Extending intracranial treatment options with Leksell Gamma Knife® Icon™ Key Statements from Customer Perspective by University Medical Centre Mannheim

Department of Radiation Oncology University Medical Centre Mannheim The centre serves a population of around 2.5 million people in the Rhine-Neckar region In addition to offering standard radiotherapy treatment options, the centre’s Department of Radiation Oncology specializes in a range of complex radiation techniques; Intensity modulated radiation therapy (IMRT) Volumetric modulated arc therapy (VMAT) Stereotactic body radiation therapy (SBRT) Brain stereotactic radiosurgery (SRS) Intraoperative radiotherapy (IORT) Total body radiotherapy (TBI) The department currently has 6 linear accelerators (2 Elekta Versa HD systems, 2 Elekta Synergy systems on site at the University Medical Centre in Mannheim, and an Elekta Synergy at each of 2 satellite centres) The centre treats 2800-3000 patients every year The department has been using Leksell Gamma Knife Icon since 2015 and the number of intracranial SRS treatments per year has doubled compared to before Key Statements from Customer Perspective by University Medical Centre Mannheim

Workflow capabilities “Our department has a long history in IGRT and frameless SRS with linacs, so we were looking forward to upgrading to Gamma Knife Icon with image guidance and the opportunity to use a mask, while retaining the option of frame-based treatments when the situation demands it.” Dr. Stieler, Medical Physicist Workflow capabilities Icon increases departmental efficiency The addition of Icon allows an increased number of patients to receive intracranial SRS, and an increased number of indications treated, both malignant and benign disease Virtually all patients with intracranial benign tumors who are undergoing SRS are treated with Icon. This gives more linac availability for other special time-consuming treatments like SBRT and also the advantage of using both modalities for certain patients With linac SRS, there were 2 days between the planning CT and the first treatment, during which time contouring, planning and plan acceptance was performed. With LGK, virtually everything is performed on the same day, apart from a preplanning MRI scan, which is performed 1-2 days prior to treatment LGK Icon offers new capabilities such as adaptive dose control and continuous patient monitoring The availability of the Gamma Knife Icon system has been very high with no significant downtime Leksell Gamma Knife is fully integrated and managed just like any other irradiation machine with MOSAIQ, the center's oncology information system (OIS) Key Statements from Customer Perspective by University Medical Centre Mannheim

Icon reduces dose to healthy tissue Key Statements from Customer Perspective by University Medical Centre Mannheim Clinical advantages Icon reduces dose to healthy tissue Before getting Icon, some benign conditions, such as pituitary adenoma and acoustic neuroma, were treated using linac. Now, such conditions are treated with Icon, with even smaller margins. Due to these reduced margins it is possible to treat targets located close to critical structures and thereby provide patients with safer treatments. “Firstly, there is evidence that Gamma Knife treatments have very low extracranial dose compared to other modalities, such as a linac or Cyber Knife […] In addition, we are able to achieve highly conformal plans with steep dose gradients, which is extremely important when high doses are being delivered close to critical structures, such as the optical nerve or chiasm […] Another benefit for patients is that we can reduce margins around the target compared to linac SRS […] Smaller margins mean less irradiation of healthy tissue.” Dr. Mai, Radiation Oncologist The ability to fractionate treatments, particularly for patients with benign disease, is an important feature of Icon Benign meningioma with a hypofractionated radiotherapy regime (5 x 5 Gy) Acoustic neuroma using normal fractionation on Gamma Knife Icon Allowing patients to benefit from all advantages of Gamma Knife, such as the low extracranial dose, conformality and high precision, even with the mask system “After some experience with the mask system on Gamma Knife Icon, we have been able to reduce our safety margins for the majority of acoustic neuromas to just one mm. With the linac, we typically use a safety margin of 3 mm. This is a significant reduction in volume when treating benign disease in young patients.” Dr. Mai, Radiation Oncologist

Management of brain metastases Icon removes barriers In the past, brain metastases patients were often treated using whole brain radiotherapy (WBRT), delivered using a linac In the literature, there is a clear trend away from WBRT and towards SRS, due to the severe toxicities and poor outcomes associated with WBRT, including cognitive function impairment  German guidelines now recommend that patients who are in good condition with a limited number of brain metastases should be treated using SRS. This has been the trend at Mannheim When treating brain metastases using linac SRS, the maximum number of lesions were three Now with Gamma Knife, patients with up to 10 metastases can be treated in a single session, even when they have had previous treatment with WBRT Key Statements from Customer Perspective by University Medical Centre Mannheim

CASE REPORT Combining linac and Gamma Knife treatments Large Nasopharynx Carcinoma A young male patient had a large tumor in his nasopharynx (left) A small area of under dosage near the inner ear with the VMAT plan (upper right) – a cold spot Improvement of this plan would have required a lot of additional treatment time for the patient In addition to the linac treatment, a single treatment with Leksell Gamma Knife of the cold spot was performed (lower right)  This allowed the team to deliver all the dose where they wanted it.