Randomized Trial of Postoperative Radiation Therapy After Wide Excision of Neurotropic Melanoma of the Head and Neck (RTN2 Trial 01.09).

BACKGROUND: Cutaneous neurotropic melanoma (NM) of the head and neck (H&N) is prone to local relapse, possibly due to difficulties widely excising the tumor. This trial assessed radiation therapy (RT) to the primary site after local excision. METHODS: Participants from 15 international centers were randomized to observation or RT. The participants were required to have microscopically negative excision margins 5 mm wide or wider and no evidence of disease elsewhere. The primary outcome was time to local relapse. The secondary outcomes included time to any recurrence, overall survival (OS), and toxicity. RESULTS: The trial ceased prematurely due to slow recruitment and the COVID-19 pandemic. During 2009-2020, 50 participants were randomized: 23 to observation and 27 to RT. The most common NM subsites were scalp (32%), midface (22%), and lip (20%). The median depth of invasion was 5 mm, and desmoplasia observed in 69%. The median duration from randomization to last contact was 4.8 years. Four participants (8%) experienced local relapse as a first recurrence during the study period: 3 in the observation arm and 1 in the RT arm (hazard ratio [HR] 0.29; 95% confidence interval [CI] 0.03-2.76; p = 0.279). No statistically significant difference in time to any relapse or OS was observed. More than 6 months after randomization, grade 3 or greater toxicity was experienced by 10% of the participants in the observation arm and 12.5% of the participants in the RT arm of the study. CONCLUSION: Due to low accrual, the role of adjuvant RT for cutaneous NM of the H&N excised with microscopically negative margins 5 mm wide or wider remains undefined. Its routine use cannot be recommended. Local relapse might be less common than previously anticipated based on retrospective reports.

Gender differences in doxorubicin pharmacology for subjects with chemosensitive cancers of young adulthood.

PURPOSE: For many cancers, adolescents and young adults (AYA) have worse outcomes than for children and adults. Many factors may contribute to the AYA survival gap, including differences in biology, therapeutic intent, and adherence to therapy. It has been observed that male AYAs have poorer outcomes than females. The purpose of this work was to test the proposition that gender-related pharmacologic factors may account for a component of the AYA survival gap. PATIENTS AND METHODS: A prospective, multi-institutional pharmacologic study of 79 patients in total with chemosensitive cancers (Ewing sarcoma, osteosarcoma and Hodgkin lymphoma) was conducted, with conventional doxorubicin treatment. Pharmacokinetic data of 13 children, 40 AYAs and 13 adults were valid for analysis. Population pharmacokinetics models were developed for doxorubicin and its metabolite doxorubicinol based on the data created in this study. Consequently, model-based analysis was conducted to investigate the relevant topics. RESULTS: The clearance of doxorubicinol (normalized to body surface area), the main active metabolite of doxorubicin, appears faster in male AYAs than female (p = 0.04, 95% CI 0.1-3.9 L/h). The exposure of doxorubicinol (normalized to dose) is lower in male AYA than female (p = 0.03, 95% CI - 0.005 to - 0.0002 h/L). These might be correlated to the observed difference on nadir neutrophil count between male AYA and female (p = 0.027, 95% CI 0.09-1.4). CONCLUSION: Gender-related differences in doxorubicin pharmacology may account for worse outcomes for male AYAs with chemosensitive cancers compared to females. These findings may reduce the AYA survival gap compared to other age groups.

Surveillance imaging with FDG-PET/CT in the post-operative follow-up of stage 3 melanoma.

Background: As early detection of recurrent melanoma maximizes treatment options, patients usually undergo post-operative imaging surveillance, increasingly with FDG-PET/CT (PET). To assess this, we evaluated stage 3 melanoma patients who underwent prospectively applied and sub-stage-specific schedules of PET surveillance. Patients and methods: From 2009, patients with stage 3 melanoma routinely underwent PET +/- MRI brain scans via defined schedules based on sub-stage-specific relapse probabilities. Data were collected regarding patient characteristics and outcomes. Contingency analyses were carried out of imaging outcomes. Results: One hundred and seventy patients (stage 3A: 34; 3B: 93; 3C: 43) underwent radiological surveillance. Relapses were identified in 65 (38%) patients, of which 45 (69%) were asymptomatic. False-positive imaging findings occurred in 7%, and 6% had treatable second (non-melanoma) malignancies. Positive predictive values (PPV) of individual scans were 56%-83%. Negative scans had predictive values of 89%-96% for true non-recurrence [negative predictive values (NPV)] until the next scan. A negative PET at 18 months had NPVs of 80%-84% for true non-recurrence at any time in the 47-month (median) follow-up period. Sensitivity and specificity of the overall approach of sub-stage-specific PET surveillance were 70% and 87%, respectively. Of relapsed patients, 33 (52%) underwent potentially curative resection and 10 (16%) remained disease-free after 24 months (median). Conclusions: Application of sub-stage-specific PET in stage 3 melanoma enables asymptomatic detection of most recurrences, has high NPVs that may provide patient reassurance, and is associated with a high rate of detection of resectable and potentially curable disease at relapse.

