CyberKnife Radiosurgery of Skull-base Tumors: A UK Center Experience.

The study aim was to evaluate patient individualized Cyberknife® treatment for heterogeneous skull-base tumors. Patients treated between 2009 and 2013 at The Harley Street Clinic were studied. In total, 66 patients received 15-30 Gy in 1-5 fractions to a median planning target volume (PTV) of 6.4 cc, including patients with secondary, multiple, residual and recurrent tumors, and those with tumors of uncertain pathological type. Outcome analysis was pragmatically restricted to 35 patients who had single, primary tumors treated with curative intent, and sufficient diagnostic and outcome information. Sixteen vestibular schwannoma patients with median PTV 3.8 cc (range 0.81-19.6) received 18-25 Gy in 3-5 fractions: 81% showed no acute toxicity, 50% reported no late toxicity, 71% of symptoms were stable/improved and local control was 100% at 11.4 months median follow-up. Twelve meningioma patients with median PTV of 5.5 cc (range 0.68-22.3) received 17-30 Gy in 1-5 fractions: 83% experienced no acute toxicity, 33% reported no late toxicity, 88% of symptoms were stable/improved and local control was 100% at 22.1 months median follow-up. Seven patients with other tumor types with median PTV of 24.3 cc (range 7.6-100.5) received 15-28.5 Gy in 1-5 fractions: 57% experienced no acute toxicity, 57% reported no late toxicities, 66% of symptoms were stable and local control was 43% at 14.9 months median follow-up. When tumor types were considered together, smaller tumors (PTV < 6.4 cc) showed reduced acute toxicity (p = 0.01). Overall, smaller benign tumors showed low acute toxicity, excellent local control, and good symptom management: a focus on enhanced neurological preservation may refine outcomes. For other tumor types outcome was encouraging: a focus on optimal dose and fractionation scheduling may reduce toxicity and improve local control. Individual patient experiences are detailed where valuable lessons were gained for optimizing local control and minimizing toxicity.

Active dendritic cell immunotherapy for glioblastoma: Current status and challenges.

Dendritic cell (DC) immunotherapy is developing as a promising treatment modality for patients with glioblastoma multiforme (GBM). The aim of this article is to review the data from clinical trials and prospective studies evaluating the safety and efficacy of DC vaccines for newly diagnosed (ND)- and recurrent (Rec)-GBM and for other high-grade gliomas (HGGs). By searching all major databases we identified and reviewed twenty-two (n=22) such studies, twenty (n=20) of which were phase I and II trials, one was a pilot study towards a phase I/II trial and one was a prospective study. GBM patients were exclusively recruited in 12/22 studies, while 10/22 studies enrolled patients with any diagnosis of a HGG. In 7/22 studies GBM was newly diagnosed. In the vast majority of studies the vaccine was injected subcutaneously or intradermally and consisted of mature DCs pulsed with tumour lysate or peptides. Median overall survival ranged between 16.0 and 38.4 months for ND-GBM and between 9.6 and 35.9 months for Rec-GBM. Vaccine-related side effects were in general mild (grade I and II), with serious adverse events (grade III, IV and V) reported only rarely. DC immunotherapy therefore appears to have the potential to increase the overall survival in patients with HGG, with an acceptable side effect profile. The findings will require confirmation by the ongoing and future phase III trials.

Stereotactic radiosurgery in the treatment of brain metastases: the current evidence.

