Treating liver and prostate tumors with radiotherapy presents unique challenges. In addition to organ drift, the liver moves more than most organs because of respiration, and prostate tumors often move due to bladder filling or gas in the rectum. Treatment requires the accurate delivery of high-radiation dose with a steep gradient and minimal margins around the target to optimize effectiveness and safety.
Varian’s Calypso® system and Soft Tissue and Surface Beacon® transponders are helping clinicians treat liver and prostate tumors more precisely by providing real-time targeting and motion management as well as accurate and efficient patient setup during radiotherapy.
Smaller than a grain of rice, each Calypso soft tissue beacon transponder continuously transmits location information about the tumor in real-time through a nonionizing signal to the Calypso tracking system. By monitoring a tumor’s location—or, in the case of a surface transponder, patient motion that could compromise treatment accuracy—Calypso makes it possible to reduce margins between the clinical target volume (CTV) and the planning target volume (PTV) and provides clinicians with confidence that the prescribed dose is being delivered accurately and precisely.
This article profiles four radiotherapy centers that are using Calypso to accurately target tumors while reducing treatment margins, with a goal of offering cancer patients fewer treatment side effects and a better quality of life.
Treating Liver Tumors with Calypso: Aarhus University Hospital, Denmark, and Humanitas Research Hospital, Milan, Italy
At Aarhus University Hospital, about 25 patients each year present with primary liver cancer or liver metastases, for whom the size and location of their tumors preclude surgery or ablative approaches. Using the TrueBeam® radiotherapy system along with Calypso, clinicians can deliver high-dose stereotactic body radiotherapy (SBRT) with increased accuracy and improved motion-management and setup, reducing geometrical treatment errors and required margins.
“In the past, we had to apply a more generous treatment margin around the tumor because of uncertainties regarding the precise tumor position from day to day. Calypso allows us to monitor treatment in real time and reduce the treatment margin, so less healthy tissue is treated,” says Morten Hoyer, professor of clinical oncology at Aarhus.
Calypso also helps guide patient set up and manage the intrafraction motion that is characteristic of targets in the liver.
“The liver may move as much as three centimeters due to respiration, or it may move up to one centimeter during a single treatment because of target drift. In addition, the liver is close to critical structures like the spinal cord, esophagus, intestines, and kidneys. Therefore, we need Calypso to exactly track the position of the tumor when delivering a large dose to spare healthy tissue,” adds Esben Worm, PhD, department of medical physics.
Delivering SBRT using the Calypso system hasn’t lengthened the procedure time at Aarhus. In an outpatient procedure that typically takes 20 minutes, three transponders are implanted around the tumor at the edges, guided by sonography. “We use the 17G Beacon transponder with 50 percent smaller cross sectional area than the 14G version – bleeding is less of an issue with the thinner needle,” explains Lars Peter Larsen, MD, department of radiology.
Respiratory Gated Stereotactic Treatments
Calypso is allowing the team at Aarhus to deliver respiratory-gated stereotactic treatments. “Calypso allows us to see intrafraction baseline drifts that we couldn’t see before,” says Per Poulsen, associate professor responsible for motion management tools at Aarhus. “When we see the drifts during treatment, we can pause the treatment and correct for them by making couch adjustments.”
With gated treatments and real-time tracking, the Aarhus team has been able to reduce margins to 7 mm from the 10 mm generally used for non-gated treatments. “We believe that real-time tracking with the Calypso system reduces side effects and may, in the future, enable us to increase the dose for improved outcomes,” says Hoyer.
Radiotherapy and Radiosurgery Unit Director Marta Scorsetti and her colleagues have successfully treated upwards of 75 patients at the Humanitas Research Hospital in Milan, Italy, using noninvasive Calypso surface transponders to guide radiotherapy, especially focusing on cases involving hypofractionation.
“We use surface transponders placed on the skin for SBRT treatments of liver and pancreatic disease along with an abdominal compressor to minimize internal motion,” says Scorsetti. “We use the Edge™ radiotherapy system to deliver the treatments because it is well integrated with Calypso for patient positioning and tumor tracking.”
The surface transponders allow Scorsetti to check the efficacy of the abdominal compressor. In a series of ten patients being treated for pancreatic cancer, she and her team observed a residual motion of greater than 2 mm in three cases, while in one case, the shift was greater than 5 mm, which required re-simulation.
