for HCC. Future improvement in intra-arterial therapies will include resorbable loadable embolic material, new emulsion used for c-TACE and platforms releasing multikinase inhibitors.

Contribution of Low-Dose Computerized Tomography With Digital Multiplanar Reconstructions in Thoracic Epidurography and Correlation With Sensory Block in Postoperative Analgesia

Background The level of sensory block in postoperative epidural analgesia has been correlated with conventional contrast epidurography in only one study, while low-dose CT scan epidurography with multiplanar reconstruction may be a better tool for this purpose. Objectives The primary objective of this study was to evaluate, by CT imaging and digital multiplanar reconstruction, the spread and distribution of contrast medium injected into the epidural space through a catheter inserted in a low thoracic position for postoperative analgesia. Materials and Methods Ten patients undergoing major abdominal cancer surgery with effective epidural analgesia were prospectively included at postoperative day three. Two consecutive boluses of 5 mL of a mixture of ropivacaine and contrast medium were injected at 15 minutes intervals into the epidural space. Multislice low-dose CT scan epidurography and an assessment of the sensory block were performed before and after injection of the second bolus. The primary objective was to assess the contribution of CT scan epidurography to predict a correlation between the level of sensory block and the spread of the contrast medium in the epidural space; the secondary objective was to determine the agreement between the two methods. Results The spread of contrast material and the clinical sensory block significantly increased after the second injection (32%; P < 0.05). However, no highly significant correlation was observed between the two methods. A gap of two spinal segments of CT opacification was observed in two patients and was confirmed by clinical assessment. Conclusions CT epidurography is not closely correlated with a clinical assessment of epidural block; thus, a clinical assessment of the sensory block is mandatory. The use of opioid analgesia in combination with local anesthetics may compensate for the lack of efficacy of local anesthetics alone.