The technique, known as irreversible electroporation, or IRE, works on an entirely different physical principle from conventional ablation. Between two and six thin needle-electrodes are placed around the tumour, and short, intense electric pulses are fired between them. The resulting electric field is strong enough to destabilise the cell membrane itself, punching nanoscale pores into the lipid bilayer. These pores allow the cell’s contents to leak out and trigger apoptosis, a form of programmed cell death, rather than the coagulative necrosis produced by burning or freezing tissue. Because the mechanism is predominantly non-thermal, the collagen scaffolding of ducts and vessels within the treated zone is largely preserved, a property that makes the technique attractive precisely where thermal energy would be most hazardous.

Crucially, IRE also sidesteps the so-called heat sink effect, the Achilles heel of radiofrequency and microwave ablation. When a tumour abuts a large blood vessel, flowing blood continuously carries heat away from the ablation zone, leaving a rim of viable tumour cells that can seed recurrence. Since IRE does not rely on raising tissue temperature, blood flow confers no such protection, and the ablation zone remains predictable even immediately adjacent to major vessels. The technique is not entirely free of thermal effects, the authors caution; temperature rises have been documented near the needle tips during long pulses at very high voltages, a detail that must inform needle placement. Still, the absence of a clinically meaningful heat sink is the central reason IRE has carved out a niche for tumours hugging the portal triad, hepatic veins, inferior vena cava, gallbladder and bowel.

In the new study, published in CVIR Oncology, researchers retrospectively analysed 56 IRE procedures performed in 54 patients at their centre between February 2014 and February 2022. All patients had solitary tumours smaller than three centimetres that a multidisciplinary team had deemed unsuitable for surgery or thermal ablation because the lesions lay within five millimetres of critical structures. The median tumour size was 22 millimetres, and the median age of patients was 61 years. Most had underlying liver disease, with hepatitis C infection and alcohol-related liver disease the most common risk factors, and all patients had well-preserved liver function, classified as Child-Pugh A. Twenty-three patients had already undergone transarterial chemoembolization for larger tumours and still harboured residual disease, while five had recurrent tumours at sites of previous thermal ablation or surgery; the remaining 26 were treatment-naive.

The procedures themselves are technically demanding. Performed under general anaesthesia with deep neuromuscular blockade to eliminate involuntary muscle contraction, they were carried out by interventional radiologists with more than a decade of ablation experience, using CT guidance to position the needles. Accurate probe parallelism, three-dimensional orientation and inter-needle spacing, maintained between 15 and 25 millimetres, are critical to success. Using the NanoKnife system, the team delivered a standard regimen of 90 pulses per electrode pair at voltages between 1000 and 1500 volts, producing currents of 20 to 40 amperes. For larger or irregularly shaped lesions, the electrodes were withdrawn by about a centimetre and a further 90 pulses delivered to extend the ablation margin, a manoeuvre performed in more than three-quarters of cases. Technical success, defined as completion of the full pulse protocol, was achieved in all 56 procedures.

The oncological results were encouraging. On the first follow-up scan four to six weeks after treatment, assessed with the modified Response Evaluation Criteria in Solid Tumours, radiologic complete response was achieved after 83.9 percent of procedures. Neither age, sex, tumour size, adjacent anatomy nor previous treatment significantly influenced the likelihood of complete response. Over a median imaging follow-up of 31.7 months, local recurrence after an initial complete response occurred in 15 of 47 procedures, or 31.9 percent. Mean local tumour progression-free survival was 41.6 months, with 91.5 percent of patients free of local progression at six months, 78.4 percent at one year and 73.7 percent at two years. Notably, outcomes were statistically indistinguishable between treatment-naive patients and those who had undergone prior locoregional therapy, suggesting IRE performs reliably regardless of tumour history.

Safety data were equally important. There were no procedure-related deaths within 30 days, and the overall complication rate was 10.7 percent, with only two major complications, both graded IIIa on the Clavien-Dindo scale: a haemothorax attributed to suspected intercostal artery injury, managed with angiography and chest drainage, and a pneumothorax treated with needle aspiration. Minor complications included transient post-ablation syndrome in two patients and asymptomatic portal vein thrombosis in two others, detected on follow-up imaging. One of these thromboses resolved fully with anticoagulation, while the other led to right lobe atrophy and secondary bile duct damage. The authors point out that although IRE is designed to spare vessels, the tissue swelling that follows treatment can compress adjacent vascular structures and promote thrombosis, and that needles should never be passed directly through vessels. Tumour seeding, a feared complication of needle-based therapies, was not observed, possibly because IRE needles bracket the tumour rather than traversing it.

The findings place IRE within a rapidly evolving therapeutic landscape. The authors note that fewer than 20 percent of patients with early-stage disease are suitable for resection, and donor shortages constrain transplantation, so percutaneous options carry disproportionate weight. Selective internal radiotherapy, in which yttrium-90 microspheres are delivered into the tumour’s arterial supply, has produced excellent results in recent trials, with the LEGACY study reporting three-year overall survival of 86.6 percent and local control above 90 percent for solitary unresectable tumours, and newer single-session workflows eliminating the need for a separate mapping angiogram. Stereotactic body radiotherapy likewise delivers local control rates of 80 to 95 percent at two to three years without requiring anaesthesia, though both alternatives involve radiation exposure, logistical complexity and cost, and both are limited by proximity to radiosensitive organs and by compromised liver function.

