Rectal Shielding Research Articles

Development of prototype shielded cervical intracavitary brachytherapy applicators compatible with CT and MR imaging

Intracavitary brachytherapy (ICBT) is an integral part of the treatment regimen for cervical cancer and, generally, outcome in terms of local disease control and complications is a function of dose to the disease bed and critical structures, respectively. Therefore, it is paramount to accurately determine the dose given via ICBT to the tumor bed as well as critical structures. This is greatly facilitated through the use of advanced three-dimensional imaging modalities, such as CT and MR, to delineate critical and target structures with an ICBT applicator inserted in vivo. These methods are not possible when using a shielded applicator due to the image artifacts generated by interovoid shielding. The authors present two prototype shielded ICBT applicators that can be utilized for artifact-free CT image acquisition. They also investigate the MR amenability and dosimetry of a novel tungsten-alloy shielding material to extend the functionality of these devices. To accomplish artifact-free CT image acquisition, a "step-and-shoot" (S&S) methodology was utilized, which exploits the prototype applicators movable interovoid shielding. Both prototypes were placed in imaging phantoms that positioned the applicators in clinically applicable orientations. CT image sets were acquired of the prototype applicators as well as a shielded Fletcher-Williamson (sFW) ovoid. Artifacts present in each CT image set were qualitatively compared for each prototype applicator following the S&S methodology and the sFW. To test the novel tungsten-alloy shielding material's MR amenability, they constructed a phantom applicator that mimics the basic components of an ICBT ovoid. This phantom applicator positions the MR-compatible shields in orientations equivalent to the sFW bladder and rectal shields. MR images were acquired within a gadopentetate dimeglumine-doped water tank using standard pulse sequences and examined for artifacts. In addition, Monte Carlo simulations were performed to match the attenuation due to the thickness of this new shield type with current, clinically utilized ovoid shields and a 192Ir HDR/PDR source. Artifact-free CT images could be acquired of both generation applicators in a clinically applicable geometry using the S&S method. MR images were acquired of the phantom applicator containing shields, which contained minimal, clinically relevant artifacts. The thickness required to match the dosimetry of the MR-compatible and sFW rectal shields was determined using Monte Carlo simulations. Utilizing a S&S imaging method in conjunction with prototype applicators that feature movable interovoid shields, they were able to acquire artifact-free CT image sets in a clinically applicable geometry. MR images were acquired of a phantom applicator that contained shields composed of a novel tungsten alloy. Artifacts were largely limited to regions within the ovoid cap and are of no clinical interest. The second generation A3 utilizes this material for interovoid shielding.

WE-D-BRB-08: Effects of Shielded Ovoids in HDR 192Ir Cervical Brachytherapy: A Monte Carlo Study Using Cone-Beam CT Images

Purpose: To investigate the effects of the Fletcher‐Williamson applicator set on the bladder and rectal dose for high‐dose‐rate (HDR) 192 Ir treatment of cervical cancer.Method and Materials: Twenty HDR cervical treatment plans were calculated using an applicator‐based dose superposition method. Pre‐calculated Monte Carlo dose data were used to account for the effects of the tandem and ovoids. A library of 3D dose distributions around all possible dwell positions in water were generated using the PTRAN code. Both the plastic ovoids and the ones with bladder and rectal shields made of tungsten alloy were modeled. The patient calculations were based upon the treatment plans previously created using cone‐beam computed tomographyimages.Results: The stainless steel tandem together with either shielded or unshielded ovoids reduced the dose to Points A and B by 2.5% and 2.2%, respectively. The dose to the hottest 0.1 cm3 and 2 cm3 of the bladder and rectum was reduced by 3.5%–4.5% with plastic ovoids. When shielded ovoids were used, the maximum dose reduction to the hottest 0.1 cm3 of the bladder was 19.5%, while the ICRU bladder point was reduced by up to 24.5%. However, the dose to the bladder point was reduced by over 10% in only 3 out of the 20 plans. The bladder point dose was decreased by 6.6% on average. On the other hand, there was a 1% additional decrease in the rectal dose compared to the unshielded case. The ICRU rectal point did not correspond to the part of the rectum receiving the highest dose.Conclusion: The ovoid shields in the Fletcher‐Williamson applicator set were found ineffective in shielding the high‐dose region in the rectum. The orientations of the ovoids also strongly influenced the dose to the bladder. Conflict of Interest: Research sponsored by Nucletron.

A comparison of conformal and intensity modulated treatment planning techniques for early prostate cancer

The aim of this article was to quantify improvements in external beam treatment plans for early prostate cancer, going from standard four-field conformal radiotherapy (CRT4) to multi-segment, inverse-planned intensity-modulated radiotherapy (IMRTinv). We selected 18 low-, medium- and high-risk early prostate cancer patients requiring external beam radiotherapy and generated standard CRT4 plans. We compared this with five-field conformal radiotherapy (CRT5) plans with beam angles 45 degrees, 100 degrees, 180 degrees, 260 degrees and 315 degrees, five-field plans combining an open beam and rectal shielding segment (forward-planned IMRT (IMRT(for))) and a five-field inverse-planned multi-segment solution (IMRT(inv)) with planning target volume and bladder dose volume histogram characteristics similar to IMRT(for). The CRT5 plans showed significant rectal sparing compared with CRT4 producing 10-22% reductions in rectal volume receiving 95, 85, 67 and 55% prescription dose (V(95), V(85), V(67) and V(55)) depending on patient risk group and conforming better to the planning target volume. The IMRT(for) plans showed a concave dose distribution, further reducing rectal V(95), V(85), V(67) and V(55) between 6 and 50%. We did not find further reductions in rectal doses with IMRT(inv) compared with IMRT(for). The benefit of IMRT over CRT was achieved by increasing the number of beams, changing beam weights and adding a rectal shielding segment to each beam.