“Surface transponders are very efficient and precise for monitoring patient motion. Using the Calypso tracking system to deliver SBRT and hypofractionated body radiotherapy protocols,” says Scorsetti, “we are able to treat liver metastases in 3 fractions and pancreatic cancer in 6 fractions.”
To date, Dr. Scorsetti and her team have not observed any major toxicities in the 75 patients they have treated. “In our experience, the use of Calypso prevented unwanted irradiation to healthy tissue, otherwise undetectable by standard methods. Using Calypso, we feel we can safely implement unconventional fractionation schemes, reducing toxicity and the total number of fractions.”
Calypso for Prostate Treatments: 21st Century Oncology in Fort Myers, Florida, and Cedars-Sinai Medical Center, Los Angeles, California
21st Century Oncology
Constantine Mantz, MD, chief medical officer for 21st Century Oncology in Fort Myers, Florida, has been using Calypso to track prostate movement since 2006 for his patients treated with stereotactic ablative radiotherapy (SABR). During that time, Dr. Mantz has treated over 2,000 patients with Calypso.
“Using Calypso during SABR allows us to reduce the overall treatment time compared to other hypofractionated and conventional radiotherapy schedules while maintaining a low rate of serious side effects,” remarks Mantz.
Conventional radiotherapy (fractionated) for prostate cancer typically requires a dose of 1.8 or 2.0 gray (Gy) per treatment over 35 to 45 treatments. Using SABR in conjunction with the Calypso system, Mantz reduces the number of treatments to five by delivering a dose of 8.0 Gy per treatment for selected patients such as those with a Gleason score of six or seven, prostate gland size smaller than 60 cubic cm, and a PSA less than 15.
“There is no room for error when compressing the number of treatments from forty-five to five and delivering a much higher dose per treatment; we must be absolutely accurate,” notes Mantz. “The Calypso system allows me to accurately track and quickly adjust for tumor motion. I know that each of the five treatments I’m delivering to my patient is precisely targeting the tumor and avoiding healthy tissue as much as possible.”
During an outpatient procedure, Dr. Mantz implants three 17G soft tissue Beacon transponders at least 1.5 cm apart in the prostate. “Using the thinner 17G soft tissue Beacon transponder, I can now treat more patients, particularly those who were not able to tolerate placement of the larger transponder,” remarks Mantz. “The smaller 17G transponders are not only more comfortable and better tolerated by patients but also produce as good a quality signal to the tracking system as did the larger devices.”
Once SABR treatment begins, the Calypso system alerts Mantz and his team in real-time if the target moves by continuously sending positional information.
“Because of the accuracy of the Calypso system, we can reduce our treatment margins to a threshold of 2 mm. Calypso tracks whenever the target motion exceeds our threshold, the treatment beam is automatically stopped, and we realign the target with minimal impact on workflow,” states Mantz.
An intervention threshold of 2 mm offers great advantages by reducing the PTV, which protects healthy tissue and reduces side effects. “Our Calypso patients experience better outcomes,” observes Mantz. “They report fewer sides effects and a better quality of life.”
Dr. Mantz is currently expanding his protocol to treat patients with cancer of the cervix for whom surgery and brachytherapy are not an option. “We are now implanting Calypso transponders into the lower part of the uterus to monitor motion during SABR for our protocol cervix cancer patients and have had success thus far. We will be reporting our results at the 2017 ASTRO meeting.”
Cedars-Sinai Medical Center, Los Angeles, California
While SABR is helping a great deal of patients, for some patients conventional fractionated radiotherapy is more appropriate. For these patients, Howard Sandler, MD, MS, professor and chair, Department of Radiation Oncology at Cedars-Sinai Medical Center, Los Angeles, California, has found that using Calypso not only improves precision but reduces side effects, as reported in a 2010 study.1
“Calypso allows us to deliver more precise treatments by using tighter windows around the prostate and delivering less radiation to healthy tissue. It gives us more confidence that the prostate will be within the threshold all the time,” says Sandler.
Using Calypso along with a TrueBeam system in RapidArc® mode, Sandler and his team are offering prostate cancer patients conventional fractionated radiotherapy, hypofractionated radiotherapy, or SABR, depending on the clinical situation.
