Multimodal Biomarkers That Predict the Presence of Gleason Pattern 4: Potential Impact for Active Surveillance.

PURPOSE: Latent grade group ≥2 prostate cancer can impact the performance of active surveillance protocols. To date, molecular biomarkers for active surveillance have relied solely on RNA or protein. We trained and independently validated multimodal (mRNA abundance, DNA methylation, and/or DNA copy number) biomarkers that more accurately separate grade group 1 from grade group ≥2 cancers. MATERIALS AND METHODS: Low- and intermediate-risk prostate cancer patients were assigned to training (n=333) and validation (n=202) cohorts. We profiled the abundance of 342 mRNAs, 100 DNA copy number alteration loci, and 14 hypermethylation sites at 2 locations per tumor. Using the training cohort with cross-validation, we evaluated methods for training classifiers of pathological grade group ≥2 in centrally reviewed radical prostatectomies. We trained 2 distinct classifiers, PRONTO-e and PRONTO-m, and validated them in an independent radical prostatectomy cohort. RESULTS: PRONTO-e comprises 353 mRNA and copy number alteration features. PRONTO-m includes 94 clinical, mRNAs, copy number alterations, and methylation features at 14 and 12 loci, respectively. In independent validation, PRONTO-e and PRONTO-m predicted grade group ≥2 with respective true-positive rates of 0.81 and 0.76, and false-positive rates of 0.43 and 0.26. Both classifiers were resistant to sampling error and identified more upgrading cases than a well-validated presurgical risk calculator, CAPRA (Cancer of the Prostate Risk Assessment; P < .001). CONCLUSIONS: Two grade group classifiers with superior accuracy were developed by incorporating RNA and DNA features and validated in an independent cohort. Upon further validation in biopsy samples, classifiers with these performance characteristics could refine selection of men for active surveillance, extending their treatment-free survival and intervals between surveillance.

Initial Investigation into Microbleeds and White Matter Signal Changes following Radiotherapy for Low-Grade and Benign Brain Tumors Using Ultra-High-Field MRI Techniques.

BACKGROUND AND PURPOSE: External beam radiation therapy is a common treatment for many brain neoplasms. While external beam radiation therapy adheres to dose limits to protect the uninvolved brain, areas of high dose to normal tissue still occur. Patients treated with chemoradiotherapy can have adverse effects such as microbleeds and radiation necrosis, but few studies exist of patients treated without chemotherapy. MATERIALS AND METHODS: Ten patients were treated for low-grade or benign neoplasms with external beam radiation therapy only and scanned within 12-36 months following treatment with a 7T MR imaging scanner. A multiecho gradient-echo sequence was acquired and postprocessed into SWI, quantitative susceptibility mapping, and apparent transverse relaxation maps. Six patients returned for follow-up imaging approximately 18 months following their first research scan and were imaged with the same techniques. RESULTS: At the first visit, 7/10 patients had microbleeds evident on SWI, quantitative susceptibility mapping, and apparent transverse relaxation. All microbleeds were within a dose region of >45 Gy. Additionally, 4/10 patients had asymptomatic WM signal changes evident on standard imaging. Further analysis with our technique revealed that these lesions were venocentric, suggestive of a neuroinflammatory process. CONCLUSIONS: There exists a potential for microbleeds in patients treated with external beam radiation therapy without chemotherapy. This finding is of clinical relevance because it could be a precursor of future neurovascular disease and indicates that additional care should be taken when using therapies such as anticoagulants. Additionally, the appearance of venocentric WM lesions could be suggestive of a neuroinflammatory mechanism that has been suggested in diseases such as MS. Both findings merit further investigation in a larger population set.

[MRI methods for pulmonary ventilation and perfusion imaging]. / Methoden der MRT zur Ventilations- und Perfusionsbildgebung der Lunge.

