Automated contouring and statistical process control for plan quality in a breast clinical trial.

Background and purpose: Automatic review of breast plan quality for clinical trials is time-consuming and has some unique challenges due to the lack of target contours for some planning techniques. We propose using an auto-contouring model and statistical process control to independently assess planning consistency in retrospective data from a breast radiotherapy clinical trial. Materials and methods: A deep learning auto-contouring model was created and tested quantitatively and qualitatively on 104 post-lumpectomy patients' computed tomography images (nnUNet; train/test: 80/20). The auto-contouring model was then applied to 127 patients enrolled in a clinical trial. Statistical process control was used to assess the consistency of the mean dose to auto-contours between plans and treatment modalities by setting control limits within three standard deviations of the data's mean. Two physicians reviewed plans outside the limits for possible planning inconsistencies. Results: Mean Dice similarity coefficients comparing manual and auto-contours was above 0.7 for breast clinical target volume, supraclavicular and internal mammary nodes. Two radiation oncologists scored 95% of contours as clinically acceptable. The mean dose in the clinical trial plans was more variable for lymph node auto-contours than for breast, with a narrower distribution for volumetric modulated arc therapy than for 3D conformal treatment, requiring distinct control limits. Five plans (5%) were flagged and reviewed by physicians: one required editing, two had clinically acceptable variations in planning, and two had poor auto-contouring. Conclusions: An automated contouring model in a statistical process control framework was appropriate for assessing planning consistency in a breast radiotherapy clinical trial.

Radiation Sciences Education in Africa: An Assessment of Current Training Practices and Evaluation of a High-Yield Course in Radiation Biology and Radiation Physics.

PURPOSE: Formal education in the radiation sciences is critical for the safe and effective delivery of radiotherapy. Practices and patterns of radiation sciences education and trainee performance in the radiation sciences are poorly described. This study assesses the current state of radiation sciences education in Africa and evaluates a high-yield, on-site educational program in radiation biology and radiation physics for oncology and radiation therapy trainees in Africa. METHODS: An anonymous survey was distributed to members of the African Organization for Research and Treatment in Cancer Training Interest Group to assess current attitudes and practices toward radiation sciences education. A 2-week, on-site educational course in radiation biology and radiation physics was conducted at the Cancer Diseases Hospital in Lusaka, Zambia. Pre- and postcourse assessments in both disciplines were administered to gauge the effectiveness of an intensive high-yield course in the radiation sciences. RESULTS: Significant deficiencies were identified in radiation sciences education, especially in radiation biology. Lack of expert instructors in radiation biology was reported by half of all respondents and was the major contributing factor to deficient education in the radiation sciences. The educational course resulted in marked improvements in radiation biology assessment scores (median pre- and posttest scores, 27% and 55%, respectively; P < .0001) and radiation physics assessment scores (median pre- and posttest scores, 30% and 57.5%, respectively; P < .0001). CONCLUSION: Radiation sciences education in African oncology training programs is inadequate. International collaboration between expert radiation biology and radiation physics instructors can address this educational deficiency and improve trainee competence in the foundational radiation sciences that is critical for the safe and effective delivery of radiotherapy.

Radiation-induced lung toxicity in mice irradiated in a strong magnetic field.

Strong magnetic fields affect radiation dose deposition in MRI-guided radiation therapy systems, particularly at interfaces between tissues of differing densities such as those in the thorax. In this study, we evaluated the impact of a 1.5 T magnetic field on radiation-induced lung damage in C57L/J mice. We irradiated 140 mice to the whole thorax with parallel-opposed Co-60 beams to doses of 0, 9.0, 10.0, 10.5, 11.0, 12.0, or 13.0 Gy (20 mice per dose group). Ten mice per dose group were irradiated while a 1.5 T magnetic field was applied transverse to the radiation beam and ten mice were irradiated with the magnetic field set to 0 T. We compared survival and noninvasive assays of radiation-induced lung damage, namely respiratory rate and metrics derived from thoracic cone-beam CTs, between the two sets of mice. We report two main results. First, the presence of a transverse 1.5 T field during irradiation had no impact on survival of C57L/J mice. Second, there was a small but statistically significant effect on noninvasive assays of radiation-induced lung damage. These results provide critical safety data for the clinical introduction of MRI-guided radiation therapy systems.

