C. Menard

Boosting imaging defined dominant prostatic tumors: A systematic review

INTRODUCTIONnDominant cancer foci within the prostate are associated with sites of local recurrence post radiotherapy. In this systematic review we sought to address the question: what is the clinical evidence to support differential boosting to an imaging defined GTV volume within the prostate when delivered by external beam or brachytherapy.nnnMATERIALS AND METHODSnA systematic review was conducted to identify clinical series reporting the use of radiation boosts to imaging defined GTVs.nnnRESULTSnThirteen papers describing 11 unique patient series and 833 patients in total were identified. Methods and details of GTV definition and treatment varied substantially between series. GTV boosts were on average 8 Gy (range 3-35 Gy) for external beam, or 150% for brachytherapy (range 130-155%) and GTV volumes were small (<10 ml). Reported toxicity rates were low and may reflect the modest boost doses, small volumes and conservative DVH constraints employed in most studies. Variability in patient populations, study methodologies and outcomes reporting precluded conclusions regarding efficacy.nnnCONCLUSIONSnDespite a large cohort of patients treated differential boosts to imaging defined intra-prostatic targets, conclusions regarding optimal techniques and/or efficacy of this approach are elusive, and this approach cannot be considered standard of care. There is a need to build consensus and evidence. Ongoing prospective randomized trials are underway and will help to better define the role of differential prostate boosts based on imaging defined GTVs.

Impact of glycemia on survival of glioblastoma patients treated with radiation and temozolomide

Evidence suggests hyperglycemia is associated with worse outcomes in glioblastoma (GB). This study aims to confirm the association between glycemia during radiotherapy (RT) and temozolomide (TMZ) treatment and overall survival (OS) in patients with newly diagnosed GB. This retrospective study included GB patients treated with RT and TMZ from 2004 to 2011, randomly divided into independent derivation and validation datasets. Time-weighted mean (TWM) glucose and dexamethasone dose were collected from start of RT to 4xa0weeks after RT. Univariate (UVA) and multivariable (MVA) analyses investigated the association of TWM glucose and other prognostic factors with overall survival (OS). In total, 393 patients with median follow-up of 14xa0months were analyzed. In the derivation set (nxa0=xa0196) the median OS was 15xa0months and median TWM glucose was 6.3xa0mmol/L. For patients with a TWM glucose ≤6.3 and >6.3xa0mmol/L, median OS was 16 and 13xa0months, respectively (pxa0=xa00.03). On UVA, TWM glucose, TWM dexamethasone, age, extent of surgery, and performance status were associated with OS. On MVA, TWM glucose remained an independent predictor of OS (pxa0=xa00.03) along with TWM dexamethasone, age, and surgery. The validation set (nxa0=xa0197), with similar baseline characteristics, confirmed that TWM glucose ≤6.3xa0mmol/L was independently associated with longer OS (pxa0=xa00.005). This study demonstrates and validates that glycemia is an independent predictor for survival in GB patients treated with RT and TMZ.

Salvage radiosurgery for brain metastases: Prognostic factors to consider in patient selection

PURPOSEnStereotactic radiosurgery (SRS) is offered to patients for recurrent brain metastases after prior brain radiation therapy (RT), but few studies have evaluated the efficacy of salvage SRS or factors to consider in selecting patients for this treatment. This study reports overall survival (OS), intracranial progression-free survival (PFS), and local control (LC) after salvage SRS, and factors associated with outcomes.nnnMETHODS AND MATERIALSnThis is a retrospective review of patients treated from 2009 to 2011 with salvage SRS after prior brain RT for brain metastases. Survival from salvage SRS and from initial brain metastases diagnosis (IBMD) was calculated. Univariate and multivariable (MVA) analyses included age, performance status, recursive partitioning analysis (RPA) class, extracranial disease control, and time from initial RT to salvage SRS.nnnRESULTSnThere were 106 patients included in the analysis with a median age of 56.9 years (range 32.5-82 years). A median of 2 metastases were treated per patient (range, 1-12) with a median dose of 21 Gy (range, 12-24) prescribed to the 50% isodose. With a median follow-up of 10.5 months (range, 0.1-68.2), LC was 82.8%, 60.1%, and 46.8% at 6 months, 1 year, and 3 years, respectively. Median PFS was 6.2 months (95% confidence interval [CI]=4.9-7.6). Median OS was 11.7 months (95% CI=8.1-13) from salvage SRS, and 22.1 months from IBMD (95% CI=18.4-26.8). On MVA, age (P=.01; hazard ratio [HR]=1.04; 95% CI=1.01-1.07), extracranial disease control (P=.004; HR=0.46; 95% CI=0.27-0.78), and interval from initial RT to salvage SRS of at least 265 days (P=.001; HR=2.46; 95% CI=1.47-4.09) were predictive of OS.nnnCONCLUSIONSnThis study demonstrates that patients can have durable local control and survival after salvage SRS for recurrent brain metastases. In particular, younger patients with controlled extracranial disease and a durable response to initial brain RT are likely to benefit from salvage SRS.

