Intensity-modulated Radiotherapy For Cancer Research Articles

A predictive model for dysphagia following IMRT for head and neck cancer: Introduction of the EMLasso technique

Background and purposeDesign a model for prediction of acute dysphagia following intensity-modulated radiotherapy (IMRT) for head and neck cancer. Illustrate the use of the EMLasso technique for model selection. Material and methodsRadiation-induced dysphagia was scored using CTCAE v.3.0 in 189 head and neck cancer patients. Clinical data (gender, age, nicotine and alcohol use, diabetes, tumor location), treatment parameters (chemotherapy, surgery involving the primary tumor, lymph node dissection, overall treatment time), dosimetric parameters (doses delivered to pharyngeal constrictor (PC) muscles and esophagus) and 19 genetic polymorphisms were used in model building. The predicting model was achieved by EMLasso, i.e. an EM algorithm to account for missing values, applied to penalized logistic regression, which allows for variable selection by tuning the penalization parameter through crossvalidation on AUC, thus avoiding overfitting. ResultsFifty-three patients (28%) developed acute⩾grade 3 dysphagia. The final model has an AUC of 0.71 and contains concurrent chemotherapy, D2 to the superior PC and the rs3213245 (XRCC1) polymorphism. The model’s false negative rate and false positive rate in the optimal operation point on the ROC curve are 21% and 49%, respectively. ConclusionsThis study demonstrated the utility of the EMLasso technique for model selection in predictive radiogenetics.

Hematologic Toxicity in RTOG 0418: A Phase 2 Study of Postoperative IMRT for Gynecologic Cancer

Intensity modulated radiation therapy (IMRT), compared with conventional 4-field treatment, can reduce the volume of bone marrow irradiated. Pelvic bone marrow sparing has produced a clinically significant reduction in hematologic toxicity (HT). This analysis investigated HT in Radiation Therapy Oncology Group (RTOG) 0418, a prospective study to test the feasibility of delivering postoperative IMRT for cervical and endometrial cancer in a multiinstitutional setting. Patients in the RTOG 0418 study were treated with postoperative IMRT to 50.4 Gy to the pelvic lymphatics and vagina. Endometrial cancer patients received IMRT alone, whereas patients with cervical cancer received IMRT and weekly cisplatin (40 mg/m(2)). Pelvic bone marrow was defined within the treatment field by using a computed tomography density-based autocontouring algorithm. The volume of bone marrow receiving 10, 20, 30, and 40 Gy and the median dose to bone marrow were correlated with HT, graded by Common Terminology Criteria for Adverse Events, version 3.0, criteria. Eighty-three patients were eligible for analysis (43 with endometrial cancer and 40 with cervical cancer). Patients with cervical cancer treated with weekly cisplatin and pelvic IMRT had grades 1-5 HT (23%, 33%, 25%, 0%, and 0% of patients, respectively). Among patients with cervical cancer, 83% received 5 or more cycles of cisplatin, and 90% received at least 4 cycles of cisplatin. The median percentage volume of bone marrow receiving 10, 20, 30, and 40 Gy in all 83 patients, respectively, was 96%, 84%, 61%, and 37%. Among cervical cancer patients with a V40 >37%, 75% had grade 2 or higher HT compared with 40% of patients with a V40 less than or equal to 37% (P =.025). Cervical cancer patients with a median bone marrow dose of >34.2 Gy also had higher rates of grade ≥ 2 HT than did those with a dose of ≤ 34.2 Gy (74% vs 43%, P=.049). Pelvic IMRT with weekly cisplatin is associated with low rates of HT and high rates of weekly cisplatin use. The volume of bone marrow receiving 40 Gy and the median dose to bone marrow correlated with higher rates of grade ≥ 2 toxicity among patients receiving weekly cisplatin (cervical cancer patients). Evaluation and limitation of the volume of bone marrow treated with pelvic IMRT is warranted in patients receiving concurrent chemotherapy.