SU‐FF‐T‐24: A Monte Carlo Phantom Study for Brachytherapy Dose Perturbation in Henschke Type GYN Applicator

Purpose: The commercial brachytherapy planning system does not evaluate the dose perturbation of the rectal shielding material near the Iridium source. Because the electron equilibrium can't exist around the Iridium source, the dose measurement near the source will be very difficult. In this study, Monte Carlo simulation has been used to estimate the dose perturbation near the source. In order to realize the volume dose of normal tissue, phantom study is need. According to this study, the dose of rectum by brachytherapy will be assessed more accurately. Materials and Methods: The first Monte Carlo simulation result of the Iridium source in water is based on the brachytherapy planning result. This first step is used to verify the simulation parameter. Another simulation condition included with rectal shielding material will be compare to the first condition. The dose difference between these two simulation conditions will suggest the extent of influence rectal shielding material. In the co‐operative hospital, physician used Henksche applicator to treat GYN patient, so the three source positions will be put into three individual tandems to cover the mucosa layer of treatment area. Results: When the Henksche applicator is used for the treatment of GYN patient, the rectal shielding material which is made by tungsten alloy will reduce the tissue dose around the Iridium source. So the brachytherapy planning system will overestimate the rectum point dose. Through this study, the dose of rectum can be defined more precisely. Because the limited dose of rectum can be assessed, the physicist will adjust the dose distribution to achieve the optimization dose distribution more reasonable. Conclusions: The influence of rectal shielding material can be assessed more precisely by this study. By adding simulation results to the volume rectum dose of external beam treatment can give the physician a comprehensive assessment.

WE-A-350-02: IMRT for Prostate Cancer

The prostate is a mobile structure compared to the surrounding bony anatomy. Daily setup, immobilization and localization uncertainties can be addressed by increasing the PTV but results in additional dose to surrounding normal structures. At FCCC we attempt to reduce the uncertainty by employing daily localization using BAT ultrasound, implanted fiducials or through target tracking using implanted Calypso beacons. We currently use an 8mm growth in all directions except posteriorly where 5mm is typical. Patients with fiducials and those being irradiated in the post‐prostatectomy setting undergo localization via an inroom CT scanner or CBCT. These methods allow for minimal PTV expansion by moving the prostate or prostate bed into the intended dose region. All patients are simulated and treated supine without a thermoplastic immobilizer to minimize respiratory related prostatic motion and to facilitate the use of ultrasound. Patients undergo CT and MR simulations with the rectum empty. These data are fused with emphasis on soft tissue structures particularly for those with implanted fiducials or beacons. Dose limiting structures primarily include the rectum, bladder, and femoral heads, but may also include bowel and erectile tissues. The delivery of high doses (70–80+Gy) using 3D CRT invariably includes rectal shielding to some degree in order to avoid unwanted complications. Rectal shielding also creates a dose gradient across the posterior prostate. Our initial comparisons at 78Gy between 3D CRT and IMRT resulted in an increase in 95% PTV coverage from approximately 76Gy to 78Gy, respectively and a reduction of approximately 6Gy to the “hottest” 20% of the rectum. We have developed “plan acceptance criteria” based on published data with respect to rectal complications. DVH analysis is used to ensure that the rectal volumes receiving 65Gy and 40Gy are less than 17% and 35%, respectively. Additionally, the bladder volumes receiving 65Gy and 40Gy are less than 25% and 50%, respectively. The volume of either femoral head receiving 50Gy should be less than 10%. PTV coverage should result in at least 95% of the volume receiving the prescription dose. It should be noted that the 3D dose distribution itself plays an important role in IMRT delivery and DVH analysis alone may not be sufficient. The isodose distribution should be such that the 50% and 90% lines do not traverse the full or half width of the rectum on any CT slice, respectively. Quality assurance includes verification of absolute dose as well as the resultant spatial distribution and our plan acceptance is based on ±3% and 3mm DTA, respectively. We have been able to meet the absolute dose criteria in approximately 94% of cases. Educational Objectives: 1. To understand the practical steps associated with IMRT of the prostate. 2. To understand the planning methods utilized to achieve the numerical values presented for plan acceptance. 3. To be aware of MR‐CT fusion issues for patients with implanted fiducials or beacons.