Advances in Magnetic Resonance Imaging and Positron Emission Tomography Imaging for Grading and Molecular Characterization of Glioma

In recent years, the management of glioma has evolved significantly, reflecting our better understanding of the underlying mechanisms of tumor development, tumor progression, and treatment response. Glioma grade, along with a number of underlying molecular and genetic biomarkers, has been recognized as an important prognostic and predictive factor that can help guide the management of patients. This article highlights advances in magnetic resonance imaging (MRI), including diffusion-weighted imaging, diffusion tensor imaging, magnetic resonance spectroscopy, dynamic contrast-enhanced imaging, and perfusion MRI, as well as position emission tomography using various tracers including methyl-(11)C-l-methionine and O-(2-(18)F-fluoroethyl)-l-tyrosine. Use of multiparametric imaging data has improved the diagnostic strength of imaging, introduced the potential to noninvasively interrogate underlying molecular features of low-grade glioma and to guide local therapies such as surgery and radiotherapy.

Readout-segmented echo-planar diffusion-weighted imaging improves geometric performance for image-guided radiation therapy of pelvic tumors

BACKGROUND AND PURPOSEnDiffusion-weighted imaging using echo-planar imaging (EPI) is prone to geometric inaccuracy, which may limit application to image-guided radiation therapy planning, as well as for voxel-based quantitative multi-parametric or multi-modal approaches. This research investigates pelvic applications at 3 T of a standard single-shot (ssEPI) and a prototype readout-segmented (rsEPI) technique.nnnMATERIALS AND METHODSnApparent diffusion coefficient (ADC) accuracy and geometric performance of rsEPI and ssEPI were compared using phantoms, and in vivo, involving 8 patients prior to MR-guided brachytherapy for locally advanced cervical cancer, and 19 patients with prostate cancer planned for tumor-targeted radiotherapy. Global and local deviations in geometric performance were tested using Dice Similarity Coefficients (DC) and Hausdorff Distances (HD).nnnRESULTSnIn cervix patients, DC increased from 0.76±0.14 to 0.91±0.05 for the high risk clinical target volume, and 0.62±0.26 to 0.85±0.08 for the gross tumor target volume. Tumors in the peripheral zone of the prostate gland were partly projected erroneously outside of the posterior anatomic boundary of the gland by 3.1±1.6 mm in 11 of 19 patients using ADC-ssEPI but not with ADC-rsEPI.nnnCONCLUSIONSnBoth cervix and prostate ssEPI are prone to clinically relevant geometric distortions at 3T. rsEPI provides improved geometric performance without post-processing.

Neutrophil–lymphocyte ratio dynamics during concurrent chemo-radiotherapy for glioblastoma is an independent predictor for overall survival

Elevated neutrophil–lymphocyte ratio (NLR) may predict worse outcomes in cancer, including glioblastoma (GBM). This study assessed whether change in NLR during focal radiotherapy and concomitant temozolomide (RT-TMZ) provides further prognostic information. This was a retrospective review of patients treated with RT-TMZ for histologically confirmed GBM from January 2004 to September 2010. Variables assessed included age, ECOG performance status (PS), dexamethasone use and extent of surgery. Hematological results were collected at baseline, during and 4 weeks post RT-TMZ. Kaplan–Meier method was used to calculate overall survival (OS). Multivariable analysis (MVA) assessed for joint effect of covariates on OS and Pearson Correlation Coefficients assessed for association between dexamethasone dose and NLR change. With a median age of 55 (range 18–70), 369 patients were included. Median follow up was 15.1 month (range 1.6–134.6). The OS was 66.1% (95% CI 61.2–70.6) and 31.4 (95% CI 26.8–36.1) at 1 and 2 years, respectively. On univariate analysis, both decrease in NLR post RT-TMZ (HR 0.641, pu2009<u20090.0001) and baseline NLRu2009<u20097.5 (HR 0.628, pu2009<u20090.0001) were associated with longer OS. On MVA decrease in NLR (HR 0.727, 95% CI 0.578–0.915), age (HR 1.025, 95% CI 1.012–1.038), baseline neutrophil (<8) (HR 0.689, 95% CI 0.532–0.891), total TMZ cycles (HR 0.89, 95% CI 0.867–0.913) and PS (HR 0.476, 95% CI 0.332–0.683) were independent predictors of OS. These findings suggest that a decrease in NLR during RT-TMZ, accounting for known prognostic factors, is an independent prognostic factor for survival in GBM.

Advancements in brachytherapy

Brachytherapy is a radiotherapy modality associated with a highly focal dose distribution. Brachytherapy treats the cancer tissue from the inside, and the radiation does not travel through healthy tissue to reach the target as with external beam radiotherapy techniques. The nature of brachytherapy makes it attractive for boosting limited size target volumes to very high doses while sparing normal tissues. Significant developments over the last decades have increased the use of 3D image guided procedures with the utilization of CT, MRI, US and PET. This has taken brachytherapy to a new level in terms of controlling dose and demonstrating excellent clinical outcome. Interests in focal, hypofractionated and adaptive treatments are increasing, and brachytherapy has significant potential to develop further in these directions with current and new treatment indications.