Re: Proton vs Intensity-Modulated Radiotherapy for Prostate Cancer: Patterns of Care and Early Toxicity

Yu and colleagues used the Medicare billing database to compare intensity-modulated radiotherapy (IMRT) to proton beam radiotherapy (PRT) (1). Unfortunately, this comparison is difficult because of the nature of the groups compared, data within the database, retrospective study design, and various biases. Inherent to this analysis was the attempt to make valid conclusions about endpoints this database was not designed to measure. The most valid conclusion was that PRT was more expensive. Regarding the statement, “Patients were assigned to the PRT group if there were any codes for PRT delivery,” the methodology of including PRT patients who had any PRT may have introduced bias. It is likely that some patients received PRT as a boost after photon radiotherapy (RT). These appear to have been included in the proton group. Patients treated in this manner generally received two-thirds of their radiation as photons. Their inclusion would bias the study, making interpretation incomprehensible. Assuming they were assigned to the PRT arm, they would likely have more toxicity because greater volumes of bladder and intestine would have been irradiated than with PRT alone. Because the majority of their dose was photons, the results would be more likely to reflect photon therapy. Toxicities included that appear unrelated to radiotherapy include genitourinary infection, upper tract dysfunction, and systemic derangements. Including toxicity codes that are likely unrelated to radiotherapy serve to make the outcomes appear more similar than different. The most frequent radiotherapy toxicities are irritative bladder and rectal voiding side effects, which were not considered in this analysis. Also left out was bleeding that did not result in transfusion, which is a common toxicity. Leaving out the more common side effects/toxicities would also make the outcomes appear more similar than different. The problem with the statement, “This study represents the most robust comparison of early toxicity for PRT vs IMRT for prostate cancer to date” is that this study is not robust. The authors did not include the majority of RT-related toxicity and included toxicity unrelated to RT. Then, they make the conclusion that this is robust, whereas the prospective clinical data suggest extremely low risk of PRT-related toxicity (2,3). The Medicare databases do

Uptake and outcomes of intensity-modulated radiation therapy for uterine cancer

ObjectiveWhile intensity-modulated radiation therapy (IMRT) allows more precise radiation planning, the technology is substantially more costly than conformal radiation and, to date, the benefits of IMRT for uterine cancer are not well defined. We examined the use of IMRT and its effect on late toxicity for uterine cancer. MethodsWomen with uterine cancer treated from 2001 to 2007 and registered in the SEER-Medicare database were examined. We investigated the extent and predictors of IMRT administration. The incidence of acute and late-radiation toxicities was compared for IMRT and conformal radiation. ResultsWe identified a total of 3555 patients including 328 (9.2%) who received IMRT. Use of IMRT increased rapidly and reached 23.2% by 2007. In a multivariable model, residence in the western U.S. and receipt of chemotherapy were associated with receipt of IMRT. Women who received IMRT had a higher rate of bowel obstruction (rate ratio=1.41; 95% CI, 1.03–1.93), but other late gastrointestinal and genitourinary toxicities as well as hip fracture rates were similar between the cohorts. After accounting for other characteristics, the cost of IMRT was $14,706 (95% CI, $12,073 to $17,339) greater than conformal radiation. ConclusionThe use of IMRT for uterine cancer is increasing rapidly. IMRT was not associated with a reduction in radiation toxicity, but was more costly.

Assessment of Interfraction Patient Setup for Head-and-Neck Cancer Intensity Modulated Radiation Therapy Using Multiple Computed Tomography-Based Image Guidance

