Alterations in anatomic and functional imaging parameters with repeated FDG PET-CT and MRI during radiotherapy for head and neck cancer: a pilot study.

BACKGROUND: The use of imaging to implement on-treatment adaptation of radiotherapy is a promising paradigm but current data on imaging changes during radiotherapy is limited. This is a hypothesis-generating pilot study to examine the changes on multi-modality anatomic and functional imaging during (chemo)radiotherapy treatment for head and neck squamous cell carcinoma (HNSCC). METHODS: Eight patients with locally advanced HNSCC underwent imaging including computed tomography (CT), Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)-CT and magnetic resonance imaging (MRI) (including diffusion weighted (DW) and dynamic contrast enhanced (DCE)) at baseline and during (chemo)radiotherapy treatment (after fractions 11 and 21). Regions of interest (ROI) were drawn around the primary tumour at baseline and during treatment. Imaging parameters included gross tumour volume (GTV) assessment, SUVmax, mean ADC value and DCE-MRI parameters including Plasma Flow (PF). On treatment changes and correlations between these parameters were analysed using a Wilcoxon rank sum test and Pearson's linear correlation coefficient respectively. A p-value <0.05 was considered statistically significant. RESULTS: Statistically significant reductions in GTV-CT, GTV-MRI and GTV-DW were observed between all imaging timepoints during radiotherapy. Changes in GTV-PET during radiotherapy were heterogeneous and non-significant. Significant changes in SUVmax, mean ADC value, Plasma Flow and Plasma Volume were observed between the baseline and the fraction 11 timepoint, whilst only changes in SUVmax between baseline and the fraction 21 timepoint were statistically significant. Significant correlations were observed between multiple imaging parameters, both anatomical and functional; 20 correlations between baseline to the fraction 11 timepoint; 12 correlations between baseline and the fraction 21 timepoints; and 4 correlations between the fraction 11 and fraction 21 timepoints. CONCLUSIONS: Multi-modality imaging during radiotherapy treatment demonstrates early changes (by fraction 11) in both anatomic and functional imaging parameters. All functional imaging modalities are potentially complementary and should be considered in combination to provide multi-parametric tumour assessment, to guide potential treatment adaptation strategies. TRIAL REGISTRATION: ISRCTN Registry: ISRCTN34165059 . Registered 2nd February 2015.

Multimodality imaging with CT, MR and FDG-PET for radiotherapy target volume delineation in oropharyngeal squamous cell carcinoma.

BACKGROUND: This study aimed to quantify the variation in oropharyngeal squamous cell carcinoma gross tumour volume (GTV) delineation between CT, MR and FDG PET-CT imaging. METHODS: A prospective, single centre, pilot study was undertaken where 11 patients with locally advanced oropharyngeal cancers (2 tonsil, 9 base of tongue primaries) underwent pre-treatment, contrast enhanced, FDG PET-CT and MR imaging, all performed in a radiotherapy treatment mask. CT, MR and CT-MR GTVs were contoured by 5 clinicians (2 radiologists and 3 radiation oncologists). A semi-automated segmentation algorithm was used to contour PET GTVs. Volume and positional analyses were undertaken, accounting for inter-observer variation, using linear mixed effects models and contour comparison metrics respectively. RESULTS: Significant differences in mean GTV volume were found between CT (11.9 cm(3)) and CT-MR (14.1 cm(3)), p < 0.006, CT-MR and PET (9.5 cm(3)), p < 0.0009, and MR (12.7 cm(3)) and PET, p < 0.016. Substantial differences in GTV position were found between all modalities with the exception of CT-MR and MR GTVs. A mean of 64 %, 74 % and 77 % of the PET GTVs were included within the CT, MR and CT-MR GTVs respectively. A mean of 57 % of the MR GTVs were included within the CT GTV; conversely a mean of 63 % of the CT GTVs were included within the MR GTV. CT inter-observer variability was found to be significantly higher in terms of position and/or volume than both MR and CT-MR (p < 0.05). Significant differences in GTV volume were found between GTV volumes delineated by radiologists (9.7 cm(3)) and oncologists (14.6 cm(3)) for all modalities (p = 0.001). CONCLUSIONS: The use of different imaging modalities produced significantly different GTVs, with no single imaging technique encompassing all potential GTV regions. The use of MR reduced inter-observer variability. These data suggest delineation based on multimodality imaging has the potential to improve accuracy of GTV definition. TRIAL REGISTRATION: ISRCTN Registry: ISRCTN34165059 . Registered 2nd February 2015.