Treatment Planning System Calculation Errors Are Present in Most Imaging and Radiation Oncology Core-Houston Phantom Failures.

PURPOSE: The anthropomorphic phantom program at the Houston branch of the Imaging and Radiation Oncology Core (IROC-Houston) is an end-to-end test that can be used to determine whether an institution can accurately model, calculate, and deliver an intensity modulated radiation therapy dose distribution. Currently, institutions that do not meet IROC-Houston's criteria have no specific information with which to identify and correct problems. In the present study, an independent recalculation system was developed to identify treatment planning system (TPS) calculation errors. METHODS AND MATERIALS: A recalculation system was commissioned and customized using IROC-Houston measurement reference dosimetry data for common linear accelerator classes. Using this system, 259 head and neck phantom irradiations were recalculated. Both the recalculation and the institution's TPS calculation were compared with the delivered dose that was measured. In cases in which the recalculation was statistically more accurate by 2% on average or 3% at a single measurement location than was the institution's TPS, the irradiation was flagged as having a "considerable" institutional calculation error. The error rates were also examined according to the linear accelerator vendor and delivery technique. RESULTS: Surprisingly, on average, the reference recalculation system had better accuracy than the institution's TPS. Considerable TPS errors were found in 17% (n=45) of the head and neck irradiations. Also, 68% (n=13) of the irradiations that failed to meet the IROC-Houston criteria were found to have calculation errors. CONCLUSIONS: Nearly 1 in 5 institutions were found to have TPS errors in their intensity modulated radiation therapy calculations, highlighting the need for careful beam modeling and calculation in the TPS. An independent recalculation system can help identify the presence of TPS errors and pass on the knowledge to the institution.

Technical Note: A Monte Carlo study of magnetic-field-induced radiation dose effects in mice.

PURPOSE: Magnetic fields are known to alter radiation dose deposition. Before patients receive treatment using an MRI-linear accelerator (MRI-Linac), preclinical studies are needed to understand the biological consequences of magnetic-field-induced dose effects. In the present study, the authors sought to identify a beam energy and magnetic field strength combination suitable for preclinical murine experiments. METHODS: Magnetic field dose effects were simulated in a mouse lung phantom using various beam energies (225 kVp, 350 kVp, 662 keV [Cs-137], 2 MV, and 1.25 MeV [Co-60]) and magnetic field strengths (0.75, 1.5, and 3 T). The resulting dose distributions were compared with those in a simulated human lung phantom irradiated with a 6 or 8 MV beam and orthogonal 1.5 T magnetic field. RESULTS: In the human lung phantom, the authors observed a dose increase of 45% and 54% at the soft-tissue-to-lung interface and a dose decrease of 41% and 48% at the lung-to-soft-tissue interface for the 6 and 8 MV beams, respectively. In the mouse simulations, the magnetic fields had no measurable effect on the 225 or 350 kVp dose distribution. The dose increases with the Cs-137 beam for the 0.75, 1.5, and 3 T magnetic fields were 9%, 29%, and 42%, respectively. The dose decreases were 9%, 21%, and 37%. For the 2 MV beam, the dose increases were 16%, 33%, and 31% and the dose decreases were 9%, 19%, and 30%. For the Co-60 beam, the dose increases were 19%, 54%, and 44%, and the dose decreases were 19%, 42%, and 40%. CONCLUSIONS: The magnetic field dose effects in the mouse phantom using a Cs-137, 3 T combination or a Co-60, 1.5 or 3 T combination most closely resemble those in simulated human treatments with a 6 MV, 1.5 T MRI-Linac. The effects with a Co-60, 1.5 T combination most closely resemble those in simulated human treatments with an 8 MV, 1.5 T MRI-Linac.

Spot scanning proton therapy for malignancies of the base of skull: treatment planning, acute toxicities, and preliminary clinical outcomes.

