NRG brain tumor specialists consensus guidelines for glioblastoma contouring.

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.

Preliminary patient-reported outcomes analysis of 3-dimensional radiation therapy versus intensity-modulated radiation therapy on the high-dose arm of the Radiation Therapy Oncology Group (RTOG) 0126 prostate cancer trial.

BACKGROUND: The authors analyzed a preliminary report of patient-reported outcomes (PROs) among men who received high-dose radiation therapy (RT) on Radiation Therapy Oncology Group study 0126 (a phase 3 dose-escalation trial) with either 3-dimensional conformal RT (3D-CRT) or intensity-modulated RT (IMRT). METHODS: Patients in the 3D-CRT group received 55.8 gray (Gy) to the prostate and proximal seminal vesicles and were allowed an optional field reduction; then, they received 23.4 Gy to the prostate only. Patients in the IMRT group received 79.2 Gy to the prostate and proximal seminal vesicles. PROs were assessed at 0 months (baseline), 3 months, 6 months, 12 months, and 24 months and included bladder and bowel function assessed with the Functional Alterations due to Changes in Elimination (FACE) instrument and erectile function assessed with the International Index of Erectile Function (IIEF). Analyses included the patients who completed all data at baseline and for at least 1 follow-up assessment, and the results were compared with an imputed data set. RESULTS: Of 763 patients who were randomized to the 79.2-Gy arm, 551 patients and 595 patients who responded to the FACE instrument and 505 patients and 577 patients who responded to the IIEF were included in the completed and imputed analyses, respectively. There were no significant differences between modalities for any of the FACE or IIEF subscale scores or total scores at any time point for either the completed data set or the imputed data set. CONCLUSIONS: Despite significant reductions in dose and volume to normal structures using IMRT, this robust analysis of 3D-CRT and IMRT demonstrated no difference in patient-reported bowel, bladder, or sexual functions for similar doses delivered to the prostate and proximal seminal vesicles with IMRT compared with 3D-CRT delivered either to the prostate and proximal seminal vesicles or to the prostate alone.

NRG Oncology/RTOG 0921: A phase 2 study of postoperative intensity-modulated radiotherapy with concurrent cisplatin and bevacizumab followed by carboplatin and paclitaxel for patients with endometrial cancer.

BACKGROUND: The current study was conducted to assess acute and late adverse events (AEs), overall survival (OS), pelvic failure, regional failure, distant failure, and disease-free survival in a prospective phase 2 clinical trial of bevacizumab and pelvic intensity-modulated radiotherapy (IMRT) with chemotherapy in patients with high-risk endometrial cancer. METHODS: Patients underwent a hysterectomy and lymph node removal, and had ≥1 of the following high-risk factors: grade 3 carcinoma with >50% myometrial invasion, grade 2 or 3 disease with any cervical stromal invasion, or known extrauterine extension confined to the pelvis. Treatment included pelvic IMRT and concurrent cisplatin on days 1 and 29 of radiation and bevacizumab (at a dose of 5 mg/kg on days 1, 15, and 29 of radiation) followed by adjuvant carboplatin and paclitaxel for 4 cycles. The primary endpoint was grade ≥3 AEs occurring within the first 90 days (toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). RESULTS: A total of 34 patients were accrued from November 2009 through December 2011, 30 of whom were eligible and received study treatment. Seven of 30 patients (23.3%; 1-sided 95% confidence interval, 10.6%-36.0%) developed grade ≥3 treatment-related nonhematologic toxicities within 90 days; an additional 6 patients experienced grade ≥3 toxicities between 90 and 365 days after treatment. The 2-year OS rate was 96.7% and the disease-free survival rate was 79.1%. No patient developed a within-field pelvic failure and no patients with International Federation of Gynecology and Obstetrics stage I to IIIA disease developed disease recurrence after a median follow-up of 26 months. CONCLUSIONS: Postoperative bevacizumab added to chemotherapy and pelvic IMRT appears to be well tolerated and results in high OS rates at 2 years for patients with high-risk endometrial carcinoma.

Order From Chaos: The Benefits of Standardized Nomenclature in Radiation Oncology.

Although standardization has been shown to improve patient safety and improve the efficiency of workflows, implementation of standards can take considerable effort and requires the engagement of all clinical stakeholders. Engaging team members includes increasing awareness of the proposed benefit of the standard, a clear implementation plan, monitoring for improvements, and open communication to support successful implementation. The benefits of standardization often focus on large institutions to improve research endeavors, yet all clinics can benefit from standardization to increase quality and implement more efficient or automated workflow. The benefits of nomenclature standardization for all team members and institution sizes, including success stories, are discussed with practical implementation guides to facilitate the adoption of standardized nomenclature in radiation oncology.

