To give a preliminary report of clinical and treatment factors associated with toxicity in men receiving high-dose radiation therapy (RT) on a phase 3 dose-escalation trial.
The trial was initiated ...with 3-dimensional conformal RT (3D-CRT) and amended after 1 year to allow intensity modulated RT (IMRT). Patients treated with 3D-CRT received 55.8 Gy to a planning target volume that included the prostate and seminal vesicles, then 23.4 Gy to prostate only. The IMRT patients were treated to the prostate and proximal seminal vesicles to 79.2 Gy. Common Toxicity Criteria, version 2.0, and Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late morbidity scores were used for acute and late effects.
Of 763 patients randomized to the 79.2-Gy arm of Radiation Therapy Oncology Group 0126 protocol, 748 were eligible and evaluable: 491 and 257 were treated with 3D-CRT and IMRT, respectively. For both bladder and rectum, the volumes receiving 65, 70, and 75 Gy were significantly lower with IMRT (all P<.0001). For grade (G) 2+ acute gastrointestinal/genitourinary (GI/GU) toxicity, both univariate and multivariate analyses showed a statistically significant decrease in G2+ acute collective GI/GU toxicity for IMRT. There were no significant differences with 3D-CRT or IMRT for acute or late G2+ or 3+ GU toxicities. Univariate analysis showed a statistically significant decrease in late G2+ GI toxicity for IMRT (P=.039). On multivariate analysis, IMRT showed a 26% reduction in G2+ late GI toxicity (P=.099). Acute G2+ toxicity was associated with late G3+ toxicity (P=.005). With dose-volume histogram data in the multivariate analysis, RT modality was not significant, whereas white race (P=.001) and rectal V70 ≥15% were associated with G2+ rectal toxicity (P=.034).
Intensity modulated RT is associated with a significant reduction in acute G2+ GI/GU toxicity. There is a trend for a clinically meaningful reduction in late G2+ GI toxicity with IMRT. The occurrence of acute GI toxicity and large (>15%) volumes of rectum >70 Gy are associated with late rectal toxicity.
To define a male and female pelvic normal tissue contouring atlas for Radiation Therapy Oncology Group (RTOG) trials.
One male pelvis computed tomography (CT) data set and one female pelvis CT data ...set were shared via the Image-Guided Therapy QA Center. A total of 16 radiation oncologists participated. The following organs at risk were contoured in both CT sets: anus, anorectum, rectum (gastrointestinal and genitourinary definitions), bowel NOS (not otherwise specified), small bowel, large bowel, and proximal femurs. The following were contoured in the male set only: bladder, prostate, seminal vesicles, and penile bulb. The following were contoured in the female set only: uterus, cervix, and ovaries. A computer program used the binomial distribution to generate 95% group consensus contours. These contours and definitions were then reviewed by the group and modified.
The panel achieved consensus definitions for pelvic normal tissue contouring in RTOG trials with these standardized names: Rectum, AnoRectum, SmallBowel, Colon, BowelBag, Bladder, UteroCervix, Adnexa_R, Adnexa_L, Prostate, SeminalVesc, PenileBulb, Femur_R, and Femur_L. Two additional normal structures whose purpose is to serve as targets in anal and rectal cancer were defined: AnoRectumSig and Mesorectum. Detailed target volume contouring guidelines and images are discussed.
Consensus guidelines for pelvic normal tissue contouring were reached and are available as a CT image atlas on the RTOG Web site. This will allow uniformity in defining normal tissues for clinical trials delivering pelvic radiation and will facilitate future normal tissue complication research.
To assess the results of a multi-institutional study of intensity-modulated radiation therapy (IMRT) for early oropharyngeal cancer.