The enhanced recovery after surgery (ERAS) Greenie Board: a Navy-inspired quality improvement tool.

The United States Navy uses a visual feedback system for pilots, named 'the Greenie Board', to improve flight manoeuvres on aircraft carriers. Given that increased compliance with enhanced recovery after surgery protocols reduces postoperative complications, we decided to apply a similar feedback system to our institutional enhanced recovery programme. We undertook a prospective 12-month audit of 194 patients assigned to our enhanced recovery programme and evaluated adherence to the anaesthesia-related components of our protocol, before and after implementing a Greenie Board. A compliance score was calculated by summing points for adherence to: intra-operative antibiotic prophylaxis; temperature management; goal-directed intravenous fluid therapy; postoperative nausea and vomiting prophylaxis; and postoperative fluid restriction. The score for each patient was then colour-coded and anonymously displayed for each anaesthetist on a Greenie Board within the operating theatre suite. Protocol adherence improved significantly following introduction, with 'Green' scores (acceptable compliance) increasing from 33% to 72% of patients (p < 0.0001). The greatest improvement was seen with anti-emetic prophylaxis (49% to 70%, p = 0.004) with a consequent reduction in postoperative nausea and vomiting (OR 0.42, 95% CI 0.19-0.88, p = 0.021). We did not observe a decrease in other postoperative complications nor hospital length of stay. We conclude that this US Navy-inspired feedback system is an easily implemented, low-cost quality improvement tool that significantly improved adherence to intra-operative components of our enhanced recovery protocol. The system lends itself to global scaling to drive quality improvement in healthcare delivery and would be suited to institutions without electronic medical records, including low-resource countries.

Stereotactic Ablative Body Radiotherapy for the Treatment of Spinal Oligometastases.

AIMS: To report multicentre outcomes of patients with spinal oligometastases treated with stereotactic ablative body radiotherapy (SABR). The primary objective was to estimate the widespread failure-free survival (WFFS) at 2 years - defined as freedom from metastases not amenable to local salvage therapy and death. MATERIALS AND METHODS: Patients with one to three metastases treated with spinal SABR between January 2010 and July 2014 at four academic institutions were included in this retrospective review. The median dose/fractionation was 24 Gy (range 16-52.5 Gy) in two fractions (range one to three) and the median biologically effective dose (α/ß=10) was 52.5 Gy (range 40-144.4 Gy). The WFFS, overall survival, freedom from local progression and toxicity rates were described using Kaplan-Meier statistics. RESULTS: In total, 60 patients with 72 spinal metastases were analysed. The median follow-up was 21 months. Patients had a median age of 66 years, Eastern Cooperative Oncology Group performance 0-1 in 97% and metachronous oligometastases in 85%. The 1 and 2 year WFFS rates were 67% (95% confidence interval 55-80) and 59% (95% confidence interval 47-75), respectively. The 1 and 2 year overall survival rates were 90% (95% confidence interval 83-98) and 76% (95% confidence interval 64-91), respectively. The 1 and 2 year freedom from local progression were 92% (95% confidence interval 85-99) and 86% (95% confidence interval 75-99), respectively. There were four cases (6.7%) of vertebral compression fracture and no cases of radiation myelopathy. CONCLUSION: Despite the use of relatively low biological doses respecting spinal cord constraints, SABR results in excellent 2 year local control rates with low morbidity. Through careful selection of patients with oligometastases, most patients are alive and free from widespread metastases at 2 years. This cohort warrants further investigation in clinical trials of SABR.

Real-time Image-guided Adaptive-predictive Prostate Radiotherapy using Rectal Diameter as a Predictor of Motion.

