Characterisation of rectal motion during neo-adjuvant radiochemotherapy for rectal cancer with image-guided tomotherapy: implications for adaptive dose escalation strategies.

BACKGROUND: Interest in boosting the dose to the tumour during neo-adjuvant radiochemotherapy for rectal cancer is ever increasing, especially within the frame of adaptive radiotherapy. Rectal motion remains a potentially important obstacle to the full exploitation of this approach and needs to be carefully investigated. MATERIAL AND METHODS: The main purposes of this work were to: a) quantify rectal motion on all fractions of a treatment course; and b) assess margins for adaptive boosting in the second part of the treatment in order to benefit of tumour reduction during treatment. Ten consecutive patients treated with image-guided tomotherapy (41.4 Gy, 18 fractions) were selected. The cranial half of the rectum (subject to motion) was contoured by a single observer on daily MVCTs. The variations of rectal volume and of the envelope of rectum positions were investigated (169 MVCTs). The impact of applying different margins to the rectum in including all its possible positions was also investigated when considering the planning kVCT, the first fraction MVCT, the half-treatment MVCT or the median rectal contours of the whole or second half of treatment as reference volumes. RESULTS: Rectal volume reduced during treatment in all patients, with a significant time-trend in 6/10 patients. The median values of the envelope volumes were 129 cm(3) and 87 cm(3) in the first and second half of the treatment, respectively. On average, 95% of the rectal envelope was included by an isotropic expansion of 12 mm and 5 mm of the median contours when considering the whole or the second half of the treatment, respectively. CONCLUSION: A significant reduction of rectal volume was found in the second part of the treatment where rectal mobility was limited. As a consequence, relatively small margins may be used around the residual tumour volume when adaptive boost is delivered in the second half of the treatment.

Inter-observer variability in contouring the penile bulb on CT images for prostate cancer treatment planning.

Several investigations have recently suggested the existence of a correlation between the dose received by the penile bulb (PB) and the risk of erectile dysfunction (ED) after radical radiotherapy for clinically localized prostate carcinoma. A prospective multi-Institute study (DUE-01) was implemented with the aim to assess the predictive parameters of ED. Previously, an evaluation of inter-observer variations of PB contouring was mandatory in order to quantify its impact on PB dose-volume parameters by means of a dummy run exercise. Fifteen observers, from different Institutes, drew the PB on the planning CT images of ten patients; inter-observer variations were analysed in terms of PB volume variation and cranial/caudal limits. 3DCRT treatment plans were simulated to evaluate the impact of PB contouring inter-variability on dose-volume statistics parameters. For DVH analysis the values of PB mean dose and the volume of PB receiving more than 50 Gy and 70 Gy (V50 and V70, respectively) were considered. Systematic differences from the average values were assessed by the Wilcoxon test. Seven observers systematically overestimated or underestimated the PB volume with deviations from the average volumes ranging between -48% and +34% (p < 0.05). The analysis of the cranial and caudal borders showed a prevalence of random over systematic deviations. Inter-observer contouring variability strongly impacts on DVH parameters, although standard deviations of inter-patient differences were larger than inter-observer variations: 14.5 Gy versus 6.8 Gy for mean PB dose, 23.0% versus 11.0% and 16.8% versus 9.3% for V50 and V70 respectively. In conclusion, despite the large inter-observer variation in contouring PB, a large multi-centric study may have the possibility to detect a possible correlation between PB % dose-volume parameters and ED. The impact of contouring uncertainty could be reduced by "a posteriori" contouring from a single observer or by introducing Magnetic Resonance Imaging (MRI) in the planning procedures and/or in improving the skill of observers through post-dummy run tutoring of those observers showing large systematic deviations from the mean.

Introducing the Jacobian-volume-histogram of deforming organs: application to parotid shrinkage evaluation.

The Jacobian of the deformation field of elastic registration between images taken during radiotherapy is a measure of inter-fraction local deformation. The histogram of the Jacobian values (Jac) within an organ was introduced (JVH-Jacobian-volume-histogram) and first applied in quantifying parotid shrinkage. MVCTs of 32 patients previously treated with helical tomotherapy for head-neck cancers were collected. Parotid deformation was evaluated through elastic registration between MVCTs taken at the first and last fractions. Jac was calculated for each voxel of all parotids, and integral JVHs were calculated for each parotid; the correlation between the JVH and the planning dose-volume histogram (DVH) was investigated. On average, 82% (±17%) of the voxels shrinks (Jac < 1) and 14% (±17%) shows a local compression >50% (Jac < 0.5). The best correlation between the DVH and the JVH was found between V10 and V15, and Jac < 0.4-0.6 (p < 0.01). The best constraint predicting a higher number of largely compressing voxels (Jac0.5<7.5%, median value) was V15 ≥ 75% (OR: 7.6, p = 0.002). Jac and the JVH are promising tools for scoring/modelling toxicity and for evaluating organ/contour variations with potential applications in adaptive radiotherapy.

A two-variable linear model of parotid shrinkage during IMRT for head and neck cancer.

