Lung tumor segmentation methods: Impact on the uncertainty of radiomics features for non-small cell lung cancer.

PURPOSE: To evaluate the uncertainty of radiomics features from contrast-enhanced breath-hold helical CT scans of non-small cell lung cancer for both manual and semi-automatic segmentation due to intra-observer, inter-observer, and inter-software reliability. METHODS: Three radiation oncologists manually delineated lung tumors twice from 10 CT scans using two software tools (3D-Slicer and MIM Maestro). Additionally, three observers without formal clinical training were instructed to use two semi-automatic segmentation tools, Lesion Sizing Toolkit (LSTK) and GrowCut, to delineate the same tumor volumes. The accuracy of the semi-automatic contours was assessed by comparison with physician manual contours using Dice similarity coefficients and Hausdorff distances. Eighty-three radiomics features were calculated for each delineated tumor contour. Informative features were identified based on their dynamic range and correlation to other features. Feature reliability was then evaluated using intra-class correlation coefficients (ICC). Feature range was used to evaluate the uncertainty of the segmentation methods. RESULTS: From the initial set of 83 features, 40 radiomics features were found to be informative, and these 40 features were used in the subsequent analyses. For both intra-observer and inter-observer reliability, LSTK had higher reliability than GrowCut and the two manual segmentation tools. All observers achieved consistently high ICC values when using LSTK, but the ICC value varied greatly for each observer when using GrowCut and the manual segmentation tools. For inter-software reliability, features were not reproducible across the software tools for either manual or semi-automatic segmentation methods. Additionally, no feature category was found to be more reproducible than another feature category. Feature ranges of LSTK contours were smaller than those of manual contours for all features. CONCLUSION: Radiomics features extracted from LSTK contours were highly reliable across and among observers. With semi-automatic segmentation tools, observers without formal clinical training were comparable to physicians in evaluating tumor segmentation.

Dosimetric advantages of a "butterfly" technique for intensity-modulated radiation therapy for young female patients with mediastinal Hodgkin's lymphoma.

PURPOSE: High cure rates for Hodgkin's lymphoma must be balanced with long-term treatment-related toxicity. Here we report an intensity-modulated radiation therapy (IMRT) technique that achieves adequate target coverage for mediastinal disease while minimizing high- and low-dose exposure of critical organs. METHODS AND MATERIALS: Treatment plans for IMRT and conventional anteroposterior-posteroanterior (AP-PA) techniques, with comparable coverage of the planning target volume (PTV), were generated for 9 female patients with mediastinal Hodgkin's lymphoma assuming use of inclined positioning, daily breath-hold, and CT-on-rails verification. Our "butterfly" IMRT beam arrangement involved anterior beams of 300°-30° and posterior beams of 160°-210°. Percentages of normal structures receiving 30 Gy (V30), 20 Gy (V20), and 5 Gy (V5) were tabulated for the right and left breasts, total lung, heart, left and right ventricles, left anterior descending coronary artery (LAD), and spinal cord. Differences in each variable, conformity index, homogeneity index, and V107% between the two techniques were calculated (IMRT minus conventional). RESULTS: Use of IMRT generally reduced the V30 and V20 to critical structures: -1.4% and +0.1% to the right breast, -1.7% and -0.9% to the left breast, -14.6% and -7.7% to the total lung, -12.2% and -10.5% to the heart, -2.4% and -14.2% to the left ventricle, -16.4% and -8.4% to the right ventricle, -7.0% and -14.2% to the LAD, and -52.2% and -13.4% to the spinal cord. Differences in V5 were +6.2% for right breast, +2.8% for left breast, +12.9% for total lung, -3.5% for heart, -8.2% for left ventricle, -1.5% for right ventricle, +0.1% for LAD, and -0.1% for spinal cord. Use of IMRT significantly reduced the volume of tissue receiving 107% of the dose (mean 754 cm3 reduction). CONCLUSIONS: This butterfly technique for IMRT avoids excess exposure of heart, breast, lung, and spinal cord to doses of 30 or 20 Gy; mildly increases V5 to the breasts; and decreases the V107%.

Hematologic toxicity in RTOG 0418: a phase 2 study of postoperative IMRT for gynecologic cancer.

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

Involved field radiation for Hodgkin's lymphoma: the actual dose to breasts in close proximity.