TU‐SAMS‐AUD‐03: IMRT Site Specific: Prostate

Treatment of prostate cancer with IMRT requires great care in order to achieve the intended results. The prostate is a mobile structure compared to the surrounding bony anatomy. Daily setup, immobilization and localization uncertainties can be addressed by increasing the PTV but results in additional dose to surrounding normal structures. At FCCC we attempt to reduce the uncertainty by employing daily localization using BAT ultrasound or implanted fiducials and currently use an 8mm growth in all directions except posteriorly where 5mm is typical. Patients with fiducials and those being irradiated in the post‐prostatectomy setting undergo localization via an in‐room CT scanner. These methods allow for minimal PTV expansion by moving the prostate or prostate bed into the intended dose region.All patients are simulated and treated supine without a thermoplastic immobilizer to minimize respiratory related prostatic motion and to facilitate the use of ultrasound. Patients undergo CT followed immediately by MR simulations with the rectum empty. These data are fused and all soft tissue structures contoured based on MR. We believe the apex of the prostate is more accurately visualized with MR without the potential prostate distortion associated with a retrograde urethrogram. Dose limiting structures primarily include the rectum, bladder, and femoral heads, but may also include bowel and erectile tissues. The delivery of high doses (70–80+Gy) using 3D CRT invariably includes rectal shielding to some degree in order to avoid unwanted complications. Rectal shielding also creates a dose gradient across the posterior prostate. Our initial comparisons at 78Gy between 3D CRT and IMRT resulted in an increase in 95% PTV coverage from approximately 76Gy to 78Gy, respectively and a reduction of approximately 6Gy to the “hottest” 20% of the rectum. We have developed “plan acceptance criteria” based on published data with respect to rectal complications. DVH analysis is used to ensure that the rectal volumes receiving 65Gy and 40Gy are less than 17% and 35%, respectively. Additionally, the bladder volumes receiving 65Gy and 40Gy are less than 25% and 50%, respectively. The volume of either femoral head receiving 50Gy should be less than 10%. PTV coverage should result in at least 95% of the volume receiving the prescription dose. It should be noted that the 3D dose distribution itself plays an important role in IMRT delivery and DVH analysis alone may not be sufficient. The isodose distribution should be such that the 50% and 90% lines do not traverse the full or half width of the rectum on any CT slice, respectively. Additionally, emphasis is given to treatment time not only for throughput but also for patient comfort. Quality assurance includes verification of absolute dose as well as the resultant spatial distribution and our plan acceptance is based on ±3% and 3mm DTA, respectively. We have been able to meet the absolute dose criteria in approximately 94% of cases.Educational Objectives:1. To understand the practical steps associated with IMRT of the prostate.2. To understand the planning methods utilized to achieve the numerical values presented for plan acceptance.

Comparison of dose distributions around the pulsed-dose-rate Fletcher–Williamson and the low-dose-rate Fletcher–Suit–Delclos ovoids: a Monte Carlo study

We performed a Monte Carlo study to compare dose distributions for a Fletcher–Suit–Delclos (FSD) ovoid used with 137Cs low-dose-rate (LDR) sources with those for a Fletcher–Williamson (FW) ovoid used with an 192Ir pulsed-dose-rate (PDR) source for intracavitary brachytherapy of cervical cancer. We recently reported on extensive validation of Monte Carlo MCNPX models of these ovoids using radiochromic film measurements. Here, we compared these models assuming identical loading of 10, 15 and 20 mgRaEq (72, 108 and 145 cGy cm2 h−1, respectively) in three dose mesh planes: one perpendicular to the ovoid long axis bisecting the ovoid, one parallel to and displaced 2 cm medially from the long axis of the ovoid, and a ‘rectal’ plane perpendicular to the long axis located 1 cm distal to the distal face of the ovoid cap. The FW ovoid delivered slightly higher doses (within 10%) over all loadings to regions away from the bladder and rectal shields when compared to the FSD ovoid. However, the FW ovoid delivered much higher doses (>50%) in regions near these shields. In the rectal plane, the FW ovoid delivered a slightly higher dose, but within the region directly behind the rectal shield, the FW ovoid delivered a dose ranging from +35% to –35% of the FSD dose distribution. We attribute these differences to intrinsic differences in source characteristics (radial dose function and anisotropy factors) and extrinsic factors such as the solid-angle effect between sources and shields and applicator design.

MO‐E‐ValA‐02: IMRT for Prostate Cancer

Treatment of prostate cancer with IMRT requires great care in order to achieve the intended results. The prostate is a mobile structure compared to the surrounding bony anatomy. Daily setup, immobilization and localization uncertainties can be addressed by increasing the PTV but results in additional dose to surrounding normal structures. At FCCC we attempt to reduce the uncertainty by employing daily localization using BAT ultrasound or implanted fiducials and currently use an 8mm growth in all directions except posteriorly where 5mm is typical. Patients with fiducials and those being irradiated in the post‐prostatectomy setting undergo localization via an in‐room CT scanner. These methods allow for minimal PTV expansion by moving the prostate or prostate bed into the intended dose region.All patients are simulated and treated supine without a thermoplastic immobilizer to minimize respiratory related prostatic motion and to facilitate the use of ultrasound. Patients undergo CT followed immediately by MR simulations with the rectum empty. These data are fused and all soft tissue structures contoured based on MR. We believe the apex of the prostate is more accurately visualized with MR without the potential prostate distortion associated with a retrograde urethrogram. Dose limiting structures primarily include the rectum, bladder, and femoral heads, but may also include bowel and erectile tissues. The delivery of high doses (70–80+Gy) using 3D CRT invariably includes rectal shielding to some degree in order to avoid unwanted complications. Rectal shielding also creates a dose gradient across the posterior prostate. Our initial comparisons at 78Gy between 3D CRT and IMRT resulted in an increase in 95% PTV coverage from approximately 76Gy to 78Gy, respectively and a reduction of approximately 6Gy to the “hottest” 20% of the rectum. We have developed “plan acceptance criteria” based on published data with respect to rectal complications. DVH analysis is used to ensure that the rectal volumes receiving 65Gy and 40Gy are less than 17% and 35%, respectively. Additionally, the bladder volumes receiving 65Gy and 40Gy are less than 25% and 50%, respectively. The volume of either femoral head receiving 50Gy should be less than 10%. PTV coverage should result in at least 95% of the volume receiving the prescription dose. It should be noted that the 3D dose distribution itself plays an important role in IMRT delivery and DVH analysis alone may not be sufficient. The isodose distribution should be such that the 50% and 90% lines do not traverse the full or half width of the rectum on any CT slice, respectively. Additionally, emphasis is given to treatment time not only for throughput but also for patient comfort. Quality assurance includes verification of absolute dose as well as the resultant spatial distribution and our plan acceptance is based on ±3% and 3mm DTA, respectively. We have been able to meet the absolute dose criteria in approximately 94% of cases.Educational Objectives:1. To understand the practical steps associated with IMRT of the prostate.2. To understand the planning methods utilized to achieve the numerical values presented for plan acceptance.