Patients with oropharyngeal carcinoma Stage T1-2, N0-1, M0 ...requiring treatment of the bilateral neck were eligible. Chemotherapy was not permitted. Prescribed planning target volumes (PTVs) doses to primary tumor and involved nodes was 66 Gy at 2.2 Gy/fraction over 6 weeks. Subclinical PTVs received simultaneously 54-60 Gy at 1.8-2.0 Gy/fraction. Participating institutions were preapproved for IMRT, and quality assurance review was performed by the Image-Guided Therapy Center.
69 patients were accrued from 14 institutions. At median follow-up for surviving patients (2.8 years), the 2-year estimated local-regional failure (LRF) rate was 9%. 2/4 patients (50%) with major underdose deviations had LRF compared with 3/49 (6%) without such deviations (p = 0.04). All cases of LRF, metastasis, or second primary cancer occurred among patients who were current/former smokers, and none among patients who never smoked. Maximal late toxicities Grade >or=2 were skin 12%, mucosa 24%, salivary 67%, esophagus 19%, osteoradionecrosis 6%. Longer follow-up revealed reduced late toxicity in all categories. Xerostomia Grade >or=2 was observed in 55% of patients at 6 months but reduced to 25% and 16% at 12 and 24 months, respectively. In contrast, salivary output did not recover over time.
Moderately accelerated hypofractionatd IMRT without chemotherapy for early oropharyngeal cancer is feasible, achieving high tumor control rates and reduced salivary toxicity compared with similar patients in previous Radiation Therapy Oncology Group studies. Major target underdose deviations were associated with higher LRF rate.
To develop a Radiation Therapy Oncology Group (RTOG) atlas of the elective clinical target volume (CTV) definitions to be used for planning pelvic intensity-modulated radiotherapy (IMRT) for anal and ...rectal cancers.
The Gastrointestinal Committee of the RTOG established a task group (the nine physician co-authors) to develop this atlas. They responded to a questionnaire concerning three elective CTVs (CTVA: internal iliac, presacral, and perirectal nodal regions for both anal and rectal case planning; CTVB: external iliac nodal region for anal case planning and for selected rectal cases; CTVC: inguinal nodal region for anal case planning and for select rectal cases), and to outline these areas on individual computed tomographic images. The imaging files were shared via the Advanced Technology Consortium. A program developed by one of the co-authors (I.E.N.) used binomial maximum-likelihood estimates to generate a 95% group consensus contour. The computer-estimated consensus contours were then reviewed by the group and modified to provide a final contouring consensus atlas.
The panel achieved consensus CTV definitions to be used as guidelines for the adjuvant therapy of rectal cancer and definitive therapy for anal cancer. The most important difference from similar atlases for gynecologic or genitourinary cancer is mesorectal coverage. Detailed target volume contouring guidelines and images are discussed.
This report serves as a template for the definition of the elective CTVs to be used in IMRT planning for anal and rectal cancers, as part of prospective RTOG trials.
To define a prostate fossa clinical target volume (PF-CTV) for Radiation Therapy Oncology Group (RTOG) trials using postoperative radiotherapy for prostate cancer.
An RTOG-sponsored meeting was held ...to define an appropriate PF-CTV after radical prostatectomy. Data were presented describing radiographic failure patterns after surgery. Target volumes used in previous trials were reviewed. Using contours independently submitted by 13 radiation oncologists, a statistical imputation method derived a preliminary "consensus" PF-CTV.
Starting from the model-derived CTV, consensus was reached for a CT image-based PF-CTV. The PF-CTV should extend superiorly from the level of the caudal vas deferens remnant to >8-12 mm inferior to vesicourethral anastomosis (VUA). Below the superior border of the pubic symphysis, the anterior border extends to the posterior aspect of the pubis and posteriorly to the rectum, where it may be concave at the level of the VUA. At this level, the lateral border extends to the levator ani. Above the pubic symphysis, the anterior border should encompass the posterior 1-2 cm of the bladder wall; posteriorly, it is bounded by the mesorectal fascia. At this level, the lateral border is the sacrorectogenitopubic fascia. Seminal vesicle remnants, if present, should be included in the CTV if there is pathologic evidence of their involvement.