CLINICAL/METHODICAL ISSUE: Separate assessment of respiratory mechanics, gas exchange and pulmonary circulation is essential for the diagnosis and therapy of pulmonary diseases. Due to the global character of the information obtained clinical lung function tests are often not sufficiently specific in the differential diagnosis or have a limited sensitivity in the detection of early pathological changes. STANDARD RADIOLOGICAL METHODS: The standard procedures of pulmonary imaging are computed tomography (CT) for depiction of the morphology as well as perfusion/ventilation scintigraphy and single photon emission computed tomography (SPECT) for functional assessment. METHODICAL INNOVATIONS: Magnetic resonance imaging (MRI) with hyperpolarized gases, O2-enhanced MRI, MRI with fluorinated gases and Fourier decomposition MRI (FD-MRI) are available for assessment of pulmonary ventilation. For assessment of pulmonary perfusion dynamic contrast-enhanced MRI (DCE-MRI), arterial spin labeling (ASL) and FD-MRI can be used. PERFORMANCE: Imaging provides a more precise insight into the pathophysiology of pulmonary function on a regional level. The advantages of MRI are a lack of ionizing radiation, which allows a protective acquisition of dynamic data as well as the high number of available contrasts and therefore accessible lung function parameters. ACHIEVEMENTS: Sufficient clinical data exist only for certain applications of DCE-MRI. For the other techniques, only feasibility studies and case series of different sizes are available. The clinical applicability of hyperpolarized gases is limited for technical reasons. PRACTICAL RECOMMENDATIONS: The clinical application of the techniques described, except for DCE-MRI, should be restricted to scientific studies.

The significance of circulating tumor cells in prostate cancer patients undergoing adjuvant or salvage radiation therapy.

BACKGROUND: Following radical prostatectomy, success of adjuvant and salvage radiation therapy (RT) is dependent on the absence of micrometastatic disease. However, reliable prognostic/predictive factors for determining this are lacking. Therefore, novel biomarkers are needed to assist with clinical decision-making in this setting. Enumeration of circulating tumor cells (CTCs) using the regulatory-approved CellSearch System (CSS) is prognostic in metastatic prostate cancer. We hypothesize that CTCs may also be prognostic in the post-prostatectomy setting. METHODS: Patient blood samples (n=55) were processed on the CSS to enumerate CTCs at 0, 6, 12 and 24 months after completion of RT. CTC values were correlated with predictive/prognostic factors and progression-free survival. RESULTS: CTC status (presence/absence) correlated significantly with positive margins (increased likelihood of CTC(neg) disease; P=0.032), and trended toward significance with the presence of seminal vesicle invasion (CTC(pos); P=0.113) and extracapsular extension (CTC(neg); P=0.116). Although there was a trend toward a decreased time to biochemical failure (BCF) in baseline CTC-positive patients (n=9), this trend was not significant (hazard ratio (HR)=0.3505; P=0.166). However, CTC-positive status at any point (n=16) predicted for time to BCF (HR=0.2868; P=0.0437). CONCLUSIONS: One caveat of this study is the small sample size utilized (n=55) and the low number of patients with CTC-positive disease (n=16). However, our results suggest that CTCs may be indicative of disseminated disease and assessment of CTCs during RT may be helpful in clinical decision-making to determine, which patients may benefit from RT versus those who may benefit more from systemic treatments.

3D prostate histology reconstruction: an evaluation of image-based and fiducial-based algorithms.

PURPOSE: Evaluation of in vivo prostate imaging modalities for determining the spatial distribution and aggressiveness of prostate cancer ideally requires accurate registration of images to an accepted reference standard, such as histopathological examination of radical prostatectomy specimens. Three-dimensional (3D) reconstruction of prostate histology facilitates these registration-based evaluations by reintroducing 3D spatial information lost during histology processing. Because the reconstruction accuracy may constrain the clinical questions that can be answered with these data, it is important to assess the tradeoffs between minimally disruptive methods based on intrinsic image information and potentially more robust methods based on extrinsic fiducial markers. METHODS: Ex vivo magnetic resonance (MR) images and digitized whole-mount histology images from 12 radical prostatectomy specimens were used to evaluate four 3D histology reconstruction algorithms. 3D reconstructions were computed by registering each histology image to the corresponding ex vivo MR image using one of two similarity metrics (mutual information or fiducial registration error) and one of two search domains (affine transformations or a constrained subset thereof). The algorithms were evaluated for accuracy using the mean target registration error (TRE) computed from homologous intrinsic point landmarks (3-16 per histology section; 232 total) identified on histology and MR images, and for the sensitivity of TRE to rotational, translational, and scaling initialization errors. RESULTS: The algorithms using fiducial registration error and mutual information had mean ± standard deviation TREs of 0.7 ± 0.4 and 1.2 ± 0.7 mm, respectively, and one algorithm using fiducial registration error and affine transforms had negligible sensitivities to initialization errors. The postoptimization values of the mutual information-based metric showed evidence of errors due to both the optimizer and the similarity metric, and variation of parameters of the mutual information-based metric did not improve its performance. CONCLUSIONS: The extrinsic fiducial-based algorithm had lower mean TRE and lower sensitivity to initialization than the intrinsic intensity-based algorithm using mutual information. A model relating statistical power to registration error for certain imaging validation study designs estimated that a reconstruction algorithm with a mean TRE of 0.7 mm would require 27% fewer subjects than the method used to initialize the algorithms (mean TRE 1.3 ± 0.7 mm), suggesting the choice of reconstruction technique can have a substantial impact on the design of imaging validation studies, and on their overall cost.

