Tara Rosewall

Image guided dose escalated prostate radiotherapy: still room to improve

BackgroundProstate radiotherapy (RT) dose escalation has been reported to result in improved biochemical control at the cost of greater late toxicity. We report on the application of 79.8 Gy in 42 fractions of prostate image guided RT (IGRT). The primary objective was to assess 5-year biochemical control and potential prognostic factors by the Phoenix definition. Secondary endpoints included acute and late toxicity by the Radiotherapy Oncology Group (RTOG) scoring scales.MethodsFrom October/2001 and June/2003, 259 men were treated with at least 2-years follow-up. 59 patients had low, 163 intermediate and 37 high risk disease. 43 had adjuvant hormonal therapy (HT), mostly for high- or multiple risk factor intermediate-risk disease (n = 25). They received either 3-dimensional conformal RT (3DCRT, n = 226) or intensity modulated RT (IMRT) including daily on-line IGRT with intraprostatic fiducial markers.ResultsMedian follow-up was 67.8 months (range 24.4-84.7). There was no severe (grade 3-4) acute toxicity, and grade 2 acute gastrointestinal (GI) toxicity was unusual (10.1%). The 5-year incidence of grade 2-3 late GI and genitourinary (GU) toxicity was 13.7% and 12.1%, with corresponding grade 3 figures of 3.5% and 2.0% respectively. HT had an association with an increased risk of grade 2-3 late GI toxicity (11% v 21%, p = 0.018). Using the Phoenix definition for biochemical failure, the 5 year-bNED is 88.4%, 76.5% and 77.9% for low, intermediate and high risk patients respectively. On univariate analysis, T-category and Gleason grade correlated with Phoenix bNED (p = 0.006 and 0.039 respectively). Hormonal therapy was not a significant prognostic factor on uni- or multi-variate analysis. Men with positive prostate biopsies following RT had a lower chance of bNED at 5 years (34.4% v 64.3%; p = 0.147).ConclusionIGRT to 79.8 Gy results in favourable rates of late toxicity compared with published non-IGRT treated cohorts. Future avenues of investigation for toxicity reduction include IMRT, margin reduction, and dose modulation targeted to sites of disease burden. Further work is required to maximize efficacy beyond that achieved through radiation dose escalation alone.

A Cinematic Magnetic Resonance Imaging Study of Milk of Magnesia Laxative and an Antiflatulent Diet to Reduce Intrafraction Prostate Motion

PURPOSE To determine the reduction of prostate motion during a typical radiotherapy (RT) fraction from a bowel regimen comprising an antiflatulent diet and daily milk of magnesia. METHODS AND MATERIALS Forty-two patients with T1c-T2c prostate cancer voided the bladder and rectum before three cinematic magnetic resonance imaging scans obtained every 9 s for 9 min in a vacuum immobilization device. The MRIs were at baseline without bowel regimen (MRI-BL), before CT planning with bowel regimen (MRI-CT), and before a randomly assigned RT fraction (1-42) with bowel regimen (MRI-RT). A single observer tracked displacement of the posterior midpoint (PM) of the prostate. The primary endpoints were comparisons of the proportion of time that the PM was displaced >3 mm (PTPM3) from its initial position, and the secondary endpoints were comparisons of the reduction of initial rectal area, with and without the bowel regimen. RESULTS The mean rectal area was: 13.5 cm(2) at MRI-BL, 12.7 cm(2) at MRI-CT, and 12.3 cm(2) at MRI-RT (MRI-BL vs. MRI-CT, p = 0.11; MRI-BL vs. MRI-CT, p = 0.07). Moving rectal gas alone (56%) and moving gas and stool (18%) caused 74% of intrafraction prostate motion. The PTPM3 was 11.3% at MRI-BL, 4.8% at MRI-CT, and 12.0% at MRI-RT (MRI-BL vs. MRI-CT, p = 0.12; MRI-BL vs. MRI-RT, p = 0.89). CONCLUSION For subjects voiding their rectum before imaging, an antiflatulent diet and milk of magnesia laxative did not significantly reduce initial rectal area or intrafraction prostate motion.