Consensus on postoperative PF-CTV for RT after prostatectomy was reached and is available as a CT image atlas on the RTOG website. This will allow uniformity in defining PF-CTV for clinical trials that include postprostatectomy RT.
Accurate target definition is critical for the appropriate application of radiation therapy. In 2008, the Radiation Therapy Oncology Group (RTOG) published an international collaborative atlas to ...define the clinical target volume (CTV) for intensity modulated pelvic radiation therapy in the postoperative treatment of endometrial and cervical cancer. The current project is an updated consensus of CTV definitions, with removal of all references to bony landmarks and inclusion of the para-aortic and inferior obturator nodal regions.
An international consensus guideline working group discussed modifications of the current atlas and areas of controversy. A document was prepared to assist in contouring definitions. A sample case abdominopelvic computed tomographic image was made available, on which experts contoured targets. Targets were analyzed for consistency of delineation using an expectation-maximization algorithm for simultaneous truth and performance level estimation with kappa statistics as a measure of agreement between observers.
Sixteen participants provided 13 sets of contours. Participants were asked to provide separate contours of the following areas: vaginal cuff, obturator, internal iliac, external iliac, presacral, common iliac, and para-aortic regions. There was substantial agreement for the common iliac region (sensitivity 0.71, specificity 0.981, kappa 0.64), moderate agreement in the external iliac, para-aortic, internal iliac and vaginal cuff regions (sensitivity 0.66, 0.74, 0.62, 0.59; specificity 0.989, 0.966, 0.986, 0.976; kappa 0.60, 0.58, 0.52, 0.47, respectively), and fair agreement in the presacral and obturator regions (sensitivity 0.55, 0.35; specificity 0.986, 0.988; kappa 0.36, 0.21, respectively). A 95% agreement contour was smoothed and a final contour atlas was produced according to consensus.
Agreement among the participants was most consistent in the common iliac region and least in the presacral and obturator nodal regions. The consensus volumes formed the basis of the updated NRG/RTOG Oncology postoperative atlas. Continued patterns of recurrence research are encouraged to refine these volumes.
Current guidelines for esophageal cancer contouring are derived from traditional 2-dimensional fields based on bony landmarks, and they do not provide sufficient anatomic detail to ensure consistent ...contouring for more conformal radiation therapy techniques such as intensity modulated radiation therapy (IMRT). Therefore, we convened an expert panel with the specific aim to derive contouring guidelines and generate an atlas for the clinical target volume (CTV) in esophageal or gastroesophageal junction (GEJ) cancer.
Eight expert academically based gastrointestinal radiation oncologists participated. Three sample cases were chosen: a GEJ cancer, a distal esophageal cancer, and a mid-upper esophageal cancer. Uniform computed tomographic (CT) simulation datasets and accompanying diagnostic positron emission tomographic/CT images were distributed to each expert, and the expert was instructed to generate gross tumor volume (GTV) and CTV contours for each case. All contours were aggregated and subjected to quantitative analysis to assess the degree of concordance between experts and to generate draft consensus contours. The panel then refined these contours to generate the contouring atlas.
The κ statistics indicated substantial agreement between panelists for each of the 3 test cases. A consensus CTV atlas was generated for the 3 test cases, each representing common anatomic presentations of esophageal cancer. The panel agreed on guidelines and principles to facilitate the generalizability of the atlas to individual cases.
This expert panel successfully reached agreement on contouring guidelines for esophageal and GEJ IMRT and generated a reference CTV atlas. This atlas will serve as a reference for IMRT contours for clinical practice and prospective trial design. Subsequent patterns of failure analyses of clinical datasets using these guidelines may require modification in the future.
Using a retrospective analysis of treatment plans submitted from multiple institutions accruing patients to the Radiation Therapy Oncology Group (RTOG) 0236 non-small-cell stereotactic body ...radiotherapy protocol, the present study determined the dose prescription and critical structure constraints for future stereotactic body radiotherapy lung protocols that mandate density-corrected dose calculations.