Assessing fitness to drive in brain tumour patients: a grey matter of law, ethics, and medicine.

BACKGROUND: Neurocognitive deficits from brain tumours may impair the ability to safely operate a motor vehicle. Although certain jurisdictions in Canada legally require that physicians report patients who are unfit to drive, criteria for determining fitness are not clearly defined for brain tumours. METHODS: Patients receiving brain radiotherapy at our institution from January to June 2009 were identified using the Oncology Patient Information System. In addition to descriptive statistics, details of driving assessment were reviewed retrospectively. The Fisher exact test was used to determine factors predictive of reporting a patient to the Ontario Ministry of Transportation (mto) as unfit to drive. A logistic regression model was constructed to further determine factors predictive of reporting. RESULTS: Of the 158 patients available for analysis, 48 (30%) were reported to the mto, and 64 (41%) were advised to stop driving. With respect to the 53 patients with seizures, a report was submitted to the mto for 30 (57%), and a documented discussion about the implications of driving was held with 35 (66%). On univariate analysis, younger age, a central nervous system primary, higher brain radiotherapy dose, unifocal disease, and the presence of seizures were predictive of physician reporting (p < 0.05). On logistic regression modelling, the presence of seizures (odds ratio: 3.9) and a higher radiotherapy dose (odds ratio: 1.3) remained predictive of reporting. INTERPRETATION: Physicians frequently do not discuss the implications of driving with brain tumour patients or are not properly documenting such advice (or both). Clear and concise reporting guidelines need to be drafted given the legal, medical, and ethical concerns surrounding this public health issue.

Multidisciplinary assessment of fitness to drive in brain tumour patients in southwestern Ontario: a grey matter.

BACKGROUND: Neurocognitive impairments from brain tumours may interfere with the ability to drive safely. In 9 of 13 Canadian provinces and territories, physicians have a legal obligation to report patients who may be medically unfit to drive. To complicate matters, brain tumour patients are managed by a multidisciplinary team; the physician most responsible to make the report of unfitness is often not apparent. The objective of the present study was to determine the attitudes and reporting practices of physicians caring for these patients. METHODS: A 17-question survey distributed to physicians managing brain tumour patients elicited Respondent demographicsKnowledge about legislative requirementsExperience of reportingBarriers and attitudes to reporting Fisher exact tests were performed to assess differences in responses between family physicians (fps) and specialists. RESULTS: Of 467 physicians sent surveys, 194 responded (42%), among whom 81 (42%) were specialists and 113 (58%) were fps. Compared with the specialists, the fps were significantly less comfortable with reporting, less likely to consider reporting, less likely to have patients inquire about driving, and less likely to discuss driving implications. A lack of tools, concern for the patient-physician relationship, and a desire to preserve patient quality of life were the most commonly cited barriers in determining medical fitness of patients to drive. CONCLUSIONS: Legal requirements to report medically unfit drivers put physicians in the difficult position of balancing patient autonomy and public safety. More comprehensive and definitive guidelines would be helpful in assisting physicians with this public health issue.

A statistical comparison of prognostic index systems for brain metastases after stereotactic radiosurgery or fractionated stereotactic radiation therapy.