To decrease the risk of late toxicities in Hodgkin's lymphoma (HL) patients treated with radiation therapy (RT) (HL), involved field radiation therapy (IFRT) has largely replaced the extended fields. To determine the out-of-field dose delivered from a typical IFRT to surrounding critical structures, we measured the dose at various points in an anthropomorphic phantom. The phantom is divided into 1-inch-thick slices with the ability to insert TLDs at 3-cm intervals grid spacing. Two treatment fields were designed, and a total of 45 TLDs were placed (equally spaced) at the margin of the each of the 2 radiation fields. After performing a computed tomography simulation, 2 treatment plans targeting the mediastinum, a typical treatment field in patients with early stage HL, were generated. A total dose of 3060 cGy was delivered to the gross tumor volume for each field consecutively. The highest measured dose detected at 1 cm from the field edge in the planning target volume was 496 cGy, equivalent to 16% of the isocentric dose. The dose dropped significantly with increasing distance from the field edge. It ranged from 1.1-3.9% of the isocentric dose at a distance of 3.2-4 cm to <1.6% at a distance of >6 cm. Although the computer treatment planning system (CTPS) frequently underestimated the dose delivered, the difference in dose between measured and generated by CTPS was <2.5% in 90 positions measured. The collateral dose of radiation to breasts from IFRT is minimal. The out-of-field dose, although mildly underestimated by CTPS, becomes insignificant at >3 cm from the field edge of the radiation field.

Radiation for Hodgkin's lymphoma in young female patients: a new technique to avoid the breasts and decrease the dose to the heart.

PURPOSE: To demonstrate how, in young female patients with Hodgkin's lymphoma, using an inclined board technique can further decrease the volume of breasts and heart in the treatment field. METHODS AND MATERIALS: An inclined board was constructed with the ability to mount an Aquaplast face mask, a Vacu-Lock, and a hip stopper. Eight female patients with early-stage Hodgkin's lymphoma were planned and compared using the conventional flat position and the inclined board position. All patients on the inclined board were planned with 90° degree table position and 15° gantry angle rotation to compensate for the beam divergence resulting from the patient's position on the inclined board. Dose-volume histograms were generated, as well as the mean V30 and V5 of both breasts and heart using both treatment positions. RESULTS: The mean value of V30 of the right breast, left breast, and heart decreased from 3%, 3%, and 13%, respectively, using the flat position to 0, 0.4%, and 5%, respectively, using the inclined board. The mean value of V5 of the right breast, left breast, and heart decreased from 6%, 13%, and 36%, respectively, using the flat position to 2%, 8%, and 29%, respectively, using the inclined board. CONCLUSIONS: Compared with conventional flat positioning, this simple device and technique allows better sparing of the breasts and the heart while maintaining comparable target coverage and total lung dose.

Successful treatment of a free-moving abdominal mass with radiation therapy guided by cone-beam computed tomography: a case report.

INTRODUCTION: Because tumors in the abdomen can change position, targeting these tumors for radiation therapy should be done with caution; use of daily image-guided radiation therapy is advised. CASE PRESENTATION: We report the case of a 72-year-old Caucasian man with recurrent mantle cell lymphoma who was referred for palliative radiation therapy for an abdominopelvic tumor. Computed tomography was used to generate images for radiation treatment planning. Comparison of those planning images with a positron emission tomography/computed tomography scan ordered during the planning period revealed that the tumor had moved from one side of the abdomen to the other during the three-day interval between scans. To account for this unusual tumor movement, we obtained a second set of planning computed tomography scans and used a Varian cone-beam computed tomography scanner with on-board imaging capability to target the tumor before each daily treatment session, leading to successful treatment and complete resolution of the mass. CONCLUSION: Abdominal masses associated with the mesentery should be considered highly mobile; thus, radiation therapy for such masses should be used with the utmost caution. Modern radiation therapy techniques offer the ability to verify the tumor location in real time and shift the treatment ports accordingly over the course of treatment.

Validation of a new grid-based Boltzmann equation solver for dose calculation in radiotherapy with photon beams.

