Examination of the Dose-Effect Relationship of Radiation-Induced Hypopituitarism: Results of a Case-Control Study.

PURPOSE: Previous reports have documented a dose-effect relationship for radiation-induced hypopituitarism in patients receiving therapy near or at the base of the skull. We aimed to characterize this long-term endocrinopathy further by examining the effect of dose on both the incidence and severity of toxicity, as well as exploring a possible dose threshold for this effect. METHODS AND MATERIALS: Out of an initial 346 patients who had received radiation therapy to the base of the skull, 53 patients with adequate endocrine evaluation were found. Of these, 19 patients who subsequently developed at least 1 endocrinopathy (cases) as well as 17 patients who did not (controls) were identified, for a total of 36. Patients' charts were reviewed, and endocrinologic laboratory tests recorded. Treatment plans were reviewed and doses to the hypothalamus and pituitary gland were calculated. One-way analysis of variance was used to determine differences between cases and controls, and Pearson's correlation coefficient was used to relate mean pituitary dose to serum free thyroxine, insulin-like growth factor 1, prolactin, cortisol, and luteinizing hormone. RESULTS: There were 20 men and 16 women, with a median age of 58. Median follow-up was 32 months (range, 18- 85 months). Median total plan dose delivered was 54 Gy (range, 50.4-70 Gy). Independent sample t tests as well as univariate analysis showed a significantly greater dose to the hypothalamus and pituitary of the cases compared with the controls, while other factors were not significantly different between the 2 groups. There was a statistically significant negative correlation (Pearson's correlation coefficient = -0.65, P = .001) between the mean dose to the pituitary gland and the serum free thyroxine. No case of endocrine toxicity was observed at a mean dose to the pituitary below 30 Gy. CONCLUSIONS: Our results suggest that late endocrinopathy is a true deterministic effect, with a dose threshold, and with both the incidence and severity of toxicity being related to the dose.

Rigid and Deformable Image Registration for Radiation Therapy: A Self-Study Evaluation Guide for NRG Oncology Clinical Trial Participation.

PURPOSE: The registration of multiple imaging studies to radiation therapy computed tomography simulation, including magnetic resonance imaging, positron emission tomography-computed tomography, etc. is a widely used strategy in radiation oncology treatment planning, and these registrations have valuable roles in image guidance, dose composition/accumulation, and treatment delivery adaptation. The NRG Oncology Medical Physics subcommittee formed a working group to investigate feasible workflows for a self-study credentialing process of image registration commissioning. METHODS AND MATERIALS: The American Association of Physicists in Medicine (AAPM) Task Group 132 (TG132) report on the use of image registration and fusion algorithms in radiation therapy provides basic guidelines for quality assurance and quality control of the image registration algorithms and the overall clinical process. The report recommends a series of tests and the corresponding metrics that should be evaluated and reported during commissioning and routine quality assurance, as well as a set of recommendations for vendors. The NRG Oncology medical physics subcommittee working group found incompatibility of some digital phantoms with commercial systems. Thus, there is still a need to provide further recommendations in terms of compatible digital phantoms, clinical feasible workflow, and achievable thresholds, especially for future clinical trials involving deformable image registration algorithms. Nine institutions participated and evaluated 4 commonly used commercial imaging registration software and various versions in the field of radiation oncology. RESULTS AND CONCLUSIONS: The NRG Oncology Working Group on image registration commissioning herein provides recommendations on the use of digital phantom/data sets and analytical software access for institutions and clinics to perform their own self-study evaluation of commercial imaging systems that might be employed for coregistration in radiation therapy treatment planning and image guidance procedures. Evaluation metrics and their corresponding values were given as guidelines to establish practical tolerances. Vendor compliance for image registration commissioning was evaluated, and recommendations were given for future development.

NRG Oncology Survey on Practice and Technology Use in SRT and SBRT Delivery.