After a urologist implants three transponders in the prostate in an outpatient procedure lasting about 15 minutes, Sandler and his team make sure the tumor is positioned properly prior to treatment and then monitor the tumor in real-time using Calypso.
“Compared to positioning using cone-beam CT, Calypso is like a continuously running movie because it gives us a live, continuous view of tumor position. An X-ray image from cone-beam CT only gives us a static snapshot of the tumor’s position at one point in time,” adds Sandler.
AIM Study: Assessing the Impact of Margin Reduction
As Sandler and his colleagues discovered in their AIM study, margin reduction decreases side effects. They measured the effect of reduced PTV margins in prostate cancer patients undergoing high dose intensity-modulated radiotherapy (IMRT) using the Calypso tracking system, as measured by patient reported outcomes.
64 patients were treated with 81 Gy in 1.8 Gy fractions using the Calypso system, which enabled clinicians to use a reduced PTV margin of 3 mm and an intervention threshold of 2 mm.
By allowing Sandler to accurately track and manage tumor motion, the Calypso system enabled the reduction of treatment margins leading to a reduction of side effects -- even with a dose of 81 Gy.
“Patients completed the Expanded Prostate Cancer Index Composite (EPIC) questionnaires, and their scores were compared with those of a published EPIC data for a comparator cohort,” notes Sandler. “The AIM study results suggest that Calypso real-time tracking reduces sexual dysfunction at two months even though this is sometimes a side effect that is seen later. The study authors explain: “Sexual interest may be better maintained in the absence of bowel and urinary toxicity.”
Intended Use Summary
The Calypso system, including its associated Soft Tissue Beacon transponder, is intended to align and/or monitor the patient’s position in relation to the radiation beam used for treatment. The Calypso system may also be used to regulate the treatment beam on Varian and Siemens radiation delivery systems by turning the beam on and off (“gating” it) due to movement during treatment. Soft Tissue Beacon transponders used as part of the Calypso system for monitoring patient motion are indicated for use for permanent implantation in the prostate gland and prostatic bed and in soft tissue.
Important Safety Information
Implanted Beacon transponders may migrate such that they pass from the patient’s body or move to a different location within the body. The most frequent side effects associated with implantation of Soft Tissue Beacon transponders are typically temporary and may include, but are not limited to, pain, bleeding and infection. In some patients, these side effects may be serious. Use of the Calypso system and its associated Soft Tissue Beacon transponders is not appropriate for all patients. Patients should discuss the potential for side effects and their severity, as well as the benefits of the Calypso system and its associated Beacon transponders with their doctors to make sure it is right for them.
1. Sandler HM, Liu PY, Dunn RL, et al. Reduction in patient-reported acute morbidity in prostate cancer patients treated with 81-Gy intensity-modulated radiotherapy using reduced planning target volume margins and electromagnetic tracking: assessing the impact of margin reduction study. Urology 2010;75(5):1004-8.
One-shot Radiosurgery for Localized Prostate Cancer: The Swiss-Italian Transalpine (SIT) Prospective Multicentric Phase-II Trial
The objective of this single-arm phase II study is to determine if single-fraction SBRT at a dose of 19 Gy using the Calypso system is a valid treatment option for patients with localized prostate cancer with a simultaneous dose reduction to the urethral planning at-risk volume (PRV).
Decreasing the number of radiosurgery treatments to five or fewer fractions not only has the potential to reduce side effects and improve patient convenience but may also reduce the cost of external beam radiotherapy while increasing the availability of treatment slots.
“Through this single-session approach, we expect to have satisfying long-term cure rates--equivalent to standard fractionated treatment protocols--with an optimal quality of life and low rate of side effects. Calypso will enable us to precisely track the position of our target in real-time while administering the prescribed dose with the lowest possible dose to the bladder and rectum,” notes Marta Scorsetti, MD, radiotherapy and radiosurgery unit director, Humanitas Research Hospital, Milan, Italy.
Three of the five European centers participating in the study are located in Switzerland (Chur, Geneva, and Zurich), and two centers are located in Italy (Milan and Verona). The trial is scheduled to take place from June 2017 – Dec 2018.