Framework for Quality Assurance of Ultrahigh Dose Rate Clinical Trials Investigating FLASH Effects and Current Technology Gaps.

FLASH radiation therapy (FLASH-RT), delivered with ultrahigh dose rate (UHDR), may allow patients to be treated with less normal tissue toxicity for a given tumor dose compared with currently used conventional dose rate. Clinical trials are being carried out and are needed to test whether this improved therapeutic ratio can be achieved clinically. During the clinical trials, quality assurance and credentialing of equipment and participating sites, particularly pertaining to UHDR-specific aspects, will be crucial for the validity of the outcomes of such trials. This report represents an initial framework proposed by the NRG Oncology Center for Innovation in Radiation Oncology FLASH working group on quality assurance of potential UHDR clinical trials and reviews current technology gaps to overcome. An important but separate consideration is the appropriate design of trials to most effectively answer clinical and scientific questions about FLASH. This paper begins with an overview of UHDR RT delivery methods. UHDR beam delivery parameters are then covered, with a focus on electron and proton modalities. The definition and control of safe UHDR beam delivery and current and needed dosimetry technologies are reviewed and discussed. System and site credentialing for large, multi-institution trials are reviewed. Quality assurance is then discussed, and new requirements are presented for treatment system standard analysis, patient positioning, and treatment planning. The tables and figures in this paper are meant to serve as reference points as we move toward FLASH-RT clinical trial performance. Some major questions regarding FLASH-RT are discussed, and next steps in this field are proposed. FLASH-RT has potential but is associated with significant risks and complexities. We need to redefine optimization to focus not only on the dose but also on the dose rate in a manner that is robust and understandable and that can be prescribed, validated, and confirmed in real time. Robust patient safety systems and access to treatment data will be critical as FLASH-RT moves into the clinical trials.

Feasibility of Same-Day Prostate Fiducial Markers, Perirectal Hydrogel Spacer Placement, and Computed Tomography and Magnetic Resonance Imaging Simulation for External Beam Radiation Therapy for Low-Risk and Intermediate-Risk Prostate Cancer.

PURPOSE: The use of prostate fiducial markers and perirectal hydrogel spacers can reduce the acute and late toxic effects associated with prostate radiation therapy. These procedures are usually performed days to weeks before simulation during a separate clinic visit to ensure resolution of procedure-related inflammation. The purpose of this study was to assess whether same-day intraprostatic fiducial marker placement, perirectal hydrogel injection, and computed tomography (CT) and magnetic resonance imaging (MRI) simulation were feasible without adversely affecting hydrogel volume, perirectal spacing, or rectal dose. If feasible, performing these procedures on the same day as simulation would expedite the start of radiation therapy, improve patient convenience, and reduce costs. METHODS AND MATERIALS: Twenty-one patients with clinically localized prostate cancer who were enrolled on a prospective clinical trial (NCT01617161) underwent same-day marker placement, hydrogel injection, and CT and MRI simulation, then underwent T2 MRI verification scans 3 to 4 weeks later. The MRI scans were fused to the CT planning scans by clinical target volumes (CTVs) to generate comparison treatment plans (70 Gy in 28 fractions). Hydrogel volume and symmetry, perirectal spacing, CTV dose, and organ-at-risk dose were evaluated. RESULTS: Verification scans occurred a mean of 24.9 ± 4.6 days after simulation and 9.3 ± 4.9 days after treatment start. Prostate volume did not change between scans (median, 67.3 ± 22.1 cm3 vs 64.1 ± 21.8 cm3; P = .64). The median hydrogel change between simulation and verification was -1.8% ± 4.5% (P = .27). No significant differences in perirectal spacing (midgland: 1.33 ± 0.45 cm vs 1.3 ± 0.7 cm; 1 cm superior: 1.25 ± 0.95 cm vs 1.43 ± 0.91 cm; 1 cm inferior: 1.16 ± 0.28 cm vs 1.41 ± 0.49 cm) were identified. No significant differences in rectal V66 (median 2.3 ± 2.18% vs 2.3 ± 2.28%; P = .99), V35 (median 14.79 ± 7.61 vs 14.67 ± 8.4; P = .73), or D1cc (65.7 ± 9.2 Gy vs 68.2 ± 9.0 Gy; P = .80) were found. All plans met CTV and organ-at-risk constraints. CONCLUSION: Same-day placement of intraprostatic fiducial markers, perirectal hydrogel, and simulation scans was feasible and did not significantly affect hydrogel volume, position, CTV coverage, or rectal dose.

