Radionecrosis is a well-characterized effect of stereotactic radiosurgery (SRS) and is occasionally associated with serious neurologic sequelae. Here, we investigated the incidence of and clinical variables associated with the development of radionecrosis and related radiographic changes after SRS for brain metastases in a cohort of patients with long-term follow up. 271 brain metastases treated with single-fraction linear accelerator-based SRS were analyzed. Radionecrosis was diagnosed either pathologically or radiographically. Univariate and multivariate Cox regression was performed to determine the association between radionecrosis and clinical factors available prior to treatment planning. After median follow up of 17.2 months, radionecrosis was observed in 70 (25.8 %) lesions, including 47 (17.3 %) symptomatic cases. 22 of 70 cases (31.4 %) were diagnosed pathologically and 48 (68.6 %) were diagnosed radiographically. The actuarial incidence of radionecrosis was 5.2 % at 6 months, 17.2 % at 12 months and 34.0 % at 24 months. On univariate analysis, radionecrosis was associated with maximum tumor diameter (HR 3.55, p < 0.001), prior whole brain radiotherapy (HR 2.21, p = 0.004), prescription dose (HR 0.56, p = 0.02) and histology other than non-small cell lung, breast or melanoma (HR 1.85, p = 0.04). On multivariate analysis, only maximum tumor diameter (HR 3.10, p < 0.001) was associated with radionecrosis risk. This data demonstrates that with close imaging follow-up, radionecrosis after single-fraction SRS for brain metastases is not uncommon. Maximum tumor diameter on pre-treatment MR imaging can provide a reliable estimate of radionecrosis risk prior to treatment planning, with the greatest risk among tumors measuring >1 cm.

Purpose/Objective To evaluate local control following surgical resection and postoperative stereotactic radiosurgery (SRS) for brain metastases. Methods and Materials Forty-nine patients (50 lesions) were enrolled and available for analysis. Eligibility criteria included histologically confirmed malignancy with 1 or 2 intraparenchymal brain metastases, age ≥18, and KPS ≥70. Cox proportional hazard regression model was used to test for significant association between clinical factors and overall survival (OS). Competing risks regression models, as well as cumulative incidence functions, were fit using the method of Fine and Gray in order to assess the association between clinical factors and both local failure (LF, recurrence within surgical cavity or SRS target), and regional failure (RF, intracranial metastasis outside of treated volume). Results The median follow-up was 12.0 months (mos, range: 1.0–94.1 mos). Following surgical resection, 39 patients with 40 lesions were treated a median of 31 days (range: 7–56 days) later with SRS to the surgical bed to a median dose of 1800 cGy (range: 1500–2200 cGy). Of the 50 lesions, 15 (30%) demonstrated LF after surgery. The cumulative LF and RF rates were 22% and 44% at 12 mos. Patients who went on to receive SRS had significantly lower incidence of LF (p=0.008). Other factors associated with improved local control includes NSCLC histology (p=0.048), tumor diameter <3 cm (p=0.010), and deep parenchymal tumors (p=0.036). Large tumors (≥3 cm) with superficial dural/pial involvement showed the highest risk for LF (53.3% at 12 mos). Large, superficial lesions treated with SRS had 54.5% LF. Infratentorial lesions were at higher risk of developing RF compared to supratentorial lesions (p <0.001). Conclusions Postoperative SRS is associated with high local control, especially for deep brain metastases <3 cm. Tumors ≥3 cm with superficial dural/pial involvement demonstrate the highest risk in LF.

The OSI system is capable of detecting 0.1 +/- 0.1 mm 1D spatial displacement of a phantom in near real time and useful in head-motion monitoring. This new frameless SRS procedure using the mask-less head-fixation system provides immobilization similar to that of conventional frame-based SRS. Head-motion monitoring using near-real-time surface imaging provides adequate accuracy and is necessary for frameless SRS in case of unexpected head motion that exceeds a set tolerance.

The liposomal delivery of cancer therapeutics, including gene therapy vectors, is an area of intense study. Poor penetration of liposomes into interstitial tumor spaces remains a problem, however. In this work, the penetration of different liposomal formulations into prostate carcinoma spheroids was examined.

Unlike β particle–emitting isotopes, α emitters can selectively kill individual cancer cells with a single atomic decay. HuM195, a humanized anti-CD33 monoclonal antibody, specifically targets myeloid leukemia cells and has activity against minimal disease. When labeled with the β-emitters 131I and 90Y, HuM195 can eliminate large leukemic burdens in patients, but it produces prolonged myelosuppression requiring hematopoietic stem cell transplantation at high doses. To enhance the potency of native HuM195 yet avoid the nonspecific cytotoxicity of β-emitting constructs, the α-emitting isotope 213Bi was conjugated to HuM195. Eighteen patients with relapsed and refractory acute myelogenous leukemia or chronic myelomonocytic leukemia were treated with 10.36 to 37.0 MBq/kg 213Bi-HuM195. No significant extramedullary toxicity was seen. All 17 evaluable patients developed myelosuppression, with a median time to recovery of 22 days. Nearly all the 213Bi-HuM195 rapidly localized to and was retained in areas of leukemic involvement, including the bone marrow, liver, and spleen. Absorbed dose ratios between these sites and the whole body were 1000-fold greater than those seen with β-emitting constructs in this antigen system and patient population. Fourteen (93%) of 15 evaluable patients had reductions in circulating blasts, and 14 (78%) of 18 patients had reductions in the percentage of bone marrow blasts. This study demonstrates the safety, feasibility, and antileukemic effects of 213Bi-HuM195, and it is the first proof-of-concept for systemic targeted α particle immunotherapy in humans.