Interventional oncology at the time of COVID-19 pandemic: Problems and solutions.

The COVID-19 pandemic has deeply impacted the activity of interventional oncology in hospitals and cancer centers. In this review based on official recommendations of different international societies, but also on local solutions found in different expert large-volume centers, we discuss the changes that need to be done for the organization, safety, and patient management in interventional oncology. A literature review of potential solutions in a context of scarce anesthesiologic resources, limited staff and limited access to hospital beds are proposed and discussed based on the literature data.

Thermal-ablation of vertebral metastases prevents adverse events in patients with differentiated thyroid carcinoma.

PURPOSE: To evaluate a strategy that used thermal-ablation of vertebral metastases (VM) to prevent vertebral related events (VRE) in patients with differentiated thyroid cancer (DTC). METHODS: This single center study retrospectively reviewed records and post-operative imaging of all DTC patients treated with thermal-ablation for asymptomatic VMs. Rate of local tumor control at first post-operative imaging, 12 and 24 months after thermal-ablation and rate of VREs at 12 and 24 months among the treated VMs were reported. New VMs that occurred during the follow-up and were not considered for additional thermal-ablation were moniroted and VREs were reported. RESULTS: Thermal-ablation was used to achieve local control of 41 VMs in 28 patients. Median post-treatment follow-up was 22 months [range: 12-80] and the mean delay for first post-operative imaging was 2 months [range: 0.6-7.5]. Local control at first post-operative imaging, 12 and 24 months was achieved in 87.8%, 82.9% and 75.6%, respectively. Among the treated VMs the rates of VRE was 7.3% at 2 years, significantly lower if local control was achieved at first post-operative imaging than if it was not (0% vs 30%, p = 0.011, OR = 0.184 [95%CI = 0.094-0.360]). After thermal-ablation procedures, 19 news VMs occurred in 11 patients (39.2%) with a median interval of 8 months [range 1-26] and remained untreated. Among these untreated VMs, the rate of VREs at 2 years was significantly higher compared to the treated VMs: (36.8% vs. 7.3%, p = 0.008, OR = 0.135, [95%CI = 0.030-0.607]). CONCLUSION: local tumor control of VMs using thermal-ablation decreases the risk of VREs in DTC patients.

Parameters for Stable Water-in-Oil Lipiodol Emulsion for Liver Trans-Arterial Chemo-Eembolization.

PURPOSE: Water-in-oil type and stability are important properties for Lipiodol emulsions during conventional trans-arterial chemo-embolization. Our purpose is to evaluate the influence of 3 technical parameters on those properties. MATERIALS AND METHODS: The Lipiodol emulsions have been formulated by repetitive back-and-forth pumping of two 10-ml syringes through a 3-way stopcock. Three parameters were compared: Lipiodol/doxorubicin ratio (2/1 vs. 3/1), doxorubicin concentration (10 vs. 20 mg/ml) and speed of incorporation of doxorubicin in Lipiodol (bolus vs. incremental vs. continuous). The percentage of water-in-oil emulsion obtained and the duration until complete coalescence (stability) for water-in-oil emulsions were, respectively, evaluated with the drop-test and static light scattering technique (Turbiscan). RESULTS: Among the 48 emulsions formulated, 32 emulsions (67%) were water-in-oil. The percentage of water-in-oil emulsions obtained was significantly higher for incremental (94%) and for continuous (100%) injections compared to bolus injection (6%) of doxorubicin. Emulsion type was neither influenced by Lipiodol/doxorubicin ratio nor by doxorubicin concentration. The mean stability of water-in-oil emulsions was 215 ± 257 min. The emulsions stability was significantly longer when formulated using continuous compared to incremental injection (326 ± 309 vs. 96 ± 101 min, p = 0.018) and using 3/1 compared to 2/1 ratio of Lipiodol/doxorubicin (372 ± 276 vs. 47 ± 43 min, p = <0.0001). Stability was not influenced by the doxorubicin concentration. CONCLUSION: The continuous and incremental injections of doxorubicin in the Lipiodol result in highly predictable water-in-oil emulsion type. It also demonstrates a significant increase in stability compared to bolus injection. Higher ratio of Lipiodol/doxorubicin is a critical parameter for emulsion stability too.

Stabilization Improves Theranostic Properties of Lipiodol®-Based Emulsion During Liver Trans-arterial Chemo-embolization in a VX2 Rabbit Model.

