Intensity-modulated Radiotherapy For Prostate Cancer Research Articles

Photon and Proton Radiation Therapy Utilization in a Population of over 100 Million Commercially Insured Patients

Over the last decade there have been substantial changes in the availability of various forms of radiation therapy. The aim of our study was to better understand the changes in the use of radiation therapy among patients with prostate cancer, adults with other non-prostate cancer malignancies, and pediatric cancers. We specifically evaluated the changes in use of conventional radiation therapy (RT), 3D conformal radiation therapy (3DRT), intensity modulated radiation therapy (IMRT), stereotactic body radiation therapy (SBRT), and proton beam radiation therapy (PBRT) over a 10-year period in a commercially insured population. We conducted a retrospective analysis of data from the Optum Labs Data Warehouse (OLDW), an administrative claims database of privately insured and Medicare Advantage enrollees from throughout the US. The database contains data for over 100 million enrollees, from geographically diverse regions across the US. The plan provides fully insured coverage for professional (e.g., physician), facility (e.g., hospital), and outpatient prescription medication services. Descriptive analyses were undertaken to evaluate the utilization rates of radiation therapy from 2002-2012. From 2002 through 2012, 474 533 patients were treated with RT. The percent change in utilization per modality over the time period studied is shown in the table below. The most significant change in utilization occurred in the increase of utilization of IMRT for the treatment of prostate cancer, growing from 3.5% in 2002 to 64.0% by 2012. For non-prostate cancer in adults, IMRT adoption has demonstrated only modest growth. Proton beam radiation therapy utilization in adult patients remains very low. For children, its utilization has increased, but remains under 10% of cases treated in this population. For all patients, adoption of advanced technologies such as SBRT and PBRT has led to a combined utilization rate of less than 2% versus 22% for IMRT.Poster Viewing Abstracts 2891; TablePatient typeYearPBRT (%)SBRT (%)IMRT (%)3DRT (%)Other RT (%)All patients20020.10.02.134.563.4All patients20120.60.121.940.436.0Prostate20020.00.03.558.937.5Prostate20122.60.564.022.710.4Adult non-prostate20020.10.01.729.069.2Adult non-prostate20120.31.216.441.540.7Pediatric20020.30.03.529.167.1Pediatric20129.71.27.524.257.4 Open table in a new tab The introduction of SBRT and PBRT have had little impact on overall patterns of utilization and expenditure to date, in contrast to the shift in utilization seen after introduction of IMRT. The largest shift in utilization has occurred in the adoption of IMRT for prostate cancer for approximately two-thirds of adults with that diagnosis. Efforts to reduce costs in radiation oncology should focus on utilization patterns as well as the technological base used to deliver therapy.

Dosimetric evaluation of planning target volume margin reduction for prostate cancer via image-guided intensity-modulated radiation therapy

The aim of this study was to quantitatively estimate the dosimetric benefits of the image-guided radiation therapy (IGRT) system for the prostate intensity-modulated radiation therapy (IMRT) delivery. The cases of eleven patients who underwent IMRT for prostate cancer without a prostatectomy at our institution between October 2012 and April 2014 were retrospectively analyzed. For every patient, clinical target volume (CTV) to planning target volume (PTV) margins were uniformly used: 3 mm, 5 mm, 7 mm, 10 mm, 12 mm, and 15 mm. For each margin size, the IMRT plans were independently optimized by one medical physicist using Pinnalce3 (ver. 8.0.d, Philips Medical System, Madison, WI) in order to maintain the plan quality. The maximum geometrical margin (MGM) for every CT image set, defined as the smallest margin encompassing the rectum at least at one slice, was between 13 mm and 26 mm. The percentage rectum overlapping PTV (%V ROV ), the rectal normal tissue complication probability (NTCP) and the mean rectal dose (%RD mean ) increased in proportion to the increase of PTV margin. However the bladder NTCP remained around zero to some extent regardless of the increase of PTV margin while the percentage bladder overlapping PTV (%V BOV ) and the mean bladder dose (%BD mean ) increased in proportion to the increase of PTV margin. Without relatively large rectum or small bladder, the increase observed for rectal NTCP, %RDmean and %BD mean per 1-mm PTV margin size were 1.84%, 2.44% and 2.90%, respectively. Unlike the behavior of the rectum or the bladder, the maximum dose on each femoral head had little effect on PTV margin. This quantitative study of the PTV margin reduction supported that IG-IMRT has enhanced the clinical effects over prostate cancer with the reduction of normal organ complications under the similar level of PTV control.