Focal radiotherapy as focal therapy of prostate cancer.

PURPOSE OF REVIEW: Focal radiotherapy treatment procedures play an increasingly important role in function-preservation and organ-preservation treatment techniques. As an alternative to traditional whole-gland radiotherapy regimes, focal prostate radiotherapy may be of benefit for both primary tumor as well as locally recurrent disease. This is a review of the current literature on the topic, including patient selection, preliminary toxicity, and outcome data as well as a technical overview on treatment delivery techniques. RECENT FINDINGS: Partial organ treatment in early prostate cancer (PCa) is now technically feasible with both newer external-beam and brachytherapy technology. To date, only small and generally monoinstitutional series have been published in the literature. Early feasibility and toxicity data are encouraging, and demonstrate potential advantages for the role of focal brachytherapy in early PCa. Although some advanced external-beam techniques can also be used to deliver focal therapy within the prostate, there is no relevant publication in the literature. SUMMARY: Radiotherapy, especially interventional radiotherapy (brachytherapy), is a technically feasible treatment technique to deliver focal radiotherapy for PCa. To date, only preliminary results are available for all forms of interventional radiotherapy (high dose rate, low dose rate, and pulsed dose rate) for focal PCa treatment and no large cohort comparative results are published. As interventional radiotherapy (brachytherapy) as yet lacks any such long-term studies, comparative outcome data are not available to suggest differences in efficacy for one form of brachytherapy or another.

Scoring systems used for the interpretation and reporting of multiparametric MRI for prostate cancer detection, localization, and characterization: could standardization lead to improved utilization of imaging within the diagnostic pathway?

Multiparametric magnetic resonance imaging (mpMRI) is increasingly being used earlier in the prostate cancer diagnostic pathway in order to detect and localize disease. Its results can be used to help decide on the indication, type, and localization of a prostate biopsy for cancer diagnosis. In addition, mpMRI has the potential to contribute information on the characterization, or aggressiveness, of detected cancers including tumor progression over time. There is considerable variation in the way results of different MRI sequences are reported. We conducted a review of scoring systems that have been used in the detection and characterization of prostate cancer. This revealed that existing scoring and reporting systems differ in purpose, scale, and range. We evaluate these differences in this review. This first step in collating all methods of scoring and reporting mpMRI will ultimately lead to consensus approaches to develop a standardized reporting scheme that can be widely adopted and validated to ensure comparability of research outputs and optimal clinical practice.

Importance of dynamic contrast enhanced magnetic resonance imaging for targeting biopsy and salvage treatments after prostate cancer recurrence.

PURPOSE: Evaluate T2 weighted MRI (T2W), diffusion weighted imaging (DWI), and dynamic contrast enhanced MRI (DCE-MRI) for determining areas of prostate cancer recurrence to target biopsy or salvage treatment in patients previously treated with I-125 seed brachytherapy. MATERIAL AND METHODS: MRI data from 15 patients, whose primary treatment was I-125 seed brachytherapy and who were subsequently treated with partial gland salvage high-dose-rate brachytherapy were retrospectively analyzed. Two radiologists independently reviewed imaging on two occasions blinded to clinical and biopsy information. At first review, the T2W and DWI sequences were assessed for likely presence of tumor and at second review, the additional DCE-MRI sequence was assessed. Results were recorded and compared on a prostate diagram divided into 12 sectors (quadrants at each of base, mid-gland, and apex) plus seminal vesicles (SV). RESULTS: Number of patients for whom recurrence was visible was 7/15 for T2W, 6.5/15 for DWI, and 15/15 for DCE-MRI (average of results for the two radiologists). Approximately, half of the sectors identified as showing recurrence were at the anterior base of the prostate. CONCLUSIONS: In prostate cancer patients previously treated with I-125 permanent seed implants, DCE-MRI is superior to T2W and DWI in defining areas of recurrence, and should be used to target biopsy and for treatment planning of focal salvage therapies.

