The IMRiS Trial: A Phase II Study of Intensity-Modulated Radiotherapy in Extremity Soft Tissue Sarcoma.

PURPOSE: Primary soft tissue sarcoma (STS) is rare, with many tumours occurring in extremities. Local management is limb-sparing surgery and pre-operative/post-operative radiotherapy (RT) for patients at high risk of local recurrence. We prospectively investigated late normal tissue toxicity and limb function observed after intensity modulated RT (IMRT) in extremity STS. METHODS AND MATERIALS: Patients with extremity STS, age ≥16 years. Two treatment cohorts: IMRT 50Gy in 25 × 2Gy fractions (pre-operative) or 60/66Gy in 30/33 × 2Gy fractions (post-operative). Primary endpoint was rate of ≥ grade 2 late subcutaneous fibrosis at 24 months after IMRT (RTOG late radiation morbidity scoring). RESULTS: One hundred and sixty-eight patients were registered between March 2016-July 2017. Of those, 159 (95%) received IMRT (106, 67% pre-operative RT and 53, 33% post-operative RT) with a median follow-up of 35.2 months (IQR: 32.9 to 36.6); 62% male; median age 58 years. Of 111 patients assessable for primary endpoint at 24 months, 12 (10.8%, 95%CI: 5.7%-18.1%) had ≥ grade 2 subcutaneous fibrosis. The overall rate at 24 months of RTOG late skin, bone and joint toxicity was 7/112 (6.3%), 3/112 (2.7%) and 10/113 (8.8%), respectively, and for Stern's scale oedema was 6/113 (5.3%). More wound complications were observed with pre-operative than post-operative RT (29.2% vs 3.8%). Overall survival at 24 months was 84.6%, and local recurrence event rate at 24 months was 10%. CONCLUSIONS: The rate of ≥ grade 2 subcutaneous fibrosis at 24 months after IMRT was 10.8%, consistent with other recent trials of IMRT, and lower than historical reported rates in patients treated with 3D-CRT. This trial provides further evidence for the benefits of IMRT in this patient population.

Radiopaque drug-eluting embolisation beads as fiducial markers for stereotactic liver radiotherapy.

OBJECTIVE: To determine the feasibility of using radiopaque (RO) beads as direct tumour surrogates for image-guided radiotherapy (IGRT) in patients with liver tumours after transarterial chemoembolisation (TACE). METHODS: A novel vandetanib-eluting RO bead was delivered via TACE as part of a first-in-human clinical trial in patients with either hepatocellular carcinoma or liver metastases from colorectal cancer. Following TACE, patients underwent simulated radiotherapy imaging with four-dimensional computed tomography (4D-CT) and cone-beam CT (CBCT) imaging. RO beads were contoured using automated thresholding, and feasibility of matching between the simulated radiotherapy planning dataset (AVE-IP image from 4D data) and CBCT scans assessed. Additional kV, MV, helical CT and CBCT images of RO beads were obtained using an in-house phantom. Stability of RO bead position was assessed by comparing 4D-CT imaging to CT scans taken 6-20 days following TACE. RESULTS: Eight patients were treated and 4D-CT and CBCT images acquired. RO beads were visible on 4D-CT and CBCT images in all cases and matching successfully performed. Differences in centre of mass of RO beads between CBCT and simulated radiotherapy planning scans (AVE-IP dataset) were 2.0 mm mediolaterally, 1.7 mm anteroposteriorally and 3.5 mm craniocaudally. RO beads in the phantom were visible on all imaging modalities assessed. RO bead position remained stable up to 29 days post TACE. CONCLUSION: RO beads are visible on IGRT imaging modalities, showing minimal artefact. They can be used for on-set matching with CBCT and remain stable over time. ADVANCES IN KNOWLEDGE: The role of RO beads as fiducial markers for stereotactic liver radiotherapy is feasible and warrants further exploration as a combination therapy approach.

Meningioma causing visual impairment: outcomes and toxicity after intensity modulated radiation therapy.

PURPOSE: To evaluate ophthalmologic outcomes and toxicity of intensity modulated radiation therapy (IMRT) in patients with meningiomas causing visual deficits. METHODS AND MATERIALS: A prospective observational study with formal ophthalmologic and clinical assessment of 30 consecutive cases of meningioma affecting vision treated with IMRT from 2007 to 2011. Prescriptions were 50.4 Gy to mean target dose in 28 daily fractions. The median follow-up time was 28 months. Twenty-six meningiomas affected the anterior visual pathway (including 3 optic nerve sheath meningiomas); 4 were posterior to the chiasm. RESULTS: Vision improved objectively in 12 patients (40%). Improvements were in visual field (5/16 patients), color vision (4/9 patients), acuity (1/15 patients), extraocular movements (3/11 patients), ptosis (1/5 patients), and proptosis (2/6 patients). No predictors of clinical response were found. Two patients had minor reductions in tumor dimensions on magnetic resonance imaging, 1 patient had radiological progression, and the other patients were stable. One patient experienced grade 2 keratitis, 1 patient had a minor visual field loss, and 5 patients had grade 1 dry eye. CONCLUSION: IMRT is an effective method for treating meningiomas causing ophthalmologic deficits, and toxicity is minimal. Thorough ophthalmologic assessment is important because clinical responses often occur in the absence of radiological change.

Targeted intraoperative radiotherapy for breast cancer in patients in whom external beam radiation is not possible.

PURPOSE: External beam radiation therapy (EBRT) following wide local excision of the primary tumor is the standard treatment in early breast cancer. In some circumstances this procedure is not possible or is contraindicated or difficult. The purpose of this study was to determine the safety and efficacy of targeted intraoperative radiotherapy (TARGIT) when EBRT is not feasible. METHODS AND MATERIALS: We report our experience with TARGIT in three centers (Australia, Germany, and the United Kingdom) between 1999 and 2008. Patients at these centers received a single radiation dose of 20 Gy to the breast tissue in contact with the applicator (or 6 Gy at 1-cm distance), as they could not be given EBRT and were keen to avoid mastectomy. RESULTS: Eighty patients were treated with TARGIT. Reasons for using TARGIT were 21 patients had previously received EBRT, and 31 patients had clinical reasons such as systemic lupus erythematosus, motor neuron disease, Parkinson's disease, ankylosing spondylitis, morbid obesity, and cardiovascular or severe respiratory disease. Three of these patients received percutaneous radiotherapy without surgery; 28 patients were included for compelling personal reasons, usually on compassionate grounds. After a median follow-up of 38 months, only two local recurrences were observed, an annual local recurrence rate of 0.75% (95% confidence interval, 0.09%-2.70%). CONCLUSIONS: While we await the results of the randomized trial (over 2,000 patients have already been recruited), TARGIT is an acceptable option but only in highly selected cases that cannot be recruited in the trial and in whom EBRT is not feasible/possible.