The management of hepatocellular carcinoma. Current expert opinion and recommendations derived from the 24th ESMO/World Congress on Gastrointestinal Cancer, Barcelona, 2022.

This article summarises expert discussion on the management of patients with hepatocellular carcinoma (HCC), which took place during the 24th World Gastrointestinal Cancer Congress (WGICC) in Barcelona, July 2022. A multidisciplinary approach is mandatory to ensure an optimal diagnosis and staging of HCC, planning of curative and therapeutic options, including surgical, embolisation, ablative strategies, or systemic therapy. Furthermore, in many patients with HCC, underlying liver cirrhosis represents a challenge and influences the therapeutic options.

Postgraduate oncology educational shifts during the COVID-19 pandemic: results of faculty and medical student surveys.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has disrupted clinical practice, research and teaching. During peaks, virtual courses were implemented but these changes are poorly described, especially for oncology postgraduate students and faculty teachers. PATIENTS AND METHODS: We administered two surveys from June 2021 to October 2021 to students and faculty teachers (250 and 80 responses, respectively) who registered at Gustave Roussy School of Cancer Sciences (Université Paris-Saclay) during 3 consecutive university years (October 2018 to October 2021), where a major shift to e-learning was associated with COVID-19 pandemic. RESULTS: Most students were female (53%), attending physicians (50%), aged 30-39 years (54%) and 2020-2021 (66.4%) was the main year of training. Most faculty teachers were male (58%), aged 40-50 years (44%) and had participated in training for at least 3 years (83%). More than half of the students received 100% virtual training [55% versus 45% face-to-face/mixed teaching modalities; online (84%) versus remote teaching (16%)]. Only 34% of students declared >80% 'active listening' and only 16% of teachers considered e-learning to be more suitable (compared with face-to-face) for postgraduate education. Virtual teaching decreased student-teacher interactions as compared with mixed/face-to-face (lessons were sufficiently interactive for 54% students if virtual only teaching versus for 71% if other teaching modalities; P = 0.009). Teachers stated that virtual learning did not lead to any improvements in terms of attendance (68%), interaction (74%) and quality of teaching (68%). However, most faculty (76%) acknowledged that partial e-learning training should be maintained outside the pandemic, if it represents ≤50% of the whole teaching (teachers: 79% versus student: 66%; P = 0.04). CONCLUSIONS: COVID-19 accelerated the transition toward novel practices. Students and faculty teachers agreed on the need for future mixed (≤50% e-learning) teaching modalities. Adequate formation and the use of codified best newer virtual practices are required.

Percutaneous Transpedicular Fixation by PEEK Polymer Implants Combined with Cementoplasty for Vertebral Compression Fractures: A Pilot Study.

PURPOSE: To evaluate the feasibility and safety of percutaneous transpedicular fixation by PEEK polymer implants and cementoplasty for vertebral compression fracture (VCF). MATERIALS AND METHODS: From February 2019 to December 2019, 6 consecutive patients (3 men and 3 women; mean age 55 ± 8 years; range 40-64 years) who had percutaneous transpedicular fixation with cementoplasty for the treatment of VCF (5 tumor lesions, 1 traumatic) were included. The procedure duration, length of hospital stay, and complications were reported. Visual analog scale (VAS) and the Oswestry disability index (ODI) for pain and disability were assessed before and 2 months after the procedure. RESULTS: The mean procedure duration was 74 ± 47 min (range 20-140 min). The median length of hospital stay was 3 days (range 2-63) after the procedure. Only minor adverse events were reported (4 asymptomatic cement leakages) but no severe complications. No cases of procedural site fracture during follow-up were noted (median 198 days; range 78-238 days). The mean VAS score decreased from 6.2 ± 1.8 mm (median 6 mm; range 4-9 mm) before the procedure to 1.7 ± 2.1 mm (median 1; range 0-5 mm) after the procedure. The ODI decreased from 36 ± 14% (range 18-54%) before the procedure to 23 ± 10% (range 11-30%) at 2-months follow-up. CONCLUSIONS: Percutaneous transpedicular fixation of VCF by PEEK implants with cementoplasty appears feasible and safe.

Radiofrequency ablation versus surgical resection for the treatment of oligometastatic lung disease.