IRE, by contrast, demands general anaesthesia, has a genuine learning curve, takes longer than thermal ablation and uses more expensive electrodes. Bracketing a tumour with four to six parallel needles is particularly challenging for central lesions or those near the dome of the liver approached between the ribs, and the study found that tumours larger than two centimetres required significantly more needles than smaller ones. Overlapping treatments with too few needles, the authors warn, yield higher rates of incomplete ablation. These practical constraints mean the technique is best reserved for carefully selected patients: those with small tumours adjacent to bile ducts, the hepatic hilum, gallbladder, bowel or central vasculature, who are unfit for surgery but can tolerate general anaesthesia, and in whom immediate local control is the priority.

For a disease in which anatomical bad luck often forecloses curative treatment, the message from this single-centre experience is quietly significant. With complete response rates comparable to published IRE series and to thermal ablation of perivascular tumours, and safety figures in the same range as heat-based techniques despite the hostile anatomy of the treated lesions, irreversible electroporation appears to be a viable definitive option for a patient group that has long had few. The retrospective design and modest sample size mean randomised comparisons with radioembolization and stereotactic radiotherapy remain desirable, but the study suggests that for small, anatomically treacherous hepatocellular carcinomas, the answer may lie not in turning up the heat, but in switching off the heat altogether.

Subject of Research: Irreversible electroporation as a non-thermal treatment for early-stage hepatocellular carcinoma unsuitable for thermal ablation

Article Title: Irreversible electroporation as a definitive treatment for early-stage HCC unsuitable for thermal ablation: insights from a tertiary liver centre

Article References: Peddu, P., Seneviratne, N., Hashem, E., & Fang, C. (2025). Irreversible electroporation as a definitive treatment for early-stage HCC unsuitable for thermal ablation: insights from a tertiary liver centre. CVIR Oncology, 1(1), Article 17. https://doi.org/10.1007/s44343-025-00018-y

Image Credits: AI Generated

DOI: 10.1007/s44343-025-00018-y

Keywords: hepatocellular carcinoma, irreversible electroporation, thermal ablation, liver cancer, interventional radiology, heat sink effect, locoregional therapy, radiofrequency ablation, microwave ablation, transarterial chemoembolization, radioembolization, stereotactic body radiotherapy

The concept of oligoprogression sits within a broader revolution in how clinicians understand metastatic cancer. For most of the twentieth century, spread beyond the primary tumour was treated as a uniformly systemic disease, best managed with drugs rather than directed local therapy. That binary view began to crumble in 1995, when Samuel Hellman and Ralph Weichselbaum described oligometastasis, an intermediate state in which the metastatic burden is limited enough that aggressive local treatment might genuinely alter the disease course. Oligoprogression refines this idea further: the patient’s overall disease is broadly controlled, often by targeted drugs or immunotherapy, but a small number of lesions, defined in this study as five or fewer, begin to grow while everything else stays stable. These resistant clones represent a unique clinical window, because eliminating them locally could preserve the effectiveness of a systemic regimen that is still suppressing the rest of the disease.

Until now, the dominant local therapy for oligoprogressive disease has been stereotactic body radiotherapy, or SBRT, which delivers precisely focused, high-dose radiation to individual lesions. Clinical trials, including a randomised phase 2 study published in The Lancet in 2024, have shown that adding SBRT to standard systemic therapy can delay disease progression in patients with oligoprogressive breast and lung cancers. But radiation has inherent limits. Cumulative dose constraints restrict how often a region can be retreated, previously irradiated tissue may be off-limits entirely, and tumours sitting close to the bowel, nerves, or other sensitive structures can be difficult to treat safely. The literature on non-radiation ablative alternatives for soft-tissue metastases in this setting has been, until this study, essentially nonexistent.

Cryoablation offers a fundamentally different physical approach. Thin cryoprobes, ranging from 14 to 17 gauge in this study, are inserted into or alongside the target tumour under CT guidance, sometimes supplemented by ultrasound. Argon-based gas expansion drops the probe tip temperature to levels that freeze the tissue, forming an ice ball whose edges are visible in real time on the CT images. This visibility is one of the technique’s greatest assets: the interventional radiologist can watch the frozen zone expand and confirm that it envelops the tumour with a safety margin, in this case 5 millimetres beyond the lesion boundary, before declaring technical success. The standard protocol used at Royal Marsden consisted of two 10-minute freezing cycles separated by a 9-minute passive thaw and a 1-minute active thaw, a freeze-thaw-freeze sequence that maximises cellular destruction through a combination of direct ice-crystal injury and vascular compromise.