Radiosurgery for brainstem metastases with and without whole brain radiotherapy: clinical series and literature review

ObjectiveThe objective of this study was to investigate outcomes for patients with brainstem metastases treated with stereotactic radiosurgery (SRS).MethodsPatients with brainstem metastases treated with SRS between April 2006 and June 2012 were identified from a prospective database. Patient and treatment-related factors were recorded. Kaplan-Meier analysis was used to calculate survival and freedom from local and distant brain progression. Univariate and multivariate Cox regression was used to identify factors important for overall survival.ResultsIn total, 44 patients received SRS for 48 brainstem metastases of whom 33 (75xa0%) also received whole brain radiotherapy (WBRT): 23 patients (52xa0%) WBRT prior to SRS, 6 (13.6xa0%) WBRT concurrently with SRS and 4 (9.0xa0%) WBRT after SRS. Eight patients received a second course of WBRT at further progression. Median target volume was 1.33xa0cc (range 0.04–12.17) and median prescribed marginal dose was 15xa0Gy (range 10–22). There were four cases of local failure, and 6-month and 1-year freedom from local failure was 84.6 and 76.9xa0%, respectively. Median overall survival (OS) was 5.4xa0months. There were four cases of radionecrosis, 2 (4.8xa0%) of which were symptomatic. The absence of external beam brain radiotherapy (predominantly WBRT) showed a trend towards improved OS on univariate analysis. Neither local nor distant brain failure significantly impacted OS.ConclusionThis retrospective series of patients treated with SRS for brainstem metastases, largely in combination with at least one course of WBRT, demonstrates that this approach is safe and results in good local control. In this cohort, no variables significantly impacted OS, including intracranial control.

Introduction: Magnetic resonance imaging comes of age in radiation oncology.

Introduction: Magnetic Resonance Imaging Comes of Age in Radiation Oncology With the invention of spatial encoding of the nuclear magnetic resonance (MR) signal by Lauterbur and Mansfield, MR imaging (MRI) was born. After the first image of in vivo human anatomy in 1977, evolution of the technology accelerated over the ensuing decade, and clinical translation to the field of diagnostic radiology flourished. Because MRI, much like radiation oncology, is at the crossroads betweenmedicine and chemistry, physics, and computer science, groups with strong interdisciplinary relationships and cross-fertilization became scientifically fruitful. Its potential for radiotherapy was recognized soon thereafter. The integration of MR images in the treatment planning process for radiosurgery, followed by radiotherapy and brachytherapy, was initially reported in the late 1980s. In 1996, the first MRI simulator was reported in Japan, whereby patients were imaged in the treatment position using a permanent open-magnet system with high-precision lasers used exclusively for radiotherapy. Owing to geometric considerations, the open MRI scanner architecture was later adapted and dedicated to MRI simulation by radiotherapy departments in Bristol, Heidelberg, and Philadelphia. As the delivery techniques in radiotherapy have reached unprecedented levels of accuracy, high-quality imaging to plan such treatments has become essential (Fig.). As a result, many radiation oncology departments have acquired either their own dedicated equipment or protected access to MRI scanners for the purpose of radiotherapy planning. In the clinical practice of our respective institutes, approximately 20% of all patients undergo MRI simulation as a component of their radiotherapy planning process, with brain, head-neck, gynecological, urological, and gastrointestinal malignancies as the predominant applications. The individualization of radiotherapy has clearly evolved as the overriding clinical objective drivingmuch of this change. MRI physics and radiology constitute large research fields by themselves, but it is clear that new opportunities and specific questions arise when these techniques are applied in radiotherapy. For example, the geometric accuracy of MR images is of limited importance in a diagnostic setting but is critical for high-precision radiotherapy. Diagnostic scans, typically optimized to allow a differential diagnosis, are not optimal for

Assessment of nonrespiratory stomach motion in healthy volunteers in fasting and postprandial states

PURPOSEnTo characterize nonrespiratory stomach motion in the fasting state and postprandial.nnnMETHODS AND MATERIALSnTen healthy volunteers underwent 2-dimensional Fiesta cine magnetic resonance imaging studies in 30-second voluntary breath hold, in axial, coronal, and 2 oblique planes while fasting, and 5, 15, 30, 45, and 60 minutes postmeal. Each stomach contour was delineated and sampled with 200 points. Matching points were found for all contours in the same 30-second acquisition. Using deformable parametric analysis (Matlab, version 7.1), mean magnitude, and standard deviation of displacement of each point were determined for each patient. Maximal, minimal, and median population values in 6 cardinal, and in any direction, were calculated.nnnRESULTSnThe median of mean displacements for the baseline position of each point was small and rarely exceeded 1.1 mm; greatest value was 1.6 mm superior-inferior. Median displacement (pooled across time) in the right-left, superior-inferior, and anterior-posterior directions was 0.3 (range, -0.7 to 1.3), 0.8 (-0.4 to 2.4), and 0.3 (-1.1 to 1.6) mm, respectively. Fasting and postprandial standard deviation did not differ.nnnCONCLUSIONSnNonrespiratory stomach displacement is small and stomach position is stable after a small, standard meal. Radiation therapy may be delivered at any time within the first hour after eating without significant compromise of planned planning target volumes.