PURPOSE: To demonstrate that stability is a crucial parameter for theranostic properties of Lipiodol®-based emulsions during liver trans-arterial chemo-embolization. MATERIALS AND METHODS: We compared the theranostic properties of two emulsions made of Lipiodol® and doxorubicin in two successive animal experiments (One VX2 tumour implanted in the left liver lobe of 30 rabbits). Emulsion-1 reproduced one of the most common way of preparation (ratio of oil/water: 1/1), and emulsion-2 was designed to obtain a water-in-oil emulsion with enhanced stability (ratio of oil/water: 3/1, plus an emulsifier). The first animal experiment compared the tumour selectivity of the two emulsions: seven rabbits received left hepatic arterial infusion (HAI) of emulsion-1 and eight received HAI of emulsion-2. 3D-CBCT acquisitions were acquired after HAI of every 0.1 mL to measure the densities' ratios between the tumours and the left liver lobes. The second animal experiment compared the plasmatic and tumour doxorubicin concentrations after HAI of 1.5 mg of doxorubicin administered either alone (n = 3) or in emulsion-1 (n = 6) or in emulsion-2 (n = 6). RESULTS: Emulsion-2 resulted in densities' ratios between the tumours and the left liver lobes that were significantly higher compared to emulsion-1 (up to 0.4 mL infused). Plasmatic doxorubicin concentrations (at 5 min) were significantly lower after HAI of emulsion-2 (19.0 µg/L) than emulsion-1 (275.3 µg/L, p < 0.01) and doxorubicin alone (412.0 µg/L, p < 0.001), and tumour doxorubicin concentration (day-1) was significantly higher after HAI of emulsion-2 (20,957 ng/g) than in emulsion-1 (8093 ng/g, p < 0.05) and doxorubicin alone (2221 ng/g, p < 0.01). CONCLUSION: Stabilization of doxorubicin in a water-in-oil Lipiodol®-based emulsion results in better theranostic properties.

Conversion to resection of liver metastases from colorectal cancer with hepatic artery infusion of combined chemotherapy and systemic cetuximab in multicenter trial OPTILIV.

BACKGROUND: Systemic chemotherapy typically converts previously unresectable liver metastases (LM) from colorectal cancer to curative intent resection in ∼15% of patients. This European multicenter phase II trial tested whether hepatic artery infusion (HAI) with triplet chemotherapy and systemic cetuximab could increase this rate to 30% in previously treated patients. PATIENTS AND METHODS: Participants had unresectable LM from wt KRAS colorectal cancer. Main non-inclusion criteria were advanced extra hepatic disease, prior HAI and grade 3 neuropathy. Irinotecan (180 mg/m(2)), oxaliplatin (85 mg/m(2)) and 5-fluorouracil (2800 mg/m(2)) were delivered via an implanted HAI access port and combined with i.v. cetuximab (500 mg/m(2)) every 14 days. Multidisciplinary decisions to resect LM were taken after every three courses. The rate of macroscopic complete resections (R0 + R1) of LM, progression-free survival (PFS) and overall survival (OS) were computed according to intent to treat. RESULTS: The patient population consisted of 42 men and 22 women, aged 33-76 years, with a median of 10 LM involving a median of six segments. Up to 3 extrahepatic lesions of <1 cm were found in 41% of the patients. A median of six courses was delivered. The primary end point was met, with R0-R1 hepatectomy for 19 of the 64 previously treated patients, 29.7% (95% confidence interval 18.5-40.9). Grade 3-4 neutropenia (42.6%), abdominal pain (26.2%), fatigue (18%) and diarrhea (16.4%) were frequent. Objective response rate was 40.6% (28.6-52.3). Median PFS and OS reached 9.3 (7.8-10.9) and 25.5 months (18.8-32.1) respectively. Those with R0-R1 hepatectomy had a median OS of 35.2 months (32.6-37.8), with 37.4% (23.6-51.2) alive at 4 years. CONCLUSION: The coordination of liver-specific intensive chemotherapy and surgery had a high curative intent potential that deserves upfront randomized testing. PROTOCOL NUMBERS: EUDRACT 2007-004632-24, NCT00852228.

Percutaneous radiofrequency ablation of hepatic tumors during temporary venous occlusion.

OBJECTIVE: We evaluated the feasibility, tolerance, and efficacy of percutaneous hepatic vein or segmental portal branch balloon occlusion during radiofrequency ablation of hepatic malignancies. SUBJECTS AND METHODS: Ten tumors were treated by percutaneous radiofrequency ablation during balloon occlusion of a hepatic vein (n = 8) or a segmental portal branch (n = 2). Venous occlusion was undertaken because the tumor was in contact with a hepatic vein (n = 3) or a portal branch (n = 1); because the tumor exceeded 35 mm in width (mean, 44 mm), which was considered the maximum size amenable to ablation in a single session (n = 2); or because of both large size and contact with a hepatic vein (n = 3) or a portal branch (n = 1). RESULTS: Vascular occlusion was always technically possible. Radiofrequency was delivered to one to three locations (mean, 1.9 locations) with a cluster electrode. The largest axis of radiofrequency-induced lesions after ablation with the cluster needle-between 42 and 51 mm (mean, 49 mm)-was always larger than the targeted tumor. These sizes were statistically larger than in a matched control group of patients who underwent radiofrequency ablation without vascular occlusion (p < 0.0003). After a mean follow-up of 12.6 months, CT and MR imaging revealed complete destruction of nine tumors after a single radiofrequency ablation treatment; one tumor required three treatments to achieve ablation. Five patients are tumor-free 12-18 months (mean, 14.4 months) after the first radiofrequency ablation treatment, and five developed new liver metastases. CONCLUSION: Temporary hepatic vein or portal branch occlusion during radiofrequency ablation can safely facilitate the treatment of large tumors or tumors in contact with the walls of large vessels.

