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2024 International Expert Consensus on US-guided Thermal Ablation for T1N0M0 Papillary Thyroid Cancer

An international expert panel has issued a consensus document on the use of ultrasound (US)-guided thermal ablation for the treatment of T1N0M0 papillary thyroid carcinoma (PTC). The consensus — created through in-depth discussions, systematic literature review with meta-analysis, and expert evaluations — features 27 recommendations. These focus on the indications and contraindications for thermal ablation for PTC, physician training, preoperative preparation, technical procedures, complications, efficacy assessment, and follow-up techniques. In sum, the panel report that "US-guided thermal ablation is endorsed by a majority of experts and supported by extensive literature as one of the first-line treatments for T1aN0M0" PTC. The technique is also recommended as an alternative approach for individuals with T1bN0M0 PTC who are unwilling to pursue active surveillance or surgery. Additionally, it is recommended as an option for T1N0M0 PTC with specific characteristics (minor extrathyroidal extension, isthmus location, or three or fewer multifocal nodules) for patients who decline or are ineligible for surgery, after thorough evaluation. "As technological advancements in ablation therapy continue to evolve, it is imperative that their application be guided by continual evidence-based studies and reviews," the experts conclude. "Ensuring the safe and effective use of these technologies in clinical practice should remain a focal point amid growing interest from the medical community and patients."

Navigational Bronchoscopy or Transthoracic Needle Biopsy for Lung Nodules

Navigational bronchoscopy is noninferior to transthoracic needle biopsy among patients with peripheral pulmonary nodules, but with fewer complications, new research shows. The study, conducted at seven centers across the United States, compared the two approaches in 234 patients with intermediate-risk or high-risk peripheral pulmonary nodules measuring 10-30 mm. Through 12 months of clinical follow-up, navigational bronchoscopy yielded a diagnostic accuracy of 79.0% (94 of 119 patients) versus 73.6% for patients who underwent transthoracic needle biopsy (81 of 110 patients). The risk of pneumothorax was 3.3% (4 patients) in the navigational bronchoscopy group and 28.3% (32 patients) in the transthoracic needle biopsy group, resulting in the placement of a chest tube, hospital admission, or both in 0.8% (1 patient) and 11.5% (13 patients), respectively. There were no hemorrhages requiring medical intervention, nor were there any deaths in the follow-up period for the primary analysis. "The results of this trial suggest that navigational bronchoscopy, which elicited diagnostic accuracy similar to that of transthoracic needle biopsy but with fewer complications, should be the procedure of choice for biopsy of indeterminate lung nodules that appear to be technically amenable to both approaches," the researchers conclude.

Thermal Ablation for Local Tumor Recurrence After Previous Partial Nephrectomy: Perioperative and Oncological Outcomes

Percutaneous thermal ablation (PTA) is a safe and promising approach for managing on-site recurrences following partial nephrectomy (PN), a new trial shows. The study included 27 patients treated with PTA for renal cell carcinoma (RCC) local recurrence from 2008 to 2022. The median treatment duration was 75 minutes, with an interquartile range of 63 to 106 minutes. One patient experienced intraoperative complications, while two patients had postoperative complications. Due to incomplete ablations, one patient required an adjunctive PTA and two others underwent radical nephrectomy. After a median follow-up of 30 months, four patients developed on-site recurrence, three of whom achieved complete local control with subsequent PTA. After a median follow-up of 16 months, six patients had out-site recurrences. The median creatinine drop at 1 month after PTA was -0.03 and -0.11 at 1 year after PTA. The median estimated glomerular filtration rate reductions at 1 month and 1 year after PTA were 2 and 9.5, respectively. For most patients, this treatment approach yielded low perioperative complication rates and optimal local cancer control, with minimal impact on residual kidney function.