One of the study’s most technically interesting features is its systematic use of thermoprotective manoeuvres. Because many soft-tissue metastases lie near the gastrointestinal tract, major nerves, or blood vessels, the team frequently created physical buffers between the ice ball and vulnerable structures. Hydrodissection, injecting fluid to push organs away, was used in 19 cases, while carbodissection, insufflating carbon dioxide to achieve the same separation, was used in 6, with 2 cases combining both and 3 relying on a thermocouple device. Warm saline compresses and subcutaneous saline injections protected overlying skin. These techniques, refined at the centre over years, were instrumental in keeping the overall complication rate to 13 percent across 46 sessions, with the six complications comprising two pneumothoraces, two transient nerve palsies affecting the femoral and obturator nerves, and two skin injuries, all of which resolved without long-term sequelae.

The oncologic results are equally noteworthy. Of the 52 treated tumours, which had a median diameter of 20 millimetres and arose from primary cancers including colorectal tumours, sarcomas, breast, cholangiocarcinoma, and lung cancer, 41 were ablated with curative-intent local control in mind, while 11 were treated purely for symptom palliation and excluded from the survival analysis. Among the 41 lesions treated for control, only three showed residual unablated tumour at first follow-up imaging, and two of those were successfully retreated, yielding a primary technique efficacy of 93 percent and a secondary efficacy of 98 percent. Local tumour progression occurred in 20 percent of lesions during a median follow-up of 11.3 months, producing an estimated two-year local tumour progression-free survival of 76 percent, a figure that aligns with or exceeds outcomes reported for SBRT and surgery in comparable cohorts.

Perhaps the most clinically meaningful number, however, is the divergence between local and systemic outcomes. While local control at two years stood at 76 percent, progression-free survival across the whole body was just 27 percent at two years, with a median of 5.8 months. This gap is not a failure of the technique; it is a window into the biology of oligoprogression itself. Freezing a lesion eliminates the resistant clone at that site, but the underlying systemic disease continues to evolve under the pressure of ongoing therapy. The value of ablation lies in buying time: by removing the progressing foci, clinicians can keep a patient on a systemic regimen that is otherwise working, rather than switching to a next-line drug with its own toxicity profile and uncertain benefit. Notably, the authors report that nearly one-third of patients avoided a change in systemic therapy or remained on a treatment break for at least two years after the procedure, a substantial gain in treatment-free interval and quality of life.

Cryoablation also carries practical advantages over radiotherapy that could reshape multidisciplinary decision-making. There is no cumulative radiation dose to worry about, so previously irradiated sites can be treated and retreatment is possible if a lesion recurs. The ice ball can be monitored continuously, giving immediate visual confirmation of coverage. Crucially, patients do not need to interrupt their systemic therapy around the procedure, which means the pharmaceutical control of the wider disease is never suspended. The team even exploited the percutaneous approach diagnostically: in 10 patients, an image-guided biopsy was performed immediately before ablation in the same session, allowing molecular characterisation of the progressing clone that could inform subsequent lines of systemic treatment. Most procedures were performed under general anaesthesia, took a median of 88 minutes, and required a median hospital stay of just 27 hours, with superficial lesions managed entirely on an outpatient basis.

The authors are candid about the limitations of their work. The study was retrospective and single-centre, with the selection biases that implies, and the heterogeneity of tumour histologies and sizes complicates interpretation of the survival data. Follow-up imaging varied between CT, PET-CT, and MRI depending on the clinical scenario. Yet even with these caveats, the consistency of the safety profile and the strength of the local control figures give the findings considerable weight, particularly as the first reported application of cryoablation to non-visceral, non-nodal soft-tissue metastases in the oligoprogressive setting. The research was supported by the National Institute for Health Research Biomedical Research Centre at The Royal Marsden and the Institute of Cancer Research, and the underlying data are available on request.

What comes next could be decisive. The team argues that prospective controlled trials comparing cryoablation directly with SBRT and surgical resection are now warranted to define where freezing fits within the evolving treatment paradigm for limited disease progression. If those trials confirm the London results, interventional oncology may gain a new pillar in the management of metastatic cancer, one in which a handful of needles, a CT scanner, and precisely controlled cold can hold resistant tumour clones at bay while the drugs that keep the rest of the disease in check continue to do their work. For patients caught in the narrow but consequential gap between remission and widespread progression, that could translate into months or years of continued benefit from their existing therapy, without the burden of yet another drug switch.