A new grid-based Boltzmann equation solver, Acuros, was developed specifically for performing accurate and rapid radiotherapy dose calculations. In this study we benchmarked its performance against Monte Carlo for 6 and 18 MV photon beams in heterogeneous media. Acuros solves the coupled Boltzmann transport equations for neutral and charged particles on a locally adaptive Cartesian grid. The Acuros solver is an optimized rewrite of the general purpose Attila software, and for comparable accuracy levels, it is roughly an order of magnitude faster than Attila. Comparisons were made between Monte Carlo (EGSnrc) and Acuros for 6 and 18 MV photon beams impinging on a slab phantom comprising tissue, bone and lung materials. To provide an accurate reference solution, Monte Carlo simulations were run to a tight statistical uncertainty (sigma approximately 0.1%) and fine resolution (1-2 mm). Acuros results were output on a 2 mm cubic voxel grid encompassing the entire phantom. Comparisons were also made for a breast treatment plan on an anthropomorphic phantom. For the slab phantom in regions where the dose exceeded 10% of the maximum dose, agreement between Acuros and Monte Carlo was within 2% of the local dose or 1 mm distance to agreement. For the breast case, agreement was within 2% of local dose or 2 mm distance to agreement in 99.9% of voxels where the dose exceeded 10% of the prescription dose. Elsewhere, in low dose regions, agreement for all cases was within 1% of the maximum dose. Since all Acuros calculations required less than 5 min on a dual-core two-processor workstation, it is efficient enough for routine clinical use. Additionally, since Acuros calculation times are only weakly dependent on the number of beams, Acuros may ideally be suited to arc therapies, where current clinical algorithms may incur long calculation times.

Clinical implementation of electron energy changes of varian linear accelerators.

Modern dual photon energy linear accelerators often come with a few megavoltage electron beams. The megavoltage electron beam has limited range and relative sharp distal falloff in its depth dose curve compared to that of megavoltage photon beam. Its radiation dose is often delivered appositionally to cover the target volume to its distal 90% depth dose (d90), while avoiding the normal--sometimes critical--structure immediately distal to the target. Varian linear accelerators currently offer selected electron beams of 4, 6, 9, 12, 16 and 20 MeV electron beam energies. However, intermediate electron energy is often needed for optimal dose distribution. In this study we investigated electron beam characteristics and implemented two intermediate 7 and 11 MeV electron beams on Varian linear accelerators. Comprehensive tests and measurements indicated the new electron beams met all dosimetry parameter criteria and operational safety standards. Between the two new electron beams and the existing electron beams we were able to provide a choice of electron beams of 4, 6, 7, 9, 11, 12, 16 and 20 MeV electron energies, which had d90 depth between 1.5 cm and 6.0 cm (from 1.5 cm to 4.0 cm in 0.5 cm increments) to meet our clinical needs.

Quantifying tumor-selective radiation dose enhancements using gold nanoparticles: a monte carlo simulation study.

Gold nanoparticles can enhance the biological effective dose of radiation delivered to tumors, but few data exist to quantify this effect. The purpose of this project was to build a Monte Carlo simulation model to study the degree of dose enhancement achievable with gold nanoparticles. A Monte Carlo simulation model was first built using Geant4 code. An Ir-192 brachytherapy source in a water phantom was simulated and the calculation model was first validated against previously published data. We then introduced up to 10(13) gold nanospheres per cm(3) into the water phantom and examined their dose enhancement effect. We compared this enhancement against a gold-water mixture model that has been previously used to attempt to quantify nanoparticle dose enhancement. In our benchmark test, dose-rate constant, radial dose function, and two-dimensional anisotropy function calculated with our model were within 2% of those reported previously. Using our simulation model we found that the radiation dose was enhanced up to 60% with 10(13) gold nanospheres per cm(3) (9.6% by weight) in a water phantom selectively around the nanospheres. The comparison study indicated that our model more accurately calculated the dose enhancement effect and that previous methodologies overestimated the dose enhancement up to 16%. Monte Carlo calculations demonstrate that biologically-relevant radiation dose enhancement can be achieved with the use of gold nanospheres. Selective tumor labeling with gold nanospheres may be a strategy for clinically enhancing radiation effects.

Intensity-modulated radiation therapy (IMRT) of cancers of the head and neck: comparison of split-field and whole-field techniques.