The relationship between external beam radiotherapy dose and chronic urinary dysfunction – A methodological critique

PURPOSE To perform a methodological critique of the literature evaluating the relationship between external beam radiotherapy dose/volume parameters and chronic urinary dysfunction to determine why consistent associations between dose and dysfunction have not been found. METHODS AND MATERIALS The radiotherapy literature was reviewed using various electronic medical search engines with appropriate keywords and MeSH headings. Inclusion criteria comprised of; English language articles, published between 1999 and June 2009, incorporating megavoltage external beam photons in standard-sized daily fraction. A methodological critique was then performed, evaluating the factors affected in the quantification of radiotherapy dose and chronic urinary dysfunction. RESULTS Nine of 22 eligible studies successfully identified a clinically and statistically significant relationship between dose and dysfunction. Accurate estimations of external beam radiotherapy dose were compromised by the frequent use of dosimetric variables which are poor surrogates for the dose received by the lower urinary tract tissue and do not incorporate the effect of daily variations in isocentre and bladder position. The precise categorization of chronic urinary dysfunction was obscured by reliance on subjective and aggregated toxicity metrics which vary over time. CONCLUSIONS A high-level evidence-base for the relationship between external beam radiotherapy dose and chronic urinary dysfunction does not currently exist. The quantification of the actual external beam dose delivered to the functionally important tissues using dose accumulation strategies and the use of objective measures of individual manifestations of urinary dysfunction will assist in the identification of robust relationships between dose and urinary dysfunction for application in widespread clinical practice.

Applying usability heuristics to radiotherapy systems

BACKGROUND AND PURPOSE Heuristic evaluations have been used to evaluate safety of medical devices by identifying and assessing usability issues. Since radiotherapy treatment delivery systems often consist of multiple complex user-interfaces, a heuristic evaluation was conducted to assess the potential safety issues of such a system. MATERIAL AND METHODS A heuristic evaluation was conducted to evaluate the treatment delivery system at Princess Margaret Hospital (Toronto, Canada). Two independent evaluators identified usability issues with the user-interfaces and rated the severity of each issue. RESULTS The evaluators identified 75 usability issues in total. Eighteen of them were rated as high severity, indicating the potential to have a major impact on patient safety. A majority of issues were found on the record and verify system, and many were associated with the patient setup process. While the hospital has processes in place to ensure patient safety, recommendations were developed to further mitigate the risks of potential consequences. CONCLUSIONS Heuristic evaluation is an efficient and inexpensive method that can be successfully applied to radiotherapy delivery systems to identify usability issues and improve patient safety. Although this study was conducted only at one site, the findings may have broad implications for the design of these systems.

The use of human factors methods to identify and mitigate safety issues in radiation therapy

BACKGROUND AND PURPOSE New radiation therapy technologies can enhance the quality of treatment and reduce error. However, the treatment process has become more complex, and radiation dose is not always delivered as intended. Using human factors methods, a radiotherapy treatment delivery process was evaluated, and a redesign was undertaken to determine the effect on system safety. MATERIAL AND METHODS An ethnographic field study and workflow analysis was conducted to identify human factors issues of the treatment delivery process. To address specific issues, components of the user interface were redesigned through a user-centered approach. Sixteen radiation therapy students were then used to experimentally evaluate the redesigned system through a usability test to determine the effectiveness in mitigating use errors. RESULTS According to findings from the usability test, the redesigned system successfully reduced the error rates of two common errors (p<.04 and p<.01). It also improved the mean task completion time by 5.5% (p<.02) and achieved a higher level of user satisfaction. CONCLUSIONS These findings demonstrated the importance and benefits of applying human factors methods in the design of radiation therapy systems. Many other opportunities still exist to improve patient safety in this area using human factors methods.