Chemotherapy has made substantial progress in the therapy of systemic cancer, but the pharmacological efficacy is insufficient in the treatment of brain metastases. Fractionated whole brain radiotherapy (WBRT) has been a standard treatment of brain metastases, but provides limited local tumor control and often unsatisfactory clinical results. Stereotactic radiosurgery using Gamma Knife, Linac or Cyberknife has overcome several of these limitations, which has influenced recent treatment recommendations. This present review summarizes the current literature of single session radiosurgery concerning survival and quality of life, specific responses, tumor volumes and numbers, about potential treatment combinations and radioresistant metastases. Gamma Knife and Linac based radiosurgery provide consistent results with a reproducible local tumor control in both single and multiple brain metastases. Ideally minimum doses of ≥18Gy are applied. Reported local control rates were 90-94% for breast cancer metastases and 81-98% for brain metastases of lung cancer. Local tumor control rates after radiosurgery of otherwise radioresistant brain metastases were 73-90% for melanoma and 83-96% for renal cell cancer. Currently, there is a tendency to treat a larger number of brain metastases in a single radiosurgical session, since numerous studies document high local tumor control after radiosurgical treatment of >3 brain metastases. New remote brain metastases are reported in 33-42% after WBRT and in 39-52% after radiosurgery, but while WBRT is generally applied only once, radiosurgery can be used repeatedly for remote recurrences or new metastases after WBRT. Larger metastases (>8-10cc) should be removed surgically, but for smaller metastases Gamma Knife radiosurgery appears to be equally effective as surgical tumor resection (level I evidence). Radiosurgery avoids the impairments in cognition and quality of life that can be a consequence of WBRT (level I evidence). High local efficacy, preservation of cerebral functions, short hospitalization and the option to continue a systemic chemotherapy are factors in favor of a minimally invasive approach with stereotactic radiosurgery.

An analysis of intraoperative versus post-operative dosimetry with CT, CT-MRI fusion and XMR for the evaluation of permanent prostate brachytherapy implants.

BACKGROUND AND PURPOSE: To assess the agreement between intraoperative and post-operative dosimetry and to identify factors that influence dose calculations of prostate brachytherapy implants. MATERIALS AND METHODS: Patients treated with prostate brachytherapy implants underwent post-operative CT and XMR (combined X-ray and MR) imaging. Dose-volume histograms were calculated from CT, XMR and CT-MR fusion data and compared with intraoperative values for two observers. Multiple linear regression models assessed the influences of intraoperative D90, gland oedema, gland volume, source loss and migration, and implanted activity/volume prostate on post-operative D90. RESULTS: Forty-nine patients were studied. The mean D90 differences (95% confidence limits) between intraoperative and post-operative CT, XMR and CT-MR fusion assessments were: 11 Gy (-22, 45), 18 Gy (-13, 49) and 20 Gy (-17, 58) for Observer 1; and 15 Gy (-34, 63), 13 Gy (-29, 55) and 14 Gy (-27, 54) for Observer 2. Multiple linear regression modelling showed that the observed oedema and intraoperative D90 were significant independent variables for the prediction of post-operative D90 values for both observers using all modalities. CONCLUSION: This is the first study to report Bland-Altman agreement analysis between intraoperative and post-operative dosimetry. Agreement is poor. Post-operative dosimetry is dependent on the intraoperative D90 and the subjectively outlined gland volume.

Comparison of combined x-ray radiography and magnetic resonance (XMR) imaging-versus computed tomography-based dosimetry for the evaluation of permanent prostate brachytherapy implants.

PURPOSE: To present a method for the dosimetric analysis of permanent prostate brachytherapy implants using a combination of stereoscopic X-ray radiography and magnetic resonance (MR) imaging (XMR) in an XMR facility, and to compare the clinical results between XMR- and computed tomography (CT)-based dosimetry. METHODS AND MATERIALS: Patients who had received nonstranded iodine-125 permanent prostate brachytherapy implants underwent XMR and CT imaging 4 weeks later. Four observers outlined the prostate gland on both sets of images. Dose-volume histograms (DVHs) were derived, and agreement was compared among the observers and between the modalities. RESULTS: A total of 30 patients were evaluated. Inherent XMR registration based on prior calibration and optical tracking required a further automatic seed registration step that revealed a median root mean square registration error of 4.2 mm (range, 1.6-11.4). The observers agreed significantly more closely on prostate base and apex positions as well as outlining contours on the MR images than on those from CT. Coefficients of variation were significantly higher for observed prostate volumes, D90, and V100 parameters on CT-based dosimetry as opposed to XMR. The XMR-based dosimetry showed little agreement with that from CT for all observers, with D90 95% limits of agreement ranges of 65, 118, 79, and 73 Gy for Observers 1, 2, 3, and 4, respectively. CONCLUSIONS: The study results showed that XMR-based dosimetry offers an alternative to other imaging modalities and registration methods with the advantages of MR-based prostate delineation and confident three-dimensional reconstruction of the implant. The XMR-derived dose-volume histograms differ from the CT-derived values and demonstrate less interobserver variability.

