Duration of androgen suppression in the treatment of prostate cancer.

BACKGROUND: The combination of radiotherapy plus long-term medical suppression of androgens (> or = 2 years) improves overall survival in patients with locally advanced prostate cancer. We compared the use of radiotherapy plus short-term androgen suppression with the use of radiotherapy plus long-term androgen suppression in the treatment of locally advanced prostate cancer. METHODS: We randomly assigned patients with locally advanced prostate cancer who had received external-beam radiotherapy plus 6 months of androgen suppression to two groups, one to receive no further treatment (short-term suppression) and the other to receive 2.5 years of further treatment with a luteinizing hormone-releasing hormone agonist (long-term suppression). An outcome of noninferiority of short-term androgen suppression as compared with long-term suppression required a hazard ratio of more than 1.35 for overall survival, with a one-sided alpha level of 0.05. An interim analysis showed futility, and the results are presented with an adjusted one-sided alpha level of 0.0429. RESULTS: A total of 1113 men were registered, of whom 970 were randomly assigned, 483 to short-term suppression and 487 to long-term suppression. After a median follow-up of 6.4 years, 132 patients in the short-term group and 98 in the long-term group had died; the number of deaths due to prostate cancer was 47 in the short-term group and 29 in the long-term group. The 5-year overall mortality for short-term and long-term suppression was 19.0% and 15.2%, respectively; the observed hazard ratio was 1.42 (upper 95.71% confidence limit, 1.79; P=0.65 for noninferiority). Adverse events in both groups included fatigue, diminished sexual function, and hot flushes. CONCLUSIONS: The combination of radiotherapy plus 6 months of androgen suppression provides inferior survival as compared with radiotherapy plus 3 years of androgen suppression in the treatment of locally advanced prostate cancer. (ClinicalTrials.gov number, NCT00003026.)

Assessment of rectal distention in radiotherapy of prostate cancer using daily megavoltage CT image guidance.

PURPOSE: Assessment of rectal distention in a group of patients who are not receiving daily rectum emptying procedures during a course of prostate cancer radiotherapy to investigate which patients could benefit from daily rectum emptying. METHODS AND MATERIALS: Eighteen patients underwent daily megavoltage CT (MVCT) scanning with positioning based on bony anatomy. Emptying the rectum was only performed before planning CT and not during the actual treatment. The rectal average cross-sectional area (CSA) was determined on the MVCTs. The relative CSA (CSA(rel)) was defined as CSA on MVCT / CSA on planning CT. Additional prostate soft tissue matching was performed to verify the influence of rectal distention on prostate motion. RESULTS: Two distinct subgroups could be defined a posteriori. One group had a limited and stable rectal distention with a CSA (mean+/-SD) of 6.6+/-2.1cm(2), in contrast with a second group with large and variable rectal filling with a CSA of 9.5+/-3.7cm(2) (p<0.01). Mean anterior-posterior prostate displacement was 0.4+/-2.4 mm in the stable group versus -2.4+/-6.1 mm in the unstable group (p<0.01). A mean CSA(rel) of 1.35 of the first 3 days as cut-off value allowed for a correct a priori classification of 90% and 85% of the patients from groups 1 and 2, respectively. CONCLUSION: Based on a few measurements of the CSA by daily MVCT imaging at the first days of treatment, rectum emptying may be omitted in part of the patients.

The effect of adjuvant radiotherapy on mortality differs according to primary tumor location in women with node-positive breast cancer.

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.

Helical tomotherapy with simultaneous integrated boost for high-risk and lymph node-positive prostate cancer: early report on acute and late toxicity.