Clinical Application of High-Dose, Image-Guided Intensity-Modulated Radiotherapy in High-Risk Prostate Cancer

PURPOSE To report the feasibility and early toxicity of dose-escalated image-guided IMRT to the pelvic lymph nodes (LN), prostate (P), and seminal vesicles (SV). METHODS AND MATERIALS A total of 103 high-risk prostate cancer patients received two-phase, dose-escalated, image-guided IMRT with 3 years of androgen deprivation therapy. Clinical target volumes (CTVs) were delineated using computed tomography/magnetic resonance co-registration and included the prostate, portions of the SV, and the LN. Planning target volume margins (PTV) used were as follows: P (10 mm, 7 mm posteriorly), SV (10 mm), and LN (5 mm). Organs at risk (OaR) were the rectal and bladder walls, femoral heads, and large and small bowel. The IMRT was planned with an intended dose of 55.1 Gy in 29 fractions to all CTVs (Phase 1), with P+SV consecutive boost of 24.7 Gy in 13 fractions. Daily online image guidance was performed using bony landmarks and intraprostatic markers. Feasibility criteria included delivery of intended doses in 80% of patients, 95% of CTV displacements incorporated within PTV during Phase 1, and acute toxicity rate comparable to that of lower-dose pelvic techniques. RESULTS A total of 91 patients (88%) received the total prescription dose. All patients received at least 72 Gy. In Phase 1, 63 patients (61%) received the intended 55.1 Gy, whereas 87% of patients received at least 50 Gy. Dose reductions were caused by small bowel and rectal wall constraints. All CTVs received the planned dose in >95% of treatment fractions. There were no Radiation Therapy Oncology Group acute toxicities greater than Grade 3, although there were five incidences equivalent to Grade 3 within a median follow-up of 23 months. CONCLUSION These results suggest that dose escalation to the PLN+P+SV using IMRT is feasible, with acceptable rates of acute toxicity.

A randomized comparison of interfraction and intrafraction prostate motion with and without abdominal compression

BACKGROUND AND PURPOSE To quantify inter- and intrafraction prostate motion in a standard VacLok (VL) immobilization device or in the BodyFix (BF) system incorporating a compression element which may reduce abdominal movement. MATERIALS AND METHODS Thirty-two patients were randomly assigned to VL or BF. Interfraction prostate motion >3 mm was corrected pre-treatment. EPIs were taken daily at the start and end of the first and last treatment beams. Interfraction and intrafraction prostate motion were measured for centre of mass (COM) and individual markers. RESULTS There were no significant differences in interfraction (p0.002) or intrafraction (p0.16) prostate motion with or without abdominal compression. Median intrafraction motion was slightly smaller than interfraction motion in the AP (7.0 mm vs. 7.6 mm) and SI direction (3.2 mm vs. 4.7 mm). The final image captured the maximal intrafraction displacement in only 40% of fractions. Our PTV incorporated >95% of total prostate motion. CONCLUSIONS Intrafraction motion became the major source of error during radiotherapy after online correction of interfraction prostate motion. The addition of 120 mbar abdominal compression to custom pelvic immobilization influenced neither interfraction nor intrafraction prostate motion.

Prostate delineation using CT and MRI for radiotherapy patients with bilateral hip prostheses.

BACKGROUND AND PURPOSE Prostate cancer patients with bilateral hip prostheses (b-HP) are rare, but pose unique challenges for high-dose radiotherapy. The purpose of this study was to determine the effect of b-HP on prostate delineation using CT and MR. METHODS AND MATERIALS The planning CT and MR of 7 patients with b-HP were co-registered. Four observers delineated the prostate on both data sets, blinded to the volumes delineated by their peers and those on the alternate image set. Inter-modality differences and inter-observer variability were quantified by calculating 3D volume overlaps. The effect of prostheses physical extent on these variables was evaluated. MR geometric distortion was explored using the differences in vector distances between three intra-prostatic markers (IPMs) on CT and MR. RESULTS Prostate volumes on CT were consistently larger than MR volumes in all patients when averaged over the 4 observers (+10% to +46%, p<0.001). The mean inter-modality volume overlap was 1.59, which varied significantly between patients (1.35 to 1.82, p=0.04). There was a trend toward smaller inter-observer variability in the MR volumes (1.95 vs. 1.71, p=0.08). No differences could be identified between the IPM vectors on CT and MR. CONCLUSIONS Although limited by a small sample size, this study found that MR prostate volumes were significantly smaller than those from CT for b-HP patients. The largest differences between CT and MR prostate volumes and the greatest inter-observer variability on CT tended to be seen in patients with the largest prostheses. b-HP do not appear to cause measurable MR geometric distortions in the sequences used.