Subject of Research: Image-guided percutaneous cryoablation of soft-tissue metastases in patients with oligoprogressive cancer

Article Title: Image-guided cryoablation of soft-tissue metastases in patients with oligoprogressive disease: analysis of feasibility, safety, and efficacy

Article References: Fotiadis, N., Ahmed, N., Johnston, E. W., Starling, N., Jones, R., Hayes, A., Popat, S., Cunningham, D., & Tekkis, P. (2025). Image-guided cryoablation of soft-tissue metastases in patients with oligoprogressive disease: analysis of feasibility, safety, and efficacy. CVIR Oncology, 1(1), Article 20. https://doi.org/10.1007/s44343-025-00019-x

Image Credits: AI Generated

DOI: 10.1007/s44343-025-00019-x

Keywords: cryoablation, oligoprogressive disease, soft-tissue metastases, interventional oncology, local ablative therapy, stereotactic body radiotherapy, oligometastasis, local tumour control, progression-free survival, minimally invasive surgery, cancer treatment, Royal Marsden Hospital

The concept of oligometastatic disease sits at one of the most consequential fault lines in modern oncology. It describes an intermediate state in which cancer has spread beyond the primary organ but only to a small number of sites, conventionally defined in this study as three or fewer metastatic lesions. Unlike widespread metastatic disease, which is managed with systemic therapy aimed at control rather than cure, oligometastatic prostate cancer may be amenable to metastasis-directed therapies such as stereotactic body radiotherapy or surgery targeting individual lesions. Randomized trials including STOMP and ORIOLE have suggested that ablating these limited deposits can delay progression, and trials such as ARTO and RADIOSA have explored combining such approaches with hormonal therapy. But every one of these strategies depends on one thing: knowing exactly which patients truly have only a handful of metastases. That is where the accuracy of the staging scan becomes decisive.

PSMA-PET works on a fundamentally different principle from conventional imaging. Rather than relying on anatomical changes, such as an enlarged lymph node or a bone lesion visible on a scintigram, it uses a radioactive tracer that binds to prostate-specific membrane antigen, a molecule abundantly expressed on the surface of most prostate cancer cells. When injected intravenously, the labeled ligand accumulates in PSMA-expressing tissue, and the PET scanner maps this molecular signal across the whole body, typically fused with computed tomography for anatomical correlation. The result is a functional image that can reveal metastases only a few millimeters in size, long before they distort anatomy enough to be caught by CT or bone scan. Joint procedure guidelines from the European Association of Nuclear Medicine and the Society of Nuclear Medicine and Molecular Imaging, along with standardized reporting frameworks such as E-PSMA and PROMISE version 2, have progressively codified how these scans should be acquired and interpreted.

To test how this translates into everyday clinical practice, the researchers assembled a retrospective cohort of 497 patients with intermediate- to high-risk prostate cancer drawn from multiple centers. Of these, 255 men had undergone both PSMA-PET and conventional imaging within a four-month window, satisfying the strict inclusion criteria for the primary analysis. The primary endpoint was the detection rate of oligometastatic disease, defined as three or fewer metastatic sites, under each modality. The secondary endpoint examined whether the PSMA-PET findings altered the intended clinical management, as judged by a retrospective multidisciplinary review of each case.

The numbers tell a clear story. PSMA-PET identified oligometastatic disease in 11.4 percent of the analyzed patients, or 29 of 255 men, compared with just 6.7 percent, or 17 of 255, using conventional imaging, a difference that reached statistical significance with a p-value of 0.040. In other words, for every hundred men staged with conventional scans alone, roughly five who actually harbored limited metastatic disease would have been misclassified as having localized cancer. The molecular technique also detected more patients with multimetastatic disease, meaning widespread spread beyond the oligometastatic threshold. This pattern of reclassification, in which a more sensitive test shifts patients into more advanced disease categories, is what epidemiologists call stage migration, and it has profound implications for how clinical statistics and treatment decisions are framed.

Perhaps the most clinically resonant finding concerned treatment planning. When a multidisciplinary panel re-reviewed each case in light of the PSMA-PET results, the intended management changed in 36.5 percent of patients, or 93 of the 255 studied. These changes split roughly evenly into major and minor categories, each accounting for about 18 percent of the cohort. A major change typically meant a fundamental shift in therapeutic strategy, for example abandoning a planned curative treatment such as radical surgery or radiotherapy in favor of systemic therapy once previously invisible metastases came to light. Minor changes included adjustments within a general strategy, such as modifying the radiation field or adding hormonal therapy. The authors are careful to note that these figures reflect the intended treatment plan rather than the treatment actually delivered, an important distinction given the retrospective design.

The study’s authors are equally candid about its limitations, and understanding them is essential to interpreting the results correctly. Because the analysis was retrospective, there was no independent reference standard, such as histopathological confirmation of every detected lesion, against which the two imaging modalities could be judged. No central review of the images was performed, meaning scans were interpreted at the originating institutions under routine conditions. Crucially, no patient follow-up was available, so the study cannot say whether the additional detections by PSMA-PET translate into longer survival or better disease control. The authors explicitly state that their findings demonstrate increased detection and reclassification, not proven improvements in diagnostic accuracy or outcomes. This is a common and honest caveat in the stage migration literature: a more sensitive test will always find more disease, but only longitudinal data can confirm that finding it earlier and more completely helps patients live longer.

