Clinical Study: Assessing the Impact of Margin Reduction (AIM)

The prospective, multi-site study, entitled “Assessing the Impact of Margin Reduction (AIM),” is the first outcome-based study to evaluate the quality of life of high-dose intensity modulated radiation therapy (IMRT) to the prostate with tightly contoured treatment technically described as “reduced treatment margins.” The findings of the AIM study, which are published in Urology (The GOLD JOURNAL), demonstrate that the use of the Calypso® System during high-dose external beam radiation for prostate cancer resulted in a significant reduction in rectal and urinary treatment-related side effects.

Study Overview

The multi-site clinical study tested 64 patients receiving IMRT therapy tracked on the Calypso System. This level of precision allowed researchers to reduce the Planning Target Volume (PTV) margin while at the same time increase the radiation dose to 81 gray (Gy) to more effectively treat the cancer. Researchers compared the AIM study group of 64 patients to a 153-patient comparator study published in the New England Journal of Medicine in 2008 (1). In both groups, patient-reported quality of life was assessed before and after the completion of radiation therapy using a clinically validated questionnaire, the Expanded Prostate Cancer Index Composite (EPIC) that measures several different domains of the patient’s health. The AIM study group experienced significantly fewer side effects associated with bowel urgency and frequency, fecal incontinence and urinary irritation than the comparator group. The AIM study group also experienced a smaller, yet statistically significant, advantage over the comparator group in urinary incontinence and sexual function.

Key Findings:

• Real-time target tracking and objective patient setup with the Calypso System enabled PTV margin reduction and resulted in improved outcomes for patients.
• Clinically significant reductions in side effects were attained even with an increased dose of 81 Gy.
• Efficiency of delivering increased dose with narrow margins was determined to be compatible with standard treatment time slots when using real-time localization and tracking.

Results

• AIM patients experienced fewer acute GI and acute sexual side effects as well as some reduction in acute GU side effects than those patients in the comparator study despite a high dose of 81 Gy (Figure 1).

• Overall bowel problems were fewer among AIM patients than the NEJM patients as evidenced by the 19 point spread in Figure 2. EPIC scores for men experiencing rectal/bowel symptoms (urgency, frequency, incontinence, bloody stools and/or rectal pain) in the AIM study cohort were clinically stable (improved 3 points) while the percentage of comparator patients worsened by 16 points (Figure 2).

• Real-time tracking used for procedure setup and interventions was performed within standard 15-mintue treatment slots.
• 57% of fractions required realignment to avoid dosing healthy tissue and increasing the incidence of acute side effects
  (Figure 3).

Conclusions

• The Calypso System provides the accuracy, precision and  efficiency necessary to confidently manage interfraction and intrafraction prostate motion.
• Clinically significant reductions in side effects were attained with a dose of 81 Gy.
• Efficiency of delivering increased dose with narrow margins was determined to be compatible with standard treatment slots when using real-time localization and tracking.

"Without any tracking at all, I used a 10 millimeter treatment margin. With Calypso, I use a 3 millimeter treatment margin, and the AIM study results demonstrate an improvement in patient-reported quality of life.”

Howard Sandler, M.D

Download the AIM Study Brochure

1. Sanda, Martin G., et al. "Quality of Life and Satisfaction With Outcome Among Prostate-cancer Survivors." New England Journal of Medicine 358 no. 12, (2008): 1250-61.
2. Sandler, Howard, 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 75 no. 5, (2010): 1004-1008.
3. Tropper, Scott, et al. "Efficiency and Clinical Workflow of Delivering IMRT to the Prostate Within 2 mm Tolerances" International Journal of Radiation Oncology Biology Physics 75 no. 3 Supplement, (2009): S580. Abstract no. 2889.