Making Sure to Get the Entire Tumor: Using PET/CT to Guide Therapies

By Stephen B. Solomon, MD,

Sunday, April 5, 2015

Over the past several decades, engineering and imaging advances have created a revolution in minimally invasive procedures and treatments, leading to faster patient recovery with fewer complications. One of the most exciting therapies to arise is the percutaneous thermal ablation of tumor cells. The success of such therapies hinges on coupling the use of specialized needles used for percutaneous ablation with the development of detailed imaging to accurately guide these needles. At Memorial Sloan Kettering Cancer Center (MSK), we are striving to advance such technologies to the level where ablative treatments can be delivered precisely and until all of a tumor’s cells are destroyed, thus avoiding recurrence several months later due to incomplete treatment.

A number of ablation therapies are available for patients at MSK.  Radiofrequency ablation (RFA) and more recently microwave ablation (MWA) have been used to deliver heat.  Additionally, cryoablation has been used to deliver lethal freezing temperatures, and new electric field techniques (i.e., NanoKnife) have been developed to disrupt cell membranes.  The goal has been to create a reliable, precise tool that ablates only around the needle tip, and thereby avoid damage to surrounding tissue.  Well over 1,000 patients have been treated at MSK using these novel techniques.

Researchers at MSK are also leaders in the development of tools to better visualize the tumor, guide needle placement, and assess treatment. Ultrasound, CT, and MRI have all been used to guide biopsies and ablations, but unlike PET, they cannot detect metabolic activity of tumor cells. PET enables visualization of tumors that are difficult to discern via other imaging methods.  By exploiting this capability, scientists at MSK have been able to improve diagnostic success of biopsies and to provide immediate assessment of ablative treatments. Consequently, one of the most exciting imaging developments at MSK is the interventional PET/CT, which combines the structural information from CT with the metabolic information from PET.

MSK has the only interventional PET/CT scanner in the world completely dedicated to in-room, real-time guidance of procedures for patients with cancer (Figure 1). Two of our clinical studies evaluating 18FDG PET/CT-guided procedures have recently been published in the medical literature.

View of the Interventional PET/CT Procedure Room at MSK

PET/CT-guided Biopsies for Lesions Poorly Visualized With Other Modalities

In a retrospective study, Cornelis et al (1) evaluated the safety and diagnostic success rate of 18FDG PET/CT-guided percutaneous biopsies of 106 masses (mean size, 3.3 cm; range, 0.7-15.9 cm) in 105 consecutive patients (2011-2013) in several anatomic locations, including the liver (n=26).  The lesions targeted were poorly visualized with conventional imaging and known to be FDG-avid. The scan’s purpose was to visualize an already identified lesion and guide the biopsy (Figure 2).

<sup>18</sup>FDG PET/CT-guided biopsy of the liver.

The mean dose of 18FDG injected was 255 MBq (SD, 74).  Early in the series, patients received a diagnostic dose of ~440 MBq, but the dose was reduced when it became apparent that a lower dose was sufficient to visualize the target. Biopsies were positive for malignancy in 71.7 percent (76/106) and for benign tissue in 28.3 percent (30/106), indicating that not all PET-positive lesions are cancer. Immediate on-site cytology results were considered adequate for 100 PET/CT biopsies, and benign diagnoses were confirmed for the other six after surgery or follow-up. Overall sensitivity and diagnostic success of biopsies were 100 percent. No significant differences were observed in detection of malignancy between locations.

Unlike other guidance methods, PET/CT enables needle positioning in the region of highest 18FDG uptake. Consequently, no false-negative biopsies were observed.  Also, relative to other image-fusion techniques, in-suite direct PET/CT biopsy is less susceptible to registration bias or misalignment. Further studies are needed to determine a lower and best dose sufficient to visualize the lesions during biopsy.

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Split-dose Technique for PET/CT-guided Ablation and Immediate Assessment

In contrast with surgical resection, pathologic evaluation of the margin is not currently feasible for percutaneous ablation. To address this gap, researchers at MSK have advanced a split-dose technique in which the first dose is used to localize the lesion, and the second to assess ablation response (Figure 3).

Split-dose <sup>18</sup>FDG PET/CT-guided ablation of the liver.

In their retrospective study, Ryan et al (2) evaluated percutaneous split-dose 18FDG PET/CT-guided localization and ablation assessment in 23 consecutive patients (July – December 2011) for 29 known FDG-avid lesions; 79 percent (23/29) of lesions were in the liver. Tumor pathology showed metastatic colorectal adenocarcinoma in 18 lesions, primary hepatocellular carcinoma in one lesion, and a variety of metastatic tumors in the remaining 10 lesions.

A standard 18FDG dose was administered, but with the smaller portion (~148 MBq) administered prior to ablation and the second, larger portion (~296 MBq) administered after ablation.  Immediate post-ablation assessment via 18FDG PET/CT allows for re-treatment, if necessary, during the same procedure. The targeting dose was based on FDG half-life and the length of procedure before post-ablation imaging. The intention is to minimize contamination of the post-procedure scan with the pre-procedure scan.

Ninety-seven percent (28/29) of ablated lesions showed no residual FDG activity after the second intra-procedural 18FDG dose.  One patient with residual activity underwent immediate biopsy that revealed residual viable tumor. After replacement of the needle, an additional ablation was performed to the region of persistent FDG activity and effective ablation was confirmed via imaging. To determine if immediate post-ablation imaging after the second dose of 18FDG reliably helped predict complete tumor ablation, results of follow-up imaging at a median of 155 days (range, 92-257 days) were analyzed. Marginal recurrence was observed in seven percent (2/29) of patients. Although both lesions were negative at the post-ablation PET, they were in challenging locations.

Accuracy of the immediate PET/CT compared to the 12-month follow-up as the gold standard was 87.5% to evaluate the ablative margins. This study suggests that patients with a high value of FDG activity immediately after ablation should be carefully followed, biopsied, or re-treated due to the high sensitivity (87.5 percent) and positive predictive value (82.4 percent [55.8-95.3]) of immediate 18FDG PET/CT for recurrence. Additionally, patients with a low value of FDG activity may need less rigorous follow-up due to the high specificity (87.5 percent) and negative predictive value (91.3 percent [70.5-98.5]) of the immediate post-ablation 18FDG PET/CT.

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Future Directions

The demonstrated capability of 18FDG PET/CT to precisely target and image masses suggests a wide range of possibilities for PET/CT-guided interventional procedures. New work at the MSK Center for Molecular Imaging & Nanotechnology has increased the potential radiotracer options beyond FDG, promising more specific targeting of cancer. With the dedicated PET/CT, MSK is leading the field of interventional oncology, and we look forward to continued advances.

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