IMRT to Escalate the Dose to the Prostate while Treating the Pelvic Nodes

To assess and quantify the benefit of introducing intensity-modulated radiotherapy (IMRT) over conventional approaches to cover the pelvic nodes while escalating the dose to the prostate gland. The pelvic lymphatics were planned to receive 50 Gy at 2 Gy per fraction by four-field box (4FB) technique and standard field blocks drawn on digitally reconstructed radiographs (DRR), 4FB with field blocks according to the position of pelvic nodes as contoured on serial planning CT slices, or IMRT. The lateral fields included three different variations of field blocks to assess the role of various degrees of rectal shielding. The boost consisted in 26 Gy in 13 fractions delivered via six-field three-dimensional conformal radiotherapy (3DCRT) or IMRT. By the combination of a pelvic treatment and boost, several plans were obtained for each patient, all normalized to be isoeffective with regard to prostate-planning target volume (PTV-P) coverage. Plans were compared with respect to dose-volume histogram (DVH) of pelvic nodes/seminal vesicles-PTV (PTV-PN/SV), rectum, bladder and intestinal cavity. Reported are the results obtained in eight patients. Pelvic IMRT with a conformal boost provided superior sparing of both bladder and rectum over any of the 4FB plans with the same boost. For the rectum the advantage was around 10% at V70 and even larger for lower doses. Coverage of the pelvic nodes was adequate with initial IMRT with about 98% of the volume receiving 100% of the prescribed dose. An IMRT boost provided a gain in rectal sparing as compared to a conformal boost. However, the benefit was always greater with pelvic IMRT followed by a conformal boost as compared to 4FB with IMRT boost. Finally, the effect of utilizing an IMRT boost with initial pelvic IMRT was greater for the bladder than for the rectum (at V70, about 9% and 3% for the bladder and rectum, respectively). IMRT to pelvic nodes with a conformal boost allows dose escalation to the prostate while respecting current dose objectives in the majority of patients and it is dosimetrically superior to 4FB. An IMRT boost should be considered for patients who fail to meet bladder dose objectives.

WE-E-T-618-02: IMRT for Prostate Cancer

While arguably the most mature site for IMRT use, prostate treatments still require great care in order to achieve the intended results. The prostate is a mobile structure compared to the surrounding bony anatomy. Daily setup, immobilization and localization uncertainties can be addressed by increasing the PTV but this results in additional dose to surrounding normal structures. We attempt to reduce the uncertainty by employing active localization using BAT ultrasound and currently use a 8mm PTV in all directions except posteriorly where a 5mm margin is typical. Patients being irradiated in the post-prostatectomy setting undergo localization via an in-room CT scanner. These methods allow for minimal expansion of the PTV by moving the prostate or prostate bed into the appropriate dose region on a daily basis. All patients are simulated and treated supine without a thermoplastic immobilizer to facilitate the use of ultrasound and to minimize respiratory related prostatic motion. Patients undergo CT followed immediately by MR simulations with the rectum empty. These data are fused and all soft tissue structures contoured based on the MR scan. We believe the apex of the prostate is more accurately visualized with MR without the potential prostate distortion associated with a retrograde urethrogram. Dose limiting structures primarily include the rectum, bladder, and femoral heads, but may also include bowel and erectile tissues. It should be noted that the 3D dose distribution itself plays an important role in IMRT delivery and DVH analysis alone may not be sufficient. The delivery of modern doses (70–80+Gy) using 3D CRT invariably includes rectal shielding to some degree in order to avoid unwanted complications. Rectal shielding also creates a dose gradient across the posterior prostate. Our initial comparisons at 78Gy between 3D CRT and IMRT resulted in an increase in 95% PTV coverage from approximately 76Gy to 78Gy, respectively and a reduction of approximately 6Gy to the “hottest” 20% of the rectum. We have developed “plan acceptance criteria” based on published data with respect to rectal complications. DVH analysis is used to ensure that the volumes of rectum receiving 65Gy and 40Gy are less than 17% and 35%, respectively. Additionally, the volumes of bladder receiving 65Gy and 40Gy are less than 25% and 50%, respectively. The volume of either femoral head receiving 50Gy should be less than 10%. The isodose distribution should be such that the 50% and 90% lines do not traverse the full or half width of the rectum on any CT slice, respectively. PTV coverage should result in at least 95% of the volume receiving the prescription dose. Quality assurance includes verification of absolute dose as well as the resultant spatial distribution and our plan acceptance is based on ±3% and 3mm DTA, respectively. We have been able to meet the absolute dose criteria in approximately 94% of cases. Educational Objectives: 1. To understand the practical steps associated with IMRT of the prostate 2. To understand the planning methods utilized resulting in the safe use of the numerical values presented for plan acceptance