Even with those caveats, the results align with a growing body of prospective evidence. The landmark proPSMA trial, published in The Lancet in 2020, randomized men with high-risk prostate cancer to PSMA-PET or conventional imaging before curative-intent treatment and found superior accuracy for the molecular approach. Subsequent work has shown that PSMA-PET-guided staging is potentially cost-effective in European and American health systems, and diagnostic accuracy studies have confirmed high sensitivity for pelvic nodal metastases prior to radical prostatectomy. On the therapeutic side, the same PSMA target has been exploited for treatment, most notably with lutetium-177-PSMA-617 radioligand therapy, which improved survival in metastatic castration-resistant prostate cancer in a landmark New England Journal of Medicine trial. The imaging and therapeutic applications of PSMA thus form a theranostic pipeline in which the molecule that reveals the cancer also becomes the vehicle for destroying it.

Why does accurate identification of oligometastatic disease matter so much right now? Because the treatment landscape for advanced prostate cancer is fragmenting into increasingly tailored options. Men with de novo metastatic hormone-sensitive disease benefit from intensification strategies, including androgen deprivation therapy combined with docetaxel or androgen receptor pathway inhibitors such as abiraterone and darolutamide, as established by trials including CHAARTED, LATITUDE, PEACE-1 and ARASENS. Men with limited metastatic disease, by contrast, may be candidates for metastasis-directed therapy, potentially avoiding or deferring systemic side effects. The boundary between these populations is exactly where PSMA-PET is drawing a sharper line. If conventional imaging leaves oligometastatic patients hidden within the localized cohort, they may receive curative-intent local therapy that cannot address their occult spread. If it leaves them hidden within the multimetastatic cohort, they may receive systemic therapy forgoing potentially curative ablative treatment. Either misclassification carries a cost.

The practical consequence of this study is likely to be a strengthening of the case for PSMA-PET as the default staging modality for intermediate- and high-risk prostate cancer, a position already reflected in contemporary European Association of Urology guidelines. For patients, the message is that the type of staging scan they receive can genuinely determine which treatment pathway they are offered. For clinicians and trialists, the stage migration documented here means that historical survival statistics, which were built on conventional imaging cohorts, cannot be directly compared with outcomes in PSMA-PET-era populations, since the same label now describes patients with different underlying disease burdens. Future prospective studies with long-term follow-up will need to establish whether reclassifying these men improves survival. What this real-world analysis establishes today is simpler but consequential: the scans that medicine relied on for decades were missing metastatic disease in a meaningful fraction of men, and a molecular imaging technique that sees what those scans cannot is already changing the plan of care for more than one in three patients.

Subject of Research: The role of PSMA-PET in detecting oligometastatic prostate cancer and driving stage migration compared with conventional imaging

Article Title: Stage migration in prostate cancer: the role of PSMA-PET in identifying oligometastatic disease

Article References: Mattana, F., Luzzago, S., Dragonetti, V., Kasivisvanathan, V., Conlon, S., Castellucci, P., Farolfi, A., Miszczyk, M., Techmański, T., Rajwa, P., Shariat, S. F., Zattoni, F., Reitano, G., Briganti, A., Montorsi, F., Frassoni, S., Bagnardi, V., Gandaglia, G., & Ceci, F. (2026). Stage migration in prostate cancer: the role of PSMA-PET in identifying oligometastatic disease. European Journal of Nuclear Medicine and Molecular Imaging. https://doi.org/10.1007/s00259-026-08166-w

Image Credits: AI Generated

DOI: 10.1007/s00259-026-08166-w

Keywords: prostate cancer, PSMA-PET, oligometastatic disease, stage migration, nuclear medicine, cancer staging, metastasis-directed therapy, conventional imaging, molecular imaging, stereotactic body radiotherapy, theranostics, clinical staging

The context matters enormously. Colorectal cancer is one of the most common malignancies worldwide, and the liver is its most frequent destination for metastatic spread. Roughly a quarter to a third of patients already have distant metastases at diagnosis, and another half or more will develop them during the course of their illness. For a carefully defined subgroup, those with so-called oligometastatic disease, typically fewer than five tumours in no more than two organs, aggressive local treatment with curative intent can produce prolonged disease control and even long-term survival. Surgical resection remains the gold standard, delivering local control rates above 90 percent and five-year survival between 35 and 60 percent. But not every patient is a surgical candidate, and for those who are not, the field has lacked rigorous comparative data to guide the choice between thermal ablation and ablative radiation.

Microwave ablation, or MWA, works by inserting a needle-like probe directly into the tumour, usually under general anaesthesia and real-time ultrasound guidance. Electromagnetic waves at microwave frequencies agitate water molecules within the tissue, generating frictional heat that coagulates and destroys the tumour along with a margin of surrounding liver. Operators in the trial tailored power delivery between 40 and 100 watts over sessions lasting four to fifteen minutes, and performed track ablation as the probe was withdrawn to reduce the risk of needle-track seeding. The technique is well established, supported by robust evidence for durable local control, and is generally preferred over other thermal methods when technically feasible. Yet it remains an invasive procedure, carrying the procedural risks of anaesthesia, probe placement, and in some cases laparoscopic or open surgical access.

