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BackgroundTo retrospectively assess liver tumor ablation margins using intraprocedural PET/CT images from FDG PET/CT-guided microwave or cryoablation procedures and to correlate minimum margin measurements with local progression outcomes.MethodsFifty-six patients (ages 36 to 85, median 62; 32 females) with 77 FDG-avid liver tumors underwent 60 FDG PET/CT guided, percutaneous microwave, or cryoablation procedures. Single breath-hold PET/CT images were used for intraprocedural assessment of the tumor ablation margin: liver tumors remained visible on PET immediately following ablation; microwave ablation zones were visible using contrast-enhanced CT; cryoablation zones (ice balls) were visible using unenhanced CT. Two readers retrospectively determined ablation margin assessability and measured the minimum ablation margin on intraprocedural PET/CT (n = 77) and postprocedural MRI (n = 56). Local tumor progression was assessed on all available follow-up imaging (1–49 months, mean 15). Local tumor progression was correlated with PET/CT minimum margin measurements using clustered survival models for 61 tumors.ResultsMinimum ablation margins were more often assessable using intraprocedural PET/CT (≥ 73/77 tumors, 95%) than postprocedural MRI (≤ 35/56 tumors, 63%). In 61 tumors with PET/CT-assessable margins (excluding tumors with overlapping ablations after PET/CT), there was a 6-fold increased risk of local tumor progression [hazard ratio (HR) 6.05; P = 0.004] for minimum ablation margins < 5 mm.ConclusionBreath-hold PET/CT scans, during PET/CT-guided microwave or cryoablation procedures for FDG-avid liver tumors, enable reliable intraprocedural assessment of the entire tumor ablation margin; a minimum PET/CT ablation margin threshold of 5 mm correlates well with local tumor progression outcomes.

PurposePoor liver tumor visibility after microwave ablation (MWA) limits direct tumor ablation margin assessments using contrast-enhanced CT or ultrasound (US). Positron emission tomography (PET) or PET/CT may offer improved intraprocedural assessment of liver tumor ablation margins versus current imaging techniques, as 18F-fluorodeoxyglucose (18F-FDG)-avid tumors remain visible on PET immediately following ablation. The purpose of this study was to assess intraprocedural 18F-FDG PET scans before and immediately after PET/CT-guided MWA for visualization and quantification of metabolic liver tumor tissue contraction resulting from MWA.MethodsThis retrospective study, conducted at a large academic medical center after Institutional Review Board approval, included 36 patients (20 men; mean age 63 [range 37–85]) who underwent PET/CT-guided MWA of 42 18F-FDG-avid liver tumors from May 2013 to March 2018. Tumor metabolic diameters (short/long axes) were measured for each tumor on pre- and post-ablation PET images. Tumor metabolic volumes were calculated using tumor diameter measurements and compared with automated volumes using an SUV threshold algorithm. A two-tailed paired t test was used for the analyses.ResultsComparing intraprocedural pre- and post-ablation PET images, mean metabolic tumor short- and long-axis diameters decreased from 21.4 to 14.9 mm [− 29%, p < 0.001, standard deviation (SD) 18%] and from 24.0 to 18.0 mm (− 24%, p < 0.001, SD 16%), respectively. The mean calculated tumor metabolic volume decreased from 10.5 to 4.6 mm3 (− 55%, p < 0.001, SD 26%). The mean automated tumor metabolic volume decreased from 10.6 to 5.8 mm3 (− 45%, p < 0.001, SD 30%).ConclusionIntraprocedural PET images of 18F-FDG-avid liver tumors allow visualization and quantification of MWA-induced metabolic tumor tissue contraction during 18F-FDG PET/CT-guided procedures. The ability to visualize contracted tumor immediately post-MWA may facilitate emerging intraprocedural PET and PET/CT imaging techniques that address a clinical gap in directly assessing the ablation margin.

Tumor ablation technologies, such as radiofrequency-, cryo- or high-intensity focused ultrasound (HIFU) ablation will destroy tumor tissue in a minimally invasive manner. Ablation generates large volumes of tumor debris in situ, releasing multiple bio-molecules like tumor antigens and damage-associated molecular patterns. To initiate an adaptive antitumor immune response, antigen-presenting cells need to take up tumor antigens and, following activation, present them to immune effector cells. The impact of the type of tumor ablation on the precise nature, availability and suitability of the tumor debris for immune response induction, however, is poorly understood. In this review, we focus on immune effects after HIFU-mediated ablation and compare these to findings using other ablation technologies. HIFU can be used both for thermal and mechanical destruction of tissue, inducing coagulative necrosis or subcellular fragmentation, respectively. Preclinical and clinical results of HIFU tumor ablation show increased infiltration and activation of CD4 + and CD8 + T cells. As previously observed for other types of tumor ablation technologies, however, this ablation-induced enhanced infiltration alone appears insufficient to generate consistent protective antitumor immunity. Therapies combining ablation with immune stimulation are therefore expected to be key to boost HIFU-induced immune effects and to achieve systemic, long-lasting, antitumor immunity.