Can the completeness of radiological cancer staging reports be improved using proforma reporting? A prospective multicentre non-blinded interventional study across 21 centres in the UK.

OBJECTIVES: Following a diagnosis of cancer, the detailed assessment of prognostic stage by radiology is a crucial determinant of initial therapeutic strategy offered to patients. Pretherapeutic stage by imaging is known to be inconsistently documented. We tested whether the completeness of cancer staging radiology reports could be improved through a nationally introduced pilot of proforma-based reporting for a selection of six common cancers. DESIGN: Prospective interventional study comparing the completeness of radiology cancer staging reports before and after the introduction of proforma reporting. SETTING: Twenty-one UK National Health Service hospitals. PARTICIPANTS: 1283 cancer staging radiology reports were submitted. MAIN OUTCOME MEASURES: Radiology staging reports across the six cancers types were evaluated before and after the implementation of proforma-based reporting. Report completeness was assessed using scoring forms listing the presence or absence of predetermined key staging data. Qualitative data regarding proforma implementation and usefulness were collected from questionnaires provided to radiologists and end-users. RESULTS: Electronic proforma-based reporting was successfully implemented in 15 of the 21 centres during the evaluation period. A total of 787 preproforma and 496 postproforma staging reports were evaluated. In the preproforma group, only 48.7% (5586/11 470) of key staging items were present compared with 87.3% (6043/6920) in the postproforma group. Thus, the introduction of proforma reporting produced a 78% improvement in staging completeness . This increase was seen across all cancer types and centres. The majority of participants found proforma reporting improved cancer reporting quality for their clinical practice . CONCLUSION: The implementation of proforma reporting results in a significant improvement in the completeness of cancer staging reports. Proforma-based assessment of cancer stage enables objective comparisons of patient outcomes across centres. It should therefore become an auditable quality standard for cancer care.

A prospective analysis of long-term quality of life after permanent I-125 brachytherapy for localised prostate cancer.

BACKGROUND AND PURPOSE: To prospectively evaluate long-term urinary, bowel and sexual function after I-125 brachytherapy for localised prostate cancer using patient administered validated Quality of Life (QoL) instruments. MATERIALS AND METHODS: Between March 1995 and March 2004, 673 men underwent brachytherapy and recorded urinary symptoms prospectively using the International Prostate Symptom Score (IPSS). In addition, in a subgroup of 116 patients, the Expanded Prostate Cancer Index Composite (EPIC) was used to record QoL information on urinary, bowel and sexual function before treatment and at regular time intervals for at least two years. RESULTS: Initially, there was a sharp rise in urinary symptoms which was most marked within the first three months. Scores then resolved slowly and returned to within one or two units of pre-treatment level at one year. Subsequently, there was no significant deterioration in urinary symptoms up to nine years following brachytherapy. Few had significant bowel symptoms. Sexual function deteriorated initially and then improved but failed to return to pre-treatment levels by two years. Patients requiring neo-adjuvant hormones experienced significantly more dysfunction. CONCLUSIONS: After an initial period of mild to moderate urinary symptoms prostate brachytherapy is well tolerated with relatively little deterioration in long-term quality of life. Long-term reduction in sexual function may be seen particularly in those requiring hormones.

Side effects of permanent I125 prostate seed implants in 667 patients treated in Leeds.

