Effects of mechanical forces exerted on mammalian skeletal muscle cells during development were studied using an in vitro model to unidirectionally stretch cultured C2C12 cells grown on silastic membrane. Previous models to date have not studied these responses of the mammalian system specifically. The silastic membrane upon which these cells were grown exhibited linear strain behavior over the range of 3.6-14.6% strain, with a Poisson's ratio of approximately 0.5. To mimic murine in utero long bone growth, cell substrates were stretched at an average strain rate of 2.36%/day for 4 days or 1.77%/day for 6 days with an overall membrane strain of 9.5% and 10.6%, respectively. Both control and stretched fibers stained positively for the contractile protein, alpha-actinin, demonstrating muscle fiber development. An effect of stretch on orientation and length of myofibers was observed. At both strain rates, stretched fibers aligned at a smaller angle relative to the direction of stretch and were significantly longer compared to randomly oriented control fibers. There was no effect of duration of stretch on orientation or length, suggesting the cellular responses are independent of strain rate for the range tested. These results demonstrate that, under conditions simulating mammalian long bone growth, cultured myocytes respond to mechanical forces by lengthening and orienting along the direction of stretch.

Dual energy (DE) imaging consists of obtaining kilovoltage (kV) x-ray images at two different diagnostic energies and performing a weighted subtraction of these images. A third image is then produced that highlights soft tissue. DE imaging has been used by radiologists to aid in the detection of lung malignancies. However, it has not been used clinically in radiotherapy. The goal of this study is to assess the feasibility of performing DE imaging using a commercial on-board imaging system. Both a simple and an anthropomorphic phantom were constructed for this analysis. Planar kV images of the phantoms were obtained using varied imaging energies and mAs. Software was written to perform DE subtraction using empirically determined weighting factors. Tumor detectability was assessed quantitatively using the signal-difference-tonoise ratio (SDNR). Overall DE subtraction suppressed high density objects in both phantoms. The optimal imaging technique, providing the largest SDNR with a dose less than our reference technique was 140 kVp, 1.0 mAs and 60 kVp, 3.2 mAs. Based on this analysis, DE subtraction imaging is feasible using a commercial on-board imaging system and may improve the visualization of tumors in lung cancer patients undergoing image-guided radiotherapy.

ObjectFollowing resection of a brain metastasis, stereotactic radiosurgery (SRS) to the cavity is an emerging alternative to postoperative whole-brain radiation therapy (WBRT). This approach attempts to achieve local control without the neurocognitive risks associated with WBRT. The authors aimed to report the outcomes of a large patient cohort treated with this strategy.MethodsA retrospective review identified 91 patients without a history of WBRT who received Gamma Knife (GK) SRS to 96 metastasis resection cavities between 2007 and 2013. Patterns of intracranial control were examined in the 86 cases with post-GK imaging. Survival, local failure, and distant failure were estimated by the Kaplan-Meier method. Prognostic factors were tested by univariate (log-rank test) and multivariate (Cox proportional hazards model) analyses.ResultsCommon primary tumors were non–small cell lung (43%), melanoma (14%), and breast (13%). The cases were predominantly recursive partitioning analysis Class I (25%) or II (70%). Median preoperative metastasis diameter was 2.8 cm, and 82% of patients underwent gross-total resection. A median dose of 16 Gy was delivered to the 50% isodose line, encompassing a median treatment volume of 9.2 cm3. Synchronous intact metastases were treated in addition to the resection bed in 43% of cases. Patients survived a median of 22.3 months from the time of GK. Local failure developed in 16 cavities, for a crude rate of 18% and 1-year actuarial local control of 81%. Preoperative metastasis diameter ≥ 3 cm and residual or recurrent tumor at the time of GK were associated with local failure (p = 0.04 and 0.008, respectively). Distant intracranial failure occurred in 55 cases (64%) at a median of 7.3 months from GK. Salvage therapies included WBRT and additional SRS in 33% and 31% of patients, respectively. Leptomeningeal carcinomatosis developed in 12 cases (14%) and was associated with breast histology and infratentorial cavities (p = 0.024 and 0.012, respectively).ConclusionsThis study bolsters the existing evidence for SRS to the resection bed. Local control rates are high, but patients with larger preoperative metastases or residual/recurrent tumor at the time of SRS are more likely to fail at the cavity. While most patients develop distant intracranial failure, an SRS approach spared or delayed WBRT in the majority of cases. The risk of leptomeningeal carcinomatosis does not appear to be elevated with this strategy.

This is the largest series on SBRT for sarcoma PM's and demonstrates that SBRT is well-tolerated with excellent LC across tumor locations and sizes. SBRT should be considered in these patients, and prospective studies are warranted. J. Surg. Oncol. 2016;114:65-69. © 2016 Wiley Periodicals, Inc.

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