NRG Oncology/RTOG Consensus Guidelines for Delineation of Clinical Target Volume for Intensity Modulated Pelvic Radiation Therapy in Postoperative Treatment of Endometrial and Cervical Cancer: An Update.

PURPOSE: 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. METHODS AND MATERIALS: 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. RESULTS: 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. CONCLUSIONS: 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.

Explicit-VR transfer syntax limits the value multiplicity of DICOM data elements with decimal string (DS) value representation.

The Advanced Technology QA Consortium (ATC) has identified a problem in the encoding of DICOM RT Dose objects when these objects are converted from Implicit-VR (Little-Endian) transfer syntax to an Explicit-VR transfer syntax. There exist data elements, which can be represented in Implicit-VR Little-Endian transfer syntax but that cannot be represented in Explicit-VR Little-Endian transfer syntax.

Development and Validation of Consensus Contouring Guidelines for Adjuvant Radiation Therapy for Bladder Cancer After Radical Cystectomy.

PURPOSE: To develop multi-institutional consensus clinical target volumes (CTVs) and organs at risk (OARs) for male and female bladder cancer patients undergoing adjuvant radiation therapy (RT) in clinical trials. METHODS AND MATERIALS: We convened a multidisciplinary group of bladder cancer specialists from 15 centers and 5 countries. Six radiation oncologists and 7 urologists participated in the development of the initial contours. The group proposed initial language for the CTVs and OARs, and each radiation oncologist contoured them on computed tomography scans of a male and female cystectomy patient with input from ≥1 urologist. On the basis of the initial contouring, the group updated its CTV and OAR descriptions. The cystectomy bed, the area of greatest controversy, was contoured by another 6 radiation oncologists, and the cystectomy bed contouring language was again updated. To determine whether the revised language produced consistent contours, CTVs and OARs were redrawn by 6 additional radiation oncologists. We evaluated their contours for level of agreement using the Landis-Koch interpretation of the κ statistic. RESULTS: The group proposed that patients at elevated risk for local-regional failure with negative margins should be treated to the pelvic nodes alone (internal/external iliac, distal common iliac, obturator, and presacral), whereas patients with positive margins should be treated to the pelvic nodes and cystectomy bed. Proposed OARs included the rectum, bowel space, bone marrow, and urinary diversion. Consensus language describing the CTVs and OARs was developed and externally validated. The revised instructions were found to produce consistent contours. CONCLUSIONS: Consensus descriptions of CTVs and OARs were successfully developed and can be used in clinical trials of adjuvant radiation therapy for bladder cancer.

Expert Consensus Contouring Guidelines for Intensity Modulated Radiation Therapy in Esophageal and Gastroesophageal Junction Cancer.

PURPOSE/OBJECTIVE(S): 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. METHODS AND MATERIALS: 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. RESULTS: 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. CONCLUSIONS: 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.

Treatment planning guidelines regarding the use of CT/PET-guided IMRT for cervical carcinoma with positive paraaortic lymph nodes.

PURPOSE: Computed tomography (CT)/positron emission tomography (PET)-guided intensity-modulated radiotherapy of the paraaortic lymph nodes (PALNs) has been proposed for patients with cervical carcinoma and paraaortic metastasis. This investigation attempted to determine the guidelines regarding the selection of appropriate treatment parameters (e.g., number of beams, beam geometry) and organ-specific parameters (e.g., importance weighting and tolerance dose) for intensity-modulated radiotherapy planning for the PALNs. METHODS AND MATERIALS: Patients underwent imaging using CT and PET. The images were registered, and the structures were contoured. A goal dose of 50.4 Gy and 59.4 Gy was assigned to the clinical target volume (lymph node bed) and gross tumor volume (PET-delineated PALNs), respectively. For each patient, multiple treatment plans using various beam geometries and planning parameters were executed and evaluated in terms of the dose-volume histograms of the target and critical structures. RESULTS: Acceptable sparing of the stomach, liver, and colon was achieved, regardless of the number of beams used. Sparing of the spinal cord was strongly dependent on the number and arrangement of the beams. Varying the number and arrangement of the beams affected small intestine sparing, but the amount of sparing was limited because the small intestine overlapped the target volumes, and, therefore, received the prescription dose. Adjusting the number of beams, beam angles, and prescription parameters provided minimal improvement in kidney sparing. CONCLUSION: We successfully developed treatment plans that deliver 59.4 Gy to the positive PALNs and 50.4 Gy to the paraaortic region using CT/PET-guided intensity-modulated radiotherapy.

