Treatment planning and dosimetry of a multi-axis dynamic arc technique for prostate cancer: A comparison with IMRT

Purpose Intensity-modulated radiation therapy (IMRT) allows greater dose conformity to the tumor target. However, IMRT, especially static delivery, usually requires more time to deliver a dose fraction than conventional external beam radiotherapy (EBRT). The authors have been using a “two-axis dynamic arc therapy” (2A-DAT) technique for prostate cancer treatment to make a concave dose distribution to spare the rectum and bladder while working with limited time and human resources. The objectives of this study were to (1) clinically implement the 2A-DAT technique, (2) evaluate the dosimetry in comparison with IMRT, and (3) analyze the initial treatment outcome. Materials and Methods The 2A-DAT consists of two dynamic arc therapies (DATs) with half rotation around two isocenters each in two separate symmetrical rhombi. Treatment planning is forward and on a trial-and-error basis. Thirty-four patients received 2A-DAT with a median prescribed dose of 70 Gy. Results Although inferior in dose uniformity, the 2A-DAT provided equivalent sparing of normal structures to IMRT. Daily fraction delivery time for the 34 patients ranged from 6.4 to 9.6 minutes, with an average of 7.4 minutes. Five-year survival and five-year prostate specific autigen (PSA) failure-free survival were 89.3% and 79.5%, respectively. Three patients developed grade 2 procitis. Conclusion This technique is a possible alternative to IMRT in EBRT of prostate cancer This research was partially supported by the Ministry of Education, Science, Sports and Culture, Grant-in-Aid for Scientific Research (C) 2002, and was presented at the 4th Shinji Takahashi Memorial International Workshop on 3D-CRT.     

A dosimetric comparison of RapidArc and IMRT with hypofractionated simultaneous integrated boost to the prostate for treatment of prostate cancer

Objective:

To compare the dosimetric results and treatment delivery efficiency among RapidArc® (Varian Medical Systems, Palo Alto, CA), 7-field intensity-modulated radiotherapy (7-f IMRT) and 9-field IMRT (9-f IMRT) with hypofractionated simultaneous integrated boost to the prostate.

Methods:

RapidArc, 7-f IMRT and 9-f IMRT plans were created for 21 consecutive patients treated for high-risk prostate cancer using the Eclipse™ treatment planning system (Varian Medical Systems). All plans were designed to deliver 70.0 Gy in 28 fractions to the prostate planning target volume (PTV) while simultaneously delivering 50.4 Gy in 28 fractions to the pelvic nodal PTV. Target coverage and sparing of organs at risk (OARs) were compared across techniques. The total number of monitor units (MUs) and the treatment time were used to assess treatment delivery efficiency.

Results:

RapidArc resulted in slightly superior conformity and homogeneity of prostate PTV, whereas all plans were comparable with respect to dose to the nodal PTV. Although OARs sparing for RapidArc and 7-f IMRT plans were almost equivalent, 9-f IMRT achieved better sparing of the rectum and bladder than RapidArc and 7-f IMRT. RapidArc provided the highest treatment delivery efficiency with the lowest MUs and shortest treatment time.

Conclusion:

RapidArc resulted in similar OAR sparing to 7-f IMRT, whereas 9-f IMRT provided the best OAR sparing. Treatment delivery efficiency is significantly higher for RapidArc.

Advances in knowledge:

This study validated the feasibility and limitations of RapidArc in the treatment of high-risk prostate cancer with complex pelvic target volumes.Radiotherapy has played an important role in the treatment of locally advanced prostate cancer. Several randomised controlled trials have demonstrated that high-dose radiotherapy improves prostate-specific antigen control, and a recently published meta-analysis [1] showed that high-dose radiotherapy is superior to conventional-dose radiotherapy in preventing biochemical or clinical failure and prostate cancer-specific death. However, dose escalation has been limited by toxicity in conventional techniques. Therefore, prostate cancer is one of the most common tumour sites treated with intensity-modulated radiation therapy (IMRT), which enables the delivery of highly conformal dose distribution to the target while reducing the dose to critical organs. IMRT also has the ability to produce inhomogeneous dose distribution, which allows for simultaneous differential dose delivery to multiple tumour targets (simultaneous integrated boost). Despite the obvious benefits of IMRT, there are some disadvantages. The potential downsides of IMRT include the increased time required for radiotherapy delivery and increased monitor units (MUs) needed compared with conventional three-dimensional conformal radiation therapy.Volumetric-modulated arc therapy (VMAT) is a relatively new rotational radiation therapy technique based on the idea of delivering IMRT with continuous dynamic modulation of the dose rate, field aperture and gantry speed. Compared with IMRT, the potential benefit of VMAT is the increase in delivery efficiency, including a shorter treatment time and a lower number of MUs.Several recent studies have compared VMAT with IMRT for prostate radiotherapy [2–13]. Although shortened treatment time is a common finding, there are inconsistencies in the dosimetric outcome. Many studies considering relatively simple target volumes that included prostate only or prostate with seminal vesicles found that VMAT achieved equal or better normal tissue sparing over IMRT [2,3,5,6,8–10,12]. However, very few studies have focused on more complex pelvic target volumes, including the prostate, seminal vesicles and pelvic lymph nodes [4,7,11,13]. Some of these studies found largely equivalent sparing of organs at risk (OARs) between VMAT and IMRT [7,13]. However, other planning studies have reported contradictory results. Yoo et al [4] noted superior OARs sparing with IMRT to VMAT. Myrehaug et al [11] found VMAT to have no consistent dosimetric advantage over IMRT. Thus, those studies have yielded mixed results. Our study aims to expand such studies to quantitatively evaluate VMAT for prostate cancer cases with complex pelvic target volumes and simultaneous integrated boost techniques.RapidArc® is one of the VMAT techniques implementing the progressive resolution optimisation algorithm in the Eclipse™ planning system by Varian Medical Systems (Palo Alto, CA). In the present study, we compare the performance of RapidArc, 7-field IMRT (7-f IMRT) and 9-field IMRT (9-f IMRT) with hypofractionated simultaneous integrated boost to the prostate for patients with high-risk prostate cancer. This study focused on the evaluation of the dosimetric results and treatment delivery efficiency.     

Biological effective dose for comparison and combination of external beam and low-dose rate interstitial brachytherapy prostate cancer treatment plans.

We report a methodology for comparing and combining dose information from external beam radiotherapy (EBRT) and interstitial brachytherapy (IB) components of prostate cancer treatment using the biological effective dose (BED). On a prototype early-stage prostate cancer patient treated with EBRT and low-dose rate I-125 brachytherapy, a 3-dimensional dose distribution was calculated for each of the EBRT and IB portions of treatment. For each component of treatment, the BED was calculated on a point-by-point basis to produce a BED distribution. These individual BED distributions could then be summed for combined therapies. BED dose-volume histograms (DVHs) of the prostate, urethra, rectum, and bladder were produced and compared for various combinations of EBRT and IB. Transformation to BED enabled computation of the relative contribution of each modality to the prostate dose, as the relative weighting of EBRT and IB was varied. The BED-DVHs of the prostate and urethra demonstrated dramatically increased inhomogeneity with the introduction of even a small component of IB. However, increasing the IB portion relative to the EBRT component resulted in lower dose to the surrounding normal structures, as evidenced by the BED-DVHs of the bladder and rectum. Conformal EBRT and low-dose rate IB conventional dose distributions were successfully transformed to the common "language" of BED distributions for comparison and for merging prostate cancer radiation treatment plans. The results of this analysis can assist physicians in quantitatively determining the best combination and weighting of radiation treatment modalities for individual patients.     

A systematic benchmark method for analysis and comparison of IMRT treatment planning algorithms

Tools and procedures for evaluating and comparing different intensity-modulated radiation therapy (IMRT) systems are presented. IMRT is increasingly in demand and there are numerous systems available commercially. These programs introduce significantly different software to dosimetrists and physicists than conventional planning systems, and the options often seem initially overwhelmingly complex to the user. By creating geometric target volumes and critical normal tissues, the characteristics of the algorithms may be investigated, and the influence of the different parameters explored. Overall optimization strategies of the algorithm may be characterized by treating a square target volume (TV) with 2 perpendicular beams, with and without heterogeneities. A half-donut (hemi-annulus) TV with a “donut hole” (central cylinder) critical normal tissue (CNT) on a CT of a simulated quality assurance phantom is suggested as a good geometry to explore the IMRT algorithm parameters. Using this geometry, the order of varying parameters is suggested. First is to determine the effects of the number of stratifications of optimized intensity fluence on the resulting dose distribution, and selecting a fixed number of stratifications for further studies. To characterize the dose distributions, a dose-homogeneity index (DHI) is defined as the ratio of the dose received by 90% of the volume to the minimum dose received by the “hottest” 10% of the volume. The next step is to explore the effects of priority and penalty on both the TV and the CNT. Then, choosing and fixing these parameters, the effects of varying the number of beams can be looked at. As well as evaluating the dose distributions (and DHI), the number of subfields and the number of monitor units required for different numbers of stratifications and beams can be evaluated.     