Various image guidance systems are commonly used in conjunction with intensity modulated radiation therapy (IMRT) in head-and-neck cancer irradiation. The purpose of this study was to assess interfraction patient setup variations for 3 computed tomography (CT)-based on-board image guided radiation therapy (IGRT) modalities. A total of 3302 CT scans for 117 patients, including 53 patients receiving megavoltage cone-beam CT (MVCBCT), 29 receiving kilovoltage cone-beam CT (KVCBCT), and 35 receiving megavoltage fan-beam CT (MVFBCT), were retrospectively analyzed. The daily variations in the mediolateral (ML), craniocaudal (CC), and anteroposterior (AP) dimensions were measured. The clinical target volume-to-planned target volume (CTV-to-PTV) margins were calculated using 2.5Σ + 0.7 σ, where Σ and σ were systematic and random positioning errors, respectively. Various patient characteristics for the MVCBCT group, including weight, weight loss, tumor location, and initial body mass index, were analyzed to determine their possible correlation with daily patient setup. The average interfraction displacements (± standard deviation) in the ML, CC, and AP directions were 0.5 ± 1.5, -0.3 ± 2.0, and 0.3 ± 1.7 mm (KVCBCT); 0.2 ± 1.9, -0.2 ± 2.4, and 0.0 ± 1.7 mm (MVFBCT); and 0.0 ± 1.8, 0.5 ± 1.7, and 0.8 ± 3.0 mm (MVCBCT). The day-to-day random errors for KVCBCT, MVFBCT, and MVCBCT were 1.4-1.6, 1.7, and 2.0-2.1mm. The interobserver variations were 0.8, 1.1, and 0.7 mm (MVCBCT); 0.5, 0.4, and 0.8 mm (MVFBCT); and 0.5, 0.4, and 0.6 mm (KVCBCT) in the ML, CC, and AP directions, respectively. The maximal calculated uniform CTV-to-PTV margins were 5.6, 6.9, and 8.9 mm for KVCBCT, MVFBCT, and MVCBCT, respectively. For the evaluated patient characteristics, the calculated margins for different patient parameters appeared to differ; analysis of variance (ANOVA) and/or t test analysis found no statistically significant setup difference in any direction. Daily random setup errors and CTV-to-PTV margins for treatment of head-and-neck cancer were affected by imaging quality. Our data indicated that larger margins were associated with MVFBCT and MVCBCT, compared with smaller margins for KVCBCT. IGRT modalities with better image quality are encouraged in clinical practice.

Risk of second cancer from scattered radiation of intensity-modulated radiotherapies with lung cancer.

PurposeTo compare the risk of secondary cancer from scattered and leakage doses following intensity-modulated radiotherapy (IMRT), volumetric arc therapy (VMAT) and tomotherapy (TOMO) in patients with lung cancer.MethodsIMRT, VMAT and TOMO were planned for five lung cancer patients. Organ equivalent doses (OEDs) are estimated from the measured corresponding secondary doses during irradiation at various points 20 to 80 cm from the iso-center by using radio-photoluminescence glass dosimeter (RPLGD).ResultsThe secondary dose per Gy from IMRT, VMAT and TOMO for lung cancer, measured 20 to 80 cm from the iso-center, are 0.02~2.03, 0.03~1.35 and 0.04~0.46 cGy, respectively. The mean values of relative OED of secondary dose of VMAT and TOMO, which is normalized by IMRT, ranged between 88.63% and 41.59% revealing 88.63% and 41.59% for thyroid, 82.33% and 41.85% for pancreas, 77.97% and 49.41% for bowel, 73.42% and 72.55% for rectum, 74.16% and 81.51% for prostate. The secondary dose and OED from TOMO became similar to those from IMRT and VMAT as the distance from the field edge increased.ConclusionsOED based estimation suggests that the secondary cancer risk from TOMO is less than or comparable to the risks from conventional IMRT and VMAT.

Intensity-modulated radiation therapy versus 3D conformal radiation therapy for squamous cell carcinoma of the anal canal.

494 Background: The emergence of intensity-modulated radiation therapy (IMRT) in the treatment of anal cancer has dramatically lowered the incidence of severe toxicity while maintaining excellent long-term outcomes. We compared our institutional experience using 3D conformal radiation therapy (3DCRT) versus IMRT for anal cancer. Methods: We performed a single-institution retrospective review of all non-metastatic squamous cell carcinoma anal cancer patients treated between 2000-2011 using definitive chemoradiation with curative intent. Results: This study included 89 consecutive anal cancer patients (37 3DCRT, 52 IMRT). Median follow-up for all patients, IMRT patients alone, and CRT patients alone was 26.5 months (range, 3.5-133.6), 20 months (range, 3.5-125.5), and 61.9 months (range, 7.6-133.6), respectively. Three-year overall survival (OS), progression free survival (PFS), locoregional control (LRC), and colostomy free survival (CFS) were 91.1%, 82.3%, 90.8%, and 91.3% in the IMRT cohort and 86.1%, 72.5%, 91.9%, and 93.7% for the 3DCRT patients (all p>0.1). More patients in the 3DCRT group required a treatment break (11 vs. 4; p=0.006), although the difference in median treatment break duration was not significant (12.2 vs. 8.0 days; p=0.35). Survival outcomes did not differ based on whether a treatment break was required (all p>0.1). Acute grade ≥3 non-hematologic toxicity was significantly decreased in the IMRT cohort (21.1 vs. 59.5%; p<0.0001). Acute grade ≥3 skin toxicity was significantly worse in the 3DCRT group (p<0.0001) while an improvement in late grade ≥3 GI toxicity was observed in the IMRT patients (p=0.012). Conclusions: This is the largest retrospective review comparing 3DCRT and IMRT for definitive treatment of anal cancer. In contrast to previously published data, this study demonstrates that while long-term outcomes do not significantly differ based on RT technique, a marked decrease in adverse effects and the need for a treatment break can be achieved using IMRT.