AIMS: To investigate a relationship between maximum rectal diameter (MRD) on pre-treatment cone beam computed tomography (CBCT) and intra-fraction prostate motion, in the context of an adaptive image-guided radiotherapy (IGRT) method. MATERIALS AND METHODS: The MRD was measured on 2125 CBCTs from 55 retrospective patient datasets and related to prostate displacement from intra-fraction imaging. A linear regression model was developed to determine a threshold MRD associated with a high probability of small prostate displacement. Standard and reduced adaptive margin plans were created to compare rectum and bladder normal tissue complication probability (NTCP) with each method. RESULTS: A per-protocol analysis carried out on 1910 fractions from 51 patients showed with 90% confidence that for a MRD≤3 cm, prostate displacement will be ≤5 mm and that for a MRD≤3.5 cm, prostate displacement will be ≤5.5 mm. In the first scenario, if adaptive therapy was used instead of standard therapy, median reductions in NTCP for rectum and bladder were 0.5% (from 9.5% to 9%) and 1.3% (from 6.6% to 5.3%), respectively. In the second scenario, the NTCP for rectum and bladder would have median reductions of 1.1% and 2.6%, respectively. CONCLUSIONS: We have identified a potential method for adaptive prostate IGRT based upon predicting small prostate intra-fraction motion by measuring MRD on pre-treatment CBCT.

Calculating radiotherapy margins based on Bayesian modelling of patient specific random errors.

Collected real-life clinical target volume (CTV) displacement data show that some patients undergoing external beam radiotherapy (EBRT) demonstrate significantly more fraction-to-fraction variability in their displacement ('random error') than others. This contrasts with the common assumption made by historical recipes for margin estimation for EBRT, that the random error is constant across patients. In this work we present statistical models of CTV displacements in which random errors are characterised by an inverse gamma (IG) distribution in order to assess the impact of random error variability on CTV-to-PTV margin widths, for eight real world patient cohorts from four institutions, and for different sites of malignancy. We considered a variety of clinical treatment requirements and penumbral widths. The eight cohorts consisted of a total of 874 patients and 27 391 treatment sessions. Compared to a traditional margin recipe that assumes constant random errors across patients, for a typical 4 mm penumbral width, the IG based margin model mandates that in order to satisfy the common clinical requirement that 90% of patients receive at least 95% of prescribed RT dose to the entire CTV, margins be increased by a median of 10% (range over the eight cohorts -19% to +35%). This substantially reduces the proportion of patients for whom margins are too small to satisfy clinical requirements.

A phase Ib/II translational study of sunitinib with neoadjuvant radiotherapy in soft-tissue sarcoma.

BACKGROUND: Preoperative radiotherapy (RT) is commonly used to treat localised soft-tissue sarcomas (STS). Hypoxia is an important determinant of radioresistance. Whether antiangiogenic therapy can 'normalise' tumour vasculature, thereby improving oxygenation, remains unknown. METHODS: Two cohorts were prospectively enrolled. Cohort A evaluated the implications of hypoxia in STS, using the hypoxic tracer (18)F-azomycin arabinoside (FAZA-PET). In cohort B, sunitinib was added to preoperative RT in a dose-finding phase 1b/2 design. RESULTS: In cohort A, 13 out of 23 tumours were hypoxic (FAZA-PET), correlating with metabolic activity (r(2)=0.85; P<0.001). Two-year progression-free (PFS) and overall (OS) survival were 61% (95% CI: 0.44-0.84) and 87% (95% CI: 0.74-1.00), respectively. Hypoxia was associated with radioresistance (P=0.012), higher local recurrence (Hazard ratio (HR): 10.2; P=0.02), PFS (HR: 8.4; P=0.02), and OS (HR: 41.4; P<0.04). In Cohort B, seven patients received sunitinib at dose level (DL): 0 (50 mg per day for 2 weeks before RT; 25 mg per day during RT) and two patients received DL: -1 (37.5 mg per day for entire period). Dose-limiting toxicities were observed in 4 out of 7 patients at DL 0 and 2 out of 2 patients at DL -1, resulting in premature study closure. Although there was no difference in PFS or OS, patients receiving sunitinib had higher local failure (HR: 8.1; P=0.004). CONCLUSION: In STS, hypoxia is associated with adverse outcomes. The combination of sunitinib with preoperative RT resulted in unacceptable toxicities, and higher local relapse rates.

