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.

Results of Radiation Therapy as Local Ablative Therapy for Oligometastatic Non-Small Cell Lung Cancer

Oligometastatic cancer is characterized by a limited number of metastatic deposits. Compared with lung cancer patients who have more widespread disease, oligometastatic lung cancer patients have more favorable survival outcomes. Therefore, it has been hypothesized that local ablative therapy (LAT) directed at the metastatic deposits in addition to standard-of-care systemic therapy may further improve survival outcomes in oligometastatic lung cancer patients. One LAT modality that has been utilized in oligometastatic lung cancer is radiation therapy. In particular, ultra-hypofractionated radiotherapy, also known as stereotactic body radiotherapy (SBRT), has been shown to provide excellent local control with a favorable safety profile. Here, we reviewed the retrospective studies and prospective trials that have deployed radiation therapy as LAT in oligometastatic lung cancer, including randomized studies showing benefits for progression-free survival and overall survival with the addition of LAT. We also discuss the impact of targeted therapies and immunotherapy on radiation as LAT.

Left atrial strain for predicting arrhythmia recurrence after atrial fibrillation ablation: cardiac magnetic resonance rapid strain vs. feature tracking strain

Background Global left atrial (LA) strain is a predictor of atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI). Recently, novel rapid LA strain assessment approaches have emerged: LA long axis strain and LA AV junction strain. Currently, it remains unknown whether these rapid strain approaches can predict AF recurrence after AF ablative therapy and hence may be a simple alternative for the cumbersome LA feature tracking strain analysis. Purpose The present study focusses on the predictive value of different atrial strain quantification methods in relation to AF recurrence after PVI. Rapid LA strain analysis is compared to LA feature tracking strain in AF patients. Methods A total of 58 AF patients (78% paroxysmal AF, 64% male, mean age 61±7 years) undergoing first radiofrequency PVI ablation were included. Prior to ablation, all patients underwent cardiac magnetic resonance imaging being in sinus rhythm. LA rapid strain (long axis strain and AV junction strain) and LA feature tracking strain were derived from 2-chamber and 4-chamber cine CMR images. All patients were routinely followed up for arrhythmia recurrence through 12-lead ECGs, mobile-based one-lead ECGs, and/or Holter monitoring. Results After one year follow-up, arrhythmia recurrence (after the 90-day blanking period) was observed in 21 patients (36%), occurring after a median of 159 (119–320) days. LA long axis strain, AV junction strain, and feature tracking strain were all significantly reduced in patients with AF recurrence compared to patients without AF recurrence (long axis strain: −19.96±11.03% vs. −28.18±9.93%, P=0.005; AV junction strain: −18.08±9.69% vs. −25.60±8.79%, P=0.004; feature tracking strain: −12.54±4.16% vs. −15.94±3.50%, P=0.002, respectively, figure A to C). ROC analysis identified LA feature tracking strain as having the highest area under the curve (AUC) for predicting AF recurrence after ablative therapy (AUC: 0.75 for LA feature tracking strain, 0.71 for LA long axis strain, 0.70 for AV junction strain, figure D). Both LA rapid strain methods had a significant correlation with LA feature tracking strain (LA long axis strain vs. LA feature tracking strain, r=0.76, P<0.001 and LA AV junction strain vs. LA feature tracking strain, r=0.77, P<0.001). Conclusion LA rapid strain and LA feature tracking strain both have clinically relevant predictive power for prediction of AF recurrence after index PVI in AF patients. Considering the ease of LA rapid strain analysis, this method may be a valuable parameter to assess in clinical practice. FUNDunding Acknowledgement Type of funding sources: None. Figure 1

Single-Center Experience of Focal Thermo-Ablative Therapy After Pelvic Radiotherapy for In-Field Prostate Cancer Oligo-Recurrence

