Cancer Imaging Phenomics via CaPTk: Multi-Institutional Prediction of Progression-Free Survival and Pattern of Recurrence in Glioblastoma.

PURPOSE: To construct a multi-institutional radiomic model that supports upfront prediction of progression-free survival (PFS) and recurrence pattern (RP) in patients diagnosed with glioblastoma multiforme (GBM) at the time of initial diagnosis. PATIENTS AND METHODS: We retrospectively identified data for patients with newly diagnosed GBM from two institutions (institution 1, n = 65; institution 2, n = 15) who underwent gross total resection followed by standard adjuvant chemoradiation therapy, with pathologically confirmed recurrence, sufficient follow-up magnetic resonance imaging (MRI) scans to reliably determine PFS, and available presurgical multiparametric MRI (MP-MRI). The advanced software suite Cancer Imaging Phenomics Toolkit (CaPTk) was leveraged to analyze standard clinical brain MP-MRI scans. A rich set of imaging features was extracted from the MP-MRI scans acquired before the initial resection and was integrated into two distinct imaging signatures for predicting mean shorter or longer PFS and near or distant RP. The predictive signatures for PFS and RP were evaluated on the basis of different classification schemes: single-institutional analysis, multi-institutional analysis with random partitioning of the data into discovery and replication cohorts, and multi-institutional assessment with data from institution 1 as the discovery cohort and data from institution 2 as the replication cohort. RESULTS: These predictors achieved cross-validated classification performance (ie, area under the receiver operating characteristic curve) of 0.88 (single-institution analysis) and 0.82 to 0.83 (multi-institution analysis) for prediction of PFS and 0.88 (single-institution analysis) and 0.56 to 0.71 (multi-institution analysis) for prediction of RP. CONCLUSION: Imaging signatures of presurgical MP-MRI scans reveal relatively high predictability of time and location of GBM recurrence, subject to the patients receiving standard first-line chemoradiation therapy. Through its graphical user interface, CaPTk offers easy accessibility to advanced computational algorithms for deriving imaging signatures predictive of clinical outcome and could similarly be used for a variety of radiomic and radiogenomic analyses.

Acute toxicity profile of patients with low-grade gliomas and meningiomas receiving proton therapy.

OBJECTIVES: Proton therapy is an emerging treatment modality. We studied its acute side effects on patients with low-grade gliomas and meningiomas. MATERIALS AND METHODS: Twenty-three patients diagnosed with low-grade gliomas or meningiomas enrolled in an Institutional Review Board-approved prospective proton treatment protocol (NCT01024907) were treated and followed between April 2010 and August 2011. Patients received 54 Gy (relative biological effectiveness) in 1.8 Gy (relative biological effectiveness) per fraction and were assessed at the time of consult, weekly during treatment, and at 1, 3, 6, and 9 months posttreatment. At each clinic visit, nursing completed a "Symptom Assessment/Grading" table. Symptoms were graded based on National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. RESULTS: Fatigue: At on-treatment visit (OTV) week 6, 13 patients had grade 1 and 6 patients had grade 2 fatigue. At 1-month follow-up, 3 patients had grade 1 and 1 patient had grade 2 fatigue. At each timepoint, 1 patient had grade 3 fatigue. Nausea: At OTV week 3, 5 patients experienced grade 1 nausea. At OTV week 6, 3 patients experienced grade 1 nausea. Headache: At OTV week 3, 10 patients had grade 1 headaches. At OTV week 6, 4 patients experienced grade 1 headaches and 1 patient by follow-up month 1. One to 2 patients experienced grade 2 headaches at each timepoint. At OTV week 3, 1 patient experienced a grade 3 headache. CONCLUSIONS: Our results suggest that proton therapy for patients with low-grade gliomas and meningiomas has a favorable acute toxicity profile-most patients experienced mild fatigue, headache, and insomnia that largely resolved by 1-month posttreatment.

Light Dosimetry at Tissue Surfaces for Small Circular Fields.

Small circular light fields (≤ 2 cm diameter) are sometimes used for photodynamic therapy of skin and recurrent breast cancers on the chest wall. These fields have lateral dimensions comparable to the effective mean free path of photons in the turbid medium, which causes reduced light fluence rate compared to that of a broad beam of uniform incident irradiance. We have compared Monte-Carlo simulation with in-vivo dosimetry for circular fields (R = 0.25, 0.35, 0.5, 0.75, 1, 2, 3, and 8 cm) in a liquid phantom composed of intralipid and ink (µs' = 4 - 20 cm-1 and µa = 0.1 cm-1) for wavelengths between 532 and 730 nm. We used anisotropy g = 0.9 and the index of refraction n = 1.4 for all Monte-Carlo simulations. The measured light fluence rate agrees with Monte-Carlo simulation to within 10%, with the measured value lower than that of the Monte-Carlo simulation on tissue surface. The ratio of the peak fluence rates between a circular beam and a broad beam under tissue is 0.58 - 0.96 or 0.84 - 1.00 for R between 0.5 - 2 cm and µeff = 1.1 or 2.0 cm-1, respectively. The ratio of peak fluence rate and incident irradiance for the broad beam is 5.9 and 6.4 for µeff = 1.1 and 2.0 cm-1, respectively. The optical penetration depth δ varies from 0.34 - 0.48 cm for R between 0.5 and 2 cm, with the corresponding δ = 0.51 cm for a broad beam. The ratio of fluence rate and incident irradiance above tissue surface is 1.4 - 1.8 or 1.9 - 2.2 for R between 0.5 - 2 cm and µeff = 1.1 or 2.0 cm-1, respectively. At depth of 0.2 cm inside tissue, Off-axis ratio OAR, defined as the ratio of fluence rate at off-axis distance r to that on the central axis, varies between 0.91 - 0.54 or 0.93 - 0.52 for off-axis distances r between 0.6 and 1.0 cm and µeff = 1.1 or 2.1 cm-1, respectively. In conclusion, in-vivo light dosimetry agrees with Monte-Carlo simulation for small field dosimetry provided the isotropic detector is corrected for the blind spot. The light fluence rates for small circular fields are substantially lower than that of the broad beam of the same incident irradiance.