The use of whole pelvic radiotherapy (WPRT) for high-risk and lymph node-positive prostate cancer (PC) remains controversial. The purpose of this study was to evaluate the acute toxicity associated with helical tomotherapy in the treatment of high-risk and lymph node-positive prostate cancer. To do so, twenty-eight patients were treated to a dose of 54 Gy in daily fractions of 1.8 Gy to the pelvic lymph node area, while the prostate and the seminal vesicles received a simultaneous integrated boost (SIB) to a dose of 70.5 Gy. A SIB to a dose of 60 Gy was delivered to the involved lymph node region(s) in 8 patients with pelvic lymph node metastases. All patients received concurrent hormonal treatment. The incidence of grade 2 and 3 acute gastrointestinal (GI) toxicity was 7% and 0% respectively. Grade 2 and 3 acute genito-urinary (GU) side effects were observed in 14% and 4% of the patients respectively. No grade 4 side effects occurred. No increased toxicity was observed in the 8 lymph node-positive patients receiving a simultaneous pelvic nodal dose escalation. In conclusion, WPRT with a SIB to the prostate and seminal vesicles by helical tomotherapy resulted in a favourable toxicity profile. Pelvic nodal dose escalation in node-positive patients is feasible without increasing toxicity.

X-ray-assisted positioning of patients treated by conformal arc radiotherapy for prostate cancer: comparison of setup accuracy using implanted markers versus bony structures.

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.

A feasibility study of image-guided hypofractionated conformal arc therapy for inoperable patients with localized non-small cell lung cancer.

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.

Setup accuracy of stereoscopic X-ray positioning with automated correction for rotational errors in patients treated with conformal arc radiotherapy for prostate cancer.

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).

Importing measured field fluences into the treatment planning system to validate a breathing synchronized DMLC-IMRT irradiation technique.

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.

Phase II study of a four-week hypofractionated external beam radiotherapy regimen for prostate cancer: report on acute toxicity.

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.

The curative role of radiotherapy in adenocarcinoma of the prostate in patients under 55 years of age: a rare cancer network retrospective study.

To determine whether radiation therapy could be an acceptable alternative to surgery in young patients with adenocarcinoma of the prostate, we analysed the outcome of 39 patients aged under 55 with organ confined tumours who received external radiation therapy in a curative intent. Our results suggest that similar local control in younger and older patients can be expected from either external beam radiotherapy or radical prostatectomy.

Clinical use of stereoscopic X-ray positioning of patients treated with conformal radiotherapy for prostate cancer.

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.

Initial clinical experience with infrared-reflecting skin markers in the positioning of patients treated by conformal radiotherapy for prostate cancer.

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.

Omission of radiotherapy after breast-conserving surgery: survival impact and time trends.

PURPOSE: To evaluate the survival impact of omission of radiotherapy after breast-conserving surgery and the changes with time. MATERIAL AND METHODS: Women aged 40-69 with non-metastasized T1-T2 breast cancer, who underwent breast-conserving surgery with axillary node dissection, with or without post-surgery radiotherapy, selected from the SEER (Surveillance, Epidemiology, and End Results) database. The analysis uses proportional hazards models. RESULTS: Omission of radiotherapy as compared to delivery of radiotherapy was associated with an overall increased mortality hazard ratio of 1.346 (95% confidence interval: 1.204-1.504). Test of constancy showed significant changes with time. The time profile suggested an exponential-like increase from a baseline mortality hazard ratio of 1.17, or 17% excess of relative mortality risk, to a projected hazard ratio of 2.26, or more than doubling of relative mortality risk, for omission of radiotherapy. CONCLUSION: Omission of radiotherapy in breast-conserving surgery is found to be independently associated with an increase in mortality. The data do not give support to omitting radiation or give rationale to clinical trials that would omit radiation.

Considerations on treatment efficiency of different conformal radiation therapy techniques for prostate cancer.

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.

Post-surgery radiation in early breast cancer: survival analysis of registry data.