PURPOSE: To assess stereotactic radiotherapy (SRT)/stereotactic body radiotherapy (SBRT) practices by polling clinics participating in multi-institutional clinical trials. METHODS: The NRG Oncology Medical Physics Subcommittee distributed a survey consisting of 23 questions, which covered general technologies, policies, and procedures used in the Radiation Oncology field for the delivery of SRT/SBRT (9 questions), and site-specific questions for brain SRT, lung SBRT, and prostate SBRT (14 questions). Surveys were distributed to 1,996 radiotherapy institutions included on the membership rosters of the five National Clinical Trials Network (NCTN) groups. Patient setup, motion management, target localization, prescriptions, and treatment delivery technique data were reported back by 568 institutions (28%). RESULTS: 97.5% of respondents treat lung SBRT patients, 77.0% perform brain SRT, and 29.1% deliver prostate SBRT. 48.8% of clinics require a physicist present for every fraction of SBRT, 18.5% require a physicist present for the initial SBRT fraction only, and 14.9% require a physicist present for the entire first fraction, including set-up approval for all subsequent fractions. 55.3% require physician approval for all fractions, and 86.7% do not reposition without x-ray imaging. For brain SRT, most institutions (83.9%) use a planning target volume (PTV) margin of 2 mm or less. Lung SBRT PTV margins of 3 mm or more are used in 80.6% of clinics. Volumetric modulated arc therapy (VMAT) is the dominant delivery method in 62.8% of SRT treatments, 70.9% of lung SBRT, and 68.3% of prostate SBRT. CONCLUSION: This report characterizes SRT/SBRT practices in radiotherapy clinics participating in clinical trials. Data made available here allows the radiotherapy community to compare their practice with that of other clinics, determine what is achievable, and assess areas for improvement.

Trajectory-based VMAT for cranial targets with delivery at shortened SAD.

INTRODUCTION: Trajectory-based volumetric modulated arc therapy (tr-VMAT) treatment plans enable the option for noncoplanar delivery yielding steeper dose gradients and increased sparing of critical structures compared to conventional treatment plans. The addition of translational couch motion to shorten the effective source-to-axis distance (SAD) may result in improved delivery precision and an increased effective dose rate. In this work, tr-VMAT treatment plans using a noncoplanar "baseball stitch" trajectory were implemented, applied to patients presented with cranial targets, and compared to the clinical treatment plans. METHODS: A treatment planning workflow was implemented: (a) beamlet doses were calculated for control points defined along a baseball stitch trajectory using a collapsed-cone convolution-superposition algorithm; (b) VMAT treatment plans were optimized using the column generation approach; (c) a final dose distribution was calculated in Varian Eclipse using the analytical anisotropic algorithm by importing the optimized treatment plan parameters. Tr-VMAT plans were optimized for ten patients presented with cranial targets at both standard and shortened SAD, and compared to the clinical treatment plans through isodose distributions, dose-volume histograms, and dosimetric indices. The control point specifications of the optimized tr-VMAT plans were used to estimate the delivery time. RESULTS: The optimized tr-VMAT plans with both shortened and standard SAD delivery yielded a comparable plan quality to the clinical treatment plans. A statistically significant benefit was observed for dose gradient index and monitor unit efficiency for shortened SAD tr-VMAT plans, while improved target volume conformity was observed for the clinical treatment plan (P ≤ 0.05). A clear dosimetric benefit was not demonstrated between tr-VMAT delivery at shortened SAD compared to standard SAD, but shortened SAD delivery yielded a fraction size-dependent reduction in the estimated delivery time. CONCLUSION: The implementation of "baseball stitch" tr-VMAT treatment plans to patients presented with cranial targets demonstrated comparable plan quality to clinical treatment plans. The delivery at shortened SAD produced a fraction size-dependent decrease in estimated delivery time.

Computed tomography-based virtual simulation versus ultrasound-based clinical setup in electron breast boost radiotherapy: Methodology for CT-based electron virtual simulation.

PURPOSE: To compare clinical setup using ultrasound (U/S)-delineated target versus computed tomography (CT) virtual simulation using CT-outlined target in breast electron boost. To describe a methodology for electron virtual simulation and collision testing with the treatment planning system (TPS). METHODS: The two techniques were compared in a prospective study on 12 patients, who were treated using a clinical setup. Target definition was performed by both U/S and CT imaging. The U/S-based target was made visible on CT images by placing a radio-opaque wire on U/S skin markings. The dose distribution of the clinical setup was reproduced in the TPS using the actual electron patient treatment parameters. A CT-based TPS virtual simulation/dose optimization was compared to the clinical setup technique. RESULTS: Mean beam aperture was larger by 16.3 cm2 (p = 0.011) for U/S compared to CT-outlined target. Target mean depth difference (CT minus U/S) was 0.03 cm (p = 0.875). Target coverage at depth was adequate in all cases with CT-based simulation while under/overcovering the target at depth by more than 5 mm in 2 out of 12 cases with clinical setup. Mean target V90% was 98.5% (CT-based simulation) and 84.4% (clinical setup). Ipsilateral lung/breast were better spared with CT-based simulation. To date, the methodology for CT virtual simulation was applied on 152 patients and collision was avoided in all cases. CONCLUSIONS: CT-based simulation and target delineation allows for improved definition of the en-face electron field with less amount of normal tissue irradiated while including the entire target with an adequate margin and optimal electron energy.