Physiologic FDG-PET three-dimensional brachytherapy treatment planning for cervical cancer.

PURPOSE: To compare conventional two-dimensional (2D) orthogonal radiography-based brachytherapy treatment planning for cervical cancer with a three-dimensional (3D) treatment planning technique based on 18F-fluoro-deoxyglucose-positron emission tomography (FDG-PET). METHODS AND MATERIALS: Eleven cervical cancer patients were included in this prospective study that evaluated one tandem and ovoid brachytherapy procedure for each patient. The patient underwent FDG-PET of the pelvis to visualize the tumor followed by a second FDG-PET scan with the FDG isotope placed inside the tandem and ovoid applicators to visualize the treatment source positions for 3D treatment planning. The tumor volumes were delineated using a binary threshold technique in which the threshold FDG-PET image intensity was 40% of the peak tumor intensity. RESULTS: FDG-PET provides a reliable estimate of the cervical cancer volume and 3D spatial relationship of the tumor to the tandem and ovoid applicators. The maximal bladder and rectal doses determined from the 3D FDG-PET dose-volume histograms were found to be higher than those obtained using 2D treatment planning. The minimal dose to the tumor volume defined by FDG-PET ranged from 50 to 475 cGy for treatment plans designed to deliver 650 cGy to Point A and exhibited an inverse correlation with tumor volume. CONCLUSION: Physiologic FDG-PET brachytherapy treatment planning is feasible and accurate relative to conventional 2D treatment planning. The use of FDG-PET offers a unique method for tumor visualization and identifies the limitations of conventional brachytherapy treatment planning for coverage of large tumors and estimation of the dose to normal structures. This technique has the potential for improving isodose tumor coverage for patients with cervical cancer while sparing critical structures.

PET-guided IMRT for cervical carcinoma with positive para-aortic lymph nodes-a dose-escalation treatment planning study.

PURPOSE: To evaluate a treatment planning method for dose escalation to the para-aortic lymph nodes (PALNs) based on positron emission tomography (PET) with intensity-modulated radiotherapy (IMRT) for cervical cancer patients with PALN involvement. One goal of this process was not to modify the traditional treatment of the pelvic region. METHODS AND MATERIALS: PET images for 4 cervical cancer patents with PALN involvement were registered with their corresponding CT scans. Positive PALNs were identified on PET images, and the surrounding critical structures were delineated on CT images. The treatment machine central axis (CAX) was placed at the level of the L4-L5 vertebral body interspace. There were two distinct treatment regions: the para-aortic bed superior to the CAX and the whole pelvis region inferior to the CAX. IMRT was used for treatment planning of PALN bed irradiation. The positive PALNs identified on PET images were defined as the gross target volume, and the para-aortic bed was defined as the clinical target volume. The radiation doses were escalated from the conventional 45 Gy to 59.4 Gy for the gross target volume and 50.4 Gy for the clinical target volume in 33 fractions. The pelvis area was treated with conventional treatment methods, AP-PA beams to 50.4 Gy in 28 fractions with a brachytherapy implant boost. The placement of the CAX allowed the two treatment regions to be abutted using the treatment machine's independent jaws. RESULTS: Dose escalation to positive PALNs, as identified on PET images, and the PALN bed is feasible with IMRT. Treatment plans for 4 patients revealed that escalated prescription doses could be delivered to target volumes while maintaining acceptable doses to the surrounding critical structures. Strategic placement of the treatment isocenter allows the IMRT region (PALN bed) and whole pelvis fields to be treated with a relatively uniform dose distribution in the abutment region. CONCLUSION: This study indicates that PET-guided IMRT could be used in a clinical trial in an attempt to escalate doses delivered to patients with cervical cancer who have positive PALNs.

PET-guided three-dimensional treatment planning of intracavitary gynecologic implants.