Estimation of Secondary Scattered Dose from Intensity-modulated Radiotherapy for Liver Cancer Cases

We estimated secondary scattered and leakage doses for intensit y-modulated radiotherapy (IMRT), volumetric arc therapy (VMAT) and tomotherapy (TOMO) in patients with liver cancer. Five liver patients were planned by IMRT, VMAT and TOMO. Secondary scatter (and leakage) dose and organ equivalent doses (OEDs) are measured and estimated at various points 20 to 80 cm from the iso-center by using radiophotoluminescence glass dosimeter (RPLGD). The secondary dose per Gy from IMRT, VMAT and TOMO for liver cancer, measured 20 to 80 cm from the iso-center, are 0.01∼3.13, 0.03∼2.34 and 0.04∼1.29 cGy, respectively. The mean values of relative OED of secondary dose of VMAT and TOMO for five patients, which is normalized by IMRT, measured as 75.24% and 50.92% for thyroid, 75.14% and 40.61% for bowel, 72.30% and 47.77% for rectum, 76.21% and 49.93% for prostate. The secondary dose and OED from TOMO is relatively low to those from IMRT and VMAT. OED based estimation suggests that the secondary cancer risk from TOMO is less than or comparable to the risks from conventional IMRT and VMAT.

Dosimetry Analysis of Three Kinds of Radiation Technique for Postoperative Gastric Cancer

Objective: To compare dose-volume histograms (DVHs) and the dose distribution of three-dimensional conformal radiotherapy(3DCRT),7 fields radiotherapy(7FRT) and intensity-modulated radiotherapy (IMRT) of treatment planning in gastric cancer. Methods: We selected 5 patients with gastric cancer, they were pathologically confirmed stage T3,T4 or N+ gastric cancer. All patients underwent radical gastrectomy. A dosimetry study was carried out on these five patients. For each patient, three kinds of treatment planning were designed with a prescribed dose of 45Gy to 95％of PTV.Many kinds of parameters of these plans in each patient were compared: isodose distributions line、dose-volume histogram(DVH)、V95%、V110%、CI、HI、EI of target volume and the dose of related critical organs. Results: IMRT was superior to 3DCRT and 7F-RT in dose uniformity（p＜0.05）, there was no statistical difference between 3DCRT and 7FRT in CI（p>0.05）.IMRT had better dose conformity than 3DCRT and 7FRT（p＜0.05）, and 3DCRT was better than 7FRT in CI（p＜0.05）.IMRT showed better EI than 3DCRT and 7FRT（p＜0.05）,there was no statistical difference between 3DCRT and 7FRT in EI（p>0.05）.IMRT had advantage at sparing liver compared with 3DCRT and 7FRT（p＜0.05）,7FRT showed better D1/3 of liver than 3DCRT（p＜0.05）,but there was no statistical difference between 3DCRT and 7FRT in Dmean of liver（p>0.05）.IMRT expressed better Dmax of spinal cord than 3DCRT and 7F-RT（p＜0.05）, and 7FRT was better than IMRT in Dmax of spinal cord（p＜0.05）.But the dose received by the both kidneys were not significantly different. Conclusion: IMRT is superior to 3DCRT and 7FRT,and 3DCRT plans showed better CI and Dmax of spinal cord composed to 7FRT,and 7FRT was superior to 3DCRT in D1/3 of liver. IMRT for gastric cancer had physics advantage for clinical application.

