Hot and Cold
By Beth W. Orenstein
Radiology Today
Vol. 23 No. 3 P. 22

Interventionalists explain why microwave ablation or cryoablation should be frontline strategies for lung sarcomas.

Lung cancer is the second most common type of cancer in the United States. Despite decreasing mortality trends over the past 20-plus years, lung cancer remains the leading cause of cancer-related death; from 2015 to 2019, cancers of the lung and bronchus accounted for 36.7% of all cancer deaths. The American Cancer Society estimates that there will be 236,740 (117,910 men and 118,830 women) new lung cancer cases and 130,180 (68,820 men and 61,630 women) deaths due to lung cancer in the United States in 2022.

The most common type is non–small cell lung cancer, which makes up 80% to 85% of primary lung cancer cases. In addition, lungs are the second most frequent site of metastatic disease. Epithelial carcinomas, such as colorectal, renal, and breast cancers, as well as sarcomas and germ cell tumors, commonly metastasize to the lungs.

Surgery has long been the preferred treatment for both early-stage lung cancer and lung metastases. Only a minority of patients, however, meet the criteria for surgical resection. Many lung cancer patients are not candidates for surgery because they have high-risk comorbidities or poor cardiopulmonary function, or they would not have enough lung left after surgery. Other treatment options include stereotactic body radiation therapy (SBRT) and percutaneous image-guided tumor ablation (IGTA).

Different energy modalities such as radiofrequency ablation (RFA), cryoablation (CA), and microwave ablation (MWA) can be used to perform percutaneous IGTA. The National Comprehensive Cancer Network and several specialty specific societies, including the American College of Chest Physicians, list IGTA as a management option. A study published in March 2022 in the American Journal of Roentgenology supports the use of IGTA in patients with lung sarcomas. The study found that percutaneous MWA and CA are both suited for the treatment of lung metastases, especially for tumors that are 1 cm or smaller, regardless of whether they are peripheral. Complications from either type of ablation, if they occur, are not life-threatening, the researchers found.

“Treating lung lesions when they are smaller is better than waiting until they get big,” says Stephen B. Solomon, MD, chief of the IR service at Memorial Sloan Kettering Cancer Center in New York. “With the surgical mindset, one can wait for lesions to get bigger or be symptomatic. A surgery on a 1-cm lesion is not that different from a 3-cm lesion. This is counter to ablation, where smaller is easier.”

With treatments such as MWA and CA showing much promise for improving survival, especially with smaller tumors, “the mindset that surgery is best for treating lung sarcomas needs to change,” Solomon says.

Alda L. Tam, MD, MBA, FRCP, FSIR, a professor in the department of IR at the University of Texas MD Anderson Cancer Center, agrees that the paradigm for treating lung sarcomas needs updating. Ablation—whether CA or MWA—not only needs to be added to the mix but also must be considered as a frontline defense, Tam says. Surgery has its limits, and “there are not many good chemotherapy options for lung sarcomas.” SBRT, too, “is not great” she says.

Unfortunately, Tam says, not many oncologists are aware of the benefits of IGTA “and what ablation has to offer to their patients. Percutaneous ablation, when used appropriately, offers the ability to control/kill lung tumors efficaciously.”

Comparatively Speaking
RFA, which predates CA and MWA, is rarely used for treating lung tumors these days, says Scott J. Genshaft, MD, an interventional radiologist at UCLA in Calabasas, California. As a result, Genshaft says, some health insurance company policies that reimburse only for RFA are outdated. The March study that compared CA with MWA is important, he says, because it helps to show that these modalities are highly effective and should be considered frontline treatments for lung sarcomas. It is particularly good news, Genshaft says, given that lung sarcomas affect people of all ages; anyone from young children to older adults can develop various types of sarcomas. “Lung sarcoma is a relentless, prolonged disease and is seldom curable once it has spread,” he says.

The retrospective cohort study included 27 patients, 16 women and 11 men, with a median age of 64 years. From 2009 to 2021, the patients underwent 39 percutaneous CT-guided ablation sessions—21 were MWA and 18 were CA sessions. Patients underwent one to four sessions to treat 65 sarcoma lung metastases. Twenty-five percent of the tumors, which ranged in size from 5 mm to 33 mm, were nonperipheral. The researchers used generalized estimating equations to compare complications of the ablation modalities that were used. They found a 97% success rate for both modalities.

Median follow-up was 23 months. A total of seven of 61 tumors (11%) showed local progression. One- and two-year local control rates for tumors 1 cm or smaller were 97% and 95% after MWA vs 99% and 98% after CA. For tumors larger than 1 cm, one- and two-year survival rates were 74% and 62% after MWA vs 86% and 79% after CA. Using the Kaplan-Meier method, overall survival at one, two, and three years was 100%, 89%, and 82%, respectively, the study found. The authors also found that injury to adjacent lung tissue is less frequent after ablation than after SBRT.

In addition, the researchers found ablation procedures were associated with few complications; only nine instances of chest tube placement for pneumothorax were reported. The remaining pneumothorax were self-limited, and no grade 4 or 5 complications were reported. The study also showed a significantly low local progression rate of 11%.