PURPOSE: To report the side effects and complications after I-125 seeds prostate implant after 8.5 years experience. METHODS AND MATERIALS: Six hundred and sixty seven (667) patients were treated between March 1995 and December 2001. The median follow up is 31 months with a maximum of 98.2 months. Morbidity data were collected from a review of patient case-notes. Patients also provided prospective data on urinary symptoms using the International Prostate Symptom Score (IPSS) scoring chart before treatment and at regular follow up. Patients were also sent a questionnaire detailing symptoms and side effects following their brachytherapy. This enabled them to record urinary, bowel and sexual function side effects independently. Logistic regression analysis was carried out to identify the risk of catheterisation in relation to the pre-implant prostate volume and potential implant factors such as the number of seeds and needles and implant dose. RESULT: The urinary symptom score rises in the first few months after implantation and returns to within one or two points of the pre-treatment score within one year. Nine patients reported incontinence prior to treatment and 15, 12 and 10 patients reported incontinence 6, 12 and 24 months after treatment, respectively. Catheterisation was reported in 97 (14.5%) patients. At six months 84.9% of patients reported no change in bowel function and 78.9% at 12 months. 6.4% of patients complained of some increased bowel frequency at 6 months and 5.7% at 12 months. 402 (77.2%) patients reported being fully potent before treatment and that this fell to 32.4% after treatment. Logistic regression showed that the most significant factors which correlate with the probability of catheterisation are the pre-treatment prostate volume and the number of seeds and needles implanted. CONCLUSION: The side effects and complications after prostate brachytherapy as reported here and elsewhere confirm that the treatment is not only convenient but also has a low risk of serious long term side effects.

The correlation between D90 and outcome for I-125 seed implant monotherapy for localised prostate cancer.

BACKGROUND AND PURPOSE: In 1998 Stock and Stone demonstrated a dose response relationship correlating D90 with probability of biochemical control and showed that a D90 of 140 Gy is a highly significant factor in predicting PSA relapse free survival (PSA-RFS). Although, a mean D90 of over 140 Gy was achieved in our series, there is nevertheless a normal distribution with 20% of patients achieving a D90 of less than 120 Gy. We have analysed the possible causes for the low D90 and the impact on outcome. PATIENTS AND METHODS: Prospective data from 667 patients treated between 1995 and 2001 by I-125 seeds prostate implant as monotherapy were analysed. Post-implant dosimetry was performed on 413 patients. D90 and other indices were calculated for each patient. Statistical analysis was performed on D90 dose to identify the correlation that would predict the 8.2 years PSA relapse free survival as defined by the American Society for Therapeutic Radiology and Oncology (ASTRO). RESULTS: Correlation between D90 and outcome shows no significant difference for the whole population between those who receive greater or less than 140 Gy (P=0.43) and there was also no difference for those receiving more or less than 130 Gy (P=0.14). Subgroup analysis by risk group, however, showed that for low risk patients there was a significant correlation between D90 and PSA control (P<0.01). Although, post-implant dosimetry was performed 6-8 weeks after brachytherapy, post-implant CT still showed variable levels of oedema compared with the pre-implant ultrasound. A statistically significant relationship was shown between D90 and the ratio between CT and ultrasound volume (P<0.01) which suggests that some low D90s may be related to persistent oedema at the time of calculation. Segmental analysis of a subgroup of 32 patients showed that the dose was most often deficient in the anterior basal segment of the gland. CONCLUSIONS: D90 was found to be a good discriminator for those with low risk where failure to achieve local control is likely to be the dominant cause of PSA failure. No significant dose response relationship between D90 and PSA was found in the intermediate and high-risk population of patients. This could be due to (1) the presence of oedema or discrepancy between pre- and post-implant volumes causing a low D90, (2) the possibility that the underdosed area could be situated where there is unlikely to be tumour, (3) the fact that biochemical control does not equate to local control because some patients fail outside the prostate, particularly in the high and intermediate risk patients, (4) if D90 is a good discriminator only for low risk patients, the absence of a dose response correlation in this series which contained 53.8% intermediate and high risk patients could be related to case mix.