PURPOSE: Positron emission tomography (PET) provides physiologic information that is not available from computed tomography (CT) or magnetic resonance studies. PET images may allow more accurate delineation of three-dimensional treatment planning target volumes of brachytherapy gynecologic (GYN) implants. This study evaluates the feasibility of using PET as the sole source of target, normal structure, and applicator delineation for intracavitary GYN implant treatment planning. MATERIALS AND METHODS: Standard Fletcher-Suit brachytherapy tandem and colpostat applicators were used for radiation delivery. After insertion of the applicator in the operating room, the patient was taken to a PET scanner, where 555 MBq (15 mCi) 18F-fluorodeoxyglucose (18F-FDG) was administered intravenously. Forty-five minutes later, three localization tubes containing 18F-FDG were inserted into the source afterloading compartments of the tandem and colpostat. A whole-pelvis scan was performed, and the images were transferred to a commercial brachytherapy three-dimensional treatment planning system. A Foley catheter was inserted into the urinary bladder while the patient was in the operating room. The regions of radioactivity in the three applicator tube image were contoured for reconstruction of the applicator, along with the bladder, rectum, and 18F-FDG-defined target volumes. A treatment plan was generated that included dose-volume histograms and three-dimensional dose distribution displays, allowing the physician an opportunity to determine if adequate target coverage and normal-tissue sparing had been obtained. For a more conservative approach, three-dimensional dose distributions and dose-volume histograms delivered with conventional source arrangements and loading could be observed. The accuracy of applicator localization from the PET images was verified using a water phantom containing two aluminum CT-compatible tandems. The PET-defined and CT scan applicator reconstructions were compared. RESULTS: Feasibility of using PET images for treatment planning of brachytherapy intracavitary GYN implants has been demonstrated. A phantom study demonstrated applicator reconstruction accuracy in the axial direction to be better than 2 mm. Reconstruction accuracy in the longitudinal direction (principally craniocaudal) was similar to the PET scanner's voxel size of 4.3 mm. CONCLUSIONS: Brachytherapy intracavitary GYN implant design has traditionally been based on patient tumor staging, palpation, and clinical experience. PET images have the potential to provide better spatial information about the relationship of tumor and normal structures to the applicator. This information can be used to optimize the delivery of radiation therapy treatments. Thus far, six patients have been scanned using this process.

Interobserver variability in target definition for hepatocellular carcinoma with and without portal vein thrombus: radiation therapy oncology group consensus guidelines.

PURPOSE: Defining hepatocellular carcinoma (HCC) gross tumor volume (GTV) requires multimodal imaging, acquired in different perfusion phases. The purposes of this study were to evaluate the variability in contouring and to establish guidelines and educational recommendations for reproducible HCC contouring for treatment planning. METHODS AND MATERIALS: Anonymous, multiphasic planning computed tomography scans obtained from 3 patients with HCC were identified and distributed to a panel of 11 gastrointestinal radiation oncologists. Panelists were asked the number of HCC cases they treated in the past year. Case 1 had no vascular involvement, case 2 had extensive portal vein involvement, and case 3 had minor branched portal vein involvement. The agreement between the contoured total GTVs (primary + vascular GTV) was assessed using the generalized kappa statistic. Agreement interpretation was evaluated using Landis and Koch's interpretation of strength of agreement. The S95 contour, defined using the simultaneous truth and performance level estimation (STAPLE) algorithm consensus at the 95% confidence level, was created for each case. RESULTS: Of the 11 panelists, 3 had treated >25 cases in the past year, 2 had treated 10 to 25 cases, 2 had treated 5 to 10 cases, 2 had treated 1 to 5 cases, 1 had treated 0 cases, and 1 did not respond. Near perfect agreement was seen for case 1, and substantial agreement was seen for cases 2 and 3. For case 2, there was significant heterogeneity in the volume identified as tumor thrombus (range 0.58-40.45 cc). For case 3, 2 panelists did not include the branched portal vein thrombus, and 7 panelists contoured thrombus separately from the primary tumor, also showing significant heterogeneity in volume of tumor thrombus (range 4.52-34.27 cc). CONCLUSIONS: In a group of experts, excellent agreement was seen in contouring total GTV. Heterogeneity exists in the definition of portal vein thrombus that may impact treatment planning, especially if differential dosing is contemplated. Guidelines for HCC GTV contouring are recommended.

Results from the Quality Research in Radiation Oncology (QRRO) survey: Evaluation of dosimetric outcomes for low-dose-rate prostate brachytherapy.