PURPOSE: The purpose of this study was to compare efficacy and tolerance between radiofrequency ablation (RFA) and surgery for the treatment of oligometastatic lung disease. MATERIALS AND METHODS: This retrospective study reviewed patients treated in two institutions for up to 5 pulmonary metastases with a maximal diameter of 4cm and without associated pleural involvement or thoracic lymphadenopathy. Patient demographics, tumor characteristics, treatment outcome, and length of hospital stay were compared between the two groups. Efficacy endpoints were overall survival (OS), progression-free survival (PFS) and pulmonary or local tumor progression rates. RESULTS: Among 204 patients identified, 78 patients (42 men, 36 women; mean age, 53.3±14.9 [SD]; age range: 15-81 years) were treated surgically, while 126 patients (59 men, 67 women; mean age, 62.2±10.8 [SD]; age range: 33-80 years) were treated by RFA. In the RFA cohort, patients were significantly older (P<0.0001), with more extra-thoracic localisation (P=0.015) and bilateral tumour burden (P=0.0014). In comparison between surgery and RFA cohorts, respectively, the 1- and 3-year OS were 94.8 and 67.2% vs. 94 and 72.1% (P=0.46), the 1- and 3-year PFS were 49.4% and 26.1% vs. 38.9% and 14.8% (P=0.12), the pulmonary progression rates were 39.1% and 56% vs. 41.2% and 65.3% (P>0.99), and the local tumour progression rates were 5.4% and 10.6% vs. 4.8% and 18.6% (P=0.07). Tumour size>2cm was associated with a significantly higher local tumor progression in the RFA group (P=0.010). Hospitalisation stay was significantly shorter in the RFA group (median of 3 days; IQR=2 days; range: 2-12 days) than in the surgery group (median of 9 days; IQR=2 days; range: 6-21 days) (P<0.01). CONCLUSION: RFA should be considered a minimally-invasive alternative with similar OS and PFS to surgery in the treatment of solitary or multiple lung metastases measuring less than 4cm in diameter without associated pleural involvement or thoracic lymphadenopathy.

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.

Starting the fight in the tumor: expert recommendations for the development of human intratumoral immunotherapy (HIT-IT).

A European Society for Medical Oncology (ESMO)-sponsored expert meeting was held in Paris on 8 March 2018 which comprised 11 experts from academia, 11 experts from the pharmaceutical industry and 2 clinicians who were representatives of ESMO. The focus of the meeting was exclusively on the intratumoral injection/delivery of immunostimulatory agents with the aim of harmonizing the standard terms and methodologies used in the reporting of human intratumoral immunotherapy (HIT-IT) clinical trials to ensure quality assurance and avoid a blurring of the data reported from different studies. The goal was to provide a reference document, endorsed by the panel members that could provide guidance to clinical investigators, pharmaceutical companies, ethics committees, independent review boards, patient advocates and the regulatory authorities and promote an increase in the number and quality of HIT-IT clinical trials in the future. Particular emphasis was placed not only on the development of precise definitions to facilitate a better understanding between investigators but also on the importance of systematic serial biopsies as a driver for translational research and the need for the recording and reporting of data, to facilitate a better understanding of the key processes involved.

Radiofrequency ablation of stage IA non-small cell lung cancer in patients ineligible for surgery: results of a prospective multicenter phase II trial.

BACKGROUND: A prospective multicenter phase II trial to evaluate the survival outcomes of percutaneous radiofrequency ablation (RFA) for patients with stage IA non-small cell lung cancer (NSCLC), ineligible for surgery. METHODS: Patients with a biopsy-proven stage IA NSCLC, staging established by a positron emission tomography-computed tomography (PET-CT), were eligible. The primary objective was to evaluate the local control of RFA at 1-year. Secondary objectives were 1- and 3-year overall survival (OS), 3-year local control, lung function (prior to and 3 months after RFA) and quality of life (prior to and 1 month after RFA). RESULTS: Of the 42 patients (mean age 71.7 y) that were enrolled at six French cancer centers, 32 were eligible and assessable. Twenty-seven patients did not recur at 1 year corresponding to a local control rate of 84.38% (95% CI, [67.21-95.72]). The local control rate at 3 years was 81.25% (95% CI, [54.35-95.95]). The OS rate was 91.67% (95% CI, [77.53-98.25]) at 1 year and 58.33% (95% CI, [40.76-74.49]) at 3 years. The forced expiratory volume was stable in most patients apart from two, in whom we observed a 10% decrease. There was no significant change in the global health status or in the quality of life following RFA. CONCLUSION: RFA is an efficient treatment for medically inoperable stage IA NSCLC patients. RFA is well tolerated, does not adversely affect pulmonary function and the 3-year OS rate is comparable to that of stereotactic body radiotherapy, in similar patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01841060 registered in November 2008.

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.

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.

Lung ablation: Best practice/results/response assessment/role alongside other ablative therapies.