Dynamic dose-feedback prostate brachytherapy in patients with large prostates and/or planned transurethral surgery before implantation.

OBJECTIVE: To compare the quality of permanent prostate brachytherapy (PPB) implants, dosimetric outcomes and urinary morbidity between patients with large (>50 mL) and those with smaller prostates, treated with a dynamic dose-feedback technique as monotherapy for localized prostate cancer. PATIENTS AND METHODS: The series included patients with pre-existing bladder outlet obstruction managed with planned transurethral resection or incision of the prostate; 155 consecutive men had PPB implants as monotherapy for localized prostate cancer using a dynamic dose-feedback approach. Dosimetric variables assessed included the implant volume, the minimum dose to 90% of the prostate (D90), and the volumes of prostate receiving 100% and 150% of the prescribed dose as a percentage of the total volume (V100 and V150), during and after implantation. Urinary morbidity was recorded in terms of acute urinary retention (AUR), the need for surgical intervention after implantation and the American Urologic Association (AUA) symptom score at baseline, 1.5, 3, 6, 9, 12 and 18 months. RESULTS: In all, 38 patients had prostate volumes of >or=50 mL; prostate volume had no influence on any dosimetric variable assessed. Two patients with large prostates (>or=50 mL) had AUR and required delayed surgery. Three patients with small prostates (<50 mL) had transient retention; the differences were not statistically significant (Fisher's exact test). AUA symptom scores peaked at 6 weeks and returned to baseline within a year; there were no statistically significant differences between the groups. Eight patients had planned transurethral surgery at >or=4 months before implantation; they all had D90s of >130 Gy and had no incontinence. CONCLUSION: Using the dynamic feedback technique, there was no adverse dosimetric and urinary morbidity in men having PPB and with prostates of >50 mL. Likewise, there were no impediments, e.g. pubic arch interference, which precluded a favourable dosimetric implant in men with a large prostate. Large prostates should not be a contraindication to PPB and require no hormonal cytoreduction. Patients with obstructive lower urinary tract symptoms can be managed with planned transurethral prostatic surgery before implantation, without compromising implant quality or morbidity.

Permanent prostate brachytherapy: Dosimetric results and analysis of a learning curve with a dynamic dose-feedback technique.

PURPOSE: A permanent prostate brachytherapy (PPB) program utilizing intraoperative inverse-planned dynamic dose-feedback was initiated without prior firsthand experience of alternative techniques. The purpose of this study is to assess the dosimetric learning curve associated with this approach. METHODS AND MATERIALS: A total of 77 patients underwent PPB implants as monotherapy for localized prostate cancer to a prescription dose of 145 Gy with loose 125I seeds between December 2003 and June 2004. Intraoperative and postoperative dosimetric values, total implanted radioactivity, and operating room (OR) times were compared by sequential case number for all cases. RESULTS: The median intraoperative dosimetric values were: D90 (the minimum dose to 90% of the prostate) = 170 Gy (range, 135-203 Gy), V100 (the volume of the prostate that receives 100% of the prescription dose) = 96% (range, 86-100), V150 = 66% (range, 34-86). Median postoperative dosimetric values were as follows: D90 = 168 Gy (range, 132-197 Gy), V100 = 95% (range, 86-99), V150 = 74% (range, 51-84). Median implanted activity was 0.79 mCi per cubic centimeter of prostate (range, 0.541-1.13). There was no significant correlation by case number on any postoperative dosimetric parameter studied. Door-to-door OR time was reduced from median 138 to 97.5 min per case at the end of the series with a correlation coefficient of -0.76 for the initial 28 cases. CONCLUSION: Satisfactory dosimetric parameters can be achieved from the outset without a learning curve effect in an appropriately trained environment. The learning curve for dynamic dose-feedback PPB in a clinic naïve to other techniques is apparent in terms of OR time.