Is the alpha–beta ratio of prostate cancer really low? A prospective, non-randomized trial comparing standard and hyperfractionated conformal radiation therapy

Background and purpose The objectives of the current study were to compare genito-urinary (GU) and gastro-intestinal (GI) toxicities as well as biochemical control (bRFS) in prostate cancer, utilizing conventional (2.0 Gy daily) (STD) or hyperfractionated (HFX) conformal irradiation (CRT). HFX (1.2 Gy BID) was chosen as a radiobiological method to try to reduce long term sequelae without compromising local control. Patients and methods Three-hundred-and-seventy consecutive patients (pts) entered this prospective, non-randomized trial in the period January 1993–January 2003; 209 were treated with STD and 161 with HFX CRT. All were evaluable for acute toxicity analysis, 179 (STD) and 151 pts (HFX) being evaluable for late sequelae and bRFS analyses. Pt characteristics were not statistically different in the two groups. CRT consisted of a 4-field technique for prostate and/or pelvic nodes and a 5-field boost with rectal shielding. Median doses were 74 and 79.2 Gy for STD and HFX patients respectively, the latter dose being isoeffective for tumour control assuming α/ β=10 (EQD 2=73.9 Gy). Median follow-up was 29.4 months (25.2 mos for STD; 37.7 mos for HFX; P<0.01). The two regimens were compared in terms of acute and late GU and GI toxicities and 5-year bRFS by univariate and multivariate analyses. Results Acute grade≥2 GU toxicity was higher in the STD group (48.6% versus 37.3% in HFX, P=0.03), while no significant difference was found for acute GI toxicity. Late grade≥2 GU and GI toxicities were lower in the HFX group (5-year actuarial rate: GU: 10.1% versus 20.3%, P=0.05; GI: 6.0% versus 10.6%, P=0.18). Five-year bRFS were 70% (±13.8%, 95% CI) and 82.6% (±7.2%) for STD and HFX, respectively ( P=0.44); a trend favouring HFX was found in the subgroup of pts who did not receive hormonal therapy (5-year bRFS: 85.9%±12.4% versus 63.9%±23.8%, P=0.15). Multivariate analysis revealed only risk groups and age statistically related to bRFS but not fractionation regimen. Using the Nahum–Chapman TLCP model and prostate parameter set, which includes hypoxia, the TLCPs are approximately equal for the two regimens, whereas assuming α/ β=1.5 and no hypoxia we obtain 73% for the STD group but only 36% for the HFX group. Conclusions As expected from radiobiological considerations, HFX reduces GI and GU late toxicities. Concerning early bRFS, our clinical findings suggest that HFX is no less effective than STD when delivering an isoeffective ( α/ β=10) dose. Despite the relatively short follow-up, this result appears to be inconsistent with a low α/ β ratio for prostate cancer.

Long-term androgen deprivation increases Grade 2 and higher late morbidity in prostate cancer patients treated with three-dimensional conformal radiation therapy

To determine whether the use of androgen deprivation (AD) increases late morbidity when combined with high-dose three-dimensional conformal radiation therapy (3D-CRT). Between May 1989 and November 1998, 1,204 patients were treated for prostate cancer with 3D-CRT to a median dose of 74 Gy. Patients were evaluated every 3-6 months. No AD was given to 945 patients, whereas 140 and 119 patients, respectively, received short-term AD (STAD; < or =6 months) and long-term AD (LTAD; > 6 months). Radiation morbidity was graded according to the Fox Chase modification of the Late Effects Normal Tissue Task Force late morbidity scale. Covariates in the multivariate analysis (MVA) included age, history of diabetes mellitus, prostate-specific antigen (PSA) level, Gleason score, T category, RT field size, total RT dose, use of rectal shielding, and AD status (no AD vs. STAD vs. LTAD). The only independent predictor for Grade 2 or higher genitourinary (GU) morbidity in the MVA was the use of AD (p = 0.0065). The 5-year risk of Grade 2 or higher GU morbidity was 8% for no AD, 8% for STAD, and 14% for LTAD (p = 0.02). Independent predictors of Grade 2 or higher gastrointestinal (GI) morbidity in the MVA were the use of AD (p = 0.0079), higher total radiation dose (p < 0.0001), the lack of a rectal shield (p = 0.0003), and older age (p = 0.0009). The 5-year actuarial risk of Grade 2 or higher GI morbidity was 17% for no AD vs. 18% for STAD and 26% for LTAD (p = 0.017). The use of LTAD seems to significantly increase the risk of both GU and GI morbidity for patients treated with 3D-CRT.

Dose–volume histograms associated to long-term colorectal functions in patients receiving pelvic radiotherapy

Background and purposeTo correlate long-term colorectal dysfunctions following radical radiotherapy for bladder or prostate cancer with clinical parameters and dose–volume histogram parameters of the small intestine, rectum, and anal canal volume. Materials and methodsSeventy-one patients previously treated for bladder or prostate cancer were interviewed following CT-based radiotherapy of 60–70Gy with questions concerning long-term colorectal dysfunctions. Median follow-up time was 30 months (range 12–109 months). Clinical parameters and parameters from the dose–volume histograms were correlated with colorectal dysfunctions (Spearman's test). Median and quartile values of all parameters were used as cut-off values for statistical analyses. A logistic regression model was used for analysis of urgency and incontinence in relation to median or maximum radiation dose to the anal canal volume. ResultsRectum length, volume and several dose–volume parameters from the anal canal volume and rectal volume were correlated with late organ dysfunctions. In a logistic model, fecal urgency and incontinence were dependent of dose–volume parameters from the anal canal volume. No relation between age or follow-up time and late effects were found. Dose–volume parameters of the small intestine were not related to any late dysfunctions. ConclusionsA relationship between several late anorectal dysfunctions and dose–volume parameters from the rectum and anal canal volume was demonstrated. It is recommended to exclude the anal canal volume from the high dose–volume and to apply rectal shielding whenever possible to prevent late anorectal dysfunctions.