BACKGROUND: Oropharynx cancers treated with intensity-modulated radiation (IMRT) are often treated with a monoisocentric or half-beam technique (HB). IMRT is delivered to the primary tumor and upper neck alone, while the lower neck is treated with a matching anterior beam. Because IMRT can treat the entire volume or whole field (WF), the primary aim of the study was to test the ability to plan cases using WF-IMRT while obtaining an optimal plan and acceptable dose distribution and also respecting normal critical structures. METHODS AND MATERIALS: Thirteen patients with early-stage oropharynx cancers had treatment plans created with HB-IMRT and WF-IMRT techniques. Plans were deemed acceptable if they met the planning guidelines (as defined or with minor violations) of the Radiation Therapy Oncology Group protocol H0022. Comparisons included coverage to the planning target volume (PTV) of the primary (PTV66) and subclinical disease (PTV54). We also compared the ability of both techniques to respect the tolerance of critical structures. RESULTS: The volume of PTV66 treated to >110% was less in 9 of the 13 patients in the WF-IMRT plan as compared to the HB-IMRT plan. The calculated mean volume receiving >110% for all patients planned with WF-IMRT was 9.3% (0.8%-25%) compared to 13.7% (2.7%-23.7%) with HB-IMRT (p = 0.09). The PTV54 volume receiving >110% of dose was less in 10 of the 13 patients planned with WF-IMRT compared to HB-IMRT. The mean doses to all critical structures except the larynx were comparable with each plan. The mean dose to the larynx was significantly less (p = 0.001), 18.7 Gy, with HB-IMRT compared to 47 Gy with WF-IMRT. CONCLUSIONS: Regarding target volumes, acceptable plans can be generated with either WF-IMRT or HB-IMRT. WF-IMRT has an advantage if uncertainty at the match line is a concern, whereas HB-IMRT, particularly in cases not involving the base of tongue, can achieve much lower doses to the larynx.

Feasibility of dose escalation using intensity-modulated radiotherapy in posthysterectomy cervical carcinoma.

PURPOSE: To evaluate retrospectively the utility of intensity-modulated radiotherapy (IMRT) in reducing the volume of normal tissues receiving radiation at varying dose levels when the female pelvis after hysterectomy is treated to doses of 50.4 Gy and 54 Gy. METHODS AND MATERIALS: Computed tomography scans from 10 patients who had previously undergone conventional postoperative RT were selected. The clinical tumor volume (vaginal apex and iliac nodes) and organs at risk were contoured. Margins were added to generate the planning tumor volume. The Pinnacle and Corvus planning systems were used to develop conventional and IMRT plans, respectively. Conventional four-field plans were prescribed to deliver 45 Gy (4F(45 Gy)) or 50.4 Gy; eight-field IMRT plans were prescribed to deliver 50.4 Gy (IMRT(50.4 Gy)) or 54 Gy (IMRT(54 Gy)) to the planning tumor volume. All plans were normalized so that > or =97% of the planning tumor volume received the prescribed dose. Student's t test was used to compare the volumes of organs at risk receiving the same doses with different plans. RESULTS: The mean volume of bowel receiving > or =45 Gy was lower with the IMRT(50.4 Gy) (33% lower) and IMRT(54 Gy) (18% lower) plans than with the 4F(45 Gy) plan. The mean volume of rectum receiving > or =45 Gy or > or =50 Gy was also significantly reduced with the IMRT plans despite an escalation of the prescribed dose from 45 Gy with the conventional plans to 54 Gy with IMRT. The mean volume of bladder treated to 45 Gy was the same or slightly lower with the IMRT(50.4 Gy) and IMRT(54 Gy) plans compared with the 4F(45 Gy) plan. Compared with the 4F(45 Gy) plan, the IMRT(50.4 Gy) plan resulted in a smaller volume of bowel receiving 35-45 Gy and a larger volume of bowel receiving 50-55 Gy. Compared with the 4F(45 Gy) plan, the IMRT(54 Gy) plan resulted in smaller volumes of bowel receiving 45-50 Gy; however, small volumes of bowel received 55-60 Gy with the IMRT plan. CONCLUSION: Intensity-modulated RT may permit an increase in the radiation dose that can safely be delivered to the central pelvis and pelvic lymph nodes after hysterectomy. However, dose-volume calculations using individual CT scans do not account for internal organ motion. Detailed data concerning the relationships among radiation dose, treatment volume, and treatment effects are lacking, and prospective studies of pelvic IMRT are needed to determine the safety and efficacy of this treatment.