PURPOSE: To assess anatomical, clinical and dosimetric pre-treatment parameters, possibly predictors of parotid shrinkage during radiotherapy of head and neck cancer (HNC). MATERIALS: Data of 174 parotids from four institutions were analysed; patients were treated with IMRT, with radical and adjuvant intent. Parotid shrinkage was evaluated by the volumetric difference (DeltaV) between parotid volumes at the end and those at the start of the therapy, as assessed by CT images (MVCT for 40 patients, KVCT for 47 patients). Correlation between DeltaVcc/% and a number of dosimetric, clinical and geometrical parameters was assessed. Univariate as well as stepwise logistic multivariate (MVA) analyses were performed by considering as an end-point a DeltaVcc/% larger than the median value. Linear models of DeltaV (continuous variable) based on the most predictive variables found at the MVA were developed. RESULTS: Median DeltaVcc/% were 6.95 cc and 26%, respectively. The most predictive independent variables of DeltaVcc at MVA were the initial parotid volume (IPV, OR: 1.100; p=0.0002) and Dmean (OR: 1.059; p=0.038). The main independent predictors of DeltaV% at MVA were age (OR: 0.968; p=0.041) and V40 (OR: 1.0338; p=0.013). DeltaVcc and DeltaV% may be well described by the equations: DeltaVcc=-2.44+0.076 Dmean (Gy)+0.279 IPV (cc) and DeltaV%=34.23+0.192 V40 (%)-0.2203 age (year). The predictive power of the DeltaVcc model is higher than that of the DeltaV% model. CONCLUSIONS: IPV/age and Dmean/V40 are the major dosimetric and clinical/anatomic predictors of DeltaVcc and DeltaV%. DeltaVcc and DeltaV% may be well described by bi-linear models including the above-mentioned variables.

Modeling set-up error by daily MVCT for prostate adjuvant treatment delivered in 20 fractions: Implications for the assessment of the optimal correction strategies.

PURPOSE: To optimise image-guided radiotherapy (IGRT) approaches in set-up error correction for hypofractionated adjuvant treatment of prostate cancer using helical tomotherapy (HT). METHODS AND MATERIALS: HT unit provides megavoltage - CT (MVCT) imaging capability for daily patient set-up. The intrinsic uncertainty of the available image registration techniques was first investigated on a pelvic phantom. To optimise different set-up correction strategies, MVCT data of 37 patients treated with 58 Gy delivered in 20 fractions were analyzed. 620 MVCT images were globally available for the analysis. Daily on-line set-up correction without any action level was applied for 27/37 patients. The residual and the effective set-up error were assessed. For 10/37 patients an off-line correction strategy with an action level was applied. RESULTS: Phantom measurements showed an intrinsic uncertainty in MVCT imaging and registration around 0.6 mm (+/-0.5 mm) for each of the three main axes. The minimum value of the residual systematic error was found at 7th-10th session, with values between 0.7 and 1.1 mm (1 SD); a systematic residual error <2 mm for all directions was in any case found at 3rd-4th session. This result was also confirmed by the effective systematic set-up error analysis, with a minimum value within 1.5mm nearly at the 4th or 5th fraction. CONCLUSIONS: Although the minimum systematic residual error is reached at 7th-10th treatment session, the effective systematic set-up error analysis confirmed that an off-line correction at the 4th fraction without any action level may be a robust compromise with a large sparing of time and resources compared to on-line correction.

Helical tomotherapy for scalp recurrence of primary eccrine mucinous adenocarcinoma.

Primary cutaneous mucinous carcinomas originating from sweat glands are rare tumors with patterns of spread that are difficult to predict. We present a case of a five times recurring eccrine mucinous adenocarcinoma of the scalp, previously treated with surgery and adjuvant radiation therapy. After magnetic resonance imaging (MRI) and 18F-fluoro-2-deoxyglucose positron-emission tomography/computed tomography (18FDG-PET/CT), which documented local recurrence, the patient was considered eligible for salvage irradiation of the scalp. We decided to use helical tomotherapy, which combines conformity of dose delivery with the possibility of daily control of the setup accuracy. Forty gray (2Gy/fraction) to the planning target volume and 50 Gy (2.5Gy/fraction) to the biological target volume defined on the basis of 18FDG-PET/CT was prescribed with a simultaneous integrated boost technique. After 12 fractions the patient was submitted to intermediate evaluation by 18FDG-PET/CT, which showed a partial response to the treatment. After 2, 4, 8, and 12 months, 18FDG-PET/CT showed a complete metabolic local response. This experience suggests a possible role of 18FDG-PET/CT-guided helical tomotherapy as an alternative to repeated and frequently demolitive surgery approaches.

Physics aspects of prostate tomotherapy: planning optimization and image-guidance issues.