BACKGROUND AND PURPOSE: Overviews of randomized trials have shown a small survival advantage with post-surgery radiation in early breast cancer. The present study attempts to extend this observation through a systematic analysis of population data. MATERIALS AND METHODS: This retrospective cohort study used the Surveillance, Epidemiology, and End Results (SEER) data on 83,776 women with breast cancer diagnosed between 1988 and 1997, stage T1-T2, node negative or node positive. The analysis was performed using the proportional hazard models. RESULTS: Radiation was associated with a reduced mortality after breast-conserving surgery in node negative patients (hazard ratio 0.757; 95% confidence interval 0.709-0.809; using total mastectomy without radiation as reference) and in node positive patients (hazard ratio 0.777; 0.717-0.842), and after total mastectomy in node positive patients (hazard ratio 0.885; 0.815-0.961). Radiation was associated with an increased hazard ratio of 1.271 (1.080-1.496) after total mastectomy in node negative patients. Without radiation, breast-conserving surgery in node negative patients was associated with an increased hazard ratio (1.167; 1.036-1.314); a similar increase was not observed in node positive patients (hazard ratio 1.011; 0.884-1.155). In all cases, the best survival rates were found with combined breast-conserving surgery and radiation. CONCLUSION: The available data indicate that post-surgery radiation provides a survival advantage irrespective of the type of surgery in node positive patients. Likewise, survival advantage was observed with post-surgery radiation and breast-conserving procedure in node negative patients.

Quality assurance of a system for improved target localization and patient set-up that combines real-time infrared tracking and stereoscopic X-ray imaging.

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.

Impact of planning target volume margins and rectal distention on biochemical failure in image-guided radiotherapy of prostate cancer.

BACKGROUND AND PURPOSE: A previous study in our department demonstrated the negative impact on freedom from biochemical failure (FFBF) of using too narrow planning target volume (PTV) margins during prostate image-guided radiotherapy (IGRT). Here, we investigated the impact of appropriate PTV margins and rectal distention on FFBF. METHODS AND MATERIALS: A total of 50 T1-T3N0M0 prostate cancer patients were treated with daily IGRT by implanted markers. In the first 25 patients, PTV margins were 3mm laterolateral, 5mm anterioposterior and 4mm craniocaudal. The subsequent 25 patients were treated with isotropic margins of 6mm. The rectal cross-sectional area (CSA) was determined on the planning CT. Median follow-up was 61months. RESULTS: The overall 5-year FFBF was 83%. A 6mm PTV margin was related to increased 5-year FFBF on univariate analysis (96% vs 74% with the tighter PTV margins, p=0.04). The 5-year FFBF of patients with a rectal distention on the planning CT was worse compared to those with limited rectal filling (75% for CSA⩾9cm(2) vs 89% for CSA<9cm(2), p=0.02), which remained significant on multivariate analysis (p=0.04). CONCLUSION: This retrospective study illustrated the positive impact of PTV margin adaptation and addressed the importance of avoiding rectal distention at time of the planning CT.

Hypofractionated high-dose radiation therapy for prostate cancer: long-term results of a multi-institutional phase II trial.

PURPOSE: To report late gastrointestinal (GI) and genitourinary (GU) toxicity, biochemical and clinical outcomes, and overall survival after hypofractionated radiation therapy for prostate cancer (PC). METHODS AND MATERIALS: Three institutions included 113 patients with T1 to T3N0M0 PC in a phase II study. Patients were treated with 56 Gy in 16 fractions over 4 weeks. Late toxicity was scored using Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria extended with additional symptoms. Biochemical outcome was reported according to the Phoenix definition for biochemical failure. RESULTS: The incidence of late GI and GU toxicity was low. The 3-year actuarial risk of developing late GU and GI toxicity of grade≥2 was 13% and 8% respectively. Five-year biochemical non-evidence of disease (bNED) was 94%. Risk group, T stage, and deviation from planned hormone treatment were significant predictive factors for bNED. Deviation from hormone treatment remained significant in multivariate analysis. Five-year clinical non evidence of disease and overall survival was 95% and 91% respectively. No patient died from PC. CONCLUSIONS: Hypofractionated high-dose radiation therapy is a valuable treatment option for patients with PC, with excellent biochemical and clinical outcome and low toxicity.

Conformal arc radiotherapy for prostate cancer: increased biochemical failure in patients with distended rectum on the planning computed tomogram despite image guidance by implanted markers.

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.