Acute toxicity of hypofractionated intensity-modulated radiotherapy for prostate cancer.

Dose-escalated hypofractionated radiotherapy (hfrt) using intensity-modulated radiotherapy (imrt), with inclusion of the pelvic lymph nodes (plns), plus androgen suppression therapy (ast) in high-risk prostate cancer patients should improve patient outcomes, but acute toxicity could limit its feasibility. Our single-centre phase ii prospective study enrolled 40 high-risk prostate cancer patients. All patients received hfrt using imrt with daily mega-voltage computed tomography imaging guidance, with 95% of planning target volumes (ptv68 and ptv50) receiving 68 Gy and 50 Gy (respectively) in 25 daily fractions. The boost volume was targeted to the involved plns and the prostate (minus the urethra plus 3 mm and minus 3 mm from adjacent rectal wall) and totalled up to 75 Gy in 25 fractions. Acute toxicity scores were recorded weekly during and 3 months after radiotherapy (rt) administration. For the 37 patients who completed rt and the 3-month follow-up, median age was 65.5 years (range: 50-76 years). Disease was organ-confined (T1c-T2c) in 23 patients (62.1%), and node-positive in 5 patients (13.5%). All patients received long-term ast. Maximum acute genitourinary (gu) and gastrointestinal (gi) toxicity peaked at grade 2 in 6 of 36 evaluated patients (16.6%) and in 4 of 31 evaluated patients (12.9%) respectively. Diarrhea and urinary frequency were the chief complaints. Dose-volume parameters demonstrated no correlation with toxicity. The ptv treatment objectives were met in 36 of the 37 patients. This hfrt dose-escalation trial in high-risk prostate cancer has demonstrated the feasibility of administering 75 Gy in 25 fractions with minimal acute gi and gu toxicities. Further follow-up will report late toxicities and outcomes.

The evolution of evaluation and management of urinary or fecal incontinence and pelvic organ prolapse

Sexual function is an important concern in men receiving intensity modulated radiation therapy (IMRT) for prostate cancer. Our aim was to study the impact of IMRT and androgen deprivation therapy (ADT) on sexual function over time and to report the effectiveness of sexual medications or aids.A total of 179 men, median age 69, received definitive IMRT for prostate cancer and completed 2 surveys (Expanded Prostate Cancer Index Composite-26 and a sexual medicines/devices survey) for at least 2 time points. Surveys were prospectively collected at baseline (before all therapy), and 2, 6, 12, 18, and 24 months after IMRT. Median dose was 76 Gy to the prostate. ADT was administered to 59% of patients (median duration 5 months, initiated 2 months before IMRT). Global scores were generated for the Expanded Prostate Cancer Index Composite-26 questions. Longitudinal analysis was performed by constructing a generalized estimation equations model, and clinical variables were tested for association with global scores.Overall, there was a significant decline in global sexual score through 2 years. Men receiving ADT had a lower sexual score at 2 and 6 months, but this difference disappeared at 24 months. Analysis of individual sexual symptoms showed no significant difference at 24 months except that men on ADT were less likely to be sexually active (P = .02); this difference was not observed for men receiving short-term ADT only. Longitudinal analysis revealed that duration of ADT was the only factor associated with global sexual score. Phosphodiesterase inhibitors were attempted by roughly half of all men, with 66% experiencing benefit, whereas other aids were attempted by roughly 5% of men.Although ADT adversely affected short-term sexual function, there was no significant difference in global score and most sexual symptoms by 24 months. These data are useful for anticipatory guidance regarding expectations after IMRT.