The impact of hormone therapy on post-implant dosimetry and outcome following Iodine-125 implant monotherapy for localised prostate cancer.

BACKGROUND AND PURPOSE: Many patients with localised prostate cancer present with symptoms of benign prostatic hypertrophy (BPH) and require neoadjuvant hormone therapy to shrink the gland before brachytherapy. The impact of this hormone therapy has been evaluated in 667 patients treated with Iodine seed monotherapy. PATIENTS AND METHODS: Prospective data from 667 patients treated between 1995 and 2001 by I-125 seeds prostate implant as monotherapy were analysed. The mean age was 63 years (42--77 years). Three hundred and forty-six (51.9%) patients had a short course of neo adjuvant hormone therapy and 321 (49.1%) did not. The prescribed minimum peripheral dose was 145 Gy (TG 43). Patients were followed up to a maximum of 8.2 years and a minimum of 18 months. Statistical analysis was performed to identify factors that would predict PSA relapse-free survival (PSA-RFS) defined by the American Society for Therapeutic Radiology and Oncology (ASTRO). RESULTS: Overall the PSA relapse-free survival is 76.1 and 72.6% for patient cohorts being on pre-treatment hormones and not, respectively (P=0.107). Subdivided into risk groups the low risk group showed 92.5% PSA-RFS with hormones and 75.1% without (P=0.327). The intermediate group 75.7% with hormones and 72.9% without (P=0.148) and for the high-risk group 51.1% with and 51.1% without hormones (P=0.942). Evaluation of post-implant dosimetry in patients with and without hormone therapy showed that the D90 for those who received hormone therapy was 130.8 Gy compared with 145.1 Gy for those who did not (P<0.001). This may be related to the degree of oedema at the time of post-implant dosimetry. The CT to ultrasound prostate volume ratio was 1.17 for patients who received hormone therapy and 0.98 for those who did not (P<0.001). It is suggested that in the interval between stopping hormone therapy and doing post-implant dosimetry there was an increase in prostate volume, which results in a lower D90. Significant correlation was found between D90 and prostate volume on post-implant CT dosimetry with higher D90s for small volume prostates (P<0.001). CONCLUSIONS: Overall hormone therapy had no significant effect on outcome. The apparent lower D90 in hormone treated patients may be related to a change in volume between pre-implant and post-implant dosimetry.

Impact of selection of post-implant technique on dosimetry parameters for permanent prostate implants.

PURPOSE: To investigate the variability of prostate implant quality indices between three different methods of calculating the post-implant dose distribution. METHODS AND MATERIALS: In a study of 9 permanent prostate implant patients, post-implant dosimetry was carried out using three methods of identifying seed positions within the prostate volume: (1) prostate volumes defined by transrectal ultrasound (TRUS) immediately following implant were registered with shift-film defined seed positions, (2) seeds were identified directly from the post-implant TRUS images, and (3) CT was used to define seed positions and prostate volumes from images acquired at 41-65 days post-implant. For each method, the volume of prostate receiving 90%, 100%, and 150% of the prescribed dose (V90, V100, V150) and the dose delivered to 90% of the prostate volume (D90) were calculated. RESULTS: Post-implant TRUS volumes were within 15% of the preimplant TRUS volumes in 8 of the 9 patients investigated. The post-implant CT volume was within 15% of the preimplant (TRUS) volume in only 3 of the 9 cases. The value of the dosimetry parameters was dependent on the method used and varied by 5-25% for V90, 5-30% for V100, 42-134% for V150, and 9-60% for D90. No simple relationship was found between change in volume and the resultant change in dosimetry parameter. Differences in dosimetry parameters due to source localization uncertainties was found to be small (< or = 10% for V100) when comparing methods (1) and (2). CONCLUSIONS: There are many uncertainties in the calculation of parameters that are commonly used to describe the quality of a permanent prostate implant. Differences in the parameters calculated were most likely a result of a combination of factors including uncertainties in delineating the prostate with different imaging modalities, differences in source identification techniques, and intraobserver variability.