Today, in addition to surgery, other local therapies are available for patients with small-size non-small-cell lung cancer (NSCLC) and oligometastatic disease from various cancers. Local therapies include stereotactic ablation radiotherapy (SABR) and thermal ablative therapies through percutaneously inserted applicators. Although radiofrequency ablation (RFA) has been explored in series with several hundreds of patients with pulmonary tumours, investigation of the potential of other ablation technologies including microwave ablation, cryoablation, and irreversible electroporation is ongoing. There are no randomised studies available to compare surgery, SABR, and thermal ablation. In small-size lung metastases, RFA seems to produce results very close to surgical series with >90% local control and 5-year overall survival of 50%. In primary lung cancer, the technique is reserved for non-surgical candidates. In future, the low invasiveness of thermal ablative therapies will allow for a combination of ablation and systemic therapies in order to improve the outcomes of ablation alone. Another major advantage of thermal ablation is the possibility to treat several metastases in close proximity to one another and retreatment in the same location in case of failure, which is not possible with SABR.

Percutaneous thermal ablation: A new treatment line in the multidisciplinary management of metastatic leiomyosarcoma?

BACKGROUND: The role of percutaneous thermal ablation (PTA) in the multidisciplinary management of metastatic leiomyosarcoma (LMS) has not been thoroughly evaluated. MATERIALS AND METHODS: Single institution retrospective review of all patients with LMS metastases treated with PTA from June 2004 to December 2014. Iterative PTAs were performed as a multifocal treatment for all recurrent or residual macroscopic metastases discovered on imaging after completion of systemic treatment, or alternatively as a targeted treatment of selective metastases found to be progressive on systemic treatment. The primary endpoint was the time to untreatable progression (TTUP), recorded as the time elapsed between the first PTA and the re-initiation of systemic chemotherapy to treat disease progression. Secondary endpoints were overall survival, the 1, 3 and 5-year survival rates, and local control rate. RESULTS: A total of 93 LMS metastases (average diameter 18.2 mm, range 3-45 mm) were successfully treated in 30 patients over 50 treatment sessions with a median follow-up of 34.6 months. The median TTUP was 14.2 months (range 2.4-122.8). The median overall survival after PTA was 48.3 months and the 1, 3 and 5-year overall survival rates were 96.7% (95%CI 84.3-100.0%), 62.0% (95%CI 45.8-84.0%), and 28.3% (95%CI 13.5-59.1%) respectively. Local control rate at 1 year was 95.2% and at 3 years was 89.4%. CONCLUSION: Iterative PTA is an effective treatment line option for appropriately selected patients with metastatic LMS that can delay re-initiation of systemic chemotherapy.

Percutaneous thermal ablation of primary lung cancer.

Percutaneous ablation of small-size non-small-cell lung cancer (NSCLC) has demonstrated feasibility and safety in nonsurgical candidates. Radiofrequency ablation (RFA), the most commonly used technique, has an 80-90% reported rate of complete ablation, with the best results obtained in tumors less than 2-3cm in diameter. The highest one-, three-, and five-year overall survival rates reported in NSCLC following RFA are 97.7%, 72.9%, and 55.7% respectively. Tumor size, tumor stage, and underlying comorbidities are the main predictors of survival. Other ablation techniques such as microwave or cryoablation may help overcome the limitations of RFA in the future, particularly for large tumors or those close to large vessels. Stereotactic ablative radiotherapy (SABR) has its own complications and carries the risk of fiducial placement requiring multiple lung punctures. SABR has also demonstrated significant efficacy in treating small-size lung tumors and should be compared to percutaneous ablation.

Percutaneous Thermal Ablation of Breast Cancer Metastases in Oligometastatic Patients.

OBJECTIVE: To evaluate prognostic factors associated with local control and disease-free-survival (DFS) of oligometastatic breast cancer patients treated by percutaneous thermal ablation (PTA). MATERIALS AND METHODS: Seventy-nine consecutive patients (54.5 ± 11.2 years old) with 114 breast cancer metastases (28.9 ± 16.1 mm in diameter), involving the lungs, the liver, and/or the bone, were treated using PTA with a curative intent. The goal was to achieve a complete remission in association with systemic chemotherapy and hormonal therapy. We retrospectively evaluated the prognostic factors associated with 1- and 2-year local control and the 1- and 2-year DFS rates. RESULTS: The 1- and 2-year local control rates were 83.0 and 76.1 %, respectively. Tumor burden was associated with a poorer outcome for local control after PTA (HR 1.027 by additional millimeter, p = 0.026; >4 cm HR 3.90). The 1- and 2-year DFS rates were 54.2 and 30.4 %, respectively. In multivariate analysis, triple-negative histological subtype and increased size of treated metastases were associated with a poorer DFS (HR 2.22; 95 % CI [1.13-4.36]; p = 0.02 and HR 2.43; 95 % CI [1.22-4.82]; p = 0.011, respectively). CONCLUSION: PTA is effective for local control of breast cancer oligometastases. Tumor burden >4 cm and triple-negative histological subtype are associated with a poorer outcome.

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.