PURPOSE: We report on quality of dose delivery to target and normal tissues from low-dose-rate prostate brachytherapy using postimplantation dosimetric evaluations from a random sample of U.S. patients. METHODS AND MATERIALS: Nonmetastatic prostate cancer patients treated with external beam radiotherapy or brachytherapy in 2007 were randomly sampled from radiation oncology facilities nationwide. Of 414 prostate cancer cases from 45 institutions, 86 received low-dose-rate brachytherapy. We collected the 30-day postimplantation CT images of these patients and 10 test cases from two other institutions. Scans were downloaded into a treatment planning system and prostate/rectal contours were redrawn. Dosimetric outcomes were reanalyzed and compared with calculated outcomes from treating institutions. RESULTS: Median prostate volume was 33.4cm(3). Reevaluated median V(100), D(90), and V(150) were 91.1% (range, 45.5-99.8%), 101.7% (range, 59.6-145.9%), and 53.9% (range, 15.7-88.4%), respectively. Low gland coverage included 27 patients (39%) with a D(90) lower than 100% of the prescription dose (PD), 12 of whom (17% of the entire group) had a D(90) lower than 80% of PD. There was no correlation between D(90) coverage and prostate volume, number of seeds, or implanted activity. The median V(100) for the rectum was 0.3cm(3) (range, 0-4.3cm(3)). No outcome differences were observed according to the institutional strata. Concordance between reported and reevaluated D(90) values (defined as within ±10%) was observed in 44 of 69 cases. CONCLUSIONS: Central review of postimplantation CT scans to assess the quality of prostate brachytherapy is feasible. Most patients achieved excellent dosimetric outcomes, yet 17% had less than optimal target coverage by the PD. There was concordance between submitted target-coverage parameters and central dosimetric review in 64% of implants. These findings will require further validation in a larger cohort of patients.

Preliminary toxicity analysis of 3-dimensional conformal radiation therapy versus intensity modulated radiation therapy on the high-dose arm of the Radiation Therapy Oncology Group 0126 prostate cancer trial.

PURPOSE: 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. METHODS AND MATERIALS: 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. RESULTS: 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). CONCLUSIONS: 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.

Future vision for the quality assurance of oncology clinical trials.

The National Cancer Institute clinical cooperative groups have been instrumental over the past 50 years in developing clinical trials and evidence-based process improvements for clinical oncology patient care. The cooperative groups are undergoing a transformation process as we further integrate molecular biology into personalized patient care and move to incorporate international partners in clinical trials. To support this vision, data acquisition and data management informatics tools must become both nimble and robust to support transformational research at an enterprise level. Information, including imaging, pathology, molecular biology, radiation oncology, surgery, systemic therapy, and patient outcome data needs to be integrated into the clinical trial charter using adaptive clinical trial mechanisms for design of the trial. This information needs to be made available to investigators using digital processes for real-time data analysis. Future clinical trials will need to be designed and completed in a timely manner facilitated by nimble informatics processes for data management. This paper discusses both past experience and future vision for clinical trials as we move to develop data management and quality assurance processes to meet the needs of the modern trial.

Do intermediate radiation doses contribute to late rectal toxicity? An analysis of data from radiation therapy oncology group protocol 94-06.

PURPOSE: To investigate whether the volumes of rectum exposed to intermediate doses, from 30 to 50 Gy, contribute to the risk of Grade ≥ 2 late rectal toxicity among patients with prostate cancer receiving radiotherapy. METHODS AND MATERIALS: Data from 1009 patients treated on Radiation Therapy Oncology Group protocol 94-06 were analyzed using three approaches. First, the contribution of intermediate doses to a previously published fit of the Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model was determined. Next, the extent to which intermediate doses provide additional risk information, after taking the LKB model into account, was investigated. Third, the proportion of rectum receiving doses higher than a threshold, VDose, was computed for doses ranging from 5 to 85 Gy, and a multivariate Cox proportional hazards model was used to determine which of these parameters were significantly associated with time to Grade ≥ 2 late rectal toxicity. RESULTS: Doses <60 Gy had no detectable impact on the fit of the LKB model, as expected on the basis of the small estimate of the volume parameter (n = 0.077). Furthermore, there was no detectable difference in late rectal toxicity among cohorts with similar risk estimates from the LKB model but with different volumes of rectum exposed to intermediate doses. The multivariate Cox proportional hazards model selected V75 as the only value of VDose significantly associated with late rectal toxicity. CONCLUSIONS: There is no evidence from these data that intermediate doses influence the risk of Grade ≥ 2 late rectal toxicity. Instead, the critical doses for this endpoint seem to be ≥ 75 Gy. It is hypothesized that cases of Grade ≥ 2 late rectal toxicity occurring among patients with V75 less than approximately 12% may be due to a "background" level of risk, likely due mainly to biological factors.