Hepatic intraarterial 131I iodized oil for treatment of hepatocellular carcinoma in patients with impeded portal venous flow.

PURPOSE: To evaluate the efficacy and safety of intraarterial hepatic iodine 131 iodized oil for treatment of hepatocellular carcinoma in patients with impeded portal venous flow. MATERIALS AND METHODS: Twenty-four patients (mean age, 61 years) with hepatocellular carcinoma underwent 38 courses of 131I iodized oil (one to three per patient), with a mean dose of 2,146 MBq injected into the proper hepatic artery. Hepatocellular carcinoma manifested as single nodules (n = 8; mean, 7.75 cm), multiple nodules (n = 13; mean, 5.46 cm), or a mass (n = 3) occupying more than two hepatic segments. Portal venous thrombosis was complete (n = 10), right (n = 9), left (n = 2), or multisegmental (n = 1). Two patients had hepatofugal portal flow. RESULTS: Among the 23 patients with evaluable results, response to treatment was partial in three, and disease was stable in 12 and progressive in eight. Estimated actuarial survival rates were 70%, 33%, 12%, and 6% at 3, 6, 9, and 12 months, respectively, with two patients alive at 9 and 11 months. The median survival time was 147 days. Adverse events were the early death of one patient owing to hepatic failure and transient symptomatic hepatic failure after 12 courses in nine patients. CONCLUSION: In this preliminary experience, intraarterial hepatic 131I iodized oil did not demonstrate high efficacy in the treatment of hepatocellular carcinoma in patients with portal venous thrombosis, as side effects were not rare.

Modification of arterial and portal hemodynamics after injection of iodized oils and different emulsions of iodized oils in the hepatic artery: an experimental study.

PURPOSE: A strong embolic effect of iodized oil/drug mixtures injected in the hepatic artery appeared to be an efficient way of prolonging the contact time between drugs and tumor tissue. Therefore, the authors evaluated arterial and portal embolic effects after hepatic intra-arterial injection of iodized oils and various emulsions of iodized oil. MATERIALS AND METHODS: Twenty-five pigs were monitored for the Doppler resistance index (DRI) in the hepatic artery and wedge hepatic vein pressure (WHVP) during 1 hour after injection of pure iodized oil, ultra-fluid or fluid, and four different emulsions of iodized oil ultra-fluid, into the hepatic artery. RESULTS: Mean area under the curve (AUC) values of DRI increases varied from 20.3 to 24.2 after injection of pure iodized oils or water-in-oil emulsions, and were 13.2 for large-droplet oil-in-water emulsion and 8.2 for small-droplet oil-in-water emulsion. Mean AUC values of WHVP increases varied from 151.6 to 195.6 after injection of pure iodized oils or water-in-oil emulsions, and were 105.5 for large-droplet oil-in-water emulsion and 8.5 for small-droplet oil-in-water emulsion. There was a significant difference in DRI and WHVP modifications between small-droplet oil-in-water emulsions and all other products (P = .001), between the two oil-in-water emulsions and the two water-in-oil emulsions (P = .004), and between the two oil-in-water emulsions and pure iodized oils (P = .002). CONCLUSION: After hepatic intra-arterial injection, water-in-oil emulsions and pure iodized oils provided a stronger embolic effect than oil-in-water emulsion, both in the hepatic artery and in the portal vein.

Quantification of tumor uptake of iodized oils and emulsions of iodized oils: experimental study.