Comparison of focal boost high dose rate prostate brachytherapy optimisation methods.

For HDR prostate brachytherapy treatments of 15 Gy to the whole gland plus focal boost, optimisation to either tumour plus margin (F-PTV) or involved sectors was compared. For 15 patients median F-PTV D90 and V150 were 21.0 Gy and 77.2% for F-PTV optimisation and 19.8 Gy and 75.6% for sector optimisation.

EAU standardised medical terminology for urologic imaging: a taxonomic approach.

BACKGROUND: The terminology and abbreviations used in urologic imaging have generally been adopted on an ad hoc basis by different speciality groups; however, there is a need for shared nomenclature to facilitate clinical communication and collaborative research. OBJECTIVE: This work reviews the current nomenclature for urologic imaging used in clinical practice and proposes a taxonomy and terminology for urologic imaging studies. DESIGN, SETTING, AND PARTICIPANTS: A list of terms used in urologic imaging were compiled from guidelines published by the European Association of Urology and the American Urological Association and from the American College of Radiology Appropriateness Criteria. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Terms searched were grouped into broad categories based on technology, and imaging terms were further stratified based on the anatomic extent, contrast or phases, technique or modifiers, and combinations or fusions. Terms that had a high degree of utilisation were classified as accepted. RESULTS AND LIMITATIONS: We propose a new taxonomy to define a more useful and acceptable nomenclature model acceptable to all health professionals involved in urology. The major advantage of a taxonomic approach to the classification of urologic imaging studies is that it provides a flexible framework for classifying the modifications of current imaging modalities and allows the incorporation of new imaging modalities. The adoption of this hierarchical classification model ranging from the most general to the most detailed descriptions should facilitate hierarchical searches of the medical literature using both general and specific terms. This work is limited in its scope, as it is not currently all-inclusive. This will hopefully be addressed by future modification as others embrace the concept and work towards uniformity in nomenclature. CONCLUSIONS: This paper provides a noncomprehensive list of the most widely used terms across different specialties. This list can be used as the basis for further discussion, development, and enhancement. PATIENT SUMMARY: In this paper we describe a classification system for urologic imaging terms with the aim of aiding health professionals and ensuring that the terms used are more consistent.

The use of linked seeds eliminates lung embolization following permanent seed implantation for prostate cancer.

PURPOSE: A number of reports of (125)I seed migration to the lungs after prostate brachytherapy have been published. There are, however, very limited data available on how to reduce the risk of this event. The purpose of the present report is to determine whether seed embolization to the lungs can be minimized by using stranded seeds alone for brachytherapy. METHODS AND MATERIALS: Between December 2001 and December 2002, 238 patients with early prostate cancer were treated with prostate brachytherapy as monotherapy using (125)I stranded seeds (RAPIDStrand) exclusively. All patients had fluoroscopy during the implant and immediate postimplant radiographs of the pelvis. A sample of 100 patients had chest radiographs performed, on average, 55 days after implant. To determine the ease, or lack of ease, with which these (125)I seeds could be visualized, 4 patients who did not have prostate cancer and who were having routine chest radiographs as part of their management for other cancers consented to have posteroanterior and lateral radiographs performed with inactive (125)I seeds taped to the skin of the thorax. All radiographs were reviewed by a single radiologist. RESULTS: The number of seeds noted on the postimplant radiographs corresponded to the number of implanted seeds in all 238 cases: There was, therefore, no evidence of seed embolization immediately postimplant. On review of the 100 chest radiographs, no embolized seeds were found. CONCLUSION: No evidence of seed embolization was observed with the use of stranded (125)I seeds as used for prostate brachytherapy.

Impact of prostate volume evaluation by different observers on CT-based post-implant dosimetry.

