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Purpose: To evaluate the effect of rectal distention on the planning computed tomogram on freedom from biochemical failure (FFBF) of prostate cancer patients treated with image-guided conformal arc radiotherapy., Methods and Materials: The outcomes of 238 patients with T1-T3N0M0 tumors were analyzed, with a median follow-up of 53 months (range, 24-93 months). In 213 patients, daily co-registration of X-rays and digitally reconstructed radiographs was used for positioning, whereas in 25 patients positioning was done using direct prostate visualization with implanted markers. The rectal average cross-sectional area was determined on the planning computed tomogram., Results: The 5-year freedom from Grade 3 to 4 late gastrointestinal and urinary side effect, according to the Radiation Therapy Oncology Group criteria, was 100% and 99.4% respectively. The 5-year FFBF was 88.4%. On multivariate analysis the following variables were significantly related to worse FFBF: risk group according to the National Comprehensive Cancer Network (high- to very high risk vs. intermediate- to low-risk), dose (70 vs. 78 Gy), average cross-sectional area (> or =16 vs. <16 cm(2)) and, unexpectedly, the use of implanted markers as opposed to bony structures for patient positioning. In retrospect, the margins around the clinical target volume appeared to be inadequate in the cases in which markers were used., Conclusion: Overall, the outcome of patients treated with image-guided conformal arc radiotherapy is excellent. We were able to confirm the negative prognostic impact of a distended rectum on the planning computed tomogram described by others. The study illustrates the potential danger of image guidance techniques as to margin reduction around the clinical target volume.

Purpose: To evaluate the prognostic significance of primary tumor location and to examine whether the effect of adjuvant radiotherapy on survival varies according to tumor location in women with axillary node-positive (ALN+) breast cancer (BC)., Patients and Methods: Data were abstracted from the SEER database for 24,410 women aged 25-95 years, diagnosed between 1988-1997 with nonmetastatic T1-T2, ALN+ BC. Subgroup analyses were performed using interactions within proportional hazards models. Event was defined as death from any cause. Prognostic variables were selected using Akaike Information Criteria. Joint significances of subgroups were evaluated with Wald test., Results: Median follow-up was 10 years. In joint models, statistically significant interactions were found between tumor location, nodal involvement, type of surgery, and radiotherapy. Factorial presentation of interactions showed consistent 13% proportional reduction of mortality in all subgroups, except in women with medial tumors with > or = 4 ALN+ treated with mastectomy. In this subgroup, use of radiotherapy was associated with a 16% proportional increase in mortality., Conclusion: Medial tumor location is a significant adverse prognostic factor that should be considered in treatment decision- making for women with ALN+ BC. Improved survival was observed with radiotherapy use in all subgroups, except in women with medial tumors with > or = 4 ALN+ treated with postmastectomy radiotherapy. These findings raise concern that the favorable effect of radiotherapy may be offset by excess toxicities in the latter subgroup.

Purpose: To investigate predictors for gastrointestinal (GI) and genitourinary (GU) acute toxicity after a short-course hypofractionated radiotherapy regimen for prostate cancer., Materials and Methods: Three institutions included 102 patients with T1-T3N0M0 prostate cancer in a Phase II study. Patients were treated with 56 Gy in 16 fractions over 4 weeks. Acute toxicity was scored weekly during treatment and 1 and 2 months after treatment using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria extended with additional symptoms and the International Prostate Symptom Index (IPSS). Correlation with a number of clinical and dosimetric parameters was assessed by univariate and multivariate analyses., Results: No Grade 3 or 4 GI side effects were observed. Grades 1 and 2 rectal GI toxicity occurred in 36%, and 38%, respectively. Corresponding figures for Grades 1 and 2 GU toxicity were 42% and 39%, respectively. Grade 3 or higher GU toxicity was detected in 4% of patients. In multivariate analysis, percent rectal volumes higher than 8% receiving doses >/=53 Gy (V(53)) were statistically correlated to Grade 2 acute rectal reaction (p = 0.006). For GU morbidity, only the IPSS pretreatment score was independently associated (p = 0.0036) with an increase in GU acute effects., Conclusions: Acute GU and GI toxicity were comparable with other series. Our data show that increased incidence and intensity of acute toxicity is a transient effect related to shorter overall treatment time rather than a larger effect in biological equivalent dose with respect to a conventional fractionation regime.