Hypofractionated intensity-modulated radiation therapy for prostate cancer confined to the pelvis: analysis of efficacy and late toxicity

We sought to evaluate the efficacy and safety of a hypofractionated intensity-modulated radiotherapy (IMRT) regimen for pelvic-confined prostate cancer in prostate-specific antigen (PSA)-unscreened Chinese patients. We prospectively enrolled 140 prostate cancer patients (T1–4N0–1M0) on a phase II protocol who were then treated with hypofractionated IMRT (2.7 Gy × 25 fractions; total 67.5 Gy). High-risk patients (≥30 % probability of pelvic nodal involvement, 55 patients) and patients with pelvic nodal enlargement (25 patients) also received 50 Gy in 25 fractions to the pelvic lymph nodes. Outcomes and toxicity data were analyzed for all patients at a median follow-up of 35 months. The 3-year overall survival and biochemical recurrence–free survival (bRFS) rates were 94.6 and 89.1 %, respectively. The bRFS at 3 years was 100 % for low/intermediate-risk patients, 89.6 % for high-risk patients, 82.5 % for very high risk patients, and 73.5 % for those with N1 disease. Cumulative grade ≥2 Radiation Therapy Oncology Group late gastrointestinal (GI) and genitourinary (GU) toxicity at 3 years was 26.4 and 18.6 %, respectively. There were four grade 3 GI and seven grade 3 GU events and one grade 4 GI and one grade 4 GU event. At the last follow-up, 8.5 and 9.3 % of patients had late grade ≥2 GI and GU toxicity, respectively, and 1.4 and 2.9 % patients had late grade ≥3 GI and GU toxicity, respectively. Moderately hypofractionated IMRT for prostate cancer is efficacious and well-tolerated in this predominantly high-risk, locally advanced, or N1 Chinese patients and is associated with low rates of severe late toxicity during early follow-up.

Implementation of intensity modulated radiotherapy for prostate cancer in a private radiotherapy service in Mexico

Intensity modulated radiation therapy (IMRT) allows physicians to deliver higher conformal doses to the tumour, while avoiding adjacent structures. As a result the probability of tumour control is higher and toxicity may be reduced. However, implementation of IMRT is highly complex and requires a rigorous quality assurance (QA) program both before and during treatment. The present article describes the process of implementing IMRT for localized prostate cancer in a radiation therapy department. In our experience, IMRT implementation requires careful planning due to the need to simultaneously implement specialized software, multifaceted QA programs, and training of the multidisciplinary team. Establishing standardized protocols and ensuring close collaboration between a multidisciplinary team is challenging but essential.

The impact of hormonal therapy on sexual quality of life in men receiving intensity modulated radiation therapy for prostate cancer

PurposeSexual function is an important concern in men receiving intensity modulated radiation therapy (IMRT) for prostate cancer. Our aim was to study the impact of IMRT and androgen deprivation therapy (ADT) on sexual function over time and to report the effectiveness of sexual medications or aids. Methods and materialsA total of 179 men, median age 69, received definitive IMRT for prostate cancer and completed 2 surveys (Expanded Prostate Cancer Index Composite-26 and a sexual medicines/devices survey) for at least 2 time points. Surveys were prospectively collected at baseline (before all therapy), and 2, 6, 12, 18, and 24 months after IMRT. Median dose was 76 Gy to the prostate. ADT was administered to 59% of patients (median duration 5 months, initiated 2 months before IMRT). Global scores were generated for the Expanded Prostate Cancer Index Composite-26 questions. Longitudinal analysis was performed by constructing a generalized estimation equations model, and clinical variables were tested for association with global scores. ResultsOverall, there was a significant decline in global sexual score through 2 years. Men receiving ADT had a lower sexual score at 2 and 6 months, but this difference disappeared at 24 months. Analysis of individual sexual symptoms showed no significant difference at 24 months except that men on ADT were less likely to be sexually active (P = .02); this difference was not observed for men receiving short-term ADT only. Longitudinal analysis revealed that duration of ADT was the only factor associated with global sexual score. Phosphodiesterase inhibitors were attempted by roughly half of all men, with 66% experiencing benefit, whereas other aids were attempted by roughly 5% of men. ConclusionsAlthough ADT adversely affected short-term sexual function, there was no significant difference in global score and most sexual symptoms by 24 months. These data are useful for anticipatory guidance regarding expectations after IMRT.