Monte Carlo investigation of collapsed versus rotated IMRT plan verification.

IMRT QA requires, among other tests, a time-consuming process of measuring the absorbed dose, at least to a point, in a high-dose, low-dose-gradient region. Some clinics use a technique of measuring this dose with all beams delivered at a single gantry angle (collapsed delivery), as opposed to the beams delivered at the planned gantry angle (rotated delivery). We examined, established, and optimized Monte Carlo simulations of the dosimetry for IMRT verification of treatment plans for these two different delivery modes (collapsed versus rotated). The results of the simulations were compared to the treatment planning system dose calculations for the two delivery modes, as well as to measurements taken. This was done in order to investigate the validity of the use of a collapsed delivery technique for IMRT QA. The BEAMnrc, DOSXYZnrc, and egs_chamber codes were utilized for the Monte Carlo simulations along with the MMCTP system. A number of different plan complexity metrics were also used in the analysis of the dose distributions in a bid to qualify why verification in a collapsed delivery may or may not be optimal for IMRT QA. Following the Alfonso et al. formalism, the kfclin,frefQclin,Q correction factor was calculated to correct the deviation of small fields from the reference conditions used for beam calibration. We report on the results obtained for a cohort of 20 patients. The plan complexity was investigated for each plan using the complexity metrics of homogeneity index, conformity index, modulation complexity score, and the fraction of beams from a particular plan that intersect the chamber when performing the QA. Rotated QA gives more consistent results than the collapsed QA technique. The kfclin,frefQclin,Qfactor deviates less from 1 for rotated QA than for collapsed QA. If the homogeneity index is less than 0.05 then the kfclin,frefQclin,Q factor does not deviate from unity by more than 1%. A value this low for the homogeneity index can only be obtained with the rotated QA technique.

Hypofractionated radiation therapy (66 Gy in 22 fractions at 3 Gy per fraction) for favorable-risk prostate cancer: long-term outcomes.

PURPOSE: To report long-term outcomes of low- and intermediate-risk prostate cancer patients treated with high-dose hypofractionated radiation therapy (HypoRT). METHODS AND MATERIALS: Patients with low- and intermediate-risk prostate cancer were treated using 3-dimensional conformal radiation therapy to a dose of 66 Gy in 22 daily fractions of 3 Gy without hormonal therapy. A uniform 7-mm margin was created around the prostate for the planning target volume, and treatment was prescribed to the isocenter. Treatment was delivered using daily ultrasound image-guided radiation therapy. Common Terminology Criteria for Adverse Events, version 3.0, was used to prospectively score toxicity. Biochemical failure was defined as the nadir prostate-specific antigen level plus 2 ng/mL. RESULTS: A total of 129 patients were treated between November 2002 and December 2005. With a median follow-up of 90 months, the 5- and 8-year actuarial biochemical control rates were 97% and 92%, respectively. The 5- and 8-year actuarial overall survival rates were 92% and 88%, respectively. Only 1 patient died from prostate cancer at 92 months after treatment, giving an 8-year actuarial cancer-specific survival of 98%. Radiation therapy was well tolerated, with 57% of patients not experiencing any acute gastrointestinal (GI) or genitourinary (GU) toxicity. For late toxicity, the worst grade ≥2 rate for GI and GU toxicity was 27% and 33%, respectively. There was no grade >3 toxicity. At last follow-up, the rate of grade ≥2 for both GI and GU toxicity was only 1.5%. CONCLUSIONS: Hypofractionation with 66 Gy in 22 fractions prescribed to the isocenter using 3-dimensional conformal radiation therapy produces excellent biochemical control rates, with moderate toxicity. However, this regimen cannot be extrapolated to the intensity modulated radiation therapy technique.