A Randomized Trial of Stereotactic Body Radiation Therapy vs Radiofrequency Ablation for the Treatment of Small Renal Masses: A Feasibility Study (RADSTER)

A pilot study demonstrated the feasibility of a prospective randomized trial comparing stereotactic beam radiation therapy (SBRT) and radiofrequency ablation (RFA) for small renal masses (SRM). While both SBRT and RFA are good treatments for many patients, they have different adverse event profiles and their efficacy has not been compared. In this single-center study, 24 patients being treated for a SRM were randomized 1:1 to SBRT or RFA; treatment crossover was allowed for patients who became ineligible for their assigned intervention subsequent to randomization. In all, 14 patients underwent SBRT, 7 RFA, and 3 dropped out of the study. Treatment crossover occurred in 3 patients, who went from RFA to SBRT, in large part because of the technical inability to perform RFA in these patients (due the tumor's proximity to the collecting system, the tumor's proximity to adjacent bowel, and the central location of the tumor.) At 1 year, the mean estimated glomerular filtration rate (EGFR) reduction was -3 ml/minutes/1.73 m2 for RFA and -5.3 ml/minutes/1.73 m2 for SBRT. Additionally, biopsies were conducted at 1 year on 20 of the 21 patients receiving treatment. In the per protocol analysis, the pathologic response to RFA was 100% compared with 33.3% for SBRT. There were no significant safety concerns for either treatment modality during the study period, with no patients developing local failure, metastasis, or death. "Overall, we have found that both treatment modalities are safe and believe a large-scale trial can be conducted to better compare SBRT to RFA," the researchers write.

Transarterial Chemoembolisation Combined With Lenvatinib Plus Pembrolizumab Versus Dual Placebo for Unresectable, Non-Metastatic Hepatocellular Carcinoma (Leap-012): A Multicentre, Randomised, Double-Blind, Phase 3 Study

The combination of transarterial chemoembolization (TACE) plus lenvatinib and pembrolizumab resulted in significant improvements in progression-free survival (PFS) in patients with unresectable, non-metastatic hepatocellular carcinoma. The multicenter, double-blind, Phase III LEAP-012 study included 480 adult patients whose tumors were eligible for TACE. The patients, from 33 countries or regions, were randomized to receive either TACE plus lenvatinib/pembrolizumab (n=237) or TACE plus dual placebo (n=243). Results from the first interim analysis show that the median PFS were 14.6 months and 10.0 months, respectively. In addition, 29% (69 of 237) in the combination treatment group died, compared with 34% (82 of 243) of the control group. The 24-month overall survival rates were 75% and 69%, respectively. Grade 3 or higher treatment-related adverse events were higher in the combination treatment group, affecting 71% vs. 32% of the placebo group. Hypertension and decreased platelet count were the most frequently reported serious adverse events. Four patients in the TACE plus lenvatinib/pembrolizumab group died from treatment-related adverse events (one each from hepatic failure, gastrointestinal hemorrhage, myositis, and immune-mediated hepatitis) vs. one patient in the placebo (from brain stem hemorrhage). Overall, the researchers report that "the numerical improvement in overall survival is encouraging, but longer follow-up is necessary."

Cholangiocarcinoma Targeted Therapies: Mechanisms of Action and Resistance

In this review, researchers explore the clinical efficacy and mechanisms of resistance associated with targeted therapies for cholangiocarcinoma. The highly aggressive bile duct cancer has diverse genomic characteristics. While standard chemotherapy and immunotherapy are used frequently, many patients exhibit genetic alterations that are targetable with approved or emerging therapies. Precision medicine is increasingly shaping second-line treatments for specific patient subsets. Key genomic targets include: IDH1 mutations and FGFR2 fusions, which can be treated with FDA-approved small-molecule inhibitors, and BRAF-V600E mutations and HER2 amplifications, addressed with BRAF inhibitors and trastuzumab deruxtecan, respectively. Additionally, emerging therapies in clinical trials target KRAS codon 12 mutations, PRMT5 inhibition (especially with MTAP deletion), and MDM2 amplification. Challenges remain in improving response rates and duration, and many patients lack actionable genotypes. Research continues to explore resistance mechanisms and develop strategies to expand precision medicine to more patients, using insights from both clinical samples and preclinical models.

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