Stereotactic body radiotherapy, or SBRT, takes an entirely different route to the same goal. Instead of physically entering the body, it delivers very high doses of precisely sculpted radiation in a handful of fractions, exploiting steep dose gradients to destroy the tumour while sparing healthy tissue. In LAVA-CRLM, the preferred regimen was 45 Gy delivered in three fractions over one week, prescribed so that the gross tumour received a biologically effective dose exceeding 173 Gy, well above thresholds previously associated with high local control rates. Most patients in the radiotherapy arm were treated on an integrated magnetic resonance imaging linear accelerator, an MR-linac, which allows clinicians to visualise soft tissue in real time and adapt the treatment plan daily as anatomy shifts. The remaining patients received conventional linac treatment with cone-beam CT guidance and fiducial tracking. Either way, the entire process is non-invasive and requires no general anaesthesia.

Between January 2019 and December 2024, the Danish team enrolled 100 patients with one to three liver metastases smaller than 4.0 centimetres, each judged suitable for both treatments by a hepatopancreatobiliary multidisciplinary team. Participants were randomly assigned in equal numbers to MWA or SBRT. After exclusions for screening failures, disease progression, or protocol deviations, the modified intention-to-treat population comprised 92 patients, 47 treated with microwave ablation and 45 with radiotherapy. The trial’s primary endpoint was freedom from local progression, meaning the treated lesion itself remained controlled, assessed after at least one year of follow-up by a radiologist blinded to which treatment each patient had received. New lesions elsewhere were tracked separately and did not count as local failures.

The results on local control were essentially a statistical tie. With a median follow-up of roughly three and a half years, local progression occurred in 33 percent of the SBRT group and 36 percent of the MWA group. Estimated one-year freedom from local progression was 83.0 percent with radiotherapy and 77.7 percent with ablation, a difference the investigators described as showing no evidence of a separation between groups, with a hazard ratio of 0.87 and a confidence interval spanning well below and above unity. Per-protocol analyses, restricted to patients who received their assigned treatment exactly as planned, told the same story. Overall survival likewise showed no meaningful difference: three-year survival was estimated at 71.5 percent after SBRT and 63.3 percent after MWA. The trial was explicitly not powered to prove equivalence, so the wide confidence intervals leave room for clinically relevant differences, but the point estimates are remarkably close for two technologies that could hardly be more different in execution.

Safety told a sharper story. During treatment and the first month afterwards, any-grade toxicity affected 38 percent of radiotherapy patients compared with 71 percent of ablation patients. More importantly, grade 2 or higher treatment-related toxicity occurred in just 3 percent of the SBRT group versus 25 percent of the MWA group, and all grade 3 or higher treatment-related events, affecting 8 percent of ablation patients, occurred in the MWA arm. The trial also recorded one treatment-related death: a 74-year-old patient developed hepatic necrosis with capsular perforation two days after percutaneous microwave ablation and died on the day of emergency surgery. Liver pain was by far the most common complaint in the ablation group, affecting 69 percent of patients during treatment, while fatigue dominated in the radiotherapy group. The investigators attribute the more favourable safety profile of SBRT to its non-invasive delivery, which avoids the procedural risks inherent in probe placement and anaesthesia, though they caution the trial was not formally powered for toxicity comparisons.

Quality of life, measured with the EORTC QLQ-C30 questionnaire on 441 completed assessments from 98 percent of participants, showed no difference between the groups over time. The authors suggest this may reflect the dominant influence of disease progression and systemic chemotherapy on long-term wellbeing, which can drown out differences attributable to the local treatment itself. They also note a subtlety in the biology: KRAS-mutated tumours, which some evidence links to poorer local control after radiation, were numerically more frequent in the ablation group, and the trial lacked systematic molecular profiling, a limitation when interpreting the local control estimates. Tumour genetics, including KRAS and TP53 alterations, is an emerging frontier in personalising the choice between ablation and radiation for liver metastases.

The implications for clinical practice are considerable. For patients with oligometastatic colorectal liver metastases of 3 centimetres or smaller, the trial supports considering SBRT alongside MWA in multidisciplinary treatment planning, with the safety data giving radiation a potential edge for lesions where both options are technically feasible. The ability to deliver SBRT fully non-invasively, particularly with MR-guided adaptive technology that tracks tumour motion and adjusts the plan daily, may expand options for patients who cannot tolerate anaesthesia or whose lesions sit near radiosensitive structures. At the same time, ablation retains advantages of its own, including shorter overall treatment time and a single-session approach that some patients prefer over the repeated hospital visits and breath-hold manoeuvres that MR-guided radiotherapy can entail. Individualised selection based on tumour location, size, patient fitness, and institutional expertise remains essential.

The Danish investigators are careful about the limits of their evidence. This was a phase II study in a single national network, designed to detect large differences rather than establish equivalence, and all treated metastases were 3.0 centimetres or smaller despite eligibility extending to 4.0 centimetres. Larger confirmatory trials are needed, and the ongoing COLLISION-XL study is expected to address the question for intermediate-sized lesions between 3 and 5 centimetres. Still, the trial marks a genuine milestone: the first randomised evidence that a beam of precisely focused radiation can match a probe burning tumours from the inside, while sending dramatically fewer patients to hospital with severe complications. For a patient population in which every treatment decision carries curative stakes, that is a finding worth paying attention to.