PURPOSE: To review planning and image-guidance aspects of more than 3 years experience in the treatment of prostate cancer with Helical Tomotherapy (HT). METHODS AND MATERIALS: Planning issues concerning two Phase I-II clinical studies were addressed: in the first one, 58 Gy in 20 fractions were delivered to the prostatic bed for post-prostatectomy patients: in the second one, a simultaneous integrated boost (SIB) approach was applied for radical treatment, delivering 71.4-74.2 Gy to the prostate in 28 fractions. On-line daily MVCT image guidance was applied: bone match was used for post-operative patients while prostate match was applied for radically treated patients. MVCT data of a large sample of both categories of patients were reviewed. RESULTS: At now, more than 250 patients were treated. Planning data show the ability of HT in creating highly homogeneous dose distributions within PTVs. Organs at risk (OAR) sparing also showed to be excellent. HT was also found to favorably compare to inversely-optimized IMAT in terms of PTVs coverage and dose distribution homogeneity. In the case of pelvic nodes irradiation, a large sparing of bowel was evident compared to 3DCRT and conventional 5-fields IMRT. The analysis of MVCT data showed a limited motion of the prostate (about 5% of the fractions show a deviation > or =3 mm in posterior-anterior direction), due to the careful application of rectal emptying procedures. Based on phantom measurements and on the comparison with intra-prostatic calcification-based match, direct visualization prostate match seems to be sufficiently reliable in assessing shifts > or =3 mm. CONCLUSIONS: HT offers excellent planning solutions for prostate cancer, showing to be highly efficient in a SIB scenario. Daily MVCT information showed evidence of a limited motion of the prostate in the context of rectal filling control obtained by instructing patients in self-administrating a rectal enema.

Evidence of limited motion of the prostate by carefully emptying the rectum as assessed by daily MVCT image guidance with helical tomotherapy.

PURPOSE: To assess setup and organ motion error by means of analysis of daily megavoltage computed tomography (MVCT) of patients treated with hypofractionated helical tomotherapy (71.4-74.2 Gy in 28 fractions). METHODS AND MATERIALS: Data from 21 patients were analyzed. Patients were instructed to empty the rectum carefully before planning CT and every morning before therapy by means of a self-applied rectal enema. The position of the prostate was assessed by means of automatic bone matching (BM) with the planning kilovoltage CT (BM, setup error) followed by a direct visualization (DV) match on the prostate. Deviations between planning and therapy positions referred to BM and BM + DV were registered for the three main axes. In case of a full rectum at MVCT with evident shift of the prostate, treatment was postponed until after additional rectal emptying procedures; in this case, additional MVCT was performed before delivering the treatment. Data for 522 fractions were available; the impact of post-MVCT procedure was investigated for 17 of 21 patients (410 fractions). RESULTS: Prostate motion relative to bony anatomy was limited. Concerning posterior-anterior shifts, only 4.9% and 2.7% of fractions showed deviation of 3 mm or greater of the prostate relative to BM without and with consideration of post-MVCT procedures, respectively. Interobserver variability for BM + DV match was within 0.8 mm (1 SD). CONCLUSIONS: Daily MVCT-based correction is feasible. The BM + DV matching was found to be consistent between operators. Rectal emptying using a daily enema is an efficient tool to minimize prostate motion, even for centers that have not yet implemented image-guided radiotherapy.

Results of a two-year quality control program for a helical tomotherapy unit.

BACKGROUND AND PURPOSE: Image-guided helical tomotherapy (HT) is a new modality for delivering intensity modulated radiation therapy (IMRT) with helical irradiation: the slip ring continuously rotates while the couch moves into the bore. The radiation source (Linac, 6 MV) is collimated into a fan beam and modulated by means of a binary multileaf collimator (MLC). A xenon detector array, opposite the radiation source, allows a megavoltage-CT (MVCT) acquisition of patient images for set-up verification. The aim of this paper is to report the results of a two-year quality control (QC) program for the physical and dosimetric characterization of an HT unit installed at our Institute and clinically activated in November 2004, in order to monitor and verify the stability and the reliability of this promising radiation treatment unit. MATERIALS AND METHODS: Conventional Linac acceptance protocols (ATP) and QC protocols were adapted to HT with the addition of specific items reflecting important differences between the two irradiation modalities. QC tests can be summarized as: (a) mechanical and geometrical characterization of the system's components: evaluation of alignment among radiation source-gantry rotation plan-jaws-MLC-MVCT; (b) treatment beam configuration in static condition: depth dose curves (PDD) and profiles, output factors, output reproducibility and linearity; (c) dynamic component characterization: accuracy and reproducibility of MLC positioning; rotational output reproducibility and linearity, leaf latency, couch movement constancy; (d) gantry-couch and MLC-gantry synchronization; and (e) MVCT image quality. Peculiar periodicity specific tolerance and action levels were defined. Ionization chambers (Exradin A1SL 0.056 cc), films (XOmat-V/EDR2), water and solid water phantoms were used to perform quality assurance measurements. RESULTS: Over a two-year period the final average output variation after possible beam output adjustment was -0.2+/-1% for the static condition and equal to 0+/-1% for the rotational condition: around 98% of the collected output data was within the action level compared to 94% if no beam output adjustment was considered. An average energy variation of -0.4+/-0.4% was found. The daily absolute dose verification of IMRT plans showed a dose reproducibility of -0.5+/-1.2% and -0.4+/-2.2%, for low and high dose gradient regions, respectively. Source-jaws-MLC and MVCT alignment results and jaw and leaf positioning accuracy were +/-1mm. Couch-gantry-MLC synchrony tests showed good stability level (