Prostate localization for the treatment planning of prostate cancer: a comparison of two techniques

Two methods for localizing prostatic tissue for radiotherapy treatment planning are compared. The first method, using placement of gold "seed" in the urogenital diaphragm, is shown by CT scanning to accurately mark the prostatic apex. The other technique, in use at the Cross Cancer Institute for the past 18 months, employs a more rapid, less invasive method of retrograde contrast instillation. Both techniques yield equally precise localization of the prostate for subsequent treatment planning.     

Simulation for localized prostate cancer: a comparison of urethrography techniques.

Forty-five patients having conventional fluoroscopic, or CT scan simulation of the prostate gland from January 1999 to June 1999 were studied. Patients were consecutively assigned (not randomized) in groups of 15 to 3 different urethrography techniques: air contrast alone (group 1), hypaque contrast alone (group 2), and xylocaine jelly and hypaque contrast (group 3). Outcome measures were pain scores, visualization of the apex (indicated by urethrogram tip), and frequency of corrections necessary on the basis of verification port films. Group 3 patients had the lowest mean pain score and required fewer lateral setup corrections at the time of portal imaging on the first day of treatment. A comparison of radiographs also revealed that group 2 and 3 patients (hypaque contrast) had better delineation of the prostatic anatomy than group 1 patients (air contrast). We found that of the 3 techniques tested, urethrography utilizing xylocaine jelly and hypaque was associated with the least amount of pain, least amount of corrective shifts, and best quality in defining the prostatic anatomy.     

Estimation of exposure dose from CBCT for prostate IMRT and approach to reduce local exposure dose

Intensity modulated radiation therapy (IMRT) requires a precise set-up for which 3D matching using cone beam computed tomography (CBCT) is useful. Because images are acquired before every irradiation, investigating the exposure dose is essential. Such studies have been reported, but fewer reports have attempted to compare the dose with those in other modalities, as we did in this study. The exposure doses for imaging using 3 devices, including on board imager(OBI) CBCT, were measured using a tough water phantom, a self-made phantom, and a radiophotoluminescence glass dosimeter. The highest measured value was observed on OBI CBCT: the exposure dose was 4.3 times higher at some measurement sites than that from CT. Because this phenomenon is derived from the projection angle, a localized increase in the exposure dose may be prevented by changing the projection angle on each acquisition. Because the exposure dose for OBI CBCT was the highest and acquisition is performed before every irradiation, procedural modification is necessary, such as minimizing acquisition and the use of ultrasonography to confirm urine retention.     

Toxicity and outcome of pelvic IMRT for node-positive prostate cancer

Background and purpose

This study reports on the treatment techniques, toxicity, and outcome of pelvic intensity-modulated radiotherapy (IMRT) for lymph node-positive prostate cancer (LNPPC, T1-4, c/pN1 cM0).

Patients and methods

Pelvic IMRT to 45–50.4?Gy was applied in 39?cases either after previous surgery of involved lymph nodes (n?=?18) or with a radiation boost to suspicious nodes (n?=?21) with doses of 60–70?Gy, usually combined with androgen deprivation (n?=?37). The prostate and seminal vesicles received 70–74?Gy. In cases of previous prostatectomy, prostatic fossa and remnants of seminal vesicles were given 66–70?Gy. Treatment-related acute and late toxicity was graded according to the RTOG criteria.

Results

Acute radiation-related toxicity higher than ?grade?2 occurred in 2?patients (with the need for urinary catheter/subileus related to adhesions after surgery). Late toxicity was mild (grade 1–2) after a median follow-up of 70?months. Over 50% of the patients reported no late morbidity (grade 0). PSA control and cancer-specific survival reached 67% and 97% at over ?5?years.

Conclusion

Pelvic IMRT after the removal of affected nodes or with a radiation boost to clinically positive nodes led to an acceptable late toxicity (no grade 3/4 events), thus justifying further evaluation of this approach in a larger cohort.     

Biologically effective dose and definitive radiation treatment for localized prostate cancer

Background and purpose

It is not clear if prolongation of definitive external radiation therapy for prostate cancer has an effect on biochemical failure. The aim of this work was to evaluate whether the biologically effective dose (BED), and in particular the duration of radiotherapy, intended as overall treatment time, has an effect on biochemical failure rates and to develop a nomogram useful to predict the 6-year probability of biochemical failure.

Patients and methods

A total of 670 patients with T1–3 N0 prostate cancer were treated with external beam definitive radiotherapy, to a total dose of 72–79.2 Gy in 40–44 fractions. The computed BED values were treated with restricted cubic splines. Variables were checked for colinearity using Spearman’s test. The Kaplan–Meier method was used to calculate freedom from biochemical relapse (FFBR) rates. The Cox regression analysis was used to identify prognostic factors of biochemical relapse in the final most performing model and to create a nomogram. Concordance probability estimate and calibration methods were used to validate the nomogram.

Results

Neoadjuvant and concomitant androgen deprivation was administered to 475 patients (70?%). The median follow-up was 80 months (range 20–129 months). Overall, the 6-year FFBR rate was 88.3?%. BED values were associated with higher biochemical failure risk. Age, iPSA, risk category, and days of radiotherapy treatment were independent variables of biochemical failure.

Conclusion

A prolongation of RT (lower BED values) is associated with an increased risk of biochemical failure. The nomogram may be helpful in decision making for the individual patient.     

'Boomerang' technique: an improved method for conformal treatment of locally advanced nasopharyngeal cancer

The primary aim of the present study was to assess radiation dosimetry and subsequent clinical outcomes in patients with locally advanced nasopharyngeal cancer using a novel radiation technique termed the 'Boomerang'. Dosimetric comparisons were made with both conventional and intensity modulated radiation therapy (IMRT) techniques. This is a study of 22 patients treated with this technique from June 1995 to October 1998. The technique used entailed delivery of 36 Gy in 18 fractions via parallel opposed fields, then 24 Gy in 12 fractions via asymmetric rotating arc fields for a total of 60 Gy in 30 fractions. Patients also received induction and concurrent chemotherapy. The radiation dosimetry was excellent. Dose-volume histograms showed that with the arc fields, 90% of the planning target volume received 94% of the prescribed dose. Relative to other conventional radiation therapy off-cord techniques, the Boomerang technique results in a 27% greater proportion of the prescribed dose being received by 90% of the planning target volume. This translates into an overall 10% greater dose received for the same prescribed dose. At 3 years, the actuarial loco-regional control rate, the failure-free survival rate and the overall survival rate were 91, 75 and 91%, respectively. At 5 years, the actuarial loco-regional control rate, the failure-free survival rate and the overall survival rate were 74, 62 and 71%, respectively. The Boomerang technique provided excellent radiation dosimetry with correspondingly good loco-regional control rates (in conjunction with chemotherapy) and very acceptable acute and late toxicity profiles. Because treatment can be delivered with conventional standard treatment planning and delivery systems, it is a validated treatment option for centres that do not have the capability or capacity for IMRT. A derivative of the Boomerang technique, excluding the parallel opposed component, is now our standard for patients with locally advanced nasopharyngeal cancer when IMRT is not available.     

VMAT partial arc technique decreases dose to organs at risk in whole pelvic radiotherapy for prostate cancer when compared to full arc VMAT and IMRT

Whole pelvic radiotherapy (WPRT) can sterilize microscopic lymph node metastases in treatment of prostate cancer. WPRT, compared to prostate only radiotherapy (PORT), is associated with increased acute gastrointestinal, and hematological toxicities. To further explore minimizing normal tissue toxicities associated with WPRT in definitive IMRT for prostate cancer, this planning study compared dosimetric differences between static 9-field-IMRT, full arc VMAT, and mixed partial-full arc VMAT techniques. In this retrospective study, 12 prostate cancer patients who met the criteria for WPRT were randomly selected for this study. The initial volume, PTV46, included the prostate, seminal vesicles, and pelvic nodes with margin and was prescribed to 4600 cGy. The cone-down volume, PTV78, included the prostate and proximal seminal vesicles with margin to a total dose of 7800 cGy. For each CT image set, 3 plans were generated for each of the PTVs: an IMRT plan, a full arc (FA) VMAT plan, and a mixed partial-full arc (PFA) VMAT plan, using 6MV photons energy. According to RTOG protocols none of the plans had a major Conformity Index (CI) violation by any of the 3 planning techniques. PFA plan had the best mean CI index of 1.00 and significantly better than IMRT (p = 0.03) and FA (p = 0.007). For equivalent PTV coverage, the average composite gradient index of the PFA plans was better than the IMRT and the FA plans with values 1.92, 2.03, and 2.01 respectively. The defference was statistically significant between PFA/IMRT and PFA/FA, with p- values of < 0.001. The IMRT plans and the PFA plans provided very similar doses to the rectum, bladder, sigmoid colon, and femoral heads, which were lower than the dose in the FA plans. There was a significant decrease in the mean dose to the rectum from 4524 cGy with the FA to 4182 cGy with the PFA and 4091 cGy with IMRT (p < 0.001). The percent of rectum receiving 4000 cGy was also the highest with FA at 66.1% compared to 49.9% (PFA) and 47.5% (IMRT). There was a significant decrease in the mean dose to the bladder from 3922 cGy (FA) to 3551 cGy (PFA) and 3612 cGy (IMRT) (p < 0.001). The percent of bladder receiving 4000 cGy was also the highest with FA at 45.4% compared to 36.6% (PFA) and 37.4% (IMRT). The average mean dose to the sigmoid colon decreased from 4177 cGy (FA) to 3893 cGy (PFA) and 3819 cGy (IMRT). The average mean dose to the femoral heads decreased from 2091 cGy (FA) to 2026 cGy (PFA) and 1987 cGy (IMRT). Considering the improvement in plan quality indices recorded in this study including the dose gradient and the dose to organs at risk, mixed partial-full arc plans may be the preferred VMAT treatment technique over full arc plans for prostate cancer treatments that include nodal volumes.     

Development of a simultaneous boost IMRT class solution for a hypofractionated prostate cancer protocol

The purpose of this work was to develop a robust technique for planning intensity-modulated radiation therapy (IMRT) for prostate cancer patients who are to be entered into a proposed hypofractionated dose escalation study. In this study the dose escalation will be restricted to the prostate alone, which may be regarded as a concurrent boost volume within the overall planning target volume (PTV). The dose to the prostate itself is to be delivered in 3 Gy fractions, and for this phase of the study the total prostate dose will be 57 Gy in 19 fractions, with 50 Gy prescribed to the rest of the PTV. If acute toxicity results are acceptable, the next phase will escalate doses to 60 Gy in 20 x 3 Gy fractions. There will be 30 patients in each arm. This work describes the class solution which was developed to create IMRT plans for this study, and which enabled the same set of inverse planning parameters to be used during optimization for every patient with minimal planner intervention. The resulting dose distributions were compared with those that would be achieved from a 3D conformal radiotherapy (3DCRT) technique that used a multileaf collimator (MLC) but no intensity modulation to treat the PTV, followed by a sequential boost to raise the prostate to 57 Gy. The two methods were tested on anatomical data sets for a series of 10 patients who would have been eligible for this study, and the techniques were compared in terms of doses to the target volumes and the organs at risk. The IMRT method resulted in much greater sparing of the rectum and bladder than the 3DCRT technique, whilst still delivering acceptable doses to the target volumes. In particular, the volume of rectum receiving the minimum PTV dose of 47.5 Gy was reduced from a mean value of 36.9% (range 23.4% to 61.0%) to 18.6% (10.3% to 29.0%). In conclusion, it was found possible to use a class solution approach to produce IMRT dose escalated plans. This IMRT technique has since been implemented clinically for patients enrolled in the hypofractionated dose escalation study.     

Dosimetric comparison of IMRT rectal and anal canal plans generated using an anterior dose avoidance structure

To describe a dosimetric method using an anterior dose avoidance structure (ADAS) during the treatment planning process for intensity-modulated radiation therapy (IMRT) for patients with anal canal and rectal carcinomas. A total of 20 patients were planned on the Elekta/CMS XiO treatment planning system, version 4.5.1 (Maryland Heights MO) with a superposition algorithm. For each patient, 2 plans were created: one employing an ADAS (ADAS plan) and the other replanned without an ADAS (non-ADAS plan). The ADAS was defined to occupy the volume between the inguinal nodes and primary target providing a single organ at risk that is completely outside of the target volume. Each plan used the same beam parameters and was analyzed by comparing target coverage, overall plan dose conformity using a conformity number (CN) equation, bowel dose-volume histograms, and the number of segments, daily treatment duration, and global maximum dose. The ADAS and non-ADAS plans were equivalent in target coverage, mean global maximum dose, and sparing of small bowel in low-dose regions (5, 10, 15, and 20 Gy). The mean difference between the CN value for the non-ADAS plans and ADAS plans was 0.04 ± 0.03 (p < 0.001). The mean difference in the number of segments was 15.7 ± 12.7 (p < 0.001) in favor of ADAS plans. The ADAS plan delivery time was shorter by 2.0 ± 1.5 minutes (p < 0.001) than the non-ADAS one. The ADAS has proven to be a powerful tool when planning rectal and anal canal IMRT cases with critical structures partially contained inside the target volume.     

Controlling heterogeneity within the lymphatic target volume for dose painted treatment of prostate cancer

Introduction: For patients with high risk prostate cancer, conventionally fractionated treatment of the pelvic lymphatics and hypofractionated treatment to the prostate can be delivered simultaneously with dose painting. The purpose of this technical note is to highlight unexpected hot spots within the low dose lymphatic target volume as a clinical problem that we have observed with dose painting, and to describe a simple approach to account for this during treatment planning.Summary: We describe the creation of a control structure that can be incorporated into the optimization objective function. An upper constraint objective can be placed on the control structure such that heterogeneity within the plan is limited to the area near the high dose target volume and better emulates the dosimetry of a conventionally fractionated sequential boost plan.     

近距离放射治疗与根治性前列腺切除术治疗局限性前列腺癌疗效的Meta分析

目的 比较近距离放射治疗与根治性前列腺切除术治疗局限性前列腺癌的疗效.方法 通过PubMed、万方、中国生物医学文献光盘数据库(CBMdisc)、荷兰医学文献数据库(EMBASE)、Ovid、Cochrane Library数据库收集已发表的有关局限性前列腺癌近距离放射治疗与根治性前列腺切除术疗效的随机对照研究文献,按预设的标准进行筛选,对纳入研究进行质量评价,并提取5年无生化复发生存率作为终点指标,使用Cochrane系统评价软件RevMan 5.0完成Meta分析.结果 经筛选,共纳入6个研究,总样本量5903例,其中近距离放疗组3323例,根治性前列腺切除术组2580例.分析结果显示2种治疗方法的5年无生化复发生存率合并OR为1.00(95％ CI:0.69～1.45),P=0.99,差异无统计学意义.结论 局限性前列腺癌近距离放射治疗与根治性前列腺切除术疗效相当,且更具优势.但纳入文献和样本量有限,今后还需增大样本,提供更好的循证证据.     

Maximizing dosimetric benefits of IMRT in the treatment of localized prostate cancer through multicriteria optimization planning

We examine the quality of plans created using multicriteria optimization (MCO) treatment planning in intensity-modulated radiation therapy (IMRT) in treatment of localized prostate cancer. Nine random cases of patients receiving IMRT to the prostate were selected. Each case was associated with a clinically approved plan created using Corvus. The cases were replanned using MCO-based planning in RayStation. Dose-volume histogram data from both planning systems were presented to 2 radiation oncologists in a blinded evaluation, and were compared at a number of dose-volume points. Both physicians rated all 9 MCO plans as superior to the clinically approved plans (p<10^?5). Target coverage was equivalent (p = 0.81). Maximum doses to the prostate and bladder and the V50 and V70 to the anterior rectum were reduced in all MCO plans (p<0.05). Treatment planning time with MCO took approximately 60 minutes per case. MCO-based planning for prostate IMRT is efficient and produces high-quality plans with good target homogeneity and sparing of the anterior rectum, bladder, and femoral heads, without sacrificing target coverage.