A subset of 20 patients from four institutions participating in the RTOG 0236 protocol and using superposition/convolution algorithms were compared. The RTOG 0236 protocol required a prescription dose of 60 Gy delivered in three fractions to cover 95% of the planning target volume. Additional requirements were specified for target dose heterogeneity and the dose to normal tissue/structures. The protocol required each site to plan the patient's treatment using unit density, and another plan with the same monitor units and applying density corrections was also submitted. These plans were compared to determine the dose differences. Two-sided, paired Student's t tests were used to evaluate these differences.
With heterogeneity corrections applied, the planning target volume receiving >/=60 Gy decreased, on average, 10.1% (standard error, 2.7%) from 95% (p = .001). The maximal dose to any point >/=2 cm away from the planning target volume increased from 35.2 Gy (standard error, 1.7) to 38.5 Gy (standard error, 2.2).
Statistically significant dose differences were found with the heterogeneity corrections. The information provided in the present study is being used to design future heterogeneity-corrected RTOG stereotactic body radiotherapy lung protocols to match the true dose delivered for RTOG 0236.
To develop contouring guidelines to be used in the Radiation Therapy Oncology Group protocol 0848, a Phase III randomized trial evaluating the benefit of adjuvant chemoradiation in patients with ...resected head of pancreas cancer.
A consensus committee of six radiation oncologists with expertise in gastrointestinal radiotherapy developed stepwise contouring guidelines and an atlas for the delineation of the clinical target volume (CTV) in the postoperative treatment of pancreas cancer, based on identifiable regions of interest and margin expansions. Areas at risk for subclinical disease to be included in the CTV were defined, including nodal regions, anastomoses, and the preoperative primary tumor location. Regions of interest that could be reproducibly contoured on postoperative imaging after a pancreaticoduodenectomy were identified. Standardized expansion margins to encompass areas at risk were developed after multiple iterations to determine the optimal margin expansions.
New contouring recommendations based on CT anatomy were established. Written guidelines for the delineation of the postoperative CTV and normal tissues, as well as a Web-based atlas, were developed.
The postoperative abdomen has been a difficult area for effective radiotherapy. These new guidelines will help physicians create fields that better encompass areas at risk and minimize dose to normal tissues.
Introduction
NRG protocols for glioblastoma allow for clinical target volume (CTV) reductions at natural barriers; however, literature examining CTV contouring and the relevant white matter pathways ...is lacking. This study proposes consensus CTV guidelines, with a focus on areas of controversy while highlighting common errors in glioblastoma target delineation.
Methods
Ten academic radiation oncologists specializing in brain tumor treatment contoured CTVs on four glioblastoma cases. CTV expansions were based on NRG trial guidelines. Contour consensus was assessed and summarized by kappa statistics. A meeting was held to discuss the mathematically averaged contours and form consensus contours and recommendations.
Results
Contours of the cavity plus enhancement (mean kappa 0.69) and T2-FLAIR signal (mean kappa 0.74) showed moderate to substantial agreement. Experts were asked to trim off anatomic barriers while respecting pathways of spread to develop their CTVs. Submitted CTV_4600 (mean kappa 0.80) and CTV_6000 (mean kappa 0.81) contours showed substantial to near perfect agreement. Simultaneous truth and performance level estimation (STAPLE) contours were then reviewed and modified by group consensus. Anatomic trimming reduced the amount of total brain tissue planned for radiation targeting by a 13.6% (range 8.7–17.9%) mean proportional reduction. Areas for close scrutiny of target delineation were described, with accompanying recommendations.
Conclusions
Consensus contouring guidelines were established based on expert contours. Careful delineation of anatomic pathways and barriers to spread can spare radiation to uninvolved tissue without compromising target coverage. Further study is necessary to accurately define optimal target volumes beyond isometric expansion techniques for individual patients.
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