AIMS: Prognostic indices are commonly used in the context of brain metastases radiotherapy to guide patient decision-making and clinical trial stratification. The purpose of this investigation was to compare nine published brain metastases prognostic indices using traditional and novel statistical comparison metrics. MATERIALS AND METHODS: A retrospective review was carried out on two institutional databases of 501 patients diagnosed with brain metastatic disease, who received either stereotactic radiosurgery (n = 381) or fractionated stereotactic radiation therapy (n = 120) between 2002 and 2011. Descriptive statistics were generated for patient, tumour and treatment factors, as well as prognostic indices distribution. To identify predictors of overall survival, Kaplan-Meier estimates and multivariable Cox proportional hazard analyses were carried out. Prognostic indices were compared with each other using novel metrics, including: net reclassification improvement (NRI) index, integrated discrimination improvement (IDI) index and decision curve analysis (DCA). RESULTS: Multivariable Cox modelling confirmed the importance of all individual prognostic indices component factors except for 'active primary cancer' tumour status. When traditional and novel comparative metrics were incorporated, the available published prognostic indices were found to have important general classification benefits as follows: Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA; NRI and DCA), Rades et al. first index (RADES I; IDI and DCA), Golden grading system (GGS; IDI and DCA) and Rotterdam index (RDAM; major misclassification rate and NRI). The graded prognostic assessment system had the smallest misclassification rate (5%) in terms of high-risk (i.e. poor prognosis) classification. CONCLUSIONS: Summarising the various comparative approaches used in this report, we found that the RTOG RPA, GGS, RADES I and RDAM systems were superior in more than one metric studied. Of these, only the RTOG RPA has been extensively validated using large datasets and clinically utilised both at the patient level and in clinical trials.

Intensity-modulated radiotherapy in the treatment of prostate cancer.

Three-dimensional conformal radiotherapy (3DCRT) as the primary treatment for prostate cancer has improved outcomes compared with conventional radiotherapy, but with an associated increase in toxicity due to radiation effects on the bladder and rectum. Intensity-modulated radiotherapy (IMRT) is a newer method of radiotherapy that uses intensity-modulated beams that can provide multiple intensity levels for any single beam direction and any single source position allowing concave dose distributions and dose gradients with narrower margins than those possible using conventional methods. IMRT is ideal for treating complex treatment volumes and avoiding close proximity organs at risk that may be dose limiting and provides increased tumour control through an escalated dose and reduces normal tissue complications through organ at risk sparing. Given the potential advantages of IMRT and the availability of IMRT-enabled treatment planning systems and linear accelerators, IMRT has been introduced in a number of disease sites, including prostate cancer. This systematic review examined the evidence for IMRT in the treatment of prostate cancer in order to quantify the potential benefits of this new technology and to make recommendations for radiation treatment programmes considering adopting this technique. The findings were in favour of recommending IMRT over 3DCRT in the radical treatment of localised prostate cancer where doses greater than 70 Gy are required, based on a review of 11 published reports including 4559 patients. There were insufficient data to recommend IMRT over 3DCRT in the postoperative setting. Future research should examine image-guided IMRT in the post-prostatectomy setting, with altered fractionation, and in combination with hormone and chemotherapy.

Fitness to drive in patients with brain tumours: the influence of mandatory reporting legislation on radiation oncologists in Canada.

BACKGROUND: Certain jurisdictions in Canada legally require that physicians report unfit drivers. Physician attitudes and patterns of practice have yet to be evaluated in Canada for patients with brain tumours. METHODS: We conducted a survey of 97 radiation oncologists, eliciting demographics, knowledge of reporting laws, and attitudes on reporting guidelines for unfit drivers. Eight scenarios with varying disability levels were presented to determine the likelihood of a patient being reported as unfit to drive. Statistical comparisons were made using the Fisher exact test. RESULTS: Of physicians approached, 99% responded, and 97 physicians participated. Most respondents (87%) felt that laws in their province governing the reporting of medically unfit drivers were unclear. Of the responding physicians, 23 (24%) were unable to correctly identify whether their province had mandatory reporting legislation. Physicians from provinces without mandatory reporting legislation were significantly less likely to consider reporting patients to provincial authorities (p = 0.001), and for all clinical scenarios, the likelihood of reporting significantly depended on the physician's provincial legal obligations. CONCLUSIONS: The presence of provincial legislation is of primary importance in determining whether physicians will report brain tumour patients to drivers' licensing authorities. In Canada, clear guidelines have to be developed to help in the assessment of whether brain tumour patients should drive.

MRI of the lung (3/3)-current applications and future perspectives.