PURPOSE: To describe treatment planning techniques and early clinical outcomes in patients treated with spot scanning proton therapy for chordoma or chondrosarcoma of the skull base. METHODS AND MATERIALS: From June 2010 through August 2011, 15 patients were treated with spot scanning proton therapy for chordoma (n=10) or chondrosarcoma (n=5) at a single institution. Toxicity was prospectively evaluated and scored weekly and at all follow-up visits according to Common Terminology Criteria for Adverse Events, version 3.0. Treatment planning techniques and dosimetric data were recorded and compared with those of passive scattering plans created with clinically applicable dose constraints. RESULTS: Ten patients were treated with single-field-optimized scanning beam plans and 5 with multifield-optimized intensity modulated proton therapy. All but 2 patients received a simultaneous integrated boost as well. The mean prescribed radiation doses were 69.8 Gy (relative biological effectiveness [RBE]; range, 68-70 Gy [RBE]) for chordoma and 68.4 Gy (RBE) (range, 66-70) for chondrosarcoma. In comparison with passive scattering plans, spot scanning plans demonstrated improved high-dose conformality and sparing of temporal lobes and brainstem. Clinically, the most common acute toxicities included fatigue (grade 2 for 2 patients, grade 1 for 8 patients) and nausea (grade 2 for 2 patients, grade 1 for 6 patients). No toxicities of grades 3 to 5 were recorded. At a median follow-up time of 27 months (range, 13-42 months), 1 patient had experienced local recurrence and a second developed distant metastatic disease. Two patients had magnetic resonance imaging-documented temporal lobe changes, and a third patient developed facial numbness. No other subacute or late effects were recorded. CONCLUSIONS: In comparison to passive scattering, treatment plans for spot scanning proton therapy displayed improved high-dose conformality. Clinically, the treatment was well tolerated, and with short-term follow-up, disease control rates and toxicity profiles were favorable.

Anatomic variation and dosimetric consequences of neoadjuvant hormone therapy before radiation therapy for prostate cancer.

PURPOSE: To characterize anatomic variation during neoadjuvant androgen deprivation (NAD) and determine a treatment planning strategy to maintain acceptable normal tissue dose while treating potential microscopic disease in the original (pre-NAD) tumor bed. METHODS AND MATERIALS: We retrospectively examined the effects of treating the post-NAD anatomy with plans derived before and after NAD in a group of 44 patients enrolled in an institutional review board-approved protocol. An 8-field intensity modulated radiation therapy (IMRT) treatment plan was generated on anatomy both before and after NAD for the first 35 patients. The pre-NAD treatment plan was applied to the post-NAD anatomy to evaluate the effect of complete pre-NAD tumor bed treatment on normal tissue sparing, and the post-NAD treatment plan was applied to the pre-NAD anatomy to investigate whether microscopic disease might go untreated in the location of the pre-NAD tumor bed. RESULTS: The prostate decreased in volume by an average of about 14 cm(3) (24.3%) and was correlated with NAD duration (P = .002). The prostate center of volume systematically shifted in the inferior direction (mean = 1.4 mm, P = .005) and inferior shift was correlated with absolute volume reduction of the prostate (P = .044) in a multivariate model containing rectal and bladder volume change and initial prostate volume. Pre-NAD treatment planning resulted in a significant increase in the bladder volume (P < .01) but little increase in the rectal volume treated to all dose levels. Post-NAD treatment planning resulted in decreased treatment of the prostate and seminal vesicles (on the pre-NAD anatomy) at the prescribed and 95% isodose levels (prostate: P = .033 and 0.025; seminal vesicles: P < .001). CONCLUSIONS: Anisotropic volume reduction of the prostate was found during NAD and correlated with NAD duration. Post-NAD based treatment planning can minimize excess bladder and rectal dose.

A beam-specific planning target volume (PTV) design for proton therapy to account for setup and range uncertainties.