“This study represents a solid contribution to the mounting evidence that ablation of sarcoma lung metastases delivers a survival benefit,” wrote Nassir Rostambeigi, MD, MPH, of the Mallinckrodt Institute of Radiology at Washington University of Medicine in St. Louis, in an editorial accompanying the study. “This study elucidates the comparable safety and efficacy of these two ablative modalities. Their advantage over SBRT and surgery, as minimally invasive techniques, is laudable.”

Rostambeigi notes that survival rates were similar between the two modalities and that they were higher at two years (89%), which is similar to the survival rate of 82% reported after SBRT in a study published in April 2018 in Sarcoma.

Checking Preferences
According to Robert Suh, MD, of the UCLA department of radiological sciences at the Ronald Reagan UCLA Medical Center, interventional radiologists say they do not have a preference for CA or MWA when ablating sarcomas. Where IGTA is well integrated into treatment protocols, “the choice as to which thermal energy to utilize is not based on specific tumor type, as there is not significant data correlating energy type to tumor cell type,” says Suh, who utilizes both MWA and CA energies. The choice of energy for most interventional radiologists, he suspects, is dependent on many factors but largely “on operator experience and familiarity with the energy used to reach high-level success in treatment outcomes.”

Tam tailors her choice of energy “based on an evaluation of the patient’s lesion location and the potential for adverse events or complications.” CA generally takes longer than MWA and the time difference can be a consideration, depending on the patient’s condition, Tam notes.

Genshaft, who performs more than 100 ablations each year, uses moderate sedation for all of his cases, rather than anesthesia. As a result, he prefers CA for peripheral lesions that abut the pleura and MWA for lesions closer to the center of the lungs because it’s a much quicker procedure; in each case, he takes patient comfort into consideration. “There are a couple of other nuance cases,” he says, “but nuance cases are not what drives local decision-making in the majority of cases.”

Suh agrees that location—where the tumor site is within the lungs and its proximity to vital or pain-sensitive structures—drives the energy he uses. “For example,” he says, “cryoablation is generally better tolerated both during the procedure and recovery, when ablating tumors close to the sensitive lining of the lung and the sensory nerves that run along each rib. It does not mean that microwave cannot be used successfully in these locations, but the operator may employ techniques to insulate the tumor from lining and nerves while ablating.”

For the most part, Suh says, ice associated with CA is much easier to see on CT scans obtained during the ablation, which is helpful when ablating near critical structures within the thoracic cavity, such as the heart, trachea, and esophagus. “For any given desired ablation size, microwave energy is much quicker and, in general, less cumbersome to set up than cryoablation,” Suh adds.

Other Considerations
When it comes to treating multiple locations, the size of the tumor nodule within the lung is an important, but not exclusive, consideration in terms of stratifying the order of tumors for ablation, Suh says. For the most part, larger tumors are treated first because the likelihood of complete tumor ablation decreases as tumors grow over 3 cm and, especially, over 3.5 cm, he says, adding that it is important to consider the location of the lesions in another way. “A small tumor within the center of the lobe or lung may be important to treat earlier,” Suh says, “because if it continues to grow, it might impact vital structures, including the larger blood vessels and airways, which would make ablation difficult.”

Also, if the central tumor is completely ablated, a patient may avoid a surgical resection or radiation that could potentially lead to more lung tissue and function loss. Small tumors within the periphery of the lung or lobe are generally the last to be ablated because they are easier to access. “In the worst-case scenario,” Suh says, “if these peripheral tumors were to grow too large for effective ablation, they can still be readily resected or even radiated.”

Another consideration, which was not shown in the March AJR study but has been shown in other studies, is that IGTA preserves lung function better than surgical resection and SBRT, even after multiple ablations, Suh says. Frequently, in sarcoma patients, cells from the original tumor travel through the body and form a small number of metastatic tumors in one or two other parts of the body. “The ability to preserve lung function is extremely important because the majority of these oligometastatic disease patients will have additional metastases during their disease course that might be eligible for further local therapy,” Suh says.

Solomon agrees that “ablation saves the normal tissue the best for a patient who often may have more metastases in the future.”

Yet another advantage is that the medical cost of thermal ablation is notably less than other forms of local therapy, Suh says.

Also, ablation is repeatable, Solomon says. If the sarcomas come back, ablation is still a treatment option. “My philosophy on lung metastases is that I would favor using ablation as the first choice,” Solomon says. “You can only use radiation a limited number of times because it will injure more lung tissue. Save radiation for the ones you can’t treat with ablation. The same goes for surgery. Why put someone through surgery when you can do it this way? Save surgery for the ones ablation and radiation can’t treat.”

The interventional radiologists interviewed for this article believe that either CA or MWA can and should be applied to other types of cancers within the lungs and other organs. “Image-guided thermal ablation is now increasingly integrated into treatment and patient care algorithms,” Suh says. “Currently, the choice of thermal energy to be used for ablation is operator dependent.”

Solomon says others have studied and are using ablation to treat other cancers, such as colorectal and renal.

In his AJR editorial comment, Rostambeigi noted that, although the advantage of ablation over SBRT and surgery is laudable, more and larger studies are needed on the two ablative modalities. “Future research also should explore whether primary sarcoma behavior and local progression of metastases are related,” Rostambeigi wrote.

— Beth W. Orenstein of Northampton, Pennsylvania, is a freelance medical writer and regular contributor to Radiology Today.