PurposeIn-field prostate cancer (PCa) oligo-recurrence after pelvic radiotherapy is a challenging situation for which metastasis-directed treatments may be beneficial, but options for focal therapies are scarce.MethodsWe retrospectively reviewed data for patients with three or less in-field oligo-recurrent nodal, bone and/or locally recurrent (prostate, seminal vesicles, or prostatic bed) PCa lesions after radiation therapy, identified with molecular imaging (PET and/or MRI) and treated by focal ablative therapy (cryotherapy or radiofrequency) at the Institut Bergonié between 2012 and 2020. Chosen endpoints were the post-procedure PSA response (partially defined as a >50% reduction, complete as a PSA <0.05 ng/ml), progression-free survival (PFS) defined as either a biochemical relapse (defined as a rise >25% of the Nadir and above 2 ng/ml), radiological relapse (on any imaging technique), decision of treatment modification (hormonotherapy initiation or line change) or death, and tolerance.ResultsForty-three patients were included. Diagnostic imaging was mostly 18F-Choline positron emission tomography/computerized tomography (PET/CT) (75.0%), prostate specific membrane antigen (PSMA) PET/CT (9.1%) or a combination of pelvic magnetic resonance imaging (MRI), CT, and 99 mTc-bone scintigraphy (11.4%). PSA response was observed in 41.9% patients (partial in 30.3%, complete in 11.6%). In the hormone-sensitive exclusive focal ablation group (n = 31), partial and complete PSA responses were 32.3 and 12.9% respectively. Early local control (absence of visible residual active target) on the post-procedure imaging was achieved with 87.5% success. After a median follow-up of 30 months (IQR 13.3–56.8), the median PFS was 9 months overall (95% CI, 6–17), and 17 months (95% CI, 11–NA) for PSA responders. Complications occurred in 11.4% patients, with only one grade IIIb Dindo–Clavien event (uretral stenosis requiring endoscopic uretrotomy).ConclusionIn PCa patients showing in-field oligo-recurrence after pelvic radiotherapy, focal ablative treatment is a feasible option, possibly delaying a systemic treatment initiation or modification. These invasive strategies should preferably be performed in expert centers and discussed along other available focal strategies in multi-disciplinary meetings.

Should the management of high grade cervical squamous intraepithelial lesion (HSIL) be different in HIV-positive women?

Background This study compares the management and outcome of high grade squamous intraepithelial lesions (HSIL) in HIV-positive and -negative women and identifies risk factors for treatment failure. Methods This retrospective, controlled study includes 146 HIV-positive women, matched for HSIL, age and year of diagnosis, with 146 HIV-negative women. Differences were analysed using parametric and non-parametric tests and Kaplan–Meier survival curves. A binary logistic regression was used to assess risk factors for treatment failure. Results Persistence of cervical disease was observed most frequently in HIV-positive women (42 versus 17%) (p < 0.001) and the cone biopsy margins were more often invaded in HIV-positive-women than in HIV-negative ones. (37 versus 16%; p < 0.05). HIV-positive women, with successful cervical treatment had better HIV disease control: with significantly longer periods of undetectable HIV viral loads (VL) (19 versus 5 months; p < 0.001) and higher CD4 counts (491 versus 320 cells/mm3; p < 0.001). HIV-positive women with detectable VL at the time of dysplasia had 3.5 times (95% IC: 1.5–8.3) increased risk of treatment failure. Being treated through ablative therapy was associated with a 7.4, four-fold (95% IC: 3.2–17.3) increased risk of treatment failure compared to conization Conclusion HIV-positive women have a higher risk of treatment failure of HSIL than do HIV-negative women, especially when ablative therapy is used and in women with poor control of their HIV infection. The management and the follow- up of HSIL’s guidelines in this high-risk population should be adapted consequently: for HIV-positive women with uncontrolled viral load, excisional treatment should be the preferred therapy, whereas for women with undetectable viral load, CD4 + lymphocytes higher than 500 cells/mm3 and with a desire of pregnancy, ablative therapy may be considered.

Adjunctive Intravitreal Triamcinolone Acetonide for Exudative Retinal Detachment in Coats Disease

Purpose: This work aims to assess the value of intravitreal triamcinolone acetonide (IVTA) as an adjunctive therapy in advanced Coats disease with exudative retinal detachment (ERD). Methods: A retrospective review was conducted of patients with Coats disease stage 3 or higher who received IVTA to decrease subretinal fluid (SRF), facilitate retinal ablative therapy, and avoid surgical drainage. Primary outcomes were SRF resolution and avoidance of surgical SRF drainage. Results: Seventeen eyes of 17 patients (mean, [SD] age, 3.9 [3.4] years) met the inclusion criteria. ERD configuration was bullous in 7 and shallow in 10 eyes. Following a single IVTA injection, ablative therapy was achieved after a mean (SD) of 2.1 (3.0) weeks. Complete SRF resolution was observed in 13 eyes (76.4%) after a mean of 1.3 IVTA injections and a mean of 2 (SD, 1.27) laser sessions, and none of these eyes required SRF drainage up to last follow-up (mean [SD], 50.5 [26.24] months). In 4 eyes with bullous ERD at presentation, SRF persisted ( P = .015) despite additional measures including surgical drainage. Final visual acuity ranged from 20/100 to no light perception. Cataract developed in 12 of the 17 eyes (70.5%). None developed an increase in intraocular pressure at final follow-up. Conclusions: IVTA injection can be a helpful adjunctive modality to address SRF in advanced Coats disease. It may obviate the need to surgically drain SRF to effectively treat the condition, particularly when the ERD is not highly bullous.