Image-guided solid tumor ablation methods have significantly advanced in their capability to target primary and metastatic tumors. These techniques involve noninvasive or percutaneous insertion of applicators to induce thermal, electrochemical, or mechanical stress on malignant tissue to cause tissue destruction and apoptosis of the tumor margins. Ablation offers substantially lower risks compared to traditional methods. Benefits include shorter recovery periods, reduced bleeding, and greater preservation of organ parenchyma compared to surgical intervention. Due to the reduced morbidity and mortality, image-guided tumor ablation offers new opportunities for treatment in cancer patients who are not candidates for resection. Currently, image-guided ablation techniques are utilized for treating primary and metastatic tumors in various organs with both curative and palliative intent, including the liver, pancreas, kidneys, thyroid, parathyroid, prostate, lung, breast, bone, and soft tissue. The invention of new equipment and techniques is expanding the criteria of eligible patients for therapy, as now larger and more high-risk tumors near critical structures can be ablated. This article provides an overview of the different imaging modalities, noninvasive, and percutaneous ablation techniques available and discusses their applications and associated complications across various organs.

Percutaneous destruction of cancer cells using a radiofrequency energy source has become an accepted part of the modern armamentarium for managing malignancies. Radiofrequency ablation (RFA) is a relatively novel procedure for treating recurrent and metastatic tumors. It is used for debulking tumors and as adjuvant therapy for palliative care apart from its role as a pain management tool. Its use in the third world countries is limited by various factors such as cost and expertise. In the remotest parts of India, where economic development has been slow, abject poverty with poor health care facilities advanced malignancies present a challenge to health care providers. We undertook this study to assess the safety of the percutaneous RFA tumor ablation as a therapeutic or palliative measure in patients where surgery was not possible. We observed that RFA may be an effective, alternative therapeutic modality for some inoperable tumors where other therapeutic modalities cannot be considered. Palliative and therapeutic image-guided RFAs of tumors may be the only treatment option in patients who are inoperable for a variety of reasons. To assess the safety and complications of RFA in such a patient population is important before embarking upon any interventions given their physically, mentally, and socially compromised status in a country such as India. To assess the safety of percutaneous image-guided radiofrequency tumor ablation and to note the various immediate and early complications of the intervention. This was a prospective, observational study conducted in Tata Main Hospital, Jamshedpur, Jharkhand, India. After approval by the Hospital Approval Committee all patients who consented for percutaneous RFA of their tumor admitted in the hospital were included after taking fully informed consent from patient/close relative keeping the following criteria in view. Patients who were likely to derive a direct benefit in the survival or as a palliative measure for relief in their symptoms and patients who were inoperable because of any of the following reasons: (1) Exhausted conventional treatment options, (2) technical and anatomical contraindications to conventional treatment, (3) medical comorbidities precluding surgery, (4) patient refusal, (5) recurrent tumors, and (6) advanced tumor stage. Conventional Treatment has been defined as surgical resection, radiotherapy, and/or chemotherapy, although the patient eligibility for each treatment may vary. Patients with the following were excluded: (1) Severe coagulopathy, (2) heart, renal, or liver failure, (3) lesions within 1 cm of gall bladder, hilum, bowel wall, and major blood vessels, (4) patient with any metal implant, (5) patients in sepsis, and (6) tumor adjacent to structures at risk (main bile ducts, pericardium, stomach, or bowel). The duration of procedure as well as ablation of tumor free margin was significantly related to the size of the tumor. As the size of tumor increased, duration of procedure increased significantly. A good tumor-free margin also needs to be ablated for optimum results as it prevents residual tumors and recurrences in the future. We observed that tumors sized <3.1 cm were optimal in this regard. Most common adverse event in postprocedure period was pain in and around ablation site. Post-RFA syndrome is also a common and benign self-limiting side effect. Patient counseling and proper selection of patients in the early stages of malignancy can enhance the efficacy of the procedure and patient satisfaction. Percutaneous image-guided RFA is an option in patients where most other tumor management modalities have been exhausted or rejected. RFA may not be free from side effects such as postablation syndrome, pain, and there may be other serious complications such as bleeding, but based on our observations, percutaneous image-guided RFA of tumors is a safe palliative and therapeutic treatment option.