Impact of changing rectal dose volume parameters over time on late rectal and urinary toxicity after high-dose intensity-modulated radiotherapy for prostate cancer: A 10-years single centre experience

Background. External beam radiotherapy is an excellent treatment for patients with prostate cancer (PC). Assessing long-term radiotherapy-induced toxicity is important. We evaluated the impact of implementing different rectal dose volume constraints (DVC) on late rectal and urinary toxicity.Material and methods. Six hundred and thirty-seven PC patients were treated with high-dose intensity-modulated radiotherapy (IMRT) in the primary (median dose of 78 Gy to the prostate) or postoperative setting [median dose of 74 (adjuvant) and 76 Gy (salvage) to the prostatic bed]. Three groups were defined according to different DVC applied over time. The incidence of late rectal and urinary toxicity was evaluated. Three-year actuarial risk estimations of grade 2–3 rectal and urinary toxicity were calculated (Kaplan-Meier statistics).Results. Median follow-up was five years. Overall, the incidence of late grade 3 and 2 rectal toxicity was 1% and 11%. The calculated three-year actuarial risk of developing late grade ≥ 2 rectal toxicity decreased from 16% to 7% and 5% for patients in Group 1, Group 2 and Group 3, respectively (p < 0.001). Respectively, 17 (4%) and 98 (24%) patients developed grade 3 and 2 late urinary toxicity in the primary setting. In the postoperative setting, 15 (6%) and 62 (26%) patients developed grade 3 and 2 urinary toxicity, respectively. The three-year actuarial risk of developing late ≥ grade 2 urinary toxicity in primary- and postoperative-treated patients was 22% and 23%, respectively. This was not significantly different between the three groups.Conclusion. The majority of patients developed no or only moderate rectal toxicity after high-dose IMRT for PC. Implementing different rectal DVC resulted in a significant decrease of late rectal toxicity without affecting urinary toxicity.

Stereotactic body radiation therapy: Let’s not give up on progress

Stereotactic body radiation therapy (SBRT) is a promising radiation therapy technique that delivers larger fractions of radiation more precisely than standardly fractionated radiation. As a result, a course of radiation is typically only 1 or 2 weeks in duration. Given that the cost and inconvenience of radiation treatment is in large part determined by the overall treatment length, SBRT is less expensive and more convenient than standard radiation in treating cancers that have long treatment courses, such as intensity modulated radiation therapy (IMRT) for prostate cancer. Whether SBRT is truly incrementally cost-effective compared with IMRT for prostate cancer depends on whether the lower cost of radiation and convenience that favors SBRT is commensurate with any increase in toxicity or difference tumor control.1 Compared with standard fractionated schedules, SBRT is likely more convenient, although this has not been quantified for prostate cancer as it has been for non-small cell lung cancer.2 It is likely that improved convenience is also seen in prostate cancer patients, particularly in areas of the United States that are relatively underserved geographically, such as rural areas.3 Regard-

Planning magnetic resonance imaging for prostate cancer intensity-modulated radiation therapy: Impact on target volumes, radiotherapy dose and androgen deprivation administration

Magnetic resonance imaging (MRI) scans are increasingly utilized for radiotherapy planning to contour the primary tumors of patients undergoing intensity-modulated radiation therapy (IMRT). These scans may also demonstrate cancer extent and may affect the treatment plan. We assessed the impact of planning MRI detection of extracapsular extension, seminal vesicle invasion, or adjacent organ invasion on the staging, target volume delineation, doses, and hormonal therapy of patients with prostate cancer undergoing IMRT. The records of 509 consecutive patients with planning MRI scans being treated with IMRT for prostate cancer between January 2010 and July 2012 were retrospectively reviewed. Tumor staging and treatment plans before and after MRI were compared. Of the 509 patients, 103 (20%) were upstaged and 44 (9%) were migrated to a higher risk category as a result of findings at MRI. In 94 of 509 patients (18%), the MRI findings altered management. Ninety-four of 509 patients (18%) had a change to their clinical target volume (CTV) or treatment technique, and in 41 of 509 patients (8%) the duration of hormone therapy was changed because of MRI findings. The use of radiotherapy planning MRI altered CTV design, dose and/or duration of androgen deprivation in 18% of patients in this large, single institution series of men planned for dose-escalated prostate IMRT. This has substantial implications for radiotherapy target volumes and doses, as well as duration of androgen deprivation. Further research is required to investigate whether newer MRI techniques can simultaneously fulfill staging and radiotherapy contouring roles.