Subject of Research: A randomised phase II trial comparing microwave ablation and stereotactic body radiotherapy for oligometastatic colorectal liver metastases

Article Title: Microwave ablation versus stereotactic body radiotherapy for oligometastatic colorectal liver metastases (LAVA-CRLM): a prospective, randomised, phase II trial

Article References: Risumlund, S. L., Stick, L. B., Appelt, A., Vogelius, I. R., Nyhuus, B., Schultz, N. A., Penninga, L., van Overeem Felter, M., Josipovic, M., & Larsen, P. N. (2026). Microwave ablation versus stereotactic body radiotherapy for oligometastatic colorectal liver metastases (LAVA-CRLM): a prospective, randomised, phase II trial. The Lancet Regional Health – Europe, 71, Article 101879. https://doi.org/10.1016/j.lanepe.2026.101879

Image Credits: AI Generated

DOI: 10.1016/j.lanepe.2026.101879

Keywords: colorectal cancer, liver metastases, microwave ablation, stereotactic body radiotherapy, oligometastatic disease, randomised trial, local control, treatment toxicity, MR-linac, interventional oncology, radiation oncology, phase II trial

The cat arrived at the Colorado State University Veterinary Teaching Hospital after its owner noticed a growing mass in the neck. Two weeks earlier, the family veterinarian had measured it at 3.7 by 2.1 centimeters, but by the time of the referral examination it had expanded to roughly 5 centimeters long and 4 centimeters wide, filling the ventral part of the neck. The owner also described six months of gradually worsening snoring noises, lethargy, and a mildly reduced appetite. On physical examination, the cat was bright and alert but showed intermittent stertor and stridor, the harsh breathing sounds produced when the upper airway is partially obstructed. A large, fixed, painless mass dominated the left side of the throat.

Advanced imaging revealed the true scale of the problem. A triple-phase computed tomography scan showed a lobular, strongly and heterogeneously enhancing soft tissue mass measuring 5.2 by 4.1 by 3.9 centimeters that completely enveloped the common carotid artery, the main vessel supplying the head. The mass compressed and displaced the thyroid glands, pushed the pharynx, larynx, and hyoid apparatus markedly to the right, and extended toward the skull base near the tympanic bulla. Multiple branching vessels penetrated deep into the tumor interior, a hallmark of the rich blood supply characteristic of chemoreceptor tissue. A board-certified radiologist judged the growth pattern inconsistent with thyroid carcinoma, and the differential diagnosis narrowed to a carotid body tumor, a metastatic lymph node mass, or a primary soft tissue sarcoma.

Fine-needle aspiration cytology of the mass showed an epithelial neoplasm with endocrine and neuroendocrine morphology: densely cohesive clusters of round to polygonal cells with scant basophilic cytoplasm, ropey chromatin, and absent nucleoli. Critically, immunocytochemical staining for Thyroid Transcription Factor-1, a marker of thyroid origin, came back negative, making a thyroid tumor far less likely. The absence of any secretory phenotype, no hyperthyroidism and no hypercalcemia on bloodwork, further separated this tumor from the functional thyroid and parathyroid carcinomas that typically arise in the feline neck. Taken together with the tumor’s location hugging the carotid bifurcation, the team concluded the mass was most consistent with a paraganglioma of the carotid body, a tumor type never before documented in a cat.

That diagnosis matters because carotid body paragangliomas, also called chemodectomas, arise from the chemoreceptor organs that sense oxygen and carbon dioxide in blood. They are well described in dogs and humans, in whom they are notoriously invasive, enveloping major vessels at the base of the skull and causing retropharyngeal masses, difficulty swallowing, respiratory distress, stridor, gagging, and laryngeal paralysis. This cat’s presentation, including left-sided laryngeal paralysis and bilateral tonsillar protrusion noted on a sedated oral exam, matched that pattern almost exactly. Yet in cats, paragangliomas had only ever been reported in the abdomen, around the kidneys and retroperitoneum, at the aortic body, in the heart, and in the orbit, never at the carotid body, despite the fact that cats possess these normal anatomic structures.

Surgery was off the table. After reviewing the imaging, a board-certified surgical oncologist judged the mass unresectable because of its extensive involvement of the carotid artery, larynx, and hyoid apparatus, and warned that any biopsy attempt risked catastrophic hemorrhage and airway-compromising swelling. The oncology team instead offered definitive-intent stereotactic body radiotherapy, a technique that delivers ablative radiation doses in a handful of fractions with submillimeter targeting. The rationale was technical as much as biological: compared with a conventional 16 to 20 fraction course, a three-fraction protocol meant only three anesthesia episodes for a cat that was already difficult to intubate, with far less cumulative acute toxicity to the pharynx and trachea.