Standard (STD) or hyperfractionated (HFX) conformal radiation therapy (CRT) in prostate cancer: A prospective trial evaluating toxicities and early biochemical control

In 1993 we activated a prospective, non randomized trial in prostate cancer using CRT and 2 different fractionation regimens. The end points were to compare genito-urinary (GU) and gastro-intestinal (GI) toxicities (tox) as well as biochemical control (bRFS), utilizing a STD (2.0 Gy daily) or a HFX schedule. HFX (1.2 Gy BID) was chosen as a radiobiological method to try to reduce late tox without compromising local control (1). 370 consecutive patients (pts) entered the study in the period January 1993-January 2003. 209 were treated with STD and 161 with HFX CRT. 179 pts (87%) in the STD and 151 (94%) in the HFX were evaluable for late tox and bRFS analysis, while all 370 pts were considered for acute tox evaluation. Pre-treatment clinical variables (STD vs. HFX: median age 71 vs. 69; T1-2 64.8% vs. 60.4%; median iPSA 11.2 vs. 12 ng/ml; GPS ≥ 7 39% vs. 40%) and treatment characteristics (pelvis irradiation 43% vs. 44%; androgen deprivation 79% vs. 71%) were not statistically different in the 2 groups. CRT consisted of a 4-field technique for prostate and/or pelvic nodes and a 5-field boost with rectal shielding. Median doses were 74 Gy and 79.2 Gy (EQD2:73.9 Gy, isoeffective for tumor control assuming α/β = 10) for STD and HFX patients, respectively. Median follow-up was 29.4 months (STD: 25.2 mos; HFX: 37.7 mos; p < 0.01 t-test). GU/GI acute and late tox (RTOG-EORTC scoring) and 5-year bRFS were compared in the 2 fractionation regimens using univariate (Chi-square, log-rank test) and multivariate analyses (Cox regression hazard model). Acute ≥ grade 2 GU tox was higher in the STD group (48.6% vs. 37.3% in the HFX group, p = 0.03) while no significant difference was found for acute GI tox. Late ≥ grade 2 GU and GI tox were lower in the HFX group (5-year actuarial rate: GU: 10.1% vs. 20.3%, p = 0.05; GI: 6.0% vs. 10.6%, p = 0.18). 5-year bRFS were 70% (±13.8%, 95% CI) and 82.6 % (±7.2%) for STD and HFX, respectively (p = 0.44); a trend favouring HFX was found in the subgroup of pts who did not receive hormonal therapy (5-year bRFS: 85.9% ± 12.4% vs. 63.9% ± 23.8%, p = 0.15). Multivariate analysis revealed that only Pisansky risk groups and age were statistically related to bRFS but not fractionation regimens. Using the Nahum-Chapman TLCP model and prostate parameter set, which includes hypoxia, the TLCPs are approximately equal for the 2 regimens, whereas assuming α/β = 1.5 and no hypoxia we obtain 73% for the STD group but only 36% for the HFX group. As expected from radiobiology, HFX reduces GI and GU late tox. Concerning early bRFS, our clinical findings suggest that HFX is, at least, not detrimental with respect to standard fractionation when delivering an isoeffective total dose equivalent to 2 Gy/fr (considering α/β = 10). Whilst accepting that caution is appropriate due to the relatively short follow-up, this result seems to be inconsistent with a low α/β ratio for prostate cancer. The trend of a non-detrimental, possibly improved, clinical outcome with HFX is more consistent with the idea that α/β is relatively high and that some prostate tumours are hypoxic (2–4), with hyperfractionation probably reducing this hypoxic proportion through increased reoxygenation. If the bRFS with HFX is genuinely higher than with STD, then a plausible explanation is that hyperfractionation reduces this hypoxic proportion through increased reoxygenation.

Partial irradiation of the rectum

Data gathered from dose escalation protocols for the treatment of prostate cancers conducted in the past 10 years have shown that rectal toxicity can be controlled by the use of careful conformal techniques. The most severe complications of rectal irradiation (obstruction and fistula requiring colostomy) have been essentially eliminated. The most frequent gastrointestinal complications of conformal radiotherapy of prostate cancer are now rectal bleeding associated with telangiectatic changes to the vasculature of the submucosa, and in severe cases, ulceration requiring cautery procedures and or transfusion. The benefits of 3-dimensional conformal radiotherapy (3D-CRT) are strongly technique dependent, with a strong dose response for single techniques for prescription doses over 70 Gy. Studies of rectal motion show that the anterior wall can move approximately 1 cm during treatment, so portions of the anterior rectal wall will regularly receive the full prescription dose if posterior margin sizes >/= 1 cm are used in designing the planning target volume (PTV). There is strong evidence that increased rectal shielding and posterior PTV margin sizes approximately 0.6 cm reduce rectal complication rates. Despite uncertainties due to rectal motion, studies of dose-volume histograms (DVHs) show that rectal toxicity is strongly influenced by the percent volumes of rectal wall exposed to doses approximately 70 Gy and higher. Recent data suggests that percent volumes of rectal wall exposed doses between 40 to 50 Gy, and the existence of a reserve of unexposed tissue may also play a role in determining rectal bleeding rates.