The limited ability to control for the location of a tumour compromises the accuracy with which radiation can be delivered to tumour-bearing tissue. The resultant requirement for larger treatment volumes to accommodate target uncertainty restricts the radiation dose because more surrounding normal tissue is exposed. With image-guided radiotherapy (IGRT) these volumes can be optimized and tumoricidal doses can be delivered, achieving maximal tumour control with minimal complications. Moreover, with the ability of high-precision dose delivery and real-time knowledge of the target volume location, IGRT has initiated the exploration of new indications for radiotherapy, some of which were previously considered infeasible.

We treated 36 cases of stage I/II non-small cell lung cancer in inoperable patients. Treatments were planned to a total isocenter dose of 60Gy (8x7.5Gy) based on a dynamic field shaping arc, employing one arc to span as much area as possible and if needed additional weighted segments. The 2 year infield progression free probability is 65%. Disease-specific survival is 75% at 2 years. No patients experienced grade 3-4 toxicity.

Purpose: The aim of this study was to compare setup accuracy of NovalisBody stereoscopic X-ray positioning using implanted markers in the prostate vs. bony structures in patients treated with dynamic conformal arc radiotherapy for prostate cancer., Methods and Materials: Random and systematic setup errors (RE and SE) of the isocenter with regard to the center of gravity of three fiducial markers were measured by means of orthogonal verification films in 120 treatment sessions in 12 patients. Positioning was performed using NovalisBody semiautomated marker fusion. The results were compared with a control group of 261 measurements in 15 patients who were positioned with NovalisBody automated bone fusion. In addition, interfraction and intrafraction prostate motion was registered in the patients with implanted markers., Results: Marker-based X-ray positioning resulted in a reduction of RE as well as SE in the anteroposterior, craniocaudal, and left-right directions compared with those in the control group. The interfraction prostate displacements with regard to the bony pelvis that could be avoided by marker positioning ranged between 1.6 and 2.8 mm for RE and between 1.3 and 4.3 mm for SE. Intrafraction random and systematic prostate movements ranged between 1.4 and 2.4 mm and between 0.8 and 1.3 mm, respectively., Conclusion: The problem of interfraction prostate motion can be solved by using implanted markers. In addition, the NovalisBody X-ray system performs more accurately with markers compared with bone fusion. Intrafraction organ motion has become the limiting factor for margin reduction around the clinical target volume.

In this paper the clinical introduction of stereoscopic kV-imaging in combination with a 6 degrees-of-freedom (6 DOF) robotics system and breathing synchronized irradiation will be discussed in view of optimally reducing interfractional as well as intrafractional geometric uncertainties in conformal radiation therapy. Extracranial cases represent approximately 70% of the patient population on the NOVALIS treatment machine (BrainLAB A.G., Germany) at the AZ-VUB, which is largely due to the efficiency of the real-time positioning features of the kV-imaging system. The prostate case will be used as an example of those target volumes showing considerable changes in position from day-to-day, yet with negligible motion during the actual course of the treatment. As such it will be used to illustrate the on-line target localization using kV-imaging and 6 DOF patient adjustment with and without implanted radio-opaque markers prior to treatment. Small lung lesion will be used to illustrate the system's potential to synchronize the irradiation with breathing in coping with intrafractional organ motion.

We evaluated setup accuracy of NovalisBody stereoscopic X-ray positioning with automated correction for rotational errors with the Robotics Tilt Module in patients treated with conformal arc radiotherapy for prostate cancer. The correction of rotational errors was shown to reduce random and systematic errors in all directions. (NovalisBody and Robotics Tilt Module are products of BrainLAB A.G., Heimstetten, Germany).

Purpose: To evaluate the early side effects of a short course hypofractionated radiotherapy regimen in prostate cancer., Materials and Methods: Three institutions (IRE, AZ VUB, GUH) included 36 patients with T1-T3N0M0 prostate cancer in a phase II study. Patients were treated with 56 Gy in 16 fractions over 4 weeks. Early side effects were scored using the RTOG/EORTC criteria and the international prostate symptom index (IPSI) weekly during treatment and 1 and 2 months afterwards. The results were compared with two control groups of patients previously treated with conventional fractionation at AZ VUB (238 patients) and GUH (114 patients)., Results: None of the patients experienced grade 3-4 toxicity. Grade 1-2 Gastro-intestinal (GI), grade 2 GI, grade 1-2 Genito-urinary (GU) and grade 2 GU toxicity occurred in 75%, 36%, 75% and 44% for the hypofractionation schedule. The corresponding figures were 25-44%, 6-29%, 47-53% and 16-44% for the control groups (p<0.01 for grade 1-2 GI and GU toxicity). Two months after treatment all GU and the majority of GI symptoms had resolved. The IPSI increased from (average +/-1 SD) 5.6+/-4 pre-treatment to 10.0+/-6 during week 2-4 and had normalized (5.2+/-4) two months after treatment., Conclusions: Though no grade 3-4 side effects were observed, the investigated schedule results in a marked increase of grade 1-2 early side effects as compared to a conventional regimen. Side effects resolved within two months post-treatment.