Proton Versus Intensity-Modulated Radiotherapy for Prostate Cancer: Patterns of Care and Early Toxicity

Proton radiotherapy (PRT) is an emerging treatment for prostate cancer despite limited knowledge of clinical benefit or potential harms compared with other types of radiotherapy. We therefore compared patterns of PRT use, cost, and early toxicity among Medicare beneficiaries with prostate cancer with those of intensity-modulated radiotherapy (IMRT). We performed a retrospective study of all Medicare beneficiaries aged greater than or equal to 66 years who received PRT or IMRT for prostate cancer during 2008 and/or 2009. We used multivariable logistic regression to identify factors associated with receipt of PRT. To assess toxicity, each PRT patient was matched with two IMRT patients with similar clinical and sociodemographic characteristics. The main outcome measures were receipt of PRT or IMRT, Medicare reimbursement for each treatment, and early genitourinary, gastrointestinal, and other toxicity. All statistical tests were two-sided. We identified 27,647 men; 553 (2%) received PRT and 27,094 (98%) received IMRT. Patients receiving PRT were younger, healthier, and from more affluent areas than patients receiving IMRT. Median Medicare reimbursement was $32,428 for PRT and $18,575 for IMRT. Although PRT was associated with a statistically significant reduction in genitourinary toxicity at 6 months compared with IMRT (5.9% vs 9.5%; odds ratio [OR] = 0.60, 95% confidence interval [CI] = 0.38 to 0.96, P = .03), at 12 months post-treatment there was no difference in genitourinary toxicity (18.8% vs 17.5%; OR = 1.08, 95% CI = 0.76 to 1.54, P = .66). There was no statistically significant difference in gastrointestinal or other toxicity at 6 months or 12 months post-treatment. Although PRT is substantially more costly than IMRT, there was no difference in toxicity in a comprehensive cohort of Medicare beneficiaries with prostate cancer at 12 months post-treatment.

Fatal pneumonitis associated with postoperative intensity-modulated radiotherapy in lung cancer: Case report and review

Radiation pneumonitis (RP) is the most significant complication of acute treatment-related toxicities in lung cancer. Intensity-modulated radiotherapy (IMRT) with inverse planning enables us to achieve the desired dose distribution. However, there are many high-risk procedures associated with lung irradiation, including chemotherapy and surgery. We report a case of fatal treatment-related pneumonitis, where the patient had undergone postoperative IMRT for lung cancer. Following completion of radiotherapy, the patient developed progressive dyspnea. A chest computed tomography (CT) scan revealed the presence of diffuse reticular interstitial processes and honeycombing in both lungs. The fibrotic change in both lungs in a transverse view was compatible with low-dose irradiation of non-target organs at risk. Acute radiation pneumonitis was diagnosed. For patients receiving postoperative IMRT, low-dose irradiation volumes should be considered for lungs, as well as strict dose-volume histogram (DVH) parameters.

Improvement of Pollakiuria After Intensity Modulated Radiation Therapy (IMRT) for Prostate Cancer: Association With Prostate Volume

Improvement of Pollakiuria After Intensity Modulated Radiation Therapy (IMRT) for Prostate Cancer: Association With Prostate Volume

Comparative Outcomes of Intensity Modulated Radiation Therapy Versus 3D Conformal Radiation Therapy for Squamous Cell Carcinoma of the Anal Canal

Comparative Outcomes of Intensity Modulated Radiation Therapy Versus 3D Conformal Radiation Therapy for Squamous Cell Carcinoma of the Anal Canal

Is Belly Board Still Needed in IMRT for Rectal Cancer? The Change of Bladder Volume Affects the Determination