Late GI and GU complications in the treatment of prostate cancer

Purpose : To asses the factors that predict late GI and GU morbidity in radiation treatment of the prostate. Methods and Materials : Seven hundred twelve consecutive prostate cancer patients treated at this institution between 1986 and 1994 (inclusive) with conformal or conventional techniques were included in the analysis. Patients had at least 3 months follow-up and received at least 65 Gy. Late GI and Grade 3 morbidity was rectal bleeding (requiring three or more procedures) or proctitis. Late Grade 3 GU morbidity was cystitis or stricture. Multivariate analysis (MVA) was used to assess factors related to the complication-free survival. The factors assessed were age, occurrence of side effects ≥ Grade 2 during treatment, irradiated volume parameters (use of pelvic fields, treatment of seminal vesicles to full dose or 57 Gy, and use of additional rectal shielding), dose, comorbidities, and other treatments (hormonal manipulation, TURP). Results : Acute GI and GU side effects (Grade 2 or higher) were noted in 246 and 201 patients, responsibility; 67 of these patients exhibited both. GI side effects were not correlated with GU side effects acutely. Late and acute morbidities were correlated (both GI and GU). Fifteen of the 712 patients expressed Grade 3 or 4 GI injuries 3 to 32 months after the end of treatment, with a mean of 14.3 months. One hundred fifteen patients expressed Grade 2 or higher GI morbidity (mean: 13.7 months). The 43 Grade 2 or higher GU morbidities occurred significantly later (mean: 22.7 months). Central axis dose was the only independent variable significantly related to the incidence of late GI morbidity on MVA. No treatment volume parameters were significant for Grade 3. The following parameters were significantly related to (by MVA) to Grade 2 GI morbidity: central axis dose, use of the increased rectal shielding, androgen deprivation therapy starting before RT. Acute and late GI mobidities were highly correlated. History of diabetes, treatment of pelvic nodes, and age less than 60 years were significantly related to acute GI side effects. The parameters significantly related to late Grade 2 or higher GU morbidity were central axis dose, androgen deprivation therapy (Zoladex or Lupron) prior to radiation therapy (RT), history of obstructive symptoms, and acute GU side effects. There were too few late Grade 3 GU morbidities to perform multivariate analysis. Acute GU side effects were highly correlated with late GU injury. The following were correlated with acute GU side effects: history of diabetes (+), treatment with conformal fields (−), TURP before RT (−), presentation with urinary obstructive symptoms. Conclusion : Both late GI and GU morbidity demonstrate a dose dependence, but only the volume dependence observed is a reduction in late Grade 2–4 GI morbidity by increasing the rectal shielding in the lateral fields for the final 10 Gy. Moreover, both late GI and GU morbidity was increased in patients treated with hormone manipulation prior to RT. GI and GU injuries were correlated with their corresponding acute side effects. GI and GU complications must not be combined for analysis to determine the factors related to their occurrence.

Lateral rectal shielding reduces late rectal morbidity following high dose three-dimensional conformal radiation therapy for clinically localized prostate cancer: Further evidence for a significant dose effect

Purpose : Using conventional treatment methods for the treatment of clinically localized prostate cancer central axis doses must be limited to 65–70 Gray (Gy) to prevent significant damage to nearby normal tissues. A fundamental hypothesis of three-dimensional conformal radiation therapy (3DCRT) is that, by defining the target organ(s) accurately in three dimensions, it is possible to deliver higher doses to the target without a significant increase in normal tissue complications. This study examined whether this hypothesis holds true and whether a simple modification of treatment technique can reduce the incidence of late rectal morbidity in patients with prostate cancer treated with 3DCRT to minimum planning target volume (PTV) doses of 71–75 Gy. Methods and Materials : The 257 patients with clinically localized prostate cancer who completed 3DCRT by December 31, 1993 and received a minimum PTV dose of 71–75 Gy are included in th is report. The median follow-up time was 22 months (range: 4–67 months); 98% of patients had follow-up of longer than 12 months. The calculated dose at the center of prostate was < 74 Gy in 19 patients, 74–76 Gy in 206 patients, and > 76 Gy in 32 patients. Late rectal morbidity was graded according to the Late Effects Normal Tissue (LENT) scoring system. Eighty-eight consecutive patients were treated with a rectal block added to the lateral fields. In these patients the posterior margin from the prostate to the block edge was reduced from the standard 15 to 5 mm for the final 10 Gy, which reduced the dose to portions of the anterior rectal wall by approximately 4–5 Gy. Estimates of rates for rectal morbidity were determined by Kaplan-Meier actuarial analyses. Difference in morbidity percentages were evaluated by the Pearson chisquare test. Results : Grade 2–3 morbidity developed in 46 out of 257 patients (18%) and in the majority of cases consisted of rectal bleeding. No patient has developed Grade 4 or 5 rectal morbidity. The actuarial rate of Grade 2–3 morbidity is 23% at 24 months and the median time to the development of Grade 2–3 complications is 15 months. A statistically significant dose effect is evident. The incidence of Grade 2–3 rectal morbidity increased as the dose at the center of the prostate increase ( p = 0.05). In patients receiving minimum PTV doses of ≤ 76 Gy the use of a rectal block significantly reduced the incidence of Grade 2–3 toxicity; 6 out of 88 (7%) with a block vs. 30 out of 137 (22%) without a block, ( p = 0.003). Conclusion : The indcidence of late rectal morbidity with 3DCRT to minimum PTV doses of 71–75 Gy is acceptable and to date no Grade 4–5 rectal morbidities have been observed. In our experience, higher doses to the center of the protate are associated with an increased likelihood of developing Grade 2–3 rectal morbidity but treatment techniques that reduce the total dose to the anterior rectal wall have reduced the incidence of late rectal morbidity. If clinical studies indicate improved tumor control with minimum PTV doses above 71 Gy, the dose escalation above 76Gy to the center of the prostate should be persued cautiously with treatment techniques that limit the total dose to the anterior rectal wall.