Background and Purpose: Recalculating dose distributions using measured IMRT fluence fields imported into the treatment planning system (TPS) to evaluate the technical feasibility of a prototype developed for breathing synchronized irradiation., Patients and Methods: DMLC-IMRT fluence patterns acquired on radiographic film, generated by the linac in non-gated and gated mode, have been imported into the TPS. The effect of dose blurring and possible interplay between organ motion and leaf motion, and the efficacy of a breathing synchronized irradiation technique (an adapted version of a commercially available image-guidance system: NOVALIS BODY/ExacTrac4.0, BrainLAB AG) have been evaluated using radiographic film mounted to a simple phantom simulating a breathing pattern of 16 cycles per minute and covering a distance of 4 cm to obtain the resulting fluence maps. Two situations have been investigated to illustrate this principle: (a) a tumor located close to the diaphragm to assess the influence of organ motion on the dose to the target volume as well as to the gastro-intestinal tract that presents a high risk at intersecting with the beam during the breathing cycle. (b) A mediastinal lesion requiring complicated fluence patterns., Results: Importing measured fluence maps yielded highly disturbed reconstructed dose distributions in case of the non-gated delivery with the phantom in motion (both orthogonal and parallel to the leaf direction), whereas the measurements from the static (film fixed in space) and the gated delivery showed good agreement with the original theoretical dose distribution. These findings have been confirmed by the dose-volume histograms, corresponding tumor control probabilities, conformity index and dose heterogeneity values. The normal tissue complication probabilities investigated in this study seem to be affected to a lesser degree, which concurs with the observation that the motion effects result in a dose spread in the direction of motion. The applied breathing synchronization technique introduced an increased treatment time with a factor 3-4., Conclusions: The use of measured fluence fields, delivered by the linac in non-gated and gated mode, as imported fluence maps for the treatment planning system is an interesting quality assurance tool and revealed the dramatic impact of dose blurring and interplay between DMLC-IMRT dose delivery and organ motion, as well as the potential of breathing synchronization to resolve this issue. The possible advantage of breathing synchronized irradiation is compromised with an increased treatment time.

Background and Purpose: The aim of this study is to investigate the positional accuracy of a prototype X-ray imaging tool in combination with a real-time infrared tracking device allowing automated patient set-up in three dimensions., Material and Methods: A prototype X-ray imaging tool has been integrated with a commercially released real-time infrared tracking device. The system, consisting of two X-ray tubes mounted to the ceiling and a centrally located amorphous silicon detector has been developed for automated patient positioning from outside the treatment room prior to treatment. Two major functions are supported: (a) automated fusion of the actual treatment images with digitally reconstructed radiographs (DRRs) representing the desired position; (b) matching of implanted radio opaque markers. Measurements of known translational (up to 30.0mm) and rotational (up to 4.0 degrees ) set-up errors in three dimensions as well as hidden target tests have been performed on anthropomorphic phantoms., Results: The system's accuracy can be represented with the mean three-dimensional displacement vector, which yielded 0.6mm (with an overall SD of 0.9mm) for the fusion of DRRs and X-ray images. Average deviations between known translational errors and calculations varied from -0.3 to 0.6mm with a standard deviation in the range of 0.6-1.2mm. The marker matching algorithm yielded a three-dimensional uncertainty of 0.3mm (overall SD: 0.4mm), with averages ranging from 0.0 to 0.3mm and a standard deviation in the range between 0.3 and 0.4mm., Conclusions: The stereoscopic X-ray imaging device integrated with the real-time infrared tracking device represents a positioning tool allowing for the geometrical accuracy that is required for conformal radiation therapy of abdominal and pelvic lesions, within an acceptable time-frame.