Prone positioned with belly board is an efficiency method to reduce the irradiated small bowel volume (ISBV) in three-dimensional conformal radiation therapy (3DCRT) for rectal cancer patients. The downside of treating patients in prone position is that compared to supine, the setup is less reproducible between and during fractions. Intensity-modulated radiation therapy (IMRT) technique has previously been demonstrated to be effective in reducing small bowel dose in comparison to 3DCRT for rectal cancer. Whether the belly board still needed in IMRT for rectal cancer is not well answered. The aim of this study was to compare the ISBV between prone positioned with belly board and supine positioned with flat table in IMRT for rectal cancer patients. Twenty patients scheduled to receive postoperative radiation therapy for rectal cancer underwent two series of CT scans, prone positioned with a belly board and supine positioned with a flat board, both combined using a full bladder protocol. On each scan, a 7-field IMRT plan was calculated. Bladder and individual loops of small bowel were contoured on each slice of the planning CT scan. A comparison of volume for small bowel and bladder in different position were performed. Comparison of V15 (volume received dose more than 15 Gy) for small bowel was made between prone and supine position with different device. Compared with supine position, all bladder volumes were decreased in the prone position. The ISBV of eight patients were increased when use belly board. The increase of ISBV was related to the decrease of bladder volume. If the relative change of bladder volume was more than 16%, the ISBV might increase when use belly board. There were no significant differences between patients undergoing IMRT with belly board and those without in terms of V15 for small bowel and ISBV (p = 0.245 and p = 0.944, respectively). If we used 16% as cutoff value to select patients, V15 for small bowel and ISBV of different position could meet marginal statistical significant (p = 0.062 and p = 0.072, respectively). The change of bladder volume in two different positions affected the ISBV. If the change less than 16%, a belly board still attributed to a significant bowel dose reduction when using IMRT and a full bladder protocol.

Decreasing Acute and Late Toxicity Using Urethral Dose Reduction and Smaller Safety Margin Around CTV for Prostate Cancer Intensity Modulated Radiation Therapy (IMRT) With a Real-time Tumor-tracking (RTRT) System

To assess a technique using a small margin between the clinical target volume (CTV) and planning target volume (PTV) and urethral dose reduction in IMRT equipped with the RTRT system for clinical outcomes and development of acute and late toxicity in patients with prostate cancer.

Dose Volume Analysis of Grade 2+ Late GI Toxicity on RTOG 0126 After High-dose 3DCRT or IMRT

Purpose/Objective(s): To report the long-term survival and toxicity outcomes with the use of ultra-high-dose intensity modulated radiation therapy (IMRT) to a dose of 86.4 Gy for patients with localized prostate cancer. Materials/Methods: Between August 1997 and December 2008, 1002 patients were treated to a dose of 86.4 Gy using a 5-7 field IMRT technique. Patients were stratified into prognostic risk groups based on the National Comprehensive Cancer Network risk-grouping system. Five hundred eighty-seven patients (59%) were treated with neoadjuvant and concurrent androgen-deprivation therapy. The median follow-up for the entire cohort was 5.5 years (range 1-14 years). Results: The 5and 10-year actuarial prostate-specific antigen (PSA) relapse-free survival outcomes for low-, intermediate-, and high-risk groups were 98.8 and 96.3%, 89.1 and 75.4%, and 76.1 and 65.8% (p < 0.001), respectively. On multivariate analysis, T stage (p Z 0.002), Gleason score (p < 0.001), and pretreatment PSA (iPSA) (p Z 0.008) were predictors for biochemical relapse. The 5and 10-year actuarial DMFS for low-, intermediate-, and high-risk groups was 99.4 and 96.8%, 97.4 and 93.6%, and 90.1 and 74.4% (p < 0.001), respectively. On multivariate analysis, T stage (p < 0.001), Gleason score (p < 0.001), and iPSA (p < 0.033) were predictive for DM. No prostate cancer-related deaths were observed in the low-risk group. The 5and 10-year actuarial CSS for intermediateand high-risk groups was 99.4 and 93.8%, and 96.6 and 82.2% (p Z 0.008), respectively. On multivariate analysis, only T stage (p Z 0.016) and Gleason score (p Z 0.003) were predictive for prostate cancer-related death. The incidence of grade 2 or higher late gastrointestinal (GI) and genitourinary (GU) toxicities were 4.4% and 17.1%, respectively. Late grade 3 GI and GU toxicity was experienced in 7 patients (0.7%) and 22 patients (2.2%), respectively. Of the 427 men with full potency at baseline, 317 men (74%) retained sexual function at time of last follow-up. Conclusions: This represents the largest cohort of patients treated with ultra-high-dose radiation to 86.4 Gy using IMRT for localized prostate cancer with the longest follow-up to date. Our findings indicate that this treatment results in excellent clinical outcomes and is well tolerated with acceptable toxicity. Author Disclosure: D. Spratt: None. X. Pei: None. J. Yamada: None. M.A. Kollmeier: None. B. Cox: None. Z. Zhang: None. M.J. Zelefsky: None.