Prostate bed radiation therapy: the utility of ultrasound volumetric imaging of the bladder.

AIMS: To evaluate the effect of incorporating daily ultrasound scanning to reduce variation in bladder filling before prostate bed radiotherapy. The primary aim was to confirm that coverage of the planning target volume (PTV) with the 95% isodose was within tolerance when the ultrasound-determined bladder volume was within individualised patient limits. MATERIALS AND METHODS: Cone beam computed tomography (CBCT) images were acquired on 10 occasions during the course of treatment to assess systematic changes in rectal or bladder volume as part of a standard offline image-guided radiotherapy (IGRT) protocol. In addition, through a two-part study an ultrasound scan of the bladder was added to the IGRT protocol. In the Part 1 study, the ultrasound-determined bladder volume at the time of treatment simulation in 26 patients was compared with the simulation computed tomography cranio-caudal bladder length. The relationship between the two was used to establish bladder volume tolerance limits for the interventional component of the Part 2 study. In the Part 2 study, 24 patients underwent ultrasound scanning before treatment. When bladder volumes were outside the specified limits, they were asked to drink more water or void as appropriate until the volume was within tolerance. RESULTS: Based on the results of the Part 1 study, a 100 ml tolerance was applied in the Part 2 study. Seventy-six per cent of patients found to have bladder volumes outside tolerance were able to satisfactorily adjust their bladder volumes on demand. Comparing the bladder volumes with the CBCT data revealed that the bladder scanner correctly predicted that the target volume would be accurately targeted (using surrogate end points) in 83% of treatment fractions. CONCLUSION: A simple hand-held ultrasound bladder scanner provides a practical, inexpensive, online solution to confirming that the bladder volume is within acceptable, patient-specific limits before treatment delivery, with the potential to improve overall treatment accuracy.

Assessment of predictors of response and long-term survival of patients with neuroendocrine tumour treated with peptide receptor chemoradionuclide therapy (PRCRT).

PURPOSE: To review the response and outcomes of (177)Lu-DOTA-octreotate chemoradionuclide therapy (LuTate PRCRT) in patients with neuroendocrine tumour (NET) expressing high levels of somatostatin receptors with uncontrolled symptoms or disease progression. METHODS: A total of 68 patients (39 men; 17 - 76 years of age) who had completed an induction course of at least three cycles of LuTate PRCRT between January 2006 and June 2010 were reviewed. Ten patients were treated for uncontrolled symptoms and 58 had disease progression despite conventional treatment. The majority had four induction LuTate cycles (median treatment duration 5 months and cumulative activity 31 GBq), and 63 patients had concomitant 5-FU radiosensitizing infusional chemotherapy. Factors predicting overall survival were assessed using the log-rank test and Cox proportional hazards regression. RESULTS: Of those treated for uncontrolled symptoms, 70 % received benefit maintained for at least 6 months after treatment. Among patients with progressive disease 68 % showed stabilization or regression on CT, 67 % on molecular imaging and 56 % biochemically up to 12 months after treatment; 32 patients died. Overall survival rates at 2 and 5 year were 72.1 % and 52.1 %, respectively. Median overall survival was not estimable at a median follow-up of 60 months (range 5 - 86 months). Nonpancreatic primary sites, dominant liver metastases, lesion size <5 cm and the use of 5-FU chemotherapy were statistically significantly associated with objective response. A disseminated pattern and a high disease burden (whole-body retention index) were associated with an increased risk of death. Objective biochemical, molecular imaging and CT responses were all associated with longer overall survival. CONCLUSION: A high proportion of patients with progressive NET or uncontrolled symptoms received therapeutic benefit from LuTate with concomitant 5-FU chemotherapy. The achievement of objective biochemical, molecular or CT responses within 12 months was associated with improved overall survival. Patients with a primary pancreatic site and larger lesions (>5 cm) appeared to have lower objective response rates and may need a more aggressive treatment approach.

Calculating geometrical margins for hypofractionated radiotherapy.