Purpose: To evaluate accuracy and time requirements of a stereoscopic X-ray-based positioning system in patients receiving conformal radiotherapy to the prostate., Methods and Materials: Setup errors of the isocenter with regard to the bony pelvis were measured by means of orthogonal verification films and compared to conventional positioning (using skin drawings and lasers) and infrared marker (IR) based positioning in each of 261 treatments. In each direction, the random error represents the standard deviation and the systematic error the absolute value of the mean position. Time measurements were done in 75 treatments., Results: Random errors with the X-ray positioning system in the anteroposterior (AP), lateral, and longitudinal direction were (average +/- 1 standard deviation) 2 +/- 0.6 mm, 1.7 +/- 0.6 mm, and 2.4 +/- 0.7 mm. The corresponding values of conventional as well as IR positioning were significantly higher (p < 0.01). Systematic errors for X-ray positioning were 1.1 +/- 1.2 mm AP, 0.6 +/- 0.5 mm laterally, and 1.5 +/- 1.6 mm longitudinally. Conventional and IR marker-based positioning showed significantly larger systematic errors AP and laterally, but longitudinally, the difference was not significant. Depending on the axis looked at, errors of >or=5 mm occurred in 2%-14% of treatments after X-ray positioning, 13%-29% using IR markers, and 28%-53% with conventional positioning. Total linac time for one treatment session was 14 min 51 s +/- 4 min 18 s, half of which was used for the X-ray-assisted positioning procedure., Conclusion: X-ray-assisted patient positioning significantly improves setup accuracy, at the cost of an increased treatment time.

Background and Purpose: To evaluate the treatment efficiency of different conformal radiation therapy techniques in prostate cancer., Materials and Methods: Three major classes of intensity-modulated radiation therapy (IMRT) delivery as well as a conformal rotation technique have been evaluated: sequential tomotherapy, dynamic multileaf collimation (DMLC) with conventional MLC, DMLC with miniMLC and dynamic field shaping arc. Treatment planning for the IMRT techniques has been performed with inverse planning. Forward planning was used for the dynamic arc technique. The four techniques have been compared to treat two different prostate cases with a conservative target dose of 70 Gy: a convex shaped target volume and one containing concavities formed by the bladder and rectum. Cumulative dose volume histograms, tumor control probability and normal tissue complication probability, conformity index and dose heterogeneity, and finally efficiency of treatment delivery have been evaluated., Results: For the convex shaped target, all treatment modalities met the desired treatment goals, although the conventional MLC delivered more dose to the bladder. Compared to the dynamic arc modality, both tomotherapy and the conventional MLC technique needed a tenfold higher number of monitor units per target dose, and the miniMLC a twofold higher number. The same trend has been observed for the concave target, yet the dynamic arc did not meet the desired dose reduction for the rectum. The miniMLC configuration represented the best compromise for both targets with respect to treatment goals and delivery efficiency. Sequential tomotherapy performed adequately with respect to conformity at the cost of efficiency., Conclusions: Together with conformity and delivery efficiency the shape of the target should be considered as an important parameter in the selection of the treatment modality.

Purpose: To evaluate an infrared (IR) marker-based positioning system in patients receiving conformal radiotherapy for prostate cancer., Methods and Materials: During 553 treatments, the ability of the IR system to automatically position the isocenter was recorded. Setup errors were measured by means of orthogonal verification films and compared to conventional positioning (using skin drawings and lasers) in 184 treatments., Results: The standard deviation of anteroposterior (AP) and lateral setup errors was significantly reduced with IR marker positioning compared to conventional: 2 vs. 4.8 mm AP (p < 0.01) and 1.6 vs. 3.5 mm laterally (p < 0.01). Longitudinally, the difference was not significant (3.5 vs. 3.0 mm). Systematic errors were on the average smaller AP and laterally for the IR method: 4.1 vs. 7.8 mm AP (p = 0.01) and 3.1 vs. 5.6 mm lateral (p = 0.07). Longitudinally, the IR system resulted in somewhat larger systematic errors: 5.0 vs. 3.4 mm for conventional positioning (p = 0.03). The use of an off-line correction protocol, based on the average deviation measured over the first four fractions, allowed virtual elimination of systematic errors. Inability of the IR system to correctly locate the markers, leading to an executional failure, occurred in 21% of 553 fractions., Conclusion: IR marker-assisted patient positioning significantly improves setup accuracy along the AP and lateral axes. Executional failures need to be reduced.