Role of Principal Component Analysis in Predicting Toxicity in Prostate Cancer Patients Treated With Hypofractionated Intensity-Modulated Radiation Therapy

PURPOSE To determine if principal component analysis (PCA) and standard parameters of rectal and bladder wall dose-volume histograms (DVHs) of prostate cancer patients treated with hypofractionated image-guided intensity-modulated radiotherapy (hypo-IMRT) can predict acute and late gastrointestinal (GI) toxicity. METHODS AND MATERIALS One hundred twenty-one patients underwent hypo-IMRT at 3 Gy/fraction, 5 days/week to either 60 Gy or 66 Gy, with daily online image guidance. Acute and late GI and genitourinary (GU) toxicity were recorded weekly during treatment and at each follow-up. All Radiation Therapy Oncology Group (RTOG) criteria toxicity scores were dichotomized as <2 and ≥2. Standard dosimetric parameters and the first five to six principal components (PCs) of bladder and rectal wall DVHs were tested for association with the dichotomized toxicity outcomes, using logistic regression. RESULTS Median follow-up of all patients was 47 months (60 Gy cohort = 52 months; 66 Gy cohort = 31 months). The incidence rates of ≥2 acute GI and GU toxicity were 14% and 29%, respectively, with no Grade ≥3 acute GU toxicity. Late GI and GU toxicity scores ≥2 were 16% and 15%, respectively. There was a significant difference in late GI toxicity ≥2 when comparing the 66 Gy to the 60 Gy cohort (38% vs. 8%, respectively, p = 0.0003). The first PC of the rectal DVH was associated with late GI toxicity (odds ratio [OR], 6.91; p < 0.001), though it was not significantly stronger than standard DVH parameters such as Dmax (OR, 6.9; p < 0.001) or percentage of the organ receiving a 50% dose (V50) (OR, 5.95; p = 0 .001). CONCLUSIONS Hypofractionated treatment with 60 Gy in 3 Gy fractions is well tolerated. There is a steep dose response curve between 60 Gy and 66 Gy for RTOG Grade ≥2 GI effects with the dose constraints employed. Although PCA can predict late GI toxicity for patients treated with hypo-IMRT for prostate cancer, it provides no additional information over using more standard DVH parameters.

Patient-specific PTV margins in radiotherapy for bladder cancer – A feasibility study using cone beam CT ☆

PURPOSE To assess the feasibility of using cone beam computed tomography (CBCT) to generate patient-specific PTV margins for bladder cancer patients treated with radiation therapy (RT). METHODS Eleven patients underwent CT simulation and daily RT (full bladder and empty rectum). CBCT was done prior to each fraction, and the whole bladder was contoured off-line. For the first 15 CBCTs of each patient, the bladder was aligned with CT-simulation bladder (pBladder) to create an occupancy volume (OV). A 5mm isotropic margin was added to OV (OV+5). A measurement-based PTV (mPTV) was generated by measuring maximal displacement between pBladder and OV in six directions. OV, OV+5, mPTV, and a standard PTV (2cm isotropic margin) were compared for absolute and relative volume differences. Using the final 10 CBCT of each patient, the ability of each study volume to encompass the entire CBCT bladder was determined. RESULTS 161/165 CBCT images were of adequate quality for contouring. No daily trend in bladder volume variation was noted. The median absolute volumes (cm(3)) were: 221, 271, 426, 440, and 914 for pBladder, OV, OV+5, mPTV, and standard PTV, respectively. The median ratios of the study volumes/pBladder were: 1.4 OV, 2.1 OV+5, 2.4 mPTV, 4.1 standard PTV. OV+5 was smaller than mPTV in 9 patients. There was considerable inter-patient variability in study volumes and no apparent association of the magnitude of margin expansion and pBladder. The bladder was encompassed in 69%, 99%, 99%, and 100% of the final 10 fractions by OV, OV+5, mPTV, and standard PTV, respectively. CONCLUSIONS The use of daily CBCT to generate patient-specific PTV margins is feasible and results in a marked reduction in the irradiated volume compared to population-based margins. As daily bladder volume varied unpredictably with considerable differences between patients, these findings support the use of patient-specific PTV margin expansions for bladder radiotherapy.