Formulae to calculate margins for external beam radiotherapy traditionally treat the radiotherapy regimen for analysis purposes as consisting of a very large number of treatment sessions, each delivering a very small dose. It is assumed that the difference in the calculated margin for an infinitely fractionated regimen, and the margin for real world treatment scenarios with finite fractions per patient, is negligible given the usual large number of fractions used to treat most malignancies. However hypofractionated radiotherapy using five fractions or even fewer is becoming increasingly common, causing the accuracy of traditional margin formulae to break down. This work introduces an algorithm that accurately calculates margins for hypofractionated treatment regimens. A method for estimating an upper limit for the required margin is introduced, and an adjustment to the van Herk formula (van Herk et al (2000 Int. J. Radiat. Oncol. Biol. Phys. 47 1121-35)) is used to provide a lower limit. A single-term mathematical model is then used to interpolate between these limits. Results are compared to those calculated by Monte Carlo simulation, demonstrating that the proposed method yields accurate estimates of the actual margin required (consistently within ~1%) for wide ranges of values of the systematic error, random error and penumbral width, even when the number of fractions per patient is as low as 2.

Finding the optimal statistical model to describe target motion during radiotherapy delivery--a Bayesian approach.

Early approaches to characterizing errors in target displacement during a fractionated course of radiotherapy assumed that the underlying fraction-to-fraction variability in target displacement, known as the 'treatment error' or 'random error', could be regarded as constant across patients. More recent approaches have modelled target displacement allowing for differences in random error between patients. However, until recently it has not been feasible to compare the goodness of fit of alternate models of random error rigorously. This is because the large volumes of real patient data necessary to distinguish between alternative models have only very recently become available. This work uses real-world displacement data collected from 365 patients undergoing radical radiotherapy for prostate cancer to compare five candidate models for target displacement. The simplest model assumes constant random errors across patients, while other models allow for random errors that vary according to one of several candidate distributions. Bayesian statistics and Markov Chain Monte Carlo simulation of the model parameters are used to compare model goodness of fit. We conclude that modelling the random error as inverse gamma distributed provides a clearly superior fit over all alternatives considered. This finding can facilitate more accurate margin recipes and correction strategies.

Interfraction patient motion and implant displacement in prostate high dose rate brachytherapy.

PURPOSE: To quantify movement of prostate cancer patients undergoing treatment, using an in-house developed motion sensor in order to determine a relationship between patient movement and high dose rate (HDR) brachytherapy implant displacement. METHODS: An electronic motion sensor was developed based on a three axis accelerometer. HDR brachytherapy treatment for prostate is delivered at this institution in two fractions 24 h apart and 22 patients were monitored for movement over the interval between fractions. The motion sensors functioned as inclinometers, monitoring inclination of both thighs, and the inclination and roll of the abdomen. The implanted HDR brachytherapy catheter set was assessed for displacement relative to fiducial markers in the prostate. Angle measurements and angle differences over a 2 s time base were binned, and the standard deviations of the resulting frequency distributions used as a metric for patient motion in each monitored axis. These parameters were correlated to measured catheter displacement using regression modeling. RESULTS: The mean implant displacement was 12.6 mm in the caudal direction. A mean of 19.95 h data was recorded for the patient cohort. Patients generally moved through a limited range of angles with a mean of the exception of two patients who spent in excess of 2 h lying on their side. When tested for a relationship between movement in any of the four monitored axes and the implant displacement, none was significant. CONCLUSIONS: It is not likely that patient movement influences HDR prostate implant displacement. There may be benefits to patient comfort if nursing protocols were relaxed to allow patients greater freedom to move while the implant is in situ.

In pursuit of individualised margins for prostate cancer patients undergoing image-guided radiotherapy: the effect of body mass index on intrafraction prostate motion.

AIMS: To analyse the relationship between body mass index (BMI) and intrafraction displacement in patients undergoing prostate cancer image-guided radiotherapy. MATERIALS AND METHODS: An analysis was carried out on 151 prostate cancer patients treated with radical dose radiotherapy between January 2007 and March 2009. Patients had their height, weight and daily intrafraction prostate displacement data collected prospectively during fiducial marker image-guided radiotherapy with orthogonal imaging. For each of anterior-posterior, left-right and superior-inferior axes, a univariable linear regression analysis was carried out with the individual patient standard deviation of shift as the response variable and BMI as a continuous explanatory variable. RESULTS: Displacement measurements were recorded from 4764 pre- and post-treatment image sets. Patients were grouped according to BMI as normal weight (24%), overweight (52%), obese (18%), severely obese (3%) or morbidly obese (3%). For intrafraction displacement, a one unit increase in BMI affected the standard deviation of shift by: anterior-posterior -0.02 (95% confidence interval -0.040 to 0.000), left-right -0.006 (95% confidence interval -0.020 to 0.008) and superior-inferior -0.020 (95% confidence interval -0.037 to -0.003). CONCLUSIONS: Our data indicate that patients with a higher BMI have less intrafraction displacement of the prostate in the superior-inferior dimension compared with patients with a lower BMI. This has implications for individualised treatment margins for future prostate cancer patients undergoing image-guided radiotherapy. Further study is recommended.