Cost-effectiveness Analysis of SBRT Versus IMRT for Low-risk Prostate Cancer

Intensity-modulated radiation therapy (IMRT) has been established as the standard external-beam modality in treating low-risk prostate cancer. Stereotactic body radiotherapy (SBRT) is a novel approach involving high-dose radiotherapy in 5 fractions. This analysis compared their cost-effectiveness. A Markov model was constructed to delineate the health states after treatment with IMRT and SBRT. Disease, treatment, and toxicity data were extracted from the literature. Costs included both robotic (R-SBRT) and nonrobotic (NR-SBRT) reimbursement. Deterministic and probabilistic sensitivity analyses (PSA) were performed over a wide range of potential parameters. The quality-adjusted life expectancy after IMRT was slightly higher than after SBRT, because we assumed worse toxicity after SBRT. However, the incremental cost-effectiveness ratios (ICER) for IMRT over R-SBRT and NR-SBRT were $285,000 and $591,100/quality-adjusted life year (QALY), respectively. On sensitivity analysis, SBRT was almost always the cost-effective therapy, in which the ICER for IMRT was generally over $100,000/QALY. Reimbursement for R-SBRT versus NR-SBRT significantly influenced its ICER. Treatment efficacy, rectal toxicity and impotence, and the potential for unforeseen SBRT late effects were the most critical parameters in the model; when including these uncertain parameters in a PSA, SBRT was still most likely to be cost-effective at a willingness to pay of $100,000/QALY. SBRT clearly contained more value than IMRT for external-beam treatment. Given the increasing prevalence of the disease and its superb convenience, intensive research should be performed on this novel modality, including the marginal benefit and cost of robotic treatment.

Low incidence of new biochemical hypogonadism after intensity modulated radiation therapy for prostate cancer

PurposeTo evaluate serum testosterone and the incidence of biochemical hypogonadism in men treated with intensity modulated radiation therapy (IMRT) for prostate cancer. Methods and materialsSerum testosterone was evaluated prospectively in 51 men at pretreatment and at 6-month time points for 2 years posttreatment with IMRT for prostate cancer. Forty-one patients (80%) were treated with definitive intent and 10 patients with postprostatectomy radiation to median total doses of 7380 cGy and 6480 cGy, respectively. No patients received hormone therapy within 12 months of any serum testosterone value. Biochemical hypogonadism was defined as a total serum testosterone level ≤300 ng/dL. Incidental testicular dose was calculated using planning software when computed tomography information was available (n = 21) and using a published method of estimation when not available (n = 24), and was available for 45 patients. ResultsA statistically significant decrease in testosterone, though small in magnitude, was seen at 6 months after completion of therapy, with no significant difference by 1 year after completion of therapy. There was no increase in biochemical hypogonadism after IMRT. Below-normal pretreatment testosterone was not associated with a transient decrease. Estimated cumulative testicular dose, including dose from daily imaging, was not associated with a change in testosterone, nor was radiation therapy prescription dose or treatment intent (postoperative vs definitive). ConclusionsThe mild transient decrease in serum testosterone following IMRT monotherapy for prostate cancer is not associated with new biochemical hypogonadism.

Evaluation of different set-up error corrections on dose-volume metrics in prostate IMRT using CBCT images

We investigated the effect of different set-up error corrections on dose–volume metrics in intensity-modulated radiotherapy (IMRT) for prostate cancer under different planning target volume (PTV) margin settings using cone-beam computed tomography (CBCT) images. A total of 30 consecutive patients who underwent IMRT for prostate cancer were retrospectively analysed, and 7–14 CBCT datasets were acquired per patient. Interfractional variations in dose–volume metrics were evaluated under six different set-up error corrections, including tattoo, bony anatomy, and four different target matching groups. Set-up errors were incorporated into planning the isocenter position, and dose distributions were recalculated on CBCT images. These processes were repeated under two different PTV margin settings. In the on-line bony anatomy matching groups, systematic error (∑) was 0.3 mm, 1.4 mm, and 0.3 mm in the left–right, anterior–posterior (AP), and superior–inferior directions, respectively. ∑ in three successive off-line target matchings was finally comparable with that in the on-line bony anatomy matching in the AP direction. Although doses to the rectum and bladder wall were reduced for a small PTV margin, averaged reductions in the volume receiving 100% of the prescription dose from planning were within 2.5% under all PTV margin settings for all correction groups, with the exception of the tattoo set-up error correction only (≥5.0%). Analysis of variance showed no significant difference between on-line bony anatomy matching and target matching. While variations between the planned and delivered doses were smallest when target matching was applied, the use of bony anatomy matching still ensured the planned doses.