Background: Real-time split-dose PET can identify the targeted colorectal liver metastasis (CLM) and eliminate the need for repeated contrast administration before and during thermal ablation (TA). This study aimed to assess the added value of pre-ablation real-time split-dose PET when combined with non-contract CT in the detection of CLM for ablation and the evaluation of the ablation zone and margins. Methods: A total of 190 CLMs/125 participants from two IRB-approved prospective clinical trials using PET/CT-guided TA were analyzed. Based on detection on pre-TA imaging, CLMs were categorized as detectable, non-detectable, and of poor conspicuity on CT alone, and detectable, non-detectable, and low FDG-avidity on PET/CT after the initial dose. Ablation margins around the targeted CLM were evaluated using a 3D volumetric approach. Results: We found that 129/190 (67.9%) CLMs were detectable on CT alone, and 61/190 CLMs (32.1%) were undetectable or of poor conspicuity, not allowing accurate depiction and targeting by CT alone. Thus, the theoretical 5- and 10-mm margins could not be defined in these tumors (32.1%) using CT alone. When TA intraprocedural PET/CT images are obtained and inspected (fused PET/CT), only 4 CLM (2.1%) remained undetectable or had a low FDG avidity. Conclusions: The addition of PET to non-contrast CT improved CLM detection for ablation targeting, margin assessments, and continuous depiction of the FDG avid CLMs during the ablation without the need for multiple intravenous contrast injections pre- and intra-procedurally.

Immunotherapy has remarkably revolutionized the management of advanced HCC and prompted clinical trials, with therapeutic agents being used to selectively target immune cells rather than cancer cells. Currently, there is great interest in the possibility of combining locoregional treatments with immunotherapy for HCC, as this combination is emerging as an effective and synergistic tool for enhancing immunity. On the one hand, immunotherapy could amplify and prolong the antitumoral immune response of locoregional treatments, improving patients’ outcomes and reducing recurrence rates. On the other hand, locoregional therapies have been shown to positively alter the tumor immune microenvironment and could therefore enhance the efficacy of immunotherapy. Despite the encouraging results, many unanswered questions still remain, including which immunotherapy and locoregional treatment can guarantee the best survival and clinical outcomes; the most effective timing and sequence to obtain the most effective therapeutic response; and which biological and/or genetic biomarkers can be used to identify patients likely to benefit from this combined approach. Based on the current reported evidence and ongoing trials, the present review summarizes the current application of immunotherapy in combination with locoregional therapies for the treatment of HCC, and provides a critical evaluation of the current status and future directions.

In situ tumor ablation techniques, like radiotherapy, cryo- and heat-based thermal ablation are successfully applied in oncology for local destruction of tumor masses. Although diverse in technology and mechanism of inducing cell death, ablative techniques share one key feature: they generate tumor debris which remains in situ . This tumor debris functions as an unbiased source of tumor antigens available to the immune system and has led to the concept of in situ cancer vaccination. Most studies, however, report generally modest tumor-directed immune responses following local tumor ablation as stand-alone treatment. Tumors have evolved mechanisms to create an immunosuppressive tumor microenvironment (TME), parts of which may admix with the antigen depot. Provision of immune stimuli, as well as approaches that counteract the immunosuppressive TME, have shown to be key to boost ablation-induced anti-tumor immunity. Recent advances in protein engineering have yielded novel multifunctional antibody formats. These multifunctional antibodies can provide a combination of distinct effector functions or allow for delivery of immunomodulators specifically to the relevant locations, thereby mitigating potential toxic side effects. This review provides an update on immune activation strategies that have been tested to act in concert with tumor debris to achieve in situ cancer vaccination. We further provide a rationale for multifunctional antibody formats to be applied together with in situ ablation to boost anti-tumor immunity for local and systemic tumor control.

Purpose Six years ago, in 2015, the Focused Ultrasound Foundation sponsored a workshop to discuss, and subsequently transition the landscape, of focused ultrasound as a new therapy for treating glioblastoma. Methods This year, in 2021, a second workshop was held to review progress made in the field. Discussion topics included blood–brain barrier opening, thermal and nonthermal tumor ablation, immunotherapy, sonodynamic therapy, and desired focused ultrasound device improvements. Results The outcome of the 2021 workshop was the creation of a new roadmap to address knowledge gaps and reduce the time it takes for focused ultrasound to become part of the treatment armamentarium and reach clinical adoption for the treatment of patients with glioblastoma. Priority projects identified in the roadmap include determining a well-defined algorithm to confirm and quantify drug delivery following blood–brain barrier opening, identifying a focused ultrasound-specific microbubble, exploring the role of focused ultrasound for liquid biopsy in glioblastoma, and making device modifications that better support clinical needs. Conclusion This article reviews the key preclinical and clinical updates from the workshop, outlines next steps to research, and provides relevant references for focused ultrasound in the treatment of glioblastoma.