Online adaptive radiotherapy for muscle-invasive bladder cancer: results of a pilot study.

PURPOSE: To determine the advantages and disadvantages of daily online adaptive image-guided radiotherapy (RT) compared with conventional RT for muscle-invasive bladder cancer. METHODS AND MATERIALS: Twenty-seven patients with T2-T4 transitional cell carcinoma of the bladder were treated with daily online adaptive image-guided RT using cone-beam computed tomography (CBCT). From day 1 daily soft tissue-based isocenter positioning was performed using CBCT images acquired before treatment. Using a composite of the initial planning CT and the first five daily CBCT scans, small, medium, and large adaptive plans were created. Each of these adaptive plans used a 0.5-cm clinical target volume (CTV) to planning target volume expansion. For Fractions 8-32, treatment involved daily soft tissue-based isocenter positioning and selection of suitable adaptive plan of the day. Treating radiation therapists completed a credentialing program, and one radiation oncologist performed all the contouring. Comparisons were made between adaptive and conventional treatment on the basis of CTV coverage and normal tissue sparing. RESULTS: All 27 patients completed treatment per protocol. Bladder volume decreased with time or fraction number (p < 0.0001). For the adaptive component (Fractions 8-32) the small, medium, large, and conventional plans were used in 9.8%, 49.2%, 39.5%, and 1.5% of fractions, respectively. For the adaptive strategy, 2.7% of occasions resulted in a CTV V95 <99%, compared with 4.8% of occasions for the conventional approach (p = 0.42). Mean volume of normal tissue receiving a dose >45 Gy was 29% (95% confidence interval, 24-35%) less with adaptive RT compared with conventional RT. The mean volume of normal tissue receiving >5 Gy was 15% (95% confidence interval, 11-18%) less with adaptive RT compared with conventional RT. CONCLUSIONS: Online adaptive radiotherapy is feasible in an academic radiotherapy center. The volume of normal tissue irradiated can be significantly smaller without reducing CTV coverage.

Impact of 18F-fluorodeoxyglucose positron emission tomography in the staging and treatment response assessment of extra-pulmonary small-cell cancer.

The aim of this study was to retrospectively evaluate the value of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in extrapulmonary small-cell cancer (EPSCC). Patients with EPSCC who underwent PET for staging or response assessment between 1996 and 2007 were identified from a database. Patient records were reviewed. PET-based, and conventional staging and restaging results were compared. The binary staging classification of limited disease (LD) versus extensive disease (ED) was used. Patients with LD had tumours that could be encompassed within a tolerable radiation therapy (RT) volume. Of 33 eligible patients, 12 had staging PET scans, 11 had restaging scans and 10 had both. All known gross disease sites were FDG-avid. PET and conventional stage groupings were concordant in 21 of 22 cases. One patient was appropriately upstaged from LD to ED by PET. PET detected additional disease sites, without causing upstaging in three further patients. Restaging PET scans identified previously unrecognised persistent or progressive disease in 4 of 21 cases. In four further cases, persistent FDG uptake after treatment was either false positive (n = 2) or of uncertain (n = 2) aetiology. PPV was 100% for staging and 82% for restaging. In 8 of 43 imaging episodes (19%), PET appropriately influenced management in five cases by changing treatment intent from radical to palliative, and in three cases by altering the RT volume. PET has incremental value compared to conventional imaging for staging EPSCC, and may also be useful for restaging after therapy. PET influenced patient management in 19% of 43 imaging episodes.

Prospective development of an individualised predictive model for treatment coverage using offline cone beam computed tomography surrogate measures in post-prostatectomy radiotherapy.