PURPOSE: To report a method for explicitly designing a planning target volume (PTV) for treatment planning and evaluation in heterogeneous media for passively scattered proton therapy and scanning beam proton therapy using single-field optimization (SFO). METHODS AND MATERIALS: A beam-specific PTV (bsPTV) for proton beams was derived by ray-tracing and shifting ray lines to account for tissue misalignment in the presence of setup error or organ motion. Range uncertainties resulting from inaccuracies in computed tomography-based range estimation were calculated for proximal and distal surfaces of the target in the beam direction. The bsPTV was then constructed based on local heterogeneity. The bsPTV thus can be used directly as a planning target as if it were in photon therapy. To test the robustness of the bsPTV, we generated a single-field proton plan in a virtual phantom. Intentional setup and range errors were introduced. Dose coverage to the clinical target volume (CTV) under various simulation conditions was compared between plans designed based on the bsPTV and a conventional PTV. RESULTS: The simulated treatment using the bsPTV design performed significantly better than the plan using the conventional PTV in maintaining dose coverage to the CTV. With conventional PTV plans, the minimum coverage to the CTV dropped from 99% to 67% in the presence of setup error, internal motion, and range uncertainty. However, plans using the bsPTV showed minimal drop of target coverage from 99% to 94%. CONCLUSIONS: The conventional geometry-based PTV concept used in photon therapy does not work well for proton therapy. We investigated and validated a beam-specific PTV method for designing and evaluating proton plans.

Is a 3-mm intrafractional margin sufficient for daily image-guided intensity-modulated radiation therapy of prostate cancer?

PURPOSE: To determine whether a 3-mm isotropic target margin adequately covers the prostate and seminal vesicles (SVs) during administration of an intensity-modulated radiation therapy (IMRT) treatment fraction, assuming that daily image-guided setup is performed just before each fraction. MATERIALS AND METHODS: In-room computed tomographic (CT) scans were acquired immediately before and after a daily treatment fraction in 46 patients with prostate cancer. An eight-field IMRT plan was designed using the pre-fraction CT with a 3-mm margin and subsequently recalculated on the post-fraction CT. For convenience of comparison, dose plans were scaled to full course of treatment (75.6 Gy). Dose coverage was assessed on the post-treatment CT image set. RESULTS: During one treatment fraction (21.4+/-5.5 min), there were reductions in the volumes of the prostate and SVs receiving the prescribed dose (median reduction 0.1% and 1.0%, respectively, p<0.001) and in the minimum dose to 0.1 cm(3) of their volumes (median reduction 0.5 and 1.5 Gy, p<0.001). Of the 46 patients, three patients' prostates and eight patients' SVs did not maintain dose coverage above 70 Gy. Rectal filling correlated with decreased percentage-volume of SV receiving 75.6, 70, and 60 Gy (p<0.02). CONCLUSIONS: The 3-mm intrafractional margin was adequate for prostate dose coverage. However, a significant subset of patients lost SV dose coverage. The rectal volume change significantly affected SV dose coverage. For advanced-stage prostate cancers, we recommend to use larger margins or improve organ immobilization (such as with a rectal balloon) to ensure SV coverage.

Changes in the pelvic anatomy after an IMRT treatment fraction of prostate cancer.

PURPOSE: To quantify the three-dimensional variations of pelvic anatomy after a single treatment fraction. METHODS AND MATERIALS: Forty-six prostate cancer patients underwent computed tomography (CT) scanning with an in-room CT-on-rail system, before and immediately after one intensity-modulated radiotherapy (IMRT) session. To study the soft-tissue anatomy changes, the pre- and post-treatment CT images were registered using the bony structure with an in-house image registration software system. The center of volume for both the prostate and seminal vesicles was used to assess the relative displacement of the same structure after the treatment fraction. RESULTS: During one treatment fraction (21 +/- 4 min), both the prostate and seminal vesicles showed statistically significant systematic trends in the superior and anterior directions of the patient's anatomy. The net increase in bladder volume was huge (127 +/- 79 cm(3)), yet this change did not translate into large target displacements. Although the population mean displacements in either direction were 1.3 +/- 2.9 mm for the prostate and 1.2 +/- 4.1 mm for the seminal vesicles in the anterior direction, a few patients had displacements as large as 8.4 mm and 15.6 mm, respectively. These large displacements correlated strongly (p < 0.001) with large rectal volume increases caused by gaseous build-up in the rectum. CONCLUSION: The observed intrafraction variations in anatomy during prostate IMRT sessions suggest that, for any given fraction, the organ motion and volume changes can potentially lead to compromised target coverage in about 15% of patients in whom the prostate position shifted >4 mm.