A dosimetric evaluation of dose escalation for the radical treatment of locally advanced vulvar cancer by intensity-modulated radiation therapy.

The purpose of this planning study was to determine whether intensity-modulated radiation therapy (IMRT) reduces the radiation dose to organs at risk (OAR) when compared with 3D conventional radiation therapy (3D-CRT) in patients with vulvar cancer treated by irradiation. This study also investigated the use of sequential IMRT boost (seq-IMRT) and simultaneous integrated boost (SIB-IMRT) for dose escalation in the treatment of locally advanced vulvar cancer. Five vulvar cancer patients treated in the postoperative setting and 5 patients treated with definitive intent (def-group) were evaluated. For the postoperative group, 3D-CRT and IMRT plans to a total dose (TD) of 45 Gy were generated. For the def-group, 4 plans were generated: a 3D-CRT and an IMRT plan to a TD of 56.4 Gy, a SIB-IMRT plan to a TD of 56 Gy, and a SIB-IMRT with dose escalation (SIB-IMRT-esc): TD of 67.2 Gy. Mean dose and dose-volume histograms were compared using Student's t-test. IMRT significantly (all p < 0.05) reduced the D(mean), V30, and V40 for all OAR in the adjuvant setting. The V45 was also significantly reduced for all OAR except the bladder. For patients treated in the def-group, all IMRT techniques significantly reduced the D(mean), V40, and V45 for all OAR. The mean femur doses with SIB-IMRT and SIB-IMRT-esc were 47% and 49% lower compared with 3D-CRT. SIB-IMRT-esc reduced the doses to the OAR compared with seq-3D-CRT but increased the D(max.) for the small bowel, rectum, and bladder. IMRT reduces the dose to the OAR compared with 3D-CRT in patients with vulvar cancer receiving irradiation to a volume covering the vulvar region and nodal areas without compromising the dosimetric coverage of the target volume. IMRT for vulvar cancer is feasible and an attractive option for dose escalation studies.

IMRT quality assurance using a second treatment planning system.

We used a second treatment planning system (TPS) for independent verification of the dose calculated by our primary TPS in the context of patient-specific quality assurance (QA) for intensity-modulated radiation therapy (IMRT). QA plans for 24 patients treated with inverse planned dynamic IMRT were generated using the Nomos Corvus TPS. The plans were calculated on a computed tomography scan of our QA phantom that consists of three Solid Water slabs sandwiching radiochromic films, and an ion chamber that is inserted into the center slab of the phantom. For the independent verification, the dose was recalculated using the Varian Eclipse TPS using the multileaf collimator files and beam geometry from the original plan. The data was then compared in terms of absolute dose to the ion chamber volume as well as relative dose on isodoses calculated at the film plane. The calculation results were also compared with measurements performed for each case. When comparing ion chamber doses, the mean ratio was 0.999 (SD 0.010) for Eclipse vs. Corvus, 0.988 (SD 0.020) for the ionization chamber measurements vs. Corvus, and 0.989 (SD 0.017) for the ionization chamber measurements vs. Eclipse. For 2D doses with gamma histogram, the mean value of the percentage of pixels passing the criteria of 3%, 3 mm was 94.4 (SD 5.3) for Eclipse vs. Corvus, 85.1 (SD 10.6) for Corvus vs. film, and 93.7 (SD 4.1) for Eclipse vs. film; and for the criteria of 5%, 3 mm, 98.7 (SD 1.5) for Eclipse vs. Corvus, 93.0 (SD 7.8) for Corvus vs. film, and 98.0 (SD 1.9) for Eclipse vs. film. We feel that the use of the Eclipse TPS as an independent, accurate, robust, and time-efficient method for patient-specific IMRT QA is feasible in clinic.

Evaluation criteria for film based intensity modulated radiation therapy quality assurance.