Reference pricing with evidence development: a way forward for proton therapy.

Next month, the Washington State Health Technology Assessment Program (HTAP) will decide whether and under what circumstances the state’s public payers will pay for proton therapy, a promising but expensive cancer treatment. HTAP has a unique legislative mandate in the United States to evaluate health technologies and translate evidence of comparative cost-effectiveness into payment policy. HTAP’s decisions are closely scrutinized, and they influence the payment policy of other payers in the US health care system. HTAP’s examination of proton therapy comes at a decisive moment: major insurers have recently announced policies that restrict coverage for proton therapy to narrow indications. 1 HTAP should not follow suit. Proton therapy comparative effectiveness research is a particular priority. Compared with photon therapies such as intensitymodulated radiotherapy (IMRT), proton therapy reduces low and intermediate radiation dose to nearby normal tissue, holding promise as more effective or better tolerated radiation treatment. However, proton therapy has greater physical and biologic uncertainties. For example, because we cannot determine where proton therapy terminates in tissue with enough precision, we routinely overshoot tumor targets to ensure adequate radiation coverage. Proton therapy uncertainties could affect clinical outcomes; thus, we must establish whether its novel advantages actually translate into clinical benefits. Yet, as the HTAP appraisal shows, high-quality comparative effectiveness evidence is woefully lacking. 2 Moreover, the costs are consequential; median Medicare reimbursement for proton therapy is $13,000 higher than that for IMRT for prostate cancer and substantially greater in the commercial insurance market. Washington State and other payers face an unenviable choice: pay for an expensive therapy that has not been shown to be better than less expensive alternatives for prevalent malignancies or restrict coverage to rare tumors in which clinical benefit appears compelling. We propose a better way forward: reference pricing with evidence development. Reference pricing establishes a common level of payment for different therapies with similar outcomes. Under reference pricing,

A dosimetric comparison of volumetric modulated arc therapy with step-and-shoot intensity modulated radiation therapy for prostate cancer

PurposeTo compare variable dose-rate volumetric modulated arc therapy (VMAT) with 7-field, step-and-shoot intensity modulated radiation therapy (IMRT) in prostate cancer patients treated with a consistent planning target volume (PTV) to a uniform total radiation therapy dose. Methods and materialsWe studied 32 patients who received 8100 cGy in 45 daily fractions to their prostate and proximal 1 cm of the seminal vesicles using variable dose rate VMAT (n = 22) or 7-field, step-and-shoot IMRT (n = 10) for intermediate-risk or high-risk prostate cancer between July 2010 and April 2013. In 90% of patients, VMAT was delivered with 2 arcs. To have an unbiased comparison of plan quality, patients who were treated with VMAT were also planned with IMRT and vice versa. Each patient served as his own control for the comparison. ResultsVMAT reduced median radiation beam-on time from 4.3 to 3.4 minutes (P = .03). There was no statistically significant difference in PTV volumes between the VMAT and step-and-shoot IMRT groups (P = .76). VMAT dose distributions were more homogeneous (P = .003). There was no difference between groups with regard to rectal V60, V65, V70, V75, bladder V65, V70, V75, V80, or femoral heads V33. ConclusionsTwo-arc VMAT resulted in shorter beam-on times and more homogenous dose distributions than 7-field, step-and-shoot IMRT for prostate cancer. With decreased beam-on time, the intrafraction motion during irradiation is reduced, thus improving confidence that the delivered dose distribution agrees with the plan.

Quantifying cell migration distance as a contributing factor to the development of rectal toxicity after prostate radiotherapy