PURPOSE: An analysis of computed tomography (CT)-based dosimetry was performed to evaluate the variability of different observers' judgements in marking the prostate gland on CT films, and its effect on the parameters that characterise the prostate implantation quality. Accuracy of data entry by the first author in the process of dosimetry procedure has also been evaluated. MATERIALS AND METHODS: Four observers were asked to evaluate the prostate volume on CT films for six different patients. Each observer repeated the evaluation six times. The sample of patients has a prostate volume in the range of 21.4-42.0 cc derived from transrectal ultrasound volume study. After an average period of 6 weeks of the I-125 implantation, all patients had CT scans. CT-based post-implant dosimetry was performed and the dose volume histograms DVHs were calculated to report the re-constructed prostate volume, Vp100, Vp150, Vp90 and D90. Comparison between the four observers' output was performed. RESULTS: Comparison between the four observers shows that each observer has a different way of estimating the prostate on CT films. Observers' precision also varies according to the prostate volume and the image quality. This can cause a variation in the resulting D90 value by up to 50%. Analysis of data entry shows a high degree of accuracy. The error of digitizing the prostate is +/-0.19 cc. This is correlated to an error of +/-0.78 Gy of the D90. CONCLUSION: The evaluation of prostate gland volume on CT films varies between different observers. This has an effect on the dosimetric indices that characterise the implant quality in particular the D90.

Multi-parametric MRI-guided focal tumor boost using HDR prostate brachytherapy: a feasibility study.

PURPOSE: This study investigates the feasibility of delivering focal boost dose to tumor regions, identified with multi-parametric MRI, in high-dose-rate prostate brachytherapy. METHODS AND MATERIALS: T2-weighted, diffusion-weighted, and dynamic-contrast-enhanced MRI were acquired the day before treatment and analyzed retrospectively for 15 patients. Twelve patients had hormone therapy before the MRI scan. The tumor was delineated on MRI by a radiologist and registered to treatment planning transrectal ultrasound images. A margin based on analysis of delineation and registration uncertainties was applied to create a focal boost planning target volume (F-PTV). Delivered treatment plans were compared with focal boost plans optimized to increase F-PTV dose as much as allowed by urethral and rectal dose constraints. RESULTS: Tumors were delineated in all patients with volumes 0.4-23.0cc. The margin for tumor delineation and image registration uncertainties was estimated to be 4.5 mm. For F-PTV, the focal boost treatment plans increased median D90 from 17.6 to 20.9 Gy and median V150 from 27.3% to 75.9%. CONCLUSIONS: MRI-guided high-dose-rate prostate brachytherapy focal tumor boost is feasible-tumor regions can be identified even after hormone therapy, and focal boost dose can be delivered without violating urethral and rectal dose constraints.

Microfluidic chip for molecular amplification of influenza A RNA in human respiratory specimens.

A rapid, low cost, accurate point-of-care (POC) device to detect influenza virus is needed for effective treatment and control of both seasonal and pandemic strains. We developed a single-use microfluidic chip that integrates solid phase extraction (SPE) and molecular amplification via a reverse transcription polymerase chain reaction (RT-PCR) to amplify influenza virus type A RNA. We demonstrated the ability of the chip to amplify influenza A RNA in human nasopharyngeal aspirate (NPA) and nasopharyngeal swab (NPS) specimens collected at two clinical sites from 2008-2010. The microfluidic test was dramatically more sensitive than two currently used rapid immunoassays and had high specificity that was essentially equivalent to the rapid assays and direct fluorescent antigen (DFA) testing. We report 96% (CI 89%,99%) sensitivity and 100% (CI 95%,100%) specificity compared to conventional (bench top) RT-PCR based on the testing of n = 146 specimens (positive predictive value = 100%(CI 94%,100%) and negative predictive value = 96%(CI 88%,98%)). These results compare well with DFA performed on samples taken during the same time period (98% (CI 91%,100%) sensitivity and 96%(CI 86%,99%) specificity compared to our gold standard testing). Rapid immunoassay tests on samples taken during the enrollment period were less reliable (49%(CI 38%,61%) sensitivity and 98%(CI 98%,100%) specificity). The microfluidic test extracted and amplified influenza A RNA directly from clinical specimens with viral loads down to 10³ copies/ml in 3 h or less. The new test represents a major improvement over viral culture in terms of turn around time, over rapid immunoassay tests in terms of sensitivity, and over bench top RT-PCR and DFA in terms of ease of use and portability.