3 Lateral rectal shielding reduces late rectal morbidity after high dose three-dimensional conformal radiation therapy for clinically localized prostate cancer: Further evidence for a dose effect

3 Lateral rectal shielding reduces late rectal morbidity after high dose three-dimensional conformal radiation therapy for clinically localized prostate cancer: Further evidence for a dose effect

Movement of the prostate in response to the state of filling of the rectum and bladder

Traditionally prostate patients have been simulated using plain radiographs with contrast in the rectum and sometimes bladder, to aid in the design of blocks to protect the rectum and bladder. However, patients are not treated under those conditions. We currently treatment plan our prostates using a CT-based approach where both the bladder and the rectum are nearly empty or, the bladder may be partially filled; conditions which more closely approximate those in place at treatment. Target volumes, as well as bladder and rectum volumes, are generated from contours drawn in the CT dataset, and blocks are drawn based upon that information. These plans are verified before treatment on a simulator, by comparison of fluoroscopic images and radiographs to Beam's Eye View plots of the fields which include target volume contours and block edges generated from the CT dataset. Comparison of those CT-based treatment plans to simulator films taken with the rectum and bladder opacified in the classical sense revealed movement of the prostatic target volume in half of the 40 patients investigated. Our investigation reveals that 30 cc of rectal contrast can push the upper part of the prostate and seminal vesicle target volume anterior and/or superior. Movements ranged from 0.5 to 2 cm, with an average near 1 cm. The second phase of our study looked at patients that had previously received Iodine125 seed implants and came back for retreatment using external beams. The seeds are easily visualized on radiographs and CT scans. Patients were simulated and CT'ed as above, but with the addition of radio-opaque markers in the cradle and on the patient skin surfaces to aid in image correlation. Those patients also had as many as 20 surgical clips left in the pelvis from nodal dissections. Movement of the prostate was also easily seen on the CT scans (3 mm slices through the prostate) where different numbers of seeds were observed on corresponding CT images taken with rectum (bladder) full and/or rectum (bladder) empty. Digitization of seed locations, marker locations and bony anatomy give a quantitative evaluation of prostate movement similar to that above. The consequences of these changes in anatomy are appreciated in the beam's-eye-view plots of a lateral boost fields. If blocks drawn on lateral views obtained with the rectum full of contrast are used to treat a patient with rectum and bladder nearly empty, part of the target volume may be covered by the block and a greater amount of bladder can receive high dose. That is, the superior portion of the targeted volume is no longer pushed up and/or anterior. 3-D DVH analysis was performed to demonstrate the dosimetric consequences of that type of movement. Clearly, these considerations are of great importance for boost treatments of the prostate when bladder or rectal shields are used.

Mini-colpostats in the treatment of carcinoma of the uterine cervix

Between 1976 and 1982, 293 patients were treated for carcinoma of the uterine cervix at Washington University by definitive radiotherapy consisting of external beam therapy and two standard Fletcher-Suit applications (tandem plus vaginal colpostats). In ninety-nine patients (34%) mini-colpostats (MC) were used for one or both of their intracavitary insertions while 194 (66%) patients were treated twice with regular Fletcher-Suit colpostats (RC). The frequency of MC use was related to the age and parity of the patients. The distribution by stage of MC and RC groups was not significantly different. Pelvic failure in the MC group was similar to that of the RC group (21% vs 24%). Five-year disease-free survival was also similar between the two groups: 86% vs 80% Stage IB, 57% vs 61% Stage IIA, 47% vs 52% Stage IIB, and 27% vs 45% Stage III for MC and RC groups, respectively. The rate of major complications (grade 3) was 15% in the MC group and 8% in the RC group ( p = 0.08). Careful phantom dosimetric studies in both types of colpostats and correlations of dose distributions at various points in the pelvis with frequency of rectal and bladder complications were carried out. The bladder and rectum received a 5–10% higher mean radiation dose (Gy) in the MC group than in the RC group despite lower overall exposure (milligram-hours). Thermoluminescent dosimetry in a polystyrene phantom demonstrates that approximately 10% higher doses are delivered to the bladder, rectum, and point A with an MC system as compared to an RC system, for constant exposure in mgh. Phantom measurements of a newer MC with bladder and rectal shielding demonstrate no influence on the bladder and rectal point dose at a source separation of 3 cm; midline points of the bladder and rectum are not within the full shadow of the shields even if the colpostats are flush with the tandem. Implications for therapy are discussed.