Spatial information is usually neglected in mathematical models of radiation-induced toxicity. In the presence of inhomogeneous dose distributions produced by intensity modulated radiation therapy (IMRT) and volumetric arc therapy, this may be a limitation. We present a model to quantify the spatial characteristics of the dose distribution on the rectum through the quantification of the distribution of distances between dose points on the surface of the rectum in three-dimensions. The method allows us to evaluate the hypothesis that distances between lower and higher dose regions on the rectum influence radiation damage repair due to the migration of normal cells into damaged areas, and consequently, the development of radiation-induced toxicity in patients treated with radiation for prostate cancer. We present a method to compute distances between dose points on the surface of the rectum in three dimensions (3D) and to generate distance maps representing the distances between specific dose regions on the rectum. We introduce the concept of the distance dose surface histogram (DDSH), which is computed from the distance maps. The DDSH is a 2D histogram of rectum area on a grid defined by pairwise combinations of dose and distance. Each bin in the DDSH quantifies the area of the rectum exposed to a given dose and at a given distance from other another dose region on the rectum. By summing across the columns and rows of the DDSH, the authors can generate the dose surface histogram (DSH) and distance surface histogram (DiSH) for a particular dose region. The DiSH is a marginal histogram showing the distribution of distances for the dose points in a specific dose region from another region. We computed the DDSH, DiSH, and DSH for 33 patients treated with IMRT for prostate cancer, nine of whom developed late Grade 2 or higher late rectal toxicity. We show how even though the total area of the rectum exposed to a given dose may be the same for different patients, the distribution of distances for points receiving that dose can be different depending on the shape and contiguity of the region(s) containing those dose points. We also show that area of the rectum in the region receiving more than 75 Gy and at a distance of 16 to 22 mm from the 50 Gy isodose line was significantly correlated to the development of toxicity (p = 0.004, two sided t-test). This suggests that examining the distance distribution of points in specific dose regions could provide valuable additional information in predicting the risk of a patient developing radiation-induced rectal toxicity. We present a new method to quantify the spatial distribution of points in a given region relative to other regions on the rectum. The method provides a means to evaluate the hypothesis that distances between lower and higher dose regions on the rectum influence radiation damage repair due to the migration of normal cells into damaged areas, and may be a contributing factor to the development of radiation-induced toxicity in patients treated with radiation for prostate cancer.

Is “pelvic radiation disease” always the cause of bowel symptoms following prostate cancer intensity-modulated radiotherapy?

BackgroundPelvic radiation disease (PRD) also widely known as “radiation proctopathy” is a well recognised late side-effect following conventional prostate radiotherapy. However, endoscopic evaluation and/or specialist referral for new or persistent post-prostate radiotherapy bowel symptoms is not routine and serious diagnoses may potentially be missed. Here we report a policy of endoscopic evaluation of bowel symptoms persisting >90days post radiotherapy for prostate cancer. Methods and materialsA consecutive series of 102 patients who had radical prostate intensity-modulated radiotherapy (IMRT)/image-guided radiotherapy (IGRT) and who had new or ongoing bowel symptoms or positive faecal occult blood tests (FOBT) on follow up visits more than three months after treatment, were referred for endoscopic examination. All but one (99%) had full colonoscopic investigation. ResultsEndoscopic findings included gastric/colonic/rectal polyps (56%), diverticular disease (49%), haemorrhoids (38%), radiation proctopathy (29%), gastritis/oesophagitis (8%) and rarer diagnoses, including bowel cancer which was found in 3%. Only four patients (4%) had radiation proctopathy without associated pathology and 65 patients (63%) had more than one diagnosis. If flexible sigmoidoscopy alone were used, 36.6% of patients and 46.6% patients with polyp(s) would have had their diagnoses missed. ConclusionsOur study has shown that bowel symptoms following prostate IMRT/IGRT are due to numerous diagnoses other than PRD, including malignancy. Routine referral pathways should be developed for endoscopic evaluation/specialist review for patients with new or persistent bowel symptoms (or positive FOBT) following prostate radiotherapy. This recommendation should be considered for incorporation into national guidelines.

Long-term clinical and toxicity outcomes of hypofractionated intensity-modulated radiation therapy for clinically localized prostate cancer.

49 Background: As an alternative to dose-escalated conventionally fractionated radiotherapy, hypofractionation capitalizes on the unique radiobiology of prostate cancer cells. This study reports the long-term clinical outcomes and late treatment-related toxicities in patients with clinically localized prostate adenocarcinoma treated with hypofractionated radiation therapy at a single tertiary-care institution. Methods: Between 1996 and 2008, 822 patients were treated with hypofractionated intensity modulated radiation therapy (IMRT) (70 Gy in 2.5 Gy/fraction) directed to the prostate gland with or without coverage of the seminal vesicles over a 5.5 week period. Actuarial rates of biochemical relapse free survival by the nadir + 2 definition (bRFS), distant metastasis free survival (DMFS), and overall survival (OS) were calculated using the Kaplan-Meier method. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicity outcomes were available and measured according to the National Cancer Institute Common Toxicity Criteria (v3) in 773 (94%) of the patients. Results: The median follow-up was 8.5 years (range: 0-14.2 years). The overall 10-year bRFS, DMFS, and OS rates were 69.6%, 86.4%, and 71.7%, respectively. By National Comprehensive Cancer Network (NCCN) low-, intermediate-, and high-risk groups, the 10-year bRFS rates were 86.9%, 74.1%, and 41.3%, respectively. The rate of grade 2 or worse late genitourinary (GU) and gastrointestinal (GI) toxicity rates were 17.2% and 5.6 %. Only 1.4% of patients experienced late equal to or greater than grade 3 GU toxicity and 1.0% experienced late greater than or equal to grade 3 GI toxicity. Of those who had any toxicity during the follow-up period, 47% and 65% of patients experienced resolution or improvement in their GU and GI symptoms, respectively. Conclusions: Hypofractionated IMRT for localized prostate cancer provides excellent long-term relapse-free survival rates that are comparable to historical studies using conventional fractionation. With modern IMRT and image guidance, HFRT has an acceptably low incidence of late GU and GI toxicities, and appears to be a suitable treatment alternative to conventional fractionation.

Dosimetric effect of Elekta Beam Modulator micromultileaf in three-dimensional conformal radiotherapy and intensity-modulated radiotherapy for prostate cancer

The purpose of this study is to analyze the dosimetric effect of Elekta Beam Modulator in 3-dimensional conformal radiation therapy (3DCRT) and in intensity-modulated radiation therapy (IMRT) for localized prostate cancer. We compared treatment plans developed with 2 different Elekta multileaf collimators (MLC): Beam Modulator micro-MLC (mMLC) (4-mm leaf width at the isocenter) and standard MLC (10-mm leaf width at the isocenter). The comparison was performed for 15 patients with localized prostate cancer in 3DCRT and IMRT delivery; a total of 60 treatment plans were processed. The dose-volume histograms were used to provide the quantitative comparison between plans. In particular, we analyzed differences between rectum and bladder sparing in terms of a set of appropriate Vx (percentage of organ at risk [OAR] volume receiving the x dose) and differences between target conformity and coverage in terms of coverage factor and conformation number. Our analysis demonstrates that in 3DCRT there is an advantage in the use of Elekta Beam Modulator mMLC in terms of organ sparing; in particular, a significant decrease in rectal V60 and V50 (p = 0.001) and in bladder V70 and V65 (p = 0.007 and 0.002, respectively) was found. Moreover, a better target dose conformity was obtained (p = 0.002). IMRT plans comparison demonstrated no significant differences between the use of the 4 or 10-mm MLCs. Our analysis shows that in 3DCRT the use of the Elekta Beam Modulator mMLC gives a gain in target conformity and in OARs dose sparing whereas in IMRT plans there is no advantage.

Early Outcome of Prostate Intensity Modulated Radiation Therapy (IMRT) Incorporating a Simultaneous Intra-Prostatic MRI Directed Boost.

This study assessed the feasibility and outcomes of treating prostate cancer with intensity modulated radiotherapy (IMRT) incorporating a Magnetic Resonance Imaging (MRI) directed boost. Seventy-eight men received IMRT for localized prostate cancer. The entire prostate received 77.4Gy in 43 fractions and simultaneous intra-prostatic boosts (SIB) of 83Gy were administered to increase the dose to the MRI identified malignancy. In 16 (21%) patients, the MRI didn't detect a neoplasm and these patients received an SIB of 81Gy to the posterior prostate. Androgen Deprivation Therapy (ADT) was also administered to 32 (41%) patients. The 3-year rates of biochemical control, local control, distant control, and survival were 92%, 98%, 95%, and 95% respectively. While grade 1-2 toxicities were common, there were only 2 patients who suffered grade 3 toxicity. These patients developed strictures which were dilated resulting in improvement in symptoms such that both had grade 1-2 toxicity at last follow up examination. The results of this program of IMRT incorporating a MRI directed intra-prostatic boost suggest this technique is feasible and well tolerated. This technique appears to shift the therapeutic index favorably by boosting the malignancy to the highest dose without increasing the doses administered to the bladder and rectum.