Long-term Survival and Toxicity of Patients Treated With Ultra-high-dose IMRT for Localized Prostate Cancer

Purpose/Objective(s): To report the long-term survival and toxicity outcomes with the use of ultra-high-dose intensity modulated radiation therapy (IMRT) to a dose of 86.4 Gy for patients with localized prostate cancer. Materials/Methods: Between August 1997 and December 2008, 1002 patients were treated to a dose of 86.4 Gy using a 5-7 field IMRT technique. Patients were stratified into prognostic risk groups based on the National Comprehensive Cancer Network risk-grouping system. Five hundred eighty-seven patients (59%) were treated with neoadjuvant and concurrent androgen-deprivation therapy. The median follow-up for the entire cohort was 5.5 years (range 1-14 years). Results: The 5and 10-year actuarial prostate-specific antigen (PSA) relapse-free survival outcomes for low-, intermediate-, and high-risk groups were 98.8 and 96.3%, 89.1 and 75.4%, and 76.1 and 65.8% (p < 0.001), respectively. On multivariate analysis, T stage (p Z 0.002), Gleason score (p < 0.001), and pretreatment PSA (iPSA) (p Z 0.008) were predictors for biochemical relapse. The 5and 10-year actuarial DMFS for low-, intermediate-, and high-risk groups was 99.4 and 96.8%, 97.4 and 93.6%, and 90.1 and 74.4% (p < 0.001), respectively. On multivariate analysis, T stage (p < 0.001), Gleason score (p < 0.001), and iPSA (p < 0.033) were predictive for DM. No prostate cancer-related deaths were observed in the low-risk group. The 5and 10-year actuarial CSS for intermediateand high-risk groups was 99.4 and 93.8%, and 96.6 and 82.2% (p Z 0.008), respectively. On multivariate analysis, only T stage (p Z 0.016) and Gleason score (p Z 0.003) were predictive for prostate cancer-related death. The incidence of grade 2 or higher late gastrointestinal (GI) and genitourinary (GU) toxicities were 4.4% and 17.1%, respectively. Late grade 3 GI and GU toxicity was experienced in 7 patients (0.7%) and 22 patients (2.2%), respectively. Of the 427 men with full potency at baseline, 317 men (74%) retained sexual function at time of last follow-up. Conclusions: This represents the largest cohort of patients treated with ultra-high-dose radiation to 86.4 Gy using IMRT for localized prostate cancer with the longest follow-up to date. Our findings indicate that this treatment results in excellent clinical outcomes and is well tolerated with acceptable toxicity. Author Disclosure: D. Spratt: None. X. Pei: None. J. Yamada: None. M.A. Kollmeier: None. B. Cox: None. Z. Zhang: None. M.J. Zelefsky: None.

Nine-year Outcome and Toxicity in Patients Treated With IMRT for Clinically Localized Prostate Cancer