BACKGROUND: MRI of the lung is recommended in a number of clinical indications. Having a non-radiation alternative is particularly attractive in children and young subjects, or pregnant women. METHODS: Provided there is sufficient expertise, magnetic resonance imaging (MRI) may be considered as the preferential modality in specific clinical conditions such as cystic fibrosis and acute pulmonary embolism, since additional functional information on respiratory mechanics and regional lung perfusion is provided. In other cases, such as tumours and pneumonia in children, lung MRI may be considered an alternative or adjunct to other modalities with at least similar diagnostic value. RESULTS: In interstitial lung disease, the clinical utility of MRI remains to be proven, but it could provide additional information that will be beneficial in research, or at some stage in clinical practice. Customised protocols for chest imaging combine fast breath-hold acquisitions from a "buffet" of sequences. Having introduced details of imaging protocols in previous articles, the aim of this manuscript is to discuss the advantages and limitations of lung MRI in current clinical practice. CONCLUSION: New developments and future perspectives such as motion-compensated imaging with self-navigated sequences or fast Fourier decomposition MRI for non-contrast enhanced ventilation- and perfusion-weighted imaging of the lung are discussed. Main Messages • MRI evolves as a third lung imaging modality, combining morphological and functional information. • It may be considered first choice in cystic fibrosis and pulmonary embolism of young and pregnant patients. • In other cases (tumours, pneumonia in children), it is an alternative or adjunct to X-ray and CT. • In interstitial lung disease, it serves for research, but the clinical value remains to be proven. • New users are advised to make themselves familiar with the particular advantages and limitations.

Circulating tumour cells in prostate cancer patients receiving salvage radiotherapy

INTRODUCTION: Within 10 years of radical prostatectomy (RP), up to 30% of prostate cancer (PCa) patients will have a rise in prostate-specific antigen (PSA), requiring radiation therapy (RT). However, with current technology, distinction between local and distant recurrent PCa is not possible. This lack of an accurate test constrains the decision whether to offer systemic or local treatment. We hypothesise tests for detecting circulating tumour cells (CTCs) within the blood may assist with clinical decision-making and in this pilot study we investigated whether CTCs could be detected in this patient population using the CellSearch® system. MATERIALS AND METHODS: Blood samples were collected from PCa patients (n=26) prior to RT and 3 months following completion of RT. Samples were analysed for PSA level via immunoassay and CTC number using the CellSearch® system. RESULTS: CTCs could be detected in this patient population and following RT CTCs appeared to decrease. However, no association was observed between a higher PSA and an increased number of CTCs pre- or post-RT. Interestingly, patients who failed RT trended toward an increased/ unchanged number of CTCs following RT vs. a decreased number in patients with RT response. CONCLUSIONS: Our results demonstrate that CTCs can be detected in early-stage PCa and suggest the possibility that post-treatment reduction in CTC levels may be indicative of RT response . We are currently evaluating CTCs in a larger cohort of patients to validate our preliminary findings and further investigate the prognostic value of CTCs in this patient population (AU)

18F-fluorocholine for prostate cancer imaging: a systematic review of the literature.

BACKGROUND: Positron emission tomography (PET or combined PET-computed tomography (PET/CT)) allows the non-invasive interrogation of metabolic processes using radiolabeled probes. Altered choline metabolism has been noted as a characteristic of prostate cancer (PCa), and radiolabeled choline and choline analogs have been investigated as PET/CT imaging agents for prostate cancer; [(18)F]fluoromethyl-dimethyl-2-hydroxyethyl-ammonium ((18)F-FCH) shows particular promise as a PCa imaging agent given its favorable physical and pharmacokinetic properties. METHODS: We conducted a systematic review of results to date with (18)F-FCH. As the tracer was first described by DeGrado in 2001, we limited our search from January 2001 to August 2011. RESULTS: In all, 37 studies including 1244 patients met the inclusion criteria. Studies included those detailing the radiosynthesis of (18)F-FCH, preclinical and early clinical dosimetry, and biodistribution (n=7); evaluation of local disease (n=6), nodal disease (n=5), bone metastases and castrate-resistant disease (n=7), biochemical recurrence (n=11), radiotherapy planning (n=7) and sources of false-positive studies (n=2); and some studies reported on multiple indications. Potential sources of variations in the studies affecting reported performance included case series size, variation in extent of disease at imaging (including Gleason grade, and PSA), selection of gold standards for comparison and variations in scan technique. CONCLUSIONS: On the basis of the review, we suggest potential scenarios where this metabolic imaging might be considered for further evaluation in clinical trials for guiding PCa management.