The aim of this study was to use different gamma histogram criteria for the comparison of planned dose with irradiated dose distribution and find that what percent of pixels passing a certain criteria imitate a good quality plan. The dose was calculated for 156 patients by inverse planning optimization using the Corvus treatment planning system. Gafchromic films in combination with 2571 0.6 cm(3) Farmer type ionization chamber and Farmer 2570/1 electrometer from NE Technology were used to measure the delivered dose in solid water phantom. All the measurements were performed on Varian CL21EX linear accelerator (Varian Medical Systems, Palo Alto, CA) fitted with a Millennium 120 leaf collimator. In this study the mean value of the percent of passing pixels within the region of interest under the criterion of 3% DD and 3mm DTA is 90.2+/-7.1% for head and neck cases and 92.2+/-5.8% for non-head and neck cases. If we choose the criteria of 3% DD and 3mm DTA then 96.3% head and neck plans have the percent of passing pixels>or=75% and 95.1% non-head and neck plans have the percent of passing pixels>or=80%. It is evident from the results of this study that the criterion of 5% DD and 3mm DTA with the percent of passing pixels>or=90 for non-head and neck cases while the percent of passing pixels>or=85 for head and neck cases endorse that a plan is good. The results of this study may be useful for other institutions which use verification software and EBT films for patient specific IMRT QA.

Killing two birds with one stone: a dosimetric study of dual target radiosurgery using a single isocenter.

The treatment of hematogenous brain metastases is a frequent indication for stereotactic radiosurgery (SRS). It is common for more than one metastasis to be treated during the same SRS session. We retrospectively identified four cases where our m3 micro multileaf collimator (mMLC) was used to create two distinct apertures and treat adjacent lesions using a single isocenter. For these four cases, single isocenter plans with static conformal beams were dosimetrically compared to plans utilizing two isocenters with static conformal beams or conformal arcs. The effects on dose homogeneity, dose conformity, and the minimum isodose separating the two targets are minor and variable. On the other hand, the use of a single isocenter technique consistently halves delivery time and decreases the integral dose to normal tissue. For small adjacent metastases, which can simultaneously be encompassed within the high-resolution portion of the m3/Novalis mMLC collimator, the use of a single rather than a dual isocenter technique is feasible and generally advantageous.

Long-term management of patients with multiple brain metastases after shaped beam radiosurgery. Case report and review of the literature.

The role of radiosurgery in the treatment of patients with advanced-stage metastatic disease is currently under debate. Previous randomized studies have not consistently supported the use of radiosurgery to treat patients with numbers of brain metastases. In negative-results studies, however, intracranial tumor control was high but extracranial disease progressed; thus, patient survival was not greatly affected, although neurocognitive function was generally maintained until death. Because the future promises improved systemic (extracranial) therapy, the successful control of brain disease is that much more crucial. Thus, for selected patients with multiple metastases to the brain who remain in good neurological condition, aggressive lesion-targeting radiosurgery should be very useful. Although a major limitation to success of this therapy is the lack of control of extracranial disease in most patients, it is clear that well-designed, aggressive treatment substantially decreases the progression of brain metastases and also improves neurocognitive survival. The authors present the management and a methodology for rational treatment of a patient with breast cancer who has harbored 24 brain metastases during a 3-year period.

Optimal marker placement in photogrammetry patient positioning system.

A photogrammetry-based patient positioning system has been used instead of the conventional laser alignment technique for patient set-up in external beam radiotherapy. It tracks skin affixed reflective markers with multiple infrared cameras. The three-dimensional (3D) positions of the markers provide reference information to determine the treatment plan isocenter location and hence provide the ability to position the lesion at the isocenter of the treatment linear accelerator. However, in current clinical practice for lung or liver lesion treatments, fiducial markers are usually randomly affixed onto the patients' chest and abdomen, so that the actual target registration error (TRE) of the internal lesions inside the body may be large, depending on the fiducial registration error (FRE). There exists an optimal marker configuration that can minimize the TRE. In this paper, we developed methods to design the patient-specific optimal configurations of the surface makers to minimize the TRE, given the patient's surface contour, the lesion position and the FRE. Floating genetic algorithm (GA) optimization was used to optimize the positions of the skin markers. The surface curve of the patient body was determined by an automatic segmentation algorithm from the planning CT. The method was evaluated using a body phantom implanted with a metal ball (a simulated target). By registering two CT scans using the surface markers and measuring the displacement of the target, the TRE was measured. The TRE was also measured by taking two orthogonal portal films after positioning the phantom using the photogrammetry based patient positioning system. A 50% reduction in TRE has been achieved by using the optimal configuration compared to the random configuration. This result demonstrates that the optimization of a fiducial configuration can result in improved tumor targeting ability.