The aim of this study is to prospectively evaluate and model surrogate explanatory variables (SEVs) of target coverage and rectal dose pertaining to soft tissue anatomy visualised on cone beam computed tomography (CBCT) for incorporation into post-prostatectomy treatment coverage verification protocols. Twenty post-prostatectomy patients treated with conformal prostate bed radiotherapy (64-74 Gy) underwent CBCT daily at fractions 1 to 5, and then weekly. Treatment coverage was defined on each CBCT using 'PTV95', percentage of the CBCT PTV covered by original treatment fields, and 'RECTD50', dose delivered to 50% of CBCT rectal volume by original treatment fields. Three candidate SEVs for treatment coverage were defined for each scan: anterior rectal wall movement, change in bladder length and bladder base movement. Both anterior rectal wall movement and increase in bladder length predicted for the decreased PTV95 (P < 0.001 for each). Anterior movement of the anterior rectal wall predicted for increased RECTD50 (P < 0.001). Predictive models for the PTV95 and RECTD50 that accept the significant SEVs as inputs were developed. We developed simple CBCT-acquired soft tissue anatomic surrogate measures that signal changes in target coverage and rectal dose during post-prostatectomy radiotherapy. Conventional bony anatomy patient position verification protocols were inadequate in accounting for soft tissue target and organ variation seen with CBCT.

Rectal filling at planning does not predict stability of the prostate gland during a course of radical radiotherapy if patients with large rectal filling are re-imaged.

AIMS: It has been suggested that large rectal filling is associated with an increased risk of prostate motion in radiotherapy. The aim of the present study was to determine if there is a correlation between rectal distension on planning computed tomography and the intrafraction and interfraction stability of the prostate gland during a course of radical radiotherapy for prostate cancer if a protocol was used to rescan patients with excessive rectal diameter during planning. MATERIALS AND METHODS: The computed tomography planning scans of 89 patients with adenocarcinoma of the prostate treated with conformal radiotherapy were reviewed. All patients had three gold seed fiducial markers implanted into the prostate before planning computed tomography. About one in five patients had repeat computed tomography because their rectum was judged to be too large at the time of the first planning computed tomography. Rectal distension was assessed on planning computed tomography using outlines following European Organization for Research and Treatment of Cancer guidelines by measuring the rectal volume, the average cross-sectional area and the mean anterior-posterior diameter of the rectum. Daily kV images were obtained before and after treatment delivery to determine positional matching of the fiducial markers in the superior-inferior, anterior-posterior and right-left dimensions. RESULTS: In total, 2860 pre- and post-treatment daily kV image pairs were obtained of 89 patients (average 32.1 image pairs per patient). The median rectal cross-sectional area was 7.3cm(2) (range 2.8-17.1), the median rectal volume was 54.8cm(3) (range 20.9-128.2), and the median anterior-posterior rectal diameter was 3.03cm (range 1.58-8.30). Unifactor linear regression models showed no statistically significant relationship between intra- and interfraction prostate stability and rectal volume on planning computed tomography. CONCLUSIONS: No statistically significant relationship between rectal distension on planning computed tomography and the intra- and interfraction stability of the prostate gland was identified if patients with a large rectal volume were rescanned for planning.

Verification of target position in the post-prostatectomy cancer patient using cone beam CT.

We present the results of a pilot study designed to investigate methods that may be applied to develop a patient position correction protocol for the post-prostatectomy patient receiving radiotherapy. Imaging was carried out with cone beam CT (CBCT) to investigate its suitability for detecting changes in rectal and bladder volumes and movements of these organs relative to the treatment planning CT. Eligible patients were imaged daily during the first week of treatment and weekly thereafter. Surrogate explanatory variables, including distance from the isocentre to the anterior rectum and bladder length, were tested for their potential to substitute for contouring entire organs and predict for changes in coverage of the planning treatment volume (PTV) by the 95% isodose (PTV95) and the maximum dose delivered to 50% of the rectal volume (RECTD50). The PTV defined on the CBCT images was larger than that defined on the planning CT and resulted in a decrease in the PTV95. Bladder length correlated with bladder volume and changes in bladder volume were associated with a decrease in PTV95. Rectal volumes changed randomly during treatment. There was a trend for the rectum to move anteriorly as treatment progressed. CBCT may be used to define the PTV, rectum and bladder though the reason for an apparent increase in PTV on CBCT requires further investigation. The bladder length and distance to the anterior rectal wall are potential surrogate explanatory variables. Further studies will be designed to test values of these surrogates that predict the need for a change in isocentre position.