Sci-Fri PM: Delivery - 02: CT image guidance strategies for dose-adaptive IMRT of the prostate.

On-line CT imaging in the radiotherapy room has become the norm for targeted intensity-modulated radiotherapy (IMRT), enabling precise adjustments of the daily patient setup based on soft tissue visualization. Corrections for plasticity of the anatomy and dose deformation are within technological reach but will require more on-line resources. We have developed a computer model that allows exploration of "what if" scenarios for assessing the benefits of Image Guidance strategies in terms of the multi-fraction dose distribution and DVH metrics (Target D95 and rectum V70). In this work we report on changes in anatomy and resultant dose distribution as observed in 35 daily megavoltage CT (MVCT) scans of the pelvis during prostate therapy for 13 patients. Our goal is to assess the effectiveness and efficiency of various adaptive strategies involving imaging schedule with and without dose re-planning of 5-field IMRT with 18 MV x-rays. Our research questions are: To what extent do radiation dose distributions delivered to individual patients (in vivo) diverge from the planned dose distributions (in silico)? Is there a robust schedule of CT image guidance, with or without dose re-planning that will mitigate discrepancies? For prostate IMRT, we conclude that image guidance schedule can be relaxed when generous GTV margins (10/7mm) are used. Tighter margins (isotropic 5 mm) reduce the dose to the rectum as expected. However, daily re-planning may be required to maintain adequate target coverage as planned when tighter margins are used.

Sci-Fri PM: Delivery - 11: Accuracy considerations in modern radiation oncology: An update.

The most recent reviews of accuracy requirements in radiation oncology were published in the 1990s, primarily in an era that was transitioning from 2-D to 3-D conformal radiation therapy (CRT). Since then, the technology associated with radiation oncology has changed dramatically. The combination of various forms of imaging for radiation therapy planning, treatment planning software, dose delivery technology including 4-D considerations as well as in-room daily image guidance has resulted in new perspectives on accuracy considerations. The underlying hypothesis for the use of these advanced technologies is that loco-regional control of cancer remains a significant barrier to cancer cure for many common cancers and that better dose distributions will translate into better outcomes. However, further clinical gain using these new technologies may be limited by single or compounded uncertainties associated with the entire treatment process. Thus, it is important to understand what factors should be considered in determining accuracy requirements as well as the realistic expectations of uncertainties that exist within the total treatment process. The need for accuracy is based on clinical requirements such as the steepness of dose-response curves, inherent heterogeneity in patient response to treatment, and the level of accuracy that is practically achievable. Statements on accuracy are dependent on the technology used and the reality of what is practically achievable and necessary. This review highlights some of the major differences between accuracy requirements as determined in the 2-D RT and 3-D CRT era versus the modern era of intensity modulated, image-guided, 4-D radiation therapy.

Neurocytomas: long-term experience of a single institution.

There is a lack of studies reporting on outcomes of control and treatment toxicities for neurocytomas. A 25-year retrospective review of a tertiary center's experience with neurocytomas was completed to report on these outcomes. All cerebral neurocytoma cases (19 patients; median age, 31 years; range, 18-62 years; 18 intraventricular and 1 extraventricular) treated between 1984 and 2009 were analyzed, including central pathology and radiology reviews. Median follow-up was 104.5 months (range, 0.75-261.7 months). Primary treatment was surgery alone (n = 18 patients), followed by surgery and adjuvant radiotherapy (n = 1). The crude local control rate after surgery was 68% for all cases (cerebral neurocytomas) and 74% for central neurocytomas. Salvage therapies included further surgery (n = 4), radiation (n = 3), and chemotherapy (n = 1). Ten-year Kaplan-Meier overall and relapse-free survival rates were 82% and 62% and 81% and 57%, respectively, for all cases and for central neurocytomas only. The median overall survival and relapse-free survival were 104.5 and 79.3 months, respectively, for all cases and for central neurocytomas. Ten patients had grade 3/4 toxicity, and 1 patient had a grade 5 perioperative hemorrhage that resulted in death 23 days after surgery. Late grade 3/4 toxicities occurred in 9 patients. Three patients had permanent grade 2 motor or cognitive deficits. We provide the first report outlining toxicities and survival outcomes in a series of 19 patients. Our experience suggests that initial surgery provides durable local control rates in two-thirds of patients, with low risk for significant permanent deficits. Salvage therapy with surgery and/or radiation provides durable local control in tumors that recur after surgery.