The treatment plan was built on the treatment planning system using pre- and post-contrast CT sequences. The gross target volume encompassed all abnormal contrast-enhancing tissue and abnormal vasculature, including the left tonsil. A 2-millimeter planning target volume expansion accounted for setup uncertainty, but was cropped away from organs at risk, the skin, pharynx, trachea, esophagus, brain, spinal cord, and eyes, to prioritize normal tissue sparing. Two coplanar arcs of 6-megavolt photons delivered 10 Gy per day for three consecutive days, for a total of 30 Gy, using volumetric modulated arc therapy. Dosimetry was calculated with the Acuros algorithm, and quality assurance with an electronic portal imaging device achieved a gamma passing rate above 95 percent at 3 millimeters and 3 percent, confirming the planned dose distribution matched delivery.

The response was fast and durable. Two weeks after the final fraction, the tumor had shrunk roughly 30 percent in length and 37.5 percent in width on caliper measurement, the cat’s breathing signs had resolved, and its appetite had normalized. By three months, the mass was no longer palpable at all. Ultrasound at 15 months showed a residual soft tissue structure surrounding the left carotid artery, and a 24-month scan by a second radiologist documented a highly vascular mass measuring 3.2 by 2.2 centimeters, a persistent partial response under RECIST 1.0 criteria with no local or systemic progression for 755 days. Thyroid hormone values, which had been suppressed by euthyroid sick syndrome at presentation, returned to and remained within normal ranges through repeated monitoring.

Tolerability was equally striking. The only radiation-related adverse event was leukotrichia, whitening of the fur in the treatment field, graded as a mild VRTOG grade 1 late skin toxicity. A transient episode of hiding, drooling, and poor appetite after the first fraction resolved when gabapentin was stopped and an anti-nausea drug given. Later weight loss at 20 to 24 months was traced to newly diagnosed chronic kidney disease and a progressively enlarging hepatic cystadenoma, both judged unrelated to the cervical tumor or its radiation. At the time of manuscript submission, the cat was alive with no evidence of disease progression, more than two years after treatment.

The authors caution that without surgical histopathology, which was deliberately avoided given the hemorrhage risk, the diagnosis remains presumptive; cytology alone cannot fully exclude ectopic thyroid or parathyroid tumors, and the definitive classification would have required immunohistochemistry on tissue. Even so, the convergence of imaging, cytomorphology, TTF-1 negativity, and the non-secretory clinical picture makes carotid body origin the leading explanation. The team recommends that carotid body paraganglioma be added to the differential list for feline cervical neuroendocrine masses, and that endocrine function screening be built into both initial work-up and long-term follow-up, since radiation can induce endocrine changes, as seen in dogs. For veterinary oncologists facing cats with otherwise untreatable advanced neck tumors, the report suggests external beam radiotherapy, and stereotactic body radiotherapy in particular, can now be offered as a definitive local option rather than a palliative afterthought.

Beyond this single patient, the case fills a genuine gap in comparative oncology. In human medicine, carotid body paragangliomas are the most common head and neck paragangliomas, and while surgery remains the mainstay, definitive radiotherapy and stereotactic techniques are established alternatives for tumors encasing the carotid artery, where resection carries stroke risk. In dogs, these tumors are typically encountered as incidental, slowly growing masses at the heart base, and complete surgical excision is rarely achieved. The feline report suggests that the radiotherapy experience accumulated in those species may translate across species lines.

The diagnostic work-up also illustrates a subtlety of feline endocrinology. The cat’s low total thyroxine with inappropriately low thyroid-stimulating hormone was interpreted as euthyroid sick syndrome, a reversible suppression of thyroid hormone values caused by non-thyroidal illness, rather than true hypothyroidism. Recognizing this pattern prevented a misdiagnosis that could have steered the work-up toward thyroid disease, and the later normalization of thyroid values on follow-up confirmed the interpretation.

Finally, the durability of response matters for fractionation debates in veterinary radiation oncology. Ablative hypofractionated schedules trade convenience and reduced anesthesia exposure against uncertainty about late toxicity, and this report, with more than two years of follow-up and only grade 1 leukotrichia, provides early evidence that such schedules can be both effective and well tolerated in cats with deeply seated cervical disease.

Subject of Research: First reported use of stereotactic body radiotherapy to treat a suspected feline carotid body paraganglioma

Article Title: Locally advanced cervical neuroendocrine tumor of presumptive carotid body origin in a cat treated with stereotactic body radiotherapy (SBRT): a case report

Article References: Gualtieri, P., Benedict, W. M., Tremolada, G., & Boss, M.-K. (2026). Locally advanced cervical neuroendocrine tumor of presumptive carotid body origin in a cat treated with stereotactic body radiotherapy (SBRT): a case report. Veterinary Oncology, 3(1), Article 18. https://doi.org/10.1186/s44356-026-00071-6

Image Credits: AI Generated

DOI: 10.1186/s44356-026-00071-6

Keywords: cat, carotid body, paraganglioma, chemodectoma, neuroendocrine tumor, SBRT, stereotactic body radiotherapy, veterinary oncology, VMAT, cervical mass, TTF-1, radiation therapy