PURPOSE: To optimize use of iodized oil for diagnostic computed tomography (CT) enhanced with iodized oil and for interstitial radiation therapy with iodine-131-labeled iodized oil, the authors quantified the distribution of iodized oil after injection of different formulations of iodized oil into the hepatic artery. MATERIALS AND METHODS: I-125-labeled iodinated ethyl ester of poppyseed oil in two viscosities (iodized oil ultrafluid [viscosity, 0.04 Pa/sec] and iodized oil fluid [viscosity, 0.17 Pa/sec]) was injected (pure forms and three different emulsions of each) into the hepatic artery of rabbits bearing VX2 tumors in the liver. All rabbits received a radiation dose of 4 MBq per kilogram of body weight in 0.1 mL/kg iodized oil. Animals were killed 4 days later, and iodized oil uptake was evaluated in the tumor, nontumorous liver, and lung. RESULTS: There were no statistically significant differences in uptake between pure iodized oil ultrafluid or fluid or between the same type of emulsions made with each type of iodized oil. Lung uptake was significantly higher with pure iodized oil ultrafluid and fluid (19.75 kBq/g +/- 3.25 [standard error of the mean] vs 19.48 kBq/g +/- 6.15, respectively) than with any emulsions (range, 3.72-8.14 kBq/g; mean, 5.68 kBq/g) except the small-droplet oil-in-water emulsion (10.51 kBq/g +/- 1.18). The ratio of tumor to nontumorous liver uptake of iodized oil was significantly higher with large-droplet water-in-oil emulsions made of iodized oil ultrafluid or fluid (10.26 +/- 2.88 and 9.53 +/- 0.64, respectively) than with any other product (range, 4.07-5.38; mean, 4.49). CONCLUSION: Use of large-droplet water-in-oil emulsions limited lung uptake and increased tumor uptake of iodized oil after intraarterial hepatic injection in rabbits bearing VX2 tumors in the liver.

Antitumor electrochemotherapy: new advances in the clinical protocol.

BACKGROUND: Electrochemotherapy (ECT) is a new antitumor approach that combines systemic bleomycin (BLM) with electric pulses (EP) delivered locally at the tumor site. These EP permeabilize the cells in the tissue, allow BLM delivery inside the cells, and increase BLM cytotoxicity. As an extension of our initial Phase I trial on patients with head and neck squamous cell carcinoma (HNSCC) permeation nodules, we tested variations of ECT protocol to determine how to improve it. METHODS: Seven patients with multiple and/or large permeation nodules of HNSCC or of salivary or breast adenocarcinoma were treated in 10 sessions. They received BLM followed by runs of four or eight short (100 microseconds) and intense (1000 or 1300 V/cm-1) EP delivered at adjacent positions on the nodules to cover all of the tumor surface. RESULTS: We determined the therapeutic window for EP delivery to be between 8 and 28 minutes after BLM intravenous injection. We showed patient tolerance to a high number of EP, along with ECT feasibility after BLM intraarterial injection or on adenocarcinoma nodules. Clear antitumor effects were obtained, especially in the small nodules. In the largest nodules we observed extended tumor necrosis. CONCLUSIONS: Relatively efficient ECT can be performed for large and think nodules, and ECT remains safe even when a large number of EP are delivered. However, in this study, ECT's effectiveness on large nodules was lower than on the previously treated small nodules, probably due to external electrodes inadequacy. The data reported stimulated us to design a new device for EP delivery.

Circulatory alterations induced by intra-arterial injection of iodized oil and emulsions of iodized oil and doxorubicin: experimental study.

PURPOSE: To evaluate circulatory alterations induced by intra-arterial injection of iodized oil and emulsions of iodized oil with an anticancer drug. MATERIALS AND METHODS: The viscosities and stability were evaluated in arterial flow of iodized oil and the emulsions. Doppler ultrasound was used to quantify the embolic effect in the arteries of rabbits. The behavior of doxorubicin and iodized oil in the rat cremaster muscle was studied with videomicroscopy. RESULTS: The emulsions did not break up after injection, and the size of discontinuous-phase droplets did not change. The embolic effect did not correlate with viscosity. The thinnest water-in-oil emulsion had the lowest embolic effect and induced homogeneous distribution of iodized oil droplets in the arterial tree. CONCLUSION: Changes in the formulation of emulsions obtained with the same proportions of drug and iodized oil change the distribution of iodized oil in the arterial tree, the location at which the drug is released, and the embolic effect.

Transcatheter chemoembolization of progressive carcinoid liver metastasis.

PURPOSE: The authors report their experience treating progressive liver metastases from carcinoid tumor with doxorubicin, iodized oil, and gelatin sponge embolization. MATERIALS AND METHODS: Of 23 patients, 18 had carcinoid syndrome and 19 had elevated urinary 5-hydroxyindoleacetic acid (5-HIAA) levels. Relief of symptoms, changes in 5-HIAA levels, and changes in tumor size could be evaluated in 10, 11, and 17 patients, respectively. RESULTS: Symptomatic response was complete (average duration, 29 months) in 70% and partial in 30% of evaluated patients. Biologic response was complete (average duration, 21 months) in 73%, partial in 18%, and minor in 9% of evaluated patients. Morphologic response was complete in 11%, partial in 24%, and minor in 24% of evaluated patients. Survival after diagnosis of primary tumor, diagnosis of hepatic metastases, and first chemoembolization was 81, 47, and 24 months, respectively. Eight patients were alive at the end of the study. No mortality was related to chemoembolization. CONCLUSION: Chemoembolization is safe and effective for palliation of carcinoid liver metastases.