To evaluate long term results and chronic toxicities observed in patients treated with intensity-modulated radiation therapy (IMRT) for clinically localized prostate cancer. Three hundred two patients with localized prostate cancer treated with image guided (BAT ultrasound) IMRT between 7/2000 and 5/2005 were retrospectively analyzed. All patients had >12 months follow-up except for early deaths. Risk groups were designated based on NCCN guidelines for low risk, intermediate risk and high risk (including T3b). Biochemical control was based on the ASTRO (Phoenix) consensus definition. Chronic toxicity was measured both at peak symptoms and at last visit. Toxicity was scored based on CTCAE v.4. The median dose delivered was 75.6 Gy (range, 70.2-77.4 Gy). A total of 35.4% of patients received androgen deprivation therapy (ADT). With a median follow-up of 84.4 months (range, 4.5-136.4), local and distant recurrence rates were 5% and 8.6%, respectively. The 5-year biochemical control rates were 91.7% for low risk, 86.1% for intermediate risk, and 79.3% for high risk patients. At 9-years, biochemical control rates decreased to 77.3% for low risk, 69.4% for intermediate risk, and 52.7% for high risk patients (p = 0.054). ADT did not improve biochemical control in the intermediate risk group with 9-year biochemical control of 81.4% vs. 66.7% (p = 0.52). Univariate analysis found that clinical T-stage, Gleason score, and PSA group was prognostic for biochemical control. Peak chronic GU toxicity was Grade 1: 27.8%, Grade 2: 20.9%, Grade 3: 3.0% Grade 4: .3%. Peak chronic GI toxicity was Grade 1: 28.1%, Grade 2: 11.3%, Grade 3: 1%. At last follow-up, GU toxicity grade decreased to Grade 0: 76.8%, Grade 1: 16.2%, Grade 2: 6.3%, Grade 3: 0.7%. GI toxicity decreased to Grade 0: 88.4%, Grade 1: 9.6%, Grade 2: 1.7%, Grade 3: 0.3%. High risk group was associated with higher distant metastasis rate (p = 0.02) and death from prostate cancer.(p = 0.0012). This study represents one of the longest reported experiences regarding the use of IMRT for prostate cancer. IMRT was well tolerated with low late toxicity observed. Despite excellent biochemical control at 5 years, additional patients failed with longer follow-up. Subsequently, we started using image guided IMRT with implanted fiducials delivering 77.4 Gy/43 fractions with an MRI directed concurrent boost to 83 Gy in order to potentially further improve the outcome.

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

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). Pelvic IMRT to 45-50.4Gy was applied in 39cases either after previous surgery of involved lymph nodes (n = 18) or with a radiation boost to suspicious nodes (n = 21) with doses of 60-70Gy, usually combined with androgen deprivation (n = 37). The prostate and seminal vesicles received 70-74Gy. In cases of previous prostatectomy, prostatic fossa and remnants of seminal vesicles were given 66-70Gy. Treatment-related acute and late toxicity was graded according to the RTOG criteria. Acute radiation-related toxicity higher than grade2 occurred in 2patients (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 70months. Over 50% of the patients reported no late morbidity (grade 0). PSA control and cancer-specific survival reached 67% and 97% at over 5years. 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.

Long-term Survival and Toxicity in Patients Treated With High-Dose Intensity Modulated Radiation Therapy for Localized Prostate Cancer

To report long-term survival and toxicity outcomes with the use of high-dose intensity modulated radiation therapy (IMRT) to 86.4 Gy for patients with localized prostate cancer. Between August 1997 and December 2008, 1002 patients were treated to a dose of 86.4 Gy using a 5-7 field IMRT technique. Patients were stratified by prognostic risk group based on National Comprehensive Cancer Network risk classification criteria. A total of 587 patients (59%) were treated with neoadjuvant and concurrent androgen deprivation therapy. The median follow-up for the entire cohort was 5.5 years (range, 1-14 years). For low-, intermediate-, and high-risk groups, 7-year biochemical relapse-free survival outcomes were 98.8%, 85.6%, and 67.9%, respectively (P<.001), and distant metastasis-free survival rates were 99.4%, 94.1%, and 82.0% (P<.001), respectively. On multivariate analysis, T stage (P<.001), Gleason score (P<.001), and >50% of initial biopsy positive core (P=.001) were predictive for distant mestastases. No prostate cancer-related deaths were observed in the low-risk group. The 7-year prostate cancer-specific mortality (PCSM) rates, using competing risk analysis for intermediate- and high-risk groups, were 3.3% and 8.1%, respectively (P=.008). On multivariate analysis, Gleason score (P=.004), percentage of biopsy core positivity (P=.003), and T-stage (P=.033) were predictive for PCSM. Actuarial 7-year grade 2 or higher late gastrointestinal and genitourinary toxicities were 4.4% and 21.1%, respectively. Late grade 3 gastrointestinal and genitourinary toxicity was experienced by 7 patients (0.7%) and 22 patients (2.2%), respectively. Of the 427 men with full potency at baseline, 317 men (74%) retained sexual function at time of last follow-up. This study represents the largest cohort of patients treated with high-dose radiation to 86.4 Gy, using IMRT for localized prostate cancer, with the longest follow-up to date. Our findings indicate that this treatment results in excellent clinical outcomes with acceptable toxicity.