Therapeutic Response Evaluation in Advanced Melanoma Patients Incorporating Plasma cfDNA, LDH, VEGF, PD-L1, and IFN-γ Measurements.

BACKGROUND/AIM: Current treatment strategies for advanced melanoma require serial assessment of disease status in affected patients. In this study, we sought to examine the relationship between radiographic tumour burden and blood borne biomarkers including plasma cfDNA, serum LDH, plasma VEGF, PD-L1 and IFN-γ in advanced melanoma patients receiving immunotherapy. We hypothesized that a combination of these explanatory variables in a suitable regression analysis model may predict changes in tumour burden during patient treatment. MATERIALS AND METHODS: We extracted and quantified circulating cfDNA, LDH, VEGF, PD-L1, and IFN-γ from thirty patients with stage IV melanoma at baseline and at six months. All participating patients were evaluated with paired blood sample collection and CT scan assessments during treatment. RESULTS: Changes in radiographic tumour burden correlated with changes in levels of cfDNA (p≤0.001), LDH (p≤0.001), VEGF (p≤0.001), and PD-L1 (p<0.05) during treatment. Multiple regression analysis consisting of the follow-up to baseline assessment ratios of cfDNA, LDH, VEGF and PD-L1 explained changes in tumour burden (F (4, 23)=32.05, p<0.001); with an R2 of 0.8479 (Y=ß0+ß1*B+ß2*C+ß3*D+ß4*E). CONCLUSION: A quantitative measure of cfDNA, LDH, VEGF and PD-L1 may complement current methods of assessing tumour burden in advanced melanoma patients.

Implementation and preliminary clinical experience with the use of ceiling mounted mobile high field intraoperative magnetic resonance imaging between two operating rooms.

OBJECTIVE: Intraoperative magnetic resonance imaging (ioMRI) provides immediate feedback and quality assurance enabling the neurosurgeon to improve the quality of a range of neurosurgical procedures. Implementation of ioMRI is a complex and costly process. We describe our preliminary 16 months experience with the integration of an IMRIS movable ceiling mounted high field (1.5 T) ioMRI setup with two operating rooms. METHODS: Aspects of implementation of our ioMRI and our initial 16 months of clinical experience in 180 consecutive patients were reviewed. RESULTS: The installation of a ceiling mounted movable ioMRI between two operating rooms was completed in April 2008 at Barnes-Jewish Hospital in St. Louis. Experience with 180 neurosurgical cases (M:F-100:80, age range 1-79 years, 71 gliomas, 57 pituitary adenomas, 9 metastases, 11 other tumor cases, 4 Chiari decompressions, 6 epilepsy resections and 22 other miscellaneous procedures) demonstrated that this device effectively provided high quality real-time intraoperative imaging. In 74 of all 180 cases (41%) and in 54% of glioma resections, the surgeon modified the procedure based upon the ioMRI. Ninety-three percent of ioMRI glioma cases achieved gross/near total resection compared to 65% of non ioMRI glioma cases in this time frame. CONCLUSION: A movable high field strength ioMRI can be safely integrated between two neurosurgical operating rooms. This strategy leads to modification of the surgical procedure in a significant number of cases, particularly for glioma surgery. Long-term follow up is needed to evaluate the clinical and financial impact of this technology in the field of neurosurgery.

Use of movable high-field-strength intraoperative magnetic resonance imaging with awake craniotomies for resection of gliomas: preliminary experience.

BACKGROUND: Awake craniotomy with electrocortical mapping and intraoperative magnetic resonance imaging (iMRI) are established techniques for maximizing tumor resection and preserving function, but there has been little experience combining these methodologies. OBJECTIVE: To report our experience of combining awake craniotomy and iMRI with a 1.5-T movable iMRI for resection of gliomas in close proximity to eloquent cortex. METHODS: Twelve patients (9 male and 3 female patients; age, 32-60 years; mean, 41 years) undergoing awake craniotomy and iMRI for glioma resections were identified from a prospective database. Assessments were made of how these 2 modalities were integrated and what impact this strategy had on safety, surgical decision making, workflow, operative time, extent of tumor resection, and outcome. RESULTS: Twelve craniotomies were safely performed in an operating room equipped with a movable 1.5-T iMRI. The extent of resection was limited because of proximity to eloquent areas in 5 cases: language areas in 3 patients and motor areas in 2 patients. Additional tumor was identified and resected after iMRI in 6 patients. Average operating room time was 7.9 hours (range, 5.9-9.7 hours). Compared with preoperative neurological function, immediate postoperative function was stable/improved in 7 and worse in 5; after 30 days, it was stable/improved in 11 and worse in 1. CONCLUSION: Awake craniotomy and iMRI with a movable high-field-strength device can be performed safely to maximize resection of tumors near eloquent language areas.