Recurrence patterns of locally advanced head and neck squamous cell carcinoma after 3D conformal (chemo)-radiotherapy.

BACKGROUND: To establish recurrence patterns among locally advanced head and neck non-nasopharyngeal squamous cell carcinoma (HNSCC) patients treated with radical (chemo-) radiotherapy and to correlate the sites of loco-regional recurrence with radiotherapy doses and target volumes METHOD: 151 locally advanced HNSCC patients were treated between 2004-2005 using radical three-dimensional conformal radiotherapy. Patients with prior surgery to the primary tumour site were excluded. The sites of locoregional relapses were correlated with radiotherapy plans by the radiologist and a planning dosimetrist. RESULTS: Median age was 59 years (range:34-89). 35 patients had stage III disease, 116 patients had stage IV A/B. 36 patients were treated with radiotherapy alone, 42 with induction chemotherapy, 63 with induction and concomitant chemoradiotherapy and 10 concomitant chemoradiotherapy. Median follow-up was 38 months (range 3-62). 3-year cause specific survival was 66.8%. 125 of 151 (82.8%) achieved a complete response to treatment. Amongst these 125 there were 20 local-regional recurrence, comprising 8 local, 5 regional and 7 simultaneous local and regional; synchronous distant metastases occurred in 7 of the 20. 9 patients developed distant metastases in the absence of locoregional failure. For the 14 local recurrences with planning data available, 12 were in-field, 1 was marginal, and 1 was out-of-field. Of the 11 regional failures with planning data available, 7 were in-field, 1 was marginal and 3 were out-of-field recurrences. CONCLUSION: The majority of failures following non-surgical treatment for locally advanced HNSCC were loco-regional, within the radiotherapy target volume. Improving locoregional control remains a high priority.

Magnetic resonance imaging for the detection, localisation, and characterisation of prostate cancer: recommendations from a European consensus meeting.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) may have a role in detecting clinically significant prostate cancer in men with raised serum prostate-specific antigen levels. Variations in technique and the interpretation of images have contributed to inconsistency in its reported performance characteristics. OBJECTIVE: Our aim was to make recommendations on a standardised method for the conduct, interpretation, and reporting of prostate mpMRI for prostate cancer detection and localisation. DESIGN, SETTING, AND PARTICIPANTS: A consensus meeting of 16 European prostate cancer experts was held that followed the UCLA-RAND Appropriateness Method and facilitated by an independent chair. MEASUREMENT: Before the meeting, 520 items were scored for "appropriateness" by panel members, discussed face to face, and rescored. RESULTS AND LIMITATIONS: Agreement was reached in 67% of 260 items related to imaging sequence parameters. T2-weighted, dynamic contrast-enhanced, and diffusion-weighted MRI were the key sequences incorporated into the minimum requirements. Consensus was also reached on 54% of 260 items related to image interpretation and reporting, including features of malignancy on individual sequences. A 5-point scale was agreed on for communicating the probability of malignancy, with a minimum of 16 prostatic regions of interest, to include a pictorial representation of suspicious foci. Limitations relate to consensus methodology. Dominant personalities are known to affect the opinions of the group and were countered by a neutral chairperson. CONCLUSIONS: Consensus was reached on a number of areas related to the conduct, interpretation, and reporting of mpMRI for the detection, localisation, and characterisation of prostate cancer. Before optimal dissemination of this technology, these outcomes will require formal validation in prospective trials.