Evaluation of inter-fraction prostate motion using kilovoltage cone beam computed tomography during radiotherapy.

AIMS: The success of delivering the prescribed radiation dose to the prostate while sparing adjacent sensitive tissues is largely dependent on the ability to accurately target the prostate during treatment. Kilovoltage cone beam computed tomography (CBCT) imaging can be used to monitor and compensate for inter-fraction prostate motion, but this procedure increases treatment session time and adds incidental radiation dose to the patient. We carried out a retrospective study of CBCT data to evaluate the systematic and random correction shifts of the prostate with respect to bones and external marks. MATERIALS AND METHODS: A total of 449 daily CBCT studies from 17 patients undergoing intensity-modulated radiotherapy (IMRT) for localised prostate cancer were analysed. The difference between patient set-up correction shifts applied by radiation therapists (via matching prostate position in CBCT and planning computed tomography) and shifts obtained by matching bony anatomy in the same studies was used as a measure of the daily inter-fraction internal prostate motion. RESULTS: The average systematic and random shifts in prostate positions, calculated over all fractions versus only 10 fractions, were not found to be significantly different. DISCUSSION: The measured prostate shifts with respect to bony anatomy and external marks after the first 10 imaging sessions were shown to provide adequate predictive power for defining patient-specific margins in future fractions without a need for ongoing computed tomography imaging. Different options for CBCT imaging schedule are proposed that will reduce the treatment session time and imaging dose to radiotherapy patients while ensuring appropriate prostate cover and normal tissue sparing.

Schedule for CT image guidance in treating prostate cancer with helical tomotherapy.

The aim of this study was to determine the effect of reducing the number of image guidance sessions and patient-specific target margins on the dose distribution in the treatment of prostate cancer with helical tomotherapy. 20 patients with prostate cancer who were treated with helical tomotherapy using daily megavoltage CT (MVCT) imaging before treatment served as the study population. The average geometric shifts applied for set-up corrections, as a result of co-registration of MVCT and planning kilovoltage CT studies over an increasing number of image guidance sessions, were determined. Simulation of the consequences of various imaging scenarios on the dose distribution was performed for two patients with different patterns of interfraction changes in anatomy. Our analysis of the daily set-up correction shifts for 20 prostate cancer patients suggests that the use of four fractions would result in a population average shift that was within 1 mm of the average obtained from the data accumulated over all daily MVCT sessions. Simulation of a scenario in which imaging sessions are performed at a reduced frequency and the planning target volume margin is adapted provided significantly better sparing of organs at risk, with acceptable reproducibility of dose delivery to the clinical target volume. Our results indicate that four MVCT sessions on helical tomotherapy are sufficient to provide information for the creation of personalised target margins and the establishment of the new reference position that accounts for the systematic error. This simplified approach reduces overall treatment session time and decreases the imaging dose to the patient.

Consistency check of planned adaptive option on helical tomotherapy.

This study aims to evaluate a new Planned Adaptive software (TomoTherapy Inc., Madison, WI) of the helical tomotherapy system by retrospective verification and adaptive re-planning of radiation treatment. Four patients with different disease sites (brain, nasal cavity, lungs, prostate) were planned in duplicate using the diagnostic planning kVCT data set and MVCT studies of the first treatment fraction with the same optimization parameters for both plan types. The dosimetric characteristics of minimum, maximum, and mean dose to the targets as well as to organs at risk were compared. Both sets of plans were used for calculation of dose distributions in a water-equivalent phantom. Corresponding measurements of these plans in phantom were carried out with the use of radiographic film and ion chamber. In the case of the lung and prostate cancer patients, changes in dosimetric parameters compared to data generated with the kVCT study alone were less than 2%. Certain changes for the nasal cavity and brain cancer patients were greater than 2%, but they were explained in part by anatomy changes that occurred during the time between kVCT and MVCT studies. The Planned Adaptive software allows for adaptive radiotherapy